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Plant-derived nanovesicles as an emerging platform for cancer therapy

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Acta Pharmaceutica Sinica B 2024年第1期14卷 133-154页

作者： Hanzhe Liu Guo-Feng Luo Zhengjun Shang The state Key Laboratory Breeding Base of Basic Science of Stomatology(Hubei-MOST)&Key Laboratory of Oral Biomedicine Ministry of Education School and Hospital of StomatologyWuhan UniversityWuhan 430079China

Plant-derived nanovesicles(PDNVs)derived from natural green products have emerged as an attractive nanoplatform in biomedical *** are usually characterized by unique structural and biological functions,such as the bioactive lipids/proteins/nucleic acids as therapeutics and targeting groups,immune-modulation,and long-term *** the rapid development of nanotechnology,materials,and synthetic chemistry,PDNVs can be engineered with multiple functions for efficient drug delivery and specific killing of diseased cells,which represent an innovative biomaterial with high biocompatibility for fighting against *** this review,we provide an overview of the state-of-theart studies concerning the development of PDNVs for cancer *** original sources,methods for obtaining PDNVs,composition and structure are introduced *** an emphasis on the featured application,the inherent anticancer properties of PDNVs as well as the strategies in constructing multifunctional PDNVs-based nanomaterials will be discussed in ***,some scientific issues and technical challenges of PDNVs as promising options in improving anticancer therapy will be discussed,which are expected to promote the further development of PDNVs in clinical translation.

关键词： Naturally occurring nanovesicles Plant Nanotechnology Drug delivery Cancer therapy

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Expanding the horizons of targeted protein degradation:A non-small molecule perspective

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Acta Pharmaceutica Sinica B 2024年第6期14卷 2402-2427页

作者： Xiaowei Huang Fengbo Wu Jing Ye Lian Wang Xiaoyun Wang Xiang Li Gu He Department of Pharmacy and Department of Dermatology&Venerology West China HospitalSichuan UniversityChengdu 610041China Department of Urology West China HospitalSichuan UniversityChengdu 610041China Laboratory of Dermatology Clinical Institute of Inflammation and ImmunologyFrontiers Science Center for Disease-Related Molecular Network and State Key Laboratory of BiotherapyWest China HospitalSichuan UniversityChengdu 610041China

Targeted protein degradation(TPD)represented by proteolysis targeting chimeras(PROTACs)marks a significant stride in drug discovery.A plethora of innovative technologies inspired by PROTAC have not only revolutionized the landscape of TPD but have the potential to unlock functionalities beyond ***-small-molecule-based approaches play an irreplaceable role in this field.A wide variety of agents spanning a broad chemical spectrum,including peptides,nucleic acids,antibodies,and even vaccines,which not only prove instrumental in overcoming the constraints of conventional small molecule entities but also provided rapidly renewing *** we summarize the burgeoning non-small molecule technological platforms inspired by PROTACs,including three major trajectories,to provide insights for the design strategies based on novel paradigms.

关键词： Targeted protein degradation Proteolysis targeting chimera Endocytosis Autophagy Proximity-inducing modality Post-translational modification

Deamidation enables pathogenic SMAD6 variants to activate the BMP signaling pathway

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Science China Life Sciences 2024年第9期67卷 1915-1927页

作者： Ling Li Lei Lu Ziqi Xiao Jingyi Lv Hefeng Huang Bo Wu Tongjin Zhao Chengtao Li Weimin Wang Hongyan Wang Obstetrics and Gynecology hospital State Key Laboratory of Genetic Engineering Institute of Reproduction and Development and Children's Hospital Fudan University Shanghai Key Laboratory of Metabolic Remodeling and Health Institute of Metabolism and Integrative Biology Fudan University Prenatal Diagnosis Center of Shenzhen Maternity & Child Healthcare hospital Shanghai Medical College Fudan University Department of Pharmacy College of Life Sciences China Jiliang University

The BMP signaling pathway plays a crucial role in regulating early embryonic development and tissue homeostasis. SMAD6 encodes a negative regulator of BMP, and rare variants of SMAD6 are recurrently found in individuals with birth defects. However, we observed that a subset of rare pathogenic variants of SMAD6 consistently exhibited positive regulatory effects instead of the initial negative effects on the BMP signaling pathway. We sought to determine whether these SMAD6 variants have common pathogenic mechanisms. Here, we showed that pathogenic SMAD6 variants accompanying this functional reversal exhibit similar increases in deamidation. Mechanistically, increased deamidation of SMAD6 variants promotes the accumulation of the BMP receptor BMPR1A and the formation of new complexes, both of which lead to BMP signaling pathway activation. Specifically, two residues, N262 and N404, in SMAD6 were identified as the crucial sites of deamidation, which was catalyzed primarily by glutamine-fructose-6-phosphate transaminase 2(GFPT2). Additionally, treatment of cells harboring SMAD6 variants with a deamidase inhibitor restored the inhibitory effect of SMAD6 on the BMP signaling pathway. Conversely,when wild-type SMAD6 was manually simulated to mimic the deamidated state, the reversed function of activating BMP signaling was reproduced. Taken together, these findings show that deamidation of SMAD6 plays a crucial role in the functional reversal of BMP signaling activity, which can be induced by a subset of various SMAD6 variants. Our study reveals a common pathogenic mechanism shared by these variants and provides a potential strategy for preventing birth defects through deamidation regulation, which might prevent the off-target effects of gene editing.

关键词： SMAD6 deamidation BMP signaling pathway GFPT2

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Mitochondrial diseases and mtDNA editing

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Genes & Diseases 2024年第3期11卷 303-310页

作者： Min Song Lingqun Ye Yongjin Yan Xuechun Li Xinglong Han Shijun Hu Miao Yu Department of Cardiovascular Surgery of the First Affiliated hospital&Institute for Cardiovascular Science Collaborative Innovation Center of HematologyState Key Laboratory of Radiation Medicine and ProtectionSuzhou Medical CollegeSoochow UniversitySuzhouJiangsu 215000China Hai'an People's hospital NantongJiangsu 226600China

Mitochondrial diseases are a heterogeneous group of inherited disorders character-ized by mitochondrial dysfunction,and these diseases are often severe or even ***-chondrial diseases are often caused by mitochondrial DNA ***,there is no curative treatment for patients with pathogenic mitochondrial DNA *** the rapid development of traditional gene editing technologies,such as zinc finger nucleases and tran-scription activator-like effector nucleases methods,there has been a search for a mitochon-drial gene editing technology that can edit mutated mitochondrial DNA;however,there are still some problems hindering the application of these *** discovery of the DddA-derived cytosine base editor has provided hope for mitochondrial gene *** this paper,we will review the progress in the research on several mitochondrial gene editing technologies with the hope that this review will be useful for further research on mitochondrial gene editing technologies to optimize the treatment of mitochondrial diseases in the future.

关键词： Gene editing Mitochondrialdisease MitochondrialDNA mutation Transcription activator-like effectornucleases Zinc finger nucleases

Effect of pediatric Tuina on children's recurrent acute respiratory tract infections: a retrospective cohort study in Southern China

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Journal of Traditional Chinese Medicine 2024年第3期44卷 586-594页

作者： YIN Lingjia ST?LSBY LUNDBORG Cecilia WU Darong YANG Jinghua ALVESSON Helle M?lsted CAI Jianxiong LU Taoying XIE Qianwen MARRONE Gaetano Department of Global Public Health Karolinska Institutet state Key Laboratory of Dampness Syndrome of Chinese Medicine the Second Affiliated Hospital of Guangzhou University of Chinese Medicine Outcome Assessment Research Team in Chinese Medicine the Second Affiliated Hospital of Guangzhou University of Chinese Medicine Health Construction Administration Centre Guangdong Provincial Hospital of Chinese Medicine Guangdong Provincial Key Laboratory of Clinical Research on Traditional Chinese Medicine Syndrome the Second Affiliated Hospital of Guangzhou University of Chinese Medicine Department of Pediatrics the Second Affiliated Hospital of Guangzhou University of Chinese Medicine

OBJECTIVE: To determine the effectiveness of pediatric Tuina(PT) in preventing recurrent acute respiratory tract infections(ARTIs) in children. METHODS: This is a retrospective cohort study based on the electronic medical records of children with recurrent ARTIs in 2016. Children were divided into a PT group or a non-PT group, according to whether they had received PT or not in 2016. The primary outcome was the number of ARTI episodes in 2017 and 2018. The secondary outcomes were the number of ARTIs leading to outpatient department visits and outpatient antibiotic prescriptions due to ARTIs in the same time period. Negative binomial regressions were used to detect the association between PT and the outcomes. RESULTS: A total of 2303 children were included in the analysis, including 94 in the PT group and 2209 in the non-PT group. Children who received PT six or more times in 2016 had fewer episodes of ARTIs in 2017 [incidence rate ratio(IRR): 0.59, 95% confidence interval(CI)(0.42-0.84)] and 2018 [IRR: 0.58, 95% CI(0.36-0.94)] and fewer outpatient department visits due to ARTIs in 2017 [IRR: 0.56, 95% CI(0.38-0.83)] than children who had not received PT in 2016. There was no significant difference in the number of outpatient antibiotic prescriptions between the two groups. CONCLUSIONS: Receiving PT six or more times within one year is associated with a decrease in recurrent ARTIs in children in the following two years. Randomized controlled trials are needed for effect evaluation prior to establishing PT as a method for preventing recurrent ARTIs among children.

关键词： child massage pediatric Tuina respiratory tract infections

Efficacy and safety of PD-1 blockade plus long-course chemoradiotherapy in locally advanced rectal cancer(NECTAR):a multi-center phase 2 study

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Signal Transduction and Targeted Therapy 2024年第4期9卷 1721-1729页

作者： Zhengyang Yang Jiale Gao Jianyong Zheng Jiagang Han Ang Li Gang Liu Yi Sun Jie Zhang Guangyong Chen Rui Xu Xiao Zhang Yishan Liu Zhigang Bai Wei Deng Wei He Hongwei Yao Zhongtao Zhang Department of General Surgery Beijing Friendship HospitalCapital Medical UniversityState Key Lab of Digestive HealthNational Clinical Research Center for Digestive DiseasesBeijingChina Department of Gastrointestinal Surgery The First Affiliated Hospital of Air Force Medical UniversityXi'anChina Department of General Surgery Beijing Chaoyang HospitalCapital Medical UniversityBeijingChina Department of General Surgery Beijing Xuanwu HospitalCapital Medical UniversityBeijingChina Department of General Surgery Tianjin Medical University General HospitalTianjinChina Department of Anorectal Tianjin People's HospitalTianjinChina Department of Radiology Beijing Friendship hospital Capital Medical UniversityBeijingChina Department of Pathology Beijing Friendship HospitalCapital Medical UniversityBeijingChina Department of Thoracic Surgery/Institute of Thoracic Oncology West China HospitalSichuan UniversityChengduChina

Adding PD-1 blockade in the neoadjuvant regimens for locally advanced rectal cancer(LARC)patients with microsatellite stable(MsS)/mismatch repair-proficient(pMMR)tumors is an attractive,but debatable *** phase 2,multicenter,prospective,single-arm study enrolled patients from 6 centers from June 2021 to November *** advanced rectal cancer(LARC,cT_(3-4a)N_(0)M_(0) and cT_(1-4a)N_(1-2)M_(0))patients aged≥18 years with the distance from distal border of tumor to anal verge≤10 cm(identified by Magnetic Resonance Imaging)were qualifed for *** patients received long-course radiotherapy(50 Gy/25 fractions,2 Gy/fraction,5 days/week)and three 21-day cycles capecitabine(850-1000 mg/m2,bid,po,day1-14)and three 21-day cycles tislelizumab(200 mg,***,day8)as *** mesorectal excision(TME)was 6-12 weeks after the end of radiotherapy to achieve radical resection.A total of 50 patients were enrolled in this *** pathological complete response rate was 40.0%[20/50,95%confidence interval(CI):27.61-53.82%],while 15(30.0%,95%CI:19.1-43.75%),9(18.0%,95%CI:9.77-30.8%),2(4.0%,95%CI:1.10-13.46%)patients respectively achieved grade 1,2,and 3 tumor ***-related adverse events(TRAEs)occurred in 28(56.0%)LARC patients,including 26(52.0%)with grade I-II and 2(4.0%)with grade II(1 with grade 3 immune-related colitis and 1 with grade 3 rash).PD-1 blockade plus long-course chemoradiotherapy(CRT)showed promising therapeutic effects according to pathological complete response rate and is well-tolerated in LARC patients.A larger randomized controlled study is desired to further validate the above findings.

关键词： rectal cancer phase

Direct detection of C9orf72 hexanucleotide repeat expansions by nanopore biosensor

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Chinese Chemical Letters 2024年第5期35卷 351-354页

作者： Xinqiong Li Guocheng Rao Xi Peng Chan Yang Yanjing Zhang Yan Tian Xianghui Fu Jia Geng state Key Laboratory of Biotherapy and Cancer Center West China HospitalSichuan University and Collaborative Innovation Center of BiotherapyChengdu 610041China Division of Endocrinology and Metabolism West China School of Medicine/West China HospitalSichuan UniversityChengdu 610041China Department of Endocrinology and Metabolism Affiliated Hospital of North Sichuan Medical CollegeNorth Sichuan Medical CollegeNanchong 637000China Division of Endocrinology and Metabolism National Clinical Research Center for GeriatricsState Key Laboratory of Biotherapy and Cancer CenterWest China HospitalSichuan University and Collaborative Innovation Center of BiotherapyChengdu 610041China Department of Laboratory Medicine State Key Laboratory of BiotherapyMed-X Center for ManufacturingWest China HospitalSichuan University and Collaborative Innovation CenterChengdu 610041China Tianfu Jincheng Laboratory City of Future MedicineChengdu 641400China

Diagnostic C9orf72 hexanucleotide repeat expansions(C9-HRE)is essential for the early and accurate diagnosis of amyotrophic lateral sclerosis(ALS)and will provide support for the prognosis and gene therapy of *** the present study,by combining catalytic hairpin assembly(CHA)with Mycobacterium smegmatis porin A(MspA)nanopore,a new nanopore-based strategy for the detection of C9-HRE was *** than 30 repeats of C9-HRE could be detected via this method,and the results have the potential to help distinguish between patients and healthy ***,the method demonstrated its great specificity for C9-HRE by identifying other repeat *** the high selectivity,this approach had been successfully used to detect C9-HRE in cell and blood samples with high *** detection strategy is user-friendly and has a strong anti-interference ability,thus providing a powerful tool for clinical diagnosis.

关键词： MspA nanopore C9orf72 HRE Detection Biosensor Catalytic hairpin assembly

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UniBind:a novel artificial intelligence-based prediction model for SARS-CoV-2 infectivity and variant evolution

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Signal Transduction and Targeted Therapy 2024年第1期9卷 14-15页

作者： Qihong Yan Jincun Zhao state Key Laboratory of Respiratory Disease National Clinical Research Center for Respiratory DiseaseGuangzhou Institute of Respiratory Healththe First Affiliated Hospital of Guangzhou Medical UniversityGuangzhouChina

In a recent study published in Nature Medicine,Wang et *** an excellent framework called UniBind based on artificial intelligence(AI),which enables accurately predicting infectivity of SARS-CoV-2 variants and evolutionary trends of future viral variants.1 This computational method holds the possibility to not only serve as a valuable early-warning tool for monitoring potential pathogenic SARS-CoV-2 variants but also facilitate fundamental research on protein-protein interactions(PPIs).

关键词： artificial Bind prediction

Prognostic significance of SOX2 for chemotherapeutic patients with oral squamous cell carcinoma

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Journal of Pharmaceutical Analysis 2024年第4期14卷 619-621页

作者： Xuefeng Zhang Hao Xu Tong Zhou Xiaodong Feng Qianming Chen state Key Laboratory of Oral Diseases National Center of StomatologyNational Clinical Research Center for Oral DiseasesWest China Hospital of StomatologySichuan UniversityChengdu610041China

Oral squamous cell carcinoma(OSCC)is the most common oral cancers worldwide,accounting for over 90%of all oral malignancies[1].Despite encouraging improvements in therapeutic approaches,including surgical resection,chemotherapy,and radiotherapy,the five-year overall survival rate of OSCC has not been improved significantly over the past decades,mainly due to the high ratio of tumor recurrence and metastasis.

关键词： SOX2 therapeutic squamous