Spleen-dedicated stiffness measurement performed well to rule out high-risk varices in HBV-related hepatocellular carcinoma: Screening for high-risk varices in HCC.

BACKGROUND: Esophagogastroduodenoscopy (EGD) is required to screen for high-risk varices (HRV) in patients with hepatocellular carcinoma (HCC), especially since overall survival rates have dramatically improved with new systemic therapies. AIM: To assess the Baveno VI and Baveno VII algorithms' ability to rule out HRV in hepatitis B virus (HBV)-related HCC METHODS: We prospectively enrolled consecutive patients with HBV related, compensated cirrhosis and newly diagnosed HCC who underwent liver stiffness measurement, spleen stiffness measurement (SSM) using a 100-Hz shear wave frequency, and EGD. RESULTS: From September 2021 to August 2023, we enrolled 219 patients with HCC, with 107 (48.9%) Barcelona Clinic Liver Cancer (BCLC) A, 28 (12.8%) BCLC B and 84 (38.3%) BCLC C, respectively. HRV prevalence was 28.8% (63/219). Baveno VI criteria safely (HRV missing rate, 3.2%) avoided 27.4% unnecessary EGDs, while the Baveno VII algorithm avoided 49.3% with HRV missing rate at 7.9% (5/63). The SSM ≤40 kPa avoided 47.5% of EGDs safely (HRV missing rate, 4.8%), significantly better than the Baveno VI criteria (p < 0.001) and comparable to the Baveno VII algorithm (p = 0.390). The SSM ≤40 kPa safely avoided EGDs in patient subgroups within Milan criteria, with portal vein tumour thrombosis or BCLC B/C or candidates for systemic therapy. CONCLUSIONS: We validated that the SSM ≤40 kPa using a 100-Hz probe could safely eliminate more unnecessary EGDs than the Baveno VI criteria in patients with HBV-related HCC. However, the efficacy of the Baveno VII algorithm in patients with HCC requires further investigation.

A Surfactant-Free and General Strategy for the Synthesis of Bimetallic Core-Shell Nanocrystals on Reduced Graphene Oxide through Targeted Photodeposition.

Tunable physicochemical properties of bimetallic core-shell heterostructured nanocrystals (HNCs) have shown enormous potential in electrocatalytic reactions. In many cases, HNCs are required to load on supports to inhibit catalyst aggregation. However, the introduction of supports during the process of growing core-shell HNCs makes the synthesis much more complicated and difficult to control precisely. Herein, we reported a universal photochemical synthetic strategy for the controlled synthesis of well-defined surfactant-free core-shell metal HNCs on a reduced graphene oxide (rGO) support, which was assisted by the fine control of photogenerated electrons directly transferring to the targeted metal seeds via rGO and the precisely tuned adsorption capacity of the added second metal precursors. The surface photovoltage microscopy (SPVM) platform proved that photogenerated electrons flowed through rGO to Pd particles under illumination. We have successfully synthesized 24 different core-shell metal HNCs, i.,e., MA@MB (MA = Pd, Au, and Pt; MB = Au, Ag, Pt, Pd, Ir, Ru, Rh, Ni and Cu), on the rGO supports. The as-prepared Pd@Cu core-shell HNCs showed outstanding performance in the electrocatalytic reduction of CO2 to CH4. This work could shed light on the controlled synthesis of more functional bimetallic nanostructured materials on diverse supports for various applications.

Photocatalytic Cascade Reaction Driven by Directed Charge Transfer over VS -Zn0.5 Cd0.5 S/GO for Controllable Benzyl Oxidation.

Photocatalysis is an important technique for synthetic transformations. However, little attention has been paid to light-driven synergistic redox reactions for directed synthesis. Herein, the authors report tunable oxidation of benzyl to phenylcarbinol with the modest yield (47%) in 5 h via singlet oxygen (1 O2 ) and proton-coupled electron transfer (PCET) over the photocatalyst Zn0.5 Cd0.5 S (ZCS)/graphene oxide (GO) under exceptionally mild conditions. Theoretical calculations indicate that the presence of S vacancies on the surface of ZCS/GO photocatalyst is crucial for the adsorption and activation of O2 , successively generating the superoxide radical (• O2 - ) and 1 O2 , attributing to the regulation of local electron density on the surface of ZCS/GO and photogenerated holes (h+ ). Meanwhile, accelerated transfer of photogenerated electrons (e- ) to GO caused by the π-π stacking effect is conducive to the subsequent aldehyde hydrogenation to benzyl alcohol rather than non-selective oxidation of aldehyde to carboxylic acid. Anisotropic charge transport driven by the built-in electric field can further promote the separation of e- and h+ for multistep reactions. Promisingly, one-pot photocatalytic conversion of p-xylene to 4-methylbenzyl alcohol is beneficial for reducing the harmful effects of aromatics on human health. Furthermore, this study provides novel insights into the design of photocatalysts for cascade reactions.

Combined model with acoustic radiation force impulse to rule out high-risk varices in HBV-related cirrhosis with viral suppression.

AIMS: To prospectively evaluate the performance of spleen stiffness measurement (SSM) and liver stiffness measurement (LSM) via acoustic radiation force impulse (ARFI) imaging combined with platelet counts (PLT) in ruling out HRV in HBV-related cirrhotic patients with viral suppression. METHODS: Patients with cirrhosis enrolled between June 2020-March 2022 were divided into a derivation cohort and validation cohort. LSM and SSM ARFI-based, and esophagogastroduodenoscopy (EGD) were performed at enrollment. RESULTS: In the derivation cohort, overall, 236 HBV-related cirrhotic patients with maintained viral suppression were enrolled, and the prevalence of HRV was 19.5% (46/236). With the aim of identifying HRV, the most accurate LSM and SSM cut-offs were chosen of 1.46 m/s and 2.28 m/s, respectively. The combined model (LSM<1.46 m/s and PLT>150 × 109/L strategy combined with SSM ≤ 2.28 m/s) can spare 38.6% of EGDs and 4.3% of HRV cases were misclassified. In the validation cohort, we analysed 323 HBV-related cirrhotic patients with maintained viral suppression and validated the combined model can spare 33.4% (108/323) of EGD, and the HRV missed rate was 3.4%. CONCLUSIONS: A non-invasive prediction model combining LSM<1.46 m/s and PLT>150 × 109/L strategy with SSM ≤ 2.28 m/s exhibited excellent performance in ruling out HRV and avoided a significantly large number (38.6% vs 33.4%) of unnecessary EGDs in HBV-related cirrhotic patients with viral suppression.

Asiatic acid attenuates tubular injury in diabetic kidney disease by regulating mitochondrial dynamics via the Nrf-2 pathway.

BACKGROUND: Mitochondrial dynamics plays a crucial role in tubular injury in diabetic kidney disease (DKD). Asiatic acid (AA) has demonstrated renal protective effects in DKD; however, its therapeutic effect on tubular injury in DKD remains unclear. PURPOSE: This study aimed to verify the effects of AA on tubular injury in DKD and underlying mechanisms. STUDY DESIGN: In the present study, the effects of AA on tubular injury were assessed in rats with streptozotocin-induced diabetes and advanced glycation end products (AGEs)-stimulated HK-2 cells models. METHODS: After oral administration with or without AA for ten weeks, body weight and levels of fast blood glucose, serum creatinine (sCr), blood urea nitrogen (BUN), urinary albumin, and kidney injury molecule-1 (KIM-1) were detected. Histological analysis was performed to evaluate the renal function of rats. Moreover, the expression of proteins associated with the Nrf-2 pathway and mitochondrial dynamics was analyzed. AGEs-stimulated HK-2 cells were examined to evaluate the tubular protection and the mechanism of AA in vitro. RESULTS: AA remarkably decreased albumin levels, KIM-1 levels in urine, and serum Cr, and BUN levels. In addition, AA prevented tubular injury and mitochondrial injury by regulating the Nrf-2 pathway and mitochondrial dynamics. Furthermore, the effects of AA on mitochondrial dynamics and tubular protection were eliminated after treatment with ML385 (Nrf2 inhibitor). CONCLUSION: These findings suggested that AA might be developed as a potential candidate for the treatment of tubular injury in DKD, and its effects are potentially mediated via the regulation of the Nrf-2 pathway and mitochondrial dynamics.

Prognostic and therapeutic significance of microbial cell-free DNA in plasma of people with acute decompensation of cirrhosis.

BACKGROUND & AIMS: Although the effect of bacterial infection on cirrhosis has been well-described, the effect of non-hepatotropic virus (NHV) infection is unknown. This study evaluated the genome fragments of circulating microorganisms using metagenomic next-generation sequencing (mNGS) in individuals with acute decompensation (AD) of cirrhosis, focusing on NHVs, and related the findings to clinical outcomes. METHODS: Plasma mNGS was performed in 129 individuals with AD of cirrhosis in the study cohort. Ten healthy volunteers and 20, 39, and 81 individuals with stable cirrhosis, severe sepsis and hematological malignancies, respectively, were enrolled as controls. Validation assays for human cytomegalovirus (CMV) reactivation were performed in a validation cohort (n = 58) and exploratory treatment was instituted. RESULTS: In the study cohort, 188 microorganisms were detected in 74.4% (96/129) of patients, including viruses (58.0%), bacteria (34.1%), fungi (7.4%) and chlamydia (0.5%). A NHV signature was identified in individuals with AD, and CMV was the most frequent NHV, which correlated with the clinical effect of empirical antibiotic treatment, progression to acute-on-chronic liver failure, and 90-day mortality. The NHV signature in individuals with acute-on-chronic liver failure was similar to that in those with sepsis and hematological malignancies. CMV was detected in 24.1% (14/58) of patients in the validation cohort. Of the 14 cases with detectable CMV by mNGS, nine were further validated by real-time PCR or pp65 antigenemia testing. Three patients with CMV reactivation received ganciclovir therapy in an exploratory manner and experienced clinical resolutions. CONCLUSIONS: The results of this study suggest that NHVs may play a pathogenic role in complicating the course of AD. Further validation is needed to define whether this should be incorporated into the routine management of individuals with AD of cirrhosis. IMPACT AND IMPLICATIONS: A non-hepatotropic virus (NHV) signature, which was similar to that in individuals with sepsis and hematological malignancies, was identified in individuals with acute decompensation of cirrhosis. The detected viral signature had clinical correlates, including clinical efficacy of empirical antibiotic treatment, progression to acute-on-chronic liver failure and short-term mortality. Cytomegalovirus reactivation, which is treatable, may adversely affect clinical outcomes in some individuals with decompensated cirrhosis. Routine screening for NHVs, especially cytomegalovirus, may be useful for the management of individuals with acute decompensation of cirrhosis.

Baveno VII algorithm outperformed other models in ruling out high-risk varices in individuals with HBV-related cirrhosis.

BACKGROUND & AIMS: The Baveno VII consensus recommends that spleen stiffness measurement (SSM) ≤40 kPa is safe for ruling out high-risk varices (HRVs) and avoiding endoscopic screening in patients who do not meet the Baveno VI criteria. This study aimed to validate the performance of the Baveno VII algorithm in individuals with HBV-related cirrhosis. METHODS: Consecutive individuals with HBV-related cirrhosis who underwent liver stiffness measurement (LSM) and SSM - using a 50 Hz shear wave frequency, spleen diameter measurement, and esophagogastroduodenoscopy (EGD) were prospectively enrolled from June 2020. A 100 Hz probe has been adopted for additional SSM assessment since July 2021. RESULTS: From June 2020 to January 2022, 996 patients were screened and 504 were enrolled for analysis. Among the 504 patients in whom SSM was assessed using a 50 Hz probe, the Baveno VII algorithm avoided more EGDs (56.7% vs. 39.1%, p <0.001) than Baveno VI criteria, with a comparable missed HRV rate (3.8% vs. 2.5%). Missed HRV rates were >5% for all other measures: 11.3% for LSM-longitudinal spleen diameter to platelet ratio score, 20.0% for platelet count/longitudinal spleen diameter ratio, and 8.8% for Rete Sicilia Selezione Terapia-hepatitis. SSM@100 Hz was assessed in 232 patients, and the Baveno VII algorithm with SSM@100 Hz spared more EGDs (75.4% vs. 59.5%, p <0.001) than that with SSM@50 Hz, both with a missed HRV rate of 3.0% (1/33). CONCLUSIONS: We validated the Baveno VII algorithm, demonstrating the excellent performance of SSM@50 Hz and SSM@100 Hz in ruling out HRV in individuals with HBV-related cirrhosis. Furthermore, the Baveno VII algorithm with SSM@100 Hz could safely rule out more EGDs than that with SSM@50 Hz. CLINICAL TRIAL NUMBER: NCT04890730. IMPACT AND IMPLICATIONS: The Baveno VII guideline proposed that for patients who do not meet the Baveno VI criteria, SSM ≤40 kPa could avoid further unnecessary endoscopic screening. The current study validated the Baveno VII algorithm using 50 Hz and 100 Hz probes, which both exhibited excellent performance in ruling out HRVs in individuals with HBV-related cirrhosis. Compared with the Baveno VII algorithm with SSM@50 Hz, SSM@100 Hz had a better capability to safely rule out unnecessary EGDs. Baveno VII algorithm will be a practical tool to triage individuals with cirrhosis in future clinical practice.

Multifunctional N,S-doped and methionine functionalized carbon dots for on-off-on Fe3+ and ascorbic acid sensing, cell imaging, and fluorescent ink applying.

Fluorescent carbon dots (CDs) have been identified as potential nanosensors and attracted tremendous research interests in wide areas including anti-counterfeiting, environmental and biological sensing and imaging in considering of the attractive optical properties. In this work, we present a CDs based fluorescent sensor from polyvinylpyrrolidone, citric acid, and methionine as precursors by hydrothermal approach. The selective quantifying of Fe3+ and ascorbic acid (AA) are based on the fluorescent on-off-on process, in which the fluorescent quenching is induced by the coordination of the Fe3+ on the surface of the CDs, while the fluorescence recovery is mainly attributed to redox reaction between Fe3+ and AA, breaking the coordination and bringing the fluorescence back. Inspired by the good water solubility and biocompatibility, significant photostability, superior photobleaching resistance as well as high selectivity, sensitivity, and interference immunity, which are constructed mainly from the N,S-doping and methionine surface functionalization, the CDs have not only been employed as fluorescence ink in multiple anti-counterfeiting printing and confidential document writing or transmitting, but also been developed as promising fluorescence sensors in solution and solid by CDs doped test strips and hydrogels for effectively monitoring and removing of Fe3+ and AA in environmental aqueous solution. The CDs have been also implemented as effective diagnostic candidates for imaging and tracking of Fe3+ and AA in living cells, accelerating the understanding of their function and importance in related biological processes for the prevention and treatment specific diseases. Electronic Supplementary Material: Supplementary material (fluorescence spectra: UV and Xe irradiation, TG, thermo stability, ionic strength, relationship between fluorescence responses at different concentrations of Fe3+ and AA, reaction time-dependent fluorescent responses; XPS spectra of CDs + Fe3+ and Fe3+@CDs + AA; structural characterization; equations about fluorescence lifetime, quantum yield and LOD; comparison of the CDs for the detection of Fe3+ and AA with reported methods; detection of Fe3+ and AA in real samples; absorption of Fe3+ in environmental samples and MTT assay results) is available in the online version of this article at 10.1007/s12274-022-5107-7.

Effects of Bovine Pichia kudriavzevii T7, Candida glabrata B14, and Lactobacillus plantarum Y9 on Milk Production, Quality and Digestive Tract Microbiome in Dairy Cows.

Microbial administration has been used successfully to improve host health. However, the positive effects of endogenous microbials are still underexplored. This study investigated the effects of bovine Lactic acid bacteria and yeast on the milk production, quality and digestive tract microbiome of dairy cows. Lactobacillus plantarum Y9, Pichia kudriavzevii T7 and Candida glabrata B14 isolated from high-yielding dairy cows were selected to feed low-yielding Holstein cows. Pichia kudriavzevii T7 could significantly increase milk yield, meanwhile, Pichia kudriavzevii T7 and Candida glabrata B14 could obviously reduce the number of somatic cell counts (SCC). However, slight differences were found in milk fat, protein, lactose and SNF (solids not fat) percentage. High throughput sequencing showed that the dominant bacteria were Prevotella and Ruminococcaceae in rumen and feces, respectively, and the dominant fungi were Penicillium, Aspergillus and Trichoderma in both samples, before and after feeding the microbial addition. Nonetheless, microbial addition changed the abundance and structure of the microbiome in the digestive tract. Our data showed bovine yeast and LAB were beneficial for improving performance and regulating the microbial structure of dairy cows. This study was expected to enrich the knowledge of the digestive tract microbiome in dairy cows and provide a feasible strategy for the further utilization of bovine microorganisms.

Arjunolic acid from Cyclocarya paliurus ameliorates diabetic retinopathy through AMPK/mTOR/HO-1 regulated autophagy pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Cyclocarya paliurus (CP) is a traditional Chinese herb and possesses a variety of biological activities including anti-hyperglycemia, anti-hyperlipidemia, antioxidant and anti-inflammation. Arjunolic acid (AA) is an abundant and bioactive ingredient in CP that shows significant protection against many metabolic diseases such as diabetic complication. Diabetic retinopathy (DR) is a serious complication of diabetes and may lead to vision loss. However, the protective effects and underlying mechanisms of AA against DR is not still understood. AIM OF THE STUDY: We aimed to investigate whether AA activates AMPK/mTOR/HO-1 regulated autophagy pathway to alleviate DR. MATERIALS AND METHODS: In the study, the STZ-induced diabetic model of rats was established, and AA with 10 and 30 mg/kg dosages was given orally for ten weeks to investigate their effect on retinal injury of DR. H2O2-induced ARPE-19 cells were applied to evaluate anti-apoptosis and anti-oxidant effect of AA. RESULTS: The results revealed that AA could prevent STZ-induced weight loss and increase the retinal thickness and nuclei counts. The level of HO-1 protein was upregulated both in vivo and in vitro. In addition, AA prevented retinal damage and cell apoptosis through the AMPK-mTOR-regulated autophagy pathway. Furthermore, anti-apoptosis capacity, as well as the expression of HO-1 and LC3 protein, were effectively locked by AMPK inhibitor dorsomorphin dihydrochloride (compound C). CONCLUSIONS: This finding implies that AA may be a promising candidate drug by protecting retinal cells from STZ-induced oxidative stress and inflammation through the AMPK/mTOR/HO-1 regulated autophagy pathway.

Promoting electrocatalytic carbon monoxide reduction to ethylene on copper-polypyrrole interface.

The renewable energy-powered electroreduction of carbon dioxide or monoxide (CO) has been emerging as an attractive means to decarbonize the emission-intensive chemical manufacturing, which heavily relies on fossil fuels nowadays. One potential approach to promote the activity of electrocatalysts is to construct hybrid interface that can increase the stability of intermediates on electrode surfaces. Herein we developed a copper nanoparticle/polypyrrole (Cu-Ppy) nanowire composite as an efficient electrocatalyst for electrochemical CO reduction reaction. Compared to pure Cu nanoparticles, the Cu-Ppy composite exhibited a dramatically enhanced Faradaic efficiency of converting CO to ethylene (C2H4) from 34% to 69% at -0.78 V vs. reversible hydrogen electrode (RHE) in KOH electrolyte, and an excellent C2H4 partial current density of 276 mA·cm-2 at -1.18 V vs. RHE. Density functional theory calculations showed that the Cu-Ppy composite could bind CO more strongly as compared to pure Cu. As the Ppy coating allowed to stabilize OCCO*, a key intermediate in the C2H4 formation, both the activity and selectivity of Cu-Ppy for CO-to-C2H4 were increased. Our work suggests that constructing rationally designed hybrid interface can tune the local environment of catalyst surface toward enhanced activity and product selectivity.

Chitin nanocrystals assisted 3D printing of polycitrate thermoset bioelastomers.

Citrate-based thermoset bioelastomer has numerous tissue engineering applications. However, its insoluble and unmeltable features restricted processing techniques for fabricating complex scaffolds. Herein, direct ink writing (DIW) was explored for 3D printing of poly(1, 8-octanediol-co-Pluronic F127 citrate) (POFC) bioelastomer scaffolds considering that POFC prepolymer (pre-POFC) was waterborne and could form a stable emulsion. The pre-POFC emulsion couldn't be printed, however, chitin nanocrystal (ChiNC) could be as a rheological modifier to tune the flow behavior of pre-POFC emulsion, and thus DIW printing of POFC scaffolds was successfully realized; moreover, ChiNC was also as a supporting agent to prevent collapse of filaments during thermocuring, and simultaneously as a biobased nanofiller to reinforce scaffolds. The rheological analyses showed the pre-POFC/ChiNC inks fulfilled the requirements for DIW printing. The printed scaffolds exhibited low swelling, and good performances in strength and resilence. Furthermore, the entire process was easily performed and eco-friendly.

Silenced lncRNA SNHG14 restrains the biological behaviors of bladder cancer cells via regulating microRNA-211-3p/ESM1 axis.

BACKGROUND: Bladder cancer (BCa) is a malignant tumor that occurs on the mucosa of the bladder, in which dysregulated long non-coding RNAs (lncRNAs) are involved. This study investigated the effect of lncRNA small nucleolar RNA host gene 1 (SNHG14) on the biological characteristics of BCa cells from microRNA (miR)-211-3p/ESM1 signaling axis. METHODS: BCa tissues and the matched normal tissues were collected to test SNHG14, miR-211-3p and ESM1 levels. SNHG14, miR-211-3p and ESM1 levels in BCa cell lines (T24, 5637, UMUC-3 and EJ) and normal bladder epithelial cells SV-HVC-1 were detected for screening the cell lines for follow-up experiments. T24 and UMUC-3 cells were transfected with different plasmids of SNHG14, miR-211-3p or ESM1 to observe the biological characteristics of BCa cells by MTT, colony formation, Transwell assays and flow cytometry. Tumor xenograft was implemented to inspect tumor growth in vivo. The targeting relationships of SNHG14, miR-211-3p and ESM1 were verified by bioinformatics software, RNA pull down assay and luciferase reporter assay. RESULTS: Enhanced SNHG14, ESM1 and suppressed miR-211-3p were found in BCa tissues and cells. SNHG14 up-regulated ESM1 via competitive binding with miR-211-3p. Decreased SNHG14 or up-regulated miR-211-3p depressed cell cycle entry, colony formation, invasion, migration and proliferation abilities, and facilitated apoptosis of BCa cells. Decreased SNHG14 or up-regulated miR-211-3p reduced the tumor volume and weight of nude mice with BCa, as well as promoted apoptosis and restrained proliferation of tumor cells. miR-211-3p inhibition or ESM1 overexpression reversed the effects of down-regulation of SNHG14 on BCa, and miR-211-3p up-regulation or ESM1 downregulation reversed the effect of SNHG14 overexpression on BCa. SNHG14 targeted miR-211-3p to regulate ESM1 expression. CONCLUSION: Our study highlights that silenced SNHG14 or elevated miR-211-3p represses the tumorigenic ability of BCa cells, which may be linked to ESM1 knockdown.

Alterations in the Gut Microbiota and Hepatitis-B-Virus Infection in Southern Chinese Patients With Coexisting Non-Alcoholic Fatty Liver Disease and Type-2 Diabetes Mellitus.

Background: Hepatitis B virus (HBV) infection has been reported to affect the bacterial characteristics in the host. We aimed to elucidate the compositional and functional characteristics of the microbiota in southern Chinese patients with coexistent HBV infection, non-alcoholic fatty liver disease (NAFLD), and type-2 diabetes mellitus (T2DM). Methods: Healthy controls (HCs) and patients with coexistent NAFLD and T2DM were enrolled. Patients were divided into two groups: N1 (without HBV infection) and N2 (with HBV infection). Stool samples were collected for 16s RNA gene sequencing and untargeted metabolomics analysis. Results: Bacterial diversity was decreased in the N2 group. There was a significantly lower abundance of bacteria of Faecalibacterium, Gemmiger, and Clostridium_XIVA genera, but a higher abundance of Megamonas and Phascolarctobacterium genera in the N2 group. Compared with the N1 group, the abundance of Gemmiger species was even lower, and alterations in the abundance of Phascolarctobacterium and Clostridium_XIVA genera only occurred in the N2 group. There were significantly different fecal metabolic features, which were enriched in glucose and lipid metabolic pathways (e.g., fatty acid and glycerophospholipid metabolism) between the N2 and HC groups. Metabolites in glycerophospholipid metabolism, such as Sn-3-o-(geranylgeranyl)glycerol1-phosphate, were even higher in the N2 group than in the N1 group. The decreased Faecalibacterium and Gemmiger contributed to the increased level of Sn-3-o-(geranylgeranyl) glycerol1-phosphate, palmitoylcarnitine, and serum triglycerides. Clostridium_XIVA species were positively correlated to 15(s)-hpete. Megamonas species were positively correlated with the serum level of glucose indirectly. Conclusions: The distinct gut-microbiome profile associated with HBV infection has a role in lipid metabolism and glucose metabolism in patients with coexistent NAFLD and T2DM. Clinical Trial Registration: www.ClinicalTrials.gov, identifier: NCT03525769.

Baveno VI criteria and spleen stiffness measurement rule out high-risk varices in virally suppressed HBV-related cirrhosis.

BACKGROUND & AIMS: There are no data validating the performance of spleen stiffness measurement in ruling out high-risk varices in patients with HBV-related cirrhosis under maintained viral suppression. Thus, we aimed to prospectively validate the performance of spleen stiffness measurement (cut-off 46 kPa) combined with Baveno VI criteria in ruling out high-risk varices in these patients. METHODS: Patients with cirrhosis were enrolled from April to December 2019 at the hepatology unit of the Nanfang Hospital, China. Liver and spleen transient elastography and esophagogastroduodenoscopy were performed at enrollment. Antiviral regimen(s) and virological responses, evaluated every 3-6 months, were recorded. RESULTS: Overall 341 patients with HBV-related cirrhosis under maintained viral suppression were enrolled, and the prevalence of high-risk varices was 20.5% (70/341). Baveno VI criteria spared 37.0% (126/341) esophagogastroduodenoscopies and no high-risk varices were missed (0/70). Eight cases of high-risk varices (8/70, 11.4%) were misclassified in patients (208/341, 61.0%) within the expanded Baveno VI criteria. The spleen stiffness measurement cut-off (≤46.0 kPa) was shown to safely rule out high-risk varices in these patients (the percentage of missed high-risk varices was 4.3%). Over half (61.6%, 210/341) of patients met the combined model (Baveno VI criteria and spleen stiffness measurement cut-off ≤46 kPa) and 4.3% (3/70) of high-risk varices cases were misclassified. This combined model exhibited a sensitivity of 95.71%, specificity of 76.38%, negative predictive value of 98.57%, and negative likelihood ratio of 0.06 for ruling out high-risk varices. CONCLUSIONS: We validated the excellent performance of Baveno VI criteria combined with spleen stiffness measurement (cut-off 46 kPa) for safely ruling out high-risk varices in patients with HBV-related cirrhosis under viral suppression; more than half of esophagogastroduodenoscopy procedures were spared using this combination. CLINICAL TRIAL NUMBER: NCT04123509 LAY SUMMARY: Esophageal varices have important prognostic implications in patients with cirrhosis. Thus, their timely identification is important so that treatment can be initiated early. Herein, we validated the excellent performance of the combination of Baveno VI criteria with spleen stiffness measurement (cut-off 46 kPa) for ruling out high-risk esophageal varices in patients with HBV-related cirrhosis under maintained viral suppression (with antiviral treatment). This combined model was able to safely rule out high-risk varices (missed/total <5%) and over half (61.6%) of esophagogastroduodenoscopy procedures were spared.

Hydrophobic and Hydrophilic Effects in a Mussel-Inspired Citrate-Based Adhesive.

The citrate-based tissue adhesive, synthesized by citric acid, diol, and dopamine, is a kind of mussel-inspired adhesive. The adhesion of mussel-inspired adhesive is not completely dependent on 3, 4-dihydroxyphenylalanine (Dopa) groups. The backbone structure of the adhesive also greatly affects the adhesion. In this study, to explore the effects of hydrophobicity and hydrophilicity of the backbone structure on adhesion, we prepared a series of citrate-based tissue adhesives (POEC-d) by changing the molar ratio of two diols, 1, 8-octanediol (O) and poly(ethylene oxide) (E), which formed hydrophobic segment units and hydrophilic segment units, respectively, in the molecule structure. The properties of cured adhesives showed that the adhesive with high E units had high swelling, rapid degradation, and low cohesion. In the adhesion strength measurement on the porcine skin, the adhesive with higher hydrophobicity was more likely to perform better. For the interfacial adhesion, hydrophilicity was conducive to the diffusion and penetration on the skin surface, but hydrophobic interaction showed a stronger effect to adhere with skin and hydrophobic association increased the adhesive concentration on the interface; for the bulk cohesion, hydrophobicity led to coacervation, promoting the Dopa-quinone coupling for cross-linking. In this amphipathic, citrate-based, soft-tissue adhesive system, when the feed ratio of hydrophilic segment was lower than 0.7, the coacervation could be formed through hydrophobic interaction, forming an efficient underwater adhesion system similar to that of mussels.

Viral and Antibody Kinetics of COVID-19 Patients with Different Disease Severities in Acute and Convalescent Phases: A 6-Month Follow-Up Study.

Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has spread rapidly around the world, posing a major threat to human health and the economy. Currently, long-term data on viral shedding and the serum antibody responses in COVID-19 patients are still limited. Herein, we report the clinical features, viral RNA loads, and serum antibody levels in a cohort of 112 COVID-19 patients admitted to the Honghu People's Hospital, Hubei Province, China. Overall, 5.36% (6/112) of patients showed persistent viral RNA shedding (> 45 days). The peak viral load was higher in the severe disease group than in the mild group (median cycle threshold value, 36.4 versus 31.5; P = 0.002). For most patients the disappearance of IgM antibodies occurred approximately 4-6 weeks after symptoms onset, while IgG persisted for over 194 days after the onset of symptoms, although patients showed a 46% reduction in antibodies titres against SARS-CoV-2 nucleocapsid protein compared with the acute phase. We also studied 18 asymptomatic individuals with RT-qPCR confirmed SARS-CoV-2 infection together with 17 symptomatic patients, and the asymptomatic individuals were the close contacts of these symptomatic cases. Delayed IgG seroconversion and lower IgM seropositive rates were observed in asymptomatic individuals. These data indicate that higher viral loads and stronger antibody responses are related to more severe disease status in patients with SARS-CoV-2 infection, and the antibodies persisted in the recovered patient for more than 6 months so that the vaccine may provide protection against SARS-CoV-2 infection.

Validation of the GALAD Model and Establishment of GAAP Model for Diagnosis of Hepatocellular Carcinoma in Chinese Patients.

PURPOSE: GALAD is a statistical model for estimating the likelihood of having hepatocellular carcinoma (HCC) based on gender, age, AFP, AFP-L3, and PIVKA-II. We aimed to assess its performance and build new models in China, where hepatitis B virus (HBV) is the leading etiology of HCC. PATIENTS AND METHODS: We built the GALAD-C model with the same five variables in GALAD, and the GAAP model with gender, age, AFP, and PIVKA-II, using logistic regression based on 242 patients with HCC and 283 patients with chronic liver disease (CLD). We also collected 50 patients with other malignant liver tumors (OMTs) and 50 healthy controls (HCs). A test dataset (169 patients with HCC and 139 with CLD) was used to test the performance of GAAP. RESULTS: The GALAD-C and GAAP models achieved comparable performance (area under the receiver operating characteristic curve [AUC], 0.922 vs 0.914), and both were superior to GALAD, PIVKA-II, AFP, and AFP-L3% (AUCs, 0.891, 0.869, 0.750, and 0.711) for discrimination of HCC from CLD for the entire dataset. The AUCs of the GALAD, GALAD-C and GAAP models were excellent for the hepatitis C virus (HCV) subgroup (0.939, 0.958 and 0.954), and for discrimination HCC from HCs (0.988, 0.982, and 0.979), but were relatively lower for the HBV subgroup (0.855, 0.904, and 0.894), and for HCC within Milan Criteria (0.810, 0.841, and 0.840). They were not superior to AFP (0.873) for discrimination of HCC from OMT (0.873, 0.809, and 0.823). GAAP achieved an AUC of 0.922 in the test dataset. CONCLUSION: GALAD was excellent for discrimination of HCC from CLD in the HCV subgroup of a cohort of Chinese patients. The GAAP and GALAD-C models achieved better performance compared with GALAD. These three models exhibited better performance in patients with an HCV etiology than those with HBV.

Oxygen vacancies enhanced cooperative electrocatalytic reduction of carbon dioxide and nitrite ions to urea.

The electrochemical reduction of carbon dioxide and nitrite ions into value-added chemicals represents one of the most promising approaches to relieve the greenhouse gases, while a critical challenge is to search for a highly effective catalyst with low energy input and high conversion selectivity. In this work, we demonstrated low-valence Cu doped, oxygen vacancy-rich anatase TiO2 (Cu-TiO2) nanotubes as a synergetic catalyst for electrochemical co-reduction of both CO2 and NO2-. The incorporation of Cu dopants in anatase TiO2 facilitated to form abundant oxygen vacancies and bi-Ti3+ defect sites, which allowed for efficient nitrite adsorption and activation. The low-valence Cu dopants also served as effective catalytic centers to reduce CO2 into CO* adsorbate. The close proximity of CO* and NH2* intermediates was beneficial for the subsequent cooperative tandem reaction to form urea via the CN coupling. This oxygen vacancy-rich Cu-TiO2 electrocatalyst enabled excellent urea production rate (20.8 µmol⋅h-1) and corresponding Faradaic efficiency (43.1%) at a low overpotential of -0.4 V versus reversible hydrogen electrode, substantially superior than those of undoped TiO2, thus suggesting an exciting approach for cooperative CO2 and nitrogen fixation.