Improvement of Intracellular Traffic System by Overexpression of KDEL Receptor 1 in Antibody‐Producing CHO Cells

The localization of soluble endoplasmic reticulum (ER) chaperones in the cell organelle is mediated by the C‐terminal KDEL (lysine, aspartic acid, glutamic acid and leucine) motif. This motif is recognized by the KDEL receptor, a seven‐transmembrane protein that cycles between the ER and cis‐Golgi to capture missorted KDEL chaperones from post‐ER compartments in a pH‐dependent manner. The KDEL receptor's target chaperones have a substantial role in protein folding and assembly. In this study, the gene expression level of KDEL receptor 1 shows a moderate upregulation during either ER stress or growth of Chinese hamster ovary (CHO) cells in batch culture, while the ER chaperones show higher upregulation. This might indicate the possibility of saturation of the ER retention machinery or at least hindered retention during late stage batch culture in recombinant CHO cells. KDELR1 is overexpressed in a monoclonal antibody‐producing CHO cell line to improve the intracellular chaperone retention rate in the ER. An increase in the specific productivity of IgG1 by 13.2% during the exponential phase, and 23.8% in the deceleration phase of batch culture is observed. This is the first study to focus on the ER retention system as a cell engineering target for enhancing recombinant protein production.     

杉木采伐迹地营造阔叶树种对土壤微生物生态化学计量特征的影响

研究土壤微生物生物量及其生态化学计量特征对造林树种转换的响应,对深入了解森林生态系统土壤养分循环和有效性具有重要意义。本研究以1993年春在二代杉木采伐迹地上营造的26年生米老排和杉木人工林为对象,采用氯仿熏蒸法测定了0～40 cm土层土壤微生物生物量碳(MBC)、氮(MBN)、磷(MBP)的变化。结果表明: 与杉木人工林相比,米老排人工林0～10 cm土层MBC和0～20 cm土层MBN和MBP均显著提高, 0～20 cm土层MBC/MBP和10～20 cm土层MBN/MBP显著降低。两种人工林所有土层MBC/MBN均无差异。相关分析显示,土壤含水率、总有机碳、总氮、全磷、有效磷与MBC、MBN和MBP呈显著正相关,而与MBC/MBP和MBN/MBP呈显著负相关。逐步线性回归分析表明,MBN和MBP主要受土壤总氮和有效磷的影响,而MBC/MBP和MBN/MBP主要受有机碳和有效磷的驱动。研究表明,造林树种从杉木转换成米老排能够增加表层土壤微生物生物量,加速氮磷养分周转,增加土壤氮磷养分供应能力。米老排人工林土壤MBP的增加可能在一定程度上缓解了树木生长的磷限制。     

全球中华鲎资源保护现状及对策建议

鲎是古老的海洋节肢动物。中华鲎(Tachypleus tridentatus)是世界现存4种鲎中体型最大的一种, 是河口生态系统的标志物种, 同时其血液被用于生产医用检验试剂――鲎试剂。中华鲎的自然地理分布范围相当狭窄, 仅局限于日本濑户内海向南延伸至印度尼西亚爪哇岛北岸以北的太平洋西岸海域, 其中在中国东岸和日本南部海域的历史产量较高。自20世纪50年代以来中华鲎种群数量出现了显著减少, 2019年中华鲎在IUCN红色名录中的濒危等级正式更新为濒危(EN), 明确了中华鲎资源呈现全球性衰退的状态, 究其原因可归纳为鲎生境破坏和过度捕捞两个方面。在开展鲎资源保护的实践工作中, 作者深刻反思当前鲎资源保护在海洋保护区划定、增殖放流及科普和野生动物保护法宣传中存在的问题并提出相应建议, 包括加快完善种群基线数据, 制定标准化种群和生境基线监测指南, 构建科学放流体系等, 以期推进全球范围内的中华鲎资源保护与科学管理。     

中医药的抗炎机制在治疗肝纤维化中的作用

肝脏是人体腹腔内最大的实体器官,对维持机体的基本生理功能起着至关重要的作用。肝脏疾病是威胁人类健康的常见病多发病。全球约有10%人口受到不同程度的肝脏疾病的危害,其中,肝纤维化往往成为这些疾病的晚期病理特征。由于肝纤维化的发病机制复杂,尚无有效的合成类药物能够治疗肝纤维化。中药治疗肝纤维化具有多靶点和副作用小的优势。本文综述了肝纤维化的病理特征与诱发炎症的关系,讨论了中药治疗肝纤维化的单味中药、传统配方及其化学活性成分的抗炎症机制。     

Aidi injection,a traditional Chinese biomedical preparation for gynecologic tumors: a systematic review and PRISMA-compliant meta-analysis

Aidi injection (ADI), a traditional Chinese biomedical preparation, is a promising adjuvant therapy for gynecologic tumors (GTs), including cervical cancer (CC), endometrial cancer (EC), and ovarian cancer (OC). Although studies have reported positively on ADI therapy, its exact effects and safety in GT patients remain controversial. Therefore, a wide-ranging systematic search of electronic databases was performed for this meta-analysis. Data from 38 trials including 3309 GT patients were analyzed. The results indicated that the combination of conventional treatment and ADI markedly improved the patients’ overall response rate (P<0.00001), disease control rate (P<0.00001), and quality of life (P<0.05) compared with conventional treatment alone. Furthermore, patient immunity was enhanced with combined treatment, as indicated by significantly increased percentages of CD3⁺ (P=0.005) and CD4⁺ (P<0.00001) and increased CD4⁺/CD8⁺ ratio (P=0.001). Most of the adverse events caused by radiochemotherapy such as gastrointestinal issues, leukopenia, thrombocytopenia, and hepatotoxicity, (P<0.05 for all) were significantly alleviated when ADI was used in the GT patients. However, other adverse events such as nephrotoxicity, diarrhea, alopecia, and neurotoxicity did not significantly differ between the two groups. Overall, these results suggest that the combination of conventional and ADI treatment is more effective than conventional treatment alone.     

秦岭地区中段死亡斑羚空间分布规律初探

In recent years, Chinese goral (Nemorhaedus griseus) carcasses were frequently found in the mid-Qinling Mountains. In order to assess the spatial distribution pattern of goral carcasses, data of the individuals from Shaanxi's Fourth Giant Panda Survey was used in this study to analyse how the gorals/goral carcasses sites were related to altitude, slope, aspect, river, and road through quantitative analyses. The results showed:(1) the correlation between the sites of goral carcasses and topographic factors was relatively significant. Goral carcasses tend to be found at relatively low altitude (1 200-2 400 m) and mild slope (6°-25°). The chi-square test also showed that the aspect of the goral carcasses sites was significantly different from the goral sites. Most of the goral carcasses were found at south-facing/half southfacing slopes. (2) The correlation between the sites of goral carcasses and the distance to river was significant. The kernel density analysis and Z-test further showed that there were significant differences between the gorals/goral carcasses sites and the distance to river. Most of the goral carcasses sites were close to river (< 100 m). (3) The correlation between the sites of goral carcasses and the distance to road was not significant. Kernel density analysis and Z-test showed that there was no significant difference between the sites of gorals/goral carcasses and the distance to road. This study proposed several suggestions about how to strengthen the protection of gorals in the future.     

Comprehensive landscape and interference of clonal haematopoiesis mutations for liquid biopsy: A Chinese pan-cancer cohort

Tumour-derived DNA found in the plasma of cancer patients provides the probability to detect somatic mutations from circulating cell-free DNA (cfDNA) in plasma samples. However, clonal hematopoiesis (CH) mutations affect the accuracy of liquid biopsy for cancer diagnosis and treatment. Here, we integrated landscape of CH mutations in 11,725 pan-cancer patients of Chinese and explored effects of CH on liquid biopsies in real-world. We first identified 5933 CHs based on panel sequencing of matched DNA of white blood cell and cfDNA on 301 genes for 5100 patients, in which CH number of patients had positive correlation with their diagnosis age. We observed that canonical genes related to CH, including DNMT3A, TET2, ASXL1, TP53, ATM, CHEK2 and SF3B1, were dominant in the Chinese cohort and 13.29% of CH mutations only appeared in the Chinese cohort compared with the Western cohort. Analysis of CH gene distribution bias indicated that CH tended to appear in genes with functions of tyrosine kinase regulation, PI3K-Akt signalling and TP53 activity, suggesting unfavourable effects of CH mutations in cancer patients. We further confirmed effect of driver genes carried by CH on somatic mutations in liquid biopsy of cancer patients. Forty-eight actionable somatic mutations in 17 driver genes were considered CH genes in 92 patients (1.80%) of the Chinese cohort, implying potential impacts of CH on clinical decision-making. Taken together, this study exhibits strong evidence that gene mutations from CH interfere accuracy of liquid biopsies using cfDNA in cancer diagnosis and treatment in real-world.