Search Results (6,542)

Abnormal intestinal mucosal immunity plays a crucial role in ulcerative colitis (UC). Autotaxin (ATX) can promote T cell migration and was reported to have a regulatory effect on Th17 cells, while sphingosine-1-phosphate (S1P) and its receptors (S1PRs) modulate Th17/Treg balance and inflammation, with S1PR modulators approved for UC. ATX can catalyze sphingosylphosphorylcholine (SPC) to produce S1P; however, the relationship between ATX and S1P/S1PRs in UC is unclear. Understanding the role of ATX-S1P/S1PRs in intestinal immunity can provide new treatment strategies for intestinal inflammatory diseases. Both UC patients and DSS-induced colitic mice showed significantly increased levels of ATX and S1P compared with healthy controls. ATX inhibitor PF8380 treatment led to reduced levels of S1P/S1PRs in colitic mice. Consistent with this, the S1PR antagonist etrasimod was able to alleviate ATX-induced intestinal inflammation, as well as partially restore ATX-induced Th17/Treg imbalance in MLNs and the spleen. In HT-29 and Raw246.7 cells, ATX treatment led to enhanced expression of S1P/S1PRs, with S1PR1 being the most significant. Furthermore, S1PR1 mediates the effect of ATX on Th17/Treg cell differentiation and function in vivo. Therefore, ATX affects the differentiation and function of Th17/Treg cells through S1P/S1PR1 signaling, increased ATX expression leading to Th17/Treg cell imbalance, intestinal mucosal immune dysfunction, and exacerbating intestinal inflammation. Full article

Over the past two decades, organic semiconductors have attracted significant research interest due to their advantageous features, including low-cost fabrication, lightweight properties, and portability, for photonic device applications. In this study, nickel sulfide doped with cobalt $(\mathrm{N}\mathrm{i}\mathrm{S}/\mathrm{C}\mathrm{o})$ nanocomposites were successfully synthesized via a wet-chemical processing technique and used as a dopant in the active layer of thin-film organic solar cells (TFOSCs). The poly(3-hexylthiophene) (P3HT) and [6,6]-phenyl-C61-butyric acid methyl ester (PC61BM) blend was used as the active layer in this investigation. The devices were fabricated with $\mathrm{N}\mathrm{i}\mathrm{S}/\mathrm{C}\mathrm{o}$ nanocomposites at 1 wt%, 2 wt%, and 3 wt% in the active layer to determine the optimal dopant concentration. However, the experimental evidence clearly showed that the solar cell’s performance depends on the concentration of the $\mathrm{N}\mathrm{i}\mathrm{S}/\mathrm{C}\mathrm{o}$ nanocomposites. As a result, the highest power conversion efficiency (PCE) recorded in this experimental work was 6.11% at a 1% doping concentration, compared with 2.48% for the pristine reference device under AM 1.5G illumination (100 mW/cm²) in ambient conditions. The optical and electrical properties of the active layers are found to be strongly influenced by the inclusion of $\mathrm{N}\mathrm{i}\mathrm{S}/\mathrm{C}\mathrm{o}$ nanocomposites in the medium. However, the device doped with 1 wt% $\mathrm{N}\mathrm{i}\mathrm{S}/\mathrm{C}\mathrm{o}$ nanocomposite exhibits the highest absorption intensity, consistent with the better performance observed in this study, which can be attributed to the localized surface plasmon resonance (LSPR) effect. The optical and morphological characteristics of the synthesized $\mathrm{N}\mathrm{i}\mathrm{S}/\mathrm{C}\mathrm{o}$ nanocomposites were comprehensively analyzed using high-resolution transmission electron microscopy (HRTEM), high-resolution scanning electron microscopy (HRSEM), and additional complementary techniques. Full article

Serotonin transporter (SERT) precisely regulates serotonin (5–HT) signaling in the central nervous system and is a major target of antidepressants for the treatment of major depressive disorder. Despite significant progress in characterizing its structure and transport mechanism, the regulation of SERT function by various modulators remains to be fully understood. In the present study, we focused on two potential cholesterol sites in human SERT to investigate cholesterol occupation at these sites and its functional relevance by biochemical approaches. Mutations of an intramolecular site (CHOL2) significantly decreased both specific transport activity and K_m for 5–HT and stabilized the transporter in an inward-facing conformation. In addition, our NanoBiT luminescent assay for protein–protein proximity demonstrated that cholesterol mediated the protomer–protomer interactions by residing in a site at the dimeric interface. Mutations of the interfacial site remarkably reduced the interactions between SERT protomers and substantially impaired their transport activity. The structural analysis indicated that the residues participating in cholesterol residing in the interfacial site were conformationally sensitive. Thus, we have proposed that cholesterol at these sites could play a vital role in the regulation of SERT function by a conformational mechanism. Our study has provided new insights into the molecular mechanism by which cholesterol can regulate SERT function and dimerization. Full article

The clinical renaissance of psychedelic medicine has highlighted the therapeutic potential of rapid-acting neuroplastogens, or “psychoplastogens,” for psychiatric disorders. However, the widespread application of classical psychedelics—such as psilocybin and LSD—and the atypical dissociative ibogaine is severely limited by their hallucinogenic properties and, particularly in the case of ibogaine, life-threatening cardiotoxicity. Addressing these limitations, Tabernanthalog (TBG) has emerged as a frontrunner in the field. This non-hallucinogenic analog of ibogaine was rationally designed to eliminate interactions with the human ether-à-go-go-related gene (hERG, KCNH2) potassium channel, thereby mitigating cardiotoxic risks. While initially characterized for its anti-addictive and antidepressant-like properties, recent data from 2024–2025 have significantly expanded its therapeutic horizon. TBG demonstrates robust efficacy in preclinical models of neuropathic and visceral pain, as well as in the rescue of cognitive deficits associated with cancer-related cognitive impairment (CRCI). TBG has shown efficacy in reversing cognitive impairments induced directly by the presence of a tumor in preclinical models, rather than by chemotherapy-specific neurotoxicity. Crucially, emerging evidence suggests that TBG’s mechanism extends beyond simple 5-HT2A receptor agonism. New findings point to a multi-target profile involving the inhibition of nicotinic acetylcholine receptors (nAChRs), positive modulation of NMDA receptors, and functional crosstalk with mGlu2 receptors. Furthermore, TBG appears to induce structural neuroplasticity without the widespread induction of immediate early genes (IEGs) seen with classical hallucinogens, suggesting a decoupling of therapeutic rewiring from the subjective psychedelic experience. This review synthesizes current preclinical evidence to discuss TBG as a promising chemical scaffold for next-generation neurotherapeutics targeting the intersection of psychiatry and neurology. Full article

As offshore wind power develops toward larger unit capacities and deeper offshore deployments, its inherent power intermittency poses increasing challenges to system stability and reliable grid integration. To address the issues of large-scale wind power fluctuation and efficient energy utilization, an integrated hydrogen production through offshore superconducting wind power (HPOSWP) system is investigated, which combines high-temperature superconducting (HTS) wind generators with water electrolysis. This paper reviews the operational characteristics of the HPOSWP system under wide power fluctuation conditions, specifically assessing the adaptability of high-power-density HTS wind generators and the feasibility of highly reliable liquid hydrogen (LH₂) circulation cooling technologies from a qualitative perspective. This study provides valuable insights into the application of large-scale HPOSWP systems under fluctuating power conditions and establishes a solid theoretical foundation for subsequent system design and engineering implementation. Full article

Objective: This study aimed to elucidate the association between hematologic toxicity (HT) and pelvic bone marrow (PBM) dosimetric parameters in patients with cervical cancer (CC) undergoing radiotherapy (RT) combined with artificial intelligence (AI)-assisted organ at risk (OAR) delineation (Software Copyright Registration Number 2023SR0150365). Accurate delineation of bone marrow (BM) regions and analysis of radiation doses may provide a theoretical foundation for the application of AI in predicting HT. Methods: This retrospective study included 141 patients with CC who received chemotherapy (sequential or concurrent) and/or pelvic volumetric modulated arc therapy (VMAT) at the Department of Gynecology, Cancer Hospital of the Chinese Academy of Medical Sciences, between March 2019 and December 2019. PBM and its subregions (ilium, lower pelvis, lumbosacral spine, and femoral heads) were delineated using AI-based automatic segmentation of CT images. The volumes receiving 10–40 Gy (V10, V20, V30, V40) were calculated, and baseline clinical characteristics were assessed. HT endpoints included grade ≥ 2 (HT2+) and grade ≥ 3 (HT3+) leukopenia, neutropenia, anemia, or thrombocytopenia. Associations between dosimetric parameters and HT were evaluated using logistic regression models. Results: Of the 141 patients, 107 (75.8%) developed HT2+ and 33 (23.4%) developed HT3+. Univariate analysis showed that chemotherapy and age were correlated with HT2+. Multivariate analysis identified femoral head V30, femoral head V40, and chemotherapy as independent predictors of HT3+. Conclusions: This study highlights the potential of AI-based OAR delineation for assessing PBM dosimetric parameters in patients with CC. Optimizing RT to minimize BM dose and volume may mitigate HT and enhance treatment tolerance. In our cohort, receipt of combined neoadjuvant and concurrent chemotherapy (NACT+CCRT) was a stronger predictor of HT than most BM dosimetric parameters, suggesting that the systemic effect of chemotherapy may dominate the hematologic toxicity profile in this setting. Consequently, patients receiving this combined modality treatment are at particularly high risk for HT and warrant close hematologic monitoring. Full article

Background/Objectives: Alzheimer’s disease (AD) involves amyloid and tau pathology with neuroimmune dysregulation, and Yixin Yangshen Granules (YXYS) shows neuroprotective promise, though mechanisms remain unclear. This study aimed to elucidate the multi-target mechanisms of YXYS in AD. Methods: The study began by analyzing a public human AD hippocampal snRNA-seq dataset to identify cell-type-specific pathological pathways and profiled YXYS constituents by UPLC-QTOF-MS. In vitro, YXYS cytoprotection against mitochondrial dysfunction and oxidative stress was tested in Aβ_25–35-challenged HT22 cells; in vivo efficacy was assessed in Aβ_1–42-induced mice via behavioral and histopathological analyses. Integrated transcriptomic and proteomic profiling of brain tissue, with ELISA, qRT-PCR, and Western blot validation, confirmed pathway targets. Using the intersection of transcriptomic and proteomic targets as biological input, the DTIAM deep learning framework was employed to prioritize active YXYS constituents. Finally, molecular docking and 100-ns dynamics simulations demonstrated direct binding of Ganosporelactone A to HIF−1α. Results: AD snRNA-seq analysis highlighted HIF−1 and AGE-RAGE signaling as prominent pathways in the AD hippocampus, particularly enriched in brain microvascular endothelial cells, implicating neurovascular hypoxic and inflammatory stress. In Aβ-induced mice, YXYS improved cognition, reduced Aβ pathology, suppressed neuroinflammation, and promoted neuronal survival, consistent with in vitro evidence of restored mitochondrial function. Multi-omics confirmed convergence on HIF−1 and AGE-RAGE pathways, with YXYS rebalancing the neuroimmune microenvironment by reducing pro-inflammatory M0 macrophages. Screening against these consensus signaling hubs, deep learning analysis prioritized Ganosporelactone A as the top-ranked modulator, and molecular further demonstrated the stable binding of Ganosporelactone A to HIF−1α, linking YXYS to mitigation of hypoxic stress. Conclusions: Guided by multi-omics and deep learning, our findings suggest that YXYS may alleviate AD-related phenotypes through multi-target modulation of the HIF−1 and AGE-RAGE pathways, with associated improvements in neuro-immune homeostasis and reductions in oxidative stress, neuroinflammation, and hypoxia. Full article

The genus Parabacteroides comprises widespread gastrointestinal commensals, known to produce immunomodulatory molecules and extracellular vesicles, yet its full diversity is incompletely cataloged. This study describes strain ASD2025^T, isolated from healthy child feces, using a polyphasic taxonomic approach including phenotypic profiling, chemotaxonomy, and comparative genomics. Cells were non-motile, polymorphic rods that produced extracellular vesicles. Phylogenomic analysis placed ASD2025^T within the genus Parabacteroides within a species complex consisting of P. acidifaciens, P. hominis, “P. massiliensis”, P. merdae, and P. johnsonii, with average nucleotide identities to the type strains of 85.5–89.9%. The large genome (5.16 Mbp, 46.2% GC content) contained integrative conjugative elements harboring antibiotic resistance genes and hankyphage-related prophage. The strain produced succinate as the major metabolic end product, and its major fatty acids were anteiso-C_15:0, iso-C_17:0 3-OH, and C_15:0. Conditioned medium from ASD2025^T antagonized the interleukin-8 response caused by E. coli lipopolysaccharide in HT29 cells. The majority of related metagenome-assembled genomes originate from mouse microbiomes. Based on these distinct characteristics, strain ASD2025^T (=VKM B-3926^T = JCM 37967^T) represents a novel species of the genus Parabacteroides, for which the name Parabacteroides vesiculifaciens sp. nov. is proposed. Full article

Background: Chronic insomnia disorder (CID) frequently coexists with diarrhea-predominant irritable bowel syndrome (IBS-D), a comorbidity characterized by gut–brain axis dysfunction and persistent inflammatory activation. However, the molecular mechanisms underlying this overlap remain incompletely understood, and effective multitarget interventions are lacking. Objectives: This study aimed to identify quercetin as a potential bioactive compound for IBS-D-associated insomnia and to investigate whether its protective effects are associated with modulation of the PI3K/AKT/NF-κB signaling pathway. Methods: CID- and IBS-D-related targets were collected from public databases. Candidate compounds were screened using bioinformatics and network pharmacology analyses, followed by molecular docking. Experimental validation was conducted in 36 male C57BL/6J mice assigned to control, CID+IBS-D model, quercetin-treated, and quercetin-plus-Recilisib-treated groups. Sleep-related behavior, EEG/EMG-derived sleep architecture, intestinal function, inflammatory markers, and pathway-related proteins were assessed. Results: Quercetin was identified as a core candidate compound. Network pharmacology revealed 43 shared targets among CID, IBS-D, and quercetin, with significant enrichment in PI3K/AKT-related signaling. In vivo, quercetin improved sleep-associated phenotypes and intestinal dysfunction; reduced visceral hypersensitivity; restored ZO-1 and Occludin expression; suppressed hypothalamic and colonic inflammatory responses; and was accompanied by reduced phosphorylation of PI3K, AKT, IκB, and NF-κB p65 in the hypothalamus. Quercetin also increased hypothalamic 5-HT1A and GABA_A Rα5 expression. These effects were partially reversed by Recilisib, supporting the involvement of PI3K/AKT-associated signaling in quercetin-mediated protection. Conclusions: Quercetin alleviated key sleep-related and IBS-D-like phenotypes in a composite murine model of gut–sleep comorbidity. The protective effects were associated with reduced inflammatory activation and modulation of PI3K/AKT/NF-κB-related signaling. These findings support quercetin as a promising candidate for gut–brain axis-related comorbid disorders, while further studies are needed to define pathway specificity, tissue exposure, and translational applicability. Full article

Lossless image compression is pivotal for deep-space exploration. Considering the requirements of deep-space exploration for a high compression ratio and real-time processing, traditional image compression algorithms have garnered significant attention. However, existing algorithms struggle with real-time processing speed and compression degradation in high-noise regions, failing to meet the throughput demands of next-generation sensors. To address these challenges, this paper proposes a high-throughput and noise-resilient lossless image compression architecture, named HT-NRC, for deep-space CMOS cameras. First, to overcome the throughput bottleneck, we introduce a parallel processing method, which is built on index-based dispatch and Reorder mechanism. This is achieved by dynamically distributing pixel streams into parallel cores and utilizing a Reorder Buffer for sequence restoration. Second, to mitigate low compression efficiency in noisy backgrounds, we present a Heterogeneous Dual-Path Coding scheme. This system adaptively separates structural information for predictive coding and stochastic noise for raw packing with Bit-Plane Slicing (BPS) strategy. The proposed architecture was implemented on a Xilinx Virtex-7 FPGA (Xilinx, Inc., San Jose, CA, USA). Operating at 100 MHz, the system achieves a processing throughput of 414.7 Mpixel/s and a high average compression ratio under deep-space image datasets, while consuming an estimated total on-chip power of only 2.1 W. Experimental results show that our proposed method substantially outperforms existing baseline methods. Specifically, compared to the optimized serial JPEG-LS implementation processing one pixel per clock cycle, our parallel architecture achieves an approximately 314.7% increase in processing throughput. Full article

Termite guts represent a unique microbial habitat harboring bacteria with potential probiotic properties, owing to their ability to inhibit pathogenic microorganisms. This study investigated the probiotic characteristics of lactic acid bacteria newly isolated from the guts of the termite Termes propinquus, aiming to enhance growth performance and reduce the incidence of foodborne pathogen contamination in the commonly consumed edible two-spotted crickets (Gryllus bimaculatus). In this study, five morphologically different bacteria (TPL-1 to TPL-5) were isolated and respectively identified as Levilactobacillus brevis, Lactiplantibacillus plantarum, Streptococcus anginosus, Companilactobacillus alimentarius, and Aerococcus viridans based on 16S rRNA gene sequences and MALDI-TOF MS. All isolates were evaluated for tolerance to stressful conditions (pH 2.5 and 0.3% bile salts), cell surface properties, antioxidant activity, antimicrobial activity against foodborne pathogens, safety profiles, and adhesion to human colon adenocarcinoma cells (Caco-2 and HT-29). Among them, Lactiplantibacillus plantarum TPL-2 demonstrated the strongest probiotic attributes and was further assessed for anti-adhesion activity against foodborne pathogens and in vivo effects on the crickets. Dietary supplementation with Lb. plantarum TPL-2 significantly improved cricket growth, survival, and gut microbiota homeostasis. These findings point to the prospect of termite-derived lactic acid bacteria as beneficial probiotics for use in biotechnological applications and edible insect farming. Full article

The genus Psiadia (Asteraceae), widely distributed in Madagascar and the Mascarene Islands (Mauritius, La Réunion, Rodrigues), is traditionally used to treat bronchitis, asthma, colds, abdominal pain, and other inflammatory disorders. However, few studies have scientifically validated these traditional medicinal uses. To assess P. dentata as a valuable source of bioactive natural products, a combined ¹H NMR-based metabolomic, molecular networking, and phytochemical study was conducted. Multivariate analysis (PLS-DA) of crude extracts from Psiadia species collected on Reunion Island enabled rapid discrimination of active extracts from P. dentata and revealed two methoxylated flavonoids and one coumarin as metabolites correlated with its antiplasmodial and anti-inflammatory activities. Additionally, UHPLC-DAD-ESI-QTOF-MS/MS molecular networking approach enabled detailed chemical profiling of this species, allowing the annotation of 25 compounds (1–25) in this species. Subsequent phytochemical investigation of P. dentata leaves led to the isolation and identification of 25 metabolites, including nine new diterpenes (26–34), one new coumarin (35), and 15 known compounds (1–8, 11, 18, 19 and 36–39) from the diterpenoid, flavonoid, and coumarin families. The structures of the new compounds were elucidated using spectroscopic methods, including extensive 1D and 2D NMR and HRESIMS analyses. Biological evaluation of the isolated compounds showed that compounds 1, 7, 26 and 27 showed antiplasmodial activity against Plasmodium falciparum (3D7 strain, IC₅₀ = 7.25–13.46 μM). Compounds 7, 26, 27, 31 and 32 inhibited nitric oxide production (IC₅₀ = 0.87–27.71 μM), indicating potential anti-inflammatory effects. Only compound 1 displayed moderate cytotoxicity against HepG2 and HT29 cancer cell lines (IC₅₀ = 25.67 and 18.35 μM, respectively). Full article

Background: Mitophagy is a critical mitochondrial quality control mechanism that limits neuronal injury following cerebral ischemia/reperfusion injury (CI/RI). Tetramethylpyrazine (TMP), a bioactive alkaloid from Ligusticum chuanxiong Hort., exhibits neuroprotective effects in cerebrovascular disorders. However, whether these effects involve mitophagy regulation remains unclear. Methods: CI/RI was induced using a middle cerebral artery occlusion/reperfusion (MCAO/R) model in mice and an oxygen–glucose deprivation/reoxygenation (OGD/R) model in HT22 cells. Neurological function, infarct volume, mitochondrial function, and mitophagy-related markers were assessed. Pharmacological inhibitors and genetic manipulation of YAP and Parkin were used to investigate underlying mechanisms. Results: TMP treatment significantly reduced infarct volume and improved neurological deficits in MCAO/R mice, accompanied by enhanced mitophagy, as indicated by increased mitochondrial LC3 recruitment and Parkin expression. In OGD/R-injured HT22 cells, TMP promoted mitophagosome and mitolysosome formation, reduced mitochondrial reactive oxygen species, and restored mitochondrial membrane potential. Inhibition of mitophagy with Mdivi-1 attenuated TMP-mediated neuroprotection. Mechanistically, TMP promoted YAP nuclear localization, and inhibition of YAP or silencing of Parkin abolished TMP-induced mitophagy, while Parkin overexpression restored mitophagy under YAP inhibition. Conclusions: TMP alleviates CI/RI by promoting mitophagy through the YAP/Parkin signaling pathway, suggesting mitophagy modulation as a potential therapeutic strategy for ischemic brain injury. Full article

Introduction: Psychotic symptoms (PS) in Alzheimer’s disease (AD) are associated with unfavorable prognosis, including accelerated functional decline and reduced survival. Multiple neurotransmitter systems have been implicated in the pathophysiology of PS, with the serotonergic system emerging as particularly relevant. Materials and Methods: Between 2010 and 2020, 120 patients with prodromal AD and 26 cognitively healthy controls underwent comprehensive evaluation, including clinical history, neurological and neuropsychological assessment, neuroimaging, and lumbar puncture. All participants underwent longitudinal clinical monitoring for a minimum of five years or until the emergence of PS. In February 2024, baseline cerebrospinal fluid (CSF) serotonin (5-HT) concentrations were quantified using competitive ELISA (FineTest, Wuhan, China). Results: CSF 5-HT levels were significantly elevated (p < 0.003) in patients who subsequently developed psychosis (n = 49) compared with those who remained free of PS during the 8-year follow-up (n = 19). A threshold of 4.89 ng/mL yielded 80% sensitivity for identifying individuals at risk. Baseline Neuropsychiatric Inventory (NPI; p < 0.001) and Unified Parkinson’s Disease Rating Scale part III (UPDRS III; p < 0.009) scores also demonstrated strong discriminative capacity. Conclusions: Measurement of CSF 5-HT and detailed clinical profiling in prodromal AD may provide predictive value for psychosis onset within 8 years of diagnosis. To our knowledge, this is the first study to report CSF 5-HT findings in AD patients. Full article

The SARS-CoV-2 public health challenges have highlighted the urgent need for coronavirus-targeting life-saving therapeutics. Given the emergence of drug-resistant strains, the development of antivirals against viral proteins beyond the commonly targeted main protease or RNA-dependent RNA polymerase is critical. The SARS-CoV-2 nonstructural protein 13 (nsp13) is a highly conserved RNA helicase and an essential component of the viral replication–transcription complex (RTC). It unwinds double-stranded RNA to facilitate viral transcription and replication, making it a strong target for drug development. To identify nsp13 inhibitors, we used an ultra-high-throughput nucleic acid unwinding assay to screen a library of FDA-approved drugs and bioactive compounds. We identified forty inhibitors with IC₅₀ values ranging from 1.4 to 10 μM. Ten were further selected for biochemical and biophysical characterization. Four of these are bound to nsp13 without interacting with the nucleic acid substrate and without inhibiting the ATPase activity of nsp13. Hydrogen–deuterium exchange coupled with Mass Spectrometry (HDX-MS) studies show compound binding causes differential exchange in two regions of nsp13. Furthermore, these compounds have antiviral activity against infectious SARS-CoV-2 in multiple cell lines, with cytotoxicity affecting, in some cases, the apparent antiviral effect. Future optimization efforts could help develop therapeutics against SARS-CoV-2 and other potential coronavirus threats. Full article