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.

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.

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.

Central nervous system efficacy of aumolertinib versus gefitinib in patients with untreated,EGFR-mutated,advanced non-small cell lung cancer:data froma randomized phase III trial(AENEAS)

Background:The initial randomized,double-blinded,actively controlled,phase III ANEAS study(NCT03849768)demonstrated that aumolertinib showed superior efficacy relative to gefitinib as first-line therapy in epidermal growth factor receptor(EGFR)-mutated advanced non-small cell lung cancer(NSCLC).Metastatic disease in the central nervous system(CNS)remains a challenge in the management of NSCLC.This study aimed to compare the efficacy of aumolertinib versus gefitinib among patients with baseline CNS metastases in the ANEAS study.Methods:Eligible patients were enrolled and randomly assigned in a 1:1 ratio to orally receive either aumolertinib or gefitinib in a double-blinded fashion.Patients with asymptomatic,stable CNS metastases were included.Follow-up imaging of the same modality as the initial CNS imaging was performed every 6 weeks for 15 months,then every 12weeks.CNS responsewas assessed by a neuroradiological blinded,independent central review(neuroradiological-BICR).The primary endpoint for this subgroup analysis was CNS progression-free survival(PFS).Results:Of the 429 patients enrolled and randomized in the ANEAS study,106 patients were found to have CNS metastases(CNS Full Analysis Set,cFAS)at baseline by neuroradiological-BICR,and 60 of them had CNS target lesions(CNS Evaluable for Response,cEFR).Treatment with aumolertinib significantly prolonged median CNS PFS compared with gefitinib in both cFAS(29.0 vs.8.3 months;hazard ratio[HR]=0.31;95%confidence interval[CI],0.17-0.56;P<0.001)and cEFR(29.0 vs.8.3 months;HR=0.26;95%CI,0.11-0.57;P<0.001).The confirmed CNS overall response rate in cEFRwas 85.7%and 75.0%in patients treated with aumolertinib and gefitinib,respectively.Competing risk analysis showed that the estimated probability of CNS progression without prior non-CNS progression or death was consistently lower with aumolertinib than with gefitinib in patients with and without CNSmetastases at baseline.No new safety findings were observed.Conclusions:These results indicate a potential advantage of aumolertinib over gefitinib in terms of CNS PFS and the risk of CNS progression in patients with EGFR-mutated advanced NSCLC with baseline CNS metastases.

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。

Revealing the interaction mechanism of pulsed laser processing with the application of acoustic emission

The mechanisms of interaction between pulsed laser and materials are complex and indistinct,severely infuencing the stability and quality of laser processing.This paper proposes an intelligent method based on the acoustic emission(AE)technique to monitor laser processing and explore the interaction mechanisms.The validation experiment is designed to perform nanosecond laser dotting on foat glass.Processing parameters are set diferently to generate various outcomes:ablated pits and irregular-shaped cracks.In the signal processing stage,we divide the AE signals into two bands,main and tail bands,according to the laser processing duration,to study the laser ablation and crack behavior,respectively.Characteristic parameters extracted by a method that combines framework and frame energy calculation of AE signals can efectively reveal the mechanisms of pulsed laser processing.The main band features evaluate the degree of laser ablation from the time and intensity scales,and the tail band characteristics demonstrate that the cracks occur after laser dotting.In addition,from the analysis of the parameters of the tail band very large cracks can be efciently distinguished.The intelligent AE monitoring method was successfully applied in exploring the interaction mechanism of nanosecond laser dotting foat glass and can be used in other pulsed laser processing felds.

Ictal hypersalivation as a prominent symptom in a girl with insulo-opercular epilepsy

Introduction:Hypersalivation has been associated with Rolandic epilepsy and other childhood epilepsy syndromes.However,pure salivatory seizures are a rare type of focal seizure in which ictal hypersalivation is the dominant feature throughout the seizures.Case presentation:We present a case of pure salivatory seizures originating from the right post-central operculum cortex,confirmed by the favorable surgical outcome.We attempt to analyze the symptom from behavioral and neural network perspectives and propose a possible mechanism to generate ictal hypersalivation and pure salivatory seizures.Conclusion:Based on previous reports in the literature and our case,we emphasize the importance of the operculum in patients with ictal hypersalivation,particularly in patients with pure salivatory seizures.

Design and high-strength origin of novel (CoFeNi)_(80)Ti_(5)V_(15) medium entropy alloy with “fcc + L1_(2) ”structure

1.Introduction The multi-component high entropy alloys(HEAs)or medium entropy alloys(MEAs)attract reseachers’extensive attention,in particular,the single-face center cubic(fcc)HEAs or MEAs due to their some advantages,such as excellent ductility[1,2],good corrosion resistance[3]and high radiation tolerance[4].However,their strength is commonly insufficient for engineering applica-tions.Recently,many investigations are ongoing to improve their strength by traditional strengthening mechanisms,like fine-grained strengthening[5,6],solid strengthening[6-8],strain strengthening[9],polyphase strengthening[10-12],and precipitation strength-ening[13-15].Among these strengthening mechanisms,the co-herent L1_(2)-type nanoparticles precipitation strengthening has been proven to be a very effective way to improve their strength[13-15].

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.

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.

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.

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。