Browse Articles

Advances in the treatment of hepatocellular carcinoma: An overview of the current and evolving therapeutic landscape for clinicians

Abstract Hepatocellular carcinoma (HCC) is the sixth most common malignancy and the third leading cause of cancer‐related death worldwide. Contemporary advances in systemic and locoregional therapies have led to changes in peer‐reviewed guidelines regarding systemic therapy as well as the possibility of downstaging disease that may enable some patients with advanced disease to ultimately undergo partial hepatectomy or transplantation with curative intent. This review focuses on all modalities of therapy for HCC, guided by modern‐day practice‐changing randomized data where available. The surgical management of HCC, including resection and transplantation, both of which have evolving criteria for what is considered biologically resectable and transplantable, as well as locoregional therapy (i.e., therapeutic embolization, ablation, radiation, and hepatic arterial infusion), are discussed. Historical and modern‐day practice‐changing trials evaluating immunotherapy with targeted therapies for advanced disease, as well as adjuvant systemic therapy, are also summarized. In addition, this article examines the critical dimension of toxicities and patient‐oriented considerations to ensure a comprehensive and balanced discourse on treatment implications.

Structural architecture of the human long non-coding RNA-PAAN as a potential target for anti-influenza drug development

Dysregulated serum chloride and clinical outcomes in critically ill adults: A systematic review and meta-analysis

Dysregulated serum chloride levels are prevalent in critically ill patients. However, their clinical impact remains unclear. This first systematic review and meta-analysis quantified the prevalence of hypochloremia and hyperchloremia, and their associations with mortality and acute kidney injury (AKI) in critically ill populations. We searched PubMed, Embase, Web of Science, and the Cochrane Library for studies reporting hyperchloremia prevalence or outcomes in adult ICU patients until August 2025. Statistical analyses were conducted using Stata v16.0, and study quality was assessed using the Newcastle-Ottawa Scale. 34 studies (n = 175,021 patients) were included. The aggregated prevalence of hyperchloremia was 34% (95% CI [26%−43%]) and hypochloremia was 14% (95% CI [1%−28%]). Meta-analysis demonstrated that both hyperchloremia and hypochloremia were significantly associated with increased mortality, conferring a 28% (OR = 1.28, 95% CI [1.08–1.52]) and 55% (OR = 1.55%, 95% CI [1.33–1.81]) elevated risk for mortality, respectively. Crucially, a dose-response analysis revealed a non-linear relationship between serum chloride levels and mortality, confirming that the risk is independently elevated at both extremes. Furthermore, hyperchloremia was linked to an increased risk of AKI (OR = 1.40, 95% CI [1.07–1.85]). These findings establish dysregulated serum chloride as a common and clinically significant biomarker, underscoring the necessity of monitoring and managing both high and low chloride levels in critically ill patients. Future large-scale studies are warranted to validate these results and elucidate the mechanistic pathways linking chloride dysregulation to such adverse outcomes.

Redox partner adrenodoxin induces substrate binding to steroidogenic cytochrome P450 11B2 and 11A1 by promoting a conformational change

Deciphering Mn ²⁺ Solvation and Interfacial Chemistry for Rechargeable Nonaqueous Mn‐Metal Batteries

Abstract Manganese emerges as a compelling metal anode for multivalent ion batteries given its favorable redox potential (−1.18 V vs standard hydrogen electrode), high theoretical specific capacity (976 mAh g −1 ), and large abundance. However, its practical deployment is hindered by kinetic challenges, including strong Mn 2+ solvation effects, electron repulsion from the half‐filled 3d orbital, and surface passivation of oxide layer, which collectively contribute to excessive overpotential during the Mn plating/stripping process. To address these challenges, herein, we propose a synergistic strategy integrating Mn 2+ solvation regulation using 2‐methoxyethylamine (MOEA) and electrode interfacial engineering with indium nitride (InN). Spectroscopic and theoretical analyses reveal that MOEA‐regulated Mn 2+ solvation sheath reduces the energy barrier associated with charge transfer, while InN‐coated Mn anode leverages abundant nucleation sites to facilitate Mn deposition. These concerted effects enable remarkable plating/stripping stability of Mn||Mn symmetric cells over 3400 h under 0.2 mA cm −2 and 0.2 mAh cm −2 . Full cells pairing Mn anodes with pyrene–4,5,9,10–tetraone (PTO) cathodes further validate the strategy's efficacy, delivering a specific capacity of 144 mAh g −1 at 100 mA g −1 and a stable cycling for 400 cycles. This work provides fundamental insights into Mn 2+ solvation and interfacial chemistry for rechargeable Mn‐metal batteries.

Multicomponent Synthesis on a Diiron Platform of Stable Ferrabenzenes with Promising Anticancer Activity

Abstract Despite extensive research on metallabenzenes, ferrabenzenes have remained elusive, with only a single example reported to date, discovered accidentally. In this work, we present a reproducible, room‐temperature reaction on a diiron bis‐cyclopentadienyl platform, providing access to a class of four substituted ferrabenzenes ( 5a‐c ), stabilized by η 6 ‐coordination to a second iron fragment. This synthesis involves a one‐pot double C─C coupling of iminium, carbene (from a diazo compound), and carbon monoxide moieties, yielding ferra‐cyclohexadienone derivatives ( 4a‐c ), followed by O ‐alkylation with alkyl triflates. Experimental and computational studies enabled the proposal of a plausible reaction mechanism. Combined X‐ray crystallography, nuclear magnetic resonance (NMR), and computational data support the aromatic character of the ferrabenzene ring in compounds 5a‐c and, to a lesser extent, in their precursors 4a‐c . Complexes 4a‐c and 5a‐c were further characterized by IR spectroscopy, mass spectrometry, and IR spectroelectrochemistry. A selection of ferrabenzenes ( 5a , 5b , 5aEt ) revealed physicochemical properties suitable for biological applications, including permanent air stability, adequate aqueous solubility and stability, and balanced hydrophilic/lipophilic profile. These compounds exhibited potent cytotoxicity in vitro against three cancer cell lines, with 5aEt standing out for its pronounced activity, attributed to disruption of cell redox homeostasis, and marked selectivity compared to two noncancerous cell lines.

A reliable in vitro rumen culture system and workflow for screening anti-methanogenic compounds

Arguably the biggest man-made challenge of the century is halting climate change. Livestock’s methane (CH 4 ) emissions, a greenhouse gas with a higher global warming potential than carbon dioxide (CO 2 ), represent a prime target for reducing anthropogenic impact. While the reduction of enteric methane emissions through feed additives has been demonstrated, potent and affordable compounds inhibiting methanogenesis in ruminants are not yet well established. Reliable methods for reproducible cultivation of the rumen microbiome in the laboratory are an essential tool for the study of methanogenesis. We have developed a versatile setup that allows for the cultivation of the ruminal microbiome in a benchtop configuration and combines, miniaturizes, and improves existing systems. The design is based on standard laboratory equipment, including bottles, serological pipettes, tubing, and Luer-Lock valves. The apparatus enables long-term cultivation of primary cultures extracted from the rumen of slaughtered cattle. We describe rumen content acquisition, preparation, the cultivation procedure, and demonstrate the system’s performance. The efficacy of the system is demonstrated through the administration of various concentrations of state-of-the-art methanogenesis inhibitors. These inhibitors include lyophilized Asparagopsis taxiformis (AT), bromoform (BF), iodoform (IF), 3-nitrooxypropanol (3-NOP), rapeseed oil, and BF dissolved in rapeseed oil, with maximum CH 4 reductions of 96.29% (p = 5.00E-05, Cohen’s d = 30.29) , 98.22% (p = 2.88E-05, d = 23.07) , 96.26% (p = 1.03E-05, d = 30.29) , 74.63% (p = 8.88E-05, d = 13.32) , 28.96% (p = 0.001, d = 3.99), and 98.51% (p = 4.18E-06, d = 39.94) , respectively, in comparison to the negative control. The gas production dynamics in our setup align with previously published results, which supports the validity of the system. Compared to conventional methodologies, the described setup offers enhanced versatility and ease of use. Furthermore, Fourier-transform-infrared-spectroscopy is implemented in a novel and low-cost approach for quantifying CH₄ and CO₂ in the headspace gas. Together, these methodological advances provide an accessible and reproducible platform for long-term in vitro rumen cultivation for the screening of anti-methanogenic additives.

Mechanisms underlying centriole stability

A mathematical model of HCV transmission dynamics with sex stratification and environmental effects

This study primarily aims to determine how sex-specific behaviors influence Hepatitis C Virus (HCV) transmission dynamics among people who inject drugs (PWID), and to identify key parameters and interventions that most effectively reduce infection prevalence. Despite the availability of effective treatment, HCV remains a major public health challenge particularly among PWID, with sex-specific differences influencing the transmission dynamics. In this study, we developed a sex-structured deterministic mathematical model to investigate HCV transmission through contaminated needles, focusing on gender-specific patterns among PWID. Unlike previous models, our work separates transmission by sex and also captures differences between high-risk and low-risk injecting behavior through transmission and needle reuse parameters.The model classifies the population into distinct HCV related compartments for both males and females, while also incorporating an environmental pool of contaminated needles. We computed and analyzed the systems reproduction threshold and steady states, identifying conditions under which the disease persists and scenarios where backward bifurcation may occur. Sensitivity analysis identified the most influential factors on acute infection prevalence, such as rates of needle contamination, sex-specific contact behaviors, and recovery outcomes among males. Simulation results show that males experience a higher burden of acute and chronic HCV infections. Increasing the viral decay rate in needles leads to a notable decline in infections, highlighting the effectiveness of environmental interventions like needle sterilization. Additionally, reducing risky behaviors in both sexes produces the largest overall reduction in transmission, while improving needle exchange efforts by lowering the reuse of uncontaminated needles further suppresses disease spread. Our findings highlight the need for integrated harm reduction with enough, gender informed coverage, particularly ensuring sufficient reach among men, while future work should evaluate sex differential uptake and efficacy.

Structural characterization of zebrafish Ngly2, an ovary-enriched acid PNGase required for egg-free glycan production

Testing for the footprints of stabilization economic policy in forecast errors

This paper introduces a novel statistical test, the Policy Effects Lagrange Multiplier (PELM) test, to detect stabilization policy effects in the distribution of forecast errors from dynamic financial models. Traditional analyses of policy impact typically rely on explicit policy information or direct intervention data, which are often unavailable or incomplete. In contrast, the proposed PELM test infers policy footprints from the distribution of forecast errors alone. Empirically applied to sovereign bond yield data from 33 countries before the Russian financial crisis of 2014, the test identifies countries showing stabilization policy footprints. Subsequent analysis shows that significant budgetary improvements were observed for years following the crisis in the group of countries where our test statistically confirmed stabilization policies. This confirms the rationale of test foundations and also indicates its predictive properties. Robustness checks further validate these findings across various model specifications and sensitivity scenarios. The proposed PELM test offers policymakers and researchers a powerful tool for evaluating stabilization policies, facilitating better forecasting and assessing policy efficiency in diverse economic contexts without necessitating detailed policy intervention data.

Discovery and biochemical characterization of enzymes completing the 4-hydroxyphenylacetate pathway in Acinetobacter baumannii TH

What do we actually know about the biomechanics of pregnancy and labour? A systematic scoping review

Pregnancy and childbirth involve profound biomechanical transformations, adaptations, and functional demands on the maternal body. Although biomechanical complications have been identified as a major contributor to maternal morbidity and mortality, this remains one of the most under-researched areas in perinatal health. This systematic scoping review aimed to map and synthesise existing literature on the biomechanics of pregnancy and labour. Following Arksey and O’Malley’s framework and PRISMA-ScR guidance, comprehensive searches of MEDLINE, EMBASE, and MIDIRS were conducted up to May 2025. Eligible sources were peer-reviewed empirical studies assessing musculoskeletal, kinematic, kinetic, postural, or dynamic parameters in pregnant or labouring women. Titles, abstracts, and full texts were screened against predefined eligibility criteria. Data were charted using a structured extraction form and synthesised narratively across key biomechanical themes. Eighty-seven studies were included, all of which focused on pregnancy. No studies conducted during labour were identified. Most were observational with small sample sizes and limited diversity. Ethnicity was reported in only one study. Four key themes emerged: (1) Posture and spinal curvature, (2) Gait and locomotor analysis, (3) Functional tasks and interventions, and (4) Balance and stability. Findings showed high individual variability and no consistent biomechanical pattern across pregnancy. Real-world, neuromuscular, and labour-related biomechanics remain largely unexplored. This review underscores a critical gap in perinatal research: while biomechanical adaptations during pregnancy have been increasingly studied, labour remains entirely unexamined from a biomechanical perspective. Current evidence is fragmented, methodologically narrow, and lacks diversity, offering limited clinical relevance. We are effectively operating in a biomechanical vacuum, without empirical data to guide safer, more efficient, and personalised birth practices. Existing clinical approaches rely heavily on tradition, anecdotal experience, and untested theoretical assumptions. Addressing this evidence void, particularly in labour biomechanics and ethnic representation, is essential to improve perinatal outcomes and support equity in maternal care.

Mapping the intracellular HMGB1 interactome and alterations induced by Toll-like receptor 4 activation

Prevalence and genotype distribution of Human Papillomavirus (HPV) among 14,110 women in Anqing urban area: A population-based cross-sectional survey

Human papillomavirus (HPV), particularly persistent infection with high-risk types, is one of the major etiological factors for cervical cancer, posing significan health risks to women. This study aims to analyze the epidemiology of HPV infection among women in the Anqing region, and provide a valuable reference for the prevention and control strategies of cervical cancer in this region. Between 2022 and 2024, a total of 14,110 women attending the First People’s Hospital of Anqing were enrolled in this study. All participants underwent both HPV testing and ThinPrep cytology test (TCT). The overall prevalence of HPV infection in the study population was 18.97%. The predominant pattern of HPV infection identified was single infection, followed by double infection. The top five HPV genotypes detected were HPV 52 (2.78%), HPV 81 (1.55%), HPV 58 (1.42%), HPV 16 (1.20%) and HPV 53 (1.16%). The highest HPV positivity rate was observed in women aged < 20 years (79.17%), followed by those aged 50–59 (84.88%), and then those aged > 59 years (42.53%). Among all HPV-positive women, analysis of TCT results revealed that HPV 52, 53, 16, 58 and 81 were frequently detected in ASC-US, HPV 52, 16 and 58 in ASC-H, HPV 52, 58 and 81 in LSIL, and HPV 16, 58 and 18 were the most common genotypes in HSIL. HPV 52, 81, 58, 16 and 53 are the common genotypes among women in Anqing region. The highest prevalence rates of HPV infection were observed in women aged <20 years and those aged 50–59 years. Based on these findings, the 9-valent HPV vaccine is strongly recommended as a primary prevention strategy for this population.

A split luciferase system for studying coronavirus Mpro dimerization in vitro and in living cells

Asymmetric Electrosorption in a Bio‐Inspired Reactor Enables Energy Efficient Ocean Carbon Removal

Abstract Ocean carbon removal represents a promising pathway for mitigating residual anthropogenic carbon dioxide (CO 2 ), yet existing methods are constrained by high energy demands and potential ecological risks. Here, inspired by the natural calcification process of corals, we present a bio‐inspired capacitive decarbonization (CDC) reactor that sequesters dissolved inorganic carbon (DIC) from seawater as CaCO 3 using only seawater‐derived Ca 2+ and renewable electricity. The CDC system integrates a Ca 2+ ‐selective electrode with a weak electric field to regulate ion transport and disrupt the hydration shell of Ca 2+ , enhancing its reaction with CO 3 2− . To address the limited concentration of CO 3 2− relative to Ca 2+ in seawater, we introduce an asymmetric electrosorption strategy to preferentially enrich CO 3 2− at the electrode interface, achieving a DIC conversion rate of up to 34% with an ultralow intrinsic electrochemical energy input of 2.5 kJ mol −1 CO 2 for the CDC reactor. The reactor exhibits stable continuous operation for over 100 h without fouling, enabled by spatially decoupled CaCO 3 precipitation. To mitigate the reduction in seawater alkalinity, we introduce a mineral‐assisted re‐alkalinization step that effectively restores pH and supports continued CO 2 absorption. A global integrated analysis model shows the CDC technology could remove up to 11–438 million tonnes of CO 2 by 2050–2100. This work demonstrates a scalable and low‐energy solution for durable ocean carbon removal.

Correction: Spatial heterogeneity of microbial community structure and its environmental drivers in surface sediments of Erhai Lake

Structural basis of nectin-4 recognition by the antibody–drug conjugate 9MW2821

Global prevalence of E-cigarette use among students: Systematic review and meta-analysis

Background The growing use of e-cigarettes among students is a major public health concern. Yet, global data on its prevalence and associated risk factors remain limited. Therefore, this study aimed to estimate the global prevalence of e-cigarette use among students and identify key predictors influencing usage patterns. Methods A systematic review and meta-analysis were conducted using articles retrieved from databases including Science Direct, Scopus, EMBASE, Google Scholar, and PubMed, between August 15 and September 21, 2024. Data were extracted using Excel and analyzed with STATA version 14. Heterogeneity was assessed using the I 2 statistic, and publication bias was evaluated through forest plots and Begg and Egger’s tests. Subgroup analyses were conducted by geographic region, World Bank income classification, and level of education. A pooled odds ratio was calculated to identify predictors of e-cigarette use. Results A total of 40 studies with 654,853 student participants were included in the final analysis. The global prevalence of e-cigarette use among students was 22.65%. Usage varied significantly by region and demographic factors, with the highest rates observed in the Western Pacific (32.13%) and among high school students (33.62%). Students in high-income countries reported the highest usage (23.15%) as well. Key predictors of e-cigarette use included being male (AOR = 3.22), smoking conventional cigarettes (AOR = 5.35), and consuming alcohol (AOR = 3.14). Conclusion This meta-analysis reveals a high global prevalence of e-cigarette use among students, especially among high school males in high-income and Western Pacific regions, with strong associations to conventional cigarette smoking and alcohol use. Prioritize region-specific school based interventions targeting high-risk students particularly high school males in high-income countries to curb e-cigarette use and associated behaviors like smoking conventional cigarettes and alcohol consumption.