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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.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.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 were5% 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).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.NCT04890730.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.

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.

Summary Electrochemical CO2 reduction is a promising approach for upgrading excessive CO2 into value-added chemicals, while the exquisite control of the catalyst atomic structures to obtain high C2+ alcohol selectivity has remained challenging due to the intrinsically favored ethylene pathways at Cu surface. Herein, we demonstrate a rational strategy to achieve ∼70% faradaic efficiency toward C2+ alcohols. We utilized a CO-rich environment to construct Cu catalysts with stepped sites that enabled high surface coverages of ∗CO intermediates and the bridge-bound ∗CO adsorption, which allowed to trigger CO2 reduction pathways toward the formation alcohols. Using this defect-site-rich Cu catalyst, we achieved C2+ alcohols with partial current densities of > 100 mA·cm−2 in both a flow-cell electrolyzer and a membrane electrode assembly (MEA) electrolyzer. A stable alcohol faradaic efficiency of ∼60% was also obtained, with ∼500 mg C2+ alcohol production per cm2 catalyst during a continuous 30-h operation.

The electrocatalytic reduction of carbon monoxide (CO) is an emerging direction with new catalyst structures, among which the bimetallic component catalysts feature both functional diversity and high-density of active sites. In this work, we demonstrate that the fine tuning of adjacent bimetallic sites can allow us to select different reaction pathways toward C1 or C2 products in the electroreduction of CO. Cu and Cu–Au alloy catalysts with different atomic ratios were fabricated and investigated for appropriate molecular distances. The pure Cu catalyst was found to be active for electroreducing CO to C2H4, as the adjacent Cu sites were beneficial for adsorbing multiple CO molecules and subsequent C–C coupling. On the other hand, alloying Cu with Au introduced steric hindrance and a larger intermolecular distance between adjacent adsorbed *CO intermediates, thus leading to a decrease of C2H4 selectivity but an enhanced CH4 pathway. Our work revealed the importance of spacing between active sites for CO electroreduction, which can benefit the catalyst design to further improve activities and selectivities in electrocatalytic CO reduction.

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.

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. Electronic supplementary material The online version of this article (10.1007/s12250-020-00329-9) contains supplementary material, which is available to authorized users.

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.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.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.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.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.

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.

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.

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 C N 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.

The citrate-based thermoset elastomer is a promising candidate for bone scaffold material, but the harsh curing condition made it difficult to fabricate porous structure. Recently, poly (1, 8-octanediol-co-Pluronic F127 citrate) (POFC) porous scaffold was creatively fabricated by chitin nanofibrils (ChiNFs) supported emulsion-freeze-casting. Thanks to the supporting role of ChiNFs, the lamellar pore structure formed by directional freeze-drying was maintained during the subsequent thermocuring. Herein, bioactive glass (BG) was introduced into the POFC porous scaffolds to improve bioactivity. It was found the complete replacement of ChiNF particles with BG particles could not form a stable porous structure; however, existing at least 15 wt% ChiNF could ensure the formation of lamellar pore, and the interlamellar distance increased with BG ratios. Thus, the BG granules did not contribute to the formation of pore structure like ChiNFs, however, they surely endowed the scaffolds with enhanced mechanical properties, improved osteogenesis bioactivity, better cytocompatibility as well as quick degradation rate. Reasonably adjusting BG ratios could balance the requirements of porous structure and bioactivity.

Melt polycondensation of citric acid (CA) and diols can form biodegradable thermoset bioelastomers with good biological properties and designed performances. However, their cross-linked structure reveals a big challenge to fabricate submicrofibers or nanofibers via electrospinning. Herein, melt polycondensation of CA and 1,8-octanediol in the presence of poly(ε-caprolactone) (PCL) was performed to fabricate a prepolymer containing high-molecular-weight poly(1,8-octanediol- co-PCL citrate) (POCL) for facilitating direct electrospinning. The results showed that the direct electrospinning of the prepolymer was still unfeasible even if POCL had a high molecular weight; however, introducing a certain quantity of PCL as carrier polymer realized eletrospinnability and generated fibrous POCL/PCL; the thermal cured POCL/PCL still maintained fibrous structure and was endowed with elastic property; moreover, in comparison with pure PCL fiber mat, they exhibited a better resilience and hydrophilicity.

We report single-atom Cu catalysts dispersed on nitrogen-doped carbon by a nitrogen-coordination strategy. The presence of nitrogen enabled good dispersion and attachment of atomic Cu species on th...

Mussel-inspired tissue adhesives have been widely studied in recent years because of their excellent underwater adhesion. Our recent study has synthesized a series of tissue adhesives with citric acid, dopamine, 1,8-octanediol and poly(ethylene oxide) (PEO), and found that amphiphilic adhesives showed an efficient underwater adhesion mechanism. Poly(propylene oxide)-poly(ethylene oxide) block copolymer (PEO-PPO-PEO) is a thermosensitive amphiphilic material, widely used in medical field. Herein, we replaced PEO with PEO-PPO-PEO to introduce temperature-sensitivity into adhesives, and utilized the hydrophilic-to-hydrophobic transition of PEO-PPO-PEO to reduce the swelling at human temperature. Fortunately, we got positive results that all the synthetized adhesives showed obvious temperature-sensitivity. The transition from low temperature to room temperature of the high concentrated uncured adhesive dispersion made it potentially injectable. After crosslinking, the swelling ratio of cured adhesives showed a significant decrease from 4°C to 37°C. And all the swelling ratios under 37°C were low, ranging from 8.4% to 22.5%. Additionally, the lap-shear adhesion strength on wet porcine skin was in the range of 29.2–67.1 kPa, which was higher than that of commercial fibrin glue (9–15 kPa). By selecting different (PEO)y(PPO)x(PEO)y, we could obtain adhesives with wide mechanical properties and broaden the scope of use of the adhesives.

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.This study aimed to verify the effects of AA on tubular injury in DKD and underlying mechanisms.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.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.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).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.

Chitin nanocrystal is a biocompatible and biodegradable nanofiller, with great potential in enhancing the mechanical and biological properties of polymers. Poly(caprolactone-diol citrate) is a kind of citrate-based biodegradable elastomer prepared by an additive-free melt polycondensation of polycaprolactone-diol and citric acid coupled with subsequent thermocuring. Here, a facile casting/evaporation method was utilized to prepare full biodegradable poly(caprolactone-diol citrate)/chitin nanocrystal nanocomposites, and their structure and properties were characterized by Fourier transform infrared spectroscopy, scanning electron microscopy, uniaxial tensile test, dynamic mechanical analysis, surface wettability and swelling analysis, thermogravimetric analysis, in vitro degradation, and cytocompatibility test. The results showed the chitin nanocrystals were uniformly distributed in the poly(caprolactone-diol citrate) matrix; with increasing chitin nanocrystal loading, the tensile modulus and strength significantly increased; furthermore, the incorporation of chitin nanocrystals endowed the poly(caprolactone-diol citrate) with more hydrophilicity, lower swelling in phosphate buffered saline solution, slow degradation rate, and greatly improved cytocompatibility. Thus, the chitin nanocrystal was a good bio-based nanofiller that could be used to tune the properties of poly(caprolactone-diol citrate) degradable bioelastomer.

Electroreduction of CO2 into valuable molecules or fuels is a sustainable pathway for CO2 reduction as well as energy storage. However, the premature development stage of electrocatalysts with high activity, selectivity, and durability still remains a significant bottleneck that hinders this field. One-dimensional (1D) nanomaterials, including nanorods, nanotubes, nanoribbons, nanowires, and nanofibers, are generally considered as high-activity and stable electromaterials, due to their unique uniform structures, orientated electronic and mass transport, and rigid tolerance to stress variation. During the past several years, 1D nanomaterials and nanostructures have been extensively studied due to their potentials in serving as CO2 electroreduction catalysts. In this minireview, recent studies and advances in 1D nanomaterials for CO2 eletroreduction are summarized, from the viewpoints of both computational and experimental aspects. Based on the composition, the 1D nanomaterials are studied in four categories, including metals, transition-metal oxides/nitrides, transition-metal chalcogenides, and carbon-based materials. Different parameters in tuning 1D materials are also summarized and discussed, such as the crystal facets, grain boundaries, heteroatoms doping, additives and the electrochemical tuning effects. Finally, the challenges and prospects in this direction will be discussed.

Background & aims The role of cigarette smoking in the development of chronic hepatitis B (CHB) remains poorly understood. We assessed the potential contributions of cigarette smoking to liver fibrosis and its regression after starting antiviral therapy in CHB patients. Methods In this cohort study, 2144 consecutive male CHB patients under no antiviral therapy were evaluated and 206 patients with significant liver fibrosis (≥F2) initiating antiviral therapy had longitudinal follow-up. Liver fibrosis was measured by liver stiffness measurement using transient elastography. To adjust for imbalances between smoking history and never smoking groups, propensity score (PS) matching model with 1:1 ratios were performed. Cigarette smoking history and intensity (pack-years) were collected and documented using a standardized questionnaire. Results Before PS matching, 432/2144 patients had advanced fibrosis in prevalence cohort. Patients with smoking history (n = 1002) had a greater prevalence of advanced fibrosis than those without (n = 1142) (24.4% vs 16.5%, P = 0.001). Multivariate logistic regression analysis demonstrated that smoking contributed to advanced fibrosis (OR, 1.458; 95% CI, 1.114-1.908). In longitudinal cohort, multivariate logistic regression analysis demonstrated retarded fibrosis regression in patients with history of smoking ≥10 pack-years (OR, 0.288; 95% CI, 0.1-0.825). After PS matching, patients with smoking history had higher prevalence of advanced fibrosis (22.8% vs 18%, P = 0.024) than those non-smokers. In post-PS-matching logistic regression, the effect of smoking on advanced fibrosis persisted (OR, 1.415; 95% CI, 1.047-1.912; P = 0.024). Conclusions Cigarette smoking in male CHB patients aggravated liver fibrosis prior to and delayed fibrosis regression under antiviral therapy.

Poly(1, 8-octanediol citrate) (POC) degradable elastomer have attracted much attention due to its good biological properties. However, there is a compromise, i.e. to improve its extendibility inevitably leads to a sticky feature that causes inconvenient handling. Poly(e-caprolactone) (PCL) is a commonly used biodegradable, flexible polyester applied in a variety of FDA-approved products. Here, an in-situ copolymerization blending strategy, i.e. melt polycondensation of citric acid and 1, 8-octanediol in the presence of PCL was adopted to produce a POC/PCL composite elastomer, in which partial PCL took part in polycondensation reaction and chemically bonded into the POC network, and the rest physically traversed within the network structure, leading to a transparent, flexible composite elastomer. The wide angle X-ray diffraction (WAXD) and differential scanning calorimetry (DSC) analyses confirmed a full-amorphous structure and no crystallization of PCL occurring. Moreover, the introduction of PCL not only improved extendibility but avoided stickiness. Compared to the POC, the time for curing POC/PCL prepolymers was highly reduced; and the degradation of composite elastomers in PBS solution was accelerated despite the slow degradation of PCL incorporated; additionally, surface erosion degradation presumably happened for POC/PCL elastomers, which would allow the implant to retain inner strength for a longer time.