Protein kinases in plant responses to drought,salt, and cold stress

Protein kinases are major players in various signal transduction pathways. Understanding the molecular mechanisms behind plant responses to biotic and abiotic stresses has become critical for developing and breeding climate-resilient crops. In this review,we summarize recent progress on understanding plant drought, salt, and cold stress responses, with a focus on signal perception and transduction by different protein kinases, especially sucrose nonfermenting1(SNF1)-related protein kinases(Sn RKs),mitogen-activated protein kinase(MAPK) cascades,calcium-dependent protein kinases(CDPKs/CPKs),and receptor-like kinases(RLKs). We also discuss future challenges in these research fields.     

联合TCGA和GEO数据库筛选乳腺癌易感基因

本研究是利用公共基因芯片数据库筛选乳腺癌的预后基因,预测和探索这些基因在乳腺癌进展中的可能机制和临床价值.首先,我们筛选了公共基因芯片数据库(gene expression omnibus,GEO)GSE22820和癌症基因组图谱(the cancer genome atlas,TCGA)乳腺癌数据库的重叠差异表达基因,联合R语言分析乳腺癌组织与癌旁正常组织差异表达的基因;其次,基于STRING数据库及Cytoscape软件构建蛋白质相互作用网络图,分析并识别了中枢基因和前3个模块;之后进行了更多的功能分析,包括基因本体(gene ontology,GO)和京都基因与基因组百科全书(kyoto encyclopedia of genes and genomes,KEGG)通路分析以及基因集富集分析(gene set enrichment analysis,GSEA),以研究这些基因的作用以及潜在的潜在机制;最后进行了Kaplan-Meier分析和Cox比例风险分析,以阐明这些基因的诊断和预后效果.相关数据分析表明15个基因的表达水平与生存预后相关,高表达基因患者的总生存时间短于低表达患者(P＜0.05);Cox比例风险分析表明UBE2T、ER-CC6L和RAD51这3个基因是预后生存的独立因素(P＜0.05);GSEA分析表明在UBE2T、ERCC6L和RAD51基因中细胞周期、基础转录因子和卵母细胞减数分裂明显富集.最终,我们得出结论,这3种基因标志物的高表达是乳腺癌预后不良因素,可作为预测乳腺癌患者转移和预后的有效生物标志物.     

Adult-repopulating lymphoid potential of yolk sac blood vessels is not confined to arterial endothelial cells

Science China Life Sciences - During embryogenesis, hematopoietic stem progenitor cells (HSPCs) are believed to be derived from hemogenic endothelial cells (HECs). Moreover, arterial feature is...     

Molecular deconvolution of the neutralizing antibodies induced by an inactivated SARS-CoV-2 virus vaccine

Dear Editor, The rapid emergence and persistence of the pandemic caused by severe acute respiratory syndrome coronavirus 2(SARS-CoV-2) has had enormous impacts on global health and the economy.Effective vaccines against SARS-CoV-2 are urgently needed to control the coronavirus disease 2019(COVID-19) pandemic,and multiple vaccines have been found to be efficacious in preventing symptomatic COVID-19(Polack et al.,2020;Wu et al.,2020;Jones and Roy,2021).We have developed a traditional beta-propiolactone-inacti-vated aluminum hydroxide-adjuvanted whole-virion SARS-CoV-2 vaccine (BBIBP-CorV),which elicited protective immune responses in clinical trials (Wang et al.,2020;Xia et al.,2021).The vaccine has been granted conditional approvals or emergency use authorizations (EUAs) in China and other countries.     

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.     

Hydrogen sulphide reduces hyperhomocysteinaemia-induced endothelial ER stress by sulfhydrating protein disulphide isomerase to attenuate atherosclerosis

Hyperhomocysteinaemia (HHcy)-impaired endothelial dysfunction including endoplasmic reticulum (ER) stress plays a crucial role in atherogenesis. Hydrogen sulphide (H₂S), a metabolic production of Hcy and gasotransmitter, exhibits preventing cardiovascular damages induced by HHcy by reducing ER stress, but the underlying mechanism is unclear. Here, we made an atherosclerosis with HHcy mice model by ApoE knockout mice and feeding Pagien diet and drinking L-methionine water. H₂S donors NaHS and GYY4137 treatment lowered plaque area and ER stress in this model. Protein disulphide isomerase (PDI), a modulation protein folding key enzyme, was up-regulated in plaque and reduced by H₂S treatment. In cultured human aortic endothelial cells, Hcy dose and time dependently elevated PDI expression, but inhibited its activity, and which were rescued by H₂S. H₂S and its endogenous generation key enzyme-cystathionine γ lyase induced a new post-translational modification-sulfhydration of PDI. Sulfhydrated PDI enhanced its activity, and two cysteine-terminal CXXC domain of PDI was identified by site mutation. HHcy lowered PDI sulfhydration association ER stress, and H₂S rescued it but this effect was blocked by cysteine site mutation. Conclusively, we demonstrated that H₂S sulfhydrated PDI and enhanced its activity, reducing HHcy-induced endothelial ER stress to attenuate atherosclerosis development.     

Poly(ADP-ribose) polymerase inhibitor PJ34 protects against UVA-induced oxidative damage in corneal endothelium

Apoptosis - Fuchs endothelial corneal dystrophy (FECD) is one of the main causes for corneal endothelial blindness, which is characterized by the progressive decline of corneal endothelial cells....     

Breast milk contains probiotics with anti-infantile diarrhoea effects that may protect infants as they change to solid foods

Infants often experience complementary food-induced diarrhoea (CFID), which occurs when infants switch from breast milk to solid foods. The relative abundances of Prevotella and Rothia were higher in stools of infants with CFID, while the relative abundances of Enterococcus and Escherichia were higher in healthy infants. The abundance of Lactobacillus spp. normally found in breast milk fed to infants with CFID was significantly reduced, and Enterococcus spp. were less abundant when diarrhoea occurred. Furthermore, Lactobacillus and Enterococcus were present as shared bacteria in both mother and infant, and they were considered potential anti-CFID probiotics as their relative abundances in breast milk were negatively correlated to infant CFID. Kyoto encyclopedia of genes and genomes (KEGG) functional analysis showed that the function of amino acid metabolism differed between infants with CFID and healthy infants. Therefore, CFID might be related to the decomposition of proteins in food supplements. The screening revealed seven hydrolytic casein and five hydrolytic casein and rice protein isolates from 320 suspected Lactobacillus and Enterococcus isolates. The animal experiments demonstrated that a mixture of five isolates effectively hydrolysed the casein and rice protein and prevented diarrhoea in young rats. Thus, the occurrence of CFID was found to be closely related to the intestinal and breast milk microbiota, and bacteria that could assist in the digestion of cereal proteins were involved in CFID.     

Protective potential of Chinese herbal extracts against microsporidian Nosema ceranae,an emergent pathogen of western honey bees,Apis mellifera L.

Nosema ceranae, a newly emergent parasite invading western honey bees (Apis mellifera L.), is indicated to threaten honey bee health at both individual and colony levels. However, the efficient and environmentally-friendly treatments are quite limited at present. To find alternative medicine to control Nosema diseases, the effect of 8 types of herbal extracts against N. ceranae infection were screened under laboratory condition. Of which, 1% Andrographis paniculata (A. paniculata) decoction was found to significantly decrease N. ceranae spore numbers on 7 days post infection (dpi) and 13 dpi. Then, our results further revealed that A. paniculata decoction at doses ranging from 1% to 7% displayed significant efficient inhibition of Nosema spore proliferation and improved the infected bees' survival rates in a dose-dependent manner. A. paniculata decoction was found to protect the gut tissues of infected workers from damage cause by N. ceranae, which might be due to the regulation of the expression of certain genes in Wnt and JNK pathways, including armadillo, basket, frizzled2 and groucho. Additionally, our study suggested that A. paniculata decoction performed this Nosema spore-reducing potential over its two monomers, andrographolide and dehydrographolide. Taken together, this work enables us to better understand A. paniculata decoction's potential to inhibit N. ceranae infection, thus providing a new guidance for developing applicable drugs to control Nosema diseases.     

NEK2 plays an active role in Tumorigenesis and Tumor Microenvironment in Non-Small Cell Lung Cancer

Abnormal expression and dysfunction of Never-in-mitosis-A-related kinase 2 (NEK2) result in tumorigenesis. High levels of NEK2 are related to malignant progression, drug resistance, and poor prognosis. However, the relationship between NEK2 levels and the occurrence of non-small cell lung cancer (NSCLC) remains unknown. This study aimed to explore the impacts of NEK2 on the oncogenesis of NSCLC and the tumor microenvironment. Downregulation of NEK2 inhibited A549 and H1299 cell proliferation, migration, and invasion, blocking cell cycle at the G0/G1 phase. Loss of NEK2 inhibited the release of IL-10 from tumor cells, M2-like polarization of macrophages, angiogenesis, and vascular endothelial cell migration. Furthermore, NEK2 deficiency inhibited tumor growth in vivo. Taken together, NEK2 knockdown inhibited the occurrence and development of NSCLC, M2 polarization of macrophages, and angiogenesis. The abnormal expression of NEK2 might not only indicate tumor progression and patient prognosis but also serve as a potential molecular therapeutic target with great development prospects.