Safety assessment of a novel marine multi-stress-tolerant yeast Meyerozyma guilliermondii GXDK6 according to phenotype and whole genome-sequencing analysis

The application of microorganisms as probiotics is limited due to lack of safety evaluation.Here,a novel multi-stress-tolerant yeast Meyerozyma guilliermondii GXDK6 with aroma-producing properties was identified from marine mangrove microorganisms.Its safety and probiotic properties were assessed in accordance with phenotype and whole-genome sequencing analysis.Results showed that the genes and phenotypic expression of related virulence,antibiotic resistance and retroelement were rarely found.Hyphal morphogenesis genes(SIT4,HOG1,SPA2,ERK1,ICL1,CST20,HSP104,TPS1,and RHO1)and phospholipase secretion gene(VPS4)were annotated.True hyphae and phospholipase were absent.Only one retroelement(Tad1-65_BG)was found.Major biogenic amines(BAs)encoding genes were absent,except for spermidine synthase(JA9_002594),spermine synthase(JA9_004690),and tyrosine decarboxylase(inx).The production of single BAs and total BAs was far below the food-defined thresholds.GXDK6 had no resistance to common antifungal drugs.Virulence enzymes,such as gelatinase,DNase,hemolytic,lecithinase,and thrombin were absent.Acute toxicity test with mice demonstrated that GXDK6 is safe.GXDK6 has a good reproduction ability in the simulation gastrointestinal tract.GXDK6 also has a strong antioxidant ability,β-glucosidase,and inulinase activity.To sum up,GXDK6 is considered as a safe probiotic for human consumption and food fermentation.

An Assisted Diagnosis of Alzheimer’s Disease Incorporating Attention Mechanisms Med-3D Transfer Modeling

Alzheimer’s disease(AD)is a complex,progressive neurodegenerative disorder.The subtle and insidious onset of its pathogenesis makes early detection of a formidable challenge in both contemporary neuroscience and clinical practice.In this study,we introduce an advanced diagnostic methodology rooted in theMed-3D transfermodel and enhanced with an attention mechanism.We aim to improve the precision of AD diagnosis and facilitate its early identification.Initially,we employ a spatial normalization technique to address challenges like clarity degradation and unsaturation,which are commonly observed in imaging datasets.Subsequently,an attention mechanism is incorporated to selectively focus on the salient features within the imaging data.Building upon this foundation,we present the novelMed-3D transfermodel,designed to further elucidate and amplify the intricate features associated withADpathogenesis.Our proposedmodel has demonstrated promising results,achieving a classification accuracy of 92%.To emphasize the robustness and practicality of our approach,we introduce an adaptive‘hot-updating’auxiliary diagnostic system.This system not only enables continuous model training and optimization but also provides a dynamic platform to meet the real-time diagnostic and therapeutic demands of AD.

Application Value of NLR,PLR,LMR,HEART score,and POCT in Early Warning and Accurate Graded Diagnosis of High-Risk Chest Pain in Emergency Medicine

Objective: To evaluate the application value of neutrophils/lymphocytes (NLR), platelets/lymphocytes (PLR), lymphocytes/monocytes (LMR), HEART (history, electrocardiogram, age, risk factors, and troponin) score, and point-of- care testing (POCT) in the early warning and precise diagnosis of high-risk chest pain in emergency medicine. Methods: A total of 157 patients with acute chest pain who were admitted to the emergency department and chest pain treatment unit of our hospital between August 2022 and September 2023 were selected. Rapid testing of bedside myocardial markers (ultrasensitive troponin (hs-cTnI), myoglobin (MYO), creatine kinase isoenzyme (CK-MB), D-dimer (D-Dimer), and N-terminal B-type natriuretic peptide precursor (NT-proBNP)) was performed on the patients using a POCT device (ThermoKing BioMQ60proB). A HEART score was used to classify the patients into low (n = 53), intermediate (n = 59), and high-risk (n = 45) groups, and the NLR, PLR, and LMR were calculated. The NLR, PLR, and LMR values were compared among the three groups of patients, and the optimal cutoff values as well as sensitivity and specificity were determined based on receiver operating characteristic (ROC) analysis. Results: The HEART scores of patients in the low-risk, intermediate-risk, and high-risk groups were (2.72 ± 0.24), (4.75 ± 0.56), and (5.32 ± 0.73) respectively, and the differences were statistically significant (P < 0.05). Compared with the low-risk group, the intermediate-risk group and high-risk group had a significantly higher NLR and PLR, and a significantly lower LMR;the high-risk group had higher NLR and PLR and lower values of LMR as compared to the other two groups, and the difference was statistically significant (P < 0.05). The ROC curves suggested that the area under the curve, sensitivity, and specificity of the combined diagnosis of NLR, PLR, LMR, HEART score, and POCT were greater than those of LR, PLR, and LMR with HEART score and POCT alone. Conclusion: The combined application of NLR, PLR, LMR, HEART score, and POCT has significant application value in the early warning and precise diagnosis of emergency high-risk chest pain. It provides a more simple, easy-to-access, and efficient assessment index for the clinical prediction and treatment of emergency high- risk chest pain.

Recent advances in chemical protein synthesis:method developments and biological applications

The central dogma of modern biology underscores the pivotal roles proteins play in diverse biological processes,the study of which necessitates advanced methods to produce proteins with precision and versatility.Chemical protein synthesis,a powerful approach utilizing chemical reactions for the de novo construction of structurally accurate proteins,has emerged as a transformative tool for studying proteins and generating protein derivatives/mimics inaccessible by natural biological machinery,including post-translationally modified proteins,proteins comprised of unnatural amino acids,as well as mirror-image proteins.This review summarizes recent strides in synthetic method developments for chemical protein synthesis,including innovative techniques in solid-phase peptide synthesis,the challenges presented by difficult sequences in either synthesis or folding and the exploration of novel ligation reactions using both chemical and enzymatic methods.Furthermore,the review also delves into newly developed protocols for site-selective protein modifications and the generation of stapled or macrocyclized peptides/miniproteins,highlighting the power of chemical methods to make structurally diverse proteins.Recent applications of synthetic proteins in investigating post-translational modifications(phosphorylation,lipidation,glycosylation,ubiquitination,etc.),mirror-image biological processes and drug development are further discussed.Together,these topics provide a comprehensive overview of the current landscape of chemical protein synthesis.

Feedback enhanced tumor targeting delivery of albumin-based nanomedicine to amplify photodynamic therapy by regulating AMPK signaling and inhibiting GSTs

Oxidative therapies receive a limited antitumor efficiency due to the insufficient reactive oxygen species(ROS)levels at focal sites and the evolvement of antioxidant defense systems.Herein,we develop an albumin-based nanomedicine to co-deliver chlorin e6(Ce6)and COH-SR4(CS),which can simultaneously enhance the yield and lethality of intracellular ROS for amplified photodynamic therapy(PDT).In which,CS acts as both an activator of AMP-activated protein kinase(AMPK)and an inhibitor of glutathione S-transferases(GSTs).Benefiting from it,the prepared HSA-Ce6@COH-SR4(HCCS)enables positive feed-back uptake by promoting AMPK phosphorylation,leading to rapid and extensive tumor accumulation of drugs.As a result,HCCS obviously increases the ROS production to elevate intracellular oxidative stress.Furthermore,HCCS can inhibit GSTs to disturb the antioxidant defense system of tumor cells,intensifying the oxidative damage of ROS.Ultimately,the PDT of HCCS is significantly strengthened by improving the ROS yield and lethality,which greatly declines the proliferation of breast cancer in vivo.This study may open a window in the development of drug co-delivery system for enhanced oxidative therapy of tumors.

Elevated Kallistatin promotes the occurrence and progression of non-alcoholic fatty liver disease

Non-alcoholic fatty liver disease(NAFLD)is the most common chronic liver disease worldwide,and the development of nonalcoholic steatohepatitis(NASH)might cause irreversible hepatic damage.Hyperlipidemia(HLP)is the leading risk factor for NAFLD.This study aims to illuminate the causative contributor and potential mechanism of Kallistatin(KAL)mediating HLP to NAFLD.221 healthy control and 253 HLP subjects,62 healthy control and 44 NAFLD subjects were enrolled.The plasma KAL was significantly elevated in HLP subjects,especially in hypertriglyceridemia(HTG)subjects,and positively correlated with liver injury.Further,KAL levels of NAFLD patients were significantly up-regulated.KAL transgenic mice induced hepatic steatosis,inflammation,and fibrosis with time and accelerated inflammation development in high-fat diet(HFD)mice.In contrast,KAL knockout ameliorated steatosis and inflammation in high-fructose diet(HFruD)and methionine and choline-deficient(MCD)diet-induced NAFLD rats.Mechanistically,KAL induced hepatic steatosis and NASH by down-regulating adipose triglyceride lipase(ATGL)and comparative gene identification 58(CGl-58)by LRP6/Gas/PKA/GSK3βpathway through down-regulating peroxisome proliferator-activated receptor(PPARy)and up-regulating kruppel-like factor four(KLF4),respectively.CGl-58 is bound to NF-kB p65 in the cytoplasm,and diminishing CGl-58 facilitated p65 nuclear translocation and TNFa induction.Meanwhile,hepatic CGl-58-overexpress reverses NASH in KAL transgenic mice.Further,free fatty acids up-regulated KAL against thyroid hormone in hepatocytes.Moreover,Fenofibrate,one triglyceride-lowering drug,could reverse hepatic steatosis by down-regulating KAL.These results demonstrate that elevated KAL plays a crucial role in the development of HLP to NAFLD and may be served as a potential preventive and therapeutic target.

Review and prospect of NiCo_(2)O_(4)-based composite materials for supercapacitor electrodes

Supercapacitors known as typical electrochemical capacitors have been considered as one of the most promising candidates of energy storage systems owing to their advantages such as high-power density,long life span and lower production cost.The electrode materials play a crucial role on properties of supercapacitors.Hence,many researches have been focused on the development of novel electrode materials for high-performance supercapacitors.NiCo_2O_4as supercapacitor electrode material has drawn more and more attentions in recent years due to its outstanding advantages,such as high theoretical capacity,low cost,natural abundance and easy of synthesis.However,the NiCo_2O_4always suffer from severe capacity deterioration because of the low electrical conductivity and small surface area.Hence,it is necessary to systematically and comprehensively summarize the progress in understanding and modifying NiCo_2O_4-based materials from various aspects.In this review,the structure and synthesis method of NiCo_2O_4-based materials are discussed in detail.And then,the major goal of this review is to highlight new progress in using proposed strategies to improve the cycling stability and rate capacity of NiCo_2O_4-based materials,including synthesis,control of special morphologies and design of composite materials.Finally,an insight into the future research and development of Ni Co_2O_4-based materials for supercapacitors is prospected.

Recent progress of flexible aqueous multivalent ion batteries

Flexible aqueous batteries have been thriving with the growing demand for wearable and portable electrical devices.In particular,flexible aqueous mul tivalent ion batteries(FAMIBs),the charge carriers of which include Zn^(2+),Al^(3+),Mg^(2+),and Ca^(2+),have great potential for development owing to their high safety,high elemental abundance in the Earth's crust,and a multi-electron redox mechanism with a high theoretical specific capacity.Therefore,for a comprehensive understanding of this developing field,it is necessary to summarize the recent research progress of FAMIBs in a timely manner.Herein,the advancements of the state-of-the-art FAMIBs are reviewed,and the prospects toward this field are also proposed.This study focuses on the rational material and configuration design for FAMIBs in recent studies to achieve high battery performances under deformation conditions,which is elaborated on by classification of the anode,cathode,hydrogel electrolyte,and configurations of FAMIBs.Besides,the electrochemical performance of FAMIBs under flexible conditions is also reviewed from the perspective of their working voltage,specific capacity,and cycling stability.Finally,the ap proaches to improve the performance of FAMIBs are comprehensively eval uated,followed by the outlook on the challenges and opportunities in future development of FAMIBs.

Mesoporous NiCo_2O_4 nanoneedles@MnO_2 nanoparticles grown on nickel foam for electrode used in high-performance supercapacitors

Mesoporous NiCo_2O_4@MnO_2 nanoneedle arrays as electrode materials for supercapacitor grown on a conductive nickel foam were prepared by a facile hydrothermal route. The interconnected mesoporous structure of the NiCo_2O_4 nanoneedle arrays provides a large specific surface area for charge storage.The electrochemically active MnO_2 nanoparticles covered on the surface of NiCo_2O_4 nanoneedle result in a favorable synergistic storage effect because of charge redistribution at the NiCo_2O_4|MnO_2 interface,which reduces the interfacial polarization and facilitates ion diffusion. The initial specific capacitance of NiCo_2O_4@MnO_2(S2) is 1001 F g^(-1) at current density of 15 A g^(-1). The capacity retention of S2 is about87.4% after 4000 cycles, and the specific capacitance of S2 electrode only decreases from 1001 F g^(-1) to736 F g^(-1) even after 10,000 cycles. The first-principles calculations show that a chemical bonding between the NiCo_2O_4 and MnO_2 is not only helpful for stabilizing the composites but also leads to a charge redistribution at the interface, which may lead to a smaller interfacial polarization and thus beneficial for the interfacial capacity. The excellent electrochemical performance of NiCo_2O_4@MnO_2 composites(S2)can be ascribed to the high surface area, unique architecture, MnO_2 nanoparticle modification, reduced charge transfer resistance and stable interface between NiCo_2O_4 and MnO_2. The simple material synthesis and architectural design strategy provides new insights in opportunities to exhibit promising potential for practical application in energy storage.

Fast and abundant in vitro spontaneous haustorium formation in root hemiparasitic plant Pedicularis kansuensis Maxim. (Orobanchaceae)

Haustorium formation is the characteristic feature of all parasitic plants and a vital process for successful parasitism.Previous investigations on haustorium initiation and development are constricted to induced processes by host-derived signals or synthetic analogs.Spontaneous haustorium formation in the absence of host signals,a process representing an early stage in the evolution of parasitic plants,remains largely unexplored.Lack of fast and frequent formation of spontaneous haustoria greatly hinders full understanding of haustorium formation in root hemiparasites.In this study,seedlings of Pedicularis kansuensis Maxim.,a facultative root hemiparasitic species in Orobanchaceae observed to produce many spontaneous haustoria,were grown in autoclaved water agar in the absence of any known haustoriuminducing stimulants.We aimed to test the temporal and developmental pattern of spontaneous haustorium formation.Also,effects of sucrose supply and root contact on spontaneous haustorium formation were tested.Spontaneous haustoria were observed starting from six days after germination,much earlier than previously reported root hemiparasites.A majority of the spontaneous haustoria formed on lateral roots.Percentage of seedlings with spontaneous haustoria was 28.8% when grown on water agar plates,with a mean of four haustoria per seedling two weeks after germination.Haustorium formation by seedlings grown in water agar amended with 2% sucrose was more than twice of those without sucrose amendment.Singly grown seedlings were able to develop spontaneous haustoria at similar levels as those grown with another conspecific seedling.In view of the fast and abundant formation of spontaneous haustoria,P.kansuensis may be developed as an excellent experimental system in future investigations for unraveling endogenous regulation of haustorium initiation and development in root hemiparasitic plants.

Recyclable Fe_(3)O_(4)@Polydopamine(PDA) nanofluids for highly efficient solar evaporation

Volumetric solar evaporations by using light-absorbing nanoparticles suspended in liquids(nanofluids)as solar absorbers have been widely regarded as one of the promising solutions for clean water production because of its high efficiency and low capital cost compared to traditional solar distillation systems.Nevertheless,previous solar evaporation systems usually required highly concentrated solar irradiation and high capital cost,limiting the practical application on a large scale.Herein,for the first time in this work,polydopamine(PDA)-capped nano Fe_(3)O_(4)(Fe_(3)O_(4)@PDA)nanofluids were used as solar absorbers in a volumetric system for solar evaporation.The introduction of organic PDA to nano Fe_(3)O_(4)highly contributed to the high light-absorbing capacity of over 85%in wide ranges of 200–2400 nm because of the existence of numerous carbon bonds and pi(π)bonds in PDA.As a result,high evaporation efficiency of 69.93%under low irradiation of 1.0 kW m^(-2)was achieved.Compared to other nanofluids,Fe_(3)O_(4)@PDA nanofluids also provided an advantage in high unit evaporation rates.Moreover,Fe_(3)O_(4)@PDA nanofluids showed excellent reusability and recyclability owing to the preassembled nano Fe_(3)O_(4),which significantly reduced the material consumptions.These results demonstrated that the Fe_(3)O_(4)@PDA nanofluids held great promising application in highly efficient solar evaporation.

Optimization and Empirical Analysis Based on Markov Forecasting Model

The optimization model based on Markov chain is established to optimize the prediction of industrial structure and provide reference for policy adjustment.The vectorization operator is used to transform the Markov prediction model into an optimization problem with constraints,which highlights the theoretical proof and computational rigor.Based on the data of three industrial structures in Yunnan Province from 1989 to 2019,this paper establishes Markov optimization model to predict the proportion of three industrial structures in Yunnan Province from 2020 to 2030.The maximum percentage average absolute error and hill inequality coefficient of the prediction are 1.2335%and 0.2,respectively.The order-degree of the three industrial structures is a stable series,which is stable around 1 after 1996.The sample data and the predicted values show four stages of change characteristics.After 2020,the three industrial structures are stable in the"three,two and one"structure.

基于Android平台的高校辅导员管理系统设计

以Android平台为依托的先进管理系统在高校管理中的应用,能够在很大程度上缓解辅导员工作压力,在保证学生日常生活及学习质量的同时,促进了工作效率的提升。本文在对基于Android平台的高校辅导员管理系统功能需求进行分析的基础之上,从系统软件与硬件两个层面探讨了基于Android平台的高校辅导员管理系统架构设计,并且梳理了Android平台的学生、班级、成绩、考勤、勤工俭学、应急情况六大数据库表设计及管理情况。

Data Flow Analysis and Formal Method

Exceptions are those abnormal data flow which needs additional calculation to deal with. Exception analysis concerned abnormal flow contains a lot of research content, such as exception analysis method, program verification. This article introduces another research direction of exception analysis which based on formal method. The article analyses and summarizes those research literatures referring exception analysis and exception handling logic verification based on formal reasoning and model checking. In the article, we provide an overview of the relationship and difference between traditional ideas and formal method concerning program exception analysis. In the end of the article, we make some ideas about exception analysis based on formal semantic study of procedure calls. Exception handling is seen as a special semantic effect of procedures calls.

Traditional varieties of cacao(Theobroma cacao)in Madagascar:their origin and dispersal revealed by SNP markers

Cacao(Theobroma cacao L.)is an important Neotropical crop originating in South America and dispersed by European explorers,arriving in Madagascar in the late 19th century.Although Madagascar is an important producer of cocoa for the premium chocolate market,the varietal composition and genetic diversity in cacao germplasm from Madagascar,especially in traditional cacao farms,remains unknown.A total of 190 cacao accessions,including 40 farmer accessions collected from traditional cacao farms in Madagascar,and 150 accessions representing seven reference cacao populations,were analyzed using Single Nucleotide Polymorphism(SNP)markers.Multivariate analysis and Bayesian stratification resulted in the clustering of the 40 farmer accessions into three groups:Criollo,Amelonado and Trinitario.These three traditional varieties were commonly cultivated in tropical America in the 18th century,but most of them have been replaced by improved varieties.The present study demonstrated that Madagascar is distinctive in that all three traditional cacao varieties,Criollo,Amelonado and Trinitario,are still maintained on-farm for cocoa production,as in Mesoamerica and the Caribbean several hundred years ago.Results from the present study are significant in terms of understanding the early dispersal of cacao from tropical America and Asia to Africa,in addition to the well-documented route from Brazil to São Tomé&Príncipe.The results also provide new information for planning future conservation and utilization of cacao germplasm in Madagascar.

Ultrathin Ni/V-layered double hydroxide nanosheets for efficient visible-light-driven photocatalytic nitrogen reduction to ammonia

Ammonia is important for industrial development and human life.The traditional Haber Bosch method converts nitrogen into ammonia gas at high temperatures and pressures,causing serious pollution and greenhouse gas emissions.These problems prompt the nitrogen fixation method to proceed in a sustainable way.Ultrathin Ni/V-layered double hydroxides(Ni/V-LDHs)nanosheets with different proportions were prepared successfully for photocatalystic reduction of nitrogen to ammonia,through aqueous miscible organic solvent method(AMO)to achieve the higher surface area and rich oxygen vacancies,containing more carriers and active sites to enhance nitrogen reduction.And the optimal catalyst of Ni/V-LDHs 11 AMO possesses the highest photocatalytic efficiency(176μmol·g^(-1)·h^(-1)),indicating its potential application prospects in catalyst fields.Consequently,this work achieves an environmentally friendly,low-cost and efficient conversion method for nitrogen reduction to ammonia through solar energy.

Synthesis of Ras proteins and their application in biofunctional studies

Approximately 30% of human cancers are associated with RAS mutation. Ras proteins on the plasma membrane regulate a plenty of important cellular processes. The post-translational modifications(PTMs)of Ras proteins like lipidation and methylation are crucial for their correct cellular localization and biological function. Hence, obtaining Ras proteins with different kinds of modifications is the necessary prerequisite to investigate their biological properties at molecular level. In this review, we mainly summarize the developed strategies including chemical total synthesis, biosynthesis and semi-synthesis for producing Ras proteins with modifications and their application in biological studies.

基于N-磷酰化氨基酸探讨激酶磷转移机制

N-磷酰化的α-氨基酸可以发生多种磷转移反应,而且只有α-氨基酸可以被磷激活.在生命系统中,磷的转移在生物信息传递中扮演了关键角色.双组分系统(two-component system,TCS)是细菌感应并响应外界复杂环境最为重要的信号传导系统,其分子基础为磷酸根从ATP依次传递到组氨酸激酶的组氨酸(P–N键)和下游调控蛋白的天冬氨酸(P–OCO键);在高等生物中,ATP经激酶将磷酸根传递到底物蛋白的羟基(P–O键),催化中心中高度保守的酸性和碱性氨基酸不可或缺.如果N-磷酰化氨基酸是微型的TCS模型,那么高等生物激酶是否利用类似TCS的磷传递机制?本文总结了N-磷酰化α-氨基酸和激酶介导的磷转移过程,探讨N-磷酰化氨基酸模型作为磷转移系统“分子化石”的可能性,希望为激酶催化机制及基于激酶的新药研发提供新思路.