[Objective] The study was to explore whether antimicrobial activity of the antimicrobial peptides extracted from immunized Tenebrio molitor varied with different pathogens as inducers.[Method]By inducing T.molitor hun...[Objective] The study was to explore whether antimicrobial activity of the antimicrobial peptides extracted from immunized Tenebrio molitor varied with different pathogens as inducers.[Method]By inducing T.molitor hungry larvaes to generate immune response via feeding with bacteria and with fungi or actinomycete post to pricking,the antimicrobial peptides extracts were obtained by grinding and centrifuging the cultures.Its antimicrobial activity against 26 pathogens was measured by bacteriostatic ring,and evaluated by trisection to four types and inhibitory spectrum.[Result]Both the antimicrobial activity and antimicrobial spectrum of the antimicrobial peptides extracts varied remarkably among different pathogens as inducers.[Conclusion]Bio-control used strains have obvious advantage in inducing the insect to express body fluid immunity material-antimicrobial peptides.展开更多
Since the introduction of Ant Colony Optimization (ACO) technique in 1992, the algorithm starts to gain popularity due to its attractive features. However, several shortcomings such as slow convergence and stagnation ...Since the introduction of Ant Colony Optimization (ACO) technique in 1992, the algorithm starts to gain popularity due to its attractive features. However, several shortcomings such as slow convergence and stagnation motivate many researchers to stop further implementation of ACO. Therefore, in order to overcome these drawbacks, ACO is proposed to be combined with Differential Evolution (DE) and cloning process. This paper presents Differential Evolution Immunized Ant Colony Optimization (DEIANT) technique in solving economic load dispatch problem. The combination creates a new algorithm that will be termed as Differential Evolution Immunized Ant Colony Optimization (DEIANT). DEIANT was utilized to optimize economic load dispatch problem. A comparison was made between DEIANT and classical ACO to evaluate the performance of the new algorithm. In realizing the effectiveness of the proposed technique, IEEE 57-Bus Reliable Test System (RTS) has been used as the test specimen. Results obtained from the study revealed that the proposed DEIANT has superior computation time.展开更多
In order to know the cross reaction betweenBCG and Atypical Myeobaeteria(AM)anti-.genieity,1150 BCG immunized babies aged 12—24 weeks,undertook a bilateral arm control testwith H-PPD type 11 AM-PPD and BCG-PPD.The re...In order to know the cross reaction betweenBCG and Atypical Myeobaeteria(AM)anti-.genieity,1150 BCG immunized babies aged 12—24 weeks,undertook a bilateral arm control testwith H-PPD type 11 AM-PPD and BCG-PPD.The results show that all the AM—PPDtested can bring about a delayed allergy in thesebabies,but the total positive rate(42.87%)and mean reactive diameter(3.87mm)are thelowest and smallest among the above mentionedthree types of PPD.展开更多
The aim of this study was to investigate the feasibility of stimulating ovarian fol icle development in order to improve fertility in water buffalo cows by immunization against inhibin. The experiment was carried out ...The aim of this study was to investigate the feasibility of stimulating ovarian fol icle development in order to improve fertility in water buffalo cows by immunization against inhibin. The experiment was carried out in early summer (May) and included 24 multi-parity crossbred Murrah-Swamp buffaloes that were divided into immunized (n=11) and control (n=13) groups. Each immunized cow was administered with a 2-mL immunogen of mineral oil adjuvant containing 2 mg of recombinant inhibinα-subunit fusion protein. The controls were treated with the adjuvant only. Al animals received Ovsynch protocol treatment, starting on the day of the antigen administration, and they were artiifcial y inseminated upon behavioral estrus. As a result, al of the immunized buffaloes generated antibodies against inhibin during the experimental period and had higher plasma concentrations of fol icle-stimulating hormone (FSH), activin, and estradiol (E2) related to estrous expression. A higher proportion of immunized animals expressed estrus behavior than did the controls (72%vs. 30%, P<0.05). On aver-age, inhibin-immunized buffaloes had signiifcantly more large fol icles (≥9 mm in diameter) than the controls (mean±SEM;1.2±0.1 vs. 0.84±0.1, respectively;P<0.05) and a slightly higher mean total number of fol icles (≥2 mm;11.4±0.7 vs. 9.0±1.1, respectively;P=0.09) and smal (2–4 mm) fol icles (8.81±0.6 vs. 6.84±1.0, respectively;P=0.12). A higher percentage of cows ovulated in the immunized group than in the control group (91%(10/11) vs. 54%(7/13), respectively;P<0.05). Moreover, inhibin-immunized cows had slightly larger corpus luteum (CL) than the controls 9 days after ovulation and signiifcantly higher (P<0.01) post-ovulation peak plasma progesterone (P4) concentrations. Immunization against inhibin also mar-ginal y increased the conception rate 42 days after insemination (45.8%vs. 15.4%;P>0.05). These results demonstrate that immunization against inhibin, coupled with the treatment with the Ovsynch protocol, can constitute a new technique to increase fertility in water buffalo cows.展开更多
Dose-dependent IgY antibody response to different amounts oforthopox virus （OPV） antigen has been studied in immunized chickens for two different OPV strains （vaccinia virus, 7.0× 10^6 PFU and cowpox virus, 9....Dose-dependent IgY antibody response to different amounts oforthopox virus （OPV） antigen has been studied in immunized chickens for two different OPV strains （vaccinia virus, 7.0× 10^6 PFU and cowpox virus, 9.2× 10^7PFU）. The antibody responses to different immunizations were tested and compared by indirect immunofluorescence antibody test. Our results, together with the literature, show that the antigen dose used for immunization plays an important role for the production of specific Abs. An increase in antigen concentration may achieve higher Ab titers but, dependent on the immunogenicity of OPV antigen, it can also lead to an immune depression. However, in this study we found that OPV played a positive correlation between antigen concentration and Ab-titer.展开更多
Enteric disorders in pigs are related to the fimbriae F4 (K88), F5 (K99), F6 (987P), F41 and F18 of enterotoxigenic Escherichia coli (ETEC). Immunization of sows with adhesins is important to stimulate the production ...Enteric disorders in pigs are related to the fimbriae F4 (K88), F5 (K99), F6 (987P), F41 and F18 of enterotoxigenic Escherichia coli (ETEC). Immunization of sows with adhesins is important to stimulate the production of antibodies and the consequent transfer of these to the piglets via colostrum to prevent diarrhea during the neonate period and after weaning. The objective of this study was to evaluate the immune response of the sows immunized with recombinant ETEC proteins (F4, F5, F6, F18 and F41). The immune response of the sows immunized with the recombinant proteins was compared with a commercial vaccine containing ETEC bacterins. The study was performed on a commercial farm and included nine pregnant sows divided into three groups: G1 was vaccinated with recombinant proteins (n = 3);G2 was vaccinated with the commercial vaccine (n = 3);and G3 was vaccinated with sterile buffered saline (PBS) (n = 3). All the sows were fed a balanced diet without antibiotics and water ad libitum. The recombinant fimbriae stimulated the specific humoral immune response of the immunized sows. There was a statistically significant increase in the levels of antibodies to the fimbriae F4 (K88), F5 (K99), F6 (987P) and F18 in the sows vaccinated with the recombinant proteins compared with the control group. The colostrum IgG titers for all fimbriae in all the immunized sows were significantly increased compared to the control group. Additionally, all the piglets exhibited significantly increased antibody levels relative to all fimbriae when compared with those in the unimmunized control group, demonstrating successful antibody transfer via colostrum of the sows to the piglets.展开更多
To improve vaccination coverage among children under one year of age in the Tambacounda health district, a household survey was carried out among mothers or babysitters. The objective was to study the factors related ...To improve vaccination coverage among children under one year of age in the Tambacounda health district, a household survey was carried out among mothers or babysitters. The objective was to study the factors related to child’s fully immunized in children aged 12 to 23 months. The cross-sectional, descriptive and analytical survey was carried out during the month of April 2019. A multistage cluster survey selected a sample of 657 mothers and babysitters. The data was collected using a questionnaire made from the World Health Organization reference guide. Data entry and analysis were done with Epi Info software and R. Among the women surveyed, biological mothers were the most representative (96.9%). In the series, 74.1% had a good knowledge of the age for initiating vaccination, 78.2% knew the number of contacts. The vaccination record of the children was available in 92.2%, and 71.0% of them had presented an adverse event. The proportion of children fully immunized was 41.0%. Complete childhood vaccination was positively associated with income-generating activity in women (0R = 2.4) and the short distance (<100 m) between home and place of vaccination (OR = 1.5). It was also improved by having a qualified health worker as a vaccinator (OR = 1.4) satisfaction in relation to visit (OR = 2.0), the advice given by the vaccinator (OR = 1.7) and the fixing of the date of the next vaccination appointment (OR = 2.5). The implementation of a good strategy for improving the quality of immunization services is an important element for strengthening immunization coverage in the Tambacounda health district.展开更多
The experiment was conducted to study the dynamic changes of immune responses of chicks immunized with March's disease(MD)trivalent vaccine and turkey herpesvirus(HVT)at one day age.Results were found that after i...The experiment was conducted to study the dynamic changes of immune responses of chicks immunized with March's disease(MD)trivalent vaccine and turkey herpesvirus(HVT)at one day age.Results were found that after immunization of chicks with MD vaccines,the intcrlcukinc-2(IL-2)inductive activity and IL-2 receptor expression of T cells from thymus and spleen significantly increased,suggesting that the immunoregulativc function was markedly enhanced in the immune organs;the number of antibody-producing cells,the number and proliferative function of T cells rose markedly in Bursa Fabricius,spleen and thymus,indicating that the cellular and humoral immune responses were elevated remarkablly in the central and peripheral immune organs;the number of T and antibody-producing cells as well as the content of IgG,IgA and IgM obviously mounted in cecal tonsil, Harder tan gland mucosal lymphoid tissues of bronchus along with tears,trachea washings, bile and intestinal fluids,demonstrating that the local and mucosal immunity was raised in the respiratory and digestive tract;the levels of immune responses mentioned above in the trivalent vaccine-immuniaed chicks were apparently higher than those of HVT-immunized birds.展开更多
Intracerebral hemorrhage is the most dangerous subtype of stroke,characterized by high mortality and morbidity rates,and frequently leads to significant secondary white matter injury.In recent decades,studies have rev...Intracerebral hemorrhage is the most dangerous subtype of stroke,characterized by high mortality and morbidity rates,and frequently leads to significant secondary white matter injury.In recent decades,studies have revealed that gut microbiota can communicate bidirectionally with the brain through the gut microbiota–brain axis.This axis indicates that gut microbiota is closely related to the development and prognosis of intracerebral hemorrhage and its associated secondary white matter injury.The NACHT,LRR,and pyrin domain-containing protein 3(NLRP3)inflammasome plays a crucial role in this context.This review summarizes the dysbiosis of gut microbiota following intracerebral hemorrhage and explores the mechanisms by which this imbalance may promote the activation of the NLRP3 inflammasome.These mechanisms include metabolic pathways(involving short-chain fatty acids,lipopolysaccharides,lactic acid,bile acids,trimethylamine-N-oxide,and tryptophan),neural pathways(such as the vagus nerve and sympathetic nerve),and immune pathways(involving microglia and T cells).We then discuss the relationship between the activated NLRP3 inflammasome and secondary white matter injury after intracerebral hemorrhage.The activation of the NLRP3 inflammasome can exacerbate secondary white matter injury by disrupting the blood–brain barrier,inducing neuroinflammation,and interfering with nerve regeneration.Finally,we outline potential treatment strategies for intracerebral hemorrhage and its secondary white matter injury.Our review highlights the critical role of the gut microbiota–brain axis and the NLRP3 inflammasome in white matter injury following intracerebral hemorrhage,paving the way for exploring potential therapeutic approaches.展开更多
Immunotherapy has brought unprecedented breakthroughs to advanced malignant tumors,yet the immune microenvironment shaped by the tumor stroma has often been underestimated in the traditional focus on the“immune check...Immunotherapy has brought unprecedented breakthroughs to advanced malignant tumors,yet the immune microenvironment shaped by the tumor stroma has often been underestimated in the traditional focus on the“immune checkpoint-T cell”axis.Collagen not only constitutes a mechanical barrier that distinguishes between the periphery and core of solid tumors but also systematically remodels the orientation of metabolism,vasculature,and immune cell phenotypic plasticity through its spatial density,fiber arrangement,and crosslinking patterns(F igure 1)[1,2].Abundant evidence suggests that over-accumulated types I and III collagen drive CD8+T cell exhaustion,NK cell functional inhibition,and tumor-associated macrophage polarization through ligand-receptor networks involving LAIR-1,DDR2,andβ1/β3 integrins[3-6].Mechanistically,collagen engagement of LAIR-1 delivers inhibitory signals in effector lymphocytes,promoting dysfunctional or exhausted states[7-9].In parallel,collagen-β1/β3 integrin signaling activates mechanotransduction pathways(e.g.,FAK/SRC),reducing T-cell motility and immune-tumor contact,while DDR2 activation supports matrix-remodeling programs that limit lymphocyte trafficking.展开更多
Colorectal cancer(CRC)is ranked as the third most common tumor globally,representing approximately 10%of all cancer cases,and is the second primary cause of cancer-associated mortality.Existing therapeutic approaches ...Colorectal cancer(CRC)is ranked as the third most common tumor globally,representing approximately 10%of all cancer cases,and is the second primary cause of cancer-associated mortality.Existing therapeutic approaches demonstrate limited efficacy against CRC,partially due to the immunosuppressive tumor microenvironment(TME).In recent years,substantial evidence indicates that dysbiosis of the gut microbiota and its metabolic products is closely associated with the initiation,progression,and prognostic outcomes of CRC.In this minireview,we systematically elaborate on how these microbes and their metabolites directly impair intestinal epithelial integrity,activate cancer-associated fibroblasts,remodel tumor vasculature,and critically,sculpt an immunosuppressive landscape by modulating T cells,dendritic cells,and tumor-associated macrophages.We highlight the translational potential of targeting the gut microbiota,including fecal microbiota transplantation,probiotics,and engineered microbial systems,to reprogram the TME and overcome resistance to immunotherapy and chemotherapy.A deeper understanding of the microbiota-TME axis is essential for developing novel diagnostic and therapeutic paradigms for CRC.展开更多
Post-translational modifications(PTMs)regulate the occurrence and development of cancer,and lactylation modification is a new form of PTMs.Recent studies have found that lactic acid modification can regulate the immun...Post-translational modifications(PTMs)regulate the occurrence and development of cancer,and lactylation modification is a new form of PTMs.Recent studies have found that lactic acid modification can regulate the immune tolerance of cancer cells.The classical theory holds that prostate apoptosis response-4(PAR-4)is a tumor suppressor protein.However,our recent research has found that PAR-4 has a biological function of promoting cancer in hepatocellular carcinoma(HCC),and our analysis shows that PAR-4 can be modified of lactic acid.These research evidences suggest that PAR-4 lactylation modification may drive immune tolerance in HCC.Therefore,inhibiting PAR-4 lactylation modification is very likely to increase the sensitivity of HCC to immunotherapy.展开更多
Regulatory T cells,a subset of CD4^(+)T cells,play a critical role in maintaining immune tolerance and tissue homeostasis due to their potent immunosuppressive properties.Recent advances in research have highlighted t...Regulatory T cells,a subset of CD4^(+)T cells,play a critical role in maintaining immune tolerance and tissue homeostasis due to their potent immunosuppressive properties.Recent advances in research have highlighted the important therapeutic potential of Tregs in neurological diseases and tissue repair,emphasizing their multifaceted roles in immune regulation.This review aims to summarize and analyze the mechanisms of action and therapeutic potential of Tregs in relation to neurological diseases and neural regeneration.Beyond their classical immune-regulatory functions,emerging evidence points to non-immune mechanisms of regulatory T cells,particularly their interactions with stem cells and other non-immune cells.These interactions contribute to optimizing the repair microenvironment and promoting tissue repair and nerve regeneration,positioning non-immune pathways as a promising direction for future research.By modulating immune and non-immune cells,including neurons and glia within neural tissues,Tregs have demonstrated remarkable efficacy in enhancing regeneration in the central and peripheral nervous systems.Preclinical studies have revealed that Treg cells interact with neurons,glial cells,and other neural components to mitigate inflammatory damage and support functional recovery.Current mechanistic studies show that Tregs can significantly promote neural repair and functional recovery by regulating inflammatory responses and the local immune microenvironment.However,research on the mechanistic roles of regulatory T cells in other diseases remains limited,highlighting substantial gaps and opportunities for exploration in this field.Laboratory and clinical studies have further advanced the application of regulatory T cells.Technical advances have enabled efficient isolation,ex vivo expansion and functionalization,and adoptive transfer of regulatory T cells,with efficacy validated in animal models.Innovative strategies,including gene editing,cell-free technologies,biomaterial-based recruitment,and in situ delivery have expanded the therapeutic potential of regulatory T cells.Gene editing enables precise functional optimization,while biomaterial and in situ delivery technologies enhance their accumulation and efficacy at target sites.These advancements not only improve the immune-regulatory capacity of regulatory T cells but also significantly enhance their role in tissue repair.By leveraging the pivotal and diverse functions of Tregs in immune modulation and tissue repair,regulatory T cells–based therapies may lead to transformative breakthroughs in the treatment of neurological diseases.展开更多
Hepatocellular carcinoma presents with three distinct immune phenotypes,including immune-desert,immune-excluded,and immune-inflamed,indicating various treatment responses and prognostic outcomes.The clinical applicati...Hepatocellular carcinoma presents with three distinct immune phenotypes,including immune-desert,immune-excluded,and immune-inflamed,indicating various treatment responses and prognostic outcomes.The clinical application of multi-omics parameters is still restricted by the expensive and less accessible assays,although they accurately reflect immune status.A comprehensive evaluation framework based on“easy-to-obtain”multi-model clinical parameters is urgently required,incorporating clinical features to establish baseline patient profiles and disease staging;routine blood tests assessing systemic metabolic and functional status;immune cell subsets quantifying subcluster dynamics;imaging features delineating tumor morphology,spatial configuration,and perilesional anatomical relationships;immunohistochemical markers positioning qualitative and quantitative detection of tumor antigens from the cellular and molecular level.This integrated phenomic approach aims to improve prognostic stratification and clinical decision-making in hepatocellular carcinoma management conveniently and practically.展开更多
AIM:To identify metastasis-associated prognostic genes and construct a robust molecular signature for survival prediction in uveal melanoma(UVM)patients.METHODS:Transcriptomic data and clinical information from 80 UVM...AIM:To identify metastasis-associated prognostic genes and construct a robust molecular signature for survival prediction in uveal melanoma(UVM)patients.METHODS:Transcriptomic data and clinical information from 80 UVM patients in the Cancer Genome Atlas(TCGA)-UVM cohort and an external Gene Expression Omnibus(GEO)microarray dataset(GSE73652;8 non-metastatic vs 5 metastatic cases)were analyzed to identify differentially expressed genes(DEGs).Functional enrichment,proteinprotein interaction(PPI)network construction,and survival analyses identified seven metastasis-and prognosisrelated genes.Their expression was further examined using public single-cell RNA-seq data(GSE139829;11 tumors).Experimental validation was performed in UVM cell lines(92.1,OMM1,MEL270)and adult retinal pigment epithelial(ARPE-19)cells using quantitative real-time polymerase chain reaction(qRT-PCR)and Western blotting to confirm transcriptomic trends.A LASSO Cox model was applied to construct a metastasis-related risk Score signature.Tumor immune microenvironment characteristics were evaluated via single-sample gene set enrichment analysis(ssGSEA)and ESTIMATE.Somatic mutation and copy number variation(CNV)profiles were also examined.RESULTS:Seven key genes(UBE2T,KIF20A,DLGAP5,KLC3,TPX2,UBE2C,AURKA)were significantly associated with overall survival and used to construct a metastasisrelated riskScore signature,which effectively stratified patients into high-and low-risk groups and served as an independent prognostic factor.qRT-PCR and Western blot results confirmed that the expression levels of selected key genes in UVM cell lines showed significant differences compared to ARPE-19 cells,which were largely consistent with the transcriptomic findings.The high-risk group exhibited reduced immune infiltration and stromal activity.Single-cell analysis revealed these genes were predominantly expressed in a tumor cell cluster characterized by BAP1 loss and high metastatic potential.Mutation and CNV analyses further supported the relevance of these genes to UVM progression.CONCLUSION:This study establishes and validates a seven-gene signature associated with metastasis and prognosis in UVM.The findings provide a framework for understanding molecular determinants of tumor progression and immune microenvironment alterations,and may offer guidance for future mechanistic studies and therapeutic exploration.展开更多
The cerebellum is receiving increasing attention for its cognitive,emotional,and social functions,as well as its unique metabolic profiles.Cerebellar microglia exhibit specialized and highly immunogenic phenotypes und...The cerebellum is receiving increasing attention for its cognitive,emotional,and social functions,as well as its unique metabolic profiles.Cerebellar microglia exhibit specialized and highly immunogenic phenotypes under both physiological and pathological conditions.These immune cells communicate with intrinsic and systemic factors and contribute to the structural and functional compartmentalization of the cerebellum.In this review,we discuss the roles of microglia in the cerebellar microenvironment,neuroinflammation,cerebellar adaptation,and neuronal activity,the associated molecular and cellular mechanisms,and potential therapeutic strategies targeting cerebellar microglia in the context of neuroinflammation.Future directions and unresolved questions in this field are further highlighted,particularly regarding therapeutic interventions targeting cerebellar microglia,functional mechanisms and activities of microglia in the cerebellar circuitry,neuronal connectivity,and neurofunctional outcomes of their activity.Cerebellar morphology and neuronal performance are influenced by both intrinsic and systemic factors that are actively monitored by microglia in both healthy and diseased states.Under pathological conditions,local subsets of microglia exhibit diverse responses to the altered microenvironment that contribute to the structural and functional compartmentalization of the cerebellum.Microglia in the cerebellum undergo early maturation during the embryonic stage and display specialized,highly immunogenic phenotypes.In summary,cerebellar microglia have the capacity to serve as regulatory tools that influence outcomes across a wide range of neurological and systemic conditions,including neurodevelopmental,neurodegenerative,metabolic,and stress-related disorders.展开更多
BACKGROUND Chemotherapy with an immune checkpoint inhibitor is one of the standard regimens for treating advanced gastric cancer(AGC).Ascites and peritoneal dissemination are common complications and poor prognostic f...BACKGROUND Chemotherapy with an immune checkpoint inhibitor is one of the standard regimens for treating advanced gastric cancer(AGC).Ascites and peritoneal dissemination are common complications and poor prognostic factors of AGC;however,reports regarding its efficacy and safety in patients with AGC and massive ascites are limited.AIM To evaluate the safety and efficacy of nivolumab combined with chemotherapy in patients with AGC and ascites.METHODS We retrospectively collected clinical data from 124 patients with AGC who received chemotherapy plus nivolumab as first-line treatment from July 2017 to December 2024.Based on computed tomography scans,massive or moderate ascites were classified as high ascites burden(HAB),whereas mild or no ascites were classified as low ascites burden.RESULTS Ascites was detected in 47 patients(38%);26(21%)were classified into the HAB group.Patients in the HAB group exhibited a significantly poorer performance status,a higher prevalence of diffuse-type histology,and lower programmed cell death ligand 1(PD-L1)expression.Combination therapy with FOLFOX and neutropenia was significantly more common in the HAB group.Progression-free survival(PFS)(4.4 months vs 9.3 months,P=0.0012)and overall survival(OS)(7.3 months vs 21.2 months,P<0.0001)were significantly poorer in the HAB group.However,an improvement in ascites was observed in 61.5%of patients in the HAB group.PD-L1 expression did not correlate with either PFS or OS in the HAB group.CONCLUSION Nivolumab plus chemotherapy demonstrated modest efficacy and acceptable toxicity in patients with AGC and HAB.展开更多
Wu et al recently applied multi-region 16S rRNA sequencing to characterize the gastric cancer microbiome,demonstrating improved taxonomic resolution and detection sensitivity over conventional single-region approaches...Wu et al recently applied multi-region 16S rRNA sequencing to characterize the gastric cancer microbiome,demonstrating improved taxonomic resolution and detection sensitivity over conventional single-region approaches.While the study represents a valuable methodological step forward,it remains limited by singlecenter design,lack of quantitative calibration,and insufficient control for contamination and inter-laboratory variability.This editorial critically appraises these methodological gaps and emphasizes that future efforts must focus on harmonized,consensus-driven workflows to ensure reproducibility and clinical reliability.The translational potential of multi-region 16S lies in moving from descriptive microbial profiling to actionable clinical integration,particularly for recurrence prediction,treatment-response monitoring,and perioperative complication risk assessment.By addressing these methodological,economic,and ethical challenges,the field can advance toward evidence-based and clinically deployable microbiome-guided precision oncology.展开更多
Microglia are the resident macrophages of the central nervous system.They act as the first line of defense against pathogens and play essential roles in neuroinflammation and tissue repair after brain insult or in neu...Microglia are the resident macrophages of the central nervous system.They act as the first line of defense against pathogens and play essential roles in neuroinflammation and tissue repair after brain insult or in neurodegenerative and demyelinating diseases(Borst et al.,2021).Together with infiltrating monocyte-derived macrophages,microglia also play a critical role for brain tumor development,since immunosuppressive interactions between tumor cells and tumor-associated microglia and macrophages(TAM)are linked to malignant progression.This mechanism is of particular relevance in glioblastoma(GB),the deadliest form of brain cancer with a median overall survival of less than 15 months(Khan et al.,2023).Therefore,targeting microglia and macrophage activation is a promising strategy for therapeutic interference in brain disease.展开更多
Adult hippocampal neurogenesis is linked to memory formation in the adult brain,with new neurons in the hippocampus exhibiting greater plasticity during their immature stages compared to mature neurons.Abnormal adult ...Adult hippocampal neurogenesis is linked to memory formation in the adult brain,with new neurons in the hippocampus exhibiting greater plasticity during their immature stages compared to mature neurons.Abnormal adult hippocampal neurogenesis is closely associated with cognitive impairment in central nervous system diseases.Targeting and regulating adult hippocampal neurogenesis have been shown to improve cognitive deficits.This review aims to expand the current understanding and prospects of targeting neurogenesis in the treatment of cognitive impairment.Recent research indicates the presence of abnormalities in AHN in several diseases associated with cognitive impairment,including cerebrovascular diseases,Alzheimer's disease,aging-related conditions,and issues related to anesthesia and surgery.The role of these abnormalities in the cognitive deficits caused by these diseases has been widely recognized,and targeting AHN is considered a promising approach for treating cognitive impairment.However,the underlying mechanisms of this role are not yet fully understood,and the effectiveness of targeting abnormal adult hippocampal neurogenesis for treatment remains limited,with a need for further development of treatment methods and detection techniques.By reviewing recent studies,we classify the potential mechanisms of adult hippocampal neurogenesis abnormalities into four categories:immunity,energy metabolism,aging,and pathological states.In immunity-related mechanisms,abnormalities in meningeal,brain,and peripheral immunity can disrupt normal adult hippocampal neurogenesis.Lipid metabolism and mitochondrial function disorders are significant energy metabolism factors that lead to abnormal adult hippocampal neurogenesis.During aging,the inflammatory state of the neurogenic niche and the expression of aging-related microRNAs contribute to reduced adult hippocampal neurogenesis and cognitive impairment in older adult patients.Pathological states of the body and emotional disorders may also result in abnormal adult hippocampal neurogenesis.Among the current strategies used to enhance this form of neurogenesis,physical therapies such as exercise,transcutaneous electrical nerve stimulation,and enriched environments have proven effective.Dietary interventions,including energy intake restriction and nutrient optimization,have shown efficacy in both basic research and clinical trials.However,drug treatments,such as antidepressants and stem cell therapy,are primarily reported in basic research,with limited clinical application.The relationship between abnormal adult hippocampal neurogenesis and cognitive impairment has garnered widespread attention,and targeting the former may be an important strategy for treating the latter.However,the mechanisms underlying abnormal adult hippocampal neurogenesis remain unclear,and treatments are lacking.This highlights the need for greater focus on translating research findings into clinical practice.展开更多
基金Supported by Natural Science Foundation of Hebei Province(C200700450)~~
文摘[Objective] The study was to explore whether antimicrobial activity of the antimicrobial peptides extracted from immunized Tenebrio molitor varied with different pathogens as inducers.[Method]By inducing T.molitor hungry larvaes to generate immune response via feeding with bacteria and with fungi or actinomycete post to pricking,the antimicrobial peptides extracts were obtained by grinding and centrifuging the cultures.Its antimicrobial activity against 26 pathogens was measured by bacteriostatic ring,and evaluated by trisection to four types and inhibitory spectrum.[Result]Both the antimicrobial activity and antimicrobial spectrum of the antimicrobial peptides extracts varied remarkably among different pathogens as inducers.[Conclusion]Bio-control used strains have obvious advantage in inducing the insect to express body fluid immunity material-antimicrobial peptides.
文摘Since the introduction of Ant Colony Optimization (ACO) technique in 1992, the algorithm starts to gain popularity due to its attractive features. However, several shortcomings such as slow convergence and stagnation motivate many researchers to stop further implementation of ACO. Therefore, in order to overcome these drawbacks, ACO is proposed to be combined with Differential Evolution (DE) and cloning process. This paper presents Differential Evolution Immunized Ant Colony Optimization (DEIANT) technique in solving economic load dispatch problem. The combination creates a new algorithm that will be termed as Differential Evolution Immunized Ant Colony Optimization (DEIANT). DEIANT was utilized to optimize economic load dispatch problem. A comparison was made between DEIANT and classical ACO to evaluate the performance of the new algorithm. In realizing the effectiveness of the proposed technique, IEEE 57-Bus Reliable Test System (RTS) has been used as the test specimen. Results obtained from the study revealed that the proposed DEIANT has superior computation time.
文摘In order to know the cross reaction betweenBCG and Atypical Myeobaeteria(AM)anti-.genieity,1150 BCG immunized babies aged 12—24 weeks,undertook a bilateral arm control testwith H-PPD type 11 AM-PPD and BCG-PPD.The results show that all the AM—PPDtested can bring about a delayed allergy in thesebabies,but the total positive rate(42.87%)and mean reactive diameter(3.87mm)are thelowest and smallest among the above mentionedthree types of PPD.
基金supported by the National Key Technology R&D Program of China (2011BAD19B02-6)the Open Grant of Guangxi Provincial Key Laboratory of Water Buffalo Genetics, Breeding and Reproduction, China (SNKF-2012-04)
文摘The aim of this study was to investigate the feasibility of stimulating ovarian fol icle development in order to improve fertility in water buffalo cows by immunization against inhibin. The experiment was carried out in early summer (May) and included 24 multi-parity crossbred Murrah-Swamp buffaloes that were divided into immunized (n=11) and control (n=13) groups. Each immunized cow was administered with a 2-mL immunogen of mineral oil adjuvant containing 2 mg of recombinant inhibinα-subunit fusion protein. The controls were treated with the adjuvant only. Al animals received Ovsynch protocol treatment, starting on the day of the antigen administration, and they were artiifcial y inseminated upon behavioral estrus. As a result, al of the immunized buffaloes generated antibodies against inhibin during the experimental period and had higher plasma concentrations of fol icle-stimulating hormone (FSH), activin, and estradiol (E2) related to estrous expression. A higher proportion of immunized animals expressed estrus behavior than did the controls (72%vs. 30%, P<0.05). On aver-age, inhibin-immunized buffaloes had signiifcantly more large fol icles (≥9 mm in diameter) than the controls (mean±SEM;1.2±0.1 vs. 0.84±0.1, respectively;P<0.05) and a slightly higher mean total number of fol icles (≥2 mm;11.4±0.7 vs. 9.0±1.1, respectively;P=0.09) and smal (2–4 mm) fol icles (8.81±0.6 vs. 6.84±1.0, respectively;P=0.12). A higher percentage of cows ovulated in the immunized group than in the control group (91%(10/11) vs. 54%(7/13), respectively;P<0.05). Moreover, inhibin-immunized cows had slightly larger corpus luteum (CL) than the controls 9 days after ovulation and signiifcantly higher (P<0.01) post-ovulation peak plasma progesterone (P4) concentrations. Immunization against inhibin also mar-ginal y increased the conception rate 42 days after insemination (45.8%vs. 15.4%;P>0.05). These results demonstrate that immunization against inhibin, coupled with the treatment with the Ovsynch protocol, can constitute a new technique to increase fertility in water buffalo cows.
文摘Dose-dependent IgY antibody response to different amounts oforthopox virus （OPV） antigen has been studied in immunized chickens for two different OPV strains （vaccinia virus, 7.0× 10^6 PFU and cowpox virus, 9.2× 10^7PFU）. The antibody responses to different immunizations were tested and compared by indirect immunofluorescence antibody test. Our results, together with the literature, show that the antigen dose used for immunization plays an important role for the production of specific Abs. An increase in antigen concentration may achieve higher Ab titers but, dependent on the immunogenicity of OPV antigen, it can also lead to an immune depression. However, in this study we found that OPV played a positive correlation between antigen concentration and Ab-titer.
文摘Enteric disorders in pigs are related to the fimbriae F4 (K88), F5 (K99), F6 (987P), F41 and F18 of enterotoxigenic Escherichia coli (ETEC). Immunization of sows with adhesins is important to stimulate the production of antibodies and the consequent transfer of these to the piglets via colostrum to prevent diarrhea during the neonate period and after weaning. The objective of this study was to evaluate the immune response of the sows immunized with recombinant ETEC proteins (F4, F5, F6, F18 and F41). The immune response of the sows immunized with the recombinant proteins was compared with a commercial vaccine containing ETEC bacterins. The study was performed on a commercial farm and included nine pregnant sows divided into three groups: G1 was vaccinated with recombinant proteins (n = 3);G2 was vaccinated with the commercial vaccine (n = 3);and G3 was vaccinated with sterile buffered saline (PBS) (n = 3). All the sows were fed a balanced diet without antibiotics and water ad libitum. The recombinant fimbriae stimulated the specific humoral immune response of the immunized sows. There was a statistically significant increase in the levels of antibodies to the fimbriae F4 (K88), F5 (K99), F6 (987P) and F18 in the sows vaccinated with the recombinant proteins compared with the control group. The colostrum IgG titers for all fimbriae in all the immunized sows were significantly increased compared to the control group. Additionally, all the piglets exhibited significantly increased antibody levels relative to all fimbriae when compared with those in the unimmunized control group, demonstrating successful antibody transfer via colostrum of the sows to the piglets.
文摘To improve vaccination coverage among children under one year of age in the Tambacounda health district, a household survey was carried out among mothers or babysitters. The objective was to study the factors related to child’s fully immunized in children aged 12 to 23 months. The cross-sectional, descriptive and analytical survey was carried out during the month of April 2019. A multistage cluster survey selected a sample of 657 mothers and babysitters. The data was collected using a questionnaire made from the World Health Organization reference guide. Data entry and analysis were done with Epi Info software and R. Among the women surveyed, biological mothers were the most representative (96.9%). In the series, 74.1% had a good knowledge of the age for initiating vaccination, 78.2% knew the number of contacts. The vaccination record of the children was available in 92.2%, and 71.0% of them had presented an adverse event. The proportion of children fully immunized was 41.0%. Complete childhood vaccination was positively associated with income-generating activity in women (0R = 2.4) and the short distance (<100 m) between home and place of vaccination (OR = 1.5). It was also improved by having a qualified health worker as a vaccinator (OR = 1.4) satisfaction in relation to visit (OR = 2.0), the advice given by the vaccinator (OR = 1.7) and the fixing of the date of the next vaccination appointment (OR = 2.5). The implementation of a good strategy for improving the quality of immunization services is an important element for strengthening immunization coverage in the Tambacounda health district.
文摘The experiment was conducted to study the dynamic changes of immune responses of chicks immunized with March's disease(MD)trivalent vaccine and turkey herpesvirus(HVT)at one day age.Results were found that after immunization of chicks with MD vaccines,the intcrlcukinc-2(IL-2)inductive activity and IL-2 receptor expression of T cells from thymus and spleen significantly increased,suggesting that the immunoregulativc function was markedly enhanced in the immune organs;the number of antibody-producing cells,the number and proliferative function of T cells rose markedly in Bursa Fabricius,spleen and thymus,indicating that the cellular and humoral immune responses were elevated remarkablly in the central and peripheral immune organs;the number of T and antibody-producing cells as well as the content of IgG,IgA and IgM obviously mounted in cecal tonsil, Harder tan gland mucosal lymphoid tissues of bronchus along with tears,trachea washings, bile and intestinal fluids,demonstrating that the local and mucosal immunity was raised in the respiratory and digestive tract;the levels of immune responses mentioned above in the trivalent vaccine-immuniaed chicks were apparently higher than those of HVT-immunized birds.
基金supported by the Guangdong Basic and Applied Basic Research Foundation,No.2023A1515030045(to HS)Presidential Foundation of Zhujiang Hospital of Southern Medical University,No.yzjj2022ms4(to HS)。
文摘Intracerebral hemorrhage is the most dangerous subtype of stroke,characterized by high mortality and morbidity rates,and frequently leads to significant secondary white matter injury.In recent decades,studies have revealed that gut microbiota can communicate bidirectionally with the brain through the gut microbiota–brain axis.This axis indicates that gut microbiota is closely related to the development and prognosis of intracerebral hemorrhage and its associated secondary white matter injury.The NACHT,LRR,and pyrin domain-containing protein 3(NLRP3)inflammasome plays a crucial role in this context.This review summarizes the dysbiosis of gut microbiota following intracerebral hemorrhage and explores the mechanisms by which this imbalance may promote the activation of the NLRP3 inflammasome.These mechanisms include metabolic pathways(involving short-chain fatty acids,lipopolysaccharides,lactic acid,bile acids,trimethylamine-N-oxide,and tryptophan),neural pathways(such as the vagus nerve and sympathetic nerve),and immune pathways(involving microglia and T cells).We then discuss the relationship between the activated NLRP3 inflammasome and secondary white matter injury after intracerebral hemorrhage.The activation of the NLRP3 inflammasome can exacerbate secondary white matter injury by disrupting the blood–brain barrier,inducing neuroinflammation,and interfering with nerve regeneration.Finally,we outline potential treatment strategies for intracerebral hemorrhage and its secondary white matter injury.Our review highlights the critical role of the gut microbiota–brain axis and the NLRP3 inflammasome in white matter injury following intracerebral hemorrhage,paving the way for exploring potential therapeutic approaches.
文摘Immunotherapy has brought unprecedented breakthroughs to advanced malignant tumors,yet the immune microenvironment shaped by the tumor stroma has often been underestimated in the traditional focus on the“immune checkpoint-T cell”axis.Collagen not only constitutes a mechanical barrier that distinguishes between the periphery and core of solid tumors but also systematically remodels the orientation of metabolism,vasculature,and immune cell phenotypic plasticity through its spatial density,fiber arrangement,and crosslinking patterns(F igure 1)[1,2].Abundant evidence suggests that over-accumulated types I and III collagen drive CD8+T cell exhaustion,NK cell functional inhibition,and tumor-associated macrophage polarization through ligand-receptor networks involving LAIR-1,DDR2,andβ1/β3 integrins[3-6].Mechanistically,collagen engagement of LAIR-1 delivers inhibitory signals in effector lymphocytes,promoting dysfunctional or exhausted states[7-9].In parallel,collagen-β1/β3 integrin signaling activates mechanotransduction pathways(e.g.,FAK/SRC),reducing T-cell motility and immune-tumor contact,while DDR2 activation supports matrix-remodeling programs that limit lymphocyte trafficking.
基金Supported by National Natural Science Foundation of China,No.82170638Natural Science Foundation of the Science and Technology Commission of Shanghai Municipality,No.23ZR1458300+1 种基金Key Discipline Project of Shanghai Municipal Health System,No.2024ZDXK0004and Pujiang Project of Shanghai Magnolia Talent Plan,No.24PJD098.
文摘Colorectal cancer(CRC)is ranked as the third most common tumor globally,representing approximately 10%of all cancer cases,and is the second primary cause of cancer-associated mortality.Existing therapeutic approaches demonstrate limited efficacy against CRC,partially due to the immunosuppressive tumor microenvironment(TME).In recent years,substantial evidence indicates that dysbiosis of the gut microbiota and its metabolic products is closely associated with the initiation,progression,and prognostic outcomes of CRC.In this minireview,we systematically elaborate on how these microbes and their metabolites directly impair intestinal epithelial integrity,activate cancer-associated fibroblasts,remodel tumor vasculature,and critically,sculpt an immunosuppressive landscape by modulating T cells,dendritic cells,and tumor-associated macrophages.We highlight the translational potential of targeting the gut microbiota,including fecal microbiota transplantation,probiotics,and engineered microbial systems,to reprogram the TME and overcome resistance to immunotherapy and chemotherapy.A deeper understanding of the microbiota-TME axis is essential for developing novel diagnostic and therapeutic paradigms for CRC.
基金supported by the National Natural Science Foundation of China(Nos.82573045,82460602,82560459)the Hainan Provincial Graduate Student Innovative Research Project(No.Qhys2024-440).
文摘Post-translational modifications(PTMs)regulate the occurrence and development of cancer,and lactylation modification is a new form of PTMs.Recent studies have found that lactic acid modification can regulate the immune tolerance of cancer cells.The classical theory holds that prostate apoptosis response-4(PAR-4)is a tumor suppressor protein.However,our recent research has found that PAR-4 has a biological function of promoting cancer in hepatocellular carcinoma(HCC),and our analysis shows that PAR-4 can be modified of lactic acid.These research evidences suggest that PAR-4 lactylation modification may drive immune tolerance in HCC.Therefore,inhibiting PAR-4 lactylation modification is very likely to increase the sensitivity of HCC to immunotherapy.
基金supported by the National Natural Science Foundation of China,Nos.32271389,31900987(both to PY)the Natural Science Foundation of Jiangsu Province,No.BK20230608(to JJ)。
文摘Regulatory T cells,a subset of CD4^(+)T cells,play a critical role in maintaining immune tolerance and tissue homeostasis due to their potent immunosuppressive properties.Recent advances in research have highlighted the important therapeutic potential of Tregs in neurological diseases and tissue repair,emphasizing their multifaceted roles in immune regulation.This review aims to summarize and analyze the mechanisms of action and therapeutic potential of Tregs in relation to neurological diseases and neural regeneration.Beyond their classical immune-regulatory functions,emerging evidence points to non-immune mechanisms of regulatory T cells,particularly their interactions with stem cells and other non-immune cells.These interactions contribute to optimizing the repair microenvironment and promoting tissue repair and nerve regeneration,positioning non-immune pathways as a promising direction for future research.By modulating immune and non-immune cells,including neurons and glia within neural tissues,Tregs have demonstrated remarkable efficacy in enhancing regeneration in the central and peripheral nervous systems.Preclinical studies have revealed that Treg cells interact with neurons,glial cells,and other neural components to mitigate inflammatory damage and support functional recovery.Current mechanistic studies show that Tregs can significantly promote neural repair and functional recovery by regulating inflammatory responses and the local immune microenvironment.However,research on the mechanistic roles of regulatory T cells in other diseases remains limited,highlighting substantial gaps and opportunities for exploration in this field.Laboratory and clinical studies have further advanced the application of regulatory T cells.Technical advances have enabled efficient isolation,ex vivo expansion and functionalization,and adoptive transfer of regulatory T cells,with efficacy validated in animal models.Innovative strategies,including gene editing,cell-free technologies,biomaterial-based recruitment,and in situ delivery have expanded the therapeutic potential of regulatory T cells.Gene editing enables precise functional optimization,while biomaterial and in situ delivery technologies enhance their accumulation and efficacy at target sites.These advancements not only improve the immune-regulatory capacity of regulatory T cells but also significantly enhance their role in tissue repair.By leveraging the pivotal and diverse functions of Tregs in immune modulation and tissue repair,regulatory T cells–based therapies may lead to transformative breakthroughs in the treatment of neurological diseases.
文摘Hepatocellular carcinoma presents with three distinct immune phenotypes,including immune-desert,immune-excluded,and immune-inflamed,indicating various treatment responses and prognostic outcomes.The clinical application of multi-omics parameters is still restricted by the expensive and less accessible assays,although they accurately reflect immune status.A comprehensive evaluation framework based on“easy-to-obtain”multi-model clinical parameters is urgently required,incorporating clinical features to establish baseline patient profiles and disease staging;routine blood tests assessing systemic metabolic and functional status;immune cell subsets quantifying subcluster dynamics;imaging features delineating tumor morphology,spatial configuration,and perilesional anatomical relationships;immunohistochemical markers positioning qualitative and quantitative detection of tumor antigens from the cellular and molecular level.This integrated phenomic approach aims to improve prognostic stratification and clinical decision-making in hepatocellular carcinoma management conveniently and practically.
基金Supported by the National Natural Science Foundation of China(No.82460215)National Natural Science Foundation of China Pre-experimental Project(No.2025GZRYSY006)+4 种基金2025 Youth Training Project of the Xi’an Municipal Health Commission(No.2025qn05)Xi’an Medical Research-Discipline Capacity Building Project(No.23YXYJ0002)Key R&D Plan of Shaanxi Province:Key Industrial Innovation Chain(Cluster)-Social Development Field(No.2022ZDLSF03-10)Research Incubation Fund of Xi’an People’s Hospital(Xi’an Fourth HospitalNo.LH-13).
文摘AIM:To identify metastasis-associated prognostic genes and construct a robust molecular signature for survival prediction in uveal melanoma(UVM)patients.METHODS:Transcriptomic data and clinical information from 80 UVM patients in the Cancer Genome Atlas(TCGA)-UVM cohort and an external Gene Expression Omnibus(GEO)microarray dataset(GSE73652;8 non-metastatic vs 5 metastatic cases)were analyzed to identify differentially expressed genes(DEGs).Functional enrichment,proteinprotein interaction(PPI)network construction,and survival analyses identified seven metastasis-and prognosisrelated genes.Their expression was further examined using public single-cell RNA-seq data(GSE139829;11 tumors).Experimental validation was performed in UVM cell lines(92.1,OMM1,MEL270)and adult retinal pigment epithelial(ARPE-19)cells using quantitative real-time polymerase chain reaction(qRT-PCR)and Western blotting to confirm transcriptomic trends.A LASSO Cox model was applied to construct a metastasis-related risk Score signature.Tumor immune microenvironment characteristics were evaluated via single-sample gene set enrichment analysis(ssGSEA)and ESTIMATE.Somatic mutation and copy number variation(CNV)profiles were also examined.RESULTS:Seven key genes(UBE2T,KIF20A,DLGAP5,KLC3,TPX2,UBE2C,AURKA)were significantly associated with overall survival and used to construct a metastasisrelated riskScore signature,which effectively stratified patients into high-and low-risk groups and served as an independent prognostic factor.qRT-PCR and Western blot results confirmed that the expression levels of selected key genes in UVM cell lines showed significant differences compared to ARPE-19 cells,which were largely consistent with the transcriptomic findings.The high-risk group exhibited reduced immune infiltration and stromal activity.Single-cell analysis revealed these genes were predominantly expressed in a tumor cell cluster characterized by BAP1 loss and high metastatic potential.Mutation and CNV analyses further supported the relevance of these genes to UVM progression.CONCLUSION:This study establishes and validates a seven-gene signature associated with metastasis and prognosis in UVM.The findings provide a framework for understanding molecular determinants of tumor progression and immune microenvironment alterations,and may offer guidance for future mechanistic studies and therapeutic exploration.
基金supported by grants from STI2030-Major Projects,No.2021ZD0204000(to YS)Key Strategic Science and Technology Cooperation Project of the Ministry of Science and Technology of China,No.SQ2023YFE0201430(to YS)+1 种基金the National Natural Science Foundation of China,Nos.31820103005(to YS),32200620(to LW)the Natural Science Foundation of Zhejiang Province of China,No.LZ24C090003(to YS)。
文摘The cerebellum is receiving increasing attention for its cognitive,emotional,and social functions,as well as its unique metabolic profiles.Cerebellar microglia exhibit specialized and highly immunogenic phenotypes under both physiological and pathological conditions.These immune cells communicate with intrinsic and systemic factors and contribute to the structural and functional compartmentalization of the cerebellum.In this review,we discuss the roles of microglia in the cerebellar microenvironment,neuroinflammation,cerebellar adaptation,and neuronal activity,the associated molecular and cellular mechanisms,and potential therapeutic strategies targeting cerebellar microglia in the context of neuroinflammation.Future directions and unresolved questions in this field are further highlighted,particularly regarding therapeutic interventions targeting cerebellar microglia,functional mechanisms and activities of microglia in the cerebellar circuitry,neuronal connectivity,and neurofunctional outcomes of their activity.Cerebellar morphology and neuronal performance are influenced by both intrinsic and systemic factors that are actively monitored by microglia in both healthy and diseased states.Under pathological conditions,local subsets of microglia exhibit diverse responses to the altered microenvironment that contribute to the structural and functional compartmentalization of the cerebellum.Microglia in the cerebellum undergo early maturation during the embryonic stage and display specialized,highly immunogenic phenotypes.In summary,cerebellar microglia have the capacity to serve as regulatory tools that influence outcomes across a wide range of neurological and systemic conditions,including neurodevelopmental,neurodegenerative,metabolic,and stress-related disorders.
文摘BACKGROUND Chemotherapy with an immune checkpoint inhibitor is one of the standard regimens for treating advanced gastric cancer(AGC).Ascites and peritoneal dissemination are common complications and poor prognostic factors of AGC;however,reports regarding its efficacy and safety in patients with AGC and massive ascites are limited.AIM To evaluate the safety and efficacy of nivolumab combined with chemotherapy in patients with AGC and ascites.METHODS We retrospectively collected clinical data from 124 patients with AGC who received chemotherapy plus nivolumab as first-line treatment from July 2017 to December 2024.Based on computed tomography scans,massive or moderate ascites were classified as high ascites burden(HAB),whereas mild or no ascites were classified as low ascites burden.RESULTS Ascites was detected in 47 patients(38%);26(21%)were classified into the HAB group.Patients in the HAB group exhibited a significantly poorer performance status,a higher prevalence of diffuse-type histology,and lower programmed cell death ligand 1(PD-L1)expression.Combination therapy with FOLFOX and neutropenia was significantly more common in the HAB group.Progression-free survival(PFS)(4.4 months vs 9.3 months,P=0.0012)and overall survival(OS)(7.3 months vs 21.2 months,P<0.0001)were significantly poorer in the HAB group.However,an improvement in ascites was observed in 61.5%of patients in the HAB group.PD-L1 expression did not correlate with either PFS or OS in the HAB group.CONCLUSION Nivolumab plus chemotherapy demonstrated modest efficacy and acceptable toxicity in patients with AGC and HAB.
文摘Wu et al recently applied multi-region 16S rRNA sequencing to characterize the gastric cancer microbiome,demonstrating improved taxonomic resolution and detection sensitivity over conventional single-region approaches.While the study represents a valuable methodological step forward,it remains limited by singlecenter design,lack of quantitative calibration,and insufficient control for contamination and inter-laboratory variability.This editorial critically appraises these methodological gaps and emphasizes that future efforts must focus on harmonized,consensus-driven workflows to ensure reproducibility and clinical reliability.The translational potential of multi-region 16S lies in moving from descriptive microbial profiling to actionable clinical integration,particularly for recurrence prediction,treatment-response monitoring,and perioperative complication risk assessment.By addressing these methodological,economic,and ethical challenges,the field can advance toward evidence-based and clinically deployable microbiome-guided precision oncology.
基金Deutsche Forschungsgemeinschaft(DFG,German Research Foundation),project numbers 324633948 and 409784463(DFG grants Hi 678/9-3 and Hi 678/10-2,FOR2953)to HHBundesministerium für Bildung und Forschung-BMBF,project number 16LW0463K to HT.
文摘Microglia are the resident macrophages of the central nervous system.They act as the first line of defense against pathogens and play essential roles in neuroinflammation and tissue repair after brain insult or in neurodegenerative and demyelinating diseases(Borst et al.,2021).Together with infiltrating monocyte-derived macrophages,microglia also play a critical role for brain tumor development,since immunosuppressive interactions between tumor cells and tumor-associated microglia and macrophages(TAM)are linked to malignant progression.This mechanism is of particular relevance in glioblastoma(GB),the deadliest form of brain cancer with a median overall survival of less than 15 months(Khan et al.,2023).Therefore,targeting microglia and macrophage activation is a promising strategy for therapeutic interference in brain disease.
基金supported by Technological Innovation 2030-Major Projects of“Brain Science and Brain-like Research,”No.2022ZD0206200(to XG)the National Natural Science Foundation of China,No.82371245(to SJ),82102246(to XD),81701092(to XG)+2 种基金the Natural Science Foundation of Shandong Province,No.ZR2020MH129(to SJ)Shanghai Municipal Key Clinical Specialty,No.shslczdzk03601Shanghai Engineering Research Center of Peri-operative Organ Support and Function Preservation,No.20DZ2254200。
文摘Adult hippocampal neurogenesis is linked to memory formation in the adult brain,with new neurons in the hippocampus exhibiting greater plasticity during their immature stages compared to mature neurons.Abnormal adult hippocampal neurogenesis is closely associated with cognitive impairment in central nervous system diseases.Targeting and regulating adult hippocampal neurogenesis have been shown to improve cognitive deficits.This review aims to expand the current understanding and prospects of targeting neurogenesis in the treatment of cognitive impairment.Recent research indicates the presence of abnormalities in AHN in several diseases associated with cognitive impairment,including cerebrovascular diseases,Alzheimer's disease,aging-related conditions,and issues related to anesthesia and surgery.The role of these abnormalities in the cognitive deficits caused by these diseases has been widely recognized,and targeting AHN is considered a promising approach for treating cognitive impairment.However,the underlying mechanisms of this role are not yet fully understood,and the effectiveness of targeting abnormal adult hippocampal neurogenesis for treatment remains limited,with a need for further development of treatment methods and detection techniques.By reviewing recent studies,we classify the potential mechanisms of adult hippocampal neurogenesis abnormalities into four categories:immunity,energy metabolism,aging,and pathological states.In immunity-related mechanisms,abnormalities in meningeal,brain,and peripheral immunity can disrupt normal adult hippocampal neurogenesis.Lipid metabolism and mitochondrial function disorders are significant energy metabolism factors that lead to abnormal adult hippocampal neurogenesis.During aging,the inflammatory state of the neurogenic niche and the expression of aging-related microRNAs contribute to reduced adult hippocampal neurogenesis and cognitive impairment in older adult patients.Pathological states of the body and emotional disorders may also result in abnormal adult hippocampal neurogenesis.Among the current strategies used to enhance this form of neurogenesis,physical therapies such as exercise,transcutaneous electrical nerve stimulation,and enriched environments have proven effective.Dietary interventions,including energy intake restriction and nutrient optimization,have shown efficacy in both basic research and clinical trials.However,drug treatments,such as antidepressants and stem cell therapy,are primarily reported in basic research,with limited clinical application.The relationship between abnormal adult hippocampal neurogenesis and cognitive impairment has garnered widespread attention,and targeting the former may be an important strategy for treating the latter.However,the mechanisms underlying abnormal adult hippocampal neurogenesis remain unclear,and treatments are lacking.This highlights the need for greater focus on translating research findings into clinical practice.
