Evolving cognition of the JAK-STAT signaling pathway:autoimmune disorders and cancer

The Janus kinase(JAK)signal transducer and activator of transcription(JAK-STAT)pathway is an evolutionarily conserved mechanism of transmembrane signal transduction that enables cells to communicate with the exterior environment.Various cytokines,interferons,growth factors,and other specific molecules activate JAK-STAT signaling to drive a series of physiological and pathological processes,including proliferation,metabolism,immune response,inflammation,and malignancy.Dysregulated JAK-STAT signaling and related genetic mutations are strongly associated with immune activation and cancer progression.Insights into the structures and functions of the JAK-STAT pathway have led to the development and approval of diverse drugs for the clinical treatment of diseases.Currently,drugs have been developed to mainly target the JAK-STAT pathway and are commonly divided into three subtypes:cytokine or receptor antibodies,JAK inhibitors,and STAT inhibitors.And novel agents also continue to be developed and tested in preclinical and clinical studies.The effectiveness and safety of each kind of drug also warrant further scientific trials before put into being clinical applications.Here,we review the current understanding of the fundamental composition and function of the JAK-STAT signaling pathway.We also discuss advancements in the understanding of JAK-STAT–related pathogenic mechanisms;targeted JAK-STAT therapies for various diseases,especially immune disorders,and cancers;newly developed JAK inhibitors;and current challenges and directions in the field.

Health and Disease:Akkermansia muciniphila,the Shining Star of the Gut Flora

Akkermansia muciniphila(A.muciniphila)has drawn much attention as an important gut microbe strain in recent years.A.muciniphila can influence the occurrence and development of diseases of the endocrine,nervous,digestive,musculoskeletal,and respiratory systems and other diseases.It can also improve immunotherapy for some cancers.A.muciniphila is expected to become a new probiotic in addition to Lactobacillus and Bifidobacterium.An increase in A.muciniphila abundance through direct or indirect A.muciniphila supplementation may inhibit or even reverse disease progression.However,some contrary findings are found in type 2 diabetes mellitus and neurodegenerative diseases,where increased A.muciniphila abundance may aggravate the diseases.To enable a more comprehensive understanding of the role of A.muciniphila in diseases,we summarize the relevant information on A.muciniphila in different systemic diseases and introduce regulators of A.muciniphila abundance to promote the clinical transformation of A.muciniphila research.

呼伦贝尔农垦集团草畜平衡状况与粮经饲配置模式

加快生态草牧业建设以提升草原生态承载力、促进草畜动态平衡,是实现农牧场畜牧业增产和牧区可持续发展的重要举措.本文以呼伦贝尔农垦集团24个农牧场为研究区,基于MODIS,Landsat TM/OLI和高分2号等遥感数据和农牧场草牧业年度报表数据,应用遥感解译和草地净初级生产力遥感估算模型,获取了农垦集团24个农牧场草地分布现状和退化状况,测算了各农牧场草地净初级生产力,评价了草地生态承载力和超载状况,进而提出了农牧场生态草牧业建设的粮经饲配置模式.结果表明:呼伦贝尔农垦集团24个农牧场中草地总面积的66.16%出现不同程度的退化,主要表现为草地植被生产力和盖度下降,由草原开垦等导致草地破碎化面积约占草地总面积的1.55%.遥感估算的呼伦贝尔农垦集团24个农牧场平年产草总量约为34.07万t,欠年(2001年)产草总量为27.43万t,丰年(2013年)产草总量为48.89万t.2015年农垦集团24个农牧场实际载畜量为164.19万个羊单位,理论载畜量为86.83万个羊单位,在不考虑青贮草和外购饲草料的情况下,超载率为89%,饲草缺口42.35万t.农垦集团24个农牧场现有耕地面积为3.95×103 km2,基于生态草牧业建设的理念,将其中10%的耕地开展人工草地种植,理论上相当于5.86×103 km2天然草地的产草量,完全可满足整个农垦集团牲畜饲草料需求.推行"粮、经、饲‘三元结构’、草田轮作"的生产模式,适度利用现有耕地开展粮改饲和种养结合模式,提高草地产量、有助于维护草畜平衡,遏制草地退化趋势,提高草原牧区草牧业可持续发展和生态保护能力.

A fundamental theorem for eco-environmental surface modelling and its applications

We propose a fundamental theorem for eco-environmental surface modelling(FTEEM) in order to apply it into the fields of ecology and environmental science more easily after the fundamental theorem for Earth’s surface system modeling(FTESM). The Beijing-Tianjin-Hebei(BTH) region is taken as a case area to conduct empirical studies of algorithms for spatial upscaling, spatial downscaling, spatial interpolation, data fusion and model-data assimilation, which are based on high accuracy surface modelling(HASM), corresponding with corollaries of FTEEM. The case studies demonstrate how eco-environmental surface modelling is substantially improved when both extrinsic and intrinsic information are used along with an appropriate method of HASM. Compared with classic algorithms, the HASM-based algorithm for spatial upscaling reduced the root-meansquare error of the BTH elevation surface by 9 m. The HASM-based algorithm for spatial downscaling reduced the relative error of future scenarios of annual mean temperature by 16%. The HASM-based algorithm for spatial interpolation reduced the relative error of change trend of annual mean precipitation by 0.2%. The HASM-based algorithm for data fusion reduced the relative error of change trend of annual mean temperature by 70%. The HASM-based algorithm for model-data assimilation reduced the relative error of carbon stocks by 40%. We propose five theoretical challenges and three application problems of HASM that need to be addressed to improve FTEEM.

Role of main RNA modifications in cancer:N^(6)-methyladenosine,5-methylcytosine,and pseudouridine

Cancer is one of the major diseases threatening human life and health worldwide.Epigenetic modification refers to heritable changes in the genetic material without any changes in the nucleic acid sequence and results in heritable phenotypic changes.Epigenetic modifications regulate many biological processes,such as growth,aging,and various diseases,including cancer.With the advancement of next-generation sequencing technology,the role of RNA modifications in cancer progression has become increasingly prominent and is a hot spot in scientific research.This review studied several common RNA modifications.