Search Results (1,966)

Atherosclerotic cardiovascular disease treatment is being reevaluated, since a residual cardiovascular risk (RCR) persists even in patients who achieve optimal LDL-C values. Underlying causes are metabolic dysfunction, lipoprotein(a), inflammation, and triglyceride-rich lipoproteins and their remnants. Dietary treatment options like time-restricted eating (TRE) are becoming more widely acknowledged for their potential advantages in metabolic health and weight control, as a treatment of atherosclerosis expanding beyond LDL-C medication. Beyond weight loss, TRE (which restricts meals to a window of 6 to 8 h) appears as the most accessible treatment, and has been shown to improve blood pressure, lipid profiles, and glucose regulation through mechanisms like metabolic switching and circadian synchronization. We hypothesize, and will present our arguments, that a key mechanism underlying the cardiovascular and weight-related benefits of TRE is its impact on the circadian regulation of angiopoietin-like protein 4 (ANGPTL4) activity within adipose tissue. Additionally, lipolysis is accelerated by ANGPTL4 activation. TRE, via its actions on ANGPTL4, therefore not only inhibits adipose fatty acid uptake but stimulates their release as well. Additionally, TRE may increase intravascular very low-density lipoprotein (VLDL) catabolism by muscle due to the reduced exposure of lipoprotein lipase (LPL) to competing chylomicrons, known to slow the rate of VLDL catabolism. During the prolonged fasting, VLDL residence time is thus shortened, limiting the exposure to endothelium and hepatic lipases and thus reducing the amount of atherogenic remnant particles. Larger, longer-term randomized controlled studies in a variety of groups are required to further clarify TRE’s function in RCR prevention and therapy. As knowledge of triglyceride lipoprotein (TRL) metabolism expands, a comprehensive strategy for the management of RCR emerges, and a broader spectrum of LPL regulator-based therapeutics is created. Consequently, it is advisable to prioritize further research into the influence of TRE on LPL modulation via ANGPTL4 and ANGPTL8, which provides a natural, accessible, and low-cost alternative. Full article

Microwave Breast Imaging (MWBI) is an emerging imaging modality aiming to detect breast lesions, which are dielectrically contrasted against the background healthy tissue, in the microwave frequency spectrum. MWBI holds potential to outperform X-ray mammography’s low sensitivity in young and dense breasts, thus supporting timelier detection of interval cancers, as a supplemental screening or diagnostic imaging method. The specificity of MWBI remains unknown, however, as management of false positives has not been systematically addressed yet. An earlier First-In-Human clinical investigation on 24 symptomatic patients provided proof-of-concept for the Wavelia MWBI sectorized multi-static radar imaging technology, which generates clinically meaningful 3D images of the breast, performs semi-automated detection of breast lesions and extracts diagnostic features to distinguish malignant from benign lesions. This paper focuses on a set of technological upgrades, accessories and data processing modules, designed and implemented in the 2nd generation prototype of Wavelia, to handle the diversity in breast geometry, tissue consistency and deformability, in a larger clinical investigation reporting on the bilateral MWBI scan of 62 patients. The presented add-on modules contribute to enhanced quality of scan and a more valid reference reporting space for the MWBI imaging outputs, with a direct positive impact on overall specificity. Full article

Invasive fungal infections and the emergence of antifungal resistance pose significant challenges to public health. This study evaluates the antifungal activity of two 8-hydroxyquinoline derivatives, PH265 and PH276, against Cryptococcus spp., Candida auris, and Candida haemulonii. Using the EUCAST protocol, both compounds demonstrated broad-spectrum antifungal activity, with MICs ranging from 0.5 to 8 μg/mL. PH276 exhibited synergistic effects with fluconazole and caspofungin against C. haemulonii (FIC ≤ 0.5). The derivatives inhibited C. neoformans biofilm formation at higher concentrations and modulated polysaccharide capsule formation in Cryptococcus spp. In vivo toxicity assays in Tenebrio molitor, Galleria mellonella, and Caenorhabditis elegans revealed no significant adverse effects, with survival rates comparable to controls. These findings highlight PH265 and PH276 as promising antifungal agents with biofilm-disrupting properties, capsule-modulating effects, and low toxicity, supporting their potential for therapeutic development. Full article

This study employed an integrated computational approach to discover novel nucleoprotein (NP) inhibitors for influenza A virus (IAV). Beginning with virtual screening of over 10 million compounds using Schrödinger’s Glide module (HTVS, SP, XP docking), the workflow identified promising candidates with favorable binding energies. Subsequent molecular mechanics/generalized born surface area (MM-GBSA) calculations and 100 ns molecular dynamics (MD) simulations prioritized 16 compounds for experimental validation. Surface plasmon resonance (SPR) assays revealed that compounds 8, 13, and 14 demonstrated superior target engagement, showing equilibrium dissociation constants (K_D) of 7.85 × 10⁻⁵ M, 3.82 × 10⁻⁵ M, and 6.97 × 10⁻⁵ M, respectively. Molecular dynamics, alanine scanning mutagenesis, and quantum mechanics/molecular mechanics (QM/MM) analysis were conducted to analyze the binding modes, providing a reference for the design of subsequent compounds. These findings validate the efficacy of structure-based virtual screening in identifying high-affinity NP inhibitors and provide insights for the development of broad-spectrum anti-influenza therapeutics. Full article

This study proposes a novel framework to enhance inner race fault features in servo motor bearings by acquiring rotary encoder-derived instantaneous angular speed (IAS) signals, which are obtained from a servo motor encoder without requiring additional external sensors. However, such signals are often obscured by strong periodic interferences from motor pole-pair and shaft rotation order components. To address this issue, three key improvements are introduced within the cyclic blind deconvolution (CYCBD) framework: (1) a comb-notch filtering strategy based on rotation domain synchronous averaging (RDA) to suppress dominant periodic interferences; (2) an adaptive fault order estimation method using the autocorrelation of the squared envelope spectrum (SES) for robust localization of the true fault modulation order; and (3) an improved envelope harmonic product (IEHP), based on the geometric mean of harmonics, which optimizes the deconvolution filter length. These combined enhancements enable the proposed improved CYCBD (ICYCBD) method to accurately extract weak fault-induced cyclic impulses under complex interference conditions. Experimental validation on a test rig demonstrates the effectiveness of the approach in enhancing and extracting the fault-related features associated with the inner race defect. Full article

Background: Hypertensive disorders of pregnancy (HDP) affect one in six pregnancies globally. The etiology of HDP remains unclear but is known to involve oxidative stress. While the body produces endogenous antioxidants, antioxidative nutrients, like carotenoids, remain critical in modulating oxidative stress. The statuses of several carotenoids have been linked to hypertension in both pregnant and non-pregnant populations. However, their associations with the spectrum of HDP, including gestational hypertension (GH), chronic hypertension (CH), and preeclampsia (PE), remains unclear. Our objective was to quantify and compare carotenoid intake and plasma levels among HDP. Methods: We conducted a prospective cohort study of patients presenting for delivery at a Midwestern academic medical center between 2015 and 2023. Women ≥ 19 years old delivering at least one infant were eligible for inclusion. Mothers with diseases affecting nutrient metabolism or birthing newborn wards of the state were excluded. Subjects were recruited at delivery for Harvard Food Frequency Questionnaire and plasma sample collection. Plasma carotenoids were analyzed by HPLC-MS. Results: A total of 488 patients, including 270 normotensive (NT), 61 CH, 102 GH, and 55 PE, were recruited. Plasma carotenoid analyses were available for 225 subjects. Plasma total, cis-, and trans-β-carotene were significantly lower in PE (73 mcg/L) compared to NT (170 mcg/L), CH (194 mcg/L), and GH (190 mcg/L) groups. Lutein + zeaxanthin and β-cryptoxanthin were also reduced in PE (142 mcg/L and 81 mcg/L) compared to NT (209 mcg/L and 123 mcg/L) but only β-cryptoxanthin was lower in PE compared to GH (126 mcg/L). Levels of α-carotene were lower in PE (18 mcg/L) compared to both CH (43 mcg/L) and GH (48 mcg/L). Conclusions: These results demonstrate that plasma carotenoid levels differ among HDP and may suggest that oxidative stress in PE depletes circulating carotenoids, differentiating it from other HDP. Full article

Postpartum uterine diseases such as metritis and endometritis impair reproductive performance and cause substantial economic losses in dairy cows worldwide. The multifactorial etiology, involving polymicrobial infections and complex host immune responses, poses diagnostic and therapeutic challenges. Traditional treatments rely on antibiotics, e.g., cephalosporins like ceftiofur and cephapirin, with broad-spectrum efficacy. However, emerging antimicrobial resistance, biofilm formation by pathogens such as Trueperella pyogenes, Fusobacterium necrophorum, and Escherichia coli, and bacterial virulence factors have reduced effectiveness of conventional therapies. Advances in systems biology, particularly proteomics, metabolomics, and microRNA (miRNA) profiling, have provided unprecedented insights into the molecular mechanisms underpinning uterine disease pathophysiology. Proteomic analyses reveal dynamic changes in inflammatory proteins and immune pathways, whereas metabolomics highlight shifts in energy metabolism and bacterial–host interactions. Furthermore, miRNAs have critical roles in post-transcriptional gene regulation affecting immune modulation, inflammation, and tissue repair, and also in modulating neutrophil function and inflammatory signaling. Uterine inflammation not only disrupts local tissue homeostasis but also compromises early embryo development by altering endometrial receptivity, cytokine milieu, and oocyte quality. Integration of multi-omics approaches, combined with improved diagnostics and adjunct therapies—including micronutrient supplementation and immunomodulators—offers promising avenues for enhancing disease management and fertility in dairy herds. This review synthesizes current knowledge on proteomics, metabolomics, and miRNAs in postpartum uterine diseases and highlights future directions for research and clinical applications. Full article

Fetal alcohol spectrum disorder (FASD/FAS) is a chronic inflammatory process of the fetal brain induced by alcohol and mediated by pro-inflammatory (PILM) and pro-resolving (PRLM) lipid mediators of inflammation. DHA (docosahexaenoic acid) is an essential precursor of PRLM. A study examining the response of lipid mediators of inflammation to alcohol insult and DHA supplementation can provide vital information on the pathogenesis of FASD/FAS and the potential ameliorative role of DHA. Four groups of timed pregnant rats were studied: control, low-dose (1.6 g/kg/day) and high-dose (2.4 g/kg/day) alcohol, and high-dose alcohol (2.4 g/kg/day) + DHA (1250 mg/kg/day). The pups were delivered on day 20, and their whole brain was examined for lipid mediators by liquid chromatography mass spectroscopy. The following biomarkers of brain lipid mediators were studied, namely, PILM (LTB4, PGE2, PGF2α, TXB2) and PRLM (LXA5, 4-HDoHE, 17-HDoHE, and MaR1n-3, DPA). The brain PILM and PRLM concentrations decreased significantly (p < 0.001) with high-dose alcohol. However, high-dose alcohol + DHA resulted in a significant (p < 0.001) increase in PRLM levels, viz., LXA5, MaR1n-3 DPA, 17-HDoHE, and a threefold increase in 4-HDoHE. We conclude that DHA supplementation in alcohol-exposed pregnant rats significantly increased levels of brain pro-resolving lipid mediators in the offspring, suggesting a potential role in modulating the inflammatory response. Full article

Deep-well radar telemetry over ultra-long cables suffers from strong frequency-selective attenuation and impedance drift under high temperature and pressure. We have proposed a channel-adaptive “communication + acquisition” architecture for a 7500 m borehole radar system. The scheme integrates spread-spectrum time domain reflectometry (SSTDR; m-sequence with BPSK) to monitor the cable in situ, identify termination/cable impedance, and adaptively match the load, thereby reducing reflection-induced loss. On the receiving side, we combine time domain adaptive equalization—implemented as an LMS-driven FIR filter—with frequency domain OFDM equalization based on least-squares (LS) channel estimation, enabling constellation recovery and robust demodulation over the distorted channel. The full processing chain is realized in real time on a Xilinx Artix-7 (XC7A100T) FPGA with module-level reuse and pre-stored training sequences for efficient hardware scheduling. In a field deployment in the Shunbei area at 7500 m depth, radar results show high agreement with third-party geological logs: the GR-curve correlation reaches 0.92, the casing reflector at ~7250 m is clearly reproduced, and the key bottom depth error is 0.013%. These results verify that the proposed system maintains stable communication and accurate imaging in harsh deep-well environments while remaining compact and implementable on cost-effective hardware. Full article

Background/Objectives: Human ovarian granulosa cells (hGCs) are crucial to ovarian follicle development and function, exhibiting multipotency and the ability to differentiate into neuronal cells, chondrocytes, and osteoblasts in vitro. 3,4,5,4′-tetramethoxystilbene (DMU-212) is a methylated derivative of resveratrol, a natural polyphenol found in grapes and berries, with a wide spectrum of biological activities, including notable anticancer properties. Interestingly, DMU-212 exhibits cytotoxic effects predominantly on cancer cells while sparing non-cancerous ones, and evidence suggests that similar to resveratrol, it may also promote hGC differentiation. This study aimed to investigate the effects of the liposomal formulation of this methylated resveratrol analog—lipDMU-212—on the osteogenic differentiation ability of hGCs in a primary three-dimensional cell culture model. Methods: lipDMU-212 was formulated using the thin-film hydration method. GC spheroids’ viability was evaluated after exposure to lipDMU-212, an osteoinductive medium, or both. Osteogenic differentiation was confirmed using Alizarin Red staining and quantified by measuring Alkaline Phosphatase (ALP) activity on days 1, 7, and 15. RNA sequencing (RNA-seq) was performed to explore molecular mechanisms underlying lipDMU-212-induced differentiation. Results: lipDMU-212 promoted osteogenic differentiation of hGCs in the 3D cell culture model, as evidenced by increased mineralization and a ~4-fold increase in ALP activity compared with the control. RNA-seq revealed up-regulation of genes related to cell differentiation and cellular identity. Furthermore, JUN (+2.82, p = 0.003), LRP1 (+2.06, p = 0.05), AXIN1 (+3.02, p = 0.03), and FYN (+3.30, p = 0.01) were up-regulated, indicating modulation of the Wnt/β-catenin signaling pathway, a key regulator of osteoblast differentiation. Conclusions: The ability of GCs to differentiate into diverse tissue-specific cell types underscores their potential in regenerative medicine. This study contributes to the understanding of lipDMU-212’s role in osteogenic differentiation and highlights its potential in developing future therapies for degenerative bone diseases. Full article

This study examines the soliton dynamics in the time-fractional cubic–quintic nonlinear non-paraxial propagation model, applicable to optical signal processing, nonlinear optics, fiber-optic communication, and biomedical laser–tissue interactions. The fractional framework exhibits a wide range of nonlinear effects, such as self-phase modulation, wave mixing, and self-focusing, arising from the balance between cubic and quintic nonlinearities. By employing the Multivariate Generalized Exponential Rational Integral Function (MGERIF) method, we derive an extensive catalog of analytic solutions, multi-peakon structures, lump solitons, kinks, and bright and dark solitary waves, while periodic and singular solutions emerge as special cases. These outcomes are systematically constructed within a single framework and visualized through 2D, 3D, and contour plots under both anomalous and normal dispersion regimes. The analysis also addresses modulation instability (MI), interpreted as a sideband amplification of continuous-wave backgrounds that generates pulse trains and breather-type structures. Our results demonstrate that cubic–quintic contributions substantially affect MI gain spectrum, broadening instability bands and permitting MI beyond the anomalous-dispersion regime. These findings directly connect the obtained solution classes to experimentally observed routes for solitary wave shaping, pulse propagation, and instability and instability-driven waveform formation in optical communication devices, photonic platforms, and laser technologies. Full article

P2X receptors are a family of ATP-gated ion channels widely distributed in various tissues, especially in neuronal cells and hematopoietic cells. ATP activates P2X receptors, causing the opening of an ionic channel with preferential permeability to the passage of mono- and divalent cations. High concentrations of ATP stimulate the P2X7 subtype through prolonged activation, which opens pores and causes inflammation, proalgesic effects, and cell death. Peptides, including antimicrobials (antimicrobial peptides), are present in several organisms, such as amphibians, mammals, fish, arachnids, and plants, where they act as the first line of defense. Thus, these peptides have the capacity to eliminate a wide spectrum of microorganisms, such as bacteria, fungi, and some viruses. In general, the mechanism of action of antimicrobial peptides involves interactions with the lipid bilayer of the cell membrane, which can lead to an increase in the internal liquid content of liposomes. However, many peptides can act on ion channels, such as those of the P2X family, especially the P2X7 receptor. We investigated the action of peptides that directly modulate P2X7 receptors, such as beta-amyloid, LL-37/hCap18, Pep19-2.5, rCRAMP, ADESG, and polymyxin B. Additionally, we evaluated peptides that modulate the activity of P2X family receptor subtypes. In this review, we intend to describe the relationships between peptides with distinct characteristics and how they modulate the functionality of P2X receptors. Full article

The genus Lavandula represents one of the most valuable aromatic and medicinal plants, holding significant economic importance in the pharmaceutical, food, perfumery, and cosmetics industries. Among them, L. multifida is a traditionally used medicinal plant in the Mediterranean region. This work provides a comprehensive review of L. multifida, focusing on its traditional uses, phytochemistry, and pharmacological properties. Unlike conventional lavenders, its essential oil is dominated by phenolic monoterpenes, principally carvacrol, alongside significant concentrations of β-bisabolene, 1,8-cineole, and camphor. This distinct phytochemical profile is further complemented by a rich range of non-volatile constituents, including flavonoids, phenolic acids, and triterpenoids. Pharmacological investigations have validated its broad-spectrum antimicrobial activity, demonstrating efficacy against multidrug-resistant bacterial strains and fungal pathogens through mechanisms such as membrane disruption, metabolic interference, and quorum sensing inhibition. Furthermore, the species exhibits significant antioxidant and anti-inflammatory properties, mediated primarily through radical scavenging, cyclooxygenase inhibition, and cytokine modulation. Owing to its distinct chemistry, specific traditional uses for respiratory and digestive ailments, limited endemic habitat, and underexplored status, L. multifida presents a promising candidate for future research with high potential for novel drug discovery, particularly in antiparasitic and respiratory therapies. This review concludes by identifying key research priorities for L. multifida, including a detailed analysis of its non-volatile compounds, mechanistic elucidation, toxicological assessments, and standardization of extracts. Addressing these gaps is essential to validate its traditional applications and advance its development into evidence-based phytomedicines, adjuvant therapies, and natural agrochemicals. Full article

With the rise of 6G, the exponential growth of data traffic, the proliferation of emerging applications, and the ubiquity of smart devices, the demand for spectral resources is unprecedented. Terahertz communication (100 GHz–3 THz) plays a key role in alleviating spectrum scarcity through ultra-broadband transmission. In this study, terahertz optical carrier-based systems are employed, where fiber-optic components are used to generate the optical signals, and the signal is transmitted via direct detection in the receiver side, without relying on fiber-optic transmission. In these systems, deep learning-based equalization effectively compensates for nonlinear distortions, while probability shaping (PS) enhances system capacity under modulation constraints. However, the probability distribution of signals processed by PS varies with amplitude, making it challenging to extract useful information from the minority class, which in turn limits the effectiveness of nonlinear equalization. Furthermore, in IM-DD systems, optical multipath interference (MPI) noise introduces signal-dependent amplitude jitter after direct detection, degrading system performance. To address these challenges, we propose a lightweight neural network equalizer assisted by the Synthetic Minority Oversampling Technique (SMOTE) and a clustering method. Applying SMOTE prior to the equalizer mitigates training difficulties arising from class imbalance, while the low-complexity clustering algorithm after the equalizer identifies edge jitter levels for decision-making. This joint approach compensates for both nonlinear distortion and jitter-related decision errors. Based on this algorithm, we conducted a 3.75 Gbaud W-band PAM4 wireless transmission experiment over 300 m at Fudan University’s Handan campus, achieving a bit error rate of 1.32 × 10⁻³, which corresponds to a 70.7% improvement over conventional schemes. Compared to traditional equalizers, the proposed new equalizer reduces algorithm complexity by 70.6% and training sequence length by 33%, while achieving the same performance. These advantages highlight its significant potential for future optical carrier-based wireless communication systems. Full article

Clinical trials of drugs specifically targeting the sepsis response have frequently produced negative or inconclusive results. This has largely been due to the broad heterogeneity of enrolled patient populations, particularly when inclusion was based on the presence of the non-specific systemic inflammatory response syndrome (SIRS) criteria. The heterogeneity may have diluted any possible treatment effect: while some patients may have benefited from the intervention under investigation, others will have been harmed, resulting in an overall null-effect. Furthermore, an underlying infection is not always required for immune-modulating interventions to be effective; for example, patients with severe acute pancreatitis, but no infection, may still benefit from such therapies. There is therefore a need for better patient stratification or subphenotyping to identify those most likely to benefit from a particular therapy. Several trials have already adopted this approach using prognostic and/or predictive enrichment strategies. For example, measurements of triggering receptor expressed on myeloid cells (TREM) could be used to identify candidates most likely to respond to anti-TREM therapies, or patients with coagulopathy or specific inflammatory patterns could be selected for treatments like thrombomodulin or activated protein C. However, challenges remain, including the need for more rapid tools that can be used at the bedside to inform real-time treatment decisions given the rapidly evolving nature of the sepsis response. Nevertheless, the era of broad-spectrum “sepsis drugs” is now giving way to more selective, personalized interventions tailored to individual biological profiles, offering a more promising pathway for future therapeutic development—even in the absence of infection. Full article