Search Results (8,334)

The probability density function (PDF) of the product of two normal random variables remains an open discussion. Researchers have proposed many forms of PDFs. Among these, two notable PDFs are an analytical solution with infinite summation and an integral form with transformation. For practical computation, they must be estimated. The form with infinite summation must be truncated to a finite summation, and the form still in integration must be computed numerically. As a result of this estimation, an error occurs in the value of the estimation. This paper derives upper bounds for the estimation error resulting from truncation and numerical approximation in integral calculations. The upper bound error between the exact PDF and the truncated PDF is expressed as a geometric series using Bessel function inequality and Stirling’s approximation. The geometric formula allows the quantification of the total truncation error to be determined. For the PDF, which is still in integration form, the trapezoidal rule is used for numeric calculation. Hence, the error can be determined using the error-bound formula. The two estimated PDFs have their own advantages and disadvantages. The truncated PDF gives a relatively small upper bound value compared to the numerical calculation integral form PDF for a small value domain. However, the truncated PDF fails to perform for a large value domain, and only the integral form PDF can be used. The error for the estimation is applied to the conventional mass measurement. The results demonstrate that the error can be controlled through an analytical approach. Full article

Rheumatoid arthritis (RA) is the most common inflammatory polyarthritis. In addition, 60–80% of patients express anti-citrullinated protein antibodies (ACPAs), which serve as a diagnostic marker for RA. The effector functions of these autoantibodies can be heavily affected by the N-glycosylation of their Fc region. Here we present a comparison of the Fc N-glycosylation of ACPA IgG to that of non-ACPA IgG from the same patients, and of healthy controls, in an IgG isoform-specific manner. We isolated ACPA and normal serum IgG, digested by trypsin, and separated the resulting peptide mixture by a reversed-phase nanoLC coupled to a Bruker Maxis II Q-TOF, and determined the relative abundance of glycoforms. The paired analysis of galactosylation and sialylation of the IgG subclasses of ACPA and non-ACPA IgG has shown a significant, moderate negative correlation with the inflammatory markers, the level of C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR), as well as with rheuma-factor (RF), but not with the disease activity score (DAS) or cyclic citrullinated peptide specific antibodies (anti-CCP). However, we detected a significant negative correlation between glycosylation and DAS in the non-ACPA IgG fractions. Furthermore, the isoform-specific analysis revealed additional insight into the changes of the glycosylation features of IgG in RA: changes in the frequencies of the bisecting GlcNAc unit between sample groups could be explained by only the IgG1 isoform; while invariance in fucosylation is the result of the superposition of two isoforms with opposite changes. These results highlight the importance of analyzing immunoglobulin glycosylation in an isoform-specific manner. Full article

Background/Objectives: Aging is characterized by progressive physiological and metabolic decline. Aerobic exercise mitigates age-related impairments, and nicotinamide mononucleotide (NMN), a precursor in the NAD⁺ salvage pathway, has emerged as a nutritional intervention to promote healthy aging. This study investigated whether NMN supplementation combined with aerobic exercise provides synergistic benefits on physical performance and metabolic regulation in aged mice. Methods: Forty male C57BL/6J mice, including eight young (8 weeks) and thirty-two aged (85 weeks) mice, were randomly assigned to five groups: young sedentary (YS), aged sedentary (AS), aged with exercise (AE), aged with NMN (ASNMN; 300 mg/kg/day), and aged with combined NMN and exercise (AENMN). Interventions lasted six weeks. Assessments included grip strength, muscle endurance, aerobic capacity, oral glucose tolerance test (OGTT), and indirect calorimetry, followed by biochemical and molecular analyses of NAMPT and SirT1 expression. Results: The AENMN group demonstrated significant improvements in maximal strength and aerobic endurance compared with the AS group (p < 0.05). Both NMN and exercise interventions increased blood NAMPT concentrations, with the highest levels observed in the AENMN group (p < 0.05). SirT1 expression was elevated in the ASNMN and AENMN groups relative to YS (p < 0.05). Glucose tolerance improved in the ASNMN and AENMN groups (p < 0.05). Enhanced energy metabolism in the AENMN group was indicated by increased oxygen consumption, elevated energy expenditure, and reduced respiratory quotient. Conclusions: NMN supplementation, particularly when combined with aerobic exercise, effectively improved aerobic performance, glucose regulation, and systemic energy metabolism in aged mice. These findings suggest that NMN, in synergy with exercise, may serve as a promising nutritional strategy to counteract age-associated metabolic and functional decline. Full article

Postharvest shiitake mushrooms (Lentinus edodes) often undergo browning under low-temperature, high-humidity storage conditions, which significantly reduces their commercial value and constrains industry development. However, the molecular mechanisms regulating this process remain unclear. In this study, we used ‘Nongxiang No. 1’ as the experimental material and observed that during storage, the L* value of caps and stipes decreased continuously, shifting from light brown to dark brown-black. Concurrently, the relative electrical conductivity increased by approximately 3.07-fold, and the membrane lipid peroxidation product malondialdehyde (MDA) content increased by approximately 7.9-fold. Superoxide dismutase (SOD) activity initially increased then declined, indicating that elevated membrane permeability accelerates senescence. Peroxidase (POD) activity exhibited a significant upward then downward trend and improved 75.83% at day 22 of postharvest storage, with LEHP1, LEHP2, and LEHP3 gene expression patterns closely aligning with these changes. Specifically, LEHP2 and LEHP3 expression was upregulated by 23.8-fold and 2.35-fold on day 22 than day 0. Cis-element analysis identified MYB binding sites in all three LEHP genes. Genome-wide screening combined with qRT-PCR revealed two MYB transcription factors, LeMYB2 and LeMYB5, whose expression synchronized with LEHP genes. Transient expression assays in tobacco leaves confirmed their nuclear localization, consistent with transcription factor characteristics. Electrophoretic Mobility Shift Assay (EMSA) and Dual-Luciferase Reporter Assay (DLR) experiments further demonstrated that LeMYB2 and LeMYB5 directly activate LEHP2 and LEHP3 promoters, highlighting their key regulatory roles in postharvest browning of shiitake mushrooms. Full article

Background: Post-traumatic joint contracture (PTJC) remains one of the most prevalent and challenging complications arising from musculoskeletal trauma or surgical intervention. Conventional treatment modalities are largely reactive and address symptoms after onset, yet provide limited efficacy once contracture has developed. In contrast, pharmacological strategies targeting the underlying inflammatory and fibrotic pathways offer a promising strategy for preventing the development of PTJC altogether. Methods: A total of 26 male Sprague Dawley rats underwent standardized knee trauma followed by immobilization for a duration of two weeks. Rats were randomized into two groups. The experimental group (n = 13) received bosentan at a dosage of 50 mg/kg twice daily throughout the immobilization period. The control group (n = 13) received a placebo instead. Joint mobility was quantitatively assessed by measuring the contracture angle (CA) and resistance to extension. In addition, posterior joint capsule tissues were harvested for histological analysis and subjected to quantitative PCR (qPCR) to quantify the expression of profibrotic genes, including α-Sma, Il-6, Tgf-β1, Nfκ-b, Ctgf. Results: Bosentan had no relevant effect on the biomechanics of the contracture compared to the placebo group. The contracture angle was comparable between the groups (86.8° ± 14.1°, 84.8° ± 11.1°). Similarly, the force required to achieve knee joint extension was comparable between the groups. Gene expression analysis also provided no evidence of reduced expression of pro-inflammatory or profibrotic genes. Histological assessments revealed no change in the absolute or relative number of myofibroblasts, or in the number of vessels, in the posterior joint capsules of the rats treated with bosentan. Compared to the control group, the number of myofibroblasts significantly increased in both the bosentan and control groups (p < 0.001, one-way ANOVA). Conclusion: Bosentan’s purported antifibrotic properties do not appear to confer a preventative effect on the development of PTJC. These findings suggest that, despite its potential in modulating fibrosis, bosentan does not mitigate the progression of the fibrotic condition. Furthermore, the involvement of endothelin-1 (ET-1) in the pathophysiology of PTJC remains yet to be fully understood, warranting further investigation. Full article

Bulbine species (Asphodelaceae) are routinely used in many African communities to treat various dermatological disorders, including wounds, due to their relative accessibility, affordability, safety records, and reported efficacies. However, these reported biological activities lack robust empirical evidence and well-validated cellular mechanisms for plausible applications. Hence, this review was aimed at investigating the bioactive compounds of Bulbine species linked to their cellular wound healing attributes, their toxicity, and cytotoxicity. A detailed literature search was conducted using Web of Science, Google scholar, and PubMed, followed by Scopus and VOSviewer (version 1.6.20) bibliographic analyses. Bulbine frutescens (L.) Willd. and Bulbine natalensis Baker safely mediate tissue healing and coagulation cascade as adaptogens and cytotoxic agents. The wound healing activities of the Bulbine species were linked to the synergistic wound healing or tissue repair properties of bioactive compounds (such as saponins, terpenoids, luteolin, and apigenin) via the expression of collagen type-I, alpha-2 (COL1A2) gene, collagen III, increase in the wound tensile strength, and anti-cytokine interleukin-10 (IL-10) mRNA. Bulbine species were also reported to contain specialised biomarker compounds (such as naphthoquinones, bulbine-emodin, and aloe-emodin) which mediate the activation of hydroxyproline, Aryl Hydrocarbon Receptor, transforming growth factor beta—β1 (TGFβ1), and the suppressor of mothers against decapentaplegic proteins (SMAD), which ultimately induce tissue granulation, myofibroblast differentiation, re-epithelialization, higher protein complexes, and scar tissue formations. These findings give credence to the wound healing therapeutic potential of Bulbine species. However, additional clinical studies are necessary to further ascertain the reported efficacies of Bulbine species’ bioactive principles, their overall safety, and the underlying cellular mechanisms involved in the wound healing process and carcinogenesis. Full article

Background: Colorectal cancer is the third most diagnosed cancer and a leading cause of cancer-related deaths worldwide. Early detection significantly improves patient outcomes, yet many cases are identified only at late stages. The high molecular and genetic heterogeneity of colorectal cancer presents major challenges in accurate diagnosis, prognosis, and therapeutic stratification. Recent advances in gene expression profiling offer new opportunities to discover genes that play a role in colorectal cancer carcinogenesis and may contribute to early diagnosis, prognosis prediction, and the identification of novel therapeutic targets. Methods: This study involved 142 samples: 84 primary tumor samples, 27 liver metastases, and 31 adjacent non-tumor tissues serving as controls. RNA sequencing was performed on a subset of tissues (12 liver metastases and 3 adjacent non-tumor tissues) using a targeted RNA panel covering 395 cancer-related genes. Data processing and differential gene expression analysis were carried out using the DRAGEN RNA and DRAGEN Differential Expression tools. The expression of six genes involved in hypoxia and epithelial-to-mesenchymal transition (EMT) pathways (SLC16A3, ANXA2, P4HA1, SPP1, KRT19, and LGALS3) identified as significantly differentially expressed was validated across the whole cohort via quantitative real-time PCR. The relative expression levels were determined using the ΔΔct method and log2FC, and compared between different groups based on the sample type; clinical parameters; and mutational status of the genes KRAS, PIK3CA, APC, SMAD4, and TP53. Results: Our results suggest that the expression of all the validated genes is significantly altered in metastases compared to non-tumor control samples (p < 0.05). The most pronounced change occurred for the genes P4HA1 and SPP1, whose expression was significantly increased in metastases compared to non-tumor and primary tumor samples, as well as between clinical stages of CRC (p < 0.001). Furthermore, all genes, except for LGALS3, exhibited significantly altered expression between non-tumor samples and samples in stage I of the disease, suggesting that they play a role in the early stages of carcinogenesis (p < 0.05). Additionally, the results suggest the mutational status of the KRAS gene did not significantly affect the expression of any of the validated genes, indicating that these genes are not involved in the carcinogenesis of KRAS-mutated CRC. Conclusions: Based on our results, the genes P4HA1 and SPP1 appear to play a role in the progression and metastasis of colorectal cancer and are candidate genes for further investigation as potential biomarkers in CRC. Full article

Endocrine cells are dedicated to the production and processing of hormones, from peptides to small molecules, to regulate key physiological processes, including glucose homeostasis and metabolism. Because of this relatively high productivity, endocrine cells must handle a variety of stresses from oxidative stress to the unfolded protein response of the endoplasmic reticulum (UPR^ER). While much is known about the major pathways regulating the UPR^ER, the roles of endocrine cell type-specific, context-dependent, and time-dependent transcriptional changes are not well explored. To identify unique and shared responses to the UPR^ER across a subset of endocrine cell types, we tested representative lines for β-cells (insulin), α-cells (glucagon), δ-cells (somatostatin), X/A-cells (ghrelin), L-cells (glucagon-like peptide 1 (GLP1)), and thyrotropes (thyroid hormone and thyroglobulin). We exposed each cell type to the canonical ER stressor thapsigargin for 6 and 24 h, or vehicle for 24 h, and performed mRNA sequencing. Analysis of the data showed all lines responded to thapsigargin. Comparisons of differentially expressed genes between each line revealed both shared and unique transcriptional signatures. These data represent a valuable mineable set of candidate genes that may have cell type-specific functions during the UPR^ER and have the potential to lead to a new understanding of how different endocrine cells mitigate or succumb to ER stress. Full article

Catalytic upgrading of vacuum residue (VR) is critical for enhancing fuel yield and reducing waste in petroleum refining. This study explores VR cracking over a novel cerium-loaded acidified metakaolinite catalyst (MKA800–20%Ce) prepared via calcination at 800 °C, acid leaching, and wet impregnation with 20 wt.% Ce. The catalyst was characterized using FTIR, BET, XRD, TGA, and GC–MS to assess structural, textural, and thermal properties. Catalytic cracking was carried out in a fixed-bed batch reactor at 350 °C, 400 °C, and 450 °C. The MKA800@Ce20% catalyst showed excellent thermal stability and surface activity, especially at higher temperatures. At 450 °C, the catalyst yielded approximately 11.72 g of total liquid product per 20 g of VR (representing a ~61% yield), with ~3.81 g of coke (~19.1%) and the rest as gaseous products (~19.2%). GC-MS analysis revealed enhanced production of light naphtha (LN), heavy naphtha (HN), and kerosene in the 400–450 °C range, with a clear temperature-dependent shift in product distribution. Structural analysis confirmed that cerium incorporation enhanced surface acidity, redox activity, and thermal stability, promoting deeper cracking and better product selectivity. Kinetics were investigated using an eight-lump first-order model comprising 28 reactions, with kinetic parameters optimized through a genetic algorithm implemented in MATLAB. The model demonstrated strong predictive accuracy taking into account the mean relative error (MRE = 9.64%) and the mean absolute error (MAE = 0.015) [MAE: It is the absolute difference between experimental and predicted values; MAE is dimensionless (reported simply as a number, not %. MRE is relative to the experimental value; it is usually expressed as a percentage (%)] across multiple operating conditions. The above findings highlight the potential of Ce-modified kaolinite-based catalysts for efficient atmospheric pressure VR upgrading and provide validated kinetic parameters for process optimization. Full article

This study was designed to first investigate the effects of zinc phytate (ZnPA) from wheat bran in alleviating high-fat diet (HFD)-induced hepatic inflammation and metabolic disorders and its underlying mechanism. C57BL/6J mice were randomly assigned to five groups including normal diet (ND), HFD, HFD+low-dose ZnPA (100 mg/kg), HFD+high-dose ZnPA (200 mg/kg), and HFD+wheat bran (100 mg/kg). All interventions were administered orally for 12 weeks. The results indicated that ZnPA significantly mitigated HFD-induced weight gain, dyslipidemia, pathoglycemia, hepatic steatosis and inflammation (p < 0.05). ZnPA effectively corrected HFD-induced microbial dysbiosis, in which the relative abundance of the Ruminococcus torques group decreased from 11.0% to 0.75%, and Coriobacteriaceae_UCG-002 dropped from 2.47% to 0.087% (p < 0.05). Conversely, ZnPA increased the abundance of Ileibacterium from 0.32% to 17.76% and Dubosiella from 1.03% to 4.24% (p < 0.05). Meanwhile, ZnPA could be metabolized by the gut microbiota to release IP6, which was further converted into secondary inositol phosphates (InsP_3–5), resulting in increases of 52.1%, 83.3%, 62.5%, and 96.2% in the colonic contents of InsP₆, InsP₅, InsP₄, and InsP₃ (p < 0.05), respectively. In addition, ZnPA increased levels of secondary bile acids and short-chain fatty acids, especially deoxycholic acid and taurocholic acid, which were elevated by 1.95-fold and 1.88-fold (p < 0.05), respectively. Interestingly, ZnPA enhanced hepatic expressions of histone deacetylase 3, bile acid receptor FXR, and lipid metabolism coactivator PGC-1α (p < 0.05). Collectively, these results indicated that ZnPA might alleviate obesity-related hepatic inflammation and metabolic disorders by reshaping microbial composition and increasing the production of microbial metabolism such as secondary bile acids, thereby triggering FXR–PGC1α axis activation. Full article

This study develops an improved family of estimators for estimating the finite population median within a two-phase sampling method. The proposed estimators, which use transformation techniques to reduce survey costs when full auxiliary information is unavailable, yield more accurate results than traditional methods. These transformations employ robust statistical measures such as Hodges–Lehmann location, Gini mean difference, and Bowley’s skewness, which strengthen resistance against outliers and heavy-tailed distributions. Through the use of these modern tools within the two-phase sampling framework, the proposed estimators achieve greater flexibility and robustness compared to conventional quantile-based approaches. A first-order approximation is employed to derive the bias and mean squared error expressions. The performance of the proposed estimators is examined through simulation experiments across multiple distributional scenarios and validated using real datasets against standard approaches. Findings based on percent relative efficiency confirm that the proposed estimators improve the accuracy and efficiency of median estimation in two-phase sampling, demonstrating superiority over conventional methods across various practical scenarios. Full article

Background/Objectives: Alfalfa is a widely cultivated high-quality forage crop, and salinity tolerance is one of the most important breeding goals. Glycine max SALT INDUCED NAC 1 (GmSIN1) was found to enhance salinity tolerance in soybean plants. The phylogenetic analysis showed there were two homologs of GmSIN1 in Medicago truncatula, MtSIN1a and MtSIN1b. This raised questions regarding the roles of MtSIN1s in alfalfa under salinity stress. Methods: From a Tnt1 mutant collection, we identified the mutants of MtSIN1a. We recorded the survival rate and plant height of mtsin1a-1 and mtsin1a-2 after 100 mM NaCl treatment. Subsequently, we generated 35S:MtSIN1a-GFP transgenic alfalfa lines via genetic transformation. Two lines with relatively high MtSIN1a expression, 35S:MtSIN1a-GFP#3 and 35S:MtSIN1a-GFP#4, were selected for gradient NaCl treatments. In addition, DAB and NBT staining were performed, and the H₂O₂ content and catalase (CAT) activity were determined. Then, we used RNA-seq analysis and RT-qPCR to study the mechanism of its tolerance. Results: This study found that after salt treatment, the survival rate and plant height of mtsin1a-1 and mtsin1a-2 were significantly lower than those of the WT. The mutants of MtSIN1a were sensitive to salinity stress. The transgenic alfalfa plants exhibited higher plant height, weaker DAB staining, stronger NBT staining, less H₂O₂ content, and enhanced CAT activity. The transgenic alfalfa constructed by transforming MtSIN1a showed enhanced salinity tolerance with elevated ROS scavenging. We identified MsSOD1 showing elevated expression levels in transcriptomic analysis. Conclusions: MtSIN1a is a positive regulator for enhancing salinity tolerance in alfalfa with activated ROS scavenging. Full article

This paper presents an electrical thermometry method designed for kilowatt(kW)-level Gallium Nitride (GaN) High Electron Mobility Transistors (HEMTs). The dependence of the drain current on the channel temperature in GaN HEMTs is utilized as a means to measure the transient channel temperature. However, in kW-class GaN HEMTs, the gate current can reach tens of milliamperes, and trap-induced capture resulting from high doping concentrations can both influence the drain current. Through modifications to the gate bias circuit, the gate voltage self-biasing phenomenon caused by the gate current is mitigated. A theoretical model is derived to express the relationship between the drain current and the channel temperature. Experimentally, amplifier modules equipped with kW-level HEMTs were placed on thermal stages set at 45 °C, 60 °C, and 80 °C. The transient drain current curves and the corresponding channel temperature profiles were measured. The measured drain current versus channel temperature curves at different ambient temperatures were fitted and compared with the theoretically derived formula. The relative error between the measured and calculated drain current values at the same channel temperature was found to be within 1%. Full article

To investigate the effects of low net-energy (NE) diets on intestinal health in Tunchang pigs, 96 animals (25.40 ± 1.11 kg) were randomly assigned to four dietary treatment groups with NE levels of 9.82 (CG), 9.57 (EY1), 9.32 (EY2), and 9.07 (EY3) MJ/kg. Each group consisted of six replicates with four pigs per replicate. The experiment lasted for 63 days. The results showed that compared with the CG, the EY2 increased jejunal villus height and villus height-to-crypt depth ratio, as well as reduced crypt depth in the colon (p < 0.05). Both the EY1 and EY2 demonstrated improved intestinal barrier function through upregulation of zonula occludens-1 and occludin expression in the jejunum, zonula occludens-1 in the ileum, and zonula occludens-1, occludin, and claudin-1 in the colon (p < 0.05). Furthermore, EY2 significantly increased the activities of superoxide dismutase, glutathione peroxidase, and catalase, while reducing malondialdehyde content in both the jejunum and colon (p < 0.05). EY2 showed significantly downregulated relative expression of pro-inflammatory cytokines, including interleukin-1β, tumor necrosis factor-α, and interleukin-6, in the jejunum, ileum, and colon (p < 0.05). Microbial and short-chain fatty acid (SCFA) analyses showed that the EY2 increased the abundance of beneficial bacteria such as Faecalibacterium, CF231, Coprococcus, Ruminococcus, and Blautia and elevated the concentrations of acetate, propionate, and butyrate. In summary, reducing dietary NE levels to no less than 9.32 MJ/kg improved intestinal health by modulating the gut microbiota and increasing SCFA production. Full article

Gene expression measurements of tissues, tumors, or cell lines taken over multiple time points are valuable for describing dynamic biological phenomena such as the response to growth factors. However, such phenomena typically involve multiple biological processes occurring in parallel, making it difficult to identify and discern their respective contributions at any time point. Here, we demonstrate the use of unsupervised machine learning to deconvolve a series of time-dependent gene expression measurements into its underlying temporal components. We first downloaded publicly available RNAseq data obtained from synchronized HeLa cells at consecutive time points following release from cell cycle arrest. Then, we used Fourier analysis and Topic modeling to reveal three underlying components and their relative contributions at each time point. We identified two temporal components with oscillatory behavior, corresponding to the G1-S and G2-M phases of the cell cycle, and a third component with a transient expression pattern, associated with the immediate early response gene program, regulation of cell proliferation, and cervical cancer. This study demonstrates the use of unsupervised machine learning to identify hidden temporal components in biological systems, with potential applications to early detection and monitoring of diseases and recovery processes. Full article