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Cancer immunotherapy with envelopedself-amplifying mRNA CARG-2020 thatmodulates IL-12,IL-17 and PD-L1 pathways toprevent tumor recurrence

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Acta Pharmaceutica Sinica B 2024年第1期14卷 335-349页

作者： Ju Chen Bhaskara Reddy Madina Elham Ahmadi Timur Olegovich Yarovinsky Marie Marthe Krady Eileen Victoria Meehan Isabella China Wang Xiaoyang Ye Elise Pitmon Xian-Yong Ma Bijan Almassian Valerian Nakaar Kepeng Wang Department of Immunology School of MedicineUniversity of Connecticut Health CenterFarmingtonCT 06030USA CaroGen Corporation FarmingtonCT 06030USA The Eighth Clinical Medical College of Guangzhou university of Chinese medicine Foshan Hospital of Traditional Chinese MedicineFoshan 528000China The Loomis Chaffee school WindsorCT 06095USA

Targeting multiple immune mechanisms may overcome therapy resistance and further improve cancer immunotherapy for ***,we describe the application of virus-like vesicles(VLV)for delivery of three immunomodulators alone and in combination,as a promising approach for cancer *** vectors were designed to deliver single chain interleukin(IL)-12,shorthairpin RNA(shRNA)targeting programmed death ligand 1(PD-L1),and a dominant-negative form of IL-17 receptor A(dn-IL17RA)as a single payload or as a combination *** delivery of the VLV vector expressing IL-12 alone,as well as the trivalent vector(designated CARG-2020)eradicated large established ***,only CARG-2020 prevented tumor recurrence and provided long-term survival benefit to the tumor-bearing mice,indicating a benefit of the combined *** abscopal effects of CARG-2020 on the non-injected contralateral tumors,as well as protection from the tumor cell re-challenge,suggest immune-mediated mechanism of protection and establishment of immunological ***,CARG-2020 potently activates Th1 immune mechanisms and inhibits expression of genes related to T cell exhaustion and cancer-promoting *** ability of CARG-2020 to prevent tumor recurrence and to provide survival benefit makes it a promising candidate for its development for human cancer immunotherapy.

关键词： Virus-like vesicles Oncolytic virus IL-12 IL-17 PD-L1 T cell exhaustion Combination therapy Cancer immunotherapy

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Experimental Investigation of Thermal Performance of Novel Finned Radiators for Automotive Cooling System

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Journal of Thermal Science 2024年第5期33卷 1726-1743页

作者： SINGH Hardeep TING David S-K READER Graham ESHTIAGHI Nicky ICHIYANAGI Mitsuhisa SUZUKI Takashi Turbulence&Energy Laboratory University of WindsorWindsor N9B 3P4Canada Chemical and Environmental Engineering School of EngineeringRMIT UniversityMelbourneVictoria 3001Australia Department of Engineering and Applied Sciences Sophia UniversityTokyo 102-8554Japan

This research investigates innovative fin-type radiators for automobile engine cooling ***-channel and helical radiators,along with straight type,were analyzed for heat transfer characteristics under various *** uniqueness of this study is evident in the design of microchannel and helical *** helical radiators,the inner rod features 4/8 helical-shaped water galleries,while the outer tube frame with embedded fins remains *** contrast,the microchannel radiators have compact trapezoidal-shaped water galleries with separate fin ***,the novelty of the research is enhanced by the utilization of 3D printing technology in the manufacturing *** constant fin height analysis at varied water and air flow rate,Microchannel Water Air Radiator with fin height 10.5 mm(MCWAR10.5)depicted a higher heat transfer rate amongst the *** comparison to Straight Water Air Radiator with fin height 9.5 mm(SWAR9.5),the heat transfer rate is 30.3%and 1.3 times ***,in constant fin surface area analysis,microchannel radiator(MCWAR3.2)illustrates lower heat dissipation than Helical radiator(HWAR138)but higher than HWAR134 and Straight radiator(SWAR6).The examination of pumping loss indicated that the Micro-channel radiator outperformed helical radiators due to its lower pressure *** average pressure loss for Micro-channel radiators was 0.74 kPa,making it 1.2 times higher than that of a straight radiator(0.62 kPa),indicating a better trade-off.

关键词： heat exchangers multi-channel helical heat exchanger heat transfer 3D printing

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Regenerative medicine strategies for chronic complete spinal cord injury

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Neural Regeneration Research 2024年第4期19卷 818-824页

作者： Shogo Hashimoto Narihito Nagoshi Masaya Nakamura Hideyuki Okano Department of Orthopedic Surgery Keio University School of Medicine Department of Physiology Keio University School of Medicine

Spinal cord injury is a condition in which the parenchyma of the spinal cord is damaged by trauma or various *** rapid progress has been made in regenerative medicine for spinal cord injury that was previously untreatable,most research in this field has focused on the early phase of incomplete ***,the majority of patients have chronic severe injuries;therefore,treatments for these situations are of fundamental *** reason why the treatment of complete spinal cord injury has not been studied is that,unlike in the early stage of incomplete spinal cord injury,there are various inhibitors of neural ***,we assumed that it is difficult to address all conditions with a single treatment in chronic complete spinal cord injury and that a combination of several treatments is essential to target severe ***,we established a combination therapy of cell transplantation and drug-releasing scaffolds,which contributes to functional recovery after chronic complete transection spinal cord injury,but we found that functional recovery was limited and still needs further ***,for the further development of the treatment of chronic complete spinal cord injury,we review the necessary approaches to the different pathologies based on our findings and the many studies that have been accumulated to date and discuss,with reference to the literature,which combination of treatments is most effective in achieving functional recovery.

关键词： cell transplantation chronic phase complete transection regenerative medicine spinal cord injury

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Cannabinoids and endocannabinoids as therapeutics for nervous system disorders:preclinical models and clinical studies

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Neural Regeneration Research 2024年第4期19卷 788-799页

作者： R.Scott Duncan Sean M.Riordan Matthew C.Gernon Peter Koulen Department of Ophthalmology School of MedicineUniversity of Missouri Department of Biomedical Sciences School of MedicineUniversity of Missouri

Cannabinoids are lipophilic substances derived from Cannabis sativa that can exert a variety of effects in the human *** have been studied in cellular and animal models as well as in human clinical trials for their therapeutic benefits in several human *** of these include central nervous system(CNS)diseases and dysfunctions such as forms of epilepsy,multiple sclerosis,Parkinson’s disease,pain and neuropsychiatric *** addition,the endogenously produced cannabinoid lipids,endocannabinoids,are critical for normal CNS function,and if controlled or modified,may represent an additional therapeutic avenue for CNS *** review discusses in vitro cellular,ex vivo tissue and in vivo animal model studies on cannabinoids and their utility as therapeutics in multiple CNS *** addition,the review provides an overview on the use of cannabinoids in human clinical trials for a variety of CNS *** and endocannabinoids hold promise for use as disease modifiers and therapeutic agents for the prevention or treatment of neurodegenerative diseases and neurological disorders.

关键词： anandamide cannabidiol cannabinoid endocannabinoid epilepsy multiple sclerosis neurodegeneration neuroprotection tetrahydrocannabinol

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Effect of Chinese medicine in Patients with COVID-19: A Multi-center Retrospective Cohort Study

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Chinese Journal of Integrative medicine 2024年第11期30卷 974-983页

作者： ZHAO Guo-zhen YAN Shi-yan LI Bo GUO Yu-hong SONG Shuang HU Ya-hui GUO Shi-qi HU Jing DU Yuan LU Hai-tian YE Hao-ran REN Zhi-ying ZHU Ling-fei XU Xiao-long SU Rui LIU Qing-quan Beijing Hospital of Traditional Chinese medicine Capital Medical University Beijing Institute of Traditional Chinese Medicine school of Clinical medicine Beijing University of Chinese Medicine school of Acupuncture-Moxibustion and Tuina Beijing University of Chinese Medicine College of Integrated Chinese medicine Tianjin University of Traditional Chinese Medicine

Objective: To evaluate the effectiveness and safety of Chinese medicine(CM) in the treatment of coronavirus disease 2019(COVID-19) in China. Methods: A multi-center retrospective cohort study was carried out, with cumulative CM treatment period of 3 days during hospitalization as exposure. Data came from consecutive inpatients from December 19, 2019 to May 16, 2020 in 4 medical centers in Wuhan, China. After data extraction, verification and cleaning, confounding factors were adjusted by inverse probability of treatment weighting(IPTW), and the Cox proportional hazards regression model was used for statistical analysis. Results:A total of 2,272 COVID-19 patients were included. There were 1,684 patients in the CM group and 588 patients in the control group. Compared with the control group, the hazard ratio(HR) for the deterioration rate in the CM group was 0.52 [95% confidence interval(CI): 0.41 to 0.64, P<0.001]. The results were consistent across patients of varying severity at admission, and the robustness of the results were confirmed by 3 sensitivity analyses. In addition, the HR for all-cause mortality in the CM group was 0.29(95% CI: 0.19 to 0.44, P<0.001).Regarding of safety, the proportion of patients with abnormal liver function or renal function in the CM group was smaller. Conclusion: This real-world study indicates that the combination of a full-course CM therapy on the basic conventional treatment, may safely reduce the deterioration rate and all-cause mortality of COVID-19patients. This result can provide the new evidence to support the current treatment of COVID-19. Additional prospective clinical trial is needed to evaluate the efficacy and safety of specific CM interventions.(Registration No. ChiCTR2200062917)

关键词： Chinese medicine all-cause mortality cohort study coronavirus disease 2019 deterioration rate

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Pathophysiological changes of muscle after ischemic stroke:a secondary consequence of stroke injury

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Neural Regeneration Research 2024年第4期19卷 737-746页

作者： Hu Qi Dan Tian Fei Luan Ruocong Yang Nan Zeng State Key Laboratory of Southwestern Chinese medicine Resources Chengdu University of Traditional Chinese Medicine school of Pharmacy Chengdu University of Traditional Chinese Medicine Acupuncture and Tuina school Chengdu University of Traditional Chinese Medicine

Sufficient clinical evidence suggests that the damage caused by ischemic stroke to the body occurs not only in the acute phase but also during the recovery period,and that the latter has a greater impact on the long-term prognosis of the ***,current stroke studies have typically focused only on lesions in the central nervous system,ignoring secondary damage caused by this *** a phenomenon arises from the slow progress of pathophysiological studies examining the central nervous ***,the appropriate therapeutic time window and benefits of thrombolytic therapy are still controversial,leading scholars to explore more pragmatic intervention *** treatment measures targeting limb symptoms can greatly improve a patient’s quality of life,they have become a critical intervention *** the most vital component of the limbs,skeletal muscles have become potential points of *** this,to the best of our knowledge,there are no comprehensive reviews of pathophysiological changes and potential treatments for post-stroke skeletal *** current review seeks to fill a gap in the current understanding of the pathological processes and mechanisms of muscle wasting atrophy,inflammation,neuroregeneration,mitochondrial changes,and nutritional dysregulation in stroke *** addition,the challenges,as well as the optional solutions for individualized rehabilitation programs for stroke patients based on motor function are discussed.

关键词： inflammation ischemic stroke mitochondria muscle atrophy muscle fiber muscle nutrition quality of life rehabilitation ubiquitin

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Paeoniflorin ameliorates chronic colitis via the DR3 signaling pathway in group 3 innate lymphoid cells

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Journal of Pharmaceutical Analysis 2024年第6期14卷 889-901页

作者： Shaowei Huang Xueqian Xie Bo Xu Zengfeng Pan Junjie Liang Meiling Zhang Simin Pan Xiaojing Wang Meng Zhao Qing Wang Jinyan Chen Yanyang Li Lian Zhou Xia Luo school of Pharmaceutical Sciences Guangzhou University of Chinese Medicine510006China school of Basic medicine Guangzhou University of Chinese Medicine510006China First Clinical Medical College Guangzhou University of Chinese Medicine510000China

Inhibiting the death receptor 3(DR3)signaling pathway in group 3 innate lymphoid cells(ILC3s)presents a promising approach for promoting mucosal repair in individuals with ulcerative colitis(UC).Paeoniflorin,a prominent component of Paeonia lactiflora Pall.,has demonstrated the ability to restore barrier function in UC mice,but the precise mechanism remains *** this study,we aimed to delve into whether paeoniflorin may promote intestinal mucosal repair in chronic colitis by inhibiting DR3 signaling in ILC3s.C57BL/6 mice were subjected to random allocation into 7 distinct groups,namely the control group,the 2%dextran sodium sulfate(DSS)group,the paeoniflorin groups(25,50,and 100 mg/kg),the anti-tumor necrosis factor-like ligand 1A(anti-TL1A)antibody group,and the IgG *** detected the expression of DR3 signaling pathway proteins and the proportion of ILC3s in the mouse colon using Western blot and flow cytometry,***,DR3-overexpressing MNK-3 cells and 2%DSS-induced Rag1^(-/-)mice were used for *** results showed that paeoniflorin alleviated DSS-induced chronic colitis and repaired the intestinal mucosal ***,paeoniflorin inhibited the DR3 signaling pathway in ILC3s and regulated the content of cytokines(interleukin-17A,granulocyte-macrophage colony stimulating factor,and interleukin-22).Alternatively,paeoniflorin directly inhibited the DR3 signaling pathway in ILC3s to repair mucosal damage independently of the adaptive immune *** additionally confirmed that paeoniflorin-conditioned medium(CM)restored the expression of tight junctions in Caco-2 cells via *** conclusion,paeoniflorin ameliorates chronic colitis by enhancing the intestinal barrier in an ILC3-dependent manner,and its mechanism is associated with the inhibition of the DR3 signaling pathway.

关键词： Paeoniflorin Ulcerative colitis Intestinal mucosal barrier DR3 signaling pathway Group 3 innate lymphoid cells

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Therapeutic Role of Chinese medicine Targeting Nrf2/HO-1 Signaling Pathway in Myocardial Ischemia/Reperfusion Injury

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Chinese Journal of Integrative medicine 2024年第10期30卷 949-960页

作者： LIU Chang-xing GUO Xin-yi ZHOU Ya-bin WANG He First Clinical Medical school Heilongjiang University of Chinese Medicine Clinical Medical school Chengdu University of Traditional Chinese Medicine Department of Cardiology the First Affiliated Hospital of Heilongjiang University of Chinese Medicine

Acute myocardial infarction(AMI), characterized by high incidence and mortality rates, poses a significant public health threat. Reperfusion therapy, though the preferred treatment for AMI, often exacerbates cardiac damage, leading to myocardial ischemia/reperfusion injury(MI/RI). Consequently, the development of strategies to reduce MI/RI is an urgent priority in cardiovascular therapy. Chinese medicine, recognized for its multi-component, multi-pathway, and multi-target capabilities, provides a novel approach for alleviating MI/RI. A key area of interest is the nuclear factor E2-related factor 2(Nrf2)/heme oxygenase-1(HO-1) pathway. This pathway is instrumental in regulating inflammatory responses, oxidative stress, apoptosis, endoplasmic reticulum stress, and ferroptosis in MI/RI. This paper presents a comprehensive overview of the Nrf2/HO-1 signaling pathway's structure and its influence on MI/RI. Additionally, it reviews the latest research on leveraging Chinese medicine to modulate the Nrf2/HO-1 pathway in MI/RI treatment.

关键词： Chinese medicine mechanisms myocardial ischemia/reperfusion injury nuclear factor E2-related factor 2/heme oxygenase-1 signaling pathway

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Commentary on“Desialylated Platelets Maintain Immune Quiescence through Regulating Kupffer Cells”

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Research 2024年第3期6卷 621-623页

作者： Chen Li Craig N.Morrell Aab Cardiovascular Research Institute University of Rochester School of Medicine and DentistryRochesterNYUSA Department of Pharmacology and Physiology University of Rochester School of Medicine and DentistryRochesterNYUSA Department of medicine University of Rochester School of Medicine and DentistryRochesterNYUSA Department of Microbiology and Immunology University of Rochester School of Medicine and DentistryRochesterNYUSA Department of Pathology and Laboratory medicine University of Rochester School of Medicine and DentistryRochesterNYUSA.

Platelets have long been studied for their roles in hemostasis and vascular injury repair. However, there is a continually evolving and deepening understanding that platelets initiate and regulate responses to tissue injury and pathogens, leading to platelets now being considered immune modulatory cells [1]. Platelets actively participate in host immune responses directly through pathogen engulfing and killing, or by regulating both innate and adaptive immune responses to infection or tissue injury [2]. Activated platelets promote inflammatory responses to tissue injury or infection by direct contact dependent interactions with immune cells and through indirect interactions via released soluble factors. However, mice that are deficient in platelets have skewed T helper cell differentiation [3] and increased vascular permeability [4], implying poorly defined roles for platelets in maintaining healthy immune homeostasis.

关键词： Platelet homeostasis Immune

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Anti-N-methyl-D-aspartate receptor type autoimmune encephalitis with severe pneumonia:a case report

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World Journal of Emergency medicine 2024年第2期15卷 142-146页

作者： Yi Gu Xiandong Liu Tiancao Dong Qian Yang Xiaowei Bao Dongyang Zhao Lunxian Tang Department of Internal Emergency medicine Shanghai East HospitalSchool of MedicineTongji UniversityShanghai 200120China school of medicine Tongji UniversityShanghai 200120China

Autoimmune encephalitis(AE)is a type of encephalitis caused by autoimmune *** was included on a list of the first batch of 121 rare diseases published by the Chinese National Health Commission on 11^(th)May ***,patients with AE account for 10%-20% of encephalitis cases,with 54%-80% of those cases classified as the anti-N-methyl-D-aspartate receptor(NMDAR)type,which is the most common type.[1]In 2010,China reported the first case of a patient withanti-NMDARtype AE.

关键词： encephalitis autoimmune aspartate

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