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Transcriptomic analysis identifies the neuropeptide cortistatin (CORT) as an inhibitor of temozolomide (TMZ) resistance by suppressing the NF-kB-MGMT signaling axis in human glioma

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Genes & Diseases 2024年第3期11卷 385-399页

作者： Zongze He Bo Peng Qi Wang Jie Tian ping liu Jie Feng Yiwei Liao Longyi Chen ping Jia Jian Tang Department of Neurosurgery Sichuan Provincial People's HospitalUniversity of Electronic Science and Technology of ChinaChengduSichuan 610072China Department of Rehabilitation Medicine Sichuan Provincial People's HospitalUniversity of Electronic Science and Technology of ChinaChengduSichuan 610072China Department of Neurosurgery Xiangya HospitalCentral South UniversityChangshaHunan 410008China

Glioma is a common tumor originating in the brain that has a high mortality rate.Temozolomide(TMZ)is the first-line treatment for high-grade gliomas.However,a large pro-portion of gliomas are resistant to TMZ,posing a great challenge to their treatment.In the study,the specific functions and mechanism(s)by which cortistatin(CORT)regulates TMZ resis-tance and glioma progression were evaluated.The decreased expression of CoRT was detected in glioma tissues,and highly expressed CORT was associated with a better survival rate in pa-tients with glioma.CORT overexpression notably decreased the capacity of glioma cells to pro-liferate and migrate in vitro and to form tumors in vivo.CORT overexpression also markedly suppressed the viability and enhanced the apoptosis of TMZ-resistant U251 cells by regulating MGMT,p21,and Puma expression.Importantly,CORT overexpression reduced the resistance of gliomas to TMZ in vivo.CORT expression Was negatively correlated with MGMT expression in both glioma tissues and cells,and it was found that CORT inhibited NF-kB pathway activation in glioma cells,thereby inhibiting MGMT expression.In conclusion,CORT regulates glioma cell growth,migration,apoptosis,and TMZ resistance by weakening the activity of NF-kB/p65 and thereby regulating MGMT expression.The CORT/NF-kB/MGMT axis might be regarded as a molecular mechanism contributing to the resistance of glioma to TMZ.Our data also suggest that CORT regulates the viability and metastatic potential of glioma cells,independent of its effects on TMZ resistance,providing evidence of novel therapeutic targets for glioma that should be evaluated infurther studies.

关键词： Cortistatin Glioma MGMT NF-kB pathway Temozolomide

Effect of drying cracks on swelling and self-healing of bentonite-sand blocks used as engineered barriers for radioactive waste disposal

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Journal of Rock Mechanics and Geotechnical Engineering 2024年第5期16卷 1776-1787页

作者： Yu Tan Guangping Zhou Huyuan Zhang Xiaoya Li ping liu School of Civil Engineering and Mechanics Lanzhou UniversityLanzhou730000China Key Laboratory of Mechanics on Disaster and Environment in Western China (Lanzhou University) Ministry of EducationLanzhou730000China Civil and Environmental Engineering University of Wisconsin-MadisonWI53706USA

Experiments were conducted to evaluate the healing of drying cracks in air-dried bentonite-sand blocks after hydration and swelling in groundwater,providing justifications to simplify the protection of blocks prior to installation in a high-level radioactive waste repository.Synthetic groundwater was prepared to represent the geochemistry of Beishan groundwater,and was used to hydrate the blocks during the swelling pressure and swelling strain measurements,as Beishan is the most promising site for China's repository.Healing of the surface cracks was recorded by photography,and healing of the internal cracks was visualized by CT images and hydraulic conductivity of air-dried blocks.The results indicate that the maximum swelling pressure and swelling strain are primarily affected by the geochemistry of Beishan groundwater,but not affected by the drying cracks.The maximum swelling pressure and swelling strain of air-dried blocks are comparable to or even higher than the pressure and strain of fresh blocks.The maximum swelling pressure measured in strong(i.***.high ion strength)Beishan groundwater was 44%of the pressure measured in deionized(DI)water,and the maximum swelling strain was reduced to 23%of the strain measured in DI water.Nevertheless,the remained swelling of the blocks hydrated in strong Beishan groundwater was sufficient to heal the surface and internal drying cracks,as demonstrated by the pictures of surface cracks and CT images.The hydraulic conductivity of the air-dried block permeated with strong groundwater was comparable(3.7×higher)to the hydraulic conductivity of the fresh block,indicating the self-healing of drying cracks after hydration and swelling in groundwater.A simplified method of protecting the block with plastic wraps before installation is recommended,since the remained swelling of the block hydrated in Beishan groundwater is sufficient to heal the drying cracks.

关键词： Beishan groundwater chemistry Bentonite buffer Drying cracks High-level radioactive waste(HLW) Self-healing Swelling

Anisotropic shearing mechanism of Kangding slate:Experimental investigation and numerical analysis

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Journal of Rock Mechanics and Geotechnical Engineering 2024年第5期16卷 1487-1504页

作者： ping liu Quansheng liu Penghai Deng Yucong Pan Yiming Lei Chenglei Du Xianqi Xie The Key Laboratory of Geotechnical and Structural Engineering Safety of Hubei Province School of Civil EngineeringWuhan UniversityWuhan430072China State Key Laboratory of Water Resources and Hydropower Engineering Science Wuhan UniversityWuhan430072China

The shear mechanical behavior is regarded as an essential factor affecting the stability of the surrounding rocks in underground engineering.The shear strength and failure mechanisms of layered rock are significantly affected by the foliation angles.Direct shear tests were conducted on cubic slate samples with foliation angles of 0°,30°,45°,60°,and 90°.The effect of foliation angles on failure patterns,acoustic emission(AE)characteristics,and shear strength parameters was analyzed.Based on AE characteristics,the slate failure process could be divided into four stages:quiet period,step-like increasing period,dramatic increasing period,and remission period.A new empirical expression of cohesion for layered rock was proposed,which was compared with linear and sinusoidal cohesion expressions based on the results made by this paper and previous experiments.The comparative analysis demonstrated that the new expression has better prediction ability than other expressions.The proposed empirical equation was used for direct shear simulations with the combined finite-discrete element method(FDEM),and it was found to align well with the experimental results.Considering both computational efficiency and accuracy,it was recommended to use a shear rate of 0.01 m/s for FDEM to carry out direct shear simulations.To balance the relationship between the number of elements and the simulation results in the direct shear simulations,the recommended element size is 1 mm.

关键词： Anisotropy Empirical expression of cohesion foliation angles Combined finite-discrete element method(FDEM) Shear rate Element size

Identification of TMEM217 as a novel prognostic biomarker and potential therapeutic target in acute myeloid leukemia

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Genes & Diseases 2024年第4期11卷 90-93页

作者： Yunying Yao Zhizhou Xi Min Wu Bo Jiao Jiaming Gao Donghe Li Xi Xie Pengfei Xu Jiaoyang Li Lei Yan Ruibao Ren ping liu Shanghai Institute of Hematology State Key Laboratory for Medical GenomicsNational Research Center for Translational MedicineCollaborative Innovation Center of HematologyRuijin Hospital affiliated with Shanghai Jiao Tong University School of MedicineShanghai 200025China International Center for Aging and Cancer Hainan Medical UniversityHaikouHainan 570102China

Despite remarkable advances in molecular and cell biology of acute myeloid leukemia(AML),AML patients still frequently relapse and have low 5-year overall survival(OS)rates.1 It is worth noting that a recent study from the registry or clinical trial compilation has reported an improvement in the OS of adult AML patients,especially those under 60 years of age.

关键词： acute myeloid leukemia

Characterization of the effects of hyaluronan oligosaccharides on human gut microbiota using a simulated batch fermentation system

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Food Science and Human Wellness 2024年

作者： Xinwei Gao Hongkang Zhu Litao Hu Jieyu Sun Wenjie Zuo ping liu Yang Wang Guocheng Du Zhen Kang The Science Center for Future Foods Jiangnan University The Key Laboratory of Carbohydrate Chemistry and Biotechnology Ministry of Education Jiangnan University The Key Laboratory of Industrial Biotechnology Ministry of Education School of Biotechnology Jiangnan University School of Food Science and Technology Jiangnan University

The prebiotic effects of hyaluronan (HA) are widely recognized， contributing to improved gut health and immune modulation. Despite its extensive use as dietary supplement， the specific interactions between HA oligosaccharides (o-HAs) and the gut microbiome remain largely unexplored. To investigate its role and metabolic fate in gut homeostasis， 200 mg/day of o-HAs (average molecule weight 1k Da) were added to an automated computer-controlled SIMulator of the Gastrointestinal tract (SIMGI). The results revealed a significant reshaping of the intestinal flora composition by o-HAs， notably reducing the Firmicutes/Bacteroides ratio. Fermentation of o-HAs by gut microbiota significantly increased the abundance of Bifidobacteria， Prevotellaceae＿Prevotella， Dialister， Eubacterium， and Sutterella， but decreased that of Catenibacterium， Oscillospira， Klebsiella， and Citrobacter (P < 0.05). This corresponded with significant enhancements in the content of short-chain fatty acids (SCFAs) such as acetic acid， propionic acid and n-butyric acid， highlighting the significant impact of o-HAs at the genus level. Furthermore， analysis of microbial function predicted the downregulation of pathological events in nine human diseases， particularly infectious ones (parasitic and bacterial). Potential inhibitions were observed in metabolic pathways associated with pentose and glucuronate interconversions as well as cationic antimicrobial peptide resistance. These findings underscore the in vitro prebiotic effects of o-HAs and their potential relevance in managing diverticular diseases or preventing metabolic disorders through the regulation of gut microbiota.

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AG8 Reduces Hypoxia-induced Triple Negative Breast Cancer Metastasis by Stemness Regulation

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Clinical Complementary Medicine and Pharmacology 2024年第1期4卷 54-61页

作者： Lihua Mu Yuan Hu Hong Yan Rui Jing ping liu Department of Pharmacy Medical Supplies Center of Chinese PLA General HospitalBeijing 100853China Department of Obstetrics and Gynecology the First Medical Centre of Chinese PLA General HospitalBeijing 100853China

Background:AG8,a triterpenoid saponin isolated from Ardisia gigantifolia Stapf.,our previous studies found that AG8 inhibited the proliferation of triple negative breast cancers(TNBCs)by including ROS generation and triggering mitochondrial apoptotic pathways.Cancer stem cells(CSCs)capable of maintain relatively low levels of ROS,are vulnerable to the interference of redox state.Compounds capable of generating ROS can affect the finely balanced redox state of CSCs and have potency to selectively kill them.Objective:We selected BT-549 which is most sensitive to AG8 to further study the effects of AG8 on hypoxia-induced proliferation,metastasis and CSCs.Methods:The hypoxia condition was simulated by CoCl2 and cell viability assay of BT-549 cells was performed us-ing MTT.Stemness phenotype were identified using breast CSCs marker(CD24^(−)/low/CD44^(+))and mammosphere formation assay.Cell motility was determined via the wound healing assay and transwell migration.Protein levels of HIF1-α,Oct-4,SOX-2,c-MYC were tested by western blotting.Results:In this study,AG8 showed significant cytotoxic effects on BT-549 triple negative breast cancer cells,but the effects were impaired by HIF1 activation.AG8 inhibited the hypoxia-induced migration and invasion of BT-549 cells.Further studies revealed that hypoxia-induced increases of CD44^(+)CD24^(−)/low and mammosphere population were significantly inhibited by AG8 dose-dependently.Moreover,AG8 decreased the Oct-4 and SOX-2 protein expression without affecting HIF1-αand c-MYC.AG8 significantly inhibited BT-549 xenograft tumors growth in BALB/c nude mice comparing with that of the control group.Conclusion:In summary,AG8 inhibited hypoxia-induced cell migration and invasion through stemness regula-tions,indicating novel mechanisms for the antitumor effects of AG8 against triple negative breast cancer.

关键词： Triterpenoid saponin TNBC hypoxia CSC Metastasis

Control Strategies for Digital Twin Systems

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IEEE/CAA Journal of Automatica Sinica 2024年第1期11卷 170-180页

作者： Guo-ping liu IEEE the Center for Control Science and Technology Southern University of Science and TechnologyShenzhen 518055China

With the continuous breakthrough in information technology and its integration into practical applications, industrial digital twins are expected to accelerate their development in the near future. This paper studies various control strategies for digital twin systems from the viewpoint of practical applications.To make full use of advantages of digital twins for control systems, an architecture of digital twin control systems, adaptive model tracking scheme, performance prediction scheme, performance retention scheme, and fault tolerant control scheme are proposed. Those schemes are detailed to deal with different issues on model tracking, performance prediction, performance retention, and fault tolerant control of digital twin systems. Also, the stability of digital twin control systems is analysed. The proposed schemes for digital twin control systems are illustrated by examples.

关键词： Digital twin control systems fault tolerant control model tracking performance prediction performance retention

Privacy-Preserving Consensus-Based Distributed Economic Dispatch of Smart Grids via State Decomposition

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IEEE/CAA Journal of Automatica Sinica 2024年第5期11卷 1250-1261页

作者： Wei Chen Guo-ping liu The authors are with the Center for Control Science and Technology Southern University of Science and TechnologyShenzhen 518055China

This paper studies the privacy-preserving distributed economic dispatch(DED)problem of smart grids.An autonomous consensus-based algorithm is developed via local data exchange with neighboring nodes,which covers both the islanded mode and the grid-connected mode of smart grids.To prevent power-sensitive information from being disclosed,a privacy-preserving mechanism is integrated into the proposed DED algorithm by randomly decomposing the state into two parts,where only partial data is transmitted.Our objective is to develop a privacy-preserving DED algorithm to achieve optimal power dispatch with the lowest generation cost under physical constraints while preventing sensitive information from being eavesdropped.To this end,a comprehensive analysis framework is established to ensure that the proposed algorithm can converge to the optimal solution of the concerned optimization problem by means of the consensus theory and the eigenvalue perturbation approach.In particular,the proposed autonomous algorithm can achieve a smooth transition between the islanded mode and the grid-connected mode.Furthermore,rigorous analysis is given to show privacy-preserving performance against internal and external eavesdroppers.Finally,case studies illustrate the feasibility and validity of the developed algorithm.

关键词： preserving autonomous mode

Targeting tau in Alzheimer's disease:from mechanisms to clinical therapy

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Neural Regeneration Research 2024年第7期19卷 1489-1498页

作者： Jinwang Ye Huali Wan Sihua Chen Gong-ping liu Shenzhen Key Laboratory of Marine Biotechnology and Ecology College of Life Sciences and OceanographyShenzhen UniversityShenzhenGuangdong ProvinceChina Department of Laboratory Medicine Guangdong Provincial People’s Hospital(Guangdong Academy of Medical Sciences)Southern Medical UniversityGuangzhouGuangdong ProvinceChina Co-innovation Center of Neurodegeneration Nantong UniversityNantongJiangsu ProvinceChina Department of Pathophysiology School of Basic Medicine and the Collaborative Innovation Center for Brain ScienceKey Laboratory of Ministry of Education of China and Hubei Province for Neurological DisordersTongji Medical CollegeHuazhong University of Science and TechnologyWuhanHubei ProvinceChina

Alzheimer’s disease is the most prevalent neurodegenerative disease affecting older adults.Primary features of Alzheimer’s disease include extra cellular aggregation of amyloid-βplaques and the accumulation of neurofibrillary tangles,fo rmed by tau protein,in the cells.While there are amyloid-β-ta rgeting therapies for the treatment of Alzheimer’s disease,these therapies are costly and exhibit potential negative side effects.Mounting evidence suggests significant involvement of tau protein in Alzheimer’s disease-related neurodegeneration.As an important microtubule-associated protein,tau plays an important role in maintaining the stability of neuronal microtubules and promoting axonal growth.In fact,clinical studies have shown that abnormal phosphorylation of tau protein occurs before accumulation of amyloid-βin the brain.Various therapeutic strategies targeting tau protein have begun to emerge,and are considered possible methods to prevent and treat Alzheimer’s disease.Specifically,abnormalities in post-translational modifications of the tau protein,including aberrant phosphorylation,ubiquitination,small ubiquitin-like modifier(SUMO)ylation,acetylation,and truncation,contribute to its microtubule dissociation,misfolding,and subcellular missorting.This causes mitochondrial damage,synaptic impairments,gliosis,and neuroinflammation,eventually leading to neurodegeneration and cognitive deficits.This review summarizes the recent findings on the underlying mechanisms of tau protein in the onset and progression of Alzheimer’s disease and discusses tau-targeted treatment of Alzheimer’s disease.

关键词： acetylation Alzheimer’s disease cognitive deficits gliosis mitochondria damage neuroinflammation phosphorylation synaptic impairments tau tau immunotherapy