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关键词： Colon cancer   TNF-related apoptosis-inducing ligand (TRAIL)   Vascular endothelial growth factor (VEGF)   Mendelian randomization (MR)   Genome-wide association studies (GWAS)  

摘要： BackgroundObservational studies have shown that TNF-related apoptosis-inducing ligand (TRAIL) levels and vascular endothelial growth factor (VEGF) levels are associated with colon cancer risk, and TRAIL antagonizes VEGF-induced tumor angiogenesis. We aim to determine whether there is a causal relationship between TRAIL/VEGF levels and colon cancer by Mendelian randomization ***-wide association studies (GWAS) of 21,758 individuals of European ancestry were conducted to identify single nucleotide polymorphisms (SNPs) associated with TRAIL/VEGF. MR-Egger regression, heterogeneity test, pleiotropy test and leave-one-out sensitivity tests were used for sensitivity analysis, in addition to inverse variance weighting (IVW) as the main Mendelian-randomization (MR) analysis *** MR analysis using IVW indicated an inverse association between genetically predicted TRAIL levels and colon cancer risk (OR = 0.805, 95%CI = 0.681-0.953, P = 0.011), while VEGF levels showed a positive association (OR = 1.337, 95%CI = 1.163-1.536, P < 0.001). In addition, the MR Steiger test showed that the effect of TRAIL/VEGF levels on colon cancer were correct causality (P < 0.001). In multivariate MR analysis, TRAIL levels had an independent causal effect on colon cancer risk after controlling for VEGF levels (OR = 0.802, P = 0.002);likewise, the causal effect of VEGF levels on colon cancer risk remained after controlling for TRAIL levels (OR = 1.328, P < 0.001).ConclusionsThere was a inverse association between genetic variants in TRAIL levels and colon cancer risk, but a positive association between genetic variants in VEGF levels and colon cancer risk. Further research is needed to explore the mechanisms behind this putative causal relationship.

关键词： GC   IL-36RDEGs   prognosis model   risk score   prediction  

摘要： Introduction Gastric cancer (GC) is one of the most frequently encountered malignant tumors in the clinic. Because effective early screening techniques are lacking, most patients have advanced disease at first diagnosis. The interleukin (IL)-36 family plays a vital role in regulating the immune system, inflammatory responses, and the occurrence and development of cancer. Hence, this study explored the potential role of IL-36 related genes (IL-36RGs) in GC and built a prognostic risk assessment model for GC based on IL-36RGs, which can help evaluate treatment and *** First, relevant datasets were downloaded from public databases. After processing the datasets to remove batch effects, perform differential analysis, and take intersections, IL-36-related differentially expressed genes (IL-36RDEGs) were screened. A prognostic risk model containing nine model genes was constructed based on univariate Cox and least absolute shrinkage and selection operator (LASSO) regression methods. Then, to investigate the potential biological activities of the model genes in GC, we conducted enrichment, PPI interaction network, and immune infiltration analyses. Immunohistochemical staining was conducted to validate the expression of IL-36A in *** The prognostic risk model analysis revealed that mortality events in the high-risk group were substantially elevated compared to those in the low-risk group. The model demonstrated excellent predictive capability at 1, 2, and 3 years and showed the best clinical predictive performance at 3 years. Bioinformatics analysis of the model genes indicate that they primarily participate in mechanisms that promote the synthesis and secretion of cytokines in GC. And hub genes may be strongly correlated with host immune response mechanisms. According to the immunohistochemical staining results, IL-36A expression was higher in the STAD group than in the control *** The results of the above analysis suggest that IL-36RDEGs

关键词： NF-κB   TAB1   TAK1   TNFα   interleukin-1 (IL-1)  

关键词： HLA   KIR   LILR   LIBAG   HIV   PyPop   MICA   the society for immune polymorphism  

摘要： This special issue features three papers exploring HLA associations with distinct diseases-HIV 1 , dengue 2 , and type 1 diabetes 3 . Using data from the International Collaboration for the Genomics of HIV, Rahmouni et al. 1 revisited the association of SNPs (single nucleotide polymorphisms) and HLA alleles with HIV-1 elite control. This study reported that HLA-B*57:01, which is part of a very large HLA haplotype block, is significantly associated with HIV-1 elite control in European and African American cohorts. The authors suggested that, in addition to the conventional antigen-presenting role of HLA molecules, HLA class I may provide an alternative molecular mechanism for HIV-1 elite control that involves changes in immune gene expression that could be mediated by transcription factors encoded in this haploblock. Meanwhile, considering the dynamic climate change-associated expansion of vector-borne diseases, Ghosh 2 et al examined the association of HLA alleles with different stages of dengue across worldwide populations. This review 2 highlighted the complex, often contrasting, and varied nature of HLA-dengue associations worldwide, eliciting the urgent need for further studies among understudied populations to inform public health strategies and combat this emergent threat. Additionally, research 4 by Aharon et al. into macrophage migration inhibitory factor (MIF) functional polymorphism revealed associations with the progression of acute graftversus-host disease (GVHD) and steroid refractoriness in patients who underwent allogeneic hematopoietic stem cell transplantation (HSCT).The LILR genes encode for both inhibitory and activating receptors on myeloid and lymphoid cells and are a highly understudied component of the immune system. Hirayasu et al. 5 reported a novel hybrid gene between LILRB5 and LILRB3, namely LILRB5-3. The hybrid gene was detected using the JoGo-LILR 6 tool from a combination of short-read whole genome sequencing (srWGS) and a dataset gene

关键词： three-layered electroluminescent device   silver nanowire   ionic liquid   superwettability-inducedtransfer   flexible electronics  

摘要： The emergence of flexible electroluminescent (EL) devices has demonstrated significant potential in wearable technology, lighting, and biointegrated electronics, driving the need for efficient and cost-effective fabrication methods. However, the conventional multistep processes for creating five-layer flexible EL devices are often laborious and costly. In this work, we address these challenges by introducing a one-step transfer method for fabricating a three-layered flexible EL device. This innovative approach harnesses superwettability-induced transfer of silver nanowires (AgNWs), ionic liquid (i.e., 1-ethyl-3-methylimidazolium(bis-trifluoromethane sulfonyl)imide, [EMIm]NTf2), and polydimethylsiloxane (PDMS) onto the luminescent layer. The ionic liquid, [EMIm]NTf2, serves to locally organize the AgNWs, while the PDMS acts as a protective layer. This method not only streamlines the fabrication process but also enhances material utilization and enables the creation of continuous luminous patterns, thereby presenting a highly promising solution for rapid prototyping and customization in flexible EL device manufacturing.

关键词： CAR-T cell therapy   MT: Regular Issue   immunosuppressive macrophage   interleukin-1 receptor antagonist   mantle cell lymphoma   tumor microenvironment  

摘要： CD19-targeted chimeric antigen receptor T cells (CAR-T19) have shown remarkable success in B cell malignancies, but most patients relapse within 1-2 years. Here, we identified interleukin-1 (IL-1) receptor antagonist (IL-1ra) as a mediator of M2-like macrophage-derived inhibition of CAR-T19 in mantle cell lymphoma (MCL), as well as a potential target to enhance CAR-T19 efficacy. In preclinical models that recapitulated interactions between tumor, macrophages, and T cells, we demonstrated that M2-derived IL-1ra impairs IL-1 signaling and functions of CAR-T19. These findings were validated using clinical samples from the ZUMA-2 trial that led to the FDA approval of CAR-T19 in MCL. Single-cell RNA sequencing of CAR-T19 products and baseline myeloid cells indicated downregulated IL-113 production, enriched immunosuppressive phenotypes, and IL-1ra upregulation in the non-responder monocytes, as well as impaired IL-113 signaling and T cell functions in the non-responder CAR-T19 products. Furthermore, our preclinical studies of IL-113 showed enhanced CAR-T antitumor activities. Collectively, these data present a potential role for IL-1 signaling and IL-1ra in CAR-T19 failure.

关键词： 曼氏血吸虫   循环阴极抗原   核酸适配体   指数富集配基的系统进化技术   重组原核蛋白  

摘要： 目的 筛选曼氏血吸虫循环阴极抗原（circulating cathodic antigen,CCA）特异性核酸适配体，并进行鉴定。方法 构建曼氏血吸虫循环阴极抗原的重组原核表达载体（pET-28a-CCA），诱导pET-28a-CCA蛋白表达并通过Ni-NTA柱纯化。十二烷基硫酸钠-聚丙烯酰胺凝胶电泳（SDS-PAGE）分析pET-28a-CCA蛋白的表达情况。以pET-28a-CCA蛋白为靶标，进行指数富集配基的系统进化技术（systematic evolution of ligands by exponential enrichment,SELEX）筛选，利用荧光定量PCR监测分析每一轮文库富集情况。经过多轮加压筛选，获得的产物通过高通量测序分析、生物信息学分析，并采用微量热泳动技术表征测定候选核酸适配体与pET-28aCCA蛋白的结合亲和力，进行分子对接。结果 双酶切鉴定和测序结果显示，pET-28a-CCA重组质粒插入约为1 044 bp的CCA基因片段。SDS-PAGE电泳结果显示，pET-28a-CCA蛋白的相对分子质量（Mr）约为43 600;SELEX筛选结果显示，第13轮筛选文库达到最佳富集。根据测序结果筛选出的9条候选核酸适配体序列，经过MST检测，有7条候选核酸适配体与pET-28a-CCA蛋白有结合亲和力。TQ-apt1的吉布斯自由能最低（ΔG=-13.09 kcal/mol）,GC含量最高（59.20%）、熔解温度最高（102.3℃）以及G-四链体得分最高（15分），TQ-apt1与pET-28a-CCA蛋白的亲和力最高，解离常数为2.1 nmol/L。结论 成功获得了pET-28a-CCA蛋白的核酸适配体。

关键词： Fcγ受体   心血管疾病   免疫球蛋白  

摘要： Fcγ受体（Fragment crystallizable γ receptors， FcγRs）是免疫球蛋白G（immunoglobulin G， IgG）的受体，大部分表达于免疫细胞的表面，通过与IgG的Fc段结合形成免疫复合物发挥相关的生物学功能。FcγRs分为激活型和抑制型两类，在不同的细胞中发挥相似或相反的功能。在心血管疾病研究领域，越来越多的证据表明，免疫细胞及固有细胞中表达的FcγRs通过激活细胞内信号传导通路，进而调控多种细胞因子的分泌，参与心肌梗死、动脉粥样硬化、高血压等心血管疾病的发生发展。本文对FcγRs的分类、功能及其在心血管疾病中的研究进展进行综述， 以期为心血管疾病的防治提供新的思路和方法。

关键词： CD137L   MT: Regular Issue   Vd2 cells   alendronate   cancer   cell therapy   cytotoxicity   expansion   gamma delta T cells   oncology  

摘要： The increasing success of allogenic V62 T cell immunotherapy for the treatment of cancer has been demonstrated in recent studies. V62 T cells recognize phosphoantigens, intermediates of the mevalonate pathway, through butyrophilin molecules, and they are not major histocompatibility complex (MHC) restricted. Allogeneic transfer of in vitro expanded V62 T cells has shown more promising results than autologous strategies, although the clinical benefit remains limited. One of the issues leading to less-than-optimal responses relates to the polyclonal expansion of V62 T cell subsets with variable cytotoxic capacity. Previous work developed protocols to expand V62 T cells, although to our knowledge, ours is the first comprehensive study that has produced a simple, antigen-presenting feeder-free culture that produced an average expansion of 3,000-fold and more than 95% pure V62 T cells avoiding additional isolation steps. Here, we show the in vitro expansion of cytotoxic V62 T cells expressing CD16 and NKG2A enriched in granzyme B that displayed enhanced antitumor activity of up to 40% against leukemia and ovarian, breast, and lung cancer cells. Our work warrants clinical testing to evaluate the therapeutic potential of these highly cytotoxic cells, paving the way for improved efficacy of personalized cell-based immunotherapies.

关键词： knockout   type 1 interferon   IFN beta   ocular infection   eye disease   virus replication   latency   reactivation   CD8   PD-1   exhaustion  

摘要： Type I interferons (IFNs) generate strong antiviral immunity following viral infection in mice and humans. These type I IFNs are encoded by at least 14 IFN alpha genes and a single IFN beta gene. We showed that the absence of one of the IFN alpha genes (IFN alpha 2A-/-) affected latency levels in herpes simplex virus type 1 (HSV-1) ocularly infected mice but not in infected control mice, and the absence of IFN alpha 2A did not affect viral reactivation in ocularly infected mice. Since the role of IFN beta in HSV-1 latency reactivation and the potential effect of latency-associated transcript (LAT) on IFN beta activity is not known, we ocularly infected IFN beta-/- mice with different doses of LAT-plus [LAT(+)] and LAT-minus [LAT(-)] viruses. Wild-type (WT) control mice and IFN beta-/- mice were infected similarly. Virus titers in the eye, viral and cellular transcripts in the eye and trigeminal ganglia (TG) of infected mice on days 3 and 5 post-infection, eye disease, survival, latency-reactivation levels, and T cell exhaustion were measured in latently infected mice. Virus replication and viral and cellular transcripts in the eye of infected IFN beta-/- mice were similar to those in WT mice, while eye disease and survival in IFN beta-/- mice differed significantly from WT mice. WT mice infected with LAT(-) virus showed reduced latency, slower reactivation, and less T cell exhaustion than mice infected with LAT(+) virus. However, using different doses of each virus, latency levels, time of reactivation, and T cell exhaustion were similar between LAT(+) and LAT(-) viruses. These results suggest that the absence of IFN beta expression compensates for the function of LAT with regard to levels of latency, T cell exhaustion, and reactivation but does not affect viral and cellular transcripts during primary *** beta (IFN beta) is a type I interferon that plays an important role in controlling primary herpes simplex virus type 1 (HSV-1) infection