BACKGROUND Ampullary adenocarcinomas(AACs)are heterogeneous tumors currently classified into three important sub-classes(SC):Intestinal(INT),Pancreato-Biliary(PB)and Mixed-Type(MT).The different subgroups have similar...BACKGROUND Ampullary adenocarcinomas(AACs)are heterogeneous tumors currently classified into three important sub-classes(SC):Intestinal(INT),Pancreato-Biliary(PB)and Mixed-Type(MT).The different subgroups have similar clinical presentation and are treated by pancreatoduodenectomy with curative intent.However,they respond differently to chemotherapy and have different prognostic outcomes.The SC are often difficult to identify with conventional histology alone.The clinical outcome of all three remains unclear,particularly for MT.AIM To identify two main subtypes of AACs,using an immunohistochemical(IHC)score based on CDX2,CK7 and CK20.METHODS Tissue samples from 21 patients who had undergone resection of AAC were classified by HE histology and IHC expression of CDX2,CK7 and CK 20.An IHC score was obtained for each marker by counting the number of positive cells(0=no stained cells;1<25%;2<50%and 3>50%)and their intensity(1=weak;2=moderate and 3=strong).A global score(GS)was then obtained by summation of the IHC scores of each marker.The MT tumors were grouped either with the INT or PB group based on the predominant immuno-molecular phenotype,obtaining only two AACs subtypes.The overall survival in INT and PB patients was obtained by Kaplan-Meier methods.RESULTS Histological parameters defined the AACs subtypes as follows:15%INT,45%PB and 40%MT.Using IHC expression and the GS,75%and 25%of MT samples were assigned to either the INT or the PB group.The mean value of the GS was 9.5(range 4-16).All INT samples had a GS above the average,distinct from the PB samples which had a GS score significantly below the average(P=0.0011).The INT samples were identified by high expression of CDX2 and CK20,whereas PB samples exhibited high expression of CK7 and no expression of CK20(P=0.0008).The INT group had a statistically significant higher overall survival than in the PB group(85.7 mo vs 20.3 mo,HR:8.39;95%CI:1.38 to 18.90;P=0.0152).CONCLUSION The combination of histopathological and molecular criteria enables the classification of AACs into two clinically relevant histo-molecular phenotypes,which appear to represent distinct disorders with potentially significant changes to the current therapeutic strategies.展开更多
We conducted this study to determine if marker-assisted mass recurrent selection for fiberstrength and resistance to Helicoverpa armigerawithin an upland cotton complex populationcould he more efficient than conventio...We conducted this study to determine if marker-assisted mass recurrent selection for fiberstrength and resistance to Helicoverpa armigerawithin an upland cotton complex populationcould he more efficient than conventionalphenotype selection.Two cycles of marker-assisted selection,phenotypic selection,andmarker and phenotype concurrent selection,展开更多
AIM:To investigate whether celiac disease(CD)patients with tissue-transglutaminase antibody(tTGA)≥100 U/mL are different from patients with lower tTGA levels.METHODS:Biopsy-proven(MarshⅢ)pediatric CD patients(n=116)...AIM:To investigate whether celiac disease(CD)patients with tissue-transglutaminase antibody(tTGA)≥100 U/mL are different from patients with lower tTGA levels.METHODS:Biopsy-proven(MarshⅢ)pediatric CD patients(n=116)were prospectively included between March 2009 and October 2012.The biopsies were evaluated by a single pathologist who was blinded to all of the patients’clinical data.The patients were distributed into 2 groups according to their tTGA level,which was measured using enzyme-linked immunoassay:tTGA≥100 U/mL and Ttga<100 U/mL.The patients’characteristics,symptoms,human leukocyte antigen(HLA)genotype and degree of histological involvement were compared between the 2 groups.RESULTS:A total of 34(29.3%)children had tTGA values<100 U/mL and 82(70.7%)tTGA levels of≥100 U/mL.Patients with high tTGA levels had lower average body weight-for-height standard deviation scores(SDS)than did patients with tTGA<100 U/mL(-0.20±1.19 SDS vs 0.23±1.03 SDS,P=0.025).In the low tTGA group,gastrointestinal symptoms were more common(97.1%vs 75.6%,P=0.006).More specifically,abdominal pain(76.5%vs 51.2%;P=0.012)and nausea(17.6%vs 3.7%,P=0.018)were more frequent among patients with low tTGA.In contrast,patients with solely extraintestinal manifestations were only present in the high tTGA group(18.3%,P=0.005).These patients more commonly presented with aphthous stomatitis(15.9%vs 0.0%,P=0.010)and anemia(32.9%vs 11.8%,P=0.019).In addition,when evaluating the number of CD-associated HLA-DQ heterodimers(HLA-DQ2.5,HLA-DQ2.2 and HLA-DQ8),patients with low tTGA levels more commonly had only1 disease-associated heterodimer(61.8%vs 31.7%,P=0.005),while patients with high tTGA more commonly had multiple heterodimers.Finally,patients with tTGA≥100 U/mL more often had a MarshⅢc lesion(73.2%vs 20.6%,P≤0.001)while in patients with low tTGA patchy lesions were more common(42.4%vs6.8%,P≤0.001).CONCLUSION:Patients with tTGA≥100 U/mL show several signs of more advanced disease.They also carry a larger number of CD associated HLA-DQ heterodimers.展开更多
Objective:The global aim to lower preterm birth rates has been hampered by the insufficient and incomplete understanding of its etiology,classification,and diagnosis.This study was designed to evaluate the association...Objective:The global aim to lower preterm birth rates has been hampered by the insufficient and incomplete understanding of its etiology,classification,and diagnosis.This study was designed to evaluate the association of phenotypically classified preterm syndromes with neonatal outcomes;to what extent would these outcomes be modified after the obstetric interventions,including use of glucocorticoid,magnesium sulfate,and progesterone.Methods:This was a retrospective cohort study conducted at Tongji Hospital(composed of Main Branch,Optical Valley Branch and Sino-French New City Branch)in Wuhan.A total of 900 pregnant women and 1064 neonates were retrospectively enrolled.The outcomes were the distribution of different phenotypes among parturition signs and pathway to delivery,the association of phenotypically classified clusters with short-term unfavorable neonatal outcomes,and to what extent these outcomes could be modified by obstetric interventions.Results:Eight clusters were identified using two-step cluster analysis,including premature rupture of fetal membranes(PPROM)phenotype,abnormal amniotic fluid(AF)phenotype,placenta previa phenotype,mixed condition phenotype,fetal distress phenotype,preeclampsia-eclampsia&hemolysis,elevated liver enzymes,and low platelets syndrome(PE-E&HELLP)phenotype,multiple fetus phenotype,and no main condition phenotype.Except for no main condition phenotype,the other phenotypes were associated with one or more complications,which conforms to the clinical practice.Compared with no main condition phenotype,some phenotypes were significantly associated with short-term adverse neonatal outcomes.Abnormal AF phenotype,mixed condition phenotype,PE-E&HELLP phenotype,and multiple fetus phenotype were risk factors for neonatal small-for gestation age(SGA);placenta previa phenotype was not associated with adverse outcomes except low APGAR score being 0-7 at one min;mixed condition phenotype was associated with low APGAR scores,SGA,mechanical ventilation,and gradeⅢ-Ⅳintraventricular hemorrhage(IVH);fetal distress phenotype was frequently associated with neonatal SGA and mechanical ventilation;PE-E&HELLP phenotype was correlated with low APGAR score being 0-7 at one min,SGA and neonatal intensive care unit(NICU)admission;multiple fetus phenotype was not a risk factor for the outcomes included except for SGA.Not all neonates benefited from obstetric interventions included in this study.Conclusion:Our research disclosed the independent risk of different preterm phenotypes for adverse pregnancy outcomes.This study is devoted to putting forward the paradigm of classifying preterm birth phenotypically,with the ultimate purpose of defining preterm phenotypes based on multi-center studies and diving into the underlying mechanisms.展开更多
OPVs (open pollinated varieties) of cross pollinated crops are genetically heterogeneous and therefore likely to evolve over generations, under natural and human selection, which gives them a strong potential for orga...OPVs (open pollinated varieties) of cross pollinated crops are genetically heterogeneous and therefore likely to evolve over generations, under natural and human selection, which gives them a strong potential for organic and low input farming. OPVs of maize were cultivated and selected by different farmers in France and Italy for 2 generations. The third year, they were phenotypically evaluated for evolution, adaptation and level of diversity (estimated with Nei index) across evolution in a combined on farm and on station experimentation. The results showed that the varieties evolved and even adapted over 2 generations only (especially on maturity traits) but conserved their identity (no evolution of ear morphological traits). They all conserved their diversity, which demonstrated the pertinence of farmers’ selection (it is not a bottleneck). These results suggested that the genetically heterogeneous nature of OPVs is an asset for farmers because they can adapt these varieties to specific local conditions and production objectives. Therefore, farmer OPVs should receive more support through social and regulatory recognition, as well as further interest from research.展开更多
Organisms living in large groups often move together to navigate,forage for food,and increase their roaming range.Such groups are usually made up of distinct individuals that must integrate their different behaviors t...Organisms living in large groups often move together to navigate,forage for food,and increase their roaming range.Such groups are usually made up of distinct individuals that must integrate their different behaviors to migrate in the same direction at a similar pace.For instance,for the bacteria Escherichia coli(E.coli)to travel as a condensed group,they must coordinate their response to a set of chemical signals called chemoattractants that tell them where to go.展开更多
Ischemic stroke,a frequently occurring form of stroke,is caused by obstruction of cerebral blood flow,which leads to ischemia,hypoxia,and necrosis of local brain tissue.After ischemic stroke,both astrocytes and the bl...Ischemic stroke,a frequently occurring form of stroke,is caused by obstruction of cerebral blood flow,which leads to ischemia,hypoxia,and necrosis of local brain tissue.After ischemic stroke,both astrocytes and the blood–brain barrier undergo morphological and functional transformations.However,the interplay between astrocytes and the blood–brain barrier has received less attention.This comprehensive review explores the physiological and pathological morphological and functional changes in astrocytes and the blood–brain barrier in ischemic stroke.Post-stroke,the structure of endothelial cells and peripheral cells undergoes alterations,causing disruption of the blood–brain barrier.This disruption allows various pro-inflammatory factors and chemokines to cross the blood–brain barrier.Simultaneously,astrocytes swell and primarily adopt two phenotypic states:A1 and A2,which exhibit different roles at different stages of ischemic stroke.During the acute phase,A1 reactive astrocytes secrete vascular endothelial growth factor,matrix metalloproteinases,lipid carrier protein-2,and other cytokines,exacerbating damage to endothelial cells and tight junctions.Conversely,A2 reactive astrocytes produce pentraxin 3,Sonic hedgehog,angiopoietin-1,and other protective factors for endothelial cells.Furthermore,astrocytes indirectly influence blood–brain barrier permeability through ferroptosis and exosomes.In the middle and late(recovery)stages of ischemic stroke,A1 and A2 astrocytes show different effects on glial scar formation.A1 astrocytes promote glial scar formation and inhibit axon growth via glial fibrillary acidic protein,chondroitin sulfate proteoglycans,and transforming growth factor-β.In contrast,A2 astrocytes facilitate axon growth through platelet-derived growth factor,playing a crucial role in vascular remodeling.Therefore,enhancing our understanding of the pathological changes and interactions between astrocytes and the blood–brain barrier is a vital therapeutic target for preventing further brain damage in acute stroke.These insights may pave the way for innovative therapeutic strategies for ischemic stroke.展开更多
Nitrogen is essential for plant growth and development,with the ratio of ammonium(NH_(4)^(+))to nitrate(NO_(3)^(-))critically influencing physiological efficiency.This study investigated the effects of different NH_(4...Nitrogen is essential for plant growth and development,with the ratio of ammonium(NH_(4)^(+))to nitrate(NO_(3)^(-))critically influencing physiological efficiency.This study investigated the effects of different NH_(4)^(+)-N/NO_(3)^(-)-N mass ratios(0︰1,3︰7,1︰1,7︰3,1︰0)and a no-nitrogen control on Zanthoxylum planispinum var.dintanensis seedlings,using NH_(4)Cl and NaNO_(3) as nitrogen sources.Key results revealed that a 3︰7 NH_(4)^(+)︰NO_(3)^(-)ratio(T2)significantly enhanced stomatal conductance(G_(s)),amino acid content,root tip number,and the photochemical quenching parameters q_(P),q_(L),ETR,and F_(v)/F_(m).This treatment also maximized ground diameter increment,chlorophyll content,intercellular CO_(2)concentration(C_(i)),transpiration rate(T_(r)),ribulose-1,5-bisphosphate carboxylase(Rubisco)activity,nitrate reductase(NR)activity,and soluble protein content.Conversely,a 7︰3 ratio(T4)yielded the highest net photosynthetic rate(Pn)and fructose-1,6-bisphosphate aldolase(FBA)activity.Overall,the T4 treatment exhibited the second most effective promotion of Z.planispinum var.dintanensis seedling growth and development,after T2.In summary,mixed NH_(4)^(+)-N/NO_(3)^(-)-N nutrition markedly enhances seedling performance,with the 3︰7 ratio optimal for growth,photosynthesis,and nitrogen assimilation.Sole nitrogen sources,particularly pure NH_(4)^(+)-N,exert inhibitory effects.展开更多
BACKGROUND Many conditions may affect left ventricular(LV)phenotypes which have been classified according to LV mass and geometry.There is limited data on the prognostic value of LV phenotypes classified by cardiac ma...BACKGROUND Many conditions may affect left ventricular(LV)phenotypes which have been classified according to LV mass and geometry.There is limited data on the prognostic value of LV phenotypes classified by cardiac magnetic resonance(CMR).This study aimed to determine the prognostic value of LV phenotypes in elderly and non-elderly patients with known or suspected coronary artery disease.METHODS This is a retrospective cohort study among patients who underwent stress or viability CMR.LV phenotypes were classified according to the LV mass index,the LV end-diastolic volume index and the LV mass/volume ratio,into normal,concentric remodeling,concentric hypertrophy,and eccentric hypertrophy.The primary outcome was a composite of death or heart failure.RESULTS A total of 3289 patients was studied.The average age was 68.0±12.7 years,52.2%of patients were women.Elderly were defined as age≥65 years accounting for 63.9%of the cohort.LV phenotypes were normal,concentric remodeling,concentric hypertrophy,and eccentric hypertrophy at 74.5%,5.8%,9.2%,and 10.5%,respectively.The median duration of follow-up was 41.4 months.The composite outcome of death or heart failure occurred in 7.3%of patients.The prognostic impact of LV phenotypes was more pronounced in the elderly,with eccentric hypertrophy showing the worst prognosis,followed by concentric hypertrophy and concentric remodeling with the adjusted hazard ratio(95%CI)of 2.37(1.72–3.25),1.53(1.12–2.08),and 1.14(0.76–1.71),respectively,compared to normal phenotype.Patients with eccentric hypertrophy also demonstrated abnormal global longitudinal LV strain,left atrial strain,and extracellular volume fraction.CONCLUSIONS LV phenotypes by CMR independently predict adverse clinical outcomes in elderly patients with known or suspected coronary artery disease.In non-elderly patients,the prognostic value of LV phenotypes was less evident.Assessment of LV phenotypes may be useful for risk stratification.展开更多
BACKGROUND:Sepsis is a highly heterogeneous organ dysfunction syndrome.There is limited evidence regarding phenotypes and clinical outcomes in sepsis patients with initial normal lactate levels.We sought to identify t...BACKGROUND:Sepsis is a highly heterogeneous organ dysfunction syndrome.There is limited evidence regarding phenotypes and clinical outcomes in sepsis patients with initial normal lactate levels.We sought to identify the lactate-based clinical phenotypes and outcomes of sepsis patients.METHODS:The Medical Information Mart for Intensive Care IV(MIMIC-IV)and eICU databases were used to conduct a retrospective cohort study.Adult sepsis patients were included.Lactate was measured via blood gas,and the same assay type was used across both databases.Serial lactate measurements were analyzed via a two-point classification system based on the highest values recorded during two consecutive 24-hour periods following ICU admission.The fi rst measurement window(T1)comprised the initial 24 h post-admission,whereas the second window(T2)covered 24-48 h post-admission.The lactate diff erence was defi ned as the numerical change between the highest lactate level at T2 and the highest level at T1.The time interval between these two measurements was fi xed,with T2 commencing immediately after T1,together encompassing the fi rst 48 h post-ICU admission.A normal lactate level was defi ned as≤2 mmol/L,and an elevated level was defi ned as>2 mmol/L.Sepsis patients were stratifi ed into four trajectory phenotypes:(1)normal-normal(N-N);(2)normal-elevated(N-E);(3)elevated-normal(E-N);and(4)elevated-elevated(E-E).The primary outcome was in-hospital mortality.RESULTS:This study enrolled 6,926 sepsis patients.The clinical phenotypes of the sepsis patients were as follows:N-N(24.4%),N-E(3.8%),E-N(36.4%),and E-E(35.3%).The in-hospital mortality rates of sepsis patients with the four phenotypes from the MIMIC-IV and eICU databases were as follows(N-N:18.9%vs.17.6%,P=0.66;N-E:35.3%vs.29.2%,P=0.45;E-N:16.6%vs.14.2%,P=0.14;E-E:43.6%vs.37.8%,P=0.01).After adjusting for age,sex,Sequential Organ Failure Assessment(SOFA)score,vasopressor therapy,and infection sites,the N-E phenotype was associated with a higher risk of in-hospital mortality(odds ratio[OR]1.44;95%confidence intervals[95%CI]1.11-1.86;P=0.006;adjusted OR 1.61;95%CI 1.23-2.11;P<0.001).The E-N phenotype was associated with the most favorable outcomes for in-hospital mortality in the multivariable analysis(adjusted OR 0.41;95%CI 0.36-0.46;P<0.001).The E-E phenotype was associated with the highest risk of in-hospital mortality in the overall cohort(adjusted OR 3.00;95%CI 2.67-3.37;P<0.001).CONCLUSION:In sepsis patients with normal initial lactate levels,serial lactate measurements could be valuable for prognostic assessment.展开更多
Hepatocellular carcinoma presents with three distinct immune phenotypes,including immune-desert,immune-excluded,and immune-inflamed,indicating various treatment responses and prognostic outcomes.The clinical applicati...Hepatocellular carcinoma presents with three distinct immune phenotypes,including immune-desert,immune-excluded,and immune-inflamed,indicating various treatment responses and prognostic outcomes.The clinical application of multi-omics parameters is still restricted by the expensive and less accessible assays,although they accurately reflect immune status.A comprehensive evaluation framework based on“easy-to-obtain”multi-model clinical parameters is urgently required,incorporating clinical features to establish baseline patient profiles and disease staging;routine blood tests assessing systemic metabolic and functional status;immune cell subsets quantifying subcluster dynamics;imaging features delineating tumor morphology,spatial configuration,and perilesional anatomical relationships;immunohistochemical markers positioning qualitative and quantitative detection of tumor antigens from the cellular and molecular level.This integrated phenomic approach aims to improve prognostic stratification and clinical decision-making in hepatocellular carcinoma management conveniently and practically.展开更多
Objective:To investigate the efficacy and mechanism of Ditan Qingnao decoction(DTQND)in alleviating schizophrenia-like symptoms in a maternal immune activation(MIA)-induced rat model.Methods:DTQND components were anal...Objective:To investigate the efficacy and mechanism of Ditan Qingnao decoction(DTQND)in alleviating schizophrenia-like symptoms in a maternal immune activation(MIA)-induced rat model.Methods:DTQND components were analyzed using high-performance liquid chromatography-tandem mass spectrometry.An MIA-induced rat model was established by injecting Poly Ⅰ:C into pregnant dams on gestational day 9.Male offspring were administered DTQND(14.1 g/kg),risperidone(RIS;0.4 mg/kg),or distilled water,while the controls received only distilled water via gavage for 4 weeks.Behavioral assessments were conducted using the open-field,Y-maze,prepulse inhibition,and sucrose preference tests.Serum levels of interleukin(IL)-6,IL-18,IL-1β,and tumor necrosis factor-α(TNF-α)were measured via an enzyme-linked immunosorbent assay.Hippocampal protein levels of nuclear factor kappa B p65(NF-κB p65),phospho-NF-κB p65(p-p65),inhibitor of kappa B-alpha(IκB-α),phospho-IκB-α(p-IκB-α),and nucleotide-binding oligomerization domain-like receptor family pyrin domain-containing protein 3(NLRP3)were assessed via western blots.Immunohistochemistry detected hippocampal expression of ionized calcium-binding adapter molecule 1(Iba1)and cluster of differentiation 68(CD68).Results:Multiple DTQND compounds were identified,including stachyose,β-syringin,and isofraxidin,among others.DTQND treatment considerably enhanced spontaneous activity,reduced anxiety,improved spatial working memory,and alleviated sensory gating defects in male offspring with MIA.The DTQND group showed significantly lower serum levels of IL-1β(P=.002)and IL-18(P=.046)than the model group,with no discernible variations in IL-6 or TNF-α levels.In the hippocampus,DTQND significantly suppressed the expression of p-p65(P<.001),p-IκB-α(P=.023),and NLRP3(P<.001)compared to the model group.Additionally,DTQND modulated microglial activation markers,decreasing CD68 expression(P=.004)without affecting Iba1 levels.Conclusions:DTQND alleviated schizophrenia-like behavioral deficits and cognitive impairment by inhibiting the NF-κB/NLRP3 pathway,supporting its potential as an alternative therapy for schizophrenia.展开更多
Nondestructive measurement technology of phenotype can provide substantial phenotypic data support for applications such as seedling breeding,management,and quality testing.The current method of measuring seedling phe...Nondestructive measurement technology of phenotype can provide substantial phenotypic data support for applications such as seedling breeding,management,and quality testing.The current method of measuring seedling phenotypes mainly relies on manual measurement which is inefficient,subjective and destroys samples.Therefore,the paper proposes a nondestructive measurement method for the canopy phenotype of the watermelon plug seedlings based on deep learning.The Azure Kinect was used to shoot canopy color images,depth images,and RGB-D images of the watermelon plug seedlings.The Mask-RCNN network was used to classify,segment,and count the canopy leaves of the watermelon plug seedlings.To reduce the error of leaf area measurement caused by mutual occlusion of leaves,the leaves were repaired by CycleGAN,and the depth images were restored by image processing.Then,the Delaunay triangulation was adopted to measure the leaf area in the leaf point cloud.The YOLOX target detection network was used to identify the growing point position of each seedling on the plug tray.Then the depth differences between the growing point and the upper surface of the plug tray were calculated to obtain plant height.The experiment results show that the nondestructive measurement algorithm proposed in this paper achieves good measurement performance for the watermelon plug seedlings from the 1 true-leaf to 3 true-leaf stages.The average relative error of measurement is 2.33%for the number of true leaves,4.59%for the number of cotyledons,8.37%for the leaf area,and 3.27%for the plant height.The experiment results demonstrate that the proposed algorithm in this paper provides an effective solution for the nondestructive measurement of the canopy phenotype of the plug seedlings.展开更多
Peripheral artery disease(PAD)remains a significant global health issue,with current treatments primarily focused on relieving symptoms and addressingmacrovascular issues.However,critical immunoinflammatory mechanisms...Peripheral artery disease(PAD)remains a significant global health issue,with current treatments primarily focused on relieving symptoms and addressingmacrovascular issues.However,critical immunoinflammatory mechanisms are often overlooked.Recent evidence suggests that monocyte phenotypic plasticity plays a central role in PAD development,affecting atherogenesis,plaque progression,ischemia-reperfusion injury,and chronic ischemic remodeling.This narrative review aims to summarize the latest advances(2023-2025)in understanding monocyte diversity,functional states,and their changes throughout different stages of PAD.We discuss both established and emerging biomarkers,such as circulating monocyte subset proportions,functional assays,immune checkpoint expression,and multi-omics signatures,highlighting their potential for prognosis and the challenges in translating them to clinical practice.We also present a stage-specific approach to mapping out potential therapies,linking monocyte phenotypes to molecular targets and possible interventions.Additionally,we address regulatory,economic,and implementation considerations for applying these findings in a clinical setting.The goal of this review is to facilitate the development of targeted immunomodulatory strategies to improve limb and cardiovascular outcomes in PAD by combining mechanistic understanding with therapeutic innovation.展开更多
Objective:Sepsis exhibits remarkable heterogeneity in disease progression trajectories,and accurate identificationof distinct trajectory-based phenotypes is critical for implementing personalized therapeutic strategie...Objective:Sepsis exhibits remarkable heterogeneity in disease progression trajectories,and accurate identificationof distinct trajectory-based phenotypes is critical for implementing personalized therapeutic strategies and prognostic assessment.However,trajectory clustering analysis of time-series clinical data poses substantial methodological challenges for researchers.This study provides a comprehensive tutorial framework demonstrating six trajectory modeling approaches integrated with proteomic analysis to guide researchers in identifying sepsis subtypes after laparoscopic surgery.Methods:This study employs simulated longitudinal data from 300 septic patients after laparoscopic surgery to demonstrate six trajectory modeling methods(group-based trajectory modeling,latent growth mixture modeling,latent transition analysis,time-varying effect modeling,K-means for longitudinal data,agglomerative hierarchical clustering)for identifying associations between predefinedsequential organ failure assessment trajectories and 25 proteomic biomarkers.Clustering performance was evaluated via multiple metrics,and a biomarker discovery pipeline integrating principal component analysis,random forests,feature selection,and receiver operating characteristic analysis was developed.Results:The six methods demonstrated varying performance in identifying trajectory structures,with each approach exhibiting distinct analytical characteristics.The performance metrics revealed differences across methods,which may inform context-specificmethod selection and interpretation strategies.Conclusion:This study illustrates practical implementations of trajectory modeling approaches under controlled conditions,facilitating informed method selection for clinical researchers.The inclusion of complete R code and integrated proteomics workflows offers a reproducible analytical framework connecting temporal pattern recognition to biomarker discovery.Beyond sepsis,this pipeline-oriented approach may be adapted to diverse clinical scenarios requiring longitudinal disease characterization and precision medicine applications.The comparative analysis reveals that each method has distinct strengths,providing a practical guide for clinical researchers in selecting appropriate methods based on their specificstudy goals and data characteristics.展开更多
Parkinson’s disease(PD)is a neurodegenerative disorder characterized by the loss of dopaminergic neurons,and its prevalence is increasing,alongside global population aging.Neuroinflammation has been widely recognized...Parkinson’s disease(PD)is a neurodegenerative disorder characterized by the loss of dopaminergic neurons,and its prevalence is increasing,alongside global population aging.Neuroinflammation has been widely recognized as a pivotal contributor to PD pathogenesis,particularly owing to the dual role of microglia in this process.This review systematically identifies the multiple factors regulating microglial function and phenotype,thereby driving PD initiation and progression.Furthermore,aging,a major risk factor for PD,and its profound effects on microglial state and functional dynamics are discussed.Notably,microglial hyperactivation is shown to establish a self-perpetuating cycle of“inflammation–damage–reinflammation”through the excessive release of pro-inflammatory cytokines and chemokines,which exacerbates neuronal degeneration.Lastly,the potential therapeutic strategies targeting microglial dysfunction,including interventions against the senescence-associated secretory phenotype and the modulation of microglial activity,are summarized.By elucidating how multifactorial alterations in microglial states influence PD pathology,this review provides novel insights and directions for advancing therapeutic research in PD.展开更多
While methodology for determining the mode of evolution in coding sequences has been well established,evaluation of adaptation events in emerging types of phenotype data needs further development.Here,we propose an an...While methodology for determining the mode of evolution in coding sequences has been well established,evaluation of adaptation events in emerging types of phenotype data needs further development.Here,we propose an analysis framework(expression variance decomposition,EVaDe)for comparative single-cell expression data based on phenotypic evolution theory.After decomposing the gene expression variance into separate components,we use two strategies to identify genes exhibiting large between-taxon expression divergence and small within-cell-type expression noise in certain cell types,attributing this pattern to putative adaptive evolution.In a dataset of primate prefrontal cortex,we find that such humanspecific key genes enrich with neurodevelopment-related functions,while most other genes exhibit neutral evolution patterns.Specific neuron types are found to harbor more of these key genes than other cell types,thus likely to have experienced more extensive adaptation.Reassuringly,at the molecular sequence level,the key genes are significantly associated with the rapidly evolving conserved non-coding elements.An additional case analysis comparing the naked mole-rat(NMR)with the mouse suggests that innateimmunity-related genes and cell types have undergone putative expression adaptation in NMR.Overall,the EVaDe framework may effectively probe adaptive evolution mode in single-cell expression data.展开更多
Prevention of biological invasion requires understanding how alien species invade native communities.Although studies have identified mechanisms that underlie plant invasion in some habitats,limited attention has focu...Prevention of biological invasion requires understanding how alien species invade native communities.Although studies have identified mechanisms that underlie plant invasion in some habitats,limited attention has focused on invasion patterns along elevational gradients.In this study,we asked which factors drive the global and regional distribution of the invasive plant Galinsoga quadriradiata along elevational gradients.To answer this question,we examined whether human activities(i.e.,roads)promote G.quadriradiata invasion,how seed dispersal-related traits of G.quadriradiata change along elevation gradients,and whether G.quadriradiata has adapted to high-elevation environments through phenotypic plasticity or genetic variation.On the global scale,we found that human activities and road density positively contribute to the G.quadriradiata expansion in mountainous areas.Field surveys in China revealed significant elevational differences in the seed dispersal traits of G.quadriradiata,with higher-elevation populations exhibiting lower dispersal ability and generally lower genetic diversity.Under common conditions,high-elevation populations showed higher leaf mass ratio but lower root mass ratio and reproductive allocation.This suggests that high-elevation environments create a barrier to dispersal for G.quadriradiata,and that G.quadriradiata has adapted phenotypically to these conditions.Our study indicates that the elevational invasion pattern of G.quadriradiata is shaped by multiple factors,particularly human activities and phenotypic adaptability.In addition,our finding that G.quadriradiata invasion at high elevations is not constrained by low genetic diversity indicates that monitoring and management of G.quadriradiata in mountainous areas should be strengthened.展开更多
The growing recognition of the role of genetics in the development of amyotrophic lateral sclerosis is evident.However,there has yet to be a comprehensive analysis of the clinical characteristics and genetics of famil...The growing recognition of the role of genetics in the development of amyotrophic lateral sclerosis is evident.However,there has yet to be a comprehensive analysis of the clinical characteristics and genetics of familial amyotrophic lateral sclerosis in an Asian population.This study aimed to provide an in-depth analysis of the clinical features and genetic spectrum of familial amyotrophic lateral sclerosis over 15 years in a clinic-based cohort of patients from the Chinese mainland.Enrollment of 302 amyotrophic lateral sclerosis families from 28 provinces was undertaken from January 2008 to September 2023.A group-based trajectory model for disease progression based on amyotrophic lateral sclerosis Functional Rating Scale-Revised(ALSFRS-R)scores was validated using bootstrap internal validation in patients with familial amyotrophic lateral sclerosis,as well as patients with sporadic amyotrophic lateral sclerosis(matched at a 1:4 ratio,with replacement).DNA samples from 244 index patients were screened for variants in the pathogenic genes SOD1,FUS,TDP43,and C9ORF72,of which 146 were also subjected to genome-wide next-generation sequencing.Gene-level burden analysis was used to evaluate the distribution of rare variants in the cohort.We found that rapid dynamic disease progression was associated with an older age at onset,shorter diagnostic delay,lower body mass index,bulbar onset,and≥1 affected first-degree relative.Certain attributes,such as age at onset and time from onset to diagnosis,had comparable impacts on the clinical progression trajectories of both familial amyotrophic lateral sclerosis and sporadic amyotrophic lateral sclerosis.Harboring pathogenic/likely pathogenic variants in amyotrophic lateral sclerosis-causative genes reduced the age of onset of familial amyotrophic lateral sclerosis.Among the patients with familial amyotrophic lateral sclerosis,17.8%possessed≥2 pathogenic/likely pathogenic variants.Sequencing kernel association test analysis showed that the SOD1 rare variant burden(P=1.3e-15)was associated with a significant risk of familial amyotrophic lateral sclerosis.Our findings conclusively confirmed the clinical features and genetic spectrum of familial amyotrophic lateral sclerosis over 15 years in a clinical cohort from China,contributing to a deeper understanding of genotype-phenotype relationships in familial amyotrophic lateral sclerosis.This comprehensive evaluation of specific clinical characteristics,clinical prognosis,and genetic variants of amyotrophic lateral sclerosis based on detailed clinical and genetic information may lead to the development of genotype-specific treatment approaches.展开更多
Eggplant(Solanum melongena L.)is a globally important vegetable crop,renowned for its nutritional value and economic significance.It is abundant in bioactive compounds such as anthocyanins and chlorogenic acid,which h...Eggplant(Solanum melongena L.)is a globally important vegetable crop,renowned for its nutritional value and economic significance.It is abundant in bioactive compounds such as anthocyanins and chlorogenic acid,which have been associated with multiple health-promoting properties(Azuma et al.,2008;Gurbuz et al.,2018).Given its significant hybrid vigor,F1 hybrid varieties are widely preferred in commercial cultivation(Mistry et al.,2018).However,traditional breeding practices predominantly rely on phenotypic selection,a process that is not only labor-intensive but also time-consuming.展开更多
基金Supported by ARPA Foundation(www.fondazionearpa.it).
文摘BACKGROUND Ampullary adenocarcinomas(AACs)are heterogeneous tumors currently classified into three important sub-classes(SC):Intestinal(INT),Pancreato-Biliary(PB)and Mixed-Type(MT).The different subgroups have similar clinical presentation and are treated by pancreatoduodenectomy with curative intent.However,they respond differently to chemotherapy and have different prognostic outcomes.The SC are often difficult to identify with conventional histology alone.The clinical outcome of all three remains unclear,particularly for MT.AIM To identify two main subtypes of AACs,using an immunohistochemical(IHC)score based on CDX2,CK7 and CK20.METHODS Tissue samples from 21 patients who had undergone resection of AAC were classified by HE histology and IHC expression of CDX2,CK7 and CK 20.An IHC score was obtained for each marker by counting the number of positive cells(0=no stained cells;1<25%;2<50%and 3>50%)and their intensity(1=weak;2=moderate and 3=strong).A global score(GS)was then obtained by summation of the IHC scores of each marker.The MT tumors were grouped either with the INT or PB group based on the predominant immuno-molecular phenotype,obtaining only two AACs subtypes.The overall survival in INT and PB patients was obtained by Kaplan-Meier methods.RESULTS Histological parameters defined the AACs subtypes as follows:15%INT,45%PB and 40%MT.Using IHC expression and the GS,75%and 25%of MT samples were assigned to either the INT or the PB group.The mean value of the GS was 9.5(range 4-16).All INT samples had a GS above the average,distinct from the PB samples which had a GS score significantly below the average(P=0.0011).The INT samples were identified by high expression of CDX2 and CK20,whereas PB samples exhibited high expression of CK7 and no expression of CK20(P=0.0008).The INT group had a statistically significant higher overall survival than in the PB group(85.7 mo vs 20.3 mo,HR:8.39;95%CI:1.38 to 18.90;P=0.0152).CONCLUSION The combination of histopathological and molecular criteria enables the classification of AACs into two clinically relevant histo-molecular phenotypes,which appear to represent distinct disorders with potentially significant changes to the current therapeutic strategies.
文摘We conducted this study to determine if marker-assisted mass recurrent selection for fiberstrength and resistance to Helicoverpa armigerawithin an upland cotton complex populationcould he more efficient than conventionalphenotype selection.Two cycles of marker-assisted selection,phenotypic selection,andmarker and phenotype concurrent selection,
文摘AIM:To investigate whether celiac disease(CD)patients with tissue-transglutaminase antibody(tTGA)≥100 U/mL are different from patients with lower tTGA levels.METHODS:Biopsy-proven(MarshⅢ)pediatric CD patients(n=116)were prospectively included between March 2009 and October 2012.The biopsies were evaluated by a single pathologist who was blinded to all of the patients’clinical data.The patients were distributed into 2 groups according to their tTGA level,which was measured using enzyme-linked immunoassay:tTGA≥100 U/mL and Ttga<100 U/mL.The patients’characteristics,symptoms,human leukocyte antigen(HLA)genotype and degree of histological involvement were compared between the 2 groups.RESULTS:A total of 34(29.3%)children had tTGA values<100 U/mL and 82(70.7%)tTGA levels of≥100 U/mL.Patients with high tTGA levels had lower average body weight-for-height standard deviation scores(SDS)than did patients with tTGA<100 U/mL(-0.20±1.19 SDS vs 0.23±1.03 SDS,P=0.025).In the low tTGA group,gastrointestinal symptoms were more common(97.1%vs 75.6%,P=0.006).More specifically,abdominal pain(76.5%vs 51.2%;P=0.012)and nausea(17.6%vs 3.7%,P=0.018)were more frequent among patients with low tTGA.In contrast,patients with solely extraintestinal manifestations were only present in the high tTGA group(18.3%,P=0.005).These patients more commonly presented with aphthous stomatitis(15.9%vs 0.0%,P=0.010)and anemia(32.9%vs 11.8%,P=0.019).In addition,when evaluating the number of CD-associated HLA-DQ heterodimers(HLA-DQ2.5,HLA-DQ2.2 and HLA-DQ8),patients with low tTGA levels more commonly had only1 disease-associated heterodimer(61.8%vs 31.7%,P=0.005),while patients with high tTGA more commonly had multiple heterodimers.Finally,patients with tTGA≥100 U/mL more often had a MarshⅢc lesion(73.2%vs 20.6%,P≤0.001)while in patients with low tTGA patchy lesions were more common(42.4%vs6.8%,P≤0.001).CONCLUSION:Patients with tTGA≥100 U/mL show several signs of more advanced disease.They also carry a larger number of CD associated HLA-DQ heterodimers.
基金supported by the National Science Foundation of China(No.81873843)the National Science and Technology Pillar Program of China during the Twelfth Five-Year Plan Period(No.2014BAI05B05)the Fundamental Research Funds for the Central Universities(Nos.2017KFYXJJ102,2019KFYXKJC053).
文摘Objective:The global aim to lower preterm birth rates has been hampered by the insufficient and incomplete understanding of its etiology,classification,and diagnosis.This study was designed to evaluate the association of phenotypically classified preterm syndromes with neonatal outcomes;to what extent would these outcomes be modified after the obstetric interventions,including use of glucocorticoid,magnesium sulfate,and progesterone.Methods:This was a retrospective cohort study conducted at Tongji Hospital(composed of Main Branch,Optical Valley Branch and Sino-French New City Branch)in Wuhan.A total of 900 pregnant women and 1064 neonates were retrospectively enrolled.The outcomes were the distribution of different phenotypes among parturition signs and pathway to delivery,the association of phenotypically classified clusters with short-term unfavorable neonatal outcomes,and to what extent these outcomes could be modified by obstetric interventions.Results:Eight clusters were identified using two-step cluster analysis,including premature rupture of fetal membranes(PPROM)phenotype,abnormal amniotic fluid(AF)phenotype,placenta previa phenotype,mixed condition phenotype,fetal distress phenotype,preeclampsia-eclampsia&hemolysis,elevated liver enzymes,and low platelets syndrome(PE-E&HELLP)phenotype,multiple fetus phenotype,and no main condition phenotype.Except for no main condition phenotype,the other phenotypes were associated with one or more complications,which conforms to the clinical practice.Compared with no main condition phenotype,some phenotypes were significantly associated with short-term adverse neonatal outcomes.Abnormal AF phenotype,mixed condition phenotype,PE-E&HELLP phenotype,and multiple fetus phenotype were risk factors for neonatal small-for gestation age(SGA);placenta previa phenotype was not associated with adverse outcomes except low APGAR score being 0-7 at one min;mixed condition phenotype was associated with low APGAR scores,SGA,mechanical ventilation,and gradeⅢ-Ⅳintraventricular hemorrhage(IVH);fetal distress phenotype was frequently associated with neonatal SGA and mechanical ventilation;PE-E&HELLP phenotype was correlated with low APGAR score being 0-7 at one min,SGA and neonatal intensive care unit(NICU)admission;multiple fetus phenotype was not a risk factor for the outcomes included except for SGA.Not all neonates benefited from obstetric interventions included in this study.Conclusion:Our research disclosed the independent risk of different preterm phenotypes for adverse pregnancy outcomes.This study is devoted to putting forward the paradigm of classifying preterm birth phenotypically,with the ultimate purpose of defining preterm phenotypes based on multi-center studies and diving into the underlying mechanisms.
文摘OPVs (open pollinated varieties) of cross pollinated crops are genetically heterogeneous and therefore likely to evolve over generations, under natural and human selection, which gives them a strong potential for organic and low input farming. OPVs of maize were cultivated and selected by different farmers in France and Italy for 2 generations. The third year, they were phenotypically evaluated for evolution, adaptation and level of diversity (estimated with Nei index) across evolution in a combined on farm and on station experimentation. The results showed that the varieties evolved and even adapted over 2 generations only (especially on maturity traits) but conserved their identity (no evolution of ear morphological traits). They all conserved their diversity, which demonstrated the pertinence of farmers’ selection (it is not a bottleneck). These results suggested that the genetically heterogeneous nature of OPVs is an asset for farmers because they can adapt these varieties to specific local conditions and production objectives. Therefore, farmer OPVs should receive more support through social and regulatory recognition, as well as further interest from research.
文摘Organisms living in large groups often move together to navigate,forage for food,and increase their roaming range.Such groups are usually made up of distinct individuals that must integrate their different behaviors to migrate in the same direction at a similar pace.For instance,for the bacteria Escherichia coli(E.coli)to travel as a condensed group,they must coordinate their response to a set of chemical signals called chemoattractants that tell them where to go.
基金supported by the National Natural Science Foundation of China,No.U21A20400(to QW)the National Natural Science Foundation of China,No.82104560(to CL)+1 种基金the Natural Science Foundation of Beijing,No.7232279(to XW)the Project of Beijing University of Chinese Medicine,Nos.2024-JYB-JBZD-043(to CL),2022-JYB-JBZR-004(to XW)。
文摘Ischemic stroke,a frequently occurring form of stroke,is caused by obstruction of cerebral blood flow,which leads to ischemia,hypoxia,and necrosis of local brain tissue.After ischemic stroke,both astrocytes and the blood–brain barrier undergo morphological and functional transformations.However,the interplay between astrocytes and the blood–brain barrier has received less attention.This comprehensive review explores the physiological and pathological morphological and functional changes in astrocytes and the blood–brain barrier in ischemic stroke.Post-stroke,the structure of endothelial cells and peripheral cells undergoes alterations,causing disruption of the blood–brain barrier.This disruption allows various pro-inflammatory factors and chemokines to cross the blood–brain barrier.Simultaneously,astrocytes swell and primarily adopt two phenotypic states:A1 and A2,which exhibit different roles at different stages of ischemic stroke.During the acute phase,A1 reactive astrocytes secrete vascular endothelial growth factor,matrix metalloproteinases,lipid carrier protein-2,and other cytokines,exacerbating damage to endothelial cells and tight junctions.Conversely,A2 reactive astrocytes produce pentraxin 3,Sonic hedgehog,angiopoietin-1,and other protective factors for endothelial cells.Furthermore,astrocytes indirectly influence blood–brain barrier permeability through ferroptosis and exosomes.In the middle and late(recovery)stages of ischemic stroke,A1 and A2 astrocytes show different effects on glial scar formation.A1 astrocytes promote glial scar formation and inhibit axon growth via glial fibrillary acidic protein,chondroitin sulfate proteoglycans,and transforming growth factor-β.In contrast,A2 astrocytes facilitate axon growth through platelet-derived growth factor,playing a crucial role in vascular remodeling.Therefore,enhancing our understanding of the pathological changes and interactions between astrocytes and the blood–brain barrier is a vital therapeutic target for preventing further brain damage in acute stroke.These insights may pave the way for innovative therapeutic strategies for ischemic stroke.
文摘Nitrogen is essential for plant growth and development,with the ratio of ammonium(NH_(4)^(+))to nitrate(NO_(3)^(-))critically influencing physiological efficiency.This study investigated the effects of different NH_(4)^(+)-N/NO_(3)^(-)-N mass ratios(0︰1,3︰7,1︰1,7︰3,1︰0)and a no-nitrogen control on Zanthoxylum planispinum var.dintanensis seedlings,using NH_(4)Cl and NaNO_(3) as nitrogen sources.Key results revealed that a 3︰7 NH_(4)^(+)︰NO_(3)^(-)ratio(T2)significantly enhanced stomatal conductance(G_(s)),amino acid content,root tip number,and the photochemical quenching parameters q_(P),q_(L),ETR,and F_(v)/F_(m).This treatment also maximized ground diameter increment,chlorophyll content,intercellular CO_(2)concentration(C_(i)),transpiration rate(T_(r)),ribulose-1,5-bisphosphate carboxylase(Rubisco)activity,nitrate reductase(NR)activity,and soluble protein content.Conversely,a 7︰3 ratio(T4)yielded the highest net photosynthetic rate(Pn)and fructose-1,6-bisphosphate aldolase(FBA)activity.Overall,the T4 treatment exhibited the second most effective promotion of Z.planispinum var.dintanensis seedling growth and development,after T2.In summary,mixed NH_(4)^(+)-N/NO_(3)^(-)-N nutrition markedly enhances seedling performance,with the 3︰7 ratio optimal for growth,photosynthesis,and nitrogen assimilation.Sole nitrogen sources,particularly pure NH_(4)^(+)-N,exert inhibitory effects.
文摘BACKGROUND Many conditions may affect left ventricular(LV)phenotypes which have been classified according to LV mass and geometry.There is limited data on the prognostic value of LV phenotypes classified by cardiac magnetic resonance(CMR).This study aimed to determine the prognostic value of LV phenotypes in elderly and non-elderly patients with known or suspected coronary artery disease.METHODS This is a retrospective cohort study among patients who underwent stress or viability CMR.LV phenotypes were classified according to the LV mass index,the LV end-diastolic volume index and the LV mass/volume ratio,into normal,concentric remodeling,concentric hypertrophy,and eccentric hypertrophy.The primary outcome was a composite of death or heart failure.RESULTS A total of 3289 patients was studied.The average age was 68.0±12.7 years,52.2%of patients were women.Elderly were defined as age≥65 years accounting for 63.9%of the cohort.LV phenotypes were normal,concentric remodeling,concentric hypertrophy,and eccentric hypertrophy at 74.5%,5.8%,9.2%,and 10.5%,respectively.The median duration of follow-up was 41.4 months.The composite outcome of death or heart failure occurred in 7.3%of patients.The prognostic impact of LV phenotypes was more pronounced in the elderly,with eccentric hypertrophy showing the worst prognosis,followed by concentric hypertrophy and concentric remodeling with the adjusted hazard ratio(95%CI)of 2.37(1.72–3.25),1.53(1.12–2.08),and 1.14(0.76–1.71),respectively,compared to normal phenotype.Patients with eccentric hypertrophy also demonstrated abnormal global longitudinal LV strain,left atrial strain,and extracellular volume fraction.CONCLUSIONS LV phenotypes by CMR independently predict adverse clinical outcomes in elderly patients with known or suspected coronary artery disease.In non-elderly patients,the prognostic value of LV phenotypes was less evident.Assessment of LV phenotypes may be useful for risk stratification.
基金supported by grants from National Natural Science Foundation of China (82402543)National High Level Hospital Clinical Research Funding (2022-PUMCH-B-109)+2 种基金CAMS Innovation Fund for Medical Sciences (CIFMS)(2021-I2M-1-020)Opening Foundation of Agile and Intelligent Computing Key Laboratory of Sichuan ProvinceSpecial Research Fund for Central Universities,Peking Union Medical College (3332024120)
文摘BACKGROUND:Sepsis is a highly heterogeneous organ dysfunction syndrome.There is limited evidence regarding phenotypes and clinical outcomes in sepsis patients with initial normal lactate levels.We sought to identify the lactate-based clinical phenotypes and outcomes of sepsis patients.METHODS:The Medical Information Mart for Intensive Care IV(MIMIC-IV)and eICU databases were used to conduct a retrospective cohort study.Adult sepsis patients were included.Lactate was measured via blood gas,and the same assay type was used across both databases.Serial lactate measurements were analyzed via a two-point classification system based on the highest values recorded during two consecutive 24-hour periods following ICU admission.The fi rst measurement window(T1)comprised the initial 24 h post-admission,whereas the second window(T2)covered 24-48 h post-admission.The lactate diff erence was defi ned as the numerical change between the highest lactate level at T2 and the highest level at T1.The time interval between these two measurements was fi xed,with T2 commencing immediately after T1,together encompassing the fi rst 48 h post-ICU admission.A normal lactate level was defi ned as≤2 mmol/L,and an elevated level was defi ned as>2 mmol/L.Sepsis patients were stratifi ed into four trajectory phenotypes:(1)normal-normal(N-N);(2)normal-elevated(N-E);(3)elevated-normal(E-N);and(4)elevated-elevated(E-E).The primary outcome was in-hospital mortality.RESULTS:This study enrolled 6,926 sepsis patients.The clinical phenotypes of the sepsis patients were as follows:N-N(24.4%),N-E(3.8%),E-N(36.4%),and E-E(35.3%).The in-hospital mortality rates of sepsis patients with the four phenotypes from the MIMIC-IV and eICU databases were as follows(N-N:18.9%vs.17.6%,P=0.66;N-E:35.3%vs.29.2%,P=0.45;E-N:16.6%vs.14.2%,P=0.14;E-E:43.6%vs.37.8%,P=0.01).After adjusting for age,sex,Sequential Organ Failure Assessment(SOFA)score,vasopressor therapy,and infection sites,the N-E phenotype was associated with a higher risk of in-hospital mortality(odds ratio[OR]1.44;95%confidence intervals[95%CI]1.11-1.86;P=0.006;adjusted OR 1.61;95%CI 1.23-2.11;P<0.001).The E-N phenotype was associated with the most favorable outcomes for in-hospital mortality in the multivariable analysis(adjusted OR 0.41;95%CI 0.36-0.46;P<0.001).The E-E phenotype was associated with the highest risk of in-hospital mortality in the overall cohort(adjusted OR 3.00;95%CI 2.67-3.37;P<0.001).CONCLUSION:In sepsis patients with normal initial lactate levels,serial lactate measurements could be valuable for prognostic assessment.
文摘Hepatocellular carcinoma presents with three distinct immune phenotypes,including immune-desert,immune-excluded,and immune-inflamed,indicating various treatment responses and prognostic outcomes.The clinical application of multi-omics parameters is still restricted by the expensive and less accessible assays,although they accurately reflect immune status.A comprehensive evaluation framework based on“easy-to-obtain”multi-model clinical parameters is urgently required,incorporating clinical features to establish baseline patient profiles and disease staging;routine blood tests assessing systemic metabolic and functional status;immune cell subsets quantifying subcluster dynamics;imaging features delineating tumor morphology,spatial configuration,and perilesional anatomical relationships;immunohistochemical markers positioning qualitative and quantitative detection of tumor antigens from the cellular and molecular level.This integrated phenomic approach aims to improve prognostic stratification and clinical decision-making in hepatocellular carcinoma management conveniently and practically.
基金supported by the Beijing Natural Science Foundation(7222274)the Fifth Batch of National Outstanding Talents in Clinical Chinese Medicine(20221)。
文摘Objective:To investigate the efficacy and mechanism of Ditan Qingnao decoction(DTQND)in alleviating schizophrenia-like symptoms in a maternal immune activation(MIA)-induced rat model.Methods:DTQND components were analyzed using high-performance liquid chromatography-tandem mass spectrometry.An MIA-induced rat model was established by injecting Poly Ⅰ:C into pregnant dams on gestational day 9.Male offspring were administered DTQND(14.1 g/kg),risperidone(RIS;0.4 mg/kg),or distilled water,while the controls received only distilled water via gavage for 4 weeks.Behavioral assessments were conducted using the open-field,Y-maze,prepulse inhibition,and sucrose preference tests.Serum levels of interleukin(IL)-6,IL-18,IL-1β,and tumor necrosis factor-α(TNF-α)were measured via an enzyme-linked immunosorbent assay.Hippocampal protein levels of nuclear factor kappa B p65(NF-κB p65),phospho-NF-κB p65(p-p65),inhibitor of kappa B-alpha(IκB-α),phospho-IκB-α(p-IκB-α),and nucleotide-binding oligomerization domain-like receptor family pyrin domain-containing protein 3(NLRP3)were assessed via western blots.Immunohistochemistry detected hippocampal expression of ionized calcium-binding adapter molecule 1(Iba1)and cluster of differentiation 68(CD68).Results:Multiple DTQND compounds were identified,including stachyose,β-syringin,and isofraxidin,among others.DTQND treatment considerably enhanced spontaneous activity,reduced anxiety,improved spatial working memory,and alleviated sensory gating defects in male offspring with MIA.The DTQND group showed significantly lower serum levels of IL-1β(P=.002)and IL-18(P=.046)than the model group,with no discernible variations in IL-6 or TNF-α levels.In the hippocampus,DTQND significantly suppressed the expression of p-p65(P<.001),p-IκB-α(P=.023),and NLRP3(P<.001)compared to the model group.Additionally,DTQND modulated microglial activation markers,decreasing CD68 expression(P=.004)without affecting Iba1 levels.Conclusions:DTQND alleviated schizophrenia-like behavioral deficits and cognitive impairment by inhibiting the NF-κB/NLRP3 pathway,supporting its potential as an alternative therapy for schizophrenia.
基金funded by the National Key Research and Development Program of China(Grant No.2019YFD1001900)the HZAU-AGIS Cooperation Fund(Grant No.SZYJY2022006).
文摘Nondestructive measurement technology of phenotype can provide substantial phenotypic data support for applications such as seedling breeding,management,and quality testing.The current method of measuring seedling phenotypes mainly relies on manual measurement which is inefficient,subjective and destroys samples.Therefore,the paper proposes a nondestructive measurement method for the canopy phenotype of the watermelon plug seedlings based on deep learning.The Azure Kinect was used to shoot canopy color images,depth images,and RGB-D images of the watermelon plug seedlings.The Mask-RCNN network was used to classify,segment,and count the canopy leaves of the watermelon plug seedlings.To reduce the error of leaf area measurement caused by mutual occlusion of leaves,the leaves were repaired by CycleGAN,and the depth images were restored by image processing.Then,the Delaunay triangulation was adopted to measure the leaf area in the leaf point cloud.The YOLOX target detection network was used to identify the growing point position of each seedling on the plug tray.Then the depth differences between the growing point and the upper surface of the plug tray were calculated to obtain plant height.The experiment results show that the nondestructive measurement algorithm proposed in this paper achieves good measurement performance for the watermelon plug seedlings from the 1 true-leaf to 3 true-leaf stages.The average relative error of measurement is 2.33%for the number of true leaves,4.59%for the number of cotyledons,8.37%for the leaf area,and 3.27%for the plant height.The experiment results demonstrate that the proposed algorithm in this paper provides an effective solution for the nondestructive measurement of the canopy phenotype of the plug seedlings.
文摘Peripheral artery disease(PAD)remains a significant global health issue,with current treatments primarily focused on relieving symptoms and addressingmacrovascular issues.However,critical immunoinflammatory mechanisms are often overlooked.Recent evidence suggests that monocyte phenotypic plasticity plays a central role in PAD development,affecting atherogenesis,plaque progression,ischemia-reperfusion injury,and chronic ischemic remodeling.This narrative review aims to summarize the latest advances(2023-2025)in understanding monocyte diversity,functional states,and their changes throughout different stages of PAD.We discuss both established and emerging biomarkers,such as circulating monocyte subset proportions,functional assays,immune checkpoint expression,and multi-omics signatures,highlighting their potential for prognosis and the challenges in translating them to clinical practice.We also present a stage-specific approach to mapping out potential therapies,linking monocyte phenotypes to molecular targets and possible interventions.Additionally,we address regulatory,economic,and implementation considerations for applying these findings in a clinical setting.The goal of this review is to facilitate the development of targeted immunomodulatory strategies to improve limb and cardiovascular outcomes in PAD by combining mechanistic understanding with therapeutic innovation.
基金funding from the China National Key Research and Development Program(No.2023YFC3603104)the National Natural Science Foundation of China(Nos.82472243 and 82272180)+6 种基金the Fundamental Research Funds for the Central Universities(No.226-2025-00024)the Huadong Medicine Joint Funds of the Zhejiang Provincial Natural Science Foundation of China(No.LHDMD24H150001)the Key Research&Development Project of Zhejiang Province(No.2024C03240)a collaborative scientific project co-established by the Science and Technology Department of the National Administration of Traditional Chinese Medicine and the Zhejiang Provincial Administration of Traditional Chinese Medicine(No.GZY-ZJ-KJ-24082)he General Health Science and Technology Program of Zhejiang Province(No.2024KY1099)the Project of Zhejiang University Longquan Innovation Center(No.ZJDXLQCXZCJBGS2024016)Wu Jieping Medical Foundation Special Research Grant(No.320.6750.2024-23-07).
文摘Objective:Sepsis exhibits remarkable heterogeneity in disease progression trajectories,and accurate identificationof distinct trajectory-based phenotypes is critical for implementing personalized therapeutic strategies and prognostic assessment.However,trajectory clustering analysis of time-series clinical data poses substantial methodological challenges for researchers.This study provides a comprehensive tutorial framework demonstrating six trajectory modeling approaches integrated with proteomic analysis to guide researchers in identifying sepsis subtypes after laparoscopic surgery.Methods:This study employs simulated longitudinal data from 300 septic patients after laparoscopic surgery to demonstrate six trajectory modeling methods(group-based trajectory modeling,latent growth mixture modeling,latent transition analysis,time-varying effect modeling,K-means for longitudinal data,agglomerative hierarchical clustering)for identifying associations between predefinedsequential organ failure assessment trajectories and 25 proteomic biomarkers.Clustering performance was evaluated via multiple metrics,and a biomarker discovery pipeline integrating principal component analysis,random forests,feature selection,and receiver operating characteristic analysis was developed.Results:The six methods demonstrated varying performance in identifying trajectory structures,with each approach exhibiting distinct analytical characteristics.The performance metrics revealed differences across methods,which may inform context-specificmethod selection and interpretation strategies.Conclusion:This study illustrates practical implementations of trajectory modeling approaches under controlled conditions,facilitating informed method selection for clinical researchers.The inclusion of complete R code and integrated proteomics workflows offers a reproducible analytical framework connecting temporal pattern recognition to biomarker discovery.Beyond sepsis,this pipeline-oriented approach may be adapted to diverse clinical scenarios requiring longitudinal disease characterization and precision medicine applications.The comparative analysis reveals that each method has distinct strengths,providing a practical guide for clinical researchers in selecting appropriate methods based on their specificstudy goals and data characteristics.
基金supported by the National Natural Science Foundation of China(32161143021,81271410)the Henan Natural Science Foundation(182300410313).
文摘Parkinson’s disease(PD)is a neurodegenerative disorder characterized by the loss of dopaminergic neurons,and its prevalence is increasing,alongside global population aging.Neuroinflammation has been widely recognized as a pivotal contributor to PD pathogenesis,particularly owing to the dual role of microglia in this process.This review systematically identifies the multiple factors regulating microglial function and phenotype,thereby driving PD initiation and progression.Furthermore,aging,a major risk factor for PD,and its profound effects on microglial state and functional dynamics are discussed.Notably,microglial hyperactivation is shown to establish a self-perpetuating cycle of“inflammation–damage–reinflammation”through the excessive release of pro-inflammatory cytokines and chemokines,which exacerbates neuronal degeneration.Lastly,the potential therapeutic strategies targeting microglial dysfunction,including interventions against the senescence-associated secretory phenotype and the modulation of microglial activity,are summarized.By elucidating how multifactorial alterations in microglial states influence PD pathology,this review provides novel insights and directions for advancing therapeutic research in PD.
文摘While methodology for determining the mode of evolution in coding sequences has been well established,evaluation of adaptation events in emerging types of phenotype data needs further development.Here,we propose an analysis framework(expression variance decomposition,EVaDe)for comparative single-cell expression data based on phenotypic evolution theory.After decomposing the gene expression variance into separate components,we use two strategies to identify genes exhibiting large between-taxon expression divergence and small within-cell-type expression noise in certain cell types,attributing this pattern to putative adaptive evolution.In a dataset of primate prefrontal cortex,we find that such humanspecific key genes enrich with neurodevelopment-related functions,while most other genes exhibit neutral evolution patterns.Specific neuron types are found to harbor more of these key genes than other cell types,thus likely to have experienced more extensive adaptation.Reassuringly,at the molecular sequence level,the key genes are significantly associated with the rapidly evolving conserved non-coding elements.An additional case analysis comparing the naked mole-rat(NMR)with the mouse suggests that innateimmunity-related genes and cell types have undergone putative expression adaptation in NMR.Overall,the EVaDe framework may effectively probe adaptive evolution mode in single-cell expression data.
基金supported by the National Natural Science Foundation of China(32271584 and 31600445)the Natural Science Basic Research Plan in Shaanxi Province of China(2020JM-286)+2 种基金the Fundamental Research Funds for the Central Universities(GK202103072,GK202103073)the National College Students'Innovative Entrepreneurial Training Plan Program(202310718085)Special Research Project in Philosophy and Social Sciences of Shaanxi Province(2022HZ1795).
文摘Prevention of biological invasion requires understanding how alien species invade native communities.Although studies have identified mechanisms that underlie plant invasion in some habitats,limited attention has focused on invasion patterns along elevational gradients.In this study,we asked which factors drive the global and regional distribution of the invasive plant Galinsoga quadriradiata along elevational gradients.To answer this question,we examined whether human activities(i.e.,roads)promote G.quadriradiata invasion,how seed dispersal-related traits of G.quadriradiata change along elevation gradients,and whether G.quadriradiata has adapted to high-elevation environments through phenotypic plasticity or genetic variation.On the global scale,we found that human activities and road density positively contribute to the G.quadriradiata expansion in mountainous areas.Field surveys in China revealed significant elevational differences in the seed dispersal traits of G.quadriradiata,with higher-elevation populations exhibiting lower dispersal ability and generally lower genetic diversity.Under common conditions,high-elevation populations showed higher leaf mass ratio but lower root mass ratio and reproductive allocation.This suggests that high-elevation environments create a barrier to dispersal for G.quadriradiata,and that G.quadriradiata has adapted phenotypically to these conditions.Our study indicates that the elevational invasion pattern of G.quadriradiata is shaped by multiple factors,particularly human activities and phenotypic adaptability.In addition,our finding that G.quadriradiata invasion at high elevations is not constrained by low genetic diversity indicates that monitoring and management of G.quadriradiata in mountainous areas should be strengthened.
基金supported by the Natural Science Foundation of Beijing,Nos.7244428(to WZ)and 7222215(to JH)the Peking University Medicine Sailing Program forYoung Scholars’Scientific and Technological Innovation,No.BMU2023YFJHPY034(to WZ)+4 种基金the National Natural Science Foundation of China,Nos.81873784,82071426(to DF),and81974197(to JH)the Clinical Cohort Construction Program of Peking University Third Hospital,No.BYSYDL2019002(to DF)Beijing Physician-Scientist TrainingProgram,No.BJPSTP-2024-03(to JH)the China Postdoctoral Science Foundation,Nos.2022TQ0014(to LX),2022M720284(to LX)the E-Town Cooperation&Development Foundation,No.YCXJ-JZ-2023-017(to LX).
文摘The growing recognition of the role of genetics in the development of amyotrophic lateral sclerosis is evident.However,there has yet to be a comprehensive analysis of the clinical characteristics and genetics of familial amyotrophic lateral sclerosis in an Asian population.This study aimed to provide an in-depth analysis of the clinical features and genetic spectrum of familial amyotrophic lateral sclerosis over 15 years in a clinic-based cohort of patients from the Chinese mainland.Enrollment of 302 amyotrophic lateral sclerosis families from 28 provinces was undertaken from January 2008 to September 2023.A group-based trajectory model for disease progression based on amyotrophic lateral sclerosis Functional Rating Scale-Revised(ALSFRS-R)scores was validated using bootstrap internal validation in patients with familial amyotrophic lateral sclerosis,as well as patients with sporadic amyotrophic lateral sclerosis(matched at a 1:4 ratio,with replacement).DNA samples from 244 index patients were screened for variants in the pathogenic genes SOD1,FUS,TDP43,and C9ORF72,of which 146 were also subjected to genome-wide next-generation sequencing.Gene-level burden analysis was used to evaluate the distribution of rare variants in the cohort.We found that rapid dynamic disease progression was associated with an older age at onset,shorter diagnostic delay,lower body mass index,bulbar onset,and≥1 affected first-degree relative.Certain attributes,such as age at onset and time from onset to diagnosis,had comparable impacts on the clinical progression trajectories of both familial amyotrophic lateral sclerosis and sporadic amyotrophic lateral sclerosis.Harboring pathogenic/likely pathogenic variants in amyotrophic lateral sclerosis-causative genes reduced the age of onset of familial amyotrophic lateral sclerosis.Among the patients with familial amyotrophic lateral sclerosis,17.8%possessed≥2 pathogenic/likely pathogenic variants.Sequencing kernel association test analysis showed that the SOD1 rare variant burden(P=1.3e-15)was associated with a significant risk of familial amyotrophic lateral sclerosis.Our findings conclusively confirmed the clinical features and genetic spectrum of familial amyotrophic lateral sclerosis over 15 years in a clinical cohort from China,contributing to a deeper understanding of genotype-phenotype relationships in familial amyotrophic lateral sclerosis.This comprehensive evaluation of specific clinical characteristics,clinical prognosis,and genetic variants of amyotrophic lateral sclerosis based on detailed clinical and genetic information may lead to the development of genotype-specific treatment approaches.
基金supported by Yuelushan Laboratory Breeding Program(Grant No.YLS-2025-ZY02013)The Project of National Key Laboratory for Tropical Crop Breeding(Grant No.NKLTCB202341)+4 种基金The New Variety Breeding Project of the Major Science and Technology Projects of Zhejiang(Grant No.2021C02065-1-3)Hunan Provincial Agricultural Science and Technology Innovation Fund Project(Grant No.2025CX115)Key R&D Projects in Hainan Province(Grant No.ZDYF2023XDNY041)Central Public-interest Scientific Institution Basal Research Fund(Grant No.1630062022003)2024 Sanya Technology Stars Program(Grant No.2024KJFX022).
文摘Eggplant(Solanum melongena L.)is a globally important vegetable crop,renowned for its nutritional value and economic significance.It is abundant in bioactive compounds such as anthocyanins and chlorogenic acid,which have been associated with multiple health-promoting properties(Azuma et al.,2008;Gurbuz et al.,2018).Given its significant hybrid vigor,F1 hybrid varieties are widely preferred in commercial cultivation(Mistry et al.,2018).However,traditional breeding practices predominantly rely on phenotypic selection,a process that is not only labor-intensive but also time-consuming.
