Search Results (110,120)

Integrating full-coverage 2D seismic profiles, local 3D seismic volumes, and borehole data, this study characterizes the transfer structures within the Hangjinqi area of the northern Ordos Basin and elucidates their control on natural gas accumulation. We propose a novel model for hydrocarbon migration and aggregation within transfer structures under an intraplate strike-slip framework. Our findings reveal the following: (1) The transfer structures in the study area manifest as accommodation zones formed by the soft-linkage of overlapping segments of the Hangjinqi fault zone (HFZ)—comprising the Porjianghaizi fault (PF), Wulanjilinmiao fault (WF), and Sanyanjingfault (SF)—since the Hercynian period. Specifically, these consist of two diagonally distributed relay ramps. The relay ramp between the PF and WF hosts a complex reticulate tectonic pattern, characterized by NE- and NWW-trending en-echelon sub-basement fault belts. (2) Transfer structures govern natural gas accumulation through three primary mechanisms: reservoir distribution, reservoir reformation, and fluid migration. ① During the Late Carboniferous to Late Triassic (C2-T3), under N-S compression, the relay ramps controlled the strike and distribution of sedimentary channels. Simultaneously, stress concentration at these ramps under sinistral transpression induced NWW-trending en-echelon faults, which significantly enhanced reservoir petrophysical properties. ② During the Middle-Late Jurassic (J2-3) primary charging period, a shift to a NE-high/SW-low paleogeographic setting triggered a strike-slip reversal of the HFZ. Natural gas migrated northward primarily through bedding-parallel pathways at the relay ramps. ③ By the Early Cretaceous (K1) secondary charging period, weakened shale smear effects along segments of the PF provided lateral pathways, allowing simultaneous northward migration via both strata and fault surfaces. This prolonged differential activity ultimately dictated the heterogeneous distribution of natural gas across the Hangjinqi area. Full article

Conventional gummies are characterized by high sugar, sweetener, and additive content, which has increased the demand for healthier alternatives. In this context, the incorporation of unconventional ingredients has emerged as a promising strategy to improve nutritional profile and functional value. This review aimed to collect and analyze information on the nutritional, technological, and sensory properties of unconventional ingredients, such as fruits, vegetables, microalgae, natural sweeteners, coproducts, and other functional compounds, in gummy formulations. A literature search was conducted, from which 20 relevant studies were selected and analyzed. The results showed that fruit incorporation increased the content of fiber, vitamin, and antioxidant compounds, while vegetables improved the mineral composition and the presence of bioactive compounds. Similarly, agro-industrial coproducts were identified as valuable sources of functional compounds with potential for sustainable valorization. In addition, the alternative gelling agents exhibited favorable effects on the texture, gel-forming capacity, stability, and shelf life of the samples. Overall, these ingredients demonstrated nutritional, technological, sensory, and sustainability advantages. However, challenges related to industrial scalability and sensory evaluation remain. Full article

Chronic rhinosinusitis with nasal polyps (CRSwNP) is a heterogeneous inflammatory disease with a complex pathogenesis that significantly affects patients’ quality of life. Type 2 inflammation plays a dominant role in its course and is associated with the activation of immune pathways involving interleukins IL-4, IL-5 and IL-13, eosinophils, and immunoglobulin E. Standard treatment methods, including corticosteroids and surgical interventions, despite their proven efficacy, often fail to provide sustained disease control and are associated with a high rate of recurrence. The aim of this review is not only to summarize the available evidence on biological therapies in CRSwNP, but also to critically evaluate their current position within treatment algorithms, with particular emphasis on patient selection, integration with endoscopic sinus surgery, comparison of available biologic mechanisms, and remaining challenges in personalized treatment strategies. The paper discusses available monoclonal antibodies, such as dupilumab, omalizumab, mepolizumab, and benralizumab, which act by selectively inhibiting key mediators of type 2 inflammation. Analysis of clinical trial results indicates that biological therapies lead to a significant reduction in nasal polyp size, improvement in nasal patency, restoration of olfactory function, and enhancement of quality of life as measured by the SNOT-22 scale. Furthermore, they demonstrate a favourable safety profile and may represent an effective therapeutic option for patients with severe, treatment-resistant disease, particularly in cases with coexisting eosinophilic asthma. Biological therapies represent a breakthrough in the treatment of CRSwNP and align with the concept of personalised medicine. Their role in clinical practice continues to expand; however, further research is required to optimise patient selection and assess long-term treatment outcomes. Full article

Background: This study investigates the psychophysiological stress profiles of professional basketball players by simultaneously analyzing two distinct neuroendocrine pathways: the sympathetic–adrenal–medullary (SAM) system, via salivary alpha-amylase (AA), and the hypothalamic–pituitary–adrenal (HPA) axis, via salivary cortisol (C). While competitive environments are known to elicit significant stress, the interaction between game-specific variables—such as playing time (PT) and tactical position—and those biomarkers remains insufficiently explored in real-time, official match settings. Methods: Twelve professional male basketball players were monitored across four official matches. Salivary samples were collected, and stress biomarkers (AA and C) were analyzed at three timepoints: pre-match, half-time, and post-match. Results: Results indicate that stress responses are non-uniform and highly context-dependent. A significant spike in AA was observed during the first match (p < 0.001; ES = 0.82; 95% CI −0.01–1.66), where concentrations rose from a pre-match mean of 247.9 ± 232.59 U/mL to a post-match peak of 674.39 ± 693.33 U/mL. Cortisol responses did not vary significantly across matches but exhibited a strong positive correlation with PT (p = 0.01; R = 0.76), identifying that C may serve as a primary marker of individual physical workload. Positional analysis revealed significant divergence in HPA activation; guards (0.55 ± 0.31 µg/dL) and centers (0.51 ± 0.22 µg/dL) exhibited higher cortisol levels compared to forwards (0.24 ± 0.18 µg/dL), reflecting the high cognitive/decision-making load of guards and the mechanical/physical contact load of centers. Conclusions: The observed differences in AA and C liberation suggest that stress responses during matches are influenced by a complex interaction of physiological and psychological stimuli characteristic of competitive basketball. Consequently, these findings indicate the importance and value of a dual-biomarker approach which might provide a framework for optimized training load management and recovery protocols in elite basketball. Full article

Background: Pumpkin is a source of phenolics and carotenoids, but their retention during freeze-drying may depend on the drying programme. Methods: Pumpkin flesh was freeze-dried using two schedules: a stepwise schedule (SWS; gradual pressure decrease and shelf heating) or a rapid schedule (RS; deep vacuum and direct shelf heating). Final shelf temperatures of 20, 30 and 40 °C were tested. The powders were analysed for phenolic and carotenoid profiles, residual moisture, colour and basic powder functionality. Results: RS produced lower residual moisture (4.7–5.4%) than SWS (6.2–8.8%). Flowability remained poor but improved at higher shelf temperatures. Water-holding capacity increased, while swelling decreased. Higher levels of protocatechuic acid (121–130 μg/g dry weight), (-)-epicatechin (36–39 μg/g dry weight), and ethyl protocatechuate (7.7–8.8 μg/g dry weight) were determined in samples dried at the lowest shelf temperature, regardless of the drying schedule. SWS30 and SWS40 were associated with caffeic acid, syringic acid and trans-2-hydroxycinnamic acid, and all SWS samples had higher quercetin content. RS gave higher carotenoid levels at 20 °C, while responses at 30 and 40 °C depended on the compound. Conclusions: Final shelf temperature and drying schedule affected antioxidant retention and functional properties of pumpkin powder. Full article

Background: East African runners, particularly from Kenya, have long dominated long-distance running, whereas highly trained European runners represent an appropriate comparison population to investigate structural and potentially modifiable anthropometric characteristics. Objective: To compare structural and modifiable anthropometric traits between professional Kenyan and European long-distance runners and to investigate the relationship between local muscularity and skeletal robustness. Methods: A total of 52 male marathon runners (32 Kenyan and 20 European) were assessed according to the International Society for the Advancement of Kinanthropometry (ISAK) protocol. Participants were 27.2 ± 5.2 years with a BMI of 18.4 ± 1.1 kg·m⁻² and a marathon time of 02:09:26 in the Kenyan group, and 30.9 ± 4.9 years, BMI 21.1 ± 2.1 kg·m⁻², and marathon time of 02:18:31 in the European group. Corrected girths were calculated to explore correlations between skeletal breadths and muscularity. Results: European runners exhibited significantly greater body mass, sitting height, girths, skeletal breadths, and muscle mass compared to Kenyan runners (p < 0.05), with large to very large effect sizes. In contrast, Kenyan runners showed lower adiposity and more linear body proportions, including a lower Cormic index and higher intermembral index. Differences in segment lengths were generally limited. Principal component analysis showed clearer group separation for modifiable than structural traits. Significant positive correlations were observed between humeral breadth and corrected arm girth (r = 0.41, p = 0.002), femur breadth and corrected thigh girth (r = 0.66, p < 0.001), and bimalleolar breadth and corrected calf girth (r = 0.72, p < 0.001). Conclusions: These findings suggest that Kenyan long-distance runners exhibit a lighter and more linear anthropometric profile than their European counterparts, whereas European runners display greater skeletal robustness and musculoskeletal development. Furthermore, local muscularity may be partly associated with underlying skeletal robustness. Full article

To preliminarily elucidate the bidirectional metabolic effects caused by changes in PFKM expression, provide research clues for further investigation of the molecular mechanisms through which PFKM regulates porcine skeletal muscle metabolism and myogenic differentiation, and offer a reference for identifying candidate genes associated with meat production traits and studying gene regulation in pig breeding, this study compared skeletal muscle protein expression profiles between Large White and Bama pigs. Candidate regulatory factors related to muscle growth and energy metabolism were screened, and the effects of altered muscle-type phosphofructokinase (PFKM) expression on metabolic homeostasis and myogenic differentiation in porcine skeletal muscle satellite cells (SMSCs) were preliminarily evaluated. Longissimus dorsi muscle tissues from Large White and Bama pigs were analyzed using iTRAQ-based proteomics. A total of 2040 reliably quantified proteins were identified, of which 51 were relatively upregulated in Large White pigs and 73 were relatively upregulated in Bama pigs. Functional enrichment analysis showed that the differentially expressed proteins were mainly involved in glycolysis, mitochondrial energy metabolism, protein synthesis, and the regulation of muscle fiber structure and function. PFKM was therefore selected as a key candidate differentially expressed protein. Porcine SMSC models comprising a PFKM knockdown group (PFKM-KD), a PFKM overexpression group (PFKM-OE), and a normal control group (PFKM-CON) were subsequently established. Glucose consumption and lactate accumulation in the culture medium, ATP levels, reactive oxygen species (ROS), mitochondrial membrane potential, apoptosis, mitochondrial dynamics-related proteins, and myogenic differentiation markers were then examined. Compared with the PFKM-CON group, the PFKM-OE group showed significantly increased glucose consumption and lactate accumulation, together with significant increases in ROS levels, mitochondrial membrane potential, and apoptosis, whereas ATP levels were significantly reduced. In the PFKM-KD group, glucose consumption and lactate accumulation were significantly decreased, accompanied by reductions in mitochondrial membrane potential, ROS, ATP levels, and apoptosis. PFKM overexpression mainly induced oxidative stress, ATP depletion, and increased apoptosis, whereas PFKM knockdown primarily reduced mitochondrial membrane potential, ROS, and ATP levels, indicating a relatively low-metabolic state. Both treatments were accompanied by dysregulated expression of the mitochondrial dynamics-related proteins DRP1, MFN2, and OPA1, although their patterns of change were not identical. Western blotting and immunofluorescence consistently showed that the expression levels of the myogenic differentiation markers MyoD and MYH were significantly lower in both the PFKM-KD and PFKM-OE groups than in the control group, suggesting that either excessive or insufficient PFKM expression may impair the myogenic differentiation potential of SMSCs. In conclusion, changes in PFKM expression are closely associated with glycolysis-related metabolism, energy and redox homeostasis, mitochondrial function-related indicators, and myogenic differentiation capacity in porcine SMSCs. The normal biological function of PFKM may therefore depend on its expression being maintained within an appropriate range. Full article

The use of covalent warheads targeting the catalytic cysteine has been a cornerstone in the coronavirus main protease (M^pro) inhibitor development. Various electrophilic motifs have been explored, including aldehydes, nitriles, ketoamides, and hydroxymethyl ketones (HMKs). Recent efforts have mostly centered around nitrile warheads, given the success of Nirmatrelvir in the clinic. However, it is essential to identify and develop alternative chemotypes with distinct chemical and pharmacological profiles to prepare for future pandemics. Among such alternatives, HMKs are of particular interest because they balance reduced intrinsic electrophilicity with an excellent selectivity profile. Nevertheless, early HMK-based compounds, such as the clinical-stage M^pro inhibitor PF-00835231, suffered from poor oral bioavailability and therefore required intravenous administration, with or without prodrug derivatization of the hydroxyl group. In this work, we describe our efforts to advance the HMK field by discovering mCMX110, a lead compound that exhibits superior potency, increased unbound exposure in vivo, and favorable oral bioavailability in preclinical studies. Full article

Illegal parking is a persistent challenge in central areas of intermediate cities, where growing demand for curb access competes with limited road space, pedestrian circulation, and public transport operations. While previous research on parking management and curbside regulation has documented links between parking behavior, congestion, and street performance, empirical evidence based on direct street-segment observations remains limited in Latin American intermediate-city contexts. This study examines the distribution across observed street segments, user profile, and urban impacts of parking events across six commercial street segments in central Loja, Ecuador. A total of 1425 parking events were recorded between 11 and 28 May 2026 and classified by maneuver type, vehicle type, apparent use, parking reason, companions, operational conditions, and impacts on congestion, pedestrian circulation, and public transport. Descriptive statistics, exact confidence intervals, chi-square tests with Cramér’s V, false discovery rate correction, standardized residuals, and adjusted logistic regression models were applied. Results show that 64.4% of observed events were infractions, mainly prohibited-zone parking (38.9%) and double parking (25.5%). Infraction type varied strongly by street segment (Cramér’s V = 0.651). Adjusted congestion probabilities were substantially higher for double parking (45.0%) and prohibited-zone parking (41.3%) than for non-infraction events (10.2%). The findings indicate substantial heterogeneity in illegal-parking prevalence and composition among the six observed street segments, together with significant associations between parking infractions and urban street performance. These results identify segment-specific differences within the study area but should not be interpreted as evidence of spatial predictability beyond the observed locations and period. Full article

Background and Objectives: Psoriasis is a chronic immune-mediated inflammatory disease frequently accompanied by obesity and cardiometabolic disturbances. This study evaluated metabolic, inflammatory, and genetic correlates of overweight/obesity in ethnic Kazakh patients with psoriasis and explored potential multilocus genetic interactions. Materials and Methods: This study included 150 patients with clinically confirmed psoriasis, comprising 75 patients with overweight/obesity and 75 non-overweight/obese individuals frequency-matched by age and sex; because group sizes were fixed by design rather than sampled in proportion to prevalence, the reported odds ratios reflect within-sample associations rather than population-level risk estimates. Clinical, anthropometric, biochemical, inflammatory, and genetic data were collected using standardized protocols. Multivariable logistic regression was used to assess clinical, metabolic, and inflammatory correlates of overweight/obesity. Associations between three candidate polymorphisms, rs1558902 in FTO, rs696574 in CALCRL, and rs10968110 in ZTV, were evaluated. Results: In the multivariable model adjusted for age and sex, higher triglyceride levels (adjusted OR 4.73, 95% CI 1.36–18.57), higher HbA1c (adjusted OR 1.71, 95% CI 1.09–2.91), and lower HDL-C levels (adjusted OR 0.36, 95% CI 0.18–0.66) were independently associated with overweight/obesity. In genetic analyses, rs10968110 in ZTV showed significant associations with overweight/obesity in genotype, additive trend, allelic, and dominant models, while the recessive model was not significant. The FTO rs1558902 variant was also significantly associated with overweight/obesity, with the strongest support observed under additive, allelic, and dominant assumptions. In contrast, rs696574 in CALCRL was not significantly associated with overweight/obesity. Exploratory MDR analysis identified rs10968110 as the most stable single-locus model, whereas higher-order models showed only limited additional discriminatory value and lower cross-validation consistency. Conclusions: Among ethnic Kazakh patients with psoriasis, overweight/obesity was associated with an adverse cardiometabolic profile characterized by elevated triglycerides, higher HbA1c, and reduced HDL-C. Candidate genetic findings suggest that ZTV rs10968110 and FTO rs1558902 may be associated with overweight/obesity susceptibility, although these results should be considered exploratory pending validation in larger independent cohorts. These findings support integrated cardiometabolic assessment in psoriasis care and further investigation of genetic susceptibility to obesity in this population. Full article

Endoreduplication and mixoploidy are widespread but poorly characterized phenomena in Cannabis sativa, a species notable for its rapid growth and high morphological variability. In this study, we analyzed 12 accessions using flow cytometry, chromosome counts, and fluorochrome banding to investigate organ-specific patterns of endopolyploidy and the occurrence of mixoploidy. Roots and cotyledons consistently exhibited high levels of endoreduplication, with substantial proportions of 8C nuclei and above, whereas the first pair of leaves displayed a profile similar to that of adult foliage, dominated by 2C nuclei. Cycle value and endocycle index calculations confirmed significant differences among organs, with roots and cotyledons showing markedly higher endoreduplication levels than leaves. Chromosome counts revealed the expected diploid number (2n = 20), but we also detected triploid and tetraploid cells in several accessions, indicating somatic mixoploidy. The presence of endoreduplication and mixoploidy suggests that C. sativa exhibits complex cell cycle regulation during early development. Fluorochrome banding revealed GC- and AT-rich DNA regions. Sex chromosome candidates are heterochromatic and contain AT-rich DNA. These findings expand the cytogenetic knowledge of the species and provide a basis for future studies on the developmental and evolutionary significance of somatic genome variation in C. sativa. Full article

In this article, I argue that the probabilistic argument from evil rests on an assumption that weakens its conclusion. The argument presupposes epistemic conditions that we are not in a position to meet. I use combinatorial axiology to show that the world’s axiological profile is unknowable to humans, and that this fact significantly weakens the probabilistic argument. I do not contend that the probabilistic argument is refuted, but only that the version I address is undercut. To my knowledge, this is the first application of systematic combinatorial axiology against the probabilistic argument. Full article

The melon fly, Zeugodacus cucurbitae (Coquillett), is a destructive tephritid pest of cucurbit crops, and neonicotinoids remain important tools for its management. Although neonicotinoids primarily target nicotinic acetylcholine receptors (nAChRs), their possible effects on acetylcholinesterase (AChE)-mediated cholinergic homeostasis in Z. cucurbitae remain poorly understood. In this study, we molecularly characterized the Z. cucurbitae Ache gene and evaluated its expression and functional contribution under dinotefuran, acetamiprid, and thiamethoxam stress. Bioinformatics analyses confirmed conserved cholinesterase features, including the FGESAG catalytic motif, catalytic triad, choline-binding site, oxyanion hole, and conserved disulfide-bond residues. Temporal and tissue-specific expression profiling showed high Ache transcript abundance in eggs, third-instar larvae, and adult heads. Larval exposure to LC₅, LC₂₀, and LC₅₀ concentrations of the three neonicotinoids caused dose- and time-dependent mortality and significantly induced Ache expression, with dinotefuran producing the strongest transcriptional response. Parental exposure also impaired F₁ fecundity, hatchability, larval survival, and adult emergence, with acetamiprid and thiamethoxam causing stronger transgenerational effects than dinotefuran. Oral RNAi significantly increased larval susceptibility upon re-exposure to neonicotinoids after 72 h. These findings indicate that Ache contributes to cholinergic stress response and susceptibility modulation in Z. cucurbitae, supporting its possible potential as an RNAi target for integrated pest management (IPM). However, practical utility at the field level requires further evaluation. Full article

Acoramidis is a novel transthyretin stabilizer recently approved for the treatment of transthyretin amyloid cardiomyopathy. Although clinical trials showed that the drug was generally safe, comprehensive real-world safety data after its approval remain limited. This study characterizes the real-world safety profile of acoramidis using the FDA Adverse Event Reporting System (FAERS) database. The database was queried for adverse events associated with acoramidis as the primary drug suspect from 1 January 2022 through 31 December 2025. Following deduplication and removal of confounding adverse events that could have stemmed from the underlying amyloidosis, a dual-statistical framework was applied. Frequentist disproportionality analysis was followed by Bayesian shrinkage using a Bayesian Confidence Propagation Neural Network to isolate statistically robust safety signals. Frequentist disproportionality analysis of 290 unique cases identified 25 safety signals. Subsequent Bayesian refinement isolated nine signals that met both frequentist and Bayesian criteria. The dual Bayesian and frequentist approaches identified signals of renal stress and gastrointestinal distress. Neuromuscular and systemic signals such as fatigue and dizziness met frequentist thresholds but did not meet the Bayesian threshold. This study’s findings reflect the previously reported gastrointestinal distress and disproportionate laboratory shifts in renal function. This study’s real-world post-marketing surveillance of acoramidis reinforces the safety data that was established through the clinical trial, ATTRibute-CM. Full article

Quinoa (Chenopodium quinoa Willd.) is a nutrient-dense pseudocereal with a favorable nutritional profile that may improve postprandial glycemic control and satiety. This randomized crossover pilot study compared the acute effects of cooked quinoa and white bread on postprandial blood glucose and subjective appetite responses in healthy young adults. Participants consumed four test meals on separate occasions: cooked quinoa or white bread providing either 25 g or 35 g available carbohydrate. Capillary blood glucose and appetite ratings were assessed over 120 min. Quinoa produced significantly lower postprandial glucose responses and incremental area under the curve (iAUC) than white bread at both carbohydrate doses (p < 0.05). Appetite responses were also improved following quinoa consumption compared to the control. Blood glucose iAUC was positively correlated with appetite net area under the curve (r = 0.57; p < 0.001). Palatability and gastrointestinal tolerance were comparable between treatments. These findings indicate that cooked quinoa elicits more favorable postprandial glycemic and satiety responses than white bread and may serve as a functional carbohydrate alternative to support metabolic health. Full article