The rapid rise of cyberattacks and the gradual failure of traditional defense systems and approaches led to using artificial intelligence(AI)techniques(such as machine learning(ML)and deep learning(DL))to build more e...The rapid rise of cyberattacks and the gradual failure of traditional defense systems and approaches led to using artificial intelligence(AI)techniques(such as machine learning(ML)and deep learning(DL))to build more efficient and reliable intrusion detection systems(IDSs).However,the advent of larger IDS datasets has negatively impacted the performance and computational complexity of AI-based IDSs.Many researchers used data preprocessing techniques such as feature selection and normalization to overcome such issues.While most of these researchers reported the success of these preprocessing techniques on a shallow level,very few studies have been performed on their effects on a wider scale.Furthermore,the performance of an IDS model is subject to not only the utilized preprocessing techniques but also the dataset and the ML/DL algorithm used,which most of the existing studies give little emphasis on.Thus,this study provides an in-depth analysis of feature selection and normalization effects on IDS models built using three IDS datasets:NSL-KDD,UNSW-NB15,and CSE–CIC–IDS2018,and various AI algorithms.A wrapper-based approach,which tends to give superior performance,and min-max normalization methods were used for feature selection and normalization,respectively.Numerous IDS models were implemented using the full and feature-selected copies of the datasets with and without normalization.The models were evaluated using popular evaluation metrics in IDS modeling,intra-and inter-model comparisons were performed between models and with state-of-the-art works.Random forest(RF)models performed better on NSL-KDD and UNSW-NB15 datasets with accuracies of 99.86%and 96.01%,respectively,whereas artificial neural network(ANN)achieved the best accuracy of 95.43%on the CSE–CIC–IDS2018 dataset.The RF models also achieved an excellent performance compared to recent works.The results show that normalization and feature selection positively affect IDS modeling.Furthermore,while feature selection benefits simpler algorithms(such as RF),normalization is more useful for complex algorithms like ANNs and deep neural networks(DNNs),and algorithms such as Naive Bayes are unsuitable for IDS modeling.The study also found that the UNSW-NB15 and CSE–CIC–IDS2018 datasets are more complex and more suitable for building and evaluating modern-day IDS than the NSL-KDD dataset.Our findings suggest that prioritizing robust algorithms like RF,alongside complex models such as ANN and DNN,can significantly enhance IDS performance.These insights provide valuable guidance for managers to develop more effective security measures by focusing on high detection rates and low false alert rates.展开更多
Under the National Innovation-Driven Development Strategy,establishing a scientifically sound evaluation system for normal university students’innovation and entrepreneurship capabilities serves as a crucial foundati...Under the National Innovation-Driven Development Strategy,establishing a scientifically sound evaluation system for normal university students’innovation and entrepreneurship capabilities serves as a crucial foundation for optimizing innovation education models and enhancing teacher candidates’comprehensive competencies.Based on existing indicator frameworks,we designed a questionnaire and applied exploratory factor analysis(EFA)to screen indicators,reduce dimensionality,and analyze weighting.This process identified key metrics for evaluating pedagogical students’innovation capacities,ultimately constructing a targeted assessment system for normal university students.The study provides theoretical support for cultivating teacher trainees’innovative capabilities while contributing to the national innovation strategy implementation.展开更多
Fine particulatematter(PM_(2.5))samples were collected in two neighboring cities,Beijing and Baoding,China.High-concentration events of PM_(2.5) in which the average mass concentration exceeded 75μg/m^(3) were freque...Fine particulatematter(PM_(2.5))samples were collected in two neighboring cities,Beijing and Baoding,China.High-concentration events of PM_(2.5) in which the average mass concentration exceeded 75μg/m^(3) were frequently observed during the heating season.Dispersion Normalized Positive Matrix Factorization was applied for the source apportionment of PM_(2.5) as minimize the dilution effects of meteorology and better reflect the source strengths in these two cities.Secondary nitrate had the highest contribution for Beijing(37.3%),and residential heating/biomass burning was the largest for Baoding(27.1%).Secondary nitrate,mobile,biomass burning,district heating,oil combustion,aged sea salt sources showed significant differences between the heating and non-heating seasons in Beijing for same period(2019.01.10–2019.08.22)(Mann-Whitney Rank Sum Test P<0.05).In case of Baoding,soil,residential heating/biomass burning,incinerator,coal combustion,oil combustion sources showed significant differences.The results of Pearson correlation analysis for the common sources between the two cities showed that long-range transported sources and some sources with seasonal patterns such as oil combustion and soil had high correlation coefficients.Conditional Bivariate Probability Function(CBPF)was used to identify the inflow directions for the sources,and joint-PSCF(Potential Source Contribution Function)was performed to determine the common potential source areas for sources affecting both cities.These models facilitated a more precise verification of city-specific influences on PM_(2.5) sources.The results of this study will aid in prioritizing air pollution mitigation strategies during the heating season and strengthening air quality management to reduce the impact of downwind neighboring cities.展开更多
On-device Artificial Intelligence(AI)accelerators capable of not only inference but also training neural network models are in increasing demand in the industrial AI field,where frequent retraining is crucial due to f...On-device Artificial Intelligence(AI)accelerators capable of not only inference but also training neural network models are in increasing demand in the industrial AI field,where frequent retraining is crucial due to frequent production changes.Batch normalization(BN)is fundamental to training convolutional neural networks(CNNs),but its implementation in compact accelerator chips remains challenging due to computational complexity,particularly in calculating statistical parameters and gradients across mini-batches.Existing accelerator architectures either compromise the training accuracy of CNNs through approximations or require substantial computational resources,limiting their practical deployment.We present a hardware-optimized BN accelerator that maintains training accuracy while significantly reducing computational overhead through three novel techniques:(1)resourcesharing for efficient resource utilization across forward and backward passes,(2)interleaved buffering for reduced dynamic random-access memory(DRAM)access latencies,and(3)zero-skipping for minimal gradient computation.Implemented on a VCU118 Field Programmable Gate Array(FPGA)on 100 MHz and validated using You Only Look Once version 2-tiny(YOLOv2-tiny)on the PASCALVisualObjectClasses(VOC)dataset,our normalization accelerator achieves a 72%reduction in processing time and 83%lower power consumption compared to a 2.4 GHz Intel Central Processing Unit(CPU)software normalization implementation,while maintaining accuracy(0.51%mean Average Precision(mAP)drop at floating-point 32 bits(FP32),1.35%at brain floating-point 16 bits(bfloat16)).When integrated into a neural processing unit(NPU),the design demonstrates 63%and 97%performance improvements over AMD CPU and Reduced Instruction Set Computing-V(RISC-V)implementations,respectively.These results confirm that our proposed BN hardware design enables efficient,high-accuracy,and power-saving on-device training for modern CNNs.Our results demonstrate that efficient hardware implementation of standard batch normalization is achievable without sacrificing accuracy,enabling practical on-device CNN training with significantly reduced computational and power requirements.展开更多
Renormalization group analysis has been proposed to eliminate secular terms in perturbation solutions of differential equations and thus expand the domain of their validity.Here we extend the method to treat periodic ...Renormalization group analysis has been proposed to eliminate secular terms in perturbation solutions of differential equations and thus expand the domain of their validity.Here we extend the method to treat periodic orbits or limit cycles.Interesting normal forms could be derived through a generalization of the concept'resonance',which offers nontrivial analytic approximations.Compared with traditional techniques such as multi-scale methods,the current scheme proceeds in a very straightforward and simple way,delivering not only the period and the amplitude but also the transient path to limit cycles.The method is demonstrated with several examples including the Duffing oscillator,van der Pol equation and Lorenz equation.The obtained solutions match well with numerical results and with those derived by traditional analytic methods.展开更多
In recent decades,brain tumors have emerged as a serious neurological disorder that often leads to death.Hence,Brain Tumor Segmentation(BTS)is significant to enable the visualization,classification,and delineation of ...In recent decades,brain tumors have emerged as a serious neurological disorder that often leads to death.Hence,Brain Tumor Segmentation(BTS)is significant to enable the visualization,classification,and delineation of tumor regions in Magnetic Resonance Imaging(MRI).However,BTS remains a challenging task because of noise,non-uniform object texture,diverse image content and clustered objects.To address these challenges,a novel model is implemented in this research.The key objective of this research is to improve segmentation accuracy and generalization in BTS by incorporating Switchable Normalization into Faster R-CNN,which effectively captures the fine-grained tumor features to enhance segmentation precision.MRI images are initially acquired from three online datasets:Dataset 1—Brain Tumor Segmentation(BraTS)2018,Dataset 2—BraTS 2019,and Dataset 3—BraTS 2020.Subsequently,the Switchable Normalization-based Faster Regions with Convolutional Neural Networks(SNFRC)model is proposed for improved BTS in MRI images.In the proposed model,Switchable Normalization is integrated into the conventional architecture,enhancing generalization capability and reducing overfitting to unseen image data,which is essential due to the typically limited size of available datasets.The network depth is increased to obtain discriminative semantic features that improve segmentation performance.Specifically,Switchable Normalization captures the diverse feature representations from the brain images.The Faster R-CNN model develops end-to-end training and effective regional proposal generation,with an enhanced training stability using Switchable Normalization,to perform an effective segmentation in MRI images.From the experimental results,the proposed model attains segmentation accuracies of 99.41%,98.12%,and 96.71%on Datasets 1,2,and 3,respectively,outperforming conventional deep learning models used for BTS.展开更多
BACKGROUND Research has shown that several factors can influence postoperative abnormal liver function;however,most studies on this issue have focused specifically on hepatic and cardiac surgeries,leaving limited rese...BACKGROUND Research has shown that several factors can influence postoperative abnormal liver function;however,most studies on this issue have focused specifically on hepatic and cardiac surgeries,leaving limited research on contributing factors in other types of surgeries.AIM To identify the risk factors for early postoperative abnormal liver function in multiple surgery types and construct a risk prediction model.METHODS This retrospective cohort study involved 3720 surgical patients from 5 surgical departments at Guangdong Provincial Hospital of Traditional Chinese Medicine.Patients were divided into abnormal(n=108)and normal(n=3612)groups based on liver function post-surgery.Univariate analysis and LASSO regression screened variables,followed by logistic regression to identify risk factors.A prediction model was constructed based on the variables selected via logistic re-gression.The goodness-of-fit of the model was evaluated using the Hosm-er–Lemeshow test,while discriminatory ability was measured by the area under the receiver operating characteristic curve.Calibration curves were plotted to visualize the consistency between predicted probabilities and observed outcomes.RESULTS The key factors contributing to abnormal liver function after surgery include elevated aspartate aminotransferase and alanine aminotransferase levels and reduced platelet counts pre-surgery,as well as the sevoflurane use during the procedure,among others.CONCLUSION The above factors collectively represent notable risk factors for postoperative liver function injury,and the prediction model developed based on these factors demonstrates strong predictive efficacy.展开更多
Objective Coagulation abnormalities are common and prognostically significant in intensive care units(ICUs)and are associated with increased mortality.This study aimed to explore the association between the levels of ...Objective Coagulation abnormalities are common and prognostically significant in intensive care units(ICUs)and are associated with increased mortality.This study aimed to explore the association between the levels of coagulation markers and the risk of mortality among ICU patients with coagulation abnormalities.Methods This retrospective study investigated patients with coagulation abnormalities in the ICU between January 2021 and December 2022.The initial point for detecting hemostatic biomarkers due to clinical assessment of coagulation abnormalities was designated day 0.Patients were followed up for 28 days,and multivariate logistic regression analysis was utilized to identify risk factors for mortality.Results Of the 451 patients analyzed,115 died,and 336 were alive at the end of the 28-day period.Multivariate analysis revealed that elevated thrombin-antithrombin complex(TAT),tissue plasminogen activator inhibitor complex(tPAIC),prolonged prothrombin time,and thrombocytopenia were independent risk factors for mortality.For nonovert disseminated intravascular coagulation(DIC)patients,older age and thrombocytopenia were associated with increased risks of mortality,whereas elevated levels of plasminα2-plasmin inhibitor complex(PIC)were found to be independent predictors of survival.In patients with overt DIC,elevated levels of tPAIC were independently associated with increased risks of mortality.Nevertheless,thrombocytopenia was independently associated with increased risks of mortality in patients with pre-DIC.Conclusion Coagulation markers such as the TAT,tPAIC,PIC,and platelet count were significantly associated with mortality,underscoring the importance of maintaining a balance between coagulation and fibrinolysis.These findings highlight the potential for targeted therapeutic interventions based on specific coagulation markers to improve patient outcomes.展开更多
Quantitative real-time reverse transcription-polymerase chain reaction （qRT-PCR） is widely used in studies of gene expression. In most of these studies, housekeeping genes are used as internal references without val...Quantitative real-time reverse transcription-polymerase chain reaction （qRT-PCR） is widely used in studies of gene expression. In most of these studies, housekeeping genes are used as internal references without validation. To identify appropriate reference genes for qRT-PCR in Pacific abalone Haliotis discus hannai, we examined the transcription stability of six housekeeping genes in abalone tissues in the presence and absence of bacterial infection. For this purpose, abalone were infected with the bacterial pathogen Fibrio anguillarum for 12 h and 48 h. The mRNA levels of the housekeeping genes in five tissues （digestive glands, foot muscle, gill, hemocyte, and mantle） were determined by qRT-PCR. The PCR data was subsequently analyzed with the geNorm and NormFinder algorithms. The results show that in the absence of bacterial infection, elongation factor-l-alpha and beta-actin were the most stably expressed genes in all tissues, and thus are suitable as cross-tissue type normalization factors. However, we did not identify any universal reference genes post infection because the most stable genes varied between tissue types. Furthermore, for most tissues, the optimal reference genes identified by both algorithms at 12 h and 48 h post-infection differed. These results indicate that bacterial infection induced significant changes in the expression of abalone housekeeping genes in a manner that is dependent on tissue type and duration of infection. As a result, different normalization factors must be used for different tissues at different infection points.展开更多
Spinal and bulbar muscular atrophy is a neurodegenerative disease caused by extended CAG trinucleotide repeats in the androgen receptor gene,which encodes a ligand-dependent transcription facto r.The mutant androgen r...Spinal and bulbar muscular atrophy is a neurodegenerative disease caused by extended CAG trinucleotide repeats in the androgen receptor gene,which encodes a ligand-dependent transcription facto r.The mutant androgen receptor protein,characterized by polyglutamine expansion,is prone to misfolding and forms aggregates in both the nucleus and cytoplasm in the brain in spinal and bulbar muscular atrophy patients.These aggregates alter protein-protein interactions and compromise transcriptional activity.In this study,we reported that in both cultured N2a cells and mouse brain,mutant androgen receptor with polyglutamine expansion causes reduced expression of mesencephalic astrocyte-de rived neurotrophic factor.Overexpressio n of mesencephalic astrocyte-derived neurotrophic factor amelio rated the neurotoxicity of mutant androgen receptor through the inhibition of mutant androgen receptor aggregation.Conversely.knocking down endogenous mesencephalic astrocyte-derived neurotrophic factor in the mouse brain exacerbated neuronal damage and mutant androgen receptor aggregation.Our findings suggest that inhibition of mesencephalic astrocyte-derived neurotrophic factor expression by mutant androgen receptor is a potential mechanism underlying neurodegeneration in spinal and bulbar muscular atrophy.展开更多
Remodeling tumor microenvironment(TME)is a very promising and effective strategy to enhance the effects of chemotherapy,photodynamic therapy,and immunotherapy.Normalization of tumor vasculature as well as depletion of...Remodeling tumor microenvironment(TME)is a very promising and effective strategy to enhance the effects of chemotherapy,photodynamic therapy,and immunotherapy.Normalization of tumor vasculature as well as depletion of glutathione(GSH)can improve the TME.Here,we developed a novel therapeutic nanoparticle functional enzyme ultra QDAU5 nanoparticles(FEUQ Nps)based on a fluorescence-on and releasable strategy by combining a vascular normalization inducer,a GSH depleting agent,and an activated fluorophore.In which the cleavage of disulfide bonds releases active molecules that induce vascular normalization and improve the hypoxic microenvironment.In addition,it may deplete GSH in cancer cells,thus inducing the production of reactive oxygen species(ROS)and lipid peroxide(LPO)and promoting iron toxicity.It may also lead to endoplasmic stress and release of calmodulin,which activates the immune system.Meanwhile,quenched fluorophores are turned on in the presence of galactosidase(GLU)for tumor-specific labeling.In summary,we developed novel therapeutic agent nanoparticles with the function of vascular normalization inducers to achieve specific labeling of hepatocellular carcinoma while exerting efficient antitumor effects in vivo.展开更多
Tumor vascular normalization has emerged as a promising strategy for synergistic therapy recently.Based on the strategy of“fluorescence turn on-controllable release”,a novel bifunctional candidate was con-structed b...Tumor vascular normalization has emerged as a promising strategy for synergistic therapy recently.Based on the strategy of“fluorescence turn on-controllable release”,a novel bifunctional candidate was con-structed based on previous developed vascular normalization inducer QDAU5,which could self-assemble to form functional enzyme infrared QDAU5 nanoparticles(FEIRQ NPs).Subsequently,biological evaluation demonstrated that the FEIRQ NPs could induce ferroptosis,endoplasmic reticulum stress,and antigen pre-conditioning and maturation of dendritic cells and CD8^(+)T cells,leading to excellent antitumor efficacy in the absence of cytotoxic drugs.Additionally,FEIRQ NPs show high fluorescence intensity upon expo-sure to theβ-galactosidase(β-Gal)enzyme expressed in ovarian cancer,enabling real-time monitoring of therapeutic effects.Overall,our findings suggest a prospering strategy to early diagnosis and efficient therapy for ovarian cancer without cytotoxicity.展开更多
BACKGROUND At present,the influencing factors of social function in patients with residual depressive symptoms are still unclear.Residual depressive symptoms are highly harmful,leading to low mood in patients,affectin...BACKGROUND At present,the influencing factors of social function in patients with residual depressive symptoms are still unclear.Residual depressive symptoms are highly harmful,leading to low mood in patients,affecting work and interpersonal communication,increasing the risk of recurrence,and adding to the burden on families.Studying the influencing factors of their social function is of great significance.AIM To explore the social function score and its influencing factors in patients with residual depressive symptoms.METHODS This observational study surveyed patients with residual depressive symptoms(case group)and healthy patients undergoing physical examinations(control group).Participants were admitted between January 2022 and December 2023.Social functioning was assessed using the Sheehan Disability Scale(SDS),and scores were compared between groups.Factors influencing SDS scores in patients with residual depressive symptoms were analyzed by applying multiple linear regression while using the receiver operating characteristic curve,and these RESULTS The SDS scores of the 158 patients with depressive symptoms were 11.48±3.26.Compared with the control group,the SDS scores and all items in the case group were higher.SDS scores were higher in patients with relapse,discon-tinuous medication,drug therapy alone,severe somatic symptoms,obvious residual symptoms,and anxiety scores≥8.Disease history,medication compliance,therapy method,and residual symptoms correlated positively with SDS scores(r=0.354,0.414,0.602,and 0.456,respectively).Independent influencing factors included disease history,medication compliance,therapy method,somatic symptoms,residual symptoms,and anxiety scores(P<0.05).The areas under the curve for predicting social functional impairment using these factors were 0.713,0.559,0.684,0.729,0.668,and 0.628,respectively,with sensitivities of 79.2%,61.8%,76.8%,81.7%,63.6%,and 65.5%and specificities of 83.3%,87.5%,82.6%,83.3%,86.7%,and 92.1%,respectively.CONCLUSION The social function scores of patients with residual symptoms of depression are high.They are affected by disease history,medication compliance,therapy method,degree of somatic symptoms,residual symptoms,and anxiety.展开更多
BACKGROUND Simulated microgravity environment can lead to gastrointestinal motility disturbance.The pathogenesis of gastrointestinal motility disorders is closely related to the stem cell factor(SCF)/c-kit signaling p...BACKGROUND Simulated microgravity environment can lead to gastrointestinal motility disturbance.The pathogenesis of gastrointestinal motility disorders is closely related to the stem cell factor(SCF)/c-kit signaling pathway associated with intestinal flora and Cajal stromal cells.Moreover,intestinal flora can also affect the regulation of SCF/c-kit signaling pathway,thus affecting the expression of Cajal stromal cells.Cajal cells are the pacemakers of gastrointestinal motility.AIM To investigate the effects of Bifidobacterium lactis(B.lactis)BLa80 on the intestinal flora of rats in simulated microgravity and on the gastrointestinal motility-related SCF/c-kit pathway.METHODS The internationally recognized tail suspension animal model was used to simulate the microgravity environment,and 30 rats were randomly divided into control group,tail suspension group and drug administration tail suspension group with 10 rats in each group for a total of 28 days.The tail group was given B.lactis BLa80 by intragastric administration,and the other two groups were given water intragastric administration,the concentration of intragastric administration was 0.1 g/mL,and each rat was 1 mL/day.Hematoxylin&eosin staining was used to observe the histopathological changes in each segment of the intestine of each group,and the expression levels of SCF,c-kit,extracellular signal-regulated kinase(ERK)and p-ERK in the gastric antrum of each group were detected by Western blotting and PCR.The fecal flora and mucosal flora of rats in each group were detected by 16S rRNA.RESULTS Simulated microgravity resulted in severe exfoliation of villi of duodenum,jejunum and ileum in rats,marked damage,increased space between villi,loose arrangement,shortened columnar epithelium of colon,less folds,narrower mucosal thickness,reduced goblet cell number and crypts,and significant improvement after probiotic intervention.Simulated microgravity reduced the expressions of SCF and c-kit,and increased the expressions of ERK and P-ERK in the gastric antrum of rats.However,after probiotic intervention,the expressions of SCF and ckit were increased,while the expressions of ERK and P-ERK were decreased,with statistical significance(P<0.05).In addition,simulated microgravity can reduce the operational taxonomic unit(OTU)of the overall intestinal flora of rats,B.lactis BLa80 can increase the OTU of rats,simulated microgravity can reduce the overall richness and diversity of stool flora of rats,increase the abundance of firmicutes in stool flora of rats,and reduce the abundance of Bacteroides in stool flora of rats,most of which are mainly beneficial bacteria.Simulated microgravity can increase the overall richness and diversity of mucosal flora,increase the abundance of Bacteroides and Desulphurides in the rat mucosal flora,and decrease the abundance of firmicutes,most of which are proteobacteria.After probiotics intervention,the overall Bacteroidetes trend in simulated microgravity rats was increased.CONCLUSION B.lactis BLa80 can ameliorate intestinal mucosal injury,regulate intestinal flora,inhibit ERK expression,and activate the SCF/c-kit signaling pathway,which may have a facilitating effect on gastrointestinal motility in simulated microgravity rats.展开更多
This paper thoroughly explores the multifaceted factors influencing the efficacy of Chinese medicinals and categorizes them into three main groups:medicinal related factors,patient related factors,and practitioner rel...This paper thoroughly explores the multifaceted factors influencing the efficacy of Chinese medicinals and categorizes them into three main groups:medicinal related factors,patient related factors,and practitioner related factors.Regarding medicinal related factors,the place of origin,growing environment,harvesting time,storage conditions,quality control,dosage form selection,compatibility of medicinals,precise dosing,decoction methods,and administration routes all significantly impact efficacy.The place of origin determines the authenticity of medicinals,the growing environment affects their composition,harvesting time influences potency,improper storage leads to deterioration,quality control forms the foundation of efficacy,dosage forms and compatibility of medicinals affect absorption,dosing and decoction methods require precision,and administration routes should be tailored to individuals.Patient related factors include psychological state,individual differences,background,and disease condition.Psychological state affects treatment compliance,individual differences determine medicine responses,background influences patients’understanding of Chinese medicinals,and disease condition directly reflects efficacy.Practitioner related factors encompass theoretical knowledge,clinical experience,inherited practices,psychological state,and professional ethics.Theoretical knowledge guides medication use,clinical experience enhances efficacy,inherited practices influence prescribing styles,psychological state affects doctor–patient communication,and professional ethics ensure medical quality.These interrelated factors collectively influence the efficacy of Chinese medicinals,emphasizing the need for comprehensive consideration in clinical applications to achieve optimal therapeutic outcomes.展开更多
The abandonment of date palm grove of the former Al-Ahsa Oasis in the eastern region of Saudi Arabia has resulted in the conversion of delicate agricultural area into urban area.The current state of the oasis is influ...The abandonment of date palm grove of the former Al-Ahsa Oasis in the eastern region of Saudi Arabia has resulted in the conversion of delicate agricultural area into urban area.The current state of the oasis is influenced by both expansion and degradation factors.Therefore,it is important to study the spatiotemporal variation of vegetation cover for the sustainable management of oasis resources.This study used Landsat satellite images in 1987,2002,and 2021 to monitor the spatiotemporal variation of vegetation cover in the Al-Ahsa Oasis,applied multi-temporal Normalized Difference Vegetation Index(NDVI)data spanning from 1987 to 2021 to assess environmental and spatiotemporal variations that have occurred in the Al-Ahsa Oasis,and investigated the factors influencing these variation.This study reveals that there is a significant improvement in the ecological environment of the oasis during 1987–2021,with increase of NDVI values being higher than 0.10.In 2021,the highest NDVI value is generally above 0.70,while the lowest value remains largely unchanged.However,there is a remarkable increase in NDVI values between 0.20 and 0.30.The area of low NDVI values(0.00–0.20)has remained almost stable,but the region with high NDVI values(above 0.70)expands during 1987–2021.Furthermore,this study finds that in 1987–2002,the increase of vegetation cover is most notable in the northern region of the study area,whereas from 2002 to 2021,the increase of vegetation cover is mainly concentrated in the northern and southern regions of the study area.From 1987 to 2021,NDVI values exhibit the most pronounced variation,with a significant increase in the“green”zone(characterized by NDVI values exceeding 0.40),indicating a substantial enhancement in the ecological environment of the oasis.The NDVI classification is validated through 50 ground validation points in the study area,demonstrating a mean accuracy of 92.00%in the detection of vegetation cover.In general,both the user’s and producer’s accuracies of NDVI classification are extremely high in 1987,2002,and 2021.Finally,this study suggests that environmental authorities should strengthen their overall forestry project arrangements to combat sand encroachment and enhance the ecological environment of the Al-Ahsa Oasis.展开更多
Spinal cord injury represents a severe form of central nervous system trauma for which effective treatments remain limited.Microglia is the resident immune cells of the central nervous system,play a critical role in s...Spinal cord injury represents a severe form of central nervous system trauma for which effective treatments remain limited.Microglia is the resident immune cells of the central nervous system,play a critical role in spinal cord injury.Previous studies have shown that microglia can promote neuronal survival by phagocytosing dead cells and debris and by releasing neuroprotective and anti-inflammatory factors.However,excessive activation of microglia can lead to persistent inflammation and contribute to the formation of glial scars,which hinder axonal regeneration.Despite this,the precise role and mechanisms of microglia during the acute phase of spinal cord injury remain controversial and poorly understood.To elucidate the role of microglia in spinal cord injury,we employed the colony-stimulating factor 1 receptor inhibitor PLX5622 to deplete microglia.We observed that sustained depletion of microglia resulted in an expansion of the lesion area,downregulation of brain-derived neurotrophic factor,and impaired functional recovery after spinal cord injury.Next,we generated a transgenic mouse line with conditional overexpression of brain-derived neurotrophic factor specifically in microglia.We found that brain-derived neurotrophic factor overexpression in microglia increased angiogenesis and blood flow following spinal cord injury and facilitated the recovery of hindlimb motor function.Additionally,brain-derived neurotrophic factor overexpression in microglia reduced inflammation and neuronal apoptosis during the acute phase of spinal cord injury.Furthermore,through using specific transgenic mouse lines,TMEM119,and the colony-stimulating factor 1 receptor inhibitor PLX73086,we demonstrated that the neuroprotective effects were predominantly due to brain-derived neurotrophic factor overexpression in microglia rather than macrophages.In conclusion,our findings suggest the critical role of microglia in the formation of protective glial scars.Depleting microglia is detrimental to recovery of spinal cord injury,whereas targeting brain-derived neurotrophic factor overexpression in microglia represents a promising and novel therapeutic strategy to enhance motor function recovery in patients with spinal cord injury.展开更多
Background:Isotonic crystalloids are recommended as the first choice for fluid therapy in acute pan-creatitis(AP),with normal saline(NS)and lactate Ringer’s(LR)used most often.Evidence based recom-mendations on the t...Background:Isotonic crystalloids are recommended as the first choice for fluid therapy in acute pan-creatitis(AP),with normal saline(NS)and lactate Ringer’s(LR)used most often.Evidence based recom-mendations on the type of fluid are conflicting and generally come from small single-center randomized controlled trials(RCTs).We therefore conducted a systematic review and meta-analysis to compare the effect of balanced solutions(BS)versus NS on patient-centered clinical outcomes in AP.Methods:From four databases searched up to October 2024,we included only RCTs of adult patients with AP that compared the use of BS(including LR,acetate Ringer’s,etc.)with NS.The primary out-come was the disease advances from AP to moderately severe and severe AP(MSAP/SAP).Trial sequential analyses(TSA)were conducted to control for type-I and type-II errors and Grading of Recommendations Assessment,Development,and Evaluation(GRADE)was used to assess the quality of evidence.Results:Six RCTs were identified and included,involving 260 patients treated with BS and 298 patients with NS.Patients who received the BS had less MSAP/SAP[odds ratio(OR)=0.50,95%confidence in-terval(CI):0.29 to 0.85,P=0.01,I^(2)=0%;5 studies,299 patients],reduced the need of ICU admission(OR=0.60,95%CI:0.39 to 0.93,P=0.02,I^(2)=0%;5 studies,507 patients)and shorter length of hospital stay[mean difference(MD)=-0.88,95%CI:-1.48 to-0.28,P=0.004,I^(2)=0%;6 studies,558 patients;confirmed by TSA with high certainty]compared with those who received NS.The evidence for most of the clinical outcomes was rated as moderate to low due to the risk of bias,imprecision and inconsistency.Conclusions:BS,compared with NS,was associated with improved clinical outcomes in patients with AP.However,given the moderate to low quality of evidence for most of the outcomes assessed,further trials are warranted.展开更多
Retinal aging has been recognized as a significant risk factor for various retinal disorders,including diabetic retinopathy,age-related macular degeneration,and glaucoma,following a growing understanding of the molecu...Retinal aging has been recognized as a significant risk factor for various retinal disorders,including diabetic retinopathy,age-related macular degeneration,and glaucoma,following a growing understanding of the molecular underpinnings of their development.This comprehensive review explores the mechanisms of retinal aging and investigates potential neuroprotective approaches,focusing on the activation of transcription factor EB.Recent meta-analyses have demonstrated promising outcomes of transcription factor EB-targeted strategies,such as exercise,calorie restriction,rapamycin,and metformin,in patients and animal models of these common retinal diseases.The review critically assesses the role of transcription factor EB in retinal biology during aging,its neuroprotective effects,and its therapeutic potential for retinal disorders.The impact of transcription factor EB on retinal aging is cell-specific,influencing metabolic reprogramming and energy homeostasis in retinal neurons through the regulation of mitochondrial quality control and nutrient-sensing pathways.In vascular endothelial cells,transcription factor EB controls important processes,including endothelial cell proliferation,endothelial tube formation,and nitric oxide levels,thereby influencing the inner blood-retinal barrier,angiogenesis,and retinal microvasculature.Additionally,transcription factor EB affects vascular smooth muscle cells,inhibiting vascular calcification and atherogenesis.In retinal pigment epithelial cells,transcription factor EB modulates functions such as autophagy,lysosomal dynamics,and clearance of the aging pigment lipofuscin,thereby promoting photoreceptor survival and regulating vascular endothelial growth factor A expression involved in neovascularization.These cell-specific functions of transcription factor EB significantly impact retinal aging mechanisms encompassing proteostasis,neuronal synapse plasticity,energy metabolism,microvasculature,and inflammation,ultimately offering protection against retinal aging and diseases.The review emphasizes transcription factor EB as a potential therapeutic target for retinal diseases.Therefore,it is imperative to obtain well-controlled direct experimental evidence to confirm the efficacy of transcription factor EB modulation in retinal diseases while minimizing its risk of adverse effects.展开更多
BACKGROUND: This study aimed to explore the risk factors associated with intensive care unitacquired weakness(ICU-AW) in critically ill patients at risk of malnutrition and to evaluate the efficacy of early enteral nu...BACKGROUND: This study aimed to explore the risk factors associated with intensive care unitacquired weakness(ICU-AW) in critically ill patients at risk of malnutrition and to evaluate the efficacy of early enteral nutrition(EEN) and the role of biomarkers in managing ICU-AW.METHODS: This retrospective, observational cohort study included 180 patients at risk of malnutrition admitted to the emergency intensive care unit of the First Affiliated Hospital of Xiamen University Hospital from January 2022 to December 2023. Patients were divided into ICU-AW group and non-ICU-AW group according to whether they developed ICU-AW, or categorized into EEN and parenteral nutrition(PN) groups according to nutritional support. ICU-AW was diagnosed using the Medical Research Council score. The primary outcome was the occurrence of ICU-AW.RESULTS: The significant factors associated with ICU-AW included age, sex, type of nutritional therapy, mechanical ventilation(MV), body mass index(BMI), blood urea nitrogen(BUN), and creatinine(Cr) levels(P<0.05). The PN group developed ICU-AW earlier than did the EEN group, with a significant difference observed(log-rank P<0.001). Among biomarkers for ICU-AW, the mean prealbumin(PAB)/C-reactive protein(CRP) ratio had the highest diagnostic accuracy(area under the curve [AUC] 0.928, 95% confidence interval [95% CI] 0.892–0.946), surpassing the mean Cr/BUN ratio(AUC 0.740, 95% CI 0.663–0.819) and mean transferrin levels(AUC 0.653, 95% CI 0.574–0.733).CONCLUSION: Independent risk factors for ICU-AW include female sex, advanced age, PN, MV, lower BMI, and elevated BUN and Cr levels. EEN may potentially delay ICU-AW onset, and the PAB/CRP ratio may be an effective diagnostic marker for this condition.展开更多
文摘The rapid rise of cyberattacks and the gradual failure of traditional defense systems and approaches led to using artificial intelligence(AI)techniques(such as machine learning(ML)and deep learning(DL))to build more efficient and reliable intrusion detection systems(IDSs).However,the advent of larger IDS datasets has negatively impacted the performance and computational complexity of AI-based IDSs.Many researchers used data preprocessing techniques such as feature selection and normalization to overcome such issues.While most of these researchers reported the success of these preprocessing techniques on a shallow level,very few studies have been performed on their effects on a wider scale.Furthermore,the performance of an IDS model is subject to not only the utilized preprocessing techniques but also the dataset and the ML/DL algorithm used,which most of the existing studies give little emphasis on.Thus,this study provides an in-depth analysis of feature selection and normalization effects on IDS models built using three IDS datasets:NSL-KDD,UNSW-NB15,and CSE–CIC–IDS2018,and various AI algorithms.A wrapper-based approach,which tends to give superior performance,and min-max normalization methods were used for feature selection and normalization,respectively.Numerous IDS models were implemented using the full and feature-selected copies of the datasets with and without normalization.The models were evaluated using popular evaluation metrics in IDS modeling,intra-and inter-model comparisons were performed between models and with state-of-the-art works.Random forest(RF)models performed better on NSL-KDD and UNSW-NB15 datasets with accuracies of 99.86%and 96.01%,respectively,whereas artificial neural network(ANN)achieved the best accuracy of 95.43%on the CSE–CIC–IDS2018 dataset.The RF models also achieved an excellent performance compared to recent works.The results show that normalization and feature selection positively affect IDS modeling.Furthermore,while feature selection benefits simpler algorithms(such as RF),normalization is more useful for complex algorithms like ANNs and deep neural networks(DNNs),and algorithms such as Naive Bayes are unsuitable for IDS modeling.The study also found that the UNSW-NB15 and CSE–CIC–IDS2018 datasets are more complex and more suitable for building and evaluating modern-day IDS than the NSL-KDD dataset.Our findings suggest that prioritizing robust algorithms like RF,alongside complex models such as ANN and DNN,can significantly enhance IDS performance.These insights provide valuable guidance for managers to develop more effective security measures by focusing on high detection rates and low false alert rates.
基金Mid-term Results of the 2024 Langfang Normal University Special Teaching Reform Project on Innovation and Entrepreneurship Education Reform,“Research on the Evaluation System of Innovation and Entrepreneurship Ability for Normal University Students Based on Big Data Application-A Case Study of Langfang Normal University”(Project No.:CXJG2024-06)。
文摘Under the National Innovation-Driven Development Strategy,establishing a scientifically sound evaluation system for normal university students’innovation and entrepreneurship capabilities serves as a crucial foundation for optimizing innovation education models and enhancing teacher candidates’comprehensive competencies.Based on existing indicator frameworks,we designed a questionnaire and applied exploratory factor analysis(EFA)to screen indicators,reduce dimensionality,and analyze weighting.This process identified key metrics for evaluating pedagogical students’innovation capacities,ultimately constructing a targeted assessment system for normal university students.The study provides theoretical support for cultivating teacher trainees’innovative capabilities while contributing to the national innovation strategy implementation.
基金supported by the National Institute of Environmental Research(NIER)funded by the Ministry of Environment(No.NIER-2019-04-02-039)supported by Particulate Matter Management Specialized Graduate Program through the Korea Environmental Industry&Technology Institute(KEITI)funded by the Ministry of Environment(MOE).
文摘Fine particulatematter(PM_(2.5))samples were collected in two neighboring cities,Beijing and Baoding,China.High-concentration events of PM_(2.5) in which the average mass concentration exceeded 75μg/m^(3) were frequently observed during the heating season.Dispersion Normalized Positive Matrix Factorization was applied for the source apportionment of PM_(2.5) as minimize the dilution effects of meteorology and better reflect the source strengths in these two cities.Secondary nitrate had the highest contribution for Beijing(37.3%),and residential heating/biomass burning was the largest for Baoding(27.1%).Secondary nitrate,mobile,biomass burning,district heating,oil combustion,aged sea salt sources showed significant differences between the heating and non-heating seasons in Beijing for same period(2019.01.10–2019.08.22)(Mann-Whitney Rank Sum Test P<0.05).In case of Baoding,soil,residential heating/biomass burning,incinerator,coal combustion,oil combustion sources showed significant differences.The results of Pearson correlation analysis for the common sources between the two cities showed that long-range transported sources and some sources with seasonal patterns such as oil combustion and soil had high correlation coefficients.Conditional Bivariate Probability Function(CBPF)was used to identify the inflow directions for the sources,and joint-PSCF(Potential Source Contribution Function)was performed to determine the common potential source areas for sources affecting both cities.These models facilitated a more precise verification of city-specific influences on PM_(2.5) sources.The results of this study will aid in prioritizing air pollution mitigation strategies during the heating season and strengthening air quality management to reduce the impact of downwind neighboring cities.
基金supported by the National Research Foundation of Korea(NRF)grant for RLRC funded by the Korea government(MSIT)(No.2022R1A5A8026986,RLRC)supported by Institute of Information&Communications Technology Planning&Evaluation(IITP)grant funded by the Korea government(MSIT)(No.2020-0-01304,Development of Self-Learnable Mobile Recursive Neural Network Processor Technology)+3 种基金supported by the MSIT(Ministry of Science and ICT),Republic of Korea,under the Grand Information Technology Research Center support program(IITP-2024-2020-0-01462,Grand-ICT)supervised by the IITP(Institute for Information&Communications Technology Planning&Evaluation)supported by the Korea Technology and Information Promotion Agency for SMEs(TIPA)supported by the Korean government(Ministry of SMEs and Startups)’s Smart Manufacturing Innovation R&D(RS-2024-00434259).
文摘On-device Artificial Intelligence(AI)accelerators capable of not only inference but also training neural network models are in increasing demand in the industrial AI field,where frequent retraining is crucial due to frequent production changes.Batch normalization(BN)is fundamental to training convolutional neural networks(CNNs),but its implementation in compact accelerator chips remains challenging due to computational complexity,particularly in calculating statistical parameters and gradients across mini-batches.Existing accelerator architectures either compromise the training accuracy of CNNs through approximations or require substantial computational resources,limiting their practical deployment.We present a hardware-optimized BN accelerator that maintains training accuracy while significantly reducing computational overhead through three novel techniques:(1)resourcesharing for efficient resource utilization across forward and backward passes,(2)interleaved buffering for reduced dynamic random-access memory(DRAM)access latencies,and(3)zero-skipping for minimal gradient computation.Implemented on a VCU118 Field Programmable Gate Array(FPGA)on 100 MHz and validated using You Only Look Once version 2-tiny(YOLOv2-tiny)on the PASCALVisualObjectClasses(VOC)dataset,our normalization accelerator achieves a 72%reduction in processing time and 83%lower power consumption compared to a 2.4 GHz Intel Central Processing Unit(CPU)software normalization implementation,while maintaining accuracy(0.51%mean Average Precision(mAP)drop at floating-point 32 bits(FP32),1.35%at brain floating-point 16 bits(bfloat16)).When integrated into a neural processing unit(NPU),the design demonstrates 63%and 97%performance improvements over AMD CPU and Reduced Instruction Set Computing-V(RISC-V)implementations,respectively.These results confirm that our proposed BN hardware design enables efficient,high-accuracy,and power-saving on-device training for modern CNNs.Our results demonstrate that efficient hardware implementation of standard batch normalization is achievable without sacrificing accuracy,enabling practical on-device CNN training with significantly reduced computational and power requirements.
文摘Renormalization group analysis has been proposed to eliminate secular terms in perturbation solutions of differential equations and thus expand the domain of their validity.Here we extend the method to treat periodic orbits or limit cycles.Interesting normal forms could be derived through a generalization of the concept'resonance',which offers nontrivial analytic approximations.Compared with traditional techniques such as multi-scale methods,the current scheme proceeds in a very straightforward and simple way,delivering not only the period and the amplitude but also the transient path to limit cycles.The method is demonstrated with several examples including the Duffing oscillator,van der Pol equation and Lorenz equation.The obtained solutions match well with numerical results and with those derived by traditional analytic methods.
基金supported by the Basic Science Research Program through the National Research Foundation of Korea(NRF)funded by the Ministry of Science and ICT(NRF-2022R1A2C2012243).
文摘In recent decades,brain tumors have emerged as a serious neurological disorder that often leads to death.Hence,Brain Tumor Segmentation(BTS)is significant to enable the visualization,classification,and delineation of tumor regions in Magnetic Resonance Imaging(MRI).However,BTS remains a challenging task because of noise,non-uniform object texture,diverse image content and clustered objects.To address these challenges,a novel model is implemented in this research.The key objective of this research is to improve segmentation accuracy and generalization in BTS by incorporating Switchable Normalization into Faster R-CNN,which effectively captures the fine-grained tumor features to enhance segmentation precision.MRI images are initially acquired from three online datasets:Dataset 1—Brain Tumor Segmentation(BraTS)2018,Dataset 2—BraTS 2019,and Dataset 3—BraTS 2020.Subsequently,the Switchable Normalization-based Faster Regions with Convolutional Neural Networks(SNFRC)model is proposed for improved BTS in MRI images.In the proposed model,Switchable Normalization is integrated into the conventional architecture,enhancing generalization capability and reducing overfitting to unseen image data,which is essential due to the typically limited size of available datasets.The network depth is increased to obtain discriminative semantic features that improve segmentation performance.Specifically,Switchable Normalization captures the diverse feature representations from the brain images.The Faster R-CNN model develops end-to-end training and effective regional proposal generation,with an enhanced training stability using Switchable Normalization,to perform an effective segmentation in MRI images.From the experimental results,the proposed model attains segmentation accuracies of 99.41%,98.12%,and 96.71%on Datasets 1,2,and 3,respectively,outperforming conventional deep learning models used for BTS.
基金Supported by Guangdong Provincial Hospital of Chinese Medicine Science and Technology Research Special Project,No.YN2023WSSQ01State Key Laboratory of Traditional Chinese Medicine Syndrome.
文摘BACKGROUND Research has shown that several factors can influence postoperative abnormal liver function;however,most studies on this issue have focused specifically on hepatic and cardiac surgeries,leaving limited research on contributing factors in other types of surgeries.AIM To identify the risk factors for early postoperative abnormal liver function in multiple surgery types and construct a risk prediction model.METHODS This retrospective cohort study involved 3720 surgical patients from 5 surgical departments at Guangdong Provincial Hospital of Traditional Chinese Medicine.Patients were divided into abnormal(n=108)and normal(n=3612)groups based on liver function post-surgery.Univariate analysis and LASSO regression screened variables,followed by logistic regression to identify risk factors.A prediction model was constructed based on the variables selected via logistic re-gression.The goodness-of-fit of the model was evaluated using the Hosm-er–Lemeshow test,while discriminatory ability was measured by the area under the receiver operating characteristic curve.Calibration curves were plotted to visualize the consistency between predicted probabilities and observed outcomes.RESULTS The key factors contributing to abnormal liver function after surgery include elevated aspartate aminotransferase and alanine aminotransferase levels and reduced platelet counts pre-surgery,as well as the sevoflurane use during the procedure,among others.CONCLUSION The above factors collectively represent notable risk factors for postoperative liver function injury,and the prediction model developed based on these factors demonstrates strong predictive efficacy.
基金supported by grants from National Key R&D Program of China(No.2023YFC2507800)ECCM Program of Clinical Research Centre of Shandong University(No.2021SDUCRCB008)+2 种基金Young Taishan Scholar Foundation of Shandong Province(No.tsqn201812133)the Fundamental Research Funds of Shandong University(No.2020QNQT001)National Natural Science Foundation of China(No.81900124).
文摘Objective Coagulation abnormalities are common and prognostically significant in intensive care units(ICUs)and are associated with increased mortality.This study aimed to explore the association between the levels of coagulation markers and the risk of mortality among ICU patients with coagulation abnormalities.Methods This retrospective study investigated patients with coagulation abnormalities in the ICU between January 2021 and December 2022.The initial point for detecting hemostatic biomarkers due to clinical assessment of coagulation abnormalities was designated day 0.Patients were followed up for 28 days,and multivariate logistic regression analysis was utilized to identify risk factors for mortality.Results Of the 451 patients analyzed,115 died,and 336 were alive at the end of the 28-day period.Multivariate analysis revealed that elevated thrombin-antithrombin complex(TAT),tissue plasminogen activator inhibitor complex(tPAIC),prolonged prothrombin time,and thrombocytopenia were independent risk factors for mortality.For nonovert disseminated intravascular coagulation(DIC)patients,older age and thrombocytopenia were associated with increased risks of mortality,whereas elevated levels of plasminα2-plasmin inhibitor complex(PIC)were found to be independent predictors of survival.In patients with overt DIC,elevated levels of tPAIC were independently associated with increased risks of mortality.Nevertheless,thrombocytopenia was independently associated with increased risks of mortality in patients with pre-DIC.Conclusion Coagulation markers such as the TAT,tPAIC,PIC,and platelet count were significantly associated with mortality,underscoring the importance of maintaining a balance between coagulation and fibrinolysis.These findings highlight the potential for targeted therapeutic interventions based on specific coagulation markers to improve patient outcomes.
基金Supported by the Knowledge Innovation Program of Chinese Academy of Sciences(No.KSCX2-EW-G-12B)the Knowledge Innovation Program of the Chinese Academy of Sciences(No.KZCX2-EW-Q213)the National High Technology Research and Development Program of China (863 Program)(No.2012AA10A412)
文摘Quantitative real-time reverse transcription-polymerase chain reaction （qRT-PCR） is widely used in studies of gene expression. In most of these studies, housekeeping genes are used as internal references without validation. To identify appropriate reference genes for qRT-PCR in Pacific abalone Haliotis discus hannai, we examined the transcription stability of six housekeeping genes in abalone tissues in the presence and absence of bacterial infection. For this purpose, abalone were infected with the bacterial pathogen Fibrio anguillarum for 12 h and 48 h. The mRNA levels of the housekeeping genes in five tissues （digestive glands, foot muscle, gill, hemocyte, and mantle） were determined by qRT-PCR. The PCR data was subsequently analyzed with the geNorm and NormFinder algorithms. The results show that in the absence of bacterial infection, elongation factor-l-alpha and beta-actin were the most stably expressed genes in all tissues, and thus are suitable as cross-tissue type normalization factors. However, we did not identify any universal reference genes post infection because the most stable genes varied between tissue types. Furthermore, for most tissues, the optimal reference genes identified by both algorithms at 12 h and 48 h post-infection differed. These results indicate that bacterial infection induced significant changes in the expression of abalone housekeeping genes in a manner that is dependent on tissue type and duration of infection. As a result, different normalization factors must be used for different tissues at different infection points.
基金supported by the National Key R&D Program of China,No.2021YFA0805200(to SY)the National Natural Science Foundation of China,No.31970954(to SY)two grants from the Department of Science and Technology of Guangdong Province,Nos.2021ZT09Y007,2020B121201006(both to XJL)。
文摘Spinal and bulbar muscular atrophy is a neurodegenerative disease caused by extended CAG trinucleotide repeats in the androgen receptor gene,which encodes a ligand-dependent transcription facto r.The mutant androgen receptor protein,characterized by polyglutamine expansion,is prone to misfolding and forms aggregates in both the nucleus and cytoplasm in the brain in spinal and bulbar muscular atrophy patients.These aggregates alter protein-protein interactions and compromise transcriptional activity.In this study,we reported that in both cultured N2a cells and mouse brain,mutant androgen receptor with polyglutamine expansion causes reduced expression of mesencephalic astrocyte-de rived neurotrophic factor.Overexpressio n of mesencephalic astrocyte-derived neurotrophic factor amelio rated the neurotoxicity of mutant androgen receptor through the inhibition of mutant androgen receptor aggregation.Conversely.knocking down endogenous mesencephalic astrocyte-derived neurotrophic factor in the mouse brain exacerbated neuronal damage and mutant androgen receptor aggregation.Our findings suggest that inhibition of mesencephalic astrocyte-derived neurotrophic factor expression by mutant androgen receptor is a potential mechanism underlying neurodegeneration in spinal and bulbar muscular atrophy.
基金supported by the National Natural Science Foundation of China(NSFC,No.82173742)the Science Fund for Distinguished Young Scholars of Shaanxi Province(No.2022JC-54)the Key Research and Development Program of Shaanxi Province(No.2023-YBSF-131).
文摘Remodeling tumor microenvironment(TME)is a very promising and effective strategy to enhance the effects of chemotherapy,photodynamic therapy,and immunotherapy.Normalization of tumor vasculature as well as depletion of glutathione(GSH)can improve the TME.Here,we developed a novel therapeutic nanoparticle functional enzyme ultra QDAU5 nanoparticles(FEUQ Nps)based on a fluorescence-on and releasable strategy by combining a vascular normalization inducer,a GSH depleting agent,and an activated fluorophore.In which the cleavage of disulfide bonds releases active molecules that induce vascular normalization and improve the hypoxic microenvironment.In addition,it may deplete GSH in cancer cells,thus inducing the production of reactive oxygen species(ROS)and lipid peroxide(LPO)and promoting iron toxicity.It may also lead to endoplasmic stress and release of calmodulin,which activates the immune system.Meanwhile,quenched fluorophores are turned on in the presence of galactosidase(GLU)for tumor-specific labeling.In summary,we developed novel therapeutic agent nanoparticles with the function of vascular normalization inducers to achieve specific labeling of hepatocellular carcinoma while exerting efficient antitumor effects in vivo.
基金supported by the National Natural Science Foundation of China(NSFC,Nos.82373793,82173742)the Science Fund for Distinguished Young Scholars of Shaanxi Province(No.2022JC-54)the Key Research and Development Program of Shaanxi Province(No.2023-YBSF-131).
文摘Tumor vascular normalization has emerged as a promising strategy for synergistic therapy recently.Based on the strategy of“fluorescence turn on-controllable release”,a novel bifunctional candidate was con-structed based on previous developed vascular normalization inducer QDAU5,which could self-assemble to form functional enzyme infrared QDAU5 nanoparticles(FEIRQ NPs).Subsequently,biological evaluation demonstrated that the FEIRQ NPs could induce ferroptosis,endoplasmic reticulum stress,and antigen pre-conditioning and maturation of dendritic cells and CD8^(+)T cells,leading to excellent antitumor efficacy in the absence of cytotoxic drugs.Additionally,FEIRQ NPs show high fluorescence intensity upon expo-sure to theβ-galactosidase(β-Gal)enzyme expressed in ovarian cancer,enabling real-time monitoring of therapeutic effects.Overall,our findings suggest a prospering strategy to early diagnosis and efficient therapy for ovarian cancer without cytotoxicity.
文摘BACKGROUND At present,the influencing factors of social function in patients with residual depressive symptoms are still unclear.Residual depressive symptoms are highly harmful,leading to low mood in patients,affecting work and interpersonal communication,increasing the risk of recurrence,and adding to the burden on families.Studying the influencing factors of their social function is of great significance.AIM To explore the social function score and its influencing factors in patients with residual depressive symptoms.METHODS This observational study surveyed patients with residual depressive symptoms(case group)and healthy patients undergoing physical examinations(control group).Participants were admitted between January 2022 and December 2023.Social functioning was assessed using the Sheehan Disability Scale(SDS),and scores were compared between groups.Factors influencing SDS scores in patients with residual depressive symptoms were analyzed by applying multiple linear regression while using the receiver operating characteristic curve,and these RESULTS The SDS scores of the 158 patients with depressive symptoms were 11.48±3.26.Compared with the control group,the SDS scores and all items in the case group were higher.SDS scores were higher in patients with relapse,discon-tinuous medication,drug therapy alone,severe somatic symptoms,obvious residual symptoms,and anxiety scores≥8.Disease history,medication compliance,therapy method,and residual symptoms correlated positively with SDS scores(r=0.354,0.414,0.602,and 0.456,respectively).Independent influencing factors included disease history,medication compliance,therapy method,somatic symptoms,residual symptoms,and anxiety scores(P<0.05).The areas under the curve for predicting social functional impairment using these factors were 0.713,0.559,0.684,0.729,0.668,and 0.628,respectively,with sensitivities of 79.2%,61.8%,76.8%,81.7%,63.6%,and 65.5%and specificities of 83.3%,87.5%,82.6%,83.3%,86.7%,and 92.1%,respectively.CONCLUSION The social function scores of patients with residual symptoms of depression are high.They are affected by disease history,medication compliance,therapy method,degree of somatic symptoms,residual symptoms,and anxiety.
文摘BACKGROUND Simulated microgravity environment can lead to gastrointestinal motility disturbance.The pathogenesis of gastrointestinal motility disorders is closely related to the stem cell factor(SCF)/c-kit signaling pathway associated with intestinal flora and Cajal stromal cells.Moreover,intestinal flora can also affect the regulation of SCF/c-kit signaling pathway,thus affecting the expression of Cajal stromal cells.Cajal cells are the pacemakers of gastrointestinal motility.AIM To investigate the effects of Bifidobacterium lactis(B.lactis)BLa80 on the intestinal flora of rats in simulated microgravity and on the gastrointestinal motility-related SCF/c-kit pathway.METHODS The internationally recognized tail suspension animal model was used to simulate the microgravity environment,and 30 rats were randomly divided into control group,tail suspension group and drug administration tail suspension group with 10 rats in each group for a total of 28 days.The tail group was given B.lactis BLa80 by intragastric administration,and the other two groups were given water intragastric administration,the concentration of intragastric administration was 0.1 g/mL,and each rat was 1 mL/day.Hematoxylin&eosin staining was used to observe the histopathological changes in each segment of the intestine of each group,and the expression levels of SCF,c-kit,extracellular signal-regulated kinase(ERK)and p-ERK in the gastric antrum of each group were detected by Western blotting and PCR.The fecal flora and mucosal flora of rats in each group were detected by 16S rRNA.RESULTS Simulated microgravity resulted in severe exfoliation of villi of duodenum,jejunum and ileum in rats,marked damage,increased space between villi,loose arrangement,shortened columnar epithelium of colon,less folds,narrower mucosal thickness,reduced goblet cell number and crypts,and significant improvement after probiotic intervention.Simulated microgravity reduced the expressions of SCF and c-kit,and increased the expressions of ERK and P-ERK in the gastric antrum of rats.However,after probiotic intervention,the expressions of SCF and ckit were increased,while the expressions of ERK and P-ERK were decreased,with statistical significance(P<0.05).In addition,simulated microgravity can reduce the operational taxonomic unit(OTU)of the overall intestinal flora of rats,B.lactis BLa80 can increase the OTU of rats,simulated microgravity can reduce the overall richness and diversity of stool flora of rats,increase the abundance of firmicutes in stool flora of rats,and reduce the abundance of Bacteroides in stool flora of rats,most of which are mainly beneficial bacteria.Simulated microgravity can increase the overall richness and diversity of mucosal flora,increase the abundance of Bacteroides and Desulphurides in the rat mucosal flora,and decrease the abundance of firmicutes,most of which are proteobacteria.After probiotics intervention,the overall Bacteroidetes trend in simulated microgravity rats was increased.CONCLUSION B.lactis BLa80 can ameliorate intestinal mucosal injury,regulate intestinal flora,inhibit ERK expression,and activate the SCF/c-kit signaling pathway,which may have a facilitating effect on gastrointestinal motility in simulated microgravity rats.
文摘This paper thoroughly explores the multifaceted factors influencing the efficacy of Chinese medicinals and categorizes them into three main groups:medicinal related factors,patient related factors,and practitioner related factors.Regarding medicinal related factors,the place of origin,growing environment,harvesting time,storage conditions,quality control,dosage form selection,compatibility of medicinals,precise dosing,decoction methods,and administration routes all significantly impact efficacy.The place of origin determines the authenticity of medicinals,the growing environment affects their composition,harvesting time influences potency,improper storage leads to deterioration,quality control forms the foundation of efficacy,dosage forms and compatibility of medicinals affect absorption,dosing and decoction methods require precision,and administration routes should be tailored to individuals.Patient related factors include psychological state,individual differences,background,and disease condition.Psychological state affects treatment compliance,individual differences determine medicine responses,background influences patients’understanding of Chinese medicinals,and disease condition directly reflects efficacy.Practitioner related factors encompass theoretical knowledge,clinical experience,inherited practices,psychological state,and professional ethics.Theoretical knowledge guides medication use,clinical experience enhances efficacy,inherited practices influence prescribing styles,psychological state affects doctor–patient communication,and professional ethics ensure medical quality.These interrelated factors collectively influence the efficacy of Chinese medicinals,emphasizing the need for comprehensive consideration in clinical applications to achieve optimal therapeutic outcomes.
文摘The abandonment of date palm grove of the former Al-Ahsa Oasis in the eastern region of Saudi Arabia has resulted in the conversion of delicate agricultural area into urban area.The current state of the oasis is influenced by both expansion and degradation factors.Therefore,it is important to study the spatiotemporal variation of vegetation cover for the sustainable management of oasis resources.This study used Landsat satellite images in 1987,2002,and 2021 to monitor the spatiotemporal variation of vegetation cover in the Al-Ahsa Oasis,applied multi-temporal Normalized Difference Vegetation Index(NDVI)data spanning from 1987 to 2021 to assess environmental and spatiotemporal variations that have occurred in the Al-Ahsa Oasis,and investigated the factors influencing these variation.This study reveals that there is a significant improvement in the ecological environment of the oasis during 1987–2021,with increase of NDVI values being higher than 0.10.In 2021,the highest NDVI value is generally above 0.70,while the lowest value remains largely unchanged.However,there is a remarkable increase in NDVI values between 0.20 and 0.30.The area of low NDVI values(0.00–0.20)has remained almost stable,but the region with high NDVI values(above 0.70)expands during 1987–2021.Furthermore,this study finds that in 1987–2002,the increase of vegetation cover is most notable in the northern region of the study area,whereas from 2002 to 2021,the increase of vegetation cover is mainly concentrated in the northern and southern regions of the study area.From 1987 to 2021,NDVI values exhibit the most pronounced variation,with a significant increase in the“green”zone(characterized by NDVI values exceeding 0.40),indicating a substantial enhancement in the ecological environment of the oasis.The NDVI classification is validated through 50 ground validation points in the study area,demonstrating a mean accuracy of 92.00%in the detection of vegetation cover.In general,both the user’s and producer’s accuracies of NDVI classification are extremely high in 1987,2002,and 2021.Finally,this study suggests that environmental authorities should strengthen their overall forestry project arrangements to combat sand encroachment and enhance the ecological environment of the Al-Ahsa Oasis.
基金supported by the National Natural Science Foundation of China,Nos.82072165 and 82272256(both to XM)the Key Project of Xiangyang Central Hospital,No.2023YZ03(to RM)。
文摘Spinal cord injury represents a severe form of central nervous system trauma for which effective treatments remain limited.Microglia is the resident immune cells of the central nervous system,play a critical role in spinal cord injury.Previous studies have shown that microglia can promote neuronal survival by phagocytosing dead cells and debris and by releasing neuroprotective and anti-inflammatory factors.However,excessive activation of microglia can lead to persistent inflammation and contribute to the formation of glial scars,which hinder axonal regeneration.Despite this,the precise role and mechanisms of microglia during the acute phase of spinal cord injury remain controversial and poorly understood.To elucidate the role of microglia in spinal cord injury,we employed the colony-stimulating factor 1 receptor inhibitor PLX5622 to deplete microglia.We observed that sustained depletion of microglia resulted in an expansion of the lesion area,downregulation of brain-derived neurotrophic factor,and impaired functional recovery after spinal cord injury.Next,we generated a transgenic mouse line with conditional overexpression of brain-derived neurotrophic factor specifically in microglia.We found that brain-derived neurotrophic factor overexpression in microglia increased angiogenesis and blood flow following spinal cord injury and facilitated the recovery of hindlimb motor function.Additionally,brain-derived neurotrophic factor overexpression in microglia reduced inflammation and neuronal apoptosis during the acute phase of spinal cord injury.Furthermore,through using specific transgenic mouse lines,TMEM119,and the colony-stimulating factor 1 receptor inhibitor PLX73086,we demonstrated that the neuroprotective effects were predominantly due to brain-derived neurotrophic factor overexpression in microglia rather than macrophages.In conclusion,our findings suggest the critical role of microglia in the formation of protective glial scars.Depleting microglia is detrimental to recovery of spinal cord injury,whereas targeting brain-derived neurotrophic factor overexpression in microglia represents a promising and novel therapeutic strategy to enhance motor function recovery in patients with spinal cord injury.
文摘Background:Isotonic crystalloids are recommended as the first choice for fluid therapy in acute pan-creatitis(AP),with normal saline(NS)and lactate Ringer’s(LR)used most often.Evidence based recom-mendations on the type of fluid are conflicting and generally come from small single-center randomized controlled trials(RCTs).We therefore conducted a systematic review and meta-analysis to compare the effect of balanced solutions(BS)versus NS on patient-centered clinical outcomes in AP.Methods:From four databases searched up to October 2024,we included only RCTs of adult patients with AP that compared the use of BS(including LR,acetate Ringer’s,etc.)with NS.The primary out-come was the disease advances from AP to moderately severe and severe AP(MSAP/SAP).Trial sequential analyses(TSA)were conducted to control for type-I and type-II errors and Grading of Recommendations Assessment,Development,and Evaluation(GRADE)was used to assess the quality of evidence.Results:Six RCTs were identified and included,involving 260 patients treated with BS and 298 patients with NS.Patients who received the BS had less MSAP/SAP[odds ratio(OR)=0.50,95%confidence in-terval(CI):0.29 to 0.85,P=0.01,I^(2)=0%;5 studies,299 patients],reduced the need of ICU admission(OR=0.60,95%CI:0.39 to 0.93,P=0.02,I^(2)=0%;5 studies,507 patients)and shorter length of hospital stay[mean difference(MD)=-0.88,95%CI:-1.48 to-0.28,P=0.004,I^(2)=0%;6 studies,558 patients;confirmed by TSA with high certainty]compared with those who received NS.The evidence for most of the clinical outcomes was rated as moderate to low due to the risk of bias,imprecision and inconsistency.Conclusions:BS,compared with NS,was associated with improved clinical outcomes in patients with AP.However,given the moderate to low quality of evidence for most of the outcomes assessed,further trials are warranted.
基金supported by the Start-up Fund for new faculty from the Hong Kong Polytechnic University(PolyU)(A0043215)(to SA)the General Research Fund and Research Impact Fund from the Hong Kong Research Grants Council(15106018,R5032-18)(to DYT)+1 种基金the Research Center for SHARP Vision in PolyU(P0045843)(to SA)the InnoHK scheme from the Hong Kong Special Administrative Region Government(to DYT).
文摘Retinal aging has been recognized as a significant risk factor for various retinal disorders,including diabetic retinopathy,age-related macular degeneration,and glaucoma,following a growing understanding of the molecular underpinnings of their development.This comprehensive review explores the mechanisms of retinal aging and investigates potential neuroprotective approaches,focusing on the activation of transcription factor EB.Recent meta-analyses have demonstrated promising outcomes of transcription factor EB-targeted strategies,such as exercise,calorie restriction,rapamycin,and metformin,in patients and animal models of these common retinal diseases.The review critically assesses the role of transcription factor EB in retinal biology during aging,its neuroprotective effects,and its therapeutic potential for retinal disorders.The impact of transcription factor EB on retinal aging is cell-specific,influencing metabolic reprogramming and energy homeostasis in retinal neurons through the regulation of mitochondrial quality control and nutrient-sensing pathways.In vascular endothelial cells,transcription factor EB controls important processes,including endothelial cell proliferation,endothelial tube formation,and nitric oxide levels,thereby influencing the inner blood-retinal barrier,angiogenesis,and retinal microvasculature.Additionally,transcription factor EB affects vascular smooth muscle cells,inhibiting vascular calcification and atherogenesis.In retinal pigment epithelial cells,transcription factor EB modulates functions such as autophagy,lysosomal dynamics,and clearance of the aging pigment lipofuscin,thereby promoting photoreceptor survival and regulating vascular endothelial growth factor A expression involved in neovascularization.These cell-specific functions of transcription factor EB significantly impact retinal aging mechanisms encompassing proteostasis,neuronal synapse plasticity,energy metabolism,microvasculature,and inflammation,ultimately offering protection against retinal aging and diseases.The review emphasizes transcription factor EB as a potential therapeutic target for retinal diseases.Therefore,it is imperative to obtain well-controlled direct experimental evidence to confirm the efficacy of transcription factor EB modulation in retinal diseases while minimizing its risk of adverse effects.
文摘BACKGROUND: This study aimed to explore the risk factors associated with intensive care unitacquired weakness(ICU-AW) in critically ill patients at risk of malnutrition and to evaluate the efficacy of early enteral nutrition(EEN) and the role of biomarkers in managing ICU-AW.METHODS: This retrospective, observational cohort study included 180 patients at risk of malnutrition admitted to the emergency intensive care unit of the First Affiliated Hospital of Xiamen University Hospital from January 2022 to December 2023. Patients were divided into ICU-AW group and non-ICU-AW group according to whether they developed ICU-AW, or categorized into EEN and parenteral nutrition(PN) groups according to nutritional support. ICU-AW was diagnosed using the Medical Research Council score. The primary outcome was the occurrence of ICU-AW.RESULTS: The significant factors associated with ICU-AW included age, sex, type of nutritional therapy, mechanical ventilation(MV), body mass index(BMI), blood urea nitrogen(BUN), and creatinine(Cr) levels(P<0.05). The PN group developed ICU-AW earlier than did the EEN group, with a significant difference observed(log-rank P<0.001). Among biomarkers for ICU-AW, the mean prealbumin(PAB)/C-reactive protein(CRP) ratio had the highest diagnostic accuracy(area under the curve [AUC] 0.928, 95% confidence interval [95% CI] 0.892–0.946), surpassing the mean Cr/BUN ratio(AUC 0.740, 95% CI 0.663–0.819) and mean transferrin levels(AUC 0.653, 95% CI 0.574–0.733).CONCLUSION: Independent risk factors for ICU-AW include female sex, advanced age, PN, MV, lower BMI, and elevated BUN and Cr levels. EEN may potentially delay ICU-AW onset, and the PAB/CRP ratio may be an effective diagnostic marker for this condition.
