Fast inverse planning in radiosurgery planning is limited by an excessive number of isocenters, which is clinically hypothesized to be driven by the morphological irregularity of the target volume. This retrospective cross-sectional study aimed to empirically evaluate this hypothesis in vestibular schwannoma cases.

Consecutive patients diagnosed with vestibular schwannoma and receiving Gamma Knife radiosurgery in 2023 were included, and their treatment plans designed using the GammaPlan planning system were collected. Morphological irregularity–related parameters, including standard sphericity (SS), volume ratio sphericity (VRS), and the coefficient of variance of diameters (DCV), were calculated based on parameters provided by the system. Basic demographic and clinical data were collected to evaluate their impact on sphericity. The effects of different sphericity assessment methods on common treatment plan parameters were analyzed.

Treatment plans of 280 patients with vestibular schwannoma were collected. The SS, VRS, and DCV of the tumors were 0.85 (0.77–0.91), 0.46 ± 0.16, and 0.22 (0.14–0.34), respectively. Multivariate analysis showed that lesion volume, acoustic neuroma consensus on systems for reporting results grade, and age were significant factors influencing sphericity. All other planning parameters, except prescription dose and homogeneity index, were significantly correlated with sphericity. DCV was more closely correlated with SS than with VRS.

DCV may serve as a simple quantitative metric of target morphological irregularity, showing strong consistency with SS. Incorporating morphological irregularity into Gamma Knife treatment plan evaluation may help improve future planning strategies and support optimization of isocenter utilization.

Cerebrospinal fluid leakage and postoperative tissue adhesion are serious complications following dural injury. Current dural substitutes often lack the functional asymmetry of the native dura mater. This study aimed to develop a hydrophilic/hydrophobic Janus polyvinyl alcohol (PVA) hydrogel membrane with a directional structure and dual functionality for effective dural defect repair.

A PVA hydrogel with an aligned porous architecture was fabricated via directional freezing combined with salt leaching, and thermal annealing was applied to enhance mechanical strength and structural stability. The hydrogel was asymmetrically modified to obtain a Janus membrane. Morphology, mechanical properties, degradation, swelling, wettability, in vitro biocompatibility, and cell migration were evaluated by the NIH-3T3 mouse fibroblast cell line. In vivo biocompatibility was assessed using a rat subcutaneous implantation model, including blank control, Durepair®, frozen-salted PVA, and Janus-PVA groups, with 5 rats in each group. Dural repair efficacy was evaluated in a rat cranial dural defect model, including untreated defect control, frozen-salted-annealed PVA, and Janus-PVA groups, with 15 rats in each group.

The Janus membrane exhibited high tensile strength (8.93 ± 1.46 MPa), slow degradation (1.42% mass loss at 28 days), and low swelling (58.13% water content at 28 days). It displayed distinct bilateral wettability, and effectively blocked fibroblast migration on both sides, acting as a physical barrier against fibroblast-driven adhesion. In the rat dural defect model, the Janus membrane reduced cerebrospinal fluid leakage and brain–dura adhesion compared with the untreated defect and frozen-salted-annealed PVA control groups.

The engineered hydrophilic/hydrophobic Janus PVA hydrogel membrane mimics the functional asymmetry of the native dura mater and may serve as a promising candidate for further evaluation as a dural repair material.

Nonalcoholic fatty liver disease (NAFLD) is a prevalent metabolic disorder with a complex pathogenesis. Although epitranscriptomic modifications such as N6-methyladenosine (m6A) have been implicated in NAFLD, the role of N1-methyladenosine (m1A) and its regulators is largely unexplored. Recently, YTHDF1, a well-characterized m6A reader, was also shown to recognize m1A; however, the functional consequences of this dual specificity are unknown. This study aimed to investigate the role of YTHDF1 in NAFLD pathogenesis and to explore whether its function is mediated through recognition of RNA methylation modification on specific target mRNAs.

Expression of YTHDF1 in NAFLD was analyzed in the GEO database. Loss-of-function studies for YTHDF1 were conducted in vivo (high-fat diet-fed mice) and in vitro (free fatty acid-treated HepG2 cells) in models of NAFLD. We employed RNA-seq and m1A-MeRIP-seq to identify key targets, followed by mechanistic validation of the YTHDF1–m1A–NUPR1 axis using biochemical, histological, and mRNA stability assays.

We identified a critical role for YTHDF1 in promoting hepatic steatosis. NUPR1, a stress-induced transcriptional regulator, undergoes m1A modification. YTHDF1 directly binds to m1A-modified NUPR1 mRNA, enhancing its stability, thereby leading to elevated NUPR1 protein levels. Functionally, upregulated NUPR1 acts as a core driver of NAFLD pathogenesis by activating lipogenic and suppressing fatty acid β-oxidation genes, thereby exacerbating hepatic lipid accumulation.

Our study unveils a novel epitranscriptomic mechanism in which YTHDF1, functioning as a dual-specificity reader, governs NAFLD progression through the m1A-NUPR1 axis. This not only expands the understanding of RNA modification recognition but also establishes the YTHDF1–m1A–NUPR1 pathway as a promising therapeutic target for metabolic liver disease.

Porto-sinusoidal vascular disease (PSVD) is a non-cirrhotic vascular liver disorder characterized by portal and sinusoidal microvascular lesions and is frequently complicated by portal hypertension. Accurate assessment of portal pressure is essential for diagnosis, risk stratification, therapeutic decision-making, and prognostic evaluation in PSVD. However, unlike cirrhosis, portal hypertension in PSVD is predominantly presinusoidal, making hepatic venous pressure gradient measurement prone to underestimating true portal pressure. Recent advances have promoted a transition from conventional invasive assessment toward a multimodal and precision-oriented strategy integrating non-invasive and minimally invasive techniques. Ultrasound elastography, computed tomography, and magnetic resonance imaging—particularly radiomics-based approaches—provide valuable tools for differentiating PSVD from cirrhosis and estimating the severity of portal hypertension. Endoscopic ultrasound-guided portal pressure gradient measurement has emerged as a promising minimally invasive technique for direct hemodynamic assessment and prognostic stratification. In addition, laboratory biomarkers, digital modeling, and artificial intelligence-assisted analysis may further improve individualized risk prediction and dynamic monitoring. This review summarizes current advances in portal pressure assessment in PSVD, critically discusses the strengths and limitations of existing approaches, and highlights future directions toward non-invasive, digital, and precision-guided management.

Despite the surging global prevalence of metabolic dysfunction-associated steatotic liver disease (MASLD) and related liver fibrosis, effective treatments remain limited. While the traditional Chinese medicine Juanyu-Xiaozhi Formula (JYXZF) is used against MASLD, its bioactive components and mechanisms are poorly understood. This study aimed to investigate the therapeutic effects of JYXZF and elucidate its underlying mechanisms of action.

The constituents of JYXZF were characterized using ultra-high-performance liquid chromatography–tandem mass spectrometry (UPLC-MS/MS). Its efficacy was evaluated in a rat model of metabolic dysfunction-associated steatohepatitis (MASH) induced by a high-fat/calorie diet with high-fructose/high-glucose water, utilizing serum biochemistry, histology, and glucose/insulin tolerance tests. Mechanistic validation was performed in free fatty acid-treated human hepatocellular carcinoma cell line HepG2 (HepG2) cells and HepG2/human hepatic stellate cell line LX-2 (LX-2) co-culture models using luciferase assays, chromatin immunoprecipitation-quantitative polymerase chain reaction (ChIP-qPCR), and activator protein 1 (AP-1) overexpression rescue experiments. The functional relevance of stearoyl-CoA desaturase 1 (SCD1) was further assessed in vivo through liver-targeted adeno-associated virus (AAV)-mediated Scd1 overexpression.

Flavonoids were identified as the main bioactive constituents. JYXZF administration alleviated metabolic dysfunction, reduced hepatic lipid accumulation, and attenuated inflammation and fibrosis in MASH rats. Multi-omics integration and machine learning-assisted target prioritization identified lipid metabolic and inflammatory pathways. Among these pathways, we selected the AP-1/peroxisome proliferator-activated receptor gamma (PPARγ)/SCD1-related lipogenic pathway for functional validation. Target perturbation experiments supported the functional involvement of AP-1 in the regulation of the PPARγ/SCD1 pathway and its contribution to the anti-steatotic effects of JYXZF.

JYXZF alleviates MASLD-associated steatosis and fibrosis via the AP-1/PPARγ/SCD1-related lipogenic axis, demonstrating its therapeutic potential for MASLD/MASH and providing a mechanistic basis for future clinical applications.