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Autophagy and circadian rhythms:interactions and clinical implications

BIOCELL 2024年第1期48卷 33-45页

作者： TIANKAI DI ZHIFEI ZHOU FEN LIU YUJIANG CHEN lulu wang State Key Laboratory of Oral&Maxillofacial Reconstruction and Regeneration National Clinical Research Center for Oral DiseasesShaanxi Clinical Research Center for Oral DiseasesDepartment of Pediatric DentistrySchool of StomatologyThe Fourth Military Medical UniversityXi’an710032China Department of Stomatology The 969th HospitalJoint Logistics Support Force of the Chinese People’s Liberation ArmyHohhot010000China Department of Stomatology General Hospital of Tibetan Military CommandLhasa850000China Key Laboratory of Shaanxi Province for Craniofacial Precision Medicine Research Clinical Research Center of Shaanxi Province for Dental and Maxillofacial DiseasesDepartment of Pediatric DentistryCollege of StomatologyXi’an Jiaotong UniversityXi’an710000China Department of Neurobiology and Institute of Neurosciences School of Basic MedicineFourth Military Medical UniversityXi’an710032China

Autophagy is a widespread biological process that controls cellular growth,survival,development,and *** rhythm is a recurring reaction of living organisms and behaviors to variations in surrounding brightness and *** of the fundamental physiological processes in mammals,such as the sleep-wake pattern and the rhythm of nutrition and energy metabolism,are governed by circadian *** has indicated that autophagy exhibits a specific circadian pattern in both normal and abnormal *** can modulate circadian rhythms by breaking down proteins that regulate the circadian *** potential regulatory connection between the two has been a popular subject of clinical and fundamental *** the interaction between circadian rhythm and autophagy could potentially lead to the development of novel approaches for disease treatment in the *** present analysis presented a summary of the molecular processes implicated in the interplay between autophagy and circadian rhythm,as well as the pathological importance of the disrupted regulatory association between these two phenomena.

关键词： Autophagy Circadian rhythms Mechanism Application

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Selectively T cell phosphorylation activation of azvudine in the thymus tissue with immune protection effect

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Acta Pharmaceutica Sinica B 2024年第7期14卷 3140-3154页

作者： Ning Sheng Rui Li Yang Li Zhe wang lulu wang Yuhuan Li Jinlan Zhang Jiandong Jiang State Key Laboratory of Bioactive Substance and Function of Natural Medicines Institute of Materia MedicaChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100050China Institute of Medicinal Biotechnology Chinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100050China

Thymus is the important immune organ,responsible for T cell development and *** lower circulating T counts have been observed in patients who died from COVID-19 compared with ***,also known as FNC,is a thymus-homing anti-SARS-CoV-2 drug in treating COVID-19 *** this study,single-cell transcriptome,proteomics,and parallel reaction monitoring(PRM)were applied to insight into the activation process of FNC in rat and SARS-CoV-2 rhesus monkey *** results indicated that thymic immune cells possess a robust metabolic capacity for cytidine-analogue drugs such as *** enzymes involved in the FNC phosphorylation process,such as Dck,Cmpk1,and Nme2,were highly expressed in CD4+ T cells,CD8+ T cells,and DP(CD4+ CD8+)***,FNC could upregulate multiple phosphorylated kinases in various cell types while downregulating the phosphatases,phosphoribosyl transferases,and deaminases,*** robust phosphorylation capacity of the thymus for cytidine analogue drug FNC,and the activation effect of FNC on the NAs metabolism system potentially contribute to its enrichment in the thymus and immune protection *** suggests that it is crucial to consider the expression level of phosphorylation kinases when evaluating NA drug properties,as an important factor during antiviral drug design.

关键词： Azvudine T cell Thymus Phosphorylation activation Nucleoside analogue

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An overview of autophagy in the differentiation of dental stem cells

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BIOCELL 2024年第1期48卷 47-64页

作者： XITONG ZHAO TIANJUAN JU XINWEI LI CHANGFENG LIU lulu wang LI-AN WU State Key Laboratory of Oral&Maxillofacial Reconstruction and Regeneration National Clinical Research Center for Oral DiseasesShaanxi Clinical Research Center for Oral DiseasesDepartment of Pediatric DentistrySchool of StomatologyThe Fourth Military Medical UniversityXi’an710032China

Dental stem cells(DSCs)have attracted significant interest as autologous stem cells since they are easily accessible and give a minimal immune *** properties and their ability to both maintain self-renewal and undergo multi-lineage differentiation establish them as key players in regenerative *** many regulatory factors determine the differentiation trajectory of DSCs,prior research has predominantly been based on genetic,epigenetic,and molecular *** evidence suggests that DSC differentiation can also be influenced by autophagy,a highly conserved cellular process responsible for maintaining cellular and tissue homeostasis under various stress *** comprehensive review endeavors to elucidate the intricate regulatory mechanism and relationship between autophagy and DSC *** achieve this goal,we dissect the intricacies of autophagy and its ***,we elucidate its pivotal roles in impacting DSC differentiation,including osteo/odontogenic,neurogenic,and angiogenic ***,we reveal the regulatory factors that govern autophagy in DSC lineage commitment,including scaffold materials,pharmaceutical cues,and the extrinsic *** implications of this review are far-reaching,underpinning the potential to wield autophagy as a regulatory tool to expedite DSC-directed differentiation and thereby promote the application of DSCs within the realm of regenerative medicine.

关键词： Dental stem cells Cell differentiation Autophagy Mitophagy Autophagy regulation

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Active components of Dengzhan Shengmai ameliorate cognitive impairment by facilitating hippocampal long-term potentiation via the NMDA receptor-mediated Ca^(2+)/CaMKII pathway

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Journal of Pharmaceutical Analysis 2024年第3期14卷 435-438页

作者： Congyu Ma Ning Sheng Jun Wu lulu wang Jiandong Jiang Haibo Yu Jinlan Zhang State Key Laboratory of Bioactive Substance and Function of Natural Medicines Institute of Materia MedicaChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing100050China Institute of Medicinal Biotechnology Chinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing100050China

Abnormal synaptic plasticity causes cognitive *** long-term potentiation(LTP)is a critical synaptic plasticity process[1].Rescuing impaired LTP is challenging;hence,novel agents are required for LTP *** medicine Dengzhan Shengmai(DzSM)has shown notable clinical efficacy against cognitive deficits[2].However,it remains unclear how DzSM modulates *** previous study[3]revealed the influence of DZSM on glutamatergic and GABAergic synapses following chronic cerebral hypoperfusion(CCH),which motivated us to assess how DzSM affects synaptic functions.

关键词： impaired impairment hence

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Microstrip Patch Antenna with an Inverted T-Type Notch in the Partial Ground for Breast Cancer Detections

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Computer Modeling in Engineering & Sciences 2024年第2期138卷 1301-1322页

作者： Nure Alam Chowdhury lulu wang Md Shazzadul Islam Linxia Gu Mehmet Kaya Department of Biomedical Engineering and Science Florida Institute of TechnologyMelbourneFL 32901USA Biomedical Device Innovation Center Shenzhen Technology UniversityShenzhen518118China Department of Electrical and Computer Engineering International Islamic University MalaysiaJalan GombakSelangor53100Malaysia

This study designs a microstrip patch antenna with an inverted T-type notch in the partial ground to detect tumorcells inside the human *** size of the current antenna is small enough(18mm×21mm×1.6mm)todistribute around the breast *** operating frequency has been observed from6–14GHzwith a minimumreturn loss of−61.18 dB and themaximumgain of current proposed antenna is 5.8 dBiwhich is flexiblewith respectto the size of *** the distribution of eight antennas around the breast phantom,the return loss curveswere observed in the presence and absence of tumor cells inside the breast phantom,and these observations showa sharp difference between the presence and absence of tumor *** simulated results show that this proposedantenna is suitable for early detection of cancerous cells inside the breast.

关键词： Antenna microwave wideband cancer breast phantom tumor detection

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A distinct“repair”role of regulatory T cells in fracture healing

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Frontiers of Medicine 2024年第3期18卷 516-537页

作者： Tingting Wu lulu wang Chen Jian Zhenhe Zhang Ruiyin Zeng Bobin Mi Guohui Liu Yu Zhang Chen Shi Department of Pharmacy Union HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhan430022China Hubei Province Clinical Research Center for Precision Medicine for Critical Illness Wuhan430022China Department of Orthopedics Union HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhan430022China

Regulatory T cells(Tregs)suppress immune responses and ***,we described the distinct nonimmunological role of Tregs in fracture *** recruitment from the circulation pool,peripheral induction,and local expansion rapidly enriched Tregs in the injured *** Tregs in the injured bone displayed superiority in direct osteogenesis over Tregs from lymphoid *** depletion of Tregs compromised the fracture healing process,which leads to increased bone *** addition,bone callus Tregs showed unique T-cell receptor *** was the most overexpressed protein in bone callus Tregs,and it can directly facilitate the proliferation and differentiation of osteogenic precursor cells by activation of phosphatidylinositol 3-kinase/protein kinase B signaling *** results of loss-and gain-function studies further evidenced that amphiregulin can reverse the compromised healing caused by Treg *** also enriched in patient bone callus and amphiregulin can promote the osteogenesis of human pre-osteoblastic *** findings indicate the distinct and nonredundant role of Tregs in fracture healing,which will provide a new therapeutic target and strategy in the clinical treatment of fractures.

关键词： regulatory T cells fracture healing amphiregulin non-union osteogenesis

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Dual-responsive supramolecular photodynamic nanomedicine with activatable immunomodulation for enhanced antitumor therapy

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Acta Pharmaceutica Sinica B 2024年第2期14卷 765-780页

作者： Siqin He lulu wang Dongxu Wu Fan Tong Huan Zhao Hanmei Li Tao Gong Huile Gao Yang Zhou Key Laboratory of Tropical Biological Resources of Ministry of Education School of Pharmaceutical SciencesHainan UniversityHaikou 570200China Key Laboratory of Drug-Targeting and Drug Delivery System West China School of PharmacySichuan UniversityChengdu 610041China Revvity Inc. WalthamMA 02451USA School of Food and Biological Engineering Chengdu UniversityChengdu 610106China

A major challenge facing photodynamic therapy(PDT) is that the activity of the immuneinduced infiltrating CD8^(+)T cells is subject to the regulatory T lymphocytes(Tregs), leaving the tumor at risk of recurrence and metastasis after the initial ablation. To augment the antitumor response and reprogram the immunosuppressive tumor microenvironment(TME), a supramolecular photodynamic nanoparticle(DACss) is constructed by the host-guest interaction between demethylcantharidin-conjugated β-cyclodextrin(DMC-CD) and amantadine-terminated disulfide-conjugated FFVLGGGC peptide with chlorin e6 decoration(Ad-ss-pep-Ce6) to achieve intelligent delivery of photosensitizer and immunomodulator for breast cancer treatment. The acid-labile β-carboxamide bond of DMC-CD is hydrolyzed in response to the acidic TME, resulting in the localized release of DMC and subsequent inhibition of *** guest molecule Ad-ss-pep-Ce6 can be cleaved by a high level of intracellular GSH, reducing photosensitizer toxicity and increasing photosensitizer retention in the tumor. With a significant increase in the CTL/Treg ratio, the combination of Ce6-based PDT and DMC-mediated immunomodulation adequately achieved spatiotemporal regulation and remodeling of the TME, as well as improved primary tumor and in situ lung metastasis suppression with the aid of PD-1 antibody.

关键词： Photodynamic therapy Immunosuppressive microenvironment Immunomodulator Dual-responsive Supramolecularassembly Checkpointblockade

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Visualization of nasal powder distribution using biomimetic human nasal cavity model

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Acta Pharmaceutica Sinica B 2024年第1期14卷 392-404页

作者： Jiawen Su Yan Liu Hongyu Sun Abid Naeem Huipeng Xu Yue Qu Caifen wang Zeru Li Jianhua Lu lulu wang Xiaofeng wang Jie Wu Lixin Sun Jiwen Zhang Zhigang wang Rui Yang Li Wu Key Laboratory of Modern Preparation of TCM Ministry of EducationJiangxi University of Chinese MedicineNanchang 330004China Key Laboratory of Molecular Pharmacology and Drug Evaluation School of PharmacyMinistry of EducationYantai UniversityYantai 264005China Shanghai Institute of Materia Medica Chinese Academy of SciencesShanghai 201210China Nantong Haimen People’s Hospital Nantong 226199China Yangtze Delta Drug Advanced Research Institute Nantong 226126China Shenyang Pharmaceutical University Shenyang 110016China National Institutes for Food and Drug Control Beijing 100000China Nanjing University of Chinese Medicine Nanjing 210023China

Nasal drug delivery efficiency is highly dependent on the position in which the drug is deposited in the nasal ***,no reliable method is currently available to assess its impact on delivery *** this study,a biomimetic nasal model based on three-dimensional(3D)reconstruction and three-dimensional printing(3DP)technology was developed for visualizing the deposition of drug powders in the nasal *** results showed significant differences in cavity area and volume and powder distribution in the anterior part of the biomimetic nasal model of Chinese males and *** nasal cavity model was modified with dimethicone and validated to be suitable for the deposition *** experimental device produced the most satisfactory results with five spray ***,particle sizes and spray angles were found to significantly affect the experimental device’s performance and alter drug distribution,***,mometasone furoate(MF)nasal spray(NS)distribution patterns were investigated in a goat nasal cavity model and three male goat noses,confirming the in vitro and in vivo *** conclusion,the developed human nasal structure biomimetic device has the potential to be a valuable tool for assessing nasal drug delivery system deposition and distribution.

关键词： Nasal drug deposition Nasal drug distribution Nasal drug delivery Biomimetic nasal model Nasal powder Three-dimensional reconstruction Three-dimensional printing Nasal drug distribution

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AcWRKY28 mediated activation of AcCPK genes confers salt tolerance in pineapple(Ananas comosus)

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Horticultural Plant Journal 2024年第2期10卷 398-412页

作者： Qiao Zhou Samaranayaka Vidana Gamage Nirosha Priyadarshani Rongjuan Qin Han Cheng Tiantian Luo Myat Hnin Wai Mohammad Aqa Mohammadi Yanhui Liu Chang Liu Hanyang Cai Xiaomei wang Yeqiang Liu Yuan Qin lulu wang Guangxi Key Lab of Sugarcane Biology State Key Laboratory for Conservation and Utilization of Subtropical Agro-BioresourcesCollege of AgricultureGuangxi UniversityNanningGuangxi 530004China State Key Laboratory of Ecological Pest Control for Fujian and Taiwan Crops College of Life ScienceCollege of Plant ProtectionCollege of AgricultureCollege of HorticultureFujian Provincial Key Laboratory of Haixia Applied Plant Systems BiologyCenter for Genomics and BiotechnologyFujian Agriculture and Forestry UniversityFuzhouFujian 350002China Pingtan Science and Technology Research Institute of Fujian Agriculture and Forestry University PingtanFujian 350400China National Education Commission BMICHColombo00700Sri Lanka Fishery Multiplication Management Station of Lijiang River Water Supply Hub Project GuilinGuangxi 541001China Horticulture Research Institute Guangxi Academy of Agricultural SciencesNanning Investigation Station of South Subtropical Fruit TreesMinistry of AgricultureNanningGuangxi 530007China

Unfavorable environmental cues severely affect crop productivity resulting in significant economic losses to farmers. In plants, multiple regulatory genes, such as the WRKY transcription factor (TF) family, modulate the expression of defense genes. However, the role of the pineapple WRKY genes is poorly understood. Here, we studied the pineapple WRKY gene, AcWRKY28, by generating AcWRKY28 over-expressing transgenic pineapple plants. Overexpression of AcWRKY28 enhanced the salt stress resistance in transgenic pineapple lines. Comparative transcriptome analysis of transgenic and wild-type pineapple plants showed that “plant-pathogen interaction” pathway genes, including 9calcium-dependent protein kinases (CPKs), were up-regulated in AcWRKY28 over-expressing plants. Furthermore, chromatin immunoprecipitation and yeast one-hybrid assays revealed AcCPK12, AcCPK3, AcCPK8, AcCPK1, and AcCPK15 as direct targets of AcWRKY28. Consistently, the study of AcCPK12 over-expressing Arabidopsis lines showed that AcCPK12 enhances salt, drought, and disease resistance. This study shows that AcWRKY28 plays a crucial role in promoting salt stress resistance by activating the expression of AcCPK genes.

关键词： Pineapple AcWRKY AcCPK Transcription factor Salt stress ChIP

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A high-speed true random number generator based on Ag/SiNx/n-Si memristor

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Frontiers of physics 2024年第1期19卷 241-250页

作者： Xiaobing Yan Zixuan Zhang Zhiyuan Guan Ziliang Fang Yinxing Zhang Jianhui Zhao Jiameng Sun Xu Han Jiangzhen Niu lulu wang Xiaotong Jia Yiduo Shao Zhen Zhao Zhenqiang Guo Bing Bai Institute of Life Science and Green Development Key Laboratory of Brain-Like Neuromorphic Devices and Systems of Hebei ProvinceCollege of Electron and Information EngineeringHebei UniversityBaoding 071002China

The intrinsic variability of memristor switching behavior can be used as a natural source of randomness,this variability is valuable for safe applications in hardware,such as the true random number generator(TRNG).However,the speed of TRNG is still be further ***,we propose a reliable Ag/SiNx/n-Si volatile memristor,which exhibits a typical threshold switching device with stable repeat ability and fast switching *** volatile-memristor-based TRNG is combined with nonlinear feedback shift register(NFSR)to form a new type of high-speed dual output ***,the bit generation rate reaches a high speed of 112 kb/*** addition,this new TRNG passed all 15 National Institute of Standards and Technology(NIST)randomness tests without post-processing steps,proving its performance as a hardware security *** work shows that the SiNx-based volatile memristor can realize TRNG and has great potential in hardware network security.

关键词： volatile memristor true random number generator(TRNG) delay time threshold switching device

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