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Catalyst-free and Reprocessable Aromatic Polydithiourethanes

Chinese Journal of Polymer Science 2024年第10期42卷 1435-1441,I0007页

作者： Bo Yang Hai-Jun Feng Tian-Tian Ni Xiao-Rui Zhou Tao Xie Ning Zheng State Key Laboratory of Chemical Engineering College of Chemical and Biological EngineeringZhejiang UniversityHangzhou310058China Department of Colorectal Surgery and Oncology Key Laboratory of Cancer Prevention and InterventionMinistry of EducationThe Second Affiliated HospitalZhejiang University School of MedicineHangzhou310009China

The incorporation of dynamic covalent bonds into thermosets facilitates the reprocessing of polymer networks,thereby meeting the sustainable requirements for polymer ***,the mechanical properties of many materials often decline significantly upon reprocessing due to side reactions caused by harsh processing *** this work,we find that the aromatic dithiocarbamate bond can undergo dissociation under mild conditions without the need for a catalyst,enabling the efficient reprocessing of the corresponding *** a consequence,the mechanical properties of the polydithiourethane can be largely preserved after *** discovery of this dynamic chemistry is anticipated to broaden the potential for material design in dynamic covalent polymer networks.

关键词： Reprocessing Polydithiourethane Dynamic covalent bond

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Proapoptotic protein Bim regulates the suppressive function of Treg cells

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Journal of Zhejiang University-Science B(Biomedicine & Biotechnology) 2023年第12期24卷 1180-1184页

作者： Di WU Cancer Institute(Key Laboratory of Cancer Prevention and Intervention China National Ministry of Education)the Second Affiliated Hospita School of MedicineZhejiang UniversityHangzhou 310009China

Regulatory T(Treg)cells are a special immunosuppressive subset of cluster of differentiation 4-positive(CD4^(+))-T lymphocytes and play a pivotal role in the establishment of immune homeostasis in vivo(Zhang et al.,2021).The transcription factor forkhead box protein P3(Foxp3)is the master marker of Treg cells,which is highly expressed in Treg cells and is also essential for their suppressive function(Hori et al.,2003).In addition to Foxp3,other regulators of Treg cells have been discovered(Wu et al.,2017,2022;Wu and Sun,2023a,2023b);however,a deeper understanding of the regulation of these cells is required.

关键词： Foxp3 Treg

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Pan-cancer analysis of DNA epigenetic modifications by hydrophilic interaction liquid chromatography-tandem mass spectrometry

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Chinese Chemical Letters 2023年第7期34卷 214-218页

作者： Yiqiu Hu Xiujuan Hong Zhijun Yuan Jiayi Mu Xiaoxiao Zhang Zhihao Fang Ying Yuan Shu Zheng Cheng Guo Cancer Institute(Key Laboratory of Cancer Prevention and Intervention China National Ministry of Education)The Second Affiliated HospitalZhejiang UniversitySchool of MedicineHangzhou310009China Cancer Center Zhejiang UniversityHangzhou 310058China

Accumulating evidence in recent years indicates that DNA methylation(5-methyl-2-deoxycytidine,5-mdC) and hydroxymethylation(5-hydroxymethyl-2-deoxycytidine, 5-hmd C) have been implicated in various biological processes, and the aberrations of these DNA cytosine modifications is tightly associated with cancer. N6-methyl-2-deoxyadenosine(m~6dA), as a newly discovered epigenetic modification in genome of mammals, has been demonstrated to play vital regulatory roles in tumorigenesis. However, the content information of m~6dA in human tumor tissues is still limited and pan-cancer analysis of these DNA epigenetic modifications is lacked. Herein, we developed a sensitive and robust stable isotopediluted hydrophilic interaction liquid chromatography-tandem mass spectrometry(HILIC-MS/MS) method for accurate quantification of m~6dA, 5-mdC and 5-hmdC in genomic DNA from 82 pairs of human tumor tissues and matched tumor-adjacent normal tissues. The types of tumors included esophagus cancer, lung cancer, breast cancer, liver cancer, pancreatic cancer, gastric cancer, stromal tumor and colorectal *** to the normal tissues, we revealed the level of m6dA was increased in tumor tissues of esophagus cancer, lung cancer and liver cancer, whereas the level of m~6dA was diminished in tumor tissues of pancreatic cancer and gastric cancer;while the contents of 5-mdC and 5-hmdC exhibited significant decrease in tumor tissues of most types of cancer. It is worth noting that we revealed, for the first time,the content of genomic m~6dA in pancreatic cancer, stromal tumor and colorectal cancer. The significant changes of these DNA epigenetic modifications indicate they may serve as indicators of cancers. In addition, this study will benefit for better understanding of the regulatory roles of these DNA epigenetic modifications in cancers.

关键词： HILIC-MS/MS Pan-cancer analysis N~6-methyl-2-deoxyadenosine 5-Methyl-2-deoxycytidine 5-Hydroxymethyl-2-deoxycytidine

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Advances in strategies to improve the immunotherapeutic efficacy of chimeric antigen receptor-T cell therapy for lymphoma

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cancer Biology & Medicine 2025年第04期22卷 301-321页

作者： Tianshu Yu Xianhuo Wang Ou Bai Huilai Zhang Wenbin Qian Department of Hematology the Second Affiliated Hospital Zhejiang University School of Medicine Key Laboratory of Cancer Prevention and Intervention China National Ministry of Education Key Laboratory of Molecular Biology in Medical Sciences the Second Affiliated Hospital Zhejiang University School of Medicine Department of Lymphoma/State Key Laboratory of Druggability Evaluation and Systematic Translational Medicine Tianjin Medical University Cancer Institute & Hospital National Clinical Research Center for Cancer Tianjin's Clinical Research Center for Cancer Key Laboratory of Cancer Prevention and TherapyTianjin the Sino-US Center for Lymphoma and Leukemia Research Department of Hematology the First Hospital of Jilin University

Chimeric antigen receptor-T(CAR-T) cell therapy is a precise immunotherapy for lymphoma. However, its long-term efficacy faces many challenges related to tumor cell heterogeneity, interference from immunosuppressive microenvironments, CAR-T cell exhaustion, and unmanageable adverse events. Diverse modifications have been introduced into conventional CAR-T cells to overcome these obstacles; examples include addition of recognition sites to prevent immune escape, coupling of cytokine domains to enhance killing ability, blocking of immune checkpoint signals to resist tumor microenvironments, and inclusion of suicide systems or safety switches to improve safety and flexibility. With increasing understanding of the importance of metabolism and epigenetics in cancer and cytotherapy, glycolysis, methylation, and acetylation have become crucial CAR-T cell therapeutic targets. Universal and in situ CAR-T cells are also expected to be used in clinical applications, thus providing hope to patients with relapsed/refractory lymphomas.

关键词： Chimeric antigen receptor-T cell cytotherapy epigenetics immunotherapy lymphoma metabolism

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CSCO guidelines for colorectal cancer version 2024:Updates and discussions

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Chinese Journal of cancer Research 2024年第3期36卷 233-239页

作者： Liubo Chen Hanguang Hu Ying Yuan Shanshan Weng Department of Medical Oncology(Key Laboratory of Cancer Prevention and Intervention China National Ministry of EducationKey Laboratory of Molecular Biology in Medical SciencesZhejiang ProvinceChina)the Second Affiliated HospitalZhejiang University School of MedicineHangzhou 310009China Zhejiang Provincial Clinical Research Center for CANCER Hangzhou 310009China Cancer Center Zhejiang UniversityHangzhou 310058China

According to the latest global cancer statistics,colorectal cancer(CRC)is the most common malignancy of the digestive system and the second most lethal among all cancer types(1).In China,CRC is the second most prevalent cancer,following only after lung cancer(2).The first version of the Chinese Society of Clinical Oncology(CSCO)guideline was launched in 2017 and has been updated annually based on the latest findings of clinical research,drug accessibility and expert consensus(3-8).Here,we present the main updates of the 2024 version compared to the 2023 version.

关键词： CSCO colorectal cancer

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Ultratough Yet Dynamic Crystalline Poly(thiourethane)Network Directly from Low Viscosity Precursors

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CCS Chemistry 2024年第3期6卷 682-692页

作者： Haijun Feng Yi Sheng Guancong Chen Binjie Jin Zizheng Fang Bo Yang Xiaorui Zhou Wenxuan Wu Tao Xie Ning Zheng State Key Laboratory of Chemical Engineering College of Chemical and Biological EngineeringZhejiang UniversityHangzhou 310058 Department of Colorectal Surgery and Oncology Key Laboratory of Cancer Prevention and InterventionMinistry of EducationThe Second Affiliated HospitalZhejiang University School of MedicineHangzhou 310027

Thermosets based on direct curing of multifunctional monomers offer processing flexibility that thermoplastics cannot ***,this type of thermoset is typically amorphous since it is difficult to meet the stringent requirement of long-range molecular regularity for ***,we report here a crystallizable poly(thiourethane)thermoset synthesized directly from the curing of low-viscosity liquid precursors that does not employ any *** crystalline nature results in superior toughness,comparable to commercial high-density polyethylene,in sharp contrast to the brittleness of the typical,rigid,glassy thermoset *** that,the network polymer exhibits shape-memory behavior in which the crystalline transition is utilized for temporary shape fixing/recovery whereas the dynamic thiourethane bonds can be activated for bond exchange as a mechanism for complex shape *** with these combined features represent attractive options for demanding engineering applications due to their high performance and multifunctinality.

关键词： thermosets crystalline polymer thiourethane thermadapt

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Graphene as adsorbent for highly efficient extraction of modified nucleosides in urine prior to liquid chromatography-tandem mass spectrometry analysis

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Chinese Chemical Letters 2024年第4期35卷 490-495页

作者： Cheng Guo Xiaoxiao Zhang Xiujuan Hong Yiqiu Hu Lingna Mao Kezhi Jiang Cancer Institute(Key Laboratory of Cancer Prevention and Intervention China National Ministry of Education)The Second Affiliated HospitalZhejiang University School of MedicineHangzhou 310009China Cancer Center Zhejiang UniversityHangzhou 310058China Key Laboratory of Organosilicon Chemistry and Material Technology College of Material Chemistry and Chemical EngineeringHangzhou Normal UniversityHangzhou 311121China Department of General Practice The Second Affiliated HospitalZhejiang University School of MedicineHangzhou 310009China

RNA modifications have been involved in numerous biological processes, and aberrations of these modifications are tightly associated with various diseases including cancer. Herein, we developed graphenebased solid-phase extraction and robust ultra performance liquid chromatography-tandem mass spectrometry(UPLC-MS/MS) combined with stable isotope-dilution for simultaneous enrichment and accurate determination of 17 modified nucleosides in human urine. We found graphene could effectively adsorb various modified nucleosides in human urine samples. With this method, we identified and quantified these modified nucleosides in urine samples collected from lung cancer patients and healthy *** revealed that the levels of 12 modified nucleosides were all diminished in urine from lung cancer patients, compared with healthy controls. It is worth noting that we demonstrated, for the first time, the presence of 5,2-O-dimethyluridine(m~5U_m) in human urine. Together, we established a robust analytical method for simultaneous determinations of 17 modified nucleosides in human urine, and our results revealed a close correlation between the concentrations of urinary modified nucleosides and the occurrence of lung cancer, implying the potential applications of these modified nucleosides as noninvasive biomarkers for the early detection of lung cancer. Moreover, this study will stimulate future investigations on the regulatory roles of RNA modifications in the initiation and progression of lung cancer.

关键词： Mass spectrometry RNA modification Modified nucleosides Graphene Biomarker Urine

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Insights into treatment for hepatocellular carcinoma with tumor thrombus in the inferior vena cava or right atrium

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Hepatobiliary Surgery and Nutrition 2024年第1期13卷 168-171页

作者： Jia Yang Yongjie Shui Lihong Liu Genhua Yu Qichun Wei Department of Radiation Oncology The Second Affiliated HospitalZhejiang University School of MedicineHangzhouChina The Key Laboratory of Cancer Prevention and Intervention China National Ministry of EducationZhejiang University School of MedicineHangzhouChina

Hepatocellular carcinoma(HCC),one of the most common liver cancers,often has a poor prognosis when it involves macrovascular *** emergencies including pulmonary embolism,heart failure,and even sudden death could happen when it develops a tumor thrombus(TT)in the inferior vena cava(IVC)or right atrium(RA),indicating an exceptionally grim prognosis(1).Although systemic therapy is the only standard treatment recommended by guidelines(2),other treatment modalities are explored including surgery,radiotherapy,*** some ***,as the only potential curative treatment,has been explored in several selected cases.A case of long-term survival of 15 years and cancer-free survival of 9 years was reported by surgical resection with a heart-first approach under cardiopulmonary bypass(CPB)(3),suggesting that aggressive surgery together with multidisciplinary treatments might achieve long ***,due to the aggressiveness and challenge of surgical resection-massive resection area,potential significant blood loss,and bypass needed,surgical resection is applied in very limited ***,safety,efficacy,and long-term survival benefits for these patients are poorly investigated.

关键词： Hepatocellular carcinoma(HCC) inferior vena cava(IVC) right atrium(RA) tumor thrombus(TT)

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Neoadjuvant PD-1 blockade: a promising nonoperative strategy for mismatch repair–deficient, locally advanced rectal cancer

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Signal Transduction and Targeted Therapy 2022年第11期7卷 3989-3991页

作者： Mi Mi Chenyang Ye Ying Yuan Department of Medical Oncology Key Laboratory of Cancer Prevention and Interventionthe Second Affiliated Hospital of Zhejiang University School of Medicine310009HangzhouZhejiangChina Cancer Center Zhejiang University310058HangzhouZhejiangChina

In a prospective phase 2 study recently published in The New England Journal of Medicine,Cercek et *** the efficacy of the programmed death 1(PD-1)inhibitor dostarlimab in patients with mismatch repair–deficient(dMMR),locally advanced rectal cancer(LARC).The work aimed to present preliminary evidence for the revolutionary therapeutic transition from neoadjuvant chemotherapy/radiotherapy followed by surgery to immunotherapy followed by nonoperative management in this subgroup of patients.

关键词： operative al. rectal

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Neddylation Regulation of Immune Responses

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Research 2024年第3期2023卷 545-559页

作者： Hongmei Mao Xin Lin Yi Sun 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 Institute for Immunology School of MedicineTsinghua UniversityBeijing 100084China Changping Laboratory Beijing 102206China Cancer Center of Zhejiang University Hangzhou 310029China Zhejiang Provincial Clinical Research Center for Cancer HangzhouZhejiang ProvinceChina Key Laboratory of Molecular Biology in Medical Sciences HangzhouZhejiang ProvinceChina Research Center for Life Science and Human Health Binjiang Institute of Zhejiang UniversityHangzhou 310053China.

Neddylation plays a vital role in post-translational modification, intricately shaping the regulation of diverse biological processes, including those related to cellular immune responses. In fact, neddylation exerts control over both innate and adaptive immune systems via various mechanisms. Specifically, neddylation influences the function and survival of innate immune cells, activation of pattern recognition receptors and GMP-AMP synthase–stimulator of interferon genes pathways, as well as the release of various cytokines in innate immune reactions. Moreover, neddylation also governs the function and survival of antigen-presenting cells, which are crucial for initiating adaptive immune reactions. In addition, neddylation regulates T cell activation, proliferation, differentiation, survival, and their effector functions, thereby ensuring an appropriate adaptive immune response. In this review, we summarize the most recent findings in these aspects and delve into the connection between dysregulated neddylation events and immunological disorders, especially inflammatory diseases. Lastly, we propose future directions and potential treatments for these diseases by targeting neddylation.

关键词： activation thereby initiating

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