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Coxsackievirus B3 HFMD animal models in Syrian hamster and rhesus monkey

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Virologica Sinica 2024年第2期39卷 290-300页

作者： Suqin Duan Wei Zhang Yongjie Li Yanyan Li Yuan Zhao Weihua Jin Quan Liu Mingxue Li Wenting Sun Lixiong Chen Hongjie Xu Jie Tang Jinghan Hou Zijun Deng Fengmei Yang Shaohui Ma Zhanlong He Institute of medical Biology Chinese Academy of Medical Sciences Medical Primate Research Center Peking Union Medical CollegeYunnan Key Laboratory of Vaccine Research Development on Severe Infectious DiseaseKunming650118China

Coxsackievirus B3(CVB3)is the pathogen causing hand,foot and mouth disease(HFMD),which manifests across a spectrum of clinical severity from mild to severe.However,CVB3-infected mouse models mainly demonstrate viral myocarditis and pancreatitis,failing to replicate human HFMD symptoms.Although several enteroviruses have been evaluated in Syrian hamsters and rhesus monkeys,there is no comprehensive data on CVB3.In this study,we have first tested the susceptibility of Syrian hamsters to CVB3 infection via different routes.The results showed that Syrian hamsters were successfully infected with CVB3 by intraperitoneal injection or nasal drip,leading to nasopharyngeal colonization,acute severe pathological injury,and typical HFMD symptoms.Notably,the nasal drip group exhibited a longer viral excretion cycle and more severe pathological damage.In the subsequent study,rhesus monkeys infected with CVB3 through nasal drips also presented signs of HFMD symptoms,viral excretion,serum antibody conversion,viral nucleic acids and antigens,and the specific organ damages,particularly in the heart.Surprisingly,there were no significant differences in myocardial enzyme levels,and the clinical symptoms resembled those often associated with common,mild infections.In summary,the study successfully developed severe Syrian hamsters and mild rhesus monkey models for CVB3-induced HFMD.These models could serve as a basis for understanding the disease pathogenesis,conducting pre-trial prevention and evaluation,and implementing post-exposure intervention.

关键词： Coxsackievirus B3(CVB3) Hand foot and mouth disease(HFMD) Animal models Syrian hamster Rhesus monkey

Integrated analysis of public datasets for the discovery and validation of survival-associated genes in solid tumors

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The Innovation 2024年第3期5卷 129-137页

作者： Balázs Gyorffy Department of Biophysics Medical SchoolUniversity of Pecs7624 PecsHungary Department of Bioinformatics Semmelweis University1094 BudapestHungary Cancer Biomarker research group Institute of Molecular Life SciencesHUN-REN Research Centre for Natural Sciences1117 BudapestHungary

Identifying genes with prognostic significance that can act as biomarkers in solid tumors can help stratify patients and uncover novel therapy targets.Here,our goal was to expand our previous ranking analysis of survival-associated genes in various solid tumors to include colon cancer specimens with available transcriptomic and clinical data.A Gene Expression Omnibus search was performed to identify available datasets with clinical data and raw gene expression measurements.A combined database was set up and integrated into our Kaplan-Meier plotter,making it possible to identify genes with expression changes linked to altered survival.As a demonstration of the utility of the platform,the most powerful genes linked to overall survival in colon cancer were identified using uni-and multivariate Cox regression analysis.The combined colon cancer database includes 2,137 tumor samples from 17 independent cohorts.The most significant genes associated with relapse-free survival with a false discovery rate below 1%in colon cancer carcinoma were RBPMS(hazard rate[HR]=2.52),TIMP1(HR=2.44),and COL4A2(HR=2.36).The three strongest genes associated with shorter survival in stage II colon cancer include CSF1R(HR=2.86),FLNA(HR=2.88),and TPBG(HR=2.65).In summary,a new integrated database for colon cancer is presented.A colon cancer analysis subsystem was integrated into our Kaplan-Meier plotter that can be used to mine the entire database(https://***).The portal has the potential to be employed for the identification and prioritization of promising biomarkers and therapeutic target candidates in multiple solid tumors including,among others,breast,lung,ovarian,gastric,pancreatic,and colon cancers.

关键词： colon tumors analysis

Design and verification of an FPGA programmable logic element based on Sense-Switch pFLASH

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Frontiers of Information Technology & Electronic Engineering 2024年第4期25卷 485-499页

作者： Zhengzhou CAO Guozhu LIU Yanfei ZHANG Yueer SHAN Yuting XU No.58 research Institute China Electronics Technology Group CorporationWuxi 214035China

This paper proposes a kind of programmable logic element(PLE)based on Sense-Switch pFLASH technology.By programming Sense-Switch pFLASH,all three-bit look-up table(LUT3)functions,partial four-bit look-up table(LUT4)functions,latch functions,and d flip flop(DFF)with enable and reset functions can be realized.Because PLE uses a choice of operational logic(COOL)approach for the operation of logic functions,it allows any logic circuit to be implemented at any ratio of combinatorial logic to register.This intrinsic property makes it close to the basic application specific integrated circuit(ASIC)cell in terms of fine granularity,thus allowing ASIC-like cell-based mappers to apply all their optimization potential.By measuring Sense-Switch pFLASH and PLE circuits,the results show that the“on”state driving current of the Sense-Switch pFLASH is about 245.52μA,and that the“off”state leakage current is about 0.1 pA.The programmable function of PLE works normally.The delay of the typical combinatorial logic operation AND3 is 0.69 ns,and the delay of the sequential logic operation DFF is 0.65 ns,both of which meet the requirements of the design technical index.

关键词： Field programmable gate array(FPGA) Programmable logic element(PLE) Boolean logic operation Look-up table Sense-Switch pFLASH Threshold voltage

Sludge composition and characteristics shaped microbial community and further determined process performance: A study on full-scale thermal hydrolysis-anaerobic digestion processes

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Journal of Environmental Sciences 2024年第3期137卷 96-107页

作者： Wei Liu Chenxiang Sun Wei Li Tianle Li Zhan Chen Jiawei Wang Zhengran Ren Xianghua Wen School of Environment Tsinghua UniversityBeijing 100084China Jinneng Holding group DatongShanxi 037000China research and Development Center Beijing Drainage Group Co.Ltd.Beijing 100124China Beijing Dabeinong Science and Technology group Co. Ltd.Beijing 100080China

Anaerobic digestion (AD) with thermal hydrolysis (TH) pretreatment is a promising process for excess sludge treatment,while there lacks of the knowledge from full-scale process about the impact of sludge composition and characteristics on microbial community and performance.The sludge physiochemical indices,microbial community and performance data of four full-scale TH-AD plants were characterized,and their relationships was elucidated.The four plants were operated under almost similar total organic loading rate (OLR)but their methanogenesis performance differentiate into two groups,namely superior group(SupG) and the inferior group (Inf G).In both groups,TH effectively solubilized particulate organic compounds,meanwhile raised the ammonia nitrogen (NH_(4)^(+)-N) and volatile fatty acid (VFA) concentration.Compared with the Sup G,thermal hydrolyzed sludge of Inf G had higher level of VFAs,NH_(4)^(+)-N and total chemical oxygen demand (t COD),which showed higher inhibition effect on microbes,leading to a community with lower diversity,lower abundance of carbohydrate degrading functional guild,higher protein degrading one,and methanogens that adapted to limited substrates,and further declined the methane production rate.Thus,it was recommended that OLR alone was not sufficient for controlling the system in design and operation,the concentration of VFAs,NH_(4)^(+)-N and t COD should be equally considered.Their higher concentration,together with the higher abundance of Defluviitoga and Proteiniphilum were recommended as indicators for inferior running condition.Our results proposed that microbial communities played a role of bridge between environmental factors and performance,provided implications for engineering ecology and operational regulation for full-scale sludge TH-AD process.

关键词： Thermal hydrolysis Anaerobic digestion Microbial community Full-scale

Evolution of biomass particles during pelletization process

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Particuology 2024年第3期86卷 182-187页

作者： Hamid Rezaei Maryam Tajilrou Jun Sian Lee Kanages Singaraveloo Anthony Lau Shahab Sokhansanj Biomass and Bioenergy research group Department of Chemical and Biological EngineeringUniversity of British ColumbiaVancouverCanada

Pulverizing is an essential unit operation in co-firing biomass with coal.Pulverizers are only compatible with pellet forms of fibrous biomass materials and crush them down to their original forming particle sizes.That is why the data on the size distribution of the particles forming a biomass pellet is crucial to achieving optimum combustion conditions.The current study determines the internal particle size distribution of pellets after wet disintegration,following Iso 17830 standard,and aims to suggest improvements to the mentioned standard based on new measured evidence.Experiments were carried out on white wood pellets(no bark)and brown wood pellets containing bark at four water temperatures:20,40,60,and 95℃,with or without stirring.The particle size distribution of the pre-pelletizer wood particles was also measured and compared with particles in the formed pellets.Ambient water temperature of 20℃ was found to be adequate for the complete disintegration of pellets,and no mechanical stirring was required.About 30% of particles in the disintegrated pellets were 0.5-1.0 mm.Pelletization changes the particle size distribution to smaller particles.The disintegrated bark pellets contained more fines than white pellets.

关键词： Wood pellets Particle sizes distribution Wet disintegration Stirring Water temperature

Eliciting CD4-mimicking broadly neutralizing antibodies:new avenues towards the rational design of an HIV vaccine

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Signal transduction and Targeted Therapy 2024年第3期9卷 836-838页

作者： Frauke Muecksch Oliver T.Fackler Department of Infectious Diseases Heidelberg UniversityMedical Faculty HeidelbergVirologyCenter for Integrative Infectious Disease Research(CIID)HeidelbergGermany Chica and Heinz Schaller(CHS)research group Department of Infectious DiseasesVirologyUniversity Hospital HeidelbergHeidelbergGermany Department of Infectious Diseases Heidelberg UniversityMedical Faculty HeidelbergIntegrative VirologyCenter for Integrative Infectious Disease Research(CIID)HeidelbergGermany German Centre for Infection research(DZIF) Partner Site HeidelbergHeidelbergGermany

In a study recently published in Cell,Saunders et al.report that a new anti-HIV vaccine triggers antibody responses resembling CD4-binding site broadly neutralizing antibody precursors in rhesus macaques.1 This study provides important proof of concept and establishes a framework for the rational design of an effective HIV vaccine.

关键词： al. vaccine rational

Dietary supplementation of zinc oxide modulates intestinal functionality during the post-weaning period in clinically healthy piglets

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Journal of Animal Science and Biotechnology 2024年第1期15卷 313-328页

作者： Dirkjan Schokker Soumya K.Kar Els Willems Alex Bossers Ruud A.Dekker Alfons J.M.Jansman Wageningen Bioveterinary research LelystadThe Netherlands Wageningen Livestock research Wageningen University&ResearchWageningenThe Netherlands Royal Agrifirm group ApeldoornThe Netherlands Institute for Risk Assessment Sciences Utrecht UniversityUtrechtThe Netherlands

Background To improve our understanding of host and intestinal microbiome interaction,this research investigated the effects of a high-level zinc oxide in the diet as model intervention on the intestinal microbiome and small intestinal functionality in clinically healthy post-weaning piglets.In study 1,piglets received either a high concentration of zinc(Zn)as zinc oxide(Zn O,Zn,2,690 mg/kg)or a low Zn concentration(100 mg/kg)in the diet during the post weaning period(d 14–23).The effects on the piglet's small intestinal microbiome and functionality of intestinal tissue were investigated.In study 2,the impact of timing of the dietary zinc intervention was investigated,i.e.,between d 0–14 and/or d 14–23 post weaning,and the consecutive effects on the piglet's intestinal functionality,here referring to microbiota composition and diversity and gene expression profiles.Results Differences in the small intestinal functionality were observed during the post weaning period between piglets receiving a diet with a low or high concentration Zn O content.A shift in the microbiota composition in the small intestine was observed that could be characterized as a non-pathological change,where mainly the commensals inter-changed.In the immediate post weaning period,i.e.,d 0–14,the highest number of differentially expressed genes(DEGs)in intestinal tissue were observed between animals receiving a diet with a low or high concentration Zn O content,i.e.,23 DEGs in jejunal tissue and 11 DEGs in ileal tissue.These genes are involved in biological processes related to immunity and inflammatory responses.For example,genes CD59 and REG3G were downregulated in the animals receiving a diet with a high concentration Zn O content compared to low Zn O content in both jejunum and ileum tissue.In the second study,a similar result was obtained regarding the expression of genes in intestinal tissue related to immune pathways when comparing piglets receiving a diet with a high concentration Zn O content compared to low Zn O content.Conclusions Su

关键词： Immune system Intestinal functionality Microbiota Piglets Zinc oxide

Effectiveness of Acupoint Application in Patients with Pharyngeal Pain: Evidence from CHUNBO, A Prospective Real-World Study

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Chinese Journal of Integrative Medicine 2024年第1期30卷 18-24页

作者： MA Hang-kun WANG Yi-ming GUO Man-ping LI Chen-fei LI Rui GAO Rui Emergency Department Xiyuan Hospital Affiliated to China Academy of Chinese Medical SciencesBeijing(100091)China National medical Products Administration for Laboratory of Clinical research and Evaluation of Traditional Chinese Medicine Beijing(100091)China National Clinical research Center for Chinese Medicine Cardiology Beijing(100091)China Postdoctoral Workstation of Yabao Pharmaceutical group Co. Ltd.YunchengShanxi Province(044602)China

Objective: To assess the outcomes after acupoint application in patients with pharyngeal pain in a real-world settings, and analyze the characteristics of effective population and prescription characteristics of acupoint application. Methods: Based on CHUNBO platform, patients with pharyngeal pain who were candidates for acupoint application on the basis of physician-evaluation, were enrolled in a nationwide, prospective, 69-week multicenter observational study from August 2020 to February 2022. Propensity score matching(PSM) was used to match the confounding factors and the association rules were used to analyze the characteristics of effective population and prescription characteristics of acupoint application. Outcome assessments included the disappearance rate of pharyngeal pain(within 3, 7, and 14 days), disappearance time of pharyngeal pain, as well as adverse events. Results: Of 7,699 enrolled participants, 6,693(86.9%) received acupoint application and 1,450(21.7%) with non-acupoint application. After PSM, there were 1,004 patients each in the application group(AG) and non-application group(NAG). The disappearance rate of pharyngeal pain in the AG at 3, 7, and 14 days were all higher than those in the NAG(Pgroup with tonsil diseases was 2.19 times higher than that in the NAG(P<0.05). The commonly used acupoints for the effective cases were Tiantu(RN 22), Shenque(RN 8) and Dazhui(DU 14). The commonly used herbs for the effective cases were Natrii sulfas, Radix et Rhizoma Rhei, and Herba Ephedrae. Among them, Natrii sulfas was applied to RN 8 most frequently(support 84.39%). A total of 1,324(17.2%) patients experienced AEs, and mainly occurred in the AG, with significant difference in the incidence of AEs be

关键词： acupoint application Chinese medicine pharyngeal pain multicentre effectiveness characters real-world study

Study on tungsten sintering temperature field based on electromagnetic simulation and computational fluid dynamics

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Tungsten 2024年第2期6卷 355-366页

作者： Lu-Yan Wang Yue-Guang Yu Jian-Xin Dong Kai-Ping Du Shan-Yu Liu Cao-Bing Li University of Science and Technology Beijing Beijing 100083China BGRIMM Technology group Beijing 100160China China Iron&Steel research Institute group Beijing 100081China

In order to study the influence of various sintering variables more intuitively and clearly,electromagnetic field analysis and computational fl uid dynamics are used to analyze the infl uence of gas flow,heating power and other process parameters on the temperature range of medium-frequency sintering in this paper.The results indicate that the uniformity of temperature fi eld is determined by the gas flow rate and heating power.When the heating power is 50 kW,the stable temperature drops about 10 K for every 1 m^(3)·h^(−1)increase of hydrogen flow.The peak value of the maximum temperature diff erence on the tungsten rods gradually increases with the increase of the hydrogen flow rate,and it appears slightly later.The temperature distribution of tungsten rods in furnace is similar with diff erent hydrogen flow rate.At the same time,the closer to the furnace wall,the higher the temperature of the tungsten rod.The temperature diff erence between tungsten rods mainly occurred within 1 h after the beginning of heating.Increasing the heating power can improve the stable temperature,but has little eff ect on the heating time.Increasing heating power can increase the peak value of the maximum temperature diff erence on the tungsten rods,but has little eff ect on the occurrence time of the peak value of the maximum temperature diff erence on the tungsten rods.Increasing the heating power will increase the temperature diff erence of a single tungsten rod,but the temperature diff erence of a single tungsten rod never exceeds 65 K.This study can be used to guide the process optimization design.Combined with numerical simulation calculation,the sintering parameters with low energy consumption and high temperature uniformity can be quickly and eff ectively found,thus improving the microstructure and properties of sintered tungsten products.

关键词： Tungsten products Sintering Hydrogen flow rate Heating power