Glycyrrhizic acid alleviates lung injury in sepsis through SIRT1/HMGB1 pathway

Objectives:This study explores the protective effects of glycyrrhizic acid(GA)on sepsis-induced cellular damage and inflammation in acute lung injury(ALI),specifically through the modulation of the sirtuin 1(SIRT1)and high mobility group box 1(HMGB1)pathway.Methods:The study employed two experimental models:lipopolysaccharide(LPS)-induced BEAS-2B human lung epithelial cells and cecal ligation and puncture(CLP)rats,to simulate sepsis conditions.The cell model involved treatments with LPS,GA,control siRNA(si-NC),and SIRT1-specific siRNA(si-SIRT1).Evaluations included cell viability,apoptosis,and cytokine production.In the rat model,treatments included GA and the SIRT1 inhibitor EX527,with assessments on lung tissue damage,inflammation,and protein expression using Western blot and co-immunoprecipitation(Co-IP)analysis.Results:LPS exposure significantly reduced SIRT1 mRNA levels and cell viability in BEAS-2B cells,which effects were reversed by cotreatment with GA and si-NC but negated by si-SIRT1.LPS also induced apoptosis and increased pro-inflammatory cytokines and HMGB1 expression,which were mitigated by GA and si-NC and exacerbated by si-SIRT1.In CLP rats,GA treatment decreased lung tissue damage,inflammatory cytokines,and HMGB1 expression,and enhanced SIRT1 levels.However,these protective effects were reversed when GA was combined with EX527.Conclusion:GA demonstrates significant protective effects against LPS-induced damage and inflammation in lung cells and tissue by modulating the SIRT1-HMGB1 pathway.This suggests that GA could be a potential therapeutic strategy for treating sepsis and related inflammatory conditions.

科学基金项目会议评审机制刍议

项目评审是科学基金管理工作的核心。本文梳理分析了目前科学界日益关注的会议评审过程中存在的问题,重新审视会议评审的意义和功能,提出基于"确认-纠偏-择优"原则的会评评审改革建议和措施。

Cell cycle regulation and anticancer drug discovery

Cellular growth,development,and differentiation are tightly controlled by a conserved biological mechanism:the cell cycle.This cycle is primarily regulated by cyclin-dependent kinase(CDK)-cyclin complexes,checkpoint kinases,and CDK inhibitors.Deregulation of the cell cycle is a hallmark of the transformation of normal cells into tumor cells.Given its importance in tumorigenesis,several cell cycle inhibitors have emerged as potential therapeutic drugs for the treatment of cancers-both as singleagent therapy and in combination with traditional cytotoxic or molecular targeting agents.In this review,we discuss the mechanisms underlying cell cycle regulation and present small-molecule anticancer drugs that are under development,including both pan-CDK inhibitors and CDK4/6-selective inhibitors.In addition,we provide an outline of some promising CDK inhibitors currently in preclinical and clinical trials that target cell cycle abnormalities in various cancers.

Decrease in the Ki67 index during neoadjuvant chemotherapy predicts favorable relapse-free survival in patients with locally advanced breast cancer

Objective: The purpose of this study was to explore the optimal cutoffs of the three parameters of Ki67 during NAC for predicting patient prognosis and investigate whether the optimal cutoffs of the Ki67 values were associated with relapse-free survival(RFS) or breast cancer-specific survival(BCSS).Methods: A total of 92 patients with locally advanced breast cancer(LABC), who had residual disease after NAC were retrospectively investigated.The optimal cutoff values of the Ki67 parameters were assessed by the online algorithm Cutoff Finder.Kaplan-Meier analysis, the log-rank test and Cox regression analysis were carried out to analyze survival.Results: The optimal cutoff values for the postsurgical Ki67 level and the decrease in the Ki67 level during NAC were defined as 25% and 12.5%, respectively.According to the univariate survival analysis, a higher Ki67 level in residual disease was associated with poor RFS(P = 0.004) and BCSS(P = 0.014).In addition, a Ki67 expression decrease > 12.5% during NAC was related to favorable RFS(P = 0.007), but was not related to BCSS(P = 0.452).Cox regression analysis showed that the Ki67 expression decrease(> 12.5% vs.≤ 12.5%) and histological grade(grade 3 vs.grade 1-2) were the independent factors associated with RFS(P =0.020 and P = 0.023, respectively), with HR values of 0.353(95% CI: 0.147-0.850) and 3.422(95% CI: 1.188-9.858), respectively.Conclusions: The Ki67 decrease was one of the independent factors associated with RFS in LABC patients with residual disease after receiving NAC.

Insights into the transition of ductal carcinoma in situ to invasive ductal carcinoma:morphology,molecular portraits,and the tumor microenvironment

Breast cancer is posing an increasing burden and has become the cancer with the highest incidence among in women in China.The most common histological subtype of breast cancer is invasive ductal carcinoma(IDC)1,2.Ductal carcinoma in situ(DCIS)is a pre-cancerous lesion that may give rise to IDC.DCIS is a highly heterogeneous group of lesions consisting of 5 main types,which differ in clinical presentation,histologic features,biomarker profiles,genetic abnormalities,progression potential,and clinical outcomes.When cancer cells invade through the basal membrane,they acquire the ability to metastasize.This process is usually accompanied by many genetic and epigenetic changes in tumor suppressors and oncogenes.

Preface to special issue on precise electrocatalysis

Electrocatalysis plays a critical role to tackle the global challenges of energy and environment.Introduction of new concept,theory,method and paradigm has spurred its prosperous development;and as an indicator,the scientific publications have been doubled in last five years.

Insight into the evolution of breast cancer driven by genetic alterations

Breast cancer originates primarily from the epithelial cells of the mammary gland.Repeated mammary gland expansion and degeneration are accompanied by an increased risk of genetic alterations in the breast1.These mutations in breast epithelial cells dynamically occur in response to pregnancy,labor and delivery,breastfeeding,and the menstrual cycle,with a decline in mutation rates after menopause,which may be related to a decrease in estrogen levels.The breast epithelial cell mutations are also consistent with epidemiologic observations2.

Tissue Culture of Calla Lily (Zantedeschia spreng.): An Updated Review on the Present Scenario and Future Prospects

The calla lily(Zantedeschia spreng.)is a bulbousflower native to the tropical regions of Africa.Calla lily has gained significant popularity in the international market owing to its intricate morphology and prolonged flowering duration.Despite such advantages,for two sub-groups of calla lily,known as group Zantedeschia and group Aestivae,there are challenges in terms of hybrid production due to the‘plastome-genome incompatibility’there-between.Tissue culture is a fundamental biotechnological tool used in gene editing research,with a focus on disease resistance andflower color in calla lily breeding programs.The present review provides a brief background on the history and development of the calla lily,as well as a comprehensive and critical summary of calla lily tissue culture research.The regeneration pathways for both group Zantedeschia and group Aestivae can be divided into de novo organogenesis and somatic embryogenesis.Both groups are capable of obtaining replants through such means.However,only some species in group Aestivae have been reported to be successful in the somatic embryogenesis pathway.In the present review,special attention was paid to the influence of explant types,plant growth regulators,and culture conditions on both de novo organogenesis and somatic embryogenesis in calla lily tissue culture.Ultimately,future research prospects were determined based on integrated analysis of recent progress in calla lily tissue culture research.

转型中的中国化学——基金委化学部十三五规划实施纪行

创新是引领发展的第一动力,国家自然科学基金委员会化学科学部在"十三五"期间多措并举,以弘扬科学精神为主线,推动管理体制创新,深化科学基金改革,开创化学科学基金新局面.本文全面梳理了化学科学部在作风学风建设、学科布局、资助格局等方面的主要工作进展情况,并提出了学部未来工作的规划和构想.

医药化工领域研究现状和发展态势

化学工程的研究对象正不断拓展并与其他诸多学科进行交叉,医药工业在我国已进入蓬勃发展的新时期。医药与化工的融合由来已久,在“医药化工”被写入国家自然科学基金委项目指南后,这一交叉领域的发展进入新阶段。本文基于国家自然科学基金委员会化学科学部第一期科技活动项目—“食品与医药化工学科发展战略研讨会”取得的成果,凝练了医药化工这一交叉学科的科学内涵,总结了医药化工学科的重大技术难题和关键科学问题,并对该领域未来需重点研究的内容给出了建议。

变革性储能技术的化学工程科学问题

本文归纳总结了变革性储能技术的研发现状和发展趋势。从化学工程学科的角度,分析了变革性储能技术发展面临的主要挑战,凝练了储能材料—器件—系统亟需解决的关键科学问题,提出了“新能源化工”发展的新思路及未来的研究重点,助力推动我国变革性储能技术的研发能力提升,为促进绿色低碳发展发挥战略性、基础性和先导性作用。

High-entropy ceramics:Present status,challenges,and a look forward

High-entropy ceramics (HECs) are solid solutions of inorganic compounds with one or more Wyckoff sites shared by equal or near-equal atomic ratios of multi-principal elements.Although in the infant stage,the emerging of this new family of materials has brought new opportunities for material design and property tailoring.Distinct from metals,the diversity in crystal structure and electronic structure of ceramics provides huge space for properties tuning through band structure engineering and phonon engineering.Aside from strengthening,hardening,and low thermal conductivity that have already been found in high-entropy alloys,new properties like colossal dielectric constant,super ionic conductivity,severe anisotropic thermal expansion coefficient,strong electromagnetic wave absorption,etc.,have been discovered in HECs.As a response to the rapid development in this nascent field,this article gives a comprehensive review on the structure features,theoretical methods for stability and property prediction,processing routes,novel properties,and prospective applications of HECs.The challenges on processing,characterization,and property predictions are also emphasized.Finally,future directions for new material exploration,novel processing,fundamental understanding,in-depth characterization,and database assessments are given.

Bevacizumab biosimilar LY01008 compared with bevacizumab(Avastin)as first-line treatment for Chinese patients with unresectable,metastatic,or recurrent non-squamous non-small-cell lung cancer:A multicenter,randomized,double-blinded,phase Ⅲ trial

Background:Previous studies have demonstrated the preclinical pharmacological and toxicological consistency,and clinical pharmacokinetic equivalence of bevacizumab biosimilar LY01008 with reference bevacizumab(Avastin).This randomized controlled trial aimed to compare the efficacy and safety of LY01008 with Avastin in first-line treatment of Chinese patients with advanced or recurrent non-squamous non-small cell lung cancer(NSCLC).Methods:StageⅢB-ⅣNSCLC patients with evaluable lesions,good physical status,and adequate organ functions from 67 centers across China were randomized in a ratio of 1:1 to receive LY01008 or Avastin 15 mg/kg intravenously in combination with paclitaxel/carboplatin(combined treatment)for 4-6 cycles,followed by maintenance monotherapy with LY01008 until disease progression,intolerable toxicity,or death.The primary endpoint was objective response rate(ORR)in accordance with Response Evaluation Criteria in Solid Tumors(RECIST)version 1.1 confirmed by independent radiological review committees(IRRC).Secondary endpoints included disease control rate(DCR),duration of response(DoR),progression-free survival(PFS),overall survival(OS),and safety.This study was registered in Clinical Trials.gov(NCT03533127).Results:Between December 15^(th),2017,and May 15^(th),2019,a total of 649 patients were randomized to the LY01008(n=324)or Avastin(n=325)group.As of September 25th,2019 for primary endpoint analysis,589 patients received ORR evaluation,with a median number of combined treatment cycles of 5(range 1-6)andmedian duration of treatment of 3.0(range 0.0-5.1)months.ORRof responseevaluable patients in the LY01008 and Avastin groups were 48.5% and 53.0%,respectively.The stratified ORR ratio was 0.91(90%CI 0.80-1.04,within the prespecified equivalence margin of 0.75-1.33).Up to May 15^(th),2020,with a median follow-up of 13.6(range 0.8-28.4)months,no notable differences in DCR,median DoR,median PFS,median OS,and 1-year OS rate were observed between the LY01008 and Avastin groups.There were no clinically meaningful differences in safety and immunogenicity across treatment groups.Conclusions:LY01008 demonstrated similarity to Avastin in terms of efficacy and safety in Chinese patients with advanced or recurrent non-squamous NSCLC.LY01008 combined with paclitaxel/carboplatin is expected to become a new treatment option for unresectable,metastatic,LY01008 and Avastin groups.There were no clinically meaningful differences in safety and immunogenicity across treatment groups.Conclusions:LY01008 demonstrated similarity to Avastin in terms of efficacy and safety in Chinese patients with advanced or recurrent non-squamous NSCLC.LY01008 combined with paclitaxel/carboplatin is expected to become a new treatment option for unresectable,metastatic,or recurrent non-squamous NSCLC patients in the first-line setting.

从经济特区到先行示范区：深圳税务深度服务改革开放

新中国成立后,特别是改革开放以来,深圳始终坚持中国特色社会主义道路不动摇,从“一个圈”到一座城,从小渔村到国际化创新型大都市,从经济特区到先行示范区,为中国特色社会主义的发展提供了鲜活经验,充分展示了中国特色社会主义的巨大优越性。

Analytical validation of GMEX rapid point- of care CYP2C19 genotyping system for the CHANCE-2 trial

Background and purpose Rapid genotyping is useful for guiding early antiplatelet therapy in patients with high-risk nondisabling ischaemic cerebrovascular events(HR-NICE).Conventional genetic testing methods used in CYP2C19 genotype-guided antiplatelet therapy for patients with HR-NICE did not satisfy the needs of the Clopidogrel in High-Risk Patients with Acute Nondisabling Cerebrovascular Events(CHANCE)-2 trial.Therefore,we developed the rapid-genotyping GMEX(point-of care)system to meet the needs of the CHANCE-2 trial.Methods Healthy individuals and patients with history of cardiovascular diseases(n=408)were enrolled from six centres of the CHANCE-2 trial.We compared the laboratory-based genomic test results with Sanger sequencing test results for accuracy verification.Next,we demonstrated the accuracy,timeliness and clinical operability of the GMEX system compared with laboratory-based technology(YZY Kit)to verify whether the GMEX system satisfies the needs of the CHANCE-2 trial.Results Genotypes reported by the GMEX system showed 100%agreement with those determined by using the YZY Kit and Sanger sequencing for all three CYP2C19 alleles(*2,*3 and*17)tested.The average result’s turnaround times for the GMEX and YZY Kit methods were 85.0(IQR:85.0-86.0)and 1630.0(IQR:354.0-7594.0)min(p<0.001),respectively.Conclusions Our data suggest that the GMEX system is a reliable and feasible point-of care system for rapid CYP2C19 genotyping for the CHANCE-2 trial or related clinical and research applications.

Effect of assisted transverse magnetic field on distortion behavior of thin-walled components in WEDM process

Machining performance of thin-walled components made by aeronautical difficult-toprocess materials is a significant issue in the aviation manufacturing industry.Although wire electric discharge machining-low speed(WEDM-LS)is one of typical non-contact machining processes without macro cutting force,which does well in removing hardness and brittleness materials via pulsed discharge at high temperature,but few researchers have studied the thermal distortion behavior leading to a considerable geometric error in the WEDM-LS of thin-walled components.In this paper,a transverse magnetic field assisted method is applied for affecting the uniformity of discharge point distribution so as to reduce the distortion in WEDM-LS processing thin-wall component.First,the generation mechanism of this new distortion behavior and the impact mechanism of transverse magnetic field(TMF)on distortion are demonstrated by theoretical analysis.In order to further figure out the distortion behavior in the TMF-WEDM process,a new thermophysical model considering the discharge point distribution is established to simulate temperature field,residual stress field and distortion profiles.Then a large number of Taguchi experiments are carried out to investigate the influences of process parameters including pulse discharge energy(pulse on time,pulse off time,and current)and magnetic field strength on distortion in WEDM-LS.To comparatively analyze simulated and experimental results,the accuracy of established thermophysical model is verified within a relative error of 18.38%in distortion.Moreover,it can be revealed that transverse magnetic field contribute to significantly improve the longitudinal distribution uniformity with maximum increase of 12.32%at magnetic field strength:0.15 T,leading to significant reductions of 32.77%in distortion and 22.68%in recast layer.Eventually,we also presented the variation of residual stress and recast layer along thickness direction under different distortion behavior,which are in good agreement with that of distortion behavior.

Direct comparison of culture-dependent and culture-independent molecular approaches reveal the diversity of fungal endophytic communities in stems of grapevine(Vitis vinifera)

Grapevines(Vitis vinifera)are colonized by ubiquitous microorganisms known as endophytes,which may have advantageous or neutral effects without causing disease symptoms.Certain endophytes are uncultivable,so culture-independent approaches such as next generation sequencing(NGS)can help for a better understanding of their ecology and distribution.To date,there are no studies which directly link NGS results with taxa derived from a culturing approach,integrating morphological and multi-gene phylogenetic analysis of endophytes.In this study,a culture-dependent and high-resolution culture-independent approach(next generation sequencing)were used to identify endophytes in grapevine stems.In the culture-dependent approach,a total of 94 isolates were recovered from 84 of 144 healthy grapevine stem fragments(colonization rate=58.3%).The study is unique as we used subsets of combined multi-gene regions to identify the endophytes to species level.Based on each multi-gene phylogenetic analysis,28 species belong to 19 genera(Acremonium,Alternaria,Arthrinium,Ascorhizoctonia,Aspergillus,Aureobasidium,Bipolaris,Botryosphaeria,Botrytis,Chaetomium,Cladosporium,Curvularia,Hypoxylon,Lasiodiplodia,Mycosphaerella,Nigrospora,Penicillium,Phoma,Scopulariopsis)were identified.A higher number of culturable fungi were obtained from 13 year-old vines,followed by eight and three yearold vines.In the culture-independent approach,a fungal richness of 59 operational taxonomic units(OTU)was detected,being highest in 13 year-old grapevines,followed by eight and three years.Even though the cultivation approach detected lower fungal richness,the results related to stem are consistent for fungal community composition and richness.Comparison of the fungal taxa identified by the two approaches resulted in an overlap of 53%of the fungal genera.Due to interspecific variability of the sequences from NGS,in many cases the OTUs(even with the highly abundant ones)were only assignable to order,family or genus level.Incorporating multi-gene phylogenies we successfully identified many of the NGS derived OTUs with poor taxonomic information in reference databases to the genus or species levels.Hence,this study signifies the importance of applying both culture-dependent and culture-independent approaches to study the fungal endophytic community composition in Vitis vinifera.This principle could also be applied to other host species and ecosystem level studies.

Self-ball milling strategy to construct high-entropy oxide coated LiNi_(0.8)Co_(0.1)Mn_(0.1)O_(2) with enhanced electrochemical performance

High-entropy oxides(HEOs)are a new class of emerging materials with fascinating properties(such as structural stability,tensile strength,and corrosion resistance).High-entropy oxide coated Ni-rich cathode materials have great potential to improve the electrochemical performance.Here,we present a facile self-ball milling method to obtain(La_(0.2)Nd_(0.2)Sm_(0.2)Eu_(0.2)Gd_(0.2))_(2)Zr_(2)O_(7)(HEO)coated LiNi_(0.8)Co_(_(0.1))Mn_(_(0.1))O_(2)(NCM811).The HEO coating endows NCM811 with a stable surface,reduces the contact with the external environment(air and electrolyte),and inhibits side reactions between cathode and electrolyte.These favorable effects,especially when the coating amount is 5 wt%,result in a significant reduction of the battery polarization and an increase in the capacity retention from 57.3%(NCM811)to 74.2%(5HEO-NCM811)after 300 cycles at 1 C(1 C=200 mA·h·g^(−1)).Moreover,the morphology and spectroscopy analysis after the cycles confirmed the inhibitory effect of the HEO coating on electrolyte decomposition,which is important for the cycle life.Surprisingly,HEO coating reduces the viscosity of slurry by 37%–38%and significantly improves the flowability of the slurry with high solid content.This strategy confirms the feasibility of HEO-modified Ni-rich cathode materials and provides a new idea for the design of high-performance cathode materials for Li-ion batteries.

Enhanced oxidation resistance of Mo-12Si-8.5B alloys with ZrB2 addition at 1300℃

Mo-12Si-8.5B and Mo-12Si-8.5B-1.0wt%ZrB2 alloys were fabricated using mechanical alloying, fol- lowed by hot-pressing. Both alloys exhibited uniform microstructure, with the Mo3Si and MosSiB2 phases distributing dispersedly in the （x-Mo matrix. Mo-12Si-8.SB-1.0wt%ZrB2 showed a finer-grained microstructure than Mo-12Si-8.5B alloy owing to the addition of ZrB2. The results of isothermal oxidation tests at 1300 ℃ in air revealed that Mo-12Si-8.5B and Mo-12Si-8.SB-1.Owt%ZrB2 alloys initially suffered a transient stage with high mass loss due to the volatilization of MOO3, and then achieved a steady stage owing to the formation of a protective borosilicate scale on the alloy surface. Especially, the transient stage of Mo-12Si-8.5B-1.0wt%ZrB2 alloy was shortened to be less than 300 s, and the mass loss of this stage was reduced by at least 88% compared with that of Mo-12Si-8.5B alloy, indicating a significant improve- ment in the oxidation resistance. The addition of ZrB2 not only resulted in a continuous borosilicate scale quickly covering the entire base alloy during the transient stage, but also improved the protectiveness of the borosilicate scale of the steady stage by bringing out a large number of ZrO2/ZrSiO4 particles embed- ded discontinuously in the borosilicate scale, which effectively restricted the inward diffusion of oxygen by acting as diffusion barriers and decreased the thickness of inner oxide layers in particular.