Melatonin feeding changed the microbial diversity and metabolism of the broiler cecum.

To study the effect of melatonin supplementation on the gut microbes of broilers, 160 healthy 3-week-old Ross 308 broilers with similar body weights were selected and randomly divided into four groups (M0, M20, M40, and M80) supplemented with 0, 20, 40, or 80 mg/kg melatonin. The results showed that the abundance-based coverage estimator (ACE) index of cecum microorganisms was significantly lower in the M80 group. The dominant phyla of intestinal contents in the M0, M20, M40, and M80 groups were Bacteroidetes and Firmicutes. The M40 group showed an increase in the relative abundance of Bacteroidetes spp. in the intestine, while the relative abundance of Ruminococcus spp. in the intestine of the M20, M40, and M80 groups was significantly greater than that of the M0 group. Kyoto Encyclopedia of Genes and Genomes (KEGG) functional analyses revealed that the supplementation of melatonin increases the expression of genes related to cellular processes (cell motility, cell growth and death, and cellular community-eukaryotes), environmental information processing (membrane transport and signal transduction), and genetic information processing (transport and transcription), and Cluster of Orthologous Groups (COG) of proteins functional analyses revealed that the supplementation of melatonin resulted in a significant increase in cellular processes and signaling (cell motility, signal transduction mechanisms, intracellular trafficking, secretion, and vesicular transport), information storage and processing (RNA processing and modification, chromatin structure and dynamics, translation, ribosomal structure, and biogenesis), metabolism (energy production and conversion, lipid transportation and metabolism, inorganic ion transport and metabolism, secondary metabolite biosynthesis, transport, and catabolism), and poorly characterized (general function prediction only). In summary, supplementation of feed with melatonin can increase the diversity of intestinal microorganisms and the relative abundance of Bacteroides and Firmicutes in the cecum, improve digestive ability and nutrient absorption ability, and positively regulate the metabolic ability of broilers.

Controlling nutritional status score in the prediction of cardiovascular disease prevalence, all-cause and cardiovascular mortality in chronic obstructive pulmonary disease population: NHANES 1999-2018.

BACKGROUND: Malnutrition is prevalent in chronic obstructive pulmonary disease (COPD) and associated with adverse outcomes, while COPD is intricately linked to cardiovascular disease (CVD), sharing common risk factors. The controlling nutritional status (CONUT) score, a promising tool for assessing malnutrition, warrants investigation into its predictive ability for cardiovascular disease prevalence and mortality in COPD patients. METHODS: Based on the National Health and Nutrition Examination Survey (NHANES), this study analyzed 1501 adult COPD patients from 1999 to 2018. The endpoints were CVD prevalence, mortality related to CVD, and overall mortality. We evaluated the correlation of the CONUT score with each outcome using logistic regression and Cox regression models. The prognostic evaluation of patients was conducted using Kaplan-Meier curves in accordance with the CONUT score. We formed the receiver operating characteristic (ROC) curves for evaluating the CONUT score's discriminative capability. RESULTS: The prevalence of malnutrition was 21.31% in COPD populations. Logistic analyses suggested a distinct connection between the CONUT score and CVD prevalence (OR:1.86, 95%CI:1.28-2.70) in individuals with COPD. The CONUT score demonstrated a significant correlation with a heightened risk of CVD mortality (HR: 1.86, 95%CI: 1.27-2.74) and overall mortality (HR: 1.50, 95%CI: 1.18-1.91). The prognostic outcomes might be effectively discriminated by the CONUT score, as seen by the Kaplan-Meier curves. CONCLUSIONS: In summary, the CONUT score provides an uncomplicated and readily attainable marker for forecasting CVD prevalence, total mortality, and mortality from CVD among COPD patients.

MEN1 deficiency stabilizes PD-L1 and promotes tumor immune evasion of lung cancer.

Multiple Endocrine Neoplasia 1 gene (MEN1), which is known to be a tumor suppressor gene in lung tissues, encodes a 610 amino acid protein menin. Previous research has proven that MEN1 deficiency promotes the malignant progression of lung cancer. However, the biological role of this gene in the immune microenvironment of lung cancer remains unclear. In this study, we found that programmed cell death-ligand 1 (PD-L1) is upregulated in lung-specific KrasG12D mutation-induced lung adenocarcinoma in mice, after Men1 deficiency. Simultaneously, CD8+ and CD3+ T cells are depleted, and their cytotoxic effects are suppressed. In vitro, PD-L1 is inhibited by the overexpression of menin. Mechanistically, we found that MEN1 inactivation promotes the deubiquitinating activity of COP9 signalosome subunit 5 (CSN5) and subsequently increases the level of PD-L1.

Activation of trace amine-associated receptor 1 ameliorates PTSD-like symptoms.

Trace amine-associated receptor 1 (TAAR1) negatively modulates monoaminergic transmission in the mammalian brain and participates in many psychiatric disorders. Preclinical evidence indicate that selective TAAR1 agonists have anxiolytic effects and anti-stress properties. Post-traumatic stress disorder (PTSD) is an anxiety disorder triggered by experiencing or witnessing traumatic stressors. However, it remains unknown whether TAAR1 is involved in PTSD. Here, we investigated the role of TAAR1 in two PTSD animal models, including single prolonged stress (SPS)-induced impairment of fear extinction and stress-enhanced fear learning (SEFL). SPS decreased TAAR1 mRNA levels in the prefrontal cortex and ventral tegmental area. Acute treatment of the TAAR1 partial agonist RO5263397 attenuated SPS-induced anxiety-like behavior evaluated by the elevated-plus maze test. Compared to non-stressed animals, rats that experienced SPS showed higher freezing levels in the extinction retention test, indicating an impairment of fear extinction retention after SPS exposure. Acute and chronic treatment of RO5263397 ameliorated SPS-induced impairment of fear extinction retention. In the SEFL model, compared to the No-shock group, rats that experienced severe foot shock before fear conditioning showed higher freezing levels during the tests, indicating enhanced fear learning after stress exposure. Chronic treatment of RO5263397 partially attenuated the SEFL. Moreover, chronic treatment with the selective TAAR1 full agonist RO5166017 completely prevented the SEFL. Taken together, these data showed that pharmacological activation of TAAR1 could ameliorate PTSD-like symptoms. The present study thus provides the first evidence that TAAR1 might participate in the development of PTSD, and TAAR1 agonists could be potential pharmacological treatments for this disorder.

Exercise accelerates recruitment of CD8+ T cell to promotes anti-tumor immunity in lung cancer via epinephrine.

BACKGROUND AND PURPOSE: In recent years, there has been extensive research on the role of exercise as an adjunctive therapy for cancer. However, the potential mechanisms underlying the anti-tumor therapy of exercise in lung cancer remain to be fully elucidated. As such, our study aims to confirm whether exercise-induced elevation of epinephrine can accelerate CD8+ T cell recruitment through modulation of chemokines and thus ultimately inhibit tumor progression. METHOD: C57BL/6 mice were subcutaneously inoculated with Lewis lung cancer cells (LLCs) to establish a subcutaneous tumor model. The tumor mice were randomly divided into different groups to performed a moderate-intensity exercise program on a treadmill for 5 consecutive days a week, 45 min a day. The blood samples and tumor tissues were collected after exercise for IHC, RT-qPCR, ELISA and Western blot. In addition, another group of mice received daily epinephrine treatment for two weeks (0.05 mg/mL, 200 µL i.p.) (EPI, n = 8) to replicate the effects of exercise on tumors in vivo. Lewis lung cancer cells were treated with different concentrations of epinephrine (0, 5, 10, 20 µM) to detect the effect of epinephrine on chemokine levels via ELISA and RT-qPCR. RESULTS: This study reveals that both pre- and post-cancer exercise effectively impede the tumor progression. Exercise led to an increase in EPI levels and the infiltration of CD8+ T cell into the lung tumor. Exercise-induced elevation of EPI is involved in the regulation of Ccl5 and Cxcl10 levels further leading to enhanced CD8+ T cell infiltration and ultimately inhibiting tumor progression. CONCLUSION: Exercise training enhance the anti-tumor immunity of lung cancer individuals. These findings will provide valuable insights for the future application of exercise therapy in clinical practice.

Development and Validation of Knowledge Assessment Scales for Dementia and Urinary Incontinence in Community Older People.

To develop and validate scales for reliably assessing dementia and urinary incontinence knowledge of older adults in the community. Items were generated through a literature review, refined through a Delphi study (n = 19), and then revised through a pilot study (n = 29). Item analysis and exploratory factor analysis were applied to finalize the scales (n = 244). Construct validity, reliability, and acceptability were evaluated (n = 243). The two knowledge assessment scales for dementia and urinary incontinence, respectively, comprised 12 items and 8 items. Model fit indicators of both met the criteria of confirmatory factor analysis. Cronbach's α were .82 and .70, respectively. Completion ratio and completion time of the two scales was 83.51% and 4.22 ± 1.90 minutes. The knowledge assessment scales for dementia and urinary incontinence with satisfactory validity, reliability, and acceptability, could be served as valid tools for disease prevention and management among older adults in the community.

Toward the Development of Simplified Lateral Flow Assays Using Hydrogels as the Universal Control Line.

Lateral flow assays (LFA) have been widely utilized as point-of-care testing devices in diverse fields. However, it is imperative to preprint costly bioreceptors onto the lateral flow nitrocellulose membrane at the control line. The complex manufacturing process and relatively limited detection capabilities of LFA have impeded their utilization in more challenging fields. Here, we propose a novel and simple strategy to simplify the manufacture of LFA while simultaneously improving the sensitivity by modifying the hydrogel line (HL). In our study, it was observed that the sensitivity of commercial LFA strips could be enhanced by 2-5-fold by incorporating an extra HL. Particularly, a universal control line was developed to accommodate multiple LFA detection modes by substituting the conventional antibody control line with a hydrogel control line (HCL). As a proof of concept, the HCL performance could be associated with the slowdown and interception effect toward fluid, which are dependent on the permeation and hydrophilicity of the hydrogel with varying concentrations in the nitrocellulose membrane. This new design builds the foundation to enhance the sensitivity and develop the simplified LFA sensing platform without additional complicated processes.

Development and validation of frailty and malnutrition knowledge assessment scale for community-dwelling older adults.

There is a lack of reliable tools to assess the knowledge of frailty and malnutrition in community-dwelling older adults. To develop and validate reliable frailty and malnutrition knowledge assessment scales for this population, two scales were developed and validated through five phases. Phase 1: the item pools were constructed through a literature review and research panel based on the symptom interpretation model. Phase 2: the expert consultation was performed to select the items. Phase 3: a pilot survey was conducted to assess the clarity of the items and further revise the scales. Phase 4: 242 older adults were surveyed to finalize the items. Phase 5: 241 older adults were surveyed to test the psychometric properties. The two scales each comprise 3 dimensions (symptoms, risk factors, and management strategies) and 11 items. They had good construct validity, with all indicators of correlation analysis and confirmatory factor analysis meeting their specific criteria. The reliability of the frailty and malnutrition knowledge assessment scales was good, with composite reliability coefficients all >0.60, Cronbach's alpha being 0.81 and 0.83, and the Spearman-Brown coefficient being 0.74 and 0.80, respectively. Their acceptability was good, with both having a completion rate of 92.18% and an average completion time of 3 min. The two scales are reliable tools to assess the knowledge of frailty and malnutrition among community-dwelling older adults, especially for large-scale surveys. They can help identify knowledge gaps in older adults and provide a basis for developing targeted educational interventions.

Role of nutrition in patients with coexisting chronic obstructive pulmonary disease and sarcopenia.

Chronic obstructive pulmonary disease (COPD) is one of the most common chronic diseases in the elderly population and is characterized by persistent respiratory symptoms and airflow obstruction. During COPD progression, a variety of pulmonary and extrapulmonary complications develop, with sarcopenia being one of the most common extrapulmonary complications. Factors that contribute to the pathogenesis of coexisting COPD and sarcopenia include systemic inflammation, hypoxia, hypercapnia, oxidative stress, protein metabolic imbalance, and myocyte mitochondrial dysfunction. These factors, individually or in concert, affect muscle function, resulting in decreased muscle mass and strength. The occurrence of sarcopenia severely affects the quality of life of patients with COPD, resulting in increased readmission rates, longer hospital admission, and higher mortality. In recent years, studies have found that oral supplementation with protein, micronutrients, fat, or a combination of nutritional supplements can improve the muscle strength and physical performance of these patients; some studies have also elucidated the possible underlying mechanisms. This review aimed to elucidate the role of nutrition among patients with coexisting COPD and sarcopenia.

A protocol for randomized controlled trial on multidisciplinary interventions for mobility limitation in the older adults (M-MobiLE).

BACKGROUND: Mobility limitation-the loss of exercise capacity or independent living ability-is a common geriatric syndrome in older adults. As a potentially reversible precursor to disability, mobility limitation is influenced by various factors. Moreover, its complex physiological mechanism hinders good therapeutic outcomes with a single-factor intervention. Most hospitals have not incorporated the diagnosis and evaluation of mobility limitation into medical routines nor developed a multidisciplinary team (MDT) treatment plan. We aim to conduct a clinical trial titled "A Multidisciplinary-team approach for management of Mobility Limitation in Elderly (M-MobiLE)" to explore the effect of the MDT decision-making intervention for mobility limitation. METHODS: The M-MobiLE study will be a multicenter, randomized, and controlled trial. We will recruit a minimum of 66 older inpatients with mobility limitation from at least five hospitals. Older patients with mobility limitation admitted to the geriatrics department will be included. Short-Physical Performance Battery (SPPB), Activities of Daily Living (ADL), Function Impairment Screening Tool (FIST), Geriatric Depression Scale (GDS-15), Short Form - 12 (SF-12), Fried frailty phenotype, social frailty, Morse Fall Risk Scale, SARC-CalF, Mini-Mental State Examination (MMSE), Mini-Nutritional Assessment Short-Form (MNA-SF), and intrinsic capacity will be assessed. The intervention group will receive an exercise-centered individualized MDT treatment, including exercise, educational, nutritional, medical, and comorbidity interventions; the control group will receive standard medical treatment. The primary outcome is the change in the SPPB score, and the secondary outcomes include increased SF-12, ADL, FIST, MMSE, MNA-SF, and intrinsic capacity scores and decreased GDS-15 and SARC-CalF scores. CONCLUSION: Our results will help develop a multidisciplinary decision-making clinical pathway for inpatients with mobility limitation, which can be used to identify patients with mobility limitation more effectively, improve mobility, and reduce the risk of falls, frailty, and death in older inpatients. The implementation of this MDT strategy may standardize the treatment of mobility limitation, reduce adverse prognosis, and improve quality of life. TRIAL REGISTRATION: ChiCTR, ChiCTR2200056756, Registered 19 February 2022.