Targeted screening of an anti-inflammatory polypeptide from Rhopilema esculentum Kishinouye cnidoblasts and elucidation of its mechanism in alleviating ulcerative colitis based on an analysis of the gut microbiota and metabolites

Ulcerative colitis(UC)is a recurrent inflammatory bowel disease that imposes a severe burden on families and society.In recent years,exploiting the potential of marine bioactive peptides for the treatment of diseases has become a topic of intense research interest.This study revealed the mechanism underlying the protective effect of the dominant polypeptide PKKVV(Pro-Lys-Lys-Val-Val)of Rhopilema esculentum cnidoblasts against DSS-induced UC through a combined analysis of the metagenome and serum metabolome.Specifically,the polypeptide composition of R.esculentum cnidoblasts was determined by matrix-assisted laser desorption ionization time-of-flight mass spectrometry(MALDI-TOF/TOF-MS).Molecular docking showed that the dominant peptide PKKVV could bind better with tumor necrosis factor-α(TNF-α)than the original ligand.Subsequent animal experiments suggested that PKKVV could modulate disorganized gut microorganisms in mice with UC;affect serum metabolites through the arachidonic acid,glycerophospholipid and linoleic acid metabolism pathways;and further alleviate UC symptoms.This study provides a reference for the comprehensive development of marine bioactive substances and nonpharmaceutical treatments for UC.

Food-derived bio-functional peptides for the management of hyperuricemia and associated mechanism

Hyperuricemia,a metabolic disorder related to uric acid metabolism dysregulation,has become a common metabolic disease worldwide,due to changes in lifestyle and dietary structure.In recent years,owing to their high activity and few adverse effects,food-derived active peptides used as functional foods against hyperuricemia have attracted increasing attention.This article aims to focus on the challenge associated with peptide-specific preparation methods development,functional components identification,action mechanism(s)clarification,and bioavailability improvement.The current review proposed recent advances in producing the food-derived peptides with high anti-hyperuricemia activity by protein source screening and matched enzymatic hydrolysis condition adjusting,increased the knowledge about strategies to search antihyperuricemia peptides with definite structure,and emphasized the necessity of combining computer-aided approaches and activity evaluations.In addition,novel action mechanism mediated by gut microbiota was discussed,providing different insights from classical mechanism.Moreover,considering that little attention was paid previously on the structure-activity relationships of anti-hyperuricemia peptides,we collected the sequences from published studies and make a preliminary summary about the structure-activity relationships,which in turn provided guides for enzymatic hydrolysis optimization and bioavailability improvement.Hopefully,this article could promote the development,application and commercialization of food-derived anti-hyperuricemia peptides in the future.

Protective effects and microarray-based mechanism of sea cucumber hydrolysates against high-glucose induced nephrotoxicity in mouse glomerulus mesangial cells

Diabetic nephropathy(DN)is a common type of end-stage renal disease and glomerular mesangial cells(GMCs)are widely used as a cell model for DN.This study firstly investigated the inhibitory effects of the Apostichopus japonicus and Acaudina leucoprocta hydrolysates on cellular growth under high-glucose treatment,better inhibitory effect of A.japonicus hydrolysate was observed compared to that of A.leucoprocta hydrolysate.Subsequently,the global transcription profiles obtained via microarray analysis showed that 6070 and 7015 genes were identified in the A.japonicus and A.leucoprocta groups compared with the model group,respectively.Among them,transcriptions of the slc30a4,slc35dl,tppp3,tp53inpl,bcl-2,apafl,alox12b and adrala genes were restored from the levels of the model group to those of the control group,contributed to cell mitosis and proliferation in both treatment groups.In addition,other apoptosis-related genes,such as bcl-6,clu,foxo3 and akt,showed opposite trends between two groups,which might cause the difference in inhibitory effect.We preliminarily proposed that the regulation effects of A.japonicus and A.leucoprocta on the genes involved in cellular mitosis,proliferation and apoptosis,might contribute to their inhibitory activity on GMCs under high-glucose environment.

Chinese Torreya grandis cv.Merrillii seed oil affects obesity through accumulation of sciadonic acid and altering the composition of gut microbiota

Torreya grandis cv.Merrillii(Taxace,Torreya)is mainly distributed across the hilly areas of subtropical China and is well known for its nutritional value.In this study,the ameliorative effects of T.grandis seed oil on lipid metabolism were investigated,and the underlying mechanism was explored from the perspective of gut microbiota.Mice experiments showed that the rate of body mass gain in the group where the mice were fed a high-fat diet(HFD)and supplemented with 550 mg/(kg·day)T.grandis seed oil(HFD+TO550 group)was 42.27%,while it was 62.25%in the HFD group.Compared with the HFD group,the liver and fat indices,total cholesterol,triglycerides,and low-density lipoprotein cholesterol were reduced in the oil-supplement groups.Moreover,the oil supplement significantly changed the fatty acid composition and alleviated pathological damage to the liver caused by the high-fat diet.Additionally,the distinct clustering of bacteria in the composition of gut microbiota was observed in the oil treatment group compared with that in the HFD group.T.grandis seed oil significantly increased the abundance of the beneficial bacteria and short-chain fatty acid producers,including Lactobacillus,Bifidobacterium,Faecalibaculum and Allobaculum.Our results suggest that the supplements of T.grandis seed oil could alleviate hyperlipidemia caused by HFD.These positive effects are considered to be related with sciadonic acid(SCA)and are partially mediated by alterations in gut microbiota composition and functionality.

Comparative proteomic analysis reveals the effects of different fatty acid forms on high-fat diet mice

Long-chain omega-3 polyunsaturated fatty acids(LC-PUFAs),known for having many health benefits,are usually present in three forms:triglycerides(TG),ethyl esters(EE),and phospholipid(PL).In this study,the effects of these three LC-PUFAs forms(fish oil for TG and EE,krill oil for PL)on the obese mice were compared,and the proteomic changes that focused on lipid metabolism were evaluated via label-free quantitative proteomics analysis.Compared with the model group,all three of the LC-PUFA form supplementations(labeled as the FO-TG group,FO-EE group and KO-PL groups)could significantly reduce body weight gain(P<0.01).Low-density lipoprotein cholesterol levels were significantly decreased,whereas high-density lipoprotein cholesterol levels were significantly increased in the FO-TG group and FO-EE group(P<0.01),and especially in the PL group(P<0.001).Furthermore,proteomics analysis results suggested that some differentially expressed genes involved in the fatty acid degradation and oxidation pathways had a higher expression fold in the KO-PL group than in the FO-TG or FO-EE groups.Our results showed that dietary LC-PUFAs can reduce fat deposition and inhibit lipogenesis in the liver by upregulating the expression of proteins that are involved in the fatty acid degradation and oxidation pathways.Additionally,KO-PL elicits stronger effects than FO-TG or FO-EE.

Unconventional energetics of small vacancy clusters in BCC high-entropy alloy Nb_(0.75)ZrTiV_(0.5)

The stability of small vacancy clusters including divacancy,trivacancy and tetravacancy has been studied in body-centered cubic high-entropy alloy Nb_(0.75)ZrTiV_(0.5) in structures of random solid solution and short-range order by first-principles calculations and molecular dynamics simulations.Different from conventional body-centered cubic metals,the tightly bound configurations have a lower structural stability and are not preferred energetically in the studied high-entropy alloy.Instability of vacancy configurations leads to vacancy-atom exchanges that favor less compact configurations.The formation energy of small vacancy clusters is much smaller than its constituent elements of Nb and V due to the large structural adjustment induced by severe local lattice distortion.The difference in local lattice distortion and elemental arrangement in the vacancy neighborhood leads to significant site-to-site variation in vacancy cluster energy and configuration.The formation energy has a strong correlation with the local energy state of the vacancy configuration and the extent of structural relaxation.Compared to random solid solution,the structure of short-range order has a higher stability for the most compact cluster configurations and tends to have higher vacancy cluster formation energy.According to classical molecular dynamics simulations of cluster diffusion at high temperature,the studied high-entropy alloy has a higher probability of cluster dissociation compared to Nb and V.The unconventional energetics of small vacancy clusters is expected to have a profound impact on their generation,diffusion,dissociation,coalescence,as well as the defect microstructure evolution during irradiation.

Current state and prospect on the development of advanced nuclear fuel system materials:A review

The intricate balance between reactor economics and safety necessitates the emergence of new and advanced nuclear systems and,very importantly,advanced materials,which can overcome current shortcomings and bring about more economic nuclear systems with designed-in inherent safety features.These advances will achieve greater safety and better nuclear reactor economics by reaching longer reactor lives with higher levels neutron irradiation,and by providing higher operation temperatures and resistance to more aggressive corrosive environments.This paper provides a review of the current state of research and development on innovative nuclear fuel materials design and development which have the potential of benefiting simultaneously reactor economics and safety.Our discussion focuses on three areas of research:Accident-tolerant Fuels(ATFs),Oxidation Dispersion Strengthened(ODS)steels and High Entropy Alloys(HEAs).The paper also gives a prospective description of future research activities on these materials.

求职者对AI面试的接受度及其影响因素:基于公平视角的质性研究

人工智能(AI)技术已应用于人力资源选拔与面试。尽管已有研究考察了个体对AI服务的接受度,但真实参与过AI面试的求职者对AI面试的接受度尚有待挖掘。基于公平启发理论,本文采用扎根理论的研究路径,收集参加过AI面试的个体在新浪微博分享的文本数据,以及访谈了22位参与过AI面试的求职者。结果发现求职者对AI面试的接受度体现为感知易用性、感知有用性、情绪体验与参与意愿等四个维度,总体接受度较低。AI面试内容设计(评价标准相关性与合理性、AI形象设计)、面试过程设计(信息透明度、系统功能)等方面影响了求职者在AI面试中的自我表现反馈,为AI面试公平感知提供了启发式线索,并进一步塑造求职者对AI面试的接受度。AI面试环境(外界与终端)、求职者对AI面试的预期(人际互动导向、应试任务导向)起到了阶段性的调节作用。本研究将技术接受模型拓展至求职者对AI面试的接受度,挖掘了该应用场景中的独特内涵,并提出“AI面试设计-自我表现反馈-公平感知-AI面试接受度”的链式影响机制,对AI技术更好地应用于面试提供了实证依据与管理实践启示。

Prognostic value of lymphocyte count in severe COVID-19 patients with corticosteroid treatment

Dear Editor,The outbreak of coronavirus disease 2019(COVID-19)has so far caused over 108.2 million confirmed cases and over 2.3 million deaths all over the world as of February 14,2021.1 Among in-hospital patients with COVID-19,the mortality was approximately 28%,however,the percentage increased to over 60%among critically ill patients,and over 80%among those who require mechanical ventilation.2 Treatment of these severe patients is becoming one of the major challenges.

Dynein axonemal heavy chain 10 deficiency causes primary ciliary dyskinesia in humans and mice

Primary ciliary dyskinesia(PCD)is a congenital,motile ciliopathy with pleiotropic symptoms.Although nearly 50 causative genes have been identified,they only account for approximately 70%of definitive PCD cases.Dynein axonemal heavy chain 10(DNAH10)encodes a subunit of the inner arm dynein heavy chain in motile cilia and sperm flagella.Based on the common axoneme structure of motile cilia and sperm flagella,DNAH10 variants are likely to cause PCD.Using exome sequencing,we identified a novel DNAH10 homozygous variant(c.589C>T,p.R197W)in a patient with PCD from a consanguineous family.The patient manifested sinusitis,bronchiectasis,situs inversus,and asthenoteratozoospermia.Immunostaining analysis showed the absence of DNAH10 and DNALI1 in the respiratory cilia,and transmission electron microscopy revealed strikingly disordered axoneme 9+2 architecture and inner dynein arm defects in the respiratory cilia and sperm flagella.Subsequently,animal models of Dnah10-knockin mice harboring missense variants and Dnah10-knockout mice recapitulated the phenotypes of PCD,including chronic respiratory infection,male infertility,and hydrocephalus.To the best of our knowledge,this study is the first to report DNAH10 deficiency related to PCD in human and mouse models,which suggests that DNAH10 recessive mutation is causative of PCD.

A promising new class of irradiation tolerant materials:Ti_2ZrHfV_(0.5)Mo_(0.2) high-entropy alloy

Recently, high-entropy alloys(HEAs) or multi-principal-element alloys with unprecedented physical,chemical, and mechanical properties, have been considered as candidate materials used in advanced reactors due to their promising irradiation resistant behavior. Here, we report a new single-phase bodycentered cubic(BCC) structured Ti_2 ZrHfV_(0.5)Mo_(0.2) HEA possessing excellent irradiation resistance, i.e.,scarcely irradiation hardening and abnormal lattice constant reduction after helium-ion irradiation,which is completely different from conventional alloys. This is the first time to report the abnormal XRD phenomenon of metallic alloys and almost no hardening after irradiation. These excellent properties make it to be a potential candidate material used as core components in next-generation nuclear reactors. The particular irradiation tolerance derives from high density lattice vacancies/defects.

Wireless whispering-gallery-mode sensor for thermal sensing and aerial mapping

The Internet of Things(IoT)1,2 employs a large number of spatially distributed wireless sensors to monitor physical environments,e.g.,temperature,humidity,and air pressure,and has many applications,including environmental monitoring3,health care monitoring4,smart cities5,and precision agriculture.A wireless sensor can collect,analyze,and transmit measurements of its environment1,2.Currently,wireless sensors used in the IoT are predominately based on electronic devices that may suffer from electromagnetic interference in many circumstances.Being immune to the electromagnetic interference,optical sensors provide a significant advantage in harsh environments6.Furthermore,by introducing optical resonance to enhance light–matter interactions,optical sensors based on resonators exhibit small footprints,extreme sensitivity,and versatile functionalities7,8,which can significantly enhance the capability and flexibility of wireless sensors.Here we provide the first demonstration of a wireless photonic sensor node based on a whisperinggallery-mode(WGM)optical resonator,in which light propagates along the circular rim of such a structure like a sphere,a disk,or a toroid by continuous total internal reflection.The sensor node is controlled via a customized iOS app.Its performance was studied in two practical scenarios:(1)real-time measurement of the air temperature over 12 h and(2)aerial mapping of the temperature distribution using a sensor node mounted on an unmanned drone.Our work demonstrates the capability of WGM optical sensors in practical applications and may pave the way for the large-scale deployment of WGM sensors in the IoT.

Conversion of the high-yield salinomycin producer Streptomyces albus BK3-25 into a surrogate host for polyketide production

An ideal surrogate host for heterologous production of various natural products is expected to have efficient nutrient utilization,fast growth,abundant precursors and energy supply,and a pronounced gene expression.Streptomyces albus BK3-25 is a high-yield industrial strain producing type-Ⅰ polyketide sahnomycin,with a unique ability of bean oil utilization.Its potential of being a surrogate host for heterologous production of PKS was engineered and evaluated herein.Firstly,introduction of a three-gene cassette for the biosynthesis of ethylmalonyl-CoA resulted in accumulation of ethylmalonyl-CoA precursor and sahnomycin,and subsequent deletion of the sahnomycin biosynthetic gene cluster resulted in a host with rich supplies of common polyketide precursors,including malonyl-CoA,methylmalonyl-CoA,and ethylmalonyl-CoA.Secondly,the energy and reducing force were measured,and the improved accumulation of ATP and NADPH was observed in the mutant.Furthermore,the strength of a series of selected endogenous promoters based on microarray data was assessed at different growth phases,and a strong constitutive promoter was identified,providing a useful tool for further engineered gene expression.Finally,the potential of the BK3-25 derived host ZXJ-6 was evaluated with the introduction of the actinorhodin biosynthetic gene cluster from Streptomyces coelicolor,and the heterologous production of actinorhodin was obtained.This work clearly indicated the potential of the high-yield sahnomycin producer as a surrogate host for heterologous production of polyketides,although more genetic manipulation should be conducted to streamline its performance.

Dielectr ic barr ier discharge plasma-assisted modification of g-C_(3)N_(4)/Ag_(2)O/TiO_(2)-NRs composite enhanced photoelectrocatalytic activity

Dielectric barrier discharge(DBD)plasma applied as surface treatment technology was employed for the modification of Ag_(2)O and graphitic carbon nitride(g-C_(3)N_(4))powders.Subsequently,the pretreated powders were sequentially loaded onto TiO_(2)nanorods(TiO_(2)-NRs)via electro-deposition,followed by calcination at N_(2)atmosphere.The results indicated that at the optimal plasma discharge time of 5 min for modification of g-C_(3)N_(4)and Ag_(2)O,photocurrent density of ternary composite was 6 times to bare TiO_(2)-NRs under UV-visible light irradiation.Phenol was degraded by using DBD plasma-modified g-C_(3)N_(4)/Ag_(2)O/TiO_(2)-NRs electrode to analyze the photoelectrocatalytic performance.The removal rate of phenol for g-C_(3)N_(4)-5/Ag_(2)O-5/TiO_(2)-NRs electrode was about 3.07 times to that for TiO_(2)-NRs electrode.During active species scavengers'analysis,superoxide radicals and hydroxyl radicals were the main oxidation active species for pollutants degradation.A possible electron-hole separation and transfer mechanism of ternary composite with high photoelectrocatalytic performance was proposed.

一步核酸扩增技术在乳腺癌腋窝淋巴结转移评估中的应用

一步核酸扩增(OSNA)是一种针对细胞角蛋白19(CK19 mRNA)的快速半自动检测技术,可用于乳腺癌腋窝淋巴结转移的评估。目前OSNA已经在乳腺癌术中前哨淋巴结转移评估、非前哨淋巴结转移评估、pN_(2~3)腋窝淋巴结转移风险预测和一种新的基于分子的乳腺癌淋巴结分期方法[pN(mol)分类]等领域显示出了确切的临床应用价值,对于避免二次腋窝淋巴结清扫术或过度的腋窝淋巴结清扫术具有重要意义。本文综述了OSNA在乳腺癌腋窝淋巴结转移评估中的应用和研究进展,总结了这一检测方法的未来应用前景和发展方向。