MEKK1, MKK1/MKK2 and MPK4 function together in a mitogen-activated protein kinase cascade to regulate innate immunity in plants

Mitogen-activated protein kinase （MAPK） cascades play important roles in regulating plant innate immune responses. In a genetic screen to search for mutants with constitutive defense responses, we identified multiple alleles of mpk4 and mekkl that exhibit cell death and constitutive defense responses. Bimolecular fluorescence complemen- tation （BiFC） analysis showed that both MPK4 and MEKK1 interact with MKK1 and MKK2, two closely related MAPK kinases, mkkl and mkk2 single mutant plants do not have obvious mutant phenotypes. To test whether MKK1 and MKK2 function redundantly, mkkl mkk2 double mutants were generated. The mkkl mkk2 double mutant plants die at seedling stage and the seedling-lethality phenotype is temperature-dependent. Similar to the mpk4 and mekkl mutants, the mkkl mkk2 double mutant seedlings accumulate high levels of H202, display spontaneous cell death, constitutively express Pathogenesis Related （PR） genes and exhibit pathogen resistance. In addition, activation of MPK4 by fig22 is impaired in the mkkl mkk2 double mutants, suggesting that MKK1 and MKK2 function together with MPK4 and MEKK1 in a MAP kinase cascade to negatively regulate innate immune responses in plants.

Analysis of the efficacy of transcatheter arterial infusion chemotherapy in the treatment of pancreatic carcinoma

Objective:To evaluate the clinical efficacy of infusion of gemcitabine(GEM) and fluorouracil(5-FU)through the celiac artery and superior mesenteric artery in the treatment of pancreatic carcinoma(PC).Methods:We analyzed 20 patients diagnosed clinically or pathologically with PC,without metastases,who had an estimated survival duration of>3 months in our department from May 2009 to December 2014.Nine patients were treated directly without surgical resection of the tumor,while the other 11 patients were treated after surgery.In all patients,the femoral artery was punctured using the Seldinger technique,and a catheter was placed in the opening of the celiac artery or the superior mesenteric artery.We administered 500 mg/m2 GEM and 500 mg/m2 5-FU.Observational data included data on clinical efficacy and survival rates during the follow-up period of 3-72 months.Results:Twenty patients were treated 85 times with transcatheter arterial infusion chemotherapy(TAI).The survival rates were 80%,40%,35%,20%,10%,and 5% at 3,6,12,24,and 72 months,respectively.Conclusion: TAI chemotherapy with GEM and 5-FU may be a therapeutic option for the treatment of PC.

Down-regulation of Homer1b/c expression protects cultured neurons after traumatic injury

Activation of metabotropic glutamate receptor la aggravates traumatic brain injury. The constitutively expressed protein Homerlb/c participates in delivering and anchoring metabotropic glutamate receptors in neurons. Here, we aimed to verify whether down-regulation of Homerlb/c by RNA interference could protect cultured rat cortical neurons from traumatic injury. We showed that 36 hours after transfection of Homerlb/c small interfering RNA, metabotropic glutamate receptor la was present only in the neuronal cytoplasm, but not in the dendrites. Calcium fluorescence intensity was also decreased significantly. Moreover, lactate dehydrogenase concentration was significantly decreased in Homerlb/c small interfering RNA-transfected cells compared with that in untransfected and control small interfering RNA-transfected cells 24 hours after traumatic neuronal injury. Our findings indicate that down-regulation of Homerlb/c could reduce metabotropic glutamate receptor la transfer from the cell body to the dendrite, relieve calcium overload, and protect neurons from traumatic injury.

Nonlinear three-magnon scattering in low-damping La_(0.67)Sr_(0.33)MnO_(3)thin films

Three-magnon scattering,a nonlinear process in which a high-energy magnon splits into two low-energy magnons with energy and momentum conservation,has been widely studied in the magnonics community.Here,we report experimental observation of nonlinear three-magnon scattering in La_(0.67)Sr_(0.33)MnO_(3)thin films with low magnetic damping(~10^(-4))by all-electric and angle-resolved spin wave spectroscopy.The reflection spectra of the spin wave resonance with high-power excitation at Damon–Eshbach configuration demonstrate a scattering regime with gradual signal disappearance,where a magnon of Damon–Eshbach mode decays into two magnons of volume mode above the threshold power(-10 dBm)of the injected microwave.The nonlinear scattering is only allowed at low-field regime and the calculated dispersions of dipole-exchange spin wave claim the mechanism of allowed and forbidden three-magnon scattering.The films and heterostructures of La_(0.67)Sr_(0.33)MnO_(3)have been already demonstrated with rich physical phenomena and great versatility,in this work the nonlinear magnetic dynamics of La_(0.67)Sr_(0.33)MnO_(3)thin films is revealed,which offer more possibility for applications to oxide magnonics and nonlinear magnonic devices.

Research progress on chemical composition, pharmacological effects of Forsythia suspensa (Thunb.) Vahl and predictive analysis on Q-marker

Lianqiao(Forsythia suspensa(Thunb.)Vahl,Abbreviated as“F.suspensa”below)is traditional Chinese medicine in China,widely distributed all over the country and also highly rich in resources.The Northwest Territories is a genuine producing area.There are many chemical components in F.suspensa,including lignans,phenylethanolic glycosides,flavonoids,C6-C2 natural alcohols and their glycosides,phenolic acids,terpenes and volatile oils.Among them,lignans and phenylethanolic glycosides are the main active components.Based on the review of chemical components or constituents and main pharmacological activities,according to the definition of quality marker,the components of quality marker of F.suspensa were predicted and analyzed from the aspects of plant genetics and chemical composition,traditional efficacy,traditional medicine,new efficacy,blood entering composition,measurable composition,effective composition in different compatibility,and the influence of storage conditions of extract.Further research on its medicinal active ingredients will provide scientific basis for the evaluation of F.suspensa quality.

The Development of Generalized Public Bicycles in China and Its Role in the Urban Transportation System

Public bicycle service has experienced 15 years of development in Chinese cities,and China's Mainland is the world's largest public bicycle market.Choosing to use public bicycles is becoming more and more a daily habit of residents.Broadly speaking,public bicycles in Chinese cities include both public bikes with service stations and shared bicycles without service stations.Based on historical review and years of accumulated data,this paper reviews the development of general public bicycles in Chinese cities in the past 15 years.And the role of general public bicycles in China’s urban transportation system is analyzed.Finally,from the perspective of urban construction and management,some suggestions for the future development of public bicycles are put forward.

Transcriptome analysis reveals therapeutic potential of NAMPT in protecting against abdominal aortic aneurysm in human and mouse

Abdominal Aortic Aneurysm(AAA)is a life-threatening vascular disease characterized by the weakening and ballooning of the abdominal aorta,which has no effective therapeutic approaches due to unclear molecular mechanisms.Using single-cell RNA sequencing,we analyzed the molecular profile of individual cells within control and AAA abdominal aortas.We found cellular heterogeneity,with increased plasmacytoid dendritic cells and reduced endothelial cells and vascular smooth muscle cells(VSMCs)in AAA.Up-regulated genes in AAA were associated with muscle tissue development and apoptosis.Genes controlling VSMCs aberrant switch from contractile to synthetic phenotype were significantly enriched in AAA.Additionally,VSMCs in AAA exhibited cell senescence and impaired oxidative phosphorylation.Similar observations were made in a mouse model of AAA induced by Angiotensin II,further affirming the relevance of our findings to human AAA.The concurrence of gene expression changes between human and mouse highlighted the impairment of oxidative phosphorylation as a potential target for intervention.Nicotinamide phosphoribosyltransferase(NAMPT,also named VISFATIN)signaling emerged as a signature event in AAA.NAMPT was significantly downregulated in AAA.NAMPT-extracellular vesicles(EVs)derived from mesenchymal stem cells restored NAMPT levels,and offered protection against AAA.Furthermore,NAMPT-EVs not only repressed injuries,such as cell senescence and DNA damage,but also rescued impairments of oxidative phosphorylation in both mouse and human AAA models,suggesting NAMPT supplementation as a potential therapeutic approach for AAA treatment.These findings shed light on the cellular heterogeneity and injuries in AAA,and offered promising therapeutic intervention for AAA treatment.

Association of alcohol consumption with aortic aneurysm and dissection risk:results from the UK Biobank cohort study

BACKGROUND:Previous studies have reported inconsistent results with positive,negative,and J-shaped associations between alcohol consumption and the hazard of aortic aneurysm and dissection(AAD).This study aimed to examine the connections between weekly alcohol consumption and the subsequent risk of AAD.METHODS:The UK Biobank study is a population-based cohort study.Weekly alcohol consumption was assessed using self-reported questionnaires and the congenital risk of alcohol consumption was also evaluated using genetic risk score(GRS).Cox proportional hazards models were used to estimate hazard ratios(HRs)with 95% confidence intervals(CIs)for the associations between alcohol consumption and AAD.Several sensitivity analyses were performed to assess the robustness of the results.RESULTS:Among the 388,955 participants(mean age:57.1 years,47.4% male),2,895 incident AAD cases were documented during a median follow-up of 12.5 years.Compared with never-drinkers,moderate drinkers(adjusted HR:0.797,95%CI:0.646-0.984,P<0.05)and moderate-heavy drinkers(adjusted HR:0.794,95%CI:0.635-0.992,P<0.05)were significantly associated with a decreased risk of incident AAD.Interaction-based subgroup analysis revealed that the protective effect of moderate drinking was reflected mainly in participants younger than 65 years and women.CONCLUSION:Our findings support a protective effect of moderate alcohol consumption on AAD,but are limited to participants younger than 65 years and women.

Inhomogeneous-strain-induced magnetic vortex cluster in one-dimensional manganite wire

Mixed-valance manganites with strong electron correlation exhibit strong potential for spintronics,where emergent magnetic behaviors,such as propagation of high-frequency spin waves and giant topological Hall Effects can be driven by their mesoscale spin textures.Here,we create magnetic vortex clusters with flux closure spin configurations in single-crystal La0.67Sr0.33MnO3 wire.A distinctive transformation from out-of-plane domains to a vortex state is directly visualized using magnetic force microscopy at 4 K in wires when the width is below 1.0μm.The phase-field modeling indicates that the inhomogeneous strain,accompanying with shape anisotropy,plays a key role for stabilizing the flux-closure spin structure.This work offers a new perspective for understanding and manipulating the non-trivial spin textures in strongly correlated systems.

Redundant CAMTA Transcription Factors Negatively Regulate the Biosynthesis of Salicylic Acid and N-Hydroxypipecolic Acid by Modulating the Expression of SARD1 and CBP60g

Two signal molecules, salicylic acid (SA) and N-hydroxypipecolic acid (NHP), play critical roles in plant immunity. The biosynthetic genes of both compounds are positively regulated by master immune-regulating transcription factors SARD1 and CBP60g. However, the relationship between the SA and NHP pathways is unclear. CALMODULIN-BINDING TRANSCRIPTION FACTOR 1 (CAMTA1), CAMTA2, and CAMTA3 are known redundant negative regulators of plant immunity, but the underlying mechanism also remains largely unknown. In this study, through chromatin immunoprecipitation and electrophoretic mobility shift assays, we uncovered that CBP60g is a direct target of CAMTA3, which also negatively regulates the expression of SARD1, presumably via an indirect effect. The autoimmunity of camta3-1 is suppressed by sard1 cbp60g double mutant as well as ald1 and fmo1, two single mutants defective in NHP biosynthesis. Interestingly, a suppressor screen conducted in the camta1/ 2/ 3 triple mutant background yielded various mutants blocking biosynthesis or signaling of either SA or NHP, leading to nearly complete suppression of the extreme autoimmunity of camta1/ 2/ 3, suggesting that the SA and NHP pathways can mutually amplify each other. Together, these results reveal that CAMTAs repress the biosynthesis of SA and NHP by modulating the expression of SARD1 and CBP60g, and that the SA and NHP pathways are coordinated to optimize plant immune response.

Biosynthesis and Regulation of Salicylic Acid and N-Hydroxypipecolic Acid in Plant Immunity

Salicylic acid(SA)has long been known to be essential for basal defense and systemic acquired resistance(SAR).N-Hydroxypipecolic acid(NHP),a recently discovered plant metabolite,also plays a key role in SAR and to a lesser extent in basal resistance.Following pathogen infection,levels of both compounds are dramatically increased.Analysis of SA-or SAR-deficient mutants has uncovered how SA and NHP are biosynthesized.The completion of the SA and NHP biosynthetic pathways in Arabidopsis allowed better understanding of how they are regulated.In this review,we discuss recent progress on SA and NHP biosynthesis and their regulation in plant immunity.

Splicing of Receptor-Like Kinase-Encoding SNC4 and CERK1 is Regulated by Two Conserved Splicing Factors that Are Required for Plant Immunity

Plant immune receptors belonging to the receptor-like kinase （RLK） family play important roles in the recog- nition of microbial pathogens and activation of downstream defense responses. The Arabidopsis mutant snc4-1D con- tains a gain-of-function mutation in the RLK SNC4 （SUPPRESSOR OF NPRI-1, CONSTITUTIVE4）, which leads to constitutive activation of defense responses. Analysis of suppressor mutants of snc4-1D identified two conserved splicing factors, SUA （SUPPRESSOR OF ABI3-5） and RSN2 （REQUIRED FOR SNC4-1D 2）, that are required for the constitutive defense responses in snc4-1D. In sua and rsn2 mutants, SNC4 splicing is altered and the amount of 5NC4 transcripts is reduced. Further analysis showed that SUA and RSN2 are also required for the proper splicing of CERK1 （CHITIN ELICITOR RECEPTOR KINASE1）, which encodes another RLK that functions as a receptor for chitin. In sua and rsn2 mutants, induction of reactive oxygen species by chitin is reduced and the non-pathogenic bacteria Pseudomonas syringae pv. tomato DC3OOOhrcC grows to higher titers than in wild-type plants. Our study suggests that pre-mRNA splicing plays important roles in the regulation of plant immunity mediated by the RLKs SNC4 and CERK1.

Arabidopsis CALMODULIN-BINDING PROTEIN 60b plays dual roles in plant immunity

Arabidopsis SYSTEMIC ACQUIRED RESISTANCE DEFICIENT 1(SARD1)and CALMODULIN-BINDING PROTEIN 60g(CBP60g)are two master transcription factors that regulate many defense-related genes in plant immunity.They are required for immunity downstream of the receptor-like protein SUPPRESSOR OF NPR1-1,CONSTITUTIVE 2(SNC2).Constitutive defense responses in the gain-of-function autoimmune snc2-1D mutant are modestly affected in either sard1 or cbp60g single mutants but completely suppressed in the sard1 cbp60g double mutant.Here we report that CBP60b,another member of the CBP60 family,also functions as a positive regulator of SNC2-mediated immunity.Loss-of-function mutations of CBP60b suppress the constitutive expression of SARD1 and enhanced disease resistance in cbp60g-1 snc2-1D,whereas overexpression of CBP60b leads to elevated SARD1 expression and constitutive defense responses.In addition,transient expression of CBP60b in Nicotiana benthamiana activates the expression of the pSARD1::luciferase reporter gene.Chromatin immunoprecipitation assays further showed that CBP60b is recruited to the promoter region of SARD1,suggesting that it directly regulates SARD1 expression.Interestingly,knocking out CBP60b in the wild-type background leads to ENHANCED DISEASE SUSCEPTIBILITY 1(EDS1)-dependent autoimmunity,suggesting that CBP60b is required for the expression of a guardee/decoy or a negative regulator of immunity mediated by receptors carrying an N-terminal Toll-interleukin-1 receptor-like domain.

Receptor-like kinases MDS1 and MDS2 promote SUMM2-mediated immunity

Disruption of the MEKK1-MKK1/MKK2-MPK4 kinase cascade leads to activation of immunity mediated by the nucleotide-binding leucine-rich repeat(NLR)immune receptor SUMM2,which monitors the phosphorylation status of CRCK3.Here we report that two receptor-like kinases(RLKs),MDS1,and MDS2,function redundantly to promote SUMM2-mediated immunity.Activation of SUMM2-mediated immunity is dependent on MDS1,and to a less extent on MDS2.MDS1 associates with CRCK3 in planta and can phosphorylate CRCK3 in vitro,suggesting that it may target CRCK3 to positively regulate SUMM2-mediated signaling.Our finding highlights a new defense mechanism where RLKs promote NLR-mediated immunity.

Negative regulation of resistance protein-mediated immunity by master transcription factors SARD_1 and CBP60g

Summary Salicylic acid （SA） is an essential defence hormone in plants. Upon pathogen infection, induced biosynthesis of SA is mediated by Isochorismate synthase 1 （ICS1）, whose gene transcription is controlled mainly through two redundant transcription factors, SAR Deficient 1 （SARD0 and Calmodulin- binding protein 6o-like g （CBP60g）.

Deterministic reversal of single magnetic vortex circulation by an electric field

The ability to control magnetic vortex is critical for their potential applications in spintronic devices.Traditional methods including magnetic field,spin-polarized current etc.have been used to flip the core and/or reverse circulation of vortex.However,it is challenging for deterministic electric-field control of the single magnetic vortex textures with time-reversal broken symmetry and no planar magnetic anisotropy.Here it is reported that a deterministic reversal of single magnetic vortex circulation can be driven back and forth by a space-varying strain in multiferroic heterostructures,which is controlled by using a bi-axial pulsed electric field.Phase-field simulation reveals the mechanism of the emerging magnetoelastic energy with the space variation and visualizes the reversal pathway of the vortex.This deterministic electric-field control of the single magnetic vortex textures demonstrates a new approach to integrate the low-dimensional spin texture into the magnetoelectric thin film devices with low energy consumption.

Calcium channels at the center of nucleotide-binding leucine-rich repeat receptor-mediated plant immunity

Higher plants utilize a variety of immune receptors to recognize pathogens and trigger defense responses.Intracellular nucleotidebinding leucine-rich repeat receptors(NLRs)are widely used for detecting pathogen effectors(Jones et al.,2016;Zhou and Zhang,2020).NLRs are also present in animals,including mammals。

Differential requirement of BAK1 C-terminal tail in development and immunity

Summary BRI1-ASSOCIATED RECEPTOR KINASE 1 （BAK1） plays critical roles in plant developmental and immune signaling pathways. BAKI and a large number of leucine-rich repeat receptor-like kinases （LRR-RLKs） harbor a mysterious carboxyl-terminal tail （CT） beyond their kinase domain. In this study we analyzed the biological significance of this CT region using a unique bak~ mutant allele which causes deletion of the CT region. We showed that BAKt CT promotes its kinase activity and is required for pathogen-associated molec- ular pattern （PAMP）-triggered immunity, but it is dispensable for brassinosteroid responses and BAK1/ BKKl-inhibited cell death signaling. Therefore the BAK1 C-terminal tail is differentially required for its functions in development and immunity.

Epigenetic regulation of N-hydroxypipecolic acid biosynthesis by the AIPP3-PHD2-CPL2 complex

N-Hydroxypipecolic acid(NHP)is a signaling molecule crucial for systemic acquired resistance(SAR),a systemic immune response in plants that provides long-lasting and broad-spectrum protection against secondary pathogen infections.To identify negative regulators of NHP biosynthesis,we performed a forward genetic screen to search for mutants with elevated expression of the NHP biosynthesis gene FLAVIN-DEPENDENT MONOOXYGENASE 1(FMO1).Analysis of two constitutive expression of FMO1(cef)and one induced expression of FMO1(ief)mutants revealed that the AIPP3–PHD2–CPL2 protein complex,which is involved in the recognition of the histone modification H3K27me3 and transcriptional repression,contributes to the negative regulation of FMO1 expression and NHP biosynthesis.Our study suggests that epigenetic regulation plays a crucial role in controlling FMO1 expression and NHP levels in plants.

Disaster assessment for the“Belt and Road”region based on SDG landmarks

In this study,based on the EM-DAT(The Emergency Events Database)database,disaster assessment for the“Belt and Road”region was carried out in relation to the SDG_(13.1.1)indicator of the Sustainable Development Goals(SDGs)agenda launched in 2015.A new method for diagnosing trends in the SDG_(13.1.1)indicators based on the Theil-Sen median method is proposed.In addition,using the data available in the EM-DAT,an overview of disaster records is used to quantify disasters for a total of 73 countries.The disaster trends for the period 2015‒2019 were found to demon-strate the following.(1)As a result of geological and climate con-ditions,Asia and Africa are high-risk disaster areas and disasters have caused considerable economic losses and affected the popu-lations in developing and underdeveloped countries in these regions.(2)The clear positive value ofΔs_(13.1.1)found for China reflects the country’s encouraging achievements in disaster preven-tion and mitigation.(3)The value of SDG_(13.1.1)was observed to be increasing in South Asia,northwest Africa and South Africa,with the increase in India and Mauritania being the most serious.The new method proposed in this paper allows the real trend in the SDG_(13.1.1)indicator in various countries to be derived and provides critical intelligence support for international disaster risk reduction plans and sustainable development goals.