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Context:Prunus domestica Linn (Rosaceae) has been considered a functional food, owing to its various pharmacological activities, including antioxidant, anti-inflammatory, antidiabetic and anticancer.Objective: This placebo-controlled, randomized study was framed to check the beneficial activity of prune essence concentrates (PEC) in corroboration with intestinal function and lipid profile in mildly hypercholesterolemic subjects.Materials and methods: Sixty healthy mild hypercholesterolemic subjects were randomly chosen and segregated into three groups as placebo (consume 50 mL of simulated prune drink), PEC I (consume 50 mL of PEC/day) and PEC II (consume 100 mL of PEC/day) for 4 weeks with 2 weeks of follow-up without PEC consumption.Results: Intake of PEC (I and II) for 4 weeks substantially ameliorated (p < 0.05) the colony number of Bifidobacterium spp. (1.18- and 1.19-fold) and Lactobacillus spp. (1.07- and 1.16-fold), but markedly lowered (p < 0.05) the colony number of Clostridium perfringens (5.97 and 8.35%) and Escherichia coli (6.25 and 9.38%). Meanwhile, the total cholesterol (TC; 5.90 and 6.99%) levels and LDL-c (6.68 and 6.53%) were significantly reduced (p < 0.05), but no change in other lipid parameters. Whereas, the antioxidant capacity was also concomitantly elevated (p < 0.05) upon administration with PEC.Discussion and conclusion: Overall, the results suggest that the use of PEC may positively regulate the intestinal microflora and thereby effectively lower the TC levels and thus act as a hypocholesterolemic agent.

For decades, low-level laser therapy (LLLT) has widespread applications in tendon-related injuries. Although the therapeutic effect of LLLT could be explained by photostimulation of target tissue and cells, how tenocytes sense photonic energy and convert them into cascades of cellular and molecular events is still not well understood. This study was designed to elucidate the effects of LLLT on cell proliferation and collagen synthesis by examining the associated second messengers including ATP, Ca 2+ , and nitric oxide using rat Achilles tenocytes. Moreover, proliferating cell nuclear antigen (PCNA) and transforming growth factor-β1 (TGF-β1) related to cell proliferation and matrix metabolism were also studied. The results showed that 904 nm GaAs laser of 1 J/cm 2 could significantly increase the MTT activity and collagen synthesis of tenocytes. Second messengers including ATP and intracellular Ca2+ were increased after laser treatment. Quantitative PCR analysis of tenocytes treated with laser revealed up-regulated expression of PCNA, type I collagen, and TGF-β1. Besides, laser-induced TGF-β1 expression was significantly inhibited by extracellular signal-regulated kinase (ERK) specific inhibitor (PD98059). The findings suggested that LLLT stimulated ATP production and increased intracellular calcium concentration. Directly or indirectly via production of TGF-β1, these second messengers mediated the proliferation of tenocytes and synthesis of collagen.

Operation of the total heat exchangers (THXs) discussed in this article is based on thin fibrous paper, permeable to moisture but highly impermeable to air, capable of recovering both sensible and latent heat from air. By exchanging sensible and latent heat between fresh air and exhaust air, THXs show great energy-saving potential when fresh air is required for IAQ purposes in a conditioned space. Due to the fibrous permeability of the functional paper, air leakage may occur and, when significant, must be accounted for in evaluating the performance of THXs. In this study, a concept of effective fresh air efficiency defined on the basis of per-unit-effective-fresh-air is proposed and the leakage effect on efficiency is examined with experiments. Both heat and mass transfer effectiveness of THXs were compared with that of the Japan Refrigeration and Air Conditioning Industry Association standards (JRAIA). The results showed that the energy-saving index, or THX effectiveness, of JRA overestimated the performance of THXs if air leakage was present.

Audience feedback is crucial for refining video content, yet it typically comes after publication, limiting creators' ability to make timely adjustments. To bridge this gap, we introduce SimTube, a generative AI system designed to simulate audience feedback in the form of video comments before a video's release. SimTube features a computational pipeline that integrates multimodal data from the video-such as visuals, audio, and metadata-with user personas derived from a broad and diverse corpus of audience demographics, generating varied and contextually relevant feedback. Furthermore, the system's UI allows creators to explore and customize the simulated comments. Through a comprehensive evaluation-comprising quantitative analysis, crowd-sourced assessments, and qualitative user studies-we show that SimTube's generated comments are not only relevant, believable, and diverse but often more detailed and informative than actual audience comments, highlighting its potential to help creators refine their content before release.

Corn silk tea has been used in folk medicine for anti-hypertensive healthcare. Angiotensin-converting enzyme (ACE) plays a crucial role on the homeostasis of blood pressure. However, effects of corn silk tea on ACE activity and the presence of ACE inhibitory constituents in corn silk are still unknown. Here we applied proteomics and bioinformatics approaches to identify corn silk bioactive peptides (CSBps) that target ACE from the boiling water extract of corn silk (CSE). CSE significantly reduced systolic blood pressure (SBP) levels in spontaneously hypertensive rats and inhibited the ACE activity. By proteomics coupled with bioinformatics analyses, we identified a novel ACE inhibitory peptide CSBp5 in CSE. CSBp5 significantly inhibited the ACE activity and decreased SBP levels in a dose-dependent manner. Docking analysis showed that CSBp5 occupied the substrate-binding channel of ACE and interacted with ACE via hydrogen bonds. In conclusion, we identified that CSE exhibited anti-hypertensive effects in SHRs via the inhibition of ACE, the target of most anti-hypertensive drugs. In addition, an ACE inhibitory phytopeptide CSBp5 that decreased SBP levels in rats was newly identified. Our findings supported the ethnomedical use of corn silk tea on hypertension. Moreover, the identification of ACE inhibitory phytopeptide in corn silk further strengthened our findings.

5-Fluorouracil (5-FU) is a commonly used drug for the treatment of malignant cancers. However, approximately 80% of patients undergoing 5-FU treatment suffer from gastrointestinal mucositis. The aim of this report was to identify the drug target for the 5-FU-induced intestinal mucositis. 5-FU-induced intestinal mucositis was established by intraperitoneally administering mice with 100 mg/kg 5-FU. Network analysis of gene expression profile and bioluminescent imaging were applied to identify the critical molecule associated with 5-FU-induced mucositis. Our data showed that 5-FU induced inflammation in the small intestine, characterized by the increased intestinal wall thickness and crypt length, the decreased villus height, and the increased myeloperoxidase activity in tissues and proinflammatory cytokine production in sera. Network analysis of 5-FU-affected genes by transcriptomic tool showed that the expression of genes was regulated by nuclear factor-κB (NF-κB), and NF-κB was the central molecule in the 5-FU-regulated biological network. NF-κB activity was activated by 5-FU in the intestine, which was judged by in vivo bioluminescence imaging and immunohistochemical staining. However, 5-aminosalicylic acid (5-ASA) inhibited 5-FU-induced NF-κB activation and proinflammatory cytokine production. Moreover, 5-FU-induced histological changes were improved by 5-ASA. In conclusion, our findings suggested that NF-κB was the critical molecule associated with the pathogenesis of 5-FU-induced mucositis, and inhibition of NF-κB activity ameliorated the mucosal damage caused by 5-FU.

Clove ( ) is traditionally used for inflammatory skin disorders; however, its specific molecular mechanisms in psoriasis remain poorly defined. This study aimed to evaluate the efficacy of clove extract and its major component, eugenol, and to identify their molecular targets. We used an imiquimod (IMQ)-induced mouse model to assess the effects of oral clove extract and eugenol. Proteomic alterations were identified via isobaric tags for relative and absolute quantitation-based liquid chromatography-tandem mass spectrometry and bioinformatics. The specific interaction with the interleukin-17A (IL-17A)/IL-17 receptor A (IL-17RA) interface was validated through competitive binding assays and molecular docking, with further confirmation via immunohistochemistry. Eugenol was identified as the major constituent of clove extract (65.8%). Clove extract and eugenol significantly alleviated psoriasiform lesions, reducing scaling scores and epidermal thickness. Proteomic analysis revealed that both treatments reversed IMQ-induced inflammatory signatures by modulating the interleukin-36 (IL-36) and IL-17 signaling pathways, specifically increasing IL-36 receptor antagonist expression while suppressing IL-36 levels. assays demonstrated that both treatments inhibited IL-17A-IL-17RA binding in a dose-dependent manner, supported by molecular docking indicating potential interactions between eugenol and IL-17A residues. Immunohistochemical analysis further confirmed reduced nuclear factor-κB (NF-κB) activation, decreased IL-17A expression, and diminished CD11b granulocyte infiltration in psoriatic skin. Clove extract and its major bioactive constituent eugenol exert significant anti-psoriatic effects through coordinated modulation of the IL-36/IL-17A inflammatory axis and suppression of NF-κB signaling. These findings provide mechanistic insight into the traditional use of clove in inflammatory skin disorders and highlight eugenol as a key bioactive mediator with potential as a complementary therapeutic strategy for psoriasis.

BackgroundEarly retirement is highly prevalent in Taiwan. This study assesses the association between early retirement and all-cause and cause-specific mortality risks while exploring the modifying effect of sociodemographic factors.MethodsUsing Taiwan’s National Health Insurance Research Database between 2009 and 2019, 1 762 621 early retirees aged 45–64 and an equal number of employed comparators were included. The date and cause of death were identified using the National Death Registry. Cox regression models were used to estimate HRs of early retirement for all-cause mortality and cause-specific mortality. To explore modifying effects, we conducted subgroup analyses based on age groups, sexes, occupation types and general health status (Charlson Comorbid Index score).ResultsThe analysis revealed that early retirees, compared with their concurrently employed counterparts, had a higher mortality risk (adjusted HR (aHR) 1.69, 95% CI (1.67 to 1.71)). Specifically, younger individuals (aged 45–54) (aHR 2.74 (95% CI 2.68 to 2.80)), males (aHR 1.78 (95% CI 1.76 to 1.81)), those in farming or fishing occupations (aHR 2.13 (95% CI 2.06 to 2.21)) or the private sector (aHR 1.92 (95% CI 1.89 to 1.96)), and those with the poorest health conditions (aHR 1.79 (95% CI 1.76 to 1.83)) had higher mortality risks of early retirement. Regarding specific causes of death, the top three highest risks were associated with gastrointestinal disorders, followed by suicide and neurological disorders.ConclusionsThis study underscores the substantial mortality risk increase linked to early retirement, emphasising the importance of policy considerations, particularly regarding vulnerable populations and specific causes of death potentially linked to unhealthy lifestyles.

Background Rapid on‐site cytologic evaluation (ROSE) helps to improve the diagnostic accuracy in endobronchial ultrasound (EBUS) procedures. However, cytologists are seldom available to perform ROSE in many institutions. Recent studies have investigated the application of deep learning in cytologic image analysis. As such, the present study analyzed lung cytologic images obtained by EBUS procedures, and employed deep‐learning methods to distinguish between benign and malignant cells and to semantically segment malignant cells. Methods Ninety‐seven patients who underwent 104 EBUS procedures were enrolled. Four hundred and ninety‐nine lung cytologic images obtained via ROSE, including 425 malignant and 74 benign, and most malignant were lung adenocarcinoma (64.3%). All the images were used to train a residual network model with 101 layers (ResNet101), with suitable hyperparameters selected to classify benign and malignant lung cytologic images. An HRNet model was also employed to mark the area of malignant cells. Automatic patch‐cropping was adopted to facilitate dataset preparation. Results Malignant cells were successfully classified by ResNet101 with 98.8% classification accuracy, 98.8% sensitivity, and 98.8% specificity in patch‐based classification; 95.5% classification accuracy in image‐based classification; and 92.9% classification accuracy in patient‐based classification. Malignant cell area was successfully marked by HRNet with a mean intersection over union of 89.2%. The automatic cropping method enabled the system to complete diagnosis within 1 s. Conclusions This is the first study to combine lung cytologic image deep‐learning classification with semantic segmentation. The model was optimized for high accuracy and the automatic cropping facilitates the clinical application of our model. The success in both lung cytologic images classification and semantic segmentation on our dataset shows a promising result for clinical application in the future. This study leveraged the high computational speed characteristics of deep learning to distinguish and segmentally mark malignant cells in lung cytologic images obtained by EBUS procedures. Classification with ResNet101 and segmentation with HRNet were completed within 1 s and with high accuracy.

Voltage-gated CLC-1 chloride channels play a critical role in controlling the membrane excitability of skeletal muscles. Mutations in human CLC-1 channels have been linked to the hereditary muscle disorder myotonia congenita. We have previously demonstrated that disease-associated CLC-1 A531V mutant protein may fail to pass the endoplasmic reticulum quality control system and display enhanced protein degradation as well as defective membrane trafficking. Currently the molecular basis of protein degradation for CLC-1 channels is virtually unknown. Here we aim to identify the E3 ubiquitin ligase of CLC-1 channels. The protein abundance of CLC-1 was notably enhanced in the presence of MLN4924, a specific inhibitor of cullin-RING E3 ligases. Subsequent investigation with dominant-negative constructs against specific subtypes of cullin-RING E3 ligases suggested that CLC-1 seemed to serve as the substrate for cullin 4A (CUL4A) and 4B (CUL4B). Biochemical examinations further indicated that CUL4A/B, damage-specific DNA binding protein 1 (DDB1) and cereblon (CRBN) appeared to co-exist in the same protein complex with CLC-1. Moreover, suppression of CUL4A/B E3 ligase activity significantly enhanced the functional expression of the A531V mutant. Our data are consistent with the idea that the CUL4A/B-DDB1-CRBN complex catalyses the polyubiquitination and thus controls the degradation of CLC-1 channels.