Traumatic brain injury and Alzheimer's disease share pathological similarities,including neuronal loss,amyloid-βdeposition,tau hyperphosphorylation,blood-brain barrier dysfunction,neuroinflammation,and cognitive ...Traumatic brain injury and Alzheimer's disease share pathological similarities,including neuronal loss,amyloid-βdeposition,tau hyperphosphorylation,blood-brain barrier dysfunction,neuroinflammation,and cognitive deficits.Furthermore,traumatic brain injury can exacerbate Alzheimer's disease-like pathologies,potentially leading to the development of Alzheimer's disease.Nanocarriers offer a potential solution by facilitating the delive ry of small interfering RNAs across the blood-brain barrier for the targeted silencing of key pathological genes implicated in traumatic brain injury and Alzheimer's disease.U nlike traditional approaches to neuro regeneration,this is a molecula r-targeted strategy,thus avoiding non-specific drug actions.This review focuses on the use of nanocarrier systems for the efficient and precise delive ry of siRNAs,discussing the advantages,challenges,and future directions.In principle,siRNAs have the potential to target all genes and non-targetable protein s,holding significant promise for treating various diseases.Among the various therapeutic approaches currently available for neurological diseases,siRNA gene silencing can precisely"turn off"the expression of any gene at the genetic level,thus radically inhibiting disease progression;however,a significant challenge lies in delivering siRNAs across the blood-brain barrier.Nanoparticles have received increasing attention as an innovative drug delive ry tool fo r the treatment of brain diseases.They are considered a potential therapeutic strategy with the advantages of being able to cross the blood-brain barrier,targeted drug delivery,enhanced drug stability,and multifunctional therapy.The use of nanoparticles to deliver specific modified siRNAs to the injured brain is gradually being recognized as a feasible and effective approach.Although this strategy is still in the preclinical exploration stage,it is expected to achieve clinical translation in the future,creating a new field of molecular targeted therapy and precision medicine for the treatment of Alzheimer's disease associated with traumatic brain injury.展开更多
Objective Stroke is a leading cause of death and disability worldwide,with ischemic stroke accounting for 80%-85%of cases.Despite the prevalence,effective treatments remain scarce.The compelling evidence suggest that ...Objective Stroke is a leading cause of death and disability worldwide,with ischemic stroke accounting for 80%-85%of cases.Despite the prevalence,effective treatments remain scarce.The compelling evidence suggest that high concentrations of ATP in the brain post-stroke can trigger irreversible neuronal damage and necrosis,contributing to a range of neurocellular dysfunctions.Pyroptosis,a recently identified form of programmed cell death,is characterized by caspase-1 activation and the action of the Gasdermin D(GSDMD)protein family,leading to cell perforation and inflammatory death.Methods In this study,human neuroblastoma SH-SY5Y cells were used to investigate the mechanisms of ATP-induced neurotoxicity and the protective effects of hydrogen sulfide(H_(2)S)against this toxicity through the antagonization of pyroptosis.We employed CCK-8 and LDH assays to assess cell viability.YO-PRO-1 fluorescent dyes and flow cytometry were conducted for detecting changes in cell membrane permeability.Western blot analysis was used to measure protein levels associated with cellular dysfunction.Results Our results indicate that high concentrations of ATP enhance cytotoxicity and increase cell membrane permeability in SH-SY5Y cells,that are mitigated by the H_(2)S donor NaHS.Furthermore,ATP was found to promote the activation of the NOD-like receptor pyrin domain-containing 1(NLRP-1),caspase-1,and the cleavage of GSDMD,with NaHS significantly attenuating these effects.Conclusion Our research suggests that H2S protects SH-SY5Y cells from ATP-induced neurotoxicity through a mechanism mediated by the NLRP1,caspase-1,and GSDMD pathway.展开更多
BACKGROUND Emerging evidence implicates Candida albicans(C.albicans)in human oncogenesis.Notably,studies have supported its involvement in regulating outcomes in colorectal cancer(CRC).This study investigated the para...BACKGROUND Emerging evidence implicates Candida albicans(C.albicans)in human oncogenesis.Notably,studies have supported its involvement in regulating outcomes in colorectal cancer(CRC).This study investigated the paradoxical role of C.albicans in CRC,aiming to determine whether it promotes or suppresses tumor development,with a focus on the mechanistic basis linked to its metabolic profile.AIM To investigate the dual role of C.albicans in the development and progression of CRC through metabolite profiling and to establish a prognostic model that integrates the microbial and metabolic interactions in CRC,providing insights into potential therapeutic strategies and clinical outcomes.METHODSA prognostic model integrating C. albicans with CRC was developed, incorporating enrichment analysis, immuneinfiltration profiling, survival analysis, Mendelian randomization, single-cell sequencing, and spatial transcriptomics.The effects of the C. albicans metabolite mixture on CRC cells were subsequently validated in vitro. Theprimary metabolite composition was characterized using liquid chromatography-mass spectrometry.RESULTSA prognostic model based on five specific mRNA markers, EHD4, LIME1, GADD45B, TIMP1, and FDFT1, wasestablished. The C. albicans metabolite mixture significantly reduced CRC cell viability. Post-treatment analysisrevealed a significant decrease in gene expression in HT29 cells, while the expression levels of TIMP1, EHD4, andGADD45B were significantly elevated in HCT116 cells. Conversely, LIME1 expression and that of other CRC celllines showed reductions. In normal colonic epithelial cells (NCM460), GADD45B, TIMP1, and FDFT1 expressionlevels were significantly increased, while LIME1 and EHD4 levels were markedly reduced. Following metabolitetreatment, the invasive and migratory capabilities of NCM460, HT29, and HCT116 cells were reduced. Quantitativeanalysis of extracellular ATP post-treatment showed a significant elevation (P < 0.01). The C. albicans metabolitemixture had no effect on reactive oxygen species accumulation in CRC cells but led to a reduction in mitochondrialmembrane potential, increased intracellular lipid peroxidation, and induced apoptosis. Metabolomic profilingrevealed significant alterations, with 516 metabolites upregulated and 531 downregulated.CONCLUSIONThis study introduced a novel prognostic model for CRC risk assessment. The findings suggested that the C.albicans metabolite mixture exerted an inhibitory effect on CRC initiation.展开更多
This paper adopted the hydrothermal method to prepare tungsten oxide(WO_(3))nanorod films and studied the effects of precursor solution concentration(0.02,0.03,0.06 mol/L peroxytungstic acid)and annealing temperature(...This paper adopted the hydrothermal method to prepare tungsten oxide(WO_(3))nanorod films and studied the effects of precursor solution concentration(0.02,0.03,0.06 mol/L peroxytungstic acid)and annealing temperature(200,300,400℃)on their electrochromic properties.The microstructure characterization of WO_(3) films were performed using scanning electron microscope(SEM),X-ray diffraction(XRD),and transmission electron microscope(TEM),and their electrochromic properties were tested by combining an electrochemical workstation with an ultraviolet-visible spectrophotometer.The results showed that the precursor solution concentration directly affected the thickness(290,560,990 nm)and microstructure of WO_(3) films,significantly impacting their electrochromic properties.However,the annealing temperature had a negligible effect.As the precursor solution concentration increased,the optical modulation of WO_(3) films gradually decreased,reaching 51.1%,43.8%,and 35.1%,respectively.The switching time first increased and then stabilized,with coloring times of 7.3,7.7,and 7.7 s,respectively,and bleaching times of 3.8,6.5,and 6.5 s,respectively.The coloration efficiency gradually increased but the increase was relatively small,reaching 41.8,44.4,and 44.8 cm^(2)/C,respectively.Moreover,the cycling stability of WO_(3) films was poor,with the ratios of the final value of optical modulation to the initial value 0.33,0.26,and 0.34,respectively.Additionally,there were bigger differences in the bleached state transmittance,while the colored state transmittance showed smaller variations.However,the former has better cycling stability than the latter.In summary,to obtain better electrochromic properties,the thickness of WO_(3) films should not exceed 290 nm.展开更多
Objective:The objective of this research is to thoroughly investigate the extent of mutual interference among clinical internships,postgraduate entrance examinations,and employment by examining engineering contradicti...Objective:The objective of this research is to thoroughly investigate the extent of mutual interference among clinical internships,postgraduate entrance examinations,and employment by examining engineering contradictions,thus offering theoretical insights and guidance for medical students to attain high-quality outcomes in clinical internships.Methods:A combination of literature reviews,questionnaires,interviews,and observations of internships was utilized,followed by a statistical analysis to assess the levels of interference among the three factors.Results:The senior participants achieved significantly higher scores than their junior counterparts in evaluations of comprehensive humanistic quality,understanding professional values,communication abilities,clinical skills,and attitudes towards learning,with differences that were statistically significant(p<0.05).After applying an interactive training approach that merges early clinical practice with foundational medical education,both groups displayed notable enhancements in activity content,formats,instructor attitudes,clinical performance,and the blending of theory with practice(p<0.05).Conclusion:By emphasizing‘early clinical’education,students are effectively engaged in clinical practice through active involvement,leading to feedback-oriented training.This strategy not only improves the overall quality of internships but also reduces the risk of scheduling conflicts with postgraduate entrance examinations and employment opportunities.展开更多
BACKGROUND Auditory verbal hallucinations(AVHs)are believed to be characteristic symptoms of schizophrenia.The prevalence of AVHs in deaf patients with schizophrenia is comparable to that in patients with schizophreni...BACKGROUND Auditory verbal hallucinations(AVHs)are believed to be characteristic symptoms of schizophrenia.The prevalence of AVHs in deaf patients with schizophrenia is comparable to that in patients with schizophrenia who have normal hearing ability.AVHs in deaf patients with schizophrenia require treatment.CASE SUMMARY A 22-year-old deaf woman with schizophrenia had experienced AVHs for 3 months.Her psychotic symptoms were not alleviated by antipsychotic medication alone.Modified electroconvulsive therapy in combination with antipsychotic drugs effectively alleviated her AVHs and disorganized behavior.During outpatient follow-up for 6 months,her condition have remained stable,and she has been able to take care of herself.CONCLUSION Treatment with modified electroconvulsive therapy was found to be safe and might be indicated for deaf patients whose symptoms are not well managed with antipsychotic medication alone.Deaf people might be unable to communicate through spoken language;therefore,to make proper diagnoses and provide appropriate treatment for these patients,psychiatrists must have patience and seek to understand patients’mental state.展开更多
Neurodegenerative diseases,such as Alzheimer’s disease,Parkinson’s disease,and Huntington’s disease,are characterized by the progressive loss of neuronal function and structure,leading to severe morbidity and morta...Neurodegenerative diseases,such as Alzheimer’s disease,Parkinson’s disease,and Huntington’s disease,are characterized by the progressive loss of neuronal function and structure,leading to severe morbidity and mortality.Current therapeutic approaches are ineffective at stopping or reversing disease progression.Stem cell therapy has emerged as a promising candidate in research and treatment.Mesenchymal stem cells(MSCs)are considered ideal candidates for regenerative medicine because of their high proliferation rate and multi-differentiation potential.MSCs can differentiate into neurons and glial cells,modulate immune responses,and reduce inflammation,and their exosomes can promote neural repair and regulate neuronal function;thus,MSCs offer unique advantages for treating neurodegenerative diseases.However,challenges remain in optimizing cell delivery methods,ensuring the long-term survival and integration of transplanted cells,and fully understanding their therapeutic effects.This article primarily outlines the functions of MSCs in neurodegenerative diseases,with the intention that further research will fully harness their potential and translate these findings into clinical applications,offering new hope for patients suffering from neurodegenerative diseases.展开更多
Freeze-drying of structurally heterogeneous biomaterials such as porcine aorta presents considerable modeling challenges due to their inherent multilayer composition and moving sublimation interfaces.Conventional mode...Freeze-drying of structurally heterogeneous biomaterials such as porcine aorta presents considerable modeling challenges due to their inherent multilayer composition and moving sublimation interfaces.Conventional models often overlook structural anisotropy and dynamic boundary progression,while experimental determination of key parameters under cryogenic conditions remains difficult.To address these,this study develops a heat and mass transfer model incorporating a dynamic node strategy for the sublimation interface,which effectively handles continuous computational domain deformation.Additionally,specialized fixed nodes were incorporated to adapt to the multilayer structure and its spatially varying thermophysical properties.A novel non-contact gravimetric system was introduced to monitor mass loss in real time without disrupting vacuum,enabling accurate experimental validation.Combined with dehydration data,the model quantified critical parameters including effective thermal conductivity of the dried layer,vapor diffusivity,and sublimation mass transfer resistance.The results show that the migration of the sublimation fronts from both the inner and outer tunics toward the tunica media significantly alters the drying kinetics and heat-mass transfer characteristics.The proposed approach provides an adaptable and predictive framework for simulating freeze-drying processes in structurally heterogeneous systems with spatially varying thermophysical properties.展开更多
To develop an efficient thrombolytic therapy approach that addresses the limitations of current fibrinolytic drugs, such as short half-life, weak thrombus specificity and poor penetration ability, we constructed a NIR...To develop an efficient thrombolytic therapy approach that addresses the limitations of current fibrinolytic drugs, such as short half-life, weak thrombus specificity and poor penetration ability, we constructed a NIR-triggered detachable nanoplatform (PA/UK@IcpLipo) using thin-film hydration method. It was designed to integrate attack and defense mechanisms for thrombolytic therapy. This platform can actively identify thrombi by binding to GPIIb-IIIa receptors overexpressed on activated platelets. Upon NIR laser activation and interaction with thrombin in the thrombotic microenvironment, the thermosensitive liposomes rupture, releasing the PA/UK core for deep penetration into the thrombus. Our results showed that the PA/UK@IcpLipo nanoplatform efficiently promoted rapid thrombolysis under the action of UK (attack), followed by PA exerting an antiplatelet aggregation effect (defense). This dual-action approach significantly improved vascular reperfusion rates. The NIR-triggered detachable nanoplatform offered a promising solution for enhanced thrombolysis efficiency and reduced bleeding risk, addressing critical limitations of current fibrinolytic therapies.展开更多
BACKGROUND The causes of death in patients with advanced esophageal cancer are multi-factorial,with tumor metastasis being one of the important factors.Histone acetylation promotes the migration of esophageal squamous...BACKGROUND The causes of death in patients with advanced esophageal cancer are multi-factorial,with tumor metastasis being one of the important factors.Histone acetylation promotes the migration of esophageal squamous cell carcinoma(ESCC)cells,while the histone deacetylase inhibitor(HDACi)shows complex effects on tumor functions.AIM To comprehensively elucidate the impact and molecular mechanisms of trichostatin A(TSA),an HDACi,on cell migration in ESCC through bromodomain-containing protein(BRD4)/cellular myelocytomatosis oncogene(c-Myc)/endoplasmic reticulum(ER)-stress.METHODS The effects of TSA on ESCC cell lines Eca109 and EC9706 migration were evaluated using Transwell assays,with small interfering transfection and pathway-specific inhibitors to elucidate underlying mechanisms.The mRNA levels involved were examined by quantitative real-time polymerase chain reaction.Protein levels of acetylated histones H3(acH3)and acetylated histones H4,BRD4,c-Myc,as well as markers of ER stress and epithelial-mesenchymal transition(EMT),were analyzed using western blot.Additionally,this method was also used to examine acH3 levels in esophageal cancer tissues and adjacent tissues.Patient outcomes were subsequently tracked to identify prognostic indicators using Log-Rank tests and Cox multivariate analysis.RESULTS TSA promoted the migration of ESCC cells by stimulating the EMT process.TSA-mediated histone acetylation facilitated the recruitment of BRD4,a bromodomain-containing protein,triggering the expression of c-Myc.This cascade induced ER stress and enhanced EMT in ESCC cells.To further elucidate the underlying mechanism,we employed various interventions including the ER stress inhibitor 4-phenylbutyric acid,knockdown of c-Myc and BRD4 expression,and utilization of the BRD4 inhibitor carboxylic acid as well as the inhibitor of TSA 1.Mechanist-ically,these studies revealed that TSA-mediated histone acetylation facilitated the recruitment of BRD4,which in turn triggered the expression of c-Myc.This sequential activation induced ER stress and subsequently enhanced EMT,thereby promoting the migration of ESCC cells.Additionally,we examined histone acetylation levels in specimens from 43 patients with ESCC,including both tumor tissues and paired adjacent tissues.Statistical analysis unveiled a negative correlation between the level of histone acetylation and the long-term prognosis of patients with ESCC.CONCLUSION TSA promoted ESCC cell migration through the BRD4/c-Myc/ER stress pathway.Moreover,elevated histone acetylation in ESCC tissues correlated with poor ESCC prognosis.These findings enhance our understanding of ESCC migration and HDACi therapy.展开更多
Preterm birth(PTB)is defined as delivery before 37 weeks of gestation.PTB is associated with increased cardiovascular risk,neurodevelopmental disorders,and other diseases in infancy,childhood,and adulthood[1].Globally...Preterm birth(PTB)is defined as delivery before 37 weeks of gestation.PTB is associated with increased cardiovascular risk,neurodevelopmental disorders,and other diseases in infancy,childhood,and adulthood[1].Globally,approximately 15 million PTB cases are reported annually,posing a huge burden on individual families and the community economy[2].In the context of climate warming,O_(3) pollution has continuously increased in many countries in recent years,including China;therefore,scientific communities and government agencies must strive to mitigate ozone pollution.展开更多
Background:High-definition transcranial direct current stimulation(HD-tDCS)and repetitive transcranial magnetic stimulation(rTMS)demonstrate significant potential for improving depressive symptoms and cognitive functi...Background:High-definition transcranial direct current stimulation(HD-tDCS)and repetitive transcranial magnetic stimulation(rTMS)demonstrate significant potential for improving depressive symptoms and cognitive function;however,their effectiveness varies greatly among individuals.Functional near-infrared spectroscopy enables real-time monitoring of brain function during cognitive tasks in patients with psychiatric disorders.Methods:A 4-week longitudinal study was conducted involving 61 patients with depression and 26 healthy controls.Patients were randomly assigned to HD-tDCS,rTMS,and antidepressant(AD)groups.Changes in depressive symptoms,adverse event rates,and prefrontal cortical oxyhemoglobin concentrations were assessed.Result:At week 4,remission rates were 62.5%(15),61.9%(13),and 62.5%(10)in the HD-tDCS,rTMS,and AD groups,respectively(x^(2)=0.002,p=1.000).Response rates were 66.7%(16),71.4%(15),and 68.8%(11),respectively,with no significant difference between groups(x^(2)=0.12,p=0.941).All groups demonstrated significant improvement in depressive symptoms and cognitive function.The rTMS group exhibited a significantly greater decrease in Hamilton Depression Scale score compared with the HDtDCS and AD groups.After 2 weeks of treatment,patients exhibited improved depressive symptoms and reduced activation during the verbalfluency task.However,these changes were not significantly correlated(r=-0.159 to 0.240,p=0.121-0.988).Limitations:All patients had concomitant use of ADs,which may impact near-infrared spectroscopy signaling and have an indeterminate effect on cognition.Conclusion:HD-tDCS,rTMS,and ADs were equally effective,safe,and well-tolerated.HD-tDCS and rTMS were more effective for working memory,attention,executive functioning,and mood regulation.展开更多
Objective Recent studies have overturned the traditional concept of the lung as a “sterile organ” revealing that pulmonary microbiota dysbiosis and abnormal surfactant proteins(SPs) expression are involved in the pr...Objective Recent studies have overturned the traditional concept of the lung as a “sterile organ” revealing that pulmonary microbiota dysbiosis and abnormal surfactant proteins(SPs) expression are involved in the progression of silicosis. This study aimed to investigate the relationship between abnormal SPs expression and dysbiosis of lung microbiota in silica-induced lung fibrosis, providing insights into mechanisms of silicosis.Methods Lung pathology, SPs expression, and microbiota composition were evaluated in silicaexposed mice. A mouse model of antibiotic-induced microbiota depletion was established, and alveolar structure and SPs expression were assessed. The roles of the lung microbiota and SPs in silicosis progression were further evaluated in mice with antibiotic-induced microbiota depletion, both with and without silica exposure.Results Silica exposure induced lung inflammation and fibrosis, along with increased expression of SPA expression. Antibiotics(Abx)-induced microbiota depletion elevated SP-A and SP-D expression.Furthermore, silica exposure altered lung microbiota composition, enriching potentially pathogenic taxa.However, antibiotic-induced microbiota depletion prior to silica exposure reduced silica-mediated lung fibrosis and inflammation.Conclusion Lung microbiota is associated with silica-induced lung injury. Overproduction of SP-A and SP-D, induced by Abx-induced microbiota depletion, may enhance the resistance of mouse lung tissue to silica-induced injury.展开更多
BACKGROUND Mental disorders have become a major contributor to the Global Burden of Disease(GBD),a situation that has worsened with the onset of the coronavirus disease 2019(COVID-19)pandemic.Updated data on their imp...BACKGROUND Mental disorders have become a major contributor to the Global Burden of Disease(GBD),a situation that has worsened with the onset of the coronavirus disease 2019(COVID-19)pandemic.Updated data on their impact and a clear understanding of long-term trends are essential for global and national health authorities to implement effective prevention and intervention strategies for mental well-being.AIM To generate insights that will enhance global awareness of the burden of mental disorders and support the development of targeted,region-specific prevention and intervention strategies tailored to current global and local health challenges.METHODS We extracted data on incidence,disability-adjusted life years(DALYs),agestandardized incidence rate(ASIR),and age-standardized DALY rate(ASDR)for 12 categories of mental disorders from 1990 to 2021 across 204 countries and territories grouped into 21 regions.Trends in ASIR and ASDR were also analyzed during the COVID-19 period(2019-2021).RESULTS From 1990 to 2021,global ASIR rose by 15.23%(12.97%to 17.60%),while ASDR increased by 73.52%(70.24%to 76.71%).All 21 GBD regions saw a rise in cases and DALYs.In 2021,Central sub-Saharan Africa had the highest ASIR(8706.11),and East Asia reported the lowest(3340.99).Australasia recorded the highest ASDR(2787.87).On the national level,Greenland,Greece,United States,and Australia had the greatest ASDR values.During the pandemic years,ASIR and ASDR rose across all five socio-demographic index levels and GBD regions,with the exception of East Asia,where rates remained stable.Females experienced a higher ASDR than males in 2021.Major depressive disorder(557.87)and anxiety disorders(524.33)were the most burdensome among the 12 types,with depressive disorders ranking first in 13 out of the 21 regions.CONCLUSION The GBD study 2021 results highlight a continued and worsening global burden of mental disorders,further intensified by the COVID-19 crisis.This underscores the urgent need to reinforce mental health care systems.Special attention should be directed toward high-middle socio-demographic index areas and female populations.Expanding access to mental health services,enhancing public awareness,and delivering targeted interventions are essential to lessen the growing impact of mental disorders.展开更多
In this work,atomic Co catalysts are anchored on a three-dimensional(3D)interconnected g-C_(3)N_(4)(SACo-CN)through Co-N coordination,which exhibit efficient charge carrier transition and low activation energy barrier...In this work,atomic Co catalysts are anchored on a three-dimensional(3D)interconnected g-C_(3)N_(4)(SACo-CN)through Co-N coordination,which exhibit efficient charge carrier transition and low activation energy barriers for peroxymonosulfate(PMS).The incorporation of Co atoms extends the absorption spectrum and enhances the photoelectron-hole separation efficiency of the SACo-CN samples.The 3D interconnected structure,combined with the synergistic interplay between Co-N coordination and visible light irradiation,results in SACo-CN catalysts demonstrating excellent catalytic activity and stability for PMS activation.This leads to a degradation rate of 98.8%for oxytetracycline(OTC)within 30 min under visible light.The research proposes three potential mineralization pathways with eight intermediates,leading to a significant decrease in the toxicity of the intermediates.This work provides a facile and promising approach for the preparation of metal single atom catalysts with highly efficient PMS activation performance.展开更多
Ectromelia virus(ECTV),a member of the Orthopoxvirus genus,serves as both a causative agent of mousepox and a pivotal surrogate model for studying highly pathogenic orthopoxviruses.Although genomic data on ECTV remain...Ectromelia virus(ECTV),a member of the Orthopoxvirus genus,serves as both a causative agent of mousepox and a pivotal surrogate model for studying highly pathogenic orthopoxviruses.Although genomic data on ECTV remains limited,we report the isolation and characterization of a novel strain,ECTV-C-Tan-GD01,obtained from rodents in Guangdong Province,China.Nanopore sequencing yielded a complete genome(199 annotated genes,including one gene truncated at the C-terminus)with inverted terminal repeats(ITRs)harboring a conserved hairpin structure.Notably,a frameshift-inducing“G”deletion in the EV159 gene resulted in the truncation of a semaphorin-like protein.In vitro assays demonstrated cell-associated viral replication kinetics,with maximum titers achieved earlier in Vero/HeLa cells(72 h)than in BHK-21/CEF cells(84 h).Murine challenge experiments revealed extreme virulence(LD50<1 plaque-forming unit(PFU)via intranasal/footpad routes)and hepatosplenic tropism.Furthermore,ECTV-C-Tan-GD01 exhibited utility in evaluating orthopoxvirus countermeasures:a single dose of vaccinia virus Tiantan(VTT)or non-replicating vaccinia virus Tiantan(NTV)conferred cross-protection,while tecovirimat(ST-246),cidofovir(CDV),and brincidofovir(initially CMX001)significantly reduced viral loads and pathology.This study establishes ECTV-C-Tan-GD01 as a dual-purpose resource for probing orthopoxvirus evolution and advancing therapeutic development.展开更多
BACKGROUND Inflammatory bowel diseases(IBD),including ulcerative colitis(UC)and Crohn’s disease(CD),are chronic gastrointestinal disorders with an increasing global prevalence and significant healthcare impact.The ex...BACKGROUND Inflammatory bowel diseases(IBD),including ulcerative colitis(UC)and Crohn’s disease(CD),are chronic gastrointestinal disorders with an increasing global prevalence and significant healthcare impact.The exact etiology of this condition remains unclear.Neutrophils play a critical role in IBD pathogenesis.Translocator protein(TSPO),a mitochondrial protein linked to immune responses,has demonstrated potential as an inflammatory marker.However,its role in IBD remains underexplored.AIM To investigate the role of TSPO in IBD pathogenesis,particularly in neutrophils.METHODS Bioinformatics analyses of Gene Expression Omnibus datasets(GE75214,GSE94648,GSE156776)assessed TSPO expression in IBD patients.TSPO expression was evaluated in human IBD samples,neutrophiles and a chronic colitis mouse model.Neutrophil function was examined in 18 samples using reactive oxygen species(ROS)production and neutrophil extracellular trap(NET)formation assays.Positron emission tomography-computed tomography(PET-CT)imaging and histology from 12 mice revealed TSPO expression in colitis.PET-CT and immunofluorescence staining assessed TSPO expression in brain under neuroinflammation condition.RESULTS Bioinformatics analysis revealed elevated TSPO expression in the intestinal mucosa and peripheral blood of patients with IBD,especially in neutrophils.This was confirmed by quantitative real-time polymerase chain reaction and immunohistochemical staining,which showed a significant upregulation of TSPO in active IBD.Neutrophils from patients with UC and CD exhibited higher TSPO expression,which correlated with increased ROS production and NET formation.In a mouse model of dextran sodium sulfate-induced chronic colitis,TSPO was upregulated in the colonic neutrophils and brain tissues,indicating its systemic involvement.PET-CT imaging showed enhanced TSPO uptake in the inflamed colon and brain regions,particularly in the microglia,highlighting neuroinflammation.CONCLUSION TSPO is significantly upregulated in neutrophils in IBD and contributes to intestinal inflammation.Its elevated expression in gut highlights its potential as a promising therapeutic target for IBD.展开更多
Cancer remains one of the major threats to public health.Traditional chemotherapy,radiotherapy,and other anti-tumor therapies have numerous limitations in clinical treatment.Notwithstanding the considerable advances m...Cancer remains one of the major threats to public health.Traditional chemotherapy,radiotherapy,and other anti-tumor therapies have numerous limitations in clinical treatment.Notwithstanding the considerable advances made in recent years with regard to immunotherapy in both basic research and clinical practice,there remains scope for further improvement,particularly with respect to its efficacy against solid tumors.With advancements in nanotechnology,tumor nanovaccines hold immense potential for preventing tumor recurrence and treating metastatic tumors.Nevertheless,the considerable heterogeneity of tumor immunogenicity presents a number of significant challenges in the development of nanometrescale vaccines targeting solid tumors.Recent findings indicate that immune checkpoint inhibitor(ICI)therapy can improve the immunosuppressive microenvironment within tumors,while nanovaccines can also augment tumor sensitivity toward ICIs.Consequently,combining tumor nanovaccine with ICI therapy holds promise for effectively eradicating tumors or controlling their recurrence and metastasis during cancer treatment.This review delves into the mechanism behind combining tumor nanovaccine with ICI while focusing on factors influencing this combined therapy approach.Moreover,it offers an overview of the current research status regarding the combination of tumor nanovaccines with chemotherapy,radiotherapy,photothermal therapy,and sonodynamic therapy,as well as prospects for future developments in this field.展开更多
Osteoarthritis(OA)is a kind of joint diseases characterized by fibrosis,ulceration,and loss of articular cartilage and articular surrounding tissues caused by various factors,the main symptoms of OA include joint pain...Osteoarthritis(OA)is a kind of joint diseases characterized by fibrosis,ulceration,and loss of articular cartilage and articular surrounding tissues caused by various factors,the main symptoms of OA include joint pain,joint stiffness,and loss of joint function,and OA has the higher prevalence rate and has been listed as one of the four major disabling diseases,seriously affecting people’s lives and health.Traditional Chinese medicine(TCM)is a comprehensive science based on the theory of Yin Yang(one TCM theory,the material world is believed to be nurtured,developed,and changed under the influence of Yin and Yang)and Five Elements(The five most basic substances-wood,fire,earth,metal,and water-are considered indispensable elements that make up the world),based on TCM theory and practical experience it can play the important role in prevention,diagnosis,treatment,rehabilitation,and health care in OA,exhibit the great application potential for OA treatment.In this review,we have summarized the recent research progress in the application of TCM in OA,including an analysis of underlying mechanisms,application limitations,and potential solutions,found that the material basis and targets of the therapeutic component of TCM,the quality control and the mechanism of TCM application in OA are not very clear,which may become the application limitation of TCM in OA.We hope that this review will offer valuable insights to researchers in the field.展开更多
3D(three-dimensional)printing of soft/tough hydrogels has been widely used in flexible electronics,regenerative medicine,and other fields.However,due to their loose crosslinking,strong hydration and plasticizing effec...3D(three-dimensional)printing of soft/tough hydrogels has been widely used in flexible electronics,regenerative medicine,and other fields.However,due to their loose crosslinking,strong hydration and plasticizing effect of solvent(typically water)and susceptibility to swelling,the printed hydrogels always suffer from bearing compressive stress and shear stress.Here we report a 3D photo-printable hard/soft switchable hydrogel composite which is enabled by the phase transition(liquid/solid transition)of supercooled hydrated salt solution(solvents)within hydrogel.In hard status,it achieved a hardness of 86.5 Shore D(comparable to hard plastics),a compression strength of 81.7 MPa,and Young’s modulus of 1.2 GPa.These mechanical property parameters far exceed those of any currently 3D printed hydrogels.The most interesting thing is that the soft/hard states are easily switchable and this process can be repeated for many times.In the supercooled state,the random arrangement of liquid solvent molecules within hydrogels makes it as soft as conventional hydrogels.Upon artificial seeding of the crystal nucleus,the solvent in hydrogel undergoes rapid crystallization,resulting in the in-situ formation of numerous rigids,ordered rod-like nanoscale crystals uniformly embedded within the hydrogel matrix.This hierarchical structure remarkably enhances the Young’s modulus from kPa to GPa.Furthermore,the softness of hydrogel can be restored by heating and then cooling down to recover the supercooled state of the solvent.Taking advantage of soft/hard status switching,the hydrogel can conform to complex surface morphologies in its soft state and subsequently freeze that shape through crystallization,enabling rapid mold fabrication.Moreover,a shape fixation and recyclable smart hydrogel medical plaster bandage was also developed,capable of conforming the limb shapes and providing adequate support for the bone fracture patients after 10 min of crystallization.Our work suggests a bright future for the direct use of hard hydrogel as a robust industrial material.展开更多
基金supported by Open Project of the Key Laboratory of Trauma and Orthopedics Research Medicine in Henan Province,No.HZKFKT20220504(to YZ)the National Natural Science Foundation of China,No.32000877(to YZ)and Open Scientific Research Program of Military Logistics,No.BLB20J009(to YZ)。
文摘Traumatic brain injury and Alzheimer's disease share pathological similarities,including neuronal loss,amyloid-βdeposition,tau hyperphosphorylation,blood-brain barrier dysfunction,neuroinflammation,and cognitive deficits.Furthermore,traumatic brain injury can exacerbate Alzheimer's disease-like pathologies,potentially leading to the development of Alzheimer's disease.Nanocarriers offer a potential solution by facilitating the delive ry of small interfering RNAs across the blood-brain barrier for the targeted silencing of key pathological genes implicated in traumatic brain injury and Alzheimer's disease.U nlike traditional approaches to neuro regeneration,this is a molecula r-targeted strategy,thus avoiding non-specific drug actions.This review focuses on the use of nanocarrier systems for the efficient and precise delive ry of siRNAs,discussing the advantages,challenges,and future directions.In principle,siRNAs have the potential to target all genes and non-targetable protein s,holding significant promise for treating various diseases.Among the various therapeutic approaches currently available for neurological diseases,siRNA gene silencing can precisely"turn off"the expression of any gene at the genetic level,thus radically inhibiting disease progression;however,a significant challenge lies in delivering siRNAs across the blood-brain barrier.Nanoparticles have received increasing attention as an innovative drug delive ry tool fo r the treatment of brain diseases.They are considered a potential therapeutic strategy with the advantages of being able to cross the blood-brain barrier,targeted drug delivery,enhanced drug stability,and multifunctional therapy.The use of nanoparticles to deliver specific modified siRNAs to the injured brain is gradually being recognized as a feasible and effective approach.Although this strategy is still in the preclinical exploration stage,it is expected to achieve clinical translation in the future,creating a new field of molecular targeted therapy and precision medicine for the treatment of Alzheimer's disease associated with traumatic brain injury.
文摘Objective Stroke is a leading cause of death and disability worldwide,with ischemic stroke accounting for 80%-85%of cases.Despite the prevalence,effective treatments remain scarce.The compelling evidence suggest that high concentrations of ATP in the brain post-stroke can trigger irreversible neuronal damage and necrosis,contributing to a range of neurocellular dysfunctions.Pyroptosis,a recently identified form of programmed cell death,is characterized by caspase-1 activation and the action of the Gasdermin D(GSDMD)protein family,leading to cell perforation and inflammatory death.Methods In this study,human neuroblastoma SH-SY5Y cells were used to investigate the mechanisms of ATP-induced neurotoxicity and the protective effects of hydrogen sulfide(H_(2)S)against this toxicity through the antagonization of pyroptosis.We employed CCK-8 and LDH assays to assess cell viability.YO-PRO-1 fluorescent dyes and flow cytometry were conducted for detecting changes in cell membrane permeability.Western blot analysis was used to measure protein levels associated with cellular dysfunction.Results Our results indicate that high concentrations of ATP enhance cytotoxicity and increase cell membrane permeability in SH-SY5Y cells,that are mitigated by the H_(2)S donor NaHS.Furthermore,ATP was found to promote the activation of the NOD-like receptor pyrin domain-containing 1(NLRP-1),caspase-1,and the cleavage of GSDMD,with NaHS significantly attenuating these effects.Conclusion Our research suggests that H2S protects SH-SY5Y cells from ATP-induced neurotoxicity through a mechanism mediated by the NLRP1,caspase-1,and GSDMD pathway.
基金Supported by Gansu Province Joint Fund General Program,No.24JRRA878Gansu Provincial Science and Technology Program Project,No.24JRRA1020+2 种基金Gansu Province Key Talent Program,No.2025RCXM006Teaching Research and Reform Program for Postgraduate Education at Gansu University of Traditional Chinese Medicine(GUSTCM),No.YBXM-202406Special Fund for Mentors of“Qihuang Talents”in the First-Level Discipline of Chinese Medicine,No.ZYXKBD-202415。
文摘BACKGROUND Emerging evidence implicates Candida albicans(C.albicans)in human oncogenesis.Notably,studies have supported its involvement in regulating outcomes in colorectal cancer(CRC).This study investigated the paradoxical role of C.albicans in CRC,aiming to determine whether it promotes or suppresses tumor development,with a focus on the mechanistic basis linked to its metabolic profile.AIM To investigate the dual role of C.albicans in the development and progression of CRC through metabolite profiling and to establish a prognostic model that integrates the microbial and metabolic interactions in CRC,providing insights into potential therapeutic strategies and clinical outcomes.METHODSA prognostic model integrating C. albicans with CRC was developed, incorporating enrichment analysis, immuneinfiltration profiling, survival analysis, Mendelian randomization, single-cell sequencing, and spatial transcriptomics.The effects of the C. albicans metabolite mixture on CRC cells were subsequently validated in vitro. Theprimary metabolite composition was characterized using liquid chromatography-mass spectrometry.RESULTSA prognostic model based on five specific mRNA markers, EHD4, LIME1, GADD45B, TIMP1, and FDFT1, wasestablished. The C. albicans metabolite mixture significantly reduced CRC cell viability. Post-treatment analysisrevealed a significant decrease in gene expression in HT29 cells, while the expression levels of TIMP1, EHD4, andGADD45B were significantly elevated in HCT116 cells. Conversely, LIME1 expression and that of other CRC celllines showed reductions. In normal colonic epithelial cells (NCM460), GADD45B, TIMP1, and FDFT1 expressionlevels were significantly increased, while LIME1 and EHD4 levels were markedly reduced. Following metabolitetreatment, the invasive and migratory capabilities of NCM460, HT29, and HCT116 cells were reduced. Quantitativeanalysis of extracellular ATP post-treatment showed a significant elevation (P < 0.01). The C. albicans metabolitemixture had no effect on reactive oxygen species accumulation in CRC cells but led to a reduction in mitochondrialmembrane potential, increased intracellular lipid peroxidation, and induced apoptosis. Metabolomic profilingrevealed significant alterations, with 516 metabolites upregulated and 531 downregulated.CONCLUSIONThis study introduced a novel prognostic model for CRC risk assessment. The findings suggested that the C.albicans metabolite mixture exerted an inhibitory effect on CRC initiation.
基金the National Natural Science Foundation of China(No.52272009)the Henan Provincial Science and Technology Research Project(No.242102230151)+1 种基金the Henan Provincial University Science and Technology Innovation Team(No.25IRTSTHN009)the Key Scientific Research Projects of Colleges and Universities in Henan Province(Nos.24B560021,25B560020,25B560023)。
文摘This paper adopted the hydrothermal method to prepare tungsten oxide(WO_(3))nanorod films and studied the effects of precursor solution concentration(0.02,0.03,0.06 mol/L peroxytungstic acid)and annealing temperature(200,300,400℃)on their electrochromic properties.The microstructure characterization of WO_(3) films were performed using scanning electron microscope(SEM),X-ray diffraction(XRD),and transmission electron microscope(TEM),and their electrochromic properties were tested by combining an electrochemical workstation with an ultraviolet-visible spectrophotometer.The results showed that the precursor solution concentration directly affected the thickness(290,560,990 nm)and microstructure of WO_(3) films,significantly impacting their electrochromic properties.However,the annealing temperature had a negligible effect.As the precursor solution concentration increased,the optical modulation of WO_(3) films gradually decreased,reaching 51.1%,43.8%,and 35.1%,respectively.The switching time first increased and then stabilized,with coloring times of 7.3,7.7,and 7.7 s,respectively,and bleaching times of 3.8,6.5,and 6.5 s,respectively.The coloration efficiency gradually increased but the increase was relatively small,reaching 41.8,44.4,and 44.8 cm^(2)/C,respectively.Moreover,the cycling stability of WO_(3) films was poor,with the ratios of the final value of optical modulation to the initial value 0.33,0.26,and 0.34,respectively.Additionally,there were bigger differences in the bleached state transmittance,while the colored state transmittance showed smaller variations.However,the former has better cycling stability than the latter.In summary,to obtain better electrochromic properties,the thickness of WO_(3) films should not exceed 290 nm.
基金Ministry of Education Industry-University Cooperative Education Program(Project No.:231002999080311)Xinxiang Medical University Education and Teaching Reform Research(Project No.:2021-XYJG-100)。
文摘Objective:The objective of this research is to thoroughly investigate the extent of mutual interference among clinical internships,postgraduate entrance examinations,and employment by examining engineering contradictions,thus offering theoretical insights and guidance for medical students to attain high-quality outcomes in clinical internships.Methods:A combination of literature reviews,questionnaires,interviews,and observations of internships was utilized,followed by a statistical analysis to assess the levels of interference among the three factors.Results:The senior participants achieved significantly higher scores than their junior counterparts in evaluations of comprehensive humanistic quality,understanding professional values,communication abilities,clinical skills,and attitudes towards learning,with differences that were statistically significant(p<0.05).After applying an interactive training approach that merges early clinical practice with foundational medical education,both groups displayed notable enhancements in activity content,formats,instructor attitudes,clinical performance,and the blending of theory with practice(p<0.05).Conclusion:By emphasizing‘early clinical’education,students are effectively engaged in clinical practice through active involvement,leading to feedback-oriented training.This strategy not only improves the overall quality of internships but also reduces the risk of scheduling conflicts with postgraduate entrance examinations and employment opportunities.
基金the Doctoral Startup Fund of the Second Affiliated Hospital of Xinxiang Medical University.
文摘BACKGROUND Auditory verbal hallucinations(AVHs)are believed to be characteristic symptoms of schizophrenia.The prevalence of AVHs in deaf patients with schizophrenia is comparable to that in patients with schizophrenia who have normal hearing ability.AVHs in deaf patients with schizophrenia require treatment.CASE SUMMARY A 22-year-old deaf woman with schizophrenia had experienced AVHs for 3 months.Her psychotic symptoms were not alleviated by antipsychotic medication alone.Modified electroconvulsive therapy in combination with antipsychotic drugs effectively alleviated her AVHs and disorganized behavior.During outpatient follow-up for 6 months,her condition have remained stable,and she has been able to take care of herself.CONCLUSION Treatment with modified electroconvulsive therapy was found to be safe and might be indicated for deaf patients whose symptoms are not well managed with antipsychotic medication alone.Deaf people might be unable to communicate through spoken language;therefore,to make proper diagnoses and provide appropriate treatment for these patients,psychiatrists must have patience and seek to understand patients’mental state.
基金Supported by Natural Science Foundation of Henan Province,No.242300421199 and No.252300421395Henan Province Joint Fund for Science and Technology Research and Development,No.235101610002+1 种基金Key Technologies R&D Program of Henan Province,No.242102310134Henan Province Foundation for University Key Teacher,No.2024GGJS088.
文摘Neurodegenerative diseases,such as Alzheimer’s disease,Parkinson’s disease,and Huntington’s disease,are characterized by the progressive loss of neuronal function and structure,leading to severe morbidity and mortality.Current therapeutic approaches are ineffective at stopping or reversing disease progression.Stem cell therapy has emerged as a promising candidate in research and treatment.Mesenchymal stem cells(MSCs)are considered ideal candidates for regenerative medicine because of their high proliferation rate and multi-differentiation potential.MSCs can differentiate into neurons and glial cells,modulate immune responses,and reduce inflammation,and their exosomes can promote neural repair and regulate neuronal function;thus,MSCs offer unique advantages for treating neurodegenerative diseases.However,challenges remain in optimizing cell delivery methods,ensuring the long-term survival and integration of transplanted cells,and fully understanding their therapeutic effects.This article primarily outlines the functions of MSCs in neurodegenerative diseases,with the intention that further research will fully harness their potential and translate these findings into clinical applications,offering new hope for patients suffering from neurodegenerative diseases.
基金funded by the Scientific and Technological Research Projects in Henan Province(No.252102310425)the Key Scientific Research Projects of Higher Education Institutions in Henan Province(No.23A560018).
文摘Freeze-drying of structurally heterogeneous biomaterials such as porcine aorta presents considerable modeling challenges due to their inherent multilayer composition and moving sublimation interfaces.Conventional models often overlook structural anisotropy and dynamic boundary progression,while experimental determination of key parameters under cryogenic conditions remains difficult.To address these,this study develops a heat and mass transfer model incorporating a dynamic node strategy for the sublimation interface,which effectively handles continuous computational domain deformation.Additionally,specialized fixed nodes were incorporated to adapt to the multilayer structure and its spatially varying thermophysical properties.A novel non-contact gravimetric system was introduced to monitor mass loss in real time without disrupting vacuum,enabling accurate experimental validation.Combined with dehydration data,the model quantified critical parameters including effective thermal conductivity of the dried layer,vapor diffusivity,and sublimation mass transfer resistance.The results show that the migration of the sublimation fronts from both the inner and outer tunics toward the tunica media significantly alters the drying kinetics and heat-mass transfer characteristics.The proposed approach provides an adaptable and predictive framework for simulating freeze-drying processes in structurally heterogeneous systems with spatially varying thermophysical properties.
基金supported by National Natural Science Foundation of China(No.82102918)。
文摘To develop an efficient thrombolytic therapy approach that addresses the limitations of current fibrinolytic drugs, such as short half-life, weak thrombus specificity and poor penetration ability, we constructed a NIR-triggered detachable nanoplatform (PA/UK@IcpLipo) using thin-film hydration method. It was designed to integrate attack and defense mechanisms for thrombolytic therapy. This platform can actively identify thrombi by binding to GPIIb-IIIa receptors overexpressed on activated platelets. Upon NIR laser activation and interaction with thrombin in the thrombotic microenvironment, the thermosensitive liposomes rupture, releasing the PA/UK core for deep penetration into the thrombus. Our results showed that the PA/UK@IcpLipo nanoplatform efficiently promoted rapid thrombolysis under the action of UK (attack), followed by PA exerting an antiplatelet aggregation effect (defense). This dual-action approach significantly improved vascular reperfusion rates. The NIR-triggered detachable nanoplatform offered a promising solution for enhanced thrombolysis efficiency and reduced bleeding risk, addressing critical limitations of current fibrinolytic therapies.
基金Supported by the Henan Province Science and Technology Development Plan,No.242102311124Key Medical Scientific and Technological Project of Henan Province,No.SBGJ202102188+1 种基金Henan Provincial Medical Science and Technology Project,No.LHGJ20221012Fundamental Research Funds for the Universities of Henan Province,No.NSFRF240308.
文摘BACKGROUND The causes of death in patients with advanced esophageal cancer are multi-factorial,with tumor metastasis being one of the important factors.Histone acetylation promotes the migration of esophageal squamous cell carcinoma(ESCC)cells,while the histone deacetylase inhibitor(HDACi)shows complex effects on tumor functions.AIM To comprehensively elucidate the impact and molecular mechanisms of trichostatin A(TSA),an HDACi,on cell migration in ESCC through bromodomain-containing protein(BRD4)/cellular myelocytomatosis oncogene(c-Myc)/endoplasmic reticulum(ER)-stress.METHODS The effects of TSA on ESCC cell lines Eca109 and EC9706 migration were evaluated using Transwell assays,with small interfering transfection and pathway-specific inhibitors to elucidate underlying mechanisms.The mRNA levels involved were examined by quantitative real-time polymerase chain reaction.Protein levels of acetylated histones H3(acH3)and acetylated histones H4,BRD4,c-Myc,as well as markers of ER stress and epithelial-mesenchymal transition(EMT),were analyzed using western blot.Additionally,this method was also used to examine acH3 levels in esophageal cancer tissues and adjacent tissues.Patient outcomes were subsequently tracked to identify prognostic indicators using Log-Rank tests and Cox multivariate analysis.RESULTS TSA promoted the migration of ESCC cells by stimulating the EMT process.TSA-mediated histone acetylation facilitated the recruitment of BRD4,a bromodomain-containing protein,triggering the expression of c-Myc.This cascade induced ER stress and enhanced EMT in ESCC cells.To further elucidate the underlying mechanism,we employed various interventions including the ER stress inhibitor 4-phenylbutyric acid,knockdown of c-Myc and BRD4 expression,and utilization of the BRD4 inhibitor carboxylic acid as well as the inhibitor of TSA 1.Mechanist-ically,these studies revealed that TSA-mediated histone acetylation facilitated the recruitment of BRD4,which in turn triggered the expression of c-Myc.This sequential activation induced ER stress and subsequently enhanced EMT,thereby promoting the migration of ESCC cells.Additionally,we examined histone acetylation levels in specimens from 43 patients with ESCC,including both tumor tissues and paired adjacent tissues.Statistical analysis unveiled a negative correlation between the level of histone acetylation and the long-term prognosis of patients with ESCC.CONCLUSION TSA promoted ESCC cell migration through the BRD4/c-Myc/ER stress pathway.Moreover,elevated histone acetylation in ESCC tissues correlated with poor ESCC prognosis.These findings enhance our understanding of ESCC migration and HDACi therapy.
基金supported by the Natural Science Foundation of Henan Province[grant number:242300420115]Key Scientific Research Projects in Universities of Henan Province[grant number:23A330006].
文摘Preterm birth(PTB)is defined as delivery before 37 weeks of gestation.PTB is associated with increased cardiovascular risk,neurodevelopmental disorders,and other diseases in infancy,childhood,and adulthood[1].Globally,approximately 15 million PTB cases are reported annually,posing a huge burden on individual families and the community economy[2].In the context of climate warming,O_(3) pollution has continuously increased in many countries in recent years,including China;therefore,scientific communities and government agencies must strive to mitigate ozone pollution.
基金funded by the Research and Innovation Support Project for Postgraduates at Xinxiang Medical University(YJSCX202203Z,YJSCX202253Y,YJSCX202293Y,YJSCX2022115Y)the Second Affiliated Hospital of Xinxiang Medical University opened the project of psychiatry(XYEFYJSSJ-2023-07)+1 种基金Henan Provincial Key Laboratory of Nerve Repair(HNSJXF-2021-003)the Project of Higher Education Research of Henan Province(2021SXHLX072).
文摘Background:High-definition transcranial direct current stimulation(HD-tDCS)and repetitive transcranial magnetic stimulation(rTMS)demonstrate significant potential for improving depressive symptoms and cognitive function;however,their effectiveness varies greatly among individuals.Functional near-infrared spectroscopy enables real-time monitoring of brain function during cognitive tasks in patients with psychiatric disorders.Methods:A 4-week longitudinal study was conducted involving 61 patients with depression and 26 healthy controls.Patients were randomly assigned to HD-tDCS,rTMS,and antidepressant(AD)groups.Changes in depressive symptoms,adverse event rates,and prefrontal cortical oxyhemoglobin concentrations were assessed.Result:At week 4,remission rates were 62.5%(15),61.9%(13),and 62.5%(10)in the HD-tDCS,rTMS,and AD groups,respectively(x^(2)=0.002,p=1.000).Response rates were 66.7%(16),71.4%(15),and 68.8%(11),respectively,with no significant difference between groups(x^(2)=0.12,p=0.941).All groups demonstrated significant improvement in depressive symptoms and cognitive function.The rTMS group exhibited a significantly greater decrease in Hamilton Depression Scale score compared with the HDtDCS and AD groups.After 2 weeks of treatment,patients exhibited improved depressive symptoms and reduced activation during the verbalfluency task.However,these changes were not significantly correlated(r=-0.159 to 0.240,p=0.121-0.988).Limitations:All patients had concomitant use of ADs,which may impact near-infrared spectroscopy signaling and have an indeterminate effect on cognition.Conclusion:HD-tDCS,rTMS,and ADs were equally effective,safe,and well-tolerated.HD-tDCS and rTMS were more effective for working memory,attention,executive functioning,and mood regulation.
基金supported by the National Natural Science Foundation of China Joint Fund for Regional Innovation and Development(Grant numbers [U21A20334])the Postgraduate Innovation Funding Project of Hebei Province(Grant numbers [CXZZBS2022116])。
文摘Objective Recent studies have overturned the traditional concept of the lung as a “sterile organ” revealing that pulmonary microbiota dysbiosis and abnormal surfactant proteins(SPs) expression are involved in the progression of silicosis. This study aimed to investigate the relationship between abnormal SPs expression and dysbiosis of lung microbiota in silica-induced lung fibrosis, providing insights into mechanisms of silicosis.Methods Lung pathology, SPs expression, and microbiota composition were evaluated in silicaexposed mice. A mouse model of antibiotic-induced microbiota depletion was established, and alveolar structure and SPs expression were assessed. The roles of the lung microbiota and SPs in silicosis progression were further evaluated in mice with antibiotic-induced microbiota depletion, both with and without silica exposure.Results Silica exposure induced lung inflammation and fibrosis, along with increased expression of SPA expression. Antibiotics(Abx)-induced microbiota depletion elevated SP-A and SP-D expression.Furthermore, silica exposure altered lung microbiota composition, enriching potentially pathogenic taxa.However, antibiotic-induced microbiota depletion prior to silica exposure reduced silica-mediated lung fibrosis and inflammation.Conclusion Lung microbiota is associated with silica-induced lung injury. Overproduction of SP-A and SP-D, induced by Abx-induced microbiota depletion, may enhance the resistance of mouse lung tissue to silica-induced injury.
文摘BACKGROUND Mental disorders have become a major contributor to the Global Burden of Disease(GBD),a situation that has worsened with the onset of the coronavirus disease 2019(COVID-19)pandemic.Updated data on their impact and a clear understanding of long-term trends are essential for global and national health authorities to implement effective prevention and intervention strategies for mental well-being.AIM To generate insights that will enhance global awareness of the burden of mental disorders and support the development of targeted,region-specific prevention and intervention strategies tailored to current global and local health challenges.METHODS We extracted data on incidence,disability-adjusted life years(DALYs),agestandardized incidence rate(ASIR),and age-standardized DALY rate(ASDR)for 12 categories of mental disorders from 1990 to 2021 across 204 countries and territories grouped into 21 regions.Trends in ASIR and ASDR were also analyzed during the COVID-19 period(2019-2021).RESULTS From 1990 to 2021,global ASIR rose by 15.23%(12.97%to 17.60%),while ASDR increased by 73.52%(70.24%to 76.71%).All 21 GBD regions saw a rise in cases and DALYs.In 2021,Central sub-Saharan Africa had the highest ASIR(8706.11),and East Asia reported the lowest(3340.99).Australasia recorded the highest ASDR(2787.87).On the national level,Greenland,Greece,United States,and Australia had the greatest ASDR values.During the pandemic years,ASIR and ASDR rose across all five socio-demographic index levels and GBD regions,with the exception of East Asia,where rates remained stable.Females experienced a higher ASDR than males in 2021.Major depressive disorder(557.87)and anxiety disorders(524.33)were the most burdensome among the 12 types,with depressive disorders ranking first in 13 out of the 21 regions.CONCLUSION The GBD study 2021 results highlight a continued and worsening global burden of mental disorders,further intensified by the COVID-19 crisis.This underscores the urgent need to reinforce mental health care systems.Special attention should be directed toward high-middle socio-demographic index areas and female populations.Expanding access to mental health services,enhancing public awareness,and delivering targeted interventions are essential to lessen the growing impact of mental disorders.
基金financial support from the National Natural Science Foundation of China(Nos.22276159,J2224005)the Key research project plan for higher education institutions of Henan province(No.24ZX009)+1 种基金the Development Program for Key Young Teachers in Colleges and Universities of Henan Province(No.2020GGJS146)the Starting Research Fund of Xinxiang Medical University(No.XYBSKYZZ201911)。
文摘In this work,atomic Co catalysts are anchored on a three-dimensional(3D)interconnected g-C_(3)N_(4)(SACo-CN)through Co-N coordination,which exhibit efficient charge carrier transition and low activation energy barriers for peroxymonosulfate(PMS).The incorporation of Co atoms extends the absorption spectrum and enhances the photoelectron-hole separation efficiency of the SACo-CN samples.The 3D interconnected structure,combined with the synergistic interplay between Co-N coordination and visible light irradiation,results in SACo-CN catalysts demonstrating excellent catalytic activity and stability for PMS activation.This leads to a degradation rate of 98.8%for oxytetracycline(OTC)within 30 min under visible light.The research proposes three potential mineralization pathways with eight intermediates,leading to a significant decrease in the toxicity of the intermediates.This work provides a facile and promising approach for the preparation of metal single atom catalysts with highly efficient PMS activation performance.
基金supported by the Natural Science Foundation of Beijing(7254390)the Youth Science Foundation of Chinese Center for Disease Control and Prevention(2024A103)to W.C.C,the National Key ResearchDevelopment Program of China(2022YFC2304100,2023YFD1800405).
文摘Ectromelia virus(ECTV),a member of the Orthopoxvirus genus,serves as both a causative agent of mousepox and a pivotal surrogate model for studying highly pathogenic orthopoxviruses.Although genomic data on ECTV remains limited,we report the isolation and characterization of a novel strain,ECTV-C-Tan-GD01,obtained from rodents in Guangdong Province,China.Nanopore sequencing yielded a complete genome(199 annotated genes,including one gene truncated at the C-terminus)with inverted terminal repeats(ITRs)harboring a conserved hairpin structure.Notably,a frameshift-inducing“G”deletion in the EV159 gene resulted in the truncation of a semaphorin-like protein.In vitro assays demonstrated cell-associated viral replication kinetics,with maximum titers achieved earlier in Vero/HeLa cells(72 h)than in BHK-21/CEF cells(84 h).Murine challenge experiments revealed extreme virulence(LD50<1 plaque-forming unit(PFU)via intranasal/footpad routes)and hepatosplenic tropism.Furthermore,ECTV-C-Tan-GD01 exhibited utility in evaluating orthopoxvirus countermeasures:a single dose of vaccinia virus Tiantan(VTT)or non-replicating vaccinia virus Tiantan(NTV)conferred cross-protection,while tecovirimat(ST-246),cidofovir(CDV),and brincidofovir(initially CMX001)significantly reduced viral loads and pathology.This study establishes ECTV-C-Tan-GD01 as a dual-purpose resource for probing orthopoxvirus evolution and advancing therapeutic development.
基金Supported by National Natural Science Foundation of China,No.82300604Science and Technology Innovation Action Plan Star Project Application Guide/Star Project Incubation(Yangfan Special Program)of Shanghai,No.24YF2727600.
文摘BACKGROUND Inflammatory bowel diseases(IBD),including ulcerative colitis(UC)and Crohn’s disease(CD),are chronic gastrointestinal disorders with an increasing global prevalence and significant healthcare impact.The exact etiology of this condition remains unclear.Neutrophils play a critical role in IBD pathogenesis.Translocator protein(TSPO),a mitochondrial protein linked to immune responses,has demonstrated potential as an inflammatory marker.However,its role in IBD remains underexplored.AIM To investigate the role of TSPO in IBD pathogenesis,particularly in neutrophils.METHODS Bioinformatics analyses of Gene Expression Omnibus datasets(GE75214,GSE94648,GSE156776)assessed TSPO expression in IBD patients.TSPO expression was evaluated in human IBD samples,neutrophiles and a chronic colitis mouse model.Neutrophil function was examined in 18 samples using reactive oxygen species(ROS)production and neutrophil extracellular trap(NET)formation assays.Positron emission tomography-computed tomography(PET-CT)imaging and histology from 12 mice revealed TSPO expression in colitis.PET-CT and immunofluorescence staining assessed TSPO expression in brain under neuroinflammation condition.RESULTS Bioinformatics analysis revealed elevated TSPO expression in the intestinal mucosa and peripheral blood of patients with IBD,especially in neutrophils.This was confirmed by quantitative real-time polymerase chain reaction and immunohistochemical staining,which showed a significant upregulation of TSPO in active IBD.Neutrophils from patients with UC and CD exhibited higher TSPO expression,which correlated with increased ROS production and NET formation.In a mouse model of dextran sodium sulfate-induced chronic colitis,TSPO was upregulated in the colonic neutrophils and brain tissues,indicating its systemic involvement.PET-CT imaging showed enhanced TSPO uptake in the inflamed colon and brain regions,particularly in the microglia,highlighting neuroinflammation.CONCLUSION TSPO is significantly upregulated in neutrophils in IBD and contributes to intestinal inflammation.Its elevated expression in gut highlights its potential as a promising therapeutic target for IBD.
基金financially supported by the Key Scientific Research Project of Henan Provincial Universities in 2024(No.24A350013)the Project of Basic Research Fund of Henan Institute of Medical and Pharmaceutical Sciences(No.2024BP0202)+1 种基金the Key Scientific and Technological Project of Henan Province(No.242102311213)the Henan Province Postdoctoral Program(No.343915)。
文摘Cancer remains one of the major threats to public health.Traditional chemotherapy,radiotherapy,and other anti-tumor therapies have numerous limitations in clinical treatment.Notwithstanding the considerable advances made in recent years with regard to immunotherapy in both basic research and clinical practice,there remains scope for further improvement,particularly with respect to its efficacy against solid tumors.With advancements in nanotechnology,tumor nanovaccines hold immense potential for preventing tumor recurrence and treating metastatic tumors.Nevertheless,the considerable heterogeneity of tumor immunogenicity presents a number of significant challenges in the development of nanometrescale vaccines targeting solid tumors.Recent findings indicate that immune checkpoint inhibitor(ICI)therapy can improve the immunosuppressive microenvironment within tumors,while nanovaccines can also augment tumor sensitivity toward ICIs.Consequently,combining tumor nanovaccine with ICI therapy holds promise for effectively eradicating tumors or controlling their recurrence and metastasis during cancer treatment.This review delves into the mechanism behind combining tumor nanovaccine with ICI while focusing on factors influencing this combined therapy approach.Moreover,it offers an overview of the current research status regarding the combination of tumor nanovaccines with chemotherapy,radiotherapy,photothermal therapy,and sonodynamic therapy,as well as prospects for future developments in this field.
文摘Osteoarthritis(OA)is a kind of joint diseases characterized by fibrosis,ulceration,and loss of articular cartilage and articular surrounding tissues caused by various factors,the main symptoms of OA include joint pain,joint stiffness,and loss of joint function,and OA has the higher prevalence rate and has been listed as one of the four major disabling diseases,seriously affecting people’s lives and health.Traditional Chinese medicine(TCM)is a comprehensive science based on the theory of Yin Yang(one TCM theory,the material world is believed to be nurtured,developed,and changed under the influence of Yin and Yang)and Five Elements(The five most basic substances-wood,fire,earth,metal,and water-are considered indispensable elements that make up the world),based on TCM theory and practical experience it can play the important role in prevention,diagnosis,treatment,rehabilitation,and health care in OA,exhibit the great application potential for OA treatment.In this review,we have summarized the recent research progress in the application of TCM in OA,including an analysis of underlying mechanisms,application limitations,and potential solutions,found that the material basis and targets of the therapeutic component of TCM,the quality control and the mechanism of TCM application in OA are not very clear,which may become the application limitation of TCM in OA.We hope that this review will offer valuable insights to researchers in the field.
基金sponsored by the National Natural Science Foundation of China(Grant Nos.52235007,T2121004,and 52325504)Key R&D Program of Zhejiang(Grant No.2024SSYS0027)。
文摘3D(three-dimensional)printing of soft/tough hydrogels has been widely used in flexible electronics,regenerative medicine,and other fields.However,due to their loose crosslinking,strong hydration and plasticizing effect of solvent(typically water)and susceptibility to swelling,the printed hydrogels always suffer from bearing compressive stress and shear stress.Here we report a 3D photo-printable hard/soft switchable hydrogel composite which is enabled by the phase transition(liquid/solid transition)of supercooled hydrated salt solution(solvents)within hydrogel.In hard status,it achieved a hardness of 86.5 Shore D(comparable to hard plastics),a compression strength of 81.7 MPa,and Young’s modulus of 1.2 GPa.These mechanical property parameters far exceed those of any currently 3D printed hydrogels.The most interesting thing is that the soft/hard states are easily switchable and this process can be repeated for many times.In the supercooled state,the random arrangement of liquid solvent molecules within hydrogels makes it as soft as conventional hydrogels.Upon artificial seeding of the crystal nucleus,the solvent in hydrogel undergoes rapid crystallization,resulting in the in-situ formation of numerous rigids,ordered rod-like nanoscale crystals uniformly embedded within the hydrogel matrix.This hierarchical structure remarkably enhances the Young’s modulus from kPa to GPa.Furthermore,the softness of hydrogel can be restored by heating and then cooling down to recover the supercooled state of the solvent.Taking advantage of soft/hard status switching,the hydrogel can conform to complex surface morphologies in its soft state and subsequently freeze that shape through crystallization,enabling rapid mold fabrication.Moreover,a shape fixation and recyclable smart hydrogel medical plaster bandage was also developed,capable of conforming the limb shapes and providing adequate support for the bone fracture patients after 10 min of crystallization.Our work suggests a bright future for the direct use of hard hydrogel as a robust industrial material.
