Anti-atherosclerotic effects and molecular targets of ginkgolide B from Ginkgo biloba

Bioactive compounds derived from herbal medicinal plants modulate various therapeutic targets and signaling pathways associated with cardiovascular diseases(CVDs),the world’s primary cause of death.Ginkgo biloba,a well-known traditional Chinese medicine with notable cardiovascular actions,has been used as a cardio-and cerebrovascular therapeutic drug and nutraceutical in Asian countries for centuries.Preclinical studies have shown that ginkgolide B,a bioactive component in Ginkgo biloba,can ameliorate atherosclerosis in cultured vascular cells and disease models.Of clinical relevance,several clinical trials are ongoing or being completed to examine the efficacy and safety of ginkgolide B-related drug preparations in the prevention of cerebrovascular diseases,such as ischemia stroke.Here,we present a comprehensive review of the pharmacological activities,pharmacokinetic characteristics,and mechanisms of action of ginkgolide B in atherosclerosis prevention and therapy.We highlight new molecular targets of ginkgolide B,including nicotinamide adenine dinucleotide phosphate oxidases(NADPH oxidase),lectin-like oxidized LDL receptor-1(LOX-1),sirtuin 1(SIRT1),platelet-activating factor(PAF),proprotein convertase subtilisin/kexin type 9(PCSK9)and others.Finally,we provide an overview and discussion of the therapeutic potential of ginkgolide B and highlight the future perspective of developing ginkgolide B as an effective therapeutic agent for treating atherosclerosis.

高纵横比单层MoS_(2)纳米-微米带的可控合成及其在高性能光电晶体管中的应用

本文报道了一种快速、可控合成单层MoS_(2)纳米-微米带的方法:通过在蓝宝石衬底上旋涂Na_(2)MoO_(4)和NaOH的混合溶液后一步化学气相沉积硫化的方式进行生长.其中,通过改变NaOH的浓度,对气-液-固生长过程中的反应物液滴流动性进行调控,我们实现了对所获得的MoS_(2)的形貌和取向的调控;同时,通过改变生长时间,可以实现对MoS_(2)层数的调控.利用这种方法,我们获得了最窄宽度仅为200 nm,纵横比超过100的单层MoS_(2)纳米-微米带,且表征证明其具有很高的晶体质量.同时,我们还用该MoS_(2)纳米带作为沟道材料,制备了光电晶体管,测试表明其具有高达9×10^(5)的电流开/关比、超过10^(5)的光暗电流比以及高达8.6 A W^(-1)的响应度,展现了其在电子和光电子器件中的应用潜力.

Integrating 2D layered materials with 3D bulk materials as van der Waals heterostructures for photodetections:Current status and perspectives

In the last decade,two-dimensional layered materials(2DLMs)have been drawing extensive attentions due to their unique properties,such as absence of surface dangling bonds,thickness-dependent bandgap,high absorption coeffi-cient,large specific surface area,and so on.But the high-quality growth and transfer of wafer-scale 2DLMs films is still a great challenge for the commerciali-zation of pure 2DLMs-based photodetectors.Conversely,the material growth and device fabrication technologies of three-dimensional(3D)semiconductors photodetectors tend to be gradually matured.However,the further improvement of the photodetection performance is limited by the difficult heterogeneous inte-gration or the inferior crystal quality via heteroepitaxy.Fortunately,2D/3D van der Waals heterostructures(vdWH)combine the advantages of the two types of materials simultaneously,which may provide a new platform for developing high-performance optoelectronic devices.Here,we first discuss the unique advantages of 2D/3D vdWH for the future development of photodetection field and simply introduce the structure categories,working mechanisms,and the typical fabrication methods of 2D/3D vdWH photodetector.Then,we outline the recent progress on 2D/3D vdWH-based photodetection devices integrating 2DLMs with the traditional 3D semiconductor materials,including Si,Ge,GaAs,AlGaN,SiC,and so on.Finally,we highlight the current challenges and pros-pects of heterointegrating 2DLMs with traditional 3D semiconductors toward photodetection applications.

A one-step specific assay for continuous detection of sirtuin 2 activity

Sirtuins(SIRTs)are nicotinamide adenine dinucleotide(NAD^+)-dependent histone deacetylases with diverse physiological functions.A variety of small molecules have been developed to interrogate the physiological function of SIRTs.Therefore,it is desirable to establish efficient and convenient assays to screen SIRTs modulators.In this study,we designed a series of fluorescent nonapeptide probes derived from substrates of SIRTI-SIRT3.Fluorescence increment of these probes is based on SIRT-mediated removal of the acyl side chain with fluorophore,which makes this system free of lysine-recognizing protease.Comparing the reaction of these fluorescent nonapeptide substrates with SIRT1-SIRT3 and SIRT6,it was confirmed that this assessment system was the most suitable for SIRT2activity detection.Thus,SIRT2 was used to modify substrates by truncating the amino acids or lysine side chain of nonapeptide.Finally,two specific and efficient fluorescent probes for SIRT2,ne-D9 and ne-K4a,were developed.Evaluation of the results revealed that ne-K4a based assay was more suitable for modulators screening in vitro,while the other specific substrate ne-D9 was stable in cell lysate and could detect the activity of SIRT2 in the same.In summary,this study presents a novel strategy for detecting SIRT2 activity in vitro and in cell lysate.

SARS-CoV-2 immunity and functional recovery of COVID-19 patients 1-year after infection

The long-term immunity and functional recovery after SARS-CoV-2 infection have implications in preventive measures and patient quality of life.Here we analyzed a prospective cohort of 121 recovered COVID-19 patients from Xiangyang,China at 1-year after diagnosis.Among them,chemiluminescence immunoassay-based screening showed 99%(95%CI,98–100%)seroprevalence 10–12 months after infection,comparing to 0.8%(95%CI,0.7–0.9%)in the general population.Total anti-receptor-binding domain(RBD)antibodies remained stable since discharge,while anti-RBD IgG and neutralization levels decreased over time.A predictive model estimates 17%(95%CI,11–24%)and 87%(95%CI,80–92%)participants were still 50%protected against detectable and severe re-infection of WT SARS-CoV-2,respectively,while neutralization levels against B.1.1.7 and B.1.351 variants were significantly reduced.All non-severe patients showed normal chest CT and 21%reported COVID-19-related symptoms.In contrast,53%severe patients had abnormal chest CT,decreased pulmonary function or cardiac involvement and 79%were still symptomatic.Our findings suggest long-lasting immune protection after SARS-CoV-2 infection,while also highlight the risk of immune evasive variants and long-term consequences for COVID-19 survivors.

Clinical evidence of an interferon-glucocorticoid therapeutic synergy in COVID-19

Synthetic glucocorticoid dexamethasone is the first trial-proven drug that reduces COVID-19 mortality by suppressing immune system.In contrast,interferons are a crucial component of host antiviral immunity and can be directly suppressed by glucocorticoids.To investigate whether therapeutic interferons can compensate glucocorticoids-induced loss of antiviral immunity,we retrospectively analyzed a cohort of 387 PCR-confirmed COVID-19 patients with quasi-random exposure to interferons and conditional exposure to glucocorticoids.Among patients receiving glucocorticoids,early interferon therapy was associated with earlier hospital discharge(adjusted HR 1.68,95%Cl 1.19-2.37)and symptom relief(adjusted HR 1.48;95%Cl 1.06-2.08),while these associations were insignificant among glucocorticoids nonusers.Early interferon therapy was also associated with lower prevalence of prolonged viral shedding(adjusted OR 0.24,95%Cl 0.10-0.57)only among glucocorticoids users.Additionally,these associations were glucocorticoid cumulative dose-and timing-dependent.These findings reveal potential therapeutic synergy between interferons and glucocorticoids in COVID-19 that warrants further investigation.