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关键词： 光催化降解   离子液体硅铋光催化剂   氯吡苯脲   综合实验设计  

摘要： 围绕高效催化降解氯吡苯脲污染物设计了由硅烷化离子液体制备的离子液体硅铋光催化剂（BiSiOClI-IL），并开发了基于离子液体硅铋光催化剂吸附降解水中氯吡苯脲的综合实验，主要包括以硅烷化离子液体合成离子液体硅铋光催化剂、光催化剂的表征及其催化性能研究。通过优化条件，确定最优制备参数为反应温度80℃、碱式硝酸铋：硅烷化离子液体：碘化钾3∶3∶1（n/n/n）、pH 9。利用XRD、SEM、TEM、N2物理吸附等手段对一系列条件合成的BiSiOClI-IL进行表征，比表面积可达21.2 m2·g–1，在最优条件下去除率可达99%，进一步通过吸附动力学实验深入探究BiSiOClI-IL对吸附机理。该综合实验涉及物理化学、材料化学、仪器分析等课程知识，有助于锻炼学生的实验操作能力、培养学生创造性思维，同时为有机氯污染物去除方面提供一定的参考价值。

关键词： betadanovirus   IFN I-antagonism   luciferase reporter system   mx promoter  

摘要： Mx genes display strong and quick induction in response to viral infections, which varies according to the viral virulence;furthermore, mx transcription is blocked by several viruses as part of their immune evasion strategies. Therefore, the level and time course of mx induction reflect virus-host interplay. This idea prompted the development of in vitro experimental systems consisting of cells stably expressing luciferase under the control of fish mx promoters. In this study, two RTG-2 cell lines, expressing luciferase under the control of Senegalese sole (Solea senegalensis) mx (ssmx) promoter, and under the control of gilthead sea bream (Sparus aurata) mx2 (saumx2) promoter, have been applied to study betanodavirus-host interaction. Both systems were inoculated with nervous necrosis virus, NNV, isolates belonging to different genotypes. The combination of both systems has been proved to be useful to detect all of them, although each isolate triggered a characteristic profile in each system. In addition, a protocol to estimate the titre of the RGNNV isolate in sea bass (Dicentrarchus labrax) brain has been established, and a clear dose-dependent antagonistic effect of this NNV isolate was recorded. Thus, both cell lines are useful tools to study betanodavirus-host interaction and, therefore, contribute to developing measures to fight viral infections in aquaculture.

关键词： CRISPR screening   cytokine receptors   cytokine signaling   interleukin-15   natural killer cells   post-translational modifications  

摘要： Interleukin-15 receptor (IL-15R) agonists induce anti-tumor immunity in pre-clinical models. However, dose-limiting toxicity has hampered their clinical development. We performed genome-wide CRISPR screens to reveal the complete IL-15R signaling mechanism in natural killer (NK) cells and discovered that ubiquitin-dependent IL-15R degradation is the dominant mechanism restraining IL-15R signaling. Key hits included the NEDD8 E2-conjugating enzyme UBE2F, the ubiquitin E3-ligase ARIH2, and Cullin-5 RING E3 ligase (CRL5) members. We found that UBE2F was required for neddylation and activation of CUL5, whereas ARIH2 contributed to CRL5-mediated IL-15RB degradation. Ablation of ARIH2 or UBE2F increased IL-15RB surface expression and enhanced signaling, resulting in proinflammatory cytokine production and augmented natural and CAR-mediated cytotoxicity. In mice lacking Arih2 , Rnf7 , or Ube2f , we observed that the IL-15R hyperresponsive NK cells exhibited superior in vivo anti-tumor immunity against primary and disseminated metastatic tumors. Thus, we have identified the enzymes UBE2F and ARIH2 as tractable immunotherapy drug targets.

关键词： 赤羽病毒   Gc蛋白   原核表达   单克隆抗体  

摘要： 为了进一步研究赤羽病毒的感染机制和Gc蛋白的功能，利用原核表达系统成功表达赤羽病毒的Gc蛋白。用纯化后的重组蛋白免疫BALB/c小鼠，经过4次免疫、间接ELISA筛选和细胞融合，获得1株能够分泌抗Gc蛋白单克隆抗体的细胞株，命名为2D3，其抗体亚型为IgG1/Kappa型。IFA、Western-blot和间接ELISA结果表明，单克隆抗体2D3具有高特异性和亲和性，能特异性识别赤羽病毒Gc蛋白。本研究成功制备了抗赤羽病毒Gc蛋白的单克隆抗体2D3，为赤羽病毒检测方法的建立及病毒致病机制研究提供了可靠的工具。

关键词： Disease Modification   Early Intervention   IL-17 Inhibitor   Ixekizumab   Psoriasis   Secukinumab  

摘要： Background Although IL-17 inhibitors like Secukinumab and Ixekizumab have shown significant efficacy in psoriasis, the impact of early intervention with biologics to modify the disease course and achieve long-term remission remains unclear. Objectives To examine the potential of early intervention with IL-17 inhibitors for disease modification in psoriasis. Methods We conducted a multicenter retrospective cohort study on moderate-to-severe plaque psoriasis patients who received at least 4 weeks of treatment with Secukinumab or Ixekizumab between April 2019 and April 2023, taking the relapse rate one year after cessation of treatment as the primary endpoint. Results Among 400 patients who discontinued treatment after achieving PASI90, the median relapse time was 3.29 months(approximately 14 weeks). Of 141 patients who discontinued treatment after achieving PASI90 for over a year, 24 (88.89%) in the ultra-short disease duration(USDD, psoriasis duration ≤ 1 year) group and 33 (82.5%) in the short disease duration(SDD, psoriasis duration ≤ 2 year) group achieved one year of drug-free remission. Limitations The potential impact of early intervention on comorbidity development was not addressed in this study. Conclusion Early intervention with IL-17 inhibitors leads to faster responses and may promote disease modification in psoriasis.

关键词： Shexiang Tongxin Dropping Pills   ischemia reperfusion injury   oxidative stress   inflammatory factors   cardiac function  

摘要： Introduction Shexiang Tongxin Dropping Pills (STDP), a traditional Chinese medicine (TCM), is clinically used for cardiovascular diseases like myocardial ischemia. Myocardial ischemia-reperfusion injury (MIRI), worsened by oxidative stress and inflammation, remains a significant problem, and the mechanisms underlying STDP's cardioprotection are incompletely understood. This study aimed to investigate STDP's effects on the SOD/TNF-alpha/IL-6 pathway and its impact on inflammation and oxidative stress in *** A mouse model of MIRI was employed to evaluate the cardioprotective effects and mechanisms of STDP in vivo. Pretreatment with STDP was administered prior to MIRI induction. Assessments included serum SOD activity, cardiac tissue ROS levels, cardiomyocyte apoptosis rates (TUNEL assay), mRNA and protein expression of IL-1 beta, TNF-alpha, and IL-6 (qPCR, Western blot), histopathological evaluation of myocardial tissue morphology and inflammatory infiltration (H&E staining), myocardial infarction size (TTC staining), and cardiac function parameters (contractility, diastolic function).Results STDP pretreatment significantly enhanced serum SOD activity and reduced cardiac ROS levels and cardiomyocyte apoptosis. It effectively downregulated mRNA and protein expression of IL-1 beta, TNF-alpha, and IL-6. Histopathology revealed reduced inflammatory cell infiltration and more intact cardiomyocyte morphology in STDP-treated groups. TTC staining confirmed a reduction in myocardial infarction size. Cardiac function assessments showed STDP improved both contractility and diastolic function post-MIRI and reduced arrhythmia *** STDP ameliorates MIRI in mice by inhibiting inflammatory responses and oxidative stress, primarily through modulation of the SOD/TNF-alpha/IL-6 pathway. Its cardioprotective effects include reducing apoptosis, inflammation, ROS, infarction size, and arrhythmias, while improving cardiac function and tissue repair. These findings e

关键词： Cytokines   IL-18   Gene polymorphism   Infectious diseases   Precision medicine  

摘要： Purpose of reviewCytokines play a substantial role in the pathophysiology of infectious diseases. Consequently, genetic polymorphisms in cytokine genes can have profound effects on the susceptibility to or protection from infections and also influence clinical manifestations, disease severity, as well as outcome. This narrative review summarizes the recent findings on the role of genetic polymorphisms of IL-18, a recently discovered cytokine, on certain infectious diseases of public health *** findings of the review suggest that IL-18 polymorphisms can have a significant impact on multiple infectious diseases, including malaria, leishmaniasis, HIV/AIDS, HBV, tuberculosis and H. pylori. This highlights the need to understand specific polymorphisms to decipher their protective or predisposing effects. For instance, the presence of G and T alleles at position - 656 is suggested to have a probable protective effect against Visceral Leishmaniasis. Haplotypes -137 G/-607 C (GC) and -137 C/-607 C (CC) in the promoter region are associated with increased susceptibility to severe malarial anaemia. SNPs rs544354 and rs574429 (GC) are linked to a higher risk of P. falciparum infection and increased parasitemia. The -137 C/C genotype and -137 G allele (with G/G genotype) are associated with faster progression to AIDS. In contrast, the IL-18 genotype does not seem to affect HIV ***-18 polymorphisms influence the pathophysiology in infections like HBV, H. pylori, and TB. However, the conflicting results in studies conducted in different populations (e.g., genetic polymorphism, studies conducted in India and China in HBV infection) necessitate further research with larger sample sizes to resolve inconsistencies in the findings.

关键词： Astragalus injection   Melanoma   Anti-PD-1   MHC-II   STAT1   CIITA  

摘要： Ethnopharmacological relevance: Astragalus injection, a solution derived from Astragalus mongholicus Bunge, has been used in cancer patients for its immune-boosting properties. The effects of Astragalus injection combined with immune checkpoint inhibitors (ICIs) in cancer remain unsuspected. Aim of the study: This study aims to investigate the efficacy of combining Astragalus injection with anti-PD-1 and to elucidate the potential mechanisms. Materials and methods: A melanoma-bearing mouse model was established to observe the effects of Astragalus injection combined with anti-PD-1 treatment. The immune cell infiltration in tumor tissues was evaluated by flow cytometry. Subsequently, network pharmacology and RNA sequencing were conducted to anticipate latent mechanisms of Astragalus in melanoma. Finally, these predictions were validated by flow cytometry, qPCR, Western blotting, and ELISA. Results: Astragalus injection significantly antagonized the efficacy of anti-PD-1 in melanoma, resulting in a notable reduction of immune cell infiltration. The network pharmacology and RNA sequencing analysis revealed critical signaling routes, encompassing T-cell receptor activation, immune antigen presentation, and the JAK/ STAT pathway. Subsequent data suggested that Astragalus injection could down-regulate the expressions of MHCII in dendritic cells and B16-OVA cells and restrict the activation of dendritic cells. Moreover, the expressions of CIITA and phosphorylated STAT1 were prominently inhibited by Astragalus injection, whereas the overexpression of STAT1 partially reversed the Astragalus injection-induced decrease of MHC-II. Conclusions: Astragalus antagonized the therapeutic effect of anti-PD-1 in melanoma. These effects were partially through inhibiting JAK/STAT signaling and down-regulating MHC-II expression.