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With the rising epidemic of obesity, metabolic syndrome, and type 2 diabetes mellitus in China, metabolic dysfunction-associated non-alcoholic fatty liver disease has become the most prevalent chronic liver disease. This condition frequently occurs in Chinese patients with alcoholic liver disease and chronic hepatitis B. To address the impending public health crisis of non-alcoholic fatty liver disease and its underlying metabolic issues, the Chinese Society of Hepatology and the Chinese Medical Association convened a panel of clinical experts to revise and update the "Guideline of prevention and treatment of non-alcoholic fatty liver disease (2018, China)". The new edition, titled "Guideline for the prevention and treatment of metabolic dysfunction-associated fatty liver disease (Version 2024)", offers comprehensive recommendations on key clinical issues, including screening and monitoring, diagnosis and evaluation, treatment, and follow-up for metabolic dysfunction-associated fatty liver disease and metabolic dysfunction-associated steatotic liver disease. Metabolic dysfunction-associated fatty liver disease is now the preferred English term and is used interchangeably with metabolic dysfunction-associated steatotic liver disease. Additionally, the guideline emphasizes the importance of multidisciplinary collaboration among hepatologists and other specialists to manage cardiometabolic disorders and liver disease effectively., Competing Interests: JGF has been an Associate Editor of Journal of Clinical and Translational Hepatology since 2013. YMN has been an Editorial Board Member of Journal of Clinical and Translational Hepatology since 2022. JDJ and LW have been Executive Associate Editors of Journal of Clinical and Translational Hepatology since 2013. CS has been an Editorial Board Member of Journal of Clinical and Translational Hepatology since 2020. JL has been an Editorial Board Member of Journal of Clinical and Translational Hepatology since 2024. The other authors have no conflict of interests related to this publication., (© 2024 Authors.)

The gut microbiota is crucial for human health, functioning as a complex adaptive system akin to a vital organ. To identify core health-relevant gut microbes, we followed the systems biology tenet that stable relationships signify core components. By analyzing metagenomic datasets from a high-fiber dietary intervention in type 2 diabetes and 26 case-control studies across 15 diseases, we identified a set of stably correlated genome pairs within co-abundance networks perturbed by dietary interventions and diseases. These genomes formed a "two competing guilds" (TCGs) model, with one guild specialized in fiber fermentation and butyrate production and the other characterized by virulence and antibiotic resistance. Our random forest models successfully distinguished cases from controls across multiple diseases and predicted immunotherapy outcomes through the use of these genomes. Our guild-based approach, which is genome specific, database independent, and interaction focused, identifies a core microbiome signature that serves as a holistic health indicator and a potential common target for health enhancement., Competing Interests: Declaration of interests L.Z. is a co-founder of Notitia Biotechnologies Company. Patent WO2023212563A1 is related to this work. Patent app. no: 63/595,189 is related to this work., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

The escalating obesity epidemic and aging population have propelled metabolic dysfunction-associated steatohepatitis (MASH) to the forefront of public health concerns. The activation of FXR shows promise to combat MASH and its detrimental consequences. However, the specific alterations within the MASH-related transcriptional network remain elusive, hindering the development of more precise and effective therapeutic strategies. Through a comprehensive analysis of liver RNA-seq data from human and mouse MASH samples, we identified central perturbations within the MASH-associated transcriptional network, including disrupted cellular metabolism and mitochondrial function, decreased tissue repair capability, and increased inflammation and fibrosis. By employing integrated transcriptome profiling of diverse FXR agonists-treated mice, FXR liver-specific knockout mice, and open-source human datasets, we determined that hepatic FXR activation effectively ameliorated MASH by reversing the dysregulated metabolic and inflammatory networks implicated in MASH pathogenesis. This mitigation encompassed resolving fibrosis and reducing immune infiltration. By understanding the core regulatory network of FXR, which is directly correlated with disease severity and treatment response, we identified approximately one-third of the patients who could potentially benefit from FXR agonist therapy. A similar analysis involving intestinal RNA-seq data from FXR agonists-treated mice and FXR intestine-specific knockout mice revealed that intestinal FXR activation attenuates intestinal inflammation, and has promise in attenuating hepatic inflammation and fibrosis. Collectively, our study uncovers the intricate pathophysiological features of MASH at a transcriptional level and highlights the complex interplay between FXR activation and both MASH progression and regression. These findings contribute to precise drug development, utilization, and efficacy evaluation, ultimately aiming to improve patient outcomes., (© 2024. The Author(s), under exclusive licence to Shanghai Institute of Materia Medica, Chinese Academy of Sciences and Chinese Pharmacological Society.)

Accurate, non-invasive, and cost-effective tools are needed to assist pulmonary nodule diagnosis and management due to increasing detection by low-dose computed tomography (LDCT). We perform genome-wide methylation sequencing on malignant and non-malignant lung tissues and designed a panel of 263 differential DNA methylation regions, which is used for targeted methylation sequencing on blood cell-free DNA (cfDNA) in two prospectively collected and retrospectively analyzed multicenter cohorts. We develop and optimize an integrative model for risk stratification of pulmonary nodules based on 40 cfDNA methylation biomarkers, age, and five simple computed tomography (CT) imaging features using machine learning approaches and validate its good performance in two cohorts. Using the two-threshold strategy can effectively reduce unnecessary invasive surgeries, overtreatment costs, and injury for patients with benign nodules while advising immediate treatment for patients with lung cancer, which can potentially improve the overall diagnosis of lung cancer following LDCT/CT screening., Competing Interests: Declaration of interests J.T., Z.Y., S.W., L.T., and J.-B.F. are current employees of AnchorDx Medical or AnchorDx., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Ginseng, with various pharmacological activities, has received increasing attention to improve cardiovascular health (CVH). Therefore, this meta-analysis synthesized the effect of ginseng consumption on biomarkers of CVH in adults. A systematic search was performed in the databases of PubMed, Scopus, Web of Science, Embase, and the Cochrane Library through July 24, 2023 to screen out English-language randomized controlled trials (RCTs) evaluating the effects of ginseng consumption on body composition, blood pressure, vascular stiffness, lipid metabolism, glucose metabolism, insulin resistance, inflammatory cytokines, and adipocytokines in adults. The weighted mean difference (WMD) and 95% confidence interval (CI) were used to evaluate the overall effect size, and STATA 12.0 was used for comprehensive analysis. Forty-five studies were included in the meta-analysis. Ginseng consumption significantly reduced systolic blood pressure (SBP) (WMD = -2.57 mmHg, 95% CI = -4.99 to -0.14, p = 0.038), total cholesterol (TC) (WMD = -4.40 mg/dL, 95% CI = -8.67 to -0.132, p = 0.043), low density lipoprotein cholesterol (LDL-C) (WMD = -2.81 mg/dL, 95% CI = -4.89 to -0.72, p = 0.008), C-reactive protein (CRP) (WMD = -0.41 mg/L, 95% CI = -0.73 to -0.10, p = 0.010), and interleukin-6 (IL-6) (WMD = -2.82 pg./mL, 95% CI = -4.31 to -1.32, p < 0.001). Subgroup analyses suggested that supplementation with ginseng for less than 12 weeks significantly reduced SBP, but 12 weeks or more improved TC and CRP. Ginseng consumption on SBP, TC, and CRP seemed to be more effective on unhealthy participants. The meta-analysis showed that ginseng consumption might have the potential to improve SBP, TC, LDL-C, CRP, and IL-6. These findings suggest that ginseng is a potential candidate for the maintenance of CVH. However, our results had high heterogeneity. Future high-quality studies are needed to firmly establish the clinical efficacy of ginseng consumption., (© 2024 John Wiley & Sons Ltd.)

A new radical relay approach for the efficient construction of alkylsulfonated indolo[2,1- a ]isoquinoline-6(5 H )-ones in moderate to good yields under mild conditions via SO 2 insertion/Smiles rearrangement/intramolecular cyclization is developed. This approach utilizes 4-alkyl substituted Hantzsch esters as alkyl radical sources and further undergoes in situ SO 2 insertion to obtain alkylsulfonyl radical species, which avoids the use of unstable alkyl sulfonyl chlorides and highly toxic sulfonyl hydrazides. Additionally, this method for the direct assembly of alkylsulfonated polycyclic molecule skeletons displays high chemical selectivity, broad substrate scope, and step-economy.

Background & Aims: Metabolic dysfunction-associated steatohepatitis (MASH) and fibrotic MASH are significant health challenges. This multi-national study aimed to validate the acMASH index (including serum creatinine and aspartate aminotransferase concentrations) for MASH diagnosis and develop a new index (acFibroMASH) for non-invasively identifying fibrotic MASH and exploring its predictive value for liver-related events (LREs)., Methods: We analyzed data from 3004 individuals with biopsy-proven metabolic dysfunction-associated fatty liver disease (MAFLD) across 29 Chinese and 9 international cohorts to validate the acMASH index and develop the acFibroMASH index. Additionally, we utilized the independent external data from a multi-national cohort of 9034 patients with MAFLD to examine associations between the acFibroMASH index and the risk of LREs., Results: In the pooled global cohort, the acMASH index identified MASH with an area under the receiver operating characteristic curve (AUROC) of 0.802 (95% confidence interval [CI], 0.786-0.818). The acFibroMASH index (including the acMASH index plus liver stiffness measurement) accurately identified fibrotic MASH with an AUROC of 0.808 in the derivation cohort and 0.800 in the validation cohort. Notably, the AUROC for the acFibroMASH index was 0.835 (95% CI, 0.786-0.882), superior to that of the FAST score at 0.750 (95% CI, 0.693-0.800; P < .01) in predicting the 5-year risk of LREs. Patients with acFibroMASH >0.39 had a higher risk of LREs than those with acFibroMASH <0.15 (adjusted hazard ratio, 11.23; 95% CI, 3.98-31.66)., Conclusions: This multi-ethnic study validates the acMASH index as a reliable, noninvasive test for identifying MASH. The newly proposed acFibroMASH index is a reliable test for identifying fibrotic MASH and predicting the risk of LREs., (Copyright © 2024 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Aim: To elucidate the effects of sleep parameters and renal function on the risk of developing new-onset severe metabolic dysfunction-associated steatotic liver disease (MASLD)., Materials and Methods: The primary analysis involved a cohort of 305 257 participants. Multivariable Cox models were employed to calculate hazard ratios and 95% confidence intervals. Traditional mediation and two-step Mendelian randomization (MR) analyses were conducted to assess the associations and mediating roles of renal function indicators between sleep and new-onset severe MASLD., Results: Poor sleep score and renal function biomarker score (RFS) were associated with an increased risk of new-onset severe MASLD (all p trend  <0.001). Participants with poor sleep patterns and the highest RFS had a 5.45-fold higher risk of new-onset severe MASLD, compared to those with healthy sleep patterns and the lowest RFS (p < 0.001). The RFS could explain 10.08% of the correlations between poor sleep score and risk of new-onset severe MASLD. Additionally, MR analyses supported a causal link between insomnia and new-onset severe MASLD and revealed a mediating role of chronic kidney disease in the connection between insomnia and new-onset severe MASLD risk., Conclusions: This study highlights the independent and combined associations of sleep parameters and renal function indicators with new-onset severe MASLD, underscoring the bidirectional communication of the liver-kidney axis and providing modifiable strategies for preventing MASLD., (© 2024 John Wiley & Sons Ltd.)

In the past 3 decades, metabolic-associated fatty liver disease (MAFLD) has emerged as a widespread liver condition, with its global prevalence on the rise. It ranks as a leading contributor to hepatocellular carcinoma (HCC) and necessitates liver transplantation. Under the multiple parallel hits model, the pathogenesis of MAFLD stems from various liver stressors, notably nutrient overload and sedentary lifestyles. While medical management for MAFLD is well-established, encompassing non-pharmaceutical and pharmaceutical interventions, determining the most effective pharmaceutical therapy has remained elusive. This review discusses diabetic medications for MAFLD treatment, emphasizing recent studies and emerging drugs while reviewing other nondiabetic agents. Emerging evidence suggests that combination therapies hold promise for resolving MAFLD and metabolic steatohepatitis (MASH) while managing side effects. Ongoing trials play a pivotal role in elucidating the effects of mono, dual, and triple receptor agonists in individuals with MASH. With the rising burden of MAFLD/MASH and its severe consequences, the need for effective treatments is more pressing than ever. This review provides a comprehensive overview of the current landscape of pharmaceutical interventions for MAFLD and MASH, shedding light on the potential of newer drugs especially diabetic medications and the importance of ongoing research in this field., (© 2024. Asian Pacific Association for the Study of the Liver.)

Background and Aims: Metabolic dysfunction-associated steatotic liver disease (MASLD) and its more advanced form, metabolic dysfunction-associated steatohepatitis, have emerged as the most prevalent liver diseases worldwide. Currently, lifestyle modification is the foremost guideline-recommended management strategy for MASLD. However, it remains unclear which detrimental signals persist in MASLD even after disease remission. Thus, we aimed to examine the persistent changes in liver transcriptomic profiles following this reversal., Methods: Male C57BL/6J mice were divided into three groups: Western diet (WD) feeding, chow diet (CD) feeding, or diet reversal from WD to CD. After 16 weeks of feeding, RNA sequencing was performed on the mice's livers to identify persistent alterations characteristic of MASLD. Additionally, RNA sequencing databases containing high-fat diet-fed P53-knockout mice and human MASLD samples were utilized., Results: WD-induced MASLD triggered persistent activation of the DNA damage response (DDR) and its primary transcription factor, P53, long after the resolution of the hepatic phenotype through dietary reversal. Elevated levels of P53 might promote apoptosis, thereby exacerbating metabolic dysfunction-associated steatohepatitis, as they strongly correlated with hepatocyte ballooning, an indicator of apoptosis activation. Moreover, P53 knockout in mice led to downregulated expression of apoptosis signaling in the liver. Mechanistically, P53 may regulate apoptosis by transcriptionally activating the expression of apoptosis-enhancing nuclease (AEN). Consistently, P53, AEN, and the apoptosis process all exhibited persistently elevated expression and showed a strong inter-correlation in the liver following dietary reversal., Conclusions: The liver demonstrated upregulation of DDR signaling and the P53-AEN-apoptosis axis both during and after exposure to WD. Our findings provide new insights into the mechanisms of MASLD relapse, highlighting DDR signaling as a promising target to prevent MASLD recurrence., Competing Interests: JGF has been an associate editor of the Journal of Clinical and Translational Hepatology since 2013. The other authors have no conflicts of interest related to this publication., (© 2024 Authors.)

Given the global prevalence and rising incidence of metabolic dysfunction-associated steatotic liver disease (MASLD), the absence of licensed medications is striking. A deeper understanding of the heterogeneous nature of MASLD has recently contributed to the discovery of novel groups of agents and the potential repurposing of currently available medications. MASLD therapies center on four major pathways. Considering the close relationship between MASLD and type 2 diabetes, the first approach involves antidiabetic medications, including incretins, thiazolidinedione insulin sensitizers, and sodium-glucose cotransporter 2 inhibitors. The second approach targets hepatic lipid accumulation and the resultant metabolic stress. Agents in this group include peroxisome proliferator-activated receptor agonists (e.g., pioglitazone, elafibranor, saroglitazar), bile acid-farnesoid X receptor axis regulators (obeticholic acid), de novo lipogenesis inhibitors (aramchol, NDI-010976), and fibroblast growth factor 21/19 analogs. The third approach focuses on targeting oxidative stress, inflammation, and fibrosis. Agents in this group include antioxidants (vitamin E), tumor necrosis factor α pathway regulators (emricasan, pentoxifylline, ZSP1601), and immune modulators (cenicriviroc, belapectin). The final group targets the gut (IMM-124e, solithromycin). Combination therapies targeting different pathogenetic pathways may provide an alternative to MASLD treatment with higher efficacy and fewer side effects. This review aimed to provide an update on these medications., Competing Interests: JGF has been an Associate Editor of Journal of Clinical and Translational Hepatology since 2013. The other authors have no conflict of interests related to this publication., (© 2024 Authors.)

This study aimed to explore the critical role of FUNDC1 on epithelial cells in model of asthma. Patients with asthma and normal healthy volunteers were obtained from our hospital. The serum of FUNDC1 mRNA expression was down-regulated in patients with asthma. Meanwhile, the serum of FUNDC1 mRNA expression was positive correlation with IgE and anti-HDM IgE protein. FUNDC1 expression in lung tissue of mice model was decreased in mice model of asthma. Sh-FUNDC1 enhanced asthma in mice model of asthma. FUNDC1 up-regulation reduced IL-4, IL-5, IL-10 and IL-13 activity levels in vitro model of asthma.FUNDC1 down-regulation promoted IL-4, IL-5, IL-10 and IL-13 activity levels in vitro model of asthma. FUNDC1 reduced ferroptosis of epithelial cells in model of asthma through the inhibition of mitochondrial damage. FUNDC1 induced FBXL2 and AR protein expression in model of asthma. FUNDC1 interlinked with FBXL2 is modified by SUMO1 at K136. FBXL2, ASN-205, GLN-204, ARG-235, and GLN-237 form hydrogen bonds with FUNDC1's ASP-15, ASP-16, GLU-25, and ARG-29, with lengths of 2.3, 3.1, 2.9, 2.3, and 2.9 Å, respectively. The induction of FBXL2 reduced the effects of Sh-FUNDC1 on asthma in mice model of asthma. The inhibition of AR reduced the effects of Sh-FUNDC1 on asthma in mice model of asthma Overall, FUNDC1 prevents ferroptosis of airway epithelial cells of asthma through FBXL2/AR/GPX4 signaling pathway of SUMO1 at K136. FUNDC1 might benefit the treatment of asthma or other pulmonary disease.

A visible-light-mediated radical cascade cyclization of N -( o -cyanobiaryl)acrylamides with oxime esters for the assembly of acyl-containing pyrido[4,3,2- gh ]phenanthridines has been developed. The present protocol tolerates a wide range of oxime esters through a single reaction via fragmentation, radical addition, nitrile insertion, and cyclization under mild conditions.

As the magic methyl effect is well acknowledged in pharmaceutical molecules, the development of simple and efficient methods for the installment of methyl groups on complex molecules is highly coveted. Hence, we provide a general strategy for radical cascade cyclization of N -( o -cyanobiaryl)acrylamides by utilizing sulfonium salts as the sources of methyl radical and merging photoredox and copper catalysis. This novel protocol can access a wide variety of methylation or remote thioether-substituted benzo-fused N -heterocycle derivatives, which can be easily transformed into diverse highly valuable sulfone and sulfoximine compounds via late-stage diversification. Moreover, to further demonstrate the synthetic utility of this conversion, the methyl(phenyl)sulfide, which serves as both raw material and byproduct, can be recovered and reused in this transformation. The scale-up experiment for the one-pot two-step process directly offers the target product in good yield under the standard conditions.

Alkali-surfactant-polymer (ASP) flooding is one of the most effective and promising ways to enhance oil recovery (EOR). The synergistic effect between alkali, surfactant, and polymer can respectively promote emulsification performance, reduce interfacial tension, and improve bulk phase viscosity, thus effectively improving flooding efficiency. However, the displacement mechanism of ASP flooding and the contribution of different components to the oil displacement effect still need further discussion. In this study, five groups of chemical slugs were injected into the fracture model after water flooding to characterize the displacement effect of weak alkali, surfactant, polymer, and their binary/ternary combinations on residual oil. Additionally, the dominant mechanism of the ASP flooding system to improve the recovery was studied. The results showed that EOR can be improved through interfacial reaction, low oil/water interfacial tension (IFT), and increased viscosity. In particular, the synergistic effect of ASP includes sweep and oil washing. As for sweep, the swept volume is expanded by the interfacial reaction between the alkali and the acidic components in Daqing crude oil, and the polymer increases the viscosity of the system. As for oil washing, the surfactant generated by the alkali cooperates with surfactants to reduce the IFT to an ultra-low level, which promotes the formation and migration of oil-in-water emulsions and increases the efficiency of oil washing. Overall, ASP can not only activate discontinuous oil ganglia in the pores within the water flooding range, but also emulsify, decompose, and migrate the continuous residual oil in the expanded range outside the water flooding. The EOR of ASP is 38.0% higher than that of water flooding. Therefore, the ASP system is a new ternary composite flooding technology with low cost, technical feasibility, and broad application prospects.

The incidence rates of hepatocellular carcinoma (HCC) have increased in recent decades. Despite advancements in therapy and early diagnosis improving short-term prognosis, long-term outcomes remain poor. Long noncoding RNAs (lncRNAs) and lipid metabolism play crucial roles in the development and progression of HCC. Enhanced lipid synthesis promotes HCC progression, and lncRNAs can reprogram the expression of lipogenic enzymes. Consequently, lipid metabolism-related (LMR)-lncRNAs regulate lipid anabolism, accelerating the onset and progression of HCC. This suggests that LMR-lncRNAs could serve as novel prognostic biomarkers and therapeutic targets., Competing Interests: Conflict-of-interest statement: All the authors have nothing to disclose., (©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.)

Several randomized controlled trials (RCTs) have investigated the effects of fermented foods on metabolic outcomes in adult patients suffering from diabetes and prediabetes. However, the results of these RCTs are conflicting. This systematic review and meta-analysis was carried out on data from RCTs to evaluate the effects of fermented foods in patients with diabetes and prediabetes. The PubMed, Web of Science, Embase, the Cochrane Library and Scopus databases were searched up to 21 June, 2022. English-language RCTs of fermented foods consumption were included which gave metabolic outcomes on body composition, glucose control, insulin sensitivity, lipid profile, as well as blood pressure. Eighteen RCTs met the inclusion criteria and 843 participants were included in the final analysis. The pooled results showed a significant reduction of fasting blood glucose (FBG), the homeostatic model assessment of insulin resistance (HOMA-IR), total cholesterol (TC), low density lipid cholesterol (LDL-C) and diastolic blood pressure (DBP) in the intervention group versus the control group. The results of this research showed that fermented foods have the potential to improve some metabolic outcomes, including FBG, HOMA-IR, TC, LDL-C, and DBP in patients with diabetes and prediabetes.

Introduction and Objectives: Fatty liver disease is a multisystem disease. Metabolic dysfunction-associated fatty liver disease (MAFLD) is a more accurate indicator of chronic kidney disease (CKD) than nonalcoholic fatty liver disease (NAFLD). However, the relationship between recently defined metabolic dysfunction-associated steatotic liver disease (MASLD) and CKD is currently unclear. The objective of this cross-sectional study was to investigate the prevalence of CKD and albuminuria among individuals diagnosed with either MAFLD or MASLD., Patients and Methods: This study involved 5,492 participants who provided biochemical marker and liver ultrasound data from the U.S. National Health and Nutrition Examination Survey (2017-2020). Multiple logistic regression analyses were conducted to assess the independent associations of nonoverlapping MAFLD and MASLD with the presence of CKD or albuminuria (urinary albumin-to-creatinine ratio ≥ 3 mg/mmol)., Results: MAFLD and MASLD were identified in 47% and 44.5% of the participants, respectively. Individuals with MAFLD-only had a greater prevalence of CKD (24.7% vs. 8.3 %, P < 0.006) and albuminuria (18.6% vs. 5%, P < 0.01) than did those with MASLD-only. Importantly, after adjusting for factors such as sex, age, ethnicity, and alcohol use, it was demonstrated that individuals in the MAFLD-only group had a 4.73-fold greater likelihood of having prevalent CKD than those in the MASLD-only group (P < 0.03)., Conclusions: The MAFLD criteria better identify patients with CKD than do the MASLD criteria. Therefore, it is suggested that the MASLD criteria be reconsidered, as currently, the justification for changing from MAFLD to MASLD criteria may not be appropriate., Competing Interests: Conflicts of interest None., (Copyright © 2024 Fundación Clínica Médica Sur, A.C. Published by Elsevier España, S.L.U. All rights reserved.)

Metabolic dysfunction-associated steatohepatitis (MASH) is considered the progressive form of metabolic dysfunction-associated steatotic liver disease, which is the leading cause of chronic liver disease in children. However, the pathogenesis of pediatric MASH remains poorly understood because of the lack of animal models. In this study, a mouse model of pediatric MASH was developed and its hepatic transcriptomic profile was characterized using spatial transcriptomics technology. C57BL/6J mice were fed a Western diet (WD) along with weekly injections of carbon tetrachloride (CCl 4 ) from the age of 3 weeks and lasting up to 8 weeks. After 5 weeks of feeding, WD + CCl 4 -treated mice showed significant liver injury without the development of insulin resistance. Histologically, WD + CCl 4 induced key features of type 2 MASH, the most common type observed in children, characterized by liver steatosis, portal inflammation, and portal fibrosis. Spatial transcriptomics analysis of liver tissues indicated that cluster 0 in the mouse from the WD + CCl 4 group was enriched in pathways associated with lipid metabolism. Further investigation revealed that cytochrome p450 2E1 was the top marker gene of cluster 0, and its expression was increased in the periportal area of mice from the WD + CCl 4 group. These findings suggest that this mouse model of pediatric MASH mirrors the histologic features of human MASH, and the up-regulation of cytochrome p450 2E1 may be linked to the disease pathogenesis., Competing Interests: Disclosure Statement None declared., (Copyright © 2024 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.)

An efficient and operationally simple oxidative radical difunctionalization of N -aryl bicyclobutyl (BCB) amides with aldehydes is described. It was found that acylated 3-spirocyclobutyl oxindoles were generated from the coupling of BCB-amides and aromatic aldehydes, while reactions gave exclusively decarbonylative alkylarylation products using alkyl aldehydes as radical precursors.

Objectives: Artesunate (ART) is a water-soluble derivative of artemisinin, which has shown anti-inflammatory, anti-tumor, and immunomodulating effects. We aimed to investigate the potential therapeutic effects and mechanisms of ART in metabolic dysfunction-associated steatohepatitis (MASH)., Methods: The mice were randomly divided into the control group, high-fat, high-cholesterol diet-induced MASH group, and the MASH treated with ART (30 mg/kg once daily) group. Liver enzymes, lipids, and histological features were compared among groups. The molecular mechanisms were studied by transcriptomic and lipidomics analyses of liver tissues., Results: The mice of the MASH group had significantly increased hepatic fat deposition and inflammation in terms of biochemical indicators and pathological manifestations than the control group. The ART-treated group had improved plasma liver enzymes and hepatic cholesterol, especially at week 4 of intervention (p < 0.05). A total of 513 differentially expressed genes and 59 differentially expressed lipids were identified in the MASH group and the MASH+ART group. Gene Ontology analysis and Kyoto Encyclopedia of Genes and Genomes pathway enrichment test showed that ART regulated glycerolipid metabolism pathway and enhanced fatty acid degradation. Peroxisome proliferator-activated receptor (PPAR)-α acted as a key transcription factor in the treatment of MASH with ART, which was confirmed by cell experiment., Conclusions: ART significantly improved fat deposition and inflammatory manifestations in MASH mice, with potential therapeutic effects. The mechanism of artemisinin treatment for MASH may involve extensive regulation of downstream genes by upstream transcription factors, such as PPAR-α, to restore hepatic lipid homeostasis., (© 2024 Chinese Medical Association Shanghai Branch, Chinese Society of Gastroenterology, Renji Hospital Affiliated to Shanghai Jiaotong University School of Medicine and John Wiley & Sons Australia, Ltd.)

Objective To investigate the effects of pterostilbene on human colon cancer LoVo cells and study the regulatory mechanism of nuclear factor E2-related factor 2 (Nrf2) in the process of pterostilbene acting on LoVo cells. Methods LoVo cells were treated with different concentrations (5,10,20,40,60,80,100 μmol/L) of pterostilbene.Cell viability,migration,invasion,and apoptosis were examined by CCK-8,scratch,Transwell,and TUNEL assays,respectively.The mitochondrial membrane potential was measured by the mitochondrial membrane potential assay kit with JC-1.The reactive oxygen species level was measured by 2',7'-dichlorofluorescein diacetate.The protein levels of Nrf2,phosphorylated Nrf2,heme oxygenase 1,and apoptotic proteins (Bcl2 and Bax) were determined by Western blotting.In addition,cell viability,Nrf2 expression,and apoptosis rate were determined after co-application of the Nrf2-specific agonist sulforaphane. Results Compared with the control group,40,60,80,100 μmol/L pterostilbene reduced the viability of LoVo cells ( P =0.014, P <0.001, P <0.001, P <0.001).Pterostilbene at 5,10,20 μmol/L did not show effects on cell viability but inhibited cell migration ( P =0.008, P <0.001, P <0.001) and invasion (all P <0.001).Pterostilbene at 40,60,80 μmol/L increased apoptosis ( P =0.014, P <0.001, P <0.001),promoted mitochondrial membrane potential depolarization ( P =0.026, P <0.001, P <0.001) and reactive oxygen species accumulation (all P <0.001),and down-regulated the expression of phosphorylated Nrf2 ( P =0.030, P <0.001, P <0.001),heme oxygenase 1 ( P =0.015, P <0.001, P <0.001),and Bcl2 ( P =0.039, P <0.001, P <0.001) in LoVo cells.Pterostilbene at 60,80 μmol/L down-regulated Nrf2 expression ( P =0.001, P <0.001) and up-regulated Bax expression (both P <0.001).The application of sulforaphane reversed the effects of pterostilbene on cell viability ( P <0.001),apoptosis ( P <0.001),and Nrf2 expression ( P =0.022). Conclusion Pterostilbene is a compound that can effectively inhibit colon cancer cells by inhibiting the Nrf2 pathway.

Background: With the implementation of the 11th edition of the International Classification of Diseases (ICD-11) and the publication of the metabolic dysfunction-associated fatty liver disease (MAFLD) nomenclature in 2020, it is important to establish consensus for the coding of MAFLD in ICD-11. This will inform subsequent revisions of ICD-11., Methods: Using the Qualtrics XM and WJX platforms, questionnaires were sent online to MAFLD-ICD-11 coding collaborators, authors of papers, and relevant association members., Results: A total of 890 international experts in various fields from 61 countries responded to the survey. We also achieved full coverage of provincial-level administrative regions in China. 77.1% of respondents agreed that MAFLD should be represented in ICD-11 by updating NAFLD, with no significant regional differences (77.3% in Asia and 76.6% in non-Asia, p = 0.819). Over 80% of respondents agreed or somewhat agreed with the need to assign specific codes for progressive stages of MAFLD (i.e. steatohepatitis) (92.2%), MAFLD combined with comorbidities (84.1%), or MAFLD subtypes (i.e., lean, overweight/obese, and diabetic) (86.1%)., Conclusions: This global survey by a collaborative panel of clinical, coding, health management and policy experts, indicates agreement that MAFLD should be coded in ICD-11. The data serves as a foundation for corresponding adjustments in the ICD-11 revision., (© 2024. Asian Pacific Association for the Study of the Liver.)

Weak measurement is employed to measure faint signals due to its capability to amplify detection results above technical noise. However, achieving high amplification effects requires accurate adjustment to the experimental system. Estimating unknown time-varying phases, accurately estimating phases, and sensitively perceiving phase changes pose challenges, demanding the system to continuously remain at the appropriate working range. To address this issue, we propose a neural network-based adaptive weak measurement scheme via single-channel light intensity detection. Through machine learning calibrating the experimental system, the reference phase can be dynamically and accurately adjusted, accommodating time-varying phase changes and ensuring the system operates optimally. Compared with traditional dual-channel weak measurement systems, the scheme reduces experimental complexity. Meanwhile, by accurately adjusting the reference phase, the scheme has higher sensitivity and estimation precision compared to the non-modulated scheme. We validate the effectiveness of the scheme in estimating the period and stochastic time-varying phase. The proposed method highlights the advancement of machine learning in weak measurement systems and can also be applied to other quantum-enhanced measurement schemes.

To tackle misdiagnosis in lung cancer screening with low-dose computed tomography (LDCT), we aimed to compile a genome atlas for differentiating benign, preinvasive, and invasive lung nodules and characterize their molecular pathogenesis. We collected 432 lung nodule tissue samples from Chinese patients, spanning benign, atypical adenomatous hyperplasia (AAH), adenocarcinoma in situ (AIS), minimally invasive adenocarcinoma (MIA), and invasive adenocarcinoma (IA). We performed comprehensive sequencing, examining somatic variants, gene expressions, and methylation levels. Our findings uncovered EGFR and TP53 mutations as key drivers in - early lung cancer development, with EGFR mutation frequency increasing with disease progression. Both EGFR mutations and EGF/EGFR hypo-methylation activated the EGFR pathway, fueling cancer growth. Transcriptome analysis identified four lung nodule subtypes (G1-4) with distinct molecular features and immune cell infiltrations: EGFR-driven G1, EGFR/TP53 co-mutation G2, inflamed G3, stem-like G4. Estrogen/androgen response was associated with the EGFR pathway, proposing a new therapy combining tyrosine kinase inhibitors with antiestrogens. Preinvasive nodules exhibited stem cell pathway enrichment, potentially hindering invasion. Epigenetic regulation of various genes was essential for lung cancer initiation and development. This study provides insights into the molecular mechanism of neoplastic progression and identifies potential diagnostic biomarkers and therapeutic targets for lung cancer., Competing Interests: Authors Minhua Peng, Jinsheng Tao, Jun Wang, Hui Li, Zhiwei Chen, Jianbing Fan, and Bo Wang are current employees of AnchorDx Medical Co., Ltd, or AnchorDx, Inc. Jinwang Wei is a current employee of Genomicare Biotechnology (Shanghai) Co., Ltd and Shanghai CreateCured Biotechnology Co., Ltd. All other authors declare no competing financial interest., (© 2024 The Author(s). MedComm published by Sichuan International Medical Exchange & Promotion Association (SCIMEA) and John Wiley & Sons Australia, Ltd.)

The frequency evaluation of collimated blue light (CBL) generated by parametric four-wave mixing (FWM) in hot atomic vapor is presented. The cesium ( 133 Cs) atoms are excited from the 6S 1/2 ground state to 8S 1/2 excited state with the 852 and 795 nm pump lasers, producing an optical field at 4.2 µm through an amplified spontaneous emission via population inversion on the 8S 1/2  → 7P 3/2 transition and the 456 nm CBL via FWM on the 7P 3/2  → 6S 1/2 transition. The frequency shift of 456 nm CBL has been measured by velocity-selective optical pumping spectral technique when the frequency of any one of two pumping lasers is tuned. The ratio of the frequency shift of 456 nm CBL to the two-photon frequency detuning of two pumping lasers is 0.8912, implying that the generated 4.2 µm light frequency is also correspondingly shifted.

Background: Non-alcoholic fatty liver disease (NAFLD) is highly prevalent in children and adolescents, particularly those with obesity. NAFLD is considered a hepatic manifestation of the metabolic syndrome due to its close associations with abdominal obesity, insulin resistance, and atherogenic dyslipidemia. Experts have proposed an alternative terminology, metabolic dysfunction-associated fatty liver disease (MAFLD), to better reflect its pathophysiology. This study aimed to develop consensus statements and recommendations for pediatric MAFLD through collaboration among international experts., Methods: A group of 65 experts from 35 countries and six continents, including pediatricians, hepatologists, and endocrinologists, participated in a consensus development process. The process encompassed various aspects of pediatric MAFLD, including epidemiology, mechanisms, screening, and management., Findings: In round 1, we received 65 surveys from 35 countries and analyzed these results, which informed us that 73.3% of respondents agreed with 20 draft statements while 23.8% agreed somewhat. The mean percentage of agreement or somewhat agreement increased to 80.85% and 15.75%, respectively, in round 2. The final statements covered a wide range of topics related to epidemiology, pathophysiology, and strategies for screening and managing pediatric MAFLD., Conclusions: The consensus statements and recommendations developed by an international expert panel serve to optimize clinical outcomes and improve the quality of life for children and adolescents with MAFLD. These findings emphasize the need for standardized approaches in diagnosing and treating pediatric MAFLD., Funding: This work was funded by the National Natural Science Foundation of China (82070588, 82370577), the National Key R&D Program of China (2023YFA1800801), National High Level Hospital Clinical Research Funding (2022-PUMCH-C-014), the Wuxi Taihu Talent Plan (DJTD202106), and the Medical Key Discipline Program of Wuxi Health Commission (ZDXK2021007)., Competing Interests: Declaration of interests M.-H.Z. has received honoraria for lectures from AstraZeneca, Hisky Medical Technologies, and Novo Nordisk and consulting fees from Boehringer Ingelheim and serves as a consultant for Eieling Technology. L.A.B. has received speaker fees from Novo Nordisk and is on the Steering Committee of ACTION Teens, a multicountry study of adolescent obesity sponsored by Novo Nordisk. All fees received are directed to L.A.B.’s hospital research cost center. M.K. is a consultant for Mirum and Medison Pharma. A.M. has received honoraria from AstraZeneca, Boehringer Ingelheim, Novo Nordisk, and Janssen. N.B.H.N. has received honoraria for lectures and the role of advisory board member (Adolescents with Obesity) from Novo Nordisk. C.M. is chairman of the board and shareholder of DeFaire Medical AB, scientific advisor and shareholder of Oriflame Wellness AB, scientific advisor of Itrim AB, scientific advisor of and speaker for Novo Nordisk, scientific advisor of Rhythm, and speaker for Astra Zeneca, Semper, and Redeye. C.D.B. has received an independent research grant from Echosens. C.G. has acted as speaker for Merck, Gilead, Abbvie, and Novo Nordisk; has served as an advisory board member for Merck, Novo Nordisk, and Gilead; and has received unrestricted research funding from Theratechnologies Inc. M.T.A.-L. has obtained a grant from Novo Nordisk and has acted in an advisory capacity for MSD and Novo Nordisk and as speaker for Novo Nordisk, Gilead, and Abbie. J.M.P. has received consulting fees from Boehringer Ingelheim, MSD, and Novo Nordisk; speaking fees from Gilead, Intercept, and Novo Nordisk; travel expenses from Gilead, Rubió, Pfizer, Astellas, MSD, CUBICIN, and Novo Nordisk; educational and research support from Madrigal, Gilead, Pfizer, Astellas, Accelerate, Novartis, Abbvie, ViiV, and MSD; and funds from European Commission/EFPIA IMI2 853966-2, IMI2 777377, H2020 847989, and ISCIII PI19/01898. J.-G.F. has received honoraria for lectures from Sanofi, Echosens, Abbott, Novartis, AstraZeneca, Hisky Medical Technologies, and Novo Nordisk; consulting fees from Allergan, Echosens, Novartis, and Terns; and research grants from Sanofi. S.S.S. serves on Mirum and Alberio advisory boards., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Introduction: Patients with clinically significant portal hypertension (CSPH) are recommended to be treated with non-selective beta-blockers (ie, carvedilol) to prevent the first hepatic decompensation event by the renewing Baveno VII consensus. CSPH is defined by hepatic venous pressure gradient (HVPG)≥10 mm Hg; however, the HVPG measurement is not widely adopted due to its invasiveness. Liver stiffness (LS)≥25 kPa can be used as a surrogate of HVPG≥10 mm Hg to rule in CSPH with 90% of the positive predicting value in majority aetiologies of patients. A compelling argument is existing for using LS≥25 kPa to diagnose CSPH and then to initiate carvedilol in patients with compensated cirrhosis, and about 5%-6% of patients under this diagnosis criteria may not be benefited from carvedilol and are at risk of lower heart rate and mean arterial pressure. Randomised controlled trial on the use of carvedilol to prevent liver decompensation in CSPH diagnosed by LS remains to elucidate. Therefore, we aimed to investigate if compensated cirrhosis patients with LS≥25 kPa may benefit from carvedilol therapy., Methods and Analysis: This study is a randomised, double-blind, placebo-controlled, multicentre trial. We will randomly assign 446 adult compensated cirrhosis patients with LS≥25 kPa and without any previous decompensated event and without high-risk gastro-oesophageal varices. Patients are randomly divided into two groups, with 223 subjects in group A and 223 subjects in group B. Group A is a carvedilol intervention group, while group B is a placebo group. All patients in both groups will receive aetiology therapies and are followed up at an interval of 6 months. The 3-year incidences of decompensated events of cirrhosis-related and liver-related death are the primary outcome. The secondary outcomes include development of each complication of portal hypertension individually (ascites, variceal bleeding or overt hepatic encephalopathy), development of spontaneous bacterial peritonitis and other bacterial infections, development of new varices, growth of small varices to large varices, delta changes in LS and spleen stiffness, change in hepatic dysfunction assessed by Child-Pugh and model for end-stage liver disease score, change in platelet count, development of hepatocellular carcinoma, development of portal vein thrombosis and adverse events with a 3-year follow-up. A predefined interim analysis will be performed to ensure that the calculation is reasonable., Ethics and Dissemination: The study protocol has been approved by the ethics committees of the Sixth People's Hospital of Shenyang (2023-05-003-01) and independent ethics committee for clinical research of Zhongda Hospital, affiliated to Southeast University (2023ZDSYLL433-P01). The results from this trial will be submitted for publication in peer-reviewed journals and will be presented at international conferences., Trial Registration Number: ChiCTR2300073864., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Type 2 diabetes mellitus (T2DM) and obstructive sleep apnea (OSA) are mutual risk factors, with both conditions inducing cognitive impairment and anxiety. However, whether OSA exacerbates cognitive impairment and anxiety in patients with T2DM remains unclear. Moreover, TREM2 upregulation has been suggested to play a protective role in attenuating microglia activation and improving synaptic function in T2DM mice. The aim of this study was to explore the regulatory mechanisms of TREM2 and the cognitive and anxiety-like behavioral changes in mice with OSA combined with T2DM., Methods: A T2DM with OSA model was developed by treating mice with a 60% kcal high-fat diet (HFD) combined with intermittent hypoxia (IH). Spatial learning memory capacity and anxiety in mice were investigated. Neuronal damage in the brain was determined by the quantity of synapses density, the number and morphology of brain microglia, and pro-inflammatory factors. For mechanism exploration, an in vitro model of T2DM combined with OSA was generated by co-treating microglia with high glucose (HG) and IH. Regulation of TREM2 on IFNAR1-STAT1 pathway was determined by RNA sequencing and qRT-PCR., Results: Our results showed that HFD mice exhibited significant cognitive dysfunction and anxiety-like behavior, accompanied by significant synaptic loss. Furthermore, significant activation of brain microglia and enhanced microglial phagocytosis of synapses were observed. Moreover, IH was found to significantly aggravate anxiety in the HFD mice. The mechanism of HG treatment may potentially involve the promotion of TREM2 upregulation, which in turn attenuates the proinflammatory microglia by inhibiting the IFNAR1-STAT1 pathway. Conversely, a significant reduction in TREM2 in IH-co-treated HFD mice and HG-treated microglia resulted in the further activation of the IFNAR1-STAT1 pathway and consequently increased proinflammatory microglial activation., Conclusions: HFD upregulated the IFNAR1-STAT1 pathway and induced proinflammatory microglia, leading to synaptic damage and causing anxiety and cognitive deficits. The upregulated TREM2 inT2DM mice brain exerted a negative regulation of the IFNAR1-STAT1 pathway. Mice with T2DM combined with OSA exacerbated anxiety via the downregulation of TREM2, causing heightened IFNAR1-STAT1 pathway activation and consequently increasing proinflammatory microglia., (© 2024. The Author(s).)

Objective: Metabolic dysfunction-associated steatotic liver disease (MASLD) is becoming an escalating health problem in pediatric populations. This study aimed to investigate the role of N-acetyltransferase 10 (NAT10) in maternal high-fat diet (HFD)-induced MASLD in offspring at early life., Methods: We generated male hepatocyte-specific NAT10 knockout (Nat10 HKO ) mice and mated them with female Nat10 fl/fl mice under chow or HFD feeding. Body weight, liver histopathology, and expression of lipid metabolism-associated genes (Srebp1c, Fasn, Pparα, Cd36, Fatp2, Mttp, and Apob) were assessed in male offspring at weaning. Lipid uptake assays were performed both in vivo and in vitro. The mRNA stability assessment and RNA immunoprecipitation were performed to determine NAT10-regulated target genes., Results: NAT10 deletion in hepatocytes of male offspring alleviated perinatal lipid accumulation induced by maternal HFD, decreasing expression levels of Srebp1c, Fasn, Cd36, Fatp2, Mttp, and Apob while enhancing Pparα expression. Furthermore, Nat10 HKO male mice exhibited reduced lipid uptake. In vitro, NAT10 promoted lipid uptake by enhancing the mRNA stability of CD36 and FATP2. RNA immunoprecipitation assays exhibited direct interactions between NAT10 and CD36/FATP2 mRNA., Conclusions: NAT10 deletion in offspring hepatocytes ameliorates maternal HFD-induced hepatic steatosis through decreasing mRNA stability of CD36 and FATP2, highlighting NAT10 as a potential therapeutic target for pediatric MASLD., (© 2024 The Obesity Society.)

A novel strategy for the difunctionalization of electron-deficient alkenes with aryl sulfonium salts to access remote sulfur-containing oxindole derivatives by using in situ-formed copper(I)-based complexes as a photoredox catalyst is presented. This method enables the generation of the C(sp 3 )-centered radicals through site selective cleavage of the C-S bond of aryl sulfonium salts under mild conditions. Moreover, the oxidation reactions of desired products provide a new strategy for the preparation of sulfoxide or sulfone-containing compounds. Importantly, this approach can be easily applied to late-stage modification of pharmaceuticals molecules.

Polycystic ovary syndrome (PCOS), a prevalent reproductive disorder in women of reproductive age, features androgen excess, ovulatory dysfunction, and polycystic ovaries. Despite its high prevalence, specific pharmacologic intervention for PCOS is challenging. In this study, we identified artemisinins as anti-PCOS agents. Our finding demonstrated the efficacy of artemisinin derivatives in alleviating PCOS symptoms in both rodent models and human patients, curbing hyperandrogenemia through suppression of ovarian androgen synthesis. Artemisinins promoted cytochrome P450 family 11 subfamily A member 1 (CYP11A1) protein degradation to block androgen overproduction. Mechanistically, artemisinins directly targeted lon peptidase 1 (LONP1), enhanced LONP1-CYP11A1 interaction, and facilitated LONP1-catalyzed CYP11A1 degradation. Overexpression of LONP1 replicated the androgen-lowering effect of artemisinins. Our data suggest that artemisinin application is a promising approach for treating PCOS and highlight the crucial role of the LONP1-CYP11A1 interaction in controlling hyperandrogenism and PCOS occurrence.

Purpose: This study aimed to investigate the influence of size and fixation options of dorsoulnar fragments on the clinical outcomes of distal radius fractures (DRFs)., Methods: This retrospective analysis was performed on 94 patients with DFR accompanied by dorsoulnar fragments, spanning the period from October 2018 to November 2022. Mean follow-up was 15.5 (range, 12-20) months. Patients were divided into small- (<5 %, n = 28), middle- (5-15 %, n = 50), and large- (>15 %, n = 16) sized groups according to articular involvement of dorsoulnar fragments determined by three-dimensional (3D) computed tomography (CT) modeling. Subdivision also took place for the presence of postoperative fragment displacement (>2 mm) and fixation methods including volar locking plate (VLP), VLP combined with dorsal hollow compression screw (VDS), and VLP combined with dorsal low-profile mini plate (VDP). The radiographic parameters (volar tilt, radial inclination, and radial height) and functional outcome measures of wrist range of motion, wrist function (DASH, PRWE), and wrist pain (VAS) were evaluated and compared between groups., Results: Fracture healing was observed in all patients at final follow-up. No instances of dorsoulnar fragment displacement were observed in patients undergoing VDS and VDP treatment and the incidence of the dorsoulnar fragment displacement was 35 % (n = 8) in small-sized group, 21 % (n = 7) in middle-sized group, and 7 % (n = 1) in large-sized group when patients were treated with VLP. In small-sized group, no significant differences were found between patients with and without dorsoulnar fragment displacement in dorsiflexion restriction (10.6 ± 2.8°, 9.1 ± 2.3°, P = 0.159), pronosupination restriction (9.6 ± 2.1°, 8.6 ± 1.7°, P = 0.188), DASH (11.5 ± 4.1, 10.7 ± 3.2, P = 0.562), PRWE (11.9 ± 4.2, 10.6 ± 3.6, P = 0.425), and VAS (1.1 ± 1.1, 0.9 ± 1.0, P = 0.528). In middle-sized combined with large-sized group, the functional outcome measures of dorsiflexion restriction (12.5 ± 3.7°, 9.8 ± 2.9°, P = 0.022), DASH (14.6 ± 5.2, 11.4 ± 3.7, P = 0.030), and PRWE (15.0 ± 4.5, 11.3 ± 3.9, P = 0.016) were superior in patients without dorsoulnar fragment displacement. In patients treated with VLPs, no significant differences were found in dorsiflexion restriction (9.8 ± 2.5°, 10.8 ± 3.5°, 9.4 ± 2.5°, P = 0.299), pronosupination restriction (9.2 ± 1.9°, 10.1 ± 2.8°, 8.9 ± 1.5°, P = 0.200), DASH (11.1 ± 3.5, 12.9 ± 4.3, 11.1 ± 3.6, P = 0.162), PRWE (11.1 ± 3.9, 12.8 ± 4.2, 10.8 ± 3.9, P = 0.188), and VAS (1.0 ± 1.0, 1.4 ± 1.1, 0.9 ± 0.9, P = 0.151) between small-sized, middle-sized, and large-sized groups. In middle-sized group, no significant differences were found in dorsiflexion restriction (10.8 ± 3.5°, 9.4 ± 2.2°, 9.4 ± 2.4°, P = 0.316); pronosupination restriction (10.1 ± 2.8°, 8.8 ± 1.9°, 9.0 ± 2.5°, P = 0.314), DASH (12.9 ± 4.3, 10.3 ± 3.7, 10.5 ± 3.7, P = 0.133), PRWE (12.8 ± 4.2, 10.4 ± 3.8, 10.6 ± 4.1, P = 0.199), and VAS (1.4 ± 1.1, 0.8 ± 0.7, 1.0 ± 1.1, P = 0.201) between subgroups of VLP, VDS, and VDP. No significant differences were found in radiographic parameters between all groups compared., Conclusion: This study indicated that the strict reduction and fixation of a dorsoulnar fragment might be not essential when its articular involvement was less than 5 %. The volar locking plate (VLP) fixation was commonly effective in treating distal radius fractures accompanied by a dorsoulnar fragment involving over 15 % of the articular surface. Additionally, the use of an additional dorsal hollow compression screw or a dorsal low-profile mini plate can get good wrist function in the early-term follow-up when the dorsoulnar fragment involve 5-15 % of the articular surface., Competing Interests: Declaration of competing interest None., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Thanks to the extensive efforts toward optimizing perovskite crystallization properties, high-quality perovskite films with near-unity photoluminescence quantum yield are successfully achieved. However, the light outcoupling efficiency of perovskite light-emitting diodes (PeLEDs) is impeded by insufficient light extraction, which poses a challenge to the further advancement of PeLEDs. Here, an anisotropic multifunctional electron transporting material, 9,10-bis(4-(2-phenyl-1H-benzo[d]imidazole-1-yl)phenyl) anthracene (BPBiPA), with a low extraordinary refractive index (n e ) and high electron mobility is developed for fabricating high-efficiency PeLEDs. The anisotropic molecular orientations of BPBiPA can result in a low n e of 1.59 along the z-axis direction. Optical simulations show that the low n e of BPBiPA can effectively mitigate the surface plasmon polariton loss and enhance the photon extraction efficiency in waveguide mode, thereby improving the light outcoupling efficiency of PeLEDs. In addition, the high electron mobility of BPBiPA can facilitate balanced carrier injection in PeLEDs. As a result, high-efficiency green PeLEDs with a record external quantum efficiency of 32.1% and a current efficiency of 111.7 cd A -1 are obtained, which provides new inspirations for the design of electron transporting materials for high-performance PeLEDs., (© 2024 Wiley‐VCH GmbH.)

Background: Nonalcoholic fatty liver disease (NAFLD) is associated with impaired renal function, and both diseases often occur alongside other metabolic disorders. However, the prevalence and risk factors for impaired renal function in patients with NAFLD remain unclear. The objective of this study was to identify the prevalence and risk factors for renal impairment in NAFLD patients., Methods: All adults aged 18-70 years with ultrasound-diagnosed NAFLD and transient elastography examination from eight Asian centers were enrolled in this prospective study. Liver fibrosis and cirrhosis were assessed by FibroScan-aspartate aminotransferase (FAST), Agile 3+ and Agile 4 scores. Impaired renal function and chronic kidney disease (CKD) were defined by an estimated glomerular filtration rate (eGFR) with value of < 90 mL/min/1.73 m 2 and < 60 mL/min/1.73 m 2 , respectively, as estimated by the CKD-Epidemiology Collaboration (CKD-EPI) equation., Results: Among 529 included NAFLD patients, the prevalence rates of impaired renal function and CKD were 37.4% and 4.9%, respectively. In multivariate analysis, a moderate-high risk of advanced liver fibrosis and cirrhosis according to Agile 3+ and Agile 4 scores were independent risk factors for CKD (P< 0.05). Furthermore, increased fasting plasma glucose (FPG) and blood pressure were significantly associated with impaired renal function after controlling for the other components of metabolic syndrome (P< 0.05). Compared with patients with normoglycemia, those with prediabetes [FPG ≥ 5.6 mmol/L or hemoglobin A1c (HbA1c) ≥ 5.7%] were more likely to have impaired renal function (P< 0.05)., Conclusions: Agile 3+ and Agile 4 are reliable for identifying NAFLD patients with high risk of CKD. Early glycemic control in the prediabetic stage might have a potential renoprotective role in these patients., Competing Interests: Competing interest Wah-Kheong Chan has served as a consultant or advisory board member for Roche, AbbVie, Boehringer Ingelheim, and Novo Nordisk, and as a speaker for Hisky Medical and Viatris. Vincent Wai-Sun Wong has served as a consultant or advisory board member for 3V-BIO, AbbVie, Allergan, Boehringer Ingelheim, Center for Outcomes Research in Liver Diseases, Echosens, Gilead Sciences, Hanmi Pharmaceutical, Intercept, Merck, Novartis, Novo Nordisk, Perspectum Diagnostics, Pfizer, ProSciento, Sagimet Biosciences, TARGET-NASH, and Terns; and as a speaker for AbbVie, Bristol-Myers Squibb, Echosens, and Gilead Sciences. Other authors have no conflict of interest., (Copyright © 2023 First Affiliated Hospital, Zhejiang University School of Medicine in China. Published by Elsevier B.V. All rights reserved.)

Objectives: To evaluate physicians' awareness and knowledge towards pediatric nonalcoholic fatty liver disease (NAFLD) and their attitude toward change in nomenclature from NAFLD to metabolic dysfunction-associated fatty liver disease (MAFLD) or metabolic dysfunction-associated steatotic liver disease (MASLD) in China., Methods: The questionnaire survey contained five parts (characteristics of the participants, epidemiology, diagnosis, management of NAFLD, and attitudes toward the nomenclature of MAFLD/MASLD). The participants included 53 hepatologists, 88 gastroenterologists (GEs), 74 endocrinologists (ENDOs), 61 primary care physicians (PCPs), and 157 pediatricians across 31 municipalities, provinces and autonomous regions of China's mainland., Results: Hepatologists saw the largest number of pediatric NAFLD patients annually (median 9 [range 1-20]), with the lowest number by PCPs (even notwithstanding one patient annually). The primary sources of pediatric NAFLD knowledge were acquired via guidelines. Hepatologists had the highest total knowledge score among all five types of physicians. Approximately one-third of nonspecialists (ENDOs and PCPs) considered liver biopsy necessary for pediatric NAFLD patients, and this percentage increased to half in specialists (hepatologists and GEs). For nonspecialists, the major barriers to the management of pediatric NAFLD were poor patient adherence to lifestyle modifications and lacking confidence in managing NAFLD. Above 90% physicians agreed to change the nomenclature NAFLD to MAFLD; however, they were not sure whether it could reduce the economic burden., Conclusions: Despite the epidemic of pediatric NAFLD in China, a significant knowledge gap remains in the identification, diagnosis, and treatment of pediatric NAFLD, particularly among frontline workers such as pediatricians and PCPs. More education programs should be carried out in the future., (© 2024 Chinese Medical Association Shanghai Branch, Chinese Society of Gastroenterology, Renji Hospital Affiliated to Shanghai Jiaotong University School of Medicine and John Wiley & Sons Australia, Ltd.)

Lonicerae japonicae flos (LJF), Lonicerae japonicae caulis (LJC), Lonicerae folium (LF) and Lonicerae fructus (LFR) are derived from Lonicera japonica Thunb., which are formed due to different medicinal parts. The efficacy of the 4 medicinal materials has similarities and differences. However, little attention has been paid to illustrate the differences in efficacy from the perspective of phytochemistry. In this study, ultra-high performance liquid chromatography coupled with hybrid quadrupole-orbitrap mass spectrometry (UPLC-Q-Exactive-Orbitrap-MS) was used to qualitatively analyze the ingredients in 4 herbs. A total of 86 compounds were plausibly or unambiguously identified, there were 54 common components among the 4 medicinal materials, and each kind of medicinal materials had its own unique components. On the basis of qualitative analysis, ultra-performance liquid chromatography coupled with triple-quadrupole tandem mass spectrometry (UPLC-QQQ-MS/MS) was used to quantitatively analyze 31 components contained in 4 medicinal materials, and principal component analysis (PCA), orthogonal partial least squares discriminant analysis (OPLS-DA) and other multivariate statistical analysis were furtherly performed for comparing the component contents. The results showed that the samples from the same parts were clustered into one group, and the samples from different medicinal parts were significantly different. The analysis of variable importance projection (VIP) value of the OPLS-DA model showed that 10 components including chlorogenic acid, secologanic acid, isochlorogenic acid A, loganin, lonicerin, loganic acid, secoxyloganin, sweroside, luteolin and rhoifolin were the main difference components among the 4 medicinal materials. The study not only lays a solid foundation for the intrinsic quality control of 4 medicinal materials and the study of different effects of the 4 medicinal materials at the phytochemical level, but also provides a basis for more rational utilization of various parts of L. japonica and expansion of medicinal resources., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)

Objectives: To establish a rat model that accurately replicates the clinical characteristics of male infertility (MI) with Liver Depression and Kidney Deficiency (LD & KD) and investigate the pathogenesis., Methods: After subjecting the rats to chronic restraint stress (CRS) and adenine treatment, a series of tests were conducted, including ethological assessments, evaluations of reproductive characteristics, measurements of biochemical parameters, histopathological examinations, and analyses of urinary metabolites. Additionally, bioinformatics predictions were performed for comprehensive analysis., Results: Compared to the control, the model exhibited significant manifestations of MI with LD & KD, including reduced responsiveness, diminished frequency of capturing estrous female rats, and absence of mounting behavior. Additionally, the kidney coefficient increased markedly, while the coefficients of the testis and epididymis decreased significantly. Sperm counts and viabilities decreased notably, accompanied by an increase in sperm abnormalities. Dysregulation of reproductive hormone levels in the serum was observed, accompanied by an upregulation of proinflammatory cytokines expressions in the liver and kidney, as well as exacerbated oxidative stress in the penile corpus cavernosum and testis. The seminiferous tubules in the testis exhibited a loose arrangement, loss of germ cells, and infiltration of inflammatory cells. Furthermore, utilizing urinary metabolomics and bioinformatics analysis, 5 key biomarkers and 2 crucial targets most closely linked to MI were revealed., Conclusion: The study successfully established a clinically relevant animal model of MI with LD & KD. It elucidates the pathogenesis of the condition, identifies key biomarkers and targets, and provides a robust scientific foundation for the prediction, diagnosis, and treatment of MI with LD & KD., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Shen et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

2-Aminobenzothiazoles are commonly encountered in various functional compounds. Herein, we disclose an electro-oxidative three-component reaction for the effective synthesis of 2-aminobenzothiazoles under mild conditions, utilizing non-toxic and abundant elemental sulfur as the sulfur source. Both aliphatic amines and aryl amines demonstrate good compatibility at room temperature, highlighting the broad functional group tolerance of this approach. Additionally, elemental selenium demonstrated reactivities comparable to those of elemental sulfur.

Importance: Metabolic dysfunction-associated steatotic liver disease (MASLD) is currently the most common chronic liver disease worldwide. It is important to develop noninvasive tests to assess the disease severity and prognosis., Objective: To study the prognostic implications of baseline levels and dynamic changes of the vibration-controlled transient elastography (VCTE)-based scores developed for the diagnosis of advanced fibrosis (Agile 3+) and cirrhosis (Agile 4) in patients with MASLD., Design, Setting, and Participants: This cohort study included data from a natural history cohort of patients with MASLD who underwent VCTE examination at 16 tertiary referral centers in the US, Europe, and Asia from February 2004 to January 2023, of which the data were collected prospectively at 14 centers. Eligible patients were adults aged at least 18 years with hepatic steatosis diagnosed by histologic methods (steatosis in ≥5% of hepatocytes) or imaging studies (ultrasonography, computed tomography or magnetic resonance imaging, or controlled attenuation parameter ≥248 dB/m by VCTE)., Main Outcomes and Measures: The primary outcome was liver-related events (LREs), defined as hepatocellular carcinoma or hepatic decompensation (ascites, variceal hemorrhage, hepatic encephalopathy, or hepatorenal syndrome), liver transplant, and liver-related deaths. The Agile scores were compared with histologic and 8 other noninvasive tests., Results: A total of 16 603 patients underwent VCTE examination at baseline (mean [SD] age, 52.5 [13.7] years; 9600 [57.8%] were male). At a median follow-up of 51.7 (IQR, 25.2-85.2) months, 316 patients (1.9%) developed LREs. Both Agile 3+ and Agile 4 scores classified fewer patients between the low and high cutoffs than most fibrosis scores and achieved the highest discriminatory power in predicting LREs (integrated area under the time-dependent receiver-operating characteristic curve, 0.89). A total of 10 920 patients (65.8%) had repeated VCTE examination at a median interval of 15 (IQR, 11.3-27.7) months and were included in the serial analysis. A total of 81.9% of patients (7208 of 8810) had stable Agile 3+ scores and 92.6% of patients (8163 of 8810) had stable Agile 4 scores (same risk categories at both assessments). The incidence of LREs was 0.6 per 1000 person-years in patients with persistently low Agile 3+ scores and 30.1 per 1000 person-years in patients with persistently high Agile 3+ scores. In patients with high Agile 3+ score at baseline, a decrease in the score by more than 20% was associated with substantial reduction in the risk of LREs. A similar trend was observed for the Agile 4 score, although it missed more LREs in the low-risk group., Conclusions and Relevance: Findings of this study suggest that single or serial Agile scores are highly accurate in predicting LREs in patients with MASLD, making them suitable alternatives to liver biopsy in routine clinical practice and in phase 2b and 3 clinical trials for steatohepatitis.

Inflammation in the bone marrow (BM) microenvironment is a constitutive component of leukemogenesis in acute myeloid leukemia (AML). Current evidence suggests that both leukemic blasts and stroma secrete proinflammatory factors that actively suppress the function of healthy hematopoietic stem and progenitor cells (HSPCs). HSPCs are also cellular components of the innate immune system, and we reasoned that they may actively propagate the inflammation in the leukemic niche. In two separate congenic models of AML we confirm by evaluation of the BM plasma secretome and HSPC-selective single-cell RNA sequencing (scRNA-Seq) that multipotent progenitors and long-lived stem cells adopt inflammatory gene expression programs, even at low leukemic infiltration of the BM. In particular, we observe interferon gamma (IFN-γ) pathway activation, along with secretion of its chemokine target, CXCL10. We show that AML-derived nanometer-sized extracellular vesicles (EV AML ) are sufficient to trigger this inflammatory HSPC response, both in vitro and in vivo. Altogether, our studies indicate that HSPCs are an unrecognized component of the inflammatory adaptation of the BM by leukemic cells. The pro-inflammatory conversion and long-lived presence of HSPCs in the BM along with their regenerative re-expansion during remission may impact clonal selection and disease evolution., (© 2024. The Author(s).)

In situ transcriptomic techniques promise a holistic view of tissue organization and cell-cell interactions. There has been a surge of multiplexed RNA in situ mapping techniques but their application to human tissues has been limited due to their large size, general lower tissue quality and high autofluorescence. Here we report DART-FISH, a padlock probe-based technology capable of profiling hundreds to thousands of genes in centimeter-sized human tissue sections. We introduce an omni-cell type cytoplasmic stain that substantially improves the segmentation of cell bodies. Our enzyme-free isothermal decoding procedure allows us to image 121 genes in large sections from the human neocortex in <10 h. We successfully recapitulated the cytoarchitecture of 20 neuronal and non-neuronal subclasses. We further performed in situ mapping of 300 genes on a diseased human kidney, profiled >20 healthy and pathological cell states, and identified diseased niches enriched in transcriptionally altered epithelial cells and myofibroblasts., (© 2024. The Author(s).)

A visible-light-induced radical alkylarylation of N -aryl bicyclobutyl amides with α-carbonyl alkyl bromides for the synthesis of functionalized 3-spirocyclobutyl oxindoles is described in which β-selective radical addition of the alkyl radical to N -aryl bicyclobutyl amides forms a key radical intermediate followed by interception with intrinsic arene functional group. This approach can be applicable to a wide range of α-carbonyl alkyl bromides, including primary, secondary, and tertiary α-bromoalkyl esters, ketones, nitriles, and nitro compounds.

Background & Aims: Patients with nonalcoholic fatty liver disease (NAFLD)/metabolic dysfunction-associated steatotic liver disease (MASLD) face a multifaceted disease burden which includes impaired health-related quality of life (HRQL) and potential stigmatization. We aimed to assess the burden of liver disease in patients with NAFLD and the relationship between experience of stigma and HRQL., Methods: Members of the Global NASH Council created a survey about disease burden in NAFLD. Participants completed a 35-item questionnaire to assess liver disease burden (LDB) (seven domains), the 36-item CLDQ-NASH (six domains) survey to assess HRQL and reported their experience with stigmatization and discrimination., Results: A total of 2,117 patients with NAFLD from 24 countries completed the LDB survey (48% Middle East and North Africa, 18% Europe, 16% USA, 18% Asia) and 778 competed CLDQ-NASH. Of the study group, 9% reported stigma due to NAFLD and 26% due to obesity. Participants who reported stigmatization due to NAFLD had substantially lower CLDQ-NASH scores (all p <0.0001). In multivariate analyses, experience with stigmatization or discrimination due to NAFLD was the strongest independent predictor of lower HRQL scores (beta from -5% to -8% of score range size, p < 0.02). Experience with stigmatization due to obesity was associated with lower Activity, Emotional Health, Fatigue, and Worry domain scores, and being uncomfortable with the term "fatty liver disease" with lower Emotional Health scores (all p < 0.05). In addition to stigma, the greatest disease burden as assessed by LDB was related to patients' self-blame for their liver disease., Conclusions: Stigmatization of patients with NAFLD, whether it is caused by obesity or NAFLD, is strongly and independently associated with a substantial impairment of their HRQL. Self-blame is an important part of disease burden among patients with NAFLD., Impact and Implications: Patients with nonalcoholic fatty liver disease (NAFLD), recently renamed metabolic dysfunction-associated steatotic liver disease (MASLD), may experience impaired health-related quality of life and stigmatization. Using a specifically designed survey, we found that stigmatization of patients with NAFLD, whether it is caused by obesity or the liver disease per se , is strongly and independently associated with a substantial impairment of their quality of life. Physicians treating patients with NAFLD should be aware of the profound implications of stigma, the high prevalence of self-blame in the context of this disease burden, and that providers' perception may not adequately reflect patients' perspective and experience with the disease., Competing Interests: ZMY: research funding or consultation fees from AstraZeneca, Boehringer Ingelheim, Bristol Myers Squibb, Cymabay, GlaxoSmithKline, Intercept, Novo Nordisk, Siemens, Madrigal, Merck; YY: consulting/advisory board for Novo Nordisk, Cymabay, and Zydus. VWSW: served as a consultant or advisory board member for AbbVie, Boehringer Ingelheim, Echosens, Gilead Sciences, Intercept, Inventiva, Novo Nordisk, Pfizer, Sagimet Biosciences, TARGET PharmaSolutions, Visirna, speaker for Abbott, AbbVie, Gilead Sciences, Novo Nordisk, Unilab, received a research grant from Gilead Sciences, co-founder of Illuminatio Medical Technology Limited; AMA: grant funding from NIH, Novo Nordisk, Target Pharma, consulting/advisory board for Novo Nordisk. JMS: consultant for Astra Zeneca, Apollo Endosurgery, Bayer, Boehringer Ingelheim, BMS, Gilead Sciences, GSK, Intercept Pharmaceuticals, Ipsen, Inventiva Pharma, Madrigal, MSD, Northsea Therapeutics, Novartis, Novo Nordisk, Pfizer, Roche, Sanofi, Siemens Healthineers, receives research funding from Gilead Sciences, Boehringer Ingelheim, Siemens Healthcare GmbH, has stock options of AGED diagnostics, Hepta Bio, received speaker honorarium from Boehringer Ingelheim, Echosens, MedPublico GmbH, Novo Nordisk, Madrigal Pharmaceuticals, Histoindex, MedPublico GmbH. CWS: speaker bureau fees from Gilead Sciences, Abbott; RL: receives funding support from NCATS, NIDDK, NHLBI, serves as a consultant to Aardvark Therapeutics, Altimmune, Amgen, Arrowhead Pharmaceuticals, AstraZeneca, Eli Lilly, Gilead, Glympse bio, Inipharma, Intercept, Inventiva, Ionis, Janssen Inc., Madrigal, Novo Nordisk, Merck, Pfizer, Sagimet, Theratechnologies, 89 bio, Takeda, Terns Pharmaceuticals and Viking Therapeutics. In addition, his institution received research grants from Arrowhead Pharmaceuticals, Astrazeneca, Boehringer-Ingelheim, Bristol-Myers Squibb, Eli Lilly, Galectin Therapeutics, Gilead, Intercept, Hanmi, Intercept, Inventiva, Ionis, Janssen, Madrigal Pharmaceuticals, Merck, Novo Nordisk, Pfizer, Sonic Incytes, Terns Pharmaceuticals, co-founder of LipoNexus Inc. PC: received research grants by MSD and Intercept. JVL reports grants from AbbVie, MSD, Gilead Sciences and Roche Diagnostics to his institution and speaker fees from Echosens, Gilead Sciences, and Novo Nordisk. SF: holds a senior clinical investigator fellowship from the Research Foundation Flanders (FWO) (1802154N). His institution has received grants from Astellas, Falk Pharma, Genfit, Gilead Sciences, GlympsBio, Janssens Pharmaceutica, Inventiva, Merck Sharp & Dome, Pfizer, Roche. He has acted as consultant for Abbvie, Actelion, Aelin Therapeutics, AgomAb, Aligos Therapeutics, Allergan, Alnylam, Astellas, Astra Zeneca, Bayer, Boehringer Ingelheim, Bristoll-Meyers Squibb, CSL Behring, Coherus, Echosens, Dr. Falk Pharma, Eisai, Enyo, Galapagos, Galmed, Genetech, Genfit, Genflow Biosciences, Gilead Sciences, Intercept, Inventiva, Janssens Pharmaceutica, PRO.MED.CS Praha, Julius Clinical, Madrigal, Medimmune, Merck Sharp & Dome, Mursla Bio, NGM Bio, Novartis, Novo Nordisk, Promethera, Roche, Siemens Healthineers. SF has been lecturer for Abbvie, Allergan, Bayer, Eisai, Genfit, Gilead Sciences, Janssens Cilag, Intercept, Inventiva, Merck Sharp & Dome, Novo Nordisk, Promethera, Siemens. AKS: Reports personal fees from Medscape Gastroenterology, Chronic Liver Disease Foundation, Medical Speakers Network, Up-to-Date; non-financial support from American Association for Study of Liver Diseases (AASLD), American College of Gastroenterology, and American Porphyria Foundation; grants from American College of Gastroenterology and National Institute of Health (NIAAA and NIDDK). Dr. Singal is a consultant on the SBIR grant for Pleiogenix pharmaceuticals and is DSMB member for phase 2-b trial of DUR-928 in alcoholic hepatitis for Durect Pharmaceuticals. In addition, apart from a steering committee member of the portal hypertension SIG and chair of the alcohol-associated liver disease SIG (2020-2022) of the AASLD, Dr. Singal currently is vice chair of the liver and biliary section of the AGA Council. None of these disclosures conflict with this activity. LC reports lecture fees from Echosens, Gilead, Inventiva and Novo Nordisk, consultancy fees from Echosens, Novo Nordisk, Madrigal, MSD, Pfizer, Sagimet, and Siemens. NA: Grant/research support from 89Bio, AbbVie/Allergan, Akero, Better Therapeutics, Boehringer Ingelheim, Bristol-Myers Squibb, Corcept, DSM, Galectin, Genentech, Genfit, Gilead, Hepagene, Healio, Intercept, Inventiva, Ionis, Madrigal, Merck, NGM, Noom, NorthSea, Novo Nordisk, Perspectum, Pfizer, Poxel, Viking, and Zydus; speaker’s fees from AbbVie/Allergan, Alexion, Echosens, Eisai, Exelixis, Gilead, Intercept, Perspectum, Salix, and Theratechnologies; Consultant for AbbVie/Allergan, Echosens, Fibronostics, Gilead, Intercept, Madrigal, Novo Nordisk, Perspectum, Pfizer, and Zydus. MEK: investigator/speaker/advisory board member: AstraZeneca, Roche, MSD, AbbVie, Eva, Mash Premier, Takeda, Organon, AUG, Inspire, HSO, Gilead, Janssen, Intercept, Rameda, Ipsen, Onxeo, MinaPharm, Pharco, Zeta, Alfa Cure, Bayer, Oncoustics, PDC, and Spimaco. JMS: Consultant - Astra Zeneca, Apollo Endosurgery, Bayer, Boehringer Ingelheim, Gilead Sciences, GSK, Intercept Pharmaceuticals, Ipsen, Inventiva Pharma, Madrigal, MSD, Northsea Therapeutics, Novartis, Novo Nordisk, Pfizer, Roche, Sanofi, Siemens Healthineers. Research Funding: Gilead Sciences, Boehringer Ingelheim, Siemens Healthcare GmbH. Stock Options: AGED diagnostics, Hepta Bio. Speaker Honorarium: Boehringer Ingelheim, Echosens, MedPublico GmbH, Novo Nordisk, Madrigal Pharmaceuticals, Histoindex, MedPublico GmbH. MK: Research grants: Madrigal + consulting and speaking, Akero, Cymabay, Inventiva, Intercept + consulting and speaking.Gilead + consulting and speaking, Viking, Bio89, Ipsen + consulting, Genfit, Bausch + consulting, Ionis, North Sea,Celgene,Genentech, High Tide, Tobira-Allergan, Abbvie + consulting and speaking, NOT research. MLY: Research support (grant) from Abbvie, BMS, Gilead, Merck and Roche diagnostics; Consultant of Abbvie, BMS, Gilead, Roche and Roche diagnostics; Speaker of Abbvie, BMS, Eisai, Gilead, Roche and Roche diagnostics. S.Z-S has given a onetime presentation for and received support for attending meetings and/or travel from AbbVie, and a onetime consultation for Siemens, outside of the submitted work. PNN discloses the following financial relationship(s) on behalf of the University of Birmingham with a commercial interest: Grant/research support from Boehringer Ingelheim and Novo Nordisk; Consulting fees from Astra Zeneca, Boehringer Ingelheim, BMS, Gilead, GSK, Intercept, Madrigal, Novo Nordisk, Pfizer, Poxel Pharmaceuticals and Sun Pharma. Other coauthors report no conflicts of interest related to this study. Please refer to the accompanying ICMJE disclosure forms for further details., (© 2024 The Authors.)

Background & Aims: Patients with fatty liver disease may experience stigma from the disease or comorbidities. In this cross-sectional study, we aimed to understand stigma among patients with nonalcoholic fatty liver disease (NAFLD)/nonalcoholic steatohepatitis (NASH) and healthcare providers., Methods: Members of the Global NASH Council created two surveys about experiences/attitudes toward NAFLD and related diagnostic terms: a 68-item patient and a 41-item provider survey., Results: Surveys were completed by 1,976 patients with NAFLD across 23 countries (51% Middle East/North Africa [MENA], 19% Europe, 17% USA, 8% Southeast Asia, 5% South Asia) and 825 healthcare providers (67% gastroenterologists/hepatologists) across 25 countries (39% MENA, 28% Southeast Asia, 22% USA, 6% South Asia, 3% Europe). Of all patients, 48% ever disclosed having NAFLD/NASH to family/friends; the most commonly used term was "fatty liver" (88% at least sometimes); "metabolic disease" or "MAFLD" were rarely used (never by >84%). Regarding various perceptions of diagnostic terms by patients, there were no substantial differences between "NAFLD", "fatty liver disease (FLD)", "NASH", or "MAFLD". The most popular response was being neither comfortable nor uncomfortable with either term (56%-71%), with slightly greater discomfort with "FLD" among the US and South Asian patients (47-52% uncomfortable). Although 26% of patients reported stigma related to overweight/obesity, only 8% reported a history of stigmatization or discrimination due to NAFLD. Among providers, 38% believed that the term "fatty" was stigmatizing, while 34% believed that "nonalcoholic" was stigmatizing, more commonly in MENA (43%); 42% providers (gastroenterologists/hepatologists 45% vs. 37% other specialties, p = 0.03) believed that the name change to metabolic dysfunction-associated steatotic liver disease (or MASLD) might reduce stigma. Regarding the new nomenclature, the percentage of providers reporting "steatotic liver disease" as stigmatizing was low (14%)., Conclusions: The perception of NAFLD stigma varies among patients, providers, geographic locations and sub-specialties., Impact and Implications: Over the past decades, efforts have been made to change the nomenclature of nonalcoholic fatty liver disease (NAFLD) to better align with its underlying pathogenetic pathways and remove any potential stigma associated with the name. Given the paucity of data related to stigma in NAFLD, we undertook this global comprehensive survey to assess stigma in NAFLD among patients and providers from around the world. We found there is a disconnect between physicians and patients related to stigma and related nomenclature. With this knowledge, educational programs can be developed to better target stigma in NAFLD among all stakeholders and to provide a better opportunity for the new nomenclature to address the issues of stigma., Competing Interests: Conflict of interest ZMY: research funding or consultation fees from AstraZeneca, Boehringer Ingelheim, Bristol Myers Squibb, Cymabay, GlaxoSmithKline, Intercept, Novo Nordisk, Siemens, Madrigal, Merck; VWSW: served as a consultant or advisory board member for AbbVie, Boehringer Ingelheim, Echosens, Gilead Sciences, Intercept, Inventiva, Novo Nordisk, Pfizer, Sagimet Biosciences, TARGET PharmaSolutions, Visirna, speaker for Abbott, AbbVie, Gilead Sciences, Novo Nordisk, Unilab, received a research grant from Gilead Sciences, co-founder of Illuminatio Medical Technology Limited; AMA: grant funding from NIH, Novo Nordisk, Target Pharma, consulting/advisory board for Novo Nordisk; JMS: consultant for Astra Zeneca, Apollo Endosurgery, Bayer, Boehringer Ingelheim, BMS, Gilead Sciences, GSK, Intercept Pharmaceuticals, Ipsen, Inventiva Pharma, Madrigal, MSD, Northsea Therapeutics, Novartis, Novo Nordisk, Pfizer, Roche, Sanofi, Siemens Healthineers, receives research funding from Gilead Sciences, Boehringer Ingelheim, Siemens Healthcare GmbH, has stock options of AGED diagnostics, Hepta Bio, received speaker honorarium from Boehringer Ingelheim, Echosens, MedPublico GmbH, Novo Nordisk, Madrigal Pharmaceuticals, Histoindex, MedPublico GmbH; CWS: speaker bureau fees from Gilead Sciences, Abbott; RL: receives funding support from NCATS, NIDDK, NHLBI, serves as a consultant to Aardvark Therapeutics, Altimmune, Amgen, Arrowhead Pharmaceuticals, AstraZeneca, Eli Lilly, Gilead, Glympse bio, Inipharma, Intercept, Inventiva, Ionis, Janssen Inc., Madrigal, Novo Nordisk, Merck, Pfizer, Sagimet, Theratechnologies, 89 bio, Takeda, Terns Pharmaceuticals and Viking Therapeutics. In addition, his institution received research grants from Arrowhead Pharmaceuticals, Astrazeneca, Boehringer-Ingelheim, Bristol-Myers Squibb, Eli Lilly, Galectin Therapeutics, Gilead, Intercept, Hanmi, Intercept, Inventiva, Ionis, Janssen, Madrigal Pharmaceuticals, Merck, Novo Nordisk, Pfizer, Sonic Incytes, Terns Pharmaceuticals, co-founder of LipoNexus Inc; PC: received research grants by MSD and Intercept. Other coauthors report no conflicts of interest related to this study. Please refer to the accompanying ICMJE disclosure forms for further details., (Copyright © 2023 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.)