Post-translational modification of spastin enables precise spatiotemporal control of its microtubule severing activity.However,the detailed mechanism by which spastin turnover is regulated in the context of neurite ou...Post-translational modification of spastin enables precise spatiotemporal control of its microtubule severing activity.However,the detailed mechanism by which spastin turnover is regulated in the context of neurite outgrowth remains unknown.Here,we found that spastin interacted with ubiquitin and was significantly degraded by K48-mediated poly-ubiquitination.Cullin3 facilitated spastin degradation and ubiquitination.RING-box protein 1,but not RING-box protein 2,acted synergistically with Cullin3 protein to regulate spastin degradation.Overexpression of Culin3 or BRX1 markedly suppressed spastin expression,and inhibited spastin-mediated microtubule severing and promotion of neurite outgrowth.Moreover,USP14 interacted directly with spastin to mediate its deubiquitination.USP14 overexpression significantly increased spastin expression and suppressed its ubiquitination and degradation.Although co-expression of spastin and USP14 did not enhance microtubule severing,it did increase neurite length in hippocampal neurons.Taken together,these findings elucidate the intricate regulatory mechanisms of spastin turnover,highlighting the roles of the Cullin-3–Ring E3 ubiquitin ligase complex and USP14 in orchestrating its ubiquitination and degradation.The dynamic interplay between these factors governs spastin stability and function,ultimately influencing microtubule dynamics and neuronal morphology.These insights shed light on potential therapeutic targets for neurodegenerative disorders associated with spastin defects.展开更多
The effects of major veins severing on morphological and physiological features of sweetgum （Liquidambar styraciflua L.） leaves were investigated by observing leaf color change and measuring leaf temperature, green/...The effects of major veins severing on morphological and physiological features of sweetgum （Liquidambar styraciflua L.） leaves were investigated by observing leaf color change and measuring leaf temperature, green/luminance （G/L） value of half-lobes, leaf stomata conductance, and water content in Yamaguchi University, Japan. The palmately veined leaves of sweetgum （Liquidambar styraciflua L.） were found more sensitive to the major vein severing than that of other species Major veins severing resulted in serious water stresses, as indicated by the persistent reddening and/or advanced reddening of local leaf, lower leaf stomatal conductance, and higher leaf temperature, etc. Severed leaf can be clearly divided into non-severed area, transitional area, and stressed area, which the three areas have different colours and temperature. The major vein barrier can also be seen clearly. The persistent reddening and advanced reddening seem consistent with the phenomenon of red crown top of some sweetgum trees and may have similar mechanism.展开更多
Plant interphase cortical microtubules(cMTs)mediate anisotropic cell expansion in response to environmental and developmental cues.In Arabidopsis thaliana,KATANIN 1(KTN1),the p60 catalytic subunit of the conserved MT-...Plant interphase cortical microtubules(cMTs)mediate anisotropic cell expansion in response to environmental and developmental cues.In Arabidopsis thaliana,KATANIN 1(KTN1),the p60 catalytic subunit of the conserved MT-severing enzyme katanin,is essential for cMT ordering and anisotropic cell expansion.However,the regulation of KTN1-mediated cMT severing and ordering remains unclear.In this work,we report that the Arabidopsis IQ67 DOMAIN(IQD)family gene ABNORMAL SHOOT 6(ABS6)encodes a MT-associated protein.Overexpression of ABS6 leads to elongated cotyledons,directional pavement cell expansion,and highly ordered transverse cMT arrays.Genetic suppressor analysis revealed that ABS6-mediated cMT ordering is dependent on KTN1 and SHADE AVOIDANCE 4(SAV4).Live imaging of cMT dynamics showed that both ABS6 and SAV4 function as positive regulators of cMT severing.Furthermore,ABS6 directly interacts with KTN1 and SAV4 and promotes their recruitment to the cMTs.Finally,analysis of loss-of-function mutant combinations showed that ABS6,SAV4,and KTN1 work together to ensure the robust ethylene response in the apical hook of dark-grown seedlings.Together,our findings establish ABS6 and SAV4 as positive regulators of cMT severing and ordering,and highlight the role of cMT dynamics in fine-tuning differential growth in plants.展开更多
Katanin is a heterodimeric microtubule （MT） severing protein that uses energy from ATP hydrolysis to generate internal breaks along MTs. Katanin p60, one of the two subunits, possesses ATPase and MT-binding/severing...Katanin is a heterodimeric microtubule （MT） severing protein that uses energy from ATP hydrolysis to generate internal breaks along MTs. Katanin p60, one of the two subunits, possesses ATPase and MT-binding/severing activities, and the p 80 subunit is responsible for targeting of katanin to certain subcellular locations. In animals, katanin plays an important role in the release of MTs from their nucleation sites in the centrosome. It is also involved in severing MTs into smaller fragments which can serve as templates for further polymerization to increase MT number during meiotic and mitotic spindle assembly. Katanin homologs are present in a wide variety of plant species. The Arabidopsis katanin homolog has been shown to possess ATP-dependent MT severing activity in vitro and exhibit a punctate localization pattern at the cell cortex and the perinuclear region. Disruption of katanin functions by genetic mutations causes a delay in the disappearance of the perinuclear MT array and results in an aberrant organization of cortical MTs in elongating cells. Consequently, katanin mutations lead to defects in cell elongation, cellulose microfibril deposition, and hormonal responses. Studies of katanin in plants provide new insights into our understanding of its roles in cellular functions.展开更多
BACKGROUND Parkinson’s disease(PD)is a common neurodegenerative disorder in the elderly population.Non-motor symptoms such as anxiety and depression are often subtle,hindering early detection and intervention,yet the...BACKGROUND Parkinson’s disease(PD)is a common neurodegenerative disorder in the elderly population.Non-motor symptoms such as anxiety and depression are often subtle,hindering early detection and intervention,yet they markedly affect quality of life and clinical outcomes.AIM To investigate the prevalence of anxiety and depression in elderly PD patients,identify associated risk factors,and assess their relationship with fatigue severity.METHODS A cross-sectional analysis was conducted in 123 elderly PD patients treated at The Second Rehabilitation Hospital of Shanghai between January 2023 and December 2024.Demographic and clinical data were obtained using standardized questionnaires.Anxiety,depression,and fatigue were assessed using the Beck Anxiety Inventory(BAI),Geriatric Depression Scale(GDS),and Fatigue Scale-14(FS-14),respectively.Binary logistic regression identified risk factors for anxiety and depression,whereas Spearman’s correlation assessed associations with fatigue.RESULTS Anxiety and depression prevalence rates were 64.2%(mean BAI score:19.59±10.92)and 56.1%(mean GDS score:12.82±6.37),respectively.The mean FS-14 total score was 9.46±1.89,comprising physical(5.77±1.51)and mental(3.69±1.20)fatigue components.Significant positive correlations were observed between fatigue scores(total,physical,and mental)and both anxiety and depression(all P<0.05).Univariate analysis revealed statistically significant associations between anxiety/depression and monthly income,disease duration,and disease severity(all P<0.05).Multivariate logistic regression indicated higher anxiety risk in patients with lower monthly income,prolonged disease duration,advanced disease severity,or multimorbidity.Depression risk was elevated in patients with lower monthly income and severe disease,whereas longer disease duration unexpectedly served as a protective factor.CONCLUSION Elderly PD patients show high rates of anxiety and depression,both of which are significantly correlated with fatigue severity.These findings highlight the importance of psychological monitoring and targeted mental health interventions in PD management among the elderly.展开更多
This article reviews research advances in the application of early enteral nutrition(EEN)in elderly patients with severe acute pancreatitis(SAP).Elderly SAP patients are associated with higher mor tality rates due to ...This article reviews research advances in the application of early enteral nutrition(EEN)in elderly patients with severe acute pancreatitis(SAP).Elderly SAP patients are associated with higher mor tality rates due to age-related immune dysfunction,whereas EEN has been demonstrated to improve clinical prognosis,reduce infection and complication rates,and shor ten hospital stays.However,ongoing debates exist regarding the optimal timing,route selection,and complication management of EEN.Through a systematic review of the literature,this study synthesizes current evidence on EEN in elderly SAP populations,critically examines unresolved clinical controversies,and proposes future research priorities to inform evidence-based practice.展开更多
Severe trauma often involves complex injuries,leading to high disability and fatality rates.Effective treatment requires prompt and coordinated efforts across multiple disciplines to enhance success rates.Time-based c...Severe trauma often involves complex injuries,leading to high disability and fatality rates.Effective treatment requires prompt and coordinated efforts across multiple disciplines to enhance success rates.Time-based chain rescue is crucial in managing severe trauma.A patient with chest and abdominal injuries and hemorrhagic shock was transferred from an ambulance to our hospital.Our trauma team-initiated pre-hospital first aid,utilized an emergency green channel,and conducted rapid ultrasound,collaborating across disciplines.The patient eventually recovered and was discharged.展开更多
A case of imported severe falciparum malaria with spontaneous splenic rupture was reported in this paper.The patient,an African migrant worker,developed hemolytic anemia,sepsis,thrombocytopenia,coagulation dysfunction...A case of imported severe falciparum malaria with spontaneous splenic rupture was reported in this paper.The patient,an African migrant worker,developed hemolytic anemia,sepsis,thrombocytopenia,coagulation dysfunction,liver failure,renal insufficiency,electrolyte disturbance and other clinical manifestations after returning to the local area.Plasmodium falciparum was found by peripheral blood smearscopy and was diagnosed as severe falciparum malaria.After standardized anti-malaria treatment,plasma exchange+cytokine adsorption therapy,the establishment of“forewarning-forewarning-prevention-emergency”predictive nursing management model,the establishment of an integrated nursing team,the division of medical care is clear,professional knowledge is complementary,after three months of regular follow-up,the patient has no malaria recurrence,no refire,the function of all organs returned to normal.展开更多
Automated grading of dandruff severity is a clinically significant but challenging task due to the inherent ordinal nature of severity levels and the high prevalence of label noise from subjective expert annotations.S...Automated grading of dandruff severity is a clinically significant but challenging task due to the inherent ordinal nature of severity levels and the high prevalence of label noise from subjective expert annotations.Standard classification methods fail to address these dual challenges,limiting their real-world performance.In this paper,a novel,three-phase training framework is proposed that learns a robust ordinal classifier directly from noisy labels.The approach synergistically combines a rank-based ordinal regression backbone with a cooperative,semi-supervised learning strategy to dynamically partition the data into clean and noisy subsets.A hybrid training objective is then employed,applying a supervised ordinal loss to the clean set.The noisy set is simultaneously trained using a dualobjective that combines a semi-supervised ordinal loss with a parallel,label-agnostic contrastive loss.This design allows themodel to learn fromthe entire noisy subset while using contrastive learning to mitigate the risk of error propagation frompotentially corrupt supervision.Extensive experiments on a new,large-scale,multi-site clinical dataset validate our approach.Themethod achieves state-of-the-art performance with 80.71%accuracy and a 76.86%F1-score,significantly outperforming existing approaches,including a 2.26%improvement over the strongest baseline method.This work provides not only a robust solution for a practical medical imaging problem but also a generalizable framework for other tasks plagued by noisy ordinal labels.展开更多
Dengue fever is an acute infectious disease caused by the dengue virus and transmitted by mosquito vectors[1].Its clinical manifestations include high fever,headache,muscle and joint pain,and rash.It holds a significa...Dengue fever is an acute infectious disease caused by the dengue virus and transmitted by mosquito vectors[1].Its clinical manifestations include high fever,headache,muscle and joint pain,and rash.It holds a significant position in global public health.In recent years,its incidence has continued to rise worldwide[2],making it one of the major diseases threatening human health.The disease course of dengue fever is divided into three typical phases:the acute febrile phase,the critical phase,and the recovery phase.While most patients experience mild symptoms,some may progress to severe dengue and potentially fatal outcomes if not promptly and effectively treated during the critical phase.展开更多
Oxidative stress significantly contributes to secondary damage after spinal cord injury.Despite its importance,research on oxidative stress in spinal cord injury remains limited.Investigating the expression and regula...Oxidative stress significantly contributes to secondary damage after spinal cord injury.Despite its importance,research on oxidative stress in spinal cord injury remains limited.Investigating the expression and regulation of oxidative stress-related genes could enhance the diagnosis and treatment of spinal cord injury.In this study,we analyzed the sequencing data of human blood samples and injured mouse spinal cord tissue that were sourced from GEO databases and identified diagnostic biomarkers associated with the severity of spinal cord injury.We also explored the expression patterns of oxidative stress-related genes,potential regulatory mechanisms,and therapeutic drugs.To validate our findings,we performed immunofluorescence and quantitative polymerase chain reaction to assess gene expression in the injured spinal cord.Our results revealed biomarkers associated with oxidative stress and immune responses across different levels of spinal cord injury in humans.We identified differentially expressed oxidative stress-related genes and key hub genes in injured mouse spinal cord tissue and revealed their temporal expression patterns at both the tissue and single-cell levels.We also clarified the signaling pathways associated with oxidative stress and identified ligand-receptor pairs among various cell types at different time points after injury.Furthermore,we discovered microRNAs,long non-coding RNAs,and transcription factors that regulate these hub genes and revealed their roles in modulating gene expression at various stages after spinal cord injury.We also identified drugs targeting these hub genes.The findings from this study not only aid in identifying diagnostic biomarkers that reflect the severity of spinal cord injury,but also provide insights into the expression dynamics of oxidative stress-related genes.In addition,the study reveals potential regulatory mechanisms and identifies potential drugs to treat patients with spinal cord injury.展开更多
Background:Humanized mouse models are essential for studying the human immune response and antibody development.However,conventional models show limited B cell maturation and antigen-specific humoral responses.To over...Background:Humanized mouse models are essential for studying the human immune response and antibody development.However,conventional models show limited B cell maturation and antigen-specific humoral responses.To overcome these limitations,we used the NOG-EXL mice expressing human interleukin 3(IL-3)and granulocyte-macrophage colony-stimulating factor(GM-CSF)to enhance myeloid and B-cell lineage differentiation.Methods:Human CD34^(+)hematopoietic stem cells(HSC)were transplanted into NOG-EXL mice to produce humanized immune systems.After immune cell reconstitution was confirmed across 12 weeks,the mice were immunized twice with inactivated severe fever with thrombocytopenia syndrome virus(SFTSV)antigens.Peripheral blood mononuclear cells and splenocytes were analyzed using multicolor flow cytometry to assess human immune cell subsets.Antigen-specific immunoglobulin G(IgG)production was quantified using enzyme-linked immunosorbent assay(ELISA),and virus-specific B cells were isolated using antigen-labeled recombinant protein probes.Results:Twelve weeks after transplantation of HSCs into NOG-EXL mice,they exhibited robust engraftment of human leukocytes,including T,B,and dendritic cells,compared to NOG mice.Unlike NOG mice,humanized NOG-EXL mice exhibited an increase in human IgG levels,indicating the production of human antibody responses to antigens.Humanized NOG-EXL mice were immunized twice every 2 weeks with inactivated SFTSV,and antigen-specific human antibodies against the virus were detected in the mouse sera by ELISA.Sera from SFTSV-immunized humanized mice demonstrated neutralizing activity against SFTSV,confirming the induction of functional virus-specific neutralizing antibodies.Antigen-binding IgG-positive human B cells were isolated from mouse splenocytes using recombinant protein probes.Conclusion:This model provides a valuable platform for evaluating humoral immunity and isolating B cells using high-affinity human monoclonal antibodies without genetic engineering.展开更多
Recent increases in infectious diseases affecting the central nervous system have raised concerns about their role in neuroinflammation and neurodegeneration.Viral pathogens or their products can invade the central ne...Recent increases in infectious diseases affecting the central nervous system have raised concerns about their role in neuroinflammation and neurodegeneration.Viral pathogens or their products can invade the central nervous system and cause damage,leading to meningitis,encephalitis,meningoencephalitis,myelitis,or post-infectious demyelinating diseases.Although neuroinflammation initially has a protective function,chronic inflammation can contribute to the development of neurodegenerative diseases.Mechanisms such as protein aggregation and cellular disturbances are implicated with specific viruses such as herpes simplex virus type 1 and Epstein-Barr virus being associated with Alzheimer's disease and multiple sclerosis,respectively.Extracellular nucleotides,particularly adenosine triphosphate and its metabolites are released from activated,infected,and dying cells,acting as alarmins mediating neuroinflammation and neurodegeneration.When viruses infect central nervous system cells,adenosine triphosphate is released as an alarmin,triggering inflammatory responses.This process is mediated by purinergic receptors,divided into two families:P1,which responds to adenosine,and P2,activated by adenosine triphosphate and other nucleotides.This review highlights how specific viruses,such as human immunodeficiency virus type 1,Theiler's murine encephalomyelitis virus,herpes simplex virus type 1,Epstein-Barr virus,dengue virus,Zika virus,and severe acute respiratory syndrome coronavirus 2,can initiate inflammatory responses through the release of extracellular nucleotides,particularly adenosine triphosphate,which act as critical mediators in the progression of neuroinflammation and neurodegenerative disorders.A better understanding of purinergic signaling pathways in these diseases may suggest new potential therapeutic strategies for targeting neuroinflammation to mitigate the long-term consequences of viral infections in the central nervous system.展开更多
Severe acute pancreatitis(SAP)can induce acute respiratory distress syndrome(ARDS)and abdominal compartment syndrome(ACS).Although prone position ventilation(PPV)can improve outcomes in patients with ARDS,there is sig...Severe acute pancreatitis(SAP)can induce acute respiratory distress syndrome(ARDS)and abdominal compartment syndrome(ACS).Although prone position ventilation(PPV)can improve outcomes in patients with ARDS,there is significant controversy regarding its concurrent use with ACS owing to concerns of increased risk of intra-abdominal pressure(IAP).[1]We present a case of successful PPV application without adverse eff ects.展开更多
BACKGROUND The imbalance of hormone levels in the body is closely related to the occurrence and progression of schizophrenia,especially thyroid hormones.AIM To study the relationship between triiodothyronine(T3),thyro...BACKGROUND The imbalance of hormone levels in the body is closely related to the occurrence and progression of schizophrenia,especially thyroid hormones.AIM To study the relationship between triiodothyronine(T3),thyroxine(T4),free T3(FT3),free T4(FT4),thyroid stimulating hormone(TSH)and schizophrenia.METHODS In this study,100 schizophrenia patients were selected from our hospital between April 2022 and April 2024.Their clinical data were analyzed retrospectively.Based on the Positive and Negative Syndrome Scale(PANSS)score,patients were divided into mild(1-3 points,n=39),moderate(4 points,n=45),and severe groups(5-7 points,n=16).Additionally,55 healthy individuals served as a control group.Venous blood samples were collected to measure T3,T4,FT3,FT4,TSH,and cortisol concentrations,analyzing their relationship with PANSS scores.RESULTS The serum levels of T3,FT3,FT4,TSH and cortisol in the schizophrenia group were lower than those in the control group(P<0.05).With the increase of the severity of the disease,the concentrations of T3 and T4 decreased,while the con-centrations of TSH and cortisol increased(P<0.05).The concentrations of TSH and cortisol were positively correlated with the PANSS score,while T3 and T4 were negatively correlated with the PANSS score(P<0.05).The receiver ope-rating characteristic curve results showed that T3,T4,TSH,and cortisol had good efficacy in the diagnosis of schizophrenia.Logistic results showed that decreased T3 level,decreased T4 level,decreased TSH level and increased cortisol level may be independent risk factors for schizophrenia.CONCLUSION Thyroid hormone levels are associated with the severity of schizophrenia symptoms,which can provide new solutions for the diagnosis and treatment of schizophrenia.展开更多
Severe fever with thrombocytopenia syndrome(SFTS)is a novel emerging acute infectious disease caused by severe fever with thrombocytopenia syndrome virus(SFTSV),characterized by high fever and thrombocytopenia.It has ...Severe fever with thrombocytopenia syndrome(SFTS)is a novel emerging acute infectious disease caused by severe fever with thrombocytopenia syndrome virus(SFTSV),characterized by high fever and thrombocytopenia.It has been proved that traditional Chinese medicine(TCM)has displayed definite therapeutic effects on viral hemorrhagic fever,indicating its potential to treat SFTS.In this study,SFTS-relative key targets were predicted via gene ontology(GO)analysis and kyoto encyclopedia of genes and genomes(KEGG)enrichment analysis.Molecular docking was then used to select stable binders.Molecules matched TCMs were identified,and a new prescription,Qingqi Guxue decoction(QQGX),was formulated to clear heat and nourish blood,with a resulting drug composition network.We explored the optimal drug proportion for QQGX.Through an in-depth study of molecular mechanisms,we found that QQGX induces S phase arrest by promoting the degradation of cyclin A2(CCNA2)and cyclin-dependent kinase 2(CDK2),thereby inhibiting SFTSV replication.Finally,we verified the effectiveness and safety of QQGX based on the mouse liver bile duct organoid model infected with SFTSV.In summary,our study prepared a TCM decoction using the method of network pharmacology.This decoction has a significant inhibitory effect on the replication of SFTSV and provides a new treatment strategy for hemorrhagic fever with TCM.展开更多
Fibrotic remodeling of nucleus pulposus(NP)leads to structural and mechanical anomalies of intervertebral discs that prone to degeneration,leading to low back pain incidence and disability.Emergence of fibroblastic ce...Fibrotic remodeling of nucleus pulposus(NP)leads to structural and mechanical anomalies of intervertebral discs that prone to degeneration,leading to low back pain incidence and disability.Emergence of fibroblastic cells in disc degeneration has been reported,yet their nature and origin remain elusive.In this study,we performed an integrative analysis of multiple single-cell RNA sequencing datasets to interrogate the cellular heterogeneity and fibroblast-like entities in degenerative human NP specimens.We found that disc degeneration severity is associated with an enrichment of fibrocyte phenotype,characterized by CD45 and collagen I dual positivity,and expression of myofibroblast markerα-smooth muscle actin.Refined clustering and classification distinguished the fibrocyte-like populations as subtypes in the NP cells-and immunocytes-clusters,expressing disc degeneration markers HTRA1 and ANGPTL4 and genes related to response to TGF-β.In injury-induced mouse disc degeneration model,fibrocytes were found recruited into the NP undergoing fibrosis and adopted a myofibroblast phenotype.Depleting the fibrocytes in CD11b-DTR mice in which myeloid-derived lineages were ablated by diphtheria toxin could markedly attenuate fibrous modeling and myofibroblast formation in the NP of the degenerative discs,and prevent disc height loss and histomorphological abnormalities.Marker analysis supports that disc degeneration progression is dependent on a function of CD45^(+)COL1A1^(+)andαSMA^(+)cells.Our findings reveal that myeloid-derived fibrocytes play a pivotal role in NP fibrosis and may therefore be a target for modifying disc degeneration and promoting its repair.展开更多
Aging is one of the greatest risk factors for morbidity caused by the coronavirus disease 2019(COVID19).In older individuals,a dysregulated immune response to severe acute respiratory syndrome coronavirus 2(SARS-CoV-2...Aging is one of the greatest risk factors for morbidity caused by the coronavirus disease 2019(COVID19).In older individuals,a dysregulated immune response to severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)infection contributes to disease severity;however,the underlying mechanism remains elusive.In this study,we established an aging mouse model of COVID-19,successfully replicating the development of a relatively severe disease in older adults.Further single-cell transcriptome analysis revealed a distinct immune cell landscape in the infected lungs,accompanied by an over-activated inflammatory response,especially in aging mice.Compared to young mice,aging mice showed extensive neutrophil activation,NETosis,and a dramatic decrease in the number of alveolar macrophages(AMs).Moreover,as important executors of efferocytosis,AMs exhibited a low efferocytotic gene signature and downregulation of multiple efferocytosis receptors in aged mice.Further analysis indicated that the efferocytosis of neutrophils,whether undergoing apoptosis or NETosis,was compromised after SARS-CoV-2 infection.Since efferocytosis is a key process in inflammatory resolution,impaired efferocytosis may contribute to hyperinflammation in aging lungs.Our study reveals the characteristics and role of efferocytosis in aging mice after SARS-CoV-2 infection and provides valuable insights for the potential treatment of COVID-19.展开更多
Background:Coronavirus disease 2019(COVID-19)is a global pandemic with high mortality,and the treatment options for the severe patients remain limited.Previous studies reported the altered gut mi-crobiota in severe CO...Background:Coronavirus disease 2019(COVID-19)is a global pandemic with high mortality,and the treatment options for the severe patients remain limited.Previous studies reported the altered gut mi-crobiota in severe COVID-19.But there are no comprehensive data on the role of microbial metabolites in COVID-19 patients.Methods:We identified 153 serum microbial metabolites and assessed the changes in 72 COVID-19 pa-tients upon admission and one-month after their discharge,comparing these changes to those in 133 healthy control individuals from the outpatient department during the same period.Results:Our study revealed that microbial metabolites varied across different stages and severity of COVID-19 patients.These altered microbial metabolites included tryptophan,bile acids,fatty acids,amino acids,vitamins and those containing benzene.A total of 13 distinct microbial metabolites were identi-fied in COVID-19 patients compared to healthy controls.Notably,correlations were found among these disrupted metabolites and organ injury and inflammatory responses related to COVID-19.Furthermore,these metabolites did not restore to the normal levels one month after discharge.Importantly,two mi-crobial metabolites were the core microbial metabolites related to the severity of COVID-19 patients.Conclusions:The microbial metabolites were altered in the acute and recovery stage,correlating with dis-ease severity of COVID-19.These results indicated the important role of gut microbiota in the progression of COVID-19,and facilitated the potential therapeutic microbial target for severe COVID-19 patients.展开更多
BACKGROUND:The lack of a stable,easy-to-operate animal model for severe trauma has hindered the research progress.The aim of this study is to develop a mouse model that replicates the pathophysiological conditions of ...BACKGROUND:The lack of a stable,easy-to-operate animal model for severe trauma has hindered the research progress.The aim of this study is to develop a mouse model that replicates the pathophysiological conditions of severe trauma,providing a reliable research tool.METHODS:Male C57BL/6J mice(aged 8-10 weeks and weighting approximately 20 g)were used to establish the severe trauma model.Under anesthesia,a midshaft femoral fracture was created and packed with sterile cotton.A midline incision was made from the inguinal region to the sternum,exposing the abdominal organs for 30 min.The right femoral artery was cannulated to induce controlled blood loss at 30%,35%,40%,and 50%of the total blood volume.Survival rates were monitored for 24 h post-induction.In the mice that experienced 30%blood loss,the mean arterial pressure,body temperature,blood gas parameters,peripheral blood inflammatory markers,and major organ pathological changes were assessed.RESULTS:Mice with femoral fractures,soft tissue injuries,abdominal organ exposure,and 30%blood loss exhibited stable survival rates.Increased blood loss significantly reduced survival rates.Mean arterial pressure decreased initially,recovering within 0-15 min and returning to baseline by 50 min.Similarly,the body temperature decreased initially and gradually recovered to baseline within 50 min.Levels of peripheral blood inflammatory markers remained elevated for 12 h post-injury.Distant organs,including intestines,lungs,liver,spleen and kidneys,displayed varying degrees of injury.CONCLUSION:The established mouse model replicates the pathophysiological responses to severe trauma,indicating stability and reproducibility,which could be an useful tool for further trauma research.展开更多
基金supported by the National Natural Science Foundation of China,No.32071033(to MT)Basic and Applied Basic Research Foundation of Guangdong Province,Nos.2023A1515010140(to MT),2022A1515140169(to MT),2022A1515111096(to ZC)+3 种基金Science and Technology Project of Guangzhou,Nos.202201010015(to YL),2023A03J0790(to TJ)Basic and Applied Basic Research Foundation of Guangzhou,No.2023A04J1285(to ZC)Medical Research Foundation of Guangdong Province,No.A2023147(to ZC)Health Science and Technology Project of Guangzhou,No.20221A011039(to TJ)。
文摘Post-translational modification of spastin enables precise spatiotemporal control of its microtubule severing activity.However,the detailed mechanism by which spastin turnover is regulated in the context of neurite outgrowth remains unknown.Here,we found that spastin interacted with ubiquitin and was significantly degraded by K48-mediated poly-ubiquitination.Cullin3 facilitated spastin degradation and ubiquitination.RING-box protein 1,but not RING-box protein 2,acted synergistically with Cullin3 protein to regulate spastin degradation.Overexpression of Culin3 or BRX1 markedly suppressed spastin expression,and inhibited spastin-mediated microtubule severing and promotion of neurite outgrowth.Moreover,USP14 interacted directly with spastin to mediate its deubiquitination.USP14 overexpression significantly increased spastin expression and suppressed its ubiquitination and degradation.Although co-expression of spastin and USP14 did not enhance microtubule severing,it did increase neurite length in hippocampal neurons.Taken together,these findings elucidate the intricate regulatory mechanisms of spastin turnover,highlighting the roles of the Cullin-3–Ring E3 ubiquitin ligase complex and USP14 in orchestrating its ubiquitination and degradation.The dynamic interplay between these factors governs spastin stability and function,ultimately influencing microtubule dynamics and neuronal morphology.These insights shed light on potential therapeutic targets for neurodegenerative disorders associated with spastin defects.
文摘The effects of major veins severing on morphological and physiological features of sweetgum （Liquidambar styraciflua L.） leaves were investigated by observing leaf color change and measuring leaf temperature, green/luminance （G/L） value of half-lobes, leaf stomata conductance, and water content in Yamaguchi University, Japan. The palmately veined leaves of sweetgum （Liquidambar styraciflua L.） were found more sensitive to the major vein severing than that of other species Major veins severing resulted in serious water stresses, as indicated by the persistent reddening and/or advanced reddening of local leaf, lower leaf stomatal conductance, and higher leaf temperature, etc. Severed leaf can be clearly divided into non-severed area, transitional area, and stressed area, which the three areas have different colours and temperature. The major vein barrier can also be seen clearly. The persistent reddening and advanced reddening seem consistent with the phenomenon of red crown top of some sweetgum trees and may have similar mechanism.
基金the Teaching and Research Core Facility at the College of Life Sciences,NWAFU for support in this worksupported by grants from the National Natural Science Foundation of China(31770205 and 31970186 to X.L.,31870268 to F.Y.)。
文摘Plant interphase cortical microtubules(cMTs)mediate anisotropic cell expansion in response to environmental and developmental cues.In Arabidopsis thaliana,KATANIN 1(KTN1),the p60 catalytic subunit of the conserved MT-severing enzyme katanin,is essential for cMT ordering and anisotropic cell expansion.However,the regulation of KTN1-mediated cMT severing and ordering remains unclear.In this work,we report that the Arabidopsis IQ67 DOMAIN(IQD)family gene ABNORMAL SHOOT 6(ABS6)encodes a MT-associated protein.Overexpression of ABS6 leads to elongated cotyledons,directional pavement cell expansion,and highly ordered transverse cMT arrays.Genetic suppressor analysis revealed that ABS6-mediated cMT ordering is dependent on KTN1 and SHADE AVOIDANCE 4(SAV4).Live imaging of cMT dynamics showed that both ABS6 and SAV4 function as positive regulators of cMT severing.Furthermore,ABS6 directly interacts with KTN1 and SAV4 and promotes their recruitment to the cMTs.Finally,analysis of loss-of-function mutant combinations showed that ABS6,SAV4,and KTN1 work together to ensure the robust ethylene response in the apical hook of dark-grown seedlings.Together,our findings establish ABS6 and SAV4 as positive regulators of cMT severing and ordering,and highlight the role of cMT dynamics in fine-tuning differential growth in plants.
基金Supported by a grant from the US Department of Energy,Bioscience Division(DE-FG02-03ER15 415).
文摘Katanin is a heterodimeric microtubule （MT） severing protein that uses energy from ATP hydrolysis to generate internal breaks along MTs. Katanin p60, one of the two subunits, possesses ATPase and MT-binding/severing activities, and the p 80 subunit is responsible for targeting of katanin to certain subcellular locations. In animals, katanin plays an important role in the release of MTs from their nucleation sites in the centrosome. It is also involved in severing MTs into smaller fragments which can serve as templates for further polymerization to increase MT number during meiotic and mitotic spindle assembly. Katanin homologs are present in a wide variety of plant species. The Arabidopsis katanin homolog has been shown to possess ATP-dependent MT severing activity in vitro and exhibit a punctate localization pattern at the cell cortex and the perinuclear region. Disruption of katanin functions by genetic mutations causes a delay in the disappearance of the perinuclear MT array and results in an aberrant organization of cortical MTs in elongating cells. Consequently, katanin mutations lead to defects in cell elongation, cellulose microfibril deposition, and hormonal responses. Studies of katanin in plants provide new insights into our understanding of its roles in cellular functions.
基金Supported by Foundation of Shanghai Baoshan Science and Technology Commission,No.2024-E-66Shanghai Nursing Association Scientific Research Project,No.2024MS-B02.
文摘BACKGROUND Parkinson’s disease(PD)is a common neurodegenerative disorder in the elderly population.Non-motor symptoms such as anxiety and depression are often subtle,hindering early detection and intervention,yet they markedly affect quality of life and clinical outcomes.AIM To investigate the prevalence of anxiety and depression in elderly PD patients,identify associated risk factors,and assess their relationship with fatigue severity.METHODS A cross-sectional analysis was conducted in 123 elderly PD patients treated at The Second Rehabilitation Hospital of Shanghai between January 2023 and December 2024.Demographic and clinical data were obtained using standardized questionnaires.Anxiety,depression,and fatigue were assessed using the Beck Anxiety Inventory(BAI),Geriatric Depression Scale(GDS),and Fatigue Scale-14(FS-14),respectively.Binary logistic regression identified risk factors for anxiety and depression,whereas Spearman’s correlation assessed associations with fatigue.RESULTS Anxiety and depression prevalence rates were 64.2%(mean BAI score:19.59±10.92)and 56.1%(mean GDS score:12.82±6.37),respectively.The mean FS-14 total score was 9.46±1.89,comprising physical(5.77±1.51)and mental(3.69±1.20)fatigue components.Significant positive correlations were observed between fatigue scores(total,physical,and mental)and both anxiety and depression(all P<0.05).Univariate analysis revealed statistically significant associations between anxiety/depression and monthly income,disease duration,and disease severity(all P<0.05).Multivariate logistic regression indicated higher anxiety risk in patients with lower monthly income,prolonged disease duration,advanced disease severity,or multimorbidity.Depression risk was elevated in patients with lower monthly income and severe disease,whereas longer disease duration unexpectedly served as a protective factor.CONCLUSION Elderly PD patients show high rates of anxiety and depression,both of which are significantly correlated with fatigue severity.These findings highlight the importance of psychological monitoring and targeted mental health interventions in PD management among the elderly.
基金supported by the Scientific Research Project of the Health Commission of Shanxi Province(No.2024003)。
文摘This article reviews research advances in the application of early enteral nutrition(EEN)in elderly patients with severe acute pancreatitis(SAP).Elderly SAP patients are associated with higher mor tality rates due to age-related immune dysfunction,whereas EEN has been demonstrated to improve clinical prognosis,reduce infection and complication rates,and shor ten hospital stays.However,ongoing debates exist regarding the optimal timing,route selection,and complication management of EEN.Through a systematic review of the literature,this study synthesizes current evidence on EEN in elderly SAP populations,critically examines unresolved clinical controversies,and proposes future research priorities to inform evidence-based practice.
基金Jiangsu Provincial Hospital Association Hospital Management Innovation Research Fund(Project Ni.:JSYGY-3-2025-267)。
文摘Severe trauma often involves complex injuries,leading to high disability and fatality rates.Effective treatment requires prompt and coordinated efforts across multiple disciplines to enhance success rates.Time-based chain rescue is crucial in managing severe trauma.A patient with chest and abdominal injuries and hemorrhagic shock was transferred from an ambulance to our hospital.Our trauma team-initiated pre-hospital first aid,utilized an emergency green channel,and conducted rapid ultrasound,collaborating across disciplines.The patient eventually recovered and was discharged.
基金“Artificial Liver Special Fund”of Beijing Gan Dan Xiang Zhao Public Welfare Foundation(Project No.:iGandanF-1082024-RGG055)。
文摘A case of imported severe falciparum malaria with spontaneous splenic rupture was reported in this paper.The patient,an African migrant worker,developed hemolytic anemia,sepsis,thrombocytopenia,coagulation dysfunction,liver failure,renal insufficiency,electrolyte disturbance and other clinical manifestations after returning to the local area.Plasmodium falciparum was found by peripheral blood smearscopy and was diagnosed as severe falciparum malaria.After standardized anti-malaria treatment,plasma exchange+cytokine adsorption therapy,the establishment of“forewarning-forewarning-prevention-emergency”predictive nursing management model,the establishment of an integrated nursing team,the division of medical care is clear,professional knowledge is complementary,after three months of regular follow-up,the patient has no malaria recurrence,no refire,the function of all organs returned to normal.
文摘Automated grading of dandruff severity is a clinically significant but challenging task due to the inherent ordinal nature of severity levels and the high prevalence of label noise from subjective expert annotations.Standard classification methods fail to address these dual challenges,limiting their real-world performance.In this paper,a novel,three-phase training framework is proposed that learns a robust ordinal classifier directly from noisy labels.The approach synergistically combines a rank-based ordinal regression backbone with a cooperative,semi-supervised learning strategy to dynamically partition the data into clean and noisy subsets.A hybrid training objective is then employed,applying a supervised ordinal loss to the clean set.The noisy set is simultaneously trained using a dualobjective that combines a semi-supervised ordinal loss with a parallel,label-agnostic contrastive loss.This design allows themodel to learn fromthe entire noisy subset while using contrastive learning to mitigate the risk of error propagation frompotentially corrupt supervision.Extensive experiments on a new,large-scale,multi-site clinical dataset validate our approach.Themethod achieves state-of-the-art performance with 80.71%accuracy and a 76.86%F1-score,significantly outperforming existing approaches,including a 2.26%improvement over the strongest baseline method.This work provides not only a robust solution for a practical medical imaging problem but also a generalizable framework for other tasks plagued by noisy ordinal labels.
文摘Dengue fever is an acute infectious disease caused by the dengue virus and transmitted by mosquito vectors[1].Its clinical manifestations include high fever,headache,muscle and joint pain,and rash.It holds a significant position in global public health.In recent years,its incidence has continued to rise worldwide[2],making it one of the major diseases threatening human health.The disease course of dengue fever is divided into three typical phases:the acute febrile phase,the critical phase,and the recovery phase.While most patients experience mild symptoms,some may progress to severe dengue and potentially fatal outcomes if not promptly and effectively treated during the critical phase.
基金supported by Shenzhen Science and Technology Program, No. JCYJ20230807110259002 (to JL)The Seventh Affiliated Hospital of Sun Yat-sen University, No. ZSQYRSFPD0050 (to JL)The Postdoctoral Fellowship Program of CPSF, No. GZC20242074 (to KT)
文摘Oxidative stress significantly contributes to secondary damage after spinal cord injury.Despite its importance,research on oxidative stress in spinal cord injury remains limited.Investigating the expression and regulation of oxidative stress-related genes could enhance the diagnosis and treatment of spinal cord injury.In this study,we analyzed the sequencing data of human blood samples and injured mouse spinal cord tissue that were sourced from GEO databases and identified diagnostic biomarkers associated with the severity of spinal cord injury.We also explored the expression patterns of oxidative stress-related genes,potential regulatory mechanisms,and therapeutic drugs.To validate our findings,we performed immunofluorescence and quantitative polymerase chain reaction to assess gene expression in the injured spinal cord.Our results revealed biomarkers associated with oxidative stress and immune responses across different levels of spinal cord injury in humans.We identified differentially expressed oxidative stress-related genes and key hub genes in injured mouse spinal cord tissue and revealed their temporal expression patterns at both the tissue and single-cell levels.We also clarified the signaling pathways associated with oxidative stress and identified ligand-receptor pairs among various cell types at different time points after injury.Furthermore,we discovered microRNAs,long non-coding RNAs,and transcription factors that regulate these hub genes and revealed their roles in modulating gene expression at various stages after spinal cord injury.We also identified drugs targeting these hub genes.The findings from this study not only aid in identifying diagnostic biomarkers that reflect the severity of spinal cord injury,but also provide insights into the expression dynamics of oxidative stress-related genes.In addition,the study reveals potential regulatory mechanisms and identifies potential drugs to treat patients with spinal cord injury.
基金The Korea Centers for Disease Control and Prevention,Grant/Award Number:2022-ER1701-00,2022-NI-041-02,2024-ER1702-00 and 2025-NI-014-00。
文摘Background:Humanized mouse models are essential for studying the human immune response and antibody development.However,conventional models show limited B cell maturation and antigen-specific humoral responses.To overcome these limitations,we used the NOG-EXL mice expressing human interleukin 3(IL-3)and granulocyte-macrophage colony-stimulating factor(GM-CSF)to enhance myeloid and B-cell lineage differentiation.Methods:Human CD34^(+)hematopoietic stem cells(HSC)were transplanted into NOG-EXL mice to produce humanized immune systems.After immune cell reconstitution was confirmed across 12 weeks,the mice were immunized twice with inactivated severe fever with thrombocytopenia syndrome virus(SFTSV)antigens.Peripheral blood mononuclear cells and splenocytes were analyzed using multicolor flow cytometry to assess human immune cell subsets.Antigen-specific immunoglobulin G(IgG)production was quantified using enzyme-linked immunosorbent assay(ELISA),and virus-specific B cells were isolated using antigen-labeled recombinant protein probes.Results:Twelve weeks after transplantation of HSCs into NOG-EXL mice,they exhibited robust engraftment of human leukocytes,including T,B,and dendritic cells,compared to NOG mice.Unlike NOG mice,humanized NOG-EXL mice exhibited an increase in human IgG levels,indicating the production of human antibody responses to antigens.Humanized NOG-EXL mice were immunized twice every 2 weeks with inactivated SFTSV,and antigen-specific human antibodies against the virus were detected in the mouse sera by ELISA.Sera from SFTSV-immunized humanized mice demonstrated neutralizing activity against SFTSV,confirming the induction of functional virus-specific neutralizing antibodies.Antigen-binding IgG-positive human B cells were isolated from mouse splenocytes using recombinant protein probes.Conclusion:This model provides a valuable platform for evaluating humoral immunity and isolating B cells using high-affinity human monoclonal antibodies without genetic engineering.
基金supported by funds from the Conselho Nacional de Desenvolvimento Cientifico e Tecnologico do Brasil(CNPq)(312286/2023-6,307201/2023-6,and Instituto Nacional Saude Cerebral INSC,No.406020/2022-1)Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior(CAPES)Fundacao de Amparo a Pesquisa do Estado do Rio de Janeiro-FAPERJ(E-26/010.002260/2019,E-26/010.001652/2019,E-26/010.101036/2018,E-26/202.774/2018,E-26/210.240/2020,E-26/211.138/2021,26/210.823/2021,E-26/211.325/2021,E-26/210.779/2021,E-26/201.086/2022,E-26/210.312/2022,E-26/203.262/2023,E-26/200.195/2023)(to LEBS)。
文摘Recent increases in infectious diseases affecting the central nervous system have raised concerns about their role in neuroinflammation and neurodegeneration.Viral pathogens or their products can invade the central nervous system and cause damage,leading to meningitis,encephalitis,meningoencephalitis,myelitis,or post-infectious demyelinating diseases.Although neuroinflammation initially has a protective function,chronic inflammation can contribute to the development of neurodegenerative diseases.Mechanisms such as protein aggregation and cellular disturbances are implicated with specific viruses such as herpes simplex virus type 1 and Epstein-Barr virus being associated with Alzheimer's disease and multiple sclerosis,respectively.Extracellular nucleotides,particularly adenosine triphosphate and its metabolites are released from activated,infected,and dying cells,acting as alarmins mediating neuroinflammation and neurodegeneration.When viruses infect central nervous system cells,adenosine triphosphate is released as an alarmin,triggering inflammatory responses.This process is mediated by purinergic receptors,divided into two families:P1,which responds to adenosine,and P2,activated by adenosine triphosphate and other nucleotides.This review highlights how specific viruses,such as human immunodeficiency virus type 1,Theiler's murine encephalomyelitis virus,herpes simplex virus type 1,Epstein-Barr virus,dengue virus,Zika virus,and severe acute respiratory syndrome coronavirus 2,can initiate inflammatory responses through the release of extracellular nucleotides,particularly adenosine triphosphate,which act as critical mediators in the progression of neuroinflammation and neurodegenerative disorders.A better understanding of purinergic signaling pathways in these diseases may suggest new potential therapeutic strategies for targeting neuroinflammation to mitigate the long-term consequences of viral infections in the central nervous system.
文摘Severe acute pancreatitis(SAP)can induce acute respiratory distress syndrome(ARDS)and abdominal compartment syndrome(ACS).Although prone position ventilation(PPV)can improve outcomes in patients with ARDS,there is significant controversy regarding its concurrent use with ACS owing to concerns of increased risk of intra-abdominal pressure(IAP).[1]We present a case of successful PPV application without adverse eff ects.
文摘BACKGROUND The imbalance of hormone levels in the body is closely related to the occurrence and progression of schizophrenia,especially thyroid hormones.AIM To study the relationship between triiodothyronine(T3),thyroxine(T4),free T3(FT3),free T4(FT4),thyroid stimulating hormone(TSH)and schizophrenia.METHODS In this study,100 schizophrenia patients were selected from our hospital between April 2022 and April 2024.Their clinical data were analyzed retrospectively.Based on the Positive and Negative Syndrome Scale(PANSS)score,patients were divided into mild(1-3 points,n=39),moderate(4 points,n=45),and severe groups(5-7 points,n=16).Additionally,55 healthy individuals served as a control group.Venous blood samples were collected to measure T3,T4,FT3,FT4,TSH,and cortisol concentrations,analyzing their relationship with PANSS scores.RESULTS The serum levels of T3,FT3,FT4,TSH and cortisol in the schizophrenia group were lower than those in the control group(P<0.05).With the increase of the severity of the disease,the concentrations of T3 and T4 decreased,while the con-centrations of TSH and cortisol increased(P<0.05).The concentrations of TSH and cortisol were positively correlated with the PANSS score,while T3 and T4 were negatively correlated with the PANSS score(P<0.05).The receiver ope-rating characteristic curve results showed that T3,T4,TSH,and cortisol had good efficacy in the diagnosis of schizophrenia.Logistic results showed that decreased T3 level,decreased T4 level,decreased TSH level and increased cortisol level may be independent risk factors for schizophrenia.CONCLUSION Thyroid hormone levels are associated with the severity of schizophrenia symptoms,which can provide new solutions for the diagnosis and treatment of schizophrenia.
基金supported by the National Natural Science Foundation of China(32170144 and 32470146).
文摘Severe fever with thrombocytopenia syndrome(SFTS)is a novel emerging acute infectious disease caused by severe fever with thrombocytopenia syndrome virus(SFTSV),characterized by high fever and thrombocytopenia.It has been proved that traditional Chinese medicine(TCM)has displayed definite therapeutic effects on viral hemorrhagic fever,indicating its potential to treat SFTS.In this study,SFTS-relative key targets were predicted via gene ontology(GO)analysis and kyoto encyclopedia of genes and genomes(KEGG)enrichment analysis.Molecular docking was then used to select stable binders.Molecules matched TCMs were identified,and a new prescription,Qingqi Guxue decoction(QQGX),was formulated to clear heat and nourish blood,with a resulting drug composition network.We explored the optimal drug proportion for QQGX.Through an in-depth study of molecular mechanisms,we found that QQGX induces S phase arrest by promoting the degradation of cyclin A2(CCNA2)and cyclin-dependent kinase 2(CDK2),thereby inhibiting SFTSV replication.Finally,we verified the effectiveness and safety of QQGX based on the mouse liver bile duct organoid model infected with SFTSV.In summary,our study prepared a TCM decoction using the method of network pharmacology.This decoction has a significant inhibitory effect on the replication of SFTSV and provides a new treatment strategy for hemorrhagic fever with TCM.
基金jointly General Research Fund(17121619)of the Research Grant Council of Hong KongGuangdong Basic and Applied Basic Research Foundation(2024A1515010104 and 2023A1515220095)Scientific Research Foundation of Peking University Shenzhen Hospital(KYQD202100X)。
文摘Fibrotic remodeling of nucleus pulposus(NP)leads to structural and mechanical anomalies of intervertebral discs that prone to degeneration,leading to low back pain incidence and disability.Emergence of fibroblastic cells in disc degeneration has been reported,yet their nature and origin remain elusive.In this study,we performed an integrative analysis of multiple single-cell RNA sequencing datasets to interrogate the cellular heterogeneity and fibroblast-like entities in degenerative human NP specimens.We found that disc degeneration severity is associated with an enrichment of fibrocyte phenotype,characterized by CD45 and collagen I dual positivity,and expression of myofibroblast markerα-smooth muscle actin.Refined clustering and classification distinguished the fibrocyte-like populations as subtypes in the NP cells-and immunocytes-clusters,expressing disc degeneration markers HTRA1 and ANGPTL4 and genes related to response to TGF-β.In injury-induced mouse disc degeneration model,fibrocytes were found recruited into the NP undergoing fibrosis and adopted a myofibroblast phenotype.Depleting the fibrocytes in CD11b-DTR mice in which myeloid-derived lineages were ablated by diphtheria toxin could markedly attenuate fibrous modeling and myofibroblast formation in the NP of the degenerative discs,and prevent disc height loss and histomorphological abnormalities.Marker analysis supports that disc degeneration progression is dependent on a function of CD45^(+)COL1A1^(+)andαSMA^(+)cells.Our findings reveal that myeloid-derived fibrocytes play a pivotal role in NP fibrosis and may therefore be a target for modifying disc degeneration and promoting its repair.
基金supported by the National Key Research and Development Program of China(NKPs)(2022YFC2604101).
文摘Aging is one of the greatest risk factors for morbidity caused by the coronavirus disease 2019(COVID19).In older individuals,a dysregulated immune response to severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)infection contributes to disease severity;however,the underlying mechanism remains elusive.In this study,we established an aging mouse model of COVID-19,successfully replicating the development of a relatively severe disease in older adults.Further single-cell transcriptome analysis revealed a distinct immune cell landscape in the infected lungs,accompanied by an over-activated inflammatory response,especially in aging mice.Compared to young mice,aging mice showed extensive neutrophil activation,NETosis,and a dramatic decrease in the number of alveolar macrophages(AMs).Moreover,as important executors of efferocytosis,AMs exhibited a low efferocytotic gene signature and downregulation of multiple efferocytosis receptors in aged mice.Further analysis indicated that the efferocytosis of neutrophils,whether undergoing apoptosis or NETosis,was compromised after SARS-CoV-2 infection.Since efferocytosis is a key process in inflammatory resolution,impaired efferocytosis may contribute to hyperinflammation in aging lungs.Our study reveals the characteristics and role of efferocytosis in aging mice after SARS-CoV-2 infection and provides valuable insights for the potential treatment of COVID-19.
基金supported by grants from the National Key R&D Program of China(2021YFA1301001)the Natural Science Founda-tion of China(82170668)+1 种基金the Sino-German Center for Research Promotion(GZ1546)the CAMS Innovation Fund for Medical Sciences(2019-I2M-5-045).
文摘Background:Coronavirus disease 2019(COVID-19)is a global pandemic with high mortality,and the treatment options for the severe patients remain limited.Previous studies reported the altered gut mi-crobiota in severe COVID-19.But there are no comprehensive data on the role of microbial metabolites in COVID-19 patients.Methods:We identified 153 serum microbial metabolites and assessed the changes in 72 COVID-19 pa-tients upon admission and one-month after their discharge,comparing these changes to those in 133 healthy control individuals from the outpatient department during the same period.Results:Our study revealed that microbial metabolites varied across different stages and severity of COVID-19 patients.These altered microbial metabolites included tryptophan,bile acids,fatty acids,amino acids,vitamins and those containing benzene.A total of 13 distinct microbial metabolites were identi-fied in COVID-19 patients compared to healthy controls.Notably,correlations were found among these disrupted metabolites and organ injury and inflammatory responses related to COVID-19.Furthermore,these metabolites did not restore to the normal levels one month after discharge.Importantly,two mi-crobial metabolites were the core microbial metabolites related to the severity of COVID-19 patients.Conclusions:The microbial metabolites were altered in the acute and recovery stage,correlating with dis-ease severity of COVID-19.These results indicated the important role of gut microbiota in the progression of COVID-19,and facilitated the potential therapeutic microbial target for severe COVID-19 patients.
基金supported by the National Natural Science Foundation of China(82102315).
文摘BACKGROUND:The lack of a stable,easy-to-operate animal model for severe trauma has hindered the research progress.The aim of this study is to develop a mouse model that replicates the pathophysiological conditions of severe trauma,providing a reliable research tool.METHODS:Male C57BL/6J mice(aged 8-10 weeks and weighting approximately 20 g)were used to establish the severe trauma model.Under anesthesia,a midshaft femoral fracture was created and packed with sterile cotton.A midline incision was made from the inguinal region to the sternum,exposing the abdominal organs for 30 min.The right femoral artery was cannulated to induce controlled blood loss at 30%,35%,40%,and 50%of the total blood volume.Survival rates were monitored for 24 h post-induction.In the mice that experienced 30%blood loss,the mean arterial pressure,body temperature,blood gas parameters,peripheral blood inflammatory markers,and major organ pathological changes were assessed.RESULTS:Mice with femoral fractures,soft tissue injuries,abdominal organ exposure,and 30%blood loss exhibited stable survival rates.Increased blood loss significantly reduced survival rates.Mean arterial pressure decreased initially,recovering within 0-15 min and returning to baseline by 50 min.Similarly,the body temperature decreased initially and gradually recovered to baseline within 50 min.Levels of peripheral blood inflammatory markers remained elevated for 12 h post-injury.Distant organs,including intestines,lungs,liver,spleen and kidneys,displayed varying degrees of injury.CONCLUSION:The established mouse model replicates the pathophysiological responses to severe trauma,indicating stability and reproducibility,which could be an useful tool for further trauma research.
