N^(6)-腺苷甲基化修饰及其对LINE-1的调控机制

长散布元件-1(long interspersed elements-1,LINE-1)是现今在人类基因组中唯一具有自主转座能力的转座子,其转座会引起细胞基因组结构和功能的改变,是导致多种严重疾病的重要因素。在转座过程中,LINE-1 mRNA是转座中间体的核心,宿主细胞对其进行相关修饰直接影响转座。N^(6)-腺苷甲基化修饰(m^(6)A)是真核细胞RNA上最丰富且动态可逆的表观遗传修饰。目前发现m^(6)A修饰也存在于LINE-1 mRNA上,参与LINE-1整个生命周期的调控,影响其转座和基因组中LINE-1相邻基因的表达,进而影响基因组稳定性、细胞自我更新与分化潜能,在人类发育和疾病中具有重要作用。本文介绍了LINE-1 m^(6)A修饰的位置、功能以及相关机制,并总结了LINE-1的m^(6)A修饰对其转座调控的研究进展,以期为相关疾病发生发展的机制研究和治疗提供新的思路。

Comparative study of different machine learning models in landslide susceptibility assessment: A case study of Conghua District, Guangzhou, China

Machine learning is currently one of the research hotspots in the field of landslide prediction.To clarify and evaluate the differences in characteristics and prediction effects of different machine learning models,Conghua District,which is the most prone to landslide disasters in Guangzhou,was selected for landslide susceptibility evaluation.The evaluation factors were selected by using correlation analysis and variance expansion factor method.Applying four machine learning methods namely Logistic Regression(LR),Random Forest(RF),Support Vector Machines(SVM),and Extreme Gradient Boosting(XGB),landslide models were constructed.Comparative analysis and evaluation of the model were conducted through statistical indices and receiver operating characteristic(ROC)curves.The results showed that LR,RF,SVM,and XGB models have good predictive performance for landslide susceptibility,with the area under curve(AUC)values of 0.752,0.965,0.996,and 0.998,respectively.XGB model had the highest predictive ability,followed by RF model,SVM model,and LR model.The frequency ratio(FR)accuracy of LR,RF,SVM,and XGB models was 0.775,0.842,0.759,and 0.822,respectively.RF and XGB models were superior to LR and SVM models,indicating that the integrated algorithm has better predictive ability than a single classification algorithm in regional landslide classification problems.

Spatially resolved transcriptomic profiling of placental development in dairy cow

The placenta plays a crucial role in successful mammalian reproduction.Ruminant animals possess a semi-invasive placenta characterized by a highly vascularized structure formed by maternal endometrial caruncles and fetal placental cotyledons,essential for full-term fetal development.The cow placenta harbors at least two trophoblast cell populations:uninucleate(UNC)and binucleate(BNC)cells.However,the limited capacity to elucidate the transcriptomic dynamics of the placental natural environment has resulted in a poor understanding of both the molecular and cellular interactions between trophoblast cells and niches,and the molecular mechanisms governing trophoblast differentiation and functionalization.To fill this knowledge gap,we employed Stereo-seq to map spatial gene expression patterns at near single-cell resolution in the cow placenta at 90 and 130 days of gestation,attaining high-resolution,spatially resolved gene expression profiles.Based on clustering and cell marker gene expression analyses,key transcription factors,including YBX1 and NPAS2,were shown to regulate the heterogeneity of trophoblast cell subpopulations.Cell communication and trajectory analysis provided a framework for understanding cell-cell interactions and the differentiation of trophoblasts into BNCs in the placental microenvironment.Differential analysis of cell trajectories identified a set of genes involved in regulation of trophoblast differentiation.Additionally,spatial modules and co-variant genes that help shape specific tissue structures were identified.Together,these findings provide foundational insights into important biological pathways critical to the placental development and function in cows.

Wafer-scale 30°twisted bilayer graphene epitaxially grown on Cu_(0.75)Ni_(0.25)(111)

Twisted bilayer graphene(TBG) has been extensively studied because of its novel physical properties and potential application in electronic devices.Here we report the synthesis and characterization of 300 TBG naturally grown on Cu_(0.75)Ni_(0.25)(111) film and investigate the electronic structure by angle-resolved photoemission spectroscopy.Compared with other substrates,our TBG with a wafer scale is acquired with a shorter growth time.The Fermi velocity and energy gap of Dirac cones of TBG are comparable with those of a monolayer on Cu_(0.85)Ni_(0.15)(111).The signature of moré lattices has not been observed in either the low-energy electron diffraction patterns or the Fermi surface map within experimental resolution,possibly due to different Cu and Ni contents in the substrates enhancing the different couplings between the substrate and the first/second layers and hindering the formation of a quasiperiodic structure.

Vertical microbial profiling of water column reveals prokaryotic communities and distribution features of Antarctic Peninsula

Prokaryotic diversity and community composition in the water column of eight stations(63 samples) around the Antarctic Peninsula of the Southern Ocean were investigated. Through pyrosequencing of the V3–V4hypervariable regions of the 16S ribosomal RNA gene, we characterized 4 720 089 valid reads representing 48 188operational taxonomic units(OTUs, 97% similarity). The community was dominated by the phyla Pseudomonadota(original name: Proteobacteria, 47%), Oxyphotobacteria(26%), and Bacteroidota(original name: Bacteroidetes, 18%), which comprised an average of 91% of the total OTUs in all samples. The prokaryotic community composition varied vertically within the water column. Water column prokaryotic communities exhibited a clear depth profile, with higher microbial richness and higher diversity observed with increasing water depth. Cluster analysis of the community composition of water column samples exhibited a similar trend with depth. Correlation with environmental factors suggested distinct variation in prokaryotic community composition with changes in depth, salinity, temperature and dissolved oxygen levels. Functional prediction showed presence of active nitrogen, sulphur and methane metabolic cycles along the vertical transect of the studied region. These results will improve our knowledge of prokaryotic diversity and community composition at different depth of water column for better understanding of the microbial ecology and nutrient cycles in Antarctic Peninsula region of the Southern Ocean.

Chiral Dirac Fermion in a Collinear Antiferromagnet

In a Dirac semimetal, the massless Dirac fermion has zero chirality, leading to surface states connected adiabatically to a topologically trivial surface state as well as vanishing anomalous Hall effect. Recently, it is predicted that in the nonrelativistic limit of certain collinear antiferromagnets, there exists a type of chiral“Dirac-like” fermion, whose dispersion manifests four-fold degenerate crossing points formed by spin-degenerate linear bands, with topologically protected Fermi arcs. Such an unconventional chiral fermion, protected by a hidden SU(2) symmetry in the hierarchy of an enhanced crystallographic group, namely spin space group, is not experimentally verified yet. Here, by angle-resolved photoemission spectroscopy measurements, we reveal the surface origin of the electron pocket at the Fermi surface in collinear antiferromagnet CoNb3S6. Combining with neutron diffraction and first-principles calculations, we suggest a multidomain collinear antiferromagnetic configuration, rendering the the existence of the Fermi-arc surface states induced by chiral Dirac-like fermions.Our work provides spectral evidence of the chiral Dirac-like fermion caused by particular spin symmetry in CoNb_(3)S_(6), paving an avenue for exploring new emergent phenomena in antiferromagnets with unconventional quasiparticle excitations.

Anchorage properties at the interface between soil and roots with branches

Roots play an important role in stabilizing and strengthening soil. This article aims to study the mechanical properties of the interface between soil and roots with branches, using the pullout test method in the laboratory. The mechanical properties of the soil-root with branches interface is determined through the pullout-force and root-slippage curve （F-S curve）. The results of investigating 24 Pinus tabulaeformis single roots and 55 P. tabulaeformis roots with branches demonstrated three kinds of pullout test failures： breakage failure on branching root, breakage failure on branching node, and pullout failure. The branch angle had a remarkable effect on the failure mode of the roots with branches： the maximum pullout force increased with the sum of the branch diameters and the branch angle. The peak slippage and the initial force had a positive correlation with the sum of the branch diameter. The sig- nificance test of correlation between branch angle and the initial force, however, showed they had no correlation. Branch angle and branch root diameter affect the anchorage properties between root system and soil. Therefore, it is important to investigate the anchorage mechanics of the roots with branches to understand the mechanism of root reinforcement and anchorage.

Regulation of Reversible Dissociation of LHCII from PSII by Phosphorylation in Plants

LHCII is a crucial light-harvesting pigment/protein complex in photosystem II (PSII) supercomplex. It also participates in the light energy redistribution between photosystems and in the photoprotection via its reversible dissociation with PSII and PSI (photosystem I). This reversible detachment of LHCII is regulated by phosphorylation of its own and PSII core protein. Under low light conditions, LHCII is phosphorylated and dissociated with PSII core protein complex and combined with PSI, which balances the excitation energy between PSII and PSI;Under high light environment, the phosphorylation of PSII core proteins makes LHCII detach from PSII. The dissociated LHCII presents in a free state, which involves in the thermal dissipation of excess excitation energy. During photodamage, dual phosphorylations of both PSII core proteins and LHCII complexes occur. The phosphorylation of D1 is conductive to the disintegration of photodamaged PSII and the cycle of repair. In this circumstance, the phosphorylation of LHCII is induced by reactive oxygen species (ROS) and then the phosphorylated LHCII migrates to PSI, into the repair cycle of damaged PSII. The ferredoxin (Fdr) and thioredoxin (Tdr) system may play a possible central role in the phosphorylation regulation on LHCII dissociation.

Genomic prediction of the performance of hybrids and the combining abilities for line by tester trials in maize

The two most important activities in maize breeding are the development of inbred lines with high values of general combining ability(GCA)and specific combining ability(SCA),and the identification of hybrids with high yield potentials.Genomic selection(GS)is a promising genomic tool to perform selection on the untested breeding material based on the genomic estimated breeding values estimated from the genomic prediction(GP).In this study,GP analyses were carried out to estimate the performance of hybrids,GCA,and SCA for grain yield(GY)in three maize line-by-tester trials,where all the material was phenotyped in 10 to 11 multiple-location trials and genotyped with a mid-density molecular marker platform.Results showed that the prediction abilities for the performance of hybrids ranged from 0.59 to0.81 across all trials in the model including the additive effect of lines and testers.In the model including both additive and non-additive effects,the prediction abilities for the performance of hybrids were improved and ranged from 0.64 to 0.86 across all trials.The prediction abilities of the GCA for GY were low,ranging between-0.14 and 0.13 across all trials in the model including only inbred lines;the prediction abilities of the GCA for GY were improved and ranged from 0.49 to 0.55 across all trials in the model including both inbred lines and testers,while the prediction abilities of the SCA for GY were negative across all trials.The prediction abilities for GY between testers varied from-0.66 to 0.82;the performance of hybrids between testers is difficult to predict.GS offers the opportunity to predict the performance of new hybrids and the GCA of new inbred lines based on the molecular marker information,the total breeding cost could be reduced dramatically by phenotyping fewer multiple-location trials.

Genome-wide association study and genomic prediction of Fusarium ear rot resistance in tropical maize germplasm

Fusarium ear rot(FER)is a destructive maize fungal disease worldwide.In this study,three tropical maize populations consisting of 874 inbred lines were used to perform genomewide association study(GWAS)and genomic prediction(GP)analyses of FER resistance.Broad phenotypic variation and high heritability for FER were observed,although it was highly influenced by large genotype-by-environment interactions.In the 874 inbred lines,GWAS with general linear model(GLM)identified 3034 single-nucleotide polymorphisms(SNPs)significantly associated with FER resistance at the P-value threshold of 1×10^(-5),the average phenotypic variation explained(PVE)by these associations was 3%with a range from 2.33%to 6.92%,and 49 of these associations had PVE values greater than 5%.The GWAS analysis with mixed linear model(MLM)identified 19 significantly associated SNPs at the P-value threshold of 1×10^(-4),the average PVE of these associations was 1.60%with a range from 1.39%to 2.04%.Within each of the three populations,the number of significantly associated SNPs identified by GLM and MLM ranged from 25 to 41,and from 5 to 22,respectively.Overlapping SNP associations across populations were rare.A few stable genomic regions conferring FER resistance were identified,which located in bins 3.04/05,7.02/04,9.00/01,9.04,9.06/07,and 10.03/04.The genomic regions in bins 9.00/01 and 9.04 are new.GP produced moderate accuracies with genome-wide markers,and relatively high accuracies with SNP associations detected from GWAS.Moderate prediction accuracies were observed when the training and validation sets were closely related.These results implied that FER resistance in maize is controlled by minor QTL with small effects,and highly influenced by the genetic background of the populations studied.Genomic selection(GS)by incorporating SNP associations detected from GWAS is a promising tool for improving FER resistance in maize.

Back-Stepping Control for Flexible Air-Breathing Hypersonic Vehicles Based on Uncertainty and Disturbance Estimator

A theoretical framework of nonlinear flight control for a flexible air-breathing hypersonic vehicle(FAHV)is proposed in this paper.In order to suppress the system uncertainty and external disturbance,an uncertainty and disturbance estimator(UDE)based back-stepping control strategy is designed for a dynamic state-feedback controller to provide stable velocity and altitude tracking.Firstly,the longitudinal dynamics of FAHV is simplified into a closure loop form with lumped uncertainty and disturbance.Then the UDE is applied to estimate the lumped uncertainty and disturbance for the purpose of control input compensation.While a nonlinear tracking differentiator is introduced to solve the problem of“explosion of term”in the back-stepping control.The stability of the UDE-based control strategy is proved by using Lyapunov stability theorem.Finally,simulation results are presented to demonstrate the capacity of the proposed control strategy.

Discovery and development suggestions of strontium-rich groundwater in Chibi City,China

1.Objectives Chibi City is located along the key development axis of the Beijing-Guangzhou high-speed rail in Hubei Province,and is one of the key towns in the middle reaches of the Yangtze River in China.Karst ground subsidence,groundwater contamination,seasonal water shortage or water shortage are important environmental geological problems that restrict economic and social development in the region.Relying on the discovery of abundant geological heritage landscape resources of Chibi City(Ancient battlefield in the period of the Three Kingdoms,Yangloudong),geothermal resources(Wuhong Mountain hot spring),the discovery of natural mineral water rich in strontium and metasilicate provides more options for the development and utilization of geological resources in Chibi City.Strontium-rich mineral water can strengthen bones,protect hearts,soften blood vessels,and has the function of anti-oxidation,anti-aging and immunity enhancement.It is a kind of high-quality water that is very beneficial to human health.Therefore,identifying its distribution and potential is key to the development of strontium rich mineral water industry in Chibi City.

CH_3NH_3 Formed by Electron Injection at Heterojunction Inducing Peculiar Properties of CH_3NH_3PbI_3 Material

The effect of formed CH_3NH_3 at the heterojunction on properties of CH_3NH_3PbI_3 material is investigated based on experiment and theoretical calculation. Our calculation results show that the giant dielectric constant, anomalous hysteresis and long-lasting polarization for CH_3NH_3PbI_3 originate from the formed CH_3NH_3 at the heterojunction. It is found that the induced weak EPS by the reorientation of CH_3NH_3 sub-group along the built-in electric field enables us to effectively increase the ordering of entire lead-halide framework. In addition, the heterojunction has an advantage of channel separation between carrier transport and electron diffusion. These properties of the heterojunction are the main origin of the high efficiency of CH_3NH_3PbI_3 solar cells.

A Hybrid Local/Nonlocal Continuum Mechanics Modeling of Damage and Fracture in Concrete Structure at High Temperatures

This paper proposes a hybrid peridynamic and classical continuum mechanical model for the high-temperature damage and fracture analysis of concrete structures.In this model,we introduce the thermal expansion into peridynamics and then couple it with the thermoelasticity based on the Morphing method.In addition,a thermomechanical constitutive model of peridynamic bond is presented inspired by the classic Mazars model for the quasi-brittle damage evolution of concrete structures under high-temperature conditions.The validity and effectiveness of the proposed model are verified through two-dimensional numerical examples,in which the influence of temperature on the damage behavior of concrete structures is investigated.Furthermore,the thermal effects on the fracture path of concrete structures are analyzed by numerical results.

Photoinhibition of Leaves with Different Photosynthetic Carbon Assimilation Characteristics in Maize (<i>Zea mays</i>)

Strong light decreases the rate of photosynthesis and assimilates production of crop plants. Plants with different carbon reduction cycles respond differently to strong light stress. However, variation in photoinhibition in leaves with different photosynthetic characteristics in maize is not clear. In this experiment, we used the first leaves (with an incomplete C4 cycle) and fifth leaves (with a complete C4 cycle) of maize plants as well as the fifth leaves (C3 cycle) of tobacco plants as a reference to measure the photosynthetic rate (PN) and chlorophyll a parameters under strong light stress. During treatment, PN, the maximal fluorescence (Fm), the maximal quantum yield of PSII photochemistry (Fv/Fm), and the number of active photosystem II (PSII) reaction centers per excited cross-section (RC/CSm) declined dramatically in all three types of leaves but to different degrees. PN, Fm, Fv/Fm, and RC/CSm were less inhibited by strong light in C4 leaves. The results showed that maize C4 leaves with higher rates of photosynthesis are more tolerant to strong light stress than incomplete C4 leaves, and the carbon reduction cycle is more important to photoprotection in C4 leaves, while state transition is critical in incomplete C4 leaves.

Different Effects of Malate on the Activities of Photosystem II in Detached Leaves of Maize and Tobacco

Malate is the first stable product after CO2 is fixed in NADP-dependent malic enzyme (NADP-ME) type of C4 plants, which transfers CO2 and the reducing equivalent from mesophyll cell (MC) to vascular bundle sheath cell (BSC) chloroplasts and affects the redox state of BSC. The aim of this experiment is to investigate the effect of exogenous malate on the activity of photosystem II (PS II) in C4 and C3 plants. The leaf discs from the 5th fully expanded leaves of maize (NADP-ME type C4 plants) and the 10th fully expanded leaves of tobacco (C3 plants) were treated with malate of 50, 100 μM and the chlorophyll fluorescence parameters were measured. Malate treatments decreased the photochemical reaction efficiency (FV/FM) in maize leaves, as a result of rising in initial fluorescence (FO) and decreasing in maximal fluorescence (FM). The number of active PS II reaction center (RC) per excited cross section (RC/CS) declined in malate-treated maize, suggesting that malate inactivated PS II RC. Malate treatments also increased Wk, representing the severity of oxygen-evolving complex (OEC) damage, and decreased the rate of photosynthetic oxygen evolution. We conclude that exogenous malate regulates the activity and structure of PS II in C4 plant maize. No significant changes in the activity of PS II were observed in malate-treated C3 plant tobacco. It is suggested that the short term malate treatment will inhibit PS II of leaves which have C4 anatomy and C4 enzymes.

Fli1 acts in parallel with Pu.1 to control macrophage and neutrophil fate in zebrafish

Macrophages and neutrophils are key components of myeloid cells and play critical roles in innate immune responses,organ formation,and tissue homeostasis.The integrity of their functions heavily relies on the generation of a proper number of mature macrophages and neutrophils through embryonic and adult myelopoiesis.In mammalian adult myelopoiesis,oligopotent common myeloid progenitors(CMPs)are known to be the earliest myeloid progenitors,which give rise to granulocyte-macrophage progenitors(GMPs),subsequently differentiate into unipotent neutrophil and macrophage precursors,and finally,mature macrophages and neutrophils(Orkin and Zon,2008).In contrast,the ontogeny of embryonic myelopoiesis and the mechanism underlying the formation of macrophages and neutrophils remainless understood.

Celastrol suppresses colorectal cancer via covalent targeting peroxiredoxin 1

As a terpenoids natural product isolated from the plant Thunder God Vine,Celastrol is widely studied for its pharmacological activities,including anti-tumor activities.The clinical application of Celastrol is strictly limited due to its severe side effects,whereas previously revealed targets and mechanism of Celastrol seldom reduce its in vivo toxicity via structural optimization.Target identification has a far-reaching influence on the development of innovative drugs,and omics data has been widely used for unbiased target prediction.However,it is difficult to enrich target of specific phenotype from thousands of genes or proteins,especially for natural products with broad promising activities.Here,we developed a text-mining-based web-server tool to enrich targets from omics data of inquired compounds.Then peroxiredoxin 1(PRDX1)was identified as the ROS-manipulating target protein of Celastrol in colorectal cancer.Our solved high-resolution crystal structure revealed the unique covalent binding mode of Celastrol with PRDX1.New derivative compound 19-048 with improved potency against PRDX1 and selectivity towards PRDX2~PRDX6 were synthesized based on crystal structure analysis.Both Celastrol and 19-048 effectively suppressed the proliferation of colorectal cancer cells.The anti-tumor efficacy of Celastrol and 19-048 was significantly diminished on xenograft nude mice bearing PRDX1 knock-down colorectal cancer cells.Several downstream genes of p53 signaling pathway were dramatically up-regulated with Celastrol or 19-048 treatment.Our findings reveal that the side effects of Celastrol could be reduced via structural modification,and PRDX1 inhibition is promising for the treatment of colorectal cancer.

Small molecules targeting the innate immune cGAS-STING-TBK1 signaling pathway

Multiple cancer immunotherapies including chimeric antigen receptor T cell and immune checkpoint inhibitors(ICIs)have been successfully developed to treat various cancers by motivating the adaptive anti-tumor immunity.Particularly,the checkpoint blockade approach has achieved great clinic success as evidenced by several U.S.Food and Drug Administration(FDA)-approved antiprogrammed death receptor 1/ligand 1 or anti-cytotoxic T lymphocyte associated protein 4 antibodies.However,the majority of cancers have low clinical response rates to these ICIs due to poor tumor immunogenicity.Indeed,the cyclic guanosine monophosphate-adenosine monophosphate synthase-stimulator of interferon genes-TANK-binding kinase 1(cGAS-STING-TBK1)axis is now appreciated as the major signaling pathway in innate immune response across different species.Aberrant signaling of this pathway has been closely linked to multiple diseases,including auto-inflammation,virus infection and cancers.In this perspective,we provide an updated review on the latest progress on the development of small molecule modulators targeting the cGAS-STING-TBK1 signaling pathway and their preclinical and clinical use as a new immune stimulatory therapy.Meanwhile,highlights on the clinical candidates,limitations and challenges,as well as future directions in this field are also discussed.Further,small molecule inhibitors targeting this signaling axis and their potential therapeutic use for various indications are discussed as well.

Alectinib: a novel second generation anaplastic lymphoma kinase(ALK) inhibitor for overcoming clinically-acquired resistance

The development of inhibitors for the tyrosine anaplastic lymphoma kinase(ALK) has advanced rapidly, driven by biology and medicinal chemistry. The first generation ALK inhibitor crizotinib was granted US FDA approval with only four years of preclinical and clinical testing. Although this drug offers significant clinical benefit to the ALK-positive patients, resistance has been developed through a variety of mechanisms. In addition to ceritinib, alectinib is another second-generation ALK inhibitor launched in 2014 in Japan. This drug has a unique chemical structure bearing a 5H-benzo[b]carbazol-11(6H)-one structural scaffold with an IC_(50) value of 1.9 nmol/L, and is highly potent against ALK bearing the gatekeeper mutation L1196 M with an IC_(50) of 1.56 nmol/L. In the clinic, alectinib is highly efficacious in treatment of ALK-positive non-small cell lung cancer(NSCLC), and retains potency to combat crizotinib-resistant ALK mutations L1196 M, F1174 L, R1275 Q and C1156 Y.