Multi-decadal Changes of the Impact of El Niño Events on Tibetan Plateau Summer Precipitation

Precipitation on the Tibetan Plateau(TP)has an important effect on the water supply and demand of the downstream population.Involving recent climate change,the multi-decadal variations of the impact of El Niño-Southern Oscillation(ENSO)events on regional climate were observed.In this work,the authors investigated the changes in summer precipitation over TP during 1950-2019.At the multi-decadal scale,the authors found that the inhabiting impact of El Niño events on the TP summer precipitation has strengthened since the late 1970s.The main factor contributing to this phenomenon is the significant amplification in the decadal amplitude of El Niño during 1978-2019 accompanied by a discernible escalation in the frequency of El Niño events.This phenomenon induces anomalous perturbations in sea surface temperatures(SST)within the tropical Indo-Pacific region,consequently weakening the atmospheric vapor transport from the western Pacific to the TP.Additionally,conspicuous anomalies in subsidence motion are observed longitudinally and latitudinally across the TP which significantly contributes to a curtailed supply of atmospheric moisture.These results bear profound implications for the multi-decadal prediction of the TP climate.

表观遗传抗肿瘤药物的研发进展

表观遗传是指在不改变DNA序列的情况下,基因功能产生可遗传的变异,并最终导致生物表型改变的生物学现象。近年来,随着表观遗传与转录等生物过程间的关系不断被揭示,研究者逐渐认识到表观调控异常也是肿瘤发生的原因之一,这为以表观遗传元件为靶点的抗肿瘤药物的研发奠定了基础。目前,在这类药物研发领域内已有多个化合物获批上市,但其临床应用和药物种类仍存在局限性。本文以表观遗传为出发点,对表观遗传抗肿瘤药物研发热点和进展进行介绍,讨论了以编码器、擦除器和阅读器等表观元件为靶点的抑制剂研究现状和临床应用情况。分析当前表观遗传抗肿瘤药物发展的困境,对未来药物临床应用策略和研发趋势进行展望。

基于ERA5再分析资料的冬季南海北部低云日变化研究

低云对区域辐射能量平衡和天气、气候具有重要意义。利用ERA5再分析数据和中国香港探空站资料研究了冬季南海北部低云日变化机理。主要结论如下:(1)南海低云量呈现西北多东南少、夜多昼少,低云高度呈夜高昼低,低云厚度呈夜厚昼薄的特征。(2)冬季南海北部低层大气稳定性强,海气界面稳定性弱,云层下方边界层混合均匀,有利于低云形成。(3)夜间,陆风环流系统改变海洋风场和湿度场的分配,异常南风使近海水汽辐合抬升,为云层发展提供水汽。(4)夜间逆温层强度虽弱但发生频率更高,且云底以下边界层退耦减弱,边界层混合加强,云顶短波辐射加热作用消失,促使低云的产生。这都将有利于提高人们对南海低云日变化的理解和数值模拟能力。

发掘传统文化中农业气象学术资源培育大学生文化自信

“大思政”背景下,在高等学校进行文化自信的培育,是当前多元化、信息化时代加强大学生德育的迫切需求。该文以广东海洋大学大气科学本科专业课应用气象学课堂教学为例,围绕古文诗词中的农业气象话题,通过课堂互动、撰写小论文、开放式考核等方式激发学生学习的兴趣和对中国古典文化中科学精神的探索热情,培育大学生文化自信。

A Comparative Analysis of Chemical Properties and Factors Impacting Spring Sea Fog over the Northwestern South China Sea

In the present study,we analyzed the chemical properties and factors impacting the sea fog water during two sea fog events over the northwestern South China Sea in March 2017,and compared our results with those of other regions.The sea fog water during these two events were highly acidic and their average pH was below 3,which was related to the high initial acidifying potential and large amounts of NOand SOnot involved in the neutralization reaction.The dominant cations in the sea fog water were Naand NH.The primary anions in the sea fog water over the South China Sea were Cland NO,while that over the North Pacific Ocean was mainly SO,and ratios of the three fog water ions near the Donghai Island were similar.Ions in the sea fog water during the two events were mainly derived from marine aerosols,while the difference was that the first low-level sea fog airflow trajectory passed over Hainan Island.Therefore,the proportion of K+in the first sea fog was much higher than that in sea water and the second.Sulfate was the key to fog water nucleation,which made ion concentration in the sea fog water during the second event higher than that during the first.A decrease in average diameter during the first sea fog formation led to an ion concentration increase,while the average diameter of sea fog water during the second event was lower than that during the first,which corresponded with a moderate ion concentration increase.

Scientists Provide A New Option for Anti-Leukemia Therapy

RNA epitranscriptomics, the study of chemical modifications to RNA or the transcriptome (the entirety of RNA in a cell), represents a recently identified layer of regulation of genetic information. As the most abundant internal mRNA modification, N6- methyladenosine (or m6 A, adenosine tagged along with an additional methyl group) is critical for the regulation of mRNA metabolisms and impacts various biological and pathological processes.

New Computational Drug Design Method Integrates Protein-Protein Interaction Prediction and Molecular Docking

Scientists at Rice University and Shanghai Institute of Materia Medica(SIMM),CAS,have developed a computational method with dual function of predicting druggable protein-protein interaction(PPI)interface and designing molecules interfering the PPI interface.The computational method named Fd-DCA(Fragment-docking and Direct Coupling

MicroRNAs as critical regulators in liver fibrosis

Liver fibrosis,a common characteristic of chronic liver diseases,is a major challenge to global health.The progression of liver fibrosis is responsible for liver-related morbidity and mortality.Nevertheless,the pathogenesis of liver fibrosis remains unclear and an effective therapy has not yet been developed.Activation of hepatic stellate cells(HSCs)is well-known to act as a central driver of liver fibrosis,while resident and infiltrating inflammatory cells further modulate HSC activation via extracellular signals.MicroRNAs(miRNAs)are small,noncoding RNAs that are critical regulators for liver physiological and pathological processes by negatively regulating target gene expression and facilitating intercellular communication.Here,we review the involvement of miRNAs in the development and progression of liver fibrosis in various hepatic cells,including HSCs,hepatocytes,and inflammatory cells,and discuss the potential of miRNAs as biomarkers and therapeutic targets for liver fibrosis.

Localized delivery of nanomedicine and antibodies for combating COVID-19

The severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)pandemic has been a major health burden in the world.So far,many strategies have been investigated to control the spread of COVID-19,including social distancing,disinfection protocols,vaccines,and antiviral treatments.Despite the significant achievement,due to the constantly emerging new variants,COVID-19 is still a great challenge to the global healthcare system.It is an urgent demand for the development of new therapeutics and technologies for containing the wild spread of SARS-CoV-2.Inhaled administration is useful for the treatment of lung and respiratory diseases,and enables the drugs to reach the site of action directly with benefits of decreased dose,improved safety,and enhanced patient compliance.Nanotechnology has been extensively applied in the prevention and treatment of COVID-19.In this review,the inhaled nanomedicines and antibodies,as well as intranasal nanodrugs,for the prevention and treatment of COVID-19 are summarized.

Author correction to"Neutralization of SARSCoV-2 pseudovirus using ACE2-engineered extracellular vesicles"[Acta Pharmaceutica Sinica B 12(2022)1523-1533]

The authors regret in the initially published version of this article,there is a misapplied image in Fig.3C.The corrected Fig.3 is provided below.

Alectinib: a novel second generation anaplastic lymphoma kinase(ALK) inhibitor for overcoming clinically-acquired resistance

The development of inhibitors for the tyrosine anaplastic lymphoma kinase (ALK) has advanced rapidly, driven by biology and medicinal chemistry. The first generation ALK inhibitor crizotinib was granted US FDA approval with only four years of preclinical and clinical testing. Although this drug offers significant clinical benefit to the ALK-positive patients, resistance has been developed through a variety of mechanisms. In addition to ceritinib, alectinib is another second-generation ALK inhibitor launched in 2014 in Japan. This drug has a unique chemical structure bearing a 5H-benzo[b] carbazol-11(611)-one structural scaffold with an IC50 value of 1.9 nmol/L, and is highly potent against ALK bearing the gatekeeper mutation L1196M with an IC50 of 1.56 nmoL/L. In the clinic, alectinib is highly efficacious in treatment of ALK-positive non-small cell lung cancer (NSCLC), and retains potency to combat crizotinib-resistant ALK mutations L11.96.M, F1174L, R1275Q and C1156Y. (C) 2015 Chinese Pharmaceutical Association and Institute of Materia Medica, Chinese Academy of Medical Sciences. Production and hosting by Elsevier B.V. All rights reserved.

Small molecules targeting the innate immune cGAS-STING-TBK1 signaling pathway

Multiple cancer immunotherapies including chimeric antigen receptor T cell and immune checkpoint inhibitors(ICIs)have been successfully developed to treat various cancers by motivating the adaptive anti-tumor immunity.Particularly,the checkpoint blockade approach has achieved great clinic success as evidenced by several U.S.Food and Drug Administration(FDA)-approved antiprogrammed death receptor 1/ligand 1 or anti-cytotoxic T lymphocyte associated protein 4 antibodies.However,the majority of cancers have low clinical response rates to these ICIs due to poor tumor immunogenicity.Indeed,the cyclic guanosine monophosphate-adenosine monophosphate synthase-stimulator of interferon genes-TANK-binding kinase 1(cGAS-STING-TBK1)axis is now appreciated as the major signaling pathway in innate immune response across different species.Aberrant signaling of this pathway has been closely linked to multiple diseases,including auto-inflammation,virus infection and cancers.In this perspective,we provide an updated review on the latest progress on the development of small molecule modulators targeting the cGAS-STING-TBK1 signaling pathway and their preclinical and clinical use as a new immune stimulatory therapy.Meanwhile,highlights on the clinical candidates,limitations and challenges,as well as future directions in this field are also discussed.Further,small molecule inhibitors targeting this signaling axis and their potential therapeutic use for various indications are discussed as well.

Microfluidic actuators based on temperature-responsive hydrogels

The concept of using stimuli-responsive hydrogels to actuate fluids in microfluidic devices is particularly attractive,but limitations,in terms of spatial resolution,speed,reliability and integration,have hindered its development during the past two decades.By patterning and grafting poly(N-isopropylacrylamide)PNIPAM hydrogel films on plane substrates with a 2μm horizontal resolution and closing the system afterward,we have succeeded in unblocking bottlenecks that thermo-sensitive hydrogel technology has been challenged with until now.In this paper,we demonstrate,for the first time with this technology,devices with up to 7800 actuated micro-cages that sequester and release solutes,along with valves actuated individually with closing and opening switching times of 0.6±0.1 and 0.25±0.15 s,respectively.Two applications of this technology are illustrated in the domain of single cell handling and the nuclear acid amplification test(NAAT)for the Human Synaptojanin 1 gene,which is suspected to be involved in several neurodegenerative diseases such as Parkinson’s disease.The performance of the temperature-responsive hydrogels we demonstrate here suggests that in association with their moderate costs,hydrogels may represent an alternative to the actuation or handling techniques currently used in microfluidics,that are,pressure actuated polydimethylsiloxane(PDMS)valves and droplets.

Development of hedgehog pathway inhibitors by epigenetically targeting GLI through BET bromodomain for the treatment of medulloblastoma

Medulloblastoma(MB)is a common yet highly heterogeneous childhood malignant brain tumor,however,clinically effective molecular targeted therapy is lacking.Modulation of hedgehog(HH)signaling by epigenetically targeting the transcriptional factors GLI through bromodomain-containing protein 4(BRD4)has recently spurred new interest as potential treatment of HH-driven MB.Through screening of current clinical BRD4 inhibitors for their inhibitory potency against glioma-associated oncogene homolog(GLI)protein,the BRD4 inhibitor 2 was selected as the lead for further structural optimization,which led to the identification of compounds 25 and 35 as the high potency HH inhibitors.Mechanism profiling showed that both compounds suppressed HH signaling by interacting with the transcriptional factor GLI,and were equally potent against the clinical resistant mutants and the wild type of smoothened(SMO)receptor with IC50 values around 1 nmol/L.In the resistant MB allograft mice,compound 25 was well tolerated and markedly suppressed tumor growth at both 5 mg/kg(TGI=83.3%)and 10 mg/kg(TGI=87.6%)doses.Although further modification is needed to improve the pharmacokinetic(PK)parameters,compound 25 represents an efficacious lead compound of GLI inhibitors,possessing optimal safety and tolerance to fight against HH-driven MB.

南海低层季风环流对低云时空分布的影响

利用多源观测资料和再分析资料研究南海低层季风环流对冬夏季低云空间分布的影响。主要结论如下:(1)南海低云的空间分布具有显著的季节变化。冬季南海西北部低云量多且云层较薄,而东南区域低云量少且云层变厚。相应地,从南海西北部到东南部积云发生频率增加而层云发生率降低。夏季,南海以对流性云为主,其中积雨云发生率较冬季有所增加,低云量降至全年最少。(2)南海低层季风气流与山脉相互作用影响低层大气层结。冬季,南海东南"正"(风场辐合)西北"负"(风场辐散)的涡度(散度)分布可能造成东南部上升西北部下沉的次级环流,进而增加西北部大气稳定度,加之该区强烈的海面湍流和蒸发都有利于低云的形成。夏季,暖湿的西南风使南海不稳定度增强、对流云增多,因此低云量较少。该研究有助于加深地形效应对低云空间分布的调控作用的理解,并为南海低云数值模拟提供参考。

Neutralization of SARS-CoV-2 pseudovirus using ACE2-engineered extracellular vesicles

The spread of coronavirus disease 2019(COVID-19)throughout the world has resulted in stressful healthcare burdens and global health crises.Developing an effective measure to protect people from infection is an urgent need.The blockage of interaction between angiotensin-converting enzyme 2(ACE2)and S protein is considered an essential target for anti-severe acute respiratory syndrome coronavirus 2(SARS-Co V-2)drugs.A full-length ACE2 protein could be a potential drug to block early entry of SARS-Co V-2 into host cells.In this study,a therapeutic strategy was developed by using extracellular vesicles(EVs)with decoy receptor ACE2 for neutralization of SARS-Co V-2.The EVs embedded with engineered ACE2(EVs-ACE2)were prepared;the EVs-ACE2 were derived from an engineered cell line with stable ACE2 expression.The potential effect of the EVs-ACE2 on anti-SARS-Co V-2 was demonstrated by both in vitro and in vivo neutralization experiments using the pseudovirus with the S protein(S-pseudovirus).EVs-ACE2 can inhibit the infection of S-pseudovirus in various cells,and importantly,the mice treated with intranasal administration of EVs-ACE2 can suppress the entry of S-pseudovirus into the mucosal epithelium.Therefore,the intranasal EVs-ACE2 could be a preventive medicine to protect from SARS-Co V-2 infection.This EVs-based strategy offers a potential route to COVID-19 drug development.

Natural scaffolds-inspired synthesis of CF_(3)-substituted macrolides enabled by Rh-catalyzed C–H alkylation macrocyclization

The development of innovative strategies and methods to provide natural product-like macrocycles not accessible by biosynthesis, but endowed with novel bioactivities and simplified structure, is highly desirable. Inspired by the key scaffolds of rapamycin and FR252921, herein, we report a Rh(III)-catalyzed C–H alkylation macrocyclization, which enables access to CF_(3)-substituted macrolides. DFT calculations reveal that the chemoselectivity between C–H alkylation and olefination macrocyclization was highly controllable. Moreover, the unique CF_(3)-substituted macrolides showed potent anti-inflammation activities against TNF-α, IL-6 and CCL2 m RNA expression.