Roles of HIF-1α signaling in Mycobacterium tuberculosis infection: New targets for anti-TB therapeutics?

Tuberculosis (TB), a deadly infectious disease induced by Mycobacterium tuberculosis (Mtb), continues to be a global public health issue that kill millions of patents every year. Despite significant efforts have been paid to identify effective TB treatments, the emergence of drug-resistant strains of the disease and the presence of comorbidities in TB patients urges us to explore the detailed mechanisms involved in TB immunity and develop more effective innovative anti-TB strategies. HIF-1α, a protein involved in regulating cellular immune responses during TB infection, has been highlighted as a promising target for the development of novel strategies for TB treatment due to its critical roles in anti-TB host immunity. This review provides a summary of current research progress on the roles of HIF-1α in TB infection, highlighting its importance in regulating the host immune response upon Mtb infection and summarizing the influences and mechanisms of HIF-1α on anti-TB immunological responses of host cells. This review also discusses the various challenges associated with developing HIF-1α as a target for anti-TB therapies, including ensuring specificity and avoiding off-target effects on normal cell function, determining the regulation and expression of HIF-1α in TB patients, and developing drugs that can inhibit HIF-1α. More deep understanding of the molecular mechanisms involved in HIF-1α signaling, its impact on TB host status, and systematic animal testing and clinical trials may benefit the optimization of HIF-1α as a novel therapeutic target for TB.

Liver cancer-specific mutations in functional domains of ADAR2 lead to the elevation of coding and non-coding RNA editing in multiple tumor-related genes.

Mutation is the major cause of phenotypic innovations. Apart from DNA mutations, the alteration on RNA such as the ADAR-mediated A-to-I RNA editing could also shape the phenotype. These two layers of variations have not been systematically combined to study their collective roles in cancers. We collected the high-quality transcriptomes of ten hepatocellular carcinoma (HCC) and the matched control samples. We systematically identified HCC-specific mutations in the exonic regions and profiled the A-to-I RNA editome in each sample. All ten HCC samples had mutations in the CDS of ADAR2 gene (dsRNA-binding domain or catalytic domain). The consequence of these mutations converged to the elevation of ADAR2 efficiency as reflected by the global increase of RNA editing levels in HCC. The up-regulated editing sites (UES) were enriched in the CDS and UTR of oncogenes and tumor suppressor genes (TSG), indicating the possible roles of these target genes in HCC oncogenesis. We present the mutation-ADAR2-UES-oncogene/TSG-HCC axis that explains how mutations at different layers would finally lead to abnormal phenotype. In the light of central dogma, our work provides novel insights into how to fully take advantage of the transcriptome data to decipher the consequence of mutations.

Freestanding Metal-Organic Frameworks and Their Derivatives: An Emerging Platform for Electrochemical Energy Storage and Conversion.

Metal-organic frameworks (MOFs) have recently emerged as ideal electrode materials and precursors for electrochemical energy storage and conversion (EESC) owing to their large specific surface areas, highly tunable porosities, abundant active sites, and diversified choices of metal nodes and organic linkers. Both MOF-based and MOF-derived materials in powder form have been widely investigated in relation to their synthesis methods, structure and morphology controls, and performance advantages in targeted applications. However, to engage them for energy applications, both binders and additives would be required to form postprocessed electrodes, fundamentally eliminating some of the active sites and thus degrading the superior effects of the MOF-based/derived materials. The advancement of freestanding electrodes provides a new promising platform for MOF-based/derived materials in EESC thanks to their apparent merits, including fast electron/charge transmission and seamless contact between active materials and current collectors. Benefiting from the synergistic effect of freestanding structures and MOF-based/derived materials, outstanding electrochemical performance in EESC can be achieved, stimulating the increasing enthusiasm in recent years. This review provides a timely and comprehensive overview on the structural features and fabrication techniques of freestanding MOF-based/derived electrodes. Then, the latest advances in freestanding MOF-based/derived electrodes are summarized from electrochemical energy storage devices to electrocatalysis. Finally, insights into the currently faced challenges and further perspectives on these feasible solutions of freestanding MOF-based/derived electrodes for EESC are discussed, aiming at providing a new set of guidance to promote their further development in scale-up production and commercial applications.

Suspected duloxetine-induced restless legs syndrome phenotypic variant: a case report.

BACKGROUND: Restless arms syndrome (RAS) is the most common variant of restless legs syndrome (RLS), which is easy to be ignored in clinical practice due to the lack of specific diagnostic criteria. When effective therapeutic agents induced RAS and symptoms persisted after briefly observation, clinicians will face the challenge of weighing efficacy against side effects. CASE PRESENTATION: A 67-year-old woman was admitted to a geriatric psychiatric ward with depression. Upon admission, the escitalopram dose was reduced from 15 mg to 10 mg per day, and the duloxetine dose was increased from 60 mg to 80 mg per day. The next night before bedtime, she developed itching and creeping sensations deep inside bilateral shoulders and arms, with the urge to move, worsening at rest, and alleviation after hammering. The symptoms persisted when escitalopram was discontinued. A history of RLS was confirmed. Treatment with 40 mg of duloxetine and 0.125 mg of pramipexole significantly improved depression, and the paresthesia disappeared, with no recurrence occurring 6 months after discharge. DISCUSSION AND CONCLUSIONS: This case suggests that psychiatrists should pay attention to RLS variants when increasing doses of duloxetine. Long-term improvement can be achieved through dosage reduction combined with dopaminergic drugs instead of immediate discontinuation.

Melatonin relieves hepatic lipid dysmetabolism caused by aging via modifying the secondary bile acid pattern of gut microbes.

It has been reported that aging-generated gut microecosystem may promote host hepatic lipid dysmetabolism through shaping the pattern of secondary bile acids (BAs). Then as an oral drug, melatonin (Mel)-mediated beneficial efforts on the communication between gut microbiota and aging host are still not clearly. Here, we show that aging significantly shapes the pattern of gut microbiota and BAs, whereas Mel treatment reverses these phenotypes (P < 0.05), which is identified to depend on the existence of gut microbiota. Mechanistically, aging-triggered high-level expression of ileac farnesoid X receptor (FXR) is significantly decreased through Mel-mediated inhibition on Campylobacter jejuni (C. jejuni)-induced deconjugation of tauroursodeoxycholic acid (TUDCA) and glycoursodeoxycholic acid (GUDCA) (P < 0.05). The aging-induced high-level of serum taurine chenodeoxycholic acid (TCDCA) activate trimethylamine-N-oxide (TMAO)-triggered activating transcriptional factor 4 (ATF4) signaling via hepatic FXR, which further regulates hepatic BAs metabolism, whereas TUDCA inhibits aging-triggered high-level of hepatic ATF4. Overall, Mel reduces C. jejuni-mediated deconjugation of TUDCA to inhibit aging-triggered high-level expression of hepatic FXR, which further decreases hepatic TMAO production, to relieve hepatic lipid dysmetabolism.

Hoxa5 inhibits adipocyte proliferation through transcriptional regulation of Ccne1 and blocking JAK2/STAT3 signaling pathway in mice.

The highly regulated proliferation of adipocytes plays a momentous role in fat development and obesity. Hoxa5 is an important member of the Hox family, its encoded protein is an important transcription factor related to development, and its differential expression in different adipose tissues seems to indicate that Hoxa5 may be involved in the regulation of adipocyte proliferation. To evaluate the regulatory mechanism of Hoxa5 on adipocyte proliferation, we constructed a variety of Hoxa5 expression vectors in vivo and in vitro to explore its mechanism on adipocyte proliferation and its potential impact on obesity. We observed that the overexpression of Hoxa5 strongly reduces cell counts and Hoxa5 can inhibit cell proliferation and block cell cycle progression by regulating the expression of genes such as Cyclin E, Cyclin D1, and p53. Most importantly, we demonstrated that Hoxa5 exerts its effect by regulating the signaling pathway of Janus kinase 2 (JAK2) signal transduction and transcription 3 (STAT3) activator, as well as binding to the promoter region of Ccne1 and inhibiting the transcription of Ccne1. This study provides an in-depth understanding of the potential molecular mechanism of Hoxa5 inhibiting adipocyte proliferation. Our results suggest the importance of Hoxa5 in the treatment of obesity.

Interface Engineering of Aqueous Zinc/Manganese Dioxide Batteries with High Areal Capacity and Energy Density.

Commercialization of aqueous batteries is mainly hampered by their low energy density, owing to the low mass loading of active cathode materials. In this work, a MnO2 cathode structure (MnO2 /CTF) is designed to modify the MnO2 /collector interface for enhanced ion transportation properties. Such a cathode can achieve ultrahigh mass loading of MnO2 , large areal capacity, and high energy density, with excellent cycling stability and rate performance. Specifically, a 0.15 mm thick MnO2 /CTF cathode can realize a mass loading of 20 mg cm-2 with almost 100% electrochemical conversion of MnO2 , providing the maximum areal capacity of 12.08 mA h cm-2 and energy density of 191 W h kg-1 for Zn-MnO2 /CTF batteries when considering both cathode and anode. Besides the conventional low energy demonstrations, such a Zn-MnO2 /CTF battery is capable of realistic applications, such as mobile phones in our daily life, which is a promising alternative for wearable electronics.

Antitumor Applications of Photothermal Agents and Photothermal Synergistic Therapies.

As a new tumor treatment strategy, photothermal therapy (PTT) has the advantages of accuracy, ease of administration, a high efficiency and low side effects. Photothermal transduction agents (PTAs) are the key factor which play an important role in PTT. The mechanism of PTT is discussed in detail. The photothermal conversion efficiency (PCE) can be improved by increasing the light absorption and reducing the light scattering of photothermal conversion agents. Additionally, non-radiative relaxation path attenuation can also promote energy conversion to obtain a higher value in terms of PCE. The structure and photothermal characteristics of various kinds of PTAs (metal materials, carbon-based nanomaterials, two-dimensional nanomaterials, and organic materials) were compared and analyzed. This paper reviews the antitumor applications of photothermal synergistic therapies, including PTT combined with immunotherapy, chemotherapy, and photodynamic therapy. This review proposes that these PTAs promote the development of photothermal synergistic therapies and have a great potential in the application of tumor treatment.

Antibacterial Peptide NP-6 Affects Staphylococcus aureus by Multiple Modes of Action.

Our previous study extracted and identified an antibacterial peptide that was named NP-6. Herein, we investigated the physicochemical properties of NP-6, and elucidated the mechanisms underlying its antimicrobial activity against Staphylococcus aureus. The results showed that the hemolysis activity of NP-6 was 2.39 ± 0.13%, lower than Nisin A (3.91 ± 0.43%) at the same concentration (512 µg/mL). Negligible cytotoxicity towards RAW264.7 cells was found when the concentration of NP-6 was lower than 512 µg/mL. In addition, it could keep most of its activity in fetal bovine serum. Moreover, transmission electron microscopy, confocal laser scanning microscopy, and flow cytometry results showed that NP-6 can destroy the integrity of the bacterial cell membrane and increase the membrane permeability. Meanwhile, NP-6 had binding activity with bacterial DNA and RNA in vitro and strongly inhibited the intracellular ß-galactosidase activity of S. aureus. Our findings suggest that NP-6 could be a promising candidate against S. aureus.

Wireless Battery-Free Generation of Electric Fields on One-Dimensional Asymmetric Au/ZnO Nanorods for Enhanced Raman Sensing.

Wearable electronics have great potential in enhancing health monitoring, disease diagnosis, and environmental pollution tracking. Development of wearable surface-enhanced Raman spectroscopy (SERS) substrates with target sampling and sensitive sensing functions is a promising way to obtain physical and chemical information. This study describes a facile and effective approach for constructing an electrically modulated SERS (E-SERS) substrate as a wearable and wireless battery-free substrate with improved sensitivity. By integrating zinc oxide nanorods (ZnO NRs) with asymmetric gold decoration, controllable enhanced piezoelectric potentials were achieved using magnets to supply the adjustable pressure force. Owing to spatially oriented electron-hole pair separation on the asymmetric NRs, the local hotspot intensity at the Au tips is significantly improved, increasing the SERS signal by 6.7 times. This mechanism was quantitatively analyzed using Raman spectra by in situ formation of Prussian blue (PB). As a proof-of-concept, the E-SERS substrate was further used as a wearable flexible device to directly collect the sweat on a runner's skin and then monitor the lactate status of the runner. This study offers new insight into the development of E-SERS substrates and provides new design options for the construction of wearable sampling and sensing devices for the noninvasive monitoring of metabolites in healthcare and biomedical fields.

Diagnostic value of MRI-DWI signal intensity value combined with serum PGI, PGII and CA199 in early gastric cancer.

To explore the diagnostic value of MRI-DWI signal intensity value combined with serum PGI. PGII and CA199 in early gastric cancer. Sixty cases of gastric cancer patients admitted to our hospital from December 2019 to December 2020 were selected as the gastric cancer group and 80 cases of healthy volunteers who underwent physical examination in our hospital during the same period were selected as the healthy group. All the 60 patients underwent MRI-DWI examination, and the pathological diagnosis results were regarded as the gold standard. MRI-DWI images, MRI-DWI signal intensity values of patients with different degrees of gastric cancer differentiation. Serum PGI, PGII and CA199 levels of subjects in the two groups were compared. AUC was used to evaluate the diagnostic value of MRI-DWI signal intensity value combined with serum PGI, PG II and CA199 for early gastric cancer. In the healthy group, T1W1 showed relatively uniform low signal intensity. While T2WI showed no significant increase in signal intensity. In the gastric cancer group. There was diffuse gastric wall thickening, local thickening or mass formation; T1WI and WATS showed slightly lower signal intensity in the lesion area. T2WI, FLAIR and B-TFE showed slightly uneven or moderately increased signal intensity. DWI showed limited diffusion, and the signal intensity increased uniformly or more uniformly, and the range of increase was clear. The signal intensity of MRI-DWI was 89.12 ± 8.14 in patients with low differentiation, 82.17 ± 6.35 in patients with moderate differentiation, and 74.52 ± 4.53 in patients with high differentiation. There were significant differences in the signal intensity of MRI-DWI among the three groups, and the difference was statistically significant (F=12.214, P <0.05). Serum PGI levels of subjects in the gastric cancer group were significantly lower than those in the healthy group, and the levels of PGII and CA199 were significantly higher than that in the healthy group, with statistical significance (P <0.05). The AUC, sensitivity and specificity of MRI-DWI signal intensity value and serum PGI, PGII and CA199 combined indexes in the diagnosis of gastric cancer were significantly higher than those of the independent indexes, with statistical significance (P <0.05). Conclusion: MRI-DWI signal strength value, serum PGI, PGII and CA199 levels are closely related to the occurrence and development of early gastric cancer. The combined detection and diagnosis efficiency is higher, which is helpful to improve the detection rate of early gastric cancer and is worthy of extensive clinical application.

Efficacy of continuous positive airway pressure on subcutaneous adipose tissue in patients with obstructive sleep apnea: a meta-analysis of randomized controlled trials.

PURPOSE: It remains inconclusive whether continuous positive airway pressure (CPAP) therapy can significantly reduce subcutaneous adipose tissue (SAT) in patients with obstructive sleep apnea (OSA). This meta-analysis of randomized controlled trials (RCTs) aimed to evaluate the impact of CPAP treatment on SAT in patients with OSA. METHODS: We searched Pubmed, Cochrane, Web of Science, and Embase for RCTs, which investigated the effectiveness of CPAP treatment in reducing SAT among patients with OSA. Following the PRISMA guidelines, we extracted information on the study and patient characteristics, and pre- and post-CPAP measures of SAT. We then calculated the overall effects using the standardized mean difference (SMD) with a 95% confidence interval (CI). RESULTS: A total of 5 RCTs (comprising 153 patients) met inclusion criteria for the meta-analysis. We found that the SAT did not change before and after CPAP treatment in patients with OSA (SMD = - 0.02, 95% CI - 0.25 to 0.2, z = 0.19, p = 0.85). Subgroup analyses indicated that the outcome was not affected by age, CPAP therapy duration, baseline body mass index, and measure utilized. CONCLUSION: This meta-analysis of RCTs suggests that CPAP therapy does not significantly decrease the level of SAT among patients with OSA. Further large-scale, and high-quality randomized controlled trials are needed to better address this issue.

Impact of CPAP treatment for obstructive sleep apnea on visceral adipose tissue: a meta-analysis of randomized controlled trials.

BACKGROUND: It is still controversial if the continuous positive airway pressure (CPAP) treatment for patients with obstructive sleep apnea (OSA) can markedly influence an effect on visceral adipose tissue (VAT). The current study aimed to assess the efficacy of CPAP interventions in reducing VAT in OSA patients. METHODS: The Web of Science, PubMed, Embase, and Cochrane Library (up to December, 2019) were searched for randomized trials that assessed the effect of CPAP therapy in decreasing VAT in OSA patients. Information on the study, pre- and post-CPAP treatment of VAT, and patient characteristics were extracted for analysis. The standardized mean difference (SMD) was applied to measure the summary estimates. The analysis was conducted with STATA 13.0 and RevMan v.5.3. RESULTS: Five studies (6 cohorts) that involved 169 patients were enrolled in the meta-analysis. There was no significant change of VAT in patients with OSA before and after CPAP treatment (SMD = - 0.00, 95% CI = - 0.21 to 0.21, z = 0.01, p = 0.99). Subgroup analyses further demonstrated that the results were not influenced by CPAP therapy duration, patient age, sample size, or baseline body mass index. CONCLUSIONS: Among the patients with OSA, our meta-analysis revealed that treatment with CPAP does not significantly lead to a reduction of VAT. High-quality randomized controlled trials may provide further clarifying information.

Leptin Reduces Plin5 m6A Methylation through FTO to Regulate Lipolysis in Piglets.

Perilipin5 (Plin5) is a scaffold protein that plays an important role in lipid droplets (LD) formation, but the regulatory effect of leptin on it is unclear. Our study aimed to explore the underlying mechanisms by which leptin reduces the N6-methyladenosine (m6A) methylation of Plin5 through fat mass and obesity associated genes (FTO) and regulates the lipolysis. To this end, 24 Landrace male piglets (7.73 ± 0.38 kg) were randomly sorted into two groups, either a control group (Control, n = 12) or a 1 mg/kg leptin recombinant protein treatment group (Leptin, n = 12). After 4 weeks of treatment, the results showed that leptin treatment group had lower body weight, body fat percentage and blood lipid levels, but the levels of Plin5 mRNA and protein increased significantly in adipose tissue (p < 0.05). Leptin promotes the up-regulation of FTO expression level in vitro, which in turn leads to the decrease of Plin5 M6A methylation (p < 0.05). In in vitro porcine adipocytes, overexpression of FTO aggravated the decrease of M6A methylation and increased the expression of Plin5 protein, while the interference fragment of FTO reversed the decrease of m6A methylation (p < 0.05). Finally, the overexpression in vitro of Plin5 significantly reduces the size of LD, promotes the metabolism of triglycerides and the operation of the mitochondrial respiratory chain, and increases thermogenesis. This study clarified that leptin can regulate Plin5 M6A methylation by promoting FTO to affect the lipid metabolism and energy consumption, providing a theoretical basis for treating diseases related to obesity.

Effects of CPAP on visceral adipose tissue in patients with obstructive sleep apnea: a meta-analysis.

PURPOSE: The efficacy of obstructive sleep apnea (OSA) treatment with continuous positive airway pressure (CPAP) on visceral adipose tissue (VAT) yielded conflicting results. This meta-analysis was performed to assess whether OSA treatment with CPAP could reduce VAT. METHODS: The PubMed, Cochrane Library, Embase, and Web of Science were searched before April 2019. Information on characteristics of study participants, pre- and post-CPAP treatment of VAT, and study design was utilized for analysis. Standardized mean difference (SMD) and 95% confidence interval (CI) were used to fully analyze the overall effects. Eleven studies were obtained and the meta-analysis was performed using RevMan v.5.2 and STATA 12.0. RESULTS: A total of 11 studies (16 cohorts) were pooled into meta-analysis, which included 398 patients. The value of VAT before and after CPAP treatment showed no change in OSA patients (SMD = - 0.02, 95% CI - 0.16 to 0.12, z = 0.24, p = 0.81). Subgroup analyses were further conducted, which revealed that age, gender distribution, baseline body mass index, daily duration, CPAP therapy duration, measure, sample size, and study design did not affect the results. CONCLUSIONS: This meta-analysis revealed that CPAP therapy has no effect on VAT in OSA patients. Further large-scale, well-designed randomized controlled trials are required to address this issue.

Flexible and High-Voltage Coaxial-Fiber Aqueous Rechargeable Zinc-Ion Battery.

Extensive efforts have been devoted to construct a fiber-shaped energy-storage device to fulfill the increasing demand for power consumption of textile-based wearable electronics. Despite the myriad of available material selections and device architectures, it is still fundamentally challenging to develop eco-friendly fiber-shaped aqueous rechargeable batteries (FARBs) on a single-fiber architecture with high energy density and long-term stability. Here, we demonstrate flexible and high-voltage coaxial-fiber aqueous rechargeable zinc-ion batteries (CARZIBs). By utilizing a novel spherical zinc hexacyanoferrate with prominent electrochemical performance as cathode material, the assembled CARZIB offers a large capacity of 100.2 mAh cm-3 and a high energy density of 195.39 mWh cm-3, outperforming the state-of-the-art FARBs. Moreover, the resulting CARZIB delivers outstanding flexibility with the capacity retention of 93.2% after bending 3000 times. Last, high operating voltage and output current are achieved by the serial and parallel connection of CARZIBs woven into the flexible textile to power high-energy-consuming devices. Thus, this work provides proof-of-concept design for next-generation wearable energy-storage devices.

Conversion Synthesis of Self-Standing Potassium Zinc Hexacyanoferrate Arrays as Cathodes for High-Voltage Flexible Aqueous Rechargeable Sodium-Ion Batteries.

Prussian blue analogs exhibit great promise for applications in aqueous rechargeable sodium-ion batteries (ARSIBs) due to their unique open framework and well-defined discharge voltage plateau. However, traditional coprecipitation methods cannot prepare self-standing electrodes to meet the needs of wearable energy storage devices. In this work, a water bath method is reported to grow microcube-like K2 Zn3 (Fe(CN)6 )2 ·9H2 O on carbon cloth (CC) using Zn nanosheet arrays as the zinc source and reducing agent, directly serving as a self-standing cathode. Benefiting from fast ion diffusion and high conductivity, the cathode delivers a high areal capacity of 0.76 mAh cm-2 at 0.5 mA cm-2 and excellent capacity retention of 57.9% as the current density increases to 20 mA cm-2 . By coupling with NaTi2 (PO4 )3 grown on CC as an anode, a quasi-solid-state flexible ARSIB with a high output voltage plateau of 1.6 V is successfully assembled, exhibiting a superior areal capacity of 0.56 mAh cm-2 and energy density of 0.92 mWh cm-2 . In particular, the device shows admirable mechanical flexibility, maintaining 90.3% of initial capacity after 3000 bending cycles. This work is anticipated to open a new avenue for the rational design of self-standing electrodes used in high-voltage flexible ARSIBs.

Ammonium-tungstate-promoted growth of boron nitride nanotubes.

Ammonium tungstate ((NH4)10W12O41 · xH2O) is a kind of oxygen-containing ammonium salt. The following study proves that it can be successfully used as a metal oxide alternative to produce boron oxide (B2O2) by oxidizing boron (B) in a traditional boron oxide chemical vapor deposition (BOCVD) process. This special oxidant promotes the simplistic fabrication of boron nitride nanotubes (BNNTs) in a conventional horizontal tube furnace, an outcome which may have resulted from its strong oxidizability. The experimental results demonstrate that the mole ratio of B and (NH4)10W12O41 · xH2O is a key parameter in determining the formation, quality and quantity of BNNTs when stainless steel is employed as a catalyst. We also found that Mg(NO3)2 and MgO nanoparticles (NPs) can be used as catalysts to grow BNNTs with the same precursor. The BNNTs obtained from the Mg(NO3)2 catalyst were straighter than those obtained from the MgO NP catalyst. This could have been due to the different physical forms of the catalysts that were used.

Identification and characterization of circular RNAs expression profiles in obstructive sleep apnea-induced liver injury.

Circular RNAs (circRNAs) have exhibited microRNA sponge activity, related to many important biological processes. Our study attempted to explore the comprehensive changes of circRNAs expression pattern in Obstructive sleep apnea (OSA)-induced liver injury and provide a global perspective of differentially expressed circRNAs (DECs). Then, RT-qPCR was used to confirm the microarray data. Further, gene ontology (GO) and KEGG pathway analysis were performed to annotate the DECs. Finally, the circRNA-miRNA-mRNA interaction network was established to predicted the target genes and target miRNAs of DECs for a stepwise bioinformatics analysis. We revealed a total of eighty DECs. In the meantime, six circRNAs were randomly validated by RT-qPCR. Among these circRNAs, mmu_circRNA_000469, 37851, 38959, 38983, 31665 were up-regulated in both microarray and qRT-PCR tissues, while mmu_circRNA_27565 was down-regulated. GO analysis revealed that circRNAs-target genes were largely related to liver function process such as carboxylic acid metabolic process and negative regulation of mitochondrial membrane potential. Meanwhile, KEGG analysis found that there were 13 pathways related to these circRNAs- target genes. And the most enriched pathway was Natural killer cell mediated cytotoxicity, which strongly suggests that immune responses may be important for the process of OSA-induced liver injury. In addition, four significant DECs (mmu_circRNA_000469, 38959, 38983, 27565) and their target mRNA and target miRNAs were further selected to establish the regulation network. Our study revealed that circRNAs may play a crucial role in OSA-induced liver injury and thus mmu_circRNA_000469, 38959, 38983, 27565 may serve as biomarkers of biological process of OSA-induced liver injury.

HDAC11 deficiency resists obesity by converting adipose-derived stem cells into brown adipocyte-like cells.

Obesity, with complications such as type 2 diabetes, dyslipidemia, and even cancer, is rampant worldwide. Histone deacetylases (HDACs) have been extensively studied as key players in the epigenetic regulation of cellular metabolism. However, the function of HDAC11 has long been focused on the immune and nervous systems and cancer development, and its potential role in obesity has been poorly studied. We found that the expression of HDAC11 was highly upregulated in the white adipose tissue (WAT) of obese mice and was closely related to the progression of obesity. Knockdown of HDAC11 by lentiviral injection in high-fat diet-fed mice attenuated the development of obesity. Furthermore, knockdown of HDAC11 ameliorated WAT hypertrophy and induced WAT browning. At the cellular level, silencing of HDAC11 promoted the differentiation of adipose-derived stem cells (ADSCs) into brown adipocyte-like cells and inhibited the proliferation of ADSCs. More interestingly, HDAC11 expression was elevated in ADSCs isolated from obese mice, and silencing of HDAC11 facilitated the spontaneous differentiation of ADSCs into mesoderm, which is the source of adipocytes. This also superficially and effectively demonstrates the exciting prospect of HDAC11 silencing in obesity research and treatment, as a valve for "energy saving and flow reduction".