Electrospinning of Flexible Poly(vinyl alcohol)/MXene Nanofiber-Based Humidity Sensor Self-Powered by Monolayer Molybdenum Diselenide Piezoelectric Nanogenerator

Two-dimensional material has been widely investigated for potential applications in sensor and flexible electronics.In this work,a self-powered flexible humidity sensing device based on poly(vinyl alcohol)/Ti_(3)C_(2)Tx(PVA/MXene)nanofibers film and monolayer molybdenum diselenide(MoSe2)piezoelectric nanogenerator(PENG)was reported for the first time.The monolayer MoSe_(2)-based PENG was fabricated by atmospheric pressure chemical vapor deposition techniques,which can generate a peak output of 35 mV and a power density of42 mW m^(-2).The flexible PENG integrated on polyethylene terephthalate(PET)substrate can harvest energy generated by different parts of human body and exhibit great application prospects in wearable devices.The electrospinned PVA/MXene nanofiber-based humidity sensor with flexible PET substrate under the driven of monolayer MoSe_(2) PENG,shows high response of~40,fast response/recovery time of 0.9/6.3 s,low hysteresis of 1.8%and excellent repeatability.The self-powered flexible humidity sensor yields the capability of detecting human skin moisture and ambient humidity.This work provides a pathway to explore the high-performance humidity sensor integrated with PENG for the self-powered flexible electronic devices.

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。

Protein phosphorylation associated with drought priming-enhanced heat tolerance in a temperate grass species

Protein phosphorylation is known to play crucial roles in plant tolerance to individual stresses,but how protein phosphorylation is associated with cross-stress tolerance,particularly drought priming-enhanced heat tolerance is largely unknown.The objectives of the present study were to identify phosphorylated proteins and phosphorylation sites that were responsive to drought priming and to determine whether drought priming-enhanced heat tolerance in temperate grass species involves changes in protein phosphorylation.Comparative analysis of phosphoproteomic profiles was performed on leaves of tall fescue(Festuca arundinacea)exposed to heat stress(38/33°C,day/night)with or without drought priming.A total of 569 differentially regulated phosphoproteins(DRPs)with 1098 phosphorylation sites were identified in response to drought priming or heat stress individually or sequentially.Most DRPs were nuclear-localized and cytosolic proteins.Motif analysis detected[GS],[DSD],and[S..E]as major phosphorylation sites in casein kinase-II and mitogen-activated protein kinases regulated by drought priming and heat stress.Functional annotation and gene ontology analysis demonstrated that DRPs in response to drought priming and in droughtprimed plants subsequently exposed to heat stress were mostly enriched in four major biological processes,including RNA splicing,transcription control,stress protection/defense,and stress perception/signaling.These results suggest the involvement of post-translational regulation of the aforementioned biological processes and signaling pathways in drought priming memory and cross-tolerance with heat stress in a temperate grass species.

Exponential-Alpha Safety Criteria of a Class of Dynamic Systems With Barrier Functions

A classic kind of researches about the operational safety criterion for dynamic systems with barrier function can be roughly summarized as functional relationship,denoted by⊕,between the barrier function and its first derivative for time t,where⊕can be“=”,“<”,or“>”,etc.This article draws on the form of the stable condition expression for finite time stability to formulate a novel kind of relaxed safety judgement criteria called exponential-alpha safety criteria.Moreover,we initially explore to use the control barrier function under exponential-alpha safety criteria to achieve the control for the dynamic system operational safety.In addition,derived from the actual process systems,we propose multi-hypersphere methods which are used to construct barrier functions and improved them for three types of special spatial relationships between the safe state set and the unsafe state set,where both of them can be spatially divided into multiple subsets.And the effectiveness of the proposed safety criteria are demonstrated by simulation examples.

Growth and physiological effects of chitosan on heat tolerance in creeping bentgrass (Agrostis stolonifera)

High temperature is one of the major abiotic stresses limiting growth and development of cool-season grass species,but chitosan could effectively enhance heat tolerance and improve plant growth.The objective of this study was to determine the optimal concentration of chitosan that could alleviate heat stress in creeping bentgrass(Agrostis stolonifera)and investigate the effects of exogenous chitosan on photosynthesis and cell membrane stability under heat stress.Under heat stress(38/28°C,day/night),different chitosan concentrations of 0,50,100 and 500 mg·L−1 were applied on the leaves of creeping bentgrass(cv.'Penn-A4').Foliar application of chitosan exhibited the positive effects on plant growth and the optimal concentration was 100 mg·L−1 which significantly improved turf quality,root length,root-shoot ratio as well as shoot and root biomass.Chitosan-treated plants subjected to high temperature stress had a lower decline in photosynthetic rate and photochemical efficiency as well as less increase in electrolyte leakage and malondialdehyde content.The results demonstrate that chitosan-improved heat tolerance as reflected by the superior growth performance of both shoot and root,photosynthesis and cell membrane stability in creeping bentgrass under heat stress.

Clinical review considerations of class I PI3K inhibitors in hematolymphatic malignancies by Center for Drug Evaluation

Several phosphoinositide 3-kinase(PI3 K) inhibitors are currently approved to treat hematolymphatic malignant diseases worldwide, and many drugs that have the same target are in the clinical research stage. In March 2022,duvelisib became the first PI3 K inhibitor approved in China indicated for the treatment of hematolymphatic malignant diseases. Meanwhile, linperlisib and copanlisib have almost completed the technical review of the clinical specialty. The Center for Drug Evaluation(CDE) of the China National Medical Products Administration(NMPA) found that class I PI3 K inhibitors can cause various degrees of immune-related adverse events, which are associated with action mechanisms, affecting the benefit-risk assessment of the drugs. On April 21, 2021, the United States Food and Drug Administration(FDA) convened the Oncologic Drugs Advisory Committee(ODAC)meeting to discuss the safety of PI3 K inhibitors indicated for hematolymphatic malignancies and their related risk of death. The hematological tumor group of CDE of the China NMPA summarized and combined the data on PI3 K inhibitors listed or under technical review for marketing authorization applications and found that such products may have unique efficacy and safety characteristics in Chinese patients with malignant lymphoma.

Exploring the salt-and drought-tolerant genes of alfalfa through expression library screening strategy

Salinity and drought stress are major abiotic stresses negatively affecting the growth and productivity of alfalfa(Medicago sativa L.).Exploration of genes exhibiting superior tolerance to salinity and drought stress in alfalfa will help aid target molecular breeding and developing tolerant forages.In this study,we adopted a high-efficient yeast FOX hunting system for the identification of salinity and drought tolerant genes in alfalfa.Based on the Gateway-compatible vector system,a high-quality expression library was constructed,containing 1.3×10^(7) clones with an average size of 1.44 kb.Through heterologous transformation of mixed library plasmid into salt or drought sensitive yeast mutants,monoclonal resistant strains were screened and tolerant genes were captured.Eighteen salinity-tolerance genes were obtained which were involved in several pathways,containing GRAS and zinc finger transcriptional factors,PP2A interaction module,ERVT vesicle transporter and LETM transmembrane protein.Twelve drought tolerance genes were separated,including ERF and SCL transcriptional factors,CIPK and BSK protein kinases,TGL-type ligase,cPGM and cPDL protease.The mRNA transcription levels of these tolerant genes were inducible or suppressible for response to salt or drought stress conditions following quantitative PCR detection,respectively.Furthermore,heterologous transformation of ERVT and CIPK11 can improve the salt and drought stress tolerance in Arabidopsis,which indicates the conservative function of the screening gene in yeast and Arabidopsis.Obtaining these candidate genes can provide new insights for future research with respect to plant salt and drought tolerance.

Prognostic and clinical value of circPRKCI expression in diverse human cancers

Background:Highly expressed in various human cancers,circular RNA Protein Kinase C Iota(circPRKCI)has been reported to play an important role in cancer development and progression.Herein,we sought to reveal the prognostic and clinical value of circPRKCI expression in diverse human cancers.Methods:We searched the Pubmed,Web of Science,and the Cochrane Library databases from inception until May 16,2021.The relationship between circPRKCI expression and cancer patients’survival,including overall survival(OS)and disease-free survival(DFS),was assessed by pooled hazard ratios(HR)with corresponding 95%confidence interval(CI).The correlation between circPRKCI expression and clinical outcomes was evaluated using odds ratios(OR)with corresponding 95%CI.The data were analyzed by STATA software(version 12.0)or Review Manager(RevMan 5.3).Results:A total of 15 studies with 1109 patients were incorporated into our meta-analysis.The results demonstrated that high circPRKCI expression was significantly related to poor OS(HR=1.96,95%CI:1.61,2.39,P<0.001)when compared with low circPRKCI expression in diverse human cancers.However,elevated circPRKCI expression was not associated with DFS(HR=1.34,95%CI:0.93,1.95,P=0.121).Furthermore,the patient with a higher circPRKCI expression was prone to have a larger tumor size,advanced clinical stage,and lymph node metastasis,but it was not significantly correlated with age,gender,and distant metastasis.Conclusion:Elevated circPRKCI expression was correlated with worse OS and unfavorable clinical features,suggesting a novel prognostic and predictive role of circPRKCI in diverse human cancers.

Effectiveness of Frequent Viral Load Testing Plus Additional Interventions to Prevent HIV Transmission in Heterosexual,Serodiscordant Couples—Yunnan Province,China,2019-2021

Summary What is already known about this topic?HIV transmission among serodiscordant couples remains a persistent issue in China.However,the practice of combining counseling with antiretroviral therapies(ART)to enhance ART adherence is not widely implemented or recommended in Chinese health guidelines.What is added by this report?

Glioblastoma cell-derived exosomes functionalized with peptides as efficient nanocarriers for synergistic chemotherapy of glioblastoma with improved biosafety

Glioblastoma(GBM)has been regarded as one of the most deadly and challenging cancers to treat with extremely poor prognosis.The limited efficacy of current chemotherapies might be attributed to the presence of glioma stem cells(GSCs)as well as the difficulties in passing through the blood–brain barrier(BBB)and targeting tumor cells.Tumor-derived exosomes are emerging as novel and promising drug delivery systems.However,great concerns regarding the biosafety and BBB penetrability remain to be addressed.Herein,we have developed a simple and feasible strategy to engineer GBM cell-derived exosomes with improved biosafety termed“Exo@TDPs”to deliver the cargos of chemotherapeutic agents temozolomide(TMZ)and doxorubicin(DOX)into GBM tissues.Exo@TDPs decorated with angiopep-2(Ang-2)and CD133-targeted peptides improve the capacity to penetrate the BBB and target tumor cells.Both in vitro and in vivo studies demonstrate that Exo@TDPs can cross the BBB,target GBM cells,penetrate into deep tumor parenchyma,and release the therapeutic cargos effectively.Synergistic delivery of TMZ and DOX by Exo@TDPs exerts therapeutic effects to suppress the tumor growth and prolong the survival time of orthotopic syngeneic mouse GBM models.These findings suggest that our developed Exo@TDPs loaded with chemotherapeutic drugs may bring new possibilities for the application of tumor cell-derived exosomes for brain tumor treatment.

Criteria and regulatory considerations for the conditional approval of innovative antitumor drugs in China:from the perspective of clinical reviewers

1 BACKGROUND Before the State Council of the People’s Republic of China issued the“Opinions on the Reform of the Examination and Approval System of Pharmaceutical and Medical Devices”[1],several problems existed in China’s drug evaluation and approval system.The long approval time and low efficiency of new drug marketing seriously affected the enthusiasm for drug innovation.To this end,the current“Drug Registration Regulation”(DRR)[2]was initiated by the National Medical Products Administration of China and officially implemented on July 1,2020.To encourage clinical value-oriented drug innovation,four expedited drug programs were first proposed,including breakthrough therapy drugs,conditional approval,priority review,and special approval procedures.For drugs listed in the expedited programs,the drug regulatory authorities and professional technical institutions should provide policy and technical support,prioritize the allocation of communication and review resources,and thereafter shorten the review time as much as possible.

An Index–Contact Paired Data Analysis on Sexual Contact Tracing Outcomes of HIV-Infected Individuals—Yunnan Province,China,2022–2024

What is already known about this topic?A substantial proportion of people living with human immunodeficiency virus(PLWH)remain unaware of their infection status.Contact tracing serves as an effective public health tool for identifying human immunodeficiency virus(HIV)infections and supports progress toward achieving the 95-95-95-95 goals.What is added by this report?

土壤性质对其吸附短链全氟羧酸的影响

本文研究了土壤理化性质对其吸附短链全氟羧酸(PFCAs)的影响.研究结果表明, Freundlich和Virial吸附等温线均可对吸附数据进行较完美的拟合,相关系数(R^2)分别介于0.9651~0.9989和0.8670~0.9985.各种土壤性质与短链PFCAs固液分配系数(K_d)的线性回归分析结果表明,蛋白质含量、阴离子交换容量(AEC)、铁氧化物含量和黏粒含量是影响土壤吸附短链PFCAs的关键性因素;土壤总有机碳(TOC)、胡敏酸、富里酸、糖类、阳离子交换容量和比表面积等因素对吸附的影响并不显著.多元线性回归分析结果表明,土壤因素对其吸附短链PFCAs影响的重要程度依次为:AEC>蛋白质>黏粒含量>铁氧化物.

China National Medical Products Administration approval summary:anlotinib for the treatment of advanced non-small cell lung cancer after two lines of chemotherapy

Background:On May 8,2018,the China National Medical Products Administration(NMPA)approved anlotinib,an orally administered anti-angiogenesis inhibitor,for the treatment of patients with advanced non-small cell lung can-cer(NSCLC)who have progressed after treatment with two or more lines of prior systemic chemotherapy.Main body of the abstract:China NMPA reviewed and inspected a regional double-blinded,placebo-controlled,Phase III trial comparing the overall survival(OS)of NSCLC patients between the anlotinib and placebo arms.A total of 437 patients were randomized(2:1)to receive either anlotinib(n=294)or placebo(n=143)once daily on a 2-week on and 1-week off schedule.Patients with epidermal growth factor receptor(EGFR)or activating anaplastic lymphoma kinase(ALK)genomic tumor aberrations should have disease progression on NMPA-approved therapy.Anlotinib is the first NMPA-approved drug for patients with advanced NSCLC who have progressed on at least two lines of prior systemic chemotherapies in China.The approval was based on a statistically and clinically significant improvement in median OS with anlotinib(9.46 months)compared with placebo[6.37 months;hazard ratio(HR])=0.70,95%confidence interval(CI)=0.55-0.89;two-sided log-rank P=0.002].The confirmed objective response rate(ORR)was 9.2%in the anlotinib arm and 0.7%in the placebo arm.The median duration of response(DoR)was 4.83 months,with a 95%CI of 3.31-6.97 months.The toxicity profile of anlotinib was consistent with that of known anti-angiogenesis inhibitors.Common adverse drug reactions(ADRs)in anlotinib-treated patients included hypertension(67.4%),hand-foot syndrome(43.9%),hemoptysis(14.0%),thyroid stimulating hormone(TSH)elevation(46.6%),and corrected QT interval(QTc)prolongation(26.2%).Short conclusion:Anlotinib demonstrated a clinically significant OS prolongation as a novel therapeutic option for advanced or metastatic NSCLC following at least two lines of chemotherapy.

Biolistic Genetic Transformation of a Wide Range of Chinese Elite Wheat(Triticum aestivum L.)Varieties

Wheat （Triticum aestivum L.） is a major staple food crop worldwide. It is economically important because it can be grown in a wide range of climates and geographic regions, and it has made an enormous contribution to the increase in global food production over the past four decades （Dixon et al., 2009）. Wheat is produced on more than 18% of the arable land in the world, and is the most cultivated crop after maize and rice （FAOSTAT data, 2014）. Despite its global strategic significance, progress in genomic and genetic engineering research on wheat has lagged behind that on other major crops due to the difficulty of culturing tissues, and the complexity of its hexaploid genome. The first successful wheat trans- formation was achieved by particle bombardment （Vasil et al., 1992）. Since then additional transgenic wheat plants have been obtained by various transformation methods （Harwood, 2011）. Microprojectile bombardment is considered to be a promising method, since it is robust, versatile and relatively efficient in terms of gene delivery.