1.Heterogeneity of Adipose Tissue From a Single-cell Transcriptomics Perspective
Yong-Lang WANG ; Si-Si CHEN ; Qi-Long LI ; Yu GONG ; Xin-Yue DUAN ; Ye-Hui DUAN ; Qiu-Ping GUO ; Feng-Na LI
Progress in Biochemistry and Biophysics 2025;52(4):820-835
Adipose tissue is a critical energy reservoir in animals and humans, with multifaceted roles in endocrine regulation, immune response, and providing mechanical protection. Based on anatomical location and functional characteristics, adipose tissue can be categorized into distinct types, including white adipose tissue (WAT), brown adipose tissue (BAT), beige adipose tissue, and pink adipose tissue. Traditionally, adipose tissue research has centered on its morphological and functional properties as a whole. However, with the advent of single-cell transcriptomics, a new level of complexity in adipose tissue has been unveiled, showing that even under identical conditions, cells of the same type may exhibit significant variation in morphology, structure, function, and gene expression——phenomena collectively referred to as cellular heterogeneity. Single-cell transcriptomics, including techniques like single-cell RNA sequencing (scRNA-seq) and single-nucleus RNA sequencing (snRNA-seq), enables in-depth analysis of the diversity and heterogeneity of adipocytes at the single-cell level. This high-resolution approach has not only deepened our understanding of adipocyte functionality but also facilitated the discovery of previously unidentified cell types and gene expression patterns that may play key roles in adipose tissue function. This review delves into the latest advances in the application of single-cell transcriptomics in elucidating the heterogeneity and diversity within adipose tissue, highlighting how these findings have redefined the understanding of cell subpopulations within different adipose depots. Moreover, the review explores how single-cell transcriptomic technologies have enabled the study of cellular communication pathways and differentiation trajectories among adipose cell subgroups. By mapping these interactions and differentiation processes, researchers gain insights into how distinct cellular subpopulations coordinate within adipose tissues, which is crucial for maintaining tissue homeostasis and function. Understanding these mechanisms is essential, as dysregulation in adipose cell interactions and differentiation underlies a range of metabolic disorders, including obesity and diabetes mellitus type 2. Furthermore, single-cell transcriptomics holds promising implications for identifying therapeutic targets; by pinpointing specific cell types and gene pathways involved in adipose tissue dysfunction, these technologies pave the way for developing targeted interventions aimed at modulating specific adipose subpopulations. In summary, this review provides a comprehensive analysis of the role of single-cell transcriptomic technologies in uncovering the heterogeneity and functional diversity of adipose tissues.
2.PANoptosis: a New Target for Cardiovascular Diseases
Xin-Nong CHEN ; Ying-Xi YANG ; Xiao-Chen GUO ; Jun-Ping ZHANG ; Na-Wen LIU
Progress in Biochemistry and Biophysics 2025;52(5):1113-1125
The innate immune system detects cellular stressors and microbial infections, activating programmed cell death (PCD) pathways to eliminate intracellular pathogens and maintain homeostasis. Among these pathways, pyroptosis, apoptosis, and necroptosis represent the most characteristic forms of PCD. Although initially regarded as mechanistically distinct, emerging research has revealed significant crosstalk among their signaling cascades. Consequently, the concept of PANoptosis has been proposed—an inflammatory cell death pathway driven by caspases and receptor-interacting protein kinases (RIPKs), and regulated by the PANoptosome, which integrates key features of pyroptosis, apoptosis, and necroptosis. The core mechanism of PANoptosis involves the assembly and activation of the PANoptosome, a macromolecular complex composed of three structural components: sensor proteins, adaptor proteins, and effector proteins. Sensors detect upstream stimuli and transmit signals downstream, recruiting critical molecules via adaptors to form a molecular scaffold. This scaffold activates effectors, triggering intracellular signaling cascades that culminate in PANoptosis. The PANoptosome is regulated by upstream molecules such as interferon regulatory factor 1 (IRF1), transforming growth factor beta-activated kinase 1 (TAK1), and adenosine deaminase acting on RNA 1 (ADAR1), which function as molecular switches to control PANoptosis. Targeting these switches represents a promising therapeutic strategy. Furthermore, PANoptosis is influenced by organelle functions, including those of the mitochondria, endoplasmic reticulum, and lysosomes, highlighting organelle-targeted interventions as effective regulatory approaches. Cardiovascular diseases (CVDs), the leading global cause of morbidity and mortality, are profoundly impacted by PCD. Extensive crosstalk among multiple cell death pathways in CVDs suggests a complex regulatory network. As a novel cell death modality bridging pyroptosis, apoptosis, and necroptosis, PANoptosis offers fresh insights into the complexity of cell death and provides innovative strategies for CVD treatment. This review summarizes current evidence linking PANoptosis to various CVDs, including myocardial ischemia/reperfusion injury, myocardial infarction, heart failure, arrhythmogenic cardiomyopathy, sepsis-induced cardiomyopathy, cardiotoxic injury, atherosclerosis, abdominal aortic aneurysm, thoracic aortic aneurysm and dissection, and vascular toxic injury, thereby providing critical clinical insights into CVD pathophysiology. However, the current understanding of PANoptosis in CVDs remains incomplete. First, while PANoptosis in cardiomyocytes and vascular smooth muscle cells has been implicated in CVD pathogenesis, its role in other cell types—such as vascular endothelial cells and immune cells (e.g., macrophages)—warrants further investigation. Second, although pathogen-associated molecular patterns (PAMPs) and damage-associated molecular patterns (DAMPs) are known to activate the PANoptosome in infectious diseases, the stimuli driving PANoptosis in CVDs remain poorly defined. Additionally, methodological challenges persist in identifying PANoptosome assembly in CVDs and in establishing reliable PANoptosis models. Beyond the diseases discussed, PANoptosis may also play a role in viral myocarditis and diabetic cardiomyopathy, necessitating further exploration. In conclusion, elucidating the role of PANoptosis in CVDs opens new avenues for drug development. Targeting this pathway could yield transformative therapies, addressing unmet clinical needs in cardiovascular medicine.
3.Structure, content and data standardization of rehabilitation medical records
Yaru YANG ; Zhuoying QIU ; Di CHEN ; Zhongyan WANG ; Meng ZHANG ; Shiyong WU ; Yaoguang ZHANG ; Xiaoxie LIU ; Yanyan YANG ; Bin ZENG ; Mouwang ZHOU ; Yuxiao XIE ; Guangxu XU ; Jiejiao ZHENG ; Mingsheng ZHANG ; Xiangming YE ; Jian YANG ; Na AN ; Yuanjun DONG ; Xiaojia XIN ; Xiangxia REN ; Ye LIU ; Yifan TIAN
Chinese Journal of Rehabilitation Theory and Practice 2025;31(1):21-32
ObjectiveTo elucidate the critical role of rehabilitation medical records (including electronic records) in rehabilitation medicine's clinical practice and management, comprehensively analyzed the structure, core content and data standards of rehabilitation medical records, to develop a standardized medical record data architecture and core dataset suitable for rehabilitation medicine and to explore the application of rehabilitation data in performance evaluation and payment. MethodsBased on the regulatory documents Basic Specifications for Medical Record Writing and Basic Specifications for Electronic Medical Records (Trial) issued by National Health Commission of China, and referencing the World Health Organization (WHO) Family of International Classifications (WHO-FICs) classifications, International Classification of Diseases (ICD-10/ICD-11), International Classification of Functioning, Disability and Health (ICF), and International Classification of Health Interventions (ICHI Beta-3), this study constructed the data architecture, core content and data standards for rehabilitation medical records. Furthermore, it explored the application of rehabilitation record summary sheets (home page) data in rehabilitation medical statistics and payment methods, including Diagnosis-related Groups (DRG), Diagnosis-Intervention Packet (DIP) and Case Mix Index. ResultsThis study proposed a systematic standard framework for rehabilitation medical records, covering key components such as patient demographics, rehabilitation diagnosis, functional assessment, rehabilitation treatment prescriptions, progress evaluations and discharge summaries. The research analyzed the systematic application methods and data standards of ICD-10/ICD-11, ICF and ICHI Beta-3 in the fields of medical record terminology, coding and assessment. Constructing a standardized data structure and data standards for rehabilitation medical records can significantly improve the quality of data reporting based on the medical record summary sheet, thereby enhancing the quality control of rehabilitation services, effectively supporting the optimization of rehabilitation medical insurance payment mechanisms, and contributing to the establishment of rehabilitation medical performance evaluation and payment based on DRG and DIP. ConclusionStructured rehabilitation records and data standardization are crucial tools for quality control in rehabilitation. Systematically applying the three reference classifications of the WHO-FICs, and aligning with national medical record and electronic health record specifications, facilitate the development of a standardized rehabilitation record architecture and core dataset. Standardizing rehabilitation care pathways based on the ICF methodology, and developing ICF- and ICD-11-based rehabilitation assessment tools, auxiliary diagnostic and therapeutic systems, and supporting terminology and coding systems, can effectively enhance the quality of rehabilitation records and enable interoperability and sharing of rehabilitation data with other medical data, ultimately improving the quality and safety of rehabilitation services.
4.Influencing factors of neonatal red blood cell transfusion: a retrospective analysis
Na ZHOU ; Xin HE ; Yu SI ; Chen HOU ; Jialu CHEN ; Zhaohui TANG
Chinese Journal of Blood Transfusion 2025;38(3):375-381
[Objective] To analyze the effects of different factors and red blood cell transfusion thresholds on the efficacy of neonatal red blood cell (RBC) transfusion, in order to provide more references for neonatal transfusions to better achieve rational and effective blood use. [Methods] A retrospective collection of data from 282 neonates who received RBC transfusions at our hospital from 2022 to 2023 was conducted, including birth weight, gestational age, number of blood transfusions, length of hospital stay, assisted ventilation during RBC transfusion, and laboratory test results before and after transfusion. SPSS software was used for statistical analysis to comprehensively analyze the impact of different factors on the efficacy of RBC transfusion in neonates. [Results] The results showed that the gestational age and weight of newborns at birth were negatively correlated with their length of hospital stay and the number of RBC transfusions during hospitalization. Newborns with younger gestational age and lower weight had longer hospital stays and more RBC transfusions during hospitalization. After administering RBCs according to the standard of 15 mL/kg, there was a statistically significant difference in the efficacy of RBC transfusion at different transfusion thresholds. In non-critical situations, RBC transfusions were ineffective when the pre-transfusion hemoglobin (Hb) level was >120 g/L. When the pre-transfusion Hb level was ≤70 g/L, RBC transfusions achieved higher efficacy in both critical and non-critical situations. [Conclusion] In critical situations, the group with pre-transfusion Hb values ≤ 70 g/L has the best RBC transfusion effect, while in non-critical situations, the group with pre-transfusion Hb levels between 81 and 90 g/L has the best RBC transfusion effect. Overall, the efficacy of RBC transfusion in non-critical situations is higher than that in critical situations.
5.Correlation analysis between PPIs and prognosis of AECOPD patients based on MIMIC-IV database:a retrospective cohort study
Yuan WANG ; Caixia XIN ; Haiying YANG ; Dan CHEN ; Na HUANG
Chinese Journal of Pharmacoepidemiology 2024;33(9):986-992
Objective To explore the relationship between the use of proton pump inhibitors(PPIs)and the short-term and long-term prognosis of patients with acute exacerbation of chronic obstructive pulmonary disease(AECOPD).Methods Clinical data of AECOPD patients admitted to the intensive care unit(ICU)from January 2008 to December 2019 were extracted from the MIMIC-Ⅳ database.Patients were divided into PPIs group and non PPIs group based on whether PPIs were used during ICU treatment.Compare the general conditions of two groups of patients and plot survival curves using Kaplan-Meier method to compare the differences in survival rates between the two groups at 28 d and 90 d,respectively.Cox proportional hazards regression was used to analyze the association between PPIs usage and 28 d and 90 d mortality risk in two groups of patients.Results A total of 447 patients were included,including 358 in the PPIs group and 89 in the non PPIs group.The 28 d mortality rate and 90 d mortality rate of the PPIs group were 15.64%and 23.46%,respectively,which were lower than those of the non PPIs group(31.46%and 40.45%,respectively)(P<0.05).The Kaplan-Meier curve analysis showed that the 28 d and 90 d survival rates of the PPIs group were higher than those in the non PPIs group(P<0.001).The Cox proportional hazards regression analysis showed that after adjusting for all included variables,the hazard ratio(HR)for 28 d and 90 d mortality in the PPIs group were 0.58(95%CI 0.35 to 0.94,P=0.030),0.63(95%CI 0.41 to 0.96,P=0.022),respectively,compared to the non PPIs group.Conclusion In AECOPD patients,the use of PPIs may be reduce the 28 d and 90 d mortality risks.
6.Improving cognitive and psychological and behavioral symptoms in patients with mild to moderate vascular dementia by repetitive transcranial magnetic stimulation combined with cognitive function training
Conghao SUN ; Zheli CHEN ; Xin JIN ; Jinfeng FEI ; Wanqiu NA
Chinese Journal of Primary Medicine and Pharmacy 2024;31(9):1288-1294
Objective:To investigate the effect of repetitive transcranial magnetic stimulation combined with cognitive function training on improving cognitive and psychological and behavioral symptoms in patients with vascular dementia.Methods:A total of 80 patients with vascular dementia who received treatment at The Third People's Hospital of Huzhou from October 2020 to October 2022 were included in this study. They were divided into a control group and an observation group ( n = 40 per group) based on different treatment methods. The control group received repetitive transcranial magnetic stimulation, while the observation group received both repetitive transcranial magnetic stimulation and cognitive function training. Both groups were treated continuously for 4 weeks. The scores of The Mini-Mental State Examination (MMSE), the Behavioral Pathology in Alzheimer's Disease Rating Scale (BE-HAVE-AD), Activities of Daily Living (ADL), and Pittsburgh Sleep Quality Index (PSQI) of the two groups were analyzed before and after treatment. Additionally, serum levels of homocysteine and neuron-specific enolase in both groups were compared before and after treatment. The clinical efficacy of the two groups was evaluated, and the total response rate was calculated. Adverse reactions occurring during the treatment period in both groups were also recorded. Results:Before treatment, the Mini-Mental State Examination (MMSE) scores for the control and observation groups were (14.92 ± 2.43) points and (14.83 ± 2.56) points, respectively. After treatment, the scores were (22.81 ± 3.05) points for the control group and (25.62 ± 4.07) points for the observation group. After treatment, the MMSE scores in both groups were significantly higher than the respective levels before treatment in the corresponding group, and the observation group had a significantly higher score than the control group ( t = 2.25, P < 0.05). Before treatment, the BE-HAVE-AD scores for the control and observation groups were (45.28 ± 6.27) points and (44.95 ± 6.38) points, respectively. After treatment, the scores were (27.54 ± 2.22) points for the control group and (23.07 ± 1.79) points for the observation group. After treatment, the BE-HAVE-AD scores were significantly lower than those before treatment in each group, and the observation group had a significantly lower score than the control group ( t = 9.56, P < 0.05). Before treatment, the ADL scores for the control and observation groups were (23.17 ± 1.43) points and (22.83 ± 1.64) points, respectively. After treatment, the scores were (38.27 ± 3.25) points for the control group and (41.52 ± 4.26) points for the observation group. After treatment, the ADL scores in each group were significantly higher than their respective levels before treatment, and the observation group had a significantly higher score than the control group ( t = 3.83, P < 0.05). Before treatment, the PSQI scores for the control and observation groups were (16.423 ± 1.51) points and (15.86 ± 1.49) points, respectively. After treatment, the scores were (9.16 ± 1.12) points for the control group and (7.07 ± 1.07) points for the observation group. After treatment, the PSQI scores were significantly lower than those before treatment in each group, and the observation group had a significantly lower score than the control group ( t = 8.53, P < 0.05). Before treatment, the serum levels of homocysteine in the control and observation groups were (54.27 ± 8.21) ng/L and (55.13 ± 7.64) ng/L, respectively, while the serum levels of neuron-specific enolase in these two groups were (59.66 ± 9.51) μg/L and (60.97 ± 10.29) μg/L, respectively. After treatment, the serum levels of homocysteine in the control and observation groups were (30.63 ± 1.95) ng/L and (25.57 ± 2.06) ng/L, respectively, and the serum levels of neuron-specific enolase in these two groups were (49.23 ± 6.12) μg/L and (37.21 ± 7.01) μg/L, respectively. After treatment, the serum levels of homocysteine and neuron-specific enolase in each group were significantly lower than the respective levels before treatment in the corresponding group; the observation group exhibited significantly lower serum levels of homocysteine and neuron-specific enolase than the control group ( t = 11.28, 8.16, both P < 0.05). The total response rate in the observation group was 95.00% (38/40), which was significantly higher than that in the control group [72.50% (29/40), P < 0.05]. The incidence of adverse reactions in the observation group was 5.00% (2/40), which was significantly lower than that in the control group [20.00% (8/40), χ2 = 7.44, P < 0.05]. Conclusion:Repetitive transcranial magnetic stimulation combined with cognitive function training can more effectively improve cognitive and psychological and behavioral symptoms in patients with vascular dementia, has better efficacy, and is safer compared with repetitive transcranial magnetic stimulation alone.
7.Construction of immortalized tree shrew corneal stromal cell line and investigation of viral infectivity
Xiangrong DING ; Liu CHEN ; Shurui HUO ; Mengdi QI ; Xin LIU ; Wenguang WANG ; Na LI ; Jiejie DAI ; Caixia LU
Acta Laboratorium Animalis Scientia Sinica 2024;32(5):610-619
Objective To establish an immortalized tree shrew corneal stromal cells(CSCs)line and to study its response to virus infection.Methods Primary tree shrew CSCs were isolated and cultured by the tissue block adhesion method.CSCs were then transfected with a lentivirus carrying the SV40T gene and monoclonal cells were selected for passage culture.The characteristics of the CSCs were investigated by morphological observation and compared with 40 generations until the 50 generations or more,immunofluorescence identification of vimentin and SV40T genes,karyotype examination,and cell proliferation curve.The CSCs were infected with herpes simplex virus-1(HSV-1)(McKrae strain),Zika virus(ZIKV,GZ01 strain),Dengue virus typeⅡ,and H1N1(PR8).Results The immortalized tree shrew CSCs after>50 passages appeared spindle-shaped with good cell morphology and structure compared with 40 generations.Positive immunofluorescence expression of vimentin and SV40T genes.The cell growth curve showed that the cells were in logarithmic-phase growth on days 4~5 and grew vigorously.The number of chromosomes in the primary cells was stable at 62,while immortalized CSCs had 64 chromosomes at P21 and P56.The virus titer results showed that the immortalized tree shrew CSCs were sensitive to HSV-1(McKrae strain),ZIKV(GZ01 strain),Dengue virus typeⅡ,and H1N1(PR8),with virus titers of 1.32×105,5.62×106,2.69×107,and 7.76×104 CCID50/mL,respectively.Conclusions The immortalized tree shrew CSCs were established successfully,suggesting that this cell line is suitable for studies of the mechanisms of HSV,ZIKV,Dengue virus,and influenza A virus infection in relation to corneal diseases and antiviral drugs.
8.Treatment status of tyrosine kinase inhibitor for newly-diagnosed chronic myeloid leukemia: a domestic multi-centre retrospective real-world study
Xiaoshuai ZHANG ; Bingcheng LIU ; Xin DU ; Yanli ZHANG ; Na XU ; Xiaoli LIU ; Weiming LI ; Hai LIN ; Rong LIANG ; Chunyan CHEN ; Jian HUANG ; Yunfan YANG ; Huanling ZHU ; Ling PAN ; Xiaodong WANG ; Guohui LI ; Zhuogang LIU ; Yanqing ZHANG ; Zhenfang LIU ; Jianda HU ; Chunshui LIU ; Fei LI ; Wei YANG ; Li MENG ; Yanqiu HAN ; Li'e LIN ; Zhenyu ZHAO ; Chuanqing TU ; Caifeng ZHENG ; Yanliang BAI ; Zeping ZHOU ; Suning CHEN ; Huiying QIU ; Lijie YANG ; Xiuli SUN ; Hui SUN ; Li ZHOU ; Zelin LIU ; Danyu WANG ; Jianxin GUO ; Liping PANG ; Qingshu ZENG ; Xiaohui SUO ; Weihua ZHANG ; Yuanjun ZHENG ; Qian JIANG
Chinese Journal of Hematology 2024;45(3):215-224
Objective:To retrospectively analyze the treatment status of tyrosine kinase inhibitors (TKI) in newly diagnosed patients with chronic myeloid leukemia (CML) in China.Methods:Data of chronic phase (CP) and accelerated phase (AP) CML patients diagnosed from January 2006 to December 2022 from 77 centers, ≥18 years old, and receiving initial imatinib, nilotinib, dasatinib or flumatinib-therapy within 6 months after diagnosis in China with complete data were retrospectively interrogated. The choice of initial TKI, current TKI medications, treatment switch and reasons, treatment responses and outcomes as well as the variables associated with them were analyzed.Results:6 893 patients in CP ( n=6 453, 93.6%) or AP ( n=440, 6.4%) receiving initial imatinib ( n=4 906, 71.2%), nilotinib ( n=1 157, 16.8%), dasatinib ( n=298, 4.3%) or flumatinib ( n=532, 7.2%) -therapy. With the median follow-up of 43 ( IQR 22-75) months, 1 581 (22.9%) patients switched TKI due to resistance ( n=1 055, 15.3%), intolerance ( n=248, 3.6%), pursuit of better efficacy ( n=168, 2.4%), economic or other reasons ( n=110, 1.6%). The frequency of switching TKI in AP patients was significantly-higher than that in CP patients (44.1% vs 21.5%, P<0.001), and more AP patients switched TKI due to resistance than CP patients (75.3% vs 66.1%, P=0.011). Multi-variable analyses showed that male, lower HGB concentration and ELTS intermediate/high-risk cohort were associated with lower cytogenetic and molecular responses rate and poor outcomes in CP patients; higher WBC count and initial the second-generation TKI treatment, the higher response rates; Ph + ACA at diagnosis, poor PFS. However, Sokal intermediate/high-risk cohort was only significantly-associated with lower CCyR and MMR rates and the poor PFS. Lower HGB concentration and larger spleen size were significantly-associated with the lower cytogenetic and molecular response rates in AP patients; initial the second-generation TKI treatment, the higher treatment response rates; lower PLT count, higher blasts and Ph + ACA, poorer TFS; Ph + ACA, poorer OS. Conclusion:At present, the vast majority of newly-diagnosed CML-CP or AP patients could benefit from TKI treatment in the long term with the good treatment responses and survival outcomes.
9.Auto-segmentation during online adaptive MRI-guided radiotherapy for prostate cancer
Xue-Na YAN ; Xiang-Yu MA ; Qiang ZENG ; Kuo MEN ; Xin-Yuan CHEN
Chinese Medical Equipment Journal 2024;45(6):59-64
Objective To explore the effect of auto-segmentation based on deep learning(DL)and Atlas during online adaptive MRI-guided radiotherapy.Methods Totally 15 prostate cancer patients undergoing MRI-guided online adaptive radiotherapy at some hospital from January 2020 to September 2021 were selected and divided into a training set(12 cases)and a test set(3 cases)by random sampling method.With the training set data the models of clinical target volume(CTV)and organs at risk(OAR)by DL and Atlas segmentation were established,and with the test set data the two segmentation models were modified and the modification lengths were recorded.DL and Atlas segmentation methods were compared on segmentation efficiency and accuracy in terms of Dice similarity coefficient(DSC),Hausdorff distance(HD)and mean distance to agreement(MDA).A joint auto-segmentation scheme based on combined DL and Atlas was constructed with considerations on the advantages and characteristics of the two methods,which was compared with the schemes respectively based on DL or Atlas from the aspect of the time consumed for segmentation.Results Accuracy comparison showed Atlas segmentation model behaved better significantly than DL model for CTV(P<0.05),while obviously worse than the latter for DSC and MDA in bladder and rectum(P<0.05).The doctor took 9.4 min in average for CTV and OAR modification based on DL model and 12 min in average for Atlas-model-based modification.The joint auto-segmentation scheme only needed 8 min in average for CTV and OAR modification,which gained advantages over the schemes based on DL or Atlas.Conclusion The auto-segmentation based on combined DL and Atlas during online adaptive MRI-guided radiotherapy behaves well in low time consumption,high accuracy and efficiency.[Chinese Medical Equipment Journal,2024,45(6):59-64]
10.Baicalein:A potential GLP-1R agonist improves cognitive disorder of diabetes through mitophagy enhancement
Liu NA ; Cui XIN ; Yan WENHUI ; Guo TINGLI ; Wang ZHUANZHUAN ; Wei XIAOTONG ; Sun YUZHUO ; Liu JIEYUN ; Xian CHENG ; Ma WEINA ; Chen LINA
Journal of Pharmaceutical Analysis 2024;14(8):1189-1204
There is increasing evidence that the activation of glucagon-like peptide-1 receptor(GLP-1R)can be used as a therapeutic intervention for cognitive disorders.Here,we have screened GLP-1 R targeted com-pounds from Scutellaria baicalensis,which revealed baicalein is a potential GLP-1 R small-molecule agonist.Mitophagy,a selective autophagy pathway for mitochondrial quality control,plays a neuro-protective role in multiple cognitive impairment diseases.We noticed that Glp1r knock-out(KO)mice present cognitive impairment symptoms and appear worse in spatial learning memory and learning capacity in Morris water maze(MWM)test than their wide-type(WT)counterparts.Our mechanistic studies revealed that mitophagy is impaired in hippocampus tissue of diabetic mice and Glp1r KO mice.Finally,we verified that the cognitive improvement effects of baicalein on diabetic cognitive dysfunction occur through the enhancement of mitophagy in a GLP-1 R-dependent manner.Our findings shed light on the importance of GLP-1 R for cognitive function maintenance,and revealed the vital significance of GLP-1R for maintaining mitochondrial homeostasis.Furthermore,we identified the therapeutic potential of baicalein in the treatment of cognitive disorder associated with diabetes.

Result Analysis
Print
Save
E-mail