Cerebrovascular diseases are considered to be amongst the most serious public health issues,since they are the third leading cause of death（WHO,2014）and the most common cause of disability worldwide.Its monetary sig...Cerebrovascular diseases are considered to be amongst the most serious public health issues,since they are the third leading cause of death（WHO,2014）and the most common cause of disability worldwide.Its monetary significance is evidenced by the economic burden imposed on health care systems,given that the cost of medical care for a patient that has suffered a stroke is around$25,741US dollars every 5 years（Luengo-Fernandez et al.,2012）.A stroke occurs as a result of a disturbance or interruption of cerebral blood flow that significantly reduces the supply of oxygen and glucose to the neural tissue. Consequently, several cell death mechanisms （secondary lesion mechanisms） such as necrosis, excitotoxicity, free radical production and inflammation are triggered （Castillo, 2000）.展开更多
AIM: To explore the effect of immunization with copolymer-1 (COP-1) and retinal stem cells (RSCs) transplantation on interferon-gamma (IFN-gamma) levels in a rat experimental glaucoma model. METHODS: An experimental g...AIM: To explore the effect of immunization with copolymer-1 (COP-1) and retinal stem cells (RSCs) transplantation on interferon-gamma (IFN-gamma) levels in a rat experimental glaucoma model. METHODS: An experimental glaucoma was induced by argon laser photocoagulation of the episcleral veins and limbal plexus in the right eye of rats. Immediately following glaucoma induction, rats were immunized with COP-1. RSCs were cultured and transplanted intravitreally into the eyes of glaucoma model animals 1 week post-laser treatment. Six experimental groups were used: COP-1/RSC, PBS/RSC, COP-1/PBS, PBS/PBS, glaucoma model group, and a normal control group. The concentration of IFN-gamma in aqueous humor (AH) and serum was measured by enzyme-linked immunosorbent assay (ELISA) in each of the six groups. Retinal ganglion cell (RGC) survival was assessed by quantifying apoptosis using Hoechst staining. RESULTS: Concentrations of IFN-gamma in AH and serum of rats that had undergone glaucoma induction were higher than those of non-induced control rats. The concentrations of IFN-gamma in AH and serum of the COP-1/RSCs treated group were determined to be 2371.9ng/L and 710.9ng/L, respectively, which were significantly lower than those in the other treated groups (P<0.05). In fact, IFN-gamma levels in the dual treated group were reduced to background levels. The COP-1/RSC group had lower number of apoptotic RGCs than the other three experimental groups (P<0.05). CONCLUSION: The reduced levels of IFN-gamma in AH and serum of the COP-1/RSC group may be related to synergistic effects between RSCs transplantation and COP-1 immune modulation. It is likely that the lower levels of IFN-gamma prevented RGCs glaucomatous apoptasis.展开更多
[Objective] This study aimed to construct DNA vaccine of foot-and-mouth disease （FMD）.[Method] Plasmid carriers plESZP1 and pUTK3CP1 with PRV were constructed for FMDV P1 gene expression.Mice were immunized,and thei...[Objective] This study aimed to construct DNA vaccine of foot-and-mouth disease （FMD）.[Method] Plasmid carriers plESZP1 and pUTK3CP1 with PRV were constructed for FMDV P1 gene expression.Mice were immunized,and their antibody level was detected.The two eukaryotic expression plasmids constructed were transfected into Vero cells.PCR,IFA and Westem-blot were carried out to detect the transcription and expression of the objective gene.Balb/C mice were intramuscularly inoculated with the DNA plasmid which expressed the target gene correctly,and the antibody level in mice was detected by the means of ELISA and serum neutralization （SN）.[Result] DNA plasmid carrying P1 gene which encodes FMDV capsid protein caused specific body fluid immunoreaction in mice,and the antibody level of anti-FMDV had no difference in the mice induced by the two recombinant plasmids.[Conclusion] This study lays a foundation for evaluating the genetically modified vaccine by immunizing animals with recombinant PRV containing the FMDV P1 gene and recombinant virus.展开更多
Copolymer-1（Cop-1） is a peptide with immunomodulatory properties, approved by the Food and Drug Administration of United States in the treatment of multiple sclerosis. Cop-1 has been shown to exert neuroprotective e...Copolymer-1（Cop-1） is a peptide with immunomodulatory properties, approved by the Food and Drug Administration of United States in the treatment of multiple sclerosis. Cop-1 has been shown to exert neuroprotective effects and induce neurogenesis in cerebral ischemia models. Nevertheless, the mechanism involved in the neurogenic action of this compound remains unknown. The choroid plexus（CP） is a network of cells that constitute the interphase between the immune and central nervous systems, with the ability to mediate neurogenesis through the release of cytokines and growth factors. Therefore, the CP could play a role in Cop-1-induced neurogenesis. In order to determine the participation of the CP in the induction of neurogenesis after Cop-1 immunization, we evaluated the gene expression of various growth factors（brain-derived neurotrophic factor, insulin-like growth factor 1, neurotrophin-3） and cytokines（tumor necrosis factor alpha, interferon-gamma, interleukin-4（IL-4）, IL-10 and IL-17）, in the CP at 14 days after ischemia. Furthermore, we analyzed the correlation between the expression of these genes and neurogenesis. Our results showed that Cop-1 was capable of stimulating an upregulation in the expression of the genes encoding for brain-derived neurotrophic factor, insulin-like growth factor 1, neurotrophin-3 and IL-10 in the CP, which correlated with an increase in neurogenesis in the subventricular and subgranular zone. As well, we observed a downregulation of IL-17 gene expression. This study demonstrates the effect of Cop-1 on the expression of growth factors and IL-10 in the CP, in the same way, presents a possible mechanism involved in the neurogenic effect of Cop-1.展开更多
BACKGROUND Hepatocellular carcinoma(HCC)has been a pervasive malignancy throughout the world with elevated mortality.Efficient therapeutic targets are beneficial to treat and predict the disease.Currently,the exact mo...BACKGROUND Hepatocellular carcinoma(HCC)has been a pervasive malignancy throughout the world with elevated mortality.Efficient therapeutic targets are beneficial to treat and predict the disease.Currently,the exact molecular mechanisms leading to the progression of HCC are still unclear.Research has shown that the microRNA-142-3p level decreases in HCC,whereas bioinformatics analysis of the cancer genome atlas database shows the ASH1L expression increased among liver tumor tissues.In this paper,we will explore the effects and mechanisms of microRNA-142-3p and ASH1L affect the prognosis of HCC patients and HCC cell bioactivity,and the association between them.AIM To investigate the effects and mechanisms of microRNA-142-3p and ASH1L on the HCC cell bioactivity and prognosis of HCC patients.METHODS In this study,we grouped HCC patients according to their immunohistochemistry results of ASH1L with pathological tissues,and retrospectively analyzed the prognosis of HCC patients.Furthermore,explored the roles and mechanisms of microRNA-142-3p and ASH1L by cellular and animal experiments,which involved the following experimental methods:Immunohistochemical staining,western blot,quantitative real-time-polymerase chain reaction,flow cytometric analysis,tumor xenografts in nude mice,etc.The statistical methods involved in this study contained t-test,one-way analysis of variance,theχ^(2)test,the Kaplan-Meier approach and the log-rank test.RESULTS In this study,we found that HCC patients with high expression of ASH1L possess a more recurrence rate as well as a decreased overall survival rate.ASH1L promotes the tumorigenicity of HCC and microRNA-142-3p exhibits reduced expression in HCC tissues and interacts with ASH1L through targeting the ASH1L 3′untranslated region.Furthermore,microRNA-142-3p promotes apoptosis and inhibits proliferation,invasion,and migration of HCC cell lines in vitro via ASH1L.For the exploration mechanism,we found ASH1L may promote an immunosuppressive microenvironment in HCC and ASH1L affects the expression of the cell junction protein zonula occludens-1,which is potentially relevant to the immune system.CONCLUSION Loss function of microRNA-142-3p induces cancer progression and immune evasion through upregulation of ASH1L in HCC.Both microRNA-142-3p and ASH1L can feature as new biomarker for HCC in the future.展开更多
Objective:Small cell lung cancer(SCLC)is commonly recognized as the most fatal lung cancer type.Despite substantial advances in immune checkpoint blockade therapies for treating solid cancers,their benefits are limite...Objective:Small cell lung cancer(SCLC)is commonly recognized as the most fatal lung cancer type.Despite substantial advances in immune checkpoint blockade therapies for treating solid cancers,their benefits are limited to a minority of patients with SCLC.In the present study,novel indicators for predicting the outcomes and molecular targets for SCLC treatment were elucidated.Methods:We conducted bioinformatics analysis to identify the key genes associated with tumor-infiltrating lymphocytes in SCLC.The functional role of the key gene identified in SCLC was determined both in vitro and in vivo.Results:A significant correlation was observed between patient survival and CD56dim natural killer(NK)cell proportion.Furthermore,we noted that the hub gene ubiquitin-specific protease 1(USP1)is closely correlated with both CD56dim NK cells and overall survival in SCLC.Bioinformatics analysis revealed that USP1 is upregulated in SCLC.In addition,gene set enrichment analysis revealed that USP1 overexpression hinders NK cell-mediated immune responses.By co-cultivating NK-92 cells with SCLC cells,we demonstrated that NK cell cytotoxicity against SCLC could be improved either via USP1 knock-down or pharmacological inhibition.Furthermore,using a nude-mice xenograft tumor model,we noted that USP1 inhibition effectively suppressed tumor proliferation and increased the expression of NK cell-associated markers.Conclusions:Our study findings highlight the importance of NK cells in regulating SCLC.USP1 overexpression can inhibit NK cell-mediated immunity;therefore,USP1 may serve not only as a prognostic biomarker but also as a potential molecular target of SCLC therapy.展开更多
AIM:Regulatory T cells(Tregs)are a specialized subset of CD4^(+)T cells primarily involved in im⁃munosuppressive functions.AMP-activated protein kinase(AMPK)serves as a metabolic sensor that governs the differen⁃tiati...AIM:Regulatory T cells(Tregs)are a specialized subset of CD4^(+)T cells primarily involved in im⁃munosuppressive functions.AMP-activated protein kinase(AMPK)serves as a metabolic sensor that governs the differen⁃tiation,maturation,and immune functions of Tregs through metabolic reprogramming.However,the impact of AMPKα1(the catalytic subunit of AMPK)knockout specifically in Tregs on the host's immune microenvironment remains largely un⁃explored.METHODS:Histological changes in immune organs were assessed using HE staining.The types of immune cells and their relative population percentages in immune organs and blood were quantified through flow cytometry in both AMPKα1flox/flox(AMPKα1^(fl/fl))mice and Treg-specific AMPKα1 knockout mice(AMPKα1^(fl/fl)Foxp3^(cre)mice).RESULTS:Compared to AMPKα1^(fl/fl)mice,the percentage of eosinophils in the bone marrow of AMPKα1^(fl/fl)Foxp3^(cre)mice was significant⁃ly reduced.Additionally,while the thymus of AMPKα1^(fl/fl)Foxp3^(cre)mice exhibited normal structure,both its size and the ratio of thymus weight to body weight were significantly decreased.The knockout of AMPKα1 in Tregs led to a notable reduction in the total percentage of immature double-negative(DN)cells.Consequently,the percentage of CD4^(+)T cells derived from these DN cells also decreased,even though the percentages of DN1 and DN4 cells were higher in the thymus of AMPKα1^(fl/fl)Foxp3^(cre)mice compared to AMPKα1^(fl/fl)mice.Importantly,the proportion of Siglec-F+CD11b^(+)eosinophils in the thymus was significantly lower in AMPKα1^(fl/fl)Foxp3^(cre)mice.Knockout of AMPKα1 in Tregs resulted in a marked increase in the percentage of CD4^(+)T cells in peripheral blood,alongside a decrease in the proportion of mature CD8^(+)T cells.Similarly,the proportion of CD4^(+)T cells in the spleen of AMPKα1^(fl/fl)Foxp3^(cre)mice was elevated compared to AMPKα1^(fl/fl)mice.In contrast,the proportion of neutrophils significantly decreased,while mononuclear cell proportions increased in the spleen of AMPKα1^(fl/fl)Foxp3^(cre)mice.In lymph nodes,the medullary boundaries in AMPKα1^(fl/fl)Foxp3^(cre)mice were blurred,and the lymphoid follicles were missing,a feature not observed in AMPKα1^(fl/fl)mice.Furthermore,the knockout of AMPKα1 in Tregs reduced the CD3^(+)T cell population,particularly the CD8^(+)T cell population,in lymph nodes.Although the mature Treg cell population was significantly lower in AMPKα1^(fl/fl)Foxp3^(cre)mice,the percentage of CD4^(+)T cells was markedly in⁃creased.In contrast,there was no statistically significant difference in granulocyte populations between AMPKα1^(fl/fl)Foxp3^(cre)and AMPKα1^(fl/fl)mice.CONCLUSION:The populations of mature Tregs,CD8^(+)T cells and eosinophils in various im⁃mune organs were significantly altered in mice with Treg-specific AMPKα1 knockout,suggesting a potential remodeling of the host immune microenvironment in response to inflammatory stimuli.展开更多
High expression of pescadillo ribosomal biogenesis factor 1(PES1)has been re-ported across multiple cancer types and is significantly associated with poor prog-nosis.Hu et al in their recent paper described their inve...High expression of pescadillo ribosomal biogenesis factor 1(PES1)has been re-ported across multiple cancer types and is significantly associated with poor prog-nosis.Hu et al in their recent paper described their investigation of PES1 in gastric cancer and head and neck squamous cell carcinoma,demonstrating positive cor-relations between PES1 and programmed death-ligand 1(PD-L1)expression(51.72%for PES1 and 58.62%for PD-L1),as well as associations with lymph node metastasis and tumor invasion depth.However,the relationship between PES1 and PD-L1 remains incompletely defined.To further address this gap,we ana-lyzed The Cancer Genome Atlas gastric adenocarcinoma dataset and found a negative correlation between PES1 expression and CD8+T cell infiltration,along-side a positive correlation with PD-L1 expression.Based on prior findings,we hypothesize that PES1 may regulate PD-L1 through the phosphatidylinositol 3-kinase/protein kinase B pathway or cellular Myc-mediated mechanisms.While these pathways require experimental validation,our observations highlight PES1 as a potential regulator of immune evasion and a promising target for cancer immunotherapy.展开更多
Posttranslational modifications(PTMs)are essential regulatory mechanisms that play a critical role in plant immunity.Previously,we demonstrated that OsBBI1,a RING finger type E3 ligase,contributes to rice resistance a...Posttranslational modifications(PTMs)are essential regulatory mechanisms that play a critical role in plant immunity.Previously,we demonstrated that OsBBI1,a RING finger type E3 ligase,contributes to rice resistance against blast disease.In this study,we identified two Eps15 homology domain(EHD)-containing proteins,OsEHD1 and OsEHD2,as substrates of OsBBI1 and investigated their roles in rice immunity against Magnaporthe oryzae and Xanthomonas oryzae pv.oryzae(Xoo).We found that OsBBI1 ubiquitinated and promoted the degradation of OsEHD1 and OsEHD2 via ubiquitin/26S proteasome system(UPS)pathway.CRISPR/Cas9-mediated knockout of OsEHD1 and OsEHD2 led to enhanced immunity against M.oryzae and Xoo,improved expression of pathogen-induced immunity-associated genes,and strengthened pattern-triggered immunity(PTI),while overexpression of OsEHD1 resulted in opposite phenotypes.Additionally,OsEHD1 and OsEHD2 interacted with three SUMO proteins,OsSUMO3,OsSUMO5,or OsSUMO6,with SUMOylation sites in OsEHD1 and OsEHD2 being critical for these interactions.OsSUMO6 enhanced the stability of OsEHD1 and OsEHD2 to promote their negative immune regulation,whereas OsBBI1 reversed these negative immune functions.This study delineates a regulatory network of OsEHD1 and OsEHD2 proteins in rice immunity,highlighting the balance between OssBBI1-mediated ubiquitination and SUMOylation.展开更多
An article recently published in the World Journal of Diabetes,provides valuable insights into using immune biomarkers to identify renal damage in pediatric patients with newly diagnosed type 1 diabetes(T1D).Although ...An article recently published in the World Journal of Diabetes,provides valuable insights into using immune biomarkers to identify renal damage in pediatric patients with newly diagnosed type 1 diabetes(T1D).Although these findings are promising,clinical translation of these immune markers into routine diagnostics and preventive care remains challenging.In this letter,we propose building on the authors’work by exploring the integration of immune biomarkers into a more comprehensive dynamic risk stratification model for early renal injury.Com-bining immune system indicators with metabolic and genetic factors could enhance the predictive accuracy and support more personalized interventions.Longitudinal studies are needed to evaluate temporal changes in immune biomarkers and their association with long-term renal outcomes in children with T1Ds.Immunomodulatory therapies targeting early immune dysfunction can prevent or slow the progression of diabetic nephropathy.By incorporating these aspects,we hope to translate immune biomarkers from research into practical clinical tools,ultimately improving patient outcomes and reducing the burden of kidney-related complications in pediatric diabetes.展开更多
This editorial delves into the potential of systemic immune indicators(SIIs)as early predictors of renal damage in children with newly diagnosed type 1 diabetes mellitus.By exploring the recent study published by Cao ...This editorial delves into the potential of systemic immune indicators(SIIs)as early predictors of renal damage in children with newly diagnosed type 1 diabetes mellitus.By exploring the recent study published by Cao et al,this article aims to highlight the importance of early detection and intervention.This study compre-hensively analyzes various SIIs,examining their correlation with renal compli-cations in newly diagnosed type 1 diabetic children.The findings reveal a sig-nificant association between immune system dysregulation and the onset of renal damage,suggesting that certain immune indicators can be early markers for predicting renal complications.This editorial emphasizes the clinical implications and applications of utilizing SIIs for early detection in pediatric diabetes care.It underscores the importance of innovative diagnostic approaches and illustrates real-world applications and outcomes.Additionally,it addresses the challenges and considerations in adopting these indicators and outlines future research directions to enhance diabetes management in children.展开更多
BACKGROUND Patients with microsatellite stable(MSS)metastatic colorectal cancer(mCRC)typically exhibit an immunosuppressive tumor microenvironment and demonstrate a low response rate to immunotherapy.Reports suggest t...BACKGROUND Patients with microsatellite stable(MSS)metastatic colorectal cancer(mCRC)typically exhibit an immunosuppressive tumor microenvironment and demonstrate a low response rate to immunotherapy.Reports suggest that chemotherapy and anti-angiogenic therapy may have the potential to enhance the response to immunotherapy in these patients.This study aims to evaluate the effectiveness and safety of chemotherapy combined with bevacizumab with or without antiprogrammed death 1(PD-1)immunotherapy as the second-line regimen for MSS mCRC.AIM To evaluate the effectiveness and safety of chemotherapy combined with bevacizumab with or without anti-PD-1 immunotherapy as the second-line regimen for MSS mCRC.METHODS A retrospective analysis was conducted on patients with MSS mCRC diagnosed at Peking University First Hospital and Jilin Cancer Hospital from January 2020 to December 2024.The patients were divided into two groups:The experimental group receiving second-line chemotherapy combined with bevacizumab and anti-PD-1 immunotherapy,and the control group receiving chemotherapy combined with bevacizumab.Propensity score matching was applied to balance potential prognostic factors,including age,gender,Eastern Cooperative Oncology Group score,number of metastases,and primary tumor site.The progression-free survival,overall survival,disease control rate,objective response rate,and treatment-related adverse reactions were compared between the two groups.Kaplan-Meier analysis and log-rank test were used to compare survival outcomes.Inverse probability of treatment weighting was used for sensitivity analysis.RESULTS Propensity score matching resulted in 103 matched eligible patients.The median follow-up period was 13.9 months in the matched cohort.The objective response rate was 11.5%and 9%for the experimental and control groups,respectively(P=0.710),while the disease control rate was 76.9%and 53.2%,respectively(P=0.058).The median progression-free survival in the experimental group was 8.27 months[95%confidence interval(CI):6.7-14.7 months],significantly higher than that in the control group,which was 4.63 months(95%CI:3.9-5.67 months)(hazard ratio=0.4143,95%CI:0.2462-0.6972,P=0.00066).There was a trend towards the higher median overall survival in the experimental group compared to the control group(hazard ratio=0.4504,95%CI:0.1897-1.07,P=0.064).The incidences of adverse events were similar between the two groups.CONCLUSION Compared with the standard second-line chemotherapy combined with bevacizumab regimen,second-line therapy that combines chemotherapy with bevacizumab and anti-PD-1 immunotherapy has demonstrated promising efficacy in the treatment of MSS mCRC,while exhibiting a similar safety profile.展开更多
Gibberella stalk rot(GSR)caused by Fusarium graminearum is one of the most devastating diseases of maize,seriously impacting maize yield and quality,as well as the ability to use technology of mechanical harvesting.En...Gibberella stalk rot(GSR)caused by Fusarium graminearum is one of the most devastating diseases of maize,seriously impacting maize yield and quality,as well as the ability to use technology of mechanical harvesting.Environmental conditions including photoperiod affect crop disease resistance.However,the mechanism underlying photoperiod-regulated maize GSR resistance remains unexplored.We found in this study that GSR resistance is regulated by the ZmPIF4.1(Phytochrome-Interacting Factor4)-ZmPTI1c(Pto-Interacting 1)-ZmMYB31 module coupled with photoperiod.The functional analysis of zmpti1c mutant indicated that ZmPTI1c negatively regulates maize GSR resistance.Short day promoted the disease progression in both zmpti1c and wild-type plants.ZmPTI1c promoter contains multiple predicted cis-acting elements for light responses.Yeast one-hybrid assay(Y1H),Electrophoretic mobility shift analysis(EMSA),and Dual-luciferase(LUC)reporter assays demonstrated that ZmPIF4.1 binds to the G-box in ZmPTI1c promoter and activates its expression.Moreover,expression levels of ZmPIF4 and ZmPTI1c were significantly higher under short day than under long day.ZmPTI1c interacted with and phosphorylated ZmMYB31.GSR resistance in zmmyb31 mutant was significantly increased than in wild type,indicating that ZmMYB31 also negatively regulated GSR resistance.Furthermore,ZmMYB31 suppressed the transcriptional activation of ZmPTI1c by ZmPIF4.1.Overall,ZmPIF4.1-ZmPTI1c-ZmMYB31negatively regulates maize immunity to GSR,which is likely modulated by photoperiod.展开更多
BACKGROUND Colorectal cancer(CRC)is a leading cause of cancer-related mortality worldwide,primarily due to tumor heterogeneity and treatment resistance.The leucine-rich repeat-containing protein 19(LRRC19)has been lin...BACKGROUND Colorectal cancer(CRC)is a leading cause of cancer-related mortality worldwide,primarily due to tumor heterogeneity and treatment resistance.The leucine-rich repeat-containing protein 19(LRRC19)has been linked to immune regulation and tumor suppression,yet its specific role in CRC remains poorly understood.AIM To investigate the tumor-suppressive role of LRRC19 in CRC,focusing on cell cycle,immune microenvironment,and chemotherapy response.METHODS Bioinformatics analyses of Gene Expression Omnibus and The Cancer Genome Atlas databases identified differentially expressed genes in CRC.LRRC19 exp-ression was validated in CRC tissues and cell lines by quantitative PCR,immuno-histochemistry,and Western blotting.Functional assays,including proliferation,soft agar colony formation,flow cytometry,and xenograft models,assessed biological effects.Mechanistic studies with dual-luciferase reporter assays,molecular docking,and drug sensitivity testing explored LRRC19’s interaction with the cyclin-dependent kinase 6(CDK6)/E2F1 axis and oxaliplatin(OXA)response.Single-cell sequencing and immune infiltration analyses assessed its impact on the immune microenvironment.RESULTS LRRC19 expression was significantly downregulated in CRC and associated with poor prognosis.Overexpression of LRRC19 inhibited CRC cell proliferation,induced G0/G1 phase arrest,and suppressed tumor growth in vivo.Mechanistically,LRRC19 suppressed CDK6 transcription by downregulating E2F1,leading to cell cycle arrest.Additionally,LRRC19 promoted immune cell infiltration,particularly B cells and CD4+T cells,while decreasing immunosuppressive cells.LRRC19 also sensitized CRC cells to OXA,enhancing chemotherapy efficacy.CONCLUSION LRRC19 suppresses CRC by targeting the CDK6/E2F1 axis,modulating the immune microenvironment,and enhancing chemotherapy sensitivity,making it a promising therapeutic target for precision medicine in CRC.展开更多
BACKGROUND Early kidney damage is a significant complication in children with newly diagnosed type 1 diabetes mellitus(T1DM).Systemic inflammation plays a key role in the development of diabetic nephropathy.Several in...BACKGROUND Early kidney damage is a significant complication in children with newly diagnosed type 1 diabetes mellitus(T1DM).Systemic inflammation plays a key role in the development of diabetic nephropathy.Several inflammatory markers,including the systemic immune inflammation index(SII),neutrophil-to-lymphocyte ratio(NLR),and platelet-to-lymphocyte ratio(PLR),have been proposed as potential indicators of diabetic complications.AIM To investigate the association between SII,NLR,PLR,and early kidney damage in newly diagnosed T1DM children without pre-existing albuminuria,assessing their utility as predictive biomarkers.METHODS A longitudinal cohort study was conducted on 102 children aged 3-18 years with newly diagnosed T1DM[baseline urinary albumin-to-creatinine ratio(UACR)<30 mg/g]recruited between January 2020 and June 2023.Participants were followed biannually for up to three years.Demographic,clinical,and laboratory data,including inflammatory markers(SII,NLR,PLR),were collected at baseline and follow-up.Logistic regression and receiver operating characteristic analyses were used to evaluate the predictive utility of these markers for early kidney damage,defined as UACR≥30 mg/g.RESULTS SII emerged as a significant independent predictor of early kidney damage[odds ratio=1.002,95%confidence interval(CI):1.0008-1.0033,P=0.0016],with an area under the curve of 0.719(95%CI:0.612-0.826,P<0.001).Using an SII threshold of≥624.015 achieved a sensitivity of 59.6%and specificity of 92%.Combining SII with NLR and PLR improved predictive accuracy(area under the curve=0.787),with sensitivity and specificity of 63.5%and 96%,respectively.Correlation analyses revealed significant associations between SII,metabolic markers(triglycerides,glycated hemoglobin),and UACR.CONCLUSION SII is a reliable biomarker for early kidney damage in T1DM children,offering high specificity for identifying atrisk patients.Combining SII with NLR and PLR enhances diagnostic precision,supporting its integration into clinical practice.Longitudinal monitoring of these markers may facilitate early interventions to mitigate renal complications in pediatric T1DM.展开更多
Raising a heterologous tier 2 neutralizing antibody(nAb)response remains a daunting task for HIV vaccine development.In this study,we explored the utility of diverse HIV-1 envelope(Env)immunogens in a sequential immun...Raising a heterologous tier 2 neutralizing antibody(nAb)response remains a daunting task for HIV vaccine development.In this study,we explored the utility of diverse HIV-1 envelope(Env)immunogens in a sequential immunization scheme as a solution to this task.This exploration stemmed from the rationale that gp145,a membrane-bound truncation form of HIV Env,may facilitate the focusing of induced antibody response on neutralizing epitopes when sequentially combined with the soluble gp140 form as immunogens in a prime-boost mode.We first showed that gp140 DNA prime-gp145 Tiantan vaccinia(TV)boost likely represents a general format for inducing potent nAb response in mice.However,when examined in rhesus macaque,this modality showed little effectiveness.To improve the efficacy,we extended the original modality by adding a strong protein boost,namely native-like SOSIP.664 trimer displayed on ferritin-based nanoparticle(NP),which was generated by a newly developed click approach.The resulting three-immunization regimen succeeded in eliciting tier-2 nAb response with substantial breadth when implemented in rhesus macaque over a short 8-week schedule.Importantly,the elicited nAb response was able to effectively contain viremia upon a heterologous SHIV challenge.Collectively,our studies highlighted that diversification of Env immunogens,in both types and formulations,under the framework of a sequential immunization scheme might open new opportunity toward HIV vaccine development.展开更多
Objective: to observe the practical effect of predictive nursing in the 1-3 year-old childrens immunization nursing. Methods: a total of 114 children aged 1-3 years were enrolled in the study and divided into group ①...Objective: to observe the practical effect of predictive nursing in the 1-3 year-old childrens immunization nursing. Methods: a total of 114 children aged 1-3 years were enrolled in the study and divided into group ①: Control group and group ②: Observation group. Routine nursing and predictive nursing were administered respectively. Results: the data in Table 1-5 all indicate that the data obtained from the nursing methods in the observation group are more satisfactory (P < 0.05). Conclusion: predictive nursing is helpful to improve the coordination degree and comfort level of immunization for children aged 1-3 years old, reduce the incidence of stress reaction, and improve the cognitive level and satisfaction of family members.展开更多
After that the era of chemotherapy in the treatment of solid tumors have been overcome by the "translational era", with the innovation introduced by targeted therapies, medical oncology is currently looking ...After that the era of chemotherapy in the treatment of solid tumors have been overcome by the "translational era", with the innovation introduced by targeted therapies, medical oncology is currently looking at the dawn of a new "immunotherapy era" with the advent of immune checkpoint inhibitors(CKI) antibodies.The onset of PD-1/PD-L1 targeted therapy has demonstrated the importance of this axis in the immune escape across almost all human cancers.The new CKI allowed to significantly prolong survival and to generate durable response, demonstrating remarkable efficacy in a wide range of cancer types.The aim of this article is to review the most up to date literature about the clinical effectiveness of CKI antibodies targeting PD-1/PD-L1 axis for the treatment of advanced solid tumors and to explore transversal challenges in the immune checkpoint blockade.展开更多
文摘Cerebrovascular diseases are considered to be amongst the most serious public health issues,since they are the third leading cause of death（WHO,2014）and the most common cause of disability worldwide.Its monetary significance is evidenced by the economic burden imposed on health care systems,given that the cost of medical care for a patient that has suffered a stroke is around$25,741US dollars every 5 years（Luengo-Fernandez et al.,2012）.A stroke occurs as a result of a disturbance or interruption of cerebral blood flow that significantly reduces the supply of oxygen and glucose to the neural tissue. Consequently, several cell death mechanisms （secondary lesion mechanisms） such as necrosis, excitotoxicity, free radical production and inflammation are triggered （Castillo, 2000）.
基金Supported by the Program for New Century Excellent Talents in University (No. NCET-05-0684)
文摘AIM: To explore the effect of immunization with copolymer-1 (COP-1) and retinal stem cells (RSCs) transplantation on interferon-gamma (IFN-gamma) levels in a rat experimental glaucoma model. METHODS: An experimental glaucoma was induced by argon laser photocoagulation of the episcleral veins and limbal plexus in the right eye of rats. Immediately following glaucoma induction, rats were immunized with COP-1. RSCs were cultured and transplanted intravitreally into the eyes of glaucoma model animals 1 week post-laser treatment. Six experimental groups were used: COP-1/RSC, PBS/RSC, COP-1/PBS, PBS/PBS, glaucoma model group, and a normal control group. The concentration of IFN-gamma in aqueous humor (AH) and serum was measured by enzyme-linked immunosorbent assay (ELISA) in each of the six groups. Retinal ganglion cell (RGC) survival was assessed by quantifying apoptosis using Hoechst staining. RESULTS: Concentrations of IFN-gamma in AH and serum of rats that had undergone glaucoma induction were higher than those of non-induced control rats. The concentrations of IFN-gamma in AH and serum of the COP-1/RSCs treated group were determined to be 2371.9ng/L and 710.9ng/L, respectively, which were significantly lower than those in the other treated groups (P<0.05). In fact, IFN-gamma levels in the dual treated group were reduced to background levels. The COP-1/RSC group had lower number of apoptotic RGCs than the other three experimental groups (P<0.05). CONCLUSION: The reduced levels of IFN-gamma in AH and serum of the COP-1/RSC group may be related to synergistic effects between RSCs transplantation and COP-1 immune modulation. It is likely that the lower levels of IFN-gamma prevented RGCs glaucomatous apoptasis.
文摘[Objective] This study aimed to construct DNA vaccine of foot-and-mouth disease （FMD）.[Method] Plasmid carriers plESZP1 and pUTK3CP1 with PRV were constructed for FMDV P1 gene expression.Mice were immunized,and their antibody level was detected.The two eukaryotic expression plasmids constructed were transfected into Vero cells.PCR,IFA and Westem-blot were carried out to detect the transcription and expression of the objective gene.Balb/C mice were intramuscularly inoculated with the DNA plasmid which expressed the target gene correctly,and the antibody level in mice was detected by the means of ELISA and serum neutralization （SN）.[Result] DNA plasmid carrying P1 gene which encodes FMDV capsid protein caused specific body fluid immunoreaction in mice,and the antibody level of anti-FMDV had no difference in the mice induced by the two recombinant plasmids.[Conclusion] This study lays a foundation for evaluating the genetically modified vaccine by immunizing animals with recombinant PRV containing the FMDV P1 gene and recombinant virus.
基金supported by a grant from Universidad Anahuac México Norte(No.201425)
文摘Copolymer-1（Cop-1） is a peptide with immunomodulatory properties, approved by the Food and Drug Administration of United States in the treatment of multiple sclerosis. Cop-1 has been shown to exert neuroprotective effects and induce neurogenesis in cerebral ischemia models. Nevertheless, the mechanism involved in the neurogenic action of this compound remains unknown. The choroid plexus（CP） is a network of cells that constitute the interphase between the immune and central nervous systems, with the ability to mediate neurogenesis through the release of cytokines and growth factors. Therefore, the CP could play a role in Cop-1-induced neurogenesis. In order to determine the participation of the CP in the induction of neurogenesis after Cop-1 immunization, we evaluated the gene expression of various growth factors（brain-derived neurotrophic factor, insulin-like growth factor 1, neurotrophin-3） and cytokines（tumor necrosis factor alpha, interferon-gamma, interleukin-4（IL-4）, IL-10 and IL-17）, in the CP at 14 days after ischemia. Furthermore, we analyzed the correlation between the expression of these genes and neurogenesis. Our results showed that Cop-1 was capable of stimulating an upregulation in the expression of the genes encoding for brain-derived neurotrophic factor, insulin-like growth factor 1, neurotrophin-3 and IL-10 in the CP, which correlated with an increase in neurogenesis in the subventricular and subgranular zone. As well, we observed a downregulation of IL-17 gene expression. This study demonstrates the effect of Cop-1 on the expression of growth factors and IL-10 in the CP, in the same way, presents a possible mechanism involved in the neurogenic effect of Cop-1.
基金Supported by the Haihe Laboratory of Cell Ecosystem Innovation Fund,No.22HHXBJC00001the Key Discipline Special Project of Tianjin Municipal Health Commission,No.TJWJ2022XK016.
文摘BACKGROUND Hepatocellular carcinoma(HCC)has been a pervasive malignancy throughout the world with elevated mortality.Efficient therapeutic targets are beneficial to treat and predict the disease.Currently,the exact molecular mechanisms leading to the progression of HCC are still unclear.Research has shown that the microRNA-142-3p level decreases in HCC,whereas bioinformatics analysis of the cancer genome atlas database shows the ASH1L expression increased among liver tumor tissues.In this paper,we will explore the effects and mechanisms of microRNA-142-3p and ASH1L affect the prognosis of HCC patients and HCC cell bioactivity,and the association between them.AIM To investigate the effects and mechanisms of microRNA-142-3p and ASH1L on the HCC cell bioactivity and prognosis of HCC patients.METHODS In this study,we grouped HCC patients according to their immunohistochemistry results of ASH1L with pathological tissues,and retrospectively analyzed the prognosis of HCC patients.Furthermore,explored the roles and mechanisms of microRNA-142-3p and ASH1L by cellular and animal experiments,which involved the following experimental methods:Immunohistochemical staining,western blot,quantitative real-time-polymerase chain reaction,flow cytometric analysis,tumor xenografts in nude mice,etc.The statistical methods involved in this study contained t-test,one-way analysis of variance,theχ^(2)test,the Kaplan-Meier approach and the log-rank test.RESULTS In this study,we found that HCC patients with high expression of ASH1L possess a more recurrence rate as well as a decreased overall survival rate.ASH1L promotes the tumorigenicity of HCC and microRNA-142-3p exhibits reduced expression in HCC tissues and interacts with ASH1L through targeting the ASH1L 3′untranslated region.Furthermore,microRNA-142-3p promotes apoptosis and inhibits proliferation,invasion,and migration of HCC cell lines in vitro via ASH1L.For the exploration mechanism,we found ASH1L may promote an immunosuppressive microenvironment in HCC and ASH1L affects the expression of the cell junction protein zonula occludens-1,which is potentially relevant to the immune system.CONCLUSION Loss function of microRNA-142-3p induces cancer progression and immune evasion through upregulation of ASH1L in HCC.Both microRNA-142-3p and ASH1L can feature as new biomarker for HCC in the future.
基金supported by grants from the Dongguan Science and Technology of Social Development Program(No.20231800940192)the Talent Development Foundation of the First Dongguan Affiliated Hospital of Guangdong Medical University(No.PU2023002).
文摘Objective:Small cell lung cancer(SCLC)is commonly recognized as the most fatal lung cancer type.Despite substantial advances in immune checkpoint blockade therapies for treating solid cancers,their benefits are limited to a minority of patients with SCLC.In the present study,novel indicators for predicting the outcomes and molecular targets for SCLC treatment were elucidated.Methods:We conducted bioinformatics analysis to identify the key genes associated with tumor-infiltrating lymphocytes in SCLC.The functional role of the key gene identified in SCLC was determined both in vitro and in vivo.Results:A significant correlation was observed between patient survival and CD56dim natural killer(NK)cell proportion.Furthermore,we noted that the hub gene ubiquitin-specific protease 1(USP1)is closely correlated with both CD56dim NK cells and overall survival in SCLC.Bioinformatics analysis revealed that USP1 is upregulated in SCLC.In addition,gene set enrichment analysis revealed that USP1 overexpression hinders NK cell-mediated immune responses.By co-cultivating NK-92 cells with SCLC cells,we demonstrated that NK cell cytotoxicity against SCLC could be improved either via USP1 knock-down or pharmacological inhibition.Furthermore,using a nude-mice xenograft tumor model,we noted that USP1 inhibition effectively suppressed tumor proliferation and increased the expression of NK cell-associated markers.Conclusions:Our study findings highlight the importance of NK cells in regulating SCLC.USP1 overexpression can inhibit NK cell-mediated immunity;therefore,USP1 may serve not only as a prognostic biomarker but also as a potential molecular target of SCLC therapy.
基金Supported by the National Natural Science Foundation of China(No.81800423)the Guangdong Medical Science and Technology Research project(No.B2022102)。
文摘AIM:Regulatory T cells(Tregs)are a specialized subset of CD4^(+)T cells primarily involved in im⁃munosuppressive functions.AMP-activated protein kinase(AMPK)serves as a metabolic sensor that governs the differen⁃tiation,maturation,and immune functions of Tregs through metabolic reprogramming.However,the impact of AMPKα1(the catalytic subunit of AMPK)knockout specifically in Tregs on the host's immune microenvironment remains largely un⁃explored.METHODS:Histological changes in immune organs were assessed using HE staining.The types of immune cells and their relative population percentages in immune organs and blood were quantified through flow cytometry in both AMPKα1flox/flox(AMPKα1^(fl/fl))mice and Treg-specific AMPKα1 knockout mice(AMPKα1^(fl/fl)Foxp3^(cre)mice).RESULTS:Compared to AMPKα1^(fl/fl)mice,the percentage of eosinophils in the bone marrow of AMPKα1^(fl/fl)Foxp3^(cre)mice was significant⁃ly reduced.Additionally,while the thymus of AMPKα1^(fl/fl)Foxp3^(cre)mice exhibited normal structure,both its size and the ratio of thymus weight to body weight were significantly decreased.The knockout of AMPKα1 in Tregs led to a notable reduction in the total percentage of immature double-negative(DN)cells.Consequently,the percentage of CD4^(+)T cells derived from these DN cells also decreased,even though the percentages of DN1 and DN4 cells were higher in the thymus of AMPKα1^(fl/fl)Foxp3^(cre)mice compared to AMPKα1^(fl/fl)mice.Importantly,the proportion of Siglec-F+CD11b^(+)eosinophils in the thymus was significantly lower in AMPKα1^(fl/fl)Foxp3^(cre)mice.Knockout of AMPKα1 in Tregs resulted in a marked increase in the percentage of CD4^(+)T cells in peripheral blood,alongside a decrease in the proportion of mature CD8^(+)T cells.Similarly,the proportion of CD4^(+)T cells in the spleen of AMPKα1^(fl/fl)Foxp3^(cre)mice was elevated compared to AMPKα1^(fl/fl)mice.In contrast,the proportion of neutrophils significantly decreased,while mononuclear cell proportions increased in the spleen of AMPKα1^(fl/fl)Foxp3^(cre)mice.In lymph nodes,the medullary boundaries in AMPKα1^(fl/fl)Foxp3^(cre)mice were blurred,and the lymphoid follicles were missing,a feature not observed in AMPKα1^(fl/fl)mice.Furthermore,the knockout of AMPKα1 in Tregs reduced the CD3^(+)T cell population,particularly the CD8^(+)T cell population,in lymph nodes.Although the mature Treg cell population was significantly lower in AMPKα1^(fl/fl)Foxp3^(cre)mice,the percentage of CD4^(+)T cells was markedly in⁃creased.In contrast,there was no statistically significant difference in granulocyte populations between AMPKα1^(fl/fl)Foxp3^(cre)and AMPKα1^(fl/fl)mice.CONCLUSION:The populations of mature Tregs,CD8^(+)T cells and eosinophils in various im⁃mune organs were significantly altered in mice with Treg-specific AMPKα1 knockout,suggesting a potential remodeling of the host immune microenvironment in response to inflammatory stimuli.
文摘High expression of pescadillo ribosomal biogenesis factor 1(PES1)has been re-ported across multiple cancer types and is significantly associated with poor prog-nosis.Hu et al in their recent paper described their investigation of PES1 in gastric cancer and head and neck squamous cell carcinoma,demonstrating positive cor-relations between PES1 and programmed death-ligand 1(PD-L1)expression(51.72%for PES1 and 58.62%for PD-L1),as well as associations with lymph node metastasis and tumor invasion depth.However,the relationship between PES1 and PD-L1 remains incompletely defined.To further address this gap,we ana-lyzed The Cancer Genome Atlas gastric adenocarcinoma dataset and found a negative correlation between PES1 expression and CD8+T cell infiltration,along-side a positive correlation with PD-L1 expression.Based on prior findings,we hypothesize that PES1 may regulate PD-L1 through the phosphatidylinositol 3-kinase/protein kinase B pathway or cellular Myc-mediated mechanisms.While these pathways require experimental validation,our observations highlight PES1 as a potential regulator of immune evasion and a promising target for cancer immunotherapy.
基金supported by grants from the National Natural Science Foundation of China(32072403 and 31871945 to Fengming Song,and 32160455 to Yayun Yang)Postdoctoral Fellowship Program of CPSF(GZC20232353 to Yan Bi)the Opening Fund of Yunnan Provincial Key Laboratory of Agricultural Biotechnology to Yan Bi and Yayun Yang.
文摘Posttranslational modifications(PTMs)are essential regulatory mechanisms that play a critical role in plant immunity.Previously,we demonstrated that OsBBI1,a RING finger type E3 ligase,contributes to rice resistance against blast disease.In this study,we identified two Eps15 homology domain(EHD)-containing proteins,OsEHD1 and OsEHD2,as substrates of OsBBI1 and investigated their roles in rice immunity against Magnaporthe oryzae and Xanthomonas oryzae pv.oryzae(Xoo).We found that OsBBI1 ubiquitinated and promoted the degradation of OsEHD1 and OsEHD2 via ubiquitin/26S proteasome system(UPS)pathway.CRISPR/Cas9-mediated knockout of OsEHD1 and OsEHD2 led to enhanced immunity against M.oryzae and Xoo,improved expression of pathogen-induced immunity-associated genes,and strengthened pattern-triggered immunity(PTI),while overexpression of OsEHD1 resulted in opposite phenotypes.Additionally,OsEHD1 and OsEHD2 interacted with three SUMO proteins,OsSUMO3,OsSUMO5,or OsSUMO6,with SUMOylation sites in OsEHD1 and OsEHD2 being critical for these interactions.OsSUMO6 enhanced the stability of OsEHD1 and OsEHD2 to promote their negative immune regulation,whereas OsBBI1 reversed these negative immune functions.This study delineates a regulatory network of OsEHD1 and OsEHD2 proteins in rice immunity,highlighting the balance between OssBBI1-mediated ubiquitination and SUMOylation.
文摘An article recently published in the World Journal of Diabetes,provides valuable insights into using immune biomarkers to identify renal damage in pediatric patients with newly diagnosed type 1 diabetes(T1D).Although these findings are promising,clinical translation of these immune markers into routine diagnostics and preventive care remains challenging.In this letter,we propose building on the authors’work by exploring the integration of immune biomarkers into a more comprehensive dynamic risk stratification model for early renal injury.Com-bining immune system indicators with metabolic and genetic factors could enhance the predictive accuracy and support more personalized interventions.Longitudinal studies are needed to evaluate temporal changes in immune biomarkers and their association with long-term renal outcomes in children with T1Ds.Immunomodulatory therapies targeting early immune dysfunction can prevent or slow the progression of diabetic nephropathy.By incorporating these aspects,we hope to translate immune biomarkers from research into practical clinical tools,ultimately improving patient outcomes and reducing the burden of kidney-related complications in pediatric diabetes.
文摘This editorial delves into the potential of systemic immune indicators(SIIs)as early predictors of renal damage in children with newly diagnosed type 1 diabetes mellitus.By exploring the recent study published by Cao et al,this article aims to highlight the importance of early detection and intervention.This study compre-hensively analyzes various SIIs,examining their correlation with renal compli-cations in newly diagnosed type 1 diabetic children.The findings reveal a sig-nificant association between immune system dysregulation and the onset of renal damage,suggesting that certain immune indicators can be early markers for predicting renal complications.This editorial emphasizes the clinical implications and applications of utilizing SIIs for early detection in pediatric diabetes care.It underscores the importance of innovative diagnostic approaches and illustrates real-world applications and outcomes.Additionally,it addresses the challenges and considerations in adopting these indicators and outlines future research directions to enhance diabetes management in children.
基金Supported by the National High Level Hospital Clinical Research Funding(Multi-center Clinical Research Project of Peking University First Hospital),No.2022CR65.
文摘BACKGROUND Patients with microsatellite stable(MSS)metastatic colorectal cancer(mCRC)typically exhibit an immunosuppressive tumor microenvironment and demonstrate a low response rate to immunotherapy.Reports suggest that chemotherapy and anti-angiogenic therapy may have the potential to enhance the response to immunotherapy in these patients.This study aims to evaluate the effectiveness and safety of chemotherapy combined with bevacizumab with or without antiprogrammed death 1(PD-1)immunotherapy as the second-line regimen for MSS mCRC.AIM To evaluate the effectiveness and safety of chemotherapy combined with bevacizumab with or without anti-PD-1 immunotherapy as the second-line regimen for MSS mCRC.METHODS A retrospective analysis was conducted on patients with MSS mCRC diagnosed at Peking University First Hospital and Jilin Cancer Hospital from January 2020 to December 2024.The patients were divided into two groups:The experimental group receiving second-line chemotherapy combined with bevacizumab and anti-PD-1 immunotherapy,and the control group receiving chemotherapy combined with bevacizumab.Propensity score matching was applied to balance potential prognostic factors,including age,gender,Eastern Cooperative Oncology Group score,number of metastases,and primary tumor site.The progression-free survival,overall survival,disease control rate,objective response rate,and treatment-related adverse reactions were compared between the two groups.Kaplan-Meier analysis and log-rank test were used to compare survival outcomes.Inverse probability of treatment weighting was used for sensitivity analysis.RESULTS Propensity score matching resulted in 103 matched eligible patients.The median follow-up period was 13.9 months in the matched cohort.The objective response rate was 11.5%and 9%for the experimental and control groups,respectively(P=0.710),while the disease control rate was 76.9%and 53.2%,respectively(P=0.058).The median progression-free survival in the experimental group was 8.27 months[95%confidence interval(CI):6.7-14.7 months],significantly higher than that in the control group,which was 4.63 months(95%CI:3.9-5.67 months)(hazard ratio=0.4143,95%CI:0.2462-0.6972,P=0.00066).There was a trend towards the higher median overall survival in the experimental group compared to the control group(hazard ratio=0.4504,95%CI:0.1897-1.07,P=0.064).The incidences of adverse events were similar between the two groups.CONCLUSION Compared with the standard second-line chemotherapy combined with bevacizumab regimen,second-line therapy that combines chemotherapy with bevacizumab and anti-PD-1 immunotherapy has demonstrated promising efficacy in the treatment of MSS mCRC,while exhibiting a similar safety profile.
基金supported financially by the grants from the JBGS[2021]002 project from the Jiangsu Governmentthe National Nature Science Foundation of China(32472095)+2 种基金the National Key Research and Development Program of China(2020YFE02029002)Collaborative Innovation Center for Modern Crop Production(CIC-MCP)to Xiquan Gaosupported in part by the high-performance computing platform of Bioinformatics Center,Nanjing Agricultural University。
文摘Gibberella stalk rot(GSR)caused by Fusarium graminearum is one of the most devastating diseases of maize,seriously impacting maize yield and quality,as well as the ability to use technology of mechanical harvesting.Environmental conditions including photoperiod affect crop disease resistance.However,the mechanism underlying photoperiod-regulated maize GSR resistance remains unexplored.We found in this study that GSR resistance is regulated by the ZmPIF4.1(Phytochrome-Interacting Factor4)-ZmPTI1c(Pto-Interacting 1)-ZmMYB31 module coupled with photoperiod.The functional analysis of zmpti1c mutant indicated that ZmPTI1c negatively regulates maize GSR resistance.Short day promoted the disease progression in both zmpti1c and wild-type plants.ZmPTI1c promoter contains multiple predicted cis-acting elements for light responses.Yeast one-hybrid assay(Y1H),Electrophoretic mobility shift analysis(EMSA),and Dual-luciferase(LUC)reporter assays demonstrated that ZmPIF4.1 binds to the G-box in ZmPTI1c promoter and activates its expression.Moreover,expression levels of ZmPIF4 and ZmPTI1c were significantly higher under short day than under long day.ZmPTI1c interacted with and phosphorylated ZmMYB31.GSR resistance in zmmyb31 mutant was significantly increased than in wild type,indicating that ZmMYB31 also negatively regulated GSR resistance.Furthermore,ZmMYB31 suppressed the transcriptional activation of ZmPTI1c by ZmPIF4.1.Overall,ZmPIF4.1-ZmPTI1c-ZmMYB31negatively regulates maize immunity to GSR,which is likely modulated by photoperiod.
基金Supported by the Natural Science Foundation of Zhejiang Province,No.LY22H160005。
文摘BACKGROUND Colorectal cancer(CRC)is a leading cause of cancer-related mortality worldwide,primarily due to tumor heterogeneity and treatment resistance.The leucine-rich repeat-containing protein 19(LRRC19)has been linked to immune regulation and tumor suppression,yet its specific role in CRC remains poorly understood.AIM To investigate the tumor-suppressive role of LRRC19 in CRC,focusing on cell cycle,immune microenvironment,and chemotherapy response.METHODS Bioinformatics analyses of Gene Expression Omnibus and The Cancer Genome Atlas databases identified differentially expressed genes in CRC.LRRC19 exp-ression was validated in CRC tissues and cell lines by quantitative PCR,immuno-histochemistry,and Western blotting.Functional assays,including proliferation,soft agar colony formation,flow cytometry,and xenograft models,assessed biological effects.Mechanistic studies with dual-luciferase reporter assays,molecular docking,and drug sensitivity testing explored LRRC19’s interaction with the cyclin-dependent kinase 6(CDK6)/E2F1 axis and oxaliplatin(OXA)response.Single-cell sequencing and immune infiltration analyses assessed its impact on the immune microenvironment.RESULTS LRRC19 expression was significantly downregulated in CRC and associated with poor prognosis.Overexpression of LRRC19 inhibited CRC cell proliferation,induced G0/G1 phase arrest,and suppressed tumor growth in vivo.Mechanistically,LRRC19 suppressed CDK6 transcription by downregulating E2F1,leading to cell cycle arrest.Additionally,LRRC19 promoted immune cell infiltration,particularly B cells and CD4+T cells,while decreasing immunosuppressive cells.LRRC19 also sensitized CRC cells to OXA,enhancing chemotherapy efficacy.CONCLUSION LRRC19 suppresses CRC by targeting the CDK6/E2F1 axis,modulating the immune microenvironment,and enhancing chemotherapy sensitivity,making it a promising therapeutic target for precision medicine in CRC.
基金Supported by Jiangxi Provincial Health Commission Science and Technology Plan,No.SKJP220212334。
文摘BACKGROUND Early kidney damage is a significant complication in children with newly diagnosed type 1 diabetes mellitus(T1DM).Systemic inflammation plays a key role in the development of diabetic nephropathy.Several inflammatory markers,including the systemic immune inflammation index(SII),neutrophil-to-lymphocyte ratio(NLR),and platelet-to-lymphocyte ratio(PLR),have been proposed as potential indicators of diabetic complications.AIM To investigate the association between SII,NLR,PLR,and early kidney damage in newly diagnosed T1DM children without pre-existing albuminuria,assessing their utility as predictive biomarkers.METHODS A longitudinal cohort study was conducted on 102 children aged 3-18 years with newly diagnosed T1DM[baseline urinary albumin-to-creatinine ratio(UACR)<30 mg/g]recruited between January 2020 and June 2023.Participants were followed biannually for up to three years.Demographic,clinical,and laboratory data,including inflammatory markers(SII,NLR,PLR),were collected at baseline and follow-up.Logistic regression and receiver operating characteristic analyses were used to evaluate the predictive utility of these markers for early kidney damage,defined as UACR≥30 mg/g.RESULTS SII emerged as a significant independent predictor of early kidney damage[odds ratio=1.002,95%confidence interval(CI):1.0008-1.0033,P=0.0016],with an area under the curve of 0.719(95%CI:0.612-0.826,P<0.001).Using an SII threshold of≥624.015 achieved a sensitivity of 59.6%and specificity of 92%.Combining SII with NLR and PLR improved predictive accuracy(area under the curve=0.787),with sensitivity and specificity of 63.5%and 96%,respectively.Correlation analyses revealed significant associations between SII,metabolic markers(triglycerides,glycated hemoglobin),and UACR.CONCLUSION SII is a reliable biomarker for early kidney damage in T1DM children,offering high specificity for identifying atrisk patients.Combining SII with NLR and PLR enhances diagnostic precision,supporting its integration into clinical practice.Longitudinal monitoring of these markers may facilitate early interventions to mitigate renal complications in pediatric T1DM.
基金This work was supported by the National Natural Science Foundation of China(81672018,81561128008)the National Basic Research Program of China(973program#2014CB542502)+2 种基金the National 13th Five-Year Grand Program on Key Infectious Disease Control(2017ZX10202102)Shanghai Pujiang Program(19PJ1409100)Intramural Funding from Shanghai Public Health Clinical Center.
文摘Raising a heterologous tier 2 neutralizing antibody(nAb)response remains a daunting task for HIV vaccine development.In this study,we explored the utility of diverse HIV-1 envelope(Env)immunogens in a sequential immunization scheme as a solution to this task.This exploration stemmed from the rationale that gp145,a membrane-bound truncation form of HIV Env,may facilitate the focusing of induced antibody response on neutralizing epitopes when sequentially combined with the soluble gp140 form as immunogens in a prime-boost mode.We first showed that gp140 DNA prime-gp145 Tiantan vaccinia(TV)boost likely represents a general format for inducing potent nAb response in mice.However,when examined in rhesus macaque,this modality showed little effectiveness.To improve the efficacy,we extended the original modality by adding a strong protein boost,namely native-like SOSIP.664 trimer displayed on ferritin-based nanoparticle(NP),which was generated by a newly developed click approach.The resulting three-immunization regimen succeeded in eliciting tier-2 nAb response with substantial breadth when implemented in rhesus macaque over a short 8-week schedule.Importantly,the elicited nAb response was able to effectively contain viremia upon a heterologous SHIV challenge.Collectively,our studies highlighted that diversification of Env immunogens,in both types and formulations,under the framework of a sequential immunization scheme might open new opportunity toward HIV vaccine development.
文摘Objective: to observe the practical effect of predictive nursing in the 1-3 year-old childrens immunization nursing. Methods: a total of 114 children aged 1-3 years were enrolled in the study and divided into group ①: Control group and group ②: Observation group. Routine nursing and predictive nursing were administered respectively. Results: the data in Table 1-5 all indicate that the data obtained from the nursing methods in the observation group are more satisfactory (P < 0.05). Conclusion: predictive nursing is helpful to improve the coordination degree and comfort level of immunization for children aged 1-3 years old, reduce the incidence of stress reaction, and improve the cognitive level and satisfaction of family members.
文摘After that the era of chemotherapy in the treatment of solid tumors have been overcome by the "translational era", with the innovation introduced by targeted therapies, medical oncology is currently looking at the dawn of a new "immunotherapy era" with the advent of immune checkpoint inhibitors(CKI) antibodies.The onset of PD-1/PD-L1 targeted therapy has demonstrated the importance of this axis in the immune escape across almost all human cancers.The new CKI allowed to significantly prolong survival and to generate durable response, demonstrating remarkable efficacy in a wide range of cancer types.The aim of this article is to review the most up to date literature about the clinical effectiveness of CKI antibodies targeting PD-1/PD-L1 axis for the treatment of advanced solid tumors and to explore transversal challenges in the immune checkpoint blockade.
