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A Nearly 20-Year Journey to Success of Azvudine for Antiviral Therapy

Chinese Journal of Chemistry 2023年第23期41卷 3349-3357页

作者： Bin Yu Junbiao Chang College of Chemistry & School of Pharmaceutical Sciences Zhengzhou UniversityZhengzhouHenan450001 China Pingyuan Laboratory State Key Laboratory of Antiviral DrugsHenan Normal UniversityXinxiangHenan453007 China

Modified nucleosides,particularly those with 4'-modifications,are significant nucleosides used in antiviral treatments.The drug discovery campaign of Azvudine starts from 2′-deoxynucleoside,followed by extensive modifications,such as introducing the 4’-position substitutions,a 2’-β-fluoro atom,and changing the nucleobases.Azvudine acts potently toward various HIV-1 strains by inhibiting HIV-1 reverse transcription and preventing Vif-induced A3G degradation,representing the first-in-class dual-acting antiviral agent.In July 2021,the NMPA conditionally approved Azvudine as an adjunct therapy for adult patients with high levels of HIV-1 virus load when combined with NRTIs or NNRTIs.Azvudine is capable of inhibiting SARS-CoV-2,as well as its variants,including Alpha,Beta,Delta,and Omicron.Clinical trials have revealed its real-world effectiveness among hospitalized severely or critically ill COVID-19 patients or those with pre-existing conditions.On July 25th,2022,the NMPA granted conditional authorization approving Azvudine as China's first domestic oral anti-COVID-19 agent.Generally,Azvudine at therapeutic doses is safe and well-tolerated in clinical settings.Azvudine got approval from the National Health Commission and National Administration of Traditional Chinese Medicine on August 9th to be used in the"Diagnosis and Treatment Program for Novel Coronavirus Pneumonia(Ninth Edition)"for treating common COVID-19 adult patients.On August 12th,2022,it was also approved by the National Healthcare Security Administration to be added to the list of medical reimbursements.Of note,the achievements related to Azvudine were indexed in the China Basic Research Development Report in Thirty-Five of 2022.Azvudine was also approved on January 5th,2023,to be used in the"Diagnosis and Treatment Program for Novel Coronavirus Pneumonia(Tenth Edition)"for treating COVID-19 patients.In February 2023,the Ministry of Health of the Russian Federation approved the usage of Azvudine among individuals infected with SARS-CoV-2.What is the mo

关键词： Nucleosides Azvudine HIV COVID-19 Antiviral agents Infectious diseases Drug discovery

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Self-Supporting Nanoporous Copper Film with High Porosity and Broadband Light Absorption for Efficient Solar Steam Generation

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Nano-Micro Letters 2023年第7期15卷 57-71页

作者： Bin Yu Yan Wang Ying Zhang Zhonghua Zhang Key Laboratory for Liquid-Solid Structural Evolution and Processing of Materials(Ministry of Education) School of Materials Science and EngineeringShandong UniversityJingshi Road 17923Jinan 250061People’s Republic of China School of Materials Science and Engineering University of JinanWest Road of Nan Xinzhuang 336Jinan 250022People’s Republic of China

Solar steam generation(SSG)is a potential technology for freshwater production,which is expected to address the global water shortage problem.Some noble metals with good photothermal conversion performance have received wide concerns in SSG,while high cost limits their practical applications for water purification.Herein,a self-supporting nanoporous copper(NP-Cu)film was fabricated by one-step dealloying of a specially designed Al_(98)Cu_(2)precursor with a dilute solid solution structure.In-situ and ex-situ characterizations were performed to reveal the phase and microstructure evolutions during dealloying.The NP-Cu film shows a unique three-dimensional bicontinuous ligament-channel structure with high porosity(94.8%),multi scale-channels and nanoscale ligaments(24.2±4.4nm),leading to its strong broadband absorption over the 200–2500 nm wavelength More importantly,the NP-Cu film exhibits excellent SSG performance with high evaporation rate,superior efficiency and good stability.The strong desalination ability of NP-Cu also manifests its potential applications in seawater desalination.The related mechanism has been rationalized based upon the nanoporous network,localized surface plasmon resonance effect and hydrophilicity.

关键词： Solar steam generation Nanoporous copper Broadband solar absorption Localized surface plasmon resonance Seawater desalination Dealloying

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Forkhead-associated domain 2 links light signal to miRNA biogenesis

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Molecular Plant 2021年第4期14卷 541-543页

作者： Lu Gan Bin Yu School of Biological Sciences&Center for Plant Science Innovation University of Nebraska-LincolnLincolnNE 68588-0666USA

MicroRNAs(miRNAs)are one of the most important regulators of gene expression.Their biogenesis starts with the transcription of primary miRNA transcripts(pri-miRNAs).In plants,the RNase Ⅲ enzyme DICER-LIKER 1(DCL1),together with its partner,the double-stranded RNA-binding protein HYPONASTIC LEAVES 1(HYL1),and the zinc-finger protein SERRATE(SE),process the imperfect miRNA-residing stem loop of pri-miRNAs to release the miRNA/miRNA*duplexes in the nucleus,which are then methylated by HUA1 ENHANCER 1(Rogers and Chen,2013;Song et al.,2019).Then,most miRNAs are sorted into AGONAUTE 1 to mediate mRNA-cleavage or translation inhibi-tion based on sequence complementarity(Rogers and Chen,2013;Song et al.,2019).Studies have shown that miRNA biogenesis is controlled through modulating pri-miRNA transcription,stability and processing,which is often coupled with various developmental and environmental signals.

关键词： expression. genesis release

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Nanoporous black silver film with high porosity for efficient solar steam generation

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Nano Research 2023年第4期16卷 5610-5618页

作者： Bin Yu Yan Wang Ying Zhang Zhonghua Zhang Key Laboratory for Liquid-Solid Structural Evolution and Processing of Materials(Ministry of Education) School of Materials Science and EngineeringShandong UniversityJingshi Road 17923Jinan 250061China School of Materials Science and Engineering University of JinanWest Road of Nan Xinzhuang 336Jinan 250022China

Given the challenges brought by the shortage of freshwater resources,solar water evaporation has been regarded as one of the most promising technologies for harnessing abundant sunlight to harvest clean water from the sea.Nanostructured metals have attracted extensive attention in solar water evaporation due to their localized surface plasmon resonance effect,but highly porous metallic films with high evaporation efficiency are challenging.Herein,a self-supporting black nanoporous silver(NP-Ag)film was fabricated by dealloying of an extremely dilute Al99Ag1 alloy.The choice of the dilute precursor guarantees the formation of the NP-Ag film with high porosity(96.5%)and low density(0.3703 g·cm^(-3),even smaller than the lightest metal lithium).The three-dimensional ligament-channel network structure and the nanoscale(14.6 nm)of ligaments enable the NP-Ag film to exhibit good hydrophilicity and broadband absorption over 200‒2,500 nm.More importantly,the solar evaporator based on the NP-Ag film shows efficient solar steam generation,including the efficiency of 92.6%,the evaporation rate of 1.42 kg·m^(-2)·h^(-1)and good cycling stability under one sun irradiation.Moreover,the NP-Ag film exhibits acceptable seawater desalination property with the ion rejection for Mg^(2+),Ca^(2+),K^(+)and Na^(+)more than 99.3%.Our findings could provide a new idea and inspiration for the design and fabrication of metal-based photothermal films in real solar evaporation applications.

关键词： photothermal materials nanoporous silver surface plasmon resonance solar steam generation seawater desalination

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A Unified Trajectory Optimization Approach for Long-Term and Reactive Motion Planning of Legged Locomotion

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Journal of Bionic Engineering 2023年第5期20卷 2108-2122页

作者： Yapeng Shi Bin Yu Kaixian Ba Mantian Li School of Mechanical Engineering Yanshan UniversityNo.438 West Hebei AvenueQinhuangdao066004HebeiPeople’s Republic of China State Key Laboratory of Robotics and System Harbin Institute of TechnologyHarbin150001People’s Republic of China

This paper proposes a unified trajectory optimization approach that simultaneously optimizes the trajectory of the center of mass and footholds for legged locomotion.Based on a generic point-mass model,the approach is formulated as a nonlinear optimization problem,incorporating constraints such as robot kinematics,dynamics,ground reaction forces,obstacles,and target location.The unified optimization approach can be applied to both long-term motion planning and the reactive online planning through the use of model predictive control,and it incorporates vector field guidance to converge to the long-term planned motion.The effectiveness of the approach is demonstrated through simulations and physical experiments,showing its ability to generate a variety of walking and jumping gaits,as well as transitions between them,and to perform reactive walking in obstructed environments.

关键词： Legged locomotion Motion planning Trajectory optimization Bionic robot

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Combination of biomaterial transplantation and genetic enhancement of intrinsic growth capacities to promote CNS axon regeneration after spinal cord injury

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Frontiers of Medicine 2019年第2期13卷 131-137页

作者： Bin Yu Xiaosong Gu Key Laboratory of Neuroregeneration of Jiangsu and Ministry of Education Co-innovation Center of Neuroregeneration Nantong UniversityNantong 226001China

The inhibitory environment that surrounds the lesion site and the lack of intrinsic regenerative capacity of the adult mammalian central nervous system (CNS) impede the regrowth of injured axons and thereby the reestablishment of neural circuits required for functional recovery after spinal cord injuries (SCI). To circumvent these barriers, biomaterial scaffolds are applied to bridge the lesion gaps for the regrowing axons to follow, and, often by combining stem cell transplantation, to enable the local environment in the growth-supportive direction. Manipulations, such as the modulation of PTEN/mTOR pathways, can also enhance intrinsic CNS axon regrowth after injury. Given the complex pathophysiology of SCI, combining biomaterial scaffolds and genetic manipulation may provide synergistic effects and promote maximal axonal regrowth. Future directions will primarily focus on the translatability of these approaches and promote therapeutic avenues toward the functional rehabilitation of patients with SCIs.

关键词： spinal cord injury biomaterial extrinsic barrier intrinsic regeneration capacity

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Reduced cell invasion may be a characteristic of placental defects in pregnant women of advanced maternal age at single-cell level

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Journal of Zhejiang University-Science B(Biomedicine & Biotechnology) 2022年第9期23卷 747-759页

作者： bin ZHANG Feng ZHANG Fengying LU Jing WANG Wenbai ZHOU Huihui WANG Bin Yu Department of Medical Genetics Changzhou Maternal and Child Health Care HospialChangzhou Medical CenterNanjing Medical UniversityChangzhou 213000China

The mechanisms underlying pregnancy complications caused by advanced maternal age(AMA)remain unclear.We analyzed the cellular signature and transcriptomes of human placentas in AMA women to elucidate these mechanisms.Placental tissues from two AMA women and two controls were used for single-cell RNA-sequencing(scRNA-seq).Controls consisted of AMA women who did not experience any pregnancy complications and pregnant women below the age of 35 years without pregnancy complications.Trophoblast cells were obtained from the placentas of another six pregnant women(three AMA women and three controls),and in-vitro transwell assays were conducted to observe the cell invasion ability.Thirty additional samples(from 15 AMA women and 15 controls)were analyzed to verify the specific expression of serine protease inhibitor clade E member 1(SERPINE1).Preliminary study of the role of SERPINE1 in cell invasion was carried out with HTR8-S/Vneo cells.High-quality transcriptomes of 27607 cells were detected.Three types of trophoblast cells were detected,which were further classified into eight subtypes according to differences in gene expression and Gene Ontology(GO)function.We identified 110 differentially expressed genes(DEGs)in trophoblast cells between the AMA and control groups,and the DEGs were enriched in multiple pathways related to cell invasion.In-vitro transwell assays suggested that the invading trophoblast cells in AMA women were reduced.SERPINE1 was specifically expressed in the trophoblast,and its expression was higher in AMA women(P<0.05).Transfection of human SERPINE1(hSERPINE1)into HTR8-S/Vneo trophoblast cells showed fewer invading cells in the hSERPINE1 group.Impaired cell invasion may underlie the increased risk of adverse pregnancy outcomes in AMA women.Abnormal expression of SERPINE1 in extravillous trophoblast(EVT)cells appears to play an important role.

关键词： Advanced maternal age(AMA) Pregnancy complications Placenta Trophoblast Cell invasion Serine protease inhibitor clade E member 1(SERPINE1)

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Research on low carbon emission optimization operation technology of natural gas pipeline under multi-energy structure

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Petroleum Science 2022年第6期19卷 3046-3058页

作者： En-bin Liu Yong Peng Shan-Bi Peng Bin Yu Qi-Kun Chen Petroleum Engineering School Southwest Petroleum UniversityChengdu610500China School of Civil Engineering and Geomatics Southwest Petroleum UniversityChengdu610500China China Petroleum Pipeline Engineering Corporation Hebei065000China School of Engineering Cardiff UniversityCardiffCF243AAUK

In order to reduce the carbon emissions of natural gas pipelines,based on the background of different energy structures,this paper proposes a general low carbon and low consumption operation model of natural gas pipelines,which is used to fine calculate the carbon emissions and energy consumption of natural gas pipeline.In this paper,an improved particle swarm optimization(NHPSO-JTVAC)algorithm is used to solve the model and the optimal scheduling scheme is given.Taking a parallel pipeline located in western China as an example,the case is analyzed.The results show that after optimization,under the existing energy types,the pipeline system can reduce 31.14%of carbon emissions,and after introducing part of new energy,the pipeline system can reduce 34.02%of carbon emissions,but the energy consumption has increased.

关键词： Natural gas Pipeline optimization NHPSO-JTVAC algorithm Carbon emission New energy

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Small-molecule MDM2/X inhibitors and PROTAC degraders for cancer therapy:advances and perspectives

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Acta Pharmaceutica Sinica B 2020年第7期10卷 1253-1278页

作者： yuan Fang Guochao Liao Bin Yu Joint Laboratory for Translational Cancer Research of Chinese Medicine of the Ministry of Education of the People’s Republic of China International Institute for Translational Chinese MedicineGuangzhou University of Chinese MedicineGuangzhou 510006China School of Pharmaceutical Sciences Zhengzhou UniversityZhengzhou 450001China State Key Laboratory of Pharmaceutical Biotechnology Nanjing UniversityNanjing 210023China

Blocking the MDM2/X-P53 protein-protein interaction has been widely recognized as an attractive therapeutic strategy for the treatment of cancers.Numerous small-molecule MDM2 inhibitors have been reported since the release of the structure of the MDM2-P53 interaction in 1996,SAR405838,NVP-CGM097,MK-8242,RG7112,RG7388,DS-3032 b,and AMG232 currently undergo clinical evaluation for cancer therapy.This review is intended to provide a comprehensive and updated overview of MDM2 inhibitors and proteolysis targeting chimera(PROTAC)degraders with a particular focus on how these inhibitors or degraders are identified from starting points,strategies employed,structure-activity relationship(SAR)studies,binding modes or co-crystal structures,biochemical data,mechanistic studies,and preclinical/clinical studies.Moreover,we briefly discuss the challenges of designing MDM2/X inhibitors for cancer therapy such as dual MDM2/X inhibition,acquired resistance and toxicity of P53 activation as well as future directions.

关键词： MDM2/X-P53 interaction MDM2/X inhibitors PROTAC degraders Cancer therapy

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Behaviors of overlying strata in extra-thick coal seams using top-coalcaving method

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Journal of Rock Mechanics and Geotechnical Engineering 2016年第2期8卷 238-247页

作者： Bin Yu Datong Coal Mine Group Company Datong037003China

Accidents such as support failure and excessive deformation of roadways due to drastic changes in strata behaviors are frequently reported when mining the extra-thick coal seams Nos.3e5 in Datong coal mine with top-coal caving method,which significantly hampers the mine's normal production.To understand the mechanism of strata failure,this paper presented a structure evolution model with respect to strata behaviors.Then the behaviors of strata overlying the extra-thick coal seams were studied with the combined method of theoretical analysis,physical simulation,and field measurement.The results show that the key strata,which are usually thick-hard strata,play an important role in overlying movement and may influence the mining-induced strata behaviors in the working face using top-coal caving method.The structural model of far-field key strata presents a 'masonry beam' type structure when'horizontal O-X' breakage type happens.The rotational motion of the block imposed radial compressive stress on the surrounding rock mass of the roadway.This can induce excessive deformation of roadway near the goaf.Besides,this paper proposed a pre-control technology for the hard roof based on fracture holes and underground roof pre-splitting.It could effectively reduce stress concentration and release the accumulated energy of the strata,when mining underground coal resources with top-coal caving method.

关键词： Extra-thick coal seam Datong mining area Large-space structure Near-and far-field strata Strata behavior Key strata

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