Insights into microbiota community dynamics and flavor development mechanism during golden pomfret(Trachinotus ovatus)fermentation based on single-molecule real-time sequencing and molecular networking analysis

Popular fermented golden pomfret(Trachinotus ovatus)is prepared via spontaneous fermentation;however,the mechanisms underlying the regulation of its flavor development remain unclear.This study shows the roles of the complex microbiota and the dynamic changes in microbial community and flavor compounds during fish fermentation.Single-molecule real-time sequencing and molecular networking analysis revealed the correlations among different microbial genera and the relationships between microbial taxa and volatile compounds.Mechanisms underlying flavor development were also elucidated via KEGG based functional annotations.Clostridium,Shewanella,and Staphylococcus were the dominant microbial genera.Forty-nine volatile compounds were detected in the fermented fish samples,with thirteen identified as characteristic volatile compounds(ROAV>1).Volatile profiles resulted from the interactions among the microorganisms and derived enzymes,with the main metabolic pathways being amino acid biosynthesis/metabolism,carbon metabolism,and glycolysis/gluconeogenesis.This study demonstrated the approaches for distinguishing key microbiota associated with volatile compounds and monitoring the industrial production of high-quality fermented fish products.

Analysis of quality-related proteins in golden pompano(Trachinotus ovatus)fillets with modified atmosphere packaging under superchilling storage

Here,we aimed to study the changes in proteome of golden pompano fillets during post-mortem storage.Tandem mass tags(TMT)-labeled quantitative proteomic strategy was applied to investigate the relationships between protein changes and quality characteristics of modified atmosphere packaging(MAP)fillets during superchilling(-3°C)storage.Scanning electron microscopy was used to show that the muscle histology microstructure of fillets was damaged to varying degrees,and low-field nuclear magnetic resonance was used to find that the immobilized water and free water in the muscle of fillets changed significantly.Total sulfhydryl content,TCA-soluble peptides and Ca2+-ATPase activity also showed that the fillet protein had a deterioration by oxidation and denaturation.The Fresh(FS),MAP,and air packaging(AP)groups were set.Total of 150 proteins were identified as differential abundant proteins(DAPs)in MAP/FS,while 209 DAPs were in AP/FS group.The KEGG pathway analysis indicated that most DAPs were involved in binding proteins and protein turnover.Correlation analysis found that 52 DAPs were correlated with quality traits.Among them,8 highly correlated DAPs are expected to be used as potential quality markers for protein oxidation and water-holding capacity.These results provide a further understanding of the muscle deterioration mechanism of packaging golden pompano fillets during superchilling.

A multicenter randomized, double-blind, placebo-controlled trial to evaluate the safety and efficacy of rhubarb in treating acute exacerbation of chronic obstructive pulmonary disease of the syndrome type phlegm-heat obstructing the lungs

Objective:To observe the clinical efficacy and safety of oral administration of the traditional Chinese herb rhubarb to treat acute exacerbation of chronic obstructive pulmonary disease(AECOPD).Method:This was a multicenter randomized double-blinded placebo controlled study that took place in 7 provinces of China that enrolled 244 patients(aged 18e80 years)who had acute exacerbation of COPD with the traditional Chinese syndrome pattern of phlegm-heat obstructing lung.Participants were divided into experimental and control groups.The experimental group received 4.5 g of rhubarb granules twice daily and the control group received placebo granules.Both groups also received conventional Western therapy consisting of oxygen therapy,an antibiotic,expectorant,and a bronchodilator.Treatment lasted 10 days.Symptom scores for cough,sputum volume and color,wheezing and chest tightness before treatment and on days 3,5,7,and 10 during the treatment were recorded.Lung function,arterial blood gas and levels of serum inflammatory factors,interleukin-4(IL-4),interleukin-8(IL-8),and interleukin-10(IL-10)and tumor necrosis factor-alpha(TNF-a),before and after treatment were measured.Results:The sample size of the full analysis set(FAS)was 244 participants,and the sample size of per protocol set(PPS)was 235.Following 10 days’treatment,symptom scores of the experimental group were markedly lower than those of the placebo group(FAS:mean difference
1.67,95%CI:e2.66 to
0.69,P Z 0.001;PPS:mean difference
1.55,95%CI:
2.56 to
0.54,P Z 0.003).Lung function in the experimental group was significantly higher than in the placebo group(FEV1,FAS:mean difference 0.12,95%CI:0.06 to 0.18;P<0.001;PPS:mean difference 0.12,95%CI 0.05 to 0.18;P<0.001.FVC:FAS:mean difference 0.16,95%CI:0.06 to 0.26;P Z 0.002;PPS:mean difference 0.16,95%CI 0.05 to 0.26;P Z 0.003.FEV1%,FAS:mean difference 5.95,95%CI:3.36 to 8.53;P<0.001;PPS:mean difference 5.92,95%CI 3.28 to 8.56;P<0.001.).PaO2,PaCO2,as well as serum inflammatory factors were also improved when compared to the placebo group.There were no significant differences in the incidence rate of adverse reaction between the two groups.Conclusions:Compared with placebo,rhubarb granules significantly reduced symptom scores,improved blood oxygen level,controlled systemic inflammatory response,without significant adverse effects.Thus,rhubarb may be a beneficial adjuvant method for treating the phlegm-heat obstructing the lung syndrome pattern of AECOPD.

Preparation of highly stable diclofenac potassium pellet with microcrystalline cellulose by extrusionespheronization

The main purpose of this study is to prepare highly stable diclofenac potassium(DP)pellet with microcrystalline cellulose(MCC)by extrusionespheronization.Using MCC,DP pellets were prepared and the stability was investigated.Related compounds of DP pellets were analyzed by High Pressure Liquid Chromatography(HPLC).After stability test of 60℃/75%RH for 10 d,the values of two main related compounds were 0.94%and 2.17%,respectively.Compatibility tests show that instability of DP was mainly caused by MCC.To improve the stability of DP in presence of MCC,different kinds of stabilizers were investigated.Upon addition of 1.5%(w/w)sodium hydroxide,the primary related compound of pellets was reduced to be 0.159%after stability test of 60℃/75%RH for 50 d.This study demonstrated that MCC induced decomposition of DP upon exposure to moisture could be prohibited by addition of sodium hydroxide.The mechanisms were discussed and residual hydroxyl free radicals in excipients were responsible for decomposition of DP.Finally,this formulation of DP is highly stable with sustained-release behavior.

Antispasmodic effect of Bupi Yichang pill on colonic contraction of rats in vitro

Objective:To investigate the pharmacological effect of Bupi Yichang (BPYX) pill on colonic contraction of rats and explore its underlying mechanism.Methods:The experiments were performed on colonic longitudinal smooth muscle strips (CLSMs) under isometric conditions.CLSMs suspended in tissue chambers were stimulated by KCl (80 mM) or acetylcholine (ACh,0.1 mM),or exhausting intracellular Ca2+ and internal flow of extracellular Ca2+ to induce muscle contraction and their responses to different doses of BPYX pill were observed.After that,incubation with different inhibitors was conducted to verify its underlying mechanism.Results:Bupi Yichang pill dose-dependently and reversibly inhibited colonic contraction.The antispasmodic effect of BPYC pill was partially blocked by 3,4,5-trimethoxybenzoic acid 8-(diethylamino)octyl ester hydrochloride (TMB-8,an intracellular Ca2+ antagonist,500 μM),thapsigargin (a non-competitive inhibitor of the sarco/endoplasmic reticulum Ca2+ ATPase,1 μM),and nifedipine (a voltage-dependent Ca2+ channel blocker,10 μM) (P <.05).However,there were no significant difference after incubation with ethylene glycol tetraacetic acid (EGTA,a calcium chelating agent,1 mM),4-aminopyridine (4-AP,a potassium channel blocker,50 μM),NG-nitro-L-arginine methyl ester (L-NAME,an inhibitor of nitric oxide synthase,10 mM),methylene blue (an inhibitor of cyclic guanosine monophosphate,10 μM) and apamin (a selectire blocker of Ca2+-activated K+ channel,0.1 μM) (P >.05).Conclusion:Bupi Yichang pill could inhibit colonic contraction of rats in vitro and its antispasmodic effect might be partially mediated by calcium channels.

基于电池热管理系统的微通道热管阵列的传热性能

温度是影响动力电池性能的关键因素.高效热管理技术可有效控制动力电池温度和温差.本研究采用微通道热管阵列作为电池热管理系统的热传导元件,分析了其在高热功率密度下的传热性能,理论计算了其等效导热系数,优化分析了其槽道尺寸对流动传热的影响,对比了其与主流散热技术的性能差异.研究发现,热功率密度为0.3658 W cm^-2时,强制风冷散热条件下,采用微通道热管阵列技术可维持热源处表面温度45℃以下,温差1.3℃以下,低于无微通道热管阵列导热情况下的温升15℃,温差3.8℃.随着热功率密度增大至0.9176 W cm^-2,微通道热管阵列的等效导热系数增大为6027 W m^-1K^-1,其热源处表面最大瞬态温差约2.75℃.增大槽道尺寸参数可进一步改善微通道热管阵列的导热系数,改善其传热性能,但对液体回流驱动力有一定影响.该阵列具有较好的动态工况热稳定性和低温快速加热能力.与烧结热管组的温度性能相比,微通道热管阵列组最大温度可降低15.1℃,表面温差降低14℃,具有显著降温和均温优势,表明微通道热管阵列在动力电池热管理系统中具有广泛应用前景.

A reactive oxygen species-responsive dendrimer with low cytotoxicity for efficient and targeted gene delivery

Nonviral vectors have been attracting more attention for several advantages in gene delivery and the development of nonviral gene ca rriers with high delivery efficiency and low cytotoxicity has long been a key project.Starburst polyamidoamine dendrimers are a class of synthetic polymers with unique structural and physical characteristics.However,when they are used as gene carrier,the gene transfection efficiency is not satisfactory.Herein,a novel thioketal-core polyamidoamine dendrimer(i.e.,ROS-PAMAM)was synthesized and characterized.Compared to ethylenediamine-core dendrimers or widely used cationic polymers of polyetherimide,ROS-PAMAM showed lower cytotoxicity.Moreover,ROS-PAMAM demonstrated reactive oxygen species responsive characteristics,which can facilitate the release of siRNA in the tumor microenvironment.In vitro gene transfection experiments based on A549 cells confirmed that siRNA/ROS-PAMAM exhibits high gene transfection efficiency.It is concluded that ROS-PAMAM shows great potential as a generalizable vehicle for gene therapy applications.

Toripalimab in advanced biliary tract cancer

Gemcitabine combined with platinum/fluorouracil drugs is the standard firstline treatment for advanced biliary tract cancers(BTCs).We explored the safety and efficacy of toripalimab plus gemcitabine and S-1(GS)as the first-line treatment for advanced BTCs.At a one-sided significance level of 0.025,a total of 50 patients could provide 80%power to show the efficacy at targeted progression-free survival(PFS)rate at 6 months of 70%versus 40%for the combined treatment.This single-arm,phase II study enrolled 50 patients with advanced BTCs who previously received no systemic treatment.The regimen was as follows:toripalimab(240 mg,i.v.,d1),gemcitabine(1,000 mg/m2,i.v.,d1 and d8),and S-1(40–60 mg bid p.o.,d1–14,Q21d).The primary endpoint was progression-free survival.The secondary endpoints included overall survival(OS),objective response rate(ORR),duration of response(DOR),and safety.The associations between response with PDL1 expression,tumor mutational burden(TMB),and genetic variations were explored.Patients were enrolled from January 2019 to August 2020,with a median follow-up time of 24.0 months(IQR:4.3–31.0 months).

Thermal Performance of a Micro Heat Pipe Array for Battery Thermal Management Under Special Vehicle-Operating Conditions

The thermal management of battery systems is critical for maintaining the energy storage capacity,life span,and thermal safety of batteries used in electric vehicles,because the operating temperature is a key factor affecting battery performance.Excessive temperature rises and large temperature differences accelerate the degradation rate of such batteries.Currently,the increasing demand for fast charging and special on-vehicle scenarios has increased the heat dissipation requirements of battery thermal management systems.To address this demand,this work proposes a novel micro heat pipe array(MHPA)for thermal management under a broadened research scope,including high heat generation rates,large tilt angles,mild vibration,and distributed heat generation conditions.The experimental results indicate that the temperature difference is maintained 3.44°C at a large heat generation of 50 W for a limited range of tilt angles.Furthermore,a mild vehicle vibra-tion condition was found to improve temperature uniformity by 3.3°C at a heat generation of 10 W.However,the use of distributed heat sources results in a temperature variation of 3.88°C,suggesting that the heat generation distribution needs to be considered in thermal analyses.Understanding the effects of these special battery-operating conditions on the MHPA could significantly contribute to the enhancement of heat transfer capability and temperature uniformity improvement of battery thermal management systems based on heat pipe technologies.This would facilitate the realization of meeting the higher requirements of future battery systems.