COF-Based Photocatalysts for Enhanced Synthesis of Hydrogen Peroxide.

Covalent Organic Frameworks (COFs), with their intrinsic structural regularity and modifiable chemical functionality, have burgeoned as a pivotal material in the realm of photocatalytic hydrogen peroxide (H2O2) synthesis. This article reviews the recent advancements and multifaceted approaches employed in using the unique properties of COFs for high-efficient photocatalytic H2O2 production. We first introduced COFs and their advantages in the photocatalytic synthesis of H2O2. Subsequently, we spotlight the principles and evaluation of photocatalytic H2O2 generation, followed by various strategies for the incorporation of active sites aiming to optimize the separation and transfer of photoinduced charge carriers. Finally, we explore the challenges and future prospects, emphasizing the necessity for a deeper mechanistic understanding and the development of scalable and economically viable COF-based photocatalysts for sustainable H2O2 production.

aMAP Score and Its Combination With Liver Stiffness Measurement Accurately Assess Liver Fibrosis in Chronic Hepatitis B Patients.

BACKGROUND & AIMS: The changes in liver stiffness measurement (LSM) are unreliable to estimate regression of fibrosis during antiviral treatment for chronic hepatitis B (CHB) patients. The age-male-albumin-bilirubin-platelets score (aMAP), as an accurate hepatocellular carcinoma risk score, may reflect the liver fibrosis stage. Here, we aimed to evaluate the performance of aMAP for diagnosing liver fibrosis in CHB patients with or without treatment. METHODS: A total of 2053 patients from 2 real-world cohorts and 2 multicentric randomized controlled trials in China were enrolled, among which 2053 CHB patients were included in the cross-sectional analysis, and 889 CHB patients with paired liver biopsies before and after 72 or 104 weeks of treatment were included in the longitudinal analysis. RESULTS: In the cross-sectional analysis, the areas under the receiver operating characteristic curve of aMAP in diagnosing cirrhosis and advanced fibrosis were 0.788 and 0.757, which were comparable with or significantly higher than those of the fibrosis index based on 4 factors and the aspartate aminotransferase-platelet ratio. The stepwise approach using aMAP and LSM further improved performance in detecting cirrhosis and advanced fibrosis with the smallest uncertainty area (29.7% and 46.2%, respectively) and high accuracy (82.3% and 79.8%, respectively). In the longitudinal analysis, we established a novel model (aMAP-LSM model) by calculating aMAP and LSM results before and after treatment, which had satisfactory performance in diagnosing cirrhosis and advanced fibrosis after treatment (area under the receiver operating characteristic curve, 0.839 and 0.840, respectively), especially for those with a significant decrease in LSM after treatment (vs LSM alone, 0.828 vs 0.748; P < .001 [cirrhosis]; 0.825 vs 0.750; P < .001 [advanced fibrosis]). CONCLUSIONS: The aMAP score is a promising noninvasive tool for diagnosing fibrosis in CHB patients. The aMAP-LSM model could accurately estimate fibrosis stage for treated CHB patients.

Impact of nonalcoholic fatty liver disease status change on antiviral efficacy of nucleos(t)ide analogues in HBeAg-positive chronic hepatitis B.

Data on the dynamic changes in chronic hepatitis B (CHB) patients with nonalcoholic fatty liver disease (NAFLD) during antiviral therapy are scarce. We aimed to investigate the evolution of NAFLD status change in CHB patients treated with nucleos(t)ide analogues (NAs) and its influence on therapeutic outcomes. This retrospective study included 164 HBeAg-positive CHB patients from a randomized controlled trial who were treated with NAs for 104 weeks and underwent paired liver biopsies. Histological evaluation was performed at baseline and Week 104. The patients were divided into four groups according to NAFLD status changes. From baseline to Week 104, the overall percentage of CHB patients with concurrent NAFLD increased from 17.1% to 26.2% (p = 0.044). Among them, 7 of 28 patients (25.0%) with NAFLD at baseline showed NAFLD remission at week 104, while 22 of 136 patients (16.2%) without NAFLD at baseline developed new-onset NAFLD. In subgroup analyses, the new-onset and sustained NAFLD groups showed significantly lower rates of biochemical response at week 104 as compared to the sustained non-NAFLD group (77.3% and 57.1% vs. 93.9%, respectively; all p < 0.05), as well as fibrosis improvement (31.8% and 42.9% vs. 69.3%, respectively; all p < 0.05). NAFLD status changes did not influence the virological response, HBeAg seroconversion, and necroinflammation improvement (all p > 0.05). In HBeAg-positive CHB patients receiving NAs therapy, new-onset and sustained NAFLD may counteract the benefits of antiviral therapy, reducing the rate of biochemical response and fibrosis improvement.

Recent progress in noble-metal-free electrocatalysts for alkaline oxygen evolution reaction.

The practical application of splitting water to generate hydrogen is to a large extent hindered by an oxygen evolution reaction (OER) process. Electrocatalysts with low-cost, high activity, and durability are essential for the low kinetic threshold of the OER. Despite the high active performances of noble metal compound electrocatalysts like IrO2 and RuO2, they are heavily restricted by the high cost and scarcity of noble metal elements. In this context, noble-metal-free electrocatalysts have acquired increasing significance in recent years. So far, a broad spectrum of noble-metal-free electrocatalysts has been developed for improved OER performance. In this review, three types of electrolysis and some evaluation criteria are introduced, followed by recent progress in designing and synthesizing noble-metal-free alkaline OER electrocatalysts, with the classification of metal oxides/(oxy)hydroxides, carbon-based materials, and metal/carbon hybrids. Finally, perspectives are also provided on the future development of the alkaline OER on active sites and stability of electrocatalysts.

Exosomal microRNA-25 released from cancer cells targets SIK1 to promote hepatocellular carcinoma tumorigenesis.

BACKGROUND: Hepatocellular carcinoma (HCC) is recognized as a leading cause of cancer-associated fatality worldwide. Our study here aimed to probe the mechanism by which exosomes secreted by CSQT-2, an HCC cell line, affected the progression of HCC. METHODS: Exosomes were extracted from CSQT-2 cells. Colony formation, Transwell, sphere formation and flow cytometric analyses were applied to assess cell biological activities. Microarray analysis detected the change of microRNA (miRNA) expression after exosome treatment, followed by RT-qPCR validation. Luciferase reporter was applied to detect the binding between SIK1 and miR-25. Xenograft studies in nude mice manifested tumor growth and metastatic ability of miR-25 and SIK1. RESULTS: The exosome treatment enhanced cell malignant phenotype in vitro and tumor growth and liver and lung metastases in vivo. The exosomes elevated miR-25 expression in HCC cells. miR-25 targeted SIK1 which was decreased in the exosomes-treated cells. miR-25 inhibitor reduced cell malignant phenotype and attenuated tumorigenesis and metastasis in vivo. SIK1 silencing reversed the effect of miR-25 inhibitor. The exosome treatment potentiated the Wnt/ß-catenin pathway in cells, whereas miR-25 inhibitor blunted the pathway activity. CONCLUSION: MiR-25 shuttled through CSQT-2-derived exosomes promoted the development of HCC by reducing SIK1 expression and potentiating the Wnt/ß-catenin pathway.

Efficacy and safety of a nanoparticle therapeutic vaccine in patients with chronic hepatitis B: A randomized clinical trial.

BACKGROUND AND AIM: HBV DNA can be reduced using antiviral drugs in patients with chronic hepatitis B (CHB); however, the rate of HBeAg seroconversion remains low. A clinical trial was conducted to assess the efficacy and safety of a de novo designed liposome-based nanoparticle lipopeptide vaccine, εPA-44, for CHB. APPROACH AND RESULTS: A two-stage phase 2 trial, which included a 76-week, randomized, double-blind, placebo-controlled trial (stage 1) and a 68-week open-label extension (stage 2), was conducted in 15 centers across China (Clinicaltrials.gov No. NCT00869778). In stage 1, 360 human leukocyte antigen A2 (HLA-A2)-positive and HBeAg-positive patients were randomly and equally distributed to receive six subcutaneous injections of 600 µg or 900 µg εPA-44 or placebo at week 0, 4, 8, 12, 20, and 28. In stage 2, 183 patients received extended 900 µg εPA-44, and 26 patients were observed for relapse without further treatment. The primary endpoint was the percentage of patients with HBeAg seroconversion at week 76. At week 76, patients receiving 900 µg εPA-44 achieved significantly higher HBeAg seroconversion rate (38.8%) versus placebo (20.2%) (95% CI, 6.9-29.6%; p = 0.002). With a combined endpoint of HBeAg seroconversion, alanine aminotransferase normalization and HBV DNA < 2,000 IU/mL, both 900 µg (18.1%) and 600 µg (14.3%), resulted in significantly higher rate versus placebo (5.0%) (p = 0.002 and p = 0.02, respectively) at week 76. In stage 2, none (0 of 20) of 900 µg εPA-44-treated patients experienced serologic relapse. The safety profile of εPA-44 was comparable to that of placebo. CONCLUSIONS: Among HLA-A2-positive patients with progressive CHB, a finite duration of 900 µg εPA-44 monotherapy resulted in significantly higher HBeAg seroconversion rate than placebo and sustained off-treatment effect. A phase 3 trial is ongoing (ChiCTR2100043708).

Long-term outcomes in Chinese patients with chronic hepatitis B receiving nucleoside/nucleotide analogue therapy in real-world clinical practice: 5-year results from the EVOLVE study.

BACKGROUND: In China, the optimal management of individuals living with chronic HBV infection (CHB) remains an unmet need. The EVOLVE Study was a 5-year prospective, longitudinal, observational study that compared the clinical outcomes in treatment-naive CHB patients receiving entecavir (ETV) or lamivudine (LAM)-based therapies. METHODS: Males or females aged ≥18 years, diagnosed with CHB regardless of cirrhosis or hepatitis B e antigen (HBeAg) status were enrolled from tier 2 city hospitals (between 2012-2014). The choice of initial therapy and subsequent treatment modifications was at the discretion of treating physicians. Key outcomes included treatment modifications, virological response (HBV DNA <300 copies/ml) and HBV disease progression. RESULTS: Of the 3,408 patients enrolled, 1,807 and 628 received ETV and LAM-based therapy, respectively. The mean age was 39.5 years, 74% were male and 22.9% had cirrhosis. The rate of treatment modification was higher in the LAM-based versus ETV group (25.9% versus 13.7%); viral breakthrough was the most common reason in the LAM-based group versus financial reasons in the ETV group. At week 240, the virological response rate was 73% in both treatment groups. Compared with LAM-based therapy, ETV was associated with a significantly lower incidence of viral breakthrough (12.6% versus 2.1%) and genotypic resistance (10.1% versus 1.2%; P<0.0001 for both); significantly lower risk of HBV disease progression (14.0% versus 10.7%; P=0.0113); and lower rates of progression to decompensated cirrhosis (9.6% versus 6.4%) and hepatocellular carcinoma (1.9% versus 0.8%). CONCLUSIONS: This real-world, longitudinal study demonstrated a significantly lower risk of HBV-related disease progression, viral breakthrough and resistance with ETV versus LAM-based therapy. ClinicalTrials.gov NCT01726439.

Facile Synthesis of Enzyme-Embedded Metal-Organic Frameworks for Size-Selective Biocatalysis in Organic Solvent.

In situ immobilization of enzyme into metal-organic frameworks (MOFs) is performed through a one-step and facile method. Candida antarctica lipase B (CalB) is directly embedded in zeolitic imidazolate framework (ZIF)-8 by simply mixing an aqueous solution of 2-methylimidazole and zinc nitrate hexahydrate [Zn(NO3)2⋅6H2O] containing CalB at room temperature. Due to the intrinsic micropores of ZIF-8, the obtained CalB@ZIF composite is successfully applied in size-selective transesterification reaction in organic solvent. CalB@ZIF not only shows much higher catalytic activity but also exhibits higher thermal stability than free CalB. Besides, the robust ZIF-8 shell also offers the hybrid composites excellent reusability.

Exosomes secreted by chronic hepatitis B patients with PNALT and liver inflammation grade ≥ A2 promoted the progression of liver cancer by transferring miR-25-3p to inhibit the co-expression of TCF21 and HHIP.

OBJECTIVES: The current study aimed to investigate the mechanism by which exosomes secreted by CHB patients with PNALT and liver inflammation grade (≥A2) affected the development of liver cancer. MATERIALS AND METHODS: Gene expression was assessed by RT-PCR, Western blotting and immunohistochemistry. CCK-8, colony formation, transwell, scratch-wound and flow cytometry assays were used to detect cell viability, proliferation, apoptosis and metastasis. The interaction of TCF21 and HHIP was assessed by co-immunoprecipitation assay. Luciferase reporter was used to detect the combination of TCF21/HHIP and miR-25-3p. Xenograft studies in nude mice manifested tumour growth ability of miR-25-3p. Bioinformatics analyses were conducted using TargetScan, EVmiRNA, TCGA, GEO, DAVID, COEXPEDIA, UALCAN, UCSC and the Human Protein Atlas databases. RESULTS: CHB-PNALT-Exo (≥A2) promoted the proliferation and metastasis of HepG2.2.15 cells. miR-25-3p was upregulated in CHB-PNALT-Exo (≥A2). miR-25-3p overexpression promoted cell proliferation and metastasis and was related to poor survival in patients with CHB-PNALT (≥A2). The cell proliferation- and metastasis-promoting functions of CHB-PNALT-Exo (≥A2) were abolished by miR-25-3p inhibitors. TCF21 directly interacted with HHIP. Inhibition of TCF21 or HHIP promoted cell proliferation and metastasis. Knockdown of TCF21 or HHIP counteracted the effects of CHB-PNALT-Exo (≥A2) containing miR-25-3p inhibitor on cell proliferation, metastasis and the expression of Ki67, E-cadherin and caspase-3/-9. CONCLUSIONS: Transfer of miR-25-3p by CHB-PNALT-Exo promoted the development of liver cancer by inhibiting the co-expression of TCF21 and HHIP.

Resource-Efficient Low-Temperature Synthesis of Microcrystalline Pb2 B5 O9 X (X = Cl, Br) for Surfaces Studies by Optical Second Harmonic Generation.

Optically nonlinear Pb2 B5 O9 X (X = Cl, Br) borate halides are an important group of materials for second harmonic generation (SHG). Additionally, they also possess excellent photocatalytic activity and stability in the process of dechlorination of chlorophenols, which are typical persistent organic pollutants. It would be of great interest to conduct in situ (photo-) catalysis investigations during the whole photocatalytic process by SHG when considering them as photocatalytic materials. In order to get superior photocatalytic efficiency and maximum surface information, small particles are highly desired. Here, a low-cost and fast synthesis route that allows growing microcrystalline optically nonlinear Pb2 B5 O9 X borate halides at large quantities is introduced. When applying the ionothermal growth process at temperatures between 130 and 170 °C, microcrystallites with an average size of about 1 µm precipitate with an orthorhombic hilgardite-like borate halide structure. Thorough examinations using powder X-ray diffraction and scanning electron microscopy, the Pb2 B5 O9 X microcrystals are indicated to be chemically pure and single-phased. Besides, the Pb2 B5 O9 X borate halides' SHG efficiencies are confirmed using confocal SHG microscopy. The low-temperature synthesis route thus makes these borate halides a highly desirable material for surface studies such as monitoring chemical reactions with picosecond time resolution and in situ (photo-) catalysis investigations.

Combining Hepatitis B Virus RNA and Hepatitis B Core-Related Antigen: Guidance for Safely Stopping Nucleos(t)ide Analogues in Hepatitis B e Antigen-Positive Patients With Chronic Hepatitis B.

BACKGROUND: Safe nucleos(t)ide analogue discontinuation in chronic hepatitis B (CHB) is an unmet need. We aimed to investigate whether combining hepatitis B virus (HBV) RNA and hepatitis B core-related antigen (HBcrAg) could perform satisfactorily in predicting off-treatment outcomes. METHODS: The evaluation cohort included 127 hepatitis B e antigen (HBeAg)-positive patients from a multicenter prospective trial who stopped telbivudine-based therapy after achieving HBeAg seroconversion and HBV DNA < 50 IU/mL for > 48 weeks. As validation, 59 patients treated with entecavir or tenofovir before discontinuation were analyzed. RESULTS: At the end of treatment (EOT), HBV RNA and HBcrAg were significant independent predictors of the clinical relapse risk. In the evaluation cohort, no clinical relapse occurred among patients with negative HBV RNA and HBcrAg < 4 log10 U/mL at EOT (low-risk group), whereas 46.8% patients with positive HBV RNA and HBcrAg ≥ 4 log10 U/mL (high-risk group) experienced clinical relapse during 4-year posttreatment follow-up (P < .001); the corresponding incidences in the validation cohort were 0% and 69.4% (P < .001), respectively. More patients in the low-risk group achieved HBsAg loss than the other patients after treatment cessation (16.1% vs 1.3%, P = .002). CONCLUSIONS: Combining HBV RNA and HBcrAg performed satisfactorily in predicting clinical relapse and HBsAg loss after treatment cessation in HBeAg-positive patients with CHB.The combination of hepatitis B virus RNA and hepatitis B core-related antigen performed satisfactorily in predicting clinical relapse and hepatitis B surface antigen loss after stopping nucleos(t)ide analogue treatment among noncirrhotic hepatitis B e antigen-positive patients with chronic hepatitis B and could be used to guide safe discontinuation.

Polymer Brushes on Graphitic Carbon Nitride for Patterning and as a SERS Active Sensing Layer via Incorporated Nanoparticles.

Graphitic carbon nitride (gCN) has a broad range of promising applications, from energy harvesting and storage to sensing. However, most of the applications are still restricted due to gCN poor dispersibility and limited functional groups. Herein, a direct photografting of gCN using various polymer brushes with tailorable functionalities via UV photopolymerization at ambient conditions is demonstrated. The systematic study of polymer brush-functionalized gCN reveals that the polymerization did not alter the inherent structure of gCN. Compared to the pristine gCN, the gCN-polymer composites show good dispersibility in various solvents such as water, ethanol, and tetrahydrofuran (THF). Patterned polymer brushes on gCN can be realized by employing photomask and microcontact printing technology. The polymer brushes with incorporated silver nanoparticles (AgNPs) on gCN can act as a multifunctional recyclable active sensing layer for surface-enhanced Raman spectroscopy (SERS) detection and photocatalysis. This multifunctionality is shown in consecutive cycles of SERS and photocatalytic degradation processes that can be applied to in situ monitor pollutants, such as dyes or pharmaceutical waste, with high chemical sensitivity as well as to water remediation. This dual functionality provides a significant advantage to our AgNPs/polymer-gCN with regard to state-of-the-art systems reported so far that only allow SERS pollutant detection but not their decomposition. These results may provide a new methodology for the covalent functionalization of gCN and may enable new applications in the field of catalysis, biosensors, and, most interestingly, environmental remediation.

One-pot resource-efficient synthesis of SnSb powders for composite anodes in sodium-ion batteries.

SnSb alloy, which can be used as an anode in a sodium-ion cell, was synthesized following a resource-efficient route at low temperature. This one-pot approach greatly reduces the energy consumption and maximizes the efficient use of raw materials. The reaction of elemental tin and antimony in the ionic liquid (IL) trihexyltetradecylphosphonium chloride ([P66614]Cl) at 200 °C led to a microcrystalline powder of single-phase SnSb within 10 h with very high yield (95%). Liquid-state nuclear magnetic resonance spectroscopy revealed that the IL remains essentially stable during the reaction. It was recovered almost quantitatively by distilling off the organic solvent used for product separation. Composites of SnSb powder and carbon nanotubes (CNTs) were fabricated by a simple ball milling process. Electrochemical measurements demonstrate that the Na‖SnSb/CNTs cell retains close to 100% of its initial capacity after 50 cycles at a current of 50 mA g-1, which is much better than the Na‖SnSb cell. The greatly increased capacity retainability can be attributed to the conductive network formed by CNTs inside the SnSb/CNTs electrode, providing 3D effective and fast electronic pathways during sodium intercalation and de-intercalation.

Association Between Negative Results From Tests for HBV DNA and RNA and Durability of Response After Discontinuation of Nucles(t)ide Analogue Therapy.

BACKGROUND & AIMS: There is no satisfactory way to identify patients who will maintain a response after discontinuation of nuleos(t)ide analogue therapy for chronic hepatitis B virus (HBV) infection. We investigated whether patients with negative results from tests for HBV DNA and HBV RNA (double negative) at the end of treatment maintain a long-term response to treatment. METHODS: We performed a post-hoc analysis of data from a 2-year multi-center randomized controlled trial, and its long-term extension trials, on 130 patients with chronic HBV infection who were positive for the HB e antigen (HBeAg-positive; mean age, 30.8 ± 6.9 years; 72.3% male) and received telbivudine with or without adefovir and stopped therapy after they had HBeAg seroconversion and levels of HBV DNA <300 copies/mL for at least 48 weeks (evaluation cohort). Clinical and laboratory assessments were made every 12 or 16 weeks until clinical relapse (defined as HBV DNA > 2000 IU/mL and level of alanine aminotransferase more than 2-fold the upper limit of normal) or until 4 years off treatment. We validated our findings in a cohort of 40 HBeAg-positive patients (36.5 ± 9.4 years old; 72.5% male) treated with entecavir or tenofovir, and followed after discontinuation for up to 5.5 years. Patients were considered to be negative for HBV DNA if it was not detected in the COBAS Taqman assay. Patients were considered to be negative for HBV RNA if it was not detected by quantitative real-time PCR with 2 different pairs of primers. RESULTS: After 4 years off treatment, in the evaluation cohort, 30.8% of patients had a clinical relapse, 54.7% had virologic relapse (HBV DNA >2000 IU/mL in 2 tests), and 16.8% had reappearance of HBeAg in 2 tests (reversion). A significantly lower proportion of double negative patients had a clinical relapse 4 years later (2/35; 8.0%) than of patients who tested positive for either HBV DNA or RNA (32/102; 31.4%; P = .018). In the validation cohort, after 5.5 years of follow up, a lower proportion of double negative patients had clinical relapse (2/13; 15.4%) than of patients who tested positive for either HBV DNA or RNA at the end of treatment (9/27; 33.3%; P = .286) CONCLUSIONS: In an analysis of data from 2 independent cohorts, we associated negative results from tests for HBV DNA and RNA (double negative) at the end of treatment with continued response 4 or more years after discontinuation of therapy in HBeAg-positive patients. These results might be used to identify the best candidates for discontinuation of nuleos(t)ide analogue therapy.

Outcomes of Long-term Treatment of Chronic HBV Infection With Entecavir or Other Agents From a Randomized Trial in 24 Countries.

BACKGROUND & AIMS: Treatment of chronic hepatitis B virus (HBV) infection with entecavir suppresses virus replication and reduces disease progression, but could require life-long therapy. To investigate clinical outcome events and safety associated with long-term treatment with entecavir, we followed up patients treated with entecavir or another standard-of-care HBV nucleos(t)ide analogue for up to 10 years. We assessed long-term outcomes and relationships with virologic response. METHODS: Patients with chronic HBV infection at 299 centers in Asia, Europe, and North and South America were assigned randomly to groups that received entecavir (n = 6216) or an investigator-selected nonentecavir HBV nucleos(t)ide analogue (n = 6162). Study participants were followed up for up to 10 years in hospital-based or community clinics. Key end points were time to adjudicated clinical outcome events and serious adverse events. In a substudy, we examined relationships between these events and virologic response. RESULTS: There were no significant differences between groups in time to event assessments for primary end points including malignant neoplasms, liver-related HBV disease progression, and death. There were no differences between groups in the secondary end points of nonhepatocellular carcinoma malignant neoplasms and hepatocellular carcinoma. In a substudy of 5305 patients in China, virologic response, regardless of treatment group, was associated with a reduced risk of liver-related HBV disease progression (hazard ratio, 0.09; 95% CI, 0.038-0.221) and hepatocellular carcinoma (hazard ratio, 0.03; 95% CI, 0.009-0.113). Twelve patients given entecavir (0.2%) and 50 patients given nonentecavir drugs (0.8%) reported treatment-related serious adverse events. CONCLUSIONS: In a randomized controlled trial of patients with chronic HBV infection, we associated entecavir therapy with a low rate of adverse events over 10 years of follow-up evaluation. Patients receiving entecavir vs another nucleos(t)ide analogue had comparable rates of liver- and non-liver-related clinical outcome events. Participants in a China cohort who maintained a virologic response, regardless of treatment group, had a reduced risk of HBV-related outcome events including hepatocellular carcinoma. ClinicalTrials.gov identifier no: NCT00388674.

A High-Voltage, Dendrite-Free, and Durable Zn-Graphite Battery.

The intrinsic advantages of metallic Zn, like high theoretical capacity (820 mAh g-1 ), high abundance, low toxicity, and high safety have driven the recent booming development of rechargeable Zn batteries. However, the lack of high-voltage electrolyte and cathode materials restricts the cell voltage mostly to below 2 V. Moreover, dendrite formation and the poor rechargeability of the Zn anode hinder the long-term operation of Zn batteries. Here a high-voltage and durable Zn-graphite battery, which is enabled by a LiPF6 -containing hybrid electrolyte, is reported. The presence of LiPF6 efficiently suppresses the anodic oxidation of Zn electrolyte and leads to a super-wide electrochemical stability window of 4 V (vs Zn/Zn2+ ). Both dendrite-free Zn plating/stripping and reversible dual-anion intercalation into the graphite cathode are realized in the hybrid electrolyte. The resultant Zn-graphite battery performs stably at a high voltage of 2.8 V with a record midpoint discharge voltage of 2.2 V. After 2000 cycles at a high charge-discharge rate, high capacity retention of 97.5% is achieved with ≈100% Coulombic efficiency.

Long non-coding RNA MALAT1 promotes angiogenesis and immunosuppressive properties of HCC cells by sponging miR-140.

Hepatocellular carcinoma (HCC) is the most prevalent primary liver cancer in adults. Previous studies in our laboratory found that long non-coding RNA metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) was upregulated in HCC cells, which could affect the metastasis and invasion of HCC. However, the underlying mechanism remains unknown. Herein, we studied the interaction between MALAT1 and miR-140 on the regulation of angiogenesis and immunosuppressive properties. We revealed that the expression of MALAT1 and VEGF-A was significantly increased in HCC cells. Knockdown of MALAT1 in HCC cells suppressed the production of VEGF-A, impaired the angiogenesis of HUVECs, and facilitated the polarization of macrophage toward the M1 subset. Mechanistically, the interaction between MALAT1 and miR-140 or between miR-140 and VEGF-A was confirmed by multiple assays. Besides, a negative correlation between MALAT1 and miR-140 was found in HCC tissues. Furthermore, miR-140 inhibition significantly increased VEGF-A expression, promoted angiogenesis of HUVECs, and redirected the polarization of macrophages toward the M2 subset. In addition, in vivo studies also verified the regulatory network of the MALAT1/miR-140 axis on VEGF-A in HCC progression. In summary, this study revealed the mechanism that MALAT1 worked as a putative HCC promotor via inhibiting miR-140. Therefore, targeting MALAT1 or miR-140 might alleviate the progression of HCC in the future.

Plasma miR-146a predicts serological conversion of hepatitis B e-antigen (HBeAg) in chronic hepatitis B patients treated with nucleotide analogs.

BACKGROUND: To investigate the association of plasma miR-146a with serological conversion of hepatitis B e-antigen (HBeAg) in patients with chronic hepatitis B (CHB) treated with nucleotide analogs (NAs). METHODS: This was a retrospective study of 115 HBeAg-positive patients with CHB treated at Xiangya Hospital, Central South University, Changsha, China, between September 2009 and March 2014. Patients were grouped according to whether they had achieved seroconversion of HBeAg by 104 weeks of NAs treatment. We assessed plasma miR-146a using miScript polymerase chain reaction (PCR). Serum alanine transaminase (ALT), hepatitis B virus (HBV) deoxyribonucleic acid (DNA) load, hepatitis B surface antigen (HBsAg) titer, HBeAg titer, and plasma miR-146a were measured at 0, 24, 48, and 104 weeks of treatment. Finally, we also determined ΔmiR-146a24w and ΔmiR-146a48w. RESULTS: ΔmiR-146a48w was independently associated with seroconversion of HBeAg at 104 weeks [odds ratio (OR) =1.302; 95% confidence interval (CI), 1.159-1.962; P=0.029]. We obtained an area under the receiver operating characteristic (ROC) curve (AUC) of ΔmiR-14648w of 0.757 for seroconversion of HBeAg (P=0.013). At the optimal cutoff value equivalent to a Youden index of 67.9%, the specificity and sensitivity of ΔmiR-14648w were 63.7% and 88.3%, respectively. Positive (PPV) and negative (NPV) predictive values were 70.87% and 84.48%, respectively. CONCLUSIONS: ΔmiR-146a48w was independently associated with seroconversion of HBeAg in CHB patients treated with NAs.

[Expressions of miR-146a and miR-155 in different samples of chronic hepatitis B patients].

OBJECTIVE: To detect the levels of miR-146a and miR-155 in different samples from chronic hepatitis B (CHB), reveal whether there is a correlation between the 2 miRNAs in different samples, and to provide a theoretical basis for sample choice of miRNA research in liver.
 Methods: Real-time PCR was conducted to examine the expression of miR-146a and miR-155 in the plasma, peripheral blood mononuclear cell (PBMC), and liver tissues from 41 CHB patients who underwent nucleoside analogues antiviral therapy for 104 weeks. Correlations between the levels of miR-146a and miR-155 among the 3 samples were analyzed.
 Results: The expressions of miR-146a and miR-155 in the plasma, PBMC and liver tissues were significantly down-regulated at the 104th week than those at the baseline (all P<0.05). There was a correlation in the expression of miR-146a between plasma and liver tissues (r=0.560, P=0.007), PBMC and liver tissues (r=0.428, P=0.047) at baseline. There was a correlation in the expression of miR-155 between plasma and liver tissue (r=0.587, P=0.004), PBMC and liver tissue (r=0.483, P=0.023) at baseline. The expressions of miR-146a and miR-155 between the plasma and PBMC were not correlated (P>0.05).
 Conclusion: Compared with PBMC, miR-146a and miR-155 from plasma can better reflect the expression in the liver tissues, suggesting that plasma can be applied in the mechanism research on miR-146a and miR-155 in the liver diseases instead of liver tissues.