ABSTRACT
Rare genetic variants in toll-like receptor 7 (TLR7) are known to cause lupus in humans and mice. UNC93B1 is a transmembrane protein that regulates TLR7 localization into endosomes. In the present study, we identify two new variants in UNC93B1 (T314A, located proximally to the TLR7 transmembrane domain, and V117L) in a cohort of east Asian patients with childhood-onset systemic lupus erythematosus. The V117L variant was associated with increased expression of type I interferons and NF-κB-dependent cytokines in patient plasma and immortalized B cells. THP-1 cells expressing the variant UNC93B1 alleles exhibited exaggerated responses to stimulation of TLR7/-8, but not TLR3 or TLR9, which could be inhibited by targeting the downstream signaling molecules, IRAK1/-4. Heterozygous mice expressing the orthologous Unc93b1V117L variant developed a spontaneous lupus-like disease that was more severe in homozygotes and again hyperresponsive to TLR7 stimulation. Together, this work formally identifies genetic variants in UNC93B1 that can predispose to childhood-onset systemic lupus erythematosus.
Subject(s)
Genetic Predisposition to Disease , Lupus Erythematosus, Systemic , Toll-Like Receptor 7 , Lupus Erythematosus, Systemic/genetics , Humans , Animals , Toll-Like Receptor 7/genetics , Toll-Like Receptor 7/metabolism , Mice , Child , Female , Membrane Transport Proteins/genetics , Membrane Transport Proteins/metabolism , Male , Age of Onset , Genetic Variation , NF-kappa B/metabolism , B-Lymphocytes/immunology , B-Lymphocytes/metabolism , Adolescent , THP-1 Cells , Interferon Type I/metabolismABSTRACT
Ribbon synapses in the cochlear hair cells are subject to extensive pruning and maturation processes before hearing onset. Previous studies have highlighted the pivotal role of thyroid hormone (TH) in this developmental process, yet the detailed mechanisms are largely unknown. In this study, we found that the thyroid hormone receptor α (Thrα) is expressed in both sensory epithelium and spiral ganglion neurons in mice. Hypothyroidism, induced by Pax8 gene knockout, significantly delays the synaptic pruning during postnatal development in mice. Detailed spatiotemporal analysis of ribbon synapse distribution reveals that synaptic maturation involves not only ribbon pruning but also their migration, both of which are notably delayed in the cochlea of Pax8 knockout mice. Intriguingly, postnatal hyperthyroidism, induced by intraperitoneal injections of liothyronine sodium (T3), accelerates the pruning of ribbon synapses to the mature state without affecting the auditory functions. Our findings suggest that thyroid hormone does not play a deterministic role but rather controls the timing of cochlear ribbon synapse maturation.
Subject(s)
Cochlea , Synapses , Animals , Mice , Synapses/physiology , Thyroid Hormones , Spiral Ganglion , Hearing/physiology , Mice, KnockoutABSTRACT
OBJECTIVE: Over the past decade, heat shock protein 90 (HSP90) inhibitors have emerged as promising anticancer drugs in solid and hematological malignancies. Flavokawain C (FKC) is a naturally occurring chalcone that has been found to exert considerable anti-tumor efficacy by targeting multiple molecular pathways. However, the efficacy of FKC has not been studied in nasopharyngeal carcinoma (NPC). Metabolic abnormalities and uncontrolled angiogenesis are two important features of malignant tumors, and the occurrence of these two events may involve the regulation of HSP90B1. Therefore, this study aimed to explore the effects of FKC on NPC proliferation, glycolysis, and angiogenesis by regulating HSP90B1 and the underlying molecular regulatory mechanisms. METHODS: HSP90B1 expression was analyzed in NPC tissues and its relationship with patient's prognosis was further identified. Afterward, the effects of HSP90B1 on proliferation, apoptosis, glycolysis, and angiogenesis in NPC were studied by loss-of-function assays. Next, the interaction of FKC, HSP90B1, and epidermal growth factor receptor (EGFR) was evaluated. Then, in vitro experiments were designed to analyze the effect of FKC treatment on NPC cells. Finally, in vivo experiments were allowed to investigate whether FKC treatment regulates proliferation, glycolysis, and angiogenesis of NPC cells by HSP90B1/EGFR pathway. RESULTS: HSP90B1 was highly expressed in NPC tissues and was identified as a poor prognostic factor in NPC. At the same time, knockdown of HSP90B1 can inhibit the proliferation of NPC cells, trigger apoptosis, and reduce glycolysis and angiogenesis. Mechanistically, FKC affects downstream EGFR phosphorylation by regulating HSP90B1, thereby regulating the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt)/mammalian target of rapamycin (mTOR) pathway. FKC treatment inhibited the proliferation, glycolysis, and angiogenesis of NPC cells, which was reversed by introducing overexpression of HSP90B1. In addition, FKC can affect NPC tumor growth and metastasis in vivo by regulating the HSP90B1/EGFR pathway. CONCLUSION: Collectively, FKC inhibits glucose metabolism and tumor angiogenesis in NPC by targeting the HSP90B1/EGFR/PI3K/Akt/mTOR signaling axis.
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A photoredox/copper-catalyzed cascade radical cyclization/phosphorothiolation reaction of N-allylbromoacetamides and P(O)SH compounds has been established. A broad range of novel nonfluorine- or difluoro-substituted 2-pyrrolidinones bearing the C(sp3)-SP(O)(OR)2 moiety can be conveniently constructed in moderate to good yields under mild conditions. Importantly, most of the tested phosphorothiolated 2-pyrrolidinones showed potent inhibitory effects toward both AChE and BChE.
ABSTRACT
Although empathy for pain plays an important role in positive interpersonal relationships and encourages engagement in prosocial behavior, it remains largely unknown whether empathy for pain could be effectively altered by psychophysiological techniques. This study aimed to investigate the impact of a single session of diaphragmatic breathing practice on empathy for pain and examine the potential mechanism involving interoceptive awareness. A total of 66 healthy participants were randomly assigned to the intervention group or the control group. The intervention group received a 15-minute diaphragmatic breathing (DB) practice with real-time biofeedback, while the control group was to gaze at a black screen at rest and not engaged in any other activities. Before and after the invention, all participants were instructed to evaluate the intensity and unpleasantness of empathy for pain while watching different pictures with pain or non-pain conditions. The Multidimensional Assessment of Interoceptive Awareness (MAIA) was then administered to measure interoceptive awareness. The results indicated a significant interaction between group and time with regard to empathy for pain and MAIA. The DB group showed a statistically significant decrease in both pain intensity and unpleasantness during the pain picture condition, as well as a noteworthy increase in MAIA scores. The control group did not demonstrate any substantial changes. More importantly, the regulation of attention, a dimension of MAIA, had a significant mediating effect on the impact of diaphragmatic breathing on reported unpleasantness. Diaphragmatic breathing could serve as a simple, convenient, and practical strategy to optimize human empathy for pain that warrants further investigation, which has important implications not only for individuals with impaired empathy for pain but also for the improvement of interoceptive awareness.
Subject(s)
Awareness , Empathy , Interoception , Humans , Male , Empathy/physiology , Interoception/physiology , Female , Awareness/physiology , Young Adult , Adult , Breathing Exercises , Pain/physiopathology , Biofeedback, Psychology/physiologyABSTRACT
Aquatic ecosystems are being increasingly polluted by microplastics (MPs), which calls for an understanding of how MPs affect microbially driven biogenic element cycling in water environments. A 28-day incubation experiment was conducted using freshwater lake water added with three polymer types of MPs (i.e., polyethylene, polypropylene, polystyrene) separately or in combination at a concentration of 1 items/L. The effects of various MPs on microbial communities and functional genes related to carbon, nitrogen, phosphorus, and sulfur cycling were analyzed using metagenomics. Results showed that Sphingomonas and Novosphingobium, which were indicator taxa (genus level) in the polyethylene treatment group, made the largest functional contribution to biogenic element cycling. Following the addition of MPs, the relative abundances of genes related to methane oxidation (e.g., hdrD, frhB, accAB) and denitrification (napABC, nirK, norB) increased. These changes were accompanied by increased relative abundances of genes involved in organic phosphorus mineralization (e.g., phoAD) and sulfate reduction (cysHIJ), as well as decreased relative abundances of genes involved in phosphate transport (phnCDE) and the SOX system. Findings of this study underscore that MPs, especially polyethylene, increase the potential of greenhouse gas emissions (CO2, N2O) and water pollution (PO43-, H2S) in freshwater lakes at the functional gene level.
Subject(s)
Greenhouse Gases , Lakes , Metagenomics , Microplastics , Water Pollutants, Chemical , Lakes/microbiology , Lakes/chemistry , Greenhouse Gases/analysis , Microplastics/toxicity , Water Pollutants, Chemical/analysis , Water Pollutants, Chemical/toxicity , Water Pollution/analysis , Microbiota/drug effects , Bacteria/genetics , Bacteria/drug effects , Bacteria/classification , Bacteria/metabolismABSTRACT
OBJECTIVES: Frailty is a risk factor for faster cognitive decline, while plant-based dietary patterns are associated with decreased risk of cognitive decline. We aimed to explore their interaction with cognitive function among older adults. METHODS: We used data from the Chinese Longitudinal Healthy Longevity Survey between 2008 and 2018. Frailty was evaluated based on the frailty index (FI), and the plant-based diet index (PDI) was calculated using food frequency questionnaire at baseline. Repeated measures of the Mini-Mental State Examination (MMSE) were utilised to assess cognitive function. We used linear mixed models to estimate regression coefficients (ß) and 95% confidence intervals (CI). RESULTS: We included 7,166 participants with a median follow-up of 5.8 years. Participants in pre-frail (ß = -0.18, 95% CI: -0.24, -0.13) and frail (ß = -0.39, 95% CI: -0.48, -0.30) groups experienced an accelerated decline in MMSE score compared with the robust group. The PDI modified the above association, with corresponding associations with frailty being much more pronounced among participants with a lower PDI (frail vs. robust ß = -0.44, 95% CI: -0.56, -0.32), compared with those with a higher PDI (frail vs. robust ß = -0.27, 95% CI: -0.40, -0.13). In addition, A combination of frailty and a low PDI was strongly associated with a faster decline in MMSE score (ß = -0.52, 95% CI: -0.63, -0.41). CONCLUSION: Adherence to plant-based dietary patterns attenuates the association between frailty and cognitive decline. If the observed association is causal, promoting plant-based dietary patterns may be a strategy to reduce the effects of frailty on neurological health.
Subject(s)
Cognitive Dysfunction , Frailty , Humans , Aged , Frailty/diagnosis , Frailty/epidemiology , Frailty/complications , Dietary Patterns , Longitudinal Studies , Cognitive Dysfunction/diagnosis , Cognitive Dysfunction/epidemiology , Cognitive Dysfunction/etiology , China/epidemiology , Frail ElderlyABSTRACT
BACKGROUND: This study aimed to evaluate the long-term survival outcomes of esophagectomy with off-pump coronary artery bypass grafting (OPCABG) vs. esophagectomy alone. METHODS: A total of 1798 patients who received esophagectomy between January 2010 and February 2020 were included and divided into the 38 patients who underwent OPCABG followed by esophagectomy (OP + ES group) and 1760 patients had only esophagectomy (ES group). Propensity score matching (PSM) and Cox multivariable analyses were performed to compare postoperative complications, disease-free survival (DFS), and overall survival (OS) between the two groups. RESULTS: There were 37 patients in the OP + ES group matched with 74 in the ES group. The matched OP + ES group had higher total postoperative complications than the ES group, especially more pulmonary infections (P = 0.001) and arrhythmias (P = 0.018), but no other postoperative complications were the difference. The DFS was similar and the OS was a significant difference between the matching 2 groups (log-rank, P = 0.132 and 0.04, respectively). Although pT 3/4 stage, pN (+), and tumor length > 3.0 cm were independently associated with worse OS and DFS in multivariable analysis, CAD and EF < 55% were also found to be a predictive factor for OS and DFS in univariate analysis. CONCLUSION: OPCABG followed by esophagectomy for esophageal cancer associated with coronary artery disease has equivalent DFS and recurrence pattern to esophagectomy for esophageal cancer alone, but with a disadvantage in OS.
Subject(s)
Coronary Artery Bypass, Off-Pump , Esophageal Neoplasms , Esophagectomy , Postoperative Complications , Propensity Score , Humans , Esophagectomy/methods , Male , Female , Middle Aged , Coronary Artery Bypass, Off-Pump/methods , Esophageal Neoplasms/surgery , Esophageal Neoplasms/mortality , Esophageal Neoplasms/pathology , Retrospective Studies , Aged , Postoperative Complications/epidemiology , Postoperative Complications/etiology , Survival Rate , Treatment Outcome , Disease-Free SurvivalABSTRACT
INTRODUCTION: Pulmonary fibrosis is a characteristic of various interstitial lung diseases (ILDs) with differing etiologies. Clinical trials in progressive pulmonary fibrosis (PPF) enroll patients based on previously described clinical criteria for past progression, which include a clinical practice guideline for PPF classification and inclusion criteria from the INBUILD trial. In this study, we compared the ability of past FVC (forced vital capacity) progression and baseline biomarker levels to predict future progression in a cohort of patients from the PFF Patient Registry. METHODS: Biomarkers previously associated with pathobiology and/or progression in pulmonary fibrosis were selected to reflect cellular senescence (telomere length), pulmonary epithelium (SP-D, RAGE), myeloid activation (CXCL13, YKL40, CCL18, OPN) and fibroblast activation (POSTN, COMP, PROC3). RESULTS: PFF or INBUILD-like clinical criteria was used to separate patients into past progressor and non-past progressor groups, and neither clinical criterion appeared to enrich for patients with greater future lung function decline. All baseline biomarkers measured were differentially expressed in patient groups compared to healthy controls. Baseline levels of SP-D and POSTN showed the highest correlations with FVC slope over one year, though correlations were low. CONCLUSIONS: Our findings provide further evidence that prior decline in lung function may not predict future disease progression for ILD patients, and elevate the need for molecular definitions of a progressive phenotype. Across ILD subtypes, certain shared pathobiologies may be present based on the molecular profile of certain biomarker groups observed. In particular, SP-D may be a common marker of pulmonary injury and future lung function decline across ILDs.
Subject(s)
Biomarkers , Disease Progression , Lung Diseases, Interstitial , Registries , Humans , Male , Female , Middle Aged , Vital Capacity , Aged , Lung Diseases, Interstitial/physiopathology , Lung Diseases, Interstitial/diagnosis , Pulmonary Fibrosis/physiopathology , Pulmonary Fibrosis/diagnosis , Pulmonary Surfactant-Associated Protein D/blood , Lung/physiopathology , Predictive Value of Tests , Chitinase-3-Like Protein 1/blood , Chemokines, CC , Osteopontin , Receptor for Advanced Glycation End Products/blood , Idiopathic Pulmonary Fibrosis/physiopathology , Idiopathic Pulmonary Fibrosis/diagnosisABSTRACT
Chronic renal failure (CRF) is a severe syndrome affecting the urinary system for which there are no effective therapeutics. In this study, we investigate the effects and mechanisms of aminophylline in preventing CRF development. A rat model of chronic renal failure is established by 5/6 nephrectomy. The levels of serum creatinine (SCR), urinary protein (UPR), and blood urea nitrogen (BUN) are detected by ELISA. Histological evaluations of renal tissues are performed by H&E, Masson staining, and PAS staining. Functional protein expression is detected by western blot analysis or immunofluorescence microscopy. Glomerular cell apoptosis is determined using the TUNEL method. Results show that Aminophylline significantly reduces the levels of SCR, UPR, and BUN in the CRF model rats. Histological analyses show that aminophylline effectively alleviates renal tissue injuries in CRF rats. The protein expression levels of nephrin, podocin, SIRT1, p-AMPK, and p-ULK1 are greatly increased, while p-mTOR protein expression is markedly decreased by aminophylline treatment. Additionally, the protein level of LC3B in CRF rats is significantly increased by aminophylline. Moreover, aminophylline alleviates apoptosis in the glomerular tissues of CRF rats. Furthermore, resveratrol promotes SIRT1, p-AMPK, and p-ULK1 protein expressions and reduces p-mTOR and LC3B protein expressions in CRF rats. Selisistat (a SIRT1 inhibitor) mitigates the changes in SIRT1, p-AMPK, p-ULK1, p-mTOR, and LC3B expressions induced by aminophylline. Finally, RAPA alleviates renal injury and apoptosis in CRF rats, and 3-MA eliminates the aminophylline-induced inhibition of renal injury and apoptosis in CRF rats. Aminophylline suppresses chronic renal failure progression by modulating the SIRT1/AMPK/mTOR-mediated autophagy process.
ABSTRACT
BACKGROUND: Fibroblast growth factor 21 (FGF21) has a protective effect against cardiovascular disease. However, the role of FGF21 in hypertension remains elusive. METHODS: Ten-week-old male C57BL/6 mice were randomly divided into normal-salt (NS) group, NS+FGF21 group, deoxycorticosterone acetate-salt (DOCA) group and DOCA+FGF21 group. The mice in NS group underwent uninephrectomy without receiving DOCA and 1% NaCl and the mice in DOCA group were subjected to uninephrectomy and DOCA-salt (DOCA and 1% NaCl) treatment for 6 weeks. At the same time, the mice were infused with vehicle (artificial cerebrospinal fluid, aCSF) or FGF21 (1 mg/kg) into the bilateral paraventricular nucleus (PVN) of mice. RESULTS: Here, we showed that FGF21 treatment lowered DOCA salt-induced inflammation and oxidative stress in the PVN, which reduced sympathetic nerve activity and hypertension. Mechanistically, FGF21 treatment decreased the expression of HNF4α and inhibited the binding activity of HNF4α to the promoter region of ACE2 in the PVN of DOCA salt-treated mice, which further up-regulated ACE2/Ang (1-7) signals in the PVN. In addition, ACE2 deficiency abolished the protective effect of FGF21 in DOCA salt-treated mice, suggesting that FGF21-mediated antihypertensive effect was dependent on ACE2. CONCLUSIONS: The results demonstrate that FGF21 protects against salt-sensitive hypertension via regulating HNF4α/ACE2/Ang (1-7) axis in the PVN of DOCA salt-treated mice via multi-organ crosstalk between liver, brain and blood vessels.
Subject(s)
Angiotensin-Converting Enzyme 2 , Desoxycorticosterone Acetate , Fibroblast Growth Factors , Hepatocyte Nuclear Factor 4 , Hypertension , Mice, Inbred C57BL , Paraventricular Hypothalamic Nucleus , Animals , Paraventricular Hypothalamic Nucleus/metabolism , Paraventricular Hypothalamic Nucleus/drug effects , Fibroblast Growth Factors/metabolism , Male , Mice , Hypertension/metabolism , Hypertension/physiopathology , Angiotensin-Converting Enzyme 2/metabolism , Hepatocyte Nuclear Factor 4/metabolism , Hepatocyte Nuclear Factor 4/genetics , Oxidative Stress/drug effects , Blood Pressure/drug effects , Sodium Chloride, DietaryABSTRACT
BACKGROUND: Per- and poly-fluoroalkyl substances (PFAS) are ubiquitous chemicals in the environment and our daily lives. Several epidemiological studies have revealed that PFAS exposure is linked to male sex hormone levels; however, the conclusions are inconsistent across studies. Consequently, we performed a meta-analysis to systematically evaluate the association between PFAS exposure and male sex hormones. METHODS: The Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) standards were followed during the meta-analysis. PubMed, Wed of Science, Embase, Cochrane Library, and Ovid databases were used to identify suitable articles before June 2023. The 95% CI and ß values were calculated to assess the association between male sex hormone levels and PFAS exposure. Heterogeneity among the included studies was tested using inconsistency statistics (I2). RESULTS: The literature search identified 12 published articles that met our search criteria, involving 7506 participants. Our results revealed that perfluorononanoic acid (PFNA) and perfluorooctanoic acid (PFOA) exposures were negatively correlated with testosterone (ß = -0.05; 95% CI: -0.09, -0.02, P = 0.003) and (ß = -0.04; 95% CI: -0.08, 0.00, P = 0.049), respectively. CONCLUSION: Exposure to PFNA and PFOA is negatively correlated with changes in male testosterone levels. This correlation suggests that we need to pay attention in the future to whether they are potential risk factors for male reproductive health.
Subject(s)
Caprylates , Fluorocarbons , Male , Humans , Fluorocarbons/blood , Fluorocarbons/toxicity , Caprylates/toxicity , Gonadal Steroid Hormones/blood , Environmental Exposure/statistics & numerical data , Environmental Pollutants , Testosterone/blood , Fatty Acids/analysisABSTRACT
This study aims to explore the mechanisms of the inhibitory effect of kaempferol on the invasion and metastasis of gastric cancer (GC) cells through network pharmacology prediction and experimental verification. It identifies core targets via PPI network analysis and finds that kaempferol binds to these targets well. In vitro experiments showed that kaempferol could inhibit the proliferation, colony formation, migration and invasion of GC cells. Western blotting indicated kaempferol may reduce AKT and GSK3ß phosphorylation, leading to lower expression of invasion-related genes SRC, MMP9, CXCR4, KDR, and MMP2. Overall, kaempferol may prevent migration and invasion of GC cells via the AKT/GSK3ß signaling pathway.
ABSTRACT
This study investigates the synergistic effect and mechanism of gelling materials with blast furnace slag (BFS), steel slag (SS) and desulphurization gypsum (DG) as the main components on the hardening of heavy metal ions by lead and zinc tailings. It is found that lead and zinc tailing (LZT) is mainly composed of dolomite and quartz and contain small amounts of calcium, aluminum, iron, magnesium and other elements as well as heavy metals such as lead and zinc. By the mechanical activation method, it is found that the lead and zinc tailings powder has the largest specific surface area and the highest activity index when the ball milling time is 2 h. At a hardening timepoint of 28 d, the calcite crystals in the samples are intertwined with the amorphous C-S-H gel (C-S-H gels are mainly composed of 3CaOâSiO2 and 2CaOâSiO2), which enhances the structural strength of the samples. The chemical reaction analysis confirmed that the formation of calcite is a major driver for the hydration reaction of the steel slag-desulphurization gypsum (SSSDG) system. Overall, the slag, steel slag and desulphurization gypsum solid waste-based gelling materials have synergistic effects in hardening heavy metals by limiting the leaching of metal ions, adsorbing metal ions and hardening heavy metals, and facilitating the hydration process through the formation of compound salt precipitates.
ABSTRACT
The objective of this study is to develop a remediation technology for composited heavy metal-contaminated soil. Biochars (BC300, BC400, and BC500) derived from corn were combined with potassium dihydrogen phosphate (KH2PO4) to immobilize and remove heavy metal ions, including mercury (Hg2+), cadmium (Cd2+), and lead (Pb2+). The adsorption kinetics of metal ions in aqueous solutions with different concentrations was tested, and the fitting effects of the two models were compared. The findings demonstrate that the joint application of biochar and KH2PO4 could markedly enhance the immobilization efficacy of Pb2+, whereas the utilization of KH2PO4 on its own exhibited a more pronounced immobilization impact on Cd2+. Furthermore, the present study underscores the shortcomings of various remediation techniques that must be taken into account when addressing heavy metal-contaminated soils. It also emphasizes the value of comprehensive remediation techniques that integrate multiple remediation agents. This study offers a novel approach and methodology for addressing the intricate and evolving challenges posed by heavy metal contamination in soil. Its practical value and potential for application are significant.
Subject(s)
Cadmium , Charcoal , Lead , Mercury , Phosphates , Potassium Compounds , Soil Pollutants , Charcoal/chemistry , Soil Pollutants/chemistry , Cadmium/chemistry , Lead/chemistry , Adsorption , Mercury/chemistry , Phosphates/chemistry , Potassium Compounds/chemistry , Environmental Restoration and Remediation/methods , Risk Assessment , Soil/chemistry , Metals, Heavy/chemistry , KineticsABSTRACT
BACKGROUND: Cognitive impairment (CI) is a significant public health concern, and bioactive peptides have shown potential as therapeutic agents. However, information about their synergistic effects on cognitive function is still limited. Here, we investigated the synergistic effects of tilapia head protein hydrolysate (THPH) and walnut protein hydrolysate (WPH) in mitigating CI induced by scopolamine in mice. RESULTS: The results showed that the combined supplementation of THPH and WPH (mass ratio, 1:1) was superior to either individual supplement in enhancing spatial memory and object recognition abilities in CI mice, and significantly lessened brain injury in CI mice by alleviating neuronal damage, reducing oxidative stress and stabilizing the cholinergic system. In addition, the combined supplementation was found to be more conducive to remodeling the gut microbiota structure in CI mice by not only remarkably reducing the ratio of Firmicutes to Bacteroidota, but also specifically enriching the genus Roseburia. On the other hand, the combined supplementation regulated the disorders of sphingolipid and amino acid metabolism in CI mice, particularly upregulating glutathione and histidine metabolism, and displayed a stronger ability to increase the expression of genes and proteins related to the brain-derived neurotrophic factor (BDNF)/TrkB/CrEB signaling pathway in the brain. CONCLUSION: These findings demonstrate that tilapia head and walnut-derived protein hydrolysates exerted synergistic effects in ameliorating CI, which was achieved through modulation of gut microbiota, serum metabolic pathways and BDNF signaling pathways. © 2024 Society of Chemical Industry.
Subject(s)
Brain-Derived Neurotrophic Factor , Cognitive Dysfunction , Gastrointestinal Microbiome , Juglans , Protein Hydrolysates , Tilapia , Animals , Juglans/chemistry , Protein Hydrolysates/chemistry , Protein Hydrolysates/administration & dosage , Protein Hydrolysates/pharmacology , Tilapia/metabolism , Mice , Cognitive Dysfunction/drug therapy , Cognitive Dysfunction/metabolism , Male , Brain-Derived Neurotrophic Factor/metabolism , Brain-Derived Neurotrophic Factor/genetics , Gastrointestinal Microbiome/drug effects , Fish Proteins/metabolism , Fish Proteins/chemistry , Humans , Oxidative Stress/drug effects , Plant Proteins , Drug Synergism , Cognition/drug effects , Brain/metabolism , Brain/drug effects , Dietary Supplements/analysisABSTRACT
Background: To clarify the causal relationship between gut microbiota and diabetic nephropathy (DN), we employed Mendelian randomization (MR). Despite a strong correlation observed, establishing causality is still unclear. By utilizing MR, we aimed to investigate this relationship further and shed light on the potential causal effect of gut microbiota on DN. Methods: Genetic instrumental variables for gut microbiota were obtained from a GWAS with 18340 participants. DN summary statistics (1032 cases, 451248 controls) were sourced from a separate GWAS. The primary analysis used the inverse-variance weighted (IVW) method. Reverse MR analysis was conducted to explore reverse causation. Rigorous sensitivity analyses were performed to ensure the resilience and reliability of the study's findings. Results: We found two bacterial traits associated with an increased risk of DN: genus LachnospiraceaeUCG008 (OR: 1.4210; 95% CI: 1.0450, 1.9322; p = 0.0250) and genus Terrisporobacter (OR: 1.9716; 95% CI: 1.2040, 3.2285; p = 0.0070). Additionally, phylum Proteobacteria (OR: 0.4394; 95% CI: 0.2721, 0.7096; p = 0.0008) and genus Dialister (OR: 0.4841; 95% CI: 0.3171, 0.7390; p = 0.0008) were protective against DN. Sensitivity analyses consistently supported these results. In the reverse MR analysis, no statistically significant associations were observed between DN and these four bacterial traits. Conclusions: Our analyses confirmed a potential causal relationship between certain gut microbiota taxa and the risk of DN. However, additional studies are required to elucidate the underlying mechanisms through which gut microbiota influences the development of DN.
Subject(s)
Diabetic Nephropathies , Gastrointestinal Microbiome , Genome-Wide Association Study , Mendelian Randomization Analysis , Humans , Diabetic Nephropathies/microbiology , Diabetic Nephropathies/geneticsABSTRACT
A simple label-free Cd2+ fluorescent aptasensor was proposed using aptamer as a recognition element and thioflavine T (ThT) as a signal reporter. The presence of Cd(II) can induce the conformational switching of the aptamer probe, accompanied by a change in fluorescence intensity. According to the difference in fluorescence signals before and after the addition of Cd2+, a fluorescence sensor for Cd2+ assay was established. Under the better experimental conditions, the sensor displayed a good linear range from 2 to 50 nM and the excellent detection limit was 0.8 nM. The method demonstrated high sensitivity and good selectivity. The aptasensor could detect Cd2+ in simulated water samples with satisfactory results. The proposed method had obvious advantages that was without chemical modification of fluorescent groups and complicated target preconcentration. It provided a new analytical platform for the detection of heavy metal ion pollution in environmental and biomedical fields.
Subject(s)
Aptamers, Nucleotide , Biosensing Techniques , Cadmium , Aptamers, Nucleotide/chemistry , Benzothiazoles , Spectrometry, Fluorescence/methods , Limit of Detection , Biosensing Techniques/methodsABSTRACT
The structural fracture of the coal seam with its low permeability is the dominant reason for the "difficult gas out" of the broken soft coal seam. The brittleness of the roof and floor rock stratum of the broken soft coal seam has a significant effect on the fracture extension pressure of the surrounding rock after casing perforation and hydraulic fracturing of the horizontal well for coalbed methane (CBM). In this paper, 15 rock samples were scientifically collected from the roof and floor of the main mining coal seam of the Early Permian coal-bearing series in the Xinxie-1 well of the Huainan Coalfield in Anhui Province, China. On the basis of mineral composition analysis of these samples, the influence of mineral composition on the mechanics properties of the rock at the roof and floor of the coal seam was investigated. The correlation analysis and gray correlation analysis were adopted to construct an evaluation method for the brittleness of the rock at the roof and floor of the coal seam based on the mineral content. The results indicated that the most significant compositions of the minerals in the rock at the roof and floor of the broken soft coal seam were quartz and clay minerals. The most significant types of rock cementation are quartz agglomeration and rhodochrosite cementation. Pore destruction as a result of cementation was much greater than that of compaction. In comparison to clay minerals, the variation in the content of brittle minerals such as quartz, plagioclase, and siderite in the rock showed more sensitivity to the mechanics properties of the rock. The more sensitive minerals for compressive strength (CS), shear strength (SS), modulus of elasticity (E), softening coefficient (K), and Poisson's ratio (µ) are quartz, those for tensile strength (TS) are plagioclase and siderite, and those for Poisson's ratio are clay minerals. Based on the established mineral content weighting analysis method, it was calculated that the brittleness index (BI) of the rocks at the roof of the 13-1, 11-2, 9-2, and 4-2 coal seams was larger, which was advantageous for the formation of longer fracturing crack networks. This is theoretical guidance for the optimization of horizontal well fracturing design in the deep coal beds of the Huainan Coalfield.
ABSTRACT
BACKGROUND: Orthostatic hypotension (OH) is a common clinical sign, but its detection rate is low, and it is difficult to repeat because there is no standardized screening method available. AIM: This study aimed to establish a method for detecting blood pressure and assess whether it could increase the OH detection rate in the elderly. METHODS: From May to October, 2022, 178 patients with symptomatic OH and 286 subjects with asymptomatic OH were selected. BP from the bilateral brachial artery was measured using two electronic sphygmomanometers on both arms at the same time, in the order of supine, sitting, and standing at 0-3 min. OH should meet 20/10 mmHg, standing BP minus sitting BP. The OH detection rates were calculated and compared. The symptomatic OH group was more often older, slimmer, had lower ADL scores, and contained fewer smokers (all P< 0.05). RESULTS: The detection rate of the symptomatic OH group using the modified method was 59.55%, which was higher than that of the routine method (34.83% vs. 59.55%, P<0.05). The detection rate using the modified method in the OH group with asymptomatic OH was 20.63%, which was higher than that of the routine method (20.63% vs. 5.59%, P< 0.01). CONCLUSION: Synchronous measurement of bilateral brachial artery BP in supine, sitting, and standing positions increased the detection rate of OH in the elderly.