OBOX regulates mouse zygotic genome activation and early development.

Zygotic genome activation (ZGA) activates the quiescent genome to enable the maternal-to-zygotic transition1,2. However, the identity of transcription factors that underlie mammalian ZGA in vivo remains elusive. Here we show that OBOX, a PRD-like homeobox domain transcription factor family (OBOX1-OBOX8)3-5, are key regulators of mouse ZGA. Mice deficient for maternally transcribed Obox1/2/5/7 and zygotically expressed Obox3/4 had a two-cell to four-cell arrest, accompanied by impaired ZGA. The Obox knockout defects could be rescued by restoring either maternal and zygotic OBOX, which suggests that maternal and zygotic OBOX redundantly support embryonic development. Chromatin-binding analysis showed that Obox knockout preferentially affected OBOX-binding targets. Mechanistically, OBOX facilitated the 'preconfiguration' of RNA polymerase II, as the polymerase relocated from the initial one-cell binding targets to ZGA gene promoters and distal enhancers. Impaired polymerase II preconfiguration in Obox mutants was accompanied by defective ZGA and chromatin accessibility transition, as well as aberrant activation of one-cell polymerase II targets. Finally, ectopic expression of OBOX activated ZGA genes and MERVL repeats in mouse embryonic stem cells. These data thus demonstrate that OBOX regulates mouse ZGA and early embryogenesis.

UFM1 inhibits hypoxia-induced angiogenesis via promoting proteasome degradation of HIF-1α.

Angiogenesis is crucial for blood flow recovery and ischemic tissue repair of peripheral artery disease (PAD). Exploration of new mechanisms underlying angiogenesis will shed light on the treatment of PAD. Ubiquitin-fold modifier 1 (UFM1), a newly identified ubiquitin-like molecule, has been discovered to be involved in various pathophysiological processes. However, the role of UFM1 in the pathogenesis of PAD, especially in endothelial angiogenesis remains obscure, and we aimed to clarify this issue in this study. We initially found UFM1 was significantly upregulated in gastrocnemius muscles of PAD patients and hind limb ischemia mice. And UFM1 was mainly colocalized with endothelial cells in ischemic muscle tissues. Further, elevated expression of UFM1 was observed in hypoxic endothelial cells. Subsequent genetic inhibition of UFM1 dramatically enhanced migration, invasion, adhesion, and tube formation of endothelial cells under hypoxia. Mechanistically, UFM1 reduced the stability of hypoxia-inducible factor-1α (HIF-1α) and promoted the von Hippel-Lindau-mediated K48-linked ubiquitin-proteasome degradation of HIF-1α, which in turn decreased angiogenic factor VEGFA expression and suppressed VEGFA related signaling pathway. Consistently, overexpression of UFM1 inhibited the angiogenesis of endothelial cells under hypoxic conditions, whereas overexpression of HIF-1α reversed this effect. Collectively, our data reveal that UFM1 inhibits the angiogenesis of endothelial cells under hypoxia through promoting ubiquitin-proteasome degradation of HIF-1α, suggesting UFM1 might serve as a potential therapeutic target for PAD.

Changes of Gut Microbiota in Maintenance Hemodialysis Patients and Their Impact on Patient's Microinflammation Status.

This study was to investigate the changes in gut microbiota in maintenance hemodialysis patients and analyze their impact on patient's microinflammation status. For this purpose, thirty-nine chronic kidney disease (CKD) maintenance hemodialysis patients admitted to our hospital from March 2019 to March 2022 were selected as the experimental group, and 40 healthy individuals with examination results during the same period were selected as the control group. The levels of gut microbiota (Lactobacillus, Bifidobacterium, Escherichia coli, and Enterococcus faecalis) and microinflammation indicators [interleukin-6 (IL-6), tumor necrosis factor α (TNF-α), and high-sensitivity C-reactive protein (hs-CRP)] were measured in both groups. The relationship between changes in gut microbiota and microinflammation in maintenance hemodialysis CKD patients was analyzed. Results showed that the levels of Lactobacillus and Bifidobacterium in the experimental group were significantly lower than those in the control group (all, P<0.05), while the levels of Escherichia coli and Enterococcus faecalis in the experimental group were significantly higher than those in the control group (all, P<0.05). The IL-6, TNF-α, and hs-CRP levels in the experimental group were significantly higher than those in the control group (all, P<0.05). Using microinflammation indicators as dependent variables and microbiota indicators as independent variables for stepwise regression analysis, the results showed that the levels of Lactobacillus were negatively correlated with IL-6 and TNF-α levels in patients (r=-0.358, -0.942, P<0.05); the levels of Bifidobacterium were negatively correlated with IL-6, TNF-α, and hs-CRP levels in patients (r=-0.394, -0.211, -0.547, P<0.05); the levels of Escherichia coli were positively correlated with IL-6 and TNF-α levels in patients (r=0.221, 0.268, P<0.05); the levels of Enterococcus faecalis were positively correlated with IL-6 and hs-CRP levels in patients (r=0.253, 0.378, P<0.05). In conclusion, patients with maintenance hemodialysis for CKD commonly exhibit gut microbiota dysbiosis and varying degrees of low-grade inflammation. Compared to healthy individuals, maintenance hemodialysis patients with CKD have lower levels of Bifidobacterium and Lactobacillus and higher levels of Escherichia coli and Enterococcus in their gut. Bifidobacterium, Lactobacillus, Escherichia coli, and Enterococcus all have a certain impact on the low-grade inflammation status of patients with maintenance hemodialysis for CKD.

Interrelationships between sarcopenia, bone turnover markers and low bone mineral density in patients on hemodialysis.

BACKGROUND: Hemodialysis (HD) patients are at risk for sarcopenia (SP) and bone loss, which may impact falls and bone fragility and lead to poor prognosis. Patients with HD and those with osteoporosis (OP) are still underdiagnosed and untreated. The aims of the present study were to evaluate the factors that affect bone mineral density (BMD) loss in HD patients, and explore traditional and novel approaches to manage chronic kidney disease-mineral-bone disorder (CKD-MBD). METHODS: Patients who underwent regular HD at the First Affiliated Hospital of Soochow University were retrospectively evaluated. According to the WHO osteoporosis criteria, patients were categorized into three groups: normal BMD, osteopenia, and osteoporosis. Demographic and clinical data, skeletal muscle mass, and bone turnover markers(BTM) were compared between the three groups. The correlation between bone density and muscle mass was calculated, and related risk factors were analyzed. RESULTS: This study enrolled 130 HD patients, 36 patients were diagnosed with sarcopenia (27.7%), 44 patients were diagnosed with osteopenia (33.8%), 19 patients were diagnosed with osteoporosis (14.6%), and 23 patients were diagnosed with osteosarcopenia (17.7%). The SMI was positively correlated with the BMD of the lumbar spine (r = 0.23, p < 0.01) and femoral neck (r = 0.22, p < 0.05). In ordinal logistic regression analysis, the odds ratio (OR) for low BMD was high for patients with sarcopenia (OR = 5.894, 95% CI 1.592-21.830, p < 0.01), older age (OR = 1.095, 95% CI 1.041-1.153, p < 0.001), higher TRACP-5b levels (OR = 1.597, 95% CI 1.230-2.072, p < 0.01), and lower 25-OH vitamin D levels (OR = 0.631, 95% CI 0.544-0.733, p < 0.001). CONCLUSION: The preservation of skeletal muscle mass could be important to prevent a BMD decrease in HD patients. Adequate intake of vitamin D and control of TRACP-5b levels will help reduce the occurrence and progression of osteopenia/sarcopenia in HD patients.

Macular Vascular Complexity Analysis of Diabetes Mellitus by Swept-Source Optical Coherence Tomographic Angiography.

PURPOSE: This study was designed to evaluate the associations between retinal vascular complexity features, including fractal dimension (FD) and blood vessel tortuosity (BVT), and the severity of diabetic retinopathy (DR) by using optical coherence tomographic angiography (OCTA). METHODS: In this prospective cross-sectional study, 1,282 ocular-treatment-naive patients with type 2 diabetes mellitus (DM) (1,059 without DR and 223 with DR) registered in the community of Guangzhou, China, were enrolled. OCTA was used to measure FD and BVT in the superficial capillary plexus (SCP) and the deep capillary plexus (DCP). Univariate and multivariate linear regression analyses were performed to analyze the correlation of FD and BVT in different layers with DR severity. RESULTS: In this study, 1,282 patients with DM (1,282 eyes), with a mean age of 64.2 ± 7.8 years, were included. FD in the DCP decreased and BVT in the DCP increased in patients with DR compared with those in patients without DR, even after adjusting for confounding factors (p < 0.05). Trend analysis showed a significant decrease in the FD values as the DR progressed, whereas the BVT progressively increased with worsening DR severity (p < 0.01). The FD in DCP had a statistically significant positive correlation with FD in SCP and a negative correlation with BVT in SCP and BVT in DCP in all of the participants, including the non-DR group, moderate DR group, and severe DR group (p < 0.01). CONCLUSIONS: FD and BVT determined using OCTA might be useful parameters for objectively distinguishing DR from non-DR and indicating DR progression.

MiR-140-5p inhibits oxidized low-density lipoprotein-induced oxidative stress and cell apoptosis via targeting toll-like receptor 4.

Critical roles of several microRNAs have been implicated in atherosclerosis (AS). In this study, we studied the functional role of miR-140-5p in AS. An AS model was constructed in THP-1 macrophages challenged with oxidized low-density lipoprotein (ox-LDL). The expression of miR-140-5p was up- or downregulated with corresponding mimic or inhibitor regents. Our experiments showed that the levels of cell apoptosis and fatty acid accumulation were decreased in THP-1 macrophages treated with miR-140-5p mimic, whereas increased in those treated with miR-140-5p inhibitor. The levels of ROS (reactive oxygen species), MDA (malondialdehyde), TC (Triglyceride), and TG (total cholesterol) were reduced and the level of SOD (superoxide dismutase) was improved in miR-140-5p overexpressed THP-1 macrophages, which can be reversed with miR-140-5p depletion. Moreover, through bioinformatics analysis, we found toll-like receptor 4 (TLR4) was a potential target of miR-140-5p. Luciferase reporter assay demonstrated that miR-140-5p regulated TLR4 expression via binding 3'UTR of TLR4 in THP-1 macrophages. In ox-LDL challenged THP-1 macrophages, the expression of TLR4 was decreased after miR-140-5p mimic transfection, whereas improved after treatment with miR-140-5p inhibitors. As a conclusion, miR-140-5p can participate in inhibiting ox-LDL-induced oxidative stress and cell apoptosis via targeting TLR4 in macrophage-mediated ox-LDL induced AS.

SETD2 is essential for terminal differentiation of erythroblasts during fetal erythropoiesis.

SET domain-containing 2 (SETD2), the primary methyltransferase for histone 3 lysine-36 trimethylation (H3K36me3) in mammals, is associated with many hematopoietic diseases when mutated. Previous works have emphasized its role in maintaining adult hematopoietic stem cells or tumorigenesis, however, whether and how SETD2 regulates erythropoiesis during embryonic development is relatively unexplored. In this study, using a conditional SETD2 knockout (KO) mouse model, we reveal that SETD2 plays an essential role in fetal erythropoiesis. Loss of Setd2 in hematopoietic cells ablates H3K36me3, and leads to anemia with a significant decrease in erythroid cells in the peripheral blood at E18.5. This is due to impaired erythroblast differentiation in both spleen and liver. We also find increased proportions of nucleated erythrocytes in the blood of Setd2 KO embryos. Lastly, we ascribe embryonic erythropoiesis-related genes Vegfc, Vegfr3, and Prox1, as likely downstream targets of SETD2 regulation. Our study reveals a critical role of SETD2 in fetal erythropoiesis that precedes adult hematopoiesis, and provide unique insights into the defects in erythroid lineages, such as anemia.

The association between serum interleukin-1 beta and heparin sulphate in diabetic nephropathy patients.

Inflammation is considered an important mechanism in the development of diabetes mellitus (DM) and persists for a long time before the occurrence of diabetic nephropathy (DN). Many studies have demonstrated that a decrease in the endothelial glycocalyx (EG) is negatively correlated with proteinuria. To elucidate whether EG damage induced by inflammasomes in DM patients leads to the occurrence of microalbuminuria (MA) and accelerates the progression of DN, this study screened 300 diagnosed DM patients. Finally, 70 type 2 diabetes patients were invited to participate in this study and were divided into two groups: the T2DM group (patients with normal MA and without diabetic retinopathy, n = 35) and the T2DN group (patients with increased MA and diabetic retinopathy, n = 35). Circulating heparin sulphate (HS, EG biomarkers) and interleukin-1 beta (IL-1ß, inflammasome biomarkers) of the patients were measured by ELISA. Laboratory data were measured using routine laboratory methods. Patients in the T2DN group had increased serum HS, increased IL-1ß, increased CRP, decreased haemoglobin, and increased neutrophils compared to patients in the T2DM group (all P < 0.05). Increased HS and decreased haemoglobin were independently associated with T2DN patients. ROC curves showed that the AUC of HS for the prediction of T2DN was 0.67 (P < 0.05). The combination of HS and haemoglobin yielded a significant increasement in the AUC (0.75, P < 0.001) with optimal sensitivity (71.2%) and specificity (79%). Furthermore, serum IL-1ß was positively correlated with HS and was an independent associated factor of HS in the T2DN group. The relationship between HS and IL-1ß was not significant in the T2DM group. Our findings surgessed the inflammasome may be associated with and promote damage to the EG during the disease course of DN that manifests as increased MA.

Facile preparation of hierarchical micro-nano FeF3·0.33H2O by a one-pot method with dual surfactants.

To prepare a hierarchical micro-nano structure FeF3·0.33H2O simply and economically, a one-pot method with dual surfactants was used. Scanning electron microscopy and a Fourier transformation infrared spectrometer revealed that polyvinyl pyrrolidone (PVP) regulates the morphology of the material, while cetyltrimethylammonium bromide (CTAB) can reshape FF@PVP, it can not only remove PVP at room temperature, but also obtain a hierarchical micro-nano structure. The electrochemical results show that the hierarchical micro-nano structure FF(1.5CTAB 0.5PVP) has the best electrochemical performance. It maintained a high specific capacity of 109.4 mAh g-1 after 100 cycles at 1 C. In particular, under the ultra-high rate discharge of 20 C, the ultra-high specific discharge capacity of 66.4 mAh g-1 was reached. The FF(1.5CTAB 0.5PVP)'s excellent electrochemical performance is mainly due to a large contact area between the electrolyte and active materials.

Hsa_circ_0000345 regulates the cellular development of ASMCs in response to oxygenized low-density lipoprotein.

The interaction between circRNAs and atherosclerosis has been extensively studied. However, more novel circRNAs need to be explored to help establish a perfect regulatory network. In the present research, hsa_circ_0000345 was demonstrated to regulate cellular development of oxygenized low-density lipoprotein (ox-LDL)-treated aortic smooth muscle cells (ASMCs), which was closely related to the occurrence and progress of atherosclerosis. Ox-LDL exposure remarkably decreased hsa_circ_0000345 expression in ASMCs. Transfection-induced hsa_circ_0000345 overexpression activated cell viability (detected by an MTT assay) and restrained cellular apoptosis (analysed by flow cytometry) in the atherosclerosis cellular model. While down-regulation of hsa_circ_0000345 reduced cell viability and promoted cell apoptosis. In addition, the data of the cell cycle distribution analysis and trans-well assay indicated that cell cycle progression was arrested at the G1 phase while cell invasion was enhanced in ASMCs following treatment of ox-LDL in the context of hsa_circ_0000345 OE plasmids. In addition, up-regulation of hsa_circ_0000345 supported HIF-1α at both the mRNA and protein level, and down-regulation of hsa_circ_0000345 reduced HIF-1α expression. Overall, the above findings revealed that hsa_circ_0000345 was a dramatic regulator of ASMCs proliferation, apoptosis and invasion in response to ox-LDL treatment. Hsa_circ_0000345 was identified as a protector of cell viability during ox-LDL induced cell development.

Long non-coding RNA NORAD exhaustion represses prostate cancer progression through inhibiting TRIP13 expression via competitively binding to miR-495-3p.

BACKGROUND: Prostate cancer (PCa) is a malignant heterogeneous tumor that threatens men's health. Long non-coding RNA activated by DNA damage (NORAD) and microRNA-495-3p (miR-495-3p) have been revealed to be concerned with the tumorigenesis and progression of diverse cancers. Nevertheless, the regulatory mechanism between NORAD and miR-495-3p in PCa is unclear. METHODS: The expression of NORAD, miR-495-3p, and thyroid hormone receptor interactor 13 (TRIP13) mRNA was detected with quantitative real-time polymerase chain reaction (qRT-PCR). The levels of Bcl-2, Bax, Cleaved-casp-3, TRIP13, cyclin D1, and PCNA were detected through western blot analysis. The proliferation, apoptosis, migration, and invasion of PCa cells were assessed through 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT), flow cytometry, or transwell assays. The relationship between NORAD or TRIP13 and miR-495-3p was confirmed via dual-luciferase reporter, RIP, or RNA pull-down assays. RESULTS: NORAD and TRIP13 were upregulated while miR-495-3p was downregulated in PCa tissues and cells. Both NORAD silencing and miR-495-3p upregulation accelerated cell apoptosis and curbed cell proliferation, migration, and invasion in PCa cells. Also, NORAD silencing repressed tumor growth in vivo. Notably, NORAD modulated TRIP13 expression by competitively binding to miR-495-3p. Furthermore, miR-495-3p repression reversed NORAD knockdown-mediated effects on the malignant behaviors of PCa cells. Moreover, TRIP13 enhancement overturned the effects of miR-495-3p overexpression on the proliferation, apoptosis, migration, and invasion of PCa cells. CONCLUSION: NORAD depletion inhibited PCa advancement via the miR-495-3p/ TRIP13 axis, which provided a potential tactic for PCa treatment.

Advances of aptamers screened by Cell-SELEX in selection procedure, cancer diagnostics and therapeutics.

Aptamers are a class of short artificial single-stranded oligo(deoxy) nucleotides that can bind to different targets, which generated by Systematic Evolution of Ligands by Exponential Enrichment (SELEX). Due to excellent selectivity and high affinity to targets, aptamers hold considerable potential as molecular probe in diverse applications ranging from ensuring food safety, monitoring environment, disease diagnosis to therapy. This review highlights recent development and challenges about aptamers screened by Cell-SELEX, and its application about cancer diagnostics and therapeutics. Advances about some operation methods such as seperation method and culture method in aptamers selection procedure were summarized in this paper. Some common challenges and technological difficulties such as nonspecific binding and biostability were discussed. Up to now, the recent endeavors about cancer diagnostic and therapeutic applications of aptamers are summarized and expatiated. Most of aptamers screened by Cell-SELEX took tumor cells as target cells, and such aptamers have been assembled to various aptasensor for cancer diagnosis. Aptamers conjugated various drugs or nanomaterials are functioned for cancer target therapy to improve drugs delivery efficiency and reduce side effects. Furthermore, the duplexed aptamer is discussed to be applied for cancer cells detection and some conflicts of theories about duplexed aptamer designs are analyzed.

HiCDB: a sensitive and robust method for detecting contact domain boundaries.

Contact domains are closely linked to gene regulation and lineage commitment, while current understanding of contact domains and their boundaries is still limited. Here, we present a novel method HiCDB, which is constructively based on local relative insulation metric and multi-scale aggregation approach to detect contact domain boundaries (CDBs) on Hi-C maps. Compared with other 'state-of-art' methods, HiCDB shows improved sensitivity and specificity in determining CDBs at various Hi-C resolutions. The superiority of HiCDB enabled us to study the epigenetic features of detected CDBs and showed enrichment of architectural proteins and cell-type-specific transcription factor binding sites at CDBs. The further comparison of GM12878 and IMR90 Hi-C datasets suggested that cell-type-specific CDBs are marked by active regulatory signals and correlate with activation of nearby cell identity genes.

Leukotriene B4 receptor 2 regulates the proliferation, migration, and barrier integrity of bronchial epithelial cells.

The airway epithelium plays a crucial role in the pathogenesis of asthma. The functions of leukotriene B4 receptor 2 (BLT2) on the airway epithelial cells remains unknown. In our study, BLT2 expression in 16HBE bronchial epithelial cells were manipulated by transfection with BLT2 overexpression plasmid or BLT2 small interference RNA. 16HBE cells were then exposed to BLT2 antagonist (LY255283) or BLT2 agonist (12(S)-hydroxyheptadeca-5Z,8E,10E-trienoic acid [12-HHT] or CAY10583). The results showed that BLT2 overexpression, 12-HHT stimulation, or CAY10583 treatment resulted in the enhanced proliferation and migration of 16HBE cells. In addition, BLT2 showed an inhibitory effect on epithelial permeability as illustrated by the measurement of transepithelial electrical resistance (TER) and epithelial permeability, and a promoting effect on the levels of tight junction proteins (occludin and claudin-4) and phosphorylated p38 as demonstrated by real-time PCR and Western blotting analyses. These results suggest BLT2 as a key determinant of airway epithelial barrier integrity. On the contrary, RNAi-mediated knockdown or LY255283 treatment had reversed effects on the proliferation, migration, and epithelial barrier integrity. Together, our findings suggest the critical roles of BLT2 on the functions of bronchial epithelial cells and that BLT2 agonists are potential therapeutic agents for asthma treatment.

A dense mapping study of six European AITD susceptibility regions in a large Chinese Han Cohort of Graves' disease.

OBJECTIVE: We aimed to investigate the six susceptibility loci of GD identified from European population in Chinese Han population and further to estimate the genetic heterogeneity of them in stratification of our GD patients. DESIGN: Dense mapping studies based on GWAS. PATIENTS: A total of 1536 GD patients and 1516 controls in GWAS stage and 1994 GD patients and 2085 controls and 5033 GD patients and 5389 controls in two replication stages. MEASUREMENTS: Based on our previous GWAS data, independently GD-associated SNPs in each region were identified by TagSNP analysis and logistic regression analysis. The association of these SNPs was investigated in 1994 GD patients and 2085 controls, and then, the significantly associated SNPs (P < 0.05) were further genotyped in a second cohort including 5033 GD patients and 5389 controls. RESULTS: After the first replication stage, four SNPs from three regions with Pfirst  < 0.05 were further selected and genotyped in another independent cohort. The association of two SNPs with GD was confirmed in combined Chinese cohorts: rs12575636 at 11q21 (Pcombined  = 7.55 × 10-11 , OR = 1.27) and rs1881145 in TRIB2 at 2p25.1 (Pcombined  = 5.59 × 10-8 , OR = 1.14). Further study disclosed no significant difference for these SNPs between GD subsets. However, eQTL data revealed that SESN3 could be a potential susceptibility gene of GD in 11q21 region. CONCLUSIONS: Out of the six susceptibility loci of GD identified from European population, two risk loci were confirmed in a large Chinese Han population. There is variability in GD genetic susceptibility in different ethnic groups. SESN3 is a potential susceptible gene of GD in 11q21.

Osteoclast stimulatory transmembrane protein induces a phenotypic switch in macrophage polarization suppressing an M1 pro-inflammatory state.

Macrophages are the key cells in metabolic syndrome and are also a risk factor for metabolic disease. Macrophages have different functions and transcriptional profiles, but all are required for maintaining homeostasis. It is well known that macrophages play a key role in inflammation and early atherogenesis, and are present in two phenotypes: pro-inflammatory (M1) and anti-inflammatory (M2). Osteoclast stimulatory transmembrane protein (oc-stamp) is a multiple-pass transmembrane protein; however, its function remains unclear. In this study, we explored the role of oc-stamp in macrophages physiology. The results showed that oc-stamp was notably decreased under LPS and IFN-γ stimulation, while it was increased with IL-4 treatment. Furthermore, oc-stamp induced a phenotypic switch in macrophage polarization, suppressing the M1 pro-inflammatory state in the overexpression group, and promoting the M1 pro-inflammatory state in the knockdown group. Further study revealed that oc-stamp regulated macrophage polarization possibly via STAT6. Taken together, our results are the first to demonstrate that oc-stamp may play an important role in macrophage polarization and inhibit the M1 pro-inflammatory state.

TFE3 Alleviates Hepatic Steatosis through Autophagy-Induced Lipophagy and PGC1α-Mediated Fatty Acid ß-Oxidation.

Autophagy flux deficiency is closely related to the development of hepatic steatosis. Transcription factor E3 (TFE3) is reported to be a crucial gene that regulates autophagy flux and lysosome function. Therefore, we investigated the role of TFE3 in a cell model of hepatic steatosis. We constructed L02 hepatocyte lines that stably over-expressed or knocked down the expression of TFE3. Subsequently, the effects of TFE3 on hepatocellular lipid metabolism were determined by autophagy flux assay, lipid oil red O (ORO) staining, immunofluorescence staining, and mitochondrial ß-oxidation assessment. Finally, we analyzed whether peroxisome proliferative activated receptor gamma coactivator 1α (PGC1α) was the potential target gene of TFE3 in the regulation of hepatic steatosis using a chromatin immunoprecipitation (CHIP) assay and a luciferase reporter system. We found that overexpression of TFE3 markedly alleviated hepatocellular steatosis. On the contrary, downregulation of TFE3 resulted in an aggravated steatosis. The mechanistic studies revealed that the TFE3-manipulated regulatory effects on hepatocellular steatosis are dependent on autophagy-induced lipophagy and PGC1α-mediated fatty acid ß-oxidation because blocking these pathways with an Atg5 small interfering RNA (siRNA) or PGC1α siRNA dramatically blunted the TFE3-mediated regulation of steatosis. In conclusion, TFE3 gene provides a novel insight into the treatment of hepatic steatosis and other metabolic disease.

[Impact of androgen level on body adipose tissue content and distribution in middle life women].

OBJECTIVE: To investigate the relationship between androgen level and body adipose tissue content and distribution via a cross sectional survey in healthy women aged 40 to 60 years. METHODS: A total of 222 women were divided into 4 groups according menstruation status, i.e. reproductive stage, early perimenopausal stage, late perimenopausal stage and postmenopausal stage. Serum level of dehydroepiandrosterone (DHEA), total testosterone (TT) and sex hormone binding globulin (SHBG) were measured. Free androgen index (FAI) was calculated. Body adipose tissue content and distribution were measured by dual-energy X-ray absorptiometry. RESULTS: In women aged 40 to 60 years, DHEA, TT and FAI level of reproductive stage women was (12.3 ± 4.1) nmol/L, (0.56 ± 0.22) nmol/L and 1.15 (quartile: 0.71 to 1.85), respectively. DHEA, TT and FAI level of early perimenopausal stage women was (12.0 ± 3.4) nmol/L, (0.56 ± 0.24) nmol/L and 1.37 (quartile: 0.89 to 1.61), respectively. DHEA, TT and FAI level of late perimenopausal stage women was (14.2 ± 4.7) nmol/L, (0.62 ± 0.18) nmol/L and 1.38 (quartile: 1.12 to 1.63). DHEA, TT and FAI level of postmenopausal stage women was (11.6 ± 3.5) nmol/L, (0.45 ± 0.22) nmol/L and 0.94 (quartile: 0.47 to 1.49). DHEA, TT and FAI level of perimenopausal stage women was comparable with those of reproductive stage women (P > 0.05), however, TT and FAI level of postmenopausal women was significantly lower than those of reproductive stage women (P = 0.001, 0.014). The total adipose percentage of reproductive stage women, early perimenopausal stage women, late perimenopausal stage women and postmenopausal stage women were (35 ± 6)%, (35 ± 5)%, (37 ± 4)% and (37 ± 5)%. The adipose percentage in "android" area of reproductive stage women, early perimenopausal stage women, late perimenopausal stage women and postmenopausal stage women were (43 ± 5)%, (43 ± 4)%, (47 ± 5)% and (46 ± 5)%. The total adipose percentage was similar in 4 groups (P = 0.312). Compared with reproductive stage women, adipose percentage of "android" area increased in late perimenopausal and postmenopausal women (P = 0.026). Women with higher FAI level presented higher adipose tissue content and higher percentage of centrally distributed adipose tissue (r = 0.28, P = 0.003). CONCLUSIONS: Body adipose tissue tends to distribute centrally from perimenopausal stage. Androgen level is related to body adipose tissue content and distribution, but may not be the main reason of changes of fat distribution in middle life women.

Recent progress in plasma modification of 2D metal chalcogenides for electronic devices and optoelectronic devices.

Two-dimensional metal chalcogenides (2D MCs) present a great opportunity for overcoming the size limitation of traditional silicon-based complementary metal-oxide-semiconductor (CMOS) devices. Controllable modulation compatible with CMOS processes is essential for the improvement of performance and the large-scale applications of 2D MCs. In this review, we summarize the recent progress in plasma modification of 2D MCs, including substitutional doping, defect engineering, surface charge transfer, interlayer coupling modulation, thickness control, and nano-array pattern etching in the fields of electronic devices and optoelectronic devices. Finally, challenges and outlooks for plasma modulation of 2D MCs are presented to offer valuable references for future studies.