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The Newtonian gravitational constant G is determined by means of the swing time method at the Cave Laboratory of Center for Gravitational Experiment of Huazhong University of Science and Technology. The result value of G is (6.669 0 ± 0.001 6) × 10-11 m3·kg-1·s-2, which is consistent with the CODATA value of G obtained by Cohen and Taylor in 3σ. [ABSTRACT FROM AUTHOR]

Background & Aims: Previous studies indicate that bile acids (BAs) promote normal liver regeneration and repair after injury. However, the impact of insufficient BA signaling, which is observed in patients with BA sequestrant medication or cerebrotendinous xanthomatosis (CTX) disease, on liver injury is still unknown. Our aim is to determine the outcomes of reduced BA levels upon liver injury. Methods: Seventy percent partial hepatectomy (PH) and carbon tetrachloride (CCl4) treatment were performed using CYP27 −/− mice, a genetic animal model with low BA levels. The liver repair of CYP27 −/− mice after the treatments was characterized by histological staining, chemical analysis, and quantitative real-time PCR. Results: CYP27 −/− mice exhibited enhanced CCl4-induce liver injury, and defective liver regeneration and prolonged steatosis after 70% PH. Due to the insufficient BA signaling, farnesoid X receptor (FXR) activities were significantly reduced in CYP27 −/− livers after 70% PH. Activation of FXR by either 0.2% cholic acid feeding or oral infusion of an FXR agonist greatly promoted liver regeneration in CYP27 −/− mice. Conclusions: Normal physiological levels of BAs are required for liver repair. Patients with BA sequestrant medications or CTX disease due to CYP27 gene mutations may have an increased risk of liver failure, and treatment with FXR ligands can promote liver regeneration of patients with low BA levels. [Copyright &y& Elsevier]

Aging is a complex and universal process marked by gradual functional declines at the cellular and tissue levels, often leading to a range of aging-related diseases such as diabetes, cardiovascular diseases, and cancer. Delaying the aging process can help prevent, slow down, and alleviate the severity of these various conditions, enhancing overall health and well-being. Alpha-glucosidase inhibitors (AGIs) are a class of widely used antidiabetic drugs that inhibit alpha-glucosidase in the small intestinal mucosa, delaying carbohydrate absorption and reducing postprandial hyperglycemia. Beyond their roles in diabetes treatment, AGIs have shown potential in extending lifespan and effectively treating aging-related diseases by modulating oxidative stress, gut microbiota, inflammatory responses, and nutrient-sensing pathways. This review summarizes recent advancements in the application of AGIs for preventing and treating aging and aging-related diseases, with a focus on their mechanisms and roles in these processes.

Ferroptosis, an iron-dependent form of regulated cell death, is emerging as a crucial regulator of human physiology and pathology. Increasing evidence showcases a reciprocal relationship between ferroptosis and dysregulated metabolism, propagating a pathogenic vicious cycle that exacerbates pathology and human diseases, particularly metabolic disorders. Consequently, there is a rapidly growing interest in developing ferroptosis-based therapeutics. Therefore, a comprehensive understanding of the intricate interplay between ferroptosis and metabolism could provide an invaluable resource for mechanistic insight and therapeutic development. In this review, we summarize the important metabolic substances and associated pathways in ferroptosis initiation and progression, outline the cascade responses of ferroptosis in disease development, overview the roles and mechanisms of ferroptosis in metabolic diseases, introduce the methods for ferroptosis detection, and discuss the therapeutic perspectives of ferroptosis, which collectively aim to illustrate a comprehensive view of ferroptosis in basic, translational, and clinical science., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

Objectives: To investigate the expression of signal recognition particle 14 (SRP14) in hepatocellular carcinoma (HCC) and its clinical significance., Methods: The data of SRP14 expression in HCC were obtained from bioinformatics study, and from investigation with quantitative reverse transcription polymerase chain reaction (qRT-PCR), immunohistochemical staining and Western blotting in clinical samples. The Kaplan-Meier analysis was used to determine the associations between SRP14 mRNA expression and the overall survival, progression-free survival, and disease-specific survival of HCC patients. The effect of SRP14 on the proliferation and migration of HCC cells were determined by EdU staining, MTS, Transwell and wound-healing assays. The potential mechanism for SRP14 regulating HCC was explored through Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) enrichment analysis as well as qRT-PCR., Results: According to the data from GSE14520, TNMplot database and clinical samples, compared with paired tumor-adjacent tissues, non-paired tumor-adjacent tissues and normal tissues, the mRNA expression of SPR14 in HCC tissues was upregulated (all P <0.05). In clinical samples, compared with paired tumor-adjacent tissues, the protein expression of SPR14 in HCC tissues was increased ( P <0.05). The increased mRNA expression of SRP14 was associated with good overall survival, progression-free survival, and disease-specific survival in HCC patients. SRP14 inhibited the proliferation and migration of HCC cells in vitro . According to the KEGG and GO enrichment analysis, in non-specific HCC, the genes co-expressed with SRP14 may predominantly regulate protein synthesis, processing, and transport, while in nonalcoholic fatty liver disease related HCC, the genes co-expressed with SRP14 could control multiple signaling pathways such as MAPK, cAMP, PI3K-Akt, and Wnt. Mechanistically, SRP14 up-regulated the mRNA expression of tumor suppressor gene GPRC5A inHCC cells ( P <0.05)., Conclusions: SRP14 may regulate HCC progression and influence patient prognosis.

Chemoresistance is a main cause of chemotherapy failure and tumor recurrence. The effects of global protein SUMOylation on chemoresistance in colorectal cancer (CRC) remains to be investigated. Herein, we have proposed that the elevated SUMO2/3-modified proteins confer 5-fluorouracil (5-FU) chemoresistance acquisition in CRC. The SUMOylation levels of global proteins in CRC cell lines were elevated compared with normal colon cell line NCM460. 5-FU treatment obviously reduced SUMOylation of global proteins in 5-FU-sensitive CRC cells including HT29, HCT116 and HCT-8. However, in 5-FU-resistant HCT-8/5-FU cells, the expression level of SUMO2/3-modified proteins was increased under 5-FU exposure in a concentration-dependent manner. 5-FU treatment combined with SUMOylation inhibitor ML-792 significantly increased the sensitivity of 5-FU-resistant cells to 5-FU and reduced colony formation numbers in HCT-8/5-FU cells. And UBC9-mediated SUMOylation elevation contributes to 5-FU resistance in HCT116 cells. Moreover, we also identified RREB1 as a regulator of SUMOylation profiling of global cellular proteins via directly binding to the promoter of UBC9 . Overexpression of RREB1 promoted 5-FU resistance in CRC, which was partially abolished by treatment of inhibitor ML-792. In conclusion, RREB1-enhanced protein SUMOylation contributes to 5-FU resistance acquisition in CRC., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Deng, Chen, Gao, Zhang, Luo, Luo, Li, Fu and Liang.)

Background and Aims: Extrachromosomal circular DNAs (eccDNAs) are prevalent in cancer genomes and emerge as a class of crucial yet less characterized oncogenic drivers. However, the structure, composition, genome-wide frequency, and contribution of eccDNAs in HCC, one of the most fatal and prevalent cancers, remain unexplored. In this study, we provide a comprehensive characterization of eccDNAs in human HCC and demonstrate an oncogenic role of microRNA (miRNA)-17-92-containing eccDNAs in tumor progression., Approach and Results: Using the circle-sequencing method, we identify and characterize more than 230,000 eccDNAs from 4 paired samples of HCC tumor and adjacent nontumor liver tissues. EccDNAs are highly enriched in HCC tumors, preferentially originate from certain chromosomal hotspots, and are correlated with differential gene expression. Particularly, a series of eccDNAs carrying the miRNA-17-92 cluster are validated by outward PCR and Sanger sequencing. Quantitative PCR analyses reveal that miRNA-17-92-containing eccDNAs, along with the expression of their corresponding miRNAs, are elevated in HCC tumors and associated with poor outcomes and the age of HCC patients. More intriguingly, exogenous expression of artificial DNA circles harboring the miR-17-92 cluster, which is synthesized by the ligase-assisted minicircle accumulation method, can significantly accelerate HCC cell proliferation and migration., Conclusions: These findings delineate the genome-wide eccDNAs profiling of HCC and highlight the functional significance of miRNA-containing eccDNAs in tumorigenesis, providing insight into HCC pathogenesis and cancer therapy, as well as eccDNA and miRNA biology., (Copyright © 2023 American Association for the Study of Liver Diseases.)

Objective: The systemic spread of colorectal cancer (CRC) is dominated by the portal system and exhibits diverse patterns of metastasis without systematical genomic investigation. Here, we evaluated the genomic evolution of CRC with multiorgan metastases using multiregion sequencing., Design: Whole-exome sequencing was performed on multiple regions (n=74) of matched primary tumour, adjacent non-cancerous mucosa, liver metastasis and lung metastasis from six patients with CRC. Phylogenetic reconstruction and evolutionary analyses were used to investigate the metastatic seeding pattern and clonal origin. Recurrent driver gene mutations were analysed across patients and validated in two independent cohorts. Metastatic assays were performed to examine the effect of the novel driver gene on the malignant behaviour of CRC cells., Results: Based on the migration patterns and clonal origins, three models were revealed (sequential, branch-off and diaspora), which not only supported the anatomic assumption that CRC cells spread to lung after clonally expanding in the liver, but also illustrated the direct seeding of extrahepatic metastases from primary tumours independently. Unlike other cancer types, polyphyletic seeding occurs in CRC, which may result in late metastases with intermetastatic driver gene heterogeneity. In cases with rapid dissemination, we found recurrent trunk loss-of-function mutations in ZFP36L2 , which is enriched in metastatic CRC and associated with poor overall survival. CRISPR/Cas9-mediated knockout of ZFP36L2 enhances the metastatic potential of CRC cells., Conclusion: Our results provide genomic evidence for metastatic evolution and indicate that biopsy/sequencing of metastases may be considered for patients with CRC with multiorgan or late postoperative metastasis., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective To develop a model of spondyloarthritis (SpA) in mice, and analyze their clinical manifestations, radiological and histological features, and inflammatory cytokines expression levels. Methods Fourteen-week-old female BALB/c mice were immunized by intraperitoneal injection of human cartilage proteoglycan (PG), with their peripheral joints observed and scored 3 times a week. 45 weeks after immunization, micro-computed tomography (micro-CT) was used to scan the axial and peripheral joints, and bone mineral density (BMD) and bone volume/total volume (BV/TV) of the vertebral body were analyzed. The pathological changes of the axial and peripheral joints were evaluated by HE and Safranin-Fast Green staining. The levels of tumor necrosis factor alpha (TNF-α) and interleukin 17A (IL-17A) in serum were tested by ELISA. Results 30% (6/20) of PG-induced SpA (PGISpA) mice exhibited peripheral joint swelling and joint stiffness. Micro-CT showed reduced BMD and BV/TV of the vertebral body and new bone formation in sacroiliac and spinal joints in PGISpA compared with the control. Histological staining showed inflammatory cell infiltration and abnormal proliferation of synovial cells and chondrocytes in the peripheral joints. It also observed chondrocytes proliferation in the sacroiliac joints, and increased chondrocytes and osteoblasts in the spinal joints in PGISpA mice. TNF-α and IL-17A increased at week 20 after induction and TNF-α decreased at week 45 in the serum of induced mice, while IL-17A continued to increase. Conclusion The established model of PGISpA showed similar imaging and pathological features to those of human SpA, suggesting a role of IL-17A in the pathogenesis. This model, together with its research platform, can serve as the cornerstone for SpA and model animal studies.

Patients with inflammatory bowel disease are at increased risk for colitis-associated colorectal cancer (CAC). Therefore, controlling intestinal inflammation is a key therapeutic strategy for CAC. MicroRNAs (miRNAs or miRs) are a family of small noncoding RNAs that have the capacity to regulate fundamental biological processes. To date, a number of miRNAs have been identified as critical regulators of inflammation. However, the specific role of miR-26a in colonic inflammation and colitis-associated carcinogenesis is still elusive. Here, we generated mice with miR-26a myeloid-cell-specific overexpression to show that miR-26a suppressed the intestinal inflammatory response in macrophages by decreasing nuclear factor κB (NF-κB)/STAT3 activation and interleukin 6 (IL-6) production. At the molecular level, a number of NF-κB regulators, including TLR3, PTEN, and PKCδ, were identified as potential targets of miR-26a. Our results thus identify a novel miRNA-mediated mechanism that suppresses carcinogenic inflammation in the colon., Competing Interests: The authors declare no competing interests., (© 2021 The Author(s).)

Background: Chaiqin chengqi decoction (CQCQD) is a Chinese herbal formula derived from dachengqi decoction. CQCQD has been used for the management of acute pancreatitis (AP) in the West China Hospital for more than 30 years. Although CQCQD has a well-established clinical efficacy, little is known about its bioactive ingredients, how they interact with different therapeutic targets and the pathways to produce anti-inflammatory effects., Purpose: Toll-like receptor 4 (TLR4) and the nucleotide-binding oligomerization domain-like receptor family pyrin domain containing 3 (NLRP3) inflammasome-mediated pro-inflammatory signaling pathways, play a central role in AP in determining the extent of pancreatic injury and systemic inflammation. In this study, we screened the bioactive ingredients using a pharmacological sub-network analysis based on the TLR4/NLRP3 signaling pathways followed by experimental validation., Methods: The main CQCQD bioactive compounds were identified by UPLC-QTOF/MS. The TLR4/NLRP3 targets in AP for CQCQD active ingredients were confirmed through a pharmacological sub-network analysis. Mice received 7 intraperitoneal injections of cerulein (50 μg/kg; hourly) to induce AP (CER-AP), while oral gavage of CQCQD (5, 10, 15 and 20 g/kg; 3 doses, 2 hourly) was commenced at the 3rd injection of cerulein. Histopathology and biochemical indices were used for assessing AP severity, while polymerase chain reaction, Western blot and immunohistochemistry analyses were used to study the mechanisms. Identified active CQCQD compounds were further validated in freshly isolated mouse pancreatic acinar cells and cultured RAW264.7 macrophages., Results: The main compounds from CQCQD belonged to flavonoids, iridoids, phenols, lignans, anthraquinones and corresponding glycosides. The sub-network analysis revealed that emodin, rhein, baicalin and chrysin were the compounds most relevant for directly regulating the TLR4/NLRP3-related proteins TLR4, RelA, NF-κB and TNF-α. In vivo, CQCQD attenuated the pancreatic injury and systemic inflammation of CER-AP and was associated with reduced expression of TLR4/NLRP3-related mRNAs and proteins. Emodin, rhein, baicalin and chrysin significantly diminished pancreatic acinar cell necrosis with varied effects on suppressing the expression of TLR4/NLRP3-related mRNAs. Emodin, rhein and chrysin also decreased nitric oxide production in macrophages and their combination had synergistic effects on alleviating cell death as well as expression of TLR4/NLRP3-related proteins., Conclusions: CQCQD attenuated the severity of AP at least in part by inhibiting the TLR4/NLRP3 pro-inflammatory pathways. Its active ingredients, emodin, baicalin, rhein and chrysin contributed to these beneficial effects., (Copyright © 2020 The Authors. Published by Elsevier GmbH.. All rights reserved.)

The UbiA superfamily of intramembrane prenyltransferases catalyzes an isoprenyl transfer reaction in the biosynthesis of lipophilic compounds involved in cellular physiological processes. Digeranylgeranylglyceryl phosphate (DGGGP) synthase (DGGGPase) generates unique membrane core lipids for the formation of the ether bond between the glycerol moiety and the alkyl chains in archaea and has been confirmed to be a member of the UbiA superfamily. Here, the crystal structure is reported to exhibit nine transmembrane helices along with a large lateral opening covered by a cytosolic cap domain and a unique substrate-binding central cavity. Notably, the lipid-bound states of this enzyme demonstrate that the putative substrate-binding pocket is occupied by the lipidic molecules used for crystallization, indicating the binding mode of hydrophobic substrates. Collectively, these structural and functional studies provide not only an understanding of lipid biosynthesis by substrate-specific lipid-modifying enzymes but also insights into the mechanisms of lipid membrane remodeling and adaptation., Competing Interests: Declaration of Interests The authors declare no competing interests., (Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)

Background & Aims: RNA G-quadruplexes (RG4s) appear to be important in post-transcriptional gene regulation, but their pathophysiological functions remain unknown. MicroRNA-26a (miR-26a) is emerging as a therapeutic target for various human diseases, however the mechanisms underlying endogenous miR-26a regulation are poorly understood. Herein, we study the role of RG4 in miR-26a expression and function in vitro and in vivo., Methods: Putative RG4s within liver-enriched miRNAs were predicted by bioinformatic analysis, and the presence of an RG4 structure in the miR-26a-1 precursor (pre-miR-26a-1) was further analyzed by biophysical and biochemical methods. RG4 stabilizers, pre-miR-26a-1 overexpression plasmids, and luciferase reporter assays were used to assess the effect of RG4 on pre-miR-26a-1 maturation. Both miR-26a knock-in and knockout mouse models were employed to investigate the influence of this RG4 on miR-26a expression and function. Moreover, the interaction between RG4 in pre-miR-26a-1 and DEAH-box helicase 36 (DHX36) was determined by biophysical and molecular methods. Finally, miR-26a processing and DHX36 expression were quantified in the livers of obese mice., Results: We identify a guanine-rich sequence in pre-miR-26a-1 that can fold into an RG4 structure. This RG4 impairs pre-miR-26a-1 maturation, resulting in a decrease in miR-26a expression and subsequently an increase in miR-26a cognate targets. In line with known miR-26a functions, this RG4 can regulate hepatic insulin sensitivity and lipid metabolism in vitro and in vivo. Furthermore, we reveal that DHX36 can bind and unwind this RG4 structure, thereby enhancing miR-26a maturation. Intriguingly, there is a concordant decrease of miR-26a maturation and DHX36 expression in obese mouse livers., Conclusions: Our findings define a dynamic DHX36/RG4/miR-26a regulatory axis during obesity, highlighting an important role of RG4 in physiology and pathology., Lay Summary: Specific RNA sequences called G-quadruplexes (or RG4) appear to be important in post-transcriptional gene regulation. Obesity leads to the formation of these RG4 structures in pre-miR-26a-1 molecules, impairing the maturation and function of miR-26a, which has emerged as a therapeutic target in several diseases. This contributes to hepatic insulin resistance and the dysregulation of liver metabolism., Competing Interests: Conflict of interest The authors declare no conflicts of interest that pertain to this work. Please refer to the accompanying ICMJE disclosure forms for further details., (Copyright © 2020 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.)

Objectives: Anti-citrullinated protein antibodies (ACPAs) are a group of autoantibodies targeted against citrullinated proteins/peptides and are informative rheumatoid arthritis (RA) biomarkers. ACPAs also play a crucial role in RA pathogenesis, and their underlying mechanism merits investigation., Methods: Immunohistochemical (IHC) assays were carried out to determine IL-1β levels in ACPA + and ACPA - RA patients. PBMC-derived monocytes were differentiated into macrophages before stimulation with ACPAs purified from RA patients. The localization and interaction of molecules were analyzed by confocal microscopy, co-IP, and surface plasmon resonance., Results: In our study, we found that IL-1β levels were elevated in ACPA + RA patients and that ACPAs promoted IL-1β production by PBMC-derived macrophages. ACPAs interacted with CD147 to enhance the interaction between CD147 and integrin β1 and, in turn, activate the Akt/NF-κB signaling pathway. The nuclear localization of p65 promoted the expression of NLRP3 and pro-IL-1β, resulting in priming. Moreover, ACPA stimulation activated pannexin channels, leading to ATP release. The accumulated ATP bound to the P2X7 receptor, leading to NLRP3 inflammasome activation., Conclusions: Our study suggests a new hypothesis regarding IL-1β production in RA involving ACPAs, which may be a potential therapeutic target in RA treatment.

Objective: The mixed lineage kinase domain like (MLKL) protein, receptor interacting protein (RIPK) 1, and RIPK3 are key regulators of necroptosis, a highly pro-inflammatory mode of cell death that has been implicated in various pathological processes and human diseases. However, the role of these necroptotic regulators in diabetes remains unknown. Here we sought to delineate the role of MLKL in insulin resistance and type 2 diabetes (T2D)., Methods: We first analyzed the expression of key necroptotic regulators in obese/diabetic mouse models. We then utilized MLKL knockout (MLKL -/- ) mice to evaluate the effects of MLKL on obesity-induced metabolic complications. We further determined the consequences of MLKL inhibition on hepatic insulin signaling and explored the underlying mechanism. Finally, we assessed the potential therapeutic effects of necroptotic inhibitor, necrostatin-1 (Nec-1), in ob/ob mice., Results: In wild-type or obese mice (ob/ob, db/db, or diet-induced obesity), MLKL was increased in certain obesity-associated tissues, particularly in the liver. Whole-body deficiency of MLKL prevented obesity-induced insulin resistance and glucose intolerance. Inhibition of MLKL or other key necroptotic regulators enhanced hepatic insulin sensitivity. MLKL modulated insulin-stimulated PI(3,4,5)P3 production in liver cells but did not affect the expression of inflammatory genes in vitro and in vivo. Nec-1 administration ameliorated insulin resistance and glucose intolerance in ob/ob mice., Conclusions: These findings reveal MLKL as a regulator of insulin sensitivity and suggest necroptotic regulators might be potential therapeutic targets for insulin resistance and T2D., (Copyright © 2019 The Authors. Published by Elsevier GmbH.. All rights reserved.)

Purpose: Both epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) and chemotherapy are widely applied for the treatment of advanced non-small-cell lung cancer (NSCLC) with EGFR mutations, and the combination of EGFR-TKIs and chemotherapy has been used for advanced NSCLC patients; however, little is known about the efficacy of the direct comparison among them., Patients and Methods: The demographic and clinical characteristics of 92 patients harboring advanced NSCLC with EGFR mutation were retrospectively reviewed. We evaluated the effects of EGFR-TKIs, chemotherapy, and EGFR-TKIs plus chemotherapy on advanced NSCLC patients with EGFR mutations, and the efficacy of combination of chemotherapy and EGFR-TKIs vs chemotherapy or EGFR-TKIs alone in advanced NSCLC patients was evaluated., Results: The statistical results showed that the intercalated combination of EGFR-TKIs plus chemotherapy significantly improved progression-free survival (PFS; HR, 1.76; 95% CI 1.03-3.01; P =0.036; median, 20.5 vs 16 months) compared with EGFR-TKI monotherapy, but no difference in overall survival (OS) was observed between these two groups (HR, 1.52; 95% CI 0.81-2.83; P =0.19; median, 36 vs 29 months). However, patients who received the combination of chemotherapy and EGFR-TKIs had longer PFS (HR, 2.78; 95% CI 1.57-4.93; P <0.0001; median, 20.5 vs 12 months) as well as OS (HR, 2.86; 95% CI 1.56-5.27; P =0.001; median, 36 vs 18 months) than those who received chemotherapy alone. Toxicities were mild among the three treatment groups. Rash and diarrhea were common adverse events (AEs) in the EGFR-TKI group, anemia and nausea in the chemotherapy group, and anemia and diarrhea in the combination group., Conclusion: This study demonstrated that the combination of chemotherapy with EGFR-TKIs as first-line treatment has a significant effect on PFS in patients with advanced NSCLC whose tumors harbor activating EGFR mutations. The combination treatment had more toxicity, but was clinically manageable., Competing Interests: Disclosure The authors report no conflicts of interest in this work.

Type 2 diabetes (T2D) is characterized by insulin resistance and increased hepatic glucose production, yet the molecular mechanisms underlying these abnormalities are poorly understood. MicroRNAs (miRs) are a class of small, noncoding RNAs that have been implicated in the regulation of human diseases, including T2D. miR-26a is known to play a critical role in tumorigenesis; however, its function in cellular metabolism remains unknown. Here, we determined that miR-26a regulates insulin signaling and metabolism of glucose and lipids. Compared with lean individuals, overweight humans had decreased expression of miR-26a in the liver. Moreover, miR-26 was downregulated in 2 obese mouse models compared with control animals. Global or liver-specific overexpression of miR-26a in mice fed a high-fat diet improved insulin sensitivity, decreased hepatic glucose production, and decreased fatty acid synthesis, thereby preventing obesity-induced metabolic complications. Conversely, silencing of endogenous miR-26a in conventional diet-fed mice impaired insulin sensitivity, enhanced glucose production, and increased fatty acid synthesis. miR-26a targeted several key regulators of hepatic metabolism and insulin signaling. These findings reveal miR-26a as a regulator of liver metabolism and suggest miR-26a should be further explored as a potential target for the treatment of T2D.

Objective: To study the pathological process and characteristics of bleomycin (BLM)-induced interstitial lung disease (ILD) model and collagen-induced arthritis (CIA) complicated by BLM-induced ILD (CIA-ILD) model in mice and explore the correlations with circulating fibrocytes., Methods: Ninety mice were randomly divided into normal saline group (S group), BLM group (B group), CIA-BLM group (CB group), with 30 mice in each group. On the 2, 7, 14, 21 and 28 days after BLM challenge, mice of each group were sacrificed. HE staining was used to detect the degrees of acute inflammation and sirius red staining to detect lung fibrosis. Immunohistochemicstry was adopted to detect alpha-smooth muscle actin expression. The peripheral blood was obtained to count the proportion of circulating fibrocytes (CD45⁺COL1⁺) by flow cytometry. The correlations between circulating fibrocytes and pathological changes of ILD were analyzed statistically., Results: Both of the ILD model groups showed the dynamic process from pulmonary alveolitis to fibrosis gradually. Inflammatory lesion in the lungs of B group was the most obvious on the 7-14th day, and then there was a slow rehabilitation process on the 21th and 28th day. CB group began to present alveoli destruction and collagen deposition on the 14th day, and the inflammation was the most severe on the 28th day. Pulmonary hydroxyproline content was obviously ascended in CB group as compared with B group (P<0.05) after 14 days. An increase in the total number of circulating fibrocytes was observed in both B and CB groups. It tended to increase at first, and subsequently declined. The level of circulating fibrocytes was higher in CB group than in B group on day 14, 21 and 28 (P<0.05). The immunohistochemical results showed that there were many myofibroblasts infiltrating in CB group from the 14th day to 28th day. The number of circulating fibrocytes in peripheral blood was positively correlated with pulmonary inflammation, fibrosis degree and hydroxyproline content (r=0.847, 0.826, 0.735, P<0.01)., Conclusion: The pathological process of CIA-ILD animal model is more close to rheumatoid arthritis-induced ILD development. Circulating fibrocytes may be involved in the inflammation and fibrosis progression of lung.