Search Results (42,363)

Corn dust is an abundant agro-industrial by-product with potential as an alternative energy source. Its use in animal feeding, however, is restricted by high fiber content and low digestibility. This study evaluated the effects of non-starch polysaccharide (NSP) enzymes and yeast (Candida tropicalis KKU20) on the chemical composition, fermentation characteristics, and microbial populations of fermented corn dust. The experiment was conducted using a completely randomized design with a 3 × 2 factorial arrangement plus an additional control treatment. Factor A consisted of three levels of enzyme supplementation (0.02%, 0.04%, and 0.06% of dry matter), and Factor B consisted of yeast supplementation (without yeast or with C. tropicalis KKU20, approximately 1 × 10¹³ cells/g of inoculum). The control treatment consisted of fermented corn dust without enzyme or yeast supplementation. Samples were fermented for 15 days prior to analysis. Yeast inoculation increased crude protein and non-fiber carbohydrate contents while reducing neutral detergent fiber, acid detergent fiber, and acid detergent lignin (p < 0.05). Significant enzyme × yeast interactions were observed for several components, particularly fiber fractions (p < 0.05). The reduction in fiber was more pronounced when enzymes were combined with yeast. Predicted energy values, including metabolizable and digestible energy, were increased following yeast supplementation (p < 0.05). Fermentation characteristics were mainly affected by yeast. Yeast-treated samples exhibited higher pH and ammonia–nitrogen concentrations, indicating increased nitrogen turnover during fermentation. In contrast, lactic and propionic acid concentrations were higher in treatments without yeast, while yeast inoculation was associated with lower acetic acid and slightly higher butyric acid levels. Microbial analysis indicated interactions between treatments for lactic acid bacteria populations, reflecting competition for available substrates. No coliform bacteria were detected, indicating acceptable hygienic quality. Overall, yeast inoculation modified the chemical composition of corn dust, particularly by increasing crude protein and reducing fiber fractions, while NSP enzymes contributed to fiber degradation, especially when combined with yeast. However, these changes reflect compositional modification rather than confirmed feeding value, and further evaluation under rumen or in vivo conditions is required. Full article

Objective: The optimal adjuvant therapy for intermediate-risk endometrial cancer remains controversial. Although radiotherapy is commonly used in Western countries, chemotherapy is preferred in Japan; however, its real-world outcomes remain limited. This study evaluated the survival and safety outcomes of three-cycle adjuvant chemotherapy in patients with intermediate-risk endometrial cancer. Methods: We retrospectively analyzed patients who underwent primary surgery for endometrial cancer at a university hospital between 2008 and 2019. Low- and intermediate-risk patients defined by the 2013 Japan Society of Gynecologic Oncology recurrence risk classification were included. Intermediate-risk patients were classified as receiving chemotherapy (Int-Chemo+) or not (Int-Chemo−). The primary endpoint was disease-free survival (DFS); secondary endpoints included cancer-specific survival (CSS), adverse events, and treatment completion. Results: Among 232 patients, 161 were low-risk and 71 intermediate-risk; 49 intermediate-risk patients received platinum-based combination chemotherapy. The 5-year DFS rates were 92.8% (95% CI, 88.6–96.9) in the low-risk group, 89.4% (95% CI, 80.7–98.2) in the Int-Chemo+ group, and 73.5% (95% CI, 53.5–93.6) in the Int-Chemo− group (log-rank p = 0.005). DFS differed between the Int-Chemo+ and Int-Chemo− groups (HR 0.232, 95% CI 0.062–0.867), whereas the DFS outcomes of the Int-Chemo+ group were numerically similar to those of the low-risk group. CSS did not differ significantly among groups (p = 0.052). Treatment completion was 93.8%, and grade ≥ 3 adverse events were mainly hematologic, without severe late toxicities. Conclusions: Three cycles of adjuvant platinum-based combination chemotherapy for intermediate-risk patients may be associated with improved DFS, while maintaining a high treatment completion rate and manageable toxicity. Full article

Pirfenidone (PFD) shows therapeutic potential for liver fibrosis, but its molecular mechanisms are not fully elucidated. Activation of hepatic stellate cells (HSCs) is central to liver fibrosis, making their targeted elimination a prime therapeutic strategy. Since amino acid metabolism governs both HSC activation and ferroptosis, we investigated whether PFD acts by reprogramming these metabolic pathways. Analysis of primary rat HSCs revealed that their in vitro activation induced fibrotic markers, including collagen type I and α-smooth muscle actin, as well as key metabolic enzymes. Specifically, we observed upregulation of glutaminase 1, initiating glutaminolysis to produce glutamate; serine hydroxymethyltransferase 2, which generates glycine from serine; and pyrroline-5-carboxylate synthase, the rate-limiting enzyme for de novo proline synthesis. Treatment with PFD suppressed HSC activation by reducing protein levels of these enzymes, an effect consistent with PFD’s inhibition of activating transcription factor 4 nuclear accumulation. This created a dual metabolic vulnerability, limiting amino acid precursors for both collagen synthesis and the master antioxidant glutathione (GSH). Consequently, while PFD alone was not cytotoxic, GSH depletion sensitized activated HSCs to ferroptosis. Co-treatment with the ferroptosis inducer erastin triggered a synergistic increase in reactive oxygen species, labile iron, and lipid peroxidation, culminating in cell death. This synergistic lethality was abrogated by the ferroptosis inhibitor ferrostatin-1 and the antioxidant N-acetylcysteine, confirming ferroptosis as the specific cell death modality. Our study uncovers a dual anti-fibrotic mechanism for PFD: PFD inhibits collagen synthesis by limiting key amino acid precursors and depletes GSH. This compromises antioxidant defenses, creating vulnerability to ferroptosis. Our findings establish a rationale for using PFD in combination therapies designed to eliminate activated HSCs. Full article

Despite its significant water-saving potential, the adoption of alternate wetting and drying (AWD) irrigation remains limited due to infrastructure constraints and intensive manual monitoring requirements. An automated precision irrigation system was developed and tested at the Bangladesh Rice Research Institute research farm in Gazipur, Bangladesh. The system combined ultrasonic water-level sensors, capacitive soil moisture sensors, an Arduino-based microcontroller, a GSM communication module, and solar-powered automatic control gates. Field performance was evaluated following a Randomized Complete Block Design (RCBD) under four irrigation treatments: IRRISAT, IRRI35, IRRI25, and continuous flooding (CF). The first three irrigation treatments were operated using scheduled daily decision windows, in which irrigation actions were automatically triggered based on predefined schedules and sensor threshold values. In IRRISAT, irrigation started when soil moisture dropped slightly below saturation and stopped at a ponding depth of 5 cm, while IRRI35 and IRRI25 were triggered at volumetric soil water contents of 35% and 25%, respectively, with the same upper cutoff of 5 cm ponding depth; CF served as the control. The IRRI35 treatment achieved a high grain yield (7.76 t ha⁻¹) while reducing water use by 28% and energy consumption by 37% compared to CF. Water use efficiency was considerably higher under IRRI35 (9.4 kg ha⁻¹ mm⁻¹) than under CF (6.7 kg ha⁻¹ mm⁻¹). The automated system proved to be reliable and precise in scheduled irrigation control, significantly reducing water use and labor requirements. The findings suggest that large-scale adoption of the system under real-world cultivation conditions could reduce irrigation energy needs and contribute to sustainable water governance in rice production. Full article

Non-alcoholic fatty liver disease (NAFLD) is the most common liver disease worldwide. Its main contributors are obesity, insulin resistance, diabetes and metabolic syndrome. Liver pathogenesis exacerbates when oxidative stress, inflammation, lipid accumulation, and attenuated autophagy signals coexist together with the main determinants of the liver disease. These findings may indicate that the suppression of the disease requires multi-targeting compounds to alleviate more than one factor, resulting in improved histopathological outcomes. This review studies natural compounds, given as supplements, with antioxidant and anti-inflammatory properties. The compounds included are vitamins, carotenoids, low-molecular-weight thiol-containing compounds, fatty acids and others that have been investigated for their pleiotropic activity alone or in combination. They act at different pathways and signals, and at gene expression control, modulating oxidative stress and inflammation, such as collagen, TNF-α, NF-κB, Nrf2 and PPARs genes. Their mechanism of action and characteristics may be encouraging treatment options as multi-targeting compounds for NAFLD and other diseases whose pathophysiology is closely related to metabolic syndrome. However, extensive study on their safety, toxicity, mechanisms of action and dosage regimen is needed before their final establishment as potential treatment options. Full article

Upper tract urothelial carcinoma (UTUC) accounts for approximately 5–10% of urothelial malignancies and represents a clinically challenging disease due to its frequent presentation at advanced stages and its association with significant morbidity. Radical nephroureterectomy (RNU) with bladder cuff excision remains the standard treatment for high-risk disease; however, this approach inevitably results in loss of renal function and may significantly affect eligibility for cisplatin-based chemotherapy. In patients with imperative indications for renal preservation—including a solitary kidney, bilateral disease, or advanced chronic kidney disease—Kidney-Sparing Surgery (KSS) represents an essential therapeutic strategy. Technological advances in flexible ureteroscopy, improved visualization systems, and laser energy sources have significantly expanded the feasibility of conservative management. Ureteroscopic tumor ablation has become the cornerstone of KSS, allowing local disease control while preserving renal function. Although recurrence rates remain relatively high, repeated endoscopic treatment combined with strict surveillance protocols can achieve acceptable oncological outcomes in carefully selected patients. This narrative review summarizes the current evidence regarding conservative management of UTUC in imperative clinical situations, with particular emphasis on patient selection, endoscopic treatment modalities, laser technologies, economic implications, patient counselling, and follow-up strategies. Full article

Background/Objectives: The prognostic and predictive role of BMI in patients with HR+/HER2− MBC remains controversial, particularly in the era of CDK4/6 inhibitors. This study aimed to evaluate the association between baseline BMI and clinical outcomes in patients treated with palbociclib in a real-world setting. Methods: We conducted a multicenter retrospective observational cohort study including 326 patients with HR+/HER2− MBC treated with palbociclib in combination with endocrine therapy across six oncology centers in Romania. Only patients who received palbociclib for at least three months were included. Patients were stratified according to BMI into <25 kg/m² and ≥25 kg/m² groups. PFS and OS were the primary endpoints, while ORR and CBR were secondary endpoints. Results: Among the 326 patients, 66.56% were classified as overweight or obese (BMI ≥ 25 kg/m²). Median PFS was 23.66 months in the BMI < 25 group and 26.78 months in the BMI ≥ 25 group, with no statistically significant difference (HR 0.86; 95% CI 0.62–1.20; p = 0.373). Median OS was not reached in the BMI < 25 group and was 43.73 months in the BMI ≥ 25 group, also without a significant difference (HR 0.82; 95% CI 0.52–1.30; p = 0.397). ORR (29.07% vs. 28.89%) and CBR (90.70% vs. 88.33%) were comparable between BMI groups. In multivariate analysis, liver metastases and brain metastases were independently associated with worse outcomes, whereas BMI was not an independent prognostic factor. Conclusions: In this selected real-world cohort of patients with HR+/HER2− MBC who tolerated at least three months of palbociclib, baseline BMI was not associated with treatment response, PFS, or OS. While clinically informative, these results should not be interpreted as definitive evidence that body weight has no influence on palbociclib efficacy, given the methodological constraints of the analysis. BMI alone may be insufficient to capture the complex interplay between body composition and treatment outcomes, highlighting the need for more refined biomarkers of body composition in this setting. Full article

This study investigated the immobilization of Chlorella sp. in a nylon matrix to analyze its retention behavior and monitor biomass adhesion. Image capture and processing techniques were combined with capacitance measurements over time, using a Python-based data analysis code. The experiment was carried out in a 2 L photobioreactor under controlled conditions (24 °C, continuous aeration at 9.31 L/min, and light intensity of 71 μmol m⁻² s⁻¹). The methodology allowed for quantification of biomass distribution on the matrix surface, as well as changes in the capacitance and optical density of the microalgal culture. The results indicated maximum growth around day 15, showing a strong correlation between optical density (absorbance at 686 nm), image analysis of the matrix, and capacitance records. At this point, absorbance reached 3.913, coverage of 24.56% on the nylon matrix, and capacitance of 375.9 μF. Capacitance measurement proved to be a useful indirect tool to estimate biomass adhesion, while image analysis provided spatial distribution. The observed upward trend in process variables highlights the potential of electrical parameters, such as capacitance, for monitoring microalgal immobilization in suspended systems without altering biofilm structure. This approach supports future applications in scaling processes for bioactive compound production or environmental treatment systems. Full article

Hand range of motion (ROM) measurement is crucial for diagnosing joint limitations, tracking rehabilitation progress, and creating personalized treatment plans. In recent years, exergames combined with dedicated game controllers have emerged as promising tools to complement traditional hand rehabilitation; however, their validity as motor function assessment tools remains insufficiently explored. This study evaluates the validity of the eJamar game controller as a tool for measuring hand ROM and hand grip strength (HGS), by comparing its outputs with standard goniometry and dynamometry. In a prior technical validation using a robotic arm under controlled conditions, the device showed a mean error of approximately 1.5°, indicating high measurement precision under ideal conditions. In the clinical validation with 32 patients undergoing hand rehabilitation, performance was movement-dependent. Pronation and supination showed strong agreement (MAE < 3°) and higher agreement compared with other movements, whereas flexion, extension, and radial-ulnar deviation exhibited weaker correlations and substantially higher errors (around 20°). In contrast, grip strength measurements for more and less affected hands, respectively, showed high correlation (0.88–0.91) and moderate agreement (ICC 0.81–0.66) with MAE values around 4 kg-f. Overall, results suggest that the eJamar shows preliminary suitability for assessing HGS and forearm pronation and supination in clinical settings. However, for HGS, agreement should be interpreted with caution due to the observed bias and error levels, indicating that further validation and calibration are required before stronger clinical claims can be made. For wrist flexion, extension, and radial-ulnar deviation, the device currently shows limited accuracy and requires further improvement. Full article

Although numerous studies have focused on the potential application of heterotrophic nitrification–aerobic denitrification (HNAD) bacteria in wastewater treatment, research exploring their potential in aquaculture biofloc systems remains limited. In this study, a promising HNAD strain, identified as Stutzerimonas stutzeri MJ20, was isolated from mature biofloc. This strain efficiently utilized low-cost carbon sources (e.g., glucose) and small-molecule carbon sources (e.g., sodium acetate and sodium succinate). Under conditions with glucose as the carbon source, a carbon-to-nitrogen (C/N) ratio of 15, pH 6–9, temperature 25–35 °C, salinity 0–35‰, and shaker speed of 0–150 rpm, it achieved removal rates of 95–100% for NH₄⁺-N, NO₂⁻-N, and NO₃⁻-N at initial concentrations of 100 mg/L each. Even at higher concentrations (up to 200 mg/L NH₄⁺-N and 500 mg/L for both NO₂⁻-N and NO₃⁻-N), removal rates exceeded 99%. Under mixed nitrogen sources, strain MJ20 demonstrated efficient nitrogen removal, preferentially utilizing NH₄⁺-N, with only minimal and transient accumulation of nitrite and nitrate. Genomic analysis revealed that MJ20 carries key denitrification genes, including napA, nirS, norB and nosZ, and possesses complete pathways for nitrate reduction to nitrogen gas and ammonia assimilation, although typical autotrophic nitrification genes were not detected. Combined genomic data and autotrophic culture experiments indicated that, in addition to utilizing various organic carbon sources, the strain also exhibited certain autotrophic growth capabilities. Furthermore, MJ20 showed strong flocculation ability (flocculation rate > 96% within 16 h), sensitivity to multiple common antibiotics, and no toxicity to zebrafish, demonstrating favorable biosafety. In simulated seawater aquaculture wastewater with a C/N ratio of 5, it achieved a total nitrogen removal rate exceeding 94% within 72 h. These results indicate that strain MJ20 possesses comprehensive advantages, including efficient nitrogen removal, broad carbon source adaptability, strong environmental resilience, minimal accumulation of intermediate nitrogen products, excellent flocculation ability, and high biosafety. These traits highlight its potential for application in biofloc systems and in treating aquaculture tail water with a low C/N ratio. This study provides theoretical insights and practical guidance for screening HNAD bacteria suitable for biofloc systems. Full article

Immune dysregulation is being increasingly recognized as a prominent feature of a wide range inborn errors of immunity (IEIs) with different molecular backgrounds. Among the manifestations of immune dysregulation, inflammatory arthritis has emerged as an important yet underrecognized complication that may occur across multiple IEI categories, including humoral immunodeficiencies (such as X-linked agammaglobulinemia, hyper-IgM syndrome, common variable immunodeficiency, and others), complement deficiencies, disorders of immune dysregulation (STAT3 gain of function mutation, CTLA4 and LRBA haploinsufficiency), and combined immunodeficiencies. In some patients, arthritis may represent the first or predominant clinical manifestation, resulting in a diagnostic challenge in the rheumatologic setting. The pathogenesis of arthritis in IEIs reflects different immunological mechanisms, including the defective clearance of immune complexes, dysregulated B- and T-cell responses, impaired regulatory T-cell function, and aberrant cytokine signaling. Clinically, IEI-associated arthritis may mimic classical rheumatologic conditions such as juvenile idiopathic arthritis, rheumatoid arthritis, or other connective tissue diseases, although distinctive immunological and histopathological features are often present. Recognizing arthritis as a potential manifestation of IEIs has important clinical implications. The presence of specific “red flags”, including treatment refractoriness, recurrent infections, or additional signs of immune dysregulation (other autoimmune diseases, atopy, lymphoproliferation, enteropathy), should prompt targeted immunological evaluation. While management often relies on conventional immunosuppressive therapies, advances in the molecular characterization of IEIs are increasingly enabling the use of targeted treatments directed at the underlying pathogenic mechanisms. This paper provides an overview of the current knowledge of arthritis associated with IEIs, highlighting diagnostic challenges, underlying immunopathogenic mechanisms, and emerging therapeutic perspectives. Full article

The retina is a complex sensory neural tissue composed of six major types of neurons and one type of glial cell. The cell fate specification of retinal cells is tightly governed by intrinsic factors and extrinsic microenvironmental cues. Among the key regulators directing retinal cell fate differentiation is a group of bHLH family transcription factors (TFs). Our previous work demonstrated that the bHLH TF Ngn3 exhibits robust potential to induce retinogenesis in both distantly related fibroblasts in vitro and late retinal progenitor cells (RPCs) in vivo. However, the underlying molecular mechanisms remain largely elusive. In this study, we combined immunohistological examination and RNA-seq and ATAC-seq analyses to investigate the cellular and molecular mechanisms governing Ngn3-driven retinogenesis in late RPCs. Our results revealed that Ngn3 overexpression promotes premature cell cycle exit in late RPCs and remodels their transcriptomic and epigenomic landscape towards a state favoring rod photoreceptor and RGC differentiation. Furthermore, cross-comparison with Ngn3-overexpressing fibroblasts in vitro revealed cell-type-specific mechanisms underlying Ngn3-mediated neuronal fate reprogramming. These findings advance our understanding of Ngn family-mediated retinal cell fate regulation and provide a mechanistic framework for optimizing Ngn3-based retinal regeneration strategies for the treatment of retinal degeneration diseases. Full article

Hepatocellular carcinoma (HCC) is a highly aggressive malignancy with a poor prognosis. While sorafenib serves as the first-line therapy for advanced HCC, its efficacy is frequently hampered by side effects and the development of drug resistance, necessitating the development of novel agents to enhance HCC sensitivity to sorafenib. In this study, we demonstrate that the antihistamine astemizole significantly enhanced the antitumor efficacy of sorafenib in HCC cell lines. This combination treatment cooperatively inhibited HCC cells’ proliferation and induced cell cycle arrest at the G1 phase, as evidenced by decreased cyclin D1 and p-Rb levels and increased p27 expression. Furthermore, the combination of astemizole and sorafenib synergistically inhibited HCC cells’ migration, invasion, and adhesion. It also reduced F-actin polymerization and the expression of metastasis-regulating proteins, including p-Integrinβ1, FAK, and MMP1. Additionally, the combination treatment suppressed tube formation in HUVECs, accompanied by downregulation of HIF-1α and reduced VEGF secretion. Co-inhibition of Eag1 and the ERK/MAPK signaling pathway may underlie the enhanced anti-HCC effects of sorafenib by astemizole. Collectively, these findings indicate that astemizole significantly enhanced the antitumor activity of sorafenib by inhibiting proliferation, metastasis, and angiogenesis in HCC cells, suggesting its potential as a promising adjuvant to improve sorafenib-based therapy in HCC. Full article

Industrial dye wastewater poses serious environmental and health risks, demanding sustainable remediation strategies. Here, hierarchically porous hollow TiO₂ nanofibers (HNFTis) were fabricated and combined with blue, green, and orange graphene quantum dots (b-GQDs, g-GQDs, o-GQDs) to form heterojunction photocatalysts. Progressive fluorescence redshift of GQDs, induced by surface functionalization and S/B doping, narrows the bandgap and enhances visible-light absorption. Among the composites, 0.5 wt% o-GQDs/HNFTi exhibited the highest photocurrent and lowest charge-transfer resistance and degraded 99.5% of Methylene blue under visible light within 2 h, outperforming pristine HNFTi (77.7%). The synergistic effect of TiO₂ structural engineering and GQD fluorescence tuning demonstrates an effective strategy for designing high-performance photocatalysts for sustainable wastewater treatment. Full article

Background: Glioblastoma (GBM) exhibits marked cellular heterogeneity and resistance to therapy. Calcium (Ca²⁺) signaling at endoplasmic reticulum (ER)–mitochondria contact sites has emerged as a key regulator of mitochondrial function and cell fate; however, its lineage-specific role and therapeutic relevance in GBM remain unclear. Methods: ITPR1 expression was analyzed using single-cell and bulk RNA sequencing (RNA-seq) datasets and validated by immunohistochemistry and survival analyses. Functional studies were conducted using genetic silencing or CRISPR-mediated activation of ITPR1, combined with DRP1 knockdown, Ca²⁺ imaging, transmission electron microscopy, co-immunoprecipitation, mitochondrial fractionation, and mitochondrial functional assays. Therapeutic efficacy was evaluated in orthotopic GBM xenograft models treated with 2-aminoethoxydiphenyl borate (2-APB), temozolomide (TMZ), or their combination. Results: ITPR1 was enriched in mesenchymal-like malignant cell states and associated with higher tumor grade, recurrence, and poor prognosis. ITPR1 knockdown suppressed GBM cell proliferation and tumor growth while promoting intrinsic apoptosis. Mechanistically, loss of ITPR1 impaired ER-to-mitochondria Ca²⁺ transfer, disrupted ER–mitochondria contacts, and altered mitochondrial ultrastructure. This was accompanied by reduced DRP1 Ser616 phosphorylation and mitochondrial recruitment, as well as decreased autophagy and mitophagy activity. Consequently, ITPR1 knockdown led to mitochondrial depolarization, increased mitochondrial reactive oxygen species (ROS) accumulation, and activation of mitochondria-dependent apoptosis. Conversely, DRP1 knockdown attenuated the mitochondrial and pro-survival effects induced by ITPR1 overexpression. In vivo, combined treatment with 2-APB and TMZ resulted in greater tumor suppression and prolonged survival compared with either treatment alone, accompanied by increased apoptosis and reduced proliferation in tumor tissues. Conclusions: ITPR1 promotes GBM progression by sustaining ER–mitochondria Ca²⁺ coupling and DRP1-dependent mitochondrial quality control, thereby maintaining mitochondrial homeostasis and cell survival. Targeting inositol 1,4,5-trisphosphate receptor (IP₃R)-mediated Ca²⁺ signaling with 2-APB enhances the therapeutic efficacy of TMZ, suggesting that ITPR1-centered Ca²⁺ signaling may represent a potential therapeutic vulnerability in aggressive GBM. Full article