The visual system of teleost fish grows continuously,which is a useful model for studying regeneration of the central nervous system.Glial cells are key for this process,but their contribution is still not well define...The visual system of teleost fish grows continuously,which is a useful model for studying regeneration of the central nervous system.Glial cells are key for this process,but their contribution is still not well defined.We followed oligodendrocytes in the visual system of adult zebrafish during regeneration of the optic nerve at 6,24,and 72 hours post-lesion and at 7 and 14 days post-lesion via the sox10:tagRFP transgenic line and confocal microscopy.To understand the changes that these oligodendrocytes undergo during regeneration,we used Sox2 immunohistochemistry,a stem cell marker involved in oligodendrocyte differentiation.We also used the Click-iT™ Plus TUNEL assay to study cell death and a BrdU assay to determine cell proliferation.Before optic nerve crush,sox10:tagRFP oligodendrocytes are located in the retina,in the optic nerve head,and through all the entire optic nerve.Sox2-positive cells are present in the peripheral germinal zone,the mature retina,and the optic nerve.After optic nerve crush,sox10:tagRFP cells disappeared from the optic nerve crush zone,suggesting that they died,although they were not TUNEL positive.Concomitantly,the number of Sox2-positive cells increased around the crushed area,the optic nerve head,and the retina.Then,between 24 hours post-lesion and 14 days post-lesion,double sox10:tagRFP/Sox2-positive cells were detected in the retina,optic nerve head,and whole optic nerve,together with a proliferation response at 72 hours post-lesion.Our results confirm that a degenerating process may occur prior to regeneration.First,sox10:tagRFP oligodendrocytes that surround the degenerated axons stop wrapping them,change their“myelinating oligodendrocyte”morphology to a“nonmyelinating oligodendrocyte”morphology,and die.Then,residual oligodendrocyte progenitor cells in the optic nerve and retina proliferate and differentiate for the purpose of remyelination.As new axons arise from the surviving retinal ganglion cells,new sox10:tagRFP oligodendrocytes arise from residual oligodendrocyte progenitor cells to guide,nourish and myelinate them.Thus,oligodendrocytes play an active role in zebrafish axon regeneration and remyelination.展开更多
Kidney transplantation(KT)accounts for nearly three-fourths of organ transplants in India,with living donors contributing to 82%of cases.Induction immunosuppression is essential to optimize initial immunosuppression,r...Kidney transplantation(KT)accounts for nearly three-fourths of organ transplants in India,with living donors contributing to 82%of cases.Induction immunosuppression is essential to optimize initial immunosuppression,reduce acute rejections,and enable tailored use of maintenance agents.Rabbit anti-thymocyte globulin(rATG)and interleukin-2 receptor anatagonists(IL-2RA/IL-2RBs)are the most widely used induction therapies.However,data on induction practices across India are limited.To evaluate induction immunosuppression practices across KT centers in India and establish a consensus for different subsets of KT recipients.A nationwide online survey was conducted by the Indian Society of Organ Transplantation(ISOT)among its members(400 KT centers).Responses were analyzed to assess induction practices across diverse donor types,age groups,and immunological risk profiles.Heterogeneity in practices prompted consensus building using a modified Delphi process.Literature review and expert panel discussions(April 2024)were followed by structured voting,and 16 consensus statements were finalized.Of 400 centers approached,254 participated.rATG was the most commonly used induction therapy,followed by IL-2RBs;alemtuzumab was least used.Significant heterogeneity was observed in type,dose,and duration of induction therapy.Consensus recommendations were framed:rATG for high immunological risk recipients and deceased donor KTs;IL-2RB or low-dose rATG for low immunological risk;rituximab in ABOincompatible KTs;and tailoring based on age,diabetes,donor type,infection risk,and affordability.This first ISOT consensus provides 16 India-specific statements on induction therapy in KT.It emphasizes risk-stratified,evidenceinformed,and context-appropriate induction strategies,supporting standardization of care across the country.展开更多
The development of neurodegenerative diseases is closely related to the disruption of central nervous system homeostasis.Microglia,as innate immune cells,play important roles in the maintenance of central nervous syst...The development of neurodegenerative diseases is closely related to the disruption of central nervous system homeostasis.Microglia,as innate immune cells,play important roles in the maintenance of central nervous system homeostasis,injury response,and neurodegenerative diseases.Lactate has been considered a metabolic waste product,but recent studies are revealing ever more of the physiological functions of lactate.Lactylation is an important pathway in lactate function and is involved in glycolysis-related functions,macrophage polarization,neuromodulation,and angiogenesis and has also been implicated in the development of various diseases.This review provides an overview of the lactate metabolic and homeostatic regulatory processes involved in microglia lactylation,histone versus non-histone lactylation,and therapeutic approaches targeting lactate.Finally,we summarize the current research on microglia lactylation in central nervous system diseases.A deeper understanding of the metabolic regulatory mechanisms of microglia lactylation will provide more options for the treatment of central nervous system diseases.展开更多
Background:The outcomes of pediatric patients with acute lymphoblastic leukemia(ALL)remain far less than favorable.While apigenin is an anti-cancer agent,studies on the mechanism by which it regulates ALL cell cycle p...Background:The outcomes of pediatric patients with acute lymphoblastic leukemia(ALL)remain far less than favorable.While apigenin is an anti-cancer agent,studies on the mechanism by which it regulates ALL cell cycle progression are inadequate.Ferroptosis and AMP-activated protein kinase(AMPK)signaling are important processes for ALL patients.However,it remains unclear whether apigenin works by affecting AMPK and apoptosis.Materials and Methods:SUP-B15 and T-cell Jurkat ALL cells were treated with apigenin,and cell viability and apoptosis were measured using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide(MTT)and terminal deoxynucleotidyl transferase dUTP nick end labeling(TUNEL)assays,respectively.The thiobarbituric acid-reactive substances(TBARS)assay was used to evaluate lipid peroxidation.Intracellular Fe2+levels were measured using a commercial kit.Corresponding proteins were detected by western blotting.Results:Results showed that apigenin reduced cell viability and the levels of Ki67 and proliferating cell nuclear antigen(PCNA)expression in a concentration-dependent manner in both types of ALL cells.Apigenin also exerted anti-apoptotic effects on SUP-B15 and Jurkat cells.Apigenin activated AMP-activated protein kinase(AMPK)signaling and induced ferroptosis,and those effects were attenuated by inhibition of AMPK.Eventually,the reduced cell proliferation and increased cell apoptosis caused by apigenin in ALL cells were partly abolished by AMPK inhibition.Conclusion:In summary,apigenin exerted anti-leukemia activity in ALL cells,and that effect was partially achieved by activation of AMPK signaling.Our findings suggest apigenin as a potential drug for treatment of ALL.展开更多
Granular composite(GC)hydrogels have attracted considerable interest in biomedical applications due to their versatile printability and exceptional mechanical properties.However,the lack of comprehensive design guidel...Granular composite(GC)hydrogels have attracted considerable interest in biomedical applications due to their versatile printability and exceptional mechanical properties.However,the lack of comprehensive design guidelines has limited their optimal engineering,as the factors influencing their mechanical performance and printability remain largely unexamined.In this study,we developed GC hydrogels by integrating microgels with interstitial matrices of photocrosslinkable gelatin methacrylate(GelMA).We utilized confocal microscopy and nanoindentation analyses to investigate the spatial distribution and mechanical behavior of these hydrogels.Our findings indicate that the mechanical and rheological properties of GC hydrogels can be precisely tailored by adjusting the volume fraction and size of the microgels.Furthermore,hydrogen bonds were identified as significant contributors to compressive performance,although they had minimal effect on cyclic mechanical behavior.Compared to bulk GelMA hydrogels,GC hydrogels demonstrated enhanced printability and remarkable superelasticity.As a proof of concept,we illustrated their dual printability in embedded printing to create prosthetic liver models for preoperative planning.This study provides valuable insights into the design and optimization of GC hydrogels for advanced biomedical applications.展开更多
Cancer treatment often requires a multimodal approach,such as combining chemotherapy and gene therapy.However,challenges such as low therapeutic efficacy and off-target effects hinder the effectiveness of these treatm...Cancer treatment often requires a multimodal approach,such as combining chemotherapy and gene therapy.However,challenges such as low therapeutic efficacy and off-target effects hinder the effectiveness of these treatments.In this study,the use of calcium-doped metal-organic frameworks Cu_(2)(BDC)_(2)(DABCO)as a nanocarrier platform for the co-delivery of doxorubicin(DOX)and plasmid CRISPR(pCRISPR)proposed to enhance anticancer efficiency.We demonstrated that Ca-doped MOF nanocarriers significantly improved the uptake of DOX and pCRISPR by in cancer cells.The co-delivery of DOX and pCRISPR with Ca-doped MOF nanocarriers resulted in a significant rise in cell death and decreased targeted gene expression.展开更多
Objective:Early predicting response before neoadjuvant chemotherapy(NAC)is crucial for personalized treatment plans for locally advanced breast cancer patients.We aim to develop a multi-task model using multiscale who...Objective:Early predicting response before neoadjuvant chemotherapy(NAC)is crucial for personalized treatment plans for locally advanced breast cancer patients.We aim to develop a multi-task model using multiscale whole slide images(WSIs)features to predict the response to breast cancer NAC more finely.Methods:This work collected 1,670 whole slide images for training and validation sets,internal testing sets,external testing sets,and prospective testing sets of the weakly-supervised deep learning-based multi-task model(DLMM)in predicting treatment response and pCR to NAC.Our approach models two-by-two feature interactions across scales by employing concatenate fusion of single-scale feature representations,and controls the expressiveness of each representation via a gating-based attention mechanism.Results:In the retrospective analysis,DLMM exhibited excellent predictive performance for the prediction of treatment response,with area under the receiver operating characteristic curves(AUCs)of 0.869[95%confidence interval(95%CI):0.806−0.933]in the internal testing set and 0.841(95%CI:0.814−0.867)in the external testing sets.For the pCR prediction task,DLMM reached AUCs of 0.865(95%CI:0.763−0.964)in the internal testing and 0.821(95%CI:0.763−0.878)in the pooled external testing set.In the prospective testing study,DLMM also demonstrated favorable predictive performance,with AUCs of 0.829(95%CI:0.754−0.903)and 0.821(95%CI:0.692−0.949)in treatment response and pCR prediction,respectively.DLMM significantly outperformed the baseline models in all testing sets(P<0.05).Heatmaps were employed to interpret the decision-making basis of the model.Furthermore,it was discovered that high DLMM scores were associated with immune-related pathways and cells in the microenvironment during biological basis exploration.Conclusions:The DLMM represents a valuable tool that aids clinicians in selecting personalized treatment strategies for breast cancer patients.展开更多
Background:Reliable animal models are crucial to drug development for focal segmental glomerulosclerosis(FSGS),a rare kidney disease.Variability in success rates in literature and significant ethical concerns with ani...Background:Reliable animal models are crucial to drug development for focal segmental glomerulosclerosis(FSGS),a rare kidney disease.Variability in success rates in literature and significant ethical concerns with animal welfare necessitate further optimization of adriamycin(ADR)-induced FSGS model developed on BALB/c mice.Methods:High-performance liquid chromatography(HPLC)was used to assess ADR stability in water and upon light exposure.To identify the optimal ADR level,single intravenous ADR injections with dosing levels from 10 to 17 mg/kg body weight were administered to BALB/c mice to induce FSGS-like pathology.Body weight and proteinuria of FSGS mice were monitored and analyzed for FSGS model-associated morbidity.Animals were euthanized for hematological and kidney histological assessments 8 weeks post induction.To identify the suitable experiment time frame of the ADR-induced FSGS mouse model,a longitudinal study was performed,with an 11-week continuous monitoring of the symptoms.Results:ADR was found to be unstable in aqueous media and light sensitive.A dosing level of 10.5 mg/kg of ADR was optimal for consistent FSGS mouse model induction on BALB/c strain,characterized by minimal mortality and sustained FSGS-like symptoms.Findings from the longitudinal study suggest that 6 weeks post ADR induction may represent the peak of FSGS pathology severity in this mouse model.This time frame may be used for FSGS drug development projects.Conclusion:Based on the outcome from this study,we identified the optimal ADR dosing level and model testing duration.A standard operating procedure(SOP)for the ADR-induced FSGS mouse model was established to facilitate FSGS basic research and drug development.展开更多
Background:Endoplasmic reticulum(ER)stress is an important factor in the development of numerous cardiovascular disorders;nevertheless,the association between ER stress and mitral regurgitation(MR)remains inadequately...Background:Endoplasmic reticulum(ER)stress is an important factor in the development of numerous cardiovascular disorders;nevertheless,the association between ER stress and mitral regurgitation(MR)remains inadequately characterized.The molecular mechanism of pimobendan(PIMO)that contributes to the delay in congestive heart failure(CHF)in MR associated with apoptosis and fibrosis is still unclear.Our aim was to examine the impact of PIMO on ER stress,apoptosis,and fibrosis in a chronic MR rat model.Methods:MR was surgically induced in 10 Sprague–Dawley rats,with 5 serving as sham operation controls.At 8 weeks postsurgery,the MR animals were randomly allocated into two groups:MR and MR+PIMO groups.PIMO was administered twice daily through oral gavage for 4 weeks,whereas the sham and MR groups were administered similar quantities of drinking water.Echocardiography was conducted before the delivery of PIMO as a baseline measure and at the end of the study.At the end of the investigation,hearts were procured for histopathological and ER stress evaluations.Results:PIMO significantly maintained heart function and structural remodeling in the MR animals.PIMO significantly reduced MR-induced myocyte apoptosis(p=0.044)and fibrosis(p=0.002)by reducing the messenger RNA expression of genes associated with ER stress(GRP78[glucose-regulated protein 78],ATF4[activating transcription factor 4],and CHOP[C/ERP homologous protein])compared to the MR group(p<0.05,p<0.01,and p<0.001,respectively).Conclusion:PIMO demonstrated cardioprotective benefits on heart function,myocyte apoptosis,and fibrosis by regulating ER stress in an MR-induced CHF rat model.展开更多
Persistent and maladaptive drug-related memories represent a key component in drug addiction.Converging evidence from both preclinical and clinical studies has demonstrated the potential efficacy of the memory reconso...Persistent and maladaptive drug-related memories represent a key component in drug addiction.Converging evidence from both preclinical and clinical studies has demonstrated the potential efficacy of the memory reconsolidation updating procedure(MRUP),a non-pharmacological strategy intertwining two distinct memory processes:reconsolidation and extinction—alternatively termed“the memory retrieval-extinction procedure”.This procedure presents a promising approach to attenuate,if not erase,entrenched drug memories and prevent relapse.The present review delineates the applications,molecular underpinnings,and operational boundaries of MRUP in the context of various forms of substance dependence.Furthermore,we critically examine the methodological limitations of MRUP,postulating potential refinement to optimize its therapeutic efficacy.In addition,we also look at the potential integration of MRUP and neurostimulation treatments in the domain of substance addiction.Overall,existing studies underscore the significant potential of MRUP,suggesting that interventions predicated on it could herald a promising avenue to enhance clinical outcomes in substance addiction therapy.展开更多
A deficiency ofγδT cells has been described in Crohn's disease(CD).AIM To analyze the gene expression of interleukin 7(IL-7)and its receptors in the tissues of patients with CD.METHODS We studied the peripheral ...A deficiency ofγδT cells has been described in Crohn's disease(CD).AIM To analyze the gene expression of interleukin 7(IL-7)and its receptors in the tissues of patients with CD.METHODS We studied the peripheral blood of 80 patients with CD,comparing them with a group of 80 healthy subjects.The number and apoptosis ofαβandγδT cells in peripheral blood and the proportion ofαβandγδT cells in the intestinal tissues of patients with CD(n=25)were studied.The gene and protein expression of IL-7,IL-2 receptor subunitγ[cluster of differentiation 132(CD132)],receptorα(CD127),and caspase-3 in tissues was analyzed by quantitative PCR.Serum IL-7 levels were also analyzed.RESULTS In patients with CD,a decreased number ofγδT cells and an increase in the apoptosis of CD56+αβandγδT cells in peripheral blood was observed(P<0.0001 and P<0.01)respectively,and there was an inverse correlation among T subsets and their apoptosis.In addition,IL-7 gene expression and IL-7 protein in the tissues of these patients were increased.The titers of caspase-3 in tissues were low vs control group(P>0.01).The percentage of CD8+γδT cells decreased in tissues(P<0.01),and was directly related to IL-7 levels in peripheral blood.The expression of IL-2 receptor subunitγ(CD132)was greatly decreased in the tissues of patients with CD(P<0.05).CONCLUSION There may be a cause-effect relationship between the lower gene expression of the IL-2 receptor subunitγ(CD132)in tissues of patients with CD andγδT cells immunodeficiency.展开更多
Mango(Mangifera indica L.cv.‘Keitt’)is one of the core fruit delicacies produced by China.During the post-harvest storage span,the fungal pathogen colletotrichum gloeosporioides readily invades the fruits and leads ...Mango(Mangifera indica L.cv.‘Keitt’)is one of the core fruit delicacies produced by China.During the post-harvest storage span,the fungal pathogen colletotrichum gloeosporioides readily invades the fruits and leads to a significant overall yield loss.In recent years of development,the exploitation of naturally occurring fungitoxic compounds such as Sandalwood Essential Oil(SEO)has been useful in tackling various fungal species.This study demonstrates the potential of SEO as part of a storage protection strategy against C.gloeosporioides-induced postharvest anthracnose.SEO displayed a relatively higher mycelial growth inhibition rate when compared to various other essential oils.Furthermore,the Minimal Inhibitory Concentration(MIC),Minimum Fungicidal Concentration(MFC),and EC_(50)(Half maximal effective concentration)of SEO were determined to be 2000,2500,and 610.38μL/L,respectively.Moreover,the chitosan glutamate-SEO emulsion controlled the anthracnose spread for several days by multiple folds at½MIC,MIC,and 2 MIC concentrations.These results strongly support the potential for largescale production and application of SEO emulsions by agrochemical firms and post-harvest storage facilities handling Keitt mangoes.展开更多
Achieving high-performance aqueous zinc-ion batteries requires addressing the challenges associated with the stability of zinc metal anodes,particularly the formation of inhomogeneous zinc dendrites during cycling and...Achieving high-performance aqueous zinc-ion batteries requires addressing the challenges associated with the stability of zinc metal anodes,particularly the formation of inhomogeneous zinc dendrites during cycling and unstable surface electrochemistry.This study introduces a practical method for scattering untreated bulk hexagonal boron nitride(h-BN)particles onto the zinc anode surface.During cycling,stabilized zinc fills the interstices of scattered h-BN,resulting in a more favorable(002)orientation.Consequently,zinc dendrite formation is effectively suppressed,leading to improved electrochemical stability.The zinc with scattered h-BN in a symmetric cell configuration maintains stability 10 times longer than the bare zinc symmetric cell,lasting 500 hours.Furthermore,in a full cell configuration withα-MnO_(2) cathode,increased H^(+)ion activity can effectively alter the major redox kinetics of cycling due to the presence of scattered h-BN on the zinc anode.This shift in H^(+)ion activity lowers the overall redox potential,resulting in a discharge capacity retention of 96.1%for 300 cycles at a charge/discharge rate of 0.5 Ag^(-1).This study highlights the crucial role of surface modification,and the innovative use of bulk h-BN provides a practical and effective solution for improving the performance and stability.展开更多
BACKGROUND The decision to administer adjuvant chemotherapy to patients with local stage depends on specific high-risk features that are T4 tumor stage,presence of perineural invasion,lymphovascular invasion,poorly di...BACKGROUND The decision to administer adjuvant chemotherapy to patients with local stage depends on specific high-risk features that are T4 tumor stage,presence of perineural invasion,lymphovascular invasion,poorly differentiated tumor histology,inadequate lymph node sampling(fewer than 12 lymph nodes),and evidence of tumor perforation or obstruction.Tumor-stroma ratio,tumor infiltrating lymphocytes(TIL),Crohn-like reaction(CLR),desmoid reaction,poorly differentiated clusters(PDC)are new pathological markers that are being studied.AIM To examine the relationship between new pathological markers and defined high METHODS We evaluated 155 patients with the diagnosis stage I and II colorectal cancer between the years 2007 and 2021 who were treated at Trakya University Hospital,Department of Medical Oncology.We divided those with and without high-risk factors into two groups.We examined the relationship of new pathological markers with these groups and with pathological markers in risk factors.RESULTS There was no statistically significant correlation between presence of TIL,presence of PDC,presence of tumor budding,presence of CLR,presence of desmoid reaction and low and high-risk groups according to the degree of those with PDC(P=0.82,P=0.51,P=0.77,P=0.37,P=0.83,respectively).In addition,no statistically significant correlation was found between the tumor-stroma ratio and low and high risk groups(P=0.80).We found a statistically significant correlation between the presence of PDC and the presence of PDC grade 3 and T stage(P=0.001,P=0.001,respectively).It was determined that the presence of PDC and the frequency of grade 3 PDC increased with the advanced T stage.CONCLUSION No relationship was found between the presence of new pathological markers and high-low risk groups.When we examined the relationship between new and old pathological markers,only the frequency of detection of PDC and PDC grade 3 was found to be correlated with advanced T stage.展开更多
Micro/nanorobots have exhibited excellent application potential in the biomedical field,such as drug delivery,minimally invasive surgery,and bio-sensing.Furthermore,in order to achieve practical application,it is esse...Micro/nanorobots have exhibited excellent application potential in the biomedical field,such as drug delivery,minimally invasive surgery,and bio-sensing.Furthermore,in order to achieve practical application,it is essential for swimming micro/nanorobots to navigate towards specific targets or adjust their speed and morphology in complete environments.The navigation of swimming micro/nanorobots with temporal and spatial precision is critical for fulfilling the demand of applications.Here,we introduced a fully integrated wearable control system for micro/nanorobots navigation and manipulation,which is composed of a multifunctional sensor array,an artificial intelligence(AI)planner,and a magnetic field generator.The sensor array could perceive real-time changes in gestures,wrist rotation,and acoustic signals.AI planner based on machine learning offers adaptive path planning in response to dynamically changing signals to generate magnetic fields for the on-demand manipulation of micro/nanorobots.Such a novel,feasible control strategy was validated in the biological experiment in which cancer cells were targeted and killed by photothermal therapy using micro/nanorobots and integrated control platform.This wearable control system could play a crucial role in future intelligent medical applications and could be easily reconfigured toward other medical robots’control.展开更多
Very few studies have benefited from the synergetic implementation of visible,near-infrared,and shortwave infrared(VNIR-SWIR)spectra and terrain attributes in predicting Pb content in agricultural soils.To fill this g...Very few studies have benefited from the synergetic implementation of visible,near-infrared,and shortwave infrared(VNIR-SWIR)spectra and terrain attributes in predicting Pb content in agricultural soils.To fill this gap,this study aimed to predict lead(Pb)contents in agricultural soils by combining machine learning algorithms(MLAs)with VNIR-SWIR spectra or/and terrain attributes under three distinct approaches.Six MLAs were tested,including artificial neural network(ANN),partial least squares regression,support vector machine(SVM),Gaussian process regression(GPR),extreme gradient boosting(EGB),and Cubist.The VNIR-SWIR spectral data were preprocessed by methods of discrete wavelet transformation,logarithmic transformation-Savitzky Golay smoothing,standard normal variate(SNV),multiplicative scatter correction,first derivative(Fi D),and second derivative.In approach 1,MLAs were combined with the preprocessed VNIR-SWIR spectral data.The Cubist-Fi D combination was the most effective,achieving a coefficient of determination(R2)of 0.63,a concordance correlation coefficient(CCC)of 0.51,a mean absolute error(MAE)of 6.87 mg kg^(-1),and a root mean square error(RMSE)of8.66 mg kg^(-1).In approach 2,MLAs were combined with both preprocessed VNIR-SWIR spectral data and terrain attributes,and the EGB-SNV combination yielded superior results with R2of 0.75,CCC of 0.65,MAE of 5.48 mg kg^(-1),and RMSE of 7.34 mg kg^(-1).Approach 3 combined MLAs and terrain attributes,and Cubist demonstrated the best prediction results,with R^(2) of 0.75,CCC of 0.66,MAE of 6.18 mg kg^(-1),and RMSE of 7.71 mg kg^(-1).The cumulative assessment identified the fusion of terrain properties,SNV-preprocessed VNIR-SWIR spectra,and EGB as the optimal method for estimating Pb content in agricultural soils,yielding the highest R2value and minimal error.Comparatively,GPR,ANN,and SVM techniques achieved higher R2values in approaches 2 and 3 but also exhibited higher estimation errors.In conclusion,the study underscores the significance of using relevant auxiliary datasets and appropriate MLAs for accurate Pb content prediction with minimal error in agricultural soils.The findings contribute valuable insights for developing successful soil management strategies based on predictive modeling.展开更多
As the integration of medical big data and artificial intelligence advances,the secure sharing of medical data has become a key driving force for advancing disease research and clinical diagnosis.Federated learning,a ...As the integration of medical big data and artificial intelligence advances,the secure sharing of medical data has become a key driving force for advancing disease research and clinical diagnosis.Federated learning,a distributed approach enabling collaborative data processing without sharing raw data,offers promising solutions to challenges in multi-center medical data sharing.This review summarizes the progress of federated learning in multi-center medical data processing,analyzed from four perspectives:system architectures,data distribution strategies,clinical tasks,and algorithmic models.At the same time,this paper explores the challenges in practical applications,such as data heterogeneity,communication overhead,and privacy concerns.It proposes driving future research development by optimizing algorithms,strengthening privacy protection mechanisms,and enhancing computational efficiency.展开更多
BACKGROUND Inhibiting hepatic stellate cell(HSC)activation is a key therapeutic strategy in liver fibrosis(LF).During activation,aerobic glycolysis is upregulated to meet increased energy demands.Although focal adhesi...BACKGROUND Inhibiting hepatic stellate cell(HSC)activation is a key therapeutic strategy in liver fibrosis(LF).During activation,aerobic glycolysis is upregulated to meet increased energy demands.Although focal adhesion kinase(FAK)has been implicated in regulating HSC glycolysis,its precise role in activation remains unclear.AIM To investigate the effects of FAK and fructose-1,6-bisphosphatase 1(FBP1)on LF through the modulation of aerobic glycolysis in HSCs.METHODS Eighteen mice were randomly assigned to three groups:Control,carbon tetrachloride(CCl_(4))-induced LF,and CCl_(4)with FAK inhibitor treatment.Liver tissues were analyzed using transcriptomic and proteomic sequencing.Differential gene expression,Mfuzz clustering,and protein interaction network analyses identified key regulatory factors.Immunohistochemistry(IHC)and Western blot(WB)analysis were used to assess FAK and FBP1 expression,along with glycolysis-related enzymes.The migratory behavior of HSCs was evaluated using Transwell migration and scratch assays.RESULTS Transcriptomic and proteomic analyses revealed significantly reduced FBP1 expression in CCl_(4)-induced fibrosis,which was restored upon FAK inhibition.Histological staining(hematoxylin and eosin,Masson’s trichrome,Sirius red)confirmed reduced fibrosis following FAK inhibition.WB analysis demonstrated suppression of glycolysisrelated enzymes.In LX-2 cells,FAK inhibition attenuated HSC activation and glycolysis while upregulating FBP1.Exogenous recombinant FBP1 inhibited HSC activation and glycolysis.Transwell and scratch assays showed that FBP1 significantly impaired HSC migration.In addition,WB and IHC analyses confirmed lower FBP1 expression in fibrotic liver tissues from patients compared to healthy controls.CONCLUSION FAK inhibitors and increased FBP1 expression inhibit aerobic glycolysis in HSCs,thereby improving LF.Thus,FAK and FBP1 may be potential targets for LF treatment.展开更多
BACKGROUND Peritoneal lavage cytology-positive(CY1)gastric cancer(stage IV)has a poor prognosis,though some cases fare better.Therefore,identifying prognostic factors and an optimal treatment strategy is crucial.AIM T...BACKGROUND Peritoneal lavage cytology-positive(CY1)gastric cancer(stage IV)has a poor prognosis,though some cases fare better.Therefore,identifying prognostic factors and an optimal treatment strategy is crucial.AIM To investigate prognostic factors in patients with gastric cancer who underwent gastrectomy with CY1,and to evaluate the optimal postoperative chemotherapy regimen.METHODS This multicenter retrospective cohort study analyzed prognostic factors and postoperative chemotherapy in patients with CY1 gastric cancer who underwent gastrectomy,excluding those with macroscopic peritoneal dissemination.Data from 13 institutions(2015-2019)were reviewed.RESULTS Overall,82 patients met the inclusion criteria.The median overall survival was 22.8 months,and diffuse-type histology and the absence of postoperative chemotherapy were identified as independent poor prognostic factors.The 5-year survival rate was 82.4%for those receiving fluoropyrimidine plus docetaxel/oxaliplatin vs 21.8%for those with S-1 monotherapy or a cisplatin-based regimen.Median overall survival was not reached in the fluoropyrimidine+docetaxel/oxaliplatin group but was 22.9 months in the S-1/cisplatin group.Chemotherapy regimen was an independent prognostic factor(hazard ratio=5.47,P=0.004).The fluoropyrimidine plus docetaxel/oxaliplatin group had an average relative dose intensity of 82.1%,with significantly more patients achieving a relative dose intensity≥80%than in the S-1 monotherapy or cisplatin-based group(P=0.001).CONCLUSION Diffuse-type histology and the absence of postoperative chemotherapy influence the prognosis of patients with CY1 gastric cancer.Combination therapy with oxaliplatin or docetaxel may enhance the treatment intensity and improve survival outcomes after gastrectomy.展开更多
This article discusses the original article published by Lu et al in the latest issue.The article confirmed through a cohort study the clinical efficacy of the triple live bacteria of Bifidobacterium combined with mir...This article discusses the original article published by Lu et al in the latest issue.The article confirmed through a cohort study the clinical efficacy of the triple live bacteria of Bifidobacterium combined with mirtazapine in treating postoperative depression of gastric cancer patients,also explored the multi-target therapeutic mechanisms of Bifidobacterium triple viable bacteria combined with mirtazapine in managing depression in patients after radical gastrectomy for gastric cancer for the first time.The results indicated that Bifidobacterium could alleviate depression in patients after radical gastrectomy for gastric cancer.Gastric cancer patients undergoing surgery frequently experience postoperative psychological disorders,notably depression.These conditions not only impair quality of life but also negatively impact disease-free and overall survival.This editorial explores the underestimated psychological challenges following gastric cancer surgery,including depression,anxiety,adjustment disorders,and post-traumatic stress disorder.It further examines the therapeutic potential of Bifidobacterium triple viable probiotics,combined with mirtazapine,in alleviating postoperative depression through microbiological,immunological,and neurological mechanisms.Clinical evidence highlights additional benefits,such as improved gastrointestinal function,enhanced immunity,and better nutritional status,underscoring a holistic approach to postoperative care.While promising,further large-scale trials are needed to optimize and personalize probiotic-based interventions.展开更多
基金supported by the Lanzadera TCUE and C2 program(Universidad de Salamanca)(to ASL)the Spanish National Research Council(CSIC)funded by the Junta de Castilla y León and co-financed by the European Regional Development Fund(ERDF“Europe drives our growth”):Internationalization Project“CL-EI-2021-08-IBFG Unit of Excellence”,Grant(PID2022-138478OA-100)funded by MICIU/AEI/10.13039/501100011033 and,by FEDER,UE(to MGM)+3 种基金Junta de Castilla y León(SA225P23)Gerencia Regional de Salud(2701/A1/2023)(to AV)the Plan Especial Grado Medicina(USAL)(to CPM)a Ramón y Cajal researcher:Grant RYC2021-033684-I funded by MICIU/AEI/10.13039/501100011033 and,by European Union NextGenerationEU/PRTR.
文摘The visual system of teleost fish grows continuously,which is a useful model for studying regeneration of the central nervous system.Glial cells are key for this process,but their contribution is still not well defined.We followed oligodendrocytes in the visual system of adult zebrafish during regeneration of the optic nerve at 6,24,and 72 hours post-lesion and at 7 and 14 days post-lesion via the sox10:tagRFP transgenic line and confocal microscopy.To understand the changes that these oligodendrocytes undergo during regeneration,we used Sox2 immunohistochemistry,a stem cell marker involved in oligodendrocyte differentiation.We also used the Click-iT™ Plus TUNEL assay to study cell death and a BrdU assay to determine cell proliferation.Before optic nerve crush,sox10:tagRFP oligodendrocytes are located in the retina,in the optic nerve head,and through all the entire optic nerve.Sox2-positive cells are present in the peripheral germinal zone,the mature retina,and the optic nerve.After optic nerve crush,sox10:tagRFP cells disappeared from the optic nerve crush zone,suggesting that they died,although they were not TUNEL positive.Concomitantly,the number of Sox2-positive cells increased around the crushed area,the optic nerve head,and the retina.Then,between 24 hours post-lesion and 14 days post-lesion,double sox10:tagRFP/Sox2-positive cells were detected in the retina,optic nerve head,and whole optic nerve,together with a proliferation response at 72 hours post-lesion.Our results confirm that a degenerating process may occur prior to regeneration.First,sox10:tagRFP oligodendrocytes that surround the degenerated axons stop wrapping them,change their“myelinating oligodendrocyte”morphology to a“nonmyelinating oligodendrocyte”morphology,and die.Then,residual oligodendrocyte progenitor cells in the optic nerve and retina proliferate and differentiate for the purpose of remyelination.As new axons arise from the surviving retinal ganglion cells,new sox10:tagRFP oligodendrocytes arise from residual oligodendrocyte progenitor cells to guide,nourish and myelinate them.Thus,oligodendrocytes play an active role in zebrafish axon regeneration and remyelination.
文摘Kidney transplantation(KT)accounts for nearly three-fourths of organ transplants in India,with living donors contributing to 82%of cases.Induction immunosuppression is essential to optimize initial immunosuppression,reduce acute rejections,and enable tailored use of maintenance agents.Rabbit anti-thymocyte globulin(rATG)and interleukin-2 receptor anatagonists(IL-2RA/IL-2RBs)are the most widely used induction therapies.However,data on induction practices across India are limited.To evaluate induction immunosuppression practices across KT centers in India and establish a consensus for different subsets of KT recipients.A nationwide online survey was conducted by the Indian Society of Organ Transplantation(ISOT)among its members(400 KT centers).Responses were analyzed to assess induction practices across diverse donor types,age groups,and immunological risk profiles.Heterogeneity in practices prompted consensus building using a modified Delphi process.Literature review and expert panel discussions(April 2024)were followed by structured voting,and 16 consensus statements were finalized.Of 400 centers approached,254 participated.rATG was the most commonly used induction therapy,followed by IL-2RBs;alemtuzumab was least used.Significant heterogeneity was observed in type,dose,and duration of induction therapy.Consensus recommendations were framed:rATG for high immunological risk recipients and deceased donor KTs;IL-2RB or low-dose rATG for low immunological risk;rituximab in ABOincompatible KTs;and tailoring based on age,diabetes,donor type,infection risk,and affordability.This first ISOT consensus provides 16 India-specific statements on induction therapy in KT.It emphasizes risk-stratified,evidenceinformed,and context-appropriate induction strategies,supporting standardization of care across the country.
文摘The development of neurodegenerative diseases is closely related to the disruption of central nervous system homeostasis.Microglia,as innate immune cells,play important roles in the maintenance of central nervous system homeostasis,injury response,and neurodegenerative diseases.Lactate has been considered a metabolic waste product,but recent studies are revealing ever more of the physiological functions of lactate.Lactylation is an important pathway in lactate function and is involved in glycolysis-related functions,macrophage polarization,neuromodulation,and angiogenesis and has also been implicated in the development of various diseases.This review provides an overview of the lactate metabolic and homeostatic regulatory processes involved in microglia lactylation,histone versus non-histone lactylation,and therapeutic approaches targeting lactate.Finally,we summarize the current research on microglia lactylation in central nervous system diseases.A deeper understanding of the metabolic regulatory mechanisms of microglia lactylation will provide more options for the treatment of central nervous system diseases.
基金supported by The National Natural Science Foundation of China(No.31902283)Research Foundation for Master students at the Affiliated Hospital of Zunyi Medical College(No.22-2018).
文摘Background:The outcomes of pediatric patients with acute lymphoblastic leukemia(ALL)remain far less than favorable.While apigenin is an anti-cancer agent,studies on the mechanism by which it regulates ALL cell cycle progression are inadequate.Ferroptosis and AMP-activated protein kinase(AMPK)signaling are important processes for ALL patients.However,it remains unclear whether apigenin works by affecting AMPK and apoptosis.Materials and Methods:SUP-B15 and T-cell Jurkat ALL cells were treated with apigenin,and cell viability and apoptosis were measured using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide(MTT)and terminal deoxynucleotidyl transferase dUTP nick end labeling(TUNEL)assays,respectively.The thiobarbituric acid-reactive substances(TBARS)assay was used to evaluate lipid peroxidation.Intracellular Fe2+levels were measured using a commercial kit.Corresponding proteins were detected by western blotting.Results:Results showed that apigenin reduced cell viability and the levels of Ki67 and proliferating cell nuclear antigen(PCNA)expression in a concentration-dependent manner in both types of ALL cells.Apigenin also exerted anti-apoptotic effects on SUP-B15 and Jurkat cells.Apigenin activated AMP-activated protein kinase(AMPK)signaling and induced ferroptosis,and those effects were attenuated by inhibition of AMPK.Eventually,the reduced cell proliferation and increased cell apoptosis caused by apigenin in ALL cells were partly abolished by AMPK inhibition.Conclusion:In summary,apigenin exerted anti-leukemia activity in ALL cells,and that effect was partially achieved by activation of AMPK signaling.Our findings suggest apigenin as a potential drug for treatment of ALL.
基金support from the National Natural Science Foundation of China(Nos.U21A20394 and 52305314)the Beijing Natural Science Foundation(Nos.7252285 and L246001)the National Key Research and Development Program of China(No.2023YFB4605800)。
文摘Granular composite(GC)hydrogels have attracted considerable interest in biomedical applications due to their versatile printability and exceptional mechanical properties.However,the lack of comprehensive design guidelines has limited their optimal engineering,as the factors influencing their mechanical performance and printability remain largely unexamined.In this study,we developed GC hydrogels by integrating microgels with interstitial matrices of photocrosslinkable gelatin methacrylate(GelMA).We utilized confocal microscopy and nanoindentation analyses to investigate the spatial distribution and mechanical behavior of these hydrogels.Our findings indicate that the mechanical and rheological properties of GC hydrogels can be precisely tailored by adjusting the volume fraction and size of the microgels.Furthermore,hydrogen bonds were identified as significant contributors to compressive performance,although they had minimal effect on cyclic mechanical behavior.Compared to bulk GelMA hydrogels,GC hydrogels demonstrated enhanced printability and remarkable superelasticity.As a proof of concept,we illustrated their dual printability in embedded printing to create prosthetic liver models for preoperative planning.This study provides valuable insights into the design and optimization of GC hydrogels for advanced biomedical applications.
文摘Cancer treatment often requires a multimodal approach,such as combining chemotherapy and gene therapy.However,challenges such as low therapeutic efficacy and off-target effects hinder the effectiveness of these treatments.In this study,the use of calcium-doped metal-organic frameworks Cu_(2)(BDC)_(2)(DABCO)as a nanocarrier platform for the co-delivery of doxorubicin(DOX)and plasmid CRISPR(pCRISPR)proposed to enhance anticancer efficiency.We demonstrated that Ca-doped MOF nanocarriers significantly improved the uptake of DOX and pCRISPR by in cancer cells.The co-delivery of DOX and pCRISPR with Ca-doped MOF nanocarriers resulted in a significant rise in cell death and decreased targeted gene expression.
基金supported by the National Natural Science Foundation of China(No.82371933)the National Natural Science Foundation of Shandong Province of China(No.ZR2021MH120)+1 种基金the Taishan Scholars Project(No.tsqn202211378)the Shandong Provincial Natural Science Foundation for Excellent Young Scholars(No.ZR2024YQ075).
文摘Objective:Early predicting response before neoadjuvant chemotherapy(NAC)is crucial for personalized treatment plans for locally advanced breast cancer patients.We aim to develop a multi-task model using multiscale whole slide images(WSIs)features to predict the response to breast cancer NAC more finely.Methods:This work collected 1,670 whole slide images for training and validation sets,internal testing sets,external testing sets,and prospective testing sets of the weakly-supervised deep learning-based multi-task model(DLMM)in predicting treatment response and pCR to NAC.Our approach models two-by-two feature interactions across scales by employing concatenate fusion of single-scale feature representations,and controls the expressiveness of each representation via a gating-based attention mechanism.Results:In the retrospective analysis,DLMM exhibited excellent predictive performance for the prediction of treatment response,with area under the receiver operating characteristic curves(AUCs)of 0.869[95%confidence interval(95%CI):0.806−0.933]in the internal testing set and 0.841(95%CI:0.814−0.867)in the external testing sets.For the pCR prediction task,DLMM reached AUCs of 0.865(95%CI:0.763−0.964)in the internal testing and 0.821(95%CI:0.763−0.878)in the pooled external testing set.In the prospective testing study,DLMM also demonstrated favorable predictive performance,with AUCs of 0.829(95%CI:0.754−0.903)and 0.821(95%CI:0.692−0.949)in treatment response and pCR prediction,respectively.DLMM significantly outperformed the baseline models in all testing sets(P<0.05).Heatmaps were employed to interpret the decision-making basis of the model.Furthermore,it was discovered that high DLMM scores were associated with immune-related pathways and cells in the microenvironment during biological basis exploration.Conclusions:The DLMM represents a valuable tool that aids clinicians in selecting personalized treatment strategies for breast cancer patients.
基金United States Department of Defense Office of the Congressionally Directed Medical Research Programs(CDMRP),Grant/Award Number:W81XWH-22-1-0176。
文摘Background:Reliable animal models are crucial to drug development for focal segmental glomerulosclerosis(FSGS),a rare kidney disease.Variability in success rates in literature and significant ethical concerns with animal welfare necessitate further optimization of adriamycin(ADR)-induced FSGS model developed on BALB/c mice.Methods:High-performance liquid chromatography(HPLC)was used to assess ADR stability in water and upon light exposure.To identify the optimal ADR level,single intravenous ADR injections with dosing levels from 10 to 17 mg/kg body weight were administered to BALB/c mice to induce FSGS-like pathology.Body weight and proteinuria of FSGS mice were monitored and analyzed for FSGS model-associated morbidity.Animals were euthanized for hematological and kidney histological assessments 8 weeks post induction.To identify the suitable experiment time frame of the ADR-induced FSGS mouse model,a longitudinal study was performed,with an 11-week continuous monitoring of the symptoms.Results:ADR was found to be unstable in aqueous media and light sensitive.A dosing level of 10.5 mg/kg of ADR was optimal for consistent FSGS mouse model induction on BALB/c strain,characterized by minimal mortality and sustained FSGS-like symptoms.Findings from the longitudinal study suggest that 6 weeks post ADR induction may represent the peak of FSGS pathology severity in this mouse model.This time frame may be used for FSGS drug development projects.Conclusion:Based on the outcome from this study,we identified the optimal ADR dosing level and model testing duration.A standard operating procedure(SOP)for the ADR-induced FSGS mouse model was established to facilitate FSGS basic research and drug development.
基金The 100th Anniversary Chulalongkorn University Fund for Doctoral Scholarshipthe National Budget to CULAC,Grant/Award Number:390252002+1 种基金the 90th Anniversary of Chulalongkorn University Fund,Grant/Award Number:GCUGR1125641042Dthe Thailand Science Research and Innovation Fund at Chulalongkorn University,Grant/Award Number:HEAF673100100。
文摘Background:Endoplasmic reticulum(ER)stress is an important factor in the development of numerous cardiovascular disorders;nevertheless,the association between ER stress and mitral regurgitation(MR)remains inadequately characterized.The molecular mechanism of pimobendan(PIMO)that contributes to the delay in congestive heart failure(CHF)in MR associated with apoptosis and fibrosis is still unclear.Our aim was to examine the impact of PIMO on ER stress,apoptosis,and fibrosis in a chronic MR rat model.Methods:MR was surgically induced in 10 Sprague–Dawley rats,with 5 serving as sham operation controls.At 8 weeks postsurgery,the MR animals were randomly allocated into two groups:MR and MR+PIMO groups.PIMO was administered twice daily through oral gavage for 4 weeks,whereas the sham and MR groups were administered similar quantities of drinking water.Echocardiography was conducted before the delivery of PIMO as a baseline measure and at the end of the study.At the end of the investigation,hearts were procured for histopathological and ER stress evaluations.Results:PIMO significantly maintained heart function and structural remodeling in the MR animals.PIMO significantly reduced MR-induced myocyte apoptosis(p=0.044)and fibrosis(p=0.002)by reducing the messenger RNA expression of genes associated with ER stress(GRP78[glucose-regulated protein 78],ATF4[activating transcription factor 4],and CHOP[C/ERP homologous protein])compared to the MR group(p<0.05,p<0.01,and p<0.001,respectively).Conclusion:PIMO demonstrated cardioprotective benefits on heart function,myocyte apoptosis,and fibrosis by regulating ER stress in an MR-induced CHF rat model.
基金supported by the National Natural Science Foundation of China(82071498,81871046,and 32161143022)STI2030-Major Projects(2022ZD0214500).
文摘Persistent and maladaptive drug-related memories represent a key component in drug addiction.Converging evidence from both preclinical and clinical studies has demonstrated the potential efficacy of the memory reconsolidation updating procedure(MRUP),a non-pharmacological strategy intertwining two distinct memory processes:reconsolidation and extinction—alternatively termed“the memory retrieval-extinction procedure”.This procedure presents a promising approach to attenuate,if not erase,entrenched drug memories and prevent relapse.The present review delineates the applications,molecular underpinnings,and operational boundaries of MRUP in the context of various forms of substance dependence.Furthermore,we critically examine the methodological limitations of MRUP,postulating potential refinement to optimize its therapeutic efficacy.In addition,we also look at the potential integration of MRUP and neurostimulation treatments in the domain of substance addiction.Overall,existing studies underscore the significant potential of MRUP,suggesting that interventions predicated on it could herald a promising avenue to enhance clinical outcomes in substance addiction therapy.
文摘A deficiency ofγδT cells has been described in Crohn's disease(CD).AIM To analyze the gene expression of interleukin 7(IL-7)and its receptors in the tissues of patients with CD.METHODS We studied the peripheral blood of 80 patients with CD,comparing them with a group of 80 healthy subjects.The number and apoptosis ofαβandγδT cells in peripheral blood and the proportion ofαβandγδT cells in the intestinal tissues of patients with CD(n=25)were studied.The gene and protein expression of IL-7,IL-2 receptor subunitγ[cluster of differentiation 132(CD132)],receptorα(CD127),and caspase-3 in tissues was analyzed by quantitative PCR.Serum IL-7 levels were also analyzed.RESULTS In patients with CD,a decreased number ofγδT cells and an increase in the apoptosis of CD56+αβandγδT cells in peripheral blood was observed(P<0.0001 and P<0.01)respectively,and there was an inverse correlation among T subsets and their apoptosis.In addition,IL-7 gene expression and IL-7 protein in the tissues of these patients were increased.The titers of caspase-3 in tissues were low vs control group(P>0.01).The percentage of CD8+γδT cells decreased in tissues(P<0.01),and was directly related to IL-7 levels in peripheral blood.The expression of IL-2 receptor subunitγ(CD132)was greatly decreased in the tissues of patients with CD(P<0.05).CONCLUSION There may be a cause-effect relationship between the lower gene expression of the IL-2 receptor subunitγ(CD132)in tissues of patients with CD andγδT cells immunodeficiency.
基金funded by the Hainan Province Science and Technology Special Fund[grant number ZDKJ2021012]the National Key R&D Programof China[grant number 2023YFD2300801]received by Fei Qiaothe Ongoing Research Funding Program(ORF-2025-751),King Saud University,Riyadh,Saud Arabia.
文摘Mango(Mangifera indica L.cv.‘Keitt’)is one of the core fruit delicacies produced by China.During the post-harvest storage span,the fungal pathogen colletotrichum gloeosporioides readily invades the fruits and leads to a significant overall yield loss.In recent years of development,the exploitation of naturally occurring fungitoxic compounds such as Sandalwood Essential Oil(SEO)has been useful in tackling various fungal species.This study demonstrates the potential of SEO as part of a storage protection strategy against C.gloeosporioides-induced postharvest anthracnose.SEO displayed a relatively higher mycelial growth inhibition rate when compared to various other essential oils.Furthermore,the Minimal Inhibitory Concentration(MIC),Minimum Fungicidal Concentration(MFC),and EC_(50)(Half maximal effective concentration)of SEO were determined to be 2000,2500,and 610.38μL/L,respectively.Moreover,the chitosan glutamate-SEO emulsion controlled the anthracnose spread for several days by multiple folds at½MIC,MIC,and 2 MIC concentrations.These results strongly support the potential for largescale production and application of SEO emulsions by agrochemical firms and post-harvest storage facilities handling Keitt mangoes.
基金supported by the Korean Institute of Energy Technology Evaluation and Planning(KETEP)grant funded by the Korea Government(MOTIE)(RS-2023-00303581,Multiscale Simulation-Driven Development of Cost-Effective and Stable Aqueous Zn Ion Battery with Energy Density of 110 Wh/L for Energy Storage Systems:A Korea-USA Collaboration)。
文摘Achieving high-performance aqueous zinc-ion batteries requires addressing the challenges associated with the stability of zinc metal anodes,particularly the formation of inhomogeneous zinc dendrites during cycling and unstable surface electrochemistry.This study introduces a practical method for scattering untreated bulk hexagonal boron nitride(h-BN)particles onto the zinc anode surface.During cycling,stabilized zinc fills the interstices of scattered h-BN,resulting in a more favorable(002)orientation.Consequently,zinc dendrite formation is effectively suppressed,leading to improved electrochemical stability.The zinc with scattered h-BN in a symmetric cell configuration maintains stability 10 times longer than the bare zinc symmetric cell,lasting 500 hours.Furthermore,in a full cell configuration withα-MnO_(2) cathode,increased H^(+)ion activity can effectively alter the major redox kinetics of cycling due to the presence of scattered h-BN on the zinc anode.This shift in H^(+)ion activity lowers the overall redox potential,resulting in a discharge capacity retention of 96.1%for 300 cycles at a charge/discharge rate of 0.5 Ag^(-1).This study highlights the crucial role of surface modification,and the innovative use of bulk h-BN provides a practical and effective solution for improving the performance and stability.
文摘BACKGROUND The decision to administer adjuvant chemotherapy to patients with local stage depends on specific high-risk features that are T4 tumor stage,presence of perineural invasion,lymphovascular invasion,poorly differentiated tumor histology,inadequate lymph node sampling(fewer than 12 lymph nodes),and evidence of tumor perforation or obstruction.Tumor-stroma ratio,tumor infiltrating lymphocytes(TIL),Crohn-like reaction(CLR),desmoid reaction,poorly differentiated clusters(PDC)are new pathological markers that are being studied.AIM To examine the relationship between new pathological markers and defined high METHODS We evaluated 155 patients with the diagnosis stage I and II colorectal cancer between the years 2007 and 2021 who were treated at Trakya University Hospital,Department of Medical Oncology.We divided those with and without high-risk factors into two groups.We examined the relationship of new pathological markers with these groups and with pathological markers in risk factors.RESULTS There was no statistically significant correlation between presence of TIL,presence of PDC,presence of tumor budding,presence of CLR,presence of desmoid reaction and low and high-risk groups according to the degree of those with PDC(P=0.82,P=0.51,P=0.77,P=0.37,P=0.83,respectively).In addition,no statistically significant correlation was found between the tumor-stroma ratio and low and high risk groups(P=0.80).We found a statistically significant correlation between the presence of PDC and the presence of PDC grade 3 and T stage(P=0.001,P=0.001,respectively).It was determined that the presence of PDC and the frequency of grade 3 PDC increased with the advanced T stage.CONCLUSION No relationship was found between the presence of new pathological markers and high-low risk groups.When we examined the relationship between new and old pathological markers,only the frequency of detection of PDC and PDC grade 3 was found to be correlated with advanced T stage.
基金supported by the National Key Research and Development Program(2022YFB4701700)National Excellent Youth Science Fund Project of the National Natural Science Foundation of China(52322502)+6 种基金the National Outstanding Youth Science Fund Project of National Natural Science Foundation of China(52025054)National Natural Science Foundation of China(52175009),Postdoctoral Fellowship Program of CPSF(GZC20232498)Postdoctoral Innovative Talents in Shandong Province(SDBX2023011)China Postdoctoral Science Foundation Grant(2023M733341)Key R&D Program of Shandong Province,China(2021ZLGX04)National Heilongjiang Providence Nature Science Foundation of China(YQ2022E022)Fundamental Research Funds for the Central Universities。
文摘Micro/nanorobots have exhibited excellent application potential in the biomedical field,such as drug delivery,minimally invasive surgery,and bio-sensing.Furthermore,in order to achieve practical application,it is essential for swimming micro/nanorobots to navigate towards specific targets or adjust their speed and morphology in complete environments.The navigation of swimming micro/nanorobots with temporal and spatial precision is critical for fulfilling the demand of applications.Here,we introduced a fully integrated wearable control system for micro/nanorobots navigation and manipulation,which is composed of a multifunctional sensor array,an artificial intelligence(AI)planner,and a magnetic field generator.The sensor array could perceive real-time changes in gestures,wrist rotation,and acoustic signals.AI planner based on machine learning offers adaptive path planning in response to dynamically changing signals to generate magnetic fields for the on-demand manipulation of micro/nanorobots.Such a novel,feasible control strategy was validated in the biological experiment in which cancer cells were targeted and killed by photothermal therapy using micro/nanorobots and integrated control platform.This wearable control system could play a crucial role in future intelligent medical applications and could be easily reconfigured toward other medical robots’control.
基金supported by an institutional Ph.D.grant(No.21130/1312/3131)from the Faculty of Agrobiology,Food,and Natural Resources at the Czech University of Life Sciences Prague(CZU),Czech Republic。
文摘Very few studies have benefited from the synergetic implementation of visible,near-infrared,and shortwave infrared(VNIR-SWIR)spectra and terrain attributes in predicting Pb content in agricultural soils.To fill this gap,this study aimed to predict lead(Pb)contents in agricultural soils by combining machine learning algorithms(MLAs)with VNIR-SWIR spectra or/and terrain attributes under three distinct approaches.Six MLAs were tested,including artificial neural network(ANN),partial least squares regression,support vector machine(SVM),Gaussian process regression(GPR),extreme gradient boosting(EGB),and Cubist.The VNIR-SWIR spectral data were preprocessed by methods of discrete wavelet transformation,logarithmic transformation-Savitzky Golay smoothing,standard normal variate(SNV),multiplicative scatter correction,first derivative(Fi D),and second derivative.In approach 1,MLAs were combined with the preprocessed VNIR-SWIR spectral data.The Cubist-Fi D combination was the most effective,achieving a coefficient of determination(R2)of 0.63,a concordance correlation coefficient(CCC)of 0.51,a mean absolute error(MAE)of 6.87 mg kg^(-1),and a root mean square error(RMSE)of8.66 mg kg^(-1).In approach 2,MLAs were combined with both preprocessed VNIR-SWIR spectral data and terrain attributes,and the EGB-SNV combination yielded superior results with R2of 0.75,CCC of 0.65,MAE of 5.48 mg kg^(-1),and RMSE of 7.34 mg kg^(-1).Approach 3 combined MLAs and terrain attributes,and Cubist demonstrated the best prediction results,with R^(2) of 0.75,CCC of 0.66,MAE of 6.18 mg kg^(-1),and RMSE of 7.71 mg kg^(-1).The cumulative assessment identified the fusion of terrain properties,SNV-preprocessed VNIR-SWIR spectra,and EGB as the optimal method for estimating Pb content in agricultural soils,yielding the highest R2value and minimal error.Comparatively,GPR,ANN,and SVM techniques achieved higher R2values in approaches 2 and 3 but also exhibited higher estimation errors.In conclusion,the study underscores the significance of using relevant auxiliary datasets and appropriate MLAs for accurate Pb content prediction with minimal error in agricultural soils.The findings contribute valuable insights for developing successful soil management strategies based on predictive modeling.
基金supported and funded by the National Natural Science Foundation of China(82101079)the Key R&D Program of Jiangsu Province(BE2023836)the National Key Research and Development Program of China(SQ2023YFC2400025).
文摘As the integration of medical big data and artificial intelligence advances,the secure sharing of medical data has become a key driving force for advancing disease research and clinical diagnosis.Federated learning,a distributed approach enabling collaborative data processing without sharing raw data,offers promising solutions to challenges in multi-center medical data sharing.This review summarizes the progress of federated learning in multi-center medical data processing,analyzed from four perspectives:system architectures,data distribution strategies,clinical tasks,and algorithmic models.At the same time,this paper explores the challenges in practical applications,such as data heterogeneity,communication overhead,and privacy concerns.It proposes driving future research development by optimizing algorithms,strengthening privacy protection mechanisms,and enhancing computational efficiency.
基金Supported by the Science and Technology Program of the Guizhou Province,No.[2021]094National Natural Science Foundation of China,No.82060116 and No.82260129+1 种基金Guizhou Provincial Science and Technology Program,No.QKHJC-ZK[2023]214Doctoral Research Start-up Fund Project of Guizhou Medical University,No.gyfybsky[2021]63.
文摘BACKGROUND Inhibiting hepatic stellate cell(HSC)activation is a key therapeutic strategy in liver fibrosis(LF).During activation,aerobic glycolysis is upregulated to meet increased energy demands.Although focal adhesion kinase(FAK)has been implicated in regulating HSC glycolysis,its precise role in activation remains unclear.AIM To investigate the effects of FAK and fructose-1,6-bisphosphatase 1(FBP1)on LF through the modulation of aerobic glycolysis in HSCs.METHODS Eighteen mice were randomly assigned to three groups:Control,carbon tetrachloride(CCl_(4))-induced LF,and CCl_(4)with FAK inhibitor treatment.Liver tissues were analyzed using transcriptomic and proteomic sequencing.Differential gene expression,Mfuzz clustering,and protein interaction network analyses identified key regulatory factors.Immunohistochemistry(IHC)and Western blot(WB)analysis were used to assess FAK and FBP1 expression,along with glycolysis-related enzymes.The migratory behavior of HSCs was evaluated using Transwell migration and scratch assays.RESULTS Transcriptomic and proteomic analyses revealed significantly reduced FBP1 expression in CCl_(4)-induced fibrosis,which was restored upon FAK inhibition.Histological staining(hematoxylin and eosin,Masson’s trichrome,Sirius red)confirmed reduced fibrosis following FAK inhibition.WB analysis demonstrated suppression of glycolysisrelated enzymes.In LX-2 cells,FAK inhibition attenuated HSC activation and glycolysis while upregulating FBP1.Exogenous recombinant FBP1 inhibited HSC activation and glycolysis.Transwell and scratch assays showed that FBP1 significantly impaired HSC migration.In addition,WB and IHC analyses confirmed lower FBP1 expression in fibrotic liver tissues from patients compared to healthy controls.CONCLUSION FAK inhibitors and increased FBP1 expression inhibit aerobic glycolysis in HSCs,thereby improving LF.Thus,FAK and FBP1 may be potential targets for LF treatment.
文摘BACKGROUND Peritoneal lavage cytology-positive(CY1)gastric cancer(stage IV)has a poor prognosis,though some cases fare better.Therefore,identifying prognostic factors and an optimal treatment strategy is crucial.AIM To investigate prognostic factors in patients with gastric cancer who underwent gastrectomy with CY1,and to evaluate the optimal postoperative chemotherapy regimen.METHODS This multicenter retrospective cohort study analyzed prognostic factors and postoperative chemotherapy in patients with CY1 gastric cancer who underwent gastrectomy,excluding those with macroscopic peritoneal dissemination.Data from 13 institutions(2015-2019)were reviewed.RESULTS Overall,82 patients met the inclusion criteria.The median overall survival was 22.8 months,and diffuse-type histology and the absence of postoperative chemotherapy were identified as independent poor prognostic factors.The 5-year survival rate was 82.4%for those receiving fluoropyrimidine plus docetaxel/oxaliplatin vs 21.8%for those with S-1 monotherapy or a cisplatin-based regimen.Median overall survival was not reached in the fluoropyrimidine+docetaxel/oxaliplatin group but was 22.9 months in the S-1/cisplatin group.Chemotherapy regimen was an independent prognostic factor(hazard ratio=5.47,P=0.004).The fluoropyrimidine plus docetaxel/oxaliplatin group had an average relative dose intensity of 82.1%,with significantly more patients achieving a relative dose intensity≥80%than in the S-1 monotherapy or cisplatin-based group(P=0.001).CONCLUSION Diffuse-type histology and the absence of postoperative chemotherapy influence the prognosis of patients with CY1 gastric cancer.Combination therapy with oxaliplatin or docetaxel may enhance the treatment intensity and improve survival outcomes after gastrectomy.
文摘This article discusses the original article published by Lu et al in the latest issue.The article confirmed through a cohort study the clinical efficacy of the triple live bacteria of Bifidobacterium combined with mirtazapine in treating postoperative depression of gastric cancer patients,also explored the multi-target therapeutic mechanisms of Bifidobacterium triple viable bacteria combined with mirtazapine in managing depression in patients after radical gastrectomy for gastric cancer for the first time.The results indicated that Bifidobacterium could alleviate depression in patients after radical gastrectomy for gastric cancer.Gastric cancer patients undergoing surgery frequently experience postoperative psychological disorders,notably depression.These conditions not only impair quality of life but also negatively impact disease-free and overall survival.This editorial explores the underestimated psychological challenges following gastric cancer surgery,including depression,anxiety,adjustment disorders,and post-traumatic stress disorder.It further examines the therapeutic potential of Bifidobacterium triple viable probiotics,combined with mirtazapine,in alleviating postoperative depression through microbiological,immunological,and neurological mechanisms.Clinical evidence highlights additional benefits,such as improved gastrointestinal function,enhanced immunity,and better nutritional status,underscoring a holistic approach to postoperative care.While promising,further large-scale trials are needed to optimize and personalize probiotic-based interventions.
