Trimethylamine N-oxide generation process was influenced by the proportion and source of macronutrients in the diet

Trimethylamine N-oxide(TMAO)is a risk factor of various chronic diseases,which was produced by metabolism from precursors to trimethylamine(TMA)in gut and the oxidation from TMA in liver.The TMA generation was influenced by diet,mainly due to the rich TMAO precursors in diet.However,it was still unclear that the effects of different proportion and source of macronutrients in different dietary pattern on the production process of TMAO.Here,the generation of TMA from precursors and TMAO from TMA was determined after single oral choline chloride and intraperitoneal injection TMA,respectively,in mice fed with carbohydrates,proteins and fats in different proportion and sources.The results suggested that the generation of TMAO was increased by low non-meat protein and high fat via enhancing the production of TMAO from TMA,and decreased by plant protein and refined sugar via reducing TMA production from precursors in gut and TMAO transformation from TMA in liver.The high fat and high sugar diets accelerating the development of atherosclerosis did not increase the production of TMAO,the risk factor for atherosclerosis,which indicated that the dietary compositions rather than the elevated TMAO level might be a more key risk factor for atherosclerosis.

Consistent and Specific Multi-View Functional Brain Networks Fusion for Autism Spectrum Disorder Diagnosis

Functional brain networks (FBN) based on resting-state functional magnetic resonance imaging (rs-fMRI) have become an important tool for exploring underlying organization patterns in the brain, which can provide an objective basis for brain disorders such as autistic spectrum disorder (ASD). Due to its importance, researchers have proposed a number of FBN estimation methods. However, most existing methods only model a type of functional connection relationship between brain regions-of-interest (ROIs), such as partial correlation or full correlation, which is difficult to fully capture the subtle connections among ROIs since these connections are extremely complex. Motivated by the multi-view learning, in this study we propose a novel Consistent and Specific Multi-view FBNs Fusion (CSMF) approach. Concretely, we first construct multi-view FBNs (i.e., multiple types of FBNs modelling various relationships among ROIs), and then these FBNs are decomposed into a consistent representation matrix and their own specific matrices which capture their common and unique information, respectively. Lastly, to obtain a better brain representation, it is fusing the consistent and specific representation matrices in the latent representation spaces of FBNs, but not directly fusing the original FBNs. This potentially makes it more easily to find the comprehensively brain connections. The experimental results of ASD identification on the ABIDE datasets validate the effectiveness of our proposed method compared to several state-of-the-art methods. Our proposed CSMF method achieved 72.8% and 76.67% classification performance on the ABIDE dataset.

Extracting Multiple Nodes in a Brain Region of Interest for Brain Functional Network Estimation and Classification

Purpose: Brain functional networks (BFNs) has become important approach for diagnosis of some neurological or psychological disorders. Before estimating BFN, obtaining blood oxygen level dependent (BOLD) representative signals from brain regions of interest (ROIs) is important. In the past decades, the common method is generally to take a ROI as a node, averaging all the voxel time series inside it to extract a representative signal. However, one node does not represent the entire information of this ROI, and averaging method often leads to signal cancellation and information loss. Inspired by this, we propose a novel model extraction method based on an assumption that a ROI can be represented by multiple nodes. Methods: In this paper, we first extract multiple nodes (the number is user-defined) from the ROI based on two traditional methods, including principal component analysis (PCA), and K-means (Clustering according to the spatial position of voxels). Then, canonical correlation analysis (CCA) was issued to construct BFNs by maximizing the correlation between the representative signals corresponding to the nodes in any two ROIs. Finally, to further verify the effectiveness of the proposed method, the estimated BFNs are applied to identify subjects with autism spectrum disorder (ASD) and mild cognitive impairment (MCI) from health controls (HCs). Results: Experimental results on two benchmark databases demonstrate that the proposed method outperforms the baseline method in the sense of classification performance. Conclusions: We propose a novel method for obtaining nodes of ROId based on the hypothesis that a ROI can be represented by multiple nodes, that is, to extract the node signals of ROIs with K-means or PCA. Then, CCA is used to construct BFNs.

新创企业商业模式设计的机制研究——基于创业学习视角的单案例研究

商业模式设计是一个持续改进并不断完善的过程,但现有研究对新创企业在不同阶段创业学习对商业模式设计的影响机制尚不清晰。本文以赛尔公司为案例研究对象,基于企业生命周期理论,从创业学习视角,探讨了创业学习如何影响企业商业模式设计过程。研究发现,在新创企业发展的不同阶段,商业模式设计存在差异性;学习方式与新创企业成长阶段相匹配,即孕育期由先天性学习主导,婴儿期由经验学习主导,学步期由模仿学习主导,青春期由探索性学习主导,嫁接学习在婴儿期、学步期和青春期起到辅助作用;创业学习直接影响着不同阶段的商业模式设计,从孕育期形成商业模式框架,到婴儿期商业模式雏形初成,进而到学步期形成相对清晰的商业模式,再到青春期商业模式设计进一步完善,不同方式的创业学习分别发挥着积极作用。研究结论丰富和完善了商业模式设计理论,深化了创业学习与商业模式设计关系研究,对创业实践具有一定指导作用。

含硅芳炔树脂的改性及复合材料性能

合成了苯乙炔全封端含硅芳炔树脂(FEC-PSA)和含炔丙氧基苯并口恶嗪(P-appe),通过与含硅芳炔树脂(PSA)混合得到了4种不同共混质量比的改性含硅芳炔树脂,用模压成型制备了单向T800碳纤维增强改性含硅芳炔树脂复合材料。利用红外光谱、核磁共振氢谱、差示扫描量热分析和热重分析等方法对改性含硅芳炔树脂及其复合材料的结构和性能进行了研究。结果表明,共混树脂的黏度随温度的升高和加入P-appe质量分数增加而明显下降。当P-appe质量分数为30%时,共混树脂固化物5%热失重温度(Td5)为531℃,800℃残留率为85%;共混树脂浇铸体的弯曲强度为41.5 MPa,冲击强度达5.5 kJ/m2;改性PSA树脂经T800碳纤维增强,其复合材料的弯曲强度和弯曲模量在常温下为1557 MPa和153 GPa,层间剪切强度为66 MPa。

Research status and prospects of melt refining and purification technology of magnesium alloys

Refining and purification is a significant way to obtain pure and high-quality magnesium alloy melts.This paper summarizes the flux refining methods and non-flux purification methods(blowing purification,filtration purification,electromagnetic purification and ultrasonic purification).It also introduces the composite refining technologies that have been widely researched and applied in recent years,including low-voltage pulse electromagnetic technology,ultrasonic argon purification,self-purification technology and non-flux continuous purification technology.Among them,the non-flux continuous purification technology integrates a variety of purification methods,which can produce high-quality magnesium alloy continuously and steadily,realize environmental protection production,and achieve remarkable technical and economic benefits.

Reversing ferroptosis resistance by MOFs through regulation intracellular redox homeostasis

As a non-apoptotic cell death form,ferroptosis offers an alternative approach to overcome cancer chemotherapy resistance.However,accumulating evidence indicates cancer cells can develop ferroptosis resistance by evolving antioxidative defense mechanisms.To address this issue,we prepared a Buthionine-(S,R)-sulfoximine(BSO)loaded metal organic framework(MOF)of BSO-MOF-HA(BMH)with the combination effect of boosting oxidative damage and inhibiting antioxidative defense.MOF nanoparticle was constructed by the photosensitizer of[4,4,4,4-(porphine-5,10,15,20-tetrayl)tetrakis(benzoic acid)](TCPP)and the metal ion of Zr6,which was further decorated with hyaluronic acid(HA)in order to impart active targeting to CD44 receptors overexpressed cancer cells.BMH exhibited a negative charge and spherical shape with average particle size about 162.5nm.BMH was found to restore the susceptibility of 4T1 cells to ferroptosis under irradiation.This was attributed to the combination of photodynamic therapy(PDT)andγ-glutamylcysteine synthetase inhibitor of BSO,shifting the redox balance to oxidative stress.Enhanced ferroptosis also induced the release of damage associated molecular patterns(DAMPs)to maturate dendritic cells and activated T lymphocytes,leading to superior anti-tumor performance in vivo.Taken together,our findings demonstrated that boosting oxidative damage with photosensitizer serves as an effective strategy to reverse ferroptosis resistance.

The absorption kinetics of Antarctic krill oil phospholipid liposome in blood and the digestive tract of healthy mice by single gavage

Antarctic krill(Euphausia superba)oil has been gaining increasing attention due to its nutritional and functional potentials.Krill oil usually contains a high concentration(about 50%)of phospholipids(AKOP)rich in DHA and EPA accompanied with 30%–40%triacylglycerols.Phospholipids can be made into liposomes without emulsifiers due to its amphiphilic characteristics.However,the absorption kinetics of AKOP liposome in vivo is not clear,which restrict the molecular mechanism analysis related to its distinct bioactivities.The lipid analysis in serum,small intestinal content and wall was carried out after oral administration of AKOP liposome to illustrate its absorption kinetics in blood and the digestive tract of healthy mice by single gavage.The major type of the obtained AKOP was phosphatidylcholine,and the total contents of the DHA and EPA were 29.31%.AKOP liposome was almost completely digested in the small intestine in 1 h and the hydrolysis products could be quickly absorbed by intestinal enterocytes.The DHA in serum peaked at 2 h after administration of AKOP liposome.AKOP liposome could be quickly digested and absorbed in vivo.The obtained results might provide a scientific basis for the molecular mechanism analysis related to distinct bioactivities of Antarctic krill oil phospholipid.

MUTS-Based Cooperative Target Stalking for A Multi-USV System

This paper is concerned with the cooperative target stalking for a multi-unmanned surface vehicle(multi-USV)system.Based on the multi-agent deep deterministic policy gradient(MADDPG)algorithm,a multi-USV target stalking(MUTS)algorithm is proposed.Firstly,a V-type probabilistic data extraction method is proposed for the first time to overcome shortcomings of the MADDPG algorithm.The advantages of the proposed method are twofold:1)it can reduce the amount of data and shorten training time;2)it can filter out more important data in the experience buffer for training.Secondly,in order to avoid the collisions of USVs during the stalking process,an action constraint method called Safe DDPG is introduced.Finally,the MUTS algorithm and some existing algorithms are compared in cooperative target stalking scenarios.In order to demonstrate the effectiveness of the proposed MUTS algorithm in stalking tasks,mission operating scenarios and reward functions are well designed in this paper.The proposed MUTS algorithm can help the multi-USV system avoid internal collisions during the mission execution.Moreover,compared with some existing algorithms,the newly proposed one can provide a higher convergence speed and a narrower convergence domain.

CHDTEPDB:Transcriptome Expression Profile Database and Interactive Analysis Platform for Congenital Heart Disease

CHDTEPDB(URL:http://chdtepdb.com/)is a manually integrated database for congenital heart disease(CHD)that stores the expression profiling data of CHD derived from published papers,aiming to provide rich resources for investigating a deeper correlation between human CHD and aberrant transcriptome expression.The develop-ment of human diseases involves important regulatory roles of RNAs,and expression profiling data can reflect the underlying etiology of inherited diseases.Hence,collecting and compiling expression profiling data is of critical significance for a comprehensive understanding of the mechanisms and functions that underpin genetic diseases.CHDTEPDB stores the expression profiles of over 200 sets of 7 types of CHD and provides users with more convenient basic analytical functions.Due to the differences in clinical indicators such as disease type and unavoidable detection errors among various datasets,users are able to customize their selection of corresponding data for personalized analysis.Moreover,we provide a submission page for researchers to submit their own data so that increasing expression profiles as well as some other histological data could be supplemented to the database.CHDTEPDB is a user-friendly interface that allows users to quickly browse,retrieve,download,and analyze their target samples.CHDTEPDB will significantly improve the current knowledge of expression profiling data in CHD and has the potential to be exploited as an important tool for future research on the disease.

氮化碳负载铂催化剂的制备、表征及对肉桂醛加氢的催化性能

通过尿素的高温聚合制备了片层状氮化碳g-C3N4,采用乙二醇还原法载铂得到Pt/g-C3N4催化剂。以X射线衍射(XRD)、X射线光电子能谱(XPS)、扫描电子显微镜(SEM)、透射电子显微镜(TEM)、傅里叶变换红外光谱(FT-IR)、比表面与孔隙度分析和电感耦合等离子体原子发射光谱(ICP-AES)等对所制备催化剂进行了表征,并在肉桂醛加氢反应中考察了其催化性能。结果表明,载体g-C3N4含有大量的含N基团,能有效稳定金属纳米粒子;Pt纳米粒子均匀分散在g-C3N4表面,且Pt粒径在2~3 nm之间;载体煅烧温度对催化剂的择性加氢性能有明显影响,550℃煅烧后的g-C3N4,所负载Pt在较温和的条件下表现出较明显的活性,肉桂醛转化率为30%,肉桂醇选择性为66%左右。重复使用3次,催化剂活性基本不变,具有良好的稳定性。

Facile Preparation of Fe-N-C Oxygen Reduction Electrocatalysts from Metal Organic Frameworks for Zn-Air Battery

It is critical to study efficient,stable oxygen reduction reaction(ORR)electrocatalysts due to insufficient stability and expensive price of Pt/C catalysts for Zn-air batteries.Fe–N–C electrocatalysts was synthesized by a facile solvent-green method and the efficiency of Fe–N–C optimized was studied as potential ORR electrocatalysts under alkaline condition.Results indicated that it had excellent ORR activity with E_(1/2)of 0.93 V,which was competitive to that of Pt/C-JM under the same conditions.Moreover,the assembled Zn-air battery exhibited discharge potential and charge potential of 1.2 V,2.32 V at 5 mA cm^(−2)with high stability,respectively.Overall,all results illustrated that Fe–N–C is an excellent ORR electrocatalyst in the field of metal air battery.Additionally,this work opens a good way to synthesize highly efficient electrocatalysts from metal organic framework and to investigate ORR mechanism of efficient chemical energy to electricity conversion.

Asymmetric Janus Fibers with Bistable Thermochromic and Efficient Solar-Thermal Properties for Personal Thermal Management

The compelling combination of thermochromism and multifunctional wearable heaters in smart textiles has received increas-ing attention given the significant synergistic effect of green solar heat supply and energy storage.However,due to color incompatibility and poor knittability,developing fabrics with bistable thermochromic properties to achieve efficient solar-thermal management remains a challenging endeavor.Here,by combining bistable thermochromic,photochromic,and efficient solar-thermal properties,we constructed an asymmetric Janus(Janus A/B)fiber(BTCSJF)that can simultaneously display two colors and help with energy reserve while harvesting solar power.Benefiting greatly from donor-acceptor elec-tron transfer,dynamic hydrogen bonding,and supercooling properties,BTCSJF displays a quick switch in color,excellent bistability,and enhanced performance in storing phase-change energy.In addition,BTCSJF can be self-heated by 35.6℃higher than conventional fibers because it can capture and store solar energy.This research outlines a method to fabricate braided fibers with two theoretically incompatible properties that have promising implications for self-powered integrated bistable color-changing and personal thermal management applications.

Immune-related signature identifies IL1R2 as an immunological and prognostic biomarker in pancreatic cancer

Objective:Pancreatic cancer is one of the most aggressive malignancies,a robust prognostic signature and novel biomarkers are urgently needed for accurate stratification of the patients and optimization of clinical decision-making.Methods:A list of bioinformatic analysis were applied in public dataset to construct an immune-related signature.Furthermore,the most pivotal gene in the signature was identified.The potential mechanism of the core gene function was revealed through GSEA,CIBERSORT,ESTIMATE,immunophenoscore(IPS)algorithm,single-cell analysis,and functional experiment.Results:An immune-related prognostic signature and associated nomogram were constructed and validated.Among the genes constituting the signature,interleukin 1 receptor type II(IL1R2)was identified as the gene occupying the most paramount position in the risk signature.Meanwhile,knockdown of IL1R2 significantly inhibited the proliferation,invasion,and migration ability of pancreatic cancer cells.Additionally,high IL1R2 expression was associated with reduced CD8+T cell infiltration in pancreatic cancer microenvironment,which may be due to high programmed cell death-ligand-1(PD-L1)expression in cancer cells.Finally,the IPS algorithm proved that patients with high IL1R2 expression possessed a higher tumor mutation burden and a higher probability of benefiting from immunotherapy.Conclusion:In conclusion,our study constructed an efficient immune-related prognostic signature and identified the key role of IL1R2 in the development of pancreatic cancer,as well as its potential to serve as a biomarker for immunotherapy efficacy prediction for pancreatic cancer.

Early screening and diagnosis strategies of pancreatic cancer:a comprehensive review

Pancreatic cancer is a highly malignant digestive system tumor with a poor prognosis.Most pancreatic cancer patients are diagnosed at an advanced stage or even metastasis due to its highly aggressive characteristics and lack of typical early symptoms.Thus,an early diagnosis of pancreatic cancer is crucial for improving its prognosis.Currently,screening is often applied in high-risk individuals to achieve the early diagnosis of pancreatic cancer.Fully understanding the risk factors of pancreatic cancer and pathogenesis could help us identify the high-risk population and achieve early diagnosis and timely treatment of pancreatic cancer.Notably,accumulating studies have been undertaken to improve the detection rate of different imaging methods and the diagnostic accuracy of endoscopic ultrasound-guided fine-needle aspiration(EUS-FNA)which is the golden standard for pancreatic cancer diagnosis.In addition,there are currently no biomarkers with sufficient sensitivity and specificity for the diagnosis ofpancreatic cancer to be applied in the clinic. As the only serum biomarkerapproved by the United States Food and Drug Administration, carbohydrateantigen 19-9 (CA19-9) is not recommended to be used in the early screeningof pancreatic cancer because of its limited specificity. Recently, increasingnumbers of studies focused on the discovering of novel serum biomarkersand exploring their combination with CA19-9 in the detection of pancreaticcancer. Besides, the application of liquid biopsy involving circulating tumor cells(CTCs), circulating tumor DNA (ctDNA), microRNAs (miRNAs), and exosomesin blood and biomarkers in urine, and saliva in pancreatic cancer diagnosis aredrawing more and more attention. Furthermore, many innovative technologiessuch as artificial intelligence, computer-aided diagnosis system, metabolomicstechnology, ion mobility spectrometry (IMS) associated technologies, and novelnanomaterials have been tested for the early diagnosis of pancreatic cancer andhave shown promising prospects. Hence, this review aims to summarize therecent progress in the development of early screening and diagnostic methods,including imaging, pathological examination, serological examination, liquidbiopsy, as well as other potential diagnostic strategies for pancreatic cancer.

Metformin inhibits pancreatic cancer metastasis caused by SMAD4 deficiency and consequent HNF4G upregulation

Pancreatic ductal adenocarcinoma(PDAC)has poor prognosis due to limited therapeutic options.This study examines the roles of genome-wide association study identified PDAC-associated genes as therapeutic targets.We have identified HNF4G gene whose silencing most effectively repressed PDAC cell invasiveness.HNF4G overexpression is induced by the deficiency of transcriptional factor and tumor suppressor SMAD4.Increased HNF4G are correlated with SMAD4 deficiency in PDAC tumor samples and associated with metastasis and poor survival time in xenograft animal model and in patients with PDAC(log-rank P=0.036;HR=1.60,95%CI=1.03–2.47).We have found that Metformin suppresses HNF4G activity via AMPK-mediated phosphorylation-coupled ubiquitination degradation and inhibits in vitro invasion and in vivo metastasis of PDAC cells with SMAD4 deficiency.Furthermore,Metformin treatment significantly improve clinical outcomes and survival in patients with SMAD4-deficient PDAC(log-rank P=0.022;HR=0.31,95%CI=0.14–0.68)but not in patients with SMAD4-normal PDAC.Pathway analysis shows that HNF4G may act in PDAC through the cell-cell junction pathway.These results indicate that SMAD4 deficiency-induced overexpression of HNF4G plays a critical oncogenic role in PDAC progression and metastasis but may form a druggable target for Metformin treatment.

The evolving view of thermogenic fat and its implications in cancer and metabolic diseases

The incidence of metabolism-related diseases like obesity and type 2 diabetes mellitus has reached pandemic levels worldwide and increased gradually.Most of them are listed on the table of high-risk factors for malignancy,and metabolic disorders systematically or locally contribute to cancer progression and poor prognosis of patients.Importantly,adipose tissue is fundamental to the occurrence and development of these metabolic disorders.White adipose tissue stores excessive energy,while thermogenic fat including brown and beige adipose tissue dissipates energy to generate heat.In addition to thermogenesis,beige and brown adipocytes also function as dynamic secretory cells and a metabolic sink of nutrients,like glucose,fatty acids,and amino acids.Accordingly,strategies that activate and expand thermogenic adipose tissue offer therapeutic promise to combat overweight,diabetes,and other metabolic disorders through increasing energy expenditure and enhancing glucose tolerance.With a better understanding of its origins and biological functions and the advances in imaging techniques detecting thermogenesis,the roles of thermogenic adipose tissue in tumors have been revealed gradually.On the one hand,enhanced browning of subcutaneous fatty tissue results in weight loss and cancer-associated cachexia.On the other hand,locally activated thermogenic adipocytes in the tumor microenvironment accelerate cancer progression by offering fuel sources and is likely to develop resistance to chemotherapy.Here,we enumerate current knowledge about the significant advances made in the origin and physiological functions of thermogenic fat.In addition,we discuss the multiple roles of thermogenic adipocytes in different tumors.Ultimately,we summarize imaging technologies for identifying thermogenic adipose tissue and pharmacologic agents via modulating thermogenesis in preclinical experiments and clinical trials.

Mechanisms of obesity-and diabetes mellitus-related pancreatic carcinogenesis:a comprehensive and systematic

Research on obesity-and diabetes mellitus(DM)-related carcinogenesis has expanded exponentially since these two diseases were recognized as important risk factors for cancers.The growing interest in this area is prominently actuated by the increasing obesity and DM prevalence,which is partially responsible for the slight but constant increase in pancreatic cancer(PC)occurrence.PC is a highly lethal malignancy characterized by its insidious symptoms,delayed diagnosis,and devastating prognosis.The intricate process of obesity and DM promoting pancreatic carcinogenesis involves their local impact on the pancreas and concurrent wholebody systemic changes that are suitable for cancer initiation.The main mechanisms involved in this process include the excessive accumulation of various nutrients and metabolites promoting carcinogenesis directly while also aggravating mutagenic and carcinogenic metabolic disorders by affecting multiple pathways.Detrimental alterations in gastrointestinal and sex hormone levels and microbiome dysfunction further compromise immunometabolic regulation and contribute to the establishment of an immunosuppressive tumor microenvironment(TME)for carcinogenesis,which can be exacerbated by several crucial pathophysiological processes and TME components,such as autophagy,endoplasmic reticulum stress,oxidative stress,epithelialmesenchymal transition,and exosome secretion.This review provides a comprehensive and critical analysis of the immunometabolic mechanisms of obesity-and DM-related pancreatic carcinogenesis and dissects how metabolic disorders impair anticancer immunity and influence pathophysiological processes to favor cancer initiation.

Stable-isotope probing of bacterial community for dissolved inorganic carbon utilization in Microcystis aeruginosa-dominated eutrophic water

Dissolved inorganic carbon(DIC) is an important source of carbon in aquatic ecosystems,especially under conditions of increased frequency of cyanobacterial bloom. However, the importance of bacteria in direct or indirect utilization of DIC has been widely overlooked in eutrophic freshwater. To identify the functional bacteria that can actively utilize DIC in eutrophic freshwater during cyanobacterial bloom, stable-isotope probing(SIP) experiments were conducted on eutrophic river water with or without inoculation with cyanobacteria(Microcystis aeruginosa). Our 16 S rRNA sequencing results revealed the significance of Betaproteobacteria, with similar relative abundance as Alphaproteobacteria, in the active assimilation of H^(13)CO^(3-) into their DNA directly or indirectly, which include autotrophic genera Betaproteobacterial ammonia-oxidizing bacteria. Other bacterial groups containing autotrophic members, e.g. Planctomycetes and Nitrospira, also presented higher abundance among free-living bacteria in water without cyanobacteria. Microcystis aggregates showed a preference for some specific bacterial members that may utilize H^(13)CO^(3-) metabolized by Microcystis as organic matter, e.g. Bacteroidetes(Cytophagales, Sphingobacteriales), and microcystindegrading bacteria Betaproteobacteria(Paucibacter/Burkholderiaceae). This study provides some valuable information regarding the functional bacteria that can actively utilize DIC in eutrophic freshwater.