Search Results (2,874)

Background/Objectives: Advanced hepatocellular carcinoma (HCC) presents limited treatment options; however, immunotherapy demonstrates encouraging outcomes and acceptable adverse reactions in advanced HCC. This study evaluates the efficacy and safety of combining serplulimab, the bevacizumab biosimilar HLX04, and hepatic arterial infusion chemotherapy (HAIC) as a first-line therapy. Methods: This prospective, observational, single-center phase II trial enrolled untreated HCC patients with Barcelona Clinic Liver Cancer (BCLC) stage C. All patients received serplulimab (4.5 mg/kg) and HLX04 (15.0 mg/kg) every 3 weeks, followed by the HAIC-FOLFOX regimen. The primary endpoint was the objective response rate (ORR). Secondary endpoints included the disease control rate (DCR), progression-free survival (PFS), and safety. Results: A total of 32 patients were enrolled. The best outcomes showed an ORR of 53.1%, including 17 partial responses (PR, 53.1%) and 12 stable diseases (SD, 37.5%), resulting in a DCR of 90.6%. Subgroup analysis showed a higher ORR in patients with a single lesion and those receiving ≥3 treatment cycles, with an ORR of 60.7% in the latter group. Additionally, five patients underwent successful hepatectomy after ≥3 treatment cycles, with postoperative pathology confirming extensive tumor necrosis. Kaplan–Meier analysis estimated PFS rates of 89.9% (95% CI: 79.5–100.0%) at 6 months and 70.8% (95% CI: 54.2–92.4%) at 12 months. No deaths related to adverse events (AEs) occurred; four (12.5%) patients experienced grade IV AEs and twelve (37.5%) patients experienced grade III AEs. Conclusions: Serplulimab, HLX04, and HAIC combined as a first-line treatment for advanced HCC have demonstrated promising efficacy, particularly in patients completing ≥3 cycles, with an acceptable safety profile. Further investigation in larger trials is required. Full article

Dry reforming of methane and ethanol is a promising catalytic process for the conversion of carbon dioxide and hydrocarbon feedstocks into synthesis gas (H₂/CO), which serves as a key platform for the production of fuels and chemicals. Over the past decade, substantial progress has been achieved in the design of catalysts with enhanced activity and stability under the demanding conditions of these strongly endothermic reactions. This review summarizes the latest developments in catalyst systems for DRM and EDR, including Ni-based catalysts, perovskite-type oxides, MOF-derived materials, and high-entropy alloys. Particular attention is given to strategies for suppressing carbon deposition and preventing metal sintering, such as oxygen vacancy engineering in oxide supports, rare earth and transition metal doping, strong metal–support interactions, and morphological control via core–shell and mesoporous architectures. These approaches have been shown to improve coke resistance, maintain metal dispersion, and extend catalyst lifetimes. The review also highlights emerging concepts such as multifunctional hybrid systems and innovative synthesis methods. By consolidating recent findings, this work provides a comprehensive overview of current progress and future perspectives in catalyst development for DRM and EDR, offering valuable guidelines for the rational design of advanced catalytic materials. Full article

Natural laccase is an environmentally friendly biocatalyst in the degradation of a broad range of toxic pollutants because its catalysis reaction does not require or produce toxic reactants and byproducts. However, its inherent limitations, such as operational sensitivity, poor stability, and difficulty in recovery/reusability, have significantly restricted its practical environmental applications. Consequently, in recent years, researchers have focused on the development of sustainable catalysts to mimic natural laccase. This review focuses on biomolecule-based laccase mimics, which are derived from nucleotides, nucleic acids, amino acids, peptides, and proteins, summarizing their environmental applications. These biomolecule-based laccase mimics not only overcome the limitations of natural laccase by offering advantages such as high stability, ease of recycling, and long-term storage but also exhibit excellent biodegradability, making them green and sustainable catalytic materials. This study aims to present recent progress in biomolecule-based laccase mimics, as well as their challenges, and to offer future directions in laccase-like catalysts for environmental applications. Full article

Background: Although telomere length maintenance is a common characteristic of hematological malignancies, the role of telomere length as a prognostic factor to stratify acute lymphoblastic leukemia (ALL) patients depending on their risk of relapse remains elusive. Methods: This knowledge gap motivated us to examine telomere length values in children with ALL at the time of diagnosis and after treatment using quantitative polymerase chain reaction (qPCR) (n = 35). To achieve high-resolution precision and cell specificity, a quantitative fluorescence in situ hybridization (qFISH) technique was developed (n = 5). Results: The results demonstrated statistically significant evidence of telomere shortening in the lymphoblasts of children with ALL but not in the lymphocytes of children after remission following treatment. Our findings also suggested a significant association between telomere shortening and a high risk of relapse disease. Last but not least, our preliminary results showed a trend that telomere shortening was more pronounced in children with B-ALL compared to those with T-ALL in a non-significant manner. Conclusions: Consequently, the current study provides preliminary insights into the potentially substantial prognostic value of telomere length in the progression of pediatric ALL, with the possibility of predicting treatment response. To clarify the application of telomere length as a possible biomarker for disease progression and treatment response in children with ALL, the telomere length values of additional participants need to be examined in further studies. Full article

Owing to their tunable electronic structures, exceptional structural stability, and superior catalytic performance, metal–organic framework (MOF)-derived metal sulfides have emerged as promising candidates for use in energy conversion systems. This review first summarizes the various synthesis methods for MOF-derived metal sulfides. Subsequently, recent progress in electrochemical water splitting, including the hydrogen evolution reaction, oxygen evolution reaction, and overall water splitting are discussed. Finally, the current challenges of MOF-derived metal sulfides for electrochemical water splitting are also highlighted. We hope that this review will serve as a valuable reference for the rational design of novel MOF-derived metal sulfides for use in electrochemical water splitting. Full article

Objective: This study aimed to elucidate the regulatory mechanisms of the long intergenic non-protein coding RNA 02381 (LINC02381)/microRNA-let-7g-5p (let-7g-5p)/thrombospondin 1 (THBS1) signaling axis in osteosarcoma (OS). Methods: The expression levels of LINC02381, let-7g-5p, and THBS1 were quantified in OS and adjacent normal tissues via reverse transcription quantitative polymerase chain reaction. Their correlations with clinicopathological features were analyzed. Expression patterns were further validated in OS cell lines (143B, U-2OS, Saos-2, MNNG-HOS, MG-63) and normal osteoblast cell line hFOB1.19. The molecular interaction between LINC02381 and let-7g-5p and the targeting relationship of let-7g-5p with THBS1 were verified via dual-luciferase reporter and RNA pull-down assays. Functional effects were assessed using cell counting kit-8, colony formation, Transwell migration, and xenograft tumor models. Results: Compared to adjacent normal tissues, LINC02381 and THBS1 were upregulated in OS tissues (fold change > 3.0, p < 0.001), while let-7g-5p was downregulated (fold change ≈ 0.038, p < 0.001). Similar expression trends were observed in U-2OS cells. Knockdown of LINC02381 or overexpression of let-7g-5p reduced cell proliferation, colony formation, migration, THBS1 expression, and tumor volume (p < 0.001). These inhibitory effects were partially reversed by let-7g-5p inhibitors, restoring cell viability and migration by approximately 70%. Mechanistically, LINC02381 functioned as a competing endogenous RNA (ceRNA), directly binding to let-7g-5p and mitigating its suppression of THBS1. Conclusions:LINC02381 promotes OA progression by acting as a ceRNA for let-7g-5p, thereby upregulating THBS1 expression. This signaling axis represents a potential therapeutic target for OS. Full article

The potential for creating composite cements by incorporating fly ash is demonstrated. Analysis revealed that the fly ash examined consists of 69.66 wt. % silicon oxide, 21.34 wt. % aluminum oxide, 1.57 wt. % calcium oxide and 2.78 wt. % iron oxide. Fly ash mainly consists of quartz (SiO₂), goethite (FeO(OH)) and mullite (3Al₂O₃·2SiO₂). The properties of the cement composition containing 5 to 25 wt. % fly ash were studied. Incorporating fly ash enhances system dispersion, promotes mixture uniformity, and stimulates the pozzolanic reaction. Compositions of composite cements consisting of 90% CEM I 42.5 and 10% fly ash were developed. The cement stone based on the obtained composite cement had a compacted structure with a density of 2.160 g/cm³, which is 9.4% higher than the control sample. It is shown that when composite cement containing 10% fly ash interacts with water, hydration reactions of cement minerals (C₃S, C₂S, C₃A and C₄AF) begin first. This is accompanied by the formation of hydrate neoplasms, such as calcium hydroxide (Ca(OH)₂) and calcium hydrosilicates (C-S-H). Fly ash particles containing amorphous silica progressively participate in a pozzolanic reaction with Ca(OH)₂, leading to the formation of additional calcium hydrosilicates phases. This process enhances structural densification and reduces the porosity of the cement matrix. After 28 days of curing, the compressive strength of the resulting composite cements ranged from 42.1 to 54.2 MPa, aligning with the strength classes 32.5 and 42.5 as specified by GOST 31108-2020. Full article

Emerging evidence highlights the critical role of phagocytosis-related genes in CRC progression, underscoring the need for novel phagocytosis-based prognostic models to predict clinical outcomes. In this study, a four-gene (SPHK1, VSIG4, FCGR2B and FPR2) signature associated with CRC prognosis was developed using single-sample gene set enrichment analysis (ssGSEA), least absolute shrinkage and selection operator (LASSO) regression, and univariate Cox analysis. Pathway enrichment analysis was conducted on the prognostic genes, along with evaluations of the tumor microenvironment and sensitivity to immunotherapy and chemotherapy across the high- and low-risk groups. Prognostic gene validation was performed via quantitative real-time polymerase chain reaction (qRT-PCR) and immunohistochemistry (IHC) using CRC cDNA and tissue microarrays. High-risk patients showed enhanced responsiveness to immunotherapy, while chemotherapy sensitivity varied across risk subgroups. qRT-PCR results revealed upregulation of SPHK1 and FPR2 in cancer tissues, whereas FCGR2B and VSIG4 were downregulated. IHC assays confirmed increased SPHK1 and FPR2 expression in cancer samples. Single-cell RNA sequencing analysis demonstrated a decrease in SPHK1 and FCGR2B, while VSIG4 and FPR2 progressively increased during macrophage differentiation. These findings provide a potential framework for targeted therapy. Full article

Microfluidic methods are powerful platforms for synthesizing advanced functional materials because they allow for precise control of microscale reaction environments. Microfluidics manipulates reactants in lab-on-a-chip systems to enable the fabrication of highly uniform materials with tunable properties, which are crucial for drug delivery, diagnostics, catalysis, and nanomaterial design. This review emphasizes recent progress in microfluidic technologies for synthesizing functional materials, with a focus on polymeric, hydrogel, lipid-based, and inorganic particles. Microfluidics provides exceptional control over the size, morphology, composition, and surface chemistry of materials, thereby enhancing their performance through uniformity, tunability, hierarchical structuring, and on-chip functionalization. Our review provides novel insights by linking material design strategies with fabrication methods tailored to biomedical applications. We also discuss emerging trends, such as AI-driven optimization, automation, and sustainable microfluidic practices, offering a practical and forward-looking perspective. As the field advances toward robust, standardized, and user-friendly platforms, microfluidics has the potential to increase industrial adoption and enable on-demand solutions in nanotechnology and personalized medicine. Full article

Background/Objectives: Pancreatic ductal adenocarcinoma (PDAC) is a malignant tumor and leads to high human malignancy and mortality. Because PDAC is highly drug-resistant and current treatments have adverse reactions, exploring novel approaches for PDAC prevention and therapy is urgently needed. Methods: Antitumor activities of Salecan were evaluated on multiple human pancreatic adenocarcinoma cells in vitro. Cell viability, colony formation, migration and invasion, flow cytometry, caspase-3 activity, qRT-PCR and Western blotting were monitored. RNA-seq was conducted to clarify the mechanism underlying Salecan’s inhibition of pancreatic cancer cell progression. Results: Here we show that Salecan, a naturally occurring polysaccharide of β-glucan, can significantly inhibit pancreatic cancer cell proliferation and exhibit no toxicity in normal cells. We find that Salecan impedes pancreatic cancer cell migration and invasion via the epithelial-to-mesenchymal transition (EMT) pathway. Mechanistically, through RNA sequencing, we reveal that Salecan induces pancreatic cancer cell necroptosis, instead of apoptosis. Moreover, Salecan’s anti-pancreatic cancer bioactivity is attributed to its promotion of the receptor-interacting protein kinase 1 (RIPK1) and mixed lineage kinase-like (MLKL) signaling pathway. Conclusions: Salecan can inhibit pancreatic cancer cell proliferation, migration and invasion in vitro and accelerate cell death by inducing the necroptosis via the MLKL/RIPK1 pathway. These findings identify that Salecan may become a potential functional food component for preventing and treating PDAC. Full article

Alcohol metabolism in the body is a key theme in medical research on alcohol. It is primarily regulated by the alcohol dehydrogenase (ADH) and mitochondrial NADH reoxidation in the liver. Class I ADH1 is a well-known ADH isozyme and a key enzyme in alcohol metabolism, with the lowest Kms for ethanol and the highest sensitivity to pyrazole (Pz) among the ADH isozymes. However, a Pz-insensitive metabolic pathway also plays a role in systemic alcohol metabolism, with increasing metabolic contributions at higher blood alcohol concentrations (BACs) and under chronic alcohol consumption (CAC). The Pz-insensitive pathway is referred to as the non-ADH pathway—specifically, it is a non-ADH1 pathway—and is assumed to involve the microsomal ethanol oxidizing system (MEOS) or catalase, as both enzymes are insensitive to Pz and exhibit higher Kms than ADH1. The MEOS is a favored candidate for this pathway, as its activity markedly increases with the rate of alcohol metabolism under CAC. However, the role of the MEOS in alcohol metabolism has not been proven in vivo (even under CAC conditions), nor has that of catalase. Here, we report Class III ADH3 as a new candidate in the non-ADH1 pathway, as it also has a lower sensitivity to Pz and a higher Km. It is markedly activated by lowering Km following the addition of amphiphilic substances, which increases the solution’s hydrophobicity in the reaction medium; additionally, Nile red staining demonstrates a higher solution hydrophobicity in the cytoplasm of mouse liver cells. The rate of alcohol metabolism in ADH1 knockout (Adh1^−/−) mice—which depends solely on the non-ADH1 pathway—increased by more than twice under CAC and was significantly correlated with the amount of liver ADH3 protein, but not with CYP2E1 protein (a main component of the MEOS). The rate of alcohol metabolism in Adh3^−/− mice lacking ADH3 decreased in a dose-dependent manner compared with wild mice. The liver ADH3 protein in wild-type mice increased in line with the ADH1 protein under CAC. These data suggest that ADH3 contributes to alcohol metabolism in vivo as a non-ADH1 pathway and to the enhancement of alcohol metabolism under CAC through activation of the ADH1/ADH3/NADH reoxidation system. In alcoholic liver diseases, ADH1 activity decreased with the progression of liver disease, while ADH3 activity increased or was maintained even in alcoholic liver cirrhosis. Therefore, the role of ADH3 in alcohol metabolism may be increased in the context of alcoholic liver diseases, complementing the reduced role of ADH1. It has also been suggested that Class II ADH2, Class IV ADH4, and aldehyde dehydrogenase (ALDH) 2 play roles in alcohol metabolism in vivo under certain limited conditions. However, ADH2 and 4 may not contribute to the enhancement of alcohol metabolism through CAC. Full article

Background/Objectives: Urinary tract infections (UTIs) represent a considerable challenge within the field of clinical medicine, as they are responsible for significant morbidity and intensify the operational pressures encountered by healthcare systems. Conventional diagnostic approaches, which include symptom evaluation, dipstick urinalysis, and standard urine culture, often demonstrate inadequacies in identifying atypical clinical manifestations, infections with low bacterial counts, or pathogens that show growth difficulties under typical laboratory conditions. These limitations undermine diagnostic accuracy and hinder timely therapeutic measures. Methods: The present manuscript is a systematic review conducted in accordance with PRISMA guidelines. A structured search was performed in PubMed, Scopus, and Google Scholar, yielding 573 records, of which 107 studies were included for qualitative synthesis. The primary aim of this systematic review is to evaluate both conventional and emerging diagnostic methods for UTIs, with specific objectives of assessing their clinical applicability, limitations, and potential to improve patient outcomes. Results: Recent progress in diagnostic technologies offers promising alternatives. Molecular-based assays, such as multiplex polymerase chain reaction, matrix-assisted laser desorption ionization mass spectrometry, and next-generation sequencing, have substantially improved both the precision and efficiency of pathogen identification. Furthermore, contemporary techniques for evaluating antimicrobial susceptibility, including microfluidic systems and real-time phenotypic resistance assays, enable clinicians to execute targeted therapeutic strategies with enhanced efficacy. Results of this synthesis indicate that while conventional diagnostics remain the cornerstone for uncomplicated cases, innovative molecular and phenotypic approaches demonstrate superior performance in detecting low-count bacteriuria, atypical pathogens, and resistance determinants, particularly in complicated and recurrent infections. These innovations support antimicrobial stewardship by reducing dependence on empirical antibiotic treatment and lessening the risk of resistance emergence. Conclusions: Nonetheless, the incorporation of these technologies into clinical practice requires careful consideration of implementation costs, standardization protocols, and the necessary training of healthcare professionals. In conclusion, this systematic review highlights that emerging molecular diagnostics and resistance-profiling tools offer substantial promise in complementing or enhancing traditional methods, but their widespread adoption will depend on robust validation, cost-effectiveness, and integration into clinical workflows. Full article

Hepatic actinomycosis (HA) and IgG4-related inflammatory pseudotumors are rare and often overlooked causes of liver mass, which can easily be misdiagnosed as primary liver cancer or metastasis. Diagnosis is arduous due to unspecified clinical and radiological features and the fact that histology is not always conclusive. In cases of actinomycosis, the use of molecular diagnostic techniques—such as polymerase chain reaction (PCR) for bacterial DNA—can aid in establishing a definitive diagnosis, especially when conventional cultures are non-diagnostic. We present a case report of one of our patients who was incidentally diagnosed with a hepatic lesion presenting aspecific radiological features. Since radiological imaging was inconclusive, a biopsy was performed, and a diagnosis of IgG4 related hepatic inflammatory pseudotumor was then made. Because of the disease progression, during immunosuppressive therapy, our diagnosis was questioned and a new liver biopsy was carried out. At the end, it took three consequent biopsies to finally find out the presence of an actinomyces infection. Full article

The cycling stability and widespread practical implementation of aqueous zinc ion batteries (AZIBs) are impeded by dendrite growth and the hydrogen evolution reaction (HER). Herein, theaflavins, a low-cost organic bio-compounds and a major component of tea, were innovatively introduced as an electrolyte additive for AZIBs to address these challenges. When added into the electrolyte, theaflavins, with their strong de-solvation capability, facilitated the more uniform and stable diffusion of zinc ions, effectively suppressing dendrite formation and HER. This, in turn, significantly enhanced the coulombic efficiency (>95% in Zn/Cu system) and the stability of the zinc deposition/stripping process in Zn/Zn system. The Zn/Zn symmetric battery system stably cycled for approximately 3000 h at current densities of 1 mA/cm². Compared with H₂O molecules, theaflavins exhibited a narrower LUMO and HOMO gap and higher adsorption energy on zinc surfaces. These properties enabled theaflavins to be preferentially adsorbed onto zinc anode surfaces, forming a protective layer that minimized direct contact between water molecules and the zinc surface. This layer also promoted the electron transfer associated with zinc ions, thereby greatly enhancing interfacial stability and significantly mitigating HER. When 10 mmol/L of theaflavins was present in the electrolyte, the system exhibited lower impedance activation energy, a smoother zinc ion deposition process, reduced corrosion current, and higher HER overpotential. Furthermore, incorporating theaflavins into the electrolyte enhanced the vanadium redox reaction and accelerated zinc ion diffusion, thereby significantly improving battery performance. This work explores the design of a cost-effective electrolyte additive, providing essential insights for the progress of practical AZIBs. Full article

Glaciers play a crucial role in shaping global hydrology and biogeochemical cycles, yet their climate-forced dynamic impact on chemical denudation and solute yields remain poorly understood. This study compiled data on 40 well-documented cationic denudation rates (CDR) from glaciers across Northwest America, the Svalbard/Arctic Canada, Iceland, Greenland, Europe, China-Tibet, Antarctica, and the Himalayas, revealing substantial spatial variability. CDRs ranged from 46 to 4160 meq m⁻² yr⁻¹. Northwest American and Himalayan glaciers exhibited the highest CDRs, with the Himalayan denudation rate exceeding the global average by more than fourfold. The exceptionally high mean chemical weathering intensity (CWI) of 801 meq m⁻³ from the Himalayan glaciers indicate a wide range of geochemical and climatic conditions within the region, while Northwest American and Greenland glaciers show comparatively lower mean intensities (273 and 247 meq m⁻³, respectively) suggesting a consistent geochemical regime. Northwest American glaciers had the highest specific discharge rates, while Svalbard/Arctic Canada glaciers had the lowest, reflecting regional disparities influenced by climatic and geological factors. A Bonferroni post hoc test highlighted significant differences in specific discharge between Northwest American glaciers and two other basins, emphasizing their distinct hydrological behavior. Predictive modeling revealed a statistically significant but weak relationship between CDR and specific discharge (R² = 57%), suggesting that much of the variability in CDR cannot be explained by specific discharge alone. A regression coefficient of 382 meq m⁻² yr⁻¹ indicates that CDR increases with glacier discharge, although basin-specific analyses showed minimal variation in this relationship across regions. Svalbard/Arctic Canada, Antarctic, Greenlandic, Icelandic, and European Alpine glaciers displayed lower CDRs, which varied depending on underlying lithology, with higher rates observed in carbonate and basaltic terrains compared to other lithologies. We hypothesize that glacier retreat enhances the downward progression of the weathering reaction front, increasing CDR, particularly in rapidly retreating glaciers. Full article