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Development of a potent benzonitrile-based inhibitor of glutaminyl-peptide cyclotransferase-like protein(QPCTL)with antitumor efficacy

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Signal Transduction and Targeted Therapy 2024年第1期9卷 44-46页

作者： Lei Yu pengcheng zhao Yaoliang Sun Zening Zheng Wenhao Du Lishan Zhang Yaxu Li Longyan Xie Shilin Xu Ping Wang Tongji University Cancer Center Shanghai Tenth People’s HospitalSchool of MedicineTongji UniversityShanghaiChina Department of Medicinal Chemistry Shanghai Institute of Materia MedicaChinese Academy of SciencesShanghaiChina

Dear Editor,Immune checkpoint therapies manipulating the immune system to eliminate tumor cells have shown remarkable clinical efficacy in treating various cancers.CD47,an emerging efficient immune checkpoint,is crucial for cancer cells to evade macrophagemediated phagocytosis by interaction with signal-regulatory proteinα(SIRPα).Antibodies blocking the CD47/SIRPαinteraction have been effective to promote macrophage-mediated phagocytosis in various types of cancer in mice and humans.CD47 is not only highly expressed in tumor cells,but also normal cells,such as red blood cells(RBCs).Thus,during clinical trials involving cancer patients,anti-CD47 antibodies may promote the macrophagesmediated phagocytosis of RBCs,ultimately inducing undesirable anemia side effects.In contrast,small molecule inhibitors interrupting CD47/SIRPαaxis have shown potential to overcome the anemia,possibly due to their lower immunogenicity and shorter half-life compared to antibodies.1 Hence,developing the novel strategies,especially those without the anemia side effect,to intervene in CD47/SIRPαinteraction will benefit cancer immunotherapy.

关键词： anemia overcome eliminate

Analysis of COVID-19 clusters involving vertical transmission in residential buildings in Hong Kong region

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Building Simulation 2023年第5期16卷 701-711页

作者： pengcheng zhao Department of Mechanical Engineering The University of Hong KongPokfulamHong KongChina

Multiple clusters of coronavirus disease 2019(COVID-19)in Hong Kong have involved vertical transmissions in residential buildings,wherein the flats of confirmed cases were often vertically aligned.Data on the buildings and cases associated with 19 such clusters were retrieved and compared with the corresponding data on the entirety of Hong Kong region.Vertical transmissions usually occurred in old high-rise buildings with small flat areas and low estate prices during winter.In addition,infection occurred frequently among the elderly and among upstairs neighbours of index cases.Virus-laden aerosols may have been transmitted between flats mostly via shared drainpipes,and the vertical distribution of the confirmed cases in a building varied by its drainage system design.For buildings with their entire drainpipes installed indoors,both the upstairs and downstairs neighbours of the index case flats could be infected.By comparison,buildings with their drainage stacks installed outdoors had lower infection risks and demonstrated a clearer pattern of vertical transmission:most infected cases resided upstairs from the index case flats,indicating that the virus spread could be dominated by the stack effect.This study provides valuable data and analysis for developing epidemic control strategies for residential buildings.

关键词： drainage system high-rise building infection SARS-CoV-2 stack effect ventilation

Using Machine Learning to Identify and Optimize Sensitive Parameters in Urban Flood Model Considering Subsurface Characteristics

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International Journal of Disaster Risk Science 2024年第1期15卷 116-133页

作者： Hengxu Jin Yu zhao pengcheng Lu Shuliang Zhang Yiwen Chen Shanghua Zheng Zhizhou Zhu Key Laboratory of VGE of Ministry of Education Nanjing Normal UniversityNanjing 210023China Jiangsu Center for Collaborative Innovation in Geographical Information Resource Development and Application Nanjing 210023China

This study presents a novel method for optimizing parameters in urban flood models,aiming to address the tedious and complex issues associated with parameter optimization.First,a coupled one-dimensional pipe network runoff model and a two-dimensional surface runoff model were integrated to construct an interpretable urban flood model.Next,a principle for dividing urban hydrological response units was introduced,incorporating surface attribute features.The K-means algorithm was used to explore the clustering patterns of the uncertain parameters in the model,and an artificial neural network(ANN)was employed to identify the sensitive parameters.Finally,a genetic algorithm(GA) was used to calibrate the parameter thresholds of the sub-catchment units in different urban land-use zones within the flood model.The results demonstrate that the parameter optimization method based on K-means-ANN-GA achieved an average Nash-Sutcliffe efficiency coefficient(NSE) of 0.81.Compared to the ANN-GA and K-means-deep neural networks(DNN) methods,the proposed method better characterizes the runoff generation and flow processes.This study demonstrates the significant potential of combining machine learning techniques with physical knowledge in parameter optimization research for flood models.

关键词： Artifcial neural network Coupled urban fooding model Genetic algorithm K-means algorithm Subcatchment delineation Uncertain parameters

Multi-region calcium imaging in freely behaving mice with ultra-compact head-mounted fluorescence microscopes

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National Science Review 2024年第1期11卷 161-173页

作者： Feng Xue Fei Li Ke-ming Zhang Lufeng Ding Yang Wang Xingtao zhao Fang Xu Danke Zhang Mingzhai Sun Pak-Ming Lau Qingyuan Zhu pengcheng Zhou Guo-Qiang Bi Institute of Artiflcial Intelligence Hefei Comprehensive National Science Center Department of Precision Machinery and Precision Instruments University of Science and Technology of China Hefei National Laboratory for Physical Sciences at the Microscale University of Science and Technology of China Interdisciplinary Center for Brain Information the Brain Cognition and Brain Disease Institute Shenzhen Institute of Advanced Technology Chinese Academy of Sciences Faculty of Life and Health Sciences Shenzhen Institutes of Advanced Technology Chinese Academy of Sciences School of Life Sciences University of Science and Technology of China Institute of Semiconductors Chinese Academy of Sciences Department of Modern Life Sciences and Biotecnology Xiongan Institute of Innovation Xiongan New Area Shenzhen-Hong Kong Institute of Brain Science-Shenzhen Fundamental Research Institutions Suzhou Institute for Advanced Research University of Science and Technology of China

To investigate the circuit-level neural mechanisms of behavior, simultaneous imaging of neuronal activity in multiple cortical and subcortical regions is highly desired. Miniature head-mounted microscopes offer the capability of calcium imaging in freely behaving animals. However, implanting multiple microscopes on a mouse brain remains challenging due to space constraints and the cumbersome weight of the equipment.Here, we present TINIscope, a Tightly Integrated Neuronal Imaging microscope optimized for electronic and opto-mechanical design. With its compact and lightweight design of 0.43 g, TINIscope enables unprecedented simultaneous imaging of behavior-relevant activity in up to four brain regions in mice.Proof-of-concept experiments with TINIscope recorded over 1000 neurons in four hippocampal subregions and revealed concurrent activity patterns spanning across these regions. Moreover, we explored potential multi-modal experimental designs by integrating additional modules for optogenetics, electrical stimulation or local field potential recordings. Overall, TINIscope represents a timely and indispensable tool for studying the brain-wide interregional coordination that underlies unrestrained behaviors.

关键词： miniature microscope multiple sites calcium imaging multimodal integration hippocampus

A time sequential microfluid sensor with Tesla valve channels

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Nano Research 2023年第9期16卷 11667-11673页

作者： pengcheng zhao Haobin Wang Yaozheng Wang Wei zhao Mengdi Han Haixia Zhang National Key Laboratory of Science and Technology on Micro/Nano Fabrication Beijing Advanced Innovation Center for Integrated CircuitsSchool of Integrated CircuitsPeking UniversityBeijing 100871China Department of Cardiology and Institute of Vascular Medicine NHC Key Laboratory of Cardiovascular Molecular Biology and Regulatory PeptidesKey Laboratory of Molecular Cardiovascular ScienceMinistry of EducationBeijing Key Laboratory of Cardiovascular Receptors ResearchPeking University Third HospitalBeijing 100191China Department of Biomedical Engineering College of Future Technology Peking UniversityBeijing 100871China

The concentration of biomarkers in sweat can be used to evaluate human health,making efficient sweat sensing a focus of research.While flow channel design is often used to detect sweat velocity,it is rarely incorporated into the sensing of biomarkers,limiting the richness of sensing results.In this study,we report a time sequential sensing scheme for uric acid in sweat through a sequential design of Tesla valve channels.Graphene electrodes for detecting uric acid and directional Tesla valve flow channels were fabricated using laser engraving technology to realize time sequential sensing.The performance of the channels was verified through simulation.The time sequential detection of uric acid concentration in sweat can help researchers improve the establishment of human health management systems through flexible wearable devices.

关键词： time sequential sensing uric acid Tesla valves laser engraving technology

Molecularly engineered lignin to polyphenol via organocatalysis as an active sunscreen ingredient

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Journal of Bioresources and Bioproducts 2024年第2期9卷 197-210页

作者： Yuanlong Guo pengcheng Liu Lei Deng Changwei Lui Michael North Gang Hu Qitian Huang Zongbao Kent zhao Haibo Xie Department of Polymeric Materials&Engineering Guizhou UniversityGuiyang 550025China KZJ New Materials Group Guizhou Co.Ltd. Guizhou 551200China Green Chemistry Centre of Excellence Department of ChemistryUniversity of YorkYork YO105DDUK Dalian Institute of Chemical Physics Chinese Academy of SciencesDalian 116023China

Phenolation is one of the effective strategies to synthesize lignin-based polyphenols,improve lignin’s properties,and extend its value-added applications in biological,medicinal and cosmetic fields.Herein,by taking the structural feature advantage of lignin,an effective and green strategy was developed to molecularly engineer lignin into a robust lignin-3-(2-hydroxyphenyl)propionate ester(LPPE)derivative via a transesterification reaction between 3,4-dihydrocoumarin(DHC)and the aliphatic hydroxyls in lignin under organocatalysis.The strategy is optimized and the novel derivative was systematically characterized by ^(1)H,^(13)C and ^(31)P nuclear magnetic resonance(NMR)and Fourier transform infrared(FT-IR)spectroscopy.The findings indicated that the successful introduction of 3-(2-hydroxyphenyl)propionate groups using a OH groups/DHC/organic base mo-lar ratio of 1꞉1꞉0.3 at 120℃ for 6 h increased the content of phenolic hydroxyl groups from 1.7931 to 3.0179 mmol/g,and the LPPE exhibited excellent ultraviolet-absorbing and antioxidant per-formance with up to 90%free radical scavenging activity within 20 min using 5 mg/mL of LPPE.In addition,good biocompatibility and a high Sun protection factor(SPF)value of 40.9 were achieved at 5%(w)dosage of LPPE in the cream,indicating its significant application potential in sunscreen.

关键词： Phenolation of lignin Organocatalysis 3,4-dihydrocoumarin Antioxidant Sunscreen cream

AtVQ25 promotes salicylic acid-related leaf senescence by fine-tuning the self-repression of AtWRKY53

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Journal of Integrative Plant Biology 2024年第6期66卷 1126-1147页

作者： Qi Tan Mingming zhao Jingwei Gao Ke Li Mengwei Zhang Yunjia Li Zeting Liu Yujia Song Xiaoyue Lu Zhengge Zhu Rongcheng Lin pengcheng Yin Chunjiang Zhou Geng Wang Ministry of Education Key Laboratory of Molecular and Cellular Biology Hebei Research Center of the Basic Discipline of Cell BiologyHebei Collaboration Innovation Center for Cell Signaling and Environmental Adaptation Hebei Key Laboratory of Molecular and Cellular Biology College of Life Sciences Hebei Normal University College of Chemical Engineering Shijiazhuang University Institute of Botany Chinese Academy of Sciences

Most mechanistic details of chronologically ordered regulation of leaf senescence are unknown.Regulatory networks centered on AtWRKY53 are crucial for orchestrating and integrating various senescence-related signals. Notably, AtWRKY53binds to its own promoter and represses transcription of AtWRKY53, but the biological significance and mechanism underlying this selfrepression remain unclear. In this study, we identified the VQ motif-containing protein AtVQ25as a cooperator of AtWRKY53. The expression level of AtVQ25 peaked at mature stage and was specifically repressed after the onset of leaf senescence. AtVQ25-overexpressing plants and atvq25 mutants displayed precocious and delayed leaf senescence, respectively. Importantly, we identified AtWRKY53 as an interacting partner of AtVQ25. We determined that interaction between AtVQ25 and AtWRKY53 prevented AtWRKY53from binding to W-box elements on the AtWRKY53promoter and thus counteracted the selfrepression of AtWRKY53. In addition, our RNA-sequencing data revealed that the AtVQ25-AtWRKY53 module is related to the salicylic acid(SA) pathway. Precocious leaf senescence and SA-induced leaf senescence in AtVQ25-overexpressing lines were inhibited by an SA pathway mutant, atsid2, and Nah G transgenic plants; AtVQ25-overexpressing/atwrky53 plants were also insensitive to SA-induced leaf senescence. Collectively, we demonstrated that AtVQ25 directly attenuates the self-repression of AtWRKY53 during the onset of leaf senescence,which is substantially helpful for understanding the timing of leaf senescence onset modulated by AtWRKY53.

关键词： AtWRKY53 leaf senescence salicylic acid transcriptional regulation VQ motif-containing proteins

Rapid printing of 3D porous scaffolds for breast reconstruction

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Bio-Design and Manufacturing 2023年第6期6卷 691-703页

作者： pengcheng zhao Biling Wang Lu Wang Zexin Fu Jun Hu Yande Liu Ji Wang Yong He School of Mechatronics and Vehicle Engineering East China Jiaotong UniversityNanchang 330013China Center for Plastic and Reconstructive Surgery Department of Plastic and Reconstructive SurgeryZhejiang Provincial People’s Hospital(Affiliated People’s HospitalHangzhou Medical College)Hangzhou 310014China Key Laboratory of 3D Printing Process and Equipment of Zhejiang Province School of Mechanical EngineeringZhejiang UniversityHangzhou 310027China

Prosthesis implantation and fat transplantation are common breast reconstructionmethods.In general,prosthesis implantation alone does not achieve a realistic enough appearance,and fat transplantation alone is difficult to achieve in the correct capacity.To date,no reports have focused on methods of combining fat with implanted prostheses for breast reconstruction.Using a newly designed bionic ink(i.e.,polyether F127 diacrylate(F127DA)&poly(ethylene glycol)diacrylate(PEGDA))and projection-based three-dimensional bioprinting(PBP),we report the development of a new method for printing porous prostheses.PEGDA was used to improve the printing precision of the prosthesis by increasing the gel point of F127DA and reducing the impact of external temperature.The compression modulus of the printed prosthesis was very close to that of prostheses currently used in clinical practice and to that of natural breasts.Finally,stromal vascular fraction gel(SVF-gel),a human fat extract,was injected into the pores of the synthesized prostheses to prepare a prosthesis mixed with adipose tissue.These were implanted subcutaneously in nude mice to observe their biological performance.After 14 and 28 days of observation,the prosthesis showed good biocompatibility,and adipose tissues grew well in and around the prosthesis.This result shows that a porous prosthesis containing pre-placed adipose tissues is a promising breast reconstruction material.

关键词： Projection-based 3D bioprinting(PBP) F127DA Breast reconstruction Fat transplantation

Emerging phagocytosis checkpoints in cancer immunotherapy

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Signal Transduction and Targeted Therapy 2023年第4期8卷 1461-1502页

作者： Yu’e Liu Yanjin Wang Yanrong Yang Linjun Weng Qi Wu Jin Zhang pengcheng zhao Lan Fang Yufeng Shi Ping Wang Tongji University Cancer Center Shanghai Tenth People’s Hospital of Tongji UniversitySchool of MedicineTongji UniversityShanghai 200092China Department of Nephrology Shanghai East HospitalTongji University School of MedicineShanghaiChina Department of Pharmacology and Toxicology University of Mississippi Medical Center39216 JacksonMSUSA Clinical Center for Brain and Spinal Cord Research Tongji UniversityShanghai 200092China

Cancer immunotherapy,mainly including immune checkpoints-targeted therapy and the adoptive transfer of engineered immune cells,has revolutionized the oncology landscape as it utilizes patients’own immune systems in combating the cancer cells.Cancer cells escape immune surveillance by hijacking the corresponding inhibitory pathways via overexpressing checkpoint genes.Phagocytosis checkpoints,such as CD47,CD24,MHC-I,PD-L1,STC-1 and GD2,have emerged as essential checkpoints for cancer immunotherapy by functioning as“don’t eat me”signals or interacting with“eat me”signals to suppress immune responses.Phagocytosis checkpoints link innate immunity and adaptive immunity in cancer immunotherapy.Genetic ablation of these phagocytosis checkpoints,as well as blockade of their signaling pathways,robustly augments phagocytosis and reduces tumor size.Among all phagocytosis checkpoints,CD47 is the most thoroughly studied and has emerged as a rising star among targets for cancer treatment.CD47-targeting antibodies and inhibitors have been investigated in various preclinical and clinical trials.However,anemia and thrombocytopenia appear to be formidable challenges since CD47 is ubiquitously expressed on erythrocytes.Here,we review the reported phagocytosis checkpoints by discussing their mechanisms and functions in cancer immunotherapy,highlight clinical progress in targeting these checkpoints and discuss challenges and potential solutions to smooth the way for combination immunotherapeutic strategies that involve both innate and adaptive immune responses.

关键词： immunotherapy immunity utilize