Dear Editor,The pathophysiologic al mechanisms underlying mood disorders including major depressive disorder(MDD)remain to be fully characterized.Iron is a key component in the development of the central nervous syste...Dear Editor,The pathophysiologic al mechanisms underlying mood disorders including major depressive disorder(MDD)remain to be fully characterized.Iron is a key component in the development of the central nervous system and iron deficiency has been linked to impairments of mood and cognition[1].展开更多
The Tongkuangyu porphyry copper deposit in the Zhongtiao Mountains, China, is tectonically located on the southern margin of the North China platform and on the northern margin of the Late Archean Zhongtiaoshan intrac...The Tongkuangyu porphyry copper deposit in the Zhongtiao Mountains, China, is tectonically located on the southern margin of the North China platform and on the northern margin of the Late Archean Zhongtiaoshan intracontinental rift basin. The deposit occurs in a copper-bearing formation of tuffaceous variegated sandshale-K-rich bimodal volcanic rocks of the Tongkuangyu Formation of the Late Archean Jiangxian Group, and the orebodies are localized in a transition portion between tuffaceous variegated sandshale and bimodal volcanic rocks. The host rocks consist mainly of metagranodiorite-porphyry, meta-quartz monzonite-展开更多
BACKGROUND: Sepsis, a common acute and critical disease, leads to 11 million deaths annually worldwide. Probiotics are living microorganisms that are beneficial to the host and may benefit sepsis outcomes, but their e...BACKGROUND: Sepsis, a common acute and critical disease, leads to 11 million deaths annually worldwide. Probiotics are living microorganisms that are beneficial to the host and may benefit sepsis outcomes, but their effects are stil inconclusive. This study aimed to evaluate the overal eff ect of probiotics on the prognosis of patients with sepsis.DATA RESOURCES: We searched several sources for published/presented studies, including Pub Med, EMBASE, Web of Science, the Cochrane Library and the US National Library of Medicine Clinical Trials Register(www.clinicaltrials.gov) updated through July 30, 2023, to identify all relevant randomized controlled trials(RCTs) or observational studies that assessed the effectiveness of probiotics or synbiotics in patients with sepsis and reported mortality. We focused primarily on mortality during the study period and analyzed secondary outcomes, including 28-day mortality, in-intensive care unit(ICU) mortality and other outcomes.RESULTS: Data from 405 patients in five RCTs and 108 patients in one cohort study were included in the analysis. The overall quality of the studies was satisfactory, but clinical heterogeneity existed. All adult studies reported a tendency for probiotics to reduce the mortality of patients with sepsis, and most studies reported a decreasing trend in the incidence of infectious complications, length of ICU stay and duration of antibiotic use. There was only one RCT involving children.CONCLUSION: Probiotics show promise for improving the prognosis of patients with sepsis, including reducing mortality and the incidence of infectious complications, particularly in adult patients. Despite the limited number of studies, especially in children, these findings will be encouraging for clinical practice in the treatment of sepsis and suggest that gut microbiota-targeted therapy may improve the prognosis of patients with sepsis.展开更多
Graphitic carbon nitride(g-C_(3)N_(4))exhibits great mechanical as well as thermal characteristics,making it a valuable ma-terial for use in photoelectric conversion devices,an accelerator for synthesis of organic com...Graphitic carbon nitride(g-C_(3)N_(4))exhibits great mechanical as well as thermal characteristics,making it a valuable ma-terial for use in photoelectric conversion devices,an accelerator for synthesis of organic compounds,an electrolyte for fuel cell applications or power sources,and a hydrogen storage substance and a fluorescence detector.It is fabricated using dif-ferent methods,and there is a variety of morphologies and nanostructures such as zero to three dimensions that have been designed for different purposes.Ther e are many reports about g-C_(3)N_(4) in recent years,but a comprehensive review which covers nanostructure dimensions and their properties are missing.This review paper aims to give basic and comprehensive understanding of the photocatalytic and electrocatalytic usages of g-C_(3)N_(4).It highlights the recent progress of g-C_(3)N_(4) nano-structure designing by covering synthesis methods,dimensions,morphologies,applications and properties.Along with the summary,we will also discuss the challenges and prospects.Scientists,investigators,and engineers looking at g-C_(3)N_(4) nanostructures for a variety of applications might find our review paper to be a useful resource.展开更多
BACKGROUND Metabolic dysfunction-associated steatotic liver disease(MASLD)is the most common chronic liver disease worldwide.Its prevalence is closely linked to the dramatic rise in obesity and non-communicable diseas...BACKGROUND Metabolic dysfunction-associated steatotic liver disease(MASLD)is the most common chronic liver disease worldwide.Its prevalence is closely linked to the dramatic rise in obesity and non-communicable diseases.MASLD exhibits a progressive trajectory that may culminate in development of hepatic cirrhosis,thereby predisposing affected individuals to an elevated likelihood of hepatocarcinogenesis.Diet,especially dietary fatty acids,serves as a key link between nutrient intake and MASLD pathogenesis.AIM To explore the impact of various omega-6 fatty acid subtypes on the pathogenesis and therapeutic strategies of MASLD.METHODS A systematic literature search was conducted across Web of Science,PubMed,Cochrane Central,Scopus,and Embase databases from inception through June 2024 to identify all original studies linking different subtypes of omega-6 polyunsaturated fatty acids to the pathogenesis and management of MASLD.The search strategy explored the linkage between omega-6 polyunsaturated fatty acids and their subtypes,including linoleic acid(LA),gamma-linolenic acid(GLA),arachidonic acid,conjugated LA,and docosapentaenoic acid,in relation to MASLD and cardiometabolic risk.RESULTS By employing the specified search strategy,a total of 83 articles were identified as potentially eligible.During the title,abstract,and full-text screening phases,27 duplicate records were removed,leaving 56 records for relevance screening.Of these,43 records were excluded for reasons such as irrelevance and language restrictions(limited to English),resulting in 13 full-text articles being included for detailed assessment(10 human studies,1 animal study,and 2 review articles).Although certain subtypes,as GLA,dihomo-GLA,omega-6-derived oxylipins,and most arachidonic acid-derived eicosanoids,exhibit pro-inflammatory effects,our findings suggest that other subtypes such as LA,cis-9,trans-11 conjugated LA,and docosapentaenoic acid have beneficial effects on fatty liver,cardiometabolic risk factors,and inflammation,even at high intake levels.CONCLUSION The varying health effects of omega-6 fatty acids,ranging from anti-inflammatory to pro-inflammatory impacts on the liver,leave the question of their recommendation for MASLD patients unresolved.This underscores the importance of careful selection when considering omega-6 supplementation.展开更多
Colorectal cancer(CRC)is a common malignant tumor worldwide,and its tumor microenvironment(TME)plays a crucial role in tumor progression.Neutrophil extracellular traps(NETs),as an important component of the TME,have r...Colorectal cancer(CRC)is a common malignant tumor worldwide,and its tumor microenvironment(TME)plays a crucial role in tumor progression.Neutrophil extracellular traps(NETs),as an important component of the TME,have received widespread attention in recent years.This article explores the biological functions and molecular mechanisms of NETs in CRC and their impact on disease progression,while analyzing the application of single-cell sequencing technology(SCS)in this field.The development of SCS provides a new perspective for understanding the role of NETs in CRC.By combining SCS technology,targeting key regulatory nodes of NETs is expected to reverse the immunosuppressive microenvironment and provide a theoretical basis for developing novel diagnostic biomarkers and targeted therapeutic strategies,thereby promoting the development of precision medicine in CRC and helping enhance patient prognosis.Future research should further explore the integration of SCS technology with complementary methodologies to investigate NETs and develop specific detection methods and therapeutic strategies targeting NETs to enhance early diagnosis and treatment efficacy of tumors.展开更多
The rapid advancement of single-cell sequencing(SCS)technology has provided new insights into the relationship between inflammatory bowel disease(IBD)and colorectal cancer(CRC).This technique allows for detailed cellu...The rapid advancement of single-cell sequencing(SCS)technology has provided new insights into the relationship between inflammatory bowel disease(IBD)and colorectal cancer(CRC).This technique allows for detailed cellular analysis,enabling researchers to uncover the infiltration patterns of immune cells within the gut microenvironment and their roles in disease progression.This review summarizes significant research findings on the interplay between IBD and CRC,the characteristics of immune cell infiltration,and potential therapeutic targets identified through SCS.The aim is to offer references for future clinical studies and treatment strategies in this field.展开更多
Fundoscopic diagnosis involves assessing the proper functioning of the eye’s nerves,blood vessels,retinal health,and the impact of diabetes on the optic nerves.Fundus disorders are a major global health concern,affec...Fundoscopic diagnosis involves assessing the proper functioning of the eye’s nerves,blood vessels,retinal health,and the impact of diabetes on the optic nerves.Fundus disorders are a major global health concern,affecting millions of people worldwide due to their widespread occurrence.Fundus photography generates machine-based eye images that assist in diagnosing and treating ocular diseases such as diabetic retinopathy.As a result,accurate fundus detection is essential for early diagnosis and effective treatment,helping to prevent severe complications and improve patient outcomes.To address this need,this article introduces a Derivative Model for Fundus Detection using Deep NeuralNetworks(DMFD-DNN)to enhance diagnostic precision.Thismethod selects key features for fundus detection using the least derivative,which identifies features correlating with stored fundus images.Feature filtering relies on the minimum derivative,determined by extracting both similar and varying textures.In this research,the DNN model was integrated with the derivative model.Fundus images were segmented,features were extracted,and the DNN was iteratively trained to identify fundus regions reliably.The goal was to improve the precision of fundoscopic diagnosis by training the DNN incrementally,taking into account the least possible derivative across iterations,and using outputs from previous cycles.The hidden layer of the neural network operates on the most significant derivative,which may reduce precision across iterations.These derivatives are treated as inaccurate,and the model is subsequently trained using selective features and their corresponding extractions.The proposed model outperforms previous techniques in detecting fundus regions,achieving 94.98%accuracy and 91.57%sensitivity,with a minimal error rate of 5.43%.It significantly reduces feature extraction time to 1.462 s and minimizes computational overhead,thereby improving operational efficiency and scalability.Ultimately,the proposed model enhances diagnostic precision and reduces errors,leading to more effective fundus dysfunction diagnosis and treatment.展开更多
Essex-Lopresti injury is characterized by a radial head fracture accompanied by dislocation of the distal radioulnar joint and rupture of the interosseous membrane(IOM).This type of injury typically results from high-...Essex-Lopresti injury is characterized by a radial head fracture accompanied by dislocation of the distal radioulnar joint and rupture of the interosseous membrane(IOM).This type of injury typically results from high-energy axial forces transmitted through the wrist to the elbow,leading to tears in the IOM,fractures of the radial head,injuries to the distal radioulnar joint,and disruption of the triangular fibrocartilage complex,ultimately causing axial instability of the radioulnar joint.Due to its complexity,this injury is often overlooked in clinical settings,with a reported misdiagnosis rate as high as 60%.In pediatric cases,the misdiagnosis rate is even higher due to children's limited ability to articulate symptoms,the presence of substantial cartilaginous structures that have not fully ossified,and less typical radiographic findings compared to adults.This review aims to provide a comprehensive overview of the injury mechanism,clinical presentation,diagnosis,and treatment of Essex-Lopresti injuries in children,emphasizing the importance for pediatric orthopedists to recognize and manage this condition accurately to prevent misdiagnosis and inappropriate treatment.展开更多
Perianal fistulising Crohn’s disease is a challenging complication that can affect up to 20%of patients with Crohn’s disease and is associated with significant morbidity.Despite advances in medical therapies,particu...Perianal fistulising Crohn’s disease is a challenging complication that can affect up to 20%of patients with Crohn’s disease and is associated with significant morbidity.Despite advances in medical therapies,particularly anti-tumor necrosis factor agents,the majority of patients still require surgical intervention.Accurate diagnosis and monitoring are essential to optimise outcomes and guide multidisciplinary management.Although clinical scoring systems such as the perianal disease activity index are widely used,their subjective application limits their reproducibility and reliability,underscoring the need for more objective methods of evaluating perianal fistulising Crohn’s disease activity.Imaging has thus become central to the objective assessment of perianal fistulising Crohn’s disease,with magnetic resonance imaging(MRI)recognised as the gold standard in view of its ability to provide clear,detailed images of the perianal region in a radiation-free manner.Guidelines also endorse the use of imaging modalities such as endoanal ultrasound and transperineal ultrasound as viable alternatives to MRI for the assessment of perianal fistulising Crohn’s disease in centres with appropriate expertise.This article aims to evaluate and compare the diagnostic accuracy and clinical utility of MRI,endoanal ultrasound,and transperineal ultrasound in the assessment of perianal fistulising Crohn’s disease,highlighting their respective strengths,limitations,and roles in clinical practice.展开更多
Background:Developing a granulomatous liver injury preclinical model may pave the way to understanding hepatic-TB(tuberculosis)and autoimmune granulomatous liver diseases.Antitubercular(ATT)and other drugs'metabol...Background:Developing a granulomatous liver injury preclinical model may pave the way to understanding hepatic-TB(tuberculosis)and autoimmune granulomatous liver diseases.Antitubercular(ATT)and other drugs'metabolism in the presence of a specific type of liver injury is not well understood.The present study aimed to establish a preclinical model of granulomatous hepatitis by using the BCG(Bacillus CalmetteGuérin)vaccine,further studying it in the presence of ATT dosing,and analyze the pharmacokinetics of isoniazid,rifampicin,and their respective primary metabolites.Methods:We used 56 rats in seven equal groups.Group I functioned as a normal control(NC)receiving normal saline only.Groups II-IV received intravenous injections of low-,medium-,and high-dose BCG vaccine daily for 21 days.Groups V,VI,and VII received isoniazid(H)alone,rifampicin(R)alone,and isoniazid+rifampicin(HR)for a subsequent 15 days in addition to high dose BCG for the first 21 days,respectively.Liver function tests(LFT)were monitored on days 0,21,28,and 36.Rats were sacrificed later for oxidative stress and histopathological examination.Results:The study observed BCG dose-specific LFT derangements in groups II-IV compared to group I on day 21(p<0.05).Isoniazid,rifampicin,and combination intervention groups demonstrated normalization of the BCG-led LFT changes.Histology and oxidative stress parameters confirmed model development and biochemical changes.Isoniazid area under the curve(AUC)showed a reduction of 16.9%in BCG+HR group in comparison to the BCG+H group(p=0.01).Des-acetyl-rifampicin AUC and maximum-concentration value demonstrated a significant rise in BCG+HR group in comparison to the BCG+R group(p=0.001).Conclusion:A novel preclinical model of granulomatous liver injury was developed using the BCG vaccine strain and validated with ATT response.展开更多
Early and accurate detection of Heart Disease(HD)is critical for improving patient outcomes,as HD remains a leading cause of mortality worldwide.Timely and precise prediction can aid in preventive interventions,reduci...Early and accurate detection of Heart Disease(HD)is critical for improving patient outcomes,as HD remains a leading cause of mortality worldwide.Timely and precise prediction can aid in preventive interventions,reducing fatal risks associated with misdiagnosis.Machine learning(ML)models have gained significant attention in healthcare for their ability to assist professionals in diagnosing diseases with high accuracy.This study utilizes 918 instances from publicly available UCI and Kaggle datasets to develop and compare the performance of various ML models,including Adaptive Boosting(AB),Naïve Bayes(NB),Extreme Gradient Boosting(XGB),Bagging,and Logistic Regression(LR).Before model training,data preprocessing techniques such as handling missing values,outlier detection using Isolation Forest,and feature scaling were applied to improve model performance.The evaluation was conducted using performance metrics,including accuracy,precision,recall,and F1-score.Among the tested models,XGB demonstrated the highest predictive performance,achieving an accuracy of 94.34%and an F1-score of 95.19%,surpassing other models and previous studies in HD prediction.LR closely followed with an accuracy of 93.08%and an F1-score of 93.99%,indicating competitive performance.In contrast,NB exhibited the lowest performance,with an accuracy of 88.05%and an F1-score of 89.02%,highlighting its limitations in handling complex patterns within the dataset.Although ML models show superior performance as compared to previous studies,some limitations exist,including the use of publicly available datasets,which may not fully capture real-world clinical variations,and the lack of feature selection techniques,which could impact model interpretability and robustness.Despite these limitations,the findings highlight the potential of ML-based frameworks for accurate and efficient HD detection,demonstrating their value as decision-support tools in clinical settings.展开更多
Simultaneous degradation and detoxification during pharmaceutical and personal care product removal are important for water treatment.In this study,sodium niobate nanocubes decorated with graphitic carbon nitride(NbNC...Simultaneous degradation and detoxification during pharmaceutical and personal care product removal are important for water treatment.In this study,sodium niobate nanocubes decorated with graphitic carbon nitride(NbNC/g-C_(3)N_(4))were fabricated to achieve the efficient photocatalytic degradation and detoxification of ciprofloxacin(CIP)under simulated solar light.NaNbO_(3)nanocubes were in-situ transformed from Na_(2)Nb_(2)O_(6)·H_(2)O via thermal dehydration at the interface of g-C_(3)N_(4).The optimized NbNC/g-C_(3)N_(4)-1 was a type-I heterojunction,which showed a high conduction band(CB)level of−1.68 eV,leading to the efficient transfer of photogenerated electrons to O_(2) to produce primary reactive species,•O_(2)^(-).Density functional theory(DFT)calculations of the density of states indicated that C 2p and Nb 3d contributed to the CB,and 0.37 e^(-)transferred from NaNbO_(3)to g-C_(3)N_(4)in NbNC/g-C_(3)N_(4)based on the Mulliken population analysis of the built-in electric field intensity.NbNC/g-C_(3)N_(4)-1 had 3.3-and 2.3-fold of CIP degradation rate constants(k_(1)=0.173 min^(−1))compared with those of pristine g-C_(3)N_(4)and NaNbO_(3),respectively.In addition,N24,N19,and C5 in CIP with a high Fukui index were reactive sites for electrophilic attack by•O_(2)^(-),resulting in the defluorination and ring-opening of the piperazine moiety of the dominant degradation pathways.Intermediate/product identification,integrated with computational toxicity evaluation,further indicated a substantial detoxification effect during CIP degradation in the photocatalysis system.展开更多
BACKGROUND Acute respiratory distress syndrome(ARDS)is a critical condition characterized by acute hypoxemia,non-cardiogenic pulmonary edema,and decreased lung compliance.The Berlin definition,updated in 2012,classifi...BACKGROUND Acute respiratory distress syndrome(ARDS)is a critical condition characterized by acute hypoxemia,non-cardiogenic pulmonary edema,and decreased lung compliance.The Berlin definition,updated in 2012,classifies ARDS severity based on the partial pressure of arterial oxygen/fractional inspired oxygen fraction ratio.Despite various treatment strategies,ARDS remains a significant public health concern with high mortality rates.AIM To evaluate the implications of driving pressure(DP)in ARDS management and its potential as a protective lung strategy.METHODS We conducted a systematic review using databases including EbscoHost,MEDLINE,CINAHL,PubMed,and Google Scholar.The search was limited to articles published between January 2015 and September 2024.Twenty-three peer-reviewed articles were selected based on inclusion criteria focusing on adult ARDS patients undergoing mechanical ventilation and DP strategies.The literature review was conducted and reported according to PRISMA 2020 guidelines.RESULTS DP,the difference between plateau pressure and positive end-expiratory pressure,is crucial in ARDS management.Studies indicate that lower DP levels are significantly associated with improved survival rates in ARDS patients.DP is a better predictor of mortality than tidal volume or positive end-expiratory pressure alone.Adjusting DP by optimizing lung compliance and minimizing overdistension and collapse can reduce ventilator-induced lung injury.CONCLUSION DP is a valuable parameter in ARDS management,offering a more precise measure of lung stress and strain than traditional metrics.Implementing DP as a threshold for safety can enhance protective ventilation strategies,po-tentially reducing mortality in ARDS patients.Further research is needed to refine DP measurement techniques and validate its clinical application in diverse patient populations.展开更多
Evaporation of ground water is a part of moisture circulation in the field. And it is a main natural form in which water transmits from the ground water to the soil water and atmosphere water. According to the simulat...Evaporation of ground water is a part of moisture circulation in the field. And it is a main natural form in which water transmits from the ground water to the soil water and atmosphere water. According to the simulated experiments, we study the relationship among the evaporation, depth of groundwater table and negative pressure. By theoretical analysis of the experimental results, the main conclusions are drawn as follows. There are two abrupt points in every Q-H curve. The locations of the abrupt points are separately in step with the height of top of the capillary fringe and the height of maximal capillary rise in the soil section. When the depth of water table H is small, the evaporation flux of ground water is large. While the depth of water table exceeds the maximal capillary rise of media in vadose zone, the capillary rise breaks up and evaporation flux of groundwater is small. The water content ratio in ground surface tends to be zero and the surface of soil tends to be drought. These conclusions show that the maximal capillary rise of media in vadose zone is an important value in regulating rational depth of ground water to reduce the evaporation of ground water and to increase effective quantity of water resources. In the meantime, these conclusions are of important theoretical and practical significance to reduce the evaporation of ground water, to prevent and cure the salinization of soil, and to make full use of and protect water resources in the northern plains in China.展开更多
SARS-CoV-2 induced marked lymphopenia in severe patients with COVID-19.However,whether lymphocytes are targets of viral infection is yet to be determined,although SARS-CoV-2 RNA or antigen has been identified in T cel...SARS-CoV-2 induced marked lymphopenia in severe patients with COVID-19.However,whether lymphocytes are targets of viral infection is yet to be determined,although SARS-CoV-2 RNA or antigen has been identified in T cells from patients.Here,we confirmed that SARS-CoV-2 viral antigen could be detected in patient peripheral blood cells(PBCs)or postmortem lung T cells,and the infectious virus could also be detected from viral antigen-positive PBCs.We next prove that SARS-CoV-2 infects T lymphocytes,preferably activated CD4+T cells in vitro.Upon infection,viral RNA,subgenomic RNA,viral protein or viral particle can be detected in the T cells.Furthermore,we show that the infection is spike-ACE2/TMPRSS2-independent through using ACE2 knockdown or receptor blocking experiments.Next,we demonstrate that viral antigen-positive T cells from patient undergone pronounced apoptosis.In vitro infection of T cells induced cell death that is likely in mitochondria ROS-HIF-1a-dependent pathways.Finally,we demonstrated that LFA-1,the protein exclusively expresses in multiple leukocytes,is more likely the entry molecule that mediated SARS-CoV-2 infection in T cells,compared to a list of other known receptors.Collectively,this work confirmed a SARS-CoV-2 infection of T cells,in a spike-ACE2-independent manner,which shed novel insights into the underlying mechanisms of SARS-CoV2-induced lymphopenia in COVID-19 patients.展开更多
Background:Bronchial hyperresponsiveness (BHR) is a fundamental pathophysiological characteristic of asthma.Although several factors such as airway caliber can affect BHR,no study has established age-dependent cutoff ...Background:Bronchial hyperresponsiveness (BHR) is a fundamental pathophysiological characteristic of asthma.Although several factors such as airway caliber can affect BHR,no study has established age-dependent cutoff values of BHR to methacholine for the diagnosis of asthma in children.We investigated the cutoff values of the methacholine challenge test (MCT) in the diagnosis of asthma according to age.Methods:A total of 2383 individuals aged from 6 to 15 years old were included in this study.MCTs using the five-breath technique were performed in 350 children with suspected asthma based on symptoms by pediatric allergists and in 2033 healthy children from a general population-based cohort.We determined the provocative concentration of methacholine producing a 20% decrease in forced expiratory volume in 1 second from baseline (PC20).A modified Korean version of the International Study of Asthma and Allergies in Childhood questionnaire was used to distinguish asthmatics and healthy subjects.Receiveroperator characteristic curve analysis was used to assess the cutoff value of PC20 for the diagnosis of asthma.Results:Cutoff values of methacholine PC20,which provided the best combination of diagnostic sensitivity and specificity,showed an increasing pattern with age:5.8,9.1,11.8,12.6,14.9,21.7,23.3,21.1,21.1,and 24.6 mg/mL at ages 6,7,8,9,10,11,12,13,14,and 15 years,respectively.Conclusion:The application of different cutoff values of methacholine PC20 depending on age might be a practical modification for the diagnosis of asthma in children and adolescents with asthmatic symptoms.展开更多
Irisin,a myokine mainly secreted from contracted skeleton muscle,plays a profound role in bone formation and remodeling.Although irisin has been revealed to elevate bone mass in vivo,details whether there is a dosedep...Irisin,a myokine mainly secreted from contracted skeleton muscle,plays a profound role in bone formation and remodeling.Although irisin has been revealed to elevate bone mass in vivo,details whether there is a dosedependent relationship between irisin and bone formation remain unclear.In this study,we explored the dosedependent effects of irisin on osteoblast proliferation and differentiation.Our results first demonstrated a remarkable increase in cell proliferation rate and viability in response to elevated concentrations of r-irisin,which was further enhanced over time.Notably,this increase was subject to complex dose-response relationships as the proliferation-enhancing effects of r-irisin may have a saturation point between 10 ng/ml and 100 ng/ml.Furthermore,we determined that 1,10,and 100 ng/ml r-irisin were able to upregulate the expression of osteogenic transcription factors(Runx2,Osx,and Atf4),as well as osteogenic markers(Alp,Col1a1 and Spp1),albeit without significant difference among these 3 concentrations.Interestingly,nutrient-depleted osteoblasts and those with standard culture showed distinct responses to higher doses of irisin regarding osteogenic differentiation.Further investigation is required to uncover the molecular mechanisms underlying the observed tandem effects of irisin on osteogenesis.展开更多
目的:探索非综合征型唇裂伴或不伴腭裂(non-syndromic cleft lip with or without cleft palate, NSCL/P)全基因组常见遗传变异对NSCL/P风险的影响。方法:利用全基因组关联研究(genome-wide association study, GWAS)数据,以全基因组单...目的:探索非综合征型唇裂伴或不伴腭裂(non-syndromic cleft lip with or without cleft palate, NSCL/P)全基因组常见遗传变异对NSCL/P风险的影响。方法:利用全基因组关联研究(genome-wide association study, GWAS)数据,以全基因组单核苷酸多态性(single nucleotide polymorphism, SNP)遗传度和基因组不同分区SNP遗传度评估基因组上常见变异的效应。对GWAS汇总数据进行质量控制,标准包括数据中无缺失值、弱势等位基因频率≥1%、P值在0~1、SNP正负链明确等。利用连锁不平衡得分回归计算NSCL/P的SNP遗传度,采用分层的连锁不平衡得分回归计算基因组编码区、启动子区、内含子区、增强子区和超级增强子区的分区SNP遗传度,并评估不同分区内的富集度,分析工具为LDSC (v1.0.1)软件。结果:纳入中国人群806个NSCL/P核心家系(2 418人)的GWAS数据,490 593个SNP通过质量控制,被纳入到SNP遗传度的计算中。观测样本中NSCL/P的SNP遗传度为0.55(95%CI:0.28~0.82),由于观测样本患病率较高,按中国人群患病率转换为一般人群后SNP遗传度为0.37(95%CI:0.19~0.55)。SNP遗传度在增强子区的富集度为15.70(P=0.04),在超级增强子区的富集度为3.18(P=0.03)。结论:基因组常见变异有助于解释一部分中国人群NSCL/P目前未被解释的遗传度,同时中国人群NSCL/P的SNP遗传度在增强子分区和超级增强子分区中显著富集,提示该区域中可能存在未被发现的遗传致病因素。展开更多
基金the National Natural Science Foundation of China(81871852,81200935,81671867 and 81971794)the Liaoning Revitalization Talents Program(XLYC1807137)+1 种基金the Scientific Research Foundation for Returned Scholars of the Ministry of Education of China(20151098)the Natural Science Foundation of Liaoning Province,China(20170541030)。
文摘Dear Editor,The pathophysiologic al mechanisms underlying mood disorders including major depressive disorder(MDD)remain to be fully characterized.Iron is a key component in the development of the central nervous system and iron deficiency has been linked to impairments of mood and cognition[1].
文摘The Tongkuangyu porphyry copper deposit in the Zhongtiao Mountains, China, is tectonically located on the southern margin of the North China platform and on the northern margin of the Late Archean Zhongtiaoshan intracontinental rift basin. The deposit occurs in a copper-bearing formation of tuffaceous variegated sandshale-K-rich bimodal volcanic rocks of the Tongkuangyu Formation of the Late Archean Jiangxian Group, and the orebodies are localized in a transition portion between tuffaceous variegated sandshale and bimodal volcanic rocks. The host rocks consist mainly of metagranodiorite-porphyry, meta-quartz monzonite-
基金supported by the National High Level Hospital Clinical Research Funding (2022-PUMCH-B-109)Chinese Academy of Medical Science Innovation Fund for Medical Sciences (CIFMS)(2021-I2M-1-020)。
文摘BACKGROUND: Sepsis, a common acute and critical disease, leads to 11 million deaths annually worldwide. Probiotics are living microorganisms that are beneficial to the host and may benefit sepsis outcomes, but their effects are stil inconclusive. This study aimed to evaluate the overal eff ect of probiotics on the prognosis of patients with sepsis.DATA RESOURCES: We searched several sources for published/presented studies, including Pub Med, EMBASE, Web of Science, the Cochrane Library and the US National Library of Medicine Clinical Trials Register(www.clinicaltrials.gov) updated through July 30, 2023, to identify all relevant randomized controlled trials(RCTs) or observational studies that assessed the effectiveness of probiotics or synbiotics in patients with sepsis and reported mortality. We focused primarily on mortality during the study period and analyzed secondary outcomes, including 28-day mortality, in-intensive care unit(ICU) mortality and other outcomes.RESULTS: Data from 405 patients in five RCTs and 108 patients in one cohort study were included in the analysis. The overall quality of the studies was satisfactory, but clinical heterogeneity existed. All adult studies reported a tendency for probiotics to reduce the mortality of patients with sepsis, and most studies reported a decreasing trend in the incidence of infectious complications, length of ICU stay and duration of antibiotic use. There was only one RCT involving children.CONCLUSION: Probiotics show promise for improving the prognosis of patients with sepsis, including reducing mortality and the incidence of infectious complications, particularly in adult patients. Despite the limited number of studies, especially in children, these findings will be encouraging for clinical practice in the treatment of sepsis and suggest that gut microbiota-targeted therapy may improve the prognosis of patients with sepsis.
基金M Tahir is funded by EU H2020 Marie Skłodows-ka-Curie Fellowship(1439425).
文摘Graphitic carbon nitride(g-C_(3)N_(4))exhibits great mechanical as well as thermal characteristics,making it a valuable ma-terial for use in photoelectric conversion devices,an accelerator for synthesis of organic compounds,an electrolyte for fuel cell applications or power sources,and a hydrogen storage substance and a fluorescence detector.It is fabricated using dif-ferent methods,and there is a variety of morphologies and nanostructures such as zero to three dimensions that have been designed for different purposes.Ther e are many reports about g-C_(3)N_(4) in recent years,but a comprehensive review which covers nanostructure dimensions and their properties are missing.This review paper aims to give basic and comprehensive understanding of the photocatalytic and electrocatalytic usages of g-C_(3)N_(4).It highlights the recent progress of g-C_(3)N_(4) nano-structure designing by covering synthesis methods,dimensions,morphologies,applications and properties.Along with the summary,we will also discuss the challenges and prospects.Scientists,investigators,and engineers looking at g-C_(3)N_(4) nanostructures for a variety of applications might find our review paper to be a useful resource.
文摘BACKGROUND Metabolic dysfunction-associated steatotic liver disease(MASLD)is the most common chronic liver disease worldwide.Its prevalence is closely linked to the dramatic rise in obesity and non-communicable diseases.MASLD exhibits a progressive trajectory that may culminate in development of hepatic cirrhosis,thereby predisposing affected individuals to an elevated likelihood of hepatocarcinogenesis.Diet,especially dietary fatty acids,serves as a key link between nutrient intake and MASLD pathogenesis.AIM To explore the impact of various omega-6 fatty acid subtypes on the pathogenesis and therapeutic strategies of MASLD.METHODS A systematic literature search was conducted across Web of Science,PubMed,Cochrane Central,Scopus,and Embase databases from inception through June 2024 to identify all original studies linking different subtypes of omega-6 polyunsaturated fatty acids to the pathogenesis and management of MASLD.The search strategy explored the linkage between omega-6 polyunsaturated fatty acids and their subtypes,including linoleic acid(LA),gamma-linolenic acid(GLA),arachidonic acid,conjugated LA,and docosapentaenoic acid,in relation to MASLD and cardiometabolic risk.RESULTS By employing the specified search strategy,a total of 83 articles were identified as potentially eligible.During the title,abstract,and full-text screening phases,27 duplicate records were removed,leaving 56 records for relevance screening.Of these,43 records were excluded for reasons such as irrelevance and language restrictions(limited to English),resulting in 13 full-text articles being included for detailed assessment(10 human studies,1 animal study,and 2 review articles).Although certain subtypes,as GLA,dihomo-GLA,omega-6-derived oxylipins,and most arachidonic acid-derived eicosanoids,exhibit pro-inflammatory effects,our findings suggest that other subtypes such as LA,cis-9,trans-11 conjugated LA,and docosapentaenoic acid have beneficial effects on fatty liver,cardiometabolic risk factors,and inflammation,even at high intake levels.CONCLUSION The varying health effects of omega-6 fatty acids,ranging from anti-inflammatory to pro-inflammatory impacts on the liver,leave the question of their recommendation for MASLD patients unresolved.This underscores the importance of careful selection when considering omega-6 supplementation.
基金the Shandong Province Medical and Health Science and Technology Development Plan Project,No.202203030713Yantai Science and Technology Program,No.2024YD005,No.2024YD007 and No.2024YD010and Science and Technology Program of Yantai Affiliated Hospital of Binzhou Medical University,No.YTFY2022KYQD06.
文摘Colorectal cancer(CRC)is a common malignant tumor worldwide,and its tumor microenvironment(TME)plays a crucial role in tumor progression.Neutrophil extracellular traps(NETs),as an important component of the TME,have received widespread attention in recent years.This article explores the biological functions and molecular mechanisms of NETs in CRC and their impact on disease progression,while analyzing the application of single-cell sequencing technology(SCS)in this field.The development of SCS provides a new perspective for understanding the role of NETs in CRC.By combining SCS technology,targeting key regulatory nodes of NETs is expected to reverse the immunosuppressive microenvironment and provide a theoretical basis for developing novel diagnostic biomarkers and targeted therapeutic strategies,thereby promoting the development of precision medicine in CRC and helping enhance patient prognosis.Future research should further explore the integration of SCS technology with complementary methodologies to investigate NETs and develop specific detection methods and therapeutic strategies targeting NETs to enhance early diagnosis and treatment efficacy of tumors.
基金Supported by the Shandong Province Medical and Health Science and Technology Development Plan Project,No.202203030713Yantai Science and Technology Program,No.2024YD005,No.2024YD007 and No.2024YD010Science and Technology Program of Yantai Affiliated Hospital of Binzhou Medical University,No.YTFY2022KYQD06。
文摘The rapid advancement of single-cell sequencing(SCS)technology has provided new insights into the relationship between inflammatory bowel disease(IBD)and colorectal cancer(CRC).This technique allows for detailed cellular analysis,enabling researchers to uncover the infiltration patterns of immune cells within the gut microenvironment and their roles in disease progression.This review summarizes significant research findings on the interplay between IBD and CRC,the characteristics of immune cell infiltration,and potential therapeutic targets identified through SCS.The aim is to offer references for future clinical studies and treatment strategies in this field.
基金supported by the Basic Science Research Program through the National Research Foundation of Korea(NRF)funded by the Ministry of Education(No.2021R1F1A1055408)supported by the Researchers Supporting Project Number(MHIRSP2024005)Almaarefa University,Riyadh,Saudi Arabia.
文摘Fundoscopic diagnosis involves assessing the proper functioning of the eye’s nerves,blood vessels,retinal health,and the impact of diabetes on the optic nerves.Fundus disorders are a major global health concern,affecting millions of people worldwide due to their widespread occurrence.Fundus photography generates machine-based eye images that assist in diagnosing and treating ocular diseases such as diabetic retinopathy.As a result,accurate fundus detection is essential for early diagnosis and effective treatment,helping to prevent severe complications and improve patient outcomes.To address this need,this article introduces a Derivative Model for Fundus Detection using Deep NeuralNetworks(DMFD-DNN)to enhance diagnostic precision.Thismethod selects key features for fundus detection using the least derivative,which identifies features correlating with stored fundus images.Feature filtering relies on the minimum derivative,determined by extracting both similar and varying textures.In this research,the DNN model was integrated with the derivative model.Fundus images were segmented,features were extracted,and the DNN was iteratively trained to identify fundus regions reliably.The goal was to improve the precision of fundoscopic diagnosis by training the DNN incrementally,taking into account the least possible derivative across iterations,and using outputs from previous cycles.The hidden layer of the neural network operates on the most significant derivative,which may reduce precision across iterations.These derivatives are treated as inaccurate,and the model is subsequently trained using selective features and their corresponding extractions.The proposed model outperforms previous techniques in detecting fundus regions,achieving 94.98%accuracy and 91.57%sensitivity,with a minimal error rate of 5.43%.It significantly reduces feature extraction time to 1.462 s and minimizes computational overhead,thereby improving operational efficiency and scalability.Ultimately,the proposed model enhances diagnostic precision and reduces errors,leading to more effective fundus dysfunction diagnosis and treatment.
基金Supported by Science Project of Hunan Provincial Healthy Commission,No.20230844Science Project of Hunan Natural Science Foundation,No.2025JJ81181.
文摘Essex-Lopresti injury is characterized by a radial head fracture accompanied by dislocation of the distal radioulnar joint and rupture of the interosseous membrane(IOM).This type of injury typically results from high-energy axial forces transmitted through the wrist to the elbow,leading to tears in the IOM,fractures of the radial head,injuries to the distal radioulnar joint,and disruption of the triangular fibrocartilage complex,ultimately causing axial instability of the radioulnar joint.Due to its complexity,this injury is often overlooked in clinical settings,with a reported misdiagnosis rate as high as 60%.In pediatric cases,the misdiagnosis rate is even higher due to children's limited ability to articulate symptoms,the presence of substantial cartilaginous structures that have not fully ossified,and less typical radiographic findings compared to adults.This review aims to provide a comprehensive overview of the injury mechanism,clinical presentation,diagnosis,and treatment of Essex-Lopresti injuries in children,emphasizing the importance for pediatric orthopedists to recognize and manage this condition accurately to prevent misdiagnosis and inappropriate treatment.
文摘Perianal fistulising Crohn’s disease is a challenging complication that can affect up to 20%of patients with Crohn’s disease and is associated with significant morbidity.Despite advances in medical therapies,particularly anti-tumor necrosis factor agents,the majority of patients still require surgical intervention.Accurate diagnosis and monitoring are essential to optimise outcomes and guide multidisciplinary management.Although clinical scoring systems such as the perianal disease activity index are widely used,their subjective application limits their reproducibility and reliability,underscoring the need for more objective methods of evaluating perianal fistulising Crohn’s disease activity.Imaging has thus become central to the objective assessment of perianal fistulising Crohn’s disease,with magnetic resonance imaging(MRI)recognised as the gold standard in view of its ability to provide clear,detailed images of the perianal region in a radiation-free manner.Guidelines also endorse the use of imaging modalities such as endoanal ultrasound and transperineal ultrasound as viable alternatives to MRI for the assessment of perianal fistulising Crohn’s disease in centres with appropriate expertise.This article aims to evaluate and compare the diagnostic accuracy and clinical utility of MRI,endoanal ultrasound,and transperineal ultrasound in the assessment of perianal fistulising Crohn’s disease,highlighting their respective strengths,limitations,and roles in clinical practice.
文摘Background:Developing a granulomatous liver injury preclinical model may pave the way to understanding hepatic-TB(tuberculosis)and autoimmune granulomatous liver diseases.Antitubercular(ATT)and other drugs'metabolism in the presence of a specific type of liver injury is not well understood.The present study aimed to establish a preclinical model of granulomatous hepatitis by using the BCG(Bacillus CalmetteGuérin)vaccine,further studying it in the presence of ATT dosing,and analyze the pharmacokinetics of isoniazid,rifampicin,and their respective primary metabolites.Methods:We used 56 rats in seven equal groups.Group I functioned as a normal control(NC)receiving normal saline only.Groups II-IV received intravenous injections of low-,medium-,and high-dose BCG vaccine daily for 21 days.Groups V,VI,and VII received isoniazid(H)alone,rifampicin(R)alone,and isoniazid+rifampicin(HR)for a subsequent 15 days in addition to high dose BCG for the first 21 days,respectively.Liver function tests(LFT)were monitored on days 0,21,28,and 36.Rats were sacrificed later for oxidative stress and histopathological examination.Results:The study observed BCG dose-specific LFT derangements in groups II-IV compared to group I on day 21(p<0.05).Isoniazid,rifampicin,and combination intervention groups demonstrated normalization of the BCG-led LFT changes.Histology and oxidative stress parameters confirmed model development and biochemical changes.Isoniazid area under the curve(AUC)showed a reduction of 16.9%in BCG+HR group in comparison to the BCG+H group(p=0.01).Des-acetyl-rifampicin AUC and maximum-concentration value demonstrated a significant rise in BCG+HR group in comparison to the BCG+R group(p=0.001).Conclusion:A novel preclinical model of granulomatous liver injury was developed using the BCG vaccine strain and validated with ATT response.
基金funded by Princess Nourah bint Abdulrahman University Researchers Supporting Project number(PNURSP2025R235),Princess Nourah bint Abdulrahman University,Riyadh,Saudi Arabia.
文摘Early and accurate detection of Heart Disease(HD)is critical for improving patient outcomes,as HD remains a leading cause of mortality worldwide.Timely and precise prediction can aid in preventive interventions,reducing fatal risks associated with misdiagnosis.Machine learning(ML)models have gained significant attention in healthcare for their ability to assist professionals in diagnosing diseases with high accuracy.This study utilizes 918 instances from publicly available UCI and Kaggle datasets to develop and compare the performance of various ML models,including Adaptive Boosting(AB),Naïve Bayes(NB),Extreme Gradient Boosting(XGB),Bagging,and Logistic Regression(LR).Before model training,data preprocessing techniques such as handling missing values,outlier detection using Isolation Forest,and feature scaling were applied to improve model performance.The evaluation was conducted using performance metrics,including accuracy,precision,recall,and F1-score.Among the tested models,XGB demonstrated the highest predictive performance,achieving an accuracy of 94.34%and an F1-score of 95.19%,surpassing other models and previous studies in HD prediction.LR closely followed with an accuracy of 93.08%and an F1-score of 93.99%,indicating competitive performance.In contrast,NB exhibited the lowest performance,with an accuracy of 88.05%and an F1-score of 89.02%,highlighting its limitations in handling complex patterns within the dataset.Although ML models show superior performance as compared to previous studies,some limitations exist,including the use of publicly available datasets,which may not fully capture real-world clinical variations,and the lack of feature selection techniques,which could impact model interpretability and robustness.Despite these limitations,the findings highlight the potential of ML-based frameworks for accurate and efficient HD detection,demonstrating their value as decision-support tools in clinical settings.
基金the National Key Research and Development Program of China(Nos.2021YFA1202500 and 2022YFF1303004)Shenzhen Science and Technology Program(No.JCYJ20220531093205013)+6 种基金the National Natural Science Foundation of China(NSFC)(Nos.52100069,52270053 and 52200084)the Beijing Natural Science Foundation(No.8232035),the Beijing Nova Program(No.20220484215)the Beijing National Laboratory for Molecular Sciences(No.BNLMS2023011)Emerging Engineering Interdisciplinary-Young Scholars Project(Peking University),the Fundamental Research Funds for the Central Universities are greatly acknowledgedsupported by the High-Performance Computing Platform of Peking Universitythe National Key Scientific and Technological Infrastructure project“Earth System Numerical Simulation Facility”(EarthLab)are also acknowledgedsupported by the program of“Research on Advanced Treatment Technology of New Pollutants in Domestic Sewage of Residential District”.
文摘Simultaneous degradation and detoxification during pharmaceutical and personal care product removal are important for water treatment.In this study,sodium niobate nanocubes decorated with graphitic carbon nitride(NbNC/g-C_(3)N_(4))were fabricated to achieve the efficient photocatalytic degradation and detoxification of ciprofloxacin(CIP)under simulated solar light.NaNbO_(3)nanocubes were in-situ transformed from Na_(2)Nb_(2)O_(6)·H_(2)O via thermal dehydration at the interface of g-C_(3)N_(4).The optimized NbNC/g-C_(3)N_(4)-1 was a type-I heterojunction,which showed a high conduction band(CB)level of−1.68 eV,leading to the efficient transfer of photogenerated electrons to O_(2) to produce primary reactive species,•O_(2)^(-).Density functional theory(DFT)calculations of the density of states indicated that C 2p and Nb 3d contributed to the CB,and 0.37 e^(-)transferred from NaNbO_(3)to g-C_(3)N_(4)in NbNC/g-C_(3)N_(4)based on the Mulliken population analysis of the built-in electric field intensity.NbNC/g-C_(3)N_(4)-1 had 3.3-and 2.3-fold of CIP degradation rate constants(k_(1)=0.173 min^(−1))compared with those of pristine g-C_(3)N_(4)and NaNbO_(3),respectively.In addition,N24,N19,and C5 in CIP with a high Fukui index were reactive sites for electrophilic attack by•O_(2)^(-),resulting in the defluorination and ring-opening of the piperazine moiety of the dominant degradation pathways.Intermediate/product identification,integrated with computational toxicity evaluation,further indicated a substantial detoxification effect during CIP degradation in the photocatalysis system.
文摘BACKGROUND Acute respiratory distress syndrome(ARDS)is a critical condition characterized by acute hypoxemia,non-cardiogenic pulmonary edema,and decreased lung compliance.The Berlin definition,updated in 2012,classifies ARDS severity based on the partial pressure of arterial oxygen/fractional inspired oxygen fraction ratio.Despite various treatment strategies,ARDS remains a significant public health concern with high mortality rates.AIM To evaluate the implications of driving pressure(DP)in ARDS management and its potential as a protective lung strategy.METHODS We conducted a systematic review using databases including EbscoHost,MEDLINE,CINAHL,PubMed,and Google Scholar.The search was limited to articles published between January 2015 and September 2024.Twenty-three peer-reviewed articles were selected based on inclusion criteria focusing on adult ARDS patients undergoing mechanical ventilation and DP strategies.The literature review was conducted and reported according to PRISMA 2020 guidelines.RESULTS DP,the difference between plateau pressure and positive end-expiratory pressure,is crucial in ARDS management.Studies indicate that lower DP levels are significantly associated with improved survival rates in ARDS patients.DP is a better predictor of mortality than tidal volume or positive end-expiratory pressure alone.Adjusting DP by optimizing lung compliance and minimizing overdistension and collapse can reduce ventilator-induced lung injury.CONCLUSION DP is a valuable parameter in ARDS management,offering a more precise measure of lung stress and strain than traditional metrics.Implementing DP as a threshold for safety can enhance protective ventilation strategies,po-tentially reducing mortality in ARDS patients.Further research is needed to refine DP measurement techniques and validate its clinical application in diverse patient populations.
基金This research are supported by Natural Science Foundation of Henan Province of Chi-na( No:974 0 71 40 0 ) and Ph.D Subject Fou
文摘Evaporation of ground water is a part of moisture circulation in the field. And it is a main natural form in which water transmits from the ground water to the soil water and atmosphere water. According to the simulated experiments, we study the relationship among the evaporation, depth of groundwater table and negative pressure. By theoretical analysis of the experimental results, the main conclusions are drawn as follows. There are two abrupt points in every Q-H curve. The locations of the abrupt points are separately in step with the height of top of the capillary fringe and the height of maximal capillary rise in the soil section. When the depth of water table H is small, the evaporation flux of ground water is large. While the depth of water table exceeds the maximal capillary rise of media in vadose zone, the capillary rise breaks up and evaporation flux of groundwater is small. The water content ratio in ground surface tends to be zero and the surface of soil tends to be drought. These conclusions show that the maximal capillary rise of media in vadose zone is an important value in regulating rational depth of ground water to reduce the evaporation of ground water and to increase effective quantity of water resources. In the meantime, these conclusions are of important theoretical and practical significance to reduce the evaporation of ground water, to prevent and cure the salinization of soil, and to make full use of and protect water resources in the northern plains in China.
基金the Natural Science Foundation of China(excellent scholars 81822028,82041013,and 81772199 to P.Z.,and 81974456 and 82170081 to H.L.Z.)Strategic Priority Research Program of the CAS(grant number XDB29010204)to P.Z.
文摘SARS-CoV-2 induced marked lymphopenia in severe patients with COVID-19.However,whether lymphocytes are targets of viral infection is yet to be determined,although SARS-CoV-2 RNA or antigen has been identified in T cells from patients.Here,we confirmed that SARS-CoV-2 viral antigen could be detected in patient peripheral blood cells(PBCs)or postmortem lung T cells,and the infectious virus could also be detected from viral antigen-positive PBCs.We next prove that SARS-CoV-2 infects T lymphocytes,preferably activated CD4+T cells in vitro.Upon infection,viral RNA,subgenomic RNA,viral protein or viral particle can be detected in the T cells.Furthermore,we show that the infection is spike-ACE2/TMPRSS2-independent through using ACE2 knockdown or receptor blocking experiments.Next,we demonstrate that viral antigen-positive T cells from patient undergone pronounced apoptosis.In vitro infection of T cells induced cell death that is likely in mitochondria ROS-HIF-1a-dependent pathways.Finally,we demonstrated that LFA-1,the protein exclusively expresses in multiple leukocytes,is more likely the entry molecule that mediated SARS-CoV-2 infection in T cells,compared to a list of other known receptors.Collectively,this work confirmed a SARS-CoV-2 infection of T cells,in a spike-ACE2-independent manner,which shed novel insights into the underlying mechanisms of SARS-CoV2-induced lymphopenia in COVID-19 patients.
文摘Background:Bronchial hyperresponsiveness (BHR) is a fundamental pathophysiological characteristic of asthma.Although several factors such as airway caliber can affect BHR,no study has established age-dependent cutoff values of BHR to methacholine for the diagnosis of asthma in children.We investigated the cutoff values of the methacholine challenge test (MCT) in the diagnosis of asthma according to age.Methods:A total of 2383 individuals aged from 6 to 15 years old were included in this study.MCTs using the five-breath technique were performed in 350 children with suspected asthma based on symptoms by pediatric allergists and in 2033 healthy children from a general population-based cohort.We determined the provocative concentration of methacholine producing a 20% decrease in forced expiratory volume in 1 second from baseline (PC20).A modified Korean version of the International Study of Asthma and Allergies in Childhood questionnaire was used to distinguish asthmatics and healthy subjects.Receiveroperator characteristic curve analysis was used to assess the cutoff value of PC20 for the diagnosis of asthma.Results:Cutoff values of methacholine PC20,which provided the best combination of diagnostic sensitivity and specificity,showed an increasing pattern with age:5.8,9.1,11.8,12.6,14.9,21.7,23.3,21.1,21.1,and 24.6 mg/mL at ages 6,7,8,9,10,11,12,13,14,and 15 years,respectively.Conclusion:The application of different cutoff values of methacholine PC20 depending on age might be a practical modification for the diagnosis of asthma in children and adolescents with asthmatic symptoms.
基金The study was supported by National Natural Science Foundation of China(No.12172034,U2241273,11827803,U20A20390)Beijing Municipal Natural Science Foundation(7212205)+1 种基金the 111 project(B13003)the Fundamental Research Funds for the Central Universities.
文摘Irisin,a myokine mainly secreted from contracted skeleton muscle,plays a profound role in bone formation and remodeling.Although irisin has been revealed to elevate bone mass in vivo,details whether there is a dosedependent relationship between irisin and bone formation remain unclear.In this study,we explored the dosedependent effects of irisin on osteoblast proliferation and differentiation.Our results first demonstrated a remarkable increase in cell proliferation rate and viability in response to elevated concentrations of r-irisin,which was further enhanced over time.Notably,this increase was subject to complex dose-response relationships as the proliferation-enhancing effects of r-irisin may have a saturation point between 10 ng/ml and 100 ng/ml.Furthermore,we determined that 1,10,and 100 ng/ml r-irisin were able to upregulate the expression of osteogenic transcription factors(Runx2,Osx,and Atf4),as well as osteogenic markers(Alp,Col1a1 and Spp1),albeit without significant difference among these 3 concentrations.Interestingly,nutrient-depleted osteoblasts and those with standard culture showed distinct responses to higher doses of irisin regarding osteogenic differentiation.Further investigation is required to uncover the molecular mechanisms underlying the observed tandem effects of irisin on osteogenesis.
文摘目的:探索非综合征型唇裂伴或不伴腭裂(non-syndromic cleft lip with or without cleft palate, NSCL/P)全基因组常见遗传变异对NSCL/P风险的影响。方法:利用全基因组关联研究(genome-wide association study, GWAS)数据,以全基因组单核苷酸多态性(single nucleotide polymorphism, SNP)遗传度和基因组不同分区SNP遗传度评估基因组上常见变异的效应。对GWAS汇总数据进行质量控制,标准包括数据中无缺失值、弱势等位基因频率≥1%、P值在0~1、SNP正负链明确等。利用连锁不平衡得分回归计算NSCL/P的SNP遗传度,采用分层的连锁不平衡得分回归计算基因组编码区、启动子区、内含子区、增强子区和超级增强子区的分区SNP遗传度,并评估不同分区内的富集度,分析工具为LDSC (v1.0.1)软件。结果:纳入中国人群806个NSCL/P核心家系(2 418人)的GWAS数据,490 593个SNP通过质量控制,被纳入到SNP遗传度的计算中。观测样本中NSCL/P的SNP遗传度为0.55(95%CI:0.28~0.82),由于观测样本患病率较高,按中国人群患病率转换为一般人群后SNP遗传度为0.37(95%CI:0.19~0.55)。SNP遗传度在增强子区的富集度为15.70(P=0.04),在超级增强子区的富集度为3.18(P=0.03)。结论:基因组常见变异有助于解释一部分中国人群NSCL/P目前未被解释的遗传度,同时中国人群NSCL/P的SNP遗传度在增强子分区和超级增强子分区中显著富集,提示该区域中可能存在未被发现的遗传致病因素。
