Transcriptomics reveals substance biosynthesis and transport on membranes of Listeria monocytogenes affected by antimicrobial lipopeptide brevilaterin B

Listeria monocytogenes is a worrisome food-borne pathogen threatening global food safety.Our previous study proved that lipopeptide brevilaterin B showed efficient antibacterial activity against L.monocytogenes by interacting with the cell membrane.This research further explored the antibacterial mechanism of brevilaterin B against L.monocytogenes at the sub-minimum inhibition concentration via transcriptomic analysis.Brevilaterin B induced growth inhibition rather than direct membrane lysis in L.monocytogenes at the minimum inhibitory concentration.Transcriptomic analysis showed 1779 difference expressed genes,including 895 up-regulated and 884 down-regulated genes.Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analysis indicated that brevilaterin B influenced multiple pathways of L.monocytogenes,including peptidoglycan biosynthesis,membrane transport(ATP-binding cassette transports,ion transport),cellular metabolism(amino acid and lipid metabolism),ATP synthesis,and activation of the stress response(quorum sensing and bacterial chemotaxis).In conclusion,brevilaterin B affects gene expression related to biosynthesis,transport and stress response pathways on the membrane of L.monocytogenes.The present work provides the first transcriptomic assessment of the antibacterial mechanism of lipopeptide brevilaterin B at the gene level.

Feedback iterative learning control for time-delay systems based on 2D analysis approach

This paper deals with the iterative learning control （ILC） design for multiple-input multiple-output （MIMO）,time-delay systems （TDS）.Two feedback ILC schemes are considered using the so-called two-dimensional （2D） analysis approach.It shows that continuous-discrete 2D Roesser systems can be developed to describe the entire learning dynamics of both ILC schemes,based on which necessary and sufficient conditions for their stability can be provided.A numerical example is included to validate the theoretical analysis.

Optimal set integer programming algorithm for multiple maneuvering targets tracking in clutter

The aim of this paper is to solve the problems of multitarget tracking in clutter. Firstly, the data association of measurement-to-target is formulated as an integer programming problem. Through using the linear programming （LP） based branchand-bound method and adjusting the constraint conditions, an optimal set integer programming （OSIP） algorithm is then proposed for tracking multiple non-maneuvering targets in clutter. For the case of maneuvering targets, this paper introduces the OSIP algorithm into the filtering step of the interacting multiple model （IMM） algorithm resulting in the IMM based on OSIP algorithm. Extensive Monte Carlo simulations show that the presented algorithms can obtain superior estimations even in the case of high density noises.

Efficacy and safety of CM310 in moderate-to-severe atopic dermatitis:A multicenter,randomized,double-blind,placebo-controlled phase 2b trial

Background:Atopic dermatitis(AD)affects approximately 10%of adults worldwide.CM310 is a humanized monoclonal antibody targeting interleukin-4 receptor alpha that blocks interleukin-4 and interleukin-13 signaling.This trial aimed to evaluate the efficacy and safety of CM310 in Chinese adults with moderate-to-severe AD.Methods:This multicenter,randomized,double-blind,placebo-controlled,phase 2b trial was conducted in 21 medical institutions in China from February to November 2021.Totally 120 eligible patients were enrolled and randomized(1:1:1)to receive subcutaneous injections of 300 mg CM310,150 mg CM310,or placebo every 2 weeks for 16 weeks,followed by an 8-week follow-up period.The primary endpoint was the proportion of patients achieving≥75%improvement in the Eczema Area and Severity Index(EASI-75)score from baseline at week 16.Safety and pharmacodynamics were also studied.Results:At week 16,the proportion of EASI-75 responders from baseline was significantly higher in the CM310 groups(70%[28/40]for high-dose and 65%[26/40]for low-dose)than that in the placebo group(20%[8/40]).The differences in EASI-75 response rate were 50%(high vs.placebo,95%CI 31%-69%)and 45%(low vs.placebo,95%CI 26%-64%),with both P values<0.0001.CM310 at both doses also significantly improved the EASI score,Investigator’s Global Assessment score,daily peak pruritus Numerical Rating Scale,AD-affected body surface area,and Dermatology Life Quality Index compared with placebo.CM310 treatment reduced levels of thymus and activation-regulated chemokine,total immunoglobulin E,lactate dehydrogenase,and blood eosinophils.The incidence of treatment-emergent adverse events(TEAEs)was similar among all three groups,with the most common TEAEs reported being upper respiratory tract infection,atopic dermatitis,hyperlipidemia,and hyperuricemia.No severe adverse events were deemed to be attributed to CM310.Conclusion:CM310 at 150 mg and 300 mg every 2 weeks demonstrated significant efficacy and was well-tolerated in adults with moderate-to-severe AD.Trial Registration:ClinicalTrials.gov,NCT04805411.

Progress in the preparation,identification and biological activity of walnut peptides

Walnuts are rich in protein and are a high-quality plant protein resource.In recent years,with the growth of consumer demand for functional food and food for special medical purpose,the use of walnut protein for the preparation of functional walnut peptide ingredients or additives and other compositions has received increasing attention.However,the improvement of the yield of walnut peptides and the clarification of their functional activities are the bottlenecks that limit the development of these peptides.To this end,this article reviews the pretreatment,preparation,purification and identification processes of walnut peptides,as well as their biological activities such as antioxidant activity,antitumour activity,improvement of memory,antihypertension and regulation of metabolic disorders are elaborated to provide a reference for the industrial development of walnut peptides.

蝉花菌丝联合海昆肾喜胶囊对糖尿病肾小管上皮细胞自噬-溶酶体通路的影响

目的探讨蝉花菌丝联合海昆肾喜胶囊对糖尿病肾病(DN)肾小管上皮细胞自噬-溶酶体的影响与机制。方法将24只大鼠腹腔单次注射链脲佐菌素(STZ)诱导SD大鼠高血糖模型后,随机分为模型组(DN)和治疗组(DN+蝉花菌丝联合海昆肾喜胶囊),用药24周;另外10只未诱导高血糖大鼠设为对照组。检测各组大鼠肾功能指标,取肾皮质行组织病理学检查,采用Western印迹检测大鼠分离肾小管的胶原蛋白-Ⅲ、α-平滑肌肌动蛋白(α-SMA)、转录因子EB(TFEB)、自噬泡标记蛋白LC3和自噬底物p62表达。将HK-2细胞分为牛血清白蛋白(Co-BSA)组、Co-BSA治疗组、糖基化终末产物-BSA(AGEs-BSA)组及AGEs-BSA-治疗组。Western印迹检测各组细胞p62、TFEB表达;以TFEB质粒转染HK-2细胞,通过RT-PCR检测过表达效率,观察各组HK-2细胞溶酶体红色荧光探针荧光强度,并检测各组细胞组织蛋白酶活性。结果与对照组大鼠相比,模型组大鼠的血肌酐(Scr)、24 h尿蛋白水平增高、LC3、p62、胶原蛋白-Ⅲ和α-SMA表达明显增多,而肾小球滤过率(GFR)、TFEB表达明显减少。与模型组大鼠相比,治疗组大鼠的Scr、24 h尿蛋白均明显降低,GFR明显升高,LC3、p62、胶原蛋白-Ⅲ和α-SMA表达明显减少,TFEB表达明显增多。在HK-2细胞中,TFEB和p62的表达情况与在大鼠肾组织中相似。与Co-BSA组相比,AGEs-BSA组的探针荧光强度和组织蛋白酶活性明显减弱;过表达TFEB后,AGEs-BSA组的荧光强度和组织蛋白酶活性均明显增强。结论蝉花菌丝联合海昆肾喜胶囊对糖尿病肾小管上皮细胞可能具有上调TFEB表达、调节自噬-溶酶体通路的作用。

Robust stability of interval parameter matrices

This note is devoted to the problem of robust stability of interval parameter matrices. Based on some basic facts relating the H∞ norm of a transfer function to the Riccati matrixinequality and Hamilton matrix, several test conditions with parameter perturbation bounds are obtained.

Tracking control for first-order multi-agent systems

In this paper,the conventional tracking control problem is expanded to first-order multi-agent systems,which can be solved by directly guiding any agent in the group.The following three kinds of desired motions are considered for all agents to track:1)stillness in space,2)variable motion with known acceleration,3)variable motion with partly unknown acceleration.Specifically,fixed networks with time delays and switching networks without delays are both considered in case 1).Switching networks with and without time delays are both studied in case 2),while for 3),switching networks without delays are mainly investigated.A numerical simulation example is included to illustrate the results.