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Immune checkpoint inhibition mediated with liposomal nanomedicine for cancer therapy

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Military Medical Research 2024年第1期11卷 98-114页

作者： Guang-Long Ma Wei-Feng Lin Faculty of Medicine Centre for Cancer ImmunologyUniversity of SouthamptonSouthampton SO166YDUK Department of Molecular Chemistry and Materials Science Weizmann Institute of Science76100 RehovotIsrael Key laboratory of Bio-Inspired Smart Interfacial Science and Technology of Ministry of Education School of ChemistryBeihang UniversityBeijing 100191China

Immune checkpoint blockade(ICB)therapy for cancer has achieved great success both in clinical results and on the market.At the same time,success drives more attention from scientists to improve it.However,only a small portion of patients are responsive to this therapy,and it comes with a unique spectrum of side effects termed immunerelated adverse events(irAEs).The use of nanotechnology could improve ICBs’delivery to the tumor,assist them in penetrating deeper into tumor tissues and alleviate their irAEs.Liposomal nanomedicine has been investigated and used for decades,and is well-recognized as the most successful nano-drug delivery system.The successful combination of ICB with liposomal nanomedicine could help improve the efficacy of ICB therapy.In this review,we highlighted recent studies using liposomal nanomedicine(including new emerging exosomes and their inspired nanovesicles)in associating ICB therapy.

关键词： Liposome Exosome Immune checkpoint blockade(ICB)

Functional genomics of Brassica napus:Progresses,challenges,and perspectives

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Journal of Integrative Plant Biology 2024年第3期66卷 484-509页

作者： Zengdong Tan Xu Han Cheng Dai Shaoping Lu Hanzi He Xuan Yao Peng Chen Chao Yang Lun Zhao Qing-Yong Yang Jun Zou Jing Wen Dengfeng Hong Chao Liu Xianhong Ge Chuchuan Fan Bing Yi Chunyu Zhang Chaozhi Ma Kede Liu Jinxiong Shen Jinxing Tu Guangsheng Yang Tingdong Fu Liang Guo Hu Zhao National Key laboratory of Crop Genetic Improvement Hubei Hongshan LaboratoryHuazhong Agricultural UniversityWuhan 430070China Yazhouwan National laboratory Sanya 572025China

Brassica napus,commonly known as rapeseed or canola,is a major oil crop contributing over 13%to the stable supply of edible vegetable oil worldwide.Identification and understanding the gene functions in the B.napus genome is crucial for genomic breeding.A group of genes controlling agronomic traits have been successfully cloned through functional genomics studies in B.napus.In this review,we present an overview of the progress made in the functional genomics of B.napus,including the availability of germplasm resources,omics databases and cloned functional genes.Based on the current progress,we also highlight the main challenges and perspectives in this field.The advances in the functional genomics of B.napus contribute to a better understanding of the genetic basis underlying the complex agronomic traits in B.napus and will expedite the breeding of high quality,high resistance and high yield in B.napus varieties.

关键词： accelerate breeding Brassica napus functional genomics high resistance high yield

SARS-CoV-2 breakthrough infections following inactivated vaccine vaccination induce few neutralizing antibodies against the currently emerging Omicron XBB variants

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Virologica Sinica 2024年第1期39卷 173-176页

作者： Fan Shen Chun Liang Cui-Xian Yang Ying Lu An-Qi Li Ying Duan Mi Zhang c Ren-Rong Tian a Xing-Qi Dong Yong-Tang Zheng Wei Pang Key laboratory of Bioactive Peptides of Yunnan Province/Key laboratory of Animal Models and Human Disease Mechanisms of the Chinese Academy of Sciences KIZ-CUHK Joint Laboratory of Bioresources and Molecular Research in Common DiseasesKunming Institute of ZoologyChinese Academy of SciencesKunming650223China University of Chinese Academy of Sciences Beijing100049China Yunnan Provincial Infectious Disease Hospital Kunming650399China Department of Pathogen Biology and immunology Faculty of Basic Medical ScienceKunming Medical UniversityKunming650500China

Dear Editor,COVID-19 inactivated vaccines have been extensively administered inChina.However,the majority of the Chinese population has experiencedbreakthrough infections from SARS-CoV-2 ancestral,Delta or Omicronvariants over the past three years,particularly during the wave of Omicron BA.5 and BA.7 variants at the end of 2022(Zhu et al.,2023).Subsequently,new Omicron variants,such as BQ.1,BQ.1.1,XBB,XBB.1/XBB.1.9,and XBB.1.5/XBB.1.9.1,are emerging in China(Yueetal.,2023;Zhu et al.,2023).Therefore,it is an urgentneed and a publichealth imperative to assess the extent of the immunoprotection established in this population.

关键词： breakthrough neutral Omi

Hierarchical Spinning of Janus Textiles with Anisotropic Wettability for Wound Healing

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Research 2024年第1期2023卷 97-105页

作者： Han Zhang Lingyu Sun Jiahui Guo Yuanjin Zhao Department of Rheumatology and immunology Nanjing Drum Tower HospitalSchool of Biological Science and Medical EngineeringSoutheast UniversityNanjingJiangsu 210096China Oujiang laboratory(Zhejiang Lab for Regenerative Medicine Vision and Brain Health)Wenzhou InstituteUniversity of Chinese Academy of SciencesWenzhouZhejiang 325001China

Wound healing and tissue repair are recognized as basic human health problems worldwide.Attempts to accelerate the reparative process are focused on developing functional wound dressings.Herein,we present novel Janus textiles with anisotropic wettability from hierarchical microfluidic spinning for wound healing.The hydrophilic hydrogel microfibers from microfluidics are woven into textiles for freeze-drying treatment,followed by the deposition of electrostatic spinning nanofibers composed of hydrophobic polylactic acid(PLA)and silver nanoparticles.The electrospun nanofiber layer can be well coupled with the hydrogel microfiber layer to generate Janus textiles with anisotropic wettability due to the roughness of the hydrogel textile surface and the incomplete evaporation of PLA solution when reaching the surface.For wound treatment with the hydrophobic PLA side contacting the wound surface,the wound exudate can be pumped from the hydrophobic to the hydrophilic side based on the wettability differential derived drainage force.During this process,the hydrophobic side of the Janus textile can prevent excess fluid from infiltrating the wound again,preventing excessive moisture and preserving the breathability of the wound.In addition,the silver nanoparticles contained in the hydrophobic nanofibers could impart the textiles with good antibacterial effect,which further promote the wound healing efficiency.These features indicate that the described Janus fiber textile has great application potential in the field of wound treatment.

关键词： silver spinning healing

A novel structural variant of RET causes familial Hirschsprung's disease via nonsense-mediated mRNA decay

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Genes & Diseases 2024年第1期11卷 7-10页

作者： Qi Wang Siyu Pu Bo Xiang Jing Chen Department of Pediatric Surgery and laboratory of Pediatric Surgery Rare Diseases CenterInstitute of Immunology and InflammationFrontiers Science Center for Disease-Related Molecular NetworkWest China HospitalSichuan UniversityChengduSichuan 610041China

Hirschsprung's disease(HsCR)is the most common type of developmental gastrointestinal malformation causing intestinal obstruction in children,with an incidence of 1/5000 in live births.1 it is characterized by the absence of intrinsic ganglion cells in the myenteric and submucosal plexuses of the distal gastrointestinal tract,leading to the dysregulation of smooth muscle contraction/relaxation and resulting in intestinal obstruction.Depending on the length of the aganglionic intestine,HSCR can be categorized into short-segmental HSCR(S-HSCR),which affects up to the sigmoid colon from the anus,and long-segmental HSCR(LHSCR),which affects beyond the sigmoid colon.1 In some rare conditions,aganglionic lesions can affect the full length of the colon or even the whole intestine.

关键词： intestine colon relaxation

immunology demystified: A guide for transplant hepatologists

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World Journal of Transplantation 2024年第1期14卷 48-61页

作者： Iva Kosuta Tomislav Kelava Ana Ostojic Vibor Sesa Anna Mrzljak Hrvoje Lalic Department of Intensive Care Medicine University Hospital Centre ZagrebZagreb 10000Croatia Department of Physiology School of MedicineUniveristy of ZagrebZagreb 10000Croatia laboratory for Molecular immunology Croatian Institute for Brain ResearchZagreb 10000Croatia Department of Gastroenterology and Hepatology Liver Transplant CenterUniversity Hospital Centre ZagrebZagreb 10000Croatia Department of Medicine School of MedicineUniversity of ZagrebZagreb 10000Croatia Department of Physiology University of Zagreb School of MedicineZagreb 10000Croatia laboratory for Cell Biology Croatian Institute for Brain ResearchUniversity of Zagreb School of MedicineZagreb 10000Croatia Department of laboratory immunology Clinical Department of Laboratory DiagnosticsUniversity Hospital Center ZagrebZagreb 10000Croatia

Liver transplantation has become standard practice for treating end-stage liver disease.The success of the procedure relies on effective immunosuppressive medications to control the host's immune response.Despite the liver's inherent capacity to foster tolerance,the early post-transplant period is marked by significant immune reactivity.To ensure favorable outcomes,it is imperative to identify and manage various rejection types,encompassing T-cell-mediated,antibody-mediated,and chronic rejection.However,the approach to prescribing immunosuppressants relies heavily on clinical judgment rather than evidencebased criteria.Given that the majority of patients will require lifelong immunosuppression as the mechanisms underlying operational tolerance are still being investigated,healthcare providers must possess an understanding of immune responses,rejection mechanisms,and the pathways targeted by immunosuppressive drugs.This knowledge enables customization of treatments and improved patient care,even though a consensus on an optimal immunosuppressive regimen remains elusive.

关键词： Liver transplantation Allograft rejection Operational immune tolerance Immune reaction Immunosuppression

Neddylation is a novel therapeutic target for lupus by regulating double negative T cell homeostasis

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Signal Transduction and Targeted Therapy 2024年第2期9卷 738-750页

作者： Yun Zhang Lijun Du Chenxi Wang Zhangsheng Jiang Qingchi Duan Yiping Li Zhijun Xie Zhixing He Yi Sun Lin Huang Liwei Lu Chengping Wen Key laboratory of Chinese medicine rheumatology of Zhejiang Province Research Institute of Chinese Medical Clinical Foundation and ImmunologyCollege of Basic Medical ScienceZhejiang Chinese Medical UniversityHangzhou 310053China Department of General Surgery Sir Run Run Shaw HospitalZhejiang University School of MedicineHangzhou 310016China Cancer Institute(Key laboratory of Cancer Prevention and Intervention China National Ministry of Education)of the Second Affiliated Hospital and Institute of Translational MedicineZhejiang University School of MedicineHangzhou 310029China Cancer Center of Zhejiang University Hangzhou 310029China Department of Pathology and Shenzhen Institute of Research and Innovation The University of Hong KongHong KongChina Chongqing International Institute for immunology Chongqing 400038China

Systemic lupus erythematosus(SLE),a severe autoimmune disorder,is characterized by systemic inflammatory response,autoantibody accumulation and damage to organs.The dysregulation of double-negative(DN)T cells is considered as a crucial commander during SLE.Neddylation,a significant type of protein post-translational modification(PTM),has been well-proved to regulate T cell-mediated immune response.However,the function of neddylation in SLE is still unknown.Here,we reported that neddylation inactivation with MLN4924,a specific inhibitor of NEDD8-activating enzyme E1(NAE1),or genetic abrogation of Ube2m in T cells decreased DN T cell accumulation and attenuated murine lupus development.Further investigations revealed that inactivation of neddylation blocked Bim ubiquitination degradation and maintained Bim level in DN T cells,contributing to the apoptosis of the accumulated DN T cells in lupus mice.Then double knockout(KO)lupus-prone mice(Ube2m-/-Bim-/-lpr)were generated and results showed that loss of Bim reduced Ube2m deficiency-induced apoptosis in DN T cells and reversed the alleviated lupus progression.Our findings identified that neddylation inactivation promoted Bim-mediated DN T cell apoptosis and attenuated lupus progression.Clinically,we also found that in SLE patients,the proportion of DN T cells was raised and their apoptosis was reduced.Moreover,compared to healthy groups,SLE patients exhibited decreased Bim levels and elevated Cullin1 neddylation levels.Meantime,the inhibition of neddylation induced Bim-dependent apoptosis of DN T cells isolated from SLE patients.Altogether,our findings provide the direct evidence about the function of neddylation during lupus,suggesting a promising therapeutic approach for this disease.

关键词： inactivation double finding

Conversion of a single-layer ANN to photonic SNN for pattern recognition

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Science China(Information Sciences) 2024年第1期67卷 261-270页

作者： Yanan HAN Shuiying XIANG Tianrui ZHANG Yahui ZHANG Xingxing GUO Yuechun SHI State Key laboratory of Integrated Service Networks State Key Discipline Laboratory of Wide Bandgap Semiconductor TechnologyXidian University Yongjiang laboratory

This work presents a complete conversion scheme for photonic spiking neural networks(SNNs).We verified that the output of an artificial neural network(ANN) trained with the simulated optical activation function can be directly converted into the spike rate of a photonic spiking neuron model.To reveal the feasibility of hardware implementation,we considered the effects of different bit precisions of data and weight,noise level,and bias current mismatch on the converted results.The proposed scheme was evaluated using the Deterding vowel,IRIS,TIDIGITS,and MNIST datasets for pattern recognition,and achieved mean accuracies of 95.80%,98.67%,96.19%,and 92.33%,respectively.The proposed scheme can convert an ANN into a photonic SNN with almost no precision loss,and the performance was comparable to that of an ANN trained with the rectified linear unit function.The proposed scheme can enable the high-performance implementation of photonic SNNs.

关键词： photonic SNN conversion optical computing pattern recognition artificial neural network

Coming of age:the formation and function of age-associated B cells

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Cellular & Molecular immunology 2024年第4期21卷 311-312页

作者： Ke Rui Nan Che Kongyang Ma Hejian Zou Fan Xiao Liwei Lu Department of laboratory Medicine Institute of Medical Immunology of Jiangsu UniversityAffiliated Hospital of Jiangsu UniversityZhenjiangChina Department of Rheumatology and immunology Nanjing First HospitalNanjing Medical UniversityJiangsuChina Centre for Infection and Immunity Studies School of MedicineThe Sun Yat-sen UniversityShenzhen518107GuangdongChina Department of Rheumatology Huashan HospitalFudan UniversityShanghaiChina Department of Pathology and Shenzhen Institute of Research and Innovation HKU Shenzhen HospitalThe University of Hong KongHong KongChina Centre for Oncology and immunology Hong Kong Science ParkHong KongChina

B cells are generated in the bone marrow during ontogeny and migrate to peripheral lymphoid organs,where they encounter antigens to elicit humoral immunity.During the past decade,many novel B-cell subsets with distinct phenotypes and functions have been identified,and among these subsets,age-associated B cells(ABCs)were first characterized as a B-cell subset that accumulates with age[1].

关键词： organs lymphoid migrate