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Ferroptosis inhibitors reduce celastrol toxicity and preserve its insulin sensitizing effects in insulin resistant HepG2 cells

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Journal of Integrative Medicine 2024年第3期22卷 286-294页

作者： Jia-jia Liu Xue zhang bang-lan Cai Man-man Qi Yong-bin Chi Bin Peng Deng-hai zhang School of Medicine Shanghai UniversityShanghai 200444China Shanghai Health Commission Key Lab of Artificial Intelligence-Based Management of Inflammation and Chronic Diseases Shanghai Pudong Gongli HospitalSecondary Military Medical UniversityShanghai 200135China School of Basic Medicine Ningxia Medical UniversityYinchuan 750004Ningxia Hui Autonomous RegionChina

Objective:Research has shown that celastrol can effectively treat a variety of diseases,yet when passing a certain dosage threshold,celastrol becomes toxic,causing complications such as liver and kidney damage and erythrocytopenia,among others.With this dichotomy in mind,it is extremely important to find ways to preserve celastrol’s efficacy while reducing or preventing its toxicity.Methods:In this study,insulin-resistant Hep G2(IR-Hep G2)cells were prepared using palmitic acid and used for in vitro experiments.IR-Hep G2 cells were treated with celastrol alone or in combination with Nacetylcysteine(NAC)or ferrostatin-1(Fer-1)for 12,24 or 48 h,at a range of doses.Cell counting kit-8assay,Western blotting,quantitative reverse transcription-polymerase chain reaction,glucose consumption assessment,and flow cytometry were performed to measure celastrol’s cytotoxicity and whether the cell death was linked to ferroptosis.Results:Celastrol treatment increased lipid oxidation and decreased expression of anti-ferroptosis proteins in IR-Hep G2 cells.Celastrol downregulated glutathione peroxidase 4(GPX4)m RNA.Molecular docking models predicted that solute carrier family 7 member 11(SLC7A11)and GPX4 were covalently bound by celastrol.Importantly,we found for the first time that the application of ferroptosis inhibitors(especially NAC)was able to reduce celastrol’s toxicity while preserving its ability to improve insulin sensitivity in IR-Hep G2 cells.Conclusion:One potential mechanism of celastrol’s cytotoxicity is the induction of ferroptosis,which can be alleviated by treatment with ferroptosis inhibitors.These findings provide a new strategy to block celastrol’s toxicity while preserving its therapeutic effects.

关键词： Celastrol Insulin resistance Ferroptosis N-Acetylcysteine Palmitic acid Molecular docking

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Gradient inflammation in the pancreatic stump after pancreaticoduodenectomy:Two case reports and review of literature

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World Journal of Clinical Cases 2024年第9期12卷 1649-1659页

作者： tie-Gong Wang Liang Tian Xiao-Ling zhang Lei zhang Xiu-Lei Zhao De-Shuai Kong Department of Surgery Cangzhou Central HospitalCangzhou 061000Hebei ProvinceChina Department of Pathology Cangzhou Central HospitalCangzhou 061000Hebei ProvinceChina

BACKGROUND Postoperative pancreatic fistula(POPF)contributes significantly to morbidity and mortality after pancreaticoduodenectomy(PD).However,the underlying mechanisms remain unclear.This study explored this pathology in the pancreatic stumps and elucidated the mechanisms of POPF following PD.CASE SUMMARY Pathological analysis and 16S rRNA gene sequencing were performed on specimens obtained from two patients who underwent complete pancreatectomy for grade C POPF after PD.Gradient inflammation is present in the pancreatic stump.The apoptosis was lower than that in the normal pancreas.Moreover,neu-trophildominated inflammatory cells are concentrated in the ductal system.No-tably,neutrophils migrated through the ductal wall in acinar duct metaplasia-formed ducts.Additionally,evidence indicates that gut microbes migrate from the digestive tract.Gradient inflammation occurs in pancreatic stumps after PD.CONCLUSION The mechanisms underlying POPF include high biochemical activity in the pancreas,mechanical injury,and digestive reflux.To prevent POPF and address pancreatic inflammation and reflux,breaking the link with anastomotic dehi-scence is practical.

关键词： Pancreaticoduodenectomy Postoperative pancreatic fistula Inflammation Digestive reflux Case report

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Analysis of debris flow control effect and hazard assessment in Xinqiao Gully,Wenchuan M_(s)8.0 earthquake area based on numerical simulation

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China Geology 2024年第2期7卷 248-263页

作者： Chang Yang Yong-bo tie Xian-zheng zhang Yan-feng zhang Zhi-jie Ning Zong-liang Li Chinese Academy of Geological Sciences Beijing 100037China Chengdu Center of China Geological Survey China Geological SurveyChengdu 610081China Technology innovation center for risk prevention and mitigation of geohazard Ministry of Natural ResourcesChengdu 611734China Observation and Research Station of Chengdu Geological Hazards Ministry of Natural ResourcesChengdu 610000China

Xinqiao Gully is located in the area of the 2008 Wenchuan M_(s)8.0 earthquake in Sichuan province,China.Based on the investigation of the 2023"6-26"Xinqiao Gully debris flow event,this study assessed the effectiveness of the debris flow control project and evaluated the debris flow hazards.Through field investigation and numerical simulation methods,the indicators of flow intensity reduction rate and storage capacity fullness were proposed to quantify the effectiveness of the engineering measures in the debris flow event.The simulation results show that the debris flow control project reduced the flow intensity by41.05%to 64.61%.The storage capacity of the dam decreases gradually from upstream to the mouth of the gully,thus effectively intercepting and controlling the debris flow.By evaluating the debris flow of different recurrence intervals,further measures are recommended for managing debris flow events.

关键词： Landslide Debris flow Hazard assessment Numerical simulation OpenLISEM Prevention and control project Wenchuan M_(s)8.0 earthquake Xinqiao Gully Sichuan province Geological hazards survey engineering

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Clinical outcome and prognostic factors of T4N0M0 colon cancer after R0 resection:A retrospective study

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World Journal of Gastrointestinal Oncology 2024年第5期16卷 1869-1877页

作者： bang Liu Zhao-Xiong zhang Xin-Yang Nie Wei-Lin Sun Yong-Jia Yan Wei-Hua Fu Department of General Surgery Tianjin Medical University General HospitalTianjin Medical UniversityTianjin 300052China

BACKGROUND Paradoxically,patients with T4N0M0(stage II,no lymph node metastasis)colon cancer have a worse prognosis than those with T2N1-2M0(stage III).However,no previous report has addressed this issue.AIM To screen prognostic risk factors for T4N0M0 colon cancer and construct a prognostic nomogram model for these patients.METHODS Two hundred patients with T4N0M0 colon cancer were treated at Tianjin Medical University General Hospital between January 2017 and December 2021,of which 112 patients were assigned to the training cohort,and the remaining 88 patients were assigned to the validation cohort.Differences between the training and validation groups were analyzed.The training cohort was subjected to multi-variate analysis to select prognostic risk factors for T4N0M0 colon cancer,followed by the construction of a nomogram model.RESULTS The 3-year overall survival(OS)rates were 86.2%and 74.4%for the training and validation cohorts,respectively.Enterostomy(P=0.000),T stage(P=0.001),right hemicolon(P=0.025),irregular review(P=0.040),and carbohydrate antigen 199(CA199)(P=0.011)were independent risk factors of OS in patients with T4N0M0 colon cancer.A nomogram model with good concordance and accuracy was constructed.CONCLUSION Enterostomy,T stage,right hemicolon,irregular review,and CA199 were independent risk factors for OS in patients with T4N0M0 colon cancer.The nomogram model exhibited good agreement and accuracy.

关键词： T4N0M0 colon cancer Prognosis Multivariate analysis Nomogram Colon cancer

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Design and Cryogenic Performance of a Hexapod Platform for a Large Ground-based Wide Field Survey Telescope

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Research in Astronomy and Astrophysics 2024年第1期24卷 178-187页

作者： Yang Yu Xue-Wen Wang Yu zhang Jia-Lin Sun Zhen-bang Xu Jian-Li Wang Changchun Institute of Optics Fine Mechanics and PhysicsChinese Academy of SciencesChangchun 130033China Chinese Academy of Sciences Key Laboratory of On-orbit Manufacturing and Integration for Space Optics System Changchun 130033China University of Chinese Academy of Sciences Beijing 100049China

The thermal gradient is an important factor that causes degradation to the image quality of telescopes. In order to ensure the accurate alignment of the primary focus unit and the primary mirror, the hexapod platform(as a corrector) is investigated in this paper. First, a ground-based telescope with 2.5 m aperture and 3.5 deg field of view is described. The telescope is under construction, and it is expected to be finished in 2023. Second, the hexapod platform with flexure hinges utilized to adjust the primary focus unit is proposed, which is applied as a corrector.Then, the inverse kinematics of the platform is established and an open-loop control system is built based on it.Finally, the cryogenic performance test for the hexapod platform is performed. The experimental results show that the resolution and repeatability of the translation for the hexapod platform can be achieved at the micrometer level.The resolution and repeatability of the rotation can be achieved at the arc-second level. Therefore, the cryogenic performance of the hexapod platform can meet the optical imaging requirements of the wide-field ground-based telescope. The kinematic analysis and cryogenic performance tests in the paper provide a technical reference for the precise alignment of the primary focus unit and the primary mirror, which can improve the imaging quality of the telescope.

关键词： methods:miscellaneous space vehicles:instruments telescopes miscellaneous

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Isolation and culture of human primary osteoblasts:Comparing the effects of differences in method details on osteoblast characteristics

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Genes & Diseases 2024年第2期11卷 546-549页

作者： Fei Chen Yan zhang Pai Peng Xiao-Ting Huang Zi-Han Qiu Bao-Cheng Liu tie-Lin Yang Bo Yang Yan Guo Key Laboratory of Biomedical Information Engineering of Ministry of Education Biomedical Informatics & Genomics CenterSchool of Life Science and TechnologyXi'an Jiaotong UniversityXi'anShaanxi 710049China Department of Orthopaedics Shannxi Provincial People's Hospital (The Third Affiliated Hospital of Xi'an Jiaotong University)Xi'anShaanxi 710068China

Osteoblasts are essential in the maintenance of human bone homeostasis.1 The abnormal formation and impaired differentiation ability of osteoblasts are pivotal factors leading to bone-related diseases,suggesting that an indepth study of osteoblasts can provide novel treatment strategies for these diseases.2 Human primary osteoblasts are precious experimental models in bone-related research.3 However,the isolation and culture of human primary osteoblasts still have some difficulties and limitations.Here,we refined a method to isolate and culture human primary osteoblasts by taking cancellous bone through a bone tissue sampler and pre-digesting it with pancreatin,which makes the process easier,cheaper,and more efficient.Furthermore,we compared the effects of the subtle changes in isolation and culture methods on the phenotype of human primary osteoblasts and examined the differences in morphology,proliferation,and differentiation between micro-explants cultured osteoblasts(MECOBs)and explants cultured osteoblasts(EC-OBs).

关键词： impaired culture details

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一种小型化人工表面等离激元传感系统——实现自适应和高灵敏的气体检测

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Engineering 2024年第4期35卷 86-94页

作者： Xuanru zhang Jia Wen Zhu tie Jun Cui State Key Laboratory of Millimeter Waves and Institute of Electromagnetic Space Southeast UniversityNanjing 210096China School of Information Science and Engineering Southeast UniversityNanjing 210096China School of Microelectronics Southeast UniversityNanjing 210096China

Resonantly enhanced dielectric sensing has superior sensitivity and accuracy because the signal is measured from relative resonance shifts that are immune to signal fluctuations.For applications in the Internet of Things(IoT),accurate detection of resonance frequency shifts using a compact circuit is in high demand.We proposed an ultracompact integrated sensing system that merges a spoof surface plasmon resonance sensor with signal detection,processing,and wireless communication.A softwaredefined scheme was developed to track the resonance shift,which minimized the hardware circuit and made the detection adaptive to the target resonance.A microwave spoof surface plasmon resonator was designed to enhance sensitivity and resonance intensity.The integrated sensing system was constructed on a printed circuit board with dimensions of 1.8 cm×1.2 cm and connected to a smartphone wirelessly through Bluetooth,working in both frequency scanning mode and resonance tracking mode and achieving a signal-to-noise ratio of 69 dB in acetone vapor sensing.This study provides an ultracompact,accurate,adaptive,sensitive,and wireless solution for resonant sensors in the IoT.

关键词： Spoof surface plasmons Internet of Things Integrated sensing Resonance tracking Microwave sensing

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Efficacyand Safetyof Huashi Baidu Granules in Treating Patients with SARS-CoV-2Omicron Variant: A Single-Center Retrospective Cohort Study

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Chinese Journal of Integrative Medicine 2024年第2期30卷 107-114页

作者： CHEN Cai-yu zhang Wen XU Xiang-ru PU Yu-ting TU Ya-dan PENG Wei YAO Xuan ZHOU Shuang FANG bang-jiang Department of Emergency Longhua HospitalShanghai University of Traditional Chinese MedicineShanghai(200032)China Department of Classical Traditional Chinese Medicine Chongqing Hospital of Traditional Chinese MedicineChongqing(400021)China Acupuncture and Massage College Shanghai University of Traditional Chinese MedicineShanghai(201203)China Institute of Emergency and Critical Care Medicine Shanghai University of Traditional Chinese MedicineShanghai(200032)China

Objective:To evaluate the efficacy and safety of Huashi Baidu Granules(HSBD)in treating patients with severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)Omicron variant.Methods:A single-center retrospective cohort study was conducted during COVID-19 Omicron epidemic in the Mobile Cabin Hospital of Shanghai New International Expo Center from April 1st to May 23rd,2022.All COVID-19 patients with asymptomatic or mild infection were assigned to the treatment group(HSBD users)and the control group(non-HSBD users).After propensity score matching in a 1:1 ratio,496 HSBD users of treatment group were matched by propensity score to 496 non-HSBD users.Patients in the treatment group were administrated HSBD(5 g/bag)orally for 1 bag twice a day for 7 consecutive days.Patients in the control group received standard care and routine treatment.The primary outcomes were the negative conversion time of nucleic acid and negative conversion rate at day 7.Secondary outcomes included the hospitalized days,the time of the first nucleic acid negative conversion,and new-onset symptoms in asymptomatic patients.Adverse events(AEs)that occurred during the study were recorded.Further subgroup analysis was conducted in vaccinated(378 HSBD users and 390 non-HSBD users)and unvaccinated patients(118 HSBD users and 106 non-HSBD users).Results:The median negative conversion time of nucleic acid in the treatment group was significantly shortened than the control group[3 days(IQR:2-5 days)vs.5 days(IQR:4-6 days);P<0.01].The negative conversion rate of nucleic acid in the treatment group were significantly higher than those in the control group at day 7(91.73%vs.86.90%,P=0.014).Compared with the control group,the hospitalized days in the treatment group were significantly reduced[10 days(IQR:8-11 days)vs.11 days(IQR:10.25-12 days);P<0.01].The time of the first nucleic acid negative conversion had significant differences between the treatment and control groups[3 days(IQR:2-4 days)vs.5 days(IQR:4-6 days);P<0.01].The incidence of new-onset sym

关键词： Huashi Baidu Granule severe acute respiratory syndrome coronavirus 2 Omicron variant retrospective cohort trial Chinese medicine

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A multifunctional flexible sensor based on PI-MXene/SrTiO_(3) hybrid aerogel for tactile perception

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The Innovation 2024年第3期5卷 44-54页

作者： Shihao Deng Yue Li Shengzhao Li Shen Yuan Hao Zhu Ju Bai Jingyi Xu Lu Peng tie Li Ting zhang Nano Science and Technology Institute University of Science and Technology of China(USTC)Suzhou 215123China i-lab Nano-X Vacuum Interconnected WorkstationKey Laboratory of Multifunctional Nanomaterials and Smart SystemsSuzhou Institute of Nano-Tech and Nano-Bionics(SINANO)Chinese Academy of Sciences(CAS)Suzhou 215123China School of Nano-Tech and Nano-Bionics University of Science and Technology of China(USTC)Hefei 230026China Jiangxi Institute of Nanotechnology 278 Luozhu RoadXiaolan Economic and Technological Development ZoneNanchang 330200China

The inadequacy of tactile perception systems in humanoid robotic manipulators limits the breadth of available robotic applications.Here,we designed a multifunctional flexible tactile sensor for robotic fingers that provides capabilities similar to those of human skin sensing modalities.This sensor utilizes a novel PI-MXene/SrTiO_(3) hybrid aerogel developed as a sensing unit with the additional abilities of electromagnetic transmission and thermal insulation to adapt to certain complex environments.Moreover,polyimide(PI)provides a high-strength skeleton,MXene realizes a pressure-sensing function,and MXene/SrTiO_(3) achieves both thermoelectric and infrared radiation response behaviors.Furthermore,via the pressure response mechanism and unsteady-state heat transfer,these aerogel-derived flexible sensors realize multimodal sensing and recognition capabilities with minimal cross-coupling.They can differentiate among 13 types of hardness and four types of material from objects with accuracies of 94%and 85%,respectively,using a decision tree algorithm.In addition,based on the infrared radiation-sensing function,a sensory array was assembled,and different shapes of objects were successfully recognized.These findings demonstrate that this PI-MXene/SrTiO_(3) aerogel provides a new concept for expanding the multifunctionality of flexible sensors such that the manipulator can more closely reach the tactile level of the human hand.This advancement reduces the difficulty of integrating humanoid robots and provides a new breadth of application scenarios for their possibility.

关键词： utilize integrating insulation

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1,6-Conjugate addition of para-quinone methides using gem-diborylcarbanions: Practical access to gem-diborylalkanes bearing vicinal tertiary/quaternary stereocenters

Green Synthesis and Catalysis

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Green Synthesis and Catalysis 2024年第1期5卷 68-72页

作者： Pu-zhang Zi Xing-bang Liu Quan-Hong Zhao Min He Yuan Huang Department of Medicinal Chemistry School of PharmacyXi'an Jiaotong UniversityXi'an710061China

A novel,efficient and pragmatic method to prepare gem-diboron products with vicinal tertiary/quaternary stereocenters using LiTMP-mediated 1,6-conjugate addition of gem-diborylalkanes to para-quinone methides was described for the first time.The results showed that various gem-diboron products with vicinal tertiary and quaternary stereocenters could be formed within 15 min at ambient temperature.This simple protocol has also been applied for the efficient synthesis of the analogue of Bedaquiline.

关键词： gem-Diborylalkanes Quaternary stereocenter Conjugate addition para-Quinone methides Organoboron compounds

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