A small-molecule drug inhibits autophagy gene expression through the central regulator TFEB.

Autophagy supports the fast growth of established tumors and promotes tumor resistance to multiple treatments. Inhibition of autophagy is a promising strategy for tumor therapy. However, effective autophagy inhibitors suitable for clinical use are currently lacking. There is a high demand for identifying novel autophagy drug targets and potent inhibitors with drug-like properties. The transcription factor EB (TFEB) is the central transcriptional regulator of autophagy, which promotes lysosomal biogenesis and functions and systematically up-regulates autophagy. Despite extensive evidence that TFEB is a promising target for autophagy inhibition, no small molecular TFEB inhibitors were reported. Here, we show that an United States Food and Drug Administration (FDA)-approved drug Eltrombopag (EO) binds to the basic helix-loop-helix-leucine zipper domain of TFEB, specifically the bottom surface of helix-loop-helix to clash with DNA recognition, and disrupts TFEB-DNA interaction in vitro and in cellular context. EO selectively inhibits TFEB's transcriptional activity at the genomic scale according to RNA sequencing analyses, blocks autophagy in a dose-dependent manner, and increases the sensitivity of glioblastoma to temozolomide in vivo. Together, this work reveals that TFEB is targetable and presents the first direct TFEB inhibitor EO, a drug compound with great potential to benefit a wide range of cancer therapies by inhibiting autophagy.

Alcohol as a risk factor for hearing loss: A systematic review and meta-analysis.

OBJECTIVE: Growing evidence suggests that alcohol consumption is a risk factor for hearing loss; however, the evidence has been inconsistent. This systematic review and meta-analysis aimed to evaluate the effect of alcohol consumption on hearing loss. METHODS: We searched several databases up to November 2021, for published articles using the keywords "alcohol drinking" and "hearing loss". Two investigators independently conducted the study selection and data extraction. Based on the results of the heterogeneity analysis (Q statistic and I2 statistic), a fixed- or random-effects model was used to calculate the pooled odds ratios (ORs). Subgroup and sensitivity analyses were performed to assess the potential sources of heterogeneity and robustness of the pooled estimation. Publication bias in the literature was evaluated using Egger's test. RESULTS: In total, 18 (9 cross-sectional, 5 case-control, and 4 cohort) observational studies were identified in this search; 27,849 participants were included. Compared with non-drinkers, the pooled OR of drinkers was 1.22 (95% confidence interval: 1.09-1.35). CONCLUSION: Evidence suggests a positive association between alcohol consumption and hearing loss. Drinkers were at a higher risk than non-drinkers. Drinking limitations may be useful for preventing hearing loss.

A unique hyperdynamic dimer interface permits small molecule perturbation of the melanoma oncoprotein MITF for melanoma therapy.

Microphthalmia transcription factor (MITF) regulates melanocyte development and is the "lineage-specific survival" oncogene of melanoma. MITF is essential for melanoma initiation, progression, and relapse and has been considered an important therapeutic target; however, direct inhibition of MITF through small molecules is considered impossible, due to the absence of a ligand-binding pocket for drug design. Here, our structural analyses show that the structure of MITF is hyperdynamic because of its out-of-register leucine zipper with a 3-residue insertion. The dynamic MITF is highly vulnerable to dimer-disrupting mutations, as we observed that MITF loss-of-function mutations in human Waardenburg syndrome type 2 A are frequently located on the dimer interface and disrupt the dimer forming ability accordingly. These observations suggest a unique opportunity to inhibit MITF with small molecules capable of disrupting the MITF dimer. From a high throughput screening against 654,650 compounds, we discovered compound TT-012, which specifically binds to dynamic MITF and destroys the latter's dimer formation and DNA-binding ability. Using chromatin immunoprecipitation assay and RNA sequencing, we showed that TT-012 inhibits the transcriptional activity of MITF in B16F10 melanoma cells. In addition, TT-012 inhibits the growth of high-MITF melanoma cells, and inhibits the tumor growth and metastasis with tolerable toxicity to liver and immune cells in animal models. Together, this study demonstrates a unique hyperdynamic dimer interface in melanoma oncoprotein MITF, and reveals a novel approach to therapeutically suppress MITF activity.

Risk Assessment of Heavy Metal Pollution in Farmland Soils at the Northern Foot of the Qinling Mountains, China.

To provide scientific basis for the prevention and control of heavy metal pollution, a field investigation, sample collection and analysis of the heavy metal content in farmland soils at the northern foot of the Qinling Mountains were conducted. Based on the comparative analysis of the single pollution index method, the Nemerow comprehensive pollution index method, the geological accumulation index method, the potential ecological hazard index method, and the geological accumulation index method were used to comprehensively analyze and evaluate the risk of soil heavy metal pollution. The results showed that the heavy metal pollution of farmland soil at the northern foot of the Qinling Mountains was severe, among which Hg and Cr pollution was relatively obvious. Taking the soil screening values of agricultural land as the standard, the quantity of element Hg in agricultural soils at the northern foot of the Qinling Mountains was higher than the relevant screening value. In the two sample sites investigated, the intensity of the heavy metal accumulation index in Baoqizhai Village was Hg > Cr > Cu > As > Pb, and in Dayangyu Village it was Cr > Cu > As > Pb. Among them, in Baoqizhai Village it shows the heavy pollution caused by Hg (Igeo= 3.42) and the light pollution caused by Cr (Igeo < 1) in the two areas. Hg is mostly affected by mining activities and its atmospheric subsidence. At the same time, Cr is mainly derived from the weathering of rock parent material and is also affected by anthropogenic factors to a certain extent. The accumulation of heavy metals in the farmland soil around the northern foot of the Qinling Mountains was relatively high, posing a threat to the surrounding soil environment. Therefore, it is urgent to control farmland soil environmental pollution.

Bifidobacterium lactis Probio-M8 improves bone metabolism in patients with postmenopausal osteoporosis, possibly by modulating the gut microbiota.

PURPOSE: Postmenopausal osteoporosis (PMO) is usually managed by conventional drug treatment. However, prolonged use of these drugs cause side effects. Gut microbiota may be a potential target for treatment of PMO. This work was a three-month intervention trial aiming to evaluate the added effect of probiotics as adjunctive treatment for PMO. METHODS: Forty patients with PMO were randomized into probiotic (n = 20; received Bifidobacterium animalis subsp. lactis Probio-M8 [Probio-M8], calcium, calcitriol) and placebo (n = 20; received placebo material, calcium, calcitriol) groups. The bone mineral density of patients was measured at month 0 (0 M; baseline) and month 3 (3 M; after three-month intervention). Blood and fecal samples were collected 0 M and 3 M. Only 15 and 12 patients from Probio-M8 and placebo groups, respectively, provided complete fecal samples for gut microbiota analysis. RESULTS: No significant change was observed in the bone mineral density of patients at 3 M. Co-administering Probio-M8 improved the bone metabolism, reflected by an increased vitamin D3 level and decreased PTH and procalcitonin levels in serum at 3 M. Fecal metagenomic analysis revealed modest changes in the gut microbiome in both groups at 3 M. Interestingly, Probio-M8 co-administration affected the gut microbial interactive correlation network, particularly the short-chain fatty acid-producing bacteria. Probio-M8 co-administration significantly increased genes encoding some carbohydrate metabolism pathways (including ABC transporters, the phosphotransferase system, and fructose and mannose metabolism) and a choline-phosphate cytidylyltransferase. CONCLUSIONS: Co-administering Probio-M8 with conventional drugs/supplements was more efficacious than conventional drugs/supplements alone in managing PMO. Our study shed insights into the beneficial mechanism of probiotic adjunctive treatment. REGISTRATION NUMBER OF CLINICAL TRIAL: Chinese Clinical Trial Registry (identifier number: ChiCTR1800019268).

Preparation and characterization of sodium cellulose sulfate/chitosan composite films loaded with curcumin for monitoring pork freshness.

Colorimetric films were prepared by incorporating curcumin into a sodium cellulose sulfate/chitosan composite. The morphology mechanical, and water vapor properties of the films were investigated, and their practical use in pork preservation was evaluated. The formula with the same charge ratio of sodium cellulose sulfate and chitosan had the highest tensile strength (TS). After the addition of curcumin, the tensile strength increased, whereas the water vapor permeability (WVP) decreased. The colorimetric film showed distinguishable color changes between the pH ranges of 3-10. The colorimetric film packaging extended the shelf life of the pork samples by 4 days. Moreover, the composite films were able to effectively monitor pork freshness. In conclusion, curcumin incorporated into sodium cellulose sulfate/chitosan composite films may have great potential in food packaging.

Mine Personnel Positioning System Based on Dual-Wavelength Phase Unwrapping.

During the construction of coal mine laneway, due to the particularity of the geographical location and structure of the laneway, its accidents often occur, causing great trouble to the personal and property safety of the construction personnel. Therefore, according to the environmental characteristics of the coal mine tunnel and the positive correlation between the phase envelope range and the wavelength, this paper proposes a structural design of the personnel positioning system of the coal mine tunnel based on the dual wavelength phase unwrapping, which combines the coherent detection structure with the dual wavelength phase measurement method in digital holography. In order to reduce false positives in the position information, the synthetic wavelength is used to increase the spread range of the phase. The experiment shows that this structure can reduce the false positioning without reducing the positioning accuracy, and the average double wavelength phase demodulation can reduce the positioning false alarm by 82.5%, which greatly improves the accuracy of the prediction of the tunnel construction safety, brings great protection to the personal and property safety of the tunnel construction personnel, and improves the mining efficiency of the coal mine.

Strong and Flexible High-Performance Anion Exchange Membranes with Long-Distance Interconnected Ion Transport Channels for Alkaline Fuel Cells.

Anion exchange membrane fuel cells (AEMFCs), which operate on a variety of green fuels, can achieve high power without emitting greenhouse gases. However, the lack of high ionic conductivity and long-term durability of anion-exchange membranes (AEMs) as their key components is a major obstacle hindering the commercial application of AEMFCs. Here, a series of homogeneous semi-interpenetrating network (semi-IPN) AEMs formed by cross-linking a copolymer of styrene (St) and 4-vinylbenzyl chloride (VBC) with branched polyethylenimine (BPEI) were designed. The pure carbon copolymer skeleton without sulfone/ether bonds accompanied by the semi-IPN endows the AEMs with excellent chemical stability. Moreover, the cross-linking effect of flexible BPEI chains is supposed to promote the "strong-flexible" mechanical properties, while the presence of multiquaternary ammonium groups can boost the formation of microphase separation, thereby enhancing the ionic conductivity of these AEMs. Consequently, the optimized (S1V1)3Q AEM exhibits an excellent hydroxide conductivity of 106 mS cm-1 at 80 °C, as well as more than 81% residual conductivity after soaking in 1 M NaOH at 60 °C for 720 h. Furthermore, the H2/O2 fuel cell assembled with (S1V1)3Q AEM delivers a peak power density of 150.2 mW cm-2 at 60 °C and 40% relative humidity. All results indicate that the approach of combining a pure carbon backbone polymer with a semi-IPN structure may be a viable strategy for fabricating AEMs that can be used in AEMFCs for long-term applications.

Boosting the Oxygen Evolution Reaction by Controllably Constructing FeNi3/C Nanorods.

Transition bimetallic alloy-based catalysts are regarded as attractive alternatives for the oxygen evolution reaction (OER), attributed to their competitive economics, high conductivity and intrinsic properties. Herein, we prepared FeNi3/C nanorods with largely improved catalytic OER activity by combining hydrothermal reaction and thermal annealing treatment. The temperature effect on the crystal structure and chemical composition of the FeNi3/C nanorods was revealed, and the enhanced catalytic performance of FeNi3/C with an annealing temperature of 400 °C was confirmed by several electrochemical tests. The outstanding catalytic performance was assigned to the formation of bimetallic alloys/carbon composites. The FeNi3/C nanorods showed an overpotential of 250 mV to afford a current density of 10 mA cm-2 and a Tafel slope of 84.9 mV dec-1, which were both smaller than the other control samples and commercial IrO2 catalysts. The fast kinetics and high catalytic stability were also verified by electrochemical impendence spectroscopy and chronoamperometry for 15 h. This study is favorable for the design and construction of bimetallic alloy-based materials as efficient catalysts for the OER.

Sodium alginate crosslinker engineered UCST hydrogel towards superior mechanical properties and controllable dye removal.

Smart hydrogels that can adsorb both anionic and cationic dyes and have excellent mechanical properties have not been reported yet, despite bright prospect in dye adsorption. The emergence of polyampholyte made it possible for the preparation of novel hydrogels. PMAD (copolymer of AM, AA and DMC) is a novel thermo-responsive hydrogel based on polyampholyte, whereas poor mechanical properties limit its application. Herein, we designed a novel polysaccharide crosslinker, which integrates chemical-crosslinking network and physical-entanglements to fabricate PMAD hydrogels. Chemical-crosslinking network maintains the shape of hydrogel as backbone, whereas physical-entanglements enhance the energy-dissipation capacity by disentangle upon deformation. Synergistic effect of the above structure improves the fracture strength and elongation of PMAD by nearly 4700% and 900%, respectively. Moreover, the hydrogel can be used as controllable adsorption material towards both cationic and anionic dyes, which could greatly increase adsorption capacity after reaching the critical temperature due to its unique temperature-sensitive characteristics.

Zinc finger E-Box binding homeobox 2 (ZEB2)-induced astrogliosis protected neuron from pyroptosis in cerebral ischemia and reperfusion injury.

Ischemia injury can cause cell death or impairment of neuron and astrocytes, and thus induce loss of nerve function. central nervous systems injury induces an aberrant activation of astrocytes called astrogliosis. Pyroptosis, which is a kind of programmed cell death, was proved play an important role in ischemia injury. Zinc Finger E-Box Binding Homeobox 2 (ZEB2) promoted neuron astrogliosis, which play a protected role in neuron regeneration. However, its precise mechanism remains unclear. This study investigated the mechanism of ZEB2 on astrogliosis and neuron regeneration after cerebral ischemia reperfusion condition. To confirm our hypothesis, Neurons and astrocytes were isolated from fetal Sprague Dawley rats, in vivo Middle Cerebral Artery Occlusion/reperfusion (MCAO/R) rat model and in vitro oxygen-glucose deprivation/reperfusion (OGD/R)-treated astrocytes and neurocytes model were constructed. Our results showed that ZEB2 was expressed in nucleus of astrocyte and upregulated after OGD/R induction, ZEB2 promoted astrogliosis. Further upregulation of ZEB2 promoted the astrogliosis, which promoted neuron proliferation and regeneration by decreased pyroptosis. Moreover, this finding was further confirmed in vivo MCAO/R rat model. Overexpression of ZEB2 promoted astrogliosis, which decreased infarct volume and accumulated recovery of neurological function by alleviated pyroptosis. This finding revealed that ZEB2 was a regulator of the astrogliosis after ischemia/reperfusion injury, and then astrogliosis promoted neuron regeneration via decreased neuron pyroptosis. Therefore, ZEB2 may be a potential therapeutic target for ischemia/reperfusion injury.

Long-term variation of 90Sr and 137Cs in environmental and food samples around Qinshan nuclear power plant, China.

Environmental radioactivity monitoring in the surroundings of nuclear facilities is important to provide baseline data for effective detection in case of any radioactive release in the region. In this work, we report for the first time the long-term monitoring data of 137Cs and 90Sr in environmental and food samples around Qinshan nuclear power plant in 2012-2019. The distribution levels, temporal variations and source terms of 137Cs and 90Sr in the investigated samples were discussed. The annual effective dose (AED) for the local population from the ingestion of foods was also evaluated. Peak values of 90Sr and 137Cs concentrations and 137Cs/90Sr activity ratio were observed in total atmospheric deposition in 2016 and some water and food samples in the following years. This seems to be associated to an additional radioactive input, mostly likely from the operational release of a local facility. This demonstrates that 90Sr and 137Cs, especially the 137Cs/90Sr activity ratio, are sensitive indicators for detecting potential radioactive releases. Nevertheless, overall 90Sr and 137Cs activity concentrations measured during 2012-2019 in this work were at the background levels with average AED far below the internationally permissible limit and recommendation.

The dynamic, combinatorial cis-regulatory lexicon of epidermal differentiation.

Transcription factors bind DNA sequence motif vocabularies in cis-regulatory elements (CREs) to modulate chromatin state and gene expression during cell state transitions. A quantitative understanding of how motif lexicons influence dynamic regulatory activity has been elusive due to the combinatorial nature of the cis-regulatory code. To address this, we undertook multiomic data profiling of chromatin and expression dynamics across epidermal differentiation to identify 40,103 dynamic CREs associated with 3,609 dynamically expressed genes, then applied an interpretable deep-learning framework to model the cis-regulatory logic of chromatin accessibility. This analysis framework identified cooperative DNA sequence rules in dynamic CREs regulating synchronous gene modules with diverse roles in skin differentiation. Massively parallel reporter assay analysis validated temporal dynamics and cooperative cis-regulatory logic. Variants linked to human polygenic skin disease were enriched in these time-dependent combinatorial motif rules. This integrative approach shows the combinatorial cis-regulatory lexicon of epidermal differentiation and represents a general framework for deciphering the organizational principles of the cis-regulatory code of dynamic gene regulation.

Plasma Cell-Free DNA Profiling of PTEN-PI3K-AKT Pathway Aberrations in Metastatic Castration-Resistant Prostate Cancer.

Tumor tissue from metastatic castration-resistant prostate cancer (mCRPC) harbors frequent copy number variations (CNVs) in the PTEN-PI3K-AKT pathway. However, identifying CNVs in plasma cell-free DNA (cfDNA) has proven to be challenging. With emerging data supporting Akt inhibition in PTEN-deficient mCRPC, we profiled PTEN-PI3K-AKT pathway aberrations in patients with mCRPC using a novel cfDNA assay optimized for CNV detection. METHODS: A next-generation sequencing-based cfDNA assay was used to profile 231 patients with mCRPC from two independent cohorts (Australian, n = 78; United States, n = 153). PTEN-PI3K-AKT pathway genomic aberrations were correlated with clinical outcomes, including progression-free survival and overall survival (OS). RESULTS: PTEN loss and PIK3CA gain were detected in 37% (85 of 231) and 17% (39 of 231) of patients, respectively. Poorer outcomes were observed in patients with PTEN-PI3K-AKT pathway aberrations, including those with dual PTEN loss and PIK3CA gain (hazard ratio 2.3, 95% CI 1.2 to 4.4). Cumulative CNV burden in the PTEN-PI3K-AKT and androgen receptor (AR) pathways was associated with significantly worse clinical outcomes (0 v 1 v ≥ 2 CNVs in Australian cohort: median OS 33.5 v 17.2 v 9.7 months, P < .001; 0 v 1 v ≥ 2 CNVs in US cohort: median OS 35.5 v 14.3 v 9.2 months, P < .001). Notably, 21% (31 of 146) of PTEN-neutral patients harbored alternative PTEN-PI3K-AKT pathway aberrations. CONCLUSION: PTEN-PI3K-AKT pathway CNVs were readily detected using our cfDNA assay, with the prevalence of PTEN loss comparable with tissue-based studies. Additional PTEN-PI3K-AKT pathway aberrations were found in one fifth of PTEN-neutral cases. Concurrent CNVs in the PTEN-PI3K-AKT and AR pathways portended poor survival, and identifying this high-risk patient subset for dual AR/Akt inhibition may optimize precision treatment with Akt inhibitors in mCRPC.

Urinary Molecular Pathology for Patients with Newly Diagnosed Urothelial Bladder Cancer.

PURPOSE: Next-generation sequencing (NGS)-based profiling of both urinary tumor DNA (utDNA) and circulating tumor DNA (ctDNA) shows promise for noninvasive detection and surveillance of urothelial bladder cancer (UBC). However, the analytical performance of these assays remains undefined in the real-world setting. Here, we sought to evaluate the concordance between tumor DNA (tDNA) profiling and utDNA or ctDNA assays using a UBC patient cohort from the intended-use population. MATERIALS AND METHODS: Fifty-nine cases with pathologically confirmed disease and matching tissue/urine pairs were prospectively enrolled. Baseline peripheral blood mononuclear cell and plasma specimens were collected during clinic visits. The PredicineCARETM NGS assay was applied for ultra-deep targeted sequencing and somatic alteration identification in tDNA, utDNA and ctDNA. RESULTS: Diverse quantitative metrics including cancer cell fraction, variant allele frequency and tumor mutation burden were invariably concordant between tDNA and utDNA, but not ctDNA. The mutational landscapes captured by tDNA or utDNA were highly similar, whereas a considerable proportion of ctDNA aberrations stemmed from clonal hematopoiesis. Using tDNA-informed somatic events as reference, utDNA assays achieved a specificity of 99.3%, a sensitivity of 86.7%, a positive predictive value of 67.2%, a negative predictive value of 99.8% and a diagnostic accuracy of 99.1%. Higher preoperative utDNA or tDNA abundance correlated with worse relapse-free survival. Actionable variants including FGFR3 alteration and ERBB2 amplification were identified in utDNA. CONCLUSIONS: Urine-based molecular pathology provides a valid and complete genetic profile of bladder cancer, and represents a faithful surrogate for genotyping and monitoring newly diagnosed UBC.

ALDH1A3 Coordinates Metabolism With Gene Regulation in Pulmonary Arterial Hypertension.

BACKGROUND: Metabolic alterations provide substrates that influence chromatin structure to regulate gene expression that determines cell function in health and disease. Heightened proliferation of smooth muscle cells (SMC) leading to the formation of a neointima is a feature of pulmonary arterial hypertension (PAH) and systemic vascular disease. Increased glycolysis is linked to the proliferative phenotype of these SMC. METHODS: RNA sequencing was applied to pulmonary arterial SMC (PASMC) from PAH patients with and without a BMPR2 (bone morphogenetic receptor 2) mutation versus control PASMC to uncover genes required for their heightened proliferation and glycolytic metabolism. Assessment of differentially expressed genes established metabolism as a major pathway, and the most highly upregulated metabolic gene in PAH PASMC was aldehyde dehydrogenase family 1 member 3 (ALDH1A3), an enzyme previously linked to glycolysis and proliferation in cancer cells and systemic vascular SMC. We determined if these functions are ALDH1A3-dependent in PAH PASMC, and if ALDH1A3 is required for the development of pulmonary hypertension in a transgenic mouse. Nuclear localization of ALDH1A3 in PAH PASMC led us to determine whether and how this enzyme coordinately regulates gene expression and metabolism in PAH PASMC. RESULTS: ALDH1A3 mRNA and protein were increased in PAH versus control PASMC, and ALDH1A3 was required for their highly proliferative and glycolytic properties. Mice with Aldh1a3 deleted in SMC did not develop hypoxia-induced pulmonary arterial muscularization or pulmonary hypertension. Nuclear ALDH1A3 converted acetaldehyde to acetate to produce acetyl coenzyme A to acetylate H3K27, marking active enhancers. This allowed for chromatin modification at NFYA (nuclear transcription factor Y subunit α) binding sites via the acetyltransferase KAT2B (lysine acetyltransferase 2B) and permitted NFY-mediated transcription of cell cycle and metabolic genes that is required for ALDH1A3-dependent proliferation and glycolysis. Loss of BMPR2 in PAH SMC with or without a mutation upregulated ALDH1A3, and transcription of NFYA and ALDH1A3 in PAH PASMC was ß-catenin dependent. CONCLUSIONS: Our studies have uncovered a metabolic-transcriptional axis explaining how dividing cells use ALDH1A3 to coordinate their energy needs with the epigenetic and transcriptional regulation of genes required for SMC proliferation. They suggest that selectively disrupting the pivotal role of ALDH1A3 in PAH SMC, but not endothelial cells, is an important therapeutic consideration.

Effect of ionic liquid 1-buyl-3-methylimidazolium halide on the structure and tensile property of PBS/corn starch blends.

As a promising biodegradable resin, poly (butylene succinate) (PBS) is often blended with starch to reduce the cost. In this paper, 1-buyl-3-methylimidazolium halide pre-plasticized corn starch (CS) was blended with PBS to prepare PBS/corn starch blend material modified by ionic liquid (PBS/CS-IL). Ionic liquid (IL) acted as plasticizer and compatibilizer, and the effects of 1-butyl-3-methylimidazolium halide with different halogen anion on PBS/Starch blends were explored. The effects of IL on the structure and tensile property of PBS/Starch blends were evaluated by FTIR, SEM, DSC, TGA and XRD, respectively. Test results showed that the addition of IL significantly reduced the crystallinity of PBS/Starch blends, and the size of starch particles in the PBS matrix was also effectively reduced. IL also acted as a compatibilizer of starch and PBS, and induced the morphology of the blends to change from "sea-island" structure to homogeneous phase. The results of the tensile test showed that compared with the PBS/Starch blend without IL, the elongation at break of PBS/CS-IL increased from 22% to 93%. This study provided a simple and feasible method for the preparation of low-cost PBS bio-composite materials, and provided theoretical support for future industrial production.

The 96-week clinical outcomes after cessation of nucleos(t)ide analog treatment in chronic hepatitis B patients.

BACKGROUND: Chronic hepatitis B (CHB) patients have a high virological relapse rate after cessation of nucleos(t)ide analog (NA) treatment, but the clinical outcome remains unclear. This study aimed to investigate the 96-week clinical outcomes and the risk factors for relapse in CHB after cessation of NAs. METHODS: This study was a prospective trial; 74 eligible patients were enrolled. The patients underwent NA cessation and follow-up according to the 2012 Asian Pacific Association for the Study of the Liver Guideline. Symptoms, biochemical (aspartate aminotransferase [AST], alanine aminotransferase [ALT], total bilirubin, urea nitrogen, creatinine), virological data (hepatitis B surface antigen [HBsAg], hepatitis B e antigen [HBeAg], hepatitis B e antibody [HBeAb], hepatitis B virus [HBV] DNA levels), and color Doppler ultrasound examination results were recorded and analysed. RESULTS: After NA cessation, 19 cases were HBsAg-negative without relapse during the 96-week follow-up. Of the 55 cases of HBsAg-positive after cessation, four types of clinical outcomes were observed. Twelve patients had no relapse during the 96-week follow-up (type A, 21.8%), 7 patients underwent virological relapses but spontaneously had a non-virological relapse (type B, 12.7%), 10 patients maintained virological relapse (type C, 18.2%), and 26 patients turned to clinical relapse, received NA retreatment, and achieved ALT normalization and negative conversion of HBV DNA within 12 months (type D, 47.3%). The 2-year overall cumulative rates of virological and clinical relapses were 58.1% and 24.3%, respectively. Independent factors associated with virological relapse were duration of negative HBV DNA, EOT (end of treatment) HBsAg, and original status of HBeAg. The EOT HBsAg was also an independent factor for clinical relapse. CONCLUSIONS: There are four types of clinical outcomes in patients with CHB after cessation of NA treatment. Further research is needed to explore the mechanism of different clinical outcomes. The EOT HBsAg level is an independent factor associated with both virological and clinical relapse.

Construction of few-layered black phosphorus/graphite-like carbon nitride binary hybrid nanostructure for reducing the fire hazards of epoxy resin.

Black phosphorus (BP) and graphite-like carbon nitride (g-C3N4) were combined to prepare BP-CN hybrid nanostructure through a simple self-assembly method assisted by ultra-sonication, and as-obtained materials were further used as fire retardants introduced into epoxy resin to fabricate EP/BP-CNx nanocomposites. It was found that the introduction of 2 wt% BP-CNx into EP contributed to considerable decrements in peak heat release rate (up to 47.72%) and total heat release (utmost to 49.60%) of composites, and LOI value increased from 25% to 31%. SSTF results revealed that the introducing of BP-CN can distinctly reduce the production of smoke. TG-IR results demonstrated that the addition of BP-CN0.5 and BP-CN2.0 into EP matrix exert different influences on the decomposition of resin. Analyses of residual chars further validated through adjusting the proportion of BP and CN can achieve different fire performances of matrix. This work illustrates that BP can reduce the fire hazards of EP, and the hybridization of CN can achieve better flame retarded efficiency, which provides a new strategy for black phosphorus to be used as a flame retardant.

Anisotropic, low-tortuosity and ultra-thick red P@C-Wood electrodes for sodium-ion batteries.

Red phosphorus (P) is considered to be the most suitable electrode for sodium-ion batteries due to its low cost, earth abundance and high theoretical capacity. Numerous studies have focused on improving the low conductivity and the extremely large volume change of red P during the cycling process. However, these strategies heavily decrease the P mass loading in the electrode. Herein, inspired by natural wood, we successfully develop an ultra-thick bulk red Phosphorus@Carbon-Wood (red P@C-Wood) electrode via the vaporization-condensation process. The sodium-ion batteries assembled with the fabricated red P@C-Wood electrode provide a high areal capacity of 18 mA h cm-2 (≈5 times those of other reported electrodes) and the P mass loading of up to 8.4 mg cm-2 (≥2 times those of other reported electrodes). The combination of red phosphorus and carbonized wood provides a new strategy for people to improve the areal energy density of lithium and sodium batteries.