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Enhanced hepatic metabolic perturbation of polystyrene nanoplastics by UV irradiation-induced hydroxyl radical generation

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Journal of Environmental Sciences 2024年第8期142卷 259-268页

作者： Shiyu He Jingran Wang Lihong Zhou Zhen Mao Xiaodan Zhang Jin Cai Peili Huang school of Public Health and Beijing Key Laboratory of Environmental Toxicology Capital Medical UniversityBeijing 100069China

The environmental behavior of and risks associated with nanoplastics(NPs)have attracted considerable ***,compared to pristine NPs,environmental factors such as ultraviolet(UV)irradiation that lead to changes in the toxicity of NPs have rarely been *** evaluated the changes in morphology and physicochemical properties of polystyrene(PS)NPs before and after UV irradiation,and compared their hepatotoxicity in *** results showed that UV irradiation caused particle size reduction and increased the carbonyl index(CI)and negative charge on the particle ***-aged PS NPs(aPS NPs)could induce the generation of hydroxyl radicals(·OH),but also further promoted the generation of·OH in the Fenton reaction *** pathological damage was more severe in mice exposed to aPS NPs,accompanied by a large number of vacuoles and hepatocyte balloon-like changes and more marked perturbations in blood glucose and serum lipoprotein,alanine aminotransferase and aspartate aminotransferase *** addition,exposure to PS NPs and aPS NPs,especially aPS NPs,triggered oxidative stress and significantly damaged the antioxidant capacity of mice *** with PS NPs,exposure to aPS NPs increased the number of altered metabolites in hepatic and corresponding metabolic pathways,especially glutathione *** research suggests that UV irradiation can disrupt the redox balance in organisms by promoting the production of·OH,enhancing PS NPs-induced liver damage and metabolic *** study will help us understand the health risks of NPs and to avoid underestimation of the risks of NPs in nature.

关键词： Polystyrene nanoplastics Ultraviolet-aged nanoplastics Metabolic pathway Metabolomics Hydroxyl radical

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Allosteric modulation of G protein-coupled receptors as a novel therapeutic strategy in neuropathic pain

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Acta Pharmaceutica Sinica B 2024年第1期14卷 67-86页

作者： Chunhao Zhu Xiaobing Lan Zhiqiang Wei Jianqiang Yu Jian Zhang school of Pharmacy Ningxia Medical UniversityYinchuan 750004China Medicinal Chemistry and Bioinformatics Center Shanghai Jiao Tong University School of MedicineShanghai 200025China school of Basic medical Science Ningxia Medical UniversityYinchuan 750004China Medicinal Chemistry and Bioinformatics Center Ocean University of ChinaQingdao 266100China State Key Laboratory of Pharmaceutical Biotechnology Nanjing UniversityNanjing 210023China

Neuropathic pain is a debilitating pathological condition that presents significant therapeutic challenges in clinical ***,current pharmacological treatments for neuropathic pain lack clinical efficacy and often lead to harmful adverse *** G protein-coupled receptors(GPCRs)are widely distributed throughout the body,including the pain transmission pathway and descending inhibition pathway,the development of novel neuropathic pain treatments based on GPCRs allosteric modulation theory is gaining *** research has shown that allosteric modulators targeting GPCRs on the pain pathway can effectively alleviate symptoms of neuropathic pain while reducing or eliminating adverse *** review aims to provide a comprehensive summary of the progress made in GPCRs allosteric modulators in the treatment of neuropathic pain,and discuss the potential benefits and adverse factors of this *** will also concentrate on the development of biased agonists of GPCRs,and based on important examples of biased agonist development in recent years,we will describe universal strategies for designing structure-based biased *** is foreseeable that,with the continuous improvement of GPCRs allosteric modulation and biased agonist theory,effective GPCRs allosteric drugs will eventually be available for the treatment of neuropathic pain with acceptable safety.

关键词： Neuropathic pain Allosteric modulators G protein-coupled receptors Analgesia

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Decoupled deep hough voting for point cloud registration

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Frontiers of Computer Science 2024年第2期18卷 147-155页

作者： Mingzhi YUAN Kexue FU Zhihao LI Manning WANG Digital medical Research Center School of Basic Medical SciencesFudan UniversityShanghai 200032China Shanghai Key Laboratory of medical Image Computing and Computer Assisted Intervention Shanghai 200032China

Estimating rigid transformation using noisy correspondences is critical to feature-based point cloud ***,a series of studies have attempted to combine traditional robust model fitting with deep *** them,DHVR proposed a hough voting-based method,achieving new state-of-the-art ***,we find voting on rotation and translation simultaneously hinders achieving better ***,we proposed a new hough voting-based method,which decouples rotation and translation ***,we first utilize hough voting and a neural network to estimate *** based on good initialization on rotation,we can easily obtain accurate rigid *** experiments on 3DMatch and 3DLoMatch datasets show that our method achieves comparable performances over the state-of-the-art *** further demonstrate the generalization of our method by experimenting on KITTI dataset.

关键词： point cloud registration robust model fitting deep learning hough voting

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Immune checkpoint inhibitor-associated gastritis:Patterns and management

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World Journal of Gastroenterology 2024年第14期30卷 1941-1948页

作者： Jing Lin Zhong-Qiao Lin Shi-Cheng Zheng Yu Chen Department of medical Oncology Clinical Oncology School of Fujian Medical UniversityFujian Cancer HospitalFuzhou 350000Fujian ProvinceChina Phase I Clinical Trial Ward Clinical Oncology School of Fujian Medical UniversityFujian Cancer HospitalFuzhou 350000Fujian ProvinceChina school of Basic medical Sciences Fujian Medical UniversityFuzhou 350000Fujian ProvinceChina

Immune checkpoint inhibitors(ICIs)are widely used due to their effectiveness in treating various ***-related adverse events(irAEs)are defined as adverse effects resulting from ICI *** irAEs are a common type of irAEs characterized by intestinal side effects,such as diarrhea and colitis,which may lead to the cessation of *** irAE gastritis is rarely reported,it may lead to serious complications such as ***,irAE gastritis is often difficult to identify early due to its diverse *** steroid hormones and immunosuppressants are commonly used to reverse irAEs,the best regimen and dosage for irAE gastritis remains *** addition,the risk of recurrence of irAE gastritis after the reuse of ICIs should be *** this editorial,strategies such as early identification,pathological diagnosis,mana-gement interventions,and immunotherapy rechallenge are discussed to enable clinicians to better manage irAE gastritis and improve the prognosis of these patients.

关键词： Immunotherapy Immune checkpoint inhibitor Immune-related adverse events Immune checkpoint inhibitor-related gastritis

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Dynamic Treatment Strategy of Chinese Medicine for Metastatic Colorectal Cancer Based on Machine Learning Algorithm

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Chinese Journal of Integrative Medicine 2024年第11期30卷 993-1000页

作者： XU Yu-ying LI Qiu-yan YI Dan-hui CHEN Yue ZHAI Jia-wei ZHANG Tong SUN Ling-yun YANG Yu-fei Department of Oncology Xiyuan Hospital China Academy of Chinese Medical Sciences school of Statistics Renmin University of China Graduate school Beijing University of Chinese Medicine

Objective: To establish the dynamic treatment strategy of Chinese medicine(CM) for metastatic colorectal cancer(m CRC) by machine learning algorithm, in order to provide a reference for the selection of CM treatment strategies for m CRC. Methods: From the outpatient cases of m CRC in the Department of Oncology at Xiyuan Hospital, China Academy of Chinese medical Sciences, 197 cases that met the inclusion criteria were screened. According to different CM intervention strategies, the patients were divided into 3 groups: CM treatment alone, equal emphasis on Chinese and Western medicine treatment(CM combined with local treatment of tumors, oral chemotherapy, or targeted drugs), and CM assisted Western medicine treatment(CM combined with intravenous regimen of Western medicine). The survival time of patients undergoing CM intervention was taken as the final evaluation index. Factors affecting the choice of CM intervention scheme were screened as decision variables. The dynamic CM intervention and treatment strategy for m CRC was explored based on the cost-sensitive classification learning algorithm for survival(CSCLSurv). Patients' survival was estimated using the Kaplan-Meier method, and the survival time of patients who received the model-recommended treatment plan were compared with those who received actual treatment plan. Results: Using the survival time of patients undergoing CM intervention as the evaluation index, a dynamic CM intervention therapy strategy for m CRC was established based on *** CM intervention strategies for m CRC can be selected according to dynamic decision variables, such as gender, age, Eastern Cooperative Oncology Group score, tumor site, metastatic site, genotyping, and the stage of Western medicine treatment at the patient's first visit. The median survival time of patients who received the modelrecommended treatment plan was 35 months, while those who receive the actual treatment plan was 26.0 months(P=0.06). Conclusions:

关键词： Chinese medicine cost sensitive classification learning for survival dynamic treatment strategy metastatic colorectal cancer

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Application of Natural Medicinal Plants Active Ingredients in Oral Squamous Cell Carcinoma

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Chinese Journal of Integrative Medicine 2024年第9期30卷 852-864页

作者： REN Qun-li LI Xiao-lan TIAN Tian LI Shuang SHI Rong-yi WANG Qian ZHU Yuan WANG Miao HU Huan LIU Jian-guo school of Stomatology Zunyi Medical UniversityZunyiGuizhou Province563000China Microbial Resources and Drug Development Key Laboratory of Guizhou Tertiary Institution Zunyi Medical UniversityZunyiGuizhou Province563000China school of Basic Medicine Zunyi Medical UniversityZunyiGuizhou Province563000China

Oral squamous cell carcinoma(OSCC)is the most common malignant cancer of the head and neck,with high morbidity and mortality,ranking as the sixth most common cancer in the *** treatment of OSCC is mainly radiotherapy,chemotherapy and surgery,however,the prognosis of patients is still poor and the recurrence rate is *** paper reviews the range of effects of natural medicinal plant active ingredients(NMPAIs)on OSCC cancer,including the types of NMPAIs,anti-cancer mechanisms,involved signaling pathways,and clinical *** NMPAIs include terpenoids,phenols,flavonoids,glycosides,alkaloids,coumarins,and volatile *** active ingredients inhibit proliferation,induce apoptosis and autophagy,inhibit migration and invasion of OSCC cells,and regulate cancer immunity to exert anti-cancer *** mechanism involves signaling pathways such as mitogen-activated protein kinase,phosphatidylinositol 3 kinase/protein kinase B,nuclear factor kappa B,miR-22/WNT1/β-catenin and Nrf2/***,NMPAIs can inhibit the growth of OSCC,and the combined drug is more *** medicinal plants are promising candidates for the treatment of OSCC.

关键词： natural medicinal plant active ingredients oral squamous cell carcinoma mechanism signaling pathway review

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Succinylation modification:a potential therapeutic target in stroke

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Neural Regeneration Research 2024年第4期19卷 781-787页

作者： Jie Lian Wenwu Liu Qin Hu Xiaohua Zhang Department of Neurosurgery Ren Ji HospitalShanghai Jiao Tong University School of Medicine Department of Diving and Hyperbaric Medicine Naval Medical CenterNaval Medical University

Stroke is a leading cause of mortality and disability *** cell death triggered by the compromised supply of blood oxygen and glucose is one of the major pathophysiology of strokeinduced brain *** mitochondrial energy metabolism is observed minutes after stroke and is closely associated with the progression of ***,a new type of posttranslational modification,known as lysine succinylation,has been recognized to play a significant role in mitochondrial energy metabolism after ***,the role of succinylation modification in cell metabolism after stroke and its regulation are not well *** aimed to review the effects of succinylation on energy metabolism,reactive oxygen species generation,and neuroinflammation,as well as Sirtuin 5 mediated desuccinylation after *** also highlight the potential of targeting succinylation/desuccinylation as a promising strategy for the treatment of *** succinylation level is dynamically regulated by the nonenzymatic or enzymatic transfer of a succinyl group to a protein on lysine residues and the removal of succinyl catalyzed by *** evidence has suggested that succinylation can regulate the metabolic pathway through modulating the activity or stability of metabolic ***,especially Sirtuin 5,are characterized for their desuccinylation activity and have been recognized as a critical regulator of metabolism through desuccinylating numerous metabolic *** between succinylation and desuccinylation has been implicated in the pathophysiology of *** agents that enhance the activity of Sirtuin 5 have been employed to promote desuccinylation and improve mitochondrial metabolism,and neuroprotective effects of these agents have been observed in experimental stroke ***,their therapeutic efficacy in stroke patients should be validated.

关键词： mitochondria metabolism neuroprotection sirtuin 5 stroke succinylation modification

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In situ direct reprogramming of astrocytes to neurons via polypyrimidine tract-binding protein 1 knockdown in a mouse model of ischemic stroke

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Neural Regeneration Research 2024年第10期19卷 2240-2248页

作者： Meng Yuan Yao Tang Tianwen Huang Lining Ke En Huang Key Laboratory of Brain Aging and Neurodegenerative Diseases of Fujian Province Fujian Medical UniversityFuzhouFujian ProvinceChina Department of Human Anatomy School of Basic Medical SciencesFujian Medical UniversityFuzhouFujian ProvinceChina Scientific Research Center School of Basic Medical SciencesFujian Medical UniversityFuzhouFujian ProvinceChina Department of Neurology Fujian Medical University Union HospitalFuzhouFujian ProvinceChina Fujian Key Laboratory of Vascular Aging Fujian Medical UniversityFuzhouFujian ProvinceChina

In situ direct reprogramming technology can directly convert endogenous glial cells into functional neurons in vivo for central nervous system repair. Polypyrimidine tract-binding protein 1(PTB) knockdown has been shown to reprogram astrocytes to functional neurons in situ. In this study, we used AAV-PHP.e B-GFAP-sh PTB to knockdown PTB in a mouse model of ischemic stroke induced by endothelin-1, and investigated the effects of GFAP-sh PTB-mediated direct reprogramming to neurons. Our results showed that in the mouse model of ischemic stroke, PTB knockdown effectively reprogrammed GFAP-positive cells to neurons in ischemic foci, restored neural tissue structure, reduced inflammatory response, and improved behavioral function. These findings validate the effectiveness of in situ transdifferentiation of astrocytes, and suggest that the approach may be a promising strategy for stroke treatment.

关键词： astrocyte in situ direct reprogramming ischemic stroke miR-30 based shRNA neuron polypyrimidine tract-binding protein 1 transdifferentiation

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Increased N6-methyladenosine is related to the promotion of the methyltransferase METTL14 in ovarian aging

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Genes & Diseases 2024年第3期11卷 151-154页

作者： Chunfeng Qian Zhenxing Liu Yonghong Qian Jie Ding Rulei Chen Han Su Minghong Shen Hong Li Boxian Huang State Key Laboratory of Reproductive Medicine and Offspring Health Suzhou Affliated Hospital of Nanjing Medicine and Offspring HealthSuzhou Affiliated Hospital of Nanjing Medical UniversitySuzhouMunicipal HospitalGusu SchoolNanjing Medical UniversitySuzhouJiangsu 215002China Department of Gynecology Affliated Suzhou Hospital of Nanjing Medical UniversitySuzhou Municipal HospitalGusu School of Nanjing Medical UniversitySuzhouJiangsu 215002China Department of Pathology Affiliated Suzhou Hospital of Nanjing Medical UniversitySuzhou Municipal HospitalGusu School of Nanjing Medical UniversitySuzhouJiangsu 215002China

The ovary is a vital female reproductive organ that functions to produce oocyte gametes and cyclically expressed sex hormones to maintain reproductive capacity and hormone *** aging,characterized by declines in follicle quantity and oocyte quality,leads to premature ovarian failure,premature ovarian insufficiency,or diminished ovarian reserve,thus contributing to female *** gene-expression signatures from RNA transcriptional level and post-transcriptional regulation are relative to oocyte quality and reproductive age.

关键词： promotion signature maintain

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Fasn involved in the nephrotoxicity induced by polystyrene nanoplastics and the intervention of melatonin through intestinal microbiota-mediated lipid metabolism disorder

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Nano Research 2024年第8期17卷 7365-7375页

作者： Huiwen Kang Danyang Huang Jiaru Jing Wei Zhang Lei Zhang Jingyu Wang Ziyan Liu Lin Han Ziyan Wang Lefeng Zhang Ai Gao Department of Occupational Health and Environmental Health School of Public HealthCapital Medical UniversityBeijing 100069China Beijing Key Laboratory of Environmental Toxicology Capital Medical UniversityBeijing 100069China

Nanoplastics(NPs)can accumulate in the kidney and cause kidney injury,but the multi-organ interaction mechanism and preventive measures of kidney injury are still *** this study,in vivo(60μg/day,42 days)and in vitro(0.4μg/μL,24 h)exposure models of polystyrene nanoplastics(PS-NPs,80 nm)in mice and human kidney cortex proximal tubule epithelial cells(HK-2 cells)were established,*** study revealed that PS-NPs caused obvious pathological changes and impaired renal function in mice,which were related to lipid metabolism disorders mediated by intestinal ***-fatty acid synthase(Fasn)-docosahexaenoic acid(DHA)pathway may be one of the mechanisms of kidney injury in ***,we also found that melatonin attenuates PS-NPs-induced nephrotoxicity by modulating lipid metabolism disorders(represented by DHA)and affects Fasn *** conclusion,our study revealed the important role of intestinal flora-mediated lipid metabolism in PS-NPs-induced nephrotoxicity and preliminarily provided potential key gene targets and effective preventive measures for PS-NPs-induced nephrotoxicity.

关键词： nanoplastics nephrotoxicity lipid metabolism fatty acid synthase(Fasn) melatonin

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