The Magnaporthe oryzae effector Avr-PikD suppresses rice immunity by inhibiting an LSD1-like transcriptional activator

Avirulence effectors(Avrs),encoded by plant pathogens,can be recognized by plants harboring the corresponding resistance proteins,thereby initiating effector-triggered immunity(ETI).In susceptible plants,however,Avrs can function as effectors,facilitating infection via effector-triggered susceptibility(ETS).Mechanisms of Avr-mediated ETS remain largely unexplored.Here we report that the Magnaporthe oryzae effector Avr-PikD enters rice cells via the canonical cytoplasmic secretion pathway and suppresses rice basal defense.Avr-PikD interacts with an LSD1-like transcriptional activator AKIP30 of rice,and AKIP30 is also a positive regulator of rice immunity,whereas Avr-PikD impedes its nuclear localization and suppresses its transcriptional activity.In summary,M.oryzae delivers Avr-PikD into rice cells to facilitate ETS by inhibiting AKIP30-mediated transcriptional regulation of immune response against M.oryzae.

骨质疏松易感SNP rs4325274通过增强子远程调控SOX6基因的功能机制研究

骨质疏松症是一种典型的多基因复杂疾病,遗传力高达85%,其发病率已跃居常见疾病的第5位。尽管已经鉴定出大量骨质疏松易感SNP,但大多数SNP位点位于基因组非编码区,且功能机制未知。本研究旨在通过生物信息学分析和功能实验探究骨质疏松非编码功能性易感SNP rs4325274的分子调控机制。首先,通过表观注释发现该SNP所在区域处在增强子上,eQTL和Hi-C分析结果发现SNP调控的潜在靶基因是SOX6;然后,利用多种数据库进行Motif预测,并结合GEO数据库中的ChIP-seq数据分析进行了验证,结果发现转录因子HNF1A更倾向于结合SNP rs4325274-G碱基;进一步通过双荧光素酶报告基因实验验证了该SNP对SOX6基因表达的增强作用;最后,利用shRNA敲低转录因子HNF1A实验,检测靶基因SOX6的表达变化。以上研究结果初步解析了非编码区功能性SNPrs4325274作为增强子远程调控SOX6基因表达的分子机制,为复杂疾病非编码易感SNP的遗传调控研究提供新思路。

In-situ fabrication SnO2/SnS2 heterostructure for boosting the photocatalytic degradation of pollutants

Heterostructure photocatalysts with a built-in electric field have become one of the most promising strategies to enhance photogenerated electron-hole pair separation. However, close contact between the two active components of heterogeneous photocatalysts remains a problem. Herein, the in-situ fabrication of an SnO2/SnS2 heterostructure photocatalyst was performed;the structure showed enhanced photocatalytic performance resulting from the tight-contact heterostructures. The results of photoelectrochemical measurements further verified that a tight-contact heterostructure improved the separation of photogenerated electron-hole pairs. The results of EIS Bode plots also demonstrated that such in-situ fabricated SnO2/SnS2 samples exhibited the longest carrier lifetime(41.6 μs) owing to the intimate interface of SnO2/SnS2 heterostructures.

Harnessing structural instability for cell durotaxis

Cells were suggested to sense matrix rigidity by applying fluctuating forces, but the underlying mechanism remains elusive. Here with a generic filament-crosslinker modeling system for stress fibers, we demonstrate that high mechanical forces can be induced by specific protein-protein interactions with biased kinetics. Strikingly, we further find that there exist two patterns of force generation, a stable pattern and a fluctuated pattern, in agreement with previous experimental observations. Our analysis indicates that the fluctuated force profile is essentially due to force-induced structural instability during structural assembly. We suggest that how cells utilize or circumvent such stable forces or fluctuated forces may be important in other biological processes as well, though whether such forces should be regarded as passive or active is still tentative.

Mitogen activated protein kinase signaling pathways participate in the active principle region of Buyang Huanwu decoction-induced differentiation of bone marrow mesenchymal stem cells

Our preliminary studies confirmed that an active principle region of Buyang Huanwu decoction, comprising alkaloid, polysaccharide, aglycon, glucoside and volatile oil, can induce bone marrow mesenchymal stem cell differentiation into neurons. Mitogen-activated protein kinase signaling was identified as one of the key pathways underlying this differentiation process. The present study shows phosphorylated extracellular signal-regulated protein kinase and phosphorylated p38 protein expression was increased after differentiation. Cellular signaling pathway blocking agents, PD98059 and SB203580, inhibited extracellular signal-regulated protein kinase and p38 in mitogen-activated protein kinase signaling pathways respectively, mRNA and protein expression of the neuronal marker, neuron specific enolase, and neural stem cell marker, nestin, were decreased in bone marrow mesenchymal stem cells after treatment with the active principle region of Buyang Huanwu decoction. Experimental findings indicate that, extracellular signal-regulated protein kinase and p38 in mitogen-activated protein kinase signaling pathways participate in bone marrow mesenchymal stem cell differentiation into neuron-like cells, induced by the active principle region of Buyang Huanwu decoction.

Comparative Study of Global Seismicity on the Hot Engine Belt and the Cooling Seismic Belt—Improvement on Research Ideas of Earthquake Prediction

The study in this paper analyzes and compares the distribution on the global engine active seismic zone and cooling seismic belt basing on the ANSS earthquake catalog from Northern California Earthquake Data Center. An idea of the seismogenesis and earthquake prediction research is achieved by showing the stratigraphic structure in the hot engine belt. The results show that the main engine and its seismic cones are the global seismic activity area, as well as the subject of global geological disaster. Based on the conjecture of other stratum structure, the energy of crustal strong earthquake and volcano activities probably originates from the deep upper mantle. It is suggested that the research on earthquake and volcano prediction should focus on the monitor and analysis on the sub-crustal earthquake activities.

Microplastic pollution and enrichment of distinct microbiota in sediment of mangrove in Zhujiang River estuary,China

The microbial communities colonized on microplastics(MPs)have attracted widespread attention.However,few studies focused on the MPs impacts on mangrove ecosystems,particularly on bacterial communities.We investigated the MPs pollution in mangrove of Zhujiang(Pearl)River estuary(ZRE).To study the potential risk posed by MPs to the mangrove ecosystems,the differences in bacterial communities,functions,and complexity between MPs and sediment samples were reported for the first time.Microplastics(2991±1586 items/kg dry weight(dw))in sediment were mainly fibers and polyethylene,mostly transparent,and in size less than 0.5 mm.Bacterial communities and functions significantly differed from MPs in mangrove sediment.Compared with sediment,MPs significantly enriched members of Proteobacteria,Bacteroidetes,and Actinobacteria,as well as the bacteria associated with plastic-degrading and human diseases on their surface,suggesting that microbial communities on MPs may promote MPs degradation and the spread of diseases,posing potential risk to mangrove ecosystems and human health.Although bacteria on MPs exhibited a lower diversity,the co-occurrence network analysis indicated that network of bacteria colonized on MPs was bigger and more complex than those of mangrove sediment,illustrating that MPs can act as a distinct habitat in this special ecosystem.This study provides a new perspective for increasing our understanding of microplastic pollution in mangrove ecosystems.

Changes in the epigenome and transcriptome of rice in response to Magnaporthe oryzae infection

DNA methylation participates in regulating the expression of coding and non-coding regions in plants. To investigate the association between DNA methylation and pathogen infection, we used whole-genome bisulfite sequencing to survey temporal DNA methylation changes in rice after infection with the rice blast fungus Magnaporthe oryzae. In contrast to previous findings in Arabidopsis, global DNA methylation levels in rice increased slightly after rice blast infection. We identified over 38,000 differentially methylated regions(DMRs), and hypermethylated DMRs far outnumbered hypomethylated DMRs. Most DMRs were located in transposable element regions. Using transcriptome analysis, we identified 8830 differentially expressed genes(DEGs) after 1, 3, and 5 days of infection. Over one-third of DEGs, most of which were CHH-type DMRs, were associated with DMRs. Functional analysis of the CHH DMR-DEGs indicated their involvement in many important biological processes, including cell communication and response to external stimulus. The transcription of many NBS-LRR family genes was affected by changes in DNA methylation, suggesting that DNA methylation plays essential roles in the response of rice to M. oryzae infection. More broadly, the DNA methylation analysis presented here sheds light on epigenomic involvement in plant defense against fungal pathogens.

International Standardization of Blockchain and Distributed Ledger Technology:Overlaps,Gaps and Challenges

As one of the most concerned digital technologies in recent years,blockchain and distributed ledger technology are an important driving force for a new round of technological development.It is currently in the process of accelerating its evolution and maturity,and has gradually integrated with other digital technologies.It has been applied in many industries,providing decentralized solutions for various industries,realizing innovative storage models,and building a new trust system.As blockchain technology is officially incorporated into China’s new information infrastructure category,the application fields of blockchain have expanded rapidly,gradually extending from the financial field and government affairs to other fields in the real economy.At the same time,with the continuous development of the globalized economy,blockchain technology will also have a profound impact on international technological and economic development.Therefore,for the healthy and orderly development and real implementation of the blockchain industry,standardize the application of blockchain,effectively break through the cognitive and technical barriers between different countries,industries and systems on a global scale,prevent application risks,the development of the global blockchain industry needs standardization basis,which is particularly important and urgent.A sound standard system is an important key to the successful development of technology,and formulating the right standard at the right time for technology development helps ensure the ease of use and interoperability of the technology.From the perspective of international standardization,this article first introduces the general situation of ISO,ITU-T,IEEE,W3C and other international standardization organizations,and sorts out the status quo of the blockchain standardization working groups of mainstream international standardization organizations.All blockchain-related standards under development have been analyzed for the characteristics of international blockchain technology standards and industry application standards.Through data analysis,the overlaps,differences and conflicts in the field of international blockchain standard formulation are sorted out,and suggestions for blockchain standardization work in the application and development of blockchain technology standardization by international organizations and industries are put forward.The plans and layouts of future international standards are summarized to help the development of the international standardization of blockchain.

BET protein inhibitor apabetalone represses Porphyromonas gingivalis LPS-induced macrophage M1 polarization via regulating miR-130a/STAT3 axis

Periodontitis is a frequent chronic inflammatory disorder destroying periodontium.Recent studies have revealed the role of bromodomain and extraterminal domain inhibitor(BETi)and microRNA(miR)-130a in regulating macrophage polarization and pro-inflammatory response.However,little is known about whether apabetalone(a novel BETi)and miR-130a are correlated with chronic inflammatory state in periodontitis by regulating macrophage polarization.Here murine RAW264.7 macrophages were applied as an in vitro inflammatory model.After treatment with Porphyromonas gingivalis-derived lipopolysaccharide(Pg LPS)and apabetalone,the expression of macrophage M1 polarization markers and inflammatory cytokines was assessed using real-time PCR,western blot,and enzyme-linked immuno sorbent assay(ELISA).MiR-130a level was assessed using real-time PCR,and the target gene was identified using dual luciferase reporter assay.We demonstrated that apabetalone repressed Pg LPS-induced macrophage M1 polarization in a dose-dependent manner,as evidenced by decreased expression of inducible nitric oxide synthase(iNOS),CD86,and pro-inflammatory cytokines,and increased expression of Arg-1 and CD206.Mechanistically,Pg LPS increased miR-130a expression in macrophages,whereas apabetalone treatment repressed the effect.Functionally,forced expression of miR-130a promoted macrophage M1 polarization,and signal transducer and activator of transcription(STAT)-3 was the direct target gene of miR-130a in the process.Taken together,apabetalone decreases Pg LPS-induced macrophage M1 polarization via regulating miR-130a-3p/STAT3 axis,and may be a promising target for the clinical management of periodontitis.

Quantum Hierarchical Agglomerative Clustering Based on One Dimension Discrete Quantum Walk with Single-Point Phase Defects

As an important branch of machine learning,clustering analysis is widely used in some fields,e.g.,image pattern recognition,social network analysis,information security,and so on.In this paper,we consider the designing of clustering algorithm in quantum scenario,and propose a quantum hierarchical agglomerative clustering algorithm,which is based on one dimension discrete quantum walk with single-point phase defects.In the proposed algorithm,two nonclassical characters of this kind of quantum walk,localization and ballistic effects,are exploited.At first,each data point is viewed as a particle and performed this kind of quantum walk with a parameter,which is determined by its neighbors.After that,the particles are measured in a calculation basis.In terms of the measurement result,every attribute value of the corresponding data point is modified appropriately.In this way,each data point interacts with its neighbors and moves toward a certain center point.At last,this process is repeated several times until similar data points cluster together and form distinct classes.Simulation experiments on the synthetic and real world data demonstrate the effectiveness of the presented algorithm.Compared with some classical algorithms,the proposed algorithm achieves better clustering results.Moreover,combining quantum cluster assignment method,the presented algorithm can speed up the calculating velocity.

Chemokine Ligand 13 Expression is Abundant in the Tumor Microenvironment and Indicates Poor Prognosis of Kidney Clear Cell Carcinoma

The chemokine ligand 13-chemokine receptor 5(CXCL13-CXCR5)axis has been characterized as a critical tumor-promoting signaling pathway in the tumor microenvironment(TME)in multiple types of solid tumors.In this study,we analyzed the expression profile of CXCL13 in kidney clear cell carcinoma(KIRC)and its correlation with tumor-infiltrating immune cells(TIICs).A monoclonal antibody against CXCL13 with high affinity and purity was generated in our lab for western blot and immunohistochemistry(IHC).Bioinformatic analysis was performed based on bulk-seq data from the Cancer Genome Atlas(TCGA)-KIRC and single-cell RNA-seq data from scRNASeqDB and PanglaoDB.Results showed that high CXCL13 expression in TME was associated with shorter progression-free survival(PFS),disease-specific survival(DSS),and overall survival(OS).KIRC cell lines,as well as several other cancer cell lines,had negative CXCL13 expression.IHC staining from the Human Protein Atlas(HPA)and our tissue array indicated that CXCL13 might be mainly expressed by TIICs,but not KIRC tumor cells.CXCL13 expression was strongly and positively correlated withγδT cell abundance in TME.Besides,γδT cell infiltration was associated with poor survival of KIRC.Methylation 450k array data showed that CXCL13 promoter hypomethylation was common in TIICs.The methylation level of cg16361705 within the CXCL13 promoter might play an important role in modulating CXCL13 transcription.In conclusion,our study revealed that CXCL13 expression andγδT cell infiltration in TME is associated with unfavorable survival of KIRC.TIICs,most possiblyγδT cells,are the dominant source of CXCL13 in KIRC TME.

Method Research of Earthquake Prediction and Volcano Prediction in Italy

This paper adopts the earthquake catalogue of the European Mediterranean Seismological Centre (EMSC), in accordance with the principles of Seismo-Geothermics Theory and the concept of seismic cone;it discusses the integrity of the earthquake catalogue and the overview of Mediterranean seismic cones;it focuses on the structural details and structural feature of the Italian branch of the Mediterranean seismic cone;it deduces the precursory process of subcrustal earthquake activities before two earthquakes magnitude over 6 and the eruptions of Etna volcano since 2005;then it summarizes the prediction working method of Seismo-Geothermics on estimating the general shell strength, the general period, and the rough location of future earthquake or volcano activities;and finally it discusses and explains some possible problems. The principle and working process of this method were testified in card No. 0419 in 2012, the author’s prediction card, which can apply to predict for intracrustal strong earthquakes and volcano activities within the global twenty four seismic cones. The purpose of this paper is to develop the tools and methods of the prediction of future earthquake and volcano.

Preparation of High Molecular Weight Poly（L-lactide-co-caprolactone）（75/25）

P（LLA-CL）（75/25） （poly（L-lactide-co-caprolactone）（75/25）） was synthesized from high purity L-lactide and e-caprolactone using tin octoate as initiator by ring-opening polymerization, and characterized by infrared spectrum and ^1-NMR （^1H proton spectrum of nuclear magnetic resonance） spectrum. The synthesized P（LLA-CL）（75/25） is a random copolymer. The influences of polymerization temperature, polymerization time and dosage of initiator on the weight average molecular weight and the polydispersity index of P（LLA-CL）（75/25） were investigated. The optimum preparation condition of P（LLA-CL）（75/25） was： the polymerization pressure is less than 0.5 Pa, the polymerization temperature is 125℃, the n（M）/n（I） ratio is 8,000/1, the polymerization time is 36 h. Under the condition, the weight-average molecular weight of prepared P（LLA-CL）（75/25） is 45.3×10^4, and molecular weight distribution coefficient is 1.24.

Comparison of Physical Properties and Microbial Indexes of Five Kinds of Commercial Corncob Beddings

[Objectives]This study was conducted to select suitable mouse beddings from commercial corncob bedding(A-E)produced by five different manufacturers.[Methods]The physical properties and microbial indexes of the five kinds of corncob bedding were studied by means of visual inspection,dust content determination,moisture content determination,water absorption tests and microbial detection.[Results]In visual inspection,corncob bedding A was better than other four kinds.During dust content determination,corncob bedding D was higher than other 4 kinds(1.83%±0.2983%,P<0.05).In terms of moisture content,the moisture contents of the five kinds of corncob bedding were less than or equal to 10%.In the water absorption test,the water absorption capacities of the five kinds of bedding before autoclaving were all greater than 150%,and the water absorption of corncob bedding D after autoclaving was better than other four kinds(171.0±5.3,P<0.05).During microbial detection,the total number of colonies of corncob bedding B before autoclaving was higher than those of other four types(1.42×10^(5)±4.3×10^(4),P<0.05).The five kinds of commercial corncob bedding have different physical parameters and microbial conditions,and each has its own advantages and disadvantages.When purchasing and selecting corncob bedding,it is necessary to comprehensively consider the needs of daily feeding work,and choose bedding according to the effects on the health and welfare of experimental animals.[Conclusions]This study provides a reference for selecting suitable corncob bedding for mouse.

Histological and single-nucleus transcriptome analyses reveal the specialized functions of ligular sclerenchyma cells and key regulators of leaf angle in maize

Leaf angle(LA)is a crucial factor that affects planting density and yield in maize.However,the regulatory mechanisms underlying LA formation remain largely unknown.In this study,we performed a comparative histological analysis of the ligular region across various maize inbred lines and revealed that LA is significantly influenced by a two-step regulatory process involving initial cell elongation followed by subsequent lignification in the ligular adaxial sclerenchyma cells(SCs).Subsequently,we performed both bulk and single-nucleus RNA sequencing,generated a comprehensive transcriptomic atlas of the ligular region,and identified numerous genes enriched in the hypodermal cells that may influence their specialization into SCs.Furthermore,we functionally characterized two genes encoding atypical basic-helix-loop-helix(bHLH)transcription factors,bHLH30 and its homolog bHLH155,which are highly expressed in the elongated adaxial cells.Genetic analyses revealed that bHLH30 and bHLH155 positively regulate LA expansion,and molecular experiments demonstrated their ability to activate the transcription of genes involved in cell elongation and lignification of SCs.These findings highlight the specialized functions of ligular adaxial SCs in LA regulation by restricting further extension of ligular cells and enhancing mechanical strength.The transcriptomic atlas of the ligular region at single-nucleus resolution not only deepens our understanding of LA regulation but also enables identification of numerous potential targets for optimizing plant architecture in modern maize breeding.

The real-world study of the clinical characteristics,diagnosis,and treatment of advanced pancreatic cancer in China

Objective:Real-world diagnostic and treatment data for pancreatic cancer in China are lacking.As such,the present study investigated the clinical characteristics,diagnosis,and treatment of advanced pancreatic cancer(including locally advanced and metastatic disease)in the Hospital-based Advanced Pancreatic Cancer Cohort in China of the China Pancreas Data Center database.Methods:A total of 5349 Chinese patients with advanced pancreatic cancer were identified from a database.The entire course of real-world pancreatic cancer management was analyzed.Results:The proportion of patients with advanced pancreatic cancer was higher among males than females(62.4%vs 37.6%,respectively).Patients typically had a history of hypertension(30.8%),diabetes(21.6%),and cholangitis(20.2%).Abdominal pain(51.6%),abdominal distension(27.1%),jaundice(20.1%),and weight loss(16.3%)were the main symptoms observed in patients with advanced pancreatic cancer in this cohort.Serum carbohydrate antigen(CA)19-9 is one of the most common tumor markers.In the present study,2562 patients underwent first-line therapy.The median progression-free survival(PFS)for patients undergoing first-line therapy was 4.1 months.The major options for first-line therapy included gemcitabine(GEM)plus S-1(GS/X)(23.4%),nab-paclitaxel plus GEM(AG)(18.1%),oxaliplatin,irinotecan,and leucovorin-modulated fluorouracil(FOLFIRINOX;11.9%),nab-paclitaxel plus S-1(AS)(8.9%),and GEM combined with oxaliplatin/cisplatin(GEMOX/GP)(7.6%).The AS and GS/X regimens were associated with the highest PFS rates.Conclusion:This is the first study to report multicenter,real-world data regarding advanced pancreatic cancer in China.Results revealed that real-world treatment options differed from guideline recommendations,and PFS was shorter than that in previously reported data.Improving intelligent follow-up systems and standardizing diagnosis and treatment of pancreatic cancer is recommended.

First-line camrelizumab(a PD-1 inhibitor)plus apatinib(an VEGFR-2 inhibitor)and chemotherapy for advanced gastric cancer(SPACE):a phase 1 study

Patients with advanced gastric cancer typically face a grim prognosis.This phase 1a(dose escalation)and phase 1b(dose expansion)study investigated safety and efficacy of first-line camrelizumab plus apatinib and chemotherapyfor advanced gastric or gastroesophageal junction adenocarcinoma.The primary endpoints included maximum tolerated dose(MTD)in phase 1a and objective response rate(ORR)across phase 1a and 1b.Phase 1a tested three dose regimens of camrelizumab,apatinib,oxaliplatin,and S-1.Dose regimen 1:camrelizumab 200 mg on day 1,apatinib 250 mg every other day,oxaliplatin 100 mg/m^(2) on day 1,and S-140 mg twice a day on days 1-14.Dose regimen 2:same as dose regimen 1,but oxaliplatin 130mg/m.Dose regimen3:same as dose regimen 2,but apatinib 250 mg daily.Thirty-four patients were included(9 in phase 1a,25 in phase 1b).No dose-limiting toxicities occurred so no MTD was identified.Dose 3 was set for the recommended phase 2 doses and administered in phase 1b.The confrmed ORR was 76.5%(95%CI 58.8-89.3).The median progression-free survival was 8.4 months(95%CI 5.9-not evaluable[NE]),and the median overall survival(OS)was not mature(11.6-NE).Ten patients underwent surgery after treatment and the multidisciplinary team evaluation.Among 24 patients without surgery,the median OS was 19.6 months(7.8-NE).Eighteen patients(52.9%)developed grade≥3 treatment-emergent adverse events.Camrelizumab plus apatinib and chemotherapy showed favorable clinical outcomes and manageable safety for untreated advanced gastric cancer(ChiCTR2000034109).

Green Synthesized Liquid-like Dynamic Polymer Chains with Decreased Nonspecific Adhesivity for High-Purity Capture of Circulating Tumor Cells

The capture of circulating tumor cells(CTCs)is of great significance in reducing cancer mortality and complications.However,the nonspecific binding of proteins and white blood cells(WBCs)weakens the targeting capabilities of the capture surfaces,which critically hampers the efficiency and purity of the captured CTCs.Herein,we propose a liquid-like interface design strategy that consists of liquid-like polymer chains and anti-EpCAM modification processes for high-purity and high-efficiency capture of CTCs.The dynamic flexible feature of the liquid-like chains endows the modified surfaces with excellent antiadhesion property for proteins and blood cells.The liquid-like surfaces can capture the target CTCs and show high cell viability due to the environmentfriendly surface modification processes.When liquid-like surface designs were introduced in the deterministic lateral displacement(DLD)-patterned microfluidic chip,the nonspecific adhesion rate of WBCs was reduced by more than fivefold compared to that in the DLD chip without liquid-like interface design,while maintaining comparable capture efficiency.Overall,this strategy provides a novel perspective on surface design for achieving high purity and efficient capture of CTCs.

Expert consensus on the diagnosis and treatment of solid tumors with BRAF mutations

The BRAF gene is an important signaling molecule in human cells that is involved in the regulation of cell growth,differentiation,and survival.When the BRAF gene mutates,it can lead to abnormal activation of the signaling pathway,which promotes cell proliferation,inhibits cell apoptosis,and ultimately contributes to the occurrence and development of cancer.BRAF mutations are widely present in various cancers,including malignant melanoma,thyroid cancer,colorectal cancer,non-small cell lung cancer,and hairy cell leukemia,among others.BRAF is an important target for the treatment of various solid tumors,and targeted combination therapies,represented by BRAF inhibitors,have become one of the main treatment modalities for a variety of BRAF-mutation-positive solid tumors.