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Emerging mechanisms and implications of c GAS-STING signaling in cancer immunotherapy strategies

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Cancer Biology & Medicine 2024年第1期21卷 45-64页

作者： Jiawen Zhang Sihui yu Qiao Peng ping Wang Lan Fang Tongji University Cancer Center Shanghai Tenth People’s HospitalSchool of MedicineTongji UniversityShanghai 200072China Reproductive Medicine Center Department of Obstetrics and GynecologyShanghai General HospitalShanghai Jiao Tong University School of MedicineShanghai 201620China Department of Obstetrics and Gynecology Zhongshan HospitalFudan UniversityShanghai 200032China

The intricate interplay between the human immune system and cancer development underscores the central role of immunotherapy in cancer treatment.Within this landscape,the innate immune system,a critical sentinel protecting against tumor incursion,is a key player.The cyclic GMP-AMP synthase(c GAS)and stimulator of interferon genes(STING)pathway has been found to be a linchpin of innate immunity:activation of this signaling pathway orchestrates the production of type I interferon(IFN-α/β),thus fostering the maturation,differentiation,and mobilization of immune effectors in the tumor microenvironment.Furthermore,STING activation facilitates the release and presentation of tumor antigens,and therefore is an attractive target for cancer immunotherapy.Current strategies to activate the STING pathway,including use of pharmacological agonists,have made substantial advancements,particularly when combined with immune checkpoint inhibitors.These approaches have shown promise in preclinical and clinical settings,by enhancing patient survival rates.This review describes the evolving understanding of the c GAS-STING pathway's involvement in tumor biology and therapy.Moreover,this review explores classical and non-classical STING agonists,providing insights into their mechanisms of action and potential for optimizing immunotherapy strategies.Despite challenges and complexities,the c GAS-STING pathway,a promising avenue for enhancing cancer treatment efficacy,has the potential to revolutionize patient outcomes.

关键词： cGAS-STING pathway type I interferon cyclic dinucleotide STING agonist cancer immunotherapy

Therapeutic effect of Wendan Decoction combined with mosapride on gastroesophageal reflux disease after esophageal cancer surgery

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World Journal of Clinical Cases 2024年第13期12卷 2194-2200页

作者： yu-Jing Zhang Shen-ping Wu Department of Oncology Beijing Integrated Traditional Chinese and Western Medicine HospitalBeijing 100039China

BACKGROUND Gastroesophageal reflux disease(GERD)is a common complication of esophageal cancer surgery that can affect quality of life and increase the risk of esophageal stricture and anastomotic leakage.Wendan Decoction(WDD)is a traditional Chinese herbal formula used to treat various gastrointestinal disorders,such as gastritis,functional dyspepsia,and irritable bowel syndrome.Mosapride,a prokinetic agent,functions as a selective 5-hydroxytryptamine 4 agonist,enhancing gastrointestinal motility.AIM To evaluate the therapeutic effects of WDD combined with mosapride on GERD after esophageal cancer surgery.METHODS Eighty patients with GERD were randomly divided into treatment(receiving WDD combined with mosapride)and control(receiving mosapride alone)groups.The treatment was conducted from January 2021 to January 2023.The primary outcome was improved GERD symptoms as measured using the reflux disease questionnaire(RDQ).The secondary outcomes were improved esophageal motility(measured using esophageal manometry),gastric emptying(measured using gastric scintigraphy),and quality of life[measured via the Short Form-36(SF-36)Health Survey].RESULTS The treatment group showed a notably reduced RDQ score and improved esophageal motility parameters,such as lower esophageal sphincter pressure,peristaltic amplitude,and peristaltic velocity compared to the control group.The treatment group showed significantly higher gastric emptying rates and SF-36 scores(in both physical and mental domains)compared to the control group.No serious adverse effects were observed in either group.CONCLUSION WDD combined with mosapride is an effective and safe therapy for GERD after esophageal cancer surgery.It can improve GERD symptoms,esophageal motility,gastric emptying,and the quality of life of patients.Further studies with larger sample sizes and longer follow-up periods are required to confirm these findings.

关键词： Gastroesophageal reflux disease Esophageal cancer surgery Wendan Decoction Mosapride Treatment effects Gastroesophageal reflux disease symptoms

Microdeletion on Xq27.1 in a Chinese VACTERL-Like Family with Kidney and Anal Anomalies

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Biomedical and Environmental Sciences 2024年第5期37卷 503-510页

作者： LI Min ZHANG yu Lan ZHANG Kai Li LI ping ping Lyu yu Han LIANG Ya Xin yu yue Department of Gynecology and Obstetrics Beijing HospitalNational Center of GerontologyInstitute of Geriatric MedicineChinese Academy of Medical SciencesBeijing 100730China Chinese Academy of Medical Sciences and Peking Union Medical College Beijing HospitalBeijing 100730China The Key Laboratory of Geriatrics Beijing Institute of GeriatricsBeijing HospitalNational Center of GerontologyInstitute of Geriatric MedicineChinese Academy of Medical SciencesBeijing 100730China

Objective VATER/VACTERL-like association is associated with adverse pregnancy outcomes.Genetic evidence of this disorder is sporadic.In this study,we aimed to provide genetic insights to improve the diagnosis of VACTERL.Methods We have described a Chinese family in which four members were affected by renal defects or agenesis,anal atresia,and anovaginal fistula,which is consistent with the diagnosis of a VACTERL-like association.Pedigree and genetic analyses were conducted using genome and exome sequencing.Results Segregation analysis revealed the presence of a recessive X-linked microdeletion in two living affected individuals,harboring a 196–380 kb microdeletion on Xq27.1,which was identified by familial exome sequencing.Genome sequencing was performed on the affected male,confirming a-196 kb microdeletion in Xq27.1,which included a 28%loss of the CDR-1 gene.Four family members were included in the co-segregation analysis,and only VACTERL-like cases with microdeletions were reported in X27.1.Conclusion These results suggest that the 196–380 kb microdeletion in Xq27.1 could be a possible cause of the VATER/VACTERL-like association.However,further genetic and functional analyses are required to confirm or rule out genetic background as the definitive cause of the VACTERL association.

关键词： Prenatal diagnosis VACTERL whole-genome sequencing whole-exome sequencing X-linked

Optimal Cooperative Secondary Control for Islanded DC Microgrids via a Fully Actuated Approach

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IEEE/CAA Journal of Automatica Sinica 2024年第2期11卷 405-417页

作者： Yi yu Guo-ping Liu Yi Huang Peng Shi IEEE Shenzhen Key Laboratory of Control Theory and Intelligent Systems Southern University of Science and TechnologyShenzhen 518055China School of Electrical Engineering and Automation Wuhan UniversityWuhan 430072China School of Electrical and Mechanical Engineering the University of AdelaideSA 5005Australia Research and Innovation Centre Obuda University1034 BudapestHungary

DC-DC converter-based multi-bus DC microgrids(MGs) in series have received much attention, where the conflict between voltage recovery and current balancing has been a hot topic. The lack of models that accurately portray the electrical characteristics of actual MGs while is controller design-friendly has kept the issue active. To this end, this paper establishes a large-signal model containing the comprehensive dynamical behavior of the DC MGs based on the theory of high-order fully actuated systems, and proposes distributed optimal control based on this. The proposed secondary control method can achieve the two goals of voltage recovery and current sharing for multi-bus DC MGs. Additionally, the simple structure of the proposed approach is similar to one based on droop control, which allows this control technique to be easily implemented in a variety of modern microgrids with different configurations. In contrast to existing studies, the process of controller design in this paper is closely tied to the actual dynamics of the MGs. It is a prominent feature that enables engineers to customize the performance metrics of the system. In addition, the analysis of the stability of the closed-loop DC microgrid system, as well as the optimality and consensus of current sharing are given. Finally, a scaled-down solar and battery-based microgrid prototype with maximum power point tracking controller is developed in the laboratory to experimentally test the efficacy of the proposed control method.

关键词： DC microgrids distributed control high-order fully actuated system approach linear quadratic regulator microgrid modeling secondary control

Mesenchymal stem cells for repairing glaucomatous optic nerve

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International Journal of Ophthalmology(English edition) 2024年第4期17卷 748-760页

作者： Bai-yu Hu Mei Xin Ming Chen ping yu Liu-Zhi Zeng Eye School of Chengdu University of TCM Chengdu 610000Sichuan ProvinceChina Department of Ophthalmology Chengdu First People’s HospitalChengdu 610095Sichuan ProvinceChina

Glaucoma is a common and complex neurodegenerative disease characterized by progressive loss of retinal ganglion cells(RGCs)and axons.Currently,there is no effective method to address the cause of RGCs degeneration.However,studies on neuroprotective strategies for optic neuropathy have increased in recent years.Cell replacement and neuroprotection are major strategies for treating glaucoma and optic neuropathy.Regenerative medicine research into the repair of optic nerve damage using stem cells has Received considerable attention.Stem cells possess the potential for multidirectional differentiation abilities and are capable of producing RGCfriendly microenvironments through paracrine effects.This article reviews a thorough researches of recent advances and approaches in stem cell repair of optic nerve injury,raising the controversies and unresolved issues surrounding the future of stem cells.

关键词： stem cell glaucoma retinal ganglion cell optic nerve axon regeneration

Spherical Confinement Generates Entropic Force to Accelerate Polymer Chain Detachment

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Chinese Journal of Polymer Science 2024年第3期42卷 407-416,I0010页

作者： yu-Shan Zheng Jian-ping Zhou Yan Xu Kai Li Mechanical Engineering Xinjiang UniversityUrumqi 830002China

To understand the dynamic process of polymer detachment, it is necessary to determine the mean detachment time of a single breakable link, which is modeled as a spring. Normally, this time can be viewed as the escape of a Brownian particle from the potential well of the spring. However, as the free dangling length of the polymer chain increases, the conformational entropy of the chain is affected by geometric confinement. It means that the wall exerts a repulsive force on the chain, resulting in accelerated link detachment from a macroscopic perspective. In this work, we investigate the effect of entropy on the detachment rate in the case where the substrate is spherical. We demonstrate that spherical confinement accelerates chain detachment both inside and outside the sphere. An analytical expression for the mean detachment time of breakable links is given, which includes an additional pre-factor that is related to the partition function. Additionally, we analyze the expressions for entropic forces inside the sphere, outside the sphere, and on a flat wall, comparing their magnitudes to explain the difference in mean detachment time.

关键词： Polymer detachment Breakable link Entropic force Mean first passage time

Retinoic acid alleviates rotavirus-induced intestinal damage by regulating redox homeostasis and autophagic flux in piglets

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Animal Nutrition 2024年第1期16卷 409-421页

作者： Xin Lai Aimin Wu Bing yu Hui Yan Junqiu Luo ping Zheng Jie yu Daiwen Chen Institute of Animal Nutrition Sichuan Agricultural University Key Laboratory for Animal Disease-resistance Nutrition of China Ministry of Education Sichuan Agricultural University

Rotaviruses(RV) are a major cause of severe gastroenteritis, particularly in neonatal piglets. Despite the availability of effective vaccines, the development of antiviral therapies for RV remains an ongoing challenge. Retinoic acid(RA), a metabolite of vitamin A, has been shown to have anti-oxidative and antiviral properties. However, the mechanism by which RA exerts its intestinal-protective and antiviral effects on RV infection is not fully understood. The study investigates the effects of RA supplementation in Duroc × Landrace × Yorkshire(DLY) piglets challenged with RV. Thirty-six DLY piglets were assigned into six treatments, including a control group, RA treatment group with two concentration gradients(5and 15 mg/d), RV treatment group, and RV treatment group with the addition of different concentration gradients of RA(5 and 15 mg/d). Our study revealed that RV infection led to extensive intestinal architecture damage, which was mitigated by RA treatment at lower concentrations by increasing the villus height and villus height/crypt depth ratio(P < 0.05), enhancing intestinal stem cell signaling and promoting intestinal barrier functions. In addition, 15 mg/d RA supplementation significantly increased NRF2 and HO-1 protein expression(P < 0.05) and GSH content(P < 0.05), indicating that RA supplementation can enhance anti-oxidative signaling and redox homeostasis after RV challenge. Additionally,the research demonstrated that RA exerts a dual impact on the regulation of autophagy, both stimulating the initiation of autophagy and hindering the flow of autophagic flux. Through the modulation of autophagic flux, RA influence the progression of RV infection. These findings provide new insights into the regulation of redox hemostasis and autophagy by RA and its potential therapeutic application in RV infection.

关键词： Rotavirus Piglet Retinoic acid Intestinal barrier Redox hemostasis Autophagic flux

Prediction of chemical short-range order in high-/medium-entropy alloys

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Journal of Materials Science & Technology 2024年第2期169卷 115-123页

作者： Pei-yu Cao Jing Wang ping Jiang yun-Jiang Wang Fu-ping yuan Xiao-Lei Wu State Key Laboratory of Nonlinear Mechanics Institute of MechanicsChinese Academy of ScienceBeijing 100190China School of Engineering Science University of Chinese Academy of SciencesBeijing 100049China

Chemical short-range orders(CSROs),as the built-in sub-nanoscale entities in a high-/medium-entropy alloy(H/MEA),have aroused an ever-increasing interest.With multi-principal elements in an H/MEA to form a complex concentrated solution,a variety of sub-systems of species exist to induce the metastable ordered compounds as candidates for ultimate CSROs.The issues remain pending on the origin of CSROs as to how to judge if CSRO will form in an H/MEA and particularly,what kind of CSROs would be stably produced if there were multiple possibilities.Here,the first-principles method,along with the proposed local formation energy calculation in allusion to the atomic-scale chemical heterogeneities,is used to predict the CSRO formation based on the mechanical stability,thermodynamic formation energy,and electronic characteristics.The simulations are detailed in an equiatomic ternary VCoNi MEA with three kinds of potential compounds,i.e.,L1_(1),L1_(2),and B2,in the face-centered cubic matrix.It turns out that L1_(1)is stable but hard to grow up so as to become the final CSRO.L1_(1)is further predicted as CSROs in CrCoNi,but unable to form in FeCoNi and CrMnFeCoNi alloys.These predictions are consistent with the experimental observations.Our findings shed light on understanding the formation of CSROs.This method is applicable to other H/MEAs to design and tailor CSROs by tuning chemical species/contents and thermal processing for high performance.

关键词： Short-range order High-entropy alloy Microstructure First-principles calculation Gibbs free energy Local electronic density of states

Transglutaminase 2 serves as a pathogenic hub gene of KRAS mutant colon cancer based on integrated analysis

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World Journal of Gastrointestinal Oncology 2024年第5期16卷 2074-2090页

作者： Wei-Bin Peng yu-ping Li Yong Zeng Kai Chen First People’s Hospital of Foshan Foshan 528000Guangdong ProvinceChina Department of Radiation Oncology Cancer Hospital of Shantou University Medical CollegeShantou 515031Guangdong ProvinceChina

BACKGROUND Colon cancer is acknowledged as one of the most common malignancies worldwide,ranking third in United States regarding incidence and mortality.Notably,approximately 40%of colon cancer cases harbor oncogenic KRAS mutations,resulting in the continuous activation of epidermal growth factor receptor signaling.AIM To investigate the key pathogenic genes in KRAS mutant colon cancer holds considerable importance.METHODS Weighted gene co-expression network analysis,in combination with additional bioinformatics analysis,were conducted to screen the key factors driving the progression of KRAS mutant colon cancer.Meanwhile,various in vitro experiments were also conducted to explore the biological function of transglutaminase 2(TGM2).RESULTS Integrated analysis demonstrated that TGM2 acted as an independent prognostic factor for progression-free survival.Immunohistochemical analysis on tissue microarrays revealed that TGM2 was associated with an elevated probability of perineural invasion in patients with KRAS mutant colon cancer.Additionally,biological roles of the key gene TGM2 was also assessed,suggesting that the downregulation of TGM2 attenuated the proliferation,invasion,and migration of the KRAS mutant colon cancer cell line.CONCLUSION This study underscores the potential significance of TGM2 in the progression of KRAS mutant colon cancer.This insight not only offers a theoretical foundation for therapeutic approaches but also highlights the need for additional clinical trials and fundamental research to support our preliminary findings.

关键词： Colon cancer KRAS mutation Transglutaminase 2 Weighted gene co-expression network analysis