Search Results (303)

To address the persistent challenge of reliable real-time flowrate estimation in complex offshore oil production systems using Electric Submersible Pumps (ESPs), this study proposes a hybrid modeling approach that integrates a first-principles hydrodynamic model with Long Short-Term Memory (LSTM) neural networks. The aim is to enhance prediction accuracy across five offshore wells (A through E) in Brazil, particularly under conditions of limited or noisy sensor data. The methodology encompasses exploratory data analysis, preprocessing, model development, training, and validation using high-frequency operational data, including active power, frequency, and pressure, all collected at one-minute intervals. The LSTM architectures were tailored to the operational stability of each well, ranging from simpler configurations for stable wells to more complex structures for transient systems. Results indicate that prediction accuracy is strongly correlated with operational stability: LSTM models achieved near-perfect forecasts in stable wells such as Well E, with minimal residuals, and effectively captured cyclical patterns in unstable wells such as Well B, albeit with greater error dispersion during abrupt transients. The model also demonstrated adaptability to planned interruptions, as observed in Well A. Statistical validation using ANOVA, Levene’s test, and Tukey’s HSD confirmed significant performance differences (α < 0.01) among the wells, underscoring the importance of well-specific model tuning. This study confirms that the LSTM-based hybrid approach is a robust and scalable solution for real-time flowrate forecasting in digital oilfields, supporting production optimization and fault detection, while laying the groundwork for future advances in adaptive and interpretable modeling of complex petroleum systems. Full article

A fast-paced lifestyle contributes to heightened emotional stress, driving the demand for milder and safer cosmetic ingredients that can counteract stress-induced skin damage—a focus of cutting-edge research in the field. Aim: The aim was to elucidate the role and mechanistic basis of tea (Camellia sinensis) seed meal saponin (Sap) in regulating stress-induced sebum overproduction and inflammatory responses. Methods: The composition and chemical structure of Sap were analyzed using UV-vis absorption spectroscopy, Fourier-transform infrared spectroscopy (FT-IR), and ultra-high-performance liquid chromatography–mass spectrometry (UHPLC-MS). In vitro models of cortisone-induced excessive lipid accumulation and the tumor necrosis factor-alpha (TNF-α)-stimulated inflammatory models were established on sebaceous gland cells (SZ95) and normal human epidermal keratinocytes (NHEKs), respectively. Cortisol and inflammatory cytokine secretion levels in cells were detected using ELISA. Additionally, the signaling pathways were revealed by Western blot (WB) and real-time quantitative polymerase chain reaction (RT-PCR). Results: Five saponins were identified in the Sap extract, all belonging to the oleanolic-acid-type pentacyclic triterpenes. Sap treatment significantly attenuated cortisone-induced cortisol secretion and lipid accumulation in SZ95 sebocytes. Mechanistically, Sap inhibited the 11β-HSD1/SREBP-1 pathway, which mediates its sebosuppressive effects, while concurrently down-regulating the mRNA expression of key downstream transcription factors and enzymes, including SREBP-1, FAS, and ACC. Additionally, Sap treatment significantly attenuated TNF-α-stimulated cortisol secretion and inflammatory cytokine (IL-1β, IL-6, and IL-8) production in NHEK cells through the inhibition of the 11β-HSD1/TLR2/NF-κB signaling pathway. Conclusion: Sap demonstrated dual inhibitory effects, suppressing both emotional-stress-induced sebum overproduction and inflammatory cytokines secretion. Full article

In Nile tilapia, one of the most important aquaculture species, males are larger than females, and an all-male monosex culture offers significant economic benefits. Although the pituitaries of genetic female (XX) and genetic male (XY) tilapia have identical expression levels of follicle-stimulating hormone (fsh), FSH receptor (fshr) expression remains relatively low in XY-undifferentiated gonads and then increases following morphological sex differentiation. The expression patterns of genes related to androgen biosynthesis in XY-undifferentiated gonads are similar to those of fshr during testis differentiation. This might imply that FSH has a potential function in testis differentiation through regulating the expression of genes related to androgen biosynthesis. To determine whether FSH signaling regulated androgen biosynthesis, we microinjected recombinant FSH (rFsh) into XY larvae during the early sex-differentiation stage. We compared the expression of various genes related to testis differentiation after injection. The genes hsd3b, cyp17a1, dmrt1, and gsdf were found to have higher expression in the rFsh treatment group. These results suggest that FSH signaling can activate androgen biosynthesis by regulating steroidogenic enzymes, including hsd3b and cyp17a1. Moreover, injected rFsh can upregulate dmrt1, which has a positive effect on the expression of gsdf. Therefore, during testis differentiation and development, FSH plays a role in both androgen synthesis and the expression of genes related to testis differentiation in Nile tilapia. Full article

In the present study, we synthesized nine new derivatives of 2-(cyclohexylamino)thiazol-4(5H)-one and evaluated their inhibitory activity against 11β-hydroxysteroid dehydrogenase type 1 and 2 (11β-HSD1 and 11β-HSD2), an enzyme responsible for the progression of metabolic disorders and cancers. All obtained derivatives showed inhibitory potential against 11β-HSD1, and four of them highly inhibited 11β-HSD1 activity with IC₅₀ values in the low micromolar range. The most active compound, 3h with IC₅₀ = 0.04 µM, became a more potent and selective inhibitor than carbenoxolone. In addition to inhibition of 11β-HSD1, we investigated the antitumor potential and effects on intracellular redox homeostasis of all newly synthesized compounds on five cancer cell lines, namely human colon cancer (Caco-2), human pancreatic cancer (PANC-1), human glioma (U-118 MG), human breast cancer (MDA-MB-231), and skin melanoma (SK-MEL-30) and on healthy fibroblasts derived from the skin of a male neonate (BJ). Among the derivatives, all tested compounds were found to cause a decrease in cell viability for the MDA-MB-231 and Caco-2 lines and for compounds 3b–3i for SK-MEL-30. The redox-modulating activity was assessed by measuring the levels of reactive oxygen species (ROS), reactive nitrogen species (RNS), and reduced glutathione (GSH) using the same panel of cancer lines and normal cells. This study showed an increase in ROS levels for SK-MEL-30, Caco-2, and MDA-MB-231 lines, while in the case of GSH levels, its reduction was observed in most experimental sets. The presented data suggest that the tested compounds are promising therapeutic agents with dual action because they offer the possibility of simultaneous regulation of metabolic disorders by inhibiting 11β-HSD1 and play a key role in anticancer therapy, which makes them prospective candidates for further clinical studies. Full article

This study investigates the adrenal gland structure and gene expression in Acomys cahirinus compared to Mus musculus, aiming to assess its relevance for human adrenal disease modeling. We identified a well-defined zona reticularis in Acomys, resembling the human adrenal cortex. Transcriptomic analysis revealed upregulation of key steroidogenic genes (Cyp17a1, Sult1e1, Hsd3b2, Defb18, Kiss1, H2-Ke6), with validation by qRT-PCR and CAGE-seq. The gene Nupl1 showed discordant results between RNA-seq and CAGE. Pathway analysis highlighted enrichment of steroidogenesis and adrenal metabolism. Notably, a GTEx-based comparison demonstrated that Acomys adrenal gene expression closely mirrors the expression in the human adrenal cortex, whereas Mus musculus samples diverged toward brain-specific signatures. These findings suggest that Acomys cahirinus represents a promising model for adrenal research, though further studies including single-cell transcriptomics and functional assays are warranted to fully establish its translational potential. Full article

FOXL2 (forkhead box protein L2) is a transcription factor, its function and regulatory mechanism have been mainly studied in mammals; related research on marine invertebrates is still insufficient. It was found that oogenesis was affected, and even a small number of cells resembling spermatogonial morphology appeared in C. farreri ovaries after the FOXL2 was knocked down through RNA interference (RNAi) technology in our laboratory previously. Based on previous research, this paper conducted transcriptome sequencing and differential expression analysis on the ovarian tissues between the experimental group (post-RNAi) and the control group (pre-RNAi) of C. farreri, and used recombinant C. farreri FOXL2 protein for antibody production in Chromatin Immunoprecipitation Sequencing (ChIP seq) experiments to comprehensively analyze the pathways and key genes regulated by FOXL2 during oogenesis. The results showed that in the RNAi experimental group, 389 genes were upregulated, and 1615 genes were downregulated. Among the differentially expressed genes (DEGs), the differential genes related to gender or gonadal development are relatively concentrated in physiological processes such as steroid hormone synthesis, spermatogenesis, gonadal development, and ovarian function maintenance, as well as the FoxO and estrogen signaling pathways. Combining transcriptome and ChIP-seq data, it was found that there were some genes related to sex gonadal development among genes which were directly regulated by FOXL2, such as Wnt4, SIRT1, HSD17B8, GABABR1, KRAS, NOTCH1, HSD11B1, cPLA2, ADCY9, IP3R1, PLCB4, and Wnt1. This study lays the foundation for a deeper understanding of the FOXL2′s specific regulatory mechanism during oogenesis in scallops as a transcription factor. Full article

Type I restriction-modification (RMI) systems play a crucial role in bacterial defense against mobile elements by distinguishing self and foreign DNA through sequence-specific methylation and cleavage. Here, we characterize BlihIA, a novel RMI system from Bacillus licheniformis DSM13 which features redundancy in its hsdS gene copies. Using ONT sequencing, we identify the bipartite recognition site of BlihIA as RTAC(N)₅GCT. We demonstrate the system’s activity both in vivo through efficiency of plaquing (EOP) assay and in vitro in a nuclease reaction with purified BlihIA complex. Notably, mutation of the recognition site abolished in vitro DNA cleavage, confirming sequence specificity. Furthermore, we show that the antirestriction protein ArdB from plasmid R64 effectively prevents DNA cleavage by BlihIA, suggesting a direct mechanism of inhibition. This study provides the first functional characterization of a novel RM system BlihIA, extending the diversity of RM systems in Bacillus species and suggesting potential applications for improving genetic transformation in industrial strains. Full article

Allopregnanolone (allo) and isoallopregnanolone (isoallo) are neuroactive steroid epimers that differ in hydroxyl orientation at carbon three. Allo is a potent GABA-A receptor agonist, while isoallo acts as an antagonist, influencing brain function through their interconversion. Their metabolism varies across brain regions due to enzyme distribution, with AKR1C1–AKR1C3 active in the brain and AKR1C4 restricted to the liver. In rats, AKR1C9 (liver) and AKR1C14 (intestine) perform similar roles. Beyond AKR1Cs, HSD17Bs regulate steroid balance, with HSD17B6 active in the liver, thyroid, and lung, while HSD17B10, a mitochondrial enzyme, influences metabolism in high-energy tissues. Our current data obtained using the GC-MS/MS platform show that allo and isoallo in rats undergo significant metabolic conversion, suggesting a regulatory role in neurosteroid action. High allo levels following isoallo injection indicate brain interconversion, while isoallo clears more slowly from blood and undergoes extensive conjugation. Metabolite patterns differ between brain and plasma—allo injection leads to 5α-DHP and isoallo production, whereas isoallo treatment primarily yields allo. Human plasma contains mostly sulfate/glucuronided steroids (2.4–6% non-sulfate/glucuronided), whereas male rats exhibit much higher free steroid levels (29–56%), likely due to the absence of zona reticularis. These findings highlight tissue-specific enzymatic differences, which may impact neurosteroid regulation and CNS disorders. Full article

Ocular disease (OD) represents a complex medical condition affecting humans. OD diagnosis is a challenging process in the current medical system, and blindness may occur if the disease is not detected at its initial phase. Recent studies showed significant outcomes in the identification of OD using deep learning (DL) models. Thus, this work aims to develop a multi-classification DL-based model for the classification of seven ODs, including normal (NOR), age-related macular degeneration (AMD), diabetic retinopathy (DR), glaucoma (GLU), maculopathy (MAC), non-proliferative diabetic retinopathy (NPDR), and proliferative diabetic retinopathy (PDR), using color fundus images (CFIs). This work proposes a custom model named the ocular disease detection model (ODDM) based on a CNN. The proposed ODDM is trained and tested on a publicly available ocular disease dataset (ODD). Additionally, the SMOTE Tomek (SM-TOM) approach is also used to handle the imbalanced distribution of the OD images in the ODD. The performance of the ODDM is compared with seven baseline models, including DenseNet-201 (R₁), EfficientNet-B0 (R₂), Inception-V3 (R₃), MobileNet (R₄), Vgg-16 (R₅), Vgg-19 (R₆), and ResNet-50 (R₇). The proposed ODDM obtained a 98.94% AUC, along with 97.19% accuracy, a recall of 88.74%, a precision of 95.23%, and an F1-score of 88.31% in classifying the seven different types of OD. Furthermore, ANOVA and Tukey HSD (Honestly Significant Difference) post hoc tests are also applied to represent the statistical significance of the proposed ODDM. Thus, this study concludes that the results of the proposed ODDM are superior to those of baseline models and state-of-the-art models. Full article

Background and Aims: Multiple genetic variants have been associated with disease prevalence and outcomes in middle-aged people with metabolic dysfunction-associated fatty liver disease (MAFLD). However, genetic studies in older adults have been lacking. We aimed to understand their clinical relevance in healthy older persons. Methods: A secondary analysis of the ASPREE (ASPirin in Reducing Events in the Elderly) randomized trial involving community-dwelling older adults ≥ 70 years without prior cardiovascular disease events or life-limiting illness at enrolment. The Fatty Liver Index (FLI) was used to identify MAFLD at baseline. We assessed the associations between six previously reported MAFLD-associated genetic variants with prevalent MAFLD at baseline, and the associations of these variants with cardiovascular disease events and all-cause mortality. Results: A total of 8756 participants with genetic data were stratified according to the FLI, with 3310 having MAFLD at baseline. The follow-up was for a median of 8.4 (IQR 7.3–9.5) years. Variants in two genes (GCKR and HSD17B13) were associated with prevalent MAFLD (p < 0.05); PNPLA3, TM6SF2, LYPLAL1, and MBOAT7 were not. PNPLA3, TM6SF2, HSD17B13, GCKR, and LYPLAL1 were not associated with major adverse cardiovascular events (MACEs) or mortality in the overall cohort or in participants with MAFLD during the follow-up (all p > 0.05). Within the MAFLD group, homozygosity for the rs641738 C > T variant in the MBOAT7 gene was associated with a reduced risk of MACEs (HR 0.68 [95% CI 0.48–0.97]), but not all-cause mortality (HR 1.14 [95% CI 0.89–1.47]). This protective association remained significant after adjusting for multiple key covariates (aHR 0.64 [95% CI 0.44–0.92]). The results were similar when using the metabolic dysfunction-associated steatotic liver disease definition rather than MAFLD. Conclusions: The rs641738 C > T variant in MBOAT7 may confer protection against MACEs in older adults with MAFLD, independent of other clinical risk factors. Further validation using external cohorts is needed. Full article

Type 10 17β-hydroxysteroid dehydrogenase (17β-HSD10) is the HSD17B10 gene product. It plays an appreciable part in the carcinogenesis and pathogenesis of neurodegeneration, such as Alzheimer’s disease and infantile neurodegeneration. This mitochondrial, homo-tetrameric protein is a central hub in various metabolic pathways, e.g., branched-chain amino acid degradation and neurosteroid metabolism. It can bind to other proteins carrying out diverse physiological functions, e.g., tRNA maturation. It has also previously been proposed to be an Aβ-binding alcohol dehydrogenase (ABAD) or endoplasmic reticulum-associated Aβ-binding protein (ERAB), although those reports are controversial due to data analyses. For example, the reported k_m value of some substrate of ABAD/ERAB was five times higher than its natural solubility in the assay employed to measure k_m. Regarding any reported “one-site competitive inhibition” of ABAD/ERAB by Aβ, the k_i value estimations were likely impacted by non-physiological concentrations of 2-octanol at high concentrations of vehicle DMSO and, therefore, are likely artefactual. Certain data associated with ABAD/ERAB were found not reproducible, and multiple experimental approaches were undertaken under non-physiological conditions. In contrast, 17β-HSD10 studies prompted a conclusion that Aβ inhibited 17β-HSD10 activity, thus harming brain cells, replacing a prior supposition that “ABAD” mediates Aβ neurotoxicity. Furthermore, it is critical to find answers to the question as to why elevated levels of 17β-HSD10, in addition to Aβ and phosphorylated Tau, are present in the brains of AD patients and mouse AD models. Addressing this question will likely prompt better approaches to develop treatments for Alzheimer’s disease. Full article

The mineralocorticoid receptor (MR), traditionally associated with renal function, has also been identified in various extrarenal tissues, including the heart, brain, and dorsal root ganglion (DRG) neurons in rodents. Previous studies suggest a role for the MR in modulating peripheral nociception, with MR activation in rat DRG neurons by its endogenous ligand, aldosterone. This study aimed to determine whether MR, its protective enzyme 11β-hydroxysteroid dehydrogenase type 2 (11β-HSD2), its endogenous ligand aldosterone, and the aldosterone-synthesizing enzyme CYP11B2 are expressed in human DRG neurons and whether they colocalize with key pain-associated signaling molecules as potential targets for genomic regulation. To this end, we performed mRNA transcript profiling and immunofluorescence confocal microscopy on human and rat DRG tissues. We detected mRNA transcripts for MR, 11β-HSD2, and CYP11B2 in human DRG, alongside transcripts for key thermosensitive and nociceptive markers such as TRPV1, the TTX-resistant sodium channel Nav1.8, and the neuropeptides CGRP and substance P (Tac1). Immunofluorescence analysis revealed substantial colocalization of MR with 11β-HSD2 and CGRP, a marker of unmyelinated C-fibers and thinly myelinated Aδ-fibers, in human DRG. MR immunoreactivity was primarily restricted to small- and medium-diameter neurons, with lower expression in large neurons (>70 µm). Similarly, aldosterone colocalized with CYP11B2 and MR with nociceptive markers including TRPV1, Nav1.8, and TrkA in human DRG. Importantly, functional studies demonstrated that prolonged intrathecal inhibition of aldosterone synthesis within rat DRG neurons, using an aldosterone synthase inhibitor significantly downregulated pain-associated molecules and led to sustained attenuation of inflammation-induced hyperalgesia. Together, these findings identify a conserved peripheral MR signaling axis in humans and highlight its potential as a novel target for pain modulation therapies. Full article

This retrospective study aimed to evaluate the prevalence, morphological types, and distribution patterns of palatoradicular grooves (PRGs) in maxillary anterior teeth using cone-beam computed tomography (CBCT) in a Turkish population. CBCT images of 1553 patients from the radiology archive of Ordu University Faculty of Dentistry (2021–2022) were reviewed. A total of 920 patients (4012 teeth) met the inclusion criteria. The presence, type, and localization of PRGs were assessed. Groove types were classified as Type 1, 2, 3A, or 3B; localization was recorded as mesial, distal, or midpalatal. Bilateral and unilateral occurrences were also analyzed. Statistical analysis involved chi-square tests, Tukey’s HSD, and Cohen’s kappa for intra-observer reliability. PRGs were detected in 23.6% of patients and 10.42% of teeth. Lateral incisors were most affected (87.56%). Type 1 grooves were most common (71.53%), with midpalatal localization being most frequent (54.07%). Bilateral grooves were significantly more prevalent than unilateral ones (p < 0.001). No significant association was found between groove type and tooth type or between gender and bilaterality. This study revealed a high prevalence of PRGs, especially in maxillary lateral incisors, with a significant tendency toward bilateral and midpalatal presentation. CBCT proved essential for detecting palatoradicular grooves, aiding diagnosis and treatment. Full article

A rising demand for low-gluten beer fuels research into enzymatic solutions. This study optimized Aspergillus niger prolyl endopeptidase (AN-PEP) application timing during brewing to reduce gluten while preserving physicochemical quality. Ale-type beers were produced with AN-PEP (2% v/v) added at mashing, boiling, post-boiling, or post-fermentation, plus a control. Three mashing profiles (Mash A, B, C) were also tested. Gluten was quantified by R5 ELISA (LOQ > 270 mg/L). Color, bitterness, ABV, and foam stability were assessed. Statistical analysis involved ANOVA and Tukey’s HSD (p < 0.05). Enzyme activity and thermal inactivation were also evaluated. Initial gluten levels consistently exceeded LOQ. Significant gluten reduction occurred only post-fermentation. Mashing, boiling, and post-boiling additions effectively lowered gluten to below 20 mg/L. Post-fermentation addition resulted in significantly higher residual gluten (136.5 mg/L). Different mashing profiles (A, B, C) with early enzyme addition achieved similar low-gluten levels. AN-PEP showed optimal activity at 60–65 °C, inactivating rapidly at 100 °C. Physicochemical attributes (color, extract, bitterness, ABV) were largely unaffected. However, foam stability was significantly compromised by mashing and post-fermentation additions, while preserved with boiling and post-boiling additions. AN-PEP effectively produces low-gluten beers. Enzyme addition timing is critical: while mashing, boiling, or post-boiling additions reduce gluten to regulatory levels, only the beginning of boiling or post-boiling additions maintain desirable foam stability. These findings offer practical strategies for optimizing low-gluten beer production. Full article

Background/Objectives: The influence of single-nucleotide polymorphisms (SNPs) on hepatocellular carcinoma (HCC) in terms of etiological factors remains to be explored. This study evaluated the distribution of PNPLA3 rs738409, TM6SF2 rs58542926, and HSD17B13 rs6834314 and overall survival of HCC patients with metabolic dysfunction-associated steatotic liver disease (MASLD-HCC) and viral-related HCC (VIRAL-HCC). Methods: This study included 564 patients with HCC: 254 with MASLD-HCC and 310 with VIRAL-HCC. The SNPs were determined by real-time PCR using TaqMan assays. Results: The mean ages of patients with MASLD-HCC and VIRAL-HCC were 68.4 vs. 60.9 years (p < 0.001), with a significant difference between groups. The prevalence of PNPLA3 GG genotype in MASLD-HCC was significantly higher in MASLD-HCC than in VIRAL-HCC (24.0% vs. 15.5%, OR = 1.86, 95% CI = 1.14–3.05, p = 0.009). Similarly, the prevalence of TM6SF2 TT genotype in MASLD-HCC and VIRAL-HCC was 7.1% vs. 2.6% (OR = 3.39, 95% CI = 1.36–9.21, p = 0.003), while HSD17B13 GG genotype in the corresponding groups was 7.1% vs. 12.6% (OR = 0.53, 95% CI = 0.27–1.01, p = 0.039). The overall median survival of MASLD-HCC was significantly shorter than that of the VIRAL-HCC group (42 vs. 66 months, p = 0.035). In Cox regression hazard analysis, HSD17B13 GG genotype was significantly associated with a lower mortality rate in MASLD-HCC (HR = 0.38, 95% CI = 0.18–0.81, p = 0.011). In contrast, PNPLA3 and TM6SF2 were not associated with overall survival in patients with MASLD-HCC or VIRAL-HCC. Conclusions: Our data demonstrated that the prevalence of the SNPs significantly differed between MASLD-HCC and VIRAL-HCC. The HSD176B13 GG genotype was also associated with a survival benefit in Thai patients with MASLD-HCC. Thus, assessing the HSD176B13 genotype might be beneficial in risk stratification and potential therapeutic inhibition of HSD17B13 among patients with MASLD-HCC. Full article