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Besides its well‐known benefits on human health, calcitriol, the hormonally active form of vitamin D3, has been being evaluated in clinical trials as an anticancer agent. However, currently available results are contradictory and not fundamentally deciphered. To the best of our knowledge, hypercalcemia caused by high‐dose calcitriol administration and its low bioavailability limit its anticancer investigations and translations. Here, we show that the one‐step self‐assembly of calcitriol and amphiphilic cholesterol‐based conjugates leads to the formation of a stable minimalist micellar nanosystem. When administered to mice, this nanosystem demonstrates high calcitriol doses in breast tumor cells, significant tumor growth inhibition and antimetastasis capability, as well as good biocompatibility. We further reveal that the underlying molecular antimetastatic mechanisms involve downregulation of proteins facilitating metastasis and upregulation of paxillin, the key protein of focal adhesion, in primary tumors. [ABSTRACT FROM AUTHOR]

Owing to a wide variety of deployment of GPS-enabled devices, tremendous amounts of trajectories have been generated in distributed stream manner. It opens up new opportunities to track and analyze the moving behaviors of the entities. In this work, we focus on the issue of outlier detection over distributed trajectory streams, where the outliers refer to a few entities whose motion behaviors are significantly different from their local neighbors. In view of skewed distribution property and evolving nature of trajectory data, and on-the-fly detection requirement over distributed streams, we first design a high-efficiency outlier detection solution. It consists of identifying abnormal trajectory fragment and exceptional fragment cluster at the remote sites and then detecting abnormal evolving object at the coordinator site. Further, given that outlier detection accuracy would be damaged due to using inappropriate proximity thresholds or a few trajectory data not having sufficient neighbors at the remote sites, we extract proximity thresholds of different regions and spatial context relationship of each region from historical data to improve the precision. Built upon this is an improved version consisting of off-line modeling phase and on-line detection phase. During the on-line phase, the proximity thresholds that are derived from historical trajectories during the off-line phase are leveraged to assist in detecting abnormal trajectory fragments and exceptional fragment clusters at the remote sites. Additionally, at the coordinator site, the detection results of some remote sites can be refined by incorporating those of other remote sites with neighborhood relationship. Extensive experimental results on real data demonstrate that our proposed methods own high detection validity, less communication cost and linear scalability for online identifying outliers over distributed trajectory streams. [ABSTRACT FROM AUTHOR]

Aim: With the current coronavirus disease (COVID‐19) pandemic and high endemic levels of chronic hepatitis B virus (HBV) infection worldwide, it is urgent to investigate liver function changes of COVID‐19 patients with chronic HBV infection, and how severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) infection in turn affects the course of chronic HBV infection. Method: We undertook a retrospective study based on 347 COVID‐19 patients (21 vs. 326 with vs. without chronic HBV infection). With the propensity score matching (PSM) method, we yielded 20 and 51 matched patients for the HBV group and the non‐HBV group, respectively. Results: At the end of follow‐up, all of these 71 patients achieved SARS‐CoV‐2 clearance (P = 0.1). During the follow‐up, 30% versus 31.4% in the HBV group versus non‐HBV group progressed to severe COVID‐19 (P = 0.97). After PSM, the longitudinal changes of median values for liver biochemistries were not significantly different between the two groups. In the HBV group versus non‐HBV group, 35% (7/20) versus 37.25% (19/51) (P = 0.86) had abnormal alanine aminotransferase at least once during hospitalization, 30% (6/20) versus 31.37% (16/51) had abnormal aspartate aminotransferase (P = 0.91), 40% (8/20) versus 37.25% (19/51) had abnormal γ‐glutamyltransferase (P = 0.83), and 45% (9/20) versus 39.22% (20/51) had abnormal total bilirubin levels (P = 0.91). Moreover, three patients in the HBV group had hepatitis B reactivation. Conclusions: Liver dysfunction presented in COVID‐19 patients with/without chronic HBV. Moreover, those COVID‐19 patients co‐infected with chronic HBV could have a risk of hepatitis B reactivation. It is necessary to monitor liver function of COVID‐19 patients, as well as HBV‐DNA levels for those co‐infected with HBV during the whole disease course. [ABSTRACT FROM AUTHOR]

Background and aims: Hepatitis E virus (HEV), as an emerging zoonotic pathogen, is a leading cause of acute viral hepatitis worldwide, with a high risk of developing chronic infection in immunocompromised patients. However, the global epidemiology of HEV infection has not been comprehensively assessed. This study aims to map the global prevalence and identify the risk factors of HEV infection by performing a systematic review and meta‐analysis. Methods: A systematic searching of articles published in Medline, Embase, Web of science, Cochrane and Google scholar databases till July 2019 was conducted to identify studies with HEV prevalence data. Pooled prevalence among different countries and continents was estimated. HEV IgG seroprevalence of subgroups was compared and risk factors for HEV infection were evaluated using odd ratios (OR). Results: We identified 419 related studies which comprised of 1 519 872 individuals. A total of 1 099 717 participants pooled from 287 studies of general population estimated a global anti‐HEV IgG seroprevalence of 12.47% (95% CI 10.42‐14.67; I2 = 100%). Notably, the use of ELISA kits from different manufacturers has a substantial impact on the global estimation of anti‐HEV IgG seroprevalence. The pooled estimate of anti‐HEV IgM seroprevalence based on 98 studies is 1.47% (95% CI 1.14‐1.85; I2 = 99%). The overall estimate of HEV viral RNA‐positive rate in general population is 0.20% (95% CI 0.15‐0.25; I2 = 98%). Consumption of raw meat (P =.0001), exposure to soil (P <.0001), blood transfusion (P =.0138), travelling to endemic areas (P =.0244), contacting with dogs (P =.0416), living in rural areas (P =.0349) and receiving education less than elementary school (P <.0001) were identified as risk factors for anti‐HEV IgG positivity. Conclusions: Globally, approximately 939 million corresponding to 1 in 8 individuals have ever experienced HEV infection. 15‐110 million individuals have recent or ongoing HEV infection. Our study highlights the substantial burden of HEV infection and calls for increasing routine screening and preventive measures. [ABSTRACT FROM AUTHOR]

The current understanding of cancer biology and development of effective treatments for cancer remain far from satisfactory. This in turn heavily relies on the availability of easy and robust model systems that resemble the architecture/physiology of the tumors in patients to facilitate research. Cancer research in vitro has mainly been based on the use of immortalized 2D cancer cell lines that deviate in many aspects from the original primary tumors. The recent development of the organoid technology allowing generation of organ-buds in 3D culture from adult stem cells has endowed the possibility of establishing stable culture from primary tumors. Although culturing organoids from liver tumors is thought to be difficult, we now convincingly demonstrate the establishment of organoids from mouse primary liver tumors. We have succeeded in culturing 91 lines from 129 liver tissue/tumors. These organoids can be grown in long-term cultures in vitro. About 20% of these organoids form tumors in immunodeficient mice upon (serial) transplantation, confirming their tumorigenic and self-renewal properties. Interestingly, single cells from the tumor organoids have high efficiency of organoid initiation, and a single organoid derived from a cancer cell is able to initiate a tumor in mice, indicating the enrichment of tumor-initiating cells in the tumor organoids. Furthermore, these organoids recapitulate, to some extent, the heterogeneity of liver cancer in patients, with respect to phenotype, cancer cell composition and treatment response. These model systems shall provide enormous opportunities to advance our research on liver cancer (stem cell) biology, drug development and personalized medicine. [ABSTRACT FROM AUTHOR]

Keywords: COVID-19; clinical trial; prospective meta-analysis EN COVID-19 clinical trial prospective meta-analysis 501 503 3 07/15/20 20200801 NES 200801 In response to the coronavirus 2019 (COVID-19) pandemic, an overwhelming number of clinical trials have been registered to test a variety of preventive and therapeutic strategies, as comprehensively summarized by Lythgoe and Middleton [1]. For example, sofosbuvir, targeting hepatitis C virus RNA-dependent RNA polymerase (RdRp), was shown to inhibit hepatitis E virus (HEV) in cell culture model by one experimental study [3]. Challenges for Conducting High Quality COVID-19 Clinical Trials The COVID-19 pandemic has put great pressure on healthcare workers and regulatory authorities to swiftly make treatment available [7]. [Extracted from the article]

Aim: The role of tumor differentiation in the prognosis of hepatocellular carcinoma (HCC) after hepatectomy remains controversial. The present study aimed to classify the impact of tumor differentiation on solitary hepatitis B viral (HBV)-associated HCC using propensity score matching analysis.Methods: Between January 2009 and March 2015, the data of 721 HCC patients in West China Hospital were prospectively collected and analyzed. Propensity matching analysis was applied to overcome the imbalance in baseline characteristics. Survival analysis was performed using the Kaplan-Meier method. Risk factors were identified by the Cox proportional hazards model.Results: All HCC patients were classified into the moderately well-differentiated HCCs group (group A, n = 442, 61.3%) or poorly differentiated HCCs group (group B, n = 279, 38.7%). Patients with poorly differentiated HCCs commonly had a larger tumor size, more advanced tumors, and a higher alpha-fetoprotein (AFP) level. Patients with poorly differentiated HCCs had a poorer recurrence-free survival and overall survival before and after propensity score matching analysis. Poorly differentiated tumors, positive serum hepatitis B viral e antigen, positive hepatitis B virus deoxyribonucleic acid load, tumor size, microvascular invasion, and AFP > 400 ng/ml were risk factors of a poor outcome.Conclusions: Our propensity model provided strong evidence that a poorly differentiated tumor had a negative impact on the recurrence and long-term survival of solitary HBV-associated HCCs after curative hepatectomy. Antiviral therapy might improve their prognosis. [ABSTRACT FROM AUTHOR]

Hepatitis B virus and hepatitis C virus (HCV) co‐infection can add to the severity of hepatitis and the risks of liver cirrhosis and hepatocellular carcinoma. Whether chronic HCV infection decreases antibody response to hepatitis B vaccination is still controversial. We evaluate the influence of HCV infection on antibody response to hepatitis B vaccination by a systematic review of published works with a meta‐analysis of clinical trials. The random‐effects model of DerSimonian and Laird with heterogeneity and sensitivity analyses were used in this study. The end‐point of interest was the rate of patients showing seroconversion of antibody responses at completion of hepatitis B vaccination schedule among patients with chronic HCV infection versus healthy controls. We identified 11 studies involving 704 patients with HCV and 812 controls. Our results show a significant decrease in antibody seroconversion rates among patients with HCV versus healthy controls (pooled odds ratio = 0.17 [95% confidence interval, 0.11–0.28]). The P‐value was 0.21 for our test of study heterogeneity. Stratified analysis in subgroups of interest and sensitivity analysis did not meaningfully change our results. Our meta‐analysis showed patients with hepatitis C infection have a statistically significant lower rate of seroconversion in comparison to healthy controls, both in cirrhotic and non‐cirrhotic patients. Chronic HCV infection can decrease the immune response to a standard schedule of hepatitis B vaccination. Further studies are needed to investigate the optimum vaccination schedule for patients with chronic HCV infection. [ABSTRACT FROM AUTHOR]

Background Tremendous progress has been made in hepatitis B virus (HBV) prevention and control in the last 30 years in China, but it continues to be a major public health problem. The most recently reported population-based seroepidemiological survey on HBV in Shandong Province in China was published in 2006, and an updated baseline for HBV prevalence was badly needed in the province to identify the change in HBV epidemiology in the last decade. Methods Two population-based cross-sectional serosurveys were performed among the population aged 1–59 years in the same sample areas in Shandong Province, China in 2006 and 2014, respectively. Data on demographic characteristics were collected. A blood sample was obtained from each person and was tested for hepatitis B surface antigen (HBsAg), antibody against HBsAg (anti-HBs), and antibody against hepatitis B core antigen (anti-HBc). Results Overall, the prevalence rates of HBsAg, anti-HBs, and anti-HBc were 3.39% (95% confidence interval (CI) 2.51–4.26), 44.96% (95% CI 41.34–48.57), and 24.45% (95% CI 22.19–26.71), respectively, among the population aged 1–59 years in the 2006 serovsurvey; the corresponding prevalence rates were 2.49% (95% CI 1.81–3.17), 48.27% (95% CI 45.63–50.92), and 22.56% (95% CI 20.14–24.97), respectively, in 2014. The prevalence rates of HBsAg and anti-HBc were lower in 2014 than in 2006. Conversely, the prevalence of anti-HBs showed an increase. However, none of these differences were statistically significant (all p > 0.05). The prevalence of HBsAg showed an increase among persons aged 20–24 years in 2014 (3.83%) compared with 2006 (2.98%) ( t = 0.45, p = 0.67). Among all occupation groups, the prevalence of HBsAg was lower in 2014 than in 2006, while the prevalence of anti-HBc showed moderate increases in students and farmers (all p > 0.05). The prevalence of HBsAg decreased more obviously in urban areas (65.49%) than rural areas (7.07%) from 2006 to 2014. Conclusions The epidemiology of HBV infection has changed in Shandong Province, China over the last decade. More attention should be paid to HBV infection among students and farmers. [ABSTRACT FROM AUTHOR]

Side-chain functionality is critical to achieve highly conductive and chemically stable anion exchange membrane (AEM) materials. Herein, two series of quaternized poly(2,6-dimethyl-1,4-phenylene oxide) (PPO) having different lengths (n or m) of cationic side-chains were designed and prepared, including PPO-C- n QA with a triazole-containing linker and PPO- m QA without triazole groups in the side chains. The effect of the side-chain functionality on the properties of AEMs has been systematically investigated. Long cationic side chains in PPO- m QA membranes induced the formation of obvious microphase-separated morphology. However, PPO-C- n QA membranes with a triazole-containing linker showed a considerable higher hydroxide conductivity than that of PPO- m QA membranes, due to the developed hydrogen-bond networks between triazole and water/hydroxide. High retention of conductivity and low degree of crosslinking were observed for the AEMs with longer side-chains (PPO-C-3QA, PPO-C-4QA, PPO-6QA, and PPO-7QA) in the alkaline stability testing under 10 M NaOH at 80 °C for 250 h, indicating their excellent stability. Moreover, a single H 2 /O 2 AEMFC with these side-chain type AEMs demonstrated that PPO-C-1QA with highest conductivity exhibited a peak power density of 141.3 mW cm−2 at a current density of 320 mA cm−2. Image 1 • Side chain functionality has significant impact on the performance of the AEMs for fuel cells. • PPO-C- n QA membrane displayed higher conductivity and superior alkaline stability than PPO- m QA membrane. • PPO-C-1CQA membrane had a highest peak power density of 141.3 mW cm−2 of AEMFC. [ABSTRACT FROM AUTHOR]

• Lipid droplets exert a variety of key biological functions. • Lipid droplets actively interact with other organelles. • Lipid droplets play key roles in health and disease of the liver. • The biological functions of lipid droplet-organelle interactions remain obscure. Lipid droplets are cellular organelles used for lipid storage with a hydrophobic core of neutral lipids enclosed by a phospholipid monolayer. Besides presenting as giant single organelles in fat tissue, lipid droplets are also widely present as a multitude of small structures in hepatocytes, where they play key roles in health and disease of the liver. In addition to lipid storage, lipid droplets are also directly involved in lipid metabolism, membrane biosynthesis, cell signaling, inflammation, pathogen-host interaction and cancer development. In addition, they interact with other cellular organelles to regulate cellular biology. It is fair to say that the exact functions of lipid droplets in cellular physiology remain largely obscure. Thus prompted, here we aim to analyze the corpus of contemporary biomedical literature to create a framework as to how the role of lipid droplets in hepatocyte physiology and pathophysiology should be understood. The resulting framework should help understanding the interaction of lipid droplets with other organelles in important liver diseases, including fatty liver disease, viral hepatitis and liver cancer and direct further research directions. [ABSTRACT FROM AUTHOR]

The regulation behavior of oxygen vacancies (Vo) at different spatial positions (surface or bulk) in catalysts for selective O 3 catalyzation, along with the reaction pathways evolution was well-investigated in α-MnO 2−x /O 3 systems. Combined characterization methods, systematic organic removal experiments, structure-activity relationship analysis, and theoretical calculations were employed to unveil O 3 decomposition and electron transfer behaviors regulated by surface or bulk Vo. The contribution of electron transfer process (ETP) to atrazine (ATZ) removal was reinforced from 5.2 % to 34.8 % with the formation of bulk Vo, and Vo-rich α-MnO 2−x -2/O 3 system achieved ∼96.5 % ATZ removal along with improved TOC mineralization (∼38 % vs. ∼20 %). Surface Vo facilitated O 3 adsorption, promoting its decomposition into •OH, while bulk Vo not only accelerated •OH production but also withdrew electrons from organics to build ETP. This study shed light on precise modification of metal-based catalysts with Vo to modulate •OH/ETP synergistic processes in catalytic ozonation for efficient water purification. [Display omitted] • Rational Vo modification in catalysts promoted selective ozone catalyzation. • The reaction pathways (•OH and ETP) were modulated by surface and bulk Vo. • Both surface and bulk Vo boosted electrons transfer to decompose O 3 into •OH. • Bulk Vo preferred to withdraw electrons from the organics to build ETP. • •OH and ETP synergistic process facilitated the stoichiometry efficiency of O 3. [ABSTRACT FROM AUTHOR]

The long‐term benefits of interferon‐α (IFN‐α) treatment in children with chronic hepatitis B (CHB) remain unclear. We conducted a retrospective and real‐world study to evaluate the safety and long‐term clearance rates of hepatitis B e antigen (HBeAg) and hepatitis B surface antigen (HBsAg) in CHB children who received IFN‐α monotherapy for 72 weeks and were with 13‐year follow‐up visit. Participants treated with IFN‐α (n = 316) were more likely to become HBeAg negatve (39.87% vs. 27.37%; p <.05) and HBsAg negative (11.08% vs. 3.16%; p <.05) by the end of the treatment period than untreated participants (n = 95). Treated participants also had higher cumulative rates of HBeAg loss (74.13% vs. 59.27%; p <.05) and HBsAg loss (46.95 vs. 33.11%; p < 0.05) than untreated participants in parallel by the end of 13‐year follow‐up. In particular, the cumulative rate of HBsAg loss was higher in treated children aged 1–7 years than in those aged 8–17 years (71.40% vs. 39.0%; p <.01). Children who were HBeAg‐negative at the end of IFN‐α treatment or who had serum alanine aminotransferase levels of ≥80 IU/L at baseline were likely to have higher cumulative HBsAg loss rates. Accordingly, HBeAg loss at 72 weeks was positively associated with the cumulative HBsAg loss rate in untreated children. There were no serious adverse events of IFN‐α therapy for the treated patients throughout the study period. Overall, IFN‐α therapy was effective in obtaining higher long‐term cumulative rates of HBeAg and HBsAg loss in children with HBeAg‐positive immune‐active CHB, especially among those aged 1–7 years. [ABSTRACT FROM AUTHOR]

Background: The diagnosis of follicular thyroid carcinoma (FTC) prior to surgery remains a major challenge in the clinic. Methods: This multicentre diagnostic study involved 41 and 150 age- and sex-matched patients in the training cohort and validation cohort, respectively. The diagnostic properties of circulating small extracellular vesicle (sEV)-associated and cell-free RNAs were compared by RNA sequencing in the training cohort. Subsequently, using a quantitative real-time polymerase chain reaction (qRT‒PCR) assay, high-quality candidates were identified to construct an RNA classifier for FTC and verified in the validation cohort. The parallel expression, stability and influence of the RNA classifier on surgical strategy were also investigated. Results: The diagnostic properties of sEV long RNAs, cell-free long RNAs and sEV microRNAs (miRNAs) were comparable and superior to those of cell-free miRNAs in RNA sequencing. Given the clinical application, the circulating sEV miRNA (CirsEV-miR) classifier was developed from five miRNAs based on qRT‒PCR data, which could well identify FTC patients (area under curve [AUC] of 0.924 in the training cohort and 0.844 in the multicentre validation cohort). Further tests revealed that the CirsEV-miR score was significantly correlated with the tumour burden, and the levels of sEV miRNAs were also higher in sEVs from the FTC cell line, organoid and tissue. Additionally, circulating sEV miRNAs remained constant after different treatments, and the addition of the CirsEV-miR classifier as a biomarker improves the current surgical strategy. Conclusions: The CirsEV-miR classifier could serve as a noninvasive, convenient, specific and stable auxiliary test to help diagnose FTC following ultrasonography. [ABSTRACT FROM AUTHOR]

γδ T cells are evolutionarily conserved T lymphocytes that manifest unique antitumor efficacy independent of tumor mutation burden (TMB) and conventional human leukocyte antigen (HLA) recognition. However, the dynamic changes in their T cell receptor (TCR) repertoire during cancer progression and treatment courses remain unclear. Here, a comprehensive characterization of γδTCR repertoires are performed in thyroid cancers with divergent differentiation states through cross‐sectional studies. The findings revealed a significant correlation between the differentiation states and TCR repertoire diversity. Notably, highly expanded clones are prominently enriched in γδ T cell compartment of dedifferentiated patients. Moreover, by longitudinal investigations of the γδ T cell response to various antitumor therapies, it is found that the emergence and expansion of the Vδ2neg subset may be potentially associated with favorable clinical outcomes after post‐radiotherapeutic immunotherapy. These findings are further validated at single‐cell resolution in both advanced thyroid cancer patients and a murine model, underlining the importance of further investigations into the role of γδTCR in cancer immunity and therapeutic strategies. [ABSTRACT FROM AUTHOR]

Several epidemiological studies have suggested that flavonoid intake is associated with a decreased risk of cardiometabolic disease. However, the results remained inconsistent and there is no dose-response meta-analysis for specific outcomes. We conducted a meta-analysis to synthesize the knowledge about their associations and to explore their dose-response relationships. We comprehensively searched the PubMed, Embase, and Web of Science databases for prospective cohort studies published up to December 1, 2021. Summary relative risks (RR) and 95% confidence intervals (CI) were pooled for the association between flavonoid intake and cardiometabolic disease. Evaluations of linear or nonlinear dose-response were presented by restricted cubic splines. We identified 47 articles, including 1,346 676 participants and 127,507 cases in this meta-analysis. The summary of RR per 500 mg/d increase in flavonoid intake was 0.93 (95% CI 0.88–0.98) for cardiovascular disease, 0.89 (95% CI 0.84–0.94) for diabetes, and 0.97 (95% CI 0.94–0.99) for hypertension, respectively. We also found a linearity dose-response association between total flavonoid intake and cardiovascular disease (p nonlinearity = 0.541), and diabetes (p nonlinearity = 0.077). Our finding based on quantitative data suggested that a higher level of flavonoid intake is beneficial for the prevention of cardiometabolic diseases. [ABSTRACT FROM AUTHOR]

Background: Comprehensive evaluation of safety and efficacy of different combinations of direct‐acting antivirals (DAAs) in liver transplant recipients with genotype 1 (GT1) hepatitis C virus (HCV) recurrence remains limited. Therefore, we performed this systematic review and meta‐analysis in order to evaluate the clinical outcome of DAA treatment in liver transplant patients with HCV GT1 recurrence. Methods: Studies were included if they contained information of 12 weeks sustained virologic response (SVR12) after DAA treatment completion as well as treatment related complications for liver transplant recipients with GT1 HCV recurrence. Results: We identified 16 studies comprising 885 patients. The overall pooled estimate proportion of SVR12 was 93% (95% confidence interval (CI): 0.89, 0.96), with moderate heterogeneity observed (τ2 = 0.01, P < 0.01, I2=75%). High tolerability was observed in liver transplant recipients reflected by serious adverse events (sAEs) with pooled estimate proportion of 4% (95% CI: 0.01, 0.07; τ2 = 0.02, P < 0.01, I2 = 81%). For subgroup analysis, a total of five different DAA regimens were applied for treating these patients. Sofosbuvir/Ledipasvir (SOF/LDV) led the highest pooled estimate SVR12 proportion, followed by Paritaprevir/Ritonavir/Ombitasivir/Dasabuvir (PrOD), Daclatasvir (DCV)/Simeprevir (SMV) ± Ribavirin (RBV), and SOF/SMV ± RBV, Asunaprevir (ASV)/DCV. There was a tendency for favoring a higher pooled SVR12 proportion in patients with METAVIR Stage F0‐F2 of 97% (95% CI: 0.93, 0.99) compared to 85% (95% CI: 0.79, 0.90) for stage F3‐F4 (P < 0.01). There was no significant difference between LT recipients treated with or without RBV (P = 0.23). Conclusions: Direct‐acting antiviral treatment is highly effective and well‐tolerated in liver transplant recipients with recurrent GT1 HCV infection. [ABSTRACT FROM AUTHOR]

Surface engineering has been identified as an effective way to maximize the utilization of noble atoms and facilitate the oxygen reduction reaction. However, a cost-effective and highly durable platform for tailoring the electrocatalytic activity, is still absent. Herein, we demonstrate a new and promising catalytic material of antiperovskite-typed PdNFe 3 and construct a high performance PdNFe 3 @Pd catalyst with atomic layers of strained Pd shell. The PdNFe 3 @Pd/C catalyst presents a high mass activity (MA) of 1.14 A mg−1 Pd at 0.9 V, which is 9 and 6 times higher than those of the Pt/C and Pd/C, respectively. More importantly, the excellent performance of PdNFe 3 @Pd/C was also verified in anion-exchange membrane fuel cells and rechargeable Zn−air batteries. Density functional theory calculations reveal that the strain effect aroused by the lattice mismatch between PdNFe 3 core and Pd shell contributes to the enhanced ORR performance by optimizing the binding strength of oxygen intermediates on Pd. [Display omitted] • Demonstrating a new class of platform/core materials for constructing core-shell catalysts. • Elucidating catalytic mechanism of PdNFe 3 @Pd towards ORR. • Extraordinary catalytic performance towards oxygen reduction. [ABSTRACT FROM AUTHOR]

Overactive bladder (OAB) is a common, long-term symptom complex with a high prevalence in women worldwide. OAB has caused a social burden, and effective treatments are urgently needed. However, the pathogenesis of OAB has yet to be elucidated. Model rats underwent bladder outlet obstruction surgery. In the 2nd, 3rd, and 4th weeks after surgery, metabolic cages were used to detect the 12 h urine volume of rats in the sham and model groups. The urodynamic parameters bladder leak point pressure (BPLL), maximum voiding pressure (MVP), residual volume (RV), maximum bladder capacity (MBC), bladder compliance (BC), voided efficiency (VE), and non-voiding contractions (NVCs) were also detected. Moreover, the contractile responses of isolated detrusor muscles to electrical and carbachol stimulation were examined at the abovementioned time points. At the 4th week after surgery, the bladders of both groups were obtained for hematoxylin–eosin (H&E) and Masson's trichrome staining. Real-time qPCR and Western blot were performed to quantify the expression of choline acetyltransferase (ChAT) and solute carrier family 17 member 9 (SLC17A9). At week 4, compared with the sham group, the 12 h urine volume of PBOO group increased significantly. The BLPP, MVP, VE, MBC, and NVCs increased significantly, and the VE was significantly reduced in 4-week PBOO group. The contractile responses of isolated detrusor muscles to electrical and carbachol stimulation significantly increased in 4-week PBOO group. In the 4-week PBOO group, the bladder wall and the ratio of bladder muscle to collagen within the bladder smooth muscle layer wall were significantly higher than those in the sham group. ChAT and SLC17A9 mRNA and protein expression in the OAB model rats significantly increased. At 4 weeks after PBOO, the OAB model was successfully established. The gene and protein expression levels of ChAT and SLC17A9 increased in the bladder of the OAB model, suggesting that OAB may be related to increased excitatory purinergic and cholinergic expression. [ABSTRACT FROM AUTHOR]

Background & Aims: In liver cancer, leucine‐rich repeat‐containing G‐protein coupled receptor 5 (LGR5) compartment represents an important tumor‐initiating cell (TIC) population and served as a potential therapeutic target. Cancer‐associated fibroblasts (CAFs) is a critical part of the tumor microenvironment, heavily influenced TIC function and fate. However, deeply investigations have been hindered by the lack of accurate preclinical models to investigate the interaction between CAFs and TIC. Organoids model have achieved major advancements as a precious research model for recapitulating the morphological aspects of organs, and thus also serving as a candidate model to investigate the mutual interaction between different cell types. Consequently, this study aimed to construct a three‐dimensional (3D) co‐culture organoid model of primary LGR5‐expressing tumor stem cells from primary murine liver tumors with CAFs to investigate the impact of CAFs on LGR5 marked TICs in liver cancer. Materials and Methods: First, both of the transgenic LGR5‐diphtheria toxin receptor (DTR)‐GFP knock‐in mice and transgenic Rosa26‐mT mice developed primary liver tumors by diethylnitrosamine (DEN) administration. Tumor organoids and CAFs were generated from those primary liver cancer separately. Second, LGR5‐expressing TICs organoid with CAFs were established ex vivo based on cell–cell contact or trans‐well co‐culture system, and the mutual influence between those two types of cells was further investigated. Subsequently, immunodeficient mouse‐based xenograft model was further adopted to evaluate the influence of CAFs to LGR5 tumor stem cell, tumor formation, and metastasis. Results: The co‐culture organoid model composed of murine liver tumor LGR5+ tumor‐initiating cells and CAFs in 3D co‐culture was successfully established, with the intention to investigate their mutual interaction. The existence of CAFs upon engrafting tumor organoids resulted in dramatic higher number of LGR5+ cells in the neoplasia when compared with engrafting tumor organoids alone. Furthermore, ex vivo culture of isolated LGR5+ cells from tumors of co‐engrafted mice formed significantly larger size of organoids than mono‐engrafted. Our results also indicated significantly larger size and number of formed organoids, when LGR5+ cells co‐cultured with CAF in both cell–cell contact and paracrine signaling in vitro, comparing to LGR5+ cells alone. Furthermore, we found that specific knockout of LGR5 expressing cells suppressed CAF‐mediated promotion of tumor formation, growth, and metastasis in the experimental mice model. Conclusions: Altogether, in a 3D co‐culture type of murine liver LGR5+ cells and cancer‐associated fibroblasts, we have demonstrated robust effects of CAFs in the promotion of LGR5 marked liver TICs. We also further revealed the influence of tumor microenvironment on stem cell‐related therapy, suggesting the possibility of combing CAF‐targeted and tumor stem cell targeted therapy in treating liver cancer. [ABSTRACT FROM AUTHOR]

Background: We aimed to examine the evolution of blood lipids and compare the risk of dyslipidemia between antiretroviral-naive people living with HIV who received tenofovir disoproxil fumarate (TDF), lamivudine (3TC), and efavirenz (EFV) (TDF + 3TC + EFV) and those who received coformulated elvitegravir, cobicistat, emtricitabine, and tenofovir alafenamide (E/C/F/TAF). Methods: We retrospectively reviewed the medical records of 2343 antiretroviral-naive people living with HIV who initiated TDF + 3TC + EFV or E/C/F/TAF. A propensity score matching method was used to compare longitudinal changes of blood lipids between the 2 groups. Results: By using 1:3 matching ratio, we included 253 and 91 matched patients in TDF + 3TC + EFV group and E/C/F/TAF group, respectively. The levels of total cholesterol, triglyceride, low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol were higher in E/C/F/TAF group than those in TDF + 3TC + EFV group at 3, 6, 9, and 12 months (Wilcoxon test, all P s < 0.05), except for high-density lipoprotein cholesterol at 9 and 12 months. The cumulative rates of hypercholesterolemia, hypertriglyceridemia, and high LDL-C in PLWH with normal lipid levels in E/C/F/TAF group were higher than those in TDF + 3TC + EFV group (hypercholesterolemia, 59.7% vs 21.5%, P < 0.001; hypertriglyceridemia, 69.5% vs 46.3%, P < 00.001; and high LDL-C, 41.5% vs 14.2%, P < 0.001). Multivariate analysis showed treatment with E/C/F/TAF was associated with a significantly higher risk of hypercholesterolemia [adjusted hazard ratio (HR), 4.12; 95% confidence interval (CI): 2.65 to 6.41], hypertriglyceridemia (adjusted HR, 1.69; 95% CI: 1.18 to 2.43), and high LDL-C (adjusted HR, 4.60; 95% CI: 2.66 to 7.97). Conclusions: We concluded that treatment with E/C/F/TAF resulted in higher risks of dyslipidemia compared with TDF + 3TC + EFV. [ABSTRACT FROM AUTHOR]

Background: Heterologous prime-boost with ChAdOx1 nCoV-19 vector vaccine (ChAd) and a messenger RNA vaccine (BNT or mRNA-1273) has been widely facilitating mass coronavirus disease 2019 (COVID-19) immunisation. This review aimed to synthesize immunogenicity and reactogenicity of heterologous immunisations with ChAd and BNT (mRNA-1273) vaccine compared with homologous ChAd or BNT (mRNA-1273) immunisation. Methods: PubMed, Web of Science, and Embase databases were searched from inception to March 7, 2022. Immunogenicity involving serum antibodies against different SAS-CoV-2 fragments, neutralizing antibody, or spike-specific T cells response were compared. Any, local and systemic reactions were pooled by meta-analysis for comparison. Results: Of 14,571 records identified, 13 studies (3024 participants) were included for analysis. Compared with homologous BNT/BNT vaccination, heterologous ChAd/BNT schedule probably induced noninferior anti-spike protein while higher neutralizing antibody and better T cells response. Heterologous ChAd/BNT (mRNA-1273) immunisation induced superior anti-spike protein and higher neutralizing antibody and better T cells response compared with homologous ChAd/ChAd vaccination. Heterologous ChAd/BNT (mRNA-1273) had similar risk of any reaction (RR = 1.30, 95% CI: 0.86−1.96) while higher risk of local reactions (RR = 1.65, 95% CI: 1.27−2.15) and systemic reactions (RR = 1.49, 95% CI: 1.17−1.90) compared with homologous ChAd/ChAd vaccination. There was a higher risk of local reactions (RR = 1.16, 95% CI: 1.03−1.31) in heterologous ChAd/BNT (mRNA-1273) vaccination compare with homologous BNT/BNT but a similar risk of any reaction (RR = 1.03, 95% CI: 0.79−1.34) and systemic reactions (RR = 0.89, 95% CI: 0.60−1.30). Conclusions: Heterologous ChAd/BNT schedule induced at least comparable immunogenicity compared with homologous BNT/BNT and better immunogenicity compared with homologous ChAd/ChAd vaccination. The synthetical evidence supported the general application of heterologous prime-boost vaccination using ChAd and BNT COVID-19 vaccines. [ABSTRACT FROM AUTHOR]

Background: LINC00152 (long intergenic non‐protein coding RNA 152) was identified as an oncogenic lncRNA in multiple cancers. In the current study, we aimed to explore the transcriptional profile of LINC00152 in oral squamous cell carcinoma (OSCC) and its regulations at the transcriptional level. Methods: Bioinformatic analysis was performed by extracting the OSCC subset from The Cancer Genome Atlas (TCGA)‐Head and Neck Squamous Cell Carcinoma (HNSC). LINC00152 subcellular localization and its interacting transcriptional factors (TFs) were explored. Dual‐luciferase assay and ChIP‐qPCR were applied to study transcriptional regulation. In vitro and in vivo tumor cell growth models were used for functional assays. Results: NR_024206.2 was the dominant isoform that accounts for 80% of all transcripts of LINC00152. LINC00152 upregulation was associated with unfavorable survival of patients with OSCC. LINC00152 knockdown significantly impaired OSCC cell growth in vitro and in vivo. RNA FISH assay confirmed nuclear and cytoplasmic distribution of LINC00152. It physically interacted with Upstream Transcription Factor 1 (USF1), a common transcription factor in mammalian cells. USF1 could bind to the promoter region of MRPL52 (Mitochondrial Ribosomal Protein L52) and activate its transcription. LINC00152 could enhance the binding, thereby indirectly elevating MRPL52 expression. USF1 or MRPL52 knockdown slowed the proliferation of OSCC cells and partly canceled LINC00152‐mediated growth‐promoting effects. Conclusion: This study revealed a novel LINC00152‐USF1/MRPL52 axis promoting OSCC tumor growth. [ABSTRACT FROM AUTHOR]

Fatty liver disease has grown into a major global health burden, attributed to multi-factors including sedentary lifestyle, obesogenic diet and prevalence of metabolic disorders. The lack of robust experimental models is hampering the research and therapeutic development for fatty liver disease. This study aims to develop an organoid-based 3D culture model to recapitulate key features of fatty liver disease focusing on intracellular lipid accumulation and metabolic dysregulation. We used human liver-derived intrahepatic cholangiocyte organoids and hepatocyte differentiated organoids. These organoids were exposed to lactate, pyruvate, and octanoic acid (LPO) for inducing lipid accumulation and mitochondrial impairment. Lipid accumulation resulted in alternations of gene transcription with major effects on metabolic pathways, including triglyceride and glucose level increase, which is consistent with metabolic changes in fatty liver disease patients. Interestingly, lipid accumulation affected mitochondria as shown by morphological transitions, alternations in expression of mitochondrial encoded genes, and reduction of ATP production. Meanwhile, we found treatment with obeticholic acid and metformin can alleviate fat accumulation in organoids. This study demonstrated that LPO exposure can induce lipid accumulation and associated metabolic dysregulation in human liver-derived organoids. This provides an innovative model for studying fatty liver disease and testing potential therapeutics. Key messages: Lactate, pyruvate, and octanoic acid induce lipid accumulation in liver organoids. Organoids of human compared to mouse origin are more efficient in lipid accumulation. Lipid accumulation dysregulates metabolic pathway and impairs mitochondrial function. Demonstrating a proof-of-concept for testing medications in organoids. [ABSTRACT FROM AUTHOR]

B Correction: Mol Cancer 20, 51 (2021) b B https://doi.org/10.1186/s12943-021-01333-7 b In our BMC Research publication in Molecular Cancer entitled 'CircNEIL3 regulatory loop promotes pancreatic ductal adenocarcinoma progression via miRNA sponging and A-to-I RNA-editing '[[1]], we misplaced two images in Fig. Reference 1 Shen P, Yang T, Chen Q. CircNEIL3 regulatory loop promotes pancreatic ductal adenocarcinoma progression via miRNA sponging and A-to-I RNA-editing. [Extracted from the article]

Background: A growing number of studies have focused on investigating circRNAs as crucial regulators in the progression of multiple cancer types. Nevertheless, the biological effects and underlying mechanisms of circRNAs in pancreatic ductal adenocarcinoma (PDAC) remain unclear. Methods: Differentially expressed circRNAs between cancerous tissue and adjacent normal tissues were identified by RNA sequencing in PDAC. Subsequently, in vitro and in vivo functional experiments were performed to investigate the functional roles of circNEIL3 in PDAC tumour growth and metastasis. Furthermore, RNA pull-down, dual-luciferase reporter assays, RNA immunoprecipitation (RIP) assays, fluorescent in situ hybridization (FISH) and Sanger sequencing assays were performed to examine the circular interaction among circNEIL3, miR-432-5p and adenosine deaminases acting on RNA 1 (ADAR1). Results: CircNEIL3 was upregulated in PDAC and promoted the progression of PDAC cells both in vitro and in vivo. Mechanistically, circNEIL3 was shown to regulate the expression of ADAR1 by sponging miR-432-5p to induce RNA editing of glioma-associated oncogene 1 (GLI1), ultimately influencing cell cycle progression and promoting epithelial-to-mesenchymal transition (EMT) in PDAC cells. Moreover, we discovered that the circNEIL3/miR-432-5p/ADAR1 axis was correlated with the PDAC clinical stage and overall survival of PDAC patients, while ADAR1 may reduce the biogenesis of circNEIL3. Conclusions: Our findings reveal that circNEIL3 facilitates the proliferation and metastasis of PDAC through the circNEIL3/miR-432-5p/ADAR1/GLI1/cell cycle and EMT axis and that its expression is regulated by ADAR1 through a negative feedback loop. Therefore, circNEIL3 may serve as a prognostic marker and a therapeutic target for PDAC. [ABSTRACT FROM AUTHOR]

Background & Aims: Mature transfer RNAs (tRNA) charged with amino acids decode mRNA to synthesize proteins. Dysregulation of translational machineries has a fundamental impact on cancer biology. This study aims to map the tRNAome landscape in liver cancer patients and to explore potential therapeutic targets at the interface of charging amino acid with tRNA. Methods: Resected tumour and paired tumour‐free (TFL) tissues from hepatocellular carcinoma (HCC) patients (n = 69), and healthy liver tissues from organ transplant donors (n = 21), HCC cell lines, and cholangiocarcinoma (CC) patient‐derived tumour organoids were used. Results: The expression levels of different mature tRNAs were highly correlated and closely clustered within individual tissues, suggesting that different members of the tRNAome function cooperatively in protein translation. Interestingly, high expression of tRNA‐Lys‐CUU in HCC tumours was associated with more tumour recurrence (HR 1.1; P =.022) and worse patient survival (HR 1.1; P =.0037). The expression of Lysyl‐tRNA Synthetase (KARS), the enzyme catalysing the charge of lysine to tRNA‐Lys‐CUU, was significantly upregulated in HCC tumour tissues compared to tumour‐free liver tissues. In HCC cell lines, lysine deprivation, KARS knockdown or treatment with the KARS inhibitor cladosporin effectively inhibited overall cell growth, single cell‐based colony formation and cell migration. This was mechanistically mediated by cell cycling arrest and induction of apoptosis. Finally, these inhibitory effects were confirmed in 3D cultured patient‐derived CC organoids. Conclusions: The biological process of charging tRNA‐Lys‐CUU with lysine sustains liver cancer cell growth and migration, and is clinically relevant in HCC patients. This process can be therapeutically targeted and represents an unexplored territory for developing novel treatment strategies against liver cancer. [ABSTRACT FROM AUTHOR]

Since early January 2020, after the outbreak of coronavirus infection in Wuhan, China, ≈365 confirmed cases have been reported in Shenzhen, China. The mode of community and intrafamily transmission is threatening residents in Shenzhen. Strategies to strengthen prevention and interruption of these transmissions should be urgently addressed. [ABSTRACT FROM AUTHOR]

Background: Hepatitis delta virus (HDV) coinfects with hepatitis B virus (HBV) causing the most severe form of viral hepatitis. However, its exact global disease burden remains largely obscure. We aim to establish the global epidemiology, infection mode-stratified disease progression, and clinical outcome of HDV infection.Methods: We conducted a meta-analysis with a random-effects model and performed data synthesis.Results: The pooled prevalence of HDV is 0.80% (95% confidence interval [CI], 0.63-1.00) among the general population and 13.02% (95% CI, 11.96-14.11) among HBV carriers, corresponding to 48-60 million infections globally. Among HBV patients with fulminant hepatitis, cirrhosis, or hepatocellular carcinoma, HDV prevalence is 26.75% (95% CI, 19.84-34.29), 25.77% (95% CI, 20.62-31.27), and 19.80% (95% CI, 10.97-30.45), respectively. The odds ratio (OR) of HDV infection among HBV patients with chronic liver disease compared with asymptomatic controls is 4.55 (95% CI, 3.65-5.67). Hepatitis delta virus-coinfected patients are more likely to develop cirrhosis than HBV-monoinfected patients with OR of 3.84 (95% CI, 1.79-8.24). Overall, HDV infection progresses to cirrhosis within 5 years and to hepatocellular carcinoma within 10 years, on average.Conclusions: Findings suggest that HDV poses a heavy global burden with rapid progression to severe liver diseases, urging effective strategies for screening, prevention, and treatment. [ABSTRACT FROM AUTHOR]

Abstract: Interferons (IFNs) with antiviral and immune-stimulatory functions have been widely used in prevention and treatment of hepatocellular carcinoma (HCC). Signal transducer and activator of transcription 1 (STAT1) is a key element of the IFN signaling, and the function of STAT1 is critically determined by its phosphorylation state. This study aims to understand the functions of phosphorylated (p-) and unphosphorylated (u-) STAT1 in HCC. We found that u-STAT1 is significantly elevated in patient HCC tumor tissues and predominantly expressed in cytoplasm; while p-STAT1 is absent. Loss of u-STAT1 potently arrested cell cycle and inhibited cell growth in HCC cells. Induction of p-STAT1 by IFN-α treatment effectively triggers the expression of interferon-stimulated genes (ISGs), but has moderate effect on HCC cell growth. Interestingly, both u-STAT1 and p-STAT1 are induced by IFN-α, through with distinct time-dependent process. Furthermore, the ISG induction patterns mediated by p-STAT1 and u-STAT1 are also distinct. Importantly, artificial blocking of the induction of u-STAT1, but not p-STAT1, sensitizes HCC cells to treatment of IFNs. Therefore, p-STAT1 and u-STAT1 exert dichotomal functions and coordinately regulate the responsiveness to IFN treatment in HCC.Key Messages: STAT1 is upregulated and predominantly presented as u-STAT1 in HCC, while p-STAT1 is absent.U-STAT1 sustains but p-STAT1 inhibits HCC growth.The dynamic change of phosphorylation state of STAT1 control the responsiveness to IFN treatment. [ABSTRACT FROM AUTHOR]

Hepatitis B breakthrough infection (HBBI) and its risk factors are rarely reported among adults in China. In 2009–2010 in three townships of China, hepatitis B vaccine (HepB) administration and anti-HBs detection after HepB were conducted among the residents aged 18–59 years. HBsAg, anti-HBs and anti-HBc were detected for these vaccinees in 2013. A total of 252 out of 4701 vaccinees turned to be positive for anti-HBc in 2013, but nobody was positive for HBsAg. The HBBI rate was 5.36% (95% CI 4.73, 6.04). The highest rate was found in age-group of 18–29 years (7.33%, 95% CI : 5.31, 9.82). The rate was significantly different by the residential townships ( P  < 0.001) and by the antibody response to HepB ( P  = 0.003). Multivariate analysis showed that anti-HBs response to HepB was the independent risk factor of HBBI. The study documents the association between hyporesponse to HepB and HBBI among adults. It also suggests more attention should be given to new HBV infection among young adults. [ABSTRACT FROM AUTHOR]

Background: Hepatitis B vaccine is an effective measure to prevent hepatitis B virus infection. Whether chronic hepatitis C virus (HCV) infection decreases humoral and cell-mediated immunity responses to hepatitis B vaccination is still controversial.Methods: Patients with chronic HCV infection who were not in treatment and healthy controls, matched at a 1:2 ratio for community, sex, and age (within 5 years), were identified from a community-based screening. All participants received 3 doses of hepatitis B vaccine. Antibody to hepatitis B surface antigen was tested 1 month after the third vaccine dose and was compared between 2 groups. Spot-forming cells (SFCs) of interferon γ and interleukin 2, 4, 5, and 6 were counted by means of enzyme-linked immunospot, and SFC counts were compared between the 2 groups.Results: The rates of nonresponse and low, normal, and high response were 3.80%, 10.13%, 45.57%, and 40.50% respectively, in the HCV group, and the corresponding rates in the healthy control group were 1.26%, 10.13%, 39.24%, and 49.37% (all P > .05). There were no significant differences in SFC counts between the 2 groups for interferon γ or interleukin 2, 4, or 5 (all P > .05).Conclusions: This study provided preliminary evidence of the good immunogenicity and safety of hepatitis B vaccination among patients in China with chronic hepatitis C who are not in treatment.Clinical Trials Registration: NCT 02898922. [ABSTRACT FROM AUTHOR]

The Cambrian SPICE (Steptoean Positive Carbon Isotope Excursion) event is widely reported from the late Miaolingian to the early Furongian, but recent studies imply that the synchroneity and magnitude of the SPICE may be controversial. In order to test the spatial variation of the SPICE, here we present 367 carbonate δ13C data from six outcrop sections across a ~700 km transect along the eastern North China Platform. The SPICE is present in all the studied sections, but showing different features regarding the duration and magnitude. An abrupt increase in δ13C from ~1.5‰ to 3.5‰ occurs in three Shandong sections, with maximum value present only in a thin (0.5–1.2 m thick) transgressive lag deposit (crudely wave stratified, bioclastic grainstone). In contrast, the δ13C record of the Baijiashan and Shashan sections in the Liaoning region displays a gradual increase (~20 m thick) from ~1.5‰ to the maximum value of 4.7‰. Both facies analysis and trilobite collections suggest that the spatial variation of the SPICE in the North China Platform most likely resulted from missing of sedimentary record (with high δ13C values) in the Shandong sections as a result of erosion and non-deposition during sea-level lowstand, a possible coeval hiatus prior to the Sauk III transgression in the Laurentian basins. Further high-resolution, integrated studies of sedimentology, biostratigraphy, and sedimentary geochemistry on the SPICE event are required to better understand its nature. • Six outcrop sections from the eastern North China Platform were studied for SPICE. • A complete SPICE (with max. value of ~4.7‰) was recorded in northeastern NCP. • Spatial variation in SPICE resulted from stratigraphic missing in Shandong region. [ABSTRACT FROM AUTHOR]

The article discusses a study aimed at determining the circulation of Hepatitis E virus (HEV) strains among yellow cattle (Bos taurus) in Shandong Province, China. In the study, blood samples from yellow cattle of local breeds as well serum samples from domestic sheep, dogs and chickens were examined for total antibodies against HEV. The study indicated the occurrence of HEV infection in yellow cattle, suggesting their role as a reservoir of HEV.

Background: Persons with chronic hepatitis B (CHB) infection were reported to suffer severe disease after hepatitis E virus (HEV) superinfection, but the studies regarding HEV seroprevalence in this population were limited. A recent study in Vietnam found higher HEV seroprevalence among CHB patients compared with healthy controls.Methods: A community-based case-control study was conducted in two counties of Shandong province, China, where hepatitis E incidence was at the highest (Rushan) and lowest (Zhangqiu) in the province based on data from routine public health surveillance. Four townships were selected randomly from each county and all residents in these townships were tested for hepatitis B surface antigen (HBsAg). Those tested positive for HBsAg (CHB group) and the 1:1 age and sex-matched HBsAg-negative residents (control group) were included. Anti-HEV IgM and IgG were tested and positive rates of IgG and IgM were compared between the CHB group and the control group.Results: In total, 2048 CHB participants and 2054 controls were included in the study. In the CHB group, HEV IgG seroprevalence was 9.16% (95% CI: 7.47-11.09) in Zhangqiue and 38.06% (95% CI: 35.07-41.19) in Rushan (P < 0.001); the corresponding rates of IgM were 0.1% (95% CI: 0.002-0.54) and 1.57% (95% CI: 0.90-2.53), respectively (P < 0.001). HEV IgG seroprevalence was similar between CHB group and the control group in both counties (P = 0.21, P = 0.47, respectively) and the same results were found for the positive rate of IgM (P = 0.103, P = 0.262, respectively). Multivariable analysis showed the status of HBsAg was not independently associated with the status of anti-HEV IgG in either Zhangqiu or Rushan [P = 0.187, OR = 1.23(95% CI: 0.90, 1.68); P = 0.609, OR = 1.05 (95% CI: 0.87, 1.26)].Conclusions: The seroprevalence of HEV varies greatly in different geographic areas, but the seroprevalence is similar between populations with and without CHB. CHB patients residing in high HEV endemic areas might be at higher risk for HBV-HEV superinfection. [ABSTRACT FROM AUTHOR]