粘性丝孢酵母的诱变及以玉米秸秆水解液为原料产油条件优化

对粘性丝胞酵母进行紫外诱变,获得一株产油率较高的菌株,较原菌株提高了1.53倍。将该菌株接种于用1%硫酸和酶水解处理并浓缩至还原糖浓度为5%的玉米秸秆水解液中培养,生长较好。通过四因素三水平正交实验,确定培养条件为初始pH值7.0、接种量1%、发酵温度30℃、发酵时间5 d时产油率最高。对最佳产油条件进行验证,测得油脂含量为21.3%。从而为利用农业废弃物大规模生产微生物油脂提供了试验数据。气相色谱-质谱联用分析仪显示油脂脂肪酸组成为棕榈酸28.36%,油酸55.86%,10-十八烯酸9.23%,硬脂酸6.70%,可以作为原料生产生物柴油。     

干扰素刺激基因表达对Peg-IFN抗乙型肝炎病毒免疫应答的影响

为了揭示干扰素刺激基因(interferon-stimulated gene, ISG)表达的改变对乙型肝炎病毒感染治疗效果的影响,本研究检测了干扰素刺激基因STAT1、MX和SOCS3在慢性乙型肝炎患者的外周血单核细胞(peripheral blood mononuclear cell, PBMC)和肝脏样品中的表达情况。结果显示,采用聚乙二醇干扰素(Peg-IFN)治疗后,Peg-IFN应答者的PBMC和肝组织中的STAT1和MX表达水平显著升高,而非应答者的SOCS3表达显著升高。在应答者的活组织检查中,Peg-IFN治疗24 h后细胞核中磷酸化STAT1的染色比例显著增加,而非应答者在治疗前肝细胞核染色比例较高,治疗后染色比例显著减少。此外,治疗前非应答者的肝SOCS3表达水平显著高于应答者,并且随着IFN的治疗SOCS3表达继续增加。本研究表明,STAT1和MX是Peg-IFN抗病毒免疫应答的正向调节因子,而SOCS3 (JAK/STAT途径的负调节因子)激活干扰素刺激基因的负调控,并抑制Peg-IFN的免疫应答。     

小鼠超数排卵优化试验方案研究

探讨建立一种适合贵州地区、高效、稳定的小鼠超数排卵优化方案。在饲养环境相同的基础上,对激素(PMSG, hCG)不同的剂量组合、注射间隔时间、小鼠周龄等影响因素进行了相关研究。试验结果表明:(1)平均采胚数量组间、平均异常胚组间与平均可用胚组间差异显著(p<0.05),注射10 IU的激素剂量组合获得受精卵最多,且异常胚最少,效果最佳。(2)第1、第2、第3组平均采胚数量组间差异显著(p<0.05),第1组与第2组平均可用胚组间差异不显著(p>0.05),但第1、2组与第3组差异显著(p<0.05),异常胚组间差异不显著(p>0.05),选择4周龄超排效果最佳。(3)第1、第2、第3组平均采胚数量、平均可用胚组间差异显著(p<0.05),平均异常胚组间差异不显著(p>0.05),PMSG,hCG间隔注射时间为48 h为最佳。     

Nanopore sequencing: a rapid solution for infectious disease epidemics

<正>Emerging and re-emerging infectious diseases have given rise to a large number of human infections, morbidity, and heavy economic burden, including the Middle East respiratory syndrome caused by a coronavirus in 2012, global influenza pandemic caused by the H7N9 influenza A virus in2013, Ebola epidemic in West Africa in 2014, and Lassa fever epidemic in Nigeria in 2019. The healthcare war against viruses deserves constant surveillance due to the continuous emergence of new viruses and rapid evolution of     

心肌纤维化的信号转导机制及新型抑制剂的研究进展

心肌纤维化(myocardial fibrosis, MF)是心肌重构发生的重要病理过程,能够引起心脏衰竭甚至死亡。心肌组织中成纤维细胞异常增殖并转化为肌成纤维细胞以及心肌细胞外基质代谢紊乱导致沉积是心肌纤维化形成的主要病理基础。心肌纤维化发生的分子机制较复杂,已发现多种信号通路参与了心肌纤维化的发生。该文主要对参与调控心肌纤维化的信号转导机制进行了综述,并对新型信号抑制剂的研究进展进行了小结。     

Identification of a novel COL4A5 mutation in the proband initially diagnosed as IgAN from a Chinese family with X-linked Alport syndrome

Alport syndrome(AS) is a hereditary progressive nephropathy characterized by hematuria, ultrastructural lesions of the glomerular basement membrane, ocular lesions and sensorineural hearing loss. Germline mutations of COL4 A5 are associated with X-linked AS with an extreme phenotypic heterogeneity. Here, we investigated a Chinese family with Alport syndrome. The proband was a 9-year-old boy with hematuria and proteinuria. Based on the test results of renal biopsy and immunofluorescence,the proband was initially diagnosed as Ig A nephropathy and the treatment was recommended accordingly. Meanwhile, we found that the treatment outcome was poor. Therefore, for proper clinical diagnosis and appropriate treatment, targeted exome-based next-generation sequencing has been undertaken. We identified a novel hemizygous single nucleotide deletion c.1902 del A in COL4 A5 gene. Segregation analysis identified that this novel mutation is co-segregated among the affected family members but absent in unaffected family members. The clinical diagnosis of the proband was revised as AS accompanied by Ig A nephropathy,which has been rarely reported. Our findings demonstrated the significance of the application of Genetic screening, expanded the mutation spectrum of COL4 A5 associated AS patients with atypical renal phenotypes and provided a good lesson to be learned from our detour during the diagnosis.     

miR‐200c suppresses stemness and increases cellular sensitivity to trastuzumab in HER2+ breast cancer

Resistance to trastuzumab remains a major obstacle in HER2‐overexpressing breast cancer treatment. miR‐200c is important for many functions in cancer stem cells (CSCs), including tumour recurrence, metastasis and resistance. We hypothesized that miR‐200c contributes to trastuzumab resistance and stemness maintenance in HER2‐overexpressing breast cancer. In this study, we used HER2‐positive SKBR3, HER2‐negative MCF‐7, and their CD44⁺CD24^? phenotype mammospheres SKBR3‐S and MCF‐7‐S to verify. Our results demonstrated that miR‐200c was weakly expressed in breast cancer cell lines and cell line stem cells. Overexpression of miR‐200c resulted in a significant reduction in the number of tumour spheres formed and the population of CD44⁺CD24^? phenotype mammospheres in SKBR3‐S. Combining miR‐200c with trastuzumab can significantly reduce proliferation and increase apoptosis of SKBR3 and SKBR3‐S. Overexpression of miR‐200c also eliminated its downstream target genes. These genes were highly expressed and positively related in breast cancer patients. Overexpression of miR‐200c also improved the malignant progression of SKBR3‐S and SKBR3 in vivo. miR‐200c plays an important role in the maintenance of the CSC‐like phenotype and increases drug sensitivity to trastuzumab in HER2+ cells and stem cells.     

The role of tumour microenvironment: a new vision for cholangiocarcinoma

Cholangiocarcinoma (CCA) is a relatively rare malignant and lethal tumour derived from bile duct epithelium and the morbidity is now increasing worldwide. This disease is difficult to diagnose at its inchoate stage and has poor prognosis. Therefore, a clear understanding of pathogenesis and major influencing factors is the key to develop effective therapeutic methods for CCA. In previous studies, canonical correlation analysis has demonstrated that tumour microenvironment plays an intricate role in the progression of various types of cancers including CCA. CCA tumour microenvironment is a dynamic environment consisting of authoritative tumour stromal cells and extracellular matrix where tumour stromal cells and cancer cells can thrive. CCA stromal cells include immune and non‐immune cells, such as inflammatory cells, endothelial cells, fibroblasts, and macrophages. Likewise, CCA tumour microenvironment contains abundant proliferative factors and can significantly impact the behaviour of cancer cells. Through abominably intricate interactions with CCA cells, CCA tumour microenvironment plays an important role in promoting tumour proliferation, accelerating neovascularization, facilitating tumour invasion, and preventing tumour cells from organismal immune reactions and apoptosis. This review summarizes the recent research progress regarding the connection between tumour behaviours and tumour stromal cells in CCA, as well as the mechanism underlying the effect of tumour stromal cells on the growth of CCA. A thorough understanding of the relationship between CCA and tumour stromal cells can shed some light on the development of new therapeutic methods for treating CCA.     

Long non‐coding RNA cardiac hypertrophy‐associated regulator governs cardiac hypertrophy via regulating miR‐20b and the downstream PTEN/AKT pathway

Pathological cardiac hypertrophy (CH) is a key factor leading to heart failure and ultimately sudden death. Long non‐coding RNAs (lncRNAs) are emerging as a new player in gene regulation relevant to a wide spectrum of human disease including cardiac disorders. Here, we characterize the role of a specific lncRNA named cardiac hypertrophy‐associated regulator (CHAR) in CH and delineate the underlying signalling pathway. CHAR was found markedly down‐regulated in both in vivo mouse model of cardiac hypertrophy induced by pressure overload and in vitro cellular model of cardiomyocyte hypertrophy induced by angiotensin II (AngII) insult. CHAR down‐regulation alone was sufficient to induce hypertrophic phenotypes in healthy mice and neonatal rat ventricular cells (NRVCs). Overexpression of CHAR reduced the hypertrophic responses. CHAR was found to act as a competitive endogenous RNA (ceRNA) to down‐regulate miR‐20b that we established as a pro‐hypertrophic miRNA. We experimentally established phosphatase and tensin homolog (PTEN), an anti‐hypertrophic signalling molecule, as a target gene for miR‐20b. We found that miR‐20b induced CH by directly repressing PTEN expression and indirectly increasing AKT activity. Moreover, CHAR overexpression mitigated the repression of PTEN and activation of AKT by miR‐20b, and as such, it abrogated the deleterious effects of miR‐20b on CH. Collectively, this study characterized a new lncRNA CHAR and unravelled a new pro‐hypertrophic signalling pathway: lncRNA‐CHAR/miR‐20b/PTEN/AKT. The findings therefore should improve our understanding of the cellular functionality and pathophysiological role of lncRNAs in the heart.     

Pristimerin attenuates cell proliferation of uveal melanoma cells by inhibiting insulin‐like growth factor‐1 receptor and its downstream pathways

Uveal melanoma (UM) has a high mortality rate due to liver metastasis. The insulin‐like growth factor‐1 receptor (IGF‐1R) is highly expressed in UM and has been shown to be associated with hepatic metastases. Targeting IGF signalling may be considered as a promising approach to inhibit the process of metastatic UM cells. Pristimerin (PRI) has been demonstrated to inhibit the growth of several cancer cells, but its role and underlying mechanisms in the IGF‐1‐induced UM cell proliferation are largely unknown. The present study examined the anti‐proliferative effect of PRI on UM cells and its possible role in IGF‐1R signalling transduction. MTT and clonogenic assays were used to determine the role of PRI in the proliferation of UM cells. Flow cytometry was performed to detect the effect of PRI on the cell cycle distribution of UM cells. Western blotting was carried out to assess the effects of PRI and IGF‐1 on the IGF‐1R phosphorylation and its downstream targets. The results indicated that IGF‐1 promoted the UM cell proliferation and improved the level of IGF‐1R phosphorylation, whereas PRI attenuated the effect of IGF‐1. Interestingly, PRI could not only induce the G1 phase accumulation and reduce the G2 phase induced by IGF‐1, but also could stimulate the expression of p21 and inhibit the expression of cyclin D1. Besides, PRI could attenuate the phosphorylations of Akt, mTOR and ERK1/2 induced by IGF‐1. Furthermore, the molecular docking study also demonstrated that PRI had potential inhibitory effects on IGF‐1R. Taken together, these results indicated that PRI could inhibit the proliferation of UM cells through down‐regulation of phosphorylated IGF‐1R and its downstream signalling.