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Tongqiao Yizhi granule(通窍益智颗粒) repress the nuclear factor kappa-b/nucleotide oligomerization domain-like receptors 3/caspase-1 pyroptosis pathway in the hippocampus to counter vascular dementia in rats

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Journal of Traditional Chinese Medicine 2024年第4期 680-687页

作者： LI Yanjiao HAO Linyao LI Shuangyang LUO Yanqi WANG Juan WANG Raoqiong bai xue College of Integrative Medicine Southwest Medical University Department of Neurology and National Traditional Chinese Medicine Clinical Research Base the Affiliated Traditional Chinese Medicine Hospital of Southwest Medical University Institute of Integrated Chinese and Western Medicine Southwest Medical University

OBJECTIVE: To explore the mechanism by which Tongqiao Yizhi granule（通窍益智颗粒, TQYZKL） intervenes pyroptosis to treat vascular dementia（VaD） in a rat model. METHODS: The rat model of VaD was established by two-vessel occlusion（2VO）. The rats were randomly divided into Sham group, Model group, Nimodipine group, TQYZKL（6.2 g·kg-1·d-1）, TQYZKL(12.4 g·kg-1·d-1), TQYZKL(24.8 g·kg-1·d-1). The Morris water maze（MWM） test was carried out to test the learning and memory function; Hematoxylin-eosin staining and transmission electron microscopy（TEM） to observe the pathological damage in the hippocampus; Tunel fluorescence staining to detect neuronal pyroptosis in the hippocampus. The expression levels of pyroptosis-related proteins, namely Golgi peripheral membrane protein p65（P65）, nucleotide oligomerization domain-like receptors 3（NLRP3）, caspase-1 and Gasdermin D（GSDMD）, were detected using Western blotting and reverse transcription polymerase chain reaction. Moreover, the serum levels of interleukin-1β（IL-1β） and interleukin-18（IL-18） were determined through the enzyme-linked immunosorbent assay. RESULTS: The study revealed that TQYZKL effectively improved the ability of VaD ratsto learn and memorize, relieved the pathological damage in the hippocampus, restored neuronal morphology, and reduced the expression of pyroptosis-related proteins P65, NLRP3, caspase-1, GSDMD-N, IL-18 and IL-1β（P < 0.05）. CONCLUSION: TQYZKL inhibits neuronal pyroptosis in the hippocampus of VaD rats by regulating nuclear factor kappa-B/NLRP3/caspase-1 signaling pathway, thus exerting a therapeutic effect on VaD in the rats.

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Direct reprogramming of fibroblasts into functional hepatocytes via CRISPRa activation of endogenous Gata4 and Foxa3

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中华医学杂志(英文版) 2024年第11期137卷 2024 May 9页

作者： Li Jiacheng Li Ruopu bai xue Zhang Wenlong Nie Yu Hu Shengshou State Key Laboratory of Cardiovascular Disease Fuwai Hospital and Cardiovascular Institute National Center for Cardiovascular Diseases Chinese Academy of Medical Sciences and Peking Union Medical College Beijing China Department of Obstetrics and Gynecology Beijing Advanced Innovation Center for Genomics Third Hospital School of Life Sciences Peking University Beijing China

Background: The ability to generate functional hepatocytes without relying on donor liver organs holds significant therapeutic promise in the fields of regenerative medicine and potential liver disease treatments. Clustered regularly interspaced short palindromic repeats (CRISPR) activator (CRISPRa) is a powerful tool that can conveniently and efficiently activate the expression of multiple endogenous genes simultaneously, providing a new strategy for cell fate determination. The main purpose of this study is to explore the feasibility of applying CRISPRa for hepatocyte reprogramming and its application in the treatment of mouse liver fibrosis.Method: The differentiation of mouse embryonic fibroblasts (MEFs) into functional induced hepatocyte-like cells (iHeps) was achieved by utilizing the CRISPRa synergistic activation mediator (SAM) system, which drove the combined expression of three endogenous transcription factors—Gata4,Foxa3, andHnf1a—or alternatively, the expression of two transcription factors,Gata4 andFoxa3.In vivo, we injected adeno-associated virus serotype 6 (AAV6) carrying the CRISPRa SAM system into liver fibroticCol1a1-CreER;Cas9fl/fl mice, effectively activating the expression of endogenousGata4 andFoxa3 in fibroblasts. The endogenous transcriptional activation of genes was confirmed using real-time quantitative polymerase chain reaction (RT-qPCR) and RNA-seq, and the morphology and characteristics of the induced hepatocytes were observed through microscopy. The level of hepatocyte reprogrammingin vivo is detected by immunofluorescence staining, while the improvement of liver fibrosis is evaluated through Sirius red staining, alpha-smooth muscle actin (α-SMA) immunofluorescence staining, and blood alanine aminotransferase (ALT) examination.Results: Activation of only two factors,Gata4 andFoxa3, via CRISPRa was sufficient to successfully induce the transformation of MEFs into iHeps. These iHeps could be expandedin vitro and displayed functional characteristics similar to those of mature hepatocyte

关键词： Liver fibrosis CRISPRa Cell reprogramming Transcriptional activation Hepatocytes

Free-moving-state microscopic imaging of cerebral oxygenation and hemodynamics with a photoacoustic fiberscope

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Light(Science & Applications) 2024年第1期13卷 33-46页

作者： Xiaoxuan Zhong Yizhi Liang Xiaoyu Wang Haoying Lan xue bai Long Jin bai-Ou Guan Guangdong Provincial Key Laboratory of Optical Fiber Sensing and Communications Institute of Photonics TechnologyJinan UniversityGuangzhou510632China

We report the development of a head-mounted photoacoustic fiberscope for cerebral imaging in a freely behaving mouse.The 4.5-gram imaging probe has a 9-µm lateral resolution and 0.2-Hz frame rate over a 1.2-mm wide area.The probe can continuously monitor cerebral oxygenation and hemodynamic responses at single-vessel resolution,showing significantly different cerebrovascular responses to external stimuli under anesthesia and in the freely moving state.For example,when subjected to high-concentration CO_(2) respiration,enhanced oxygenation to compensate for hypercapnia can be visualized due to cerebral regulation in the freely moving state.Comparative studies exhibit significantly weakened compensation capabilities in obese rodents.This new imaging modality can be used for investigating both normal and pathological cerebrovascular functions and shows great promise for studying cerebral activity,disorders and their treatments.

关键词： cerebral anesthesia moving

Erratum to:CD146 as a promising therapeutic target for retinal and choroidal neovascularization diseases

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Science China(Life Sciences) 2024年第2期67卷 434-434页

作者： bai xue Ping Wang Wenzhen Yu Jing Feng Jie Li Rulian Zhao Zhenglin Yang Xiyun Yan Hongxia Duan Sichuan Provincial Key Laboratoryfor Human Disease Gene Study Sichuan Provincial People'sHospitalSchoolof MedicineUniversity of Electronic Science and Technology of ChinaChengdu 610054China Key Laboratory of Protein and Peptide Pharmaceutical Institute of BiophysicsChinese Academy of SciencesBeijing 100101China Department of Ophthalmology People's HospitalPeking UniversityBeijing 100044China Department of Ophthalmology Sichuan Provincial People's HospitalUniversity of Electronic Science and Technology of ChinaChengdu 61072China Research Unit for Blindness Prevention of Chinese Academy of Medical Sciences(2019RU026) Sichuan Academy of Medical Sciences and Sichuan Provincial People's HospitalChengdu 610072China Nanozyme Medical Center School of Basic Medical SciencesZhengzhou UniversityZhengzhou 450001China College of Life Sciences University of Chinese Academy of SciencesBeijing 100049China

Erratum to:Sci China Life Sciences,Volume 65,Issue 6:1157-1170(2022),https://***/10.1007/s11427-021-2020-0This paper contains four errors in Figure 4 and Figure 5.In Figure 4C,the image labeled as"1%O_(2)+IgG ctrl"is incorect.This image is another one for 1%O_(2) group.We provide a new image as follows for 1%O_(2)+IgG ctrl group.This new image does not affect the conclusion of this article.

关键词： Figure image CD146

On extended state Kalman filter-based identification algorithm for aerodynamic parameters

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Control Theory and Technology 2024年第2期22卷 235-243页

作者： Wenyan bai Ruizhe Jia Peng Yu Wenchao xue Beijing Aerospace Automatic Control Institute Beijing100854China School of Automation and Electrical Engineering University of Science and Technology BeijingBeijing100083China Key Laboratory of Knowledge Automation for Industrial Processes Ministry of EducationBeijing100083China Key Laboratory of Systems and Control Institute of Systems ScienceAcademy of Mathematics and Systems ScienceChinese Academy of SciencesBeijing100190China

In this paper, the problem of time-varying aerodynamic parameters identification under measurement noises is studied. By analyzing the key aerodynamic parameters that affect the aircraft control system, a system model with extended states for identifying equivalent aerodynamic parameters is established, and error parameters are extended to the system state, avoiding the difficulty caused by the unknown dynamic in the system. Furthermore, an identification algorithm based on extended state Kalman filter is designed, and it is proved that the algorithm has quasi-consistency, thus, the estimation error can be evaluated in real time. Finally, the simulation results under typical flight scenarios show that the designed algorithm can accurately identify aerodynamic parameters, and has desired convergence speed and convergence precision.

关键词： Aerodynamic parameters Parameter identification Extended state Kalman filter

Evolution of pore systems in low-maturity oil shales during thermal upgrading——Quantified by dynamic SEM and machine learning

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Petroleum Science 2024年第3期21卷 1739-1750页

作者： Jun Liu xue bai Derek Elsworth Key Laboratory of Deep Underground Science and Engineering(Ministry of Education) Institute of New Energy and Low-Carbon Technology Sichuan University International Quantum Academy Shenzhen Institute of Advanced Electronic Materials Shenzhen Institute of Advanced Technology Chinese Academy of Sciences Department of Energy and Mineral Engineering Pennsylvania State University

In-situ upgrading by heating is feasible for low-maturity shale oil, where the pore space dynamically evolves. We characterize this response for a heated substrate concurrently imaged by SEM. We systematically follow the evolution of pore quantity, size(length, width and cross-sectional area), orientation, shape(aspect ratio, roundness and solidity) and their anisotropy—interpreted by machine learning. Results indicate that heating generates new pores in both organic matter and inorganic minerals. However, the newly formed pores are smaller than the original pores and thus reduce average lengths and widths of the bedding-parallel pore system. Conversely, the average pore lengths and widths are increased in the bedding-perpendicular direction. Besides, heating increases the cross-sectional area of pores in low-maturity oil shales, where this growth tendency fluctuates at 300°C. In addition, the orientation and shape of the newly-formed heating-induced pores follow the habit of the original pores and follow the initial probability distributions of pore orientation and shape. Herein, limited anisotropy is detected in pore direction and shape, indicating similar modes of evolution both bedding-parallel and bedding-normal. We propose a straightforward but robust model to describe evolution of pore system in low-maturity oil shales during heating.

关键词： Low-maturity oil shale Pore elongation Organic matter pyrolysis In-situ thermal upgrading Scanning electron microscopy (SEM) Machine learning

MiRNA-145-5p inhibits gastric cancer progression via the serpin family E member 1-extracellular signal-regulated kinase-1/2 axis

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World Journal of Gastrointestinal Oncology 2024年第5期16卷 2123-2140页

作者： Hong-Xia bai xue-Mei Qiu Chun-Hong Xu Jian-Qiang Guo Department of Gastroenterology The Second Hospital of Shandong UniversityJinan 250000Shandong ProvinceChina Department of Gastroenterology Liaocheng People’s HospitalLiaocheng 252000Shandong ProvinceChina Department of Reproductive Center Zaozhuang Maternal and Child Health Care HospitalZaozhuang 277000Shandong ProvinceChina

BACKGROUND MicroRNAs(miRNAs)regulate gene expression and play a critical role in cancer physiology.However,there is still a limited understanding of the function and regulatory mechanism of miRNAs in gastric cancer(GC).AIM To investigate the role and molecular mechanism of miRNA-145-5p(miR145-5p)in the progression of GC.METHODS Real-time polymerase chain reaction(RT-PCR)was used to detect miRNA expression in human GC tissues and cells.The ability of cancer cells to migrate and invade was assessed using wound-healing and transwell assays,respectively.Cell proliferation was measured using cell counting kit-8 and colony formation assays,and apoptosis was evaluated using flow cytometry.Expression of the epithelial-mesenchymal transition(EMT)-associated protein was determined by Western blot.Targets of miR-145-5p were predicated using bioinformatics analysis and verified using a dual-luciferase reporter system.Serpin family E member 1(SERPINE1)expression in GC tissues and cells was evaluated using RT-PCR and immunohistochemical staining.The correlation between SERPINE1 expression and overall patient survival was determined using Kaplan-Meier plot analysis.The association between SERPINE1 and GC progression was also tested.A rescue experiment of SERPINE1 overexpression was conducted to verify the relationship between this protein and miR-145-5p.The mechanism by which miR-145-5p influences GC progression was further explored by assessing tumor formation in nude mice.RESULTS GC tissues and cells had reduced miR-145-5p expression and SERPINE1 was identified as a direct target of this miRNA.Overexpression of miR-145-5p was associated with decreased GC cell proliferation,invasion,migration,and EMT,and these effects were reversed by forcing SERPINE1 expression.Kaplan-Meier plot analysis revealed that patients with higher SERPINE1 expression had a shorter survival rate than those with lower SERPINE1 expression.Nude mouse tumorigenesis experiments confirmed that miR-145-5p targets SERPINE1 to regulate extracellular signal-regu

关键词： Gastric cancer MicroRNA-145-5p Serpin family E member 1 Epithelial-mesenchymal transition Proliferation Extracellular signal-regulated kinase-1/2

Hematuria after nocturnal exercise of a man: A case report

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World Journal of Clinical Cases 2024年第5期12卷 1025-1028页

作者： Ming-Jian bai Song-Tao Yang xue-Kai Liu Department of Clinical Laboratory Aerospace Center HospitalBeijing 100049China Department of Nephrology Aerospace Center HospitalBeijing 100049China

BACKGROUND A man experienced multiple episodes of macroscopic hematuria following nocturnal exercise.Urinary stones and tumors were considered the two most likely causes.The patient had two hobbies:Consuming health care products in large quantities and engaging in late-night running.CASE SUMMARY Health care products contain a large amount of calcium phosphate,and we hypothesize that this could induce the formation of small phosphate stones.After exercise,the urinary system is abraded,resulting in bleeding.The patient was advised to stop using the health care products.Consequently,the aforementioned symptoms disappeared immediately.However,the patient resumed the above two habits one year later;correspondingly,the macroscopic hematuria reap-peared.CONCLUSION This finding further confirmed the above inference and allowed for a new avenue to determine the cause of the patient’s hematuria.

关键词： Hematuria Health care products Exercise Case report

In-situ construction of PDOL electrolyte with dual-reinforced stable interface for high-voltage lithium metal batteries

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Science China Chemistry 2024年第5期67卷 1664-1671页

作者： Yingkang Wu Yuzhou bai Wujie Dong xue Wang Wenqin Ma Fuqiang Huang State Key Lab of Metal Matrix Composites School of Materials Science and EngineeringShanghai Jiao Tong UniversityShanghai 200240China School of Physical Science and Technology Shanghai Tech UniversityShanghai 201210China Shanghai Institute of Ceramics Chinese Academy of SciencesShanghai 200050China

In-situ polymerized electrolytes significantly enhance the interfacial compatibility of lithium metal batteries(LMBs). Typically,in-situ polymerized 1,3-dioxolane(PDOL) exhibits low interfacial resistance, yet still suffers from low ionic conductivity and a narrow electrochemical stability window(ESW). Here, an ultra-stable PDOL-based polymer electrolyte is developed by incorporating plasticizers of tetramethylene sulfone(TMS) and fluorinated ethylene carbonate(FEC) into the 3D cross-linked network, achieving a significant enhancement in the transport capacity and efficiency of Li-ion. The ionic conductivity reaches3.63×10^(-4)S cm^(-1)even at room temperature, and the transference number(tLi^(+)) is even higher at 0.85. Furthermore, the ESW of this electrolyte can be increased to 4.5 V with the addition of TMS, which forms a thin and robust antioxidant cathode-electrolyte interface(CEI) on the surface of high-voltage LiCoO_(2). FEC generates an inorganic-rich solid-electrolyte interface(SEI) on the Li anode, which effectively inhibits the growth of lithium dendrites. Benefiting from the aforementioned advantages, the highvoltage lithium metal battery demonstrates outstanding long-cycle stability, with 93.2% capacity retention after 200 cycles. This work offers a straightforward and accessible method for the practical implementation of high energy density in-situ polymerized solid-state LMBs.

关键词： solid polymer electrolyte in-situ polymerization PDOL high-voltage LMBs

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