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Mutations in C8orf37 cause Bardet-Biedl syndrome (BBS), retinitis pigmentosa (RP), and cone–rod dystrophy (CRD), all manifest in photoreceptor degeneration. Little is known about which proteins C8orf37 interacts with to contribute to photoreceptor survival. To determine the proteins that potentially interact with C8orf37, we carried out a yeast two-hybrid (Y2H) screen using C8orf37 as a bait. FAM161A, a microtubule-binding protein localized at the photoreceptor cilium required for photoreceptor survival, was identified as one of the preys. Double immunofluorescence staining and proximity ligation assay (PLA) of marmoset retinal sections showed that C8orf37 was enriched and was co-localized with FAM161A at the ciliary base of photoreceptors. Epitope-tagged C8orf37 and FAM161A, expressed in HEK293 cells, were also found to be co-localized by double immunofluorescence staining and PLA. Furthermore, interaction domain mapping assays identified that the N-terminal region of C8orf37 and amino acid residues 341-517 within the PFAM UPF0564 domain of FAM161A were critical for C8orf37–FAM161A interaction. These data suggest that the two photoreceptor survival proteins, C8orf37 and FAM161A, interact with each other which may contribute to photoreceptor health. [ABSTRACT FROM AUTHOR]

Background: The benefits of performing open versus laparoscopic gubernaculum-sparing second-stage Fowler-Stephens orchiopexy (FSO) remain unclear. We compared the two techniques to answer this question. Methods: We retrospectively studied a cohort of patients who underwent laparoscopic first-stage FSO and open versus laparoscopic gubernaculum-sparing second-stage FSO at our institution between September 2004 and June 2020 (all patients underwent surgery by a single surgeon). We evaluated both procedures based on the incidence of testicular atrophy, testicular ascent, and other complications. Results: The age at initial surgery was 45.7 ± 28.2 months (median, 39). One hundred nine cases were treated with open second-stage gubernaculum-sparing FSO (OFSO), and 96 cases were treated with laparoscopic second-stage gubernaculum-sparing FSO (LFSO). The mean follow-up period was 59.8 months (median, 54; standard deviation, +35). The overall testicular atrophy rate was 1.5%. Atrophy was observed in 2 and 1 patient in the OFSO and LFSO groups, respectively (1.8% versus 1.0%, P > .05). There was no significant difference in the incidence of testicular ascent between both groups (2.8% versus 3.1%). Five and four complications were noted in the OFSO and LFSO groups, respectively (P > .05). Conclusions: Second-stage gubernaculum-sparing FSO achieved high testicular survival rates and satisfactory testicular positions. Neither the open nor laparoscopic approach appeared superior, because the overall testicular survival rates and incidence of testicular ascent and other complications were equivalent between both groups. [ABSTRACT FROM AUTHOR]

Background: Negative body image is a common psychological phenomenon among Chinese college students meriting investigation. Peers and the media are important factors that negatively influence body image. This study explored the mechanisms of media and peers promoting negative body image among Chinese college students. Method: Data from 407 college students (173 men and 234 women) were collected using the Revised Social and Cultural Attitude Questionnaire of Appearance, Appearance Comparison Scale, Peer Impact Scale, and Negative Body Image Scale. Results: Correlational analysis results demonstrated that media attention was not significantly correlated with negative body image. All other variables were significantly positively correlated. Path analysis results indicated that the direct effect of media attention on negative body image was not significant, while the direct effect of peer impact was significant. In addition, appearance comparison and internalization of the thin ideal acted as a chained indirect effect between negative body image, media attention, and peer impact. Conclusions: The research revealed that focusing on perfect bodies displayed in the media did not produce a negative body image. However, focusing on the media and peer conversations regarding the body caused the participants to compare appearances and internalize ideal body shape standards, leading to negative self-evaluations. Plain English Summary: Adolescents' peers and media have far-reaching influence. This study explored their impact on the body image of Chinese college students. A questionnaire survey was distributed to 461 Chinese college students. The results showed that peers directly affected body image, while media attention did not. Media attention and peer impact further increased students' negative body image evaluations through the indirect effects of appearance comparison and internalization of the thin ideal. [ABSTRACT FROM AUTHOR]

Microplastic pollution has gradually become a major global concern, due to the widespread use of plastics. Microplastics enter the environment and are degradated, while also being ingested by organisms, affecting various physiological functions and adversely affecting the health of organisms. Microplastic pollution is currently a wide concern, but data on the impact on organisms is still not sufficient. Therefore, this review summarizes the research on microplastic pollution in marine, soil and fresh water, and its impact on organisms, focusing on the effects of microplastics on organisms' feeding behavior and oxidative stress responses, intestinal microbes and reproductive function, and the combined effects of microplastic pollutants on organisms. We also summarized the various possible ways of microplastics entering into the human body, and posing a potential threat to human health, which still needs further research. [ABSTRACT FROM AUTHOR]

Correction to: Mol Med (2021) 27:22 https://doi.org/10.1186/s10020-021-00283-6 Following publication of the original article (Ding et al. [1]), due to a typesetting error, author Ruhua Chen has been missed to be marked as corresponding author. Reference 1 Ding H, Chen J, Qin J, Chen R, Yi Z. TGF- -induced -SMA expression is mediated by C/EBP acetylation in human alveolar epithelial cells. Correction to: TGF- -induced -SMA expression is mediated by C/EBP acetylation in human alveolar epithelial cells. [Extracted from the article]

• This work proposes a parallel and distributed deep learning framework for IoT data analytics. • The proposed method is implemented and deployed with a real-world problem of energy consumption forecasting. • Comprehensive comparative study has been conducted to show the outperformance of the proposed method. Energy consumption forecasting based on IoT data and deep learning algorithm inheriting distributed and collaborative learning is a widely studied topic both in engineering and computer science fields. For different households with drastically different energy consumption patterns, the traditional centralized machine learning (ML) and deep learning (DL) methods suffer problems including inaccuracy, inefficiency and laggings of the prediction performance. In this study, we propose a sophisticated multi-channel bidirectional nested LSTM framework (MC-BiNLSTM) combined with discrete stationary wavelet transform (SWT) for highly accurate and efficient energy consumption forecasting. The main contributions of this study include the decomposition using SWT for accuracy improvement and the collaborative BiNLSTM structure for efficiency improvement. A real-world IoT energy consumption dataset, named UK-DALE, is adopted for the comparative study. The experimental results showed the outperformance of the proposed method from various perspectives over the cutting-edge methods existed in the literature. [ABSTRACT FROM AUTHOR]

• A novel nano-antibiotics (Ir(ppy) 2 dmb-PAZ-HA) was successfully fabricated. • Ir(ppy) 2 dmb-PAZ-HA hold excellent antibacterial activity in vitro and in vivo. • Ir(ppy) 2 dmb-PAZ-HA could effectively inhibit and destroy bacterial biofilm. • Ir(ppy) 2 dmb-PAZ-HA was able to induce phase separation of the protein 7C7U. • Ir(ppy) 2 dmb-PAZ-HA has excellent bacterial targeting ability in vitro and in vivo. Bacterial quorum sensing (QS) and bacterial extracellular polymeric substances (EPS) are the major challenges in treating biofilm chronic infection. Herein, we proposed targeting intervention phase separation of EPS by nano-antibiotics (Ir(ppy) 2 dmb-PAZ-HA) as an effective strategy for combating bacterial biofilm infection, in which Iridium complex (Ir(ppy) 2 dmb-CHO) and antibiotic (Pazufloxacin, PAZ) for synergistic antibacterial, and hyaluronic acid (HA) was used to enhance Ir(ppy) 2 dmb-PAZ release on-demand in biofilm microenvironment. In vitro results showed that Ir(ppy) 2 dmb-PAZ-HA holds excellent antibacterial activity and antibiofilm capacity. Importantly, Ir(ppy) 2 dmb-PAZ-HA can be target to regulate phase separation of EPS, and then interfere with biofilm formation, which is a competitive mechanism between Ir(ppy) 2 dmb-PAZ-HA and Methicillin-resistant Staphylococcus aureus (MRSA) itself. In addition, in vivo results confirmed that Ir(ppy) 2 dmb-PAZ-HA was able to accelerate biofilm chronic wound healing, and effectively alleviate bacterial acute lung infection. Accordingly, this study provides a new antibiofilm target, and provides a novel idea for the design of small molecular metal antibacterial drugs and antibiotic reuse. [ABSTRACT FROM AUTHOR]

Background & Aims: aMAP score, as a hepatocellular carcinoma risk score, is proven to be associated with the degree of chronic hepatitis B‐related liver fibrosis. We aimed to evaluate the ability of aMAP score for metabolic dysfunction‐associated steatotic liver disease (MASLD; formerly NAFLD)‐related fibrosis diagnosis and establish a machine‐learning (ML) model to improve the diagnostic performance. Methods: A total of 946 biopsy‐proved MASLD patients from China and the United States were included in the analysis. The aMAP score, demographic/clinical indices and liver stiffness measurement (LSM) were included in seven ML algorithms to build fibrosis diagnostic models in the training set (N = 703). The performance of ML models was evaluated in the external validation set (N = 125). Results: The AUROCs of aMAP versus fibrosis‐4 index (FIB‐4) and aspartate aminotransferase‐platelet ratio (APRI) in cirrhosis and advanced fibrosis were (0.850 vs. 0.857 [P = 0.734], 0.735 [P = 0.001]) and (0.759 vs. 0.795 [P = 0.027], 0.709 [P = 0.049]). When using dual cut‐off values, aMAP had a smaller uncertainty area and higher accuracy (26.9%, 86.6%) than FIB‐4 (37.3%, 85.0%) and APRI (59.0%, 77.3%) in cirrhosis diagnosis. The seven ML models performed satisfactorily in most cases. In the validation set, the ML model comprising LSM and 5 indices (including age, sex, platelets, albumin and total bilirubin used in aMAP calculator), built by logistic regression algorithm (called LSM‐plus model), exhibited excellent performance. In cirrhosis and advanced fibrosis detection, the LSM‐plus model had higher accuracy (96.8%, 91.2%) than LSM alone (86.4%, 67.2%) and Agile score (76.0%, 83.2%), respectively. Additionally, the LSM‐plus model also displayed high specificity (cirrhosis: 98.3%; advanced fibrosis: 92.6%) with satisfactory AUROC (0.932, 0.875, respectively) and sensitivity (88.9%, 82.4%, respectively). Conclusions: The aMAP score is capable of diagnosing MASLD‐related fibrosis. The LSM‐plus model could accurately identify MASLD‐related cirrhosis and advanced fibrosis. [ABSTRACT FROM AUTHOR]

Simple Summary: Rhodotorula mucilaginosa is widely detected in the environment, and it produces broad metabolites such as carotenoid pigments, amino acids, polyunsaturated fatty acids, polysaccharides, and enzymatic substances. We previously isolated a strain of Rhodotorula mucilaginosa ZTHY2 from the coastal waters of the South China Sea, which showed probiotic properties. Rhodotorula mucilaginosa ZTHY2 promoted the growth of experimental animals, increased the abundance of beneficial bacteria in gut, and enhanced immune function. Given that immunosuppression is common in livestock, environmental stresses, such as overpopulation, food contamination, and chronic diseases, contribute to immunosuppression of livestock associated with declining animal production, failed immunoprophylaxis, and economic losses. Therefore, in this study, cyclophosphamide was used to generate immunosuppressed models to further evaluate the immunomodulatory effects of Rhodotorula mucilaginosa ZTHY2. Rhodotorula mucilaginosa (R. mucilaginosa) can enhance the immune and antioxidant function of the body. However, whether R. mucilaginosa has an immunoregulatory effect on cyclophosphamide (CTX)-induced immunosuppressed animals remains to be clarified. In this study, the R. mucilaginosa ZTHY2 that we isolated from the coastal waters of the South China Sea previously was prepared in order to investigate its immunoprotective effect on CTX-induced immunosuppression in mice, and the effects were compared to those of Lactobacillus acidophilus (LA) (a well-known probiotic). Seventy-two male SPF mice were divided into six groups: The C group (control); IM group (immunosuppressive model group) (+CTX); Rl, Rm, and Rh groups (+CTX+low, medium, and high concentration of R. mucilaginosa, respectively); and PC (positive control) group (+CTX+LA). After a 28-day feeding trial, blood samples were taken for biochemical and serum immunological analysis, and the thymus and spleen were collected to analyze the organ index, lymphocyte proliferation and differentiation, and antioxidant capacity. The findings showed that R. mucilaginosa ZTHY2 improved the spleen and thymus indices, effectively attenuated immune organ atrophy caused by CTX, and enhanced the proliferation of T and B lymphocytes induced by ConA and LPS. R. mucilaginosa ZTHY2 promoted the secretion of cytokines and immunoglobulins and significantly increased the contents of IL-2, IL-4, IL-6, TNF-α, IFN-γ, IgA, IgG, IgM, CD4, CD8, CD19, and CD20 in serum. The proportion of CD4+, CD8+, CD19+, and CD20+ lymphocytes in spleen, thymus, and mesenteric lymph nodes were increased. In addition, R. mucilaginosa ZTHY2 reduced the reactive oxygen species (ROS) and malondialdehyde (MDA) levels and increased glutathione (GSH), total superoxide dismutase (SOD), and catalase (CAT) levels. Our results indicated that R. mucilaginosa ZTHY2 can significantly enhance the immune function of immunosuppressed mice, and improving antioxidant capacity thus attenuates CTX-induced immunosuppression and immune organ atrophy. [ABSTRACT FROM AUTHOR]

(1) Background: Hepatic venous occlusion type of Budd–Chiari syndrome (BCS-HV) and pyrrolizidine alkaloid-induced hepatic sinusoidal obstructive syndrome (PA-HSOS), share similar clinical features, and imaging findings, leading to misdiagnoses; (2) Methods: We retrospectively analyzed 139 patients with BCS-HV and 257 with PA-HSOS admitted to six university-affiliated hospitals. We contrasted the two groups by clinical manifestations, laboratory tests, and imaging features for the most valuable distinguishing indicators.; (3) Results: The mean patient age in BCS-HV is younger than that in PA-HSOS (p < 0.05). In BCS-HV, the prevalence of hepatic vein collateral circulation of hepatic veins, enlarged caudate lobe of the liver, and early liver enhancement nodules were 73.90%, 47.70%, and 8.46%, respectively; none of the PA-HSOS patients exhibited these features (p < 0.05). DUS showed that 86.29% (107/124) of patients with BCS-HV showed occlusion of the hepatic vein, while CT or MRI showed that only 4.55%(5/110) patients had this manifestation (p < 0.001). Collateral circulation of hepatic veins was visible in 70.97% (88/124) of BCS-HV patients on DUS, while only 4.55% (5/110) were visible on CT or MRI (p < 0.001); (4) Conclusions: In addition to an established history of PA-containing plant exposure, local hepatic vein stenosis and the presence of collateral circulation of hepatic veins are the most important differential imaging features of these two diseases. However, these important imaging features may be missed by enhanced CT or MRI, leading to an incorrect diagnosis. [ABSTRACT FROM AUTHOR]

Background the incidence of acute-on-chronic liver disease (AoCLD) is increasing. Objective to investigate the clinical features and risk factors of AoCLD and construct an effective prognostic nomogram model for older patients with AoCLD. Methods data from 3,970 patients included in the CATCH-LIFE study were used, including 2,600 and 1,370 patients in the training and validation sets, respectively. Multivariate Cox regression analyses were performed to identify predictive risk factors in older individuals, and an easy-to-use nomogram was established. Performance was assessed using area under the curve, calibration plots and decision curve analysis (DCA). Results of the 3,949 patients with AoCLD, 809 were older with a higher proportion of autoimmune-related abnormalities, hepatitis C viral infection and schistosomiasis. In the older patient group, the incidence of cirrhosis, hepatic encephalopathy (HE), infection, ascites and gastrointestinal bleeding; neutrophil-to-lymphocyte ratio (NLR), aspartate-to-alanine transaminase ratio (AST/ALT), creatinine and blood urea nitrogen levels were higher, whereas incidence of acute-on-chronic liver failure, white blood cell, platelet and haemoglobin levels; albumin, total bilirubin (TB), AST and ALT levels; international normalised ratio (INR), estimated glomerular filtration rate and blood potassium levels were lower than in the younger group. The final nomogram was developed based on the multivariate Cox analysis in training cohort using six risk factors: ascites, HE grades, NLR, TB, INR and AST/ALT. Liver transplantation-free mortality predictions were comparable between the training and validation sets. DCA showed higher net benefit for the nomograph than the treat-all or treat-none strategies, with wider threshold probabilities ranges. Conclusions our analysis will assist clinical predictions and prognoses in older patients with AoCLD. [ABSTRACT FROM AUTHOR]

Background: Whether serum hepatitis B virus (HBV) RNA associates with hepatocellular carcinoma (HCC) development in chronic hepatitis B (CHB) patients has not been fully elucidated.Methods: We enrolled 2974 patients receiving nucleos(t)ide analogues (NAs) from a prospective, observational CHB cohort to investigate the effect of serum HBV RNA, measured at study entry (baseline), on HCC development, using Cox regression analyses.Results: During median follow-up of 4.4 years, 90 patients developed HCC. Patients with detectable baseline HBV RNA (n = 2072) exhibited significantly higher HCC risk than those with undetectable level (5-year HCC incidence estimated by Kaplan-Meier method: 4.1% versus 1.8%, P = .009; adjusted hazard ratio [aHR] = 2.21, P = .005). HBV RNA levels of 609-99 999 and ≥100 000 copies/mL were associated with incrementally increasing HCC risk (aHR = 2.15 and 3.05, respectively; P for trend = .003), compared to undetectable level (<609 copies/mL). Moreover, patients with single-detectable either HBV DNA or RNA and double-detectable DNA and RNA had 1.57- and 4.02-fold higher HCC risk, respectively, than those with double-undetectable DNA and RNA (P for trend = .001).Conclusions: High-level HBV RNA is associated with increased HCC risk in NAs-treated patients. Achieving undetectable HBV RNA may contribute to better clinical outcomes, indicating it could be a valuable endpoint of anti-HBV treatment. [ABSTRACT FROM AUTHOR]

The computation offloading problem in mobile edge computing (MEC) has received a lot of attention, but service caching is also a research topic that cannot be ignored in MEC. Due to the limited resources available on the Edge Server (ES), a wise computation offloading and service caching policy must be formulated in order to maximize system offload efficiency. In this paper, a many-objective joint optimization computation offloading and service caching model (MaJOCOSC) is designed. The model takes into account the limited computing and storage resources of ES, the delay and energy consumption constraints of different types of tasks, and multiple processing modes of user tasks, and sets delay, energy consumption, task hit service rate, service cache balancing, and load balancing as the five optimization objectives of MaJOCOSC. Meanwhile, a non-dominated sorting genetic algorithm (NSGAIII-ASF&WD) based on achievement scalar function (ASF) and the k-nearest neighbor weighted distance mating selection strategy is proposed for better solving the model. The ASF ensures that the given strategy performs well for each objective value, and the k-nearest neighbor weighted distance provides the user with a diversity of strategies. Simulation results show that NSGAIII-ASF&WD can obtain better objective values when solving the model compared with other many-objective evolutionary algorithms, and a suitable computation offloading and service caching strategy is obtained. [ABSTRACT FROM AUTHOR]

Leaves and flowers of Amorphophallus konjac do not develop simultaneously thus unique features can be elucidated through study of flowering transformation in A. konjac. In this study, transcriptome libraries of A. konjac leaf buds (LB) and flower buds (FB) were constructed followed by high-throughput sequencing. A total of 68,906 unigenes with an average length of 920 bp were obtained after library assembly. Out of these genes, 24,622 unigenes had annotation information. A total of 6859 differentially expressed genes (DEGs) were identified through differential expression analysis using LB as control. Notably, 2415 DEGs were upregulated whereas 4444 DEGs were downregulated in the two transcriptomes. Go and KEGG analysis showed that the DEGs belonged to 44 functional categories and were implicated in 98 metabolic pathways and 38 DEGs involved in plant hormone signal transduction. Several genes were mined that may be involved in A. konjac flower bud differentiation and flower organ development. Eight DEGs were selected for verification of RNA-seq results using qRT-PCR analysis. Two FLOWERING LOCUS T (FT) genes named AkFT1 and AkFT2 were identified though homologous analysis may be the florigen gene implicated in modulation of A. konjac flowering. These genes were significantly upregulated in flower buds compared with the expression levels on leaf buds. Overexpression of AkFT genes though heterologous expression in Arabidopsis showed that the transgenics flowered at a very early stage relative to wild type plants. These findings indicate that AkFT1 and AkFT2 function as regulation genes in A. konjac flowering development and the two genes may present similar functions during flowering transition. [ABSTRACT FROM AUTHOR]

Spider venom boasts extensive peptide diversity, constituting a natural biochemical arsenal for defense and predation. The new family HvAMPs, including 9 homologous members, were identified from the unnormalized cDNA library of Heteropoda venatoria venom gland by Sanger sequencing. The putative mature peptide is composed of 22 aliphatic amino acid residues. The mature peptides of HvAMP1 and HvAMP5, with 3 different amino acids, were synthesized and both were shown to adopt an amphipathic α-helical structure and amphipathicity in SDS buffer by CD spectroscopy. In comparison to HvAMP1, HvAMP5 exhibits higher antibacterial activity, particularly against Gram-positive bacteria, coupled with reduced hemolytic activity and cytotoxicity. Results from SYTO 9/PI staining indicate that HvAMP5 acts by disrupting bacterial cell membranes. Analysis of the relationships between structures and functions suggests that HvAMP5 enhances antibacterial activity and reduces mammalian cell toxicity by increasing positive charge and proline substitution. The three residues variation can augment the electrostatic attraction of antibacterial peptides to the bacterial phospholipid bilayer. The present study suggests that the HvAMPs may exert lytic action against cells of different origins to increase cellular and tissue barrier permeability to facilitate spider's defense or predation. Moreover, HvAMP5 holds promise as a novel antibacterial agent for treating Gram-positive bacterial infections. Simultaneously, the numerous diverse amino acid residue substitutions within the HvAMP family offer a template for future study. [Display omitted] • Discovery of a peptide family adopting amphipathic α-helical structure from the venom gland of Heteropoda venatoria. • Enhancing the positive charge and incorporating proline substitution enhanced bactericidal and attenuated toxicity. • HvAMP5 exhibits bactericidal activity specifically against Gram-positive bacteria by targeting bacterial cell membranes. [ABSTRACT FROM AUTHOR]

With the deployment of workflow and other applications, cloud computing is accessible and offers assistance for optimizing workflow execution and enhancing performance. Existing research, however, tends to disregard the influence of dataset migration on workflow execution and focuses more on task execution time. This study suggests a new model for the problem of data-intensive workflow execution. Firstly, according to the structure of the workflow scheduling problem, it is divided into two sub-problems: data placement and task scheduling. The two sub-problems interact with each other and a bi-level optimum model is established. By seeking a better allocation strategy for the dataset placement and then seeking the best task-scheduling solution. Secondly, an improved multitasking bi-level evolutionary algorithm (IM-BLEA) is proposed. When dealing with the lower-level optimization problem (LLOP), offspring are selected by sorting individuals by their performance and overall performance in the population, and this environmental selection enhances the diversity and searchability of the population. Finally, compared with the other multitasking algorithm, IM-BLEA has good performance. Simulation results based on real scientific workflows show that the algorithm improves the values of transfer time and number of selected data centers by 56% and 10% compared to the comparison algorithm. • A bi-level optimization model in data-intensive workflows is proposed. • The upper-level and lower-level problems are data placement and task scheduling. • Multitasking evolutionary algorithms on bi-level optimization model. • Based on the modeling of the problem, an algorithm (IM-BLEA) is proposed. • Simulation experiments based on scientific workflows to validate algorithms. [ABSTRACT FROM AUTHOR]

Empirical antibiotic therapy in patients with spontaneous bacterial peritonitis (SBP) is common as pathogen(s) are identified in only 5%‐20% patients using conventional culture‐based techniques. Metagenome next‐generation sequencing (mNGS) test is a promising approach for the diagnosis of infectious disease. The clinical application of mNGS for infected ascites in cirrhotic patients is rarely reported. Here, we describe three cases to preliminarily explore the potential role of mNGS for microbiological diagnosis of ascites infection in an exploratory manner. The clinical performance of ascites mNGS in cirrhotic patients remains to be further evaluated. [ABSTRACT FROM AUTHOR]

Summary: Background: Obesity is typically associated with metabolic dysfunction, but its impact on hepatocellular carcinoma (HCC) remains unclear in patients with chronic hepatitis B (CHB). Aim: To study the effect of obesity on HCC development in patients with CHB receiving antiviral therapy. Methods: We included patients from a Chinese multicentre, prospective, observational, treated CHB cohort in this study. General obesity was evaluated by body‐mass index (BMI). Central obesity was evaluated by waist circumference, waist‐to‐hip ratio and waist‐to‐height ratio. Results: A total of 5754 nucleos(t)ide analogue treated patients were enrolled in the analysis. The 5‐year cumulative incidence of HCC was 2.9%. Waist‐to‐height ratio performed better in predicting HCC development than BMI, waist circumference or waist‐to‐hip ratio. Patients with central obesity (defined as waist‐to‐height ratio >0.5) had significantly higher 5‐year incidence of HCC than those without central obesity in the overall population (3.9% vs 2.1%, hazard ratio [HR]: 2.06, P = 0.0001) and 745 propensity score matched pairs (4.7% vs 2.3%, HR: 2.04, P = 0.026), respectively. Besides cirrhosis status and aMAP HCC risk score, central obesity was also independently associated with HCC risk (HR: 1.63, P = 0.013). Waist‐to‐height ratio gain within 1 year was associated with a significantly higher HCC risk with an adjusted HR value of 1.88 (95% confidence interval: 1.12‐3.13, P = 0.017). Conclusions: Central obesity, evaluated by the waist‐to‐height ratio, was associated with a twofold increase in HCC risk among CHB patients receiving antiviral treatment, highlighting the important role of abnormal metabolic function in the progression of liver disease. [ABSTRACT FROM AUTHOR]

The cover image is based on the Brief Definitive Report Rapid detection for infected ascites in cirrhosis using metagenome next‐generation sequencing: A case series by Beiling Li et al., https://doi.org/10.1111/liv.15083. [ABSTRACT FROM AUTHOR]

Scheme 1 Schematic illustration of immuno-RCA and Cas12a based electrochemical biosensor for quantitative analysis of E. coli O157:H7. [Display omitted] • An electrochemical biosensor based on CRISPR was established to detect bacteria. • The electrochemical biosensor can be used in the detection of actual samples. • The immuno-RCA was used to amplify the activity of CRISPR/Cas12a system. • Have a wide detection range from 10 to 107 CFU•mL−1, with a LOD of 10 CFU·mL−1. Rapid, simple, and sensitive detection of food-borne pathogenic bacteria is extremely important for preventing and controlling food-borne diseases. Herein, an electrochemical biosensor based on CRISPR/Cas12a combined with immuno-rolling circle amplification (immuno-RCA) was developed for detecting the pathogenic bacterium, Escherichia coli O157:H7. Based on a sandwich-type immunoassay on magnetic beads, immuno-RCA generated long single-stranded DNA with abundant E. coli O157:H7-specific aptamers and target repeated sequences, which allowed recognition and binding of E. coli O157:H7 and complex formation by CRISPR/Cas12a and crRNA, respectively. Stimulation of Cas12a produced trans- cleavage activity toward a non-specific methylene blue labeled DNA hairpin probe on the electrode surface. In the presence of E. coli O157:H7, the CRISPR/Cas12a non-specific trans- cleavage activity was triggered, the hairpin DNA on the Au electrode was cleaved, and the peak current was altered. Under optimal conditions, the developed biosensor presented a broad dynamic detection range from 10 to 107 CFU·mL−1, with a detection limit of 10 CFU·mL−1. Moreover, the biosensor did not exhibit any cross-reactivity with other non-target bacteria. These results revealed that the developed biosensor is a simple, sensitivity, and specific platform for E. coli O157:H7 detection. [ABSTRACT FROM AUTHOR]

In many mammalian species, including pigs, heat stress (HS) detrimentally leads to epithelium damage and increases intestinal permeability. However, the underlying molecular mechanisms are not thoroughly investigated yet. This study aimed to examine the RIP1/RIP3-ERK1/2 signaling pathway that regulates the expression of tight junction proteins in HS-treated pigs. In in vitro cultured intestinal porcine epithelial cells (IPEC-J2), HS induced the expression of tight junction proteins, ZO-1, claudin-1, and claudin-4, that are regulated by the ERK1/2-MAPK signaling pathway. Further, high expression of HSP70 in IPEC-J2 cells induced a significant decrease in receptor-interacting protein 1/3 (RIP1/3), phosphorylated ERK, and tight junction protein claudin-1 (P < 0.05). Necrostatin-1 (A selective inhibitor of RIPK1) suppressed the upregulation of phosphorylated ERK1/2 induced by HS, indicating that the RIP1/RIP3 regulates ERK1/2 phosphorylation in IPEC-J2 under heat stress. In addition, HS significantly damaged the intestinal morphology characterized by reduction of villus length and crypt depth in in vivo porcine model. Moreover, the expression of tight junction, ZO-1, and claudin-4 were downregulated, whereas phosphorylated p38 and ERK1/2 were upregulated in the duodenum of heat-stressed pigs. Interestingly, a decrease in ZO-1 and claudin-1 was observed in the colon, where phosphorylated ERK1/2 was similar to that in the duodenum. Our results demonstrate that RIP1/RIP3-ERK1/2 signaling pathway regulates the expression of tight junction proteins in HS-pigs. This finding further advances the intestinal barrier function's underlying mechanisms associated with signaling regulation. • A heat stress induced porcine inflammatory bowel disease model was constructed successfully. • Heat stress induced down – regulation of tight junction proteins play a vital role in the development inflammatory bowel disease in pigs. • Heat stress induced down-regulation of tight junction proteins was via ERK1/2 signaling pathway. [ABSTRACT FROM AUTHOR]