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Rationally designed synthetic peptide as versatile calibrant to improve the accuracy of protein sequence analysis using MALDI mass spectrometry

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Chinese Chemical Letters 2024年第3期35卷 214-220页

作者： Lingpeng Zhan Yanyi Huang Guanbo Wang Institute for Cell Analysis Shenzhen Bay LaboratoryShenzhen 518132China Biomedical Pioneering Innovation center Peking UniversityBeijing 100871China

Matrix-assisted laser desorption/ionization(MALDI)mass spectrometry(MS)plays an indispensable role in analyzing protein covalent *** reliable identification of amino acid residues and modifications relies on the mass accuracy,which is highly dependent on ***,the accuracy provided by the currently available calibrants still needs further improvement in terms of compatibility with multiple tandem MS modes or ion polarity modes,calibratable range,and minimizing suppression of and interference with analyte *** aiming at developing a versatile calibrant to solve these problem,we designed a synthetic peptide format of calibrant R_x(GDP_n)_m(referred to as“Gly-Asp-Pro,GDP”)according to the chemical natures of amino acids and polypeptide fragmentation rules in tandem *** four types of amino acid residues selected and arranged through rational designs,a GDP peptide produces highly regulated fragments that give rise to evenly spaced signals in each tandem MS mode and is compatible with both positive and negative ion *** internal calibration,its regulated fragmentation pattern minimizes interference with analyte signals,and using a single peptide as the input minimizes suppression of the analyte *** demonstrated by analyses of proteins including monoclonal antibody and Aβ-42,these features allowed significant increase of the mass accuracy and precision,which improved sequence coverage and sequence resolution in sequence analyses(including de novo sequencing).This rational design strategy may also inspire further development of synthetic calibrants that benefit structural analysis of biomolecules.

关键词： Biomolecule design Synthetic peptide Protein sequencing Covalent structure De novo sequencing Mass spectrometry Gas-phase fragmentation

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Single-cell transcriptomics systematically discloses the immune-inflammatory responses of peripheral blood mononuclear cells for diabetic nephropathy

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Genes & diseases 2024年第4期11卷 82-85页

作者： Jiangpeng wu Nan Hu Baochun Guo Hualin Ma Lulin Xie Yisha Huang Siyu Xia Yuke Jiang Zhije Li Jigang Wang Xinzhou Zhang Zhen Liang Department of Nephrology Shenzhen Key Laboratory of Kidney Diseasesand Shenzhen Clinical Research Centre for GeriatricsShenzhen People's Hospital(The Second Clinical Medical CollegeJinan UniversityThe First Affiliated HospitalSouthern University of Science and Technology)ShenzhenGuangdong 518020China Department of Geriatrics and Shenzhen Clinical Research Centre for GeriatricsShenzhen People's Hospital(The Second Clinical Medical CollegeJinan UniversityThe First Affiliated HospitalSouthern University of Science and Technology)ShenzhenGuangdong 518020China State Key Laboratory for Quality Ensurance and Sustainable Use of Dao-di Herbs Artemisinin Research Centerand Institute of Chinese Materia MedicaChina Academy of Chinese Medical SciencesBeijing 100700China

Diabetic nephropathy(DN)has become the leading cause of end-stage renal disease with high morbidity and mortality among individuals with diabetes *** functional alterations of renal infiltrating immune cells have been reported as part of the pathological mechanism of DN,the understanding of the immune response underlying peripheral blood mononuclear cells(PBMCs)in DN remains ***,single-cell RNA sequencing(scRNA-seq)was used toprofile the transcriptomic signatures of PBMCs from DN patients.

关键词： nephropathy alterations mortality

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Intermolecular hydrogen-bonding as a robust tool toward significantly improving the photothermal conversion efficiency of a NIR-II squaraine dye

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Chinese Chemical Letters 2024年第4期35卷 310-315页

作者： Songtao Cai Liuying Wu Yuan Li Soham Samanta Jinying Wang Bing Liu Feihu Wu Kaitao Lai Yingchao Liu Junle Qu Zhigang Yang center for Biomedical Photonics&Key Laboratory of Optoelectronic Devices and Systems of Ministry of Education and Guangdong Province College of Physics and Optoelectronic EngineeringShenzhen UniversityShenzhen 518060China

The photothermal therapy(PTT) has come across as a promising noninvasive therapeutic strategy for tumor treatment. However, low photothermal conversion efficiency(PCE) and hydrophobicity may impede the therapeutic efficacy of organic photothermal agents and an efficient PTT-agent must overcome these two major challenges. In this work, we developed a new strategy to promote higher PCE wherein the intermolecular hydrogen-bonding interaction between the single dye molecule and water facilitated the transformation of the absorbed energy into the heat. A hydrophilic squaraine dye(SCy1) with the second near-infrared region(NIR-II) absorption and extremely low emission were designed to exhibit much higher PCE than that of the analogues of pentamethine-dyes(PCy1, PCy2). The presence of the ‘–O-' at middle of squaric cycle enabled the intermolecular H-bonding formation between the SCy1 and water to promote the energy dissipation channel. Moreover, the introduction of long-chain phenylsulfonate groups helped in to improve the water solubility apart from serving as an additional means of further enhancing PCE through fluorescence quenching. Therefore, SCy1 with a squaraine backbone and long-chain sulfonate moieties revealed outstanding photothermal stability and anti-aggregation activity apart from showing exceptionally high PCE(74%) in water. SCy1 demonstrated excellent therapeutic efficacy when applied in the PTT treatment of tumor-bearing mice under a laser irradiation of 915 nm.

关键词： Squaraine-based cyanine Hydrogen bonds High PCE Anti-aggregation Photothermal therapy

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Targeting the Warburg effect:A revisited perspective from molecular mechanisms to traditional and innovative therapeutic strategies in cancer

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Acta Pharmaceutica Sinica B 2024年第3期14卷 953-1008页

作者： Minru Liao Dahong Yao Lifeng Wu Chaodan Luo Zhiwen Wang Jin Zhang Bo Liu Department of Biotherapy Cancer Center and State Key Laboratory of BiotherapyWest China HospitalSichuan UniversityChengdu 610041China School of Pharmaceutical Sciences Shenzhen Technology UniversityShenzhen 518118China School of Pharmacy Shenzhen University Medical SchoolShenzhen UniversityShenzhen 518055China Department of Psychology University of Southern CaliforniaLos AngelesCA 90089USA

Cancer reprogramming is an important facilitator of cancer development and survival,with tumor cells exhibiting a preference for aerobic glycolysis beyond oxidative phosphorylation,even under sufficient oxygen supply *** metabolic alteration,known as the Warburg effect,serves as a significant indicator of malignant tumor *** Warburg effect primarily impacts cancer occurrence by influencing the aerobic glycolysis pathway in cancer *** enzymes involved in this process include glucose transporters(GLUTs),HKs,PFKs,LDHs,and ***,the expression of transcriptional regulatory factors and proteins,such as FOXM1,p53,NF-κB,HIF1a,and c-Myc,can also influence cancer ***,lncRNAs,miRNAs,and circular RNAs play a vital role in directly regulating the Warburg ***,gene mutations,tumor microenvironment remodeling,and immune system interactions are closely associated with the Warburg ***,the development of drugs targeting the Warburg effect has exhibited promising potential in tumor *** comprehensive review presents novel directions and approaches for the early diagnosis and treatment of cancer patients by conducting in-depth research and summarizing the bright prospects of targeting the Warburg effect in cancer.

关键词： Warburg effect Cancer Regulatory factor LncRNAs miRNAs Traditional Chinese medicine Small-molecule drug Drug resistance

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Cryogenic transmission electron microscopy on beam-sensitive materials and quantum science

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Chinese Physics B 2024年第8期33卷 9-29页

作者：王刚林君浩 Department of Physics and shenzhen Key Laboratory of Advanced Quantum Functional Materials and Devices Southern University of Science and TechnologyShenzhen 518055China Quantum Science center of Guangdong–Hong Kong–Macao Greater Bay Area(Guangdong) Shenzhen 518045China

Transmission electron microscopy(TEM)offers unparalleled atomic-resolution imaging of complex materials and heterogeneous ***,high-energy imaging electrons can induce structural damage,posing a challenge for electron-beam-sensitive *** TEM(Cryo-TEM)has revolutionized structural biology,enabling the visualization of biomolecules in their near-native states at unprecedented *** low electron dose imaging and stable cryogenic environment in Cryo-TEM are now being harnessed for the investigation of electron-beam-sensitive materials and low-temperature quantum ***,we present a systematic review of the interaction mechanisms between imaging electrons and atomic structures,illustrating the electron beam-induced damage and the mitigating role of *** review then explores the advancements in low-dose Cryo-TEM imaging for elucidating the structures of organic-based ***,we showcase the application of Cryo-TEM in the study of strongly correlated quantum materials,including the detection of charge order and novel topological spin ***,we discuss the future prospects of Cryo-TEM,emphasizing its transformative potential in unraveling the complexities of materials and phenomena across diverse scientific disciplines.

关键词： cryogenic TEM low dose imaging quantum materials

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Concomitant and sequential administration of nirmatrelvir-ritonavir and azvudine in patients with COVID-19 caused by the Omicron variant: Safety and efficacy

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iLABMED 2024年第2期2卷 88-97页

作者： Guang-Bin Chen You-Rou Zheng Yun-Ni Yu Li-Mian Liang Chao Chen Ying-Xia Liu Hong-Zhou Lu Department of Clinical Pharmacy Third People's Hospital of ShenzhenShenzhenGuangdongChina National Clinical Research center for Infectious diseases Division of Infectious DiseasesThe Third People's Hospital of ShenzhenShenzhenGuangdongChina

Background:This study assessed the safety and efficacy of nirmatrelvir-ritonavir(Paxlovid®)and azvudine when administered sequentially or concomitantly in patients with coronavirus 2019(COVID-19)caused by the Omicron ***:Ninety-three patients confirmed to be infected with the Omicron variant by nucleic acid detection were retrospectively ***-tion was collected on general health status,medication,and adverse drug reactions(ADRs)according to whether nirmatrelvir-ritonavir and azvudine were administered sequentially or *** on times of onset,clinical manifestations,and outcomes of ADRs and on conversion to a nega-tive nucleic acid test were also ***:Possible ADRs were recorded in 41 patients(44.1%).There were 22 gastrointestinal reactions in 18 patients and 18 hematological abnormalities in 16 after sequential or concomitant treatment with nirmatrelvir-ritonavir and *** enzyme levels increased in nine cases and creatinine clearance decreased in *** of atrial fibrillation(n=1),sleep disorder(n=2),rash(n=2),dizziness(n=1),and weakness(n=5)were also *** vomiting,poor appetite,diarrhea,xerostomia,bitter taste,and rash were considered probable ADRs;others were thought to be possible *** all cases,the nucleic acid test did not turn negative after the first antiviral was *** nucleic acid test of 28 patients did not turn negative before *** remaining 65 patients(69.9%)returned a negative nucleic acid test after receiving the second antiviral ***:Treatment with nirmatrelvir-ritonavir and azvudine is safe and effective whether administered sequentially or concomitantly in patients with COVID-19 caused by the Omicron variant.

关键词： adverse drug reactions azvudine efficacy nirmatrelvir-ritonavir Omicron variant safety

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Inflammatory Factor IL1αInduces Aberrant Astrocyte Proliferation in Spinal Cord Injury Through the Grin2c/Ca^(2+)/CaMK2b Pathway

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Neuroscience Bulletin 2024年第4期40卷 421-438页

作者： Yu Xia Lu Ding Changlin Zhang Qi Xu Ming Shi Tianshun Gao Feng-Quan Zhou David Y.B.Deng Scientific Research center The Seventh Affiliated Hospital of Sun Yat-sen UniversityShenzhen518107China Department of Gynecology The Seventh Affiliated Hospital of Sun Yat-sen UniversityShenzhen518107China Pelvic Floor Disorders center The Seventh Affiliated Hospital of Sun Yat-sen UniversityShenzhen518107China Big Data center The Seventh Affiliated Hospital of Sun Yat-sen UniversityShenzhen518107China Sir Run Run Shaw Hospital Zhejiang University School of MedicineHangzhou310016China Orthopaedic and Neurological Repair center The Seventh Affiliated Hospital of Sun Yat-sen UniversityShenzhen518107China

Spinal cord injury(SCI)is one of the most devastating traumas,and the aberrant proliferation of astrocytes usually causes neurological ***,the mechanism underlying astrocyte over-proliferation after SCI is ***2c(glutamate ionotropic receptor type 2c)plays an essential role in cell *** bioinformatic analysis indicated that Grin2c and Ca^(2+)transport functions were inhibited in astrocytes after *** of Grin2c stimulated astrocyte proliferation by inhibiting the Ca^(2+)/calmodulin-dependent protein kinase 2b(CaMK2b)pathway in *** screening different inflammatory factors,interleukin 1α(IL1α)was further found to inhibit Grin2c/Ca^(2+)/CaMK2b and enhance astrocyte proliferation in an oxidative damage *** of IL1αusing neutralizing antibody resulted in increased Grin2c expression and the inhibition of astrocyte proliferation ***,this study suggests that IL1αpromotes astrocyte proliferation by suppressing the Grin2c/Ca^(2+)/CaMK2b pathway after SCI,revealing a novel pathological mechanism of astrocyte proliferation,and may provide potential targets for SCI repair.

关键词： IL1α Grin2c Astrocyte Spinal cord injury

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Single-cell transcriptomics reveals the ameliorative effect of rosmarinic acid on diabetic nephropathy-induced kidney injury by modulating oxidative stress and inflammation

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Acta Pharmaceutica Sinica B 2024年第4期14卷 1661-1676页

作者： Junhui Chen Qian Zhang Jinan Guo Di Gu Jing Liu Piao Luo Yunmeng Bai Jiayun Chen Xinzhou Zhang Sheng Nie Chunbo Chen Yulin Feng Jigang Wang National Pharmaceutical Engineering center for Solid Preparation of Chinese Herbal Medicine Jiangxi University of Chinese MedicineNanchang 330006China Department of Pulmonary and Critical Care Medicine Shenzhen Institute of Respiratory Diseasesand Shenzhen Clinical Research Centre for GeriatricsShenzhen People's HospitalFirst Affiliated Hospital of Southern University of Science and TechnologySecond Clinical Medical College of Jinan UniversityShenzhen 518020China School of Traditional Chinese Medicine and School of Pharmaceutical Sciences Southern Medical UniversityGuangzhou 510515China Department of Urology and Shenzhen Clinical Research Centre for GeriatricsShenzhen People's Hospitalthe First Affiliated HospitalSouthern University of Science and TechnologyShenzhen 518020China Department of Urology the First Affiliated Hospital of Guangzhou Medical UniversityGuangzhou 510230China Department of Nephrology Shenzhen Key Laboratory of Kidney Diseasesand Shenzhen Clinical Research Centre for GeriatricsShenzhen People's Hospitalthe First Affiliated HospitalSouthern University of Science and TechnologyShenzhen 518020China Department of Nephrology Nanfang Hospitalthe First Affiliated Hospital of Southern Medical UniversityGuangzhou 510515China Department of Critical Care Medicine Shenzhen People's Hospital(the Second Clinical Medical CollegeJinan Universitythe First Affiliated HospitalSouthern University of Science and Technology)Shenzhen 518020China State Key Laboratory for Quality Esurance and Sustainable Use of Dao-di Herbs Artemisinin Research Centerand Institute of Chinese Materia MedicaChina Academy of Chinese Medical SciencesBeijing 100700China Department of Oncology the Affiliated Hospital of Southwest Medical UniversityLuzhou 646000China

Diabetic nephropathy(DN)is a severe complication of diabetes,characterized by changes in kidney structure and *** natural product rosmarinic acid(RA)has demonstrated therapeutic effects,including anti-inflammation and anti-oxidative-stress,in renal damage or *** this study,we characterized the heterogeneity of the cellular response in kidneys to DN-induced injury and RA treatment at single cell *** results demonstrated that RA significantly alleviated renal tubular epithelial injury,particularly in the proximal tubular S1 segment and on glomerular epithelial cells known as podocytes,while attenuating the inflammatory response of macrophages,oxidative stress,and cytotox-icity of natural killer *** findings provide a comprehensive understanding of the mechanisms by which RA alleviates kidney damage,oxidative stress,and inflammation,offering valuable guidance for the clinical application of RA in the treatment of DN.

关键词： Rosmarinic acid Diabetic nephropathy scRNA sequencing Injury Oxidative stress Infiammation Proteomics

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Advanced Strategies for Overcoming Endosomal/Lysosomal Barrier in Nanodrug Delivery

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Research 2024年第1期2023卷 315-337页

作者： Chong Qiu Fei Xia Junzhe Zhang Qiaoli Shi Yuqing Meng Chen Wang Huanhuan Pang Liwei Gu Chengchao Xu Qiuyan Guo Jigang Wang Artemisinin Research center and Institute of Chinese Materia MedicaChina Academy of Chinese Medical SciencesBeijing 100700China Department of Nephrology and Shenzhen Clinical Research Centre for GeriatricsShenzhen People's HospitalThe First Affiliated HospitalSouthern University of Science and TechnologyShenzhenGuangdong 518020China

Nanocarriers have therapeutic potential to facilitate drug delivery,including biological agents,smallmolecule drugs,and nucleic ***,their efficiency is limited by several factors;among which,endosomal/lysosomal degradation after endocytosis is the most *** review summarizes advanced strategies for overcoming endosomal/lysosomal barriers to efficient nanodrug delivery based on the perspective of cellular uptake and intracellular transport *** strategies include promoting endosomal/lysosomal escape,using non-endocytic methods of delivery to directly cross the cell membrane to evade endosomes/lysosomes and making a detour pathway to evade endosomes/*** the basis of the findings of this review,we proposed several promising strategies for overcoming endosomal/lysosomal barriers through the smarter and more efficient design of nanodrug delivery systems for future clinical applications.

关键词： somal drugs finding

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Classification of spin Hall effect in two-dimensional systems

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Frontiers of physics 2024年第3期19卷 103-114页

作者： Longjun Xiang Fuming Xu Luyang Wang Jian Wang College of Physics and Optoelectronic Engineering Shenzhen UniversityShenzhen 518060China Quantum Science center of Guangdong-Hongkong-Macao Greater Bay Area(Guangdong) Shenzhen 518045China Department of Physics The University of Hong KongPokfulam RoadHong KongChina

Physical properties such as the conductivity are usually classified according to the symmetry of the underlying system using Neumann’s principle, which gives an upper bound for the number of independent components of the corresponding property tensor. However, for a given Hamiltonian, this global approach usually can not give a definite answer on whether a physical effect such as spin Hall effect (SHE) exists or not. It is found that the parity and types of spin-orbit interactions (SOIs) are good indicators that can further reduce the number of independent components of the spin Hall conductivity for a specific system. In terms of the parity as well as various Rashba-like and Dresselhaus-like SOIs, we propose a local approach to classify SHE in two-dimensional (2D) two-band models, where sufficient conditions for identifying the existence or absence of SHE in all 2D magnetic point groups are presented.

关键词： spin Hall effect symmetry two-dimensional system

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