Search Results (14,760)

RNA degradation plays a vital role in post-transcriptional regulation of gene expression. RNA stability is changed in the pathogenesis of metabolic dysfunction-associated steatotic liver disease (MASLD), but its role and underlying mechanisms in sleeve gastrectomy (SG) effectively remodeling hepatocytes and improving MASLD is unclear. A high-fat diet-induced MASLD model for SG and a hepatocyte-specific Zfp36 knockdown mouse model were established to evaluate the role of zinc finger protein 36 (ZFP36) in MASLD. The expression of ZFP36 and TEA domain transcription factor 4 (TEAD4) was examined in liver tissue samples from MASLD patients. Hepatic ZFP36 expression is downregulated in MASLD but is restored following SG. Hepatocyte-specific Zfp36 knockdown exacerbates high-fat diet-induced liver injury and impairs the therapeutic effect of SG on hepatic steatosis. Mechanistically, ZFP36 binds to TEAD4 mRNA to promote its degradation, thereby modulating the Hippo pathway. Inhibition of TEAD4 transcriptional activity reverses the aggravated MASLD phenotype caused by Zfp36 knockdown. In liver biopsy samples from MASLD patients, ZFP36 expression correlates negatively with TEAD4 expression. Collectively, these findings identify SG-induced upregulation of ZFP36 as a critical mechanism for alleviating MASLD through suppression of TEAD4. Full article

Background/Objectives: Radial extracorporeal shock wave therapy (rESWT) is used to treat neuromuscular disorders such as spasticity, but the mechanisms by which rESWT modulates muscle tone remain incompletely understood. One proposed mechanism involves mechanical perturbation of the neuromuscular junction (NMJ), particularly destabilization of acetylcholine receptor (AChR) clusters in the postsynaptic membrane. Because rapsyn knockout mice are not viable, Caenorhabditis elegans (C. elegans) provides an alternative model for studying neuromuscular signaling, expressing the rapsyn homolog RPY-1, a postsynaptic scaffolding protein involved in AChR organization at the NMJ. This study examined whether loss of RPY-1 alters locomotor responses of C. elegans to radial extracorporeal shock wave (rESW) exposure. Methods: Wild-type worms and rpy-1 knockout worms (rpy-1-KOs) were exposed to defined numbers of rESWs. Locomotor behavior was quantified using automated tracking of parameters describing speed, trajectory and body-wave dynamics. Behavioral responses were analyzed both as absolute values and relative to genotype-specific baseline values. Results: rESW exposure produced pronounced alterations in locomotor behavior across all parameters analyzed. Absolute values revealed baseline differences between genotypes. After normalization to genotype-specific baseline values, wild-type worms and rpy-1-KOs responded similarly to moderate exposure levels. At higher exposure levels, genotype-dependent differences became more apparent. Locomotor impairment was most pronounced immediately after exposure but improved during the subsequent recovery period of three hours. Conclusions: rESWs induced strong but largely reversible locomotor alterations in C. elegans during the first hours after exposure. Loss of the rapsyn homolog RPY-1 modified these responses, particularly at higher exposure levels. These findings indicate that RPY-1 influences behavioral responses to rESW exposure, while direct effects on NMJ structure or AChR organization cannot be determined from the present data. Full article

Corona discharge at the tip of buildings in a thunderstorm environment is an important factor causing changes in the near-ground electric field, but the influence of a quadratic growth law and quantitative research on the parameters is still rare. Therefore, based on the three-dimensional corona discharge model, this paper studies the influence of positive and negative symmetrical triangular wave electric fields with different amplitudes on the corona discharge of an independent lightning rod. Studies have shown that the corona current is synchronized with the peak of the background electric field. Studies have shown that the corona current is synchronized with the peak of the background electric field. When the polarity of the electric field changes from positive to negative, the positive charge accumulated in the positive half-cycle promotes the subsequent negative corona, so the negative corona starts in advance when the polarity reverses. Compared with unipolar discharge, the amplitude of the negative current and the number of negative charges have significantly improved. However, due to the counteraction of neutralization between positive and negative charges, the total corona charge is at a low level, which shows a net negative polarity result. The corona current and the amount of charge increase nonlinearly with an increase in the background electric field amplitude. Under the symmetrical triangular wave electric field, the quantitative fitting relationship between the peak value of the negative corona current in the second half-cycle and the amount of charge is established for the 5 m high independent lightning rod, which is I⁻ = −0.0532 − 0.153$E$ − 0.0682 $E^2$, Q⁻ = −3.18 × 10⁻³ + 7.762 × 10⁻⁴E − 4.671 × 10⁻⁵$E^2$, respectively. The increase in the background electric field amplitude will aggravate the disturbance of the corona discharge to the near-surface electric field. When the direction of the electric field has reverted to zero, the existence of the space charge will lead to a significant change in the strength and polarity of the ground electric field. When the thunderstorm background electric field changes from positive to negative, the corona effect reverses the polarity of the ground electric field in advance, and the larger the peak value of the background electric field, the larger the advance. The corona interference mechanism revealed by this study can provide an important reference for correcting the electric field monitoring data and improving the accuracy of lightning warnings. Full article

Objectives: To address the difficulty of data sharing under privacy constraints and the performance degradation of conventional federated models caused by pronounced inter-client data heterogeneity in rolling bearing remaining useful life prediction, an FDG-based framework is developed for this task. Methods: The proposed framework jointly optimizes client-side feature learning and server-side aggregation. On the client side, a domain-adversarial learning mechanism together with a gradient reversal strategy is introduced to suppress domain-related information in degradation representations and enhance domain-invariant feature learning. On the server side, a distribution-aware dynamic aggregation strategy is designed to adaptively assign aggregation weights by jointly considering client predictive performance and feature distribution discrepancies, thereby mitigating the adverse effects of non-IID data on model aggregation. Conclusions: A federated training scenario is constructed using the PHM 2012 and XJTU-SY datasets, which involve two different bearing types. Experimental results show that, without requiring raw data to leave local clients, the proposed framework improves the accuracy and generalization capability of rolling bearing remaining useful life prediction. Full article

This is a narrative conceptual paper, not a systematic review. Ultrasound-guided fascial hydrorelease (FHR) has been reported to provide sustained pain relief in patients with chronic musculoskeletal pain; however, its underlying biological mechanisms remain incompletely understood. In this paper, we propose the “Fascial Memory Reset Hypothesis” as an integrative framework linking mechanobiology, extracellular matrix (ECM) remodeling, peripheral nociception, microcirculatory dynamics, and ultrasound imaging findings. Mechanobiological research has demonstrated that increased tissue stiffness activates YAP/TAZ signaling, promoting fibroblast activation, ECM deposition, and mechano-epigenetic regulation. These mechanically driven processes can stabilize pathological tissue phenotypes without DNA sequence alterations. The “Fascial Memory Reset Hypothesis” proposes that targeted mechanical interventions such as FHR may partially reverse these mechanically maintained states by restoring tissue mobility and modifying stiffness-dependent mechanotransduction. We propose that “stacking fascia” (observed as layered hyperechoic bands on ultrasound) represents the macroscopic structural phenotype of mechano-epigenetic memory formed through sustained mechanical stress. Integrating molecular mechanotransduction pathways, mechano-epigenetic mechanisms, neural sensitization, and vascular factors, we propose that FHR may hypothetically partially normalize pathological fascial states by mechanically restoring tissue mobility and modifying stiffness-dependent signaling. Although direct molecular evidence of the effect of FHR in human fascia remains limited, this hypothesis provides a biologically plausible link between mechanical stress, ultrasound-visible structural alterations, and sustained clinical improvement. Full article

The central inversion tectonic belt of the Xihu Sag is a typical inversion structural zone in the East China Sea Shelf Basin and a key target for hydrocarbon exploration. The Ningbo structure underwent five evolutionary stages—rifting, post-rift transition, depression, transpressional inversion, and regional subsidence—during which the stress regime evolved from extension to transpression-dominated strike-slip deformation. This study employs seismic interpretation, fault-throw analysis and sandbox analogue modeling to clarify its genetic mechanism and controlling factors. The results show that the fault system exhibits characteristics typical of strike-slip deformation, including high-angle master faults and well-developed flower structures. Along strike, fault throw alternates between normal and reverse displacement over short distances, forming a “dolphin effect,” reflecting spatial alternation between transtensional and transpressional domains. Comparison of three experimental models demonstrates that the overlap and lateral spacing of pre-existing basement faults primarily control deformation style. Greater overlap and closer spacing promote through-going fault linkage and the formation of a principal displacement zone, generating a narrow, continuous uplift belt. A three-dimensional genetic model is established, providing a unified explanation of structural patterns, with implications for similar inversion systems. Full article

Cannabis sativa is a multipurpose dioecious species whose crop performance is governed by sex expression. Although sex is genetically determined by an X/Y chromosome system, plants can develop flowers of the opposite sex through sex reversion, commonly induced by manipulating endogenous hormone levels using plant growth regulators (PGRs). Here, we evaluated the effectiveness of PGRs that promote or inhibit major hormone pathways implicated in plant sex expression. Male and female clones from two accessions were treated with foliar applications of nine PGRs and four combinatory treatments to assess sex- and genotype-specific responses. Floral biomass and the proportion of each sex were recorded at harvest to assess treatment effectiveness. Ethylene emerged as the primary regulator of chemically modulated sex reversion in C. sativa, with its inhibition by silver thiosulfate inducing strong female-to-male reversion and its promotion by ethephon inducing equally strong male-to-female reversion in the inflorescences. Gibberellin promotion on its own resulted in female-to-male reversion at the axial nodes only, while its inhibition showed no reciprocal effects. The combination of silver thiosulfate and gibberellic acid resulted in the most complete female-to-male reversion, and all sex-reverted flowers were fertile. Together, the results indicated that flowers at axial nodes and at the terminal ends of inflorescences are under different hormonal control. Cytokinins, auxins, and jasmonates were found to exert minimal influence on sex reversion. All treatments exhibited pleiotropic effects, particularly gibberellic acid and paclobutrazol, which altered resource allocation, shifting biomass away from and towards floral tissue, respectively. These findings advance our understanding of the hormonal regulation of sex expression in C. sativa and identify optimized approaches for its manipulation. Full article

Porcine reproductive and respiratory syndrome virus (PRRSV)-positive pigs can be exposed to high concentration of gases, such as ammonia and hydrogen sulfide when manure and urine stored in the pits beneath them is agitated and pumped. Such acute exposure can lead to adverse health effects such as respiratory system irritation. This study aimed to explore whether PRRS-positive growing pigs experience changes in viremia detection after manure pit agitation and pumping has been performed. To address this objective, two PRRS-positive growing pig farms were conveniently selected and visited twice during the week before and after manure agitation and pumping. Blood samples were collected to assess detection of viremia, using reverse transcription-polymerase chain reaction (RT-PCR). A logistic regression model was used to evaluate serum detection of PRRSV before and after the manure management event, accounting for pig age. Although PRRSV was detected in the serum of some pigs, under the conditions of the study, there were no statistically significant changes that would indicate that viremia detections change after the pigs had been exposed to barn manure pit agitation and pumping. Full article

Background: Inflammatory bowel disease (IBD) is a gut-based idiopathic disease characterized by chronic and relapsing inflammatory progression and intricate pathophysiology. It is now known that the key etiologies of IBD include immune dysregulation, imbalances in the gut microbiota, and metabolic disruptions. Probiotics are now the potential treatment for IBD, due to their ability to regulate the host immune system and microbiota of the gut. Methods: The current study analytically tested the preventive benefit of Bacillus licheniformis BL-01 on dextran sulfate sodium (DSS)-induced ulcerative colitis (UC) and also expounded on its molecular pathogenesis. Results: Our results demonstrate that supplementation with BL-01 effectively mitigates DSS-induced weight loss, an elevated disease activity index (DAI), and colonic tissue injury in mice. Concomitantly, BL-01 rectifies dysregulated inflammatory cytokine profiles, attenuates oxidative stress, and restores the expression of colonic tight junction proteins as well as the number of goblet cells. Furthermore, BL-01 modulates the gut microbiota diversity by increasing the abundance of beneficial bacterial genera such as Duncaniella and decreasing the abundance of pathogenic genera such as Helicobacter. Notably, BL-01 restores DSS-induced microbial metabolic dysregulation, modulates key metabolic pathways including arachidonic acid metabolism and steroid hormone biosynthesis, and regulates associated metabolites to ameliorate UC. Finally, Bacillus licheniformis BL-01 mitigates oxidative stress, reverses gut dysbiosis and metabolic disorders, and has a protective effect on UC. Conclusions: The findings give new information on the development of probiotic-based therapeutics in the prevention and treatment of IBD. Full article

The world’s growing need for energy, fueled by industrial expansion and a rising population, continues to be a challenge for the scientific community. The heavy reliance on fossil fuels that contribute to environmental degradation and public health concerns, is shifting toward sustainable alternatives, with hydrogen production via advanced catalysts as an energy source emerging as a promising solution. This transition addresses the challenges posed by harmful combustion emissions. In this study, we developed an innovative PANI@Cu-NA-MOF nanocomposite catalyst through a sol–gel synthesis approach that strategically integrates conducting polymers with metal–organic frameworks. The catalyst was characterized using different sets of techniques. Surface morphology and elemental composition were investigated using SEM-EDX, while structural analysis was carried out with FTIR that helped to identify the chemical bonds and functional groups, and UV-Vis spectroscopy provided information on its light absorption properties. In addition, TGA was used to evaluate thermal behavior, and XPS offered detailed surface chemical analysis. It was observed by morphology that PANI@Cu-NA-MOF is a noncapsular-like structure. It is thermally highly stable; a TGA study showed that up to 550 °C, almost 2.5% of weight was lost. The single peak in UV-Vis is the preparation of a successful composite. XPS and FTIR reveal the required peaks of functional groups and elements. The PANI@Cu-NA-MOF composite turned out to be quite effective for water electrolysis, requiring an overpotential of just 0.47 V to drive the reaction. When tested against the reversible hydrogen electrode, we observed onset potentials of 1.6 V/RHE for the oxygen evolution reaction and 0.2 V/RHE for the hydrogen evolution reaction. What makes this particularly interesting is that such performance significantly cuts down on the energy needed for electrolysis, which could make hydrogen production much more practical. Since hydrogen burns cleanly and offers a real alternative to fossil fuels, having an efficient catalyst like this brings us one step closer to sustainable energy. Full article

Background: Bone metastasis is a major determinant of morbidity and therapeutic failure in advanced prostate cancer (PCa); however, the transcriptional programs and tumor microenvironmental alterations driving metastatic progression remain incompletely understood. This study aimed to systematically characterize transcriptomic differences between non-metastatic and bone-metastatic PCa and to identify key microenvironmental signaling pathways involved in tumor survival and chemoresistance. Methods: Bulk RNA sequencing was performed on 49 non-metastatic and 28 bone-metastatic PCa specimens. Differential expression analysis was integrated with weighted gene co-expression network analysis (WGCNA), gene set enrichment analysis, and immune/stromal deconvolution. Key findings were validated using in vitro functional assays, including Transwell co-culture models, small interfering RNA (siRNA)-mediated gene silencing, cell viability, apoptosis, and docetaxel resistance analyses. Results: Transcriptomic profiling identified 574 differentially expressed genes. Bone-metastatic tumors were enriched in ribosome-related and translational pathways, whereas non-metastatic tumors displayed immune-associated signatures, including natural killer (NK) cell-mediated cytotoxicity and cytokine signaling. WGCNA revealed immune-related gene modules preferentially enriched in non-metastatic disease. Immune deconvolution demonstrated significantly higher infiltration of NK cells and endothelial cells in non-metastatic tumors. Chemokine-receptor analysis highlighted upregulation of the CXCL10-CXCR3 axis in non-metastatic PCa. In vitro, PCa cells expressed CXCR3, while endothelial cells markedly increased CXCL10 expression upon co-culture. Functional assays showed that endothelial-derived CXCL10 promoted PCa cell survival, suppressed apoptosis, and conferred resistance to docetaxel via CXCR3-dependent signaling; these effects were reversed by CXCL10 or CXCR3 knockdown. Conclusions: These findings uncover a context-dependent endothelial-immune chemokine network distinguishing non-metastatic from bone-metastatic PCa and identify the CXCL10-CXCR3 axis as a critical mediator of tumor survival and chemoresistance, suggesting a potential therapeutic vulnerability in advanced prostate cancer. Full article

Multi-campus AI data centers procure identical hardware and service SKUs across geographically heterogeneous locations, yet finance and operations require a single system-level benchmark (“world price”) per SKU for budgeting, chargeback, and capacity planning. Naive deployment-weighted aggregation preserves total cost but can induce Simpson-type aggregation bias, where heterogeneous location mixes reverse global SKU rankings and weaken managerial decision signals. This study formalizes the problem of location-robust, cost-preserving aggregation and develops two mathematically structured operators for production cost pipelines. The first operator applies a two-way fixed-effects decomposition to separate global SKU effects from campus-specific premia, followed by normalization to guarantee exact cost preservation. This yields an interpretable benchmark that performs well when campus coverage is sufficiently broad and location effects remain approximately additive. The second operator solves a constrained convex common-weight optimization, producing a unified set of non-negative campus weights that preserves total cost while providing the strongest protection against dominance reversals in the ordered setting. Simulation experiments and a semi-real calibrated AI datacenter OPEX illustration show that both operators substantially improve ranking stability relative to naive blending, while the convex operator serves as the more conservative safeguard under adverse heterogeneity. The resulting detect–correct–validate workflow provides a scalable decision-support framework for robust cost aggregation in distributed AI infrastructure and illustrates how symmetry-preserving aggregation operators can stabilize benchmarking in large heterogeneous systems. Full article

DC-bias may accumulate in bidirectional full-bridge LLC converters during reverse power transfer because the magnetizing branch lacks an inherent DC-blocking mechanism. This bias may cause asymmetric flux excitation in the transformer core, thereby increasing magnetic stress and even leading to core saturation. To address this issue, a confidence-scheduled hybrid DC-bias estimation and suppression method is proposed. An integration-based indicator is constructed for sensitive weak-bias detection, while a reduced-order extended Kalman filter (EKF) is introduced to improve noise immunity and dynamic tracking under strong-bias conditions. Moreover, a confidence-scheduling mechanism is developed to adaptively fuse the two estimates according to bias severity. Based on the fused estimate, a two-level suppression strategy is implemented for severe- and weak-bias conditions. Simulations and experiments on a 2 kW prototype verify that the proposed strategy achieves fast detection, highly accurate robust estimation with a steady-state error of less than 2%, and effective suppression over a wide operating range without additional bulky DC-blocking hardware. Full article

To effectively address the challenge of faulty line selection during high-impedance grounding faults in distribution networks with a flexible grounding system, a novel fault line selection method that integrates both the amplitude and phase characteristics of zero-sequence currents is proposed. The characteristics of zero-sequence currents under single-phase grounding faults in a flexible grounding system are thoroughly investigated, with a particular focus on analyzing the phase relationship and amplitude differences between the zero-sequence currents of each feeder and that of the neutral point. Upon the switching of the parallel low-resistance device, the zero-sequence current of the faulty line is approximately equal in amplitude but opposite in phase to that of the neutral point. In contrast, the zero-sequence current amplitude of a healthy line is significantly smaller than that of the neutral point, and its phase is nearly orthogonal to the neutral point zero-sequence current. To capture these characteristic differences, the projection of each line’s zero-sequence current onto the neutral point zero-sequence current is employed. A projection coefficient criterion is subsequently constructed to enhance the reliability of line selection. Furthermore, by utilizing the neutral point zero-sequence current, the method can effectively extract the weak zero-sequence current of healthy lines, thereby mitigating the risk of misjudgment by the fault line selection device caused by the inability of zero-sequence current transformers (CT) to accurately acquire such faint signals. Simulation results obtained via PSCAD validate that the proposed method remains effective for single-phase grounding faults with transition resistances up to 3000 Ω, even under extreme operating conditions such as reverse polarity of zero-sequence CT or the presence of strong noise interference. Full article

Background: Midkine (MDK), a secreted heparin-binding growth factor, is involved in tumor progression and metastasis. While serum MDK is widely recognized as a potential prognostic biomarker for colorectal cancer (CRC), its specific functional role and underlying mechanisms in CRC development are not fully understood. Methods: The four publicly available CRC microarray datasets—GSE41258, GSE44076, GSE81558, and GSE117606—along with TCGA-COAD and TCGA-READ datasets and their associated clinical data were obtained. MDK expression was measured at both the mRNA and protein levels using quantitative real-time PCR (qRT-PCR) and Western blotting. To investigate its oncogenic functions, a comprehensive set of assays was performed: transwell and wound healing assays for invasion and migration; CCK-8 and colony formation assays for proliferation; and tail vein/spleen injection models combined with xenograft models to study metastasis and tumor growth in vivo. To uncover underlying mechanisms, Western blotting was used to examine the involvement of epithelial–mesenchymal transition (EMT) and the PI3K/AKT signaling pathway. Results: MDK is significantly overexpressed in CRC tissues and cells compared to normal tissues and cells. Notably, patients with high MDK levels show poorer overall survival (OS). Overexpression of MDK increases CRC invasion, migration, proliferation, and metastasis both in vivo and in vitro, while its knockdown reverses these effects. Mechanistically, MDK activates the PI3K/AKT pathway, leading to increased AP2A1 expression and promotion of EMT in CRC. Conclusions: MDK promotes invasion, migration, proliferation, metastasis, and EMT in CRC cells through the PI3K/AKT pathway by inducing AP2A1 expression, which could serve as a diagnostic marker. The PI3K inhibitor LY294002 significantly reduces AP2A1 levels and inhibits MDK-induced malignant behaviors. Targeting MDK-related signaling pathways may offer new strategies for CRC treatment. Full article