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Hippo(YAP)-autophagy axis protects against hepatic ischemia-reperfusion injury through JNK signaling

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Chinese Medical Journal 2024年第6期137卷 657-668页

作者： Shuguang Zhu Xiaowen Wang Haoqi Chen Wenfeng Zhu Xuejiao Li Ruiwen Cui Xiaomeng Yi Xiaolong Chen Hua Li Genshu Wang Department of Hepatic Surgery Liver TransplantationThe Third Affiliated Hospital of Sun Yat-sen UniversityGuangzhouGuangdong 510630China Department of Hepatology lab The Third Affiliated Hospital of Sun Yat-sen UniversityGuangzhouGuangdong 510630China Department of General Surgery The Third Affiliated Hospital of Sun Yat-sen UniversityGuangzhouGuangdong 510630China Department of Organ Transplantation The Third Affiliated Hospital of Sun Yat-sen UniversityGuangzhouGuangdong 510630China Department of Renal Transplantation Guangdong Provincial Hospital of Chinese MedicineGuangzhouGuangdong 510630China Department of Surgical Intensive Care Unit The Third Affiliated Hospital of Sun Yat-sen UniversityGuangzhouGuangdong 510630China Department of Hepatic Surgery Liver TransplantationGuangdong Provincial Hospital of Chinese MedicineGuangzhouGuangdong 510630China

Background:Hepatic ischemia-reperfusion injury(HIRI)remains a common complication during liver transplantation(LT)in *** a key downstream effector of the Hippo pathway,Yes-associated protein(YAP)has been reported to be involved in various physiological and pathological ***,it remains elusive whether and how YAP may control autophagy activation during ***:Human liver tissues from patients who had undergone LT were obtained to evaluate the correlation between YAP and autophagy *** an in vitro hepatocyte cell line and in vivo liver-specific YAP knockdown mice were used to establish the hepatic ischemia-reperfusion models to determine the role of YAP in the activation of autophagy and the mechanism of ***:Autophagy was activated in the post-perfusion liver grafts during LT in patients,and the expression of YAP positively correlated with the autophagic level of ***-specific knockdown of YAP inhibited hepatocytes autophagy upon hypoxia-reoxygenation and HIRI(P<0.05).YAP deficiency aggravated HIRI by promoting the apoptosis of hepatocytes both in the in vitro and in vivo models(P<0.05).Attenuated HIRI by overexpression of YAP was diminished after the inhibition of autophagy with *** addition,inhibiting autophagy activation by YAP knockdown exacerbated mitochondrial damage through increasing reactive oxygen species(P<0.05).Moreover,the regulation of autophagy by YAP during HIRI was mediated by AP1(c-Jun)N-terminal kinase(JNK)signaling through binding to the transcriptional enhanced associate domain(TEAD).Conclusions:YAP protects against HIRI by inducing autophagy via JNK signaling that suppresses the apoptosis of *** Hippo(YAP)-JNK-autophagy axis may provide a novel strategy for the prevention and treatment of HIRI.

关键词： YAP-signaling proteins Autophagy c-Jun N-terminal kinase Ischemia-reperfusion injury Liver transplantation

RNA ac^(4)C modification in cancer biology:from regulatory mechanisms to clinical applications

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Science China(Life Sciences) 2024年第4期67卷 832-835页

作者： Lijun Tao Yunqing Lu Zhuojia Chen Lichen Ge Junming He Jianxin Peng Hongsheng Wang School of Pharmaceutical Sciences Sun Yat-sen UniversityGuangzhou 510006China sun yat-sen university Cancer Center State Key Laboratory of Oncology in South ChinaCollaborative Innovation Center for Cancer MedicineGuangzhou 510060China Department of Hepatobiliary Surgery Guangdong Province Traditional Chinese Medical HospitalGuangzhou 510120China

RNA modifications are increasingly recognized for their significance in diverse physiological and pathological processes,with over 170 types of chemical modifications having been discovered since *** these modifications,N4-acetylcytidine(ac^(4)C)is the first acetylated modification identified on eukaryotic RNAs,previously reported in transfer RNA(t RNA)and ribosomal RNA(rRNA)。

关键词： clinical (4) modification

Design and discovery of a highly potent ultralong-acting GLP-1 and glucagon co-agonist for attenuating renal fibrosis

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Acta Pharmaceutica Sinica B 2024年第3期14卷 1283-1301页

作者： Qian Zhao Jiale Dong Han Liu Hui Chen Huan Yu Shuyin Ye Shuangjin Yu Yu Li Longhui Qiu Nazi Song Hongjiao Xu Qi Liu Zhiteng Luo Yuyi Li Rui Wang Guodong Chen Xianxing Jiang School of Pharmaceutical Sciences Guangdong Provincial Key Laboratory of Chiral Molecule and Drug DiscoverySun Yat-sen UniversityGuangzhou 510006China Organ Transplant Center the First Affiliated HospitalSun Yat-sen UniversityGuangzhou 510006China Zhongshan School of Medicine Sun Yat-sen UniversityGuangzhou 510006China Shenzhen Turier Biotech.Co. Ltd.Shenzhen 518118China School of Life Sciences Key Laboratory of Preclinical Study for New Drugs of Gansu ProvinceSchool of Basic Medical Sciences&Research Unit of Peptide ScienceChinese Academy of Medical SciencesLanzhou UniversityLanzhou 730000China

The role of co-agonists of glucagon-like peptide-1 receptor(GLP-1R)and glucagon receptor(GCGR)in chronic kidney disease(CKD)remains *** we found that GLP-1R and GCGR expression levels were lower in the kidneys of mice with CKD compared to healthy mice and were correlated with disease ***,GLP-1R or GCGR knockdown aggravated the progression of kidney injury in both diabetic db/db mice and non-diabetic mice undergoing unilateral ureteral obstruction(UUO).Based on the importance of GLP-1R and GCGR in CKD,we reported a novel monomeric peptide,1907-B,with dual-agonism on both GLP-1R and *** data confirmed that 1907-B had a longer half-life than long-acting semaglutide in rats or cynomolgus monkeys(~2-3 fold)and exhibited better therapeutic contribution to CKD than best-in-class monoagonists,semaglutide,or glucagon,in db/db mice and UUO *** lock-of-function models,including selective pharmacological activation and genetic knockdown,confirmed that 1907-B’s effects on ameliorating diabetic nephropathy in db/db mice,as well as inhibiting kidney fibrosis in UUO mice,were mediated through GLP-1 and glucagon *** findings highlight that 1907-B,a novel GLP-1R and GCGR co-agonist,exerts multifactorial improvement in kidney injuries and is an effective and promising therapeutic option for CKD treatment.

关键词： GLP-1 receptor Glucagon receptor Chronic kidney disease Diabetic nephropathy Kidney fibrosis Dual-agonism

Knowledge-embedded spatio-temporal analysis for euploidy embryos identification in couples with chromosomal rearrangements

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Chinese Medical Journal 2024年第6期137卷 694-703页

作者： Fangying Chen Xiang Xie Du Cai Pengxiang Yan Chenhui Ding Yangxing Wen Yanwen Xu Feng Gao Canquan Zhou Guanbin Li Qingyun Mai Reproductive Medicine Center The First Affiliated Hospital of Sun Yat-sen UniversityGuangzhouGuangdong 510080China Guangdong Provincial Key Laboratory of Reproductive Medicine GuangzhouGuangdong 510080China School of Computer Science and Engineering Sun Yat-sen UniversityGuangzhouGuangdong 510006China Department of General Surgery(Colorectal Surgery) The Sixth Affiliated Hospital of Sun Yat-sen UniversityGuangzhouGuangdong 510655China Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases The Sixth Affiliated HospitalSun Yat-sen UniversityGuangzhouGuangdong 510655China Biomedical Innovation Center The Sixth Affiliated HospitalSun Yat-sen UniversityGuangzhouGuangdong 510655China Shanghai Artificial Intelligence Laboratory Shanghai 200232China

Background:The goal of the assisted reproductive treatment is to transfer one euploid blastocyst and to help infertile women giving birth one healthy *** algorithms have been used to assess the ploidy status of embryos derived from couples with normal chromosome,who subjected to preimplantation genetic testing for aneuploidy(PGT-A)***,it is currently unknown whether artificial intelligence model can be used to assess the euploidy status of blastocyst derived from populations with chromosomal ***:From February 2020 to May 2021,we collected the whole raw time-lapse videos at multiple focal planes from in vitro cultured embryos,the clinical information of couples,and the comprehensive chromosome screening results of those blastocysts that had received PGT ***,we developed a novel deep learning model called the Attentive Multi-Focus Selection Network(AMSNet)to analyze time-lapse videos in real time and predict blastocyst *** upon AMSNet,we integrated additional clinically predictive variables and created a second deep learning model,the Attentive Multi-Focus Video and Clinical Information Fusion Network(AMCFNet),to assess the euploidy status of *** efficacy of the AMCFNet was further tested in embryos with parental chromosomal *** receiver operating characteristic curve(ROC)was used to evaluate the superiority of the ***:A total of 4112 embryos with complete time-lapse videos were enrolled for the blastocyst formation prediction task,and 1422 qualified blastocysts received PGT-A(n=589)or PGT for chromosomal structural rearrangement(PGT-SR,n=833)were enrolled for the euploidy assessment task in this *** AMSNet model using seven focal raw time-lapse videos has the best real-time *** real-time accuracy for AMSNet to predict blastocyst formation reached above 70%on the day 2 of embryo culture,and then increased to 80%on the day 4 of embryo ***

关键词： Euploidy status Embryo Time-lapse imaging Deep learning Spatio-temporal analysis Preimplantation genetic testing for chromosomal structural rearrangement

P7C3-A20 treats traumatic brain injury in rats by inhibiting excessive autophagy and apoptosis

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Neural Regeneration Research 2024年第5期19卷 1078-1083页

作者： Zhiqing Yang Zhenchao Wang Xiaoqi Deng Lingxin Zhu Zhaomeng Song Changyu Cao Xinran Li School of Life Science and Engineering Foshan UniversityFoshanGuangdong ProvinceChina foshan university Veterinary Teaching hospital FoshanGuangdong ProvinceChina

Traumatic brain injury is a severe health problem leading to autophagy and apoptosis in the brain.3,6-Dibromo-beta-fluoro-N-(3-methoxyphenyl)-9H-carbazole-9-propanamine(P7C3-A20)can be neuroprotective in various diseases,including ischemic stroke and neurodegenerative ***,whether P7C3-A20 has a therapeutic effect on traumatic brain injury and its possible molecular mechanisms are ***,in the present study,we investigated the therapeutic effects of P7C3-A20 on traumatic brain injury and explored the putative underlying molecular *** established a traumatic brain injury rat model using a modified weight drop method.P7C3-A20 or vehicle was injected intraperitoneally after traumatic brain *** neurological deficits were found in rats after traumatic brain injury,with deterioration in balance,walking function,and learning ***,hematoxylin and eosin staining showed significant neuronal cell damage,while terminal deoxynucleotidyl transferase mediated dUTP nick end labeling staining indicated a high rate of *** presence of autolysosomes was observed using transmission electron microscope.P7C3-A20 treatment reversed these pathological *** blotting showed that P7C3-A20 treatment reduced microtubule-associated protein 1 light chain 3-Ⅱ(LC3-Ⅱ)autophagy protein,apoptosis-related proteins(namely,Bcl-2/adenovirus E1B 19-kDa-interacting protein 3[BNIP3],and Bcl-2 associated x protein[Bax]),and elevated ubiquitin-binding protein p62(p62)autophagy protein ***,P7C3-A20 can treat traumatic brain injury in rats by inhibiting excessive autophagy and apoptosis.

关键词： apoptosis autophagy cortex hippocampus motor function P7C3-A20 traumatic brain injury

Inhaled nitric oxide as a salvage therapy for refractory hypoxemia in the post-transplantation period of hepatopulmonary syndrome:An explorative report of three cases

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Liver Research 2024年第3期8卷 188-192页

作者： Haijin Lyu Xiaomeng Yi Yunshan Zou Pinglan Lu Lijuan Li Jianrong Liu senbiao Chen Xuxia Wei Yang Yang Huimin Yi Surgical Intensive Care Unit The Third Affiliated Hospital of Sun Yat-sen UniversityGuangzhouGuangdongChina Guangdong Provincial Key Laboratory of Liver Disease Research GuangzhouGuangdongChina Department of Hepatic Surgery and Liver Transplantation Center The Third Affiliated Hospital of Sun Yat-sen UniversityGuangzhouGuangdongChina

Liver transplantation(LT)is the only effective treatment for hepatopulmonary syndrome(HPS).Moreover,perioperative refractory hypoxemia(pRH)is a prevalent life-threatening condition and has extremely limited treatment ***,we report three patients with HPS who experienced pRH after LT and were consecutively treated with different salvage therapies,ephedrine inhalation,intravenous use of methylene blue with nitric oxide(NO)inhalation,and NO inhalation *** results showed that unresolved severe hypoxia may induce fatal morbidity such as early biliary leakage and acute kidney *** initiation of NO inhalation,rather than ephedrine,can significantly improve oxygenation in patients with pRH and may help prevent hypoxia-related ***,based on the response to these exploratory salvage treatments,we further demonstrate the unique ventilation-perfusion mismatch pathophysiology in specific lung regions during pRH in *** propose that early inhalation of NO is an important treatment option to rescue severe hypoxia in patients with HPS during the perioperative period of LT.

关键词： Hepatopulmonary syndrome Liver transplantation Hypoxia Nitric oxide(NO) Vasodilators Ventilation-perfusion mismatch

Effect of flurbiprofen combined with prednisolone on interleukin-6 in elderly surgery patients

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Pharmacology & Pharmacy 2024年第2期15卷 15-26页

作者： Jiaxin Lin Hui Yang Shaofen Chen Jiao Xu Department of Anesthesiology The Eighth Affiliated Hospital Sun Yat-sen University Shenzhen China

Objective: To determine the effect of flurbiprofen combined with prednisolone on interleukin-6 in elderly surgery patients. Methods: In this double-blind randomized controlled study, patients aged 65 to 80 who were undergoing spinal fusion surgery for disc herniation were administered flurbiprofen 100 mg (P group, flurbiprofen group), prednisolone 0.6 mg/kg (D group, prednisolone group), prednisolone 0.6 mg/kg plus flurbiprofen 100 mg (P + D group, flurbiprofen + prednisolone group) or normal saline (S group, saline group) 15 minutes before the induction of anesthesia. Plasma samples were collected before surgery (T0) and on day 1 (T1), day 2 (T2) and day 3 (T3) following surgery. At the same time, systemic inflammatory response syndrome (SIRS) was assessed by SIRS criteria. The levels of interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α) and C-reactive protein (CRP) for collected samples were measured. Results: Other groups had significantly lower levels of IL-6, CRP and occurrence of SIRS than S group (p sented on T1 (p 0.05). The levels of CRP within three days were significantly different but did not show peak levels (p > 0.05). Conclusion: Compared to prednisolone or flurbiprofen, combining flurbiprofen with prednisolone in elderly surgery patients led to an increased suppression of IL-6.

关键词： SIRS Systemic Inflammatory Response Syndrome IL-6 Interleukin-6 CRP C-Reactive Protein

Effect of artificial natural light on the development of myopia among primary school-age children in China:a three-year longitudinal study

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International Journal of Ophthalmology(English edition) 2024年第5期17卷 924-931页

作者： Hui-Min Cai Meng-Yan Li Yi Cao Yu-Lin Wu Ming Liang Yu-Shi Chen Bi-Kun Xian Yu-Juan Huang Xiang-Bin Kong Department of Ophthalmology the Second People’s Hospital of FoshanAffiliated Foshan Hospital of Southern Medical UniversityFoshan 528000Guangdong ProvinceChina Guangdong Medical university Zhanjiang 524023Guangdong ProvinceChina Guangdong Cosio Lighting Corporation Foshan 528000Guangdong ProvinceChina

AIM:To assess the efficacy of artificial natural light in preventing incident myopia in primary school-age ***:This is a prospective,randomized control,intervention study.A total of 1840 students from 39 classes in 4 primary schools in foshan participated in this *** whole randomization method was adopted to include classes as a group according to 1:1 randomized *** in the control group were illuminated by usual light,and classrooms in the intervention group were illuminated by artificial natural *** students received uncorrected visual acuity and best-corrected visual acuity measurement,non-cycloplegic autorefraction,ocular biometric examination,slit lamp and strabismus ***-year follow-up,the students underwent same *** was defined as spherical equivalent refraction≤-0.50 D and uncorrected visual acuity<20/***:There were 894 students in the control group and 946 students in the intervention group with a mean±SD age of 7.50±*** three-year cumulative incidence rate of myopia was 26.4%(207 incident cases among 784 eligible participants at baseline)in the control group and 21.2%(164 incident cases among 774 eligible participants at baseline)in the intervention group[difference of 5.2%(95%CI,3.7%to 10.1%);P=0.035].There was also a significant difference in the three-year change in spherical equivalent refraction for the control group(-0.81 D)compared with the intervention group[-0.63 D;difference of 0.18 D(95%CI,0.08 to 0.28 D);P<0.001].Elongation of axial length was significantly different between in the control group(0.77 mm)and the intervention group[0.72 mm;difference of 0.05 mm(95%CI,0.01 to 0.09 mm);P=0.003].CONCLUSION:Artificial natural light in the classroom of primary schools can result in reducing incidence rate of myopia during a period of three years.

关键词： myopia artificial natural light school-age children efficacy

Development of a radiomics model to discriminate ammonium urate stones from uric acid stones in vivo:A remedy for the diagnostic pitfall of dual-energy computed tomography

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Chinese Medical Journal 2024年第9期137卷 1095-1104页

作者： Junjiong Zheng Jie Zhang Jinhua Cai Yuhui Yao Sihong Lu Zhuo Wu Zhaoxi Cai Aierken Tuerxun Jesur Batur Jian Huang Jianqiu Kong Tianxin Lin Department of Urology Sun Yat-Sen Memorial HospitalSun Yat-Sen UniversityGuangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene RegulationGuangdong Provincial Clinical Research Center for Urological DiseasesGuangzhouGuangdong 510120China Department of Neurology Sun Yat-Sen Memorial HospitalSun Yat-Sen UniversityGuangzhouGuangdong 510120China Department of Radiology Sun Yat-Sen Memorial HospitalSun Yat-Sen UniversityGuangzhouGuangdong 510120China Department of Urology The First People’s Hospital of Kashgar PrefectureKashgarXinjiang 844000China

Background:Dual-energy computed tomography(DECT)is purported to accurately distinguish uric acid stones from non-uric acid ***,whether DECT can accurately discriminate ammonium urate stones from uric acid stones remains ***,we aimed to explore whether they can be accurately identified by DECT and to develop a radiomics model to assist in distinguishing ***:This research included two *** the first purpose to evaluate the accuracy of DECT in the diagnosis of uric acid stones,178 urolithiasis patients who underwent preoperative DECT between September 2016 and December 2019 were *** model construction,93,40,and 109 eligible urolithiasis patients treated between February 2013 and October 2022 were assigned to the training,internal validation,and external validation sets,*** features were extracted from non-contrast CT images,and the least absolute shrinkage and selection operator(LASSO)algorithm was used to develop a radiomics ***,a radiomics model incorporating the radiomics signature and clinical predictors was *** performance of the model(discrimination,calibration,and clinical usefulness)was ***:When patients with ammonium urate stones were included in the analysis,the accuracy of DECT in the diagnosis of uric acid stones was significantly ***-two percent of ammonium urate stones were mistakenly diagnosed as uric acid stones by DECT.A radiomics model incorporating the radiomics signature,urine pH value,and urine white blood cell count was *** model achieved good calibration and discrimination{area under the receiver operating characteristic curve(AUC;95%confidence interval[CI]),0.944(0.899-0.989)},which was internally and externally validated with AUCs of 0.895(95%CI,0.796-0.995)and 0.870(95%CI,0.769-0.972),*** curve analysis revealed the clinical usefulness of the ***:DECT cannot accurately differentiate amm

关键词： Ammonium urate Dual-energy scanned projection radiography Radiomics Uric acid Urolithiasis