Search Results (633)

Usp21, a member of the ubiquitin protease family, plays a vital role in various biological functions. However, the effects of Usp21 dysfunction remain incompletely understood. In this study, we generated Usp21 knockout (KO) mice. Blood tests showed no impairment of liver function but did reveal elevated levels of total cholesterol (T-CHOL) and free fatty acid (FFA) in Usp21 KO mice compared to wild-type (WT) mice. Next, we performed RNA-sequencing (RNA-seq) to identify genes that Usp21 regulates. The results highlighted several candidate genes based on their biological relevance, and their expression levels were validated by RT-qPCR. The Usp21 KO mice exhibited significant elevations in the expression of the genes Fabp7, Nlrc5, and Ppargc1a, which play an important role in lipid metabolism, compared to WT. These data suggest that Usp21 may play roles in lipid metabolism in association with Fabp7, Nlrc5 and Ppargc1a. To clarify the involvement of USP21 in human hypercholesterolemia, we examined single-nucleotide polymorphisms (SNPs) around USP21 in non-hypercholesterolemic and hypercholesterolemic outpatients. We found that the rs11421 SNP downstream of USP21 was significantly associated with hypercholesterolemia. These data suggest that Usp21 plays a role in mice and human lipid metabolism and that its polymorphism may be a diagnostic marker for human hypercholesterolemia. Full article

Universal Stress Protein (USP) plays crucial roles in plant stress adaptation, yet their evolutionary dynamics, regulatory mechanisms, and functional diversification in rice (Oryza sativa) remain poorly understood. This study aimed to conduct a genome-wide identification and characterization of the OsUSP gene family to elucidate its role in abiotic stress responses using integrated bioinformatics approaches. Here, we identified 46 OsUSP genes that are unevenly distributed across 11 rice chromosomes and exhibit significant divergence in protein length, molecular weight, and subcellular localization. Phylogenetic analysis classified OsUSPs into three subfamilies, with conserved motif and domain architectures within groups but distinct structural variations across subfamilies. Evolutionary analysis revealed strong collinearity between rice and other monocots, which suggests functional conservation in grasses, whereas limited synteny with dicots indicates lineage-specific divergence. Cis-regulatory element analysis showed enrichment in ABA, MeJA, drought, and hypoxia response motifs, implicating OsUSPs in hormonal and stress signaling. Expression profiling indicated tissue-specific patterns, with subfamily III genes broadly expressed, while subfamily II members were anther-enriched. Stress response profiling revealed that 24 OsUSPs were significantly induced, while LOC_Os02g54590 and LOC_Os05g37970 emerged as particularly notable due to their broad-spectrum responsiveness, being upregulated under all tested stress conditions. Protein–protein interaction (PPI) analysis indicated that OsUSP proteins potentially interact with Leo1/TPR-domain proteins and are involved in stress response and phosphorylation signaling pathways. This study yields key insights into OsUSP-mediated stress adaptation in rice and pinpoints promising candidate genes to facilitate the breeding of climate-resilient rice. Full article

To address the dual challenges of cryogenic performance degradation and excessive VOC emissions in rubberized asphalt, this study proposes a synergistic optimization strategy using a polymer-based warm-mix additive (USP). The effects of USP on the rheological behavior, VOC emission characteristics, and mechanical performance of polymer-modified asphalt and fiber-reinforced RAP interlayers were systematically investigated. The results indicate that 5% USP optimally improves low-temperature flexibility (141.1% increase in ductility, 28.48% reduction in creep stiffness) while maintaining adequate high-temperature stability, and simultaneously achieves an 82.01% reduction in total VOC emissions at 150 °C. Microscopic analysis and DIC tests confirm that USP enhances polymer–asphalt–aggregate interactions, leading to improved adhesion, reduced water permeability, and extended fatigue life. This work provides a fundamental understanding of polymer–binder–aggregate synergy and offers a practical pathway toward greener, high-performance recycled asphalt pavement technologies. Full article

Atorvastatin (ATV), a widely used statin, exhibits both cholesterol-lowering and anti-inflammatory effects. Apigenin (API), a natural flavonoid, also demonstrates potent anti-inflammatory activity. This study aimed to develop and validate a novel stability-indicating reverse-phase HPLC method for the simultaneous quantification of ATV and API in standard solutions and dual ATV–API-loaded self-microemulsifying drug delivery system (SMEDDS). Quality by Design (QbD) approach was used to define the quality target product profile (QTPP), critical quality attributes (CQAs), and identify critical method parameters (CMPs) through risk assessment. A central composite design (CCD) evaluated the effects of organic phase ratio, buffer pH, and flow rate on chromatographic responses, including retention time, tailing factor, and resolution. Separation was achieved using an Agilent Eclipse XDB C-18 column (5 µm, 4.6 × 150 min) with a mobile phase of acetonitrile and 0.1 M ammonium acetate buffer (pH 7.0) in a 40:60 (v/v) ratio, UV detection at 266 nm, and a flow rate of 0.4 mL/ min. The method met ICH and USP (2021) validation criteria, showing excellent linearity (0.1–10 µg/mL), precision, accuracy, and specificity. No interference from SMEDDS excipients or degradation products during stability studies was observed. This validated method offers a reliable tool for formulation development and routine analysis of ATV and API combinations Full article

Alumina (Al₂O₃) is a key material in inorganic and hybrid electronics due to its excellent dielectric, chemical, and thermal stability properties. In this work, we present the first results of alumina films deposited by ultrasonic spray pyrolysis (USP) at low temperatures (40–100 °C) using water as the sole solvent, followed by an annealing step at 100 °C. The films were characterized by SEM, XRD, EDS, and UV-Vis spectroscopy to evaluate their morphology, structure, composition, and optical properties. Preliminary results show an average thickness of approximately 8 µm, with surface features consisting of agglomerates (average particle size ≈ 7.252 µm) distributed over the film. XRD patterns revealed the presence of tetragonal and orthorhombic phases, while EDS confirmed the presence of aluminum and oxygen with slight compositional variations depending on deposition and annealing conditions. UV-Vis absorption spectra exhibited characteristic bands between 259 nm and 263 nm. These results provide a comprehensive understanding of the optical, structural, and morphological behavior of Al₂O₃ films processed at low temperatures. The motivation for studying these films is to enable more eco-friendly gate oxides for organic MIS structures, as well as functional layers in photonic devices. This approach represents a sustainable and straightforward route for obtaining Al₂O₃ coatings compatible with temperature-sensitive substrates, paving the way for future applications in hybrid and organic electronics. Full article

Background/Objectives: HNSCC is a highly aggressive malignancy marked by the dysregulation of the cell cycle. In HPV⁻ HNSCC, mutations in the CDKN2A gene frequently result in the loss of the p16 protein, a key inhibitor of the cyclin D1/CDK4/6 complex. This loss results in unchecked G1/S phase progression. The CDK4/6 inhibitor palbociclib has shown therapeutic potential in HPV⁻ HNSCC by inducing G1 phase arrest and reducing cell viability. In this study, we investigated the molecular mechanisms by which palbociclib affects cell viability in HPV⁻ HNSCC. Methods: Four HPV⁻ HNSCC cell lines were treated with palbociclib, and RNA sequencing was performed to assess changes in gene expression. Cell viability was measured using the MTT assay. To further investigate protein localization, interactions, and function, we used immunofluorescence staining, co-immunoprecipitation, small molecule inhibitors, and siRNA-mediated knockdown. Results: We demonstrate that palbociclib downregulates survivin, a protein that plays dual roles in mitosis and apoptosis, thereby inhibiting cell proliferation. We also found that survivin is overexpressed in HPV⁻ HNSCC. Inhibiting survivin dimerization using the compound LQZ-7i significantly reduces cell viability and promotes its export from the nucleus to the cytoplasm. Additionally, we identified USP1, a deubiquitinase, as both a downstream target of CDK4/6 and a key regulator of survivin stability. Inhibiting USP1 activity or silencing its expression significantly reduces survivin levels. Conclusions: Our findings highlight survivin as a critical mediator of cell proliferation in HPV⁻ HNSCC and suggest that targeting the CDK4/6-USP1-survivin axis may offer a promising therapeutic strategy. Full article

Background/Objectives: The rational design of modified-release matrix tablets requires a thorough understanding of granulometric analysis, compaction behavior, and drug release profile. In this study, we evaluated the physicochemical, granulometric, and mechanical properties of hydroxypropyl methylcellulose, polyethylene oxide, and ethylcellulose in galantamine matrix formulations. Methods: Spectroscopic (FTIR) and thermal (DSC) analyses demonstrated drug–polymer compatibility. We assessed flowability, cohesion, and aeration behavior through granulometric analysis and applied compressibility models (Kawakita, Heckel, Leuenberger) to characterize deformation mechanisms. Results: Hydroxypropyl methylcellulose showed superior compactability (T_max = 4.61 MPa) and sustained drug release (85.4% at 12 h, DE% = 62.2%), while polyethylene oxide enabled gradual erosion and consistent delivery (88.7% at 12 h, DE% = 57.5%). In contrast, ethylcellulose exhibited high cohesiveness but poor matrix integrity, leading to premature drug release (76.6% at 1 h, DE% = 73.7%). Only hydroxypropyl methylcellulose and polyethylene oxide formulations met USP criteria. Conclusions: These results demonstrate that polymer selection critically influences powder behavior and matrix performance, underscoring the need for integrated granulometric and mechanical evaluation in the development of robust controlled-release systems. Full article

Background/Objectives: Reflecting the interaction between dissolution and absorption, the biphasic dissolution system is an appealing approach for estimating the intestinal absorption of drugs in humans. The study aims to characterize the suitability of the biphasic in vitro dissolution testing to set up an in vitro–in vivo correlation (IVIVC) for the original and generic immediate-release (IR) tablets of a Biopharmaceutics Classification System (BCS) Class II drug, bicalutamide (BIC). Methods: USP apparatus II paddle was used to conduct dissolution testing. A level A IVIVC was obtained between in vitro partitioning and in vivo absorption data of the original drug. The single-compartmental modeling was used for pharmacokinetic (PK) analysis. The generic product’s plasma concentrations were estimated. Results: There was a good correlation between in vitro and in vivo data (r² = 0.98). The area under the concentration–time curve (AUC) and maximum plasma concentration (C_max) ratios for generic/original were 1.04 ± 0.01 and 0.951 ± 0.026 (mean ± SD), respectively. Conclusions: The biphasic dissolution testing may present an in vivo predictive tool for developing generic products of poorly soluble and highly permeable drugs such as BIC, which are characterized by pH-independent poor solubility. Full article

Significant efforts have been dedicated to developing controlled-release systems for the effective management of colorectal cancer. In this study, a once-daily, delayed-release regorafenib (REG) tablet was fabricated using 3D printing technology for the treatment of colorectal cancer. For this, a hydrogel containing 80 mg of the drug in a matrix of hyaluronic acid, carboxymethyl cellulose, Pluronic F127, and glycerol was prepared to incorporate into the shell cavity of tablet via a pressure-assisted microsyringe (PAM). The shell was printed from an optimized ink formulation of Soluplus^®, Eudragit^® RS-100, corn starch 1500, propylene glycol 4000, and talc through melt extrusion-based 3D printing. In vitro release assays showed a drug release rate of 91.1% in the phosphate buffer medium at 8 h and only 8.5% in the acidic medium. Drug release kinetics followed a first-order model. The results showed smooth and uniform layers based on scanning electron microscopy (SEM) and drug stability at 135 °C upon TGA. FTIR analysis confirmed the absence of undesired covalent interactions between the materials. Weight variation and assay results complied with USP standards. Mechanical strength testing revealed a Young’s modulus of 5.18 MPa for the tablets. Overall, these findings demonstrate that 3D printing technology enables the precise fabrication of delayed-release REG tablets, offering controlled-release kinetics and accurate dosing tailored for patients in intensive care units. Full article

The progression of inflammation during sepsis represents a multifaceted biological cascade that requires effective therapeutic interventions to improve survival. In septic neonatal foals, oxidative stress (OS) arises due to a compromised antioxidant defense system. Oxidative stress may disrupt the functionality of redox-sensitive organelles, such as the endoplasmic reticulum (ER). Endoplasmic reticulum stress disorder affects multiple cellular signaling pathways, including redox balance, inflammation, and apoptosis, and contributes to the pathogenesis of sepsis. The study aimed to elucidate whether OS conditions in sepsis influenced gene expression associated with ER stress. Blood samples were collected from 7 healthy and 21 hospitalized neonatal foals and processed for RNA extraction. RNA sequencing was employed to identify ER stress-responsive genes. Novel findings reported here indicate activation of the ER stress pathway in foals with sepsis. Several genes associated with ER stress, such as clusterin (CLU), BCL2-like 1 (BCL2L1), ubiquitin specific peptidase 14 (USP14), bifunctional apoptosis regulator (BFAR), and optic atrophy 1 (OPA1), were upregulated and positively correlated with sepsis scores and negatively correlated with the combined activities of antioxidant enzymes. In contrast, X-box binding protein 1 (XBP1), homocysteine inducible ER protein with ubiquitin-like domain 1 (HERPUD1), leucine-rich repeat kinase 2 (LRRK2), and selenoprotein S (SELENOS) were negatively correlated with sepsis scores and were downregulated in sepsis and positively correlated with the combined activities of antioxidant enzymes. Furthermore, a positive correlation was observed between cAMP responsive element binding protein 3 like 2 (CREB3L2) and BCL2L1, as well as between the expressions of USP14 and YOD1 deubiquitinase (YOD1) in sepsis. Similarly, the expression levels of XBP1 and Herpud1 demonstrated a positive correlation with each other in sepsis. Additionally, the downregulation of genes with protective function against OS, such as XBP1, HERPUD1, and SELENOS, in septic foals also highlights their significance in mitigating OS in sepsis treatment. The study reported here highlights the potential of ER stress as a promising therapeutic target and prognostic marker in septic foals. Full article

Lycium barbarum is a traditional medicinal and edible plant species in China, exhibiting notable salt tolerance that enables cultivation in salt-affected soils. However, intensifying soil salinization has rendered severe salt stress a critical limiting factor for its fruit yield and quality. Universal stress proteins (USPs) serve as crucial regulators for plant abiotic stress responses through developmental process modulation. Nevertheless, the characteristics and functional divergence of USP gene family members remain unexplored in L. barbarum. Here, we performed genome-wide identification and characterization of the USP gene family in L. barbarum, revealing 52 members unevenly distributed across all 12 chromosomes. Phylogenetic analysis classified these LbUSP members into four distinct groups, demonstrating the integration of the conserved USP domain and diverse motifs within each group. Collinearity analysis indicated a stronger synteny of LbUSPs with orthologs in Solanum lycopersicum than with other species (Arabidopsis thaliana, Vitis vinifera, and Oryza sativa), demonstrating that gene duplication coupled with functional conservation represented the primary mechanism underlying USP family expansion in L. barbarum. In silico promoter screening detected abundant cis-acting elements associated with abiotic/biotic stress responses (MYB and MYC binding sites), phytohormone regulation (ABRE motif), and growth/development processes (Box-4 and G-box). Transcriptome sequencing and RT-qPCR validation revealed tissue-specific differential expression patterns of LbUSP8, LbUSP11, LbUSP12, LbUSP23, and LbUSP25 in roots and stems under salt stress, identifying them as prime candidates for mediating salt resistance in L. barbarum. Our findings establish a foundation for the functional characterization of LbUSPs and molecular breeding of salt-tolerant L. barbarum cultivars. Full article

Diabetes mellites (DM) is a chronic disease with increasing prevalence worldwide and multiple health implications. Among them, sarcopenia is a metabolic disorder characterized by loss of muscle mass and function. The two age-related diseases, DM and sarcopenia, share underlying pathophysiological pathways. This narrative literature review aims to provide an overview of the existing evidence on metabolomic studies evaluating DM associated with sarcopenia. Advancements in targeted and untargeted metabolomics techniques could provide better insight into the pathogenesis of sarcopenia in DM and describe their entangled and fluctuating interrelationship. Recent evidence showed that sarcopenia in DM induced significant changes in protein, lipid, carbohydrate, and in energy metabolisms in humans, animal models of DM, and cell cultures. Newer metabolites were reported, known metabolites were also found significantly modified, while few amino acids and lipids displayed a dual behavior. In addition, several therapeutic approaches proved to be promising interventions for slowing the progression of sarcopenia in DM, including physical activity, newer antihyperglycemic classes, D-pinitol, and genetic USP21 ablation, although none of them were yet validated for clinical use. Conversely, ceramides had a negative impact. Further research is needed to confirm the utility of these findings and to provide potential metabolomic biomarkers that might be relevant for the pathogenesis and treatment of sarcopenia in DM. Full article

Background/Objectives: Hot-melt extrusion (HME) has become a key technology in pharmaceutical formulation, particularly for enhancing the solubility of poorly soluble Active Pharmaceutical Ingredients (APIs). While horizontal HME is widely adopted, vertical HME remains underexplored despite its potential benefits in footprint reduction, feeding efficiency, temperature control, and integration into continuous manufacturing. This study investigates vertical HME as an innovative approach in order to optimize drug polymer interactions and generate stable amorphous dispersions with controlled release behavior. Methods: Extrusion trials were conducted using a vertical hot-melt extruder developed by Rondol Industrie (Nancy, France). Acetylsalicylic acid (ASA) supplied by Seqens (Écully, France) was used as a model API and processed with Soluplus^® and Kollidon^® 12 PF (BASF, Ludwigshafen, Germany). Various process parameters (temperature, screw speed, screw profile) were explored. The extrudates were characterized by powder X-ray diffraction (PXRD) and small-angle X-ray scattering (SAXS) to evaluate crystallinity and microstructure. In vitro dissolution tests were performed under sink conditions using USP Apparatus II to assess drug release profiles. Results: Vertical HME enabled the formation of homogeneous amorphous solid dispersions. PXRD confirmed the absence of residual crystallinity, and SAXS revealed nanostructural changes in the polymer matrix influenced by drug loading and thermal input. In vitro dissolution demonstrated enhanced drug release rates compared to crystalline ASA, with good reproducibility. Conclusions: Vertical HME provides a compact, cleanable, and modular platform that supports the development of stable amorphous dispersions with controlled release. It represents a robust and versatile solution for pharmaceutical innovation, with strong potential for cost-efficient continuous manufacturing and industrial-scale adoption. Full article

The high reproductive performance of Nilaparvata lugens (Stål) (Hemiptera: Delphacidae) is one of the key factors contributing to its serious damage. Studies have demonstrated that trehalose hydrolysis, catalyzed by trehalase (TRE), plays an important role in the reproductive regulation of N. lugens. However, it remains unclear how TRE regulates the reproduction of N. lugens. To address this question, the current study was designed to investigate the effects of TRE on the reproductive regulatory network of N. lugens. Specifically, RNA interference (RNAi) was conducted by injecting double-stranded RNA (dsRNA) targeting the TRE genes, and a trehalase inhibitor, validamycin, was used to suppress TRE activity. Subsequently, the relative expression levels of key genes involved in the reproductive regulatory pathway, as well as the triglyceride content in the fat body and ovary, were determined. The results indicated that both dsTREs and validamycin treatment decreased the relative expression of Vitellogenin (Vg) without affecting the expression of its receptor, VgR. However, their impact on the reproductive regulatory network differed: dsTREs injection did not affect the relative expression of JHAMT and Met in the juvenile hormone signaling pathway, but resulted in the upregulation of USP and TOR, and inhibition of InR2 and S6K. In contrast, validamycin injection inhibited the expression of Met, USP, EcR, InR1, TOR, and S6K. Both dsTREs and validamycin inhibited the expression of Fas, but only validamycin decreased the ovarian triglyceride content. These findings suggest that the inhibition of TRE leads to alterations in reproductive regulatory signals, thereby reducing the reproductive capacity of N. lugens. Full article

USP (usual temperature pitch)-modified asphalt optimizes its rheological properties through reactions between the modifier and the asphalt. This significantly enhances the high- and low-temperature adaptability and environmental friendliness of asphalt. It has now become an important research direction in the field of highway engineering. This article systematically investigates the impact of different dosages of USP warm mix modifier on asphalt binders through rheological and microstructural analysis. Base asphalt and SBS-modified asphalt were blended with USP at varying ratios. Conventional tests (penetration, softening point, ductility) were combined with dynamic shear rheometry (DSR, AASHTO T315) and bending beam rheometry (BBR, AASHTO T313) to characterize temperature/frequency-dependent viscoelasticity. High-temperature performance was quantified via multiple stress creep recovery (MSCR, ASTM D7405), while fluorescence microscopy and FTIR spectroscopy elucidated modification mechanisms. Key findings reveal that (1) optimal USP thresholds exist at 4.0% for base asphalt and 4.5% for SBS modified asphalt, beyond which the rutting resistance factor (G*/sin δ) decreases by 20–31% due to plasticization effects; (2) USP significantly improves low-temperature flexibility, reducing creep stiffness at −12 °C by 38% (USP-modified) and 35% (USP/SBS composite) versus controls; (3) infrared spectroscopy displays that no new characteristic peaks appeared in the functional group region of 4000–1300 cm⁻¹ for the two types of modified asphalt after the incorporation of USP, indicating that no chemical changes occurred in the asphalt; and (4) fluorescence imaging confirmed that the incorporation of USP led to disintegration of the spatial network structure of the control asphalt, explaining the reason for the deterioration of high-temperature performance. Full article