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Genetic diversity of Cimex hemipterus and first report of Wolbachia supergroup T in Tehran, Iran: insights from COI and 16 S rRNA analysis
A Lyapunov–PINN framework for global stability of an SEIR epidemic model with educational interventions
Creatinine-normalized urinary lipocalin-2 in children with obesity: association with insulin resistance in a cross-sectional study
Permeability calculation for glutenite reservoirs based on variable T2 cutoff value in nuclear magnetic resonance logging
Systems biology-based drug repurposing for neuroinflammation treatment in activated human microglia
Lactate Ringer’s anti-inflammatory effects in acute pancreatitis are potentially mediated by protein lactylation of extracellular vesicles
Abstract Lactated Ringer’s solution (LR) has been associated with anti-inflammatory effects in acute pancreatitis, likely attributable to its lactate content, but the underlying mechanisms remain poorly understood. Circulating small extracellular vesicles (sEVs) contribute to systemic inflammation in this condition by activating macrophages, and we investigated whether lactate could modulate their inflammatory activity. sEVs derived from BxPC-3 pancreatic cells were treated with lactate and their inflammatory potential assessed by measuring their capacity to induce pro-inflammatory cytokine expression in macrophages. Circulating sEVs were also isolated from patients with acute pancreatitis receiving either LR or normal saline and analysed using the same approach. Vesicle uptake and protein lactylation levels were evaluated by microscopy and western blot, respectively. Lactate treatment reduced sEV-induced macrophage activation without altering vesicle uptake, and was associated with a modest increase in protein lactylation. A similar reduction in inflammatory activity was observed in circulating sEVs from LR-treated patients, but not in those receiving normal saline, alongside a comparable increase in protein lactylation. These findings suggest that lactate can directly modify sEV activity and that the anti-inflammatory effects of LR in acute pancreatitis may be mediated, at least in part, through lactylation-dependent modulation of sEV inflammatory activity.
Deep learning-based automated classification of endometrial lesions in IVF patients using hysteroscopic images
Abstract Endometrial health is a key determinant of female fertility and successful pregnancy outcomes, making the accurate diagnosis of endometrial lesions essential for the success of assisted reproductive technology. While hysteroscopy remains the gold standard for uterine cavity evaluation, interpretation can vary based on clinical expertise. To address this, we developed a deep learning-based clinical decision support system to classify hysteroscopic images from high-resolution (4 K) videos into three categories: normal endometrium, endometrial polyps, and endometritis. Endometritis cases were classified based on hysteroscopic features suggestive of inflammation; no histopathological confirmation was obtained. Utilizing a dataset of 1500 expert-annotated images from 200 clinical videos, we applied transfer learning across four architectures: VGG-16, VGG-19, DenseNet-121, and EfficientNet-B0. Our results show that the models achieved classification accuracies between 85 and 89%, with DenseNet-121 demonstrating superior performance, specifically achieving a sensitivity of 93% and an AUC of 98.8% for polyp detection, alongside a precision of 90% for endometritis. Furthermore, Grad-CAM visualization confirmed that the networks focused on clinically relevant morphological features, enhancing model interpretability. These findings suggest that deep learning may serve as a supportive tool to assist clinicians in hysteroscopic analysis, pending validation on external datasets and with pathologically confirmed labels.
Long-term effects of short-term postoperative bromfenac on macular thickness after phacovitrectomy for idiopathic epiretinal membrane
Abstract Postoperative macular edema is a recognized complication following vitrectomy for idiopathic epiretinal membrane (ERM), particularly after combined phacovitrectomy. Topical nonsteroidal anti-inflammatory drugs (NSAIDs) inhibit prostaglandin-mediated disruption of the blood-retinal barrier, but their long-term anatomical impact after ERM surgery has not been established. We retrospectively reviewed 282 eyes from 279 patients who underwent vitrectomy or phacovitrectomy for idiopathic ERM. Patients were categorized into an Early Use Group (topical bromfenac initiated within 4 weeks postoperatively, n = 91) and a Late/No Use Group (n = 191). The primary outcome was the change in central subfield macular thickness (CSMT) measured by OCT over 6 months. Longitudinal analysis was performed using a linear mixed-effects model (LME) with treatment-by-time interaction as the primary term. LME analysis revealed a significant treatment-by-time interaction for CSMT in the full cohort (F = 4.62, p = 0.003) and in the phacovitrectomy subgroup (F = 6.23, p < 0.001). The Early Use Group showed a significantly greater reduction in CSMT at 6 months (93.9 ± 56.2 μm) compared with the Late/No Use Group (76.6 ± 52.8 μm), with an estimated marginal mean difference of approximately 14–15 μm maintained at all post-baseline time points ( p ≤ 0.006). For logMAR BCVA, a significant treatment-by-time interaction was also observed (F = 2.68, p = 0.046): the Early Use Group showed significantly faster visual recovery at 1 month ( p = 0.016), but both groups converged to equivalent visual acuity by 6 months ( p = 0.305). Early postoperative bromfenac within 4 weeks of phacovitrectomy for ERM significantly reduces macular thickness, and this anatomical benefit is durably maintained for at least 6 months, along with accelerated visual acuity recovery at 1 month. These findings raise the hypothesis that prostaglandin-mediated vascular permeability in the early postoperative period may influence long-term macular remodeling; however, this remains speculative, as direct evidence of permeability changes was not assessed in this study.
Optimization of bottom structure layout and key parameters in block caving: a case study of the Cukaru Peki Copper-Gold Mine in Serbia
Abstract The stability of the bottom structure and the scientific management of ore drawing are critical to the successful application of the block caving method. In view of the engineering conditions of the Lower Orebody of the Cukaru Peki Copper-Gold Mine operated by Serbia Zijin Copper Doo Bor characterized by great burial depth, high in-situ stress, and large-scale mechanized ore extraction. This study systematically optimizes the layout form and key geometric parameters of the bottom structure through a comprehensive approach combining engineering analogy, theoretical analysis, numerical simulation, and orthogonal experimental design. The results indicate that, in terms of the layout at the extraction level, the branching herringbone configuration is the optimal scheme. It not only ensures sufficient overlap of draw zones and stability of the sill pillar, but also better accommodates the efficient operation of electric load–haul–dump (LHD) machines. Regarding key parameter determination, coupled analyses of vertical and planar geometric relationships demonstrate that the optimal vertical distance between the extraction level and the undercut level is 20 m. The spacing of drawpoint crosscuts and drifts is determined to be 32 m and 18 m, respectively. The optimized dimensions of the ore pass are identified as 5.0 m for the lower opening width and 14 m for the upper opening width, which significantly reduce the incidence of drawpoint hang-ups. For the undercutting scheme, an advancing undercut method combined with an inclined narrow-section layout is recommended, with an undercut height of 6 m. Furthermore, numerical simulations reveal the influence of the advanced undercut distance on stress redistribution. It is recommended that a reasonable distance of 30–36 m be maintained between ore pass operations and the advancing undercut front to effectively mitigate structural damage caused by high stress concentrations in the bottom structure. The parameter system established in this study provides a scientific basis for the safe and efficient exploitation of the Cukaru Peki deposit operated by Serbia Zijin Copper Doo Bor and offers important engineering guidance for bottom structure design in similar deep block caving mines.
Disrupting Notch signalling by a small molecule inhibiting dihydroorotate dehydrogenase activity
Abstract The Notch signalling pathway is highly evolutionarily conserved and regulates differentiation and homeostasis in most organs. Given the critical role of Notch signalling for normal development, dysregulated Notch signalling is frequently linked to pathogenesis of disease and cancer. Hence, developing Notch-targeting therapeutics is warranted but has been challenging and Notch inhibitors have not yet reached broad clinical use. In this report, we identify potential Notch inhibitors, using a novel cell-based Notch reporter system for unbiased screening of compounds reducing Notch signalling. A library of 37,966 small organic compounds was screened for inhibitor candidates, followed by a counter screen to eliminate γ-secretase inhibitor-like compounds and an orthogonal screen based on the role of Notch signalling in myogenic differentiation. This triage led to the identification of five Notch inhibitor candidate hits with different chemical backbones and unrelated to previous Notch antagonists. One candidate hit proved to be a DHODH inhibitor, and we also provide evidence that a well-established DHODH inhibitor is a highly potent Notch inhibitor. In conclusion, our data support the notion that DHODH inhibition may be an interesting avenue to explore for the development of novel Notch inhibitors.
Aliquat IL336 vs. Cyphos IL101 extractants for the solvent extraction of heavy metals from zinc plants residues
Association of serum uric acid with cardiovascular-kidney-metabolic syndrome in elderly populations: results from Chinese and US cohorts
The variability fingerprint of a warming world informing climate risk and solutions
Fluid flow-induced deformation dynamics under biaxial loading in anisotropic (layered) analogues of unconventional reservoirs: insights from physical model experiments and numerical simulations
Ameliorating calcium homeostasis improves longevity and healthspan in progeroid and naturally aged mice
Neuroligin1 in CCK-interneurons gates social memory formation via a disinhibitory microcircuit in the hippocampal CA2 in male mice
West Antarctic Ice Sheet advance since the early Pliocene
Abstract Current understanding of past ice dynamics in the Amundsen Sea—the most vulnerable part of the West Antarctic ice sheet (WAIS)—remains incomplete, hampering future predictions. Here, sediments from International Ocean Discovery Program Site U1532 on the continental rise reveal that ice-sheet dynamics strongly influenced detrital magnetic minerals supply. Minimal magnetite concentration during ~4.1-3.8 Ma reflects the smallest WAIS extent in the Amundsen Sea sector since ~4.33 Ma. Since ~4.1 Ma, WAIS expansion was closely linked to long-term global cooling. After ~3.2 Ma, elevated fine-grained magnetite indicates a sustained increase in sediment contribution from the Thwaites Glacier catchment. The abrupt ice-sheet expansion at ~3.2 Ma may reflect the crossing of a climatic threshold that triggered qualitative transformations in ice-sheet development. Cessation of major WAIS growth after ~0.9 Ma aligns with stabilized long-term CO 2 levels and ocean temperatures. Collectively, these results underscore the high sensitivity of the Amundsen Sea sector to global climate forcing.
Superballistic flow of viscous electron fluid induced by edge magnetoplasmons in point contacts
Abstract In narrow conductors, electron-electron collisions can create a viscous fluid state, allowing conductivity beyond ballistic transport into the superballistic regime. Point contacts made from ultrahigh-mobility two-dimensional electron gas serve as a platform to study this effect. Under microwave irradiation, edge magnetoplasmons in point contacts are excited and strongly influence electron dynamics. This study uses photoconductivity signals - changes from microwave exposure - to investigate superballistic electron flow, confirmed by size-dependent photoconductivity, magnetic field effects, and microwave power analysis. At low magnetic fields, weak microwaves lead to positive photoconductivity due to superballistic flow, while strong radiation causes negative photoconductivity because of enhanced phonon scattering.