ABSTRACT
BACKGROUND: The role of periodontal ligament stem cells (PDLSCs) in repairing periodontal destruction is crucial, but their functions can be impaired by excessive oxidative stress (OS). Nocardamine (NOCA), a cyclic siderophore, has been shown to possess anti-cancer and anti-bacterial properties. This study aimed to investigate the protective mechanisms of NOCA against OS-induced cellular dysfunction in PDLSCs. METHODS: The cytotoxicity of NOCA on PDLSCs was assessed using a CCK-8 assay. PDLSCs were then treated with hydrogen peroxide (H2O2) to induce OS. ROS levels, cell viability, and antioxidant factor expression were analyzed using relevant kits after treatment. Small molecule inhibitors U0126 and XAV-939 were employed to block ERK signaling and Wnt pathways respectively. Osteogenic differentiation was assessed using alkaline phosphatase (ALP) activity staining and Alizarin Red S (ARS) staining of mineralized nodules. Expression levels of osteogenic gene markers and ERK pathway were determined via real-time quantitative polymerase chain reaction (RT-qPCR) or western blot (WB) analysis. ß-catenin nuclear localization was examined by western blotting and confocal microscopy. RESULTS: NOCA exhibited no significant cytotoxicity at concentrations below 20 µM and effectively inhibited H2O2-induced OS in PDLSCs. NOCA also restored ALP activity, mineralized nodule formation, and the expression of osteogenic markers in H2O2-stimulated PDLSCs. Mechanistically, NOCA increased p-ERK level and promoted ß-catenin translocation into the nucleus; however, blocking ERK pathway disrupted the osteogenic protection provided by NOCA and impaired its ability to induce ß-catenin nuclear translocation under OS conditions in PDLSCs. CONCLUSIONS: NOCA protected PDLSCs against H2O2-induced OS and effectively restored impaired osteogenic differentiation in PDLSCs by modulating the ERK/Wnt signaling pathway.
Subject(s)
Cell Differentiation , Hydrogen Peroxide , Osteogenesis , Oxidative Stress , Periodontal Ligament , Stem Cells , Periodontal Ligament/cytology , Periodontal Ligament/metabolism , Periodontal Ligament/drug effects , Humans , Oxidative Stress/drug effects , Stem Cells/metabolism , Stem Cells/drug effects , Hydrogen Peroxide/pharmacology , Hydrogen Peroxide/toxicity , Osteogenesis/drug effects , Cell Differentiation/drug effects , beta Catenin/metabolism , Cell Survival/drug effects , Wnt Signaling Pathway/drug effects , MAP Kinase Signaling System/drug effects , Cells, Cultured , Reactive Oxygen Species/metabolismABSTRACT
Dielectric capacitors are highly desired for electronic systems owing to their high-power density and ultrafast charge/discharge capability. However, the current dielectric capacitors suffer severely from the thermal instabilities, with sharp deterioration of energy storage performance at elevated temperatures. Here, guided by phase-field simulations, we conceived and fabricated the self-assembled metadielectric nanostructure with HfO2 as second-phase in BaHf0.17Ti0.83O3 relaxor ferroelectric matrix. The metadielectric structure can not only effectively increase breakdown strength, but also broaden the working temperature to 400 oC due to the enhanced relaxation behavior and substantially reduced conduction loss. The energy storage density of the metadielectric film capacitors can achieve to 85 joules per cubic centimeter with energy efficiency exceeding 81% in the temperature range from 25 °C to 400 °C. This work shows the fabrication of capacitors with potential applications in high-temperature electric power systems and provides a strategy for designing advanced electrostatic capacitors through a metadielectric strategy.
ABSTRACT
Cadmium (Cd) removal from soil is crucial as Cd enters the food chain and affect food safety, thus impose severe threaten to human health. We developed PPC@PC-Fe, a dual-functional core-shell sphere for efficient soil Cd reduction. The shell (PPC) was composed of encapsulated citric acid (CA) in a polylactic acid (PLA) and polyethylene glycol (PEG) network, which endows a function of activating Cd; and the core (PC-Fe) consisted of a polyacrylic acid/carboxymethyl chitosan (PAA/CMC) hydrogel with Fe3O4 nanoparticles to adsorb adjacent activated Cd. Upon water contact, the shell dissolved, releasing CA to activate soil Cd. Simultaneously, the swellable PC-Fe core absorbed water and expanded in size, promoting the disintegration of PLA in the shell, which triggered the automatic separation of core from shell, enabling the exposed PC-Fe core to rapidly adsorb Cd. Furthermore, the PC-Fe core can be magnetically removed after adsorption of Cd. Soil culture tests showed that 2 % PPC@PC-Fe reduced soil Cd from 6.009 mg/kg to 4.834 mg/kg in 10 days, with the acid-soluble Cd being the predominantly target to be activated and remove. This study demonstrates an effective stepwise activation and adsorption mechanism by a single carrier, with simple magnetic collection minimizing secondary pollution. It offers an innovative approach to the remediation of cadmium-contaminated sites in the field.
ABSTRACT
Allergic diseases like asthma, allergic rhinitis and dermatitis pose a significant global health burden, driving the search for novel therapies. The NLRP3 inflammasome, a key component of the innate immune system, is implicated in various inflammatory diseases. Upon exposure to allergens, NLRP3 undergoes a two-step activation process (priming and assembly) to form active inflammasomes. These inflammasomes trigger caspase-1 activation, leading to the cleavage of pro-inflammatory cytokines (IL-1ß and IL-18) and GSDMD. This process induces pyroptosis and amplifies inflammation. Recent studies in humans and mice strongly suggest a link between the NLRP3 inflammasome, IL-1ß, and IL-18, and the development of allergic diseases. However, further research is needed to fully understand NLRP3's specific mechanisms in allergies. This review aims to summarize the latest advances in NLRP3 activation and regulation. We will discuss small molecule drugs and natural products targeting NLRP3 as potential therapeutic strategies for allergic diseases.
Subject(s)
Hypersensitivity , Inflammasomes , Inflammation , NLR Family, Pyrin Domain-Containing 3 Protein , NLR Family, Pyrin Domain-Containing 3 Protein/metabolism , NLR Family, Pyrin Domain-Containing 3 Protein/immunology , Humans , Inflammasomes/metabolism , Inflammasomes/immunology , Animals , Hypersensitivity/immunology , Hypersensitivity/drug therapy , Hypersensitivity/metabolism , Hypersensitivity/therapy , Inflammation/immunology , Inflammation/metabolismABSTRACT
For the resource recovery of biomass waste, it is a challenge to simultaneously remove micro-/nano-plastics pollution but preserve organic resources. Wet oxidation is a promising technology for valorization of organic wastes through thermal hydrolysis and oxidation. This might in turn result in the degradation of microplastics in the presence of oxygen and high temperatures. Based on this hypothesis, this study quantified both microplastics and nanoplastics in an industrial-scale wet oxidation reactor from a full-size coverage perspective. Wet oxidation significantly reduced the size and mass of individual microplastics, and decreased total mass concentration of microplastics and nanoplastics by 94.8 % to 98.6 %. This technology also reduced the micro- and nanoplastic shapes and polymer types, resulting in a complete removal of fibers, clusters, polypropylene (PP) and poly(methyl methacrylate) (PMMA). The present study confirms that wet oxidation technology is effective in removing microplastics and nanoplastics while recovering organic waste.
Subject(s)
Microplastics , Oxidation-Reduction , Water Pollutants, Chemical/chemistry , Polypropylenes/chemistry , Plastics/chemistry , Polymethyl Methacrylate/chemistryABSTRACT
Diabetes mellitus (DM), an important public health problem, aggravates the global economic burden. Diabetic encephalopathy (DE) is a serious complication of DM in the central nervous system. Metformin has been proven to improve DE. However, the mechanism is still unclear. In this study, the db/db mice, a common model used for DE, were employed to explore and study the neuroprotective effect of metformin and related mechanisms. Behavioral tests indicated that metformin (100 or 200 mg/kg/day) could significantly improve the learning and memory abilities of db/db mice. The outcomes from the oral glucose tolerance test (OGTT) and insulin tolerance test (ITT) demonstrate that metformin effectively modulates glucose and insulin signaling pathways in db/db mice. The results of body weight and blood lipid panel (total cholesterol, triglycerides, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol) show that metformin promotes the level of lipid metabolism in db/db mice. Furthermore, data from oxidative stress assays, which measured levels of malondialdehyde, superoxide dismutase, catalase, and glutathione peroxidase, suggest that metformin suppresses oxidative stress-induced brain damage in db/db mice. In addition, western blot, Nissl staining, and immunofluorescence results showed that metformin increased the expressions of nerve growth factor and postsynaptic density 95 and repaired neuronal structural damage. For the mechanism study, metformin activated SIRT1 and inhibited the expression of NLRP3 inflammasome (NLRP3, ASC, caspase-1, IL-1ß, and IL-18) and inflammatory cytokines (TNFα and IL-6). In conclusion, metformin could ameliorate cognitive dysfunction through the SIRT1/NLRP3 pathway, which might be a promising mechanism for DE treatment.
ABSTRACT
Introduction: Studies on the use of direct oral anticoagulants (DOACs) for preventing venous thromboembolism (VTE) in hospitalized cancer patients are lacking. Therefore, we conducted a multicenter retrospective cohort study to evaluate the efficacy and safety of DOACs versus low-molecular-weight heparin (LMWH) for the primary prevention of VTE in hospitalized cancer patients. Methods: Clinical outcomes included thrombosis, VTE, other thrombosis, all bleeding, major bleeding, nonmajor bleeding, and all-cause death. A 1:1 cohort of rivaroxaban and LMWH patients was created by propensity score matching. Results: A total of 2,385 cancer patients were included in this study. During the 3-month follow-up period, 129 (5.4%) thrombosis events occurred, 63 (2.7%) of which were VTEs and 66 (2.8%) of which were other thrombosis events. All bleeding occurred in 163 (6.8%) patients, 68 (2.9%) had major bleeding, and 95 (4.0%) had nonmajor bleeding. All-cause deaths occurred in 113 (4.7%) patients. After adjusting for various confounders, the incidence of thrombosis and other thromboses was significantly lower in the rivaroxaban group than in the LMWH group [OR 0.543, 95% CI (0.343-0.859), p = 0.009; OR 0.461, 95% CI (0.241-0.883), p = 0.020]. There were no significant differences in incidence of VTE, total bleeding, major bleeding, nonmajor bleeding, or all-cause death. Conclusion: In oncology patients receiving thromboprophylaxis, rivaroxaban has a lower incidence of thrombosis and other thrombosis and a similar incidence of VTE as LMWH and does not increase the risk of bleeding. Rivaroxaban may be an attractive alternative to LMWH for preventing VTE in hospitalized cancer patients.
ABSTRACT
The normal modes, i.e., the eigensolutions to the dispersion relation equation, are the most fundamental properties of a plasma. The real part indicates the intrinsic oscillation frequency while the imaginary part the Landau damping rate. In most of the literature, the normal modes of quantum plasmas are obtained by means of small damping approximation, which is invalid for high-k modes. In this paper, we solve the exact dispersion relations via the analytical continuation scheme, and, due to the multi-value nature of the Fermi-Dirac distribution, reformation of the complex Riemann surface is required. It is found that the topological shape of the root locus in quantum plasmas is quite different from classical ones, in which both real and imaginary frequencies of high-k modes increase with k steeper than the typical linear behavior in classical plasmas. As a result, the time-evolving behavior of a high-k initial perturbation becomes ballistic-like in quantum plasmas.
ABSTRACT
In order to augment the efficacy of the intelligent evaluation model for assessing the suitability of ice and snow tourism, this study refines the model by incorporating the Long Short-Term Memory (LSTM) network within the framework of the Internet of Things (IoT). The investigation commences with an elucidation of the application of IoT technology in environmental detection. After this, an analysis is conducted on the structure of LSTM and its merits in the realm of time series prediction. Ultimately, a novel model for appraising the suitability of ice and snow tourism is formulated. The efficacy of this model is substantiated through empirical experiments. The results of these experiments reveal that the refined model exhibits exceptional performance across diverse climatic conditions, encompassing mild, cold, humid, and arid climates. In regions characterized by mild climates, the predictive accuracy of the refined model progressively ascends from 88% in the initial quarter to 94% in the fourth quarter, surpassing the capabilities of conventional models. Consistently robust performance is demonstrated by the refined model throughout each quarter. In terms of operational efficiency, comparative analysis indicates that the refined model attains a moderate level, manifesting a 30-33 s runtime and maintaining a Central Processing Unit (CPU) usage rate between 40 and 43%. This observation implies that the refined model adeptly balances precision against resource consumption. Consequently, this study holds significance as a scholarly reference for the integration of IoT and LSTM networks in the domain of tourism evaluation.
ABSTRACT
Reference electrode is the foundation of electrochemical study; thus, most electrode materials are tested in a three-electrode mode to acquire potential-dependent kinetics. However, it is difficult to directly use conventional reference electrodes to detect potential information in solid electrolyte devices due to their compact assembly structure. Therefore, the kinetic study of an electrochemical device faces challenges in precise identification of specific problems originating from the anode or cathode. Here, focusing on proton exchange membrane water electrolysis, we design a solid electrolyte reversible hydrogen electrode (SE-RHE), which can be used for electrode diagnosis under various operating conditions. Compared to the reference electrodes reported in the literature, which are mainly based on liquid electrolyte, the SE-RHE is highly sensitive and compatible, as well as easy to assemble. The potential deviation is less than ±0.5 mV, and the cell voltage derived from the electrode potential well reproduces the value that was directly measured with a deviation less than 0.2%. The reference electrode developed in this work enables the kinetic study of a specific electrode rather than the entire cell. For instance, an interesting observation is that the cathode shows distinct stability under stable and fluctuating operations. Differing from the high stability under stable operation, the cathode degrades significantly under fluctuating operations.
ABSTRACT
BACKGROUND: The prevalence of dementia around the world is increasing, and these patients are more likely to have cognitive impairments, mood and anxiety disorders (depression, anxiety, and panic disorder), and attention deficit disorders over their lifetime. Previous studies have proven that melatonin could improve memory loss, but its specific mechanism is still confused. METHODS: In this study, we used in vivo and in vitro models to examine the neuroprotective effect of melatonin on scopolamine (SCOP)-induced cognitive dysfunction. The behavioral tests were performed. 18F-FDG PET imaging was used to assess the metabolism of the brain. Protein expressions were determined through kit detection, Western blot, and immunofluorescence. Nissl staining was conducted to reflect neurodegeneration. MTT assay and RNAi transfection were applied to perform the in vitro experiments. RESULTS: We found that melatonin could ameliorate SCOP-induced cognitive dysfunction and relieve anxious-like behaviors or HT22 cell damage. 18F-FDG PET-CT results showed that melatonin could improve cerebral glucose uptake in SCOP-treated mice. Melatonin restored the cholinergic function, increased the expressions of neurotrophic factors, and ameliorated oxidative stress in the brain of SCOP-treated mice. In addition, melatonin upregulated the expression of silent information regulator 1 (SIRT1), which further relieved endoplasmic reticulum (ER) stress by decreasing the expression of phosphorylate inositol-requiring enzyme (p-IRE1α) and its downstream, X-box binding protein 1 (XBP1). CONCLUSIONS: These results indicated that melatonin could ameliorate SCOP-induced cognitive dysfunction through the SIRT1/IRE1α/XBP1 pathway. SIRT1 might be the critical target of melatonin in the treatment of dementia.
Subject(s)
Cognitive Dysfunction , Melatonin , Scopolamine , Signal Transduction , Sirtuin 1 , X-Box Binding Protein 1 , Melatonin/pharmacology , Melatonin/therapeutic use , Animals , Sirtuin 1/metabolism , Cognitive Dysfunction/chemically induced , Cognitive Dysfunction/drug therapy , Cognitive Dysfunction/metabolism , X-Box Binding Protein 1/metabolism , Mice , Male , Signal Transduction/drug effects , Mice, Inbred C57BL , Neuroprotective Agents/pharmacology , Neuroprotective Agents/therapeutic use , Maze Learning/drug effectsABSTRACT
Familiar information is more likely to be accepted as true. This illusory truth effect has a tremendous negative impact on misinformation intervention. Previous studies focused on the familiarity from repeated exposure in the laboratory, ignoring preexisting familiarity with real-world misinformation. Over three studies (total N = 337), we investigated the cognitive mechanisms behind the truth biases from these two familiarity sources, and whether fact-checking can curb such biased truth perceptions. Studies 1 and 2 found robust truth effects induced by two sources of familiarity but with different cognitive processes. According to the cognitive process model, repetition-induced familiarity reduced decision prudence. Preexisting familiarity instead enhanced truth-congruent evidence accumulation. Study 3 showed that pre-exposing statements with warning flags eliminated the bias to truth induced by repetition but not that from preexisting familiarity. These repeated statements with warning labels also reduced decision caution. These findings furthered the understanding of how different sources of familiarity affect truth perceptions and undermine the intervention through different cognitive processes.
ABSTRACT
BACKGROUND: Insomnia is common in college students, but its impact on health and wellbeing is often neglected. Enhancing sleep quality through targeted interventions could improve overall health and reduce the risk of consequent co-morbidities and mental health problems. Qigong exercises have been shown to significantly improve sleep quality and relieve insomnia. Three-circle Post Standing (TCPS) can help integrate body, breath, and mind, a fundamental principle of Qigong that promotes holistic wellbeing. In this clinical trial, we aim to (1) evaluate the feasibility, safety, and therapeutic efficacy of administering TCPS to improve sleep quality and quality of life in college students with insomnia; (2) explore the neurophysiological mechanisms underlying the mind adjustments mediated by TCPS in insomnia; (3) investigate body and breath pathophysiology mediated by TCPS in insomnia; and (4) assess the long-term efficacy of TCPS in terms of sleep quality and quality of life. METHODS: This will be a prospective, parallel, four-arm, double-blind randomized controlled trial to investigate the effects and underlying mechanisms of TCPS on college students with insomnia. One hundred college students meeting diagnostic criteria for insomnia will be randomly assigned to receive either 14 weeks of standardized TCPS training (two weeks of centralized training followed by 12 weeks of supervised training) or sham-control Post Standing training. Efficacy outcomes including sleep quality, quality of life, neurophysiological assessments, plantar pressure, biomechanical balance, and physical measures will be collected at baseline, eight weeks (mid-point of supervised training), and 14 weeks (end of supervised training). Sleep quality and quality of life will also be evaluated during the four- and eight-week follow-up. DISCUSSION: This trial will be an important milestone in the development of new therapeutic approaches for insomnia and should be easily implementable by college students with insomnia. The neuro- and pathophysiological assessments will provide new insights into the mechanisms underlying TCPS. CLINICAL TRIAL REGISTRATION: This trial has been registered in the China Clinical Trials Registry (registration number: ChiCTR2400080763).
Subject(s)
Qigong , Sleep Initiation and Maintenance Disorders , Students , Humans , Sleep Initiation and Maintenance Disorders/therapy , Qigong/methods , Double-Blind Method , Universities , Young Adult , Quality of Life , Prospective Studies , Male , Adult , Female , Sleep QualityABSTRACT
BACKGROUND: To compare the effects of proton pump inhibitor (PPI) and histamine-2 receptor antagonist (H2RA) use on the occurrence of acute kidney injury (AKI) in septic patients at high risk for developing stress ulcers. METHODS: Using the Medical Information Mart for Intensive Care IV version 2.2 database, septic patients with high-risk factors for stress ulcers (i.e., shock, coagulopathy, invasive mechanical ventilation, or chronic liver diseases) were included. Exposures included PPIs and H2RAs within 24 h of intensive care unit (ICU) admission or prior to ICU admission. The primary end point was severe sepsis-associated AKI as defined by the Kidney Disease Improving Global Outcomes criteria stage 3 (KDIGO-3). Propensity score matching (PSM) was performed to balance baseline characteristics. Multivariable Cox proportional hazards regression was used to estimate the effect size. RESULTS: 4731 PPI users and 4903 H2RA users were included. After PSM, there were 1785 pairs exposed to PPIs and H2RAs. In the PSM cohort, the cumulative incident KDIGO-3 rate was higher in the PPI group than in the H2RA group (log-rank test, p = 0.009). Regression analyses showed that PPI exposure [adjusted hazard ratio 1.32, 95% confidence interval (CI) 1.11-1.58, p = 0.002] was associated with incident KDIGO-3 compared with H2RA use. This association remained consistent in sensitivity analyses. Additionally, the PPI group had a higher need for kidney replacement therapy compared with the H2RA group (3.6% vs. 2.1%, P = 0.012). CONCLUSIONS: Among septic patients at high risk for developing stress ulcers, PPI exposure was associated with incident KDIGO-3 AKI compared with H2RA use.
Subject(s)
Acute Kidney Injury , Histamine H2 Antagonists , Proton Pump Inhibitors , Sepsis , Humans , Proton Pump Inhibitors/adverse effects , Proton Pump Inhibitors/administration & dosage , Proton Pump Inhibitors/therapeutic use , Histamine H2 Antagonists/therapeutic use , Histamine H2 Antagonists/adverse effects , Male , Female , Sepsis/complications , Middle Aged , Aged , Risk Factors , Intensive Care Units , Retrospective Studies , Propensity Score , Peptic Ulcer/complications , Peptic Ulcer/drug therapy , Cohort StudiesABSTRACT
BACKGROUND: The strong invasiveness and rapid expansion of dengue virus (DENV) pose a great challenge to global public health. However, dengue epidemic patterns and mechanisms at a genetic scale, particularly in term of cross-border transmissions, remain poorly understood. Importation is considered as the primary driver of dengue outbreaks in China, and since 1990 a frequent occurrence of large outbreaks has been triggered by the imported cases and subsequently spread to the western and northern parts of China. Therefore, this study aims to systematically reveal the invasion and diffusion patterns of DENV-1 in Guangdong, China from 1990 to 2019. METHODS: These analyses were performed on 179 newly assembled genomes from indigenous dengue cases in Guangdong, China and 5152 E gene complete sequences recorded in Chinese mainland. The genetic population structure and epidemic patterns of DENV-1 circulating in Chinese mainland were characterized by phylogenetics, phylogeography, phylodynamics based on DENV-1 E-gene-based globally unified genotyping framework. RESULTS: Multiple serotypes of DENV were co-circulating in Chinese mainland, particularly in Guangdong and Yunnan provinces. A total of 189 transmission clusters in 38 clades belonging to 22 subgenotypes of genotype I, IV and V of DENV-1 were identified, with 7 Clades of Concern (COCs) responsible for the large outbreaks since 1990. The epidemic periodicity was inferred from the data to be approximately 3 years. Dengue transmission events mainly occurred from Great Mekong Subregion-China (GMS-China), Southeast Asia (SEA), South Asia Subcontinent (SASC), and Oceania (OCE) to coastal and land border cities respectively in southeastern and southwestern China. Specially, Guangzhou was found to be the most dominant receipting hub, where DENV-1 diffused to other cities within the province and even other parts of the country. Genome phylogeny combined with epidemiological investigation demonstrated a clear local consecutive transmission process of a 5C1 transmission cluster (5C1-CN4) of DENV-1 in Guangzhou from 2013 to 2015, while the two provinces of Guangdong and Yunnan played key roles in ongoing transition of dengue epidemic patterns. In contextualizing within Invasion Biology theories, we have proposed a derived three-stage model encompassing the stages of invasion, colonization, and dissemination, which is supposed to enhance our understanding of dengue spreading patterns. CONCLUSIONS: This study demonstrates the invasion and diffusion process of DENV-1 in Chinese mainland within a global genotyping framework, characterizing the genetic diversities of viral populations, multiple sources of importation, and periodic dynamics of the epidemic. These findings highlight the potential ongoing transition trends from epidemic to endemic status offering a valuable insight into early warning, prevention and control of rapid spreading of dengue both in China and worldwide.
Subject(s)
Dengue Virus , Dengue , Genotype , Phylogeny , Serogroup , Dengue Virus/genetics , Dengue Virus/classification , Dengue Virus/physiology , China/epidemiology , Dengue/epidemiology , Dengue/virology , Dengue/transmission , Humans , Disease Outbreaks , Phylogeography , Genome, ViralABSTRACT
Dihuang Baoyuan Granules is a prescription endorsed by HU Tianbao, a renowned and elderly Chinese medicine practitioner from Beijing, and has demonstrated definite clinical efficacy. The composition of this prescription is intricate as it includes 7 distinct herbal medicines. This study aims to analyze the chemical composition of Dihuang Baoyuan Granules, evaluate its efficacy in the treatment of diabetes and analyze the distribution of the drug components in the plasma, liver, and kidney after administration. The findings will serve as a reference for future research on pharmacodynamic substances of this prescription. UHPLC-LTQ-Orbitrap MS was employed to analyze the main chemical components of Dihuang Baoyuan Granules. A Waters ACQUITY Premier HSS T3 column(2.1 mm×100 mm, 1.8 µm) was used for chromatographic separation with 0.1% formic acid(A)-acetonitrile(B) as the mobile phases in a gradient elution at a flow rate of 0.3 mL·min~(-1). Electrospray ionization(ESI) source was used to acquire data in positive and negative ion modes. Furthermore, a rat model of diabetes mellitus was established by feeding with a high-sugar high-fat diet, and injection with streptozocin at a dose of 35 mg·kg~(-1), and the modeled rats were then administrated with Dihuang Baoyuan Granules. The fasting blood glucose, hemoglobin A1c, and other relevant indicators were measured, and the substances present in the plasma, liver, and kidney were identified. By reference to quasi-molecular ions, MS/MS fragment ions, MS spectra of reference substances, and compound information in available reports, 191 components were identified in Dihuang Baoyuan Granules, including 29 alkaloids, 24 flavonoids, 22 organic acids, 16 amino acids, 12 terpenes, 11 steroid saponins, 9 sugars, 8 phenylethanoid glycosides, 8 nucleosides, 2 phenylpropanoids, and 49 others compounds. Eighty-three chemical components were identified in rat plasma, 109 in the liver, and 98 in the kidney. Component identification and characterization of Dihuang Baoyuan Granules in vitro and in vivo provide efficacy information and guidance for the basic research on the pharmacodynamic substances and further clinical application of this prescription.
Subject(s)
Drugs, Chinese Herbal , Rats, Sprague-Dawley , Drugs, Chinese Herbal/chemistry , Drugs, Chinese Herbal/pharmacokinetics , Chromatography, High Pressure Liquid/methods , Animals , Rats , Male , Humans , Liver/drug effects , Liver/chemistry , Liver/metabolism , Mass Spectrometry/methods , Kidney/drug effects , Kidney/chemistry , Diabetes Mellitus, Experimental/drug therapy , Diabetes Mellitus, Experimental/blood , Diabetes Mellitus/drug therapyABSTRACT
Protein ubiquitination is an enzymatic cascade reaction and serves as an important protein post-translational modification (PTM) that is involved in the vast majority of cellular life activities. The key enzyme in the ubiquitination process is E3 ubiquitin ligase (E3), which catalyzes the binding of ubiquitin (Ub) to the protein substrate and influences substrate specificity. In recent years, the relationship between the subfamily of neuron-expressed developmental downregulation 4 (NEDD4), which belongs to the E3 ligase system, and digestive diseases has drawn widespread attention. Numerous studies have shown that NEDD4 and NEDD4L of the NEDD4 family can regulate the digestive function, as well as a series of related physiological and pathological processes, by controlling the subsequent degradation of proteins such as PTEN, c-Myc, and P21, along with substrate ubiquitination. In this article, we reviewed the appropriate functions of NEDD4 and NEDD4L in digestive diseases including cell proliferation, invasion, metastasis, chemotherapeutic drug resistance, and multiple signaling pathways, based on the currently available research evidence for the purpose of providing new ideas for the prevention and treatment of digestive diseases.
Subject(s)
Nedd4 Ubiquitin Protein Ligases , Ubiquitination , Humans , Nedd4 Ubiquitin Protein Ligases/metabolism , Nedd4 Ubiquitin Protein Ligases/genetics , Digestive System Diseases/metabolism , Digestive System Diseases/pathology , Animals , Signal Transduction , Cell Proliferation , Ubiquitin-Protein Ligases/metabolism , Ubiquitin-Protein Ligases/geneticsABSTRACT
We proposed that the pharynx, as a common organ of the respiratory and digestive tracts, may be a respiratory and digestive tract cross cryptic transmission pathway for 2019-nCoV infection from the nasal cavities to the pharynx and lung, then to nasal cavities by aerosol (respiratory route) to the pharynx and the gastrointestinal tract, then to the oral cavity by feces (fecal-oral route) and to pharynx, lungs, or gastrointestinal tract.
Subject(s)
COVID-19 , Pharynx , SARS-CoV-2 , Humans , COVID-19/transmission , Pharynx/virology , Cross Infection/transmission , Gastrointestinal Tract/virology , Feces/virology , Feces/microbiology , Respiratory Tract Infections/transmission , Respiratory Tract Infections/virologyABSTRACT
Background: There is growing evidence of associations between the gut microbiota and anxiety disorders, where changes in gut microbiotas may affect brain function and behavior via the microbiota-gut-brain axis. However, population-level studies offering a higher level of evidence for causality are lacking. Our aim was to investigate the specific gut microbiota and associated metabolites that are closely related to anxiety disorders to provide mechanistic insights and novel management perspectives for anxiety disorders. Method: This study used summary-level data from publicly available Genome-Wide Association Studies (GWAS) for 119 bacterial genera and the phenotype "All anxiety disorders" to reveal the causal effects of gut microbiota on anxiety disorders and identify specific bacterial genera associated with anxiety disorders. A two-sample, bidirectional Mendelian randomization (MR) design was deployed, followed by comprehensive sensitivity analyses to validate the robustness of results. We further conducted multivariable MR (MVMR) analysis to investigate the potential impact of neurotransmitter-associated metabolites, bacteria-associated dietary patterns, drug use or alcohol consumption, and lifestyle factors such as smoking and physical activity on the observed associations. Results: Bidirectional MR analysis identified three bacterial genera causally related to anxiety disorders: the genus Eubacterium nodatum group and genus Ruminococcaceae UCG011 were protective, while the genus Ruminococcaceae UCG011 was associated with an increased risk of anxiety disorders. Further MVMR suggested that a metabolite-dependent mechanism, primarily driven by tryptophan, tyrosine, phenylalanine, glycine and cortisol, which is consistent with previous research findings, probably played a significant role in mediating the effects of these bacterial genera to anxiety disorders. Furthermore, modifying dietary pattern such as salt, sugar and processed meat intake, and adjusting smoking state and physical activity levels, appears to be the effective approaches for targeting specific gut microbiota to manage anxiety disorders. Conclusion: Our findings offer potential avenues for developing precise and effective management approaches for anxiety disorders by targeting specific gut microbiota and associated metabolites.
ABSTRACT
The high cost of proton exchange membrane water electrolysis (PEMWE) originates from the usage of precious materials, insufficient efficiency, and lifetime. In this work, an important degradation mechanism of PEMWE caused by dynamics of ionomers over time in anode catalyst layer (ACL), which is a purely mechanical degradation of microstructure, is identified. Contrary to conventional understanding that the microstructure of ACL is static, the micropores are inclined to be occupied by ionomers due to the localized swelling/creep/migration, especially near the ACL/PTL (porous transport layer) interface, where they form transport channels of reactant/product couples. Consequently, the ACL with increased ionomers at PTL/ACL interface exhibit rapid and continuous degradation. In addition, a close correlation between the microstructure of ACL and the catalyst ink is discovered. Specifically, if more ionomers migrate to the top layer of the ink, more ionomers accumulate at the ACL/PEM interface, leaving fewer ionomers at the ACL/PTL interface. Therefore, the ionomer distribution in ACL is successfully optimized, which exhibits reduced ionomers at the ACL/PTL interface and enriches ionomers at the ACL/PEM interface, reducing the decay rate by a factor of three when operated at 2.0 A cm-2 and 80 °C. The findings provide a general way to achieve low-cost hydrogen production.