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摘要： We introduce HLAIIPred, a deep learning model to predict peptides presented by class II human leukocyte antigens (HLAII) on the surface of antigen presenting cells. HLAIIPred is trained using a Transformer-based neural network and a dataset comprising of HLAII-presented peptides identified by mass spectrometry. In addition to predicting peptide presentation, the model can also provide important insights into peptide-HLAII interactions by identifying core peptide residues that form such interactions. We evaluate the performance of HLAIIPred on three different tasks, peptide presentation in monoallelic samples, immunogenicity prediction of therapeutic antibodies, and neoantigen prioritization for cancer immunotherapy. Additionally, we created a dataset of biotherapeutics HLAII peptides presented by human dendritic cells. This data is used to develop screening strategies to predict the unwanted immunogenic segments of therapeutic antibodies by HLAII presentation models. HLAIIPred demonstrates superior or equivalent performance when compared to the latest models across all evaluated benchmark datasets. We achieve a 16% increase in prediction of presented peptides compared to the second-best model on a set of unseen peptides presented by less frequent alleles. The model improves clinical immunogenicity prediction, identifies epitopes in therapeutic antibodies and prioritize neoantigens with high accuracy.

关键词： tetrahedral framework nucleic acids   microneedles   aptamer   anti-inflammation   wound healing  

摘要： Excessive secretion of Interleukin-6 (IL-6) is a critical barrier to the healing of inflammatory wounds. Previous attempts aimed to overcome this challenge by using antibodies to neutralize IL-6. However, the immunogenicity of an antibody may trigger antidrug antibody formation, resulting in reduced therapeutic efficacy and possible adverse reactions. In contrast, aptamers (Ap) exhibit better target specificity and anti-inflammatory performance, and have wide applications. Recently, tetrahedral framework nucleic acids (tFNAs) have emerged as promising drug delivery platforms that provide nanomedicines with enhanced stability and tissue penetration. In this work, we first modified IL-6 aptamers onto tFNAs (tFNAs Ap), and then the tFNAs Ap was embedded into the hydrogel microneedle to form a skin dressing (tFNAs Ap MN). These hydrogel microneedles present excellent mechanical strength, swelling capacity, and good biocompatibility, which show significant anti-inflammatory and wound-healing outcomes by inhibiting the regulation of inflammatory factors IL-6 and TNF-alpha and promoting keratinocyte proliferation and migration. The results of animal experiments indicate that such microneedles suppress the excessive expression of IL-6 efficiently and significantly reduce the time required for healing full-thickness skin wound models with inflammation. Overall, the prepared the DNA materials functionalized microneedles may have potential clinical value in inflammation treatment and wound healing.

关键词： Flexible Zn-air battery   Multi-functional gel electrolyte   Ionic liquid   Wide temperature range  

摘要： Flexible zinc-air batteries (FZABs) employing gel electrolytes hold considerable promise for next-generation wearable electronics, yet their practical deployment is hindered by two critical limitations: inadequate water retention capacity of conventional hydrogels under extreme thermal conditions and irreversible zinc anode degradation through corrosion and passivation. To overcome these challenges, we engineer a multifunctional polyacrylamide imidazolium bromide ionic liquid (PAM-BBr) hydrogel electrolyte through strategic incorporation of 1-butyl-3-methylimidazolium bromide (BBr) ionic liquid into a polyacrylamide PAM. The BBr integration confers dual functionality: First, the hygroscopic ionic liquid establishes a hydrogen-bonded network with water molecules and PAM chains, achieving exceptional hydration stability (81.2 % water retention after 50 h at 25 degrees C/ 60 % RH) and enhanced ionic conductivity (340 mS cm- 1). Second, the hydrogen bonds among cations in ionic liquid BBr and the PAM network further weaken the anion-cation interactions, thus allowing the abundant Br- to stabilize the zinc and significantly reducing ZnO growth to avoid passivation and corrosion of the zinc anode surface. Moreover, the FZABs employing the PAM-BBr hydrogel electrolyte present a 433 cycles cycle life, 101.2 mW cm- 2 power density, and 727.8 mAh g- 1 discharge capacity. Even at extreme temperatures (-20 degrees C to 80 degrees C) PAM-BBr based FZABs always maintain excellent electrochemical stability and practicality.

关键词： clear cell renal cell carcinoma (ccRCC)   drugs   nuclear factor kappa B (NF-κB)   Ras homolog family member J (RhoJ)   tumor necrosis factor (TNF)  

摘要： Background: Clear cell renal cell carcinoma (ccRCC) represents the predominant form of kidney cancer. The Ras homology (Rho) GTPases family plays essential roles in several tumors. However, few studies have reported the function and clinical value of the Rho GTPases family in ccRCC. Our study aimed to systematically investigate the expression profiles, functional roles, and clinical significance of Rho GTPases in ccRCC, with the goal of identifying potential biomarkers and novel therapeutic targets to improve the treatment outcomes and survival rates of this aggressive kidney cancer. Methods: The expression level of Ras homolog family member J (RhoJ) was detected in ccRCC cells and tissues using quantitative polymerase chain reaction (qPCR), western blotting, and immunohistochemistry (IHC). The biological functions of RhoJ were evaluated via in vitro and in vivo assays. RNA sequencing was used to investigate the underlying mechanisms. Potential RhoJ inhibitors were identified using virtual screening in a Food and Drug Administration (FDA)-approved drugs repository. Results: Our study identified RhoJ as the only Ras-homologous guanosine triphosphate (GTP)-binding protein (Rho GTPase) associated with poor prognosis in ccRCC patients. Using ccRCC cells and tumor tissues, we found that RhoJ was significantly highly expressed in ccRCC. Moreover, RhoJ apparently enhanced ccRCC cell proliferation, migration, and invasion. Further, upregulated RhoJ could accelerate cell cycle progression, inhibit apoptosis, and enhance epithelial-mesenchymal transition (EMT). Through orthotopic tumor models, we found that knocking down RhoJ inhibited tumor growth. Mechanically, RhoJ influenced ccRCC progression through the tumor necrosis factor-alpha/nuclear factor kappa B (TNF-α/NFκB) axis. Blocking this axis could partially rescue malignant phenotypes caused by RhoJ. Finally, since there are no available drugs targeting RhoJ, the virtual screening was used to identify potential RhoJ inhib

关键词： chimeric antigen receptor   T-cell therapy   IL-7   IL-7R   solid tumor   pancreatic cancer   PSCA   MUC 1  

摘要： Introduction Clinical studies of T cells engineered with chimeric antigen receptor (CAR) targeting CD19 in B-cell malignancies have demonstrated that relapse due to target antigen (CD19) loss or limited CAR T cell persistence is a common occurrence. The possibility of such events is greater in solid tumors, which typically display more heterogeneous antigen expression patterns and are known to directly suppress effector cell proliferation and persistence. T cell engineering strategies to overcome these barriers are being explored. However, strategies to simultaneously address both antigen heterogeneity and T cell longevity, while localizing anti-tumor effects at disease sites, remain *** In this study we explore a dual antigen targeting strategy by directing independent CARs against the solid tumor targets PSCA and MUC1. To enhance functional persistence in a tumor-localized manner, we expressed the transgenic IL-7 cytokine and receptor (IL-7R alpha) in respective CAR *** This binary strategy, which incorporates dual antigen targeting with transgenic cytokine support, resulted in enhanced potency, T cell expansion, and durable antitumor effects in a pancreatic tumor model compared to single antigen targeting or dual antigen targeting in absence of the transgenic cytokine *** The transgenic IL-7 armed binary CAR T cell approach could improve the efficacy of CAR-based therapies for solid tumors.

关键词： HLA-DPB1*1763:01   next generation sequencing   novel allele  

摘要： HLA-DPB1*1763:01 differs from DPB1*02:01:64 by a single nucleotide substitution in codon-14 of exon 1.

摘要： Toxoplasmosis is a serious disease that affects all age groups and may even threaten the lives of some people. Fifty serum samples were taken from patients has Toxoplasmosis who attended Rizgary Teaching Hospital in Erbil City, and 38 serum samples were taken from healthy individuals as a control group, with ages between 18-60 years old, from the period January 2024 to March 2025. The purpose of the research is to determine the gene sequence of TNFα and IFNϒ associated with Toxoplasmosis. The results showed that the infection prevalence rate in the age group (18-27) years was 17 (56.7%) in comparison to healthy individuals 13 (43.3%), and in the age group (28-37) years was 20 (62.5%) compared to healthy control 12 (37.5%), and in the age group (38-47) years was 10 (76.9%) in comparison to the controls 3 (23.1%), while in the age group (≥47) years was 3 (23.1%) compared to the controls 10 (76.9%) with significant variations (P=0.03). The prevalence rate of Toxoplasmosis in males was 17 (48.6%) in comparison to the healthy controls 18 (51.4%), while in females it was 33 (62.3%) compared to the healthy individuals 18 (51.4%), with no significant variations (P=0.29). The mean level of Toxoplasmosis IgM was (2.28±0.18) when compared to healthy group (0.12±0.03), and the mean level of Toxoplasmosis IgG was (2.12±0.18) when compared to healthy control (0.09±0.02). The mean level of TNF-α (pg/ml) was (10.34±0.39) in comparison to the control group (4.89±0.31), and the mean level of INF-γ (pg/ml) was (10.72±0.36) in comparison to the controls (4.80±0.29) with highly significant variations (P=0.001).  Moreover, direct correlation between Toxoplasma IgM with IgG was (r=.568), with TNF-α was (r=.607), with INF-γ was (r=.528), with highly significant variations P= (.000, .000, .000) respectively. Also, there were direct correlations between Toxoplasma IgG with IgM (r=1), with TNF-α (r=.550), with INF-γ (r=.576), with highly significant variations P= (.000, .000, .000) respective

关键词： HLA-DQB1*06:02:01:41 novel allele   Illumina   next-generation sequencing  

摘要： The HLA-DQB1*06:02:01:41 allele differs from HLA-DQB1*06:02:01:01 by a single nucleotide substitution in intron 2.

关键词： MPP   hs-CRP   Saa   IL-6   PCT   预后   MPP   hs-CRP   SAA   IL-6   PCT   Prognosis  

摘要： 目的：本研究聚焦于血清超敏C反应蛋白(hs-CRP)、淀粉样蛋白A (SAA)、白介素-6 (IL-6)及降钙素原(PCT)这四种生物标志物，旨在探讨它们与儿童肺炎支原体肺炎治疗效果及预后之间的关联性，以期为临床提供更为精准的评估工具。方法：收集甘肃徽县妇幼保健院2023年5月~2025年1月120例儿童肺炎支原体肺炎患儿作为研究对象，根据治疗反应分为有效组(n = 90)和无效组(n = 30)。在治疗前、治疗3天及7天三个时间点分别检测了两组患儿血清中的hs-CRP、SAA、IL-6及PCT水平，并深入分析了这些生物标志物的动态变化及其与患儿预后之间的相关性。结果：无效组患儿在治疗前的hs-CRP、SAA、IL-6及PCT水平均显著高于有效组，且这些生物标志物的高水平与患儿的不良预后密切相关。结论：血清hs-CRP、SAA、IL-6及PCT水平与儿童MPP治疗反应密切相关。联合检测这些生物标志物能够更全面地反映患儿的炎症状态和疾病进展。

关键词： extracellular vesicles   visceral leishmaniasis   immunosuppression   TNF antagonist   antimonials   quantitative proteomics   LFQ proteomics analyses   biomarkers  

摘要： Introduction Visceral leishmaniasis (VL) occurs more frequently in immunosuppressed individuals, especially those undergoing immunosuppressive drug therapy for an autoimmune disease. In those receiving TNF antagonist therapy (anti-TNF), the course of VL is more severe and the response to traditional leishmanicidal treatments, such as antimonials (Sb), is often reduced. This effect of anti-TNF treatment is observed in our immunosuppressed-mouse model of VL. In this model, we compared anti-TNF immunosuppression with no immunosuppression before and after VL treatment with *** Serum-derived extracellular vesicles (EVs) were analyzed through label-free quantitative proteomics to identify proteins involved in both VL severity and the impact of anti-TNF immunosuppression on treatment *** In total, 223 dysregulated proteins were found in the pre-treatment groups, the majority of which, such as vitronectin, haemopexin or caveolin-1, were downregulated in the anti-TNF samples. In contrast, 173 proteins were identified in the Sb-treatment groups, most of which were found enriched in the anti-TNF plus treatment samples (anti-TNF+Sb) including fibronectin, transferrin, vitronectin and dipeptidyl peptidase-4. These differentially-expressed proteins were associated with pathways related to the immune system, liver regeneration, and ion *** Our findings have useful implications for the clinical management of VL patients under anti-TNF immunosuppression.