Mannan oligosaccharides alleviate oxidative injury in the head kidney and spleen in grass carp(Ctenopharyngodon idella)via the Nrf2 signaling pathway after Aeromonas hydrophila infection

Background Mannan oligosaccharides(MOS)are recommended as aquaculture additives owing to their excellent antioxidant properties.In the present study,we examined the effects of dietary MOS on the head kidney and spleen of grass carp(Ctenopharyngodon idella)with Aeromonas hydrophila infection.Methods A total of 540 grass carp were used for the study.They were administered six gradient dosages of the MOS diet(0,200,400,600,800,and 1,000 mg/kg)for 60 d.Subsequently,we performed a 14-day Aeromonas hydrophila challenge experiment.The antioxidant capacity of the head kidney and spleen were examined using spectrophotometry,DNA fragmentation,qRT-PCR,and Western blotting.Results After infection with Aeromonas hydrophila,400-600 mg/kg MOS supplementation decreased the levels of reactive oxygen species,protein carbonyl,and malonaldehyde and increased the levels of anti-superoxide anion,antihydroxyl radical,and glutathione in the head kidney and spleen of grass carp.The activities of copper-zinc superoxide dismutase,manganese superoxide dismutase,catalase,glutathione S-transferase,glutathione reductase,and glutathione peroxidase were also enhanced by supplementation with 400-600 mg/kg MOS.Furthermore,the expression of most antioxidant enzymes and their corresponding genes increased significantly with supplementation of 200-800 mg/kg MOS.mRNA and protein levels of nuclear factor erythroid 2-related factor 2 also increased following supplementation with 400-600 mg/kg MOS.In addition,supplementation with 400-600 mg/kg MOS reduced excessive apoptosis by inhibiting the death receptor pathway and mitochondrial pathway processes.Conclusions Based on the quadratic regression analysis of the above biomarkers(reactive oxygen species,malondialdehyde,and protein carbonyl)of oxidative damage in the head kidney and spleen of on-growing grass carp,the recommended MOS supplementation is 575.21,557.58,531.86,597.35,570.16,and 553.80 mg/kg,respectively.Collectively,MOS supplementation could alleviate oxidative injury in the head kidney and spleen of grass carp infected with Aeromonas hydrophila.

Behavior and controlling factors of methane adsorption in Jurassic continental shale,northeastern Sichuan Basin

The behavior and controlling factors of natural gas adsorption in the Jurassic continental shale in the northeastern Sichuan Basin are studied based on the organic geochemical features,mineral compositions and pore structure parameters through a series of experiments on samples from the shale.Results show that the total gas content of the shale measured on-site is 0.1-5.3 cm^(3)/g,with an average of 0.7 cm^(3)/g.The methane isothermal adsorption curves show a trend of increasing first and then decreasing,indicating an obvious excessive adsorption.The shale has a maximum adsorption capacity(V^(L))of 0.44-3.59 cm^(3)/g,with an average of 1.64 cm^(3)/g,lower than that of marine shale in the same basin.The organic matter content and pore structure characteristics are identified as the two main factors controlling the adsorption capacity of the shale.Micropores in the shale are the main storage space for gas to be adsorbed.Due to well developed shell laminae and interlayers in the shale,calcite plays a more important role than clay minerals in affecting the adsorption of gas to the rock.The formation temperature and water content also significantly inhibit the gas adsorption to the shale.Compared with marine shale in the basin,the Jurassic continental shale is more heterogeneous and lower in TOC values.Furthermore,with a more widely developed clayey shale lithofacies and shell limy shale lithofacies as well as relatively less developed organic pores and micropores,the continental shale is inferior to marine shale in terms of gas adsorption capacity.

Impacts of high temperature,relative air humidity,and vapor pressure deficit on the seed set of contrasting maize genotypes during flowering

Heat stress is a major constraint to current and future maize production at the global scale.Male and female reproductive organs both play major roles in increasing seed set under heat stress at flowering,but their relative contributions to seed set are unclear.In this study,a 2-year field experiment including three sowing dates in each year and 20 inbred lines was conducted.Seed set,kernel number per ear,and grain yield were all reduced by more than 80%in the third sowing dates compared to the first sowing dates.Pollen viability,silk emergence ratio,and anthesis-silking interval were the key determinants of seed set under heat stress;and their correlation coefficients were 0.89^(***),0.65^(***),and-0.72^(***),respectively.Vapor pressure deficit(VPD)and relative air humidity(RH)both had significant correlations with pollen viability and the silk emergence ratio.High RH can alleviate the impacts of heat on maize seed set by maintaining high pollen viability and a high silk emergence ratio.Under a warming climate from 2020 to 2050,VPD will decrease due to the increased RH.Based on their pollen viability and silk emergence ratios,the 20 genotypes fell into four different groups.The group with high pollen viability and a high silk emergence ratio performed better under heat stress,and their performance can be further improved by combining the improved flowering pattern traits.

Recent Advances in Mechanistic Understanding of Metal-Free Carbon Thermocatalysis and Electrocatalysis with Model Molecules

Metal-free carbon,as the most representative heterogeneous metal-free catalysts,have received considerable interests in electro-and thermo-catalytic reac-tions due to their impressive performance and sustainability.Over the past decade,well-designed carbon catalysts with tunable structures and heteroatom groups coupled with various characterization techniques have proposed numerous reaction mechanisms.However,active sites,key intermediate species,precise structure-activity relationships and dynamic evolution processes of carbon catalysts are still rife with controversies due to the monotony and limitation of used experimental methods.In this Review,we sum-marize the extensive efforts on model catalysts since the 2000s,particularly in the past decade,to overcome the influences of material and structure limitations in metal-free carbon catalysis.Using both nanomolecule model and bulk model,the real contribution of each alien species,defect and edge configuration to a series of fundamentally important reactions,such as thermocatalytic reactions,electrocatalytic reactions,were systematically studied.Combined with in situ techniques,isotope labeling and size control,the detailed reaction mechanisms,the precise 2D structure-activity relationships and the rate-determining steps were revealed at a molecular level.Furthermore,the outlook of model carbon catalysis has also been proposed in this work.

Preparation and Methicillin-Resistant Staphylococcus aureus Biofilm Elimination Effect of Baicalein-Loaded Hyaluronic acid/β-Cyclodextrin grafted Chitosan Nanoparticles

Methicillin-resistant Staphylococcus aureus(MRSA)is a common pathogen causing acquired infections.Antibiotics are routinely employed for bacterial infection treatment.Excessive antibiotic use for bacterial infections heightens resistance,and MRSA resistance is being prevalent[1].MRSA exhibits substantial resistance to conventional antibiotics,which is associated with its biofilm-forming capability.The bacterial biofilm serves as a barrier,restricting nutrient access and slowing internal metabolism,increasing antibiotic resistance.The bacterial biofilm forms a defensive layer,resisting antibiotic penetration while preventing nutrient entry,inducing a slow bacterial metabolism,and increasing bacterial resistance[2].Consequently,biofilm formation and the emergence of resistance to conventional antibiotics have become substantial challenges in the field of infectious diseases.The development of agents to remove biofilm barriers is urgently required because biofilms are extremely hazardous.

Meta-analysis of transarterial chemoembolization combined with cryoablation vs transarterial chemoembolization alone for≥5 cm hepatocellular carcinoma

BACKGROUND Hepatocellular carcinoma(HCC)ranks sixth globally in cancer incidence and third in mortality rates.Unfortunately,over 70% of HCC patients forego the opportunity for curative surgery or liver transplantation due to inadequate physical examinations,poor physical condition,and limited organ availability upon diagnosis.Clinical guidelines endorse transarterial chemoembolization(TACE)as the frontline treatment for intermediate to advanced-stage HCC.Cryoablation(CRA)is an emerging local ablative therapy increasingly used in HCC management.Recent studies suggest that combining CRA with TACE offers complementary and synergistic effects,potentially improving long-term survival rates.However,the superiority of combined TACE+CRA therapy over TACE alone for HCC lesions equal to or exceeding 5 cm requires further investigation.AIM To compare the efficacy and safety of TACE combined with CRA vs TACE alone in the treatment of HCC with a diameter of≥5 cm.METHODS PubMed,EMBASE,Cochrane Library,CNKI,Wanfang,and VIP databases were searched to retrieve all relevant studies on TACE and CRA up to July 2022.Meta-analysis was performed using RevMan 5.3 software.RESULTS After screening according to the inclusion and exclusion criteria,6 articles were included,including 2 randomized controlled trials and 4 nonrandomized controlled trials,with a total of 575 patients included in the meta-analysis.The results showed that the objective response rate[odds ratio(OR)=2.56,95%confidence interval(CI):1.66-3.96,P<0.0001],disease control rate(OR=3.03,95%CI:1.88-4.89,P<0.00001),1-year survival rate(OR=3.79,95%CI:2.50-5.76,P<0.00001),2-year survival rate(OR=2.34,95%CI:1.43-3.85,P=0.0008),and 3-year survival rate(OR=3.34,95%CI:1.61-6.94,P=0.001)were all superior to those of the control group;the postoperative decrease in alpha-fetoprotein value(OR=295.53,95%CI:250.22-340.85,P<0.0001),the postoperative increase in CD4 value(OR=10.59,95%CI:8.78-12.40,P<0.00001),and the postoperative decrease in CD8 value(OR=6.47,95%CI:4.44-8.50,P<0.00001)were also significantly higher than those in the TACE-alone treatment group.CONCLUSION Compared with TACE-alone treatment,TACE+CRA combined treatment not only improves the immune function of HCC patients with a diameter of≥5 cm,but also enhances the therapeutic efficacy and long-term survival rate,without increasing the risk of complications.Therefore,TACE+CRA combined treatment may be a more recommended treatment for patients with HCC with a diameter of≥5 cm.

A systematic review of the efficacy of traditional Chinese medicine retention enema in the treatment of ulcerative colitis

The objective of this study is to summarize the efficacy and safety of traditional Chinese medicine(TCM)enema in the treatment of ulcerative colitis(UC).The randomized controlled trials on TCM enema intervention in the treatment of UC were searched in seven databases:PubMed,Embase,Web of Science,CBM,CNKI,Wanfang Database,and VIP Database from January 1,2013 to June 6,2022,and the data were analyzed using RevMan 5.3 software.A total of 18 studies involving 1514 UC patients were included.Meta analysis results showed that compared with conventional Western medicine,Chinese medicine enema had a significant effect on UC,and the clinical effective rate of the experimental group using Chinese medicine enema was 4.45 times that of the control group using conventional Western medicine(odds ratio=4.45,95%confidence interval[3.27,6.06]).Therefore,Chinese medicine enema is effective in the treatment of UC,and can significantly reduce related symptoms.

Specification of manual lactation traditional Chinese medicine technology

Acute mastitis is one of the common diseases of postpartum lactating women,also known as lactational mastitis,which can occur during breastfeeding,especially in the postpartum 3–4 weeks.Acute mastitis can lead to the cessation of breastfeeding.Improving breastfeeding behavior and extending breastfeeding duration have become a global strategy to promote maternal and child health.Manual lactation traditional Chinese medicine technology is one of the important measures to improve the rate of breastfeeding,which can solve the problems of breast swelling,pain,and reduction of milk production.This article introduces the definition,indications,standard operating procedures,precautions,and treatment of adverse events of manual lactation in traditional Chinese medicine technology,so as to provide more comprehensive guidance for clinical workers to carry out manual lactation operations.

Psychological experience of breastfeeding among primiparous women with lactating mastitis:A qualitative research

Objective:The objective of this study is to comprehensively understand the psychological experience of primiparous women during breastfeeding while dealing with lactating mastitis and to establish a reliable foundation for tailored support measures.Methods:Twenty primiparous mothers from a tertiary hospital in Beijing between January and March 2023 were chosen using purposive sampling for semi-structured interviews.After conducting 20 interviews,data saturation was achieved.The Colaizzi’s seven-step analytical approach was employed to analyze,summarize,and refine the identified themes.Results:Among primiparous women afflicted by lactating mastitis,the primary themes regarding breastfeeding attitudes included three key aspects:(1)uncertainty during the initial diagnosis phase,(2)intricate emotional journey during treatment,and(3)positive psychological outlook during the recovery stage.Conclusion:Primiparous women undergoing lactating mastitis experience substantial physical and psychological strain.It is crucial for medical personnel,family caregivers,and society at large to be attuned to the emotions of these patients.Tailored support measures should be offered to enhance patients’physical and mental well-being and facilitate disease recovery.

Relationship between Muscle Strength, Muscle Mass and BMD in Postmenopausal Female of Zhuang in Guangxi Province of China

Objective: To explore the correlation between muscle strength, muscle mass and bone mineral density (BMD) in Zhuang female population, body composition analysis and grip strength, and to analyze the possible influencing factors of BMD. Methods: 182 postmenopausal women were selected from Guangxi Province of China. Broadband ultrasound attenuation (BUA) was used to evaluate BMD. Grip dynamometer to assess muscle strength. Height, weight and muscle mass of each part were measured by body composition measuring instrument. Body mass index (BMI), skeletal muscle mass index (SMI) and limb skeletal muscle mass (SM) were calculated according to the measurement results. Results: BUA, grip strength and SMI in postmenopausal women of Zhuang nationality showed a decreasing trend with age (p p p r = 0.305, p Conclusion: With the increase of age, the decline rate of muscle strength of postmenopausal Zhuang women in Guangxi is slower than that of BMD and muscle mass. SM can better reflect the BMD level of the body than SMI, and the LSM is the main influencing factor of BMD.

The relationship between dietary methionine and growth,digestion,absorption,and antioxidant status in intestinal and hepatopancreatic tissues of sub-adult grass carp(Ctenopharyngodon idella)

Background: Methionine is an essential amino acid for fish. The present study was conducted to investigate the effects of dietary methionine on growth performance, digestive and absorptive ability, as well as antioxidant capacity in the intestine and hepatopancreas of sub-adult grass carp(Ctenopharyngodon idella).Results: Dietary methionine deficiency significantly decreased percentage weight gain(PWG), feed intake, feed efficiency and protein efficiency ratio, as well as activities of hepatopancreatic glutamate-oxaloacetate transaminase and muscle glutamate-pyruvate transaminase in sub-adult grass carp(P < 0.05). Furthermore, methionine deficiency significantly reduced activities of trypsin, lipase and amylase in the intestine, Na^+/K^+-ATPase, alkaline phosphatase and γ-glutamyl transpeptidase in three intestinal segments, and creatine kinase(CK) in the proximal intestine(P < 0.05). However, an unexplained and significant increase in CK activity in the mid intestine was associated with dietary methionine deficiency. Malondialdehyde and protein carbonyl contents in the intestine and hepatopancreas were significantly increased by methionine deficiency(P < 0.05), whereas anti-hydroxyl radical capacity in the hepatopancreas and intestine, and anti-superoxide anion capacity in the intestine, were significantly decreased by methionine deficiency(P < 0.05). Moreover, methionine deficiency significantly decreased superoxide dismutase and glutathione reductase activities, glutathione contents in the hepatopancreas and intestine, as well as glutathione peroxidase activity in the intestine(P < 0.05), whereas it significantly increased activities of catalase in the hepatopancreas and glutathione-S-transferase in the hepatopancreas and intestine(P < 0.05).(Continued on next page)(Continued from previous page)Conclusions: The present results demonstrated that dietary methionine deficiency induced poor growth, and decreased digestive and absorptive function and antioxidant capacity in the hepatopancreas and intestine of sub-adult grass carp. Methionine requirements for sub-adult grass carp(450-1, 170 g) based on PWG, intestinal trypsin, and hepatopancreatic anti-hydroxyl radical activities were estimated to be 6.12 g/kg diet(21.80 g/kg protein),6.99 g/kg diet(24.90 g/kg protein) and 5.42 g/kg diet(19.31 g/kg protein), respectively, in the presence of 1.50 g cysteine/kg(5.35 g/kg protein).

中国国家药品监督管理局批准安罗替尼用于经两种系统化疗后疾病进展的晚期非小细胞肺癌的治疗

背景2018年5月8日,中国国家药品监督管理局(National Medical Products Administration,NMPA)批准了小分子多靶点抗血管抑制剂盐酸安罗替尼,用于既往经过至少两种系统化疗后疾病进展的晚期非小细胞肺癌(non-small cell lung cancer,NSCLC)患者的治疗。概要中国NMPA审查了一项随机双盲、安慰剂对照的III期临床试验,该临床试验的主要终点为总生存期(overall survival,OS)。试验共纳入437例患者随机分组(2∶1)接受安罗替尼(n=294)或安慰剂(n=143)治疗,每日1次,连服2周,停药1周。表皮生长因子受体(epidermal growth factor receptor,EGFR)基因敏感突变或间变性淋巴瘤激酶(activating anaplasticlymphomakinase,ALK)阳性的患者须经过NMPA已批准的药物治疗后出现疾病进展。安罗替尼为中国NMPA批准的用于治疗既往经过两种及以上系统化疗后疾病进展的晚期NSCLC患者的首个药物。安罗替尼组的中位OS(9.46个月)较安慰剂组[6.37个月;风险比(hazard ratio,HR)=0.70,95%置信区间(confidence Interval,CI):0.55–0.89;双侧log-rank P=0.002]显著延长。安罗替尼组的客观缓解率(objective responserate,ORR)为9.2%,安慰剂组为0.7%。安罗替尼组的中位缓解持续时间(durationofresponse,DoR)为4.83个月,95%CI为3.31–6.97个月。安罗替尼的常见不良反应(adverse drug reactions,ADRs)包括高血压(67.4%)、手足综合征(43.9%)、咳血(14.0%)、促甲状腺激素(thyroid stimulating hormone,TSH)升高(46.6%)、心电图QT间期(corrected QT Interval,QTc)延长(26.2%)。结论安罗替尼显著延长了患者的OS,可作为经二线及以上化疗后晚期或转移性非小细胞肺癌的一种新的治疗方案。

Oxidized low-density lipoprotein receptor 1:a novel potential therapeutic target for intracerebral hemorrhage

Oxidized low-density lipoprotein receptor 1(OLR1)is upregulated in neurons and participates in hypertension-induced neuronal apoptosis.OLR1 deletion exerts protective effects on cerebral damage induced by hypertensive-induced stroke.Therefore,OLR1 is likely involved in the progress of intracerebral hemorrhage.In this study,we examined the potential role of OLR1 in intracerebral hemorrhage using a rat model.OLR1 small interfering RNA(10μL;50 pmol/μL)was injected into the right basal ganglia to knock down OLR1.Twenty-four hours later,0.5 U collagenase type VII was injected to induce intracerebral hemorrhage.We found that knockdown of OLR1 attenuated neurological behavior impairment in rats with intracerebral hemorrhage and reduced hematoma,neuron loss,inflammatory reaction,and oxidative stress in rat brain tissue.We also found that silencing of OLR1 suppressed ferroptosis induced by intracerebral hemorrhage and the p38 signaling pathway.Therefore,silencing OLR1 exhibits protective effects against secondary injury of intracerebral hemorrhage.These findings suggest that OLR1 may be a novel potential therapeutic target for intracerebral hemorrhage.

Two new secolignans from the roots of Urtica mairei Levi.

Two new secolignans （1 and 2） were isolated from the roots of Urtica mairei Levi. The structures of these two compounds were determined on the basis of extensive spectroscopic methods including HR-EI-MS, 1D and 2D NMR experiments.

Social credit:a comprehensive literature review

To avoid credit fraud,social credit within an economic system has become an increasingly important criterion for the evaluation of economic agent activity and guaranteeing the development of a market economy with minimal supervision costs.This paper provides a comprehensive review of the social credit literature from the perspectives of theoretical foundation,scoring methods,and regulatory mechanisms.The study considers the credit of various economic agents within the social credit system such as countries(or governments),corporations,and individuals and their credit variations in online markets(i.e.,network credit).A historical review of the theoretical(or model)development of economic agents is presented together with significant works and future research directions.Some interesting conclusions are summarized from the literature review.(1)Credit theory studies can be categorized into traditional and emerging schools both focusing on the economic explanation of social credit in conjunction with creation and evolution mechanisms.(2)The most popular credit scoring methods include expert systems,econometric models,artificial intelligence(AI)techniques,and their hybrid forms.Evaluation indexes should vary across different target agents.(3)The most pressing task for regulatory mechanisms that supervise social credit to avoid credit fraud is the establishment of shared credit databases with consistent data standards.

Review of the electrochemical performance and interfacial issues of high-nickel layered cathodes in inorganic all-solid-state batteries

All-solid-state batteries potentially exhibit high specific energy and high safety,which is one of the development directions for nextgeneration lithium-ion batteries.The compatibility of all-solid composite electrodes with high-nickel layered cathodes and inorganic solid electrolytes is one of the important problems to be solved.In addition,the interface and mechanical problems of high-nickel layered cathodes and inorganic solid electrolyte composite electrodes have not been thoroughly addressed.In this paper,the possible interface and mechanical problems in the preparation of high-nickel layered cathodes and inorganic solid electrolytes and their interface reaction during charge–discharge and cycling are reviewed.The mechanical contact problems from phenomena to internal causes are also analyzed.Uniform contact between the high-nickel cathode and solid electrolyte in space and the ionic conductivity of the solid electrolyte are the prerequisites for the good performance of a high-nickel layered cathode.The interface reaction and contact loss between the high-nickel layered cathode and solid electrolyte in the composite electrode directly affect the passage of ions and electrons into the active material.The buffer layer constructed on the high-nickel cathode surface can prevent direct contact between the active material and electrolyte and slow down their interface reaction.An appropriate protective layer can also slow down the interface contact loss by reducing the volume change of the high-nickel layered cathode during charge and discharge.Finally,the following recommendations are put forward to realize the development vision of high-nickel layered cathodes:(1)develop electrochemical systems for high-nickel layered cathodes and inorganic solid electrolytes;(2)elucidate the basic science of interface and electrode processes between high-nickel layered cathodes and inorganic solid electrolytes,clarify the mechanisms of the interfacial chemical and electrochemical reactions between the two materials,and address the intrinsic safety issues;(3)strengthen the development of research and engineering technologies and their preparation methods for composite electrodes with high-nickel layered cathodes and solid electrolytes and promote the industrialization of all-solid-state batteries.

Growth,digestive and absorptive capacity and antioxidant status in intestine and hepatopancreas of sub-adult grass carp Ctenopharyngodonidella fed graded levels of dietary threonine

Background： This study was carried out to investigate effects of threonine levels on growth, digestive and absorptive capacity and antioxidant status in intestine and hepatopancreas of sub-adult grass carp （ Ctenopharyngodonidella）. Results： Weight gain, specific growth rate, feed intake and feed efficiency were significantly improved by dietary threonine （P 〈 0.05）. Intestinal activities of trypsin, chymotrypsin, alpha-amylase, lipase, alkaline phosphatase, y-glutamyl transpeptidase and creatine kinase took the similar trends. Contents of malondialdehyde and protein carbonyl in intestine and hepatopancreas were significantly decreased by dietary optimal threonine supplementation （P 〈 0.05）. Anti-superoxide anion capacity, anti-hydroxyl radical capacity, glutathione content and activities of superoxide dismutase, catalase and glutathione-S-transferase in intestine and hepatopancreas were enhanced by dietary threonine （P 〈 0.05）. Conclusions： Dietary threonine could improve growth, enhance digestive and absorptive capacity and antioxidant status in intestine and hepatopancreas of sub-adult grass carp. The dietary threonine requirement of sub-adult grass carp （441.9-1,013.4 g） based on weight gain was 11.6 g/kg diet or 41.5 g/kg of dietary protein by quadratic regression analysis.

Investigation on step overcharge to self-heating behavior and mechanism analysis of lithium ion batteries

To obtain intrinsic overcharge boundary and investigate overcharge mechanism,here we propose an innovative method,the step overcharge test,to reduce the thermal crossover and distinguish the overcharge thermal behavior,including 5%state of charge(SOC)with small current overcharge and resting until the temperature equilibrium under adiabatic conditions.The intrinsic thermal response and the self-excitation behaviour are analysed through temperature and voltage changes during the step overcharge period.Experimental results show that the deintercalated state of the cathode is highly correlated to self-heating parasitic reactions.Before reaching the upper limit of Negative/Positive(N/P)ratio,the temperature changes little,the heat generation is significantly induced by the reversible heat(endothermic)and ohmic heat,which could balance each other.Following that the lithium metal is gradually deposited on the surface of the anode and reacts with electrolyte upon overcharge,inducing selfheating side reaction.However,this spontaneous thermal reaction could be“self-extinguished”.When the lithium in cathode is completely deintercalated,the boundary point of overcharge is about 4.7 V(~148%SOC,>40℃),and from this point,the self-heating behaviour could be continuously triggered until thermal runaway(TR)without additional overcharge.The whole static and spontaneous process lasts for 115 h and the side reaction heat is beyond 320,000 J.The continuous self-excitation behavior inside the battery is attributed to the interaction between the highly oxidized cathode and the solvent,which leads to the dissolution of metal ions.The dissolved metal ions destroy the SEI(solid electrolyte interphase)film on the surface of the deposited Li of anode,which induces the thermal reaction between lithium metal and the solvent.The interaction between cathode,the deposited Li of anode,and solvent promotes the temperature of the battery to rise slowly.When the temperature of the battery reaches more than 60℃,the reaction between lithium metal and solvent is accelerated.After the temperature rises rapidly to the melting point of the separator,it triggers the thermal runaway of the battery due to the short circuit of the battery.

Dietary protein levels changed the hardness of muscle by acting on muscle fiber growth and the metabolism of collagen in sub-adult grass carp(Ctenopharyngodon idella)

Background:Nutrient regulation has been proven to be an effective way to improve the flesh quality in fish.As a necessary nutrient for fish growth,protein accounts for the highest proportion in the fish diet and is expensive.Although our team found that the effect of protein on the muscle hardness of grass carp was probably related to an increased collagen content,the mechanism for this effect has not been deeply explored.Moreover,few studies have explored the protein requirements of sub-adult grass crap(Ctenopharyngodon idella).Therefore,the effects of different dietary protein levels on the growth performance,nutritional value,muscle hardness,muscle fiber growth,collagen metabolism and related molecule expression in grass carp were investigated.Methods:A total of 450 healthy grass carp(721.16±1.98 g)were selected and assigned randomly to six experimen-tal groups with three replicates each(n=25/replicate),and were fed six diets with 15.91%,19.39%,22.10%,25.59%,28.53%and 31.42%protein for 60 d.Results:Appropriate levels of dietary protein increased the feed intake,percentage weight gain,specific growth rate,body composition,unsaturated fatty acid content in muscle,partial free amino acid content in muscle,and muscle hardness of grass carp.These protein levels also increased the muscle fiber density,the frequency of new muscle fibers,the contents of collagen and IGF-1,and the enzyme activities of prolyl 4-hydroxylases and lysyloxidase,and decreased the activity of matrix metalloproteinase-2.At the molecular level,the optimal dietary protein increased col-lagen type Iα1(Colα1),Colα2,PI3K,Akt,S6K1,La ribonucleoprotein domain family member 6a(LARP6a),TGF-β1,Smad2,Smad4,Smad3,tissue inhibitor of metalloproteinase-2,MyoD,Myf5,MyoG and MyHC relative mRNA levels.The levels of the myostatin-1 and myostatin-2 genes were downregulated,and the protein expression levels of p-Smad2,Smad2,Smad4,p-Akt,Akt,LARP6 and Smad3 were increased.Conclusions:The appropriate levels of dietary protein promoted the growth of sub-adult grass carp and improved muscle hardness by promoting the growth of muscle fibers,improving collagen synthesis and depressing collagen degradation.In addition,the dietary protein requirements of sub-adult grass carp were 26.21%and 24.85%according to the quadratic regression analysis of growth performance(SGR)and the muscle hardness(collagen content),respectively.

境外授权许可引进抗肿瘤新药临床研发策略的审评考虑

随着我国创新药产业的蓬勃发展,授权许可引进逐渐成为创新药企的重要研发模式。不同研发阶段引进的药物,在中国的研发策略有所不同。企业需全面整理药物已产生的境外临床数据,对临床药理学、安全性、有效性和种族敏感性进行详细的分析。应基于上述数据和分析的结果制定合理的临床研发策略。我们鼓励引进中国境内真正未满足临床需求的优质药物,尽可能在研发的早期阶段引进,以实现国内外的同步研发。新药引进后的临床研发策略对于药物能否顺利上市尤为重要,企业应遵循国家药品监督管理局已发布的指导原则和相应的临床指南进行临床试验设计,积极与监管部门进行沟通。