Polyphenol Compound 18a Modulates UCP1-Dependent Thermogenesis to Counteract Obesity.

Recent studies increasingly suggest that targeting brown/beige adipose tissues to enhance energy expenditure offers a novel therapeutic approach for treating metabolic diseases. Brown/beige adipocytes exhibit elevated expression of uncoupling protein 1 (UCP1), which is a thermogenic protein that efficiently converts energy into heat, particularly in response to cold stimulation. Polyphenols possess potential anti-obesity properties, but their pharmacological effects are limited by their bioavailability and distribution within tissue. This study discovered 18a, a polyphenol compound with a favorable distribution within adipose tissues, which transcriptionally activates UCP1, thereby promoting thermogenesis and enhancing mitochondrial respiration in brown adipocytes. Furthermore, in vivo studies demonstrated that 18a prevents high-fat-diet-induced weight gain and improves insulin sensitivity. Our research provides strong mechanistic evidence that UCP1 is a complex mediator of 18a-induced thermogenesis, which is a critical process in obesity mitigation. Brown adipose thermogenesis is triggered by 18a via the AMPK-PGC-1α pathway. As a result, our research highlights a thermogenic controlled polyphenol compound 18a and clarifies its underlying mechanisms, thus offering a potential strategy for the thermogenic targeting of adipose tissue to reduce the incidence of obesity and its related metabolic problems.

Enhanced immunosuppressive capability of mesenchymal stem cell-derived small extracellular vesicles with high expression of CD73 in experimental autoimmune uveitis.

BACKGROUND: Autoimmune uveitis is an inflammatory disease triggered by an aberrant immune response. Mesenchymal stem cell-derived small extracellular vesicles (MSC-sEVs) are emerging as potential therapeutic agents for this condition. CD73, an ectoenzyme present on MSC-sEVs, is involved in mitigating inflammation by converting extracellular adenosine monophosphate into adenosine. We hypothesize that the inhibitory effect of MSC-sEVs on experimental autoimmune uveitis (EAU) could be partially attributed to the surface expression of CD73. METHODS: To investigate novel therapeutic approaches for autoimmune uveitis, we performed lentiviral transduction to overexpress CD73 on the surface of MSC-sEVs, yielding CD73-enriched MSC-sEVs (sEVs-CD73). Mice with interphotoreceptor retinoid-binding protein (IRBP)-induced EAU were grouped randomly and treated with 50 µg MSC-sEVs, vector infected MSC-sEVs, sEVs-CD73 or PBS via single tail vein injection. We evaluated the clinical and histological features of the induced mice and analyzed the proportion and functional capabilities of T helper cells. Furthermore, T-cells were co-cultured with various MSC-sEVs in vitro, and we quantified the resulting inflammatory response to assess the potential therapeutic benefits of sEVs-CD73. RESULTS: Compared to MSC-sEVs, sEVs-CD73 significantly alleviates EAU, leading to reduced inflammation and diminished tissue damage. Treatment with sEVs-CD73 results in a decreased proportion of Th1 cells in the spleen, draining lymph nodes, and eyes, accompanied by an increased proportion of regulatory T-cells (Treg cells). In vitro assays further reveal that sEVs-CD73 inhibits T-cell proliferation, suppresses Th1 cells differentiation, and enhances Treg cells proportion. CONCLUSION: Over-expression of CD73 on MSC-sEVs enhances their immunosuppressive effects in EAU, indicating that sEVs-CD73 has the potential as an efficient immunotherapeutic agent for autoimmune uveitis.

Explore on the Mechanism of miRNA-146a/TAB1 in the Regulation of Cellular Apoptosis and Inflammation in Ulcerative Colitis Based on NF-κB Pathway.

OBJECTIVE: Ulcerative colitis (UC) is a chronic non-specific inflammatory disease of the rectum and colon with unknown etiology. A growing number of evidence suggest that the pathogenesis of UC is related to excessive apoptosis and production of inflammatory cytokines. However, the functions and molecular mechanisms associated with UC remain unclear. MATERIALS AND METHODS: The in vivo and in vitro models of UC were established in this study. MiRNA or gene expression was measured by qRT-PCR assay. ELISA, CCK-8, TUNEL, and flow cytometry assays were applied for analyzing cellular functions. The interactions between miR-146a and TAB1 were verified by luciferase reporter and miRNA pull-down assays. RESULTS: MiR-146a was obviously increased in UC patients, DSS-induced colitis mice, and TNF-ɑ-induced YAMC cells, when compared to the corresponding controls. MiR- 146a knockdown inhibited the inflammatory response and apoptosis in DSS-induced colitis mice and TNF-ɑ-induced YAMC cells. Mechanistically, we found that TAB1 was the target of miR-146a and miR-146a knockdown suppressed the activation of NF-κB pathway in UC. More importantly, TAB1 could overturn the inhibitory effect of antagomiR-146a on cell apoptosis and inflammation in UC. CONCLUSION: MiR-146a knockdown inhibited cell apoptosis and inflammation via targeting TAB1 and suppressing NF-κB pathway, suggesting that miR-146a may be a new therapeutic target for UC treatment.

Multi-omics analysis of human mesenchymal stem cells shows cell aging that alters immunomodulatory activity through the downregulation of PD-L1.

Mesenchymal stem cells (MSCs) possess potent immunomodulatory activity and have been extensively investigated for their therapeutic potential in treating inflammatory disorders. However, the mechanisms underlying the immunosuppressive function of MSCs are not fully understood, hindering the development of standardized MSC-based therapies for clinical use. In this study, we profile the single-cell transcriptomes of MSCs isolated from adipose tissue (AD), bone marrow (BM), placental chorionic membrane (PM), and umbilical cord (UC). Our results demonstrate that MSCs undergo a progressive aging process and that the cellular senescence state influences their immunosuppressive activity by downregulating PD-L1 expression. Through integrated analysis of single-cell transcriptomic and proteomic data, we identify GATA2 as a regulator of MSC senescence and PD-L1 expression. Overall, our findings highlight the roles of cell aging and PD-L1 expression in modulating the immunosuppressive efficacy of MSCs and implicating perinatal MSC therapy for clinical applications in inflammatory disorders.

Correlation between inflammatory marker and lipid metabolism in patients with uterine leiomyomas.

Introduction: Obesity is a risk factor for the development of uterine leiomyoma (UL), and the inflammatory response plays a key role in the pathogenesis of UL. Our objective was to assess whether there was an independent relationship between inflammatory markers and triglycerides (TG) in patients with UL. Methods: 1,477 UL participants who were hospitalized at the Jining Medical University between January 2016 and December 2022 were included in this cross-sectional study. The independent and dependent variables measured at baseline were inflammatory markers and TG levels, respectively. The covariates were age, body mass index (BMI), UL and menstrual status. Based on the number of fibroids, the study population was divided into Single-group and Multiple-group. Results: Univariate and multiple regression analyses and stratified analyses revealed significant positive correlations between neutrophil-lymphocyte ratio and systemic immune inflammation index and TG, and significant negative correlations between monocyte-lymphocyte ratio and TG. Conclusion: The findings show a significant correlation between the inflammatory response and lipid metabolism levels in UL patients. This provides direction for further research into the pathophysiology of UL and also helps to formulate hypotheses for predictive models of UL.

Incidence of pneumonitis following the use of different anaplastic lymphoma kinase tyrosine kinase inhibitor regimens: An updated systematic review and meta-analysis.

OBJECTIVES: Anaplastic lymphoma kinase tyrosine kinase inhibitors (ALK TKIs) have shown remarkable clinical activity in patients with non-small-cell lung cancer (NSCLC). However, pneumonitis is a serious side effect of ALK TKIs in NSCLC patients. In this meta-analysis, we aimed to determine the incidence of ALK-TKI-associated pneumonitis. MATERIALS AND METHODS: We searched electronic databases to identify relevant studies published until August 2022. The incidence of pneumonitis was calculated using a fixed-effects model when no substantial heterogeneity was observed. Otherwise, a random-effects model was used. Subgroup analyses of different treatment groups were performed. Statistical analyses were conducted using STATA 17.0. RESULTS: Twenty-six clinical trials involving 4752 patients were eligible for analysis. All-grade pneumonitis incidence was 2.92% (95% confidence interval [CI]: 1.79%-4.27%), high-grade (Grade 3-4) pneumonitis incidence was 1.42% (95% CI: 0.84%-2.12%) and Grade 5 pneumonitis incidence was 0.09% (95% CI: 0.00%-0.28%). The subgroup analysis showed that brigatinib was associated with the highest incidence of both all-grade and high-grade pneumonitis (7.09% and 3.06%, respectively). ALK TKI treatment after chemotherapy was associated with a higher incidence of all-grade and high-grade pneumonitis than first-line ALK TKI treatment (7.73% vs. 2.26% and 3.64% vs. 1.26%, respectively). Cohorts from Japanese trials had a higher incidence of all-grade and high-grade pneumonitis. CONCLUSION: Our study provides precise data on the incidence of pneumonitis in patients receiving treatment with ALK TKIs. Overall, ALK TKIs have tolerable pulmonary toxicity. Early pneumonitis identification and treatment are required to prevent further deterioration in patients receiving treatment with brigatinib and in those who received prior chemotherapy, particularly in the Japanese population.

Inflammatory Markers in Women with Infertility: A Cross-Sectional Study.

Purpose: Infertility is highly correlated with inflammation. We sought to evaluate the independent relationships between each inflammatory marker in women with infertility. Patients and Methods: This cross-sectional study included 1028 infertile patients who were hospitalized at Jining Medical University between January 2016 and December 2022. NLR and PLR were the independent and dependent variables measured at baseline, respectively. Age, body mass index (BMI), and menstrual status were covariates. Based on BMI, the study population was split into two groups: Low-BMI and High-BMI. Results: A stratified analysis revealed that the overweight group had significantly higher levels of WBC, platelet count, lymphocyte count, neutrophil count and NLR. Comparing the overweight group to the normal weight group, the levels were noticeably higher in the overweight group. Significantly positive correlations between NLR and PLR were found in both univariate and multiple regression analyses. Conclusion: There was a significant positive correlation between NLR and PLR in infertility patients. These results will help in the search for biomarkers of infertility and in the development of infertility prediction models.

The activation of peroxymonosulfate by biochar derived from anaerobic and aerobic iron-containing excess sludge.

The excess sludge from municipal sewage treatment plants is rich in Fe (III) due to chemical dephosphorization. The activation of peroxymonosulfate (PMS) by biochar derived from anaerobic and aerobic iron-containing excess sludge was studied systematically in this research. Fe (III)-containing excess sludge was cultured in an anaerobic environment for conversion of partial Fe (III) to Fe (II), which was further carbonized to prepare biochar labeled AnSx@Fe. Meanwhile, aerobic sludge with different Fe (III) content was directly carbonized to produce biochar labeled AeS@Fe. For biochar (AnS20@Fe-15%) prepared from 15% Fe(III)-containing anaerobic cultured 20 days sludge, the relative contents of Fe (III) and Fe (II) were 21.26% and 78.74%, which were 31.03% and 68.97% for biochar (AeS@Fe-10%) prepared from 10% Fe (III)-containing aerobic sludge. Fe (III) can be reduced to Fe (II) by both anaerobic culture and carbonization. Their removal rates of tetracycline (TC) through 60 min PMS activation were 97% and 98%, with TOC (Total organic carbon) removal of 61.8% and 53.4% respectively. The reactive species including sulfate radical [Formula: see text], hydroxyl radical (·OH) and singlet oxygen (1O2) were produced during PMS activation. After O2-aeration treatment of both AeS@Fe and AnSx@Fe, the relative content of Fe (II) was decreased and group C = O was disappeared, which resulted in reduction of [Formula: see text], ·OH and 1O2. The generation of [Formula: see text] and ·OH was dominated by the Fe (II) activation and the 1O2 generation was originated from graphite type N and C = O. Direct carbonization of aerobic and anaerobic sludge is a feasible method to produce biochar for PMS activation.

Experimental and DFT study of Cu(II) removed by Na-montmorillonite.

The experimental and theoretical studies on the adsorption of Cu(II) on the surface of Na-montmorillonite (Na-Mt) were reported. Effects of batch adsorption experimental parameters were studied. Density functional theory and molecular dynamics simulations were used to study the adsorption of Cu(II) on montmorillonite (001) surface. The adsorption reached equilibrium within 80 min and the adsorption capacity was 35.23 mg·g-1 at 25 °C. The adsorption data of Cu(II) were consistent with pseudo-second-order kinetics and Langmuir isotherm models. The adsorption process was dominated by physical adsorption (Ea was 37.08 kJ·mol-1) with spontaneous endothermic behavior. The influence of coexisting cations on the adsorption capacity of Cu(II) was Mg(II) > Co(II) > Ca(II) > Na(I). The simulation results demonstrated that there were no significant differences in the adsorption energy of Cu(II) at the four adsorption sites on the montmorillonite (001) surface. Cu(II) had more electron transfer than Na(I). The diffusion coefficient of Cu(II) in the aqueous solution system containing montmorillonite was 0.85×10-10 m2·s-1. Considerable amounts of Cu(II) ions were adsorbed at a distance of 0.26 and 2.25 Å from the montmorillonite (001) surface. The simulation results provided strong supporting evidence for experimental conclusions.

Chiral phosphoric acid-catalyzed enantioselective phosphinylation of 3,4-dihydroisoquinolines with diarylphosphine oxides.

Chiral phosphorous-containing compounds are playing a more and more significant role in several different research fields. Here, we show a chiral phosphoric acid-catalyzed enantioselective phosphinylation of 3,4-dihydroisoquinolines with diarylphosphine oxides for the efficient and practical construction of a family of chiral α-amino diarylphosphine oxides with a diverse range of functional groups. The phosphine products are suitable for transforming to several kinds of chiral (thio)ureas, which might be employed as chiral ligands or catalysts with potential applications in asymmetric catalysis. Control and NMR tracking experiments show that the reaction proceeds via the tert-butyl 1-(tert-butoxy)-3,4-dihydroiso-quinoline-2(1H)-carboxylate intermediate, followed by C-P bond formation. Furthermore, computational studies elucidated that the hydrogen bonding strength between the phosphonate and isoquinolinium determines the stereoselectivity of the phosphinylation reaction.

Safety and Efficacy of Concurrent or Sequential Radiotherapy Plus (PD-1) Inhibitors in Oligometastatic Esophageal Cancer.

Purpose: We assess real-world outcomes, including safety and efficacy, of concurrent or sequential treatment with radiotherapy plus programmed cell death protein 1 (PD-1) inhibitors in patients with oligometastatic esophageal cancer (OMEC). Methods: This cohort study retrospectively collected clinical data of patients with synchronous or metachronous OMEC. All patients underwent concurrent or sequential treatment with radiotherapy plus PD-1 inhibitors. Each patient had up to five measurable metastatic lesions and up to three organs involved. Study endpoints were progression-free survival (PFS), treatment-related toxicities, locoregional progression-free survival (LRPFS), objective response rate (ORR), and disease control rate (DCR). Description statistics and Kaplan-Meier models were used for statistical analysis. Results: A total of 86 patients were included, most of whom were diagnosed with squamous cell carcinoma histology (98%) and presented with synchronous OMEC (64%). The median follow-up period was 17 months (range: 6-32 months), the median PFS was 15.2 months (95% confidence interval: 12.1-18.2 months); and the 1- and 2-year PFS rates were 61.4% and 26.7%, respectively. The 1- and 2-year LRPFS were 91.3% and 57.3%, respectively. The ORR and DCR were 46.5% and 91.8%, respectively. Forty-two patients (48.8%) experienced grade 3 or higher treatment-related adverse events (TRAEs); a grade 5 treatment-related adverse event was observed in one patient (1.2%) who died of immune-related pneumonitis. Conclusion: Combining radiotherapy with PD-1 inhibitors is a safe and effective treatment option for patients with OMEC. No new safety concerns were identified in this study. However, due to the potential risk of cumulative toxicity, an individual risk-benefit assessment for each patient is required prior to treatment initiation.

In Situ Hypoiodite-Catalyzed Oxidative Rearrangement of Chalcones: Scope and Mechanistic Investigation.

It is highly desirable to avoid using rare or toxic metals for oxidative reactions in the synthesis of pharmaceuticals and fine chemicals. Hypervalent iodine compounds are environmentally benign alternatives, but their catalytic use has been quite limited. Herein, the protocol for in situ hypoiodite-catalyzed oxidative rearrangement of chalcones is first realized under mild and metal-free conditions, which provided a nontoxic, environmental-benign, and catalytic alternative to the thallium-based protocol. Also, the applicability and effectiveness of this catalytic protocol got well demonstrated via gram-scale synthesis and product derivatization. What is more, control and NMR tracking experiments were performed to figure out the possible catalytic species and intermediates.

Homogeneous Dearomative Hydrogenation with a Co/P4 N2 Catalyst: A Nucleophilic Approach.

Arene hydrogenation is the most straightforward method to prepare carbo- and heterocycles. However, the high resonance energy prevents aromatic substrates from hydrogenation. Herein the homogeneous, nucleophilic hydrogenation of less electron-rich arenes and heteroarenes is reported. The Co(P4 N2 )H species that has been demonstrated to be a strong hydride donor could deliver a hydride ion to the cyano (hetero)arene substrates. Deuterium labeling experiments supported a Michael-type reaction pathway. Theoretical analyses have been conducted to investigate the hydricity of the catalytically active CoH species and the electrophilicity of the arene substrates. An outlook for the synthesis of more challenging substituted benzenes was proposed based on the in silico modification of the CoH species.

Integration of Milstein Ru-PNN and Rh-Tribi/Tetrabi for Isomerization Linear Selective Hydroformylation of Far Internal Alkenes.

Converting cheap and abundant internal alkenes to value-added linear aldehydes is of great importance but not an addressed issue. In this paper, an integration of a Milstein-type Ru-PNN catalyst and our Rh-Tribi/Tetrabi catalyst was first demonstrated in highly improved isomerization linear selective hydroformylation of 2-, 3-, and 4-alkenes, yielding excellent linear selectivities and activities (linear selectivity improvements of 2.2-58%, up to 94.2-98.6%, and turnover numbers improvements of 61-335 TON, up to 385-851) compared to the Ru-PNN/Rh-Bisbi system.

Association between immune-related adverse events and the efficacy of PD-1 inhibitors in advanced esophageal cancer.

Introduction: Recent developments in immune checkpoint inhibitors (ICIs) have improved the treatment outcomes of esophageal cancer (EC); however, it may initiate immune-related adverse events (irAEs) in some patients. The ICIs' therapeutic efficacy is associated with irAEs in patients with non-small cell lung cancer or renal cell carcinoma, although this association is unknown in EC. The purpose of this study was to explore the association between irAEs and the efficacy of programmed death 1 (PD-1) inhibitors in EC patients. Patients and methods: This study included patients with advanced EC treated with PD-1 inhibitors. The patients were divided into two groups according to the occurrence of irAEs. Afterward, the efficacy was compared between the irAE-negative and irAE-positive groups, and we analyzed the predictive factors of irAEs and survival. Results: Overall, 295 patients were included in this study. Baseline characteristics were balanced in the irAE-negative and irAE-positive groups. In total, 143 (48.47%) patients experienced irAEs. The most frequent irAEs were anemia (49, 16.61%), hyperthyroidism (45, 15.25%), and pneumonitis (44, 14.92%). In total, 33 (11.19%) patients had grade ≥ 3 irAEs and pneumonitis have 15 (5.08%). No grade 5 adverse events were observed. A total of 52 (17.63%) and 91 (30.85%) patients had single and multiple irAEs, respectively. Compared with patients without irAEs, those with irAEs had significantly higher objective response rate (ORR) (37.76% vs. 25.00%, p = 0.018) and disease control rate (DCR) (92.31% vs. 83.55%, p = 0.022). Univariate Cox analyses indicated the significant association between irAEs and improved median progression-free survival (PFS) (10.27 vs. 6.2 months, p < 0.001) and overall survival (OS) (15.4 vs. 9.2 months, p < 0.001). In multivariate analyses, irAEs were independently associated with longer PFS (p = 0.011) and OS (p = 0.002). Moreover, multivariate analysis revealed that cycles > 8, radiation, as well as antiangiogenic therapy were strongly associated with irAEs development (p < 0.001, p = 0.002, and p = 0.025, respectively). Conclusion: In advanced EC, patients with irAEs showed markedly better efficacy in ORR, DCR, PFS, and OS compared with patients without irAEs.

Mesenchymal-Stem-Cell-Based Strategies for Retinal Diseases.

Retinal diseases are major causes of irreversible vision loss and blindness. Despite extensive research into their pathophysiology and etiology, pharmacotherapy effectiveness and surgical outcomes remain poor. Based largely on numerous preclinical studies, administration of mesenchymal stem cells (MSCs) as a therapeutic strategy for retinal diseases holds great promise, and various approaches have been applied to the therapies. However, hindered by the retinal barriers, the initial vision for the stem cell replacement strategy fails to achieve the anticipated effect and has now been questioned. Accumulating evidence now suggests that the paracrine effect may play a dominant role in MSC-based treatment, and MSC-derived extracellular vesicles emerge as a novel compelling alternative for cell-free therapy. This review summarizes the therapeutic potential and current strategies of this fascinating class of cells in retinal degeneration and other retinal dysfunctions.

Correlation Between Platelet-Lymphocyte Ratio and Neutrophil-Lymphocyte Ratio in Patients with Uterine Leiomyoma: A Cross-Sectional Study.

The inflammatory reaction has been proven to be a key factor in the pathogenesis of uterine leiomyoma. The platelet-lymphocyte ratio (PLR) and the neutrophil-lymphocyte ratio (NLR) are inexpensive and reliable inflammatory biomarkers. However, evidence of the relationship between PLR and NLR in patients with uterine leiomyoma is limited. This study aimed to explore the relationship between PLR and NLR in patients with incident uterine leiomyoma. This cross-sectional study included 763 patients with uterine leiomyoma who were first diagnosed in our hospital between January 2016 and December 2016. Patient characteristics were collected for univariate analysis, smooth curve fitting, and multivariate piecewise linear regression. Overall, 722 patients with an average age of 40.16 ± 5.99 years were included. The average PLR was 161.22 ± 65.33. Univariate analysis revealed a significant positive correlation between PLR and NLR (P < 0.0001). In addition, the non-linear relationship between the PLR and NLR was tested using smooth curve fitting after adjusting for potential confounding factors. The multivariate piecewise linear regression model showed that there was a significant positive correlation between PLR and NLR in both PLR <226.45 (ß 0.01, 95% CI: 0.01, 0.01;P < 0.0001) and >226.45 (ß 0.00, 95% CI: 0.00, 0.00; P=0.0026). In conclusion, PLR and NLR are positively correlated in patients with uterine leiomyoma. This result clarifies the promoting role of inflammation in the occurrence of uterine leiomyoma.

Transcriptome changes associated with apple (Malus domestica) root defense response after Fusarium proliferatum f. sp. malus domestica infection.

BACKGROUND: Apple replant disease is a soilborne disease caused by Fusarium proliferatum f. sp. malus domestica strain MR5 (abbreviated hereafter as Fpmd MR5) in China. This pathogen causes root tissue rot and wilting leaves in apple seedlings, leading to plant death. A comparative transcriptome analysis was conducted using the Illumina Novaseq platform to identify the molecular defense mechanisms of the susceptible M.26 and the resistant M9T337 apple rootstocks to Fpmd MR5 infection. RESULTS: Approximately 518.1 million high-quality reads were generated using RNA sequencing (RNA-seq). Comparative analysis between the mock-inoculated and Fpmd MR5 infected apple rootstocks revealed 28,196 significantly differentially expressed genes (DEGs), including 14,572 up-regulated and 13,624 down-regulated genes. Among them, the transcriptomes in the roots of the susceptible genotype M.26 were reflected by overrepresented DEGs. MapMan analysis indicated that a large number of DEGs were involved in the response of apple plants to Fpmd MR5 stress. The important functional groups identified via gene ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment were responsible for fundamental biological regulation, secondary metabolism, plant-pathogen recognition, and plant hormone signal transduction (ethylene and jasmonate). Furthermore, the expression of 33 up-regulated candidate genes (12 related to WRKY DNA-binding proteins, one encoding endochitinase, two encoding beta-glucosidases, ten related to pathogenesis-related proteins, and eight encoding ethylene-responsive transcription factors) were validated by quantitative real-time PCR. CONCLUSION: RNA-seq profiling was performed for the first time to analyze response of apple root to Fpmd MR5 infection. We found that the production of antimicrobial compounds and antioxidants enhanced plant resistance to pathogens, and pathogenesis-related protein (PR10 homologs, chitinase, and beta-glucosidase) may play unique roles in the defense response. These results provide new insights into the mechanisms of the apple root response to Fpmd MR5 infection.

The evolutionary trends of health inequality among elderly Chinese people and influencing factors of these trends from 2005 to 2017.

Reducing health inequality and ensuring national health equity have become issues of great concern to all countries in the world. This paper based on the ordered Probit model and concentrated index decomposition method, analysed the influencing factors and evolution trend of health inequality among the elderly with high age in China from 2005 to 2017. The study found that in 2005-2017, the self-rated health distribution of the elderly with high age in China showed an obvious inverted "U" shape, with the proportion of general and relatively healthy being the largest, while the proportion of unhealthy and very healthy was lower. Lifestyle, family income, and age were the main important factors to expand health inequality. Therefore, encouraging the elderly with high age to develop good living habits and narrowing the income gap of the elderly are conducive to solving the health inequality of the elderly with high age and achieving the goals of active ageing and healthy ageing.

Rutaecarpine Promotes Adipose Thermogenesis and Protects against HFD-Induced Obesity via AMPK/PGC-1α Pathway.

Pharmacological activation of adaptive thermogenesis to increase energy expenditure is considered to be a novel strategy for obesity. Peroxisome-proliferator-activated receptor γ co-activator-1α (PGC-1α), which serves as an inducible co-activator in energy expenditure, is highly expressed in brown adipose tissues (BAT). In this study, we found a PGC-1α transcriptional activator, natural compound rutaecarpine (Rut), which promoted brown adipocytes mitochondrial biogenesis and thermogenesis in vitro. Chronic Rut treatment reduced the body weight gain and mitigated insulin sensitivity through brown and beige adipocyte thermogenesis. Mechanistic study showed that Rut activated the energy metabolic pathway AMP-activated protein kinase (AMPK)/PGC-1α axis, and deficiency of AMPK abolished the beneficial metabolic phenotype of the Rut treatment in vitro and in vivo. In summary, a PGC-1α transcriptional activator Rut was found to activate brown and beige adipose thermogenesis to resist diet-induced obesity through AMPK pathway. Our findings serve as a further understanding of the natural compound in adipose tissue and provides a possible strategy to combat obesity and related metabolic disorders.