African swine fever virus MGF505-3R inhibits cGAS-STING-mediated IFN-βpathway activation by degrading TBK1

African swine fever virus(ASFV)is an important pathogen causing acute infectious disease in domestic pigs and wild boars that seriously endangers the global swine industry.As ASFV is structurally complex and encodes a large number of functional proteins,no effective vaccine has been developed to date.Thus,dissecting the mechanisms of immune escape induced by ASFV proteins is crucial.A previous study showed that the ASFV-encoded protein is an important factor in host immunity.In this study,we identified a negative regulator,MGF505-3R,that significantly downregulated cGAS/STING-and poly(dG:dC)-mediated IFN-βand interferon stimulation response element(ISRE)reporter activity and suppressed IFNB1 and IFIT2 mRNA levels.In addition,TBK1,IRF3 and IκBαphosphorylation levels were also inhibited.Mechanistically,MGF505-3R interacted with cGAS/TBK1/IRF3 and targeted TBK1 for degradation,thereby disrupting the cGAS-STING-mediated IFN-βsignaling pathway,which appears to be highly correlated with autophagy.Knockdown MGF505-3R expression enhanced IFN-βand IL-1βproduction.Taken together,our study revealed a negative regulatory mechanism involving the MGF505-3R-cGAS-STING axis and provided insights into an evasion strategy employed by ASFV that involves autophagy and innate signaling pathways.

“哲理-数理-技理”的机器学习教学方法研究

针对机器学习课程内容较为抽象,数学公式难以理解,机器学习理论远离实际应用以及教学内容多而课时少等问题,提出了哲理-数理-技理的机器学习课程教学方法。该方法以学生理解课堂教学内容为目的,更加注重对每个知识点元问题的讲解,更加注重对学习目标,课程目标的讲述,同时该方法依托实际例子激发学生学习机器学习知识的动力,使得学生能更好地理解课程内容。该方法达到了较好的课堂学习效果。

KRT4 suppresses oral squamous cell carcinoma development by reducing ATG4B-mediated autophagy

Head and neck squamous cell carcinoma is the sixth most common tumor worldwide,and half of head and neck squamous cell carcinoma patients are with oral squamous cell carcinoma(OSCC).300,000 new cases of OSCC were reported annually.Even with multi-modality treatment,the prognosis of OSCC remains unsatisfactory.Thus,it is urgent to discover novel therapeutic targets for OSCC.Some microarray studies have revealed that Keratin 4(KRT4)is downregulated in OSCC,whereas its role in OSCC development remains unknown.The present study revealed that KRT4 suppressed OSCC progression by inducing cell apoptosis and inhibiting cell invasion.In addition,KRT4 over-expression inhibited autophagy by blocking the interaction of autophagy-related 4B cysteine peptidase(ATG4B)and microtubule-associated protein 1A/1B light chain 3(LC3)to regulate apoptosis and invasion of OSCC.In conclusion,KRT4 played an important role in OSCC development through regulating ATG4B-mediated autophagy and may be a novel therapeutic drug target of OSCC.

Emerging roles of activating transcription factor (ATF) family members in tumourigenesis and immunity: Implications in cancer immunotherapy

Activating transcription factors, ATFs, are a group of bZIP transcription factors that act as homodimers or heterodimers with a range of other bZIP factors. In general, ATFs respond to extracellular signals, indicating their important roles in maintaining homeostasis. The ATF family includes ATF1, ATF2, ATF3, ATF4, ATF5, ATF6, and ATF7. Consistent with the diversity of cellular processes reported to be regulated by ATFs, the functions of ATFs are also diverse. ATFs play an important role in cell proliferation, apoptosis, differentiation and inflammation-related pathological processes. The expression and phosphorylation status of ATFs are also related to neurodegenerative diseases and polycystic kidney disease. Various miRNAs target ATFs to regulate cancer proliferation, apoptosis, autophagy, sensitivity and resistance to radiotherapy and chemotherapy. Moreover, ATFs are necessary to maintain cell redox homeostasis. Therefore, deepening our understanding of the regulation and function of ATFs will provide insights into the basic regulatory mechanisms that influence how cells integrate extracellular and intracellular signals into genomic responses through transcription factors. Under pathological conditions, especially in cancer biology and response to treatment, the characterization of ATF dysfunction is important for understanding how to therapeutically utilize ATF2 or other pathways controlled by transcription factors. In this review, we will demonstrate how ATF1, ATF2, ATF3, ATF4, ATF5, ATF6, and ATF7 function in promoting or suppressing cancer development and identify their roles in tumour immunotherapy.

The RALF1-FERONIA complex interacts with and activates TOR signaling in response to low nutrients

Target of rapamycin(TOR)kinase is an evolutionarily conserved major regulator of nutrient metabolism and organismal growth in eukaryotes.In plants,nutrients are remobilized and reallocated between shoots and roots under low-nutrient conditions,and nitrogen and nitrogen-related nutrients(e.g.,amino acids)are key upstream signals leading to TOR activation in shoots under low-nutrient conditions.However,how these forms of nitrogen can be sensed to activate TOR in plants is still poorly understood.Here we report that the Arabidopsis receptor kinase FERON IA(FER)interacts with the TOR pathway to regulate nutrient(nitrogen and amino acid)signaling under low-nutrient conditions and exerts similar metabolic effects in response to nitrogen deficiency.We found that FER and its partner,RPM1-induced protein kinase(RIPK),interact with the TOR/RAPTOR complex to positively modulate TOR signaling activity.During this process,the receptor complex FER/RIPK phosphorylates the TOR complex component RAPTOR1B.The RALF1 peptide,a ligand of the FER/RIPK receptor complex,increases TOR activation in the young leaf by enhancing FER-TOR interactions,leading to promotion of true leaf growth in Arabidopsis under lownutrient conditions.Furthermore,we showed that specific amino acids(e.g.,Gin,Asp,and Gly)promote true leaf growth under nitrogen-deficient conditions via the FER-TOR axis.Collectively,our study reveals a mechanism by which the RALF1-FER pathway activates TOR in the plant adaptive response to low nutrients and suggests that plants prioritize nutritional stress response over RALF1-mediated inhibition of cell growth under low-nutrient conditions.

植物根内皮层的发育与功能研究进展

根是植物进行水分和矿质营养吸收的重要器官.水分和矿质离子进入根的表皮,径向穿过外皮层、皮层、内皮层等结构到达中柱,在木质部中通过蒸腾作用向上运输,满足地上部分的需要.其中,内皮层结构是包围中央维管系统的最内层皮层细胞,仅由单层细胞构成,主要经历两个特殊的分化阶段,分别形成凯氏带和木栓质片层两种屏障结构,在控制植物水分吸收、营养摄取、抵御病原体入侵,以及响应胁迫环境等过程中发挥重要作用.本文就内皮层的发育、凯氏带和木栓质片层的结构与形成调控机制、内皮层在胁迫条件下的可塑性等方面进行综述,对内皮层参与植物响应非生物胁迫的研究进展展开讨论,并对未来的研究方向加以展望,为培育抗逆新物种提供了新思路.

MYB44 regulates PTI by promoting the expression of EIN2 and MPK3/6 in Arabidopsis

The plant signaling pathway that regulates pathogen-associated molecular pattern(PAMP)-triggered immunity(PTI)involves mitogen-activated protein kinase(MAPK)cascades that comprise sequential activation of several protein kinases and the ensuing phosphorylation of MAPKs,which activate transcription factors(TFs)to promote downstream defense responses.To identify plant TFs that regulate MAPKs,we investigated TF-defective mutants of Arabidopsis thaliana and identified MYB44 as an essential constituent of the PTI pathway.MYB44 confers resistance against the bacterial pathogen Pseudomonas syringae by cooperating with MPK3 and MPK6.Under PAMP treatment,MYB44 binds to the promoters of MPK3 and MPK6 to activate their expression,leading to phosphorylation of MPK3 and MPK6 proteins.In turn,phosphorylated MPK3 and MPK6 phosphorylate MYB44 in a functionally redundant manner,thus enabling MYB44 to activate MPK3 and MPK6 expression and further activate downstream defense responses.Activation of defense responses has also been attributed to activation of EIN2 transcription by MYB44,which has previously been shown to affect PAMP recognition and PTI development.AtMYB44 thus functions as an integral component of the PTI pathway by connecting transcriptional and posttranscriptional regulation of the MPK3/6 cascade.

室内空气中致病微生物的种类及检测技术概述

生物气溶胶是存在于空气中的微小生物组分,主要包含各类真菌、细菌及其代谢产物、病毒、花粉等.室内空气中生物气溶胶含有丰富的致病成分,并且这些致病成分已经引发了各种健康问题,因此受到了人们的广泛关注.各类流行性疾病的发生也促使研究者更加致力于生物气溶胶的相关研究工作.探究室内空气中的致病微生物的种类分布、可能的释放源头以及有效的检测方法,对降低生物气溶胶危害风险、实现室内致病性生物气溶胶的有效控制有重要意义.本文将从室内空气生物气溶胶可引发的疾病角度对其种类和危害展开概述,同时,也对室内生物气溶胶的可能来源以及检测方法进行了详细的讨论,旨在帮助人们了解室内生物气溶胶与人类健康之间的关系,同时为相关微生物的重点检测和防治提供有价值的信息.

CLE14 functions as a "brake signal" to suppress age-dependent and stress-induced leaf senescence by promoting JUB1-mediated ROS scavenging in Arabidopsis

Leaf senescence is an important developmental process in the plant life cycle and has a significant impact on agriculture.When facing harsh environmental conditions,monocarpic plants often initiate early leaf senes-cence as an adaptive mechanism to ensure a complete life cycle.Upon initiation,the senescence process is fine-tuned through the coordination of both positive and negative regulators.Here,we report that the small secreted peptide CLAVATA3/ESR-RELATED 14(CLE14)functions in the suppression of leaf senescence by regulating ROS homeostasis in Arabidopsis.Expression of the CLE14-encoding gene in leaves was signifi-cantly induced by age,high salinity,abscisic acid(ABA),salicylic acid,and jasmonic acid.CLE14 knockout plants displayed accelerated progression of both natural and salinity-induced leaf senescence,whereas increased CLE14 expression or treatments with synthetic CLE14 peptides delayed senescence.CLE14 pep-tide treatments also delayed ABA-induced senescence in detached leaves.Further analysis showed that over-expression of CLE14 led to reduced.ROS levels in leaves,where higher expression of ROS scavenging genes was detected.Moreover,CLE14 signaling resulted in transcriptional activation of JUB1,a NAC family tran-scription factor previously identified as a negative regulator of senescence.Notably,the delay of leaf senes-cence,reduction in H202 level,and activation of ROS scavenging genes by CLE14 peptides were dependent on JUB1.Collectively,these results suggest that the small peptide CLE14 serves as a novel"brake signal"to regulate age-dependent and stress-induced leaf senescence through JUB1-mediated ROS scavenging.

Phosphorylation of a wheat aquaporin at two sites enhances both plant growth and defense

Eukaryotic aquaporins share the characteristic of functional multiplicity in transporting distinct substrates and regulating various processes,but the underlying molecular basis for this is largely unknown.Here,we report that the wheat(Triticum aestivum)aquaporin TaPIP2;10 undergoes phosphorylation to promote photosynthesis and productivity and to confer innate immunity against pathogens and a generalist aphid pest.In response to elevated atmospheric CO_(2)concentrations,TaPIP2;10 is phosphorylated at the serine residue S280 and thereafter transports CO_(2)into wheat cells,resulting in enhanced photosynthesis and increased grain yield.In response to apoplastic H_(2)O_(2) induced by pathogen or insect attacks,TaPIP2;10 is phosphorylated at S121 and this phosphorylated form transports H_(2)O_(2) into the cytoplasm,where H_(2)O_(2)intensifies host defenses,restricting further attacks.Wheat resistance and grain yield could be simultaneously increased by TaPIP2;10 overexpression or by expressing a TaPIP2;10 phosphomimic with aspartic acid substitutions at S121 and S280,thereby improving both crop productivity and immunity.