Search Results (21,544)

Background: We aimed to evaluate ability of a novel scoring system that combines fluorodeoxyglucose-uptake parameters and systemic inflammatory response indicators to predict hepatocellular carcinoma (HCC) prognosis. Methods: Clinical data were collected from patients with HCC who underwent hepatectomy at our hospital in 2014–2022. The tumor-to-liver ratio (TLR) was adopted as a positron emission tomography/computed tomography (PET/CT) standardized uptake value (SUV)-related indicator and calculated as the ratio of the SUV_max of tumor tissue to the SUV_mean of normal liver tissue. The patients’ immune microenvironment reflected the NLR. Postoperative overall survival (OS)- and disease-free survival (DFS)-related independent prognostic factors were analyzed using Cox proportional hazards regression modeling. Results: Eighty-nine patients were included. TLR, NLR, and alpha-fetoprotein levels were independently associated with OS and DFS. The OS and DFS in the zero-point group were significantly longer than those in the one- and two-point groups. Time-dependent ROC curve analyses revealed area under the curve values of 0.830 and 0.752 for 5-year OS and DFS, respectively, for the scoring system, outperforming single evaluation indices. Conclusions: The proposed scoring system, which incorporates both TLR and NLR, simultaneously reflects metabolic tumor characteristics and the host’s immune microenvironment, enabling more accurate patients with early to intermediate-stage HCC undergoing hepatectomy classification and better prognostic evaluation. Full article

Fine particulate matter (PM2.5) is a major air pollutant linked to lung cancer progression. In Southeast Asia, seasonal smoke-haze produces biomass-derived PM2.5, yet its acute effects on genetically diverse lung tumours remain unclear. We investigate how Chiang Mai haze-derived PM2.5 impacts oxidative stress and gene expression in three non-small-cell lung cancer (NSCLC) cell lines: A549 (KRAS-mutant), NCI-H1975 (EGFR-mutant), and NCI-H460 (KRAS/PIK3CA-mutant). Cells were exposed to PM2.5 (0–200 µg/mL) and assessed for viability (MTT), reactive oxygen species (ROS; H₂O₂, •OH) and malondialdehyde (MDA) levels, mitochondrial-associated fluorescence, and whole-transcriptome responses. Acute exposure caused dose- and time-dependent viability loss, with A549 and NCI-H1975 more sensitive than NCI-H460. ROS profiling normalized to viable cells revealed genotype-specific oxidative patterns: cumulative increases in A549, sharp reversible spikes in NCI-H1975, and modest changes in NCI-H460. MitoTracker intensity trended downward without significance, with subtle fluorescence changes and particulate uptake. RNA-seq identified robust induction of xenobiotic metabolism (CYP1A1, CYP1B1), oxidative/metabolic stress mediators (GDF15, TIPARP), and tumour-associated genes (FOSB, VGF), alongside repression of tumour suppressors (FAT1, LINC00472). Pathway enrichment analyses highlighted oxidative stress, IL-17, NF-κB, and immune checkpoint signaling. Together, biomass haze-derived PM2.5 from Northern Thailand drives genotype-dependent oxidative stress and transcriptional remodeling in NSCLC cells. Full article

Copper and nickel ions play pivotal, albeit distinct, roles as essential trace elements in living systems, and primarily serve as co-factors for a range of enzymes. However, as with all trace metal ions, excessive concentrations can exert adverse toxicological properties. Interestingly, the incorporation of these in cell culture media can establish novel chemical interactions, with their speciation status markedly influencing characteristics, including cell maturation, and cellular uptake mechanisms. Thus, the primary objective of this study was to investigate and determine the speciation status (i.e., complexation) of nickel(II) and copper(II) ions by biomolecules present in RPMI 1640 mammalian cell culture medium using virtually non-invasive high-resolution proton NMR analysis, an investigation of much relevance to now routine studies of their toxicological actions towards cultured cells. Samples of the above aqueous culture medium were ¹H NMR-titrated with increasing added concentrations of 71–670 µmol/L Ni(II)(aq.), and 0.71–6.7, 7.1–67 and 71–670 µmol/L Cu(II)(aq.), in duplicate or triplicate. ¹H NMR spectra were acquired on a JEOL ECZ-600 spectrometer at 298 K. Results demonstrated that addition of increasing concentrations of Ni(II) and Cu(II) ions to the culture medium led to the selective broadening of a series of biomolecule resonances, results demonstrating their complexation by these agents. The most important complexants for Ni(II) were histidine > glutamine > acetate ≈ methionine ≈ lysine ≈ threonine ≈ branched-chain amino acids (BCAAs) > asparagine ≈ aspartate > tyrosine ≈ tryptophan, whereas for Cu(II) they were found to be histidine > glutamine > phenylalanine ≈ tyrosine ≈ nearly all remaining aliphatic metabolites (particularly the wealth of amino acids detectable) > 4-hydroxyphenylacetate (trace culture medium contaminant), in these orders. However, Cu(II) had the ability to influence the linewidths of these signals at much lower added levels (≤7 µmol/L) than that of Ni(II), the broadening effects of the latter occurring at concentrations which were approximately 10-fold greater. Virtually all of these added metal ion-induced resonance modifications were, as expected, reversible on addition of equivalent or excess levels of the chelator EDTA. From this study, changes in the co-ordination sphere of metal ions in physiological environments can give rise to marked modifications in their physicochemical properties (e.g., redox potentials, electronic charges, the potential catalytic generation of reactive oxygen species (ROS), and cell membrane passages). Moreover, given that the above metabolites may also function as potent hydroxyl radical (^●OH) scavengers, these findings suggest that generation of this aggressively reactive oxidant directly from Cu(II) and Ni(II) ions in physiologically-relevant complexes may be scavenged in a ‘site-dependent’ manner. This study is of further relevance to trace metal ion research in general since it enhances our understanding of the nature of their interactions with culture medium biomolecules, and therefore provides valuable information regarding their overall chemical and biological activities, and toxicities. Full article

This study investigates the carbonation degree of reclaimed water (RW) and its potential use as mixing water for cementitious materials under controlled laboratory conditions using a simplified CO₂ injection method. To reproduce the chemical environment of actual RW, a synthetic reclaimed water (SRW) system with a cement-to-sand ratio of 8:2 was prepared and used throughout the evaluation. Thermogravimetric analysis revealed that the cementitious solids suspended in SRW exhibit high reactivity with CO₂, achieving a net CO₂ uptake of 16.8%, equivalent to 8.31 g of CO₂ sequestered per kilogram of RW. The use of untreated RW as mixing water slightly reduced flowability and increased superplasticizer demand compared with distilled water, whereas carbonation treatment of RW improved workability and mitigated the rapid initial setting typically observed with untreated RW. Notably, replacing 3% of the cement with carbonated RW solids did not cause any reduction in compressive strength, indicating that the carbonated solids can be incorporated without compromising mechanical performance. These results confirm that the CaCO₃ formed during RW carbonation remains stably retained within mortar and concrete, demonstrating the feasibility of using carbonated RW as a dual-function material—serving both as mixing water and as a medium for CO₂ sequestration. Full article

Background: Pancreatic hamartoma (PH) is an exceptionally rare, benign, mass-forming lesion accounting for less than 1% of all pancreatic tumors. Its rarity and non-neoplastic nature contribute to significant diagnostic challenges, often leading to misclassification as malignant disease. This study presents a case of PH and a systematic review of all reported cases, with emphasis on histopathological and imaging characteristics. Methods: A comprehensive electronic search of PubMed, Scopus, and Web of Science was conducted up to 1 April 2025, to identify eligible case reports and series. Results: We describe a 37-year-old woman with a cystic lesion of the pancreatic tail, ultimately confirmed histologically as a cystic pancreatic hamartoma following distal pancreatectomy with splenectomy, with an uneventful postoperative course. Of 687 screened studies, 51 met the inclusion criteria, comprising 77 cases (68 adults, 9 pediatric). PHs occurred most frequently in males (52.9%), with a mean age of 59.5 ± 12.9 years, and were often asymptomatic (57.4%). The pancreatic head was the most common site (52.9%). On MRI, PHs typically exhibited low T1-weighted and high T2-weighted signal intensity, with no FDG uptake (82%) and moderate or no restriction on DWI, distinguishing them from neuroendocrine tumors (NETs). Histologically, most lesions were solid (64.7%) or solid–cystic (35.3%), with low spindle cell cellularity and absent Langerhans islets. Conclusions: Low T1WI signal and moderate DWI signal are the key features distinguishing PHs from NETs. Incorporating these findings with EUS-FNA and immunohistochemistry can support a provisional diagnosis and help avoid unnecessary radical surgery. Full article

(1) Background: Oat (Avena sativa L.) is a crop that is widely used in human nutrition, while it also plays an important role in animal husbandry as a high-quality forage crop. However, this crop is particularly susceptible to combined biotic stressors, including insect pests (Agriotes lineatus) and fungal infections (Fusarium spp.). These stresses act synergistically: root damage caused by wireworms increases the plant’s susceptibility to fungal infection, while pathogens further limit nutrient uptake and root system development. In recent years, the reduced efficacy of chemical pesticides against both insect pests and fungal pathogens has highlighted the need for alternative strategies in oat protection, leading to an increased focus on developing bacterial bio-inoculants as sustainable and effective biocontrol agents. (2) Methods: This study aimed to identify bacterial strains capable of suppressing wireworms (Agriotes lineatus) and Fusarium spp. in oats, while simultaneously promoting plant growth. Bacterial isolates were screened for key Plant Growth Promoting (PGP) and biocontrol traits, including IAA and siderophore production, phosphate solubilization, and the presence of toxin- and antibiotic-coding genes. (3) Results: The highest insecticidal effect against wireworms was recorded for Bacillus velezensis BHC 3.1 (63.33%), while this isolate also suppressed the growth of F. proliferatum for 59%, F. oxysporum for 65%, F. poae for 71%, and F. graminearum for 15%. The most effective Bacillus strains (with insecticidal and antifungal activity) were identified and tested in two pot experiments, where their ability to enhance plant growth in the presence of insects and fungi was evaluated under semi-controlled conditions. An increase in plant biomass, grain yield, and nitrogen content was observed in oat inoculated with B. velezensis BHC 3.1 and B. thuringiensis BHC 2.4. (4) Conclusions: These results demonstrate the strong potential of both strains as multifunctional bio-inoculants for enhancing oat growth and mitigating the adverse effects of wireworm damage and Fusarium infection. Full article

Citrus species develop fruits through both sexual reproduction and parthenocarpy, following a growth pattern with an initial exponential phase dominated by cell division in the ovary wall, followed by a linear phase driven by cell expansion in juice vesicles. Sustained carbohydrate supply is essential to support the metabolic energy required for these processes, which are tightly regulated by hormonal signaling pathways involving gibberellins (GAs), auxins (IAA), cytokinins, and abscisic acid (ABA). Recent studies across cultivars have identified genes associated with hormone biosynthesis, carbohydrate metabolism, cell cycle regulation, and abscission in ovule and pericarp tissues. Manipulation of these hormones through targeted treatments and cultural practices has shown potential to enhance fruit set and growth. Notably, exogenous GA₃ application promotes fruit set in parthenocarpic cultivars by upregulating GA20ox2/GA3ox and CYCA1.1, whereas synthetic auxins enhance fruit enlargement by improving assimilate partitioning and water uptake. Optimizing such treatments, however, requires a comprehensive understanding of physiological, environmental, and agronomic factors influencing fruit development. This review summarizes recent advances in hormonal and molecular regulation of citrus fruit set and developments, assesses applied strategies to improve productivity, and identifies current knowledge gaps needed to refine biotechnological and management aimed at enhancing both yield and fruit quality. Full article

To better understand recent adolescent (10–19 years) HIV trends in Central America, we analyzed routine data from countries supported by the United States President’s Emergency Plan for AIDS Relief (PEPFAR): Guatemala, El Salvador, Honduras, Panama, and Nicaragua, over the period from October 2020 to September 2024. Key PEPFAR indicators included HIV testing, HIV positivity rates, new treatment initiations, advanced HIV disease (AHD) at diagnosis, viral load coverage (VLC), viral load suppression (VLS), and multi-month dispensing (MMD) uptake for children and adolescents living with HIV (CALHIV) from 10–19 years of age. Since October 2020, the number of HIV tests conducted among adolescents has increased; however, the positivity rate has remained stable at approximately 2%. The number of adolescents initiating treatment increased by 21%. At the same time, VLS has shown steady regional improvement (from 73% to 90%), though VLC is a persistent challenge (80%). Treatment interruption rates have been relatively stable, fluctuating between 2% and 3%. Advanced HIV is high in adolescents new to treatment (34%), especially among females (40%), though cluster of differentiation 4 (CD4) testing at diagnosis has only been collected recently and coverage is not complete. The high prevalence of AHD among adolescents underscores the need to reinforce earlier and more targeted interventions for adolescents, especially in countries with greater HIV prevalence such as Panama and Guatemala. Full article

Accurate evaluation of plant-available phosphorus (P) in flooded paddy soils requires consideration of redox dynamics and soil-specific properties. This study evaluated five soil P extraction methods, such as Truog, Bray 2, Mehlich 3, Olsen, and ascorbic acid-reduced Bray 2 (AR Bray 2), using soils collected from 20 paddy fields in a cold region of Japan that have received long-term fertilization. All four methods, except AR Bray 2, were conducted under air-dried and flooded incubation conditions. Additionally, we conducted pot experiments with the two rice cultivars to measure P uptake. Bray 2 extracted the highest amount of P (543.6–1045.4 mg P kg⁻¹). Incubation increased extractable P by factors of 2.4–4.9 with the Mehlich 3 and Truog methods, indicating enhanced P solubility under reduced conditions. The Olsen method showed minimal sensitivity to redox changes (−31.4 mg P kg⁻¹). Principal component and cluster analyses suggested three patterns of soil P behavior under changing redox conditions: (1) stable P extractability regardless of redox status; (2) increased P availability after incubation; and (3) P extractability depending on the extraction method used. These patterns were not explained by regional or taxonomic classifications. A comparison of soil extractions and P uptake indicated that no single method consistently predicted shoot P concentrations across all soils, suggesting that conventional P extraction methods may have limited ability in long-term fertilized paddy soils. Our findings demonstrate that soil-specific redox behavior and cultivar-specific P demand critically influence the effectiveness of standard P tests. Therefore, selecting diagnostic methods tailored to soil characteristics and crop requirements is essential for accurate P evaluation and sustainable fertilizer management in rice cultivation. Full article

Background: The survival of newly diagnosed multiple myeloma (NDMM) has improved markedly worldwide with the introduction of proteasome inhibitors (PIs), immunomodulatory drugs (IMiDs), and anti-CD38 monoclonal antibodies. However, real-world progress among Chinese patients remains underexplored. This study evaluated 20-year survival trends in patients with NDMM treated in our institute and benchmarked them against outcomes from the Flatiron Health database in the United States. Patients and methods: Consecutive adults diagnosed with NDMM in our institute between 2003 and 2023 were retrospectively analyzed. U.S. patients were identified from the Flatiron Health database using similar inclusion criteria. Clinical characteristics, first-line regimens, and autologous stem cell transplantation (ASCT) rates were summarized. Overall survival (OS) and progression-free survival (PFS) were estimated by Kaplan–Meier methods. Results: Among 1622 Chinese and 12,582 US patients, median age was 57 vs. 68 years. The median PFS and OS of NDMM patients in our institute was 40.1 months and 99.6 months, respectively. Induction therapy in the NICHE cohort changed markedly from primarily chemo-based therapy to combined PIs + IMIDs-based treatment, whereas these treatments were used much earlier in Flatiron. Uptake of new therapies in China increased rapidly after their inclusion in national health insurance. ASCT utilization was higher overall in China (34.9% vs. 22.1%) but remained lower among patients >65 years (6.7% vs. 12.1%). Conclusions: Two decades of real-world data from a major Chinese myeloma center demonstrate substantial improvements in survival and modernization of NDMM treatment, while highlighting persistent disparities amongst older adults. Full article

The sodium iodide symporter (NIS) is a key protein in thyroid function responsible for iodine uptake, and it may be involved in the pathogenesis of autoimmune thyroiditis. However, it is also expressed in the salivary glands, the primary target of autoreactive cells in Sjögren’s syndrome (SS). Given the common link between the two diseases, we computationally investigated whether the epitopes of NIS can trigger an immune response leading to SS in Hashimoto’s thyroiditis (HT) patients genetically predisposed to both diseases. The TepiTool 2016, ABCpred 2006, and DiscoTope 2.0 servers were used to predict T-cell and B-cell epitopes by inputting the FASTA sequences and 3D structures of NIS, thyroid peroxidase (TPO) and Ro60 Y RNA-binding protein (Ro60), which served as reference antigens for HT and SS, respectively. T-cell epitopes were selected based on their binding to a panel of human leukocyte antigen (HLA) alleles associated with both SS and HT. We identified a total of 376 linear T-cell epitopes, 64 linear B-cell epitopes and 68 conformational B-cell epitopes of NIS. Compared to TPO, NIS T-cell epitopes showed significantly lower affinity for HLA alleles (p < 0.0001), while no significant difference was found compared to Ro60. While linear B-cell epitopes of NIS, TPO, and Ro60 showed similar binding affinity, conformational epitopes of NIS were predicted to have higher immunogenicity than Ro60 (p = 0.04), while no significant difference was found compared to TPO. These pivotal findings, discovered by the methods of computer modeling, suggest that NIS can potentially activate T cells and B cells in patients with genetic predisposition to SS and HT and need to be confirmed by further laboratory studies. Full article

Objectives: Despite high overall vaccination coverage in Galicia, Spain, human papillomavirus (HPV) vaccine uptake remains below the 90% target set by the World Health Organization for 2030. This study aimed to assess baseline knowledge of HPV and attitudes towards HPV vaccination among Galician adolescents and to evaluate the impact of a brief educational intervention delivered as a “pill of knowledge”. Methods: A quasi-experimental pre-/post-intervention study was conducted among 967 students aged 12–16 years from 16 secondary schools in Galicia during the 2023–2024 academic year. A concise, structured 15-min educational session termed a “pill of knowledge” was delivered, and HPV-related knowledge and vaccination intention were measured immediately before and after the intervention using a standardized questionnaire. Results: Following the “pill of knowledge”, the mean proportion of correct responses increased by 30.1 ± 16.6% across all knowledge items. Among unvaccinated participants, intention to accept HPV vaccination rose from 77.7% to 94.4% in girls and from 64.7% to 85.8% in boys. Pre-intervention predictors of vaccination intention included perceived vaccine efficacy and baseline HPV knowledge. Post-intervention independent predictors comprised being female, younger age (12–13 years), and prior sexual education delivered by teachers or parents. The overall predictive accuracy of the logistic regression model for vaccination intention improved from 75.6% before the intervention to 92.7% afterwards. Conclusions: A brief, school-based “pill of knowledge” produced substantial and immediate improvements in HPV knowledge and vaccination acceptance among Galician adolescents. These findings strongly support the systematic incorporation of short, evidence-based educational interventions of this kind into the school setting as an effective public health measure to increase HPV vaccine coverage and advance progress toward WHO elimination targets. Full article

Iron is essential for numerous physiological processes, including oxygen transport, energy metabolism, and immune function. This study evaluated the efficacy and safety of three iron formulations combining heme and non-heme iron, comparing them with existing market products and the original form of iron. The formulations tested were GlobiFer^® Forte, a combination of heme and non-heme iron containing 18 mg of elemental iron (hereinafter referred to as nutraceutical product 1); GlobiFer^®, a combination of heme and non-heme iron containing 14 mg of elemental iron (hereinafter referred to as nutraceutical product 2); and a double dose of nutraceutical product 2. Using an in vitro 3D intestinal barrier model, all three formulations significantly increased tight junction protein expression and TEER values, indicating preserved barrier integrity. Iron absorption analysis revealed that all three iron formulations had higher absorption rates than controls. Nutraceutical product 1 showed the highest absorption, associated with increased expression of the iron transporters such as the primary non-heme iron transporter, DMT1, and the leading apical heme transporter, HCP-1. All three new formulations increased ferritin and ferroportin levels, markers of systemic iron storage and regulation. Nutraceutical product 1 was found to be the most effective, based on percentage. Overall, combining heme and non-heme iron improved intestinal absorption and supported iron metabolism, with Nutraceutical Product 1 proving the most promising in terms of efficacy and safety. These results support the development of optimised dual-source iron supplements to improve bioavailability and maintain intestinal barrier integrity, prerequisites for better efficacy and tolerability in clinical use. Full article

Fibroblast growth factor 21 (FGF21) is a key hormone for metabolic homeostasis under conditions such as obesity, aging and diabetes. While extensively studied in males, its role in female physiology remains poorly defined. This study evaluated the effects of hepatic FGF21 deletion in 12-month-old female mice using a liver-specific FGF21 knockout (FKO) model. FKO females exhibited reduced body weight and improved glucose tolerance, with no changes in circulating FGF21 levels. In the liver, RT-qPCR analysis showed that the expression of genes involved in de novo lipogenesis, including Srebp1c, Fasn, and Scd1, was downregulated, whereas markers of fatty acid uptake (Cd36) and β-oxidation (Cpt1a) were upregulated without alterations in hepatic triglyceride content and lower levels of serum adiponectin. Remarkably, telomere length in both liver and adipose tissue was preserved, indicating improved cellular aging. Hepatic transcriptomic analysis revealed a global downregulation of genes linked to cytoskeletal organization, immune processes and fibrosis. Among these, Chrna4, a hepatocyte-specific nicotinic acetylcholine receptor subunit implicated in protection against metabolic-associated steatohepatitis (MASH), was significantly reduced. These findings suggest that hepatic FGF21 deficiency in aged female mice promotes metabolic health by limiting pro-inflammatory and fibrotic pathways and preserving telomere integrity, with Chrna4 emerging as a potential mediator. Full article

Introduction: Vaccination has led to significant decreases in mortality over the last century but requires high levels of uptake to be successful in reducing a wide range of infectious diseases in communities. Vaccine hesitancy is on the rise in the United States with most adults not receiving all recommended vaccinations, and childhood vaccinations are declining. Living in a rural community with a lack of access to resources may further limit uptake of vaccines. Identifying strategies to enhance vaccine confidence and access may assist in increasing vaccine uptake. The purpose of this study was to describe the landscape of existing community-based vaccination efforts and assess the components of a successful community-based vaccination program in rural eastern North Carolina. To reach this purpose, we conducted qualitative interviews with those involved in running community-based vaccine education and navigation programming in rural eastern North Carolina.” Methods: Researchers conducted 25 semi-structured interviews with participants involved in vaccination efforts in three rural counties in Eastern North Carolina. Interviews were transcribed, coded in NVivo version 14, and analyzed using thematic analysis to synthesize insights from participants. Results: Study participants held manager or coordinator roles in area health agencies, clinics, and pharmacies. Reported strengths of current vaccine efforts in Eastern North Carolina included patient education, strong partnerships between organizations providing vaccines, and ability to engage community members. Successful vaccine efforts have engaged participants through social media, flyers, trusted leaders, and the provision of convenient vaccine appointments. Areas for improvement in vaccine efforts included engaging a wider audience at vaccine events, building trust in vaccines among community members, and expanding vaccine education for hard-to-reach populations. Participants supported the development of a proposed community-based education and navigation program and felt that community members would be interested. Identified challenges included low participation due to vaccine hesitancy which could be overcome through incentives and delivery from trusted individuals. Conclusions: We found that there is still a need for trust building, education, and patient engagement within the landscape of existing community-based vaccination efforts for vulnerable populations in rural eastern North Carolina. Study participants indicated support for the development of a vaccine education program and researchers determined the project to be feasible. Based on the results of this study, researchers developed and implemented an integrated vaccine education and navigation program in Eastern North Carolina. Full article