DNMT3b SUMOylation Mediated MMP-2 Upregulation Contribute to Paclitaxel Induced Neuropathic Pain

Neurochemical Research - Paclitaxel is a common chemotherapeutic agent in cancer treatment, while it often causes chemotherapy-induced peripheral neuropathy (CIPN), which...     

Gibberellin-Induced Alterations to the Expression of Cell Wall-Related Genes in the Xylem of Carrot Root

Journal of Plant Growth Regulation - Gibberellins (GAs) are a group of plant hormones that play important roles in various processes. Previous studies demonstrated that GA can increase the...     

Extracellular HMGB1 augments macrophage inflammation by facilitating the endosomal accumulation of ALD-DNA via TLR2/4-mediated endocytosis

Systemic lupus erythematosus (SLE) is a chronic autoimmune disease with unclear pathogenesis. We previously reported that syngenetic, activated lymphocyte-derived DNA (ALD-DNA) could robustly elicit macrophage activation, which plays an important role in the pathogenesis of murine lupus nephritis. In addition, extracellular HMGB1 obviously facilitated the accumulation of ALD-DNA in endosomes and promoted macrophage inflammation. While the detailed mechanism was still unknown. In this study, we found that HMGB1 could obviously change the DNA uptake pathways in macrophages. ALD-DNA alone was mainly uptake by the low efficient and unselective macropinocytosis, while extracellular HMGB1 potently promoted the more efficient and specific clathrin-/caveolin-1-dependent receptor-mediated endocytosis pathways, and led to the rapid and abundant aggregation of ALD-DNA in endosomes. This effect relied on the DNA binding ability and TLR2/TLR4 of HMGB1. Our study not only helped us to understand the promotion mechanisms of extracellular HMGB1 on ALD-DNA-induced macrophage inflammation, but also provided some clues to the pathogenesis of SLE.     

Modelling the effect of birth and feeding modes on the development of human gut microbiota

The human gut microbiota is transmitted from mother to infant through vaginal birth and breastfeeding. Bifidobacterium, a genus that dominates the infants’ gut, is adapted to breast milk in its ability to metabolize human milk oligosaccharides; it is regarded as a mutualist owing to its involvement in the development of the immune system. The composition of microbiota, including the abundance of Bifidobacteria, is highly variable between individuals and some microbial profiles are associated with diseases. However, whether and how birth and feeding practices contribute to such variation remains unclear. To understand how early events affect the establishment of microbiota, we develop a mathematical model of two types of Bifidobacteria and a generic compartment of commensal competitors. We show how early events affect competition between mutualists and commensals and microbe-host-immune interactions to cause long-term alterations in gut microbial profiles. Bifidobacteria associated with breast milk can trigger immune responses with lasting effects on the microbial community structure. Our model shows that, in response to a change in birth environment, competition alone can produce two distinct microbial profiles post-weaning. Adding immune regulation to our competition model allows for variations in microbial profiles in response to different feeding practices. This analysis highlights the importance of microbe–microbe and microbe–host interactions in shaping the gut populations following different birth and feeding modes.     

脆弱拟杆菌BF839治疗寻常型银屑病：一项单臂、开放初步临床试验

银屑病被认为是一种T细胞主导的炎症性疾病,其发病与肠道菌群失调密切相关。脆弱拟杆菌 (Bacteroides fragilis,BF) 可通过调节T细胞的细胞因子表达起抗炎作用。目前尚无脆弱拟杆菌用于治疗银屑病的相关报道,文中率先探究脆弱拟杆菌BF839对银屑病的治疗效果。选择2019年4月至2019年10月广州医科大学附属第二医院就诊的27例银屑病患者,维持原治疗不变,口服脆弱拟杆菌BF839 12周,对比治疗前后银屑病皮损面积与严重程度指数 (Psoriasis area and severity index,PASI) 评分,统计治疗12周后药物减停率。结果表明,12周试验完成率为96.3% (26/27),12周PASI30 (PASIN定义为治疗后PASI评分下降≥N%的患者比例) 为65.4%,PASI50为42.3%,PASI75为19.2%;治疗前PASI评分为9.1±5.9,治疗12周后PASI评分为5.8±4.9,具有显著统计学差异 (P<0.01);治疗12周后皮肤瘙痒程度用视觉模拟量表 (Visual analog scale,VAS) 评分有效率为42.3%,治疗前VAS评分为2.9±2.2,治疗12周后VAS评分为2.3±2.1,无显著统计学差异 (P>0.05)。患者治疗12周内不良反应率为3.8% (1/26),其中便秘1例,药物减停率为60.0%。以上结果提示脆弱拟杆菌BF839可能对银屑病治疗有一定疗效,可降低PASI评分及药物使用率,不良反应少,值得进一步研究。     

新工科背景下生物反应工程课程的多元化教学模式 改革与探索

生物反应工程作为一门理论性与应用性都很强的专业课程,在生物工程等相关专业的课程设置中处于桥梁和纽带地位,对新型应用型工科人才的培养发挥着重要的作用。但由于该课程中公式等抽象理论知识过多,导致学生学习效率十分低下。因此,为了适应新工科教育背景下对创新型人才培养的需求,提高学生的学习兴趣和积极性,并培养学生的自主学习等创新能力,教学团队在课程教学中通过引入虚拟仿真技术、开展微课教学、采用案例式教学模式、利用科研平台等多元化方式,对该课程的教学模式、方法和手段尝试改革和探索,取得了一定的教学效果,并就此进行了一些探讨,以期能为相关课程的教学改革提供一些思路和启示。     

Genetic Analysis of Human Adenovirus Type 7 Strains Circulating in Different Parts of China

To investigate the molecular epidemiology and genetic variation of human adenovirus type 7(HAdV-7) in children with acute respiratory infections(ARI) in China. HAdV-7-positive respiratory samples collected from children with ARI in Beijing, Shijiazhuang, Wenzhou and Guangzhou from 2014–2018 were selected for gene amplification and sequence analysis. Fifty-seven HAdV-7 clinical strains with hexon, penton base and fiber gene sequences were obtained. Meanwhile17 strains were selected randomly from different cities for whole genome sequencing. Phylogenetic and variation analyses were performed based on the obtained sequences, HAdV-7 prototype strain Gomen(AY594255), vaccine strains(AY495969 and AY594256) and representative sequences of strains. The phylogenetic trees constructed based on whole genome sequences, major capsid protein genes(hexon, penton base and fiber) and the early genes(E1, E2, E3 and E4) were not completely consistent. The HAdV-7 strains obtained in this study always clustered with most of the circulating strains worldwide from the 1980 s to the present. Compared with the HAdV-7 prototype strain Gomen(AY594255), some amino acid mutations in loop1 and loop2 of hexon and the RGD loop region of the penton base gene were observed. Recombination analysis showed that partial regions of 55 k Da protein and 100 kDa hexon-assembly associated protein genes among all HAdV-7 strains in this study were from HAdV-16 and HAdV-3, respectively. Our study demonstrated the molecular evolution characteristics of HAdV-7 strains circulating in China and provided basic reference data for the prevention, control and vaccine development of HAdV-7.     

Leptin gene-targeted editing in ob/ob mouse adipose tissue based on the CRISPR/Cas9 system

Gene therapy has become the most effective treatment for monogenic diseases. Congenital LEPTIN deficiency is a rare autosomal recessive monogenic obesity syndrome caused by mutations in the Leptin gene. Ob/ob mouse is a monogenic obesity model, which carries a homozygous point mutation of C to T in Exon 2 of the Leptin gene. Here, we attempted to edit the mutated Leptin gene in ob/ob mice preadipocytes and inguinal adipose tissues using CRISPR/Cas9 to correct the C to T mutation and restore the production of LEPTIN protein by adipocytes. The edited preadipocytes exhibit a correction of 5.5% of Leptin alleles and produce normal LEPTIN protein when differentiated into mature adipocytes. The ob/ob mice display correction of 1.67% of Leptin alleles, which is sufficient to restore the production and physiological functions of LEPTIN protein, such as suppressing appetite and alleviating insulin resistance. Our study suggests CRISPR/Cas9-mediated in situ genome editing as a feasible therapeutic strategy for human monogenic diseases, and paves the way for further research on efficient delivery system in potential future clinical application.