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Objective: To assess safety of ustekinumab (UST) on treatment of patients with psoriasis and psoriatic arthritis (PsA) by analyze UST related adverse drug events (ADEs)., Methods: Data on ADEs associated with UST on psoriasis and PsA were collected from the fourth quarter of 2009 through the third quarter of 2024 in the U.S. Food and Drug Administration (FDA) Adverse Event Reporting System (FEARS) database. A variety of signal quantization techniques such as reporting odds ratio (ROR), proportional reporting ratio (PRR), bayesian confidence propagation neural network (BCPNN), and multi-item gamma poisson shrinker (MGPS) are used for analysis., Results: A total of 67,765 ADE reports with UST on psoriasis and PsA as the primary suspected agent covered 25 system organ classes (SOCs). The three most common ADEs are infections and infestations (n = 9698), general disorders and administration site conditions (n = 6336), and injury, poisoning, and procedural complications (n = 6091). Specifically, reproductive system diseases (n = 262) was identified as unique adverse reactions not mentioned in official drug labels. At the preferred term (PT) level, the most common ADEs were psoriasis exacerbation (n = 3486), lower respiratory tract infection (n = 1302) and latent tuberculosis (n = 121). Strong yet rare signals, including notalgia paraesthetica (n = 3, empirical bayesian geometric mean [EBGM] 154.7) and chronic actinic dermatitis (n = 3, EBGM 101.15), were also detected. Compared to patients with PsA, patients with psoriasis treated with UST exhibit significantly stronger associations with hepatobiliary disorders (n = 955, ROR 2.44, PRR 2.4, information component [IC] 1.26, EBGM 2.4) and neoplasms (n = 3150, ROR 2.61, PRR 2.49, IC 1.31, EBGM 2.49). Spontaneous reports consistently demonstrated higher signal strength for infections and skin disorders compared to healthcare professional (HCP) reports. In contrast, at the PT level, HCP reports tended to emphasize stronger signals for rare or specific conditions., Conclusion: This study highlights a spectrum of UST-associated ADEs covering 25 SOCs in the treatment of patients with psoriasis and PsA, which emphasizes the need for vigilant clinical monitoring, particularly for infections, hepatobiliary disorders, and rare but high-signal events such as notalgia paraesthetica, chronic actinic dermatitis and pure testicular seminoma stage I. Clinicians should combine insights from both spontaneous and HCP reports and pay special attention to infections and reproductive system disorders., Competing Interests: Declaration of competing interest 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., (Copyright © 2024. Published by Elsevier B.V.)

Background: To study the problem of male sterility of cattle-yak and improve the yak crossbreeding, this study obtained the testicular Sertoli cells of yak and cattle-yak and compared the differences in transcriptome levels between the two bovine species. The testicular tissues of 3 healthy male cattle-yaks and 3 F 1 generation male yaks were collected at the age of 24 months. The Sertoli cells were isolated after enzymatic digestion, differential adhesion and starvation treatment. DATA-4 and SOX9 immunofluorescence staining were used to identify the cell type. Sertoli cells were subjected to transcriptome sequencing, GO analysis, KEGG analysis and differentially expressed gene were validated by RT-qPCR and Western blotting., Results: The study successfully isolated and purified Sertoli cells of yak and cattle-yak. The transcriptome sequencing data were compared, analyzed and annotated. Compared to yak Sertoli cells, 6592 differentially expressed genes were identified, with 3007 genes upregulated and 3585 genes downregulated in cattle-yak Sertoli cells. GO analysis suggested that the upregulated genes might be mainly involved in processes such as translation, peptide biosynthetic process, amide biosynthetic process, peptide metabolic process, ribosome, cytoplasmic part, structural constituent of ribosome, structural molecule activity, endomembrane system, protein kinase activity, and phosphotransferase activity. The downregulated genes appeared to be primarily involved in protein phosphorylation, phosphorylation, endomembrane system, protein kinase activity, and phosphotransferase activity. KEGG analysis compared differential genes across 316 pathways, with 8 pathways showing significant enrichment. The upregulated pathways were potentially enriched in cattle-yak Sertoli cells, including ribosome, thermogenesis, and oxidative phosphorylation, while the downregulated pathways seemed to be significantly enriched in adherens junction, mTOR signaling pathway, AMPK signaling pathway, FoxO signaling pathway, and focal adhesion. Compared with yak Sertoli cells, ISOC2, RPL27A and FISI were highly expressed in cattle-yak, as confirmed by RT-qPCR analysis. PDPN, SORBS2, TF, PLSCR1, TJP2, KIF2C, ITGA3, SMTNL2, DSP, ADGRG1, DDR1, GSK3A, RBBP6, ZC3H15 and Claudin 11 showed low expression levels in cattle-yak., Conclusions: Compared with yak Sertoli cells, the expression of genes related to protein activation, cell function, and membranous organelle composition in cattle-yak Sertoli cells appeared to be abnormal. The potential defects in cattle-yak Sertoli cells may hinder the creation of a suitable environment for spermatogenesis, which could be one of the factors contributing to male cattle-yak sterility. Claudin-11 might be a potentially important gene for further research into cattle-yak male sterility., Competing Interests: Declarations. Ethics approval and consent to participate: Informed consent was obtained from all owners in this study, and samples were collected in accordance with local guidelines. All protocols were approved by the Institutional Review Board of Southwest Minzu University. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

Pancreatic ductal adenocarcinoma (PDAC) comprises a group of highly malignant tumors of the pancreas. Metabolic reprogramming in tumors plays a pivotal role in promoting cancer progression. However, little is known about the metabolic alterations in tumors that drive cancer drug resistance in patients with PDAC. Here, we identified acyl-CoA thioesterase 8 (ACOT8) as a key player in driving PDAC gemcitabine (GEM) resistance. The expression of ACOT8 is significantly upregulated in GEM-resistant PDAC tissues and is closely associated with poor survival in patients with PDAC. Gain- and loss-of-function studies have shown that ACOT8 drives PDAC GEM resistance both in vitro and in vivo. Mechanistically, ACOT8 regulates cellular cholesterol ester (CE) levels, decreases the levels of phosphatidylethanolamines (PEs) that bind to polyunsaturated fatty acids and promote peroxisome activation. The knockdown of ACOT8 promotes ferroptosis and increases the chemosensitivity of tumors to GEM by inducing ferroptosis-associated pathway activation in PDAC cell lines. The combination of orlistat, an ACOT8 inhibitor, and GEM significantly inhibited tumor growth in PDAC organoid and mouse models. This study reveals the biological importance of ACOT8 and provides a potential combination therapy for treating patients with advanced GEM-resistant PDAC., Competing Interests: Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

N 6 -methyladenosine (m 6 A) modification is an important mechanism in microRNA processing and maturation. Previous studies show the involvement of pri-miRNA methylation in regulating the occurrence and development of tumor-related diseases. In this study, we investigated the role of its aberrant regulation in cardiac diseases. Myocardial infarction (MI) mouse were established by ligation of the left anterior descending branch of the coronary artery. We showed that the expression of methyltransferase 14 (METTL14) was significantly increased in myocardium of MI mice. We demonstrated that METTL14 methylated the primary transcript miRNA (pri-miR-5099), promoting the recognition by DiGeorge critical region 8 (DGCR8) and the maturation processing of pri-miR-5099. Mature microRNA-5099-3p (miR-5099-3p) inhibited the expression of E74 like ETS transcription factor 1 (ELF1), which transcriptionally regulated pyroptosis factors such as acysteinyl aspartate-specific proteinase 1 (caspase-1) and gasdermin D (GSDMD), ultimately leading to cardiomyocyte pyroptosis. This study reveals that myocardial infarction-induced miR-5099-3p excessive maturation via m 6 A modification promotes the development and progression of cardiomyocyte pyroptosis., Competing Interests: Competing interests: The authors declare no competing interests., (© 2025. The Author(s), under exclusive licence to Shanghai Institute of Materia Medica, Chinese Academy of Sciences and Chinese Pharmacological Society.)

Articular cartilage injury is a serious bone disease that can result in disabilities. With the rapid increase in the aging population, this disorder has become an increasingly important public health issue. Recently, stem cell-based cartilage tissue engineering has emerged as a promising therapeutic option for treating articular cartilage damage. Cellular scaffolds, which are among three key elements of tissue engineering, play significant roles in the repair of damaged articular cartilage by regulating cellular responses and promoting cartilage tissue regeneration. Biological macromolecules are commonly used as scaffold materials owing to their unique properties. For example, natural and synthetic polymer hydrogel scaffolds can effectively mimic the microenvironment of the natural extracellular matrix; exhibit high cytocompatibility, biocompatibility, and biodegradability; and have attracted increasing attention in bone and cartilage tissue engineering and regeneration medicine. Several types of hydrogel scaffolds have been fabricated to treat articular cartilage abnormalities. This article outlines the recent progress in the field of hydrogel scaffolds manufactured from various biomaterials for repairing damaged articular cartilage, discusses their advantages and disadvantages, and proposes directions for their future development., Competing Interests: Declarations. Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

Background: Ex vivo lung perfusion (EVLP) is a critical strategy to rehabilitate marginal donor lungs, thereby increasing lung transplantation (LTx) rates. Ischemia-reperfusion (I/R) injury inevitably occurs during LTx. Exploring the common mechanisms between EVLP and I/R may unveil new treatment targets to enhance LTx outcomes., Methods: We obtained datasets from the public Gene Expression Omnibus (GEO) for EVLP (GSE127055 and GSE127057) and I/R (GSE145989) processes. We performed analysis of differentially expressed genes (DEGs) and Gene Set Enrichment Analysis (GSEA). Mitochondrial genes were sourced from the MitoCarta 3.0 database. Hub mitochondrial-related DEGs (MitoDEGs) were identified using a combination of protein-protein interaction networks and machine learning methods, which were further validated in cell and mice models of EVLP., Results: GSEA analysis of DEGs following EVLP and I/R revealed significant inhibition of mitochondrial function pathways, encompassing mitochondrial central dogma, mtRNA metabolism, OXPHOS assembly factors, metals and cofactors, and heme synthesis and processing processes. Machine learning algorithms including Random Forest, LASSO, and XGBoost identified five downregulated genes (MTERF1, ACACA, COX15, OSGEPL1, and COQ9) as hub MitoDEGs for both EVLP and I/R processes. We confirmed the reduced expression of these hub MitoDEGs in endothelial cells during EVLP and observed mitochondrial damage in endothelial cells characterized by swollen morphology and cristae disappearance., Conclusions: Imbalance in mitochondrial homeostasis is a shared pathological process during EVLP and I/R-induced lung injury. The identified hub mitochondrial-related genes (MTERF1, ACACA, COX15, OSGEPL1, and COQ9) suggest promising therapeutic targets for lung injury during LTx. The downregulation of these genes indicates a significant disruption in mitochondrial function. This study provides potential mitochondrial-related therapeutic targets for I/R-induced lung injury and for donor lung repair during EVLP procedure in LTx., Competing Interests: Declaration of competing interest 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., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Exploring the interactions between oxygen molecules and metal sites has been a significant topic. Most previous studies concentrated on enzyme-mimicking metal sites interacting with O 2 to form M-OO species, leaving the development of new types of O 2 -activating metal sites and novel adsorption mechanisms largely overlooked. In this study, we reported an Fe(II)-doped metal-organic framework (MOF) [Fe 3 Zn 2 H 4 (bibtz) 3 ] ( MAF-203 , H 2 bibtz = 1 H ,1' H -5,5'-bibenzo[ d ][1,2,3]triazole), featuring an unprecedented tetrahedral Fe(II)HN 3 site. This MOF exhibits selective adsorption behavior for O 2 from air, achieving an O 2 /N 2 separation selectivity of up to 67.1. Breakthrough experiments confirmed that MAF-203 can effectively capture O 2 from the air even under a high relative humidity of 60%. X-ray absorption spectroscopy, in situ diffuse reflectance infrared Fourier transform spectra, and ab initio molecular dynamics simulations were utilized to monitor the O 2 loading process on the Fe(II)HN 3 site. Interestingly, O 2 molecules could insert into the Fe-H bonds of the tetrahedral Fe II HN 3 sites, forming Fe III -OOH species (instead of the commonly observed Fe-OO species) with an ultrahigh adsorption enthalpy of -99.2 kJ mol -1 . Consequently, the O 2 capture behavior of MAF-203 enables efficient electrochemical 2e - oxygen reduction for the production of H 2 O 2 with air as the feedstock. Specifically, in a solid-state electrolyte electrolyzer without any liquid electrolyte, MAF-203 achieved selective O 2 capture and continuous production of medical-grade H 2 O 2 (3.2 wt %) solution without salts for 70 h, with performance comparable to that under pure O 2 conditions. The O 2 adsorption and activation mechanisms inaugurate a fresh chapter in grasping the interaction between O 2 molecules and metal sites.

The prevalence of chronic kidney disease (CKD) is increasing worldwide, posing a significant healthcare challenge. Despite the immense burden of CKD, optimal therapies remain limited in impact. Kidney fibrosis is a common mediator of all CKD progression, characterized by excessive extracellular matrix deposition and scarring of kidney parenchyma. Transforming growth factor-β (TGF-β) is a potent pro-fibrotic cytokine that signals through canonical and non-canonical pathways to promote kidney cell damage and fibrosis progression, thus garnering much interest as an optimal therapeutic target for CKD. However, the clinical translation of TGF-β inhibition in CKD and other disease settings has faced substantial challenges, particularly due to the highly pleiotropic effects of TGF-β in organ homeostasis and disease. Here, we review the kidney cell-specific biological effects of TGF-β signaling, discuss the current challenges in therapeutic targeting TGF-β in CKD, and provide the rationale for alternative targeting strategies of TGF-β signaling as potential approaches in CKD therapy. Selective inhibition of TGF-β signaling modulators to fine-tune TGF-β inhibition without a broad blockade may lead to new and safer treatments for CKD., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

Postoperative cognitive dysfunction (POCD) is a prevalent neurological complication that can impair learning and memory for days, months, or even years after anesthesia/surgery. POCD is strongly associated with an altered composition of the gut microbiota (dysbiosis), but the accompanying metabolic changes and their role in gut-brain communication and POCD pathogenesis remain unclear. Here, the present study reports that anesthesia/surgery in aged mice induces elevated intestinal indoleamine 2,3-dioxygenase (IDO) expression and activity, which shifts intestinal tryptophan (TRP) metabolism toward more IDO-catalyzed kynurenine (KYN) and less gut bacteria-catabolized indoleacetic acid (IAA). Both anesthesia/surgery and intraperitoneal KYN administration induce increased KYN levels that correlate with impaired spatial learning and memory, whereas dietary IAA supplementation attenuates the anesthesia/surgery-induced cognitive impairment. Mechanistically, anesthesia/surgery increases interferon-γ (IFN-γ)-producing group 1 innate lymphoid cells (ILC1) in the small intestine lamina propria and elevates intestinal IDO expression and activity, as indicated by the higher ratio of KYN to TRP. The IDO inhibitor 1-MT and antibodies targeting IFN-γ or ILCs mitigate anesthesia/surgery-induced cognitive dysfunction, suggesting that intestinal ILC1 expansion and the ensuing IFN-γ-induced IDO upregulation may be the primary pathway mediating the shift to the KYN pathway in POCD. The ILC1-KYN pathway in the intestine could be a promising therapeutic target for POCD., Competing Interests: Declaration of competing interest 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., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Ethnopharmacological Relevance: The current treatment for diabetic nephropathy (DN) is inadequate, and there is an urgent need for an effective and minimally adverse alternative therapy. Da-Chai-Hu Decoction (DCHD) is a time-honored herbal remedy from Chinese medicine, boasting a legacy spanning more than 1800 years. Clinical observations suggest that it may provide therapeutic benefits for individuals with type 2 diabetes mellitus (T2DM). Nonetheless, the specific advantages of DCHD in relation to DN and the mechanisms through which it operates are still not well understood., Aim of the Study: This research aims to investigate whether DCHD can avert renal damage in mice with T2DM and to elucidate the mechanisms by which DCHD combats DN through the integration of metabolomics and network pharmacology., Materials and Methods: The beneficial effects of DCHD on DN was initially evaluated using a renal injury model in T2DM mice. Subsequently, untargeted metabolomics analysis was utilized to investigate the potential mechanisms of DCHD against DN. Additionally, UPLC-HR MS/MS was employed to identify the chemical components in DCHD and the absorption components in DCHD-treated plasma. Network pharmacology and our newly proposed function-guided and network-based complementary methodology (FNICM) was utilized to predict the potential pathway of DCHD intervention in DN. Finally, the core pathway was validated through Western blotting analysis and ELISA., Results: A total of 260 chemical components were detected in DCHD, and 41 absorption components were found in DCHD-treated plasma by UPLC-HR MS/MS for the first time. Additionally, In vivo experiments revealed that DCHD exerts the ability to regulate the disorder in glucose/lipid metabolism and improves kidney dysfunction. Furthermore, a comprehensive analysis utilizing non-targeted urine metabolomics and the FNICM method identified a total of 33 differential metabolites, which were categorized as core metabolites. Lastly, combined FNICM, network pharmacology and experimental pharmacology studies suggest that DCHD may regulate the AGEs/RAGE/AKT pathways in combating DN., Conclusions: The results indicate that DCHD treats DN through the inhibition of the AGEs/RAGE/AKT pathway and by regulating metabolic profiles., Competing Interests: Declaration of competing interest 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., (Copyright © 2024 Elsevier B.V. All rights reserved.)

A series of N-Het·B 3 H 7 and AAE·B 3 H 7 complexes were prepared in moderate to high yields and the single-crystal structures of products 3, 31, 34, and 59 were determined. The N-Het·B 3 H 7 and AAE·B 3 H 7 complexes possess high stability, endowing these products with potential applications in luminescent and boron-containing drugs. The optical properties of the representative products have been preliminarily studied.

n-butane (n-C 4 H 10 ) and isobutane (i-C 4 H 10 ) are important raw materials in chemical industry. The separation of the two hydrocarbon isomers via distillation is challenging and energy-consuming. Herein we report the adsorption behavior of a microporous cobalt formate framework [Co 3 (HCOO) 6 ] for potential kinetic separation of butane isomers. Under ambient condition, [Co 3 (HCOO) 6 ] shows near adsorption capacity for n-C 4 H 10 (1.77 mmol g -1 ) and i-C 4 H 10 (1.36 mmol g -1 ) with different adsorption kinetics. Study on the adsorption kinetics for butane indicates that the smaller isomer is adsorbed at a higher diffusion rate, resulting in a high kinetic selectivity of 193 for n-C 4 H 10 /i-C 4 H 10 separation. Analyses of adsorption kinetics and breakthrough experiment have validated the separation potential of [Co 3 (HCOO) 6 ] for butane purification., (© 2025 Wiley-VCH GmbH.)

In this study, we present an intelligent electromagnetic-actuated microfluidic chip integrated with a G-quadruplex DNAzyme-based biocatalysis platform for rapid and sensitive tetracycline (TC) detection. In this sensing system, TC significantly quenches fluorescent magnetic carbon dots (M-CDs) via the internal filtration effect and dynamic quenching (the excitation and emission wavelength at 350 and 440 nm, respectively). Then, the G-quadruplex on the M-CDs-Aptamer is exposed and bound with hemin to form hemin-G-quadruplex DNAzyme, catalyzing the conversion of 3,3',5,5'-tetramethylbenzidine to produce blue color. This enables the fluorescence/colorimetric detection of TC. Importantly, an automatic electromagnet-integrated microfluidic chip was designed to control the shuttling of magnetic materials in each function slot according to a programmed sequence. Under the optimal conditions, the detection limits of TC for fluorescence and colorimetric methods were 11 and 43 μmol/L, respectively. The detection results for tilapia ( Oreochromis nilotica ) were comparable to those of traditional high-performance liquid chromatography. This platform offers excellent performance for TC determination and potential for portable, intelligent detection of trace pollutants in food and the environment.

The separation of C 6 cyclic hydrocarbons (benzene, cyclohexene, and cyclohexane) is one of the most challenging chemical processes in the petrochemical industry. Herein, we design and synthesize a new SOD-topology metal azolate framework (MAF) with aperture gating behaviour controlled by C-Br⋯N halogen bonds, which exhibits distinct temperature- and guest-dependent adsorption behaviours for benzene/cyclohexene/cyclohexane. More importantly, the MAF enables the efficient purification of benzene from its binary and ternary mixtures (selectivity up to 113 ± 2; purity up to 98% +), which is the highest record for benzene/cyclohexane/cyclohexene separation to date. Single-crystal diffraction analyses and computational simulations revealed that halogen bonds play a critical role in the gating and diffusion process, which is the first example of halogen-bonding controlled gating for highly effective adsorptive separation., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

Staphylococcus aureus ( S. aureus ) is the primary risk factor in food safety. Herein, a nanogap-assisted surface-enhanced Raman scattering/polymerase chain reaction (SERS/PCR) biosensor coupled with a machine-learning tool was developed for the direct and specific sensing of S. aureus in milk. The specific nuc gene ( nuc T) from S. aureus was initially amplified through PCR and subsequently captured via the nanogap effect of I - and Mg 2+ -mediated bimetallic gold and silver nanoflowers (Au/Ag FL@I - -Mg 2+ ). These nanogaps generate hotspots for the direct signal amplification of enclosed nuc T. Subsequently, machine-learning tools were used to comparatively analyze the collected SERS signals. The bootstrapping soft shrinkage-partial least-squares method exhibited superior performance (root mean-square error of prediction: 0.437, prediction set correlation coefficient: 0.967). This study demonstrated a novel label-free strategy for specifically detecting S. aureus . The strategy could be advanced to serve as a platform for application to other types of foodborne pathogenic bacteria by engineering a suitable specific primer.

Improved methods for the synthesis of B 10 H 14 and a series of N -heterocycle-coordinated B 9 H 13 complexes ( N -Het·B 9 H 13 ) have been developed with readily obtained KB 11 H 14 as the starting material. Oxidation of KB 11 H 14 could provide B 10 H 14 in over 90% yield. Then, the N -Het·B 9 H 13 complexes were prepared from the as-synthesized B 10 H 14 through in situ multistep reactions by reacting with NaH, N -heterocycles, and dilute hydrochloric acid. Among these N -Het·B 9 H 13 complexes, 4-(triphenylvinyl)pyridine-coordinated B 9 H 13 ( 1k ) exhibits a significant aggregation-induced emission (AIE) effect in a THF/H 2 O mixed solution, and 8-aminoisoquinoline-coordinated B 9 H 13 ( 2p ) exhibits a positive solvatochromism phenomenon. These improved methods provide new approaches to synthesizing B 10 H 14 and N -Het·B 9 H 13 complexes with potential applications in luminescent materials.

Purpose: This study aimed to investigate whether tumor-associated lymphatic vessel density (LVD) could predict the survival of patients with hepato-biliary-pancreatic (HBP) cancers after radical resection., Methods: A systematic search was conducted using PubMed, Embase, and Cochrane Library from the inception to July 31, 2024 for literature that reported the role of LVD in overall survival (OS) and recurrence-free survival (RFS) of patients with HBP cancers after radical resection., Results: Ten studies with 761 patients were included for the meta-analysis. The results indicated that a higher level of LVD was associated with worse OS (hazard ratio, HR = 2.87, 95% CI 1.63 to 5.04) and worse RFS (HR = 3.18, 95% CI 1.41 to 7.17) in HBP cancers. Subgroup analysis based on pathological types revealed that a higher level of LVD was significantly related to worse OS in hepatocellular carcinoma (HCC) (HR = 2.35, 95% CI 1.16 to 4.78), cholangiocarcinoma (HR = 4.65, 95% CI 1.70 to 12.70), and gallbladder cancer patients (HR = 4.64, 95% CI 1.37 to 15.71). The levels of LVD were not significantly associated with OS in pancreatic adenocarcinoma patients after radical resection (HR = 1.08, 95% CI 0.61 to 1.89). Similarly, a higher level of LVD was significantly associated with worse RFS in HCC (HR = 1.92, 95% CI 1.01 to 3.65) and cholangiocarcinoma patients (HR = 4.54, 95% CI 2.10 to 9.83)., Conclusions: A higher level of LVD was a biomarker for the prediction of worse OS and RFS in patients with hepatobiliary cancers after radical resection., Systematic Review Registration: https://www.crd.york.ac.uk/prospero/, identifier CRD42024571167., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2025 Li, Liang, Wang, Li, Chen, Luo, Lakang, Yang, Wang, Li and Ke.)

Synthesis of high-loading atomic-level dispersed catalysts for highly efficient electrochemical CO 2 reduction reaction (eCO 2 RR) to ethylene (C 2 H 4 ) in neutral electrolyte remain challenging tasks. To address common aggregation issues, a host-guest strategy is employed, by using a metal-azolate framework (MAF-4) with nanocages as the host and a dinuclear Cu(I) complex as the guest, to form precursors for pyrolysis into a series of nitrogen-doped porous carbons (NPCs) with varying loadings of dual copper sites, namely NPC MAF-4 -Cu 2 -21 (21.2 wt%), NPC MAF-4 -Cu 2 -11 (10.6 wt%), and NPC MAF-4 -Cu 2 -7 (6.9 wt%). Interestingly, as the loading of dual copper sites increased from 6.9 to 21.2 wt%, the partial current density for eCO 2 RR to yield C 2 H 4 also gradually increased from 38.7 to 93.6 mA cm -2 . In a 0.1 m KHCO 3 electrolyte, at -1.4 V versus reversible hydrogen electrode (vs. RHE), NPC MAF-4 -Cu 2 -21 exhibits the excellent performance with a Faradaic efficiency of 52% and a current density of 180 mA cm -2 . Such performance can be attributed to the presence of ultrahigh-loading dual copper sites, which promotes C─C coupling and the formation of C 2 products. The findings demonstrate the confinement effect of MAF-4 with nanocages is conducive to the preparation of high-loading atomic-level catalysts., (© 2024 Wiley‐VCH GmbH.)