E3 ligases MAC3A and MAC3B ubiquitinate UBIQUITIN-SPECIFIC PROTEASE14 to regulate organ size in Arabidopsis.

The molecular mechanisms controlling organ size during plant development ultimately influence crop yield. However, a deep understanding of these mechanisms is still lacking. UBIQUITIN-SPECIFIC PROTEASE14 (UBP14), encoded by DA3, is an essential factor determining organ size in Arabidopsis (Arabidopsis thaliana). Here, we identified two suppressors of the da3-1 mutant phenotype, namely SUPPRESSOR OF da3-1 1 and 2 (SUD1 and SUD2), which encode the E3 ligases MOS4-ASSOCIATED COMPLEX 3A (MAC3A) and MAC3B, respectively. The mac3a-1 and mac3b-1 mutations partially suppressed the high ploidy level and organ size phenotypes observed in the da3-1 mutant. Biochemical analysis showed that MAC3A and MAC3B physically interacted with and ubiquitinated UBP14/DA3 to modulate its stability. We previously reported that UBP14/DA3 acts upstream of the B-type cyclin-dependent kinase CDKB1;1 and maintains its stability to inhibit endoreduplication and cell growth. In this work, MAC3A and MAC3B were found to promote the degradation of CDKB1;1 by ubiquitinating UBP14/DA3. Genetic analysis suggests that MAC3A and MAC3B act in a common pathway with UBP14/DA3 to control endoreduplication and organ size. Thus, our findings define a regulatory module, MAC3A/MAC3B-UBP14-CDKB1;1, that plays a critical role in determining organ size and endoreduplication in Arabidopsis.

Long-term exercise preserves pancreatic islet structure and ß-cell mass through attenuation of islet inflammation and fibrosis.

Islet fibrosis is associated with the disruption of islet structure and contributes to ß-cell dysfunction, playing an essential role in the pathogenesis of type 2 diabetes. Physical exercise has been shown to attenuate fibrosis in various organs; however, the effect of exercise on islet fibrosis has not been defined. Male Sprague-Dawley rats were divided into four groups: normal diet sedentary [N-Sed], normal diet + exercise [N-Ex], high-fat diet sedentary [H-Sed], and high-fat diet + exercise [H-Ex]. After 60 weeks of exercise, 4452 islets from Masson-stained slides were analyzed. Exercise led to a 68% and 45% reduction in islet fibrosis in the normal and high-fat diet groups and was correlated with a lower serum blood glucose. Fibrotic islets were characterized by irregular shapes and substantial loss of ß-cell mass, which were significantly reduced in the exercise groups. Remarkably, the islets from exercised rats at week 60 were morphologically comparable to those of sedentary rats at 26 weeks. In addition, the protein and RNA levels of collagen and fibronectin, and the protein levels of hydroxyproline in the islets were also attenuated by exercise. This was accompanied by a significant reduction in inflammatory markers in the circulation Interleukin-1 beta (IL-1ß)] and pancreas [IL-1ß, Tumor Necrosis Factor-alpha, Transforming Growth Factor-ß, and Phosphorylated Nuclear Factor Kappa-B p65 subunit], lower macrophage infiltration, and stellate cell activation in the islets of exercised rats. In conclusion, we have demonstrated that long-term exercise preserves pancreatic islet structure and ß-cell mass through anti-inflammatory and anti-fibrotic actions, suggesting additional rationales for the success of exercise training in the prevention and treatment of type 2 diabetes that should be further explored.

Information quality of videos related to Helicobacter pylori infection on TikTok: Cross-sectional study.

BACKGROUND: Helicobacter pylori (H. pylori) poses serious threats to human health. TikTok (Douyin in Chinese), a major social media platform focused on sharing short videos, has demonstrated great potential in spreading health information, including information related to H. pylori infection. This study aims to evaluate the content and quality of the information shared in TikTok videos about H. pylori infection in mainland China. METHODS: We collected a sample of 116 videos in Chinese related to H. pylori infection from TikTok. Video contents were evaluated by the coding schema proposed by Goobie et al., and the Hexagonal Radar Schema was used to intuitively display the spotlight and weight of each aspect of the videos. The DISCERN questionnaire was used to evaluate the quality of the videos. RESULTS: We identified two major sources of videos related to H. pylori: individual users (n = 89) and organizational users (n = 27). Regarding content, the Hexagonal Radar Charts showed that more than 35% of the videos delivered moderate to high quality content (>1 point) in terms of definition, symptoms and management of the disease, whereas risk factors, evaluation and outcomes of the disease were less discussed. The DISCERN classification data showed that 0.9% of the videos were "very poor," 5.2% "poor," 68.7% "fair," 20.0% "good," and only 5.2% "excellent". Regarding total DISCERN scores, videos published by nonprofit organizations had the highest scores, followed by videos uploaded by health professionals. CONCLUSION: Although the overall quality of TikTok videos related to H. pylori infection was medium, users should be careful when obtaining information related to H. pylori infection on TikTok and opt for videos uploaded by nonprofit organizations and health professionals.

OsGADD45a1: a multifaceted regulator of rice architecture, grain yield, and blast resistance.

KEY MESSAGE: The homolog gene of the Growth Arrest and DNA Damage-inducible 45 (GADD45) in rice functions in the regulation of plant architecture, grain yield, and blast resistance. The Growth Arrest and DNA Damage-inducible 45 (GADD45) family proteins, well-established stress sensors and tumor suppressors in mammals, serve as pivotal regulators of genotoxic stress responses and tumorigenesis. In contrast, the homolog and role of GADD45 in plants have remained unclear. Herein, using forward genetics, we identified an activation tagging mutant AC13 exhibited dwarf characteristics resulting from the loss-of-function of the rice GADD45α homolog, denoted as OsGADD45a1. osgadd45a1 mutants displayed reduced plant height, shortened panicle length, and decreased grain yield compared to the wild-type Kitaake. Conversely, no obvious differences in plant height, panicle length, or grain yield were observed between wild-type and OsGADD45a1 overexpression plants. OsGADD45a1 displayed relatively high expression in germinated seeds and panicles, with localization in both the nucleus and cytoplasm. RNA-sequencing analysis suggested a potential role for OsGADD45a1 in the regulation of photosynthesis, and binding partner identification indicates OsGADD45a1 interacts with OsRML1 to regulate rice growth. Intriguingly, our study unveiled a novel role for OsGADD45a1 in rice blast resistance, as osgadd45a1 mutant showed enhanced resistance to Magnaporthe oryzae, and the expression of OsGADD45a1 was diminished upon blast fungus treatment. The involvement of OsGADD45a1 in rice blast fungus resistance presents a groundbreaking finding. In summary, our results shed light on the multifaceted role of OsGADD45a1 in rice, encompassing biotic stress response and the modulation of several agricultural traits, including plant height, panicle length, and grain yield.

Enterovirus 71 enters human brain microvascular endothelial cells through an ARF6-mediated endocytic pathway.

Infection of the central nervous system caused by enterovirus 71 (EV71) remains the main cause of death in hand-foot-and-mouth disease. However, the mechanism responsible for how EV71 breaks through the blood-brain barrier to infect brain cells has yet to be elucidated. By performing a high-throughput small interfering RNA (siRNA) screening and validation, we found that the infection of human brain microvascular endothelial cells (HBMECs) by EV71 was independent of the endocytosis pathways mediated by caveolin, clathrin, and macropinocytosis but dependent on ADP-ribosylation factor 6 (ARF6), a small guanosinetriphosphate (GTP)-binding protein of the Ras superfamily. The specific siRNA targeting ARF6 markedly inhibited HBMECs susceptibility to EV71. EV71 infectivity was inhibited by NAV-2729, a specific inhibitor of ARF6, in a dose-dependent manner. The subcellular analysis demonstrated the co-localization of the endocytosed EV71 and ARF6, while knockdown of ARF6 with siRNA remarkably influenced EV71 endocytosis. By immunoprecipitation assays, we found a direct interaction of ARF6 with EV71 viral protein. Furthermore, ARF1, another small GTP-binding protein, was also found to participate in ARF6-mediated EV71 endocytosis. Murine experiments demonstrated that NAV-2729 significantly alleviated mortality caused by EV71 infection. Our study revealed a new pathway by which EV71 enters the HBMECs and provides new targets for drug development.

HbA1c combined with glycated albumin or 1,5-anhydroglucitol improves the efficiency of diabetes screening in a Chinese population.

AIMS: This study aimed to evaluate the ability of HbA1c combined with glycated albumin (GA) or 1,5-anhydroglucitol (1,5-AG) to detect diabetes in residents of Jiangsu, China. METHODS: The oral glucose tolerance test (OGTT) was performed on 2184 people in Jiangsu. HbA1c , GA, 1,5-AG and other serum biochemical parameters were measured. Receiver operating characteristic curves were plotted to determine the optimal thresholds of HbA1c , GA and 1,5-AG according to the Youden index. RESULTS: (1) The optimal thresholds of HbA1c , GA and 1,5-AG for the screening of diabetes were ≥45 mmol/mol (6.3%), ≥13.0% and ≤23.0 µg/ml, respectively. (2) The sensitivities of HbA1c combined with GA and 1,5-AG were both 85%, higher than that of HbA1c (70%, p < 0.001). CONCLUSIONS: This study is suitable for cases where plasma glucose is unavailable. Among the residents of Jiangsu, HbA1c combined with GA or 1,5-AG can improve the sensitivity of diabetes screening, reduce the miss rate and save the use of OGTT. GA and 1,5-AG are superior in individuals with mild glucose metabolism disorder. GA enhances the detection of diabetes in the nonobese, and 1,5-AG enhances the detection in those with hyperuricaemia.

A dimethyl disulfide gas sensor based on nanosized Pt-loaded tetrakaidecahedralα-Fe2O3nanocrystals.

Surface modification by employing precious metals is one of the most effective ways to improve the gas-sensing performance of metal oxide semiconductors. Pureα-Fe2O3nanoparticles and Pt-modifiedα-Fe2O3nanoparticles were prepared sequentially using a rather simple hydrothermal synthesis and impregnation method. Compared with the originalα-Fe2O3nanomaterials, the Pt-α-Fe2O3nanocomposite sensor shows a higher response value (Ra/Rg = 58.6) and a shorter response/recovery time (1 s/168 s) to 100 ppm dimethyl disulfide (DMDS) gas at 375 °C. In addition, it has better selectivity to DMDS gas with the value of more than 9 times higher than the other target gases at 375 °C. This study indicates that the Pt-α-Fe2O3nanoparticle sensor has good prospects and can be used as a low-cost and effective DMDS gas sensor.

Reactive Oxygen Species Cause Exercise-Induced Angina in a Myocardial Ischaemia-Reperfusion Injury Model.

Percutaneous coronary intervention (PCI) effectively treats obstructive coronary artery syndrome. However, 30-40% patients continue to have angina after a successful PCI, thereby reducing patient satisfaction. The mechanisms underlying persistent angina after revascularisation therapy are still poorly understood; hence, the treatment or guideline for post-PCI angina remains unestablished. Thus, this study aimed to investigate the mechanisms underlying effort angina in animals following myocardial ischaemia-reperfusion (I/R) injury. Phosphorylated extracellular signal-regulated kinase (p-ERK), a marker for painful stimulation-induced neuronal activation, was used for the investigation. After a forced treadmill exercise (FTE), the number of p-ERK-expressing neurons increased in the superficial dorsal horn of the I/R model animals. Moreover, FTE evoked hydrogen peroxide (H2O2) production in the I/R-injured heart, inducing angina through TRPA1 activation on cardiac sensory fibres. Notably, the treatment of a TEMPOL, a reactive oxygen species scavenger, or TRPA1-/- mice successfully alleviated the FTE-induced p-ERK expression in the dorsal horn. The production of H2O2, a reactive oxygen species, through physical exercise contributes to angina development following I/R. Hence, our findings may be useful for understanding and treating angina following revascularisation therapy.

MRI-based radiomics model for preoperative prediction of 5-year survival in patients with hepatocellular carcinoma.

BACKGROUND: Recurrence is the major cause of mortality in patients with resected HCC. However, without a standard approach to evaluate prognosis, it is difficult to select candidates for additional therapy. METHODS: A total of 201 patients with HCC who were followed up for at least 5 years after curative hepatectomy were enrolled in this retrospective, multicentre study. A total of 3144 radiomics features were extracted from preoperative MRI. The random forest method was used for radiomics signature building, and five-fold cross-validation was applied. A radiomics model incorporating the radiomics signature and clinical risk factors was developed. RESULTS: Patients were divided into survivor (n = 97) and non-survivor (n = 104) groups based on the 5-year survival after surgery. The 30 most survival-related radiomics features were selected for the radiomics signature. Preoperative AFP and AST were integrated into the model as independent clinical risk factors. The model demonstrated good calibration and satisfactory discrimination, with a mean AUC of 0.9804 and 0.7578 in the training and validation sets, respectively. CONCLUSIONS: This radiomics model is a valid method to predict 5-year survival in patients with HCC and may be used to identify patients for clinical trials of perioperative therapies and for additional surveillance.

Combined Scores from the EncephalApp Stroop Test, Number Connection Test B, and Serial Dotting Test Accurately Identify Patients With Covert Hepatic Encephalopathy.

BACKGROUND & AIMS: The EncephalApp Stroop test is a high-sensitivity but low-specificity test that has been used to identify patients with covert hepatic encephalopathy (CHE). We aimed to develop a new strategy to detect CHE, combining EncephalApp Stroop test score with scores from subtests of the psychometric hepatic encephalopathy scoring system (PHES). METHODS: We performed a survey of 569 adult volunteers (229 men) in 9 communities in Shanghai, China, administering the EncephalApp Stroop test to determine the range of scores in the general population. Data from the standard PHES, including the number connection test-A, number connection test-B (NCT-B), line tracing test, serial dotting test (SDT), and digit symbol test, were used as the reference standard for diagnosis of CHE. A combination of the EncephalApp Stroop with subtests of the PHES was used to establish a new strategy for CHE diagnosis. We validated our findings using data from 160 patients with cirrhosis from 5 centers China. RESULTS: We determined the range of EncephalApp Stroop test scores for the volunteers of different decades of age, education levels, and sexes. Age, education level, and sex were independently associated with EncephalApp Stroop test scores. A combination of scores from the EncephalApp Stroop test, the NCT-B, and the SDT identified patients with CHE with the highest level of accuracy, when the standard PHES was used as the reference standard. A combination of scores of 187 sec for the EncephalApp Stroop test and below -1 for the NCT-B or below -1 for the SDT identified patients with CHE with an area under the curve (AUC) of 0.86, 81.0% sensitivity, and 91.9% specificity, and 87.5% accuracy. In the validation cohort, these cutoff scores identified patients with CHE with an AUC of 0.88, 97.1% sensitivity, 79.3% specificity, and 86.9% accuracy. The average time to calculate this score was 374±140 sec, compared 424±115 sec for the entire PHES. CONCLUSION: Scores from the EncephalApp Stroop test, NCT-B, and SDT identify patients with CHE with approximately 87% accuracy, and in a much shorter time than the standard PHES. This score combination could be a valid and convenient method for identifying patients with CHE. chictr.org.cn number, ChiCTR-EDC-17012007, ChiCTR1800019954.

Differential confocal self-collimation method for high-accuracy measurements of lens decentration.

A differential confocal self-collimation decentration measurement method (DCSDM) is proposed. It uses the differential confocal method to precisely identify the center and vertex positions of the tested lens surface, thereby obtaining the radius of curvature. Then, it uses the self-collimation light-path to detect the position of the reflected light during the rotation of the tested surface, thereby obtaining the center bias. Finally, it calculates the decentration. Theoretical analysis and experiments indicate that DCSDM achieves an accuracy of 0.069". Compared with existing methods, DCSDM significantly reduces the focusing error by using differential techniques, prevents multiple clamping errors by integrating the radius and center bias measurements in one system, and is a feasible method for decentration measurement.

Tea consumption and risk of diabetes in the Chinese population: a multi-centre, cross-sectional study.

The aim of the present study was to explore the influence of tea consumption on diabetes mellitus in the Chinese population. This multi-centre, cross-sectional study was conducted in eight sites from south, east, north, west and middle regions in China by enrolling 12 017 subjects aged 20-70 years. Socio-demographic and general information was collected by a standardised questionnaire. A standard procedure was used to measure anthropometric characteristics and to obtain blood samples. The diagnosis of diabetes was determined using a standard 75-g oral glucose tolerance test. In the final analysis, 10 825 participants were included and multiple logistic models and interaction effect analysis were applied for assessing the association between tea drinking with diabetes. Compared with non-tea drinkers, the multivariable-adjusted OR for newly diagnosed diabetes were 0·80 (95 % CI 0·67, 0·97), 0·88 (95 % CI 0·71, 1·09) and 0·86 (95 % CI 0·67, 1·11) for daily tea drinkers, occasional tea drinkers and seldom tea drinkers, respectively. Furthermore, drinking tea daily was related to decreased risk of diabetes in females by 32 %, elderly (>45 years) by 24 % and obese (BMI > 30 kg/m2) by 34 %. Moreover, drinking dark tea was associated with reduced risk of diabetes by 45 % (OR 0·55; 95 % CI 0·42, 0·72; P < 0·01). The results imply that drinking tea daily was negatively related to risk of diabetes in female, elderly and obese people. In addition, drinking dark tea was associated with decreased risk of type 2 diabetes mellitus.

Improving the ability to predict hospital mortality among adults by combining two status epilepticus outcome scoring tools.

OBJECTIVE: The goal of this study was to compare the predictive ability of the Status Epilepticus Severity Score (STESS), the Encephalitis-nonconvulsive status epilepticus (NCSE)-Diazepam resistance-Image abnormalities-Tracheal intubation (END-IT), and the combination of these two scoring tools to predict mortality among inhospital patients with status epilepticus (SE). METHODS: A retrospective analysis was conducted of adult patients with SE who were admitted to the neurology department, the emergency department, and the intensive care unit from January 2013 to December 2017. The patients were divided into two groups: survivors and nonsurvivors. The STESS data were obtained when the patient arrived at the hospital, and the END-IT data were collected 24 h after patients were initially treated in the hospital. The ability of the scoring tools to predict death in patients with SE, alone or in combination, was evaluated. RESULTS: A total of 123 patients with SE were included in the study, of which 22 died, for a mortality rate of 17.9%. The STESS and END-IT scores of nonsurvivors were both significantly higher than those of survivors (median STESS 4 vs. 2, p = 0.003; median END-IT 3 vs. 1, p < 0.001). The area under the receiver operating characteristic curve (AUC) was 0.698 for the STESS and 0.852 for the END-IT, and the cutoff values were 4 and 3, respectively. The AUC of the END-IT with the optimal cutoff value was larger than that of the STESS (p = 0.024). The sensitivity and specificity of combining the STESS and END-IT by the serial method (STESS ≥ 4∩END-IT ≥ 3) were 0.50 and 0.95, respectively, and the specificity was significantly higher than the STESS or END-IT (both p's < 0.001). The sensitivity and specificity of combining the STESS and END-IT by the parallel method (STESS ≥ 4⋃END-IT ≥ 3) were 0.91 and 0.53, respectively, and the sensitivity was higher than the STESS was (p = 0.016). CONCLUSION: Our results indicated that the combined score of the STESS and END-IT systems was a better predictor of survival of patients with SE than the scores of either the STESS system or the END-IT system alone and that combining the scores may be considered to be a new method for early identification of patients for both good and bad outcomes.

Different prognostic significance of examined lymph node count for patients with non-small-cell lung cancer ≤1 cm or >1-2 cm: a population-based study.

Aim: This study aimed to investigate the impact of examined lymph node (ELN) count on survival of resected pT1a-1bN0M0 non-small-cell lung cancer (NSCLC). Materials & methods: Data were extracted from the US Surveillance, Epidemiology and End Results database. The association between ELN count and overall survival (OS) or lung cancer-specific survival (LCSS) was investigated. Results: A total of 9603 patients were enrolled. For the first through the fourth quartiles of pT1aN0M0 group, the 5-year OS and LCSS rates were of no statistical difference. While in pT1bN0M0 group, they were 68.7, 73.8, 76.6 and 77.8% (p < 0.001) and 80.7, 84.1, 85.9 and 87.1% (p < 0.001), respectively. X-Tile analysis showed that 4 is the optimal cutoff value for ELN count in pT1bN0M0 patients for both OS and LCSS. Conclusion: These findings indicated that greater number of ELNs is associated with better survival of resected pT1bN0M0 NSCLC. But a greater number of ELNs is worth to discuss for pT1aN0M0 NSCLC during surgery.

A modified in vitro tool for isolation and characterization of rat quiescent islet stellate cells.

BACKGROUND: Islet stellate cells (ISCs) play a critical role in islet fibrosis, contributing to the progression of pancreatic diseases. Previous studies have focused on fibrosis-associated activated ISCs obtained by standard islet explant techniques. However, in vitro models of quiescent ISCs (qISCs) are lacking. This study aims to develop a method to isolate qISCs and analyze their phenotype during activation. METHODS: Immunofluorescence staining was applied to localize ISCs in normal human, rat, and mouse islets. qISCs were isolated from rat islets using density gradient centrifugation (DGC) method. qRT-PCR, immunoblotting, proliferation, and migration assays were employed for their characterization. RESULTS: Desmin-positive ISCs were detected in normal human, rat, and mouse islets. Freshly isolated qISCs, obtained by density gradient centrifugation, displayed a polygonal appearance with refringent cytoplasmic lipid droplets and expressed transcriptional markers indicating a low activation/quiescent state. With increasing culture time, the marker expression pattern changed, reflecting ISC activation. qISCs contained more lipid droplets and exhibited lower proliferation and migration abilities compared to spindle-shaped ISCs obtained by traditional explant techniques. CONCLUSIONS: This study describes a new method for efficient isolation of qISCs from rat islets, representing a useful in vitro tool to study the biology of ISCs in more physiological conditions.

Lipotoxicity reduces ß cell survival through islet stellate cell activation regulated by lipid metabolism-related molecules.

BACKGROUND: Islet stellate cells (ISCs) activation is mainly associated with islet fibrosis, which contributes to the progression of type 2 diabetes. However, the molecular mechanism underlying this process is not fully understood. METHODS: In order to investigate this process the current study examined ectopic fat accumulation in rats with high-fat diet (HFD) induced obesity. Levels of lipotoxicity-induced ISC activation and islet function were assessed via intraperitoneal glucose and insulin tolerance tests, and immunohistochemistry. The expression of lipid metabolism- and ISC activation-related markers was evaluated in cultured ISCs treated with palmitic acid (PA) using quantitative PCR and western blotting. We also overexpressed sterol regulatory element-binding protein (SREBP)-1c in ISCs by lentiviral transduction, and assessed the effects on insulin release in co-cultures with isolated rat islets. RESULTS: HFD increased body weight and ectopic fat accumulation in pancreatic islets. Lipotoxicity caused progressive glucose intolerance and insulin resistance, upregulated α-smooth muscle actin, and stimulated the secretion of extracellular matrix. Lipotoxicity reduced the expression of lipid metabolism-related molecules in ISCs treated with PA, especially SREBP-1c. Overexpression of SREBP-1c in ISCs improved islet viability and insulin secretion in co-cultures. CONCLUCIONS: These results indicate that lipotoxicity-induced ISC activation alters islet function via regulation of lipid metabolism, suggesting that therapeutic strategies targeting activated ISC may be an effective treatment for prevention of ISC activation-associated islet dysfunction.

Protective effects of Clec11a in islets against lipotoxicity via modulation of proliferation and lipid metabolism in mice.

The lipotoxicity is considered as one of the risk for diabetes. Here we report C-type lectin domain family 11, member A (Clec11a) as a new regulator in islet playing a protective role in lipotoxicity induced dysfunction. Islet transcriptome sequencing was performed using the high-fat diet induced obesity (DIO) mice model. We found a significant decrease of Clec11a expression in islets of DIO mice compared to normal control mice, which was further confirmed by real-time PCR. Immunostaining demonstrated the localization of the Clec11a protein in mouse islets. Administration of recombinant human Clec11a (rClec11a) protein promoted the proliferation of islet cells and rescued the inhibition of fatty acid on cell proliferation, which involved the activation of Erk signaling pathway. We also found that the rClec11a altered the expression of genes involved in lipid metabolism.

MicroRNA-134 deactivates hepatic stellate cells by targeting TGF-ß activated kinase 1-binding protein 1.

Aberrant expression of microRNAs is associated with liver fibrogenesis. We previously found that microRNA-134 (miR-134) expression was reduced in fibrosis-based hepatocarcinogenesis induced by diethylinitrosamine. Herein we investigate the role and mechanisms of miR-134 in hepatic fibrosis. Our data show that miR-134 expression is reduced in rat hepatic fibrogenesis induced by carbontetrachloride, bile duct ligation, and dimethylnitrosamine, as well as in activated hepatic stellate cells (HSCs). Moreover, miR-134 inhibited HSC proliferation, and decreased the expression of smooth muscle actin and collagen I in HSCs, whereas the miR-134 inhibitor increased HSC activation. MiR-134 also negatively regulated transforming growth factor-ß-activated kinase 1-binding protein 1 (TAB1) expression in both human and rat HSCs by directly binding to its 3' untranslated region. Importantly, TAB1 expression was significantly elevated during liver fibrogenesis and HSC activation. Knockdown of TAB1 inhibited the proliferation and fibrogenic behavior of HSCs, and significantly reduced the effect of the miR-134 inhibitor on HSC proliferation. Collectively, these data suggest that miR-134 inhibits the activation of HSCs via directly targeting TAB1, and the restoration of miR-134 or targeting TAB1 is of clinical significance in the treatment of liver fibrosis.

miR-124 ameliorates depressive-like behavior by targeting STAT3 to regulate microglial activation.

Major depressive disorder (MDD) is one of the most prevalent psychiatric disorders worldwide and a major public health concern that is associated with grave consequences. Systemic complexity and feedback processes among diverse drivers of the depression disorder contribute to the considerable variation in responses to the treatment of depression. Dysfunctional microRNA (miRNA) is involved in MDD. miR-124 is enriched in the brain and may be critical in neuronal differentiation. Previous studies have shown the value of miRNA-124 as a putative therapeutic target and a biomarker for major depression. However, the detailed mechanism of action of miR-124 in depression remains poorly understood. Here, we observed that miR-124 was downregulated in the hippocampus of mice with chronic unpredictable mild stress (CUMS). Restoration of miR-124 expression significantly attenuated depressive-like behavior and inhibited microglial activation induced by CUMS. Mechanistically, miR-124 directly targeted signal transducer and activator of transcription 3 (STAT3) in BV2 cells; in addition, upregulation of miR-124 inhibited the increase of inducible nitric oxide synthetase and proinflammatory cytokines, including IL-6, IL-1ß, TNF-α, and MCP-1, in LPS-stimulated BV2 cells. The collective data suggest that dysfunction of miR-124 may be a foundation for the development of depression by promoting microglial activation.

Vistriterpenoids A and B, Two New 24-Nor-oleanane Triterpenoids from Dodonaea viscosa.

Two new triterpenoids, vistriterpenoids A (1) and B (2), and four known ones, were acquired from Dodonaea viscosa. Compounds 1 and 2 represent the 24-nor-oleanane triterpenoids isolated from the genus Dodonaea for the first time. Their structures were identified based on extensive spectroscopic methods. Compounds 1, 2, 5, and 6 exerted inhibitory activities against PTP1B in vitro.