Cells of the central nervous system(CNS)are privileged in lying behind the blood-brain barrier(BBB).Unlike blood vessels in other organs,CNS blood vessels are unique in displaying high electrical resistance and low pe...Cells of the central nervous system(CNS)are privileged in lying behind the blood-brain barrier(BBB).Unlike blood vessels in other organs,CNS blood vessels are unique in displaying high electrical resistance and low permeability.With this unique structure and function,the BBB prevents potentially harmful blood components such as serum proteins,inflammatory cytokines,and inflammatory leukocytes from entering the hallowed space of the CNS and wreaking havoc.In addition to these“tightness”properties,the BBB has an array of specialized transporters designed to import essential nutrients.展开更多
Objective:Hypertension is a serious public health concern that is influenced by a variety of body composition parameters.This study examines the associations between body composition metrics and blood pressure(BP)in a...Objective:Hypertension is a serious public health concern that is influenced by a variety of body composition parameters.This study examines the associations between body composition metrics and blood pressure(BP)in a rural population,specifically how variations in body fat distribution and other metrics affect systolic blood pressure(SBP)and diastolic blood pressure(DBP).Methods:A cross-sectional study of 226 participants examined the relationships between body composition metrics—such as total body fat,visceral fat,and body mass index(BMI)—and BP.Correlation and regression analyses were used to assess these relationships.Results:The study found substantial positive correlations between visceral fat and total body fat with both SBP and DBP.Visceral fat was strongly connected with both SBP(r=0.145,P=0.030)and DBP(r=0.331,P<0.01),while total body fat was significantly correlated with DBP(r=0.268,P<0.01)but not SBP.Body composition variables explained 12.8% of the variance in SBP(R^(2)=0.128,P=0.001)and 15.0% in DBP(R^(2)=0.150,P<0.001).Conclusions:The study found substantial connections between body composition,particularly visceral and subcutaneous fat and systolic and DBP.Higher levels of visceral fat were linked to elevate BP.Body composition accounted for a significant amount of BP fluctuation.展开更多
While a healthy lifestyle is known to reduce the risk of stroke,the extent to which blood pressure(BP)mediates this association remains unclear.The present study aimed to quantify the mediating role of BP in the assoc...While a healthy lifestyle is known to reduce the risk of stroke,the extent to which blood pressure(BP)mediates this association remains unclear.The present study aimed to quantify the mediating role of BP in the association between combined lifestyle factors and stroke incidence.Using data from 51929 participants free of major cardiovascular diseases or cancer at baseline,we employed structural equation modeling to assess the mediating effects of systolic(SBP)and diastolic(DBP)blood pressure.During the follow-up,2811 incident stroke cases were identified.A healthy lifestyle was significantly associated with a reduced risk of stroke,with SBP mediating 44.70%(β=-0.0014,95%confidence interval[CI]:-0.0016 to-0.0012)and DBP mediating 37.81%(β=-0.0012,95%CI:-0.0015 to-0.0009)of this association.The mediating effects were attenuated but remained significant for ischemic stroke(SBP:33.21%;DBP:27.24%).In conclusion,approximately two-fifths of the protective association between a healthy lifestyle and stroke may be mediated by BP.These findings suggest that BP control may serve as an important early indicator for evaluating the effectiveness of lifestyle interventions in reducing stroke risk.展开更多
Sport-related concussion(SRC)and its potential neurological sequela represent an emerging global health concern,requiring improved recovery management and strategies for return-to-play(RTP)to enhance brain health in a...Sport-related concussion(SRC)and its potential neurological sequela represent an emerging global health concern,requiring improved recovery management and strategies for return-to-play(RTP)to enhance brain health in athletes.Given the dynamic and multifaceted nature of SRC recovery,the purpose of this review is to synthesize existing literature on post-SRC outcomes in adult athletes,and to outline the temporal trajectories of key recovery indicators(symptoms,cognitive function,blood biomarkers)across distinct recovery phases until resolution.In the acute phase of SRC(first 48 h),symptom scores and brain damage markers peaked immediately,while cognitive impairments and neuroinflammation emerged with a slight delay.Following the initial rise,brain damage marker concentrations rapidly dropped below baseline levels at approximately 48 h following SRC injury.During the early recovery phase,neuroinflammation and most cognitive alterations resolved after 3–5 days,though symptom burden and attention deficits persisted for up to 7 days.Despite prolonged alterations reported in some individuals,recovery markers typically returned to pre-injury levels in the transition phase(≤2 weeks),though mild attention deficits were detected up to 3 weeks,and TNF-α concentrations remained elevated throughout late recovery(>2 weeks).These results reveal distinct temporal discrepancies across recovery markers and emphasize that physiological disturbances can outlast symptom resolution,underscoring the need for both multimodal assessments and appropriately timed evaluations to accurately track recovery progression.Incorporating structured follow-ups at key time points,particularly beyond symptom resolution,may improve RTP decision-making and reduce the risk of premature return and long-term neurological consequences.展开更多
Accurate blood pressure(BP)monitoring is essential for preventing and managing cardiovascular disease.Advancements in materials science,medicine,flexible electronic,and artificial intelligence(AI)have enabled cuffless...Accurate blood pressure(BP)monitoring is essential for preventing and managing cardiovascular disease.Advancements in materials science,medicine,flexible electronic,and artificial intelligence(AI)have enabled cuffless,unobtrusive BP monitoring systems,offering an alternative to traditional sphygmomanometers.However,extending these advances to real-world cardiovascular care particularly in resource-limited settings remains challenging due to constraints in computational resources,power efficiency,and deployment scalability.This review presents a comprehensive synthesis of AI-enhanced wearable BP monitoring,emphasizing its potential for personalized,scalable,and accessible healthcare.We systematically analyze the end-to-end system architecture,from mechano-electric sensing principles and AI-based estimation models to edge-aware deployment strategies tailored for low-resource environments.We further discuss clinical validation metrics and implementation barriers and prospective strategies.To bridge lab-to-field translation,we propose an innovative"sensor-model-deployment-assessment"co-design framework.This roadmap highlights how AI-enhanced BP technologies can support proactive hypertension control and promote cardiovascular health equity on a global scale.展开更多
Objective Evidence suggests that depleted gut microbialα-diversity is associated with hypertension;however,whether metabolic markers affect this relationship remains unknown.We aimed to determine the potential metabo...Objective Evidence suggests that depleted gut microbialα-diversity is associated with hypertension;however,whether metabolic markers affect this relationship remains unknown.We aimed to determine the potential metabolites mediating the associations ofα-diversity with blood pressure(BP)and BP variability(BPV).Methods Metagenomics and plasma targeted metabolomics were conducted on 523 Chinese participants from the MetaSalt study.The 24-hour,daytime,and nighttime BP and BPV were calculated based on ambulatory BP measurements.Linear mixed models were used to characterize the relationships betweenα-diversity(Shannon and Chao1 index)and BP indices.Mediation analyses were performed to assess the contribution of metabolites to the observed associations.The influence of key metabolites on hypertension was further evaluated in a prospective cohort of 2,169 participants.Results Gut microbial richness(Chao1)was negatively associated with 24-hour systolic BP,daytime systolic BP,daytime diastolic BP,24-hour systolic BPV,and nighttime systolic BPV(P<0.05).Moreover,26 metabolites were strongly associated with richness(Bonferroni P<0.05).Among them,four key metabolites(imidazole propionate,2-hydroxy-3-methylbutyric acid,homovanillic acid,and hydrocinnamic acid)mediated the associations between richness and BP indices(proportions of mediating effects:14.1%–67.4%).These key metabolites were also associated with hypertension in the prospective cohort.For example,each 1-standard deviation unit increase in hydrocinnamic acid significantly reduced the risk of prevalent(OR[95%CI]=0.90[0.82,0.99];P=0.03)and incident hypertension(HR[95%CI]=0.83[0.71,0.96];P=0.01).Conclusion Our results suggest that gut microbial richness correlates with lower BP and BPV,and that certain metabolites mediate these associations.These findings provide novel insights into the pathogenesis and prevention of hypertension.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
The central nervous system(CNS)does not function in isolation-it engages in continuous molecular dialogue with the vascular and immune systems.Traditionally,the blood-brain barrier(BBB)was portrayed solely as an imper...The central nervous system(CNS)does not function in isolation-it engages in continuous molecular dialogue with the vascular and immune systems.Traditionally,the blood-brain barrier(BBB)was portrayed solely as an impermeable wall,safeguarding the CNS by excluding blood-derived molecules and circulating cells.However,this view has evolved.The BBB is now recognized as a dynamic interface that selectively regulates the exchange of signals,cells.展开更多
Cerebral ischemia restricts cerebral blood flow(CBF),leading to unstable hemodynamics.Past studies of ischemia mainly focused on cortical CBF reduction.However,its impact on hemodynamic changes,especially temporal var...Cerebral ischemia restricts cerebral blood flow(CBF),leading to unstable hemodynamics.Past studies of ischemia mainly focused on cortical CBF reduction.However,its impact on hemodynamic changes,especially temporal varying characteristics,remains poorly understood.Here,we collected cortical resting-state CBF in rats with left carotid artery blockage during occlusion–reperfusion,and measured the temporal variability and changes in laterality using a novel state-space method.This method was also applied to stroke EEG datasets to validate its effectiveness.After arterial occlusion,the left marginal motor,sensory,auditory,and visual cortices exhibited severe temporal variability impairments.The laterality analysis indicated that affected left regions showed inferior unilateral mean,inter-hemispheric transition probability,time fraction,and laterality duration,while the right side had a higher laterality time fraction and duration.These impairments recovered partially following blood flow restoration.Besides,the ischemic state-space metrics were positively correlated with the pre-occlusion baseline appearance.Stroke patients exhibited impaired temporal variability in the affected ischemic hemisphere.The state-space analysis revealed damaged CBF temporal variability during cerebral ischemia and predicted baseline-ischemia connections.展开更多
Objective Patients with atherosclerotic cardiovascular disease(ASCVD)following percutaneous coronary intervention(PCI)are classified as very-high-risk individuals in cardiovascular disease(CVD)risk stratification.The ...Objective Patients with atherosclerotic cardiovascular disease(ASCVD)following percutaneous coronary intervention(PCI)are classified as very-high-risk individuals in cardiovascular disease(CVD)risk stratification.The distribution pattern of traditional Chinese medicine(TCM)syndromes in this patient population,as well as its association with blood lipid profiles and clinical prognosis,remains unclear.The present prospective cohort study aims to investigate these correlations,thereby providing insights to enrich the research fields.Methods We enrolled consecutive patients with ASCVD who underwent PCI at the Integrated Cardiology Unit of China-Japan Friendship Hospital between September 1,2020 and December 31,2022.Demographics and clinical characteristics,signs and symptoms defining each TCM syndrome,and fasting venous blood samples were collected at baseline and follow up or upon major adverse cardiovascular events(MACEs).We analyzed the correlation between TCM syndromes,blood lipid profiles,and MACEs,and developed a new joint prognostic model incorporating both TCM syndromes and blood lipids using logistic regression.The analyses were based on detailed baseline and one-year follow-up data.Results A per-protocol analysis was performed on 586 patients with complete data ultimately.During the one-year follow-up,174 patients(29.69%)experienced a MACE.We performed statistical analyses on comorbidities,medication,and biochemical indicators across groups defined by TCM syndrome differentiation.When comparing different TCM syndromes,no significant differences were found in age,body mass index(BMI),history of revascularization,comorbidities,family history of CVD,smoking or drinking,or statin intensity(P>0.05).Patients with intertwined phlegm and blood stasis syndrome exhibited significantly higher levels of total cholesterol(TC,5.27±1.18 mmol/L,P<0.001),triglyceride(TG,1.96±1.33 mmol/L,P=0.008),low-density lipoprotein cholesterol(LDL-C,3.35±0.79 mmol/L,P<0.001),and high-density lipoprotein cholesterol(HDL-C,1.24±0.81 mmol/L,P<0.001)compared with those with other TCM syndromes combined.A multivariable logistic regression model was constructed to predict MACEs.The model included TCM syndrome type[with intertwined phlegm and blood stasis as a predictor,adjusted odds ratio(OR)=1.413,95%confidence interval(CI):0.517–3.864,P=0.501],age(adjusted OR=0.97,95%CI:0.955–1.001,P=0.057),male gender(adjusted OR=0.698,95%CI:0.416–1.170,P=0.173),TC(adjusted OR=1.004,95%CI:0.513–1.965,P=0.990),and LDL-C(adjusted OR=5.825,95%CI:2.214–15.326,P<0.001).This model demonstrated good discriminatory ability for MACEs in post-PCI ASCVD patients[the area under the receiver operating characteristic(ROC)curve(AUC)=0.865,95%CI:0.816–0.914].Conclusion The intertwined phlegm and blood stasis TCM syndrome is associated with a distinct atherogenic lipid profile characterized by elevated levels of TC and LDL-C.The prognostic model that incorporates this TCM syndrome type along with conventional lipid parameters(TC and LDL-C)shows good discriminatory ability for predicting MACEs in ASCVD patients after PCI,underscoring the potential clinical utility of integrating TCM syndrome differentiation into CVD risk assessment.展开更多
In Alzheimer’s disease,microglial phagocytosis is engaged in the pathogenesis as it clears abnormal protein accumulations,debris,and apoptotic cells in the early stages of Alzheimer’s disease,but fuels neuroinflamma...In Alzheimer’s disease,microglial phagocytosis is engaged in the pathogenesis as it clears abnormal protein accumulations,debris,and apoptotic cells in the early stages of Alzheimer’s disease,but fuels neuroinflammation and accelerates disease progression in later stages.In vivo parabiosis experiments in aged animals have demonstrated that blood-born factors modulate synaptic plasticity,neurogenesis,and microglial responses.We hypothesize that peripheral factors can modulate microglial function and thereby possibly influence Alzheimer’s disease pathology.The objective of this study is to investigate the effects of Alzheimer’s disease serum on microglial phagocytosis.Here,we use an immortalized human microglial cell line in an in vitro parabiosis assay to investigate the impact of the serum from individuals diagnosed with Alzheimer’s disease(n=30)and age-matched controls(n=30)(PRODEM study)on microglial phagocytosis.Exposure to Alzheimer’s disease serum increased microglial phagocytic uptake of pH-sensitive fluorescent particles and downregulated expression of the lysosomal master regulator transcription factor EB(TFEB)and of ATPase H^(+)transporting lysosomal V1 subunit B2(ATP6V1B2),a component of the vacuolar ATPase.To identify serum components that may relate to changes in phagocytosis,serum samples of the Three-City Study(3C Study)were used.In the 3C Study,blood samples were collected up to 12 years before the onset of cognitive decline or dementia and their serum metabolome is well-defined.Microglia exposed to the serum of future Alzheimer’s disease patients from the 3C Study displayed an increased phagocytic uptake compared with the serum of matched controls,depending on the presence of the apolipoprotein Eε4 allele in the Alzheimer’s disease patients.Furthermore,microglial phagocytosis correlated inversely with serum levels of the omega-3 fatty acid eicosapentaenoic acid.We confirmed this inverse correlation between eicosapentaenoic acid and phagocytosis in the serum samples of the PRODEM cohort.In addition,in vitro testing of eicosapentaenoic acid on microglial phagocytosis showed a concentration-dependent decrease in phagocytic uptake.In conclusion,following incubation with Alzheimer’s disease blood serum,we observed increased microglial phagocytic uptake and the downregulation of TFEB and ATP6V1B2,possibly indicating lysosomal dysfunction.Furthermore,microglial phagocytosis was inversely correlated with serum eicosapentaenoic acid levels,suggesting an important role for dietary eicosapentaenoic acid in microglial function.展开更多
Alzheimer’s disease(AD)is a complex,progressive neurodegenerative disorder and the leading cause of dementia worldwide.It is characterized by the accumulation of extracellular amyloid-beta(Aβ)plaques and intracellul...Alzheimer’s disease(AD)is a complex,progressive neurodegenerative disorder and the leading cause of dementia worldwide.It is characterized by the accumulation of extracellular amyloid-beta(Aβ)plaques and intracellular tau neurofibrillary tangles,leading to synaptic dysfunction,neuronal loss,and cognitive decline.These pathological changes can begin decades before clinical symptoms emerge,highlighting the critical need for early,accessible,and accurate diagnostic tools.展开更多
Background:Panacis Quinquefolii Radix(PQR)is known for its ability to nourish“Qi”(it serves as the driving force for the functional activities of the body’s organs and meridians,promoting and regulating various phy...Background:Panacis Quinquefolii Radix(PQR)is known for its ability to nourish“Qi”(it serves as the driving force for the functional activities of the body’s organs and meridians,promoting and regulating various physiological functions)and“Yin”(it represents the material foundation of the human body.It plays a role in nourishing,moistening,and cooling the body).Notoginseng Radix et Rhizoma(NRR)is recognized for its properties of resolving blood stasis(it refers to a pathological condition characterized by impaired or stagnant blood circulation within the body).Changes in the compatibility ratio of these herbs often lead to variations in their chemical composition and efficacy.However,the specific alterations in chemical composition and efficacy resulting from compatibility adjustments remain unclear.We aimed to compare the material basis and their effects of different compatibility ratios of PQR and NRR on“Qi”deficiency and blood stasis syndrome(QBS).Methods:This study employed UPLC-Q/TOF-MS to identify effective compounds in the compatibility of PQR and NRR and utilized UPLC-TQ-MS/MS to analyze the dissolution of 16 saponins in PQR and NRR at 9 different ratios.A rat model of QBS was established,and the efficacy of PQR and NRR in treating this syndrome was assessed using hemorheology and coagulation analyses.Results:The study results show that PQR and NRR exhibit significant efficacy,effectively reducing blood viscosity induced by platelet aggregation and lowering inflammatory markers such as IL-6,IL-10,TXB2 and ET associated with vascular injury.Moreover,this combination regulates ATP and ADP levels,enhances energy metabolism,and promotes overall health.A total of 104 compounds in the compatibility of PQR and NRR were identified.The ratios of 1:2 and 1:3 showed the highest total saponin content,but the ratio of 1:1 demonstrated a superior pharmacological effect for the treatment of QBS.Conclusion:In summary,the compatibility of PQR and NRR not only shows the complex interactions between traditional Chinese medicinal materials,but also provides a new idea and method for the treatment of QBS.展开更多
Objectives Dysregulated osteoclast function contributes to skeletal diseases.However,the specific ubiquitination regulators of the osteoclastogenesis repressor MafB,particularly at the post-translational level,remain ...Objectives Dysregulated osteoclast function contributes to skeletal diseases.However,the specific ubiquitination regulators of the osteoclastogenesis repressor MafB,particularly at the post-translational level,remain undefined.This study aims to identify ubiquitin-specific proteases(USPs)that deubiquitinate MafB and enhance its stability.Methods We constructed a MafB-conjugated luciferase and overexpressed 40 individual USPs,measuring changes in luciferase activity.The identified USP was overexpressed in human CD14^(+) peripheral blood mononuclear cells(PBMCs)to evaluate its effect.Osteoclast differentiation was assessed through osteoclast marker Integrin alpha-V(CD51)staining and Western blot analysis.Co-immunoprecipitation(co-IP)was performed to assess the interplay.The influence on MafB ubiquitination and degradation was evaluated via immunoprecipitation and Western blot.Finally,MafB was knocked down in the USP-overexpressing PBMCs to analyze its effect on osteoclast differentiation.Results Overexpression of ubiquitin-specific protease 29(USP29)significantly increased MafB expression by approximately 75%(p<0.0001).Elevated USP29 levels strongly inhibited osteoclastic differentiation in CD14^(+) PBMCs(p<0.0001).USP29 was found to interact with MafB,markedly reducing its ubiquitination and subsequent degradation in PBMCs(p<0.001).Knocking down MafB in USP29-overexpressing PBMCs alleviated the inhibitory effect of USP29 on osteoclastogenesis.Conclusion USP29 acts as a potent stabilizer of MafB,inhibiting osteoclastogenesis in human CD14^(+) PBMCs,at least in part,by enhancing MafB stability.These findings expand our understanding of USP29’s role and the post-translational regulation of MafB.Furthermore,USP29 serves as a vital factor that controls osteoclast differentiation,and its regulatory function is at least partially mediated by deubiquitinating and stabilizing MafB.展开更多
Studies have shown that chitosan protects against neurodegenerative diseases. However, the precise mechanism remains poorly understood. In this study, we administered chitosan intragastrically to an MPTP-induced mouse...Studies have shown that chitosan protects against neurodegenerative diseases. However, the precise mechanism remains poorly understood. In this study, we administered chitosan intragastrically to an MPTP-induced mouse model of Parkinson's disease and found that it effectively reduced dopamine neuron injury, neurotransmitter dopamine release, and motor symptoms. These neuroprotective effects of chitosan were related to bacterial metabolites, specifically shortchain fatty acids, and chitosan administration altered intestinal microbial diversity and decreased short-chain fatty acid production in the gut. Furthermore, chitosan effectively reduced damage to the intestinal barrier and the blood–brain barrier. Finally, we demonstrated that chitosan improved intestinal barrier function and alleviated inflammation in both the peripheral nervous system and the central nervous system by reducing acetate levels. Based on these findings, we suggest a molecular mechanism by which chitosan decreases inflammation through reducing acetate levels and repairing the intestinal and blood–brain barriers, thereby alleviating symptoms of Parkinson's disease.展开更多
Alzheimer’s disease-associated transcriptomic landscapes have been defined in brain tissue.However,changes in blood RNA and their clinical relevance remain poorly understood.In this study,we developed an RNA profile ...Alzheimer’s disease-associated transcriptomic landscapes have been defined in brain tissue.However,changes in blood RNA and their clinical relevance remain poorly understood.In this study,we developed an RNA profile based on 1468 blood samples from both human and mouse studies,which include bulk RNA sequencing(RNA-seq),microRNA-seq,and single-cell RNA-seq data.We developed a comprehensive analysis pipeline that conducted over 11 million comparisons and correlations to identify more than 20,000 blood features.With these findings,we established a blood RNA database related to Alzheimer’s disease,RNAs in Blood of AD(RBAD,http://www.bioinform.cn/RBAD/).Using RBAD,we initially validated well-established Alzheimer’s disease-related pathways,including olfactory transduction.We then observed a decrease in both the proportion and functionality of erythroid cells,likely attributed to their elevated CD45 levels and interactions with GZMK^(+)CD8^(+)T cells.Furthermore,we identified 449 blood RNAs linked to patients’overall survival,along with two mRNAs(H4C3 and CTU1)associated with cognitive decline.In summary,RBAD is the first web-based analysis platform dedicated to investigating blood RNA changes in Alzheimer’s disease,and provides valuable insights into potential peripheral biomarkers and pathogenic mechanisms related to Alzheimer’s disease.展开更多
Blood cell disorders are among the leading causes of serious diseases such as leukemia,anemia,blood clotting disorders,and immune-related conditions.The global incidence of hematological diseases is increasing,affecti...Blood cell disorders are among the leading causes of serious diseases such as leukemia,anemia,blood clotting disorders,and immune-related conditions.The global incidence of hematological diseases is increasing,affecting both children and adults.In clinical practice,blood smear analysis is still largely performed manually,relying heavily on the experience and expertise of laboratory technicians or hematologists.This manual process introduces risks of diagnostic errors,especially in cases with rare or morphologically ambiguous cells.The situation is more critical in developing countries,where there is a shortage of specialized medical personnel and limited access to modern diagnostic tools.High testing costs and delays in diagnosis hinder access to quality healthcare services.In this context,the integration of Artificial Intelligence(AI),particularly Explainable AI(XAI)based on deep learning,offers a promising solution for improving the accuracy,efficiency,and transparency of hematological diagnostics.In this study,we propose a Ghost Residual Network(GRsNet)integrated with XAI techniques such as Gradient-weighted Class Activation Mapping(Grad-CAM),Local Interpretable Model-Agnostic Explanations(LIME),and SHapley Additive exPlanations(SHAP)for automatic blood cell classification.These techniques provide visual explanations by highlighting important regions in the input images,thereby supporting clinical decision-making.The proposed model is evaluated on two public datasets:Naturalize 2K-PBC and Microscopic Blood Cell,achieving a classification accuracy of up to 95%.The results demonstrate the model’s strong potential for automated hematological diagnosis,particularly in resource-constrained settings.It not only enhances diagnostic reliability but also contributes to advancing digital transformation and equitable access to AI-driven healthcare in developing regions.展开更多
Erythroid cells, the predominant circulating blood cells, are essential for oxygen and carbon dioxide transport (Obeagu, 2024).Their production, erythropoiesis, involves the coordinated synthesis of globin chains and ...Erythroid cells, the predominant circulating blood cells, are essential for oxygen and carbon dioxide transport (Obeagu, 2024).Their production, erythropoiesis, involves the coordinated synthesis of globin chains and heme molecules to assemble hemoglobin(Zhang et al., 2021). The erythroid-specific enzyme δ-aminolevulinate synthase 2 (ALAS2) is a key rate-limiting factor in heme biosynthesis,with its expression increasing in late-stage erythropoiesis to meet heme demands (Sadlon et al., 1999). Zebrafish (Danio rerio) is a well-established model for studying erythropoiesis due to its genetic tractability and optical transparency (Zhang and Hamza, 2019;Zhang et al., 2021). The Tol2-mediated Gal4-UAS system has been widely applied for gene and enhancer trapping in zebrafish (Asakawa and Kawakami, 2009). However, reliable Gal4 enhancer-trap lines for erythropoiesis remain limited. Here, we report a transgenic zebrafish line with erythroid-specific Gal4FF expression under the control of the endogenous alas2 promoter, offering a more precise erythroblast labeling than the gata1a reporter line. This model provides a valuable tool for erythroid-specific investigations of blood flow dynamics and gene function.展开更多
BACKGROUND The reference ranges for biochemical parameters can fluctuate due to factors like altitude,age,gender,and socioeconomic conditions.These values are crucial for interpreting laboratory data and guide clinica...BACKGROUND The reference ranges for biochemical parameters can fluctuate due to factors like altitude,age,gender,and socioeconomic conditions.These values are crucial for interpreting laboratory data and guide clinical treatment decisions.Currently,there is no established set of reference intervals for cord blood biochemical parameters of newborns in India,particularly in Mumbai.AIM To create cord blood biochemical parameters reference intervals specifically for Mumbai,India.METHODS A cross-sectional study was conducted in an Indian tertiary care hospital.This study focused on healthy newborns with normal birth weight,born to pregnant mothers without health issues.Cord blood samples,approximately 2-3 mL in volume,were collected from 210 term neonates.These samples were divided into fluoride(glucose)and clot activator(serum)tubes and were subsequently analyzed in the institute's biochemical laboratory.The data obtained from the analysis was then subjected to statistical analysis.The result of the Shapiro-Wilk test suggested non-normality in the data distribution.Consequently,nonparametric statistics were utilized for analysis.The Mann-Whitney U test was utilized to compare parameter distributions among different factors,including the infant’s sex,delivery method,maternal age,and obstetric history.A significance level of P<0.05 was considered to indicate statistical significance.RESULTS The following represent the median figures and central 95 percentile reference intervals for biochemical parameters in umbilical cord blood of newborns:Serum direct bilirubin=(0.1-0.55)mg/dL,indirect bilirubin=(0.64-2.26)mg/dL,total bilirubin=(0.62-3.14)mg/dL,creatinine=(0.27-0.76)mg/dL,sodium=(128.19-143.26)mmol/L,chloride=(100.19-111.68)mmol/L,potassium=(1.62-9.98)mmol/L and plasma glucose=(24.75-94.23)mg/dL.Statistically significant differences were observed in serum sodium,potassium,and plasma glucose levels when comparing delivery modes.CONCLUSION This is the pioneering study in which first time,the biochemical reference intervals in cord blood for newborns are established in western India.The values are applicable for newborns from this area.Larger study throughout the country is required.展开更多
Background The co-existence of Type 2 diabetes mellitus(T2DM)and hypertension presents a significant clinical challenge due to their synergistic detrimental effects on cardiovascular outcomes.Conventional combination ...Background The co-existence of Type 2 diabetes mellitus(T2DM)and hypertension presents a significant clinical challenge due to their synergistic detrimental effects on cardiovascular outcomes.Conventional combination therapies often fall short in comprehensively addressing the intertwined pathophysiologies,particularly vascular endothelial dysfunction.This study aimed to evaluate the efficacy of a novel regimen combining sitagliptin-metformin with nifedipine in managing blood pressure,blood glucose,and vascular function in this high-risk population.Methods 150 patients with T2DM and hypertension were randomly assigned to either the control group(n=75)treated with metformin and nifedipine,or the experimental group(n=75)treated with sitagliptin-metformin compound preparation combined with nifedipine.Changes in blood pressure,blood glucose levels,flow-mediated dilation(FMD)and nitroglycerin-mediated dilation(NMD)of the brachial artery,and serum levels of biomarkers[nitric oxide(NO),endothelin-1(ET-1)]were compared before and after treatment.The incidence of adverse reactions during treatment was also monitored.Results After treatment,both groups showed significant reductions in blood pressure,blood glucose parameters,and ET-1 levels compared to baseline.The experimental group demonstrated significantly lower values in these assessments at the same time points than control group(P<0.05).Conversely,FMD,NMD,and NO levels increased significantly in both groups after treatment,with experimental group showing significantly higher values than control group(P<0.05).There was no statistically significant difference in the incidence of adverse reactions between the two groups(P>0.05).Conclusions The combination of sitagliptinmetformin compound preparation and nifedipine significantly enhanced blood pressure control and blood glucose control and exerted a positive regulatory effect on vascular endothelial function in patients with T2DM and hypertension,demonstrating high clinical value for widespread application.展开更多
基金supported by the NIH RF1 grant NS119477 jointly funded by NINDS and NIA(to RM).
文摘Cells of the central nervous system(CNS)are privileged in lying behind the blood-brain barrier(BBB).Unlike blood vessels in other organs,CNS blood vessels are unique in displaying high electrical resistance and low permeability.With this unique structure and function,the BBB prevents potentially harmful blood components such as serum proteins,inflammatory cytokines,and inflammatory leukocytes from entering the hallowed space of the CNS and wreaking havoc.In addition to these“tightness”properties,the BBB has an array of specialized transporters designed to import essential nutrients.
基金supported by Universitas Advent Indonesia(No.067/EKS-SU/V/24 and 389/KEPK-FIK.UNAI/EC/V/24)。
文摘Objective:Hypertension is a serious public health concern that is influenced by a variety of body composition parameters.This study examines the associations between body composition metrics and blood pressure(BP)in a rural population,specifically how variations in body fat distribution and other metrics affect systolic blood pressure(SBP)and diastolic blood pressure(DBP).Methods:A cross-sectional study of 226 participants examined the relationships between body composition metrics—such as total body fat,visceral fat,and body mass index(BMI)—and BP.Correlation and regression analyses were used to assess these relationships.Results:The study found substantial positive correlations between visceral fat and total body fat with both SBP and DBP.Visceral fat was strongly connected with both SBP(r=0.145,P=0.030)and DBP(r=0.331,P<0.01),while total body fat was significantly correlated with DBP(r=0.268,P<0.01)but not SBP.Body composition variables explained 12.8% of the variance in SBP(R^(2)=0.128,P=0.001)and 15.0% in DBP(R^(2)=0.150,P<0.001).Conclusions:The study found substantial connections between body composition,particularly visceral and subcutaneous fat and systolic and DBP.Higher levels of visceral fat were linked to elevate BP.Body composition accounted for a significant amount of BP fluctuation.
基金supported by grants from the National Natural Science Foundation of China(Grant Nos.82192900,82192901,82192904,81390540,and 91846303 to L.L.)the National Key Research and Development Program of China(Grant No.2016YFC0900500 to Y.G.)the Kadoorie Charitable Foundation in Hong Kong,and the Wellcome Trust in the UK(Grant/Award Nos.088158/Z/09/Z,104085/Z/14/Z,and 202922/Z/16/Z to Z.C.).
文摘While a healthy lifestyle is known to reduce the risk of stroke,the extent to which blood pressure(BP)mediates this association remains unclear.The present study aimed to quantify the mediating role of BP in the association between combined lifestyle factors and stroke incidence.Using data from 51929 participants free of major cardiovascular diseases or cancer at baseline,we employed structural equation modeling to assess the mediating effects of systolic(SBP)and diastolic(DBP)blood pressure.During the follow-up,2811 incident stroke cases were identified.A healthy lifestyle was significantly associated with a reduced risk of stroke,with SBP mediating 44.70%(β=-0.0014,95%confidence interval[CI]:-0.0016 to-0.0012)and DBP mediating 37.81%(β=-0.0012,95%CI:-0.0015 to-0.0009)of this association.The mediating effects were attenuated but remained significant for ischemic stroke(SBP:33.21%;DBP:27.24%).In conclusion,approximately two-fifths of the protective association between a healthy lifestyle and stroke may be mediated by BP.These findings suggest that BP control may serve as an important early indicator for evaluating the effectiveness of lifestyle interventions in reducing stroke risk.
文摘Sport-related concussion(SRC)and its potential neurological sequela represent an emerging global health concern,requiring improved recovery management and strategies for return-to-play(RTP)to enhance brain health in athletes.Given the dynamic and multifaceted nature of SRC recovery,the purpose of this review is to synthesize existing literature on post-SRC outcomes in adult athletes,and to outline the temporal trajectories of key recovery indicators(symptoms,cognitive function,blood biomarkers)across distinct recovery phases until resolution.In the acute phase of SRC(first 48 h),symptom scores and brain damage markers peaked immediately,while cognitive impairments and neuroinflammation emerged with a slight delay.Following the initial rise,brain damage marker concentrations rapidly dropped below baseline levels at approximately 48 h following SRC injury.During the early recovery phase,neuroinflammation and most cognitive alterations resolved after 3–5 days,though symptom burden and attention deficits persisted for up to 7 days.Despite prolonged alterations reported in some individuals,recovery markers typically returned to pre-injury levels in the transition phase(≤2 weeks),though mild attention deficits were detected up to 3 weeks,and TNF-α concentrations remained elevated throughout late recovery(>2 weeks).These results reveal distinct temporal discrepancies across recovery markers and emphasize that physiological disturbances can outlast symptom resolution,underscoring the need for both multimodal assessments and appropriately timed evaluations to accurately track recovery progression.Incorporating structured follow-ups at key time points,particularly beyond symptom resolution,may improve RTP decision-making and reduce the risk of premature return and long-term neurological consequences.
基金the Chinese University of Hong Kong for providing research resources and institutional support
文摘Accurate blood pressure(BP)monitoring is essential for preventing and managing cardiovascular disease.Advancements in materials science,medicine,flexible electronic,and artificial intelligence(AI)have enabled cuffless,unobtrusive BP monitoring systems,offering an alternative to traditional sphygmomanometers.However,extending these advances to real-world cardiovascular care particularly in resource-limited settings remains challenging due to constraints in computational resources,power efficiency,and deployment scalability.This review presents a comprehensive synthesis of AI-enhanced wearable BP monitoring,emphasizing its potential for personalized,scalable,and accessible healthcare.We systematically analyze the end-to-end system architecture,from mechano-electric sensing principles and AI-based estimation models to edge-aware deployment strategies tailored for low-resource environments.We further discuss clinical validation metrics and implementation barriers and prospective strategies.To bridge lab-to-field translation,we propose an innovative"sensor-model-deployment-assessment"co-design framework.This roadmap highlights how AI-enhanced BP technologies can support proactive hypertension control and promote cardiovascular health equity on a global scale.
基金supported by the National Science and Technology Major Program for Noncommunicable Chronic Diseases(2023ZD0503500)the National Natural Science Foundation of China(82030102,12126602,91857118)+1 种基金the Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences(2021-I2M-1-010,2019-I2M-2-003)the National High Level Hospital Clinical Research Funding(2022-GSP-GG-1,2022-GSP-GG-2)。
文摘Objective Evidence suggests that depleted gut microbialα-diversity is associated with hypertension;however,whether metabolic markers affect this relationship remains unknown.We aimed to determine the potential metabolites mediating the associations ofα-diversity with blood pressure(BP)and BP variability(BPV).Methods Metagenomics and plasma targeted metabolomics were conducted on 523 Chinese participants from the MetaSalt study.The 24-hour,daytime,and nighttime BP and BPV were calculated based on ambulatory BP measurements.Linear mixed models were used to characterize the relationships betweenα-diversity(Shannon and Chao1 index)and BP indices.Mediation analyses were performed to assess the contribution of metabolites to the observed associations.The influence of key metabolites on hypertension was further evaluated in a prospective cohort of 2,169 participants.Results Gut microbial richness(Chao1)was negatively associated with 24-hour systolic BP,daytime systolic BP,daytime diastolic BP,24-hour systolic BPV,and nighttime systolic BPV(P<0.05).Moreover,26 metabolites were strongly associated with richness(Bonferroni P<0.05).Among them,four key metabolites(imidazole propionate,2-hydroxy-3-methylbutyric acid,homovanillic acid,and hydrocinnamic acid)mediated the associations between richness and BP indices(proportions of mediating effects:14.1%–67.4%).These key metabolites were also associated with hypertension in the prospective cohort.For example,each 1-standard deviation unit increase in hydrocinnamic acid significantly reduced the risk of prevalent(OR[95%CI]=0.90[0.82,0.99];P=0.03)and incident hypertension(HR[95%CI]=0.83[0.71,0.96];P=0.01).Conclusion Our results suggest that gut microbial richness correlates with lower BP and BPV,and that certain metabolites mediate these associations.These findings provide novel insights into the pathogenesis and prevention of hypertension.
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.
基金supported by the National Institute of Neurological Disorders and Stroke of the National Institutes of Health under Award Number K02NS110973 and R01NS126498(to MAP).
文摘The central nervous system(CNS)does not function in isolation-it engages in continuous molecular dialogue with the vascular and immune systems.Traditionally,the blood-brain barrier(BBB)was portrayed solely as an impermeable wall,safeguarding the CNS by excluding blood-derived molecules and circulating cells.However,this view has evolved.The BBB is now recognized as a dynamic interface that selectively regulates the exchange of signals,cells.
基金supported by the National Natural Science Foundation of China(82250410380 and 62171101)the Natural Science Foundation of Sichuan Province(24NSFSC6257)the China MOST2030 Brain Project(2022ZD0208500).
文摘Cerebral ischemia restricts cerebral blood flow(CBF),leading to unstable hemodynamics.Past studies of ischemia mainly focused on cortical CBF reduction.However,its impact on hemodynamic changes,especially temporal varying characteristics,remains poorly understood.Here,we collected cortical resting-state CBF in rats with left carotid artery blockage during occlusion–reperfusion,and measured the temporal variability and changes in laterality using a novel state-space method.This method was also applied to stroke EEG datasets to validate its effectiveness.After arterial occlusion,the left marginal motor,sensory,auditory,and visual cortices exhibited severe temporal variability impairments.The laterality analysis indicated that affected left regions showed inferior unilateral mean,inter-hemispheric transition probability,time fraction,and laterality duration,while the right side had a higher laterality time fraction and duration.These impairments recovered partially following blood flow restoration.Besides,the ischemic state-space metrics were positively correlated with the pre-occlusion baseline appearance.Stroke patients exhibited impaired temporal variability in the affected ischemic hemisphere.The state-space analysis revealed damaged CBF temporal variability during cerebral ischemia and predicted baseline-ischemia connections.
基金Capital Health Development Scientific Research Project(2020-2-4064)National Key Research and Development Program of China(2018YFC2002502).
文摘Objective Patients with atherosclerotic cardiovascular disease(ASCVD)following percutaneous coronary intervention(PCI)are classified as very-high-risk individuals in cardiovascular disease(CVD)risk stratification.The distribution pattern of traditional Chinese medicine(TCM)syndromes in this patient population,as well as its association with blood lipid profiles and clinical prognosis,remains unclear.The present prospective cohort study aims to investigate these correlations,thereby providing insights to enrich the research fields.Methods We enrolled consecutive patients with ASCVD who underwent PCI at the Integrated Cardiology Unit of China-Japan Friendship Hospital between September 1,2020 and December 31,2022.Demographics and clinical characteristics,signs and symptoms defining each TCM syndrome,and fasting venous blood samples were collected at baseline and follow up or upon major adverse cardiovascular events(MACEs).We analyzed the correlation between TCM syndromes,blood lipid profiles,and MACEs,and developed a new joint prognostic model incorporating both TCM syndromes and blood lipids using logistic regression.The analyses were based on detailed baseline and one-year follow-up data.Results A per-protocol analysis was performed on 586 patients with complete data ultimately.During the one-year follow-up,174 patients(29.69%)experienced a MACE.We performed statistical analyses on comorbidities,medication,and biochemical indicators across groups defined by TCM syndrome differentiation.When comparing different TCM syndromes,no significant differences were found in age,body mass index(BMI),history of revascularization,comorbidities,family history of CVD,smoking or drinking,or statin intensity(P>0.05).Patients with intertwined phlegm and blood stasis syndrome exhibited significantly higher levels of total cholesterol(TC,5.27±1.18 mmol/L,P<0.001),triglyceride(TG,1.96±1.33 mmol/L,P=0.008),low-density lipoprotein cholesterol(LDL-C,3.35±0.79 mmol/L,P<0.001),and high-density lipoprotein cholesterol(HDL-C,1.24±0.81 mmol/L,P<0.001)compared with those with other TCM syndromes combined.A multivariable logistic regression model was constructed to predict MACEs.The model included TCM syndrome type[with intertwined phlegm and blood stasis as a predictor,adjusted odds ratio(OR)=1.413,95%confidence interval(CI):0.517–3.864,P=0.501],age(adjusted OR=0.97,95%CI:0.955–1.001,P=0.057),male gender(adjusted OR=0.698,95%CI:0.416–1.170,P=0.173),TC(adjusted OR=1.004,95%CI:0.513–1.965,P=0.990),and LDL-C(adjusted OR=5.825,95%CI:2.214–15.326,P<0.001).This model demonstrated good discriminatory ability for MACEs in post-PCI ASCVD patients[the area under the receiver operating characteristic(ROC)curve(AUC)=0.865,95%CI:0.816–0.914].Conclusion The intertwined phlegm and blood stasis TCM syndrome is associated with a distinct atherogenic lipid profile characterized by elevated levels of TC and LDL-C.The prognostic model that incorporates this TCM syndrome type along with conventional lipid parameters(TC and LDL-C)shows good discriminatory ability for predicting MACEs in ASCVD patients after PCI,underscoring the potential clinical utility of integrating TCM syndrome differentiation into CVD risk assessment.
基金part of the EU consortium DCog Plast ‘Diet Cognition and Plasticity” funded by the Joint Programming Initiative “A Health Diet for a Healthy Life”(JPI-HDHL) via the BMWFW (BMWFW-10.420/0009-WF/V/3c/2015 and the Medical Research Council UK:MR/N030087/1)(to LA and ST)supported by the PMU-FFF Research Fund (A-16/01/019-AIG)+9 种基金BA by the PMU-Research and Innovation Fund (PMU-RIF)(project 2023-PRE-008-Altendorfer)supported by the Center for Urban Mental Healthby Alzheimer Nederlandthe Zon MW Program Mechanisms Of DEMentia (MODEM)by the Gravitation program iCNS of the Dutch Research Council (NWO)supported by Grant PID2020-114921RB-C21Maria de Maeztu Unit of Excellence grant CEX2021-001234-M funded by MCIU/AEI/and CIBERFESCB16/10/00269, from the Instituto de Salud Carlos III all of them by “ERDF A way of making Europe”the Generalitat de Catalunya’s Agency AGAUR of 2021SGR00687ICREA Award
文摘In Alzheimer’s disease,microglial phagocytosis is engaged in the pathogenesis as it clears abnormal protein accumulations,debris,and apoptotic cells in the early stages of Alzheimer’s disease,but fuels neuroinflammation and accelerates disease progression in later stages.In vivo parabiosis experiments in aged animals have demonstrated that blood-born factors modulate synaptic plasticity,neurogenesis,and microglial responses.We hypothesize that peripheral factors can modulate microglial function and thereby possibly influence Alzheimer’s disease pathology.The objective of this study is to investigate the effects of Alzheimer’s disease serum on microglial phagocytosis.Here,we use an immortalized human microglial cell line in an in vitro parabiosis assay to investigate the impact of the serum from individuals diagnosed with Alzheimer’s disease(n=30)and age-matched controls(n=30)(PRODEM study)on microglial phagocytosis.Exposure to Alzheimer’s disease serum increased microglial phagocytic uptake of pH-sensitive fluorescent particles and downregulated expression of the lysosomal master regulator transcription factor EB(TFEB)and of ATPase H^(+)transporting lysosomal V1 subunit B2(ATP6V1B2),a component of the vacuolar ATPase.To identify serum components that may relate to changes in phagocytosis,serum samples of the Three-City Study(3C Study)were used.In the 3C Study,blood samples were collected up to 12 years before the onset of cognitive decline or dementia and their serum metabolome is well-defined.Microglia exposed to the serum of future Alzheimer’s disease patients from the 3C Study displayed an increased phagocytic uptake compared with the serum of matched controls,depending on the presence of the apolipoprotein Eε4 allele in the Alzheimer’s disease patients.Furthermore,microglial phagocytosis correlated inversely with serum levels of the omega-3 fatty acid eicosapentaenoic acid.We confirmed this inverse correlation between eicosapentaenoic acid and phagocytosis in the serum samples of the PRODEM cohort.In addition,in vitro testing of eicosapentaenoic acid on microglial phagocytosis showed a concentration-dependent decrease in phagocytic uptake.In conclusion,following incubation with Alzheimer’s disease blood serum,we observed increased microglial phagocytic uptake and the downregulation of TFEB and ATP6V1B2,possibly indicating lysosomal dysfunction.Furthermore,microglial phagocytosis was inversely correlated with serum eicosapentaenoic acid levels,suggesting an important role for dietary eicosapentaenoic acid in microglial function.
文摘Alzheimer’s disease(AD)is a complex,progressive neurodegenerative disorder and the leading cause of dementia worldwide.It is characterized by the accumulation of extracellular amyloid-beta(Aβ)plaques and intracellular tau neurofibrillary tangles,leading to synaptic dysfunction,neuronal loss,and cognitive decline.These pathological changes can begin decades before clinical symptoms emerge,highlighting the critical need for early,accessible,and accurate diagnostic tools.
基金funded by the Entrusted service project of Shaanxi Administration of Traditional Chinese Medicine(ZYJXG-L23001)2023 Sanqin Talent Special Support Program Innovation and Entrepreneurship Team Project,and Sci-Tech Innovation Talent System Construction Program of Shaanxi University of Chinese Medicine(2023).
文摘Background:Panacis Quinquefolii Radix(PQR)is known for its ability to nourish“Qi”(it serves as the driving force for the functional activities of the body’s organs and meridians,promoting and regulating various physiological functions)and“Yin”(it represents the material foundation of the human body.It plays a role in nourishing,moistening,and cooling the body).Notoginseng Radix et Rhizoma(NRR)is recognized for its properties of resolving blood stasis(it refers to a pathological condition characterized by impaired or stagnant blood circulation within the body).Changes in the compatibility ratio of these herbs often lead to variations in their chemical composition and efficacy.However,the specific alterations in chemical composition and efficacy resulting from compatibility adjustments remain unclear.We aimed to compare the material basis and their effects of different compatibility ratios of PQR and NRR on“Qi”deficiency and blood stasis syndrome(QBS).Methods:This study employed UPLC-Q/TOF-MS to identify effective compounds in the compatibility of PQR and NRR and utilized UPLC-TQ-MS/MS to analyze the dissolution of 16 saponins in PQR and NRR at 9 different ratios.A rat model of QBS was established,and the efficacy of PQR and NRR in treating this syndrome was assessed using hemorheology and coagulation analyses.Results:The study results show that PQR and NRR exhibit significant efficacy,effectively reducing blood viscosity induced by platelet aggregation and lowering inflammatory markers such as IL-6,IL-10,TXB2 and ET associated with vascular injury.Moreover,this combination regulates ATP and ADP levels,enhances energy metabolism,and promotes overall health.A total of 104 compounds in the compatibility of PQR and NRR were identified.The ratios of 1:2 and 1:3 showed the highest total saponin content,but the ratio of 1:1 demonstrated a superior pharmacological effect for the treatment of QBS.Conclusion:In summary,the compatibility of PQR and NRR not only shows the complex interactions between traditional Chinese medicinal materials,but also provides a new idea and method for the treatment of QBS.
文摘Objectives Dysregulated osteoclast function contributes to skeletal diseases.However,the specific ubiquitination regulators of the osteoclastogenesis repressor MafB,particularly at the post-translational level,remain undefined.This study aims to identify ubiquitin-specific proteases(USPs)that deubiquitinate MafB and enhance its stability.Methods We constructed a MafB-conjugated luciferase and overexpressed 40 individual USPs,measuring changes in luciferase activity.The identified USP was overexpressed in human CD14^(+) peripheral blood mononuclear cells(PBMCs)to evaluate its effect.Osteoclast differentiation was assessed through osteoclast marker Integrin alpha-V(CD51)staining and Western blot analysis.Co-immunoprecipitation(co-IP)was performed to assess the interplay.The influence on MafB ubiquitination and degradation was evaluated via immunoprecipitation and Western blot.Finally,MafB was knocked down in the USP-overexpressing PBMCs to analyze its effect on osteoclast differentiation.Results Overexpression of ubiquitin-specific protease 29(USP29)significantly increased MafB expression by approximately 75%(p<0.0001).Elevated USP29 levels strongly inhibited osteoclastic differentiation in CD14^(+) PBMCs(p<0.0001).USP29 was found to interact with MafB,markedly reducing its ubiquitination and subsequent degradation in PBMCs(p<0.001).Knocking down MafB in USP29-overexpressing PBMCs alleviated the inhibitory effect of USP29 on osteoclastogenesis.Conclusion USP29 acts as a potent stabilizer of MafB,inhibiting osteoclastogenesis in human CD14^(+) PBMCs,at least in part,by enhancing MafB stability.These findings expand our understanding of USP29’s role and the post-translational regulation of MafB.Furthermore,USP29 serves as a vital factor that controls osteoclast differentiation,and its regulatory function is at least partially mediated by deubiquitinating and stabilizing MafB.
基金supported by the National Natural Science Foundation of China,Nos. 32260196 (to JY), 81860646 (to ZY) and 31860274 (to JY)a grant from Yunnan Department of Science and Technology,Nos. 202101AT070251 (to JY), 202201AS070084 (to ZY), 202301AY070001-239 (to JY), 202101AZ070001-012, and 2019FI016 (to ZY)。
文摘Studies have shown that chitosan protects against neurodegenerative diseases. However, the precise mechanism remains poorly understood. In this study, we administered chitosan intragastrically to an MPTP-induced mouse model of Parkinson's disease and found that it effectively reduced dopamine neuron injury, neurotransmitter dopamine release, and motor symptoms. These neuroprotective effects of chitosan were related to bacterial metabolites, specifically shortchain fatty acids, and chitosan administration altered intestinal microbial diversity and decreased short-chain fatty acid production in the gut. Furthermore, chitosan effectively reduced damage to the intestinal barrier and the blood–brain barrier. Finally, we demonstrated that chitosan improved intestinal barrier function and alleviated inflammation in both the peripheral nervous system and the central nervous system by reducing acetate levels. Based on these findings, we suggest a molecular mechanism by which chitosan decreases inflammation through reducing acetate levels and repairing the intestinal and blood–brain barriers, thereby alleviating symptoms of Parkinson's disease.
基金supported by Research and Innovation Foundation of Wuhan Asia General Hospital,No.2022KYCX1-B10(to FH)the Natural ScienceFoundation of Hubei Province,No.2023AFB550(to FH)+2 种基金the National Natural Science Foundation of China,Nos.32400554(to FH),82371444(to YZ)theGuiding Project of the Scientific Research Program of the Department of Education of Hubei Province,No.B2021016(to FH)the Natural Science Foundationof Hubei Province,No.2024AFB853(to QW).
文摘Alzheimer’s disease-associated transcriptomic landscapes have been defined in brain tissue.However,changes in blood RNA and their clinical relevance remain poorly understood.In this study,we developed an RNA profile based on 1468 blood samples from both human and mouse studies,which include bulk RNA sequencing(RNA-seq),microRNA-seq,and single-cell RNA-seq data.We developed a comprehensive analysis pipeline that conducted over 11 million comparisons and correlations to identify more than 20,000 blood features.With these findings,we established a blood RNA database related to Alzheimer’s disease,RNAs in Blood of AD(RBAD,http://www.bioinform.cn/RBAD/).Using RBAD,we initially validated well-established Alzheimer’s disease-related pathways,including olfactory transduction.We then observed a decrease in both the proportion and functionality of erythroid cells,likely attributed to their elevated CD45 levels and interactions with GZMK^(+)CD8^(+)T cells.Furthermore,we identified 449 blood RNAs linked to patients’overall survival,along with two mRNAs(H4C3 and CTU1)associated with cognitive decline.In summary,RBAD is the first web-based analysis platform dedicated to investigating blood RNA changes in Alzheimer’s disease,and provides valuable insights into potential peripheral biomarkers and pathogenic mechanisms related to Alzheimer’s disease.
文摘Blood cell disorders are among the leading causes of serious diseases such as leukemia,anemia,blood clotting disorders,and immune-related conditions.The global incidence of hematological diseases is increasing,affecting both children and adults.In clinical practice,blood smear analysis is still largely performed manually,relying heavily on the experience and expertise of laboratory technicians or hematologists.This manual process introduces risks of diagnostic errors,especially in cases with rare or morphologically ambiguous cells.The situation is more critical in developing countries,where there is a shortage of specialized medical personnel and limited access to modern diagnostic tools.High testing costs and delays in diagnosis hinder access to quality healthcare services.In this context,the integration of Artificial Intelligence(AI),particularly Explainable AI(XAI)based on deep learning,offers a promising solution for improving the accuracy,efficiency,and transparency of hematological diagnostics.In this study,we propose a Ghost Residual Network(GRsNet)integrated with XAI techniques such as Gradient-weighted Class Activation Mapping(Grad-CAM),Local Interpretable Model-Agnostic Explanations(LIME),and SHapley Additive exPlanations(SHAP)for automatic blood cell classification.These techniques provide visual explanations by highlighting important regions in the input images,thereby supporting clinical decision-making.The proposed model is evaluated on two public datasets:Naturalize 2K-PBC and Microscopic Blood Cell,achieving a classification accuracy of up to 95%.The results demonstrate the model’s strong potential for automated hematological diagnosis,particularly in resource-constrained settings.It not only enhances diagnostic reliability but also contributes to advancing digital transformation and equitable access to AI-driven healthcare in developing regions.
基金supported by the National Key Research and Development Plan of China (2023YFA1802000)the National Natural Science Foundation of China for Distinguished Young Scholars (31925014),the National Natural Science Foundation of China Key Program (32130033),the National Natural Science Foundation of Original Exploratory Program (32350006)+5 种基金the Key Research Program of Frontier Sciences,Chinese Academy of Sciences (ZDBS-LY-SM010)Shanghai Pilot Program for Basic Research-Chinese Academy of Sciences,Shanghai Branch (JCYJ-SHFY-2022-006)Shanghai Science Technology Innovation Action Plan for Basic Research Program (21JC1406300)Haihe laboratory of Cell Ecosystem Innovation Fund (24HHXBSS00011)CAS project for Young Scientists in Basic Research (YSBR-077)supported by Science and Technology Commission of Shanghai Municipality (Shanghai Rising-Star Program,23QA1411300)
文摘Erythroid cells, the predominant circulating blood cells, are essential for oxygen and carbon dioxide transport (Obeagu, 2024).Their production, erythropoiesis, involves the coordinated synthesis of globin chains and heme molecules to assemble hemoglobin(Zhang et al., 2021). The erythroid-specific enzyme δ-aminolevulinate synthase 2 (ALAS2) is a key rate-limiting factor in heme biosynthesis,with its expression increasing in late-stage erythropoiesis to meet heme demands (Sadlon et al., 1999). Zebrafish (Danio rerio) is a well-established model for studying erythropoiesis due to its genetic tractability and optical transparency (Zhang and Hamza, 2019;Zhang et al., 2021). The Tol2-mediated Gal4-UAS system has been widely applied for gene and enhancer trapping in zebrafish (Asakawa and Kawakami, 2009). However, reliable Gal4 enhancer-trap lines for erythropoiesis remain limited. Here, we report a transgenic zebrafish line with erythroid-specific Gal4FF expression under the control of the endogenous alas2 promoter, offering a more precise erythroblast labeling than the gata1a reporter line. This model provides a valuable tool for erythroid-specific investigations of blood flow dynamics and gene function.
文摘BACKGROUND The reference ranges for biochemical parameters can fluctuate due to factors like altitude,age,gender,and socioeconomic conditions.These values are crucial for interpreting laboratory data and guide clinical treatment decisions.Currently,there is no established set of reference intervals for cord blood biochemical parameters of newborns in India,particularly in Mumbai.AIM To create cord blood biochemical parameters reference intervals specifically for Mumbai,India.METHODS A cross-sectional study was conducted in an Indian tertiary care hospital.This study focused on healthy newborns with normal birth weight,born to pregnant mothers without health issues.Cord blood samples,approximately 2-3 mL in volume,were collected from 210 term neonates.These samples were divided into fluoride(glucose)and clot activator(serum)tubes and were subsequently analyzed in the institute's biochemical laboratory.The data obtained from the analysis was then subjected to statistical analysis.The result of the Shapiro-Wilk test suggested non-normality in the data distribution.Consequently,nonparametric statistics were utilized for analysis.The Mann-Whitney U test was utilized to compare parameter distributions among different factors,including the infant’s sex,delivery method,maternal age,and obstetric history.A significance level of P<0.05 was considered to indicate statistical significance.RESULTS The following represent the median figures and central 95 percentile reference intervals for biochemical parameters in umbilical cord blood of newborns:Serum direct bilirubin=(0.1-0.55)mg/dL,indirect bilirubin=(0.64-2.26)mg/dL,total bilirubin=(0.62-3.14)mg/dL,creatinine=(0.27-0.76)mg/dL,sodium=(128.19-143.26)mmol/L,chloride=(100.19-111.68)mmol/L,potassium=(1.62-9.98)mmol/L and plasma glucose=(24.75-94.23)mg/dL.Statistically significant differences were observed in serum sodium,potassium,and plasma glucose levels when comparing delivery modes.CONCLUSION This is the pioneering study in which first time,the biochemical reference intervals in cord blood for newborns are established in western India.The values are applicable for newborns from this area.Larger study throughout the country is required.
文摘Background The co-existence of Type 2 diabetes mellitus(T2DM)and hypertension presents a significant clinical challenge due to their synergistic detrimental effects on cardiovascular outcomes.Conventional combination therapies often fall short in comprehensively addressing the intertwined pathophysiologies,particularly vascular endothelial dysfunction.This study aimed to evaluate the efficacy of a novel regimen combining sitagliptin-metformin with nifedipine in managing blood pressure,blood glucose,and vascular function in this high-risk population.Methods 150 patients with T2DM and hypertension were randomly assigned to either the control group(n=75)treated with metformin and nifedipine,or the experimental group(n=75)treated with sitagliptin-metformin compound preparation combined with nifedipine.Changes in blood pressure,blood glucose levels,flow-mediated dilation(FMD)and nitroglycerin-mediated dilation(NMD)of the brachial artery,and serum levels of biomarkers[nitric oxide(NO),endothelin-1(ET-1)]were compared before and after treatment.The incidence of adverse reactions during treatment was also monitored.Results After treatment,both groups showed significant reductions in blood pressure,blood glucose parameters,and ET-1 levels compared to baseline.The experimental group demonstrated significantly lower values in these assessments at the same time points than control group(P<0.05).Conversely,FMD,NMD,and NO levels increased significantly in both groups after treatment,with experimental group showing significantly higher values than control group(P<0.05).There was no statistically significant difference in the incidence of adverse reactions between the two groups(P>0.05).Conclusions The combination of sitagliptinmetformin compound preparation and nifedipine significantly enhanced blood pressure control and blood glucose control and exerted a positive regulatory effect on vascular endothelial function in patients with T2DM and hypertension,demonstrating high clinical value for widespread application.
