Neuroprotective effect of interleukin-6 regulation of voltage-gated Na^+ channels of cortical neurons is time-and dose-dependent

Interleukin-6 has been shown to be involved in nerve injury and nerve regeneration, but the effects of long-term administration of high concentrations of interleukin-6 on neurons in the central nervous system is poorly understood. This study investigated the effects of 24 hour expo-sure of interleukin-6 on cortical neurons at various concentrations （0.1, 1, 5 and 10 ng/mL） and the effects of 10 ng/mL interleukin-6 exposure to cortical neurons for various durations （2, 4, 8, 24 and 48 hours） by studying voltage-gated Na＋ channels using a patch-clamp technique. Volt-age-clamp recording results demonstrated that interleukin-6 suppressed Na＋ currents through its receptor in a time- and dose-dependent manner, but did not alter voltage-dependent activation and inactivation. Current-clamp recording results were consistent with voltage-clamp recording results. Interleukin-6 reduced the action potential amplitude of cortical neurons, but did not change the action potential threshold. The regulation of voltage-gated Na＋channels in rat corti-cal neurons by interleukin-6 is time- and dose-dependent.

Investigation on correlation between expression of CD58 molecule and severity of hepatitis B

瞄准：调查在 CD58 的表示和肝炎 B 的严厉之间的关联。方法：在有肝炎 B 的病人的浆液的可溶的 CD58 (sCD58 ) 的水平被连接酶的免疫吸着剂试金检测。在 PBMC 的膜 CD58 分子的表示的水平被直接免疫荧光检测。血清 TBIL， DBIL， IBIL，中高音和著名计算机生产厂商的层次被自动化生物化学分析器也检测。结果：在浆液的 sCD58 和在有肝炎 B 的病人的 PBMC 的膜 CD58 分子的层次在正常控制比那显著地高(P 【 0.05 ) 。CD58 的水平与血清 TBIL， DBIL， IBIL，中高音和著名计算机生产厂商的层次有关。结论：CD58 分子的水平(在浆液和 PBMC 形式) 有肝炎的病人， B 与肝的度有关损坏。

Culturable Bacterial Density and Composition in Haze Events in Xi’an, China

Industrialization and urbanization have increased air pollution in developing countries.Haze pollution is now a severe environmental concern in China;it is mainly characterized by PM2.5, a particulate matter having an aerodynamic diameter of 2.5 μm or less.Northern China experiences persistent haze pollution that affects many cities and millions of people, every winter and spring.

Targeting a disintegrin and metalloprotease(ADAM)17-CD122 axis enhances CD8^(+)T cell effector differentiation and anti-tumor immunity

CD8^(+)T cell immune responses are regulated by multi-layer networks,while the post-translational regulation remains largely unknown.Transmembrane ectodomain shedding is an important post-translational process orchestrating receptor expression and signal transduction through proteolytic cleavage of membrane proteins.Here,by targeting the sheddase A Disintegrin and Metalloprotease(ADAM)17,we defined a post-translational regulatory mechanism mediated by the ectodomain shedding in CD8^(+)T cells.Transcriptomic and proteomic analysis revealed the involvement of post-translational regulation in CD8^(+)T cells.T cellspecific deletion of ADAM17 led to a dramatic increase in effector CD8^(+)T cell differentiation and enhanced cytolytic effects to eliminate pathogens and tumors.Mechanistically,ADAM17 regulated CD8^(+)T cells through cleavage of membrane CD122.ADAM17 inhibition led to elevated CD122 expression and enhanced response to IL-2 and IL-15 stimulation in both mouse and human CD8^(+)T cells.Intriguingly,inhibition of ADAM17 in CD8^(+)T cells improved the efficacy of chimeric antigen receptor(CAR)T cells in solid tumors.Our findings reveal a critical post-translational regulation in CD8^(+)T cells,providing a potential therapeutic strategy of targeting ADAM17 for effective anti-tumor immunity.

Protease-triggered bioresponsive drug delivery for the targeted theranostics of malignancy

Proteases have a fundamental role in maintaining physiological homeostasis,but their dysregulation results in severe activity imbalance and pathological conditions,including cancer onset,progression,invasion,and metastasis.This striking importance plus superior biological recognition and catalytic performance of proteases,combining with the excellent physicochemical characteristics of nanomaterials,results in enzyme-activated nano-drug delivery systems(nanoDDS)that perform theranostic functions in highly specific response to the tumor phenotype stimulus.In the tutorial review,the key advances of protease-responsive nanoDDS in the specific diagnosis and targeted treatment for malignancies are emphatically classified according to the effector biomolecule types,on the premise of summarizing the structure and function of each protease.Subsequently,the incomplete matching and recognition between enzyme and substrate,structural design complexity,volume production,and toxicological issues related to the nanocomposites are highlighted to clarify the direction of efforts in nanotheranostics.This will facilitate the promotion of nanotechnology in the management of malignant tumors.

CD58 expression of liver tissue in patients with chronic hepatitis B virus infection

Background Several kinds of intercellular adhesion molecules closely relate to hepatitis B. The complex of CD2 and CD58 plays an important role in enhancing the adhesion of T lymphocytes to target cells, hyperplasia and activation of T lymphocytes. In this study, we explored the relationship between the expression of CD58 in liver tissue and chronic hepatitus B infection. Methods We determined the expression of the CD58 molecule on the surface of hepatoc^es by using immunohistochemistry and the levels of serum HBV DNA from patients with HBV infection and from normal controls. The biochemical parameters of hepatic function were analyzed as well. Results CD58 expression in hepatocytes significantly increased with the severity progression of chronic HBV infection. The IOD levels （log10） of CD58 in the control, mild, moderate, and severe chronic HBV infection groups were 0, （7.20±4.64）×10^3, （25.63±7.41）×10^3 and （37.47±11.17）×10^3 respectively （P〈O.05 compared with the control group, respectively） Conclusion CD58 probably increases cell mediated immunity to eliminate hepatitis B virus and leads to damage of hepatocytes.

The Expression of CD2 in Chronic HBV Infection

It was previously reported that several kinds of intercellular adhesion molecules are closely related to chronic HBV infection. The complex of CD2 and CD58 plays an important role in enhancing the adhesion of T lymphocytes to target cells, and promoting hyperplasia and activation of T lymphocytes. In this study, we detected the level of CD2 expressed on the surface of PBMC, the expression level of CD2 mRNA in PBMC and the percentage of CD2 positive cells in PBMC of patients with chronic HBV infection and compared them with the expression level of normal controls. We also determined the level of serum HBV DNA from patients with chronic HBV infection and from normal controls. The clinical characteristics of hepatic function were tested as well. The results showed that the expression of CD2 significantly increased with the severity of chronic HBV infection, which suggested that CD2 might contribute to the hepatocyte damage in chronic HBV infection. Cellular ＆ Molecular Immunology.

SARS-CoV-2 Genomic Sequencing Revealed N501Y and L452R Mutants of S/A Lineage in Tianjin Municipality, China

Dear Editor,Coronavirus Disease 2019(COVID-19)outbreak caused by sever acute respiratory syndrome coronavirus 2(SARSCo V-2)presents a global pandemic which has resulted in more than 4 million people death in the world.In China,the initial transmission of COVID-19 has already been blocked by strict control strategies and effective treatment for patients.All local COVID-19 outbreaks after April2020 were related to overseas importing.Up to February2021,207 imported COVID-19 cases have been reported in Tianjin,China(Tianjin Health Commission,2021).

Nanoparticle-based therapeutics of inflammatory bowel diseases:a narrative review of the current state and prospects

Inflammatory bowel disease(IBD),such as Crohn disease and ulcerative colitis,are chronic relapsing disorders of the gastrointestinal tract.Characterized pathologically by intestinal inflammation and epithelial injury,great challenges exist for the treatment of IBD due to its complicated etiology and incurable nature.Traditional strategies rely on frequent and long-term administration of high dosages of anti-inflammatory drugs,which inevitably cause side effects.Therefore,novel therapeutic methods and drug delivery systems capable of improving therapeutic effect while simultaneously decreasing side effects need to be developed.The emergence of nanotechnology provides alternative approaches for diagnosis and treatment of IBD,as nanoparticles(NPs)have unique physicochemical properties such as targeting to the site of inflammation and the ability to alter the pharmacokinetics of traditional drugs.This review first introduces the pathophysiological features and microenvironment of IBD,and then summarizes different strategies and mechanisms of NP-based colon-targeted drug delivery systems,including size-dependent,multi-stimuli responsive,active targeting,intestinal microbiota-related,and novel natural-derived NP-mediated drug delivery systems.We also discuss applications of nanozymes and NP-based imaging in diagnostics and treatment of IBD.Finally,challenges and prospects in the field are proposed to promote the development of targeted drug delivery for IBD treatment.

T cells in health and disease

T cells are crucial for immune functions to maintain health and prevent disease.T cell development occurs in a stepwise process in the thymus and mainly generates CD4^(+)and CD8^(+)T cell subsets.Upon antigen stimulation,naïve T cells differentiate into CD4^(+)helper and CD8^(+)cytotoxic effector and memory cells,mediating direct killing.