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Cataracts are characterized as a disease affecting lens opacity. Endoplasmic reticulum (ER) stress can cause lens epithelial cell (LEC) dysfunction, affecting normal lens transparency and function, but the role of Tribbles 3 (TRB3), an inducible gene of ER stress, in cataracts is poorly understood. This study explored how TRB3 promotes cataract progression through ER stress. We administered a subcutaneous injection of sodium selenite at a dosage of 3.46 mg/kg to rats to create an animal model of cataracts. Additionally, we exposed rat LEC cells to 0.01 µM tunicamycin (TM) for 24 h to establish a cell model of ER stress. The detection of related genes and proteins was performed via RTâqPCR and Western blot techniques. Flow cytometry, along with JC-1, TUNEL, and HE staining, was employed to assess damage to cells and lens tissues. This study revealed that TRB3 was abnormally highly expressed in both a cataract rat model and an ER stress cell model. Knocking down TRB3 has a similar effect as treatment with an ER stress inhibitor, effectively reversing the ER stress and apoptosis induced by TM. This effect includes increasing the mitochondrial membrane potential in LEC cells, lowering reactive oxygen species (ROS) levels, increasing ATP production, suppressing the expression of the apoptosis-related proteins Bax and C-caspase-3, increasing Bcl-2 expression, and decreasing apoptosis. Furthermore, TRB3 knockdown improved the pathological conditions of rat lenses and inhibited mitochondrial dysfunction and cell apoptosis to relieve the development of cataracts in rats. Mechanistically, CHOP promotes the expression of TRB3 by binding to the TRB3 promoter, thereby activating ER stress, leading to mitochondrial dysfunction and cell apoptosis in LEC cells and accelerating the development of cataracts. According to our findings, targeting TRB3 expression inhibition could emerge as a novel approach for cataract therapy.
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Background: Diabetic retinopathy (DR) is considered one of the most severe complications of diabetes mellitus, but its pathogenesis is still unclear. We hypothesize that certain genes exert a pivotal influence on the progression of DR. This study explored biomarkers for the diagnosis and treatment of DR through bioinformatics analysis. Methods: Within the GSE221521 and GSE189005 datasets, candidate genes were acquired from intersections of genes obtained using WGCNA and DESeq2 packages. Mendelian randomization (MR) analysis selected candidate biomarkers exhibiting causal relationships with DR. Receiver Operating Characteristic (ROC) analysis determined the diagnostic efficacy of biomarkers, the expression levels of biomarkers were verified in the GSE221521 and GSE189005 datasets, and a nomogram for diagnosing DR was constructed. Enrichment analysis delineated the roles and pathways associated with the biomarkers. Immune infiltration analysis analyzed the differences in immune cells between DR and control groups. The miRNet and networkanalyst databases were then used to predict the transcription factors (TFs) and miRNAs, respectively, of biomarkers. Finally, RT-qPCR was used to verify the expression of the biomarkers in vitro. Results: MR analysis identified 13 candidate biomarkers that had causal relationships with DR. The ROC curve demonstrated favorable diagnostic performance of three biomarkers (OSER1, HIPK2, and DDRGK1) for DR, and their expression trends were consistent across GSE221521 and GSE189005 datasets. The calibration curves and ROC curves indicated good predictive performance of the nomogram. The biomarkers were enriched in pathways of immune, cancer, amino acid metabolism, and oxidative phosphorylation. Ten immune cell lines showed notable disparities between the DR and control groups. Among them, effector memory CD8+ T cells, plasmacytoid dendritic cells, and activated CD4+ T cells exhibited good correlation with biomarker expression. The TF-mRNA-miRNA network suggested that hsa-mir-92a-3p, GATA2, and RELA play important roles in biomarker targeting for DR. RT-qPCR results also demonstrated a notably high expression of HIPK2 in patients with DR, whereas notably low expression of OSER1. Conclusion: OSER1, HIPK2, and DDRGK1 were identified as biomarkers for DR. The study findings provide novel insights into the pathogenesis of DR.
Subject(s)
Biomarkers , Diabetic Retinopathy , Gene Expression Profiling , Mendelian Randomization Analysis , Humans , Diabetic Retinopathy/genetics , Diabetic Retinopathy/diagnosis , Computational Biology/methods , MicroRNAs/genetics , Gene Regulatory Networks , TranscriptomeABSTRACT
OBJECTIVE: Overweight and obesity among adolescents are grave public health issues around the world. Although the conditions that contribute to obesity have been extensively researched, little is known about how multiple conditions interact to cause overweight and obesity. The current study intends to investigate the histomorphic configuration pathways of several conditions of adolescent overweight and obesity by gender. METHOD: The data came from a social survey conducted in June 2021 in Changchun, Jilin Province, China. The sample collected was 14-year-old adolescents, including 167 boys and 137 girls. The school physicians examined the participants' weight and height, and questionnaires were used to collect risk indicators from adolescents, such as sleep duration, electronic screens times, consumption of sugary drinks and fried foods, and physical activity. Simultaneously, a Fuzzy Qualitative Comparative Analysis will be performed to investigate the combinations of diverse conditions. RESULT: We found that there is no determining necessary condition that, once present, directly determines that an individual is in a state of overweight and obesity. Simultaneously, this study revealed nine alternative configurational paths of overweight and obesity in teenagers of different genders, with a concordance of 0.805 for six male groupings and 0.916 for three female groupings. The outcomes of overweight obesity in adolescents under different genders are similar but not identical. CONCLUSION: This study examined the interactions of a number of conditions from the individual, behavioral, learning and living environment that led to the same overweight obese outcome among adolescents of different genders. Our research will be useful to policymakers in that interventions should take into account the combined effects of a number of different aspects rather than focusing on a single factor that causes overweight and obesity.
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This study presents an efficient approach for the precise detection of chlorine gas (Cl2) and hydrogen chloride (HCl), harmful pollutants frequently emitted from chlor-alkali and various industrial processes. These substances, even in trace amounts, pose significant health risks. Ion mobility spectrometry (IMS), known for its sensitivity in pollutant detection, traditionally struggles to differentiate between Cl2 and HCl due to the similarity of their product ions, Cl-. To overcome this limitation, we introduce a novel technique combining dopant-assisted negative photoionization ion mobility spectrometry (DANP-IMS) with an automatic semiconductor cooling system. This unique combination utilizes the differential cryogenic removal efficiencies of Cl2 and HCl to segregate these gases before analysis. By applying DANP-IMS, we achieved selective measurement of Cl- ion signal intensities under both standard and cryogenic conditions, facilitating the accurate quantification of total chlorine and Cl2 levels. We then determined HCl concentrations by deducting the Cl2 signal from the total chlorine readings. Our approach demonstrated detection limits of 2.0 parts per billion (ppb) for Cl2 and 0.8 ppb for HCl, across a linear detection range of 0-200 ppb. Moreover, our method's capability for real-time atmospheric monitoring of Cl2 and HCl near industrial sites underscores its utility for environmental monitoring, offering a robust solution for the separate and precise measurement of these pollutants.
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Tuberculosis (TB), an airborne infectious disease caused by Mycobacterium tuberculosis, has become the leading cause of death. The subsequent emergence of multidrug-resistant, extensively drug-resistant and totally drug-resistant strains, brings an urgent need to discover novel anti-TB drugs. Among them, microbial-derived anti-mycobacterial peptides, including ribosomally synthesized and post-translationally modified peptides (RiPPs) and multimodular nonribosomal peptides (NRPs), now arise as promising candidates for TB treatment. This review presents 96 natural RiPP and NRP families from bacteria and fungi that have broad spectrum in vitro activities against non-resistant and drug-resistant mycobacteria. In addition, intracellular targets of 22 molecules are the subject of much attention. Meanwhile, chemical features of 38 families could be modified in order to improve properties. In final, structure-activity relationships suggest that the modifications of various groups, especially the peptide side chains, the amino acid moieties, the cyclic peptide skeletons, various special groups, stereochemistry and entire peptide chain length are important for increasing the potency.
Subject(s)
Antitubercular Agents , Mycobacterium tuberculosis , Antitubercular Agents/pharmacology , Antitubercular Agents/chemistry , Antitubercular Agents/chemical synthesis , Mycobacterium tuberculosis/drug effects , Humans , Microbial Sensitivity Tests , Structure-Activity Relationship , Peptides/pharmacology , Peptides/chemistry , Peptides/chemical synthesis , Molecular StructureABSTRACT
PURPOSE: Associations were assessed between demographic/lifestyle factors and tear film breakup time (TBUT) defined dry eye disease (DED) in China. METHODS: The cross-sectional study involved 50,280 subjects (54 ± 17 y) in 217 clinics (25 provinces). Data included sleep disorders; digital screen exposure; and use of cosmetics, contact lenses, and eye drops (for asthenopia). Clinical examinations included TBUT; Schirmer I test; meibomian gland plug status. TBUT-defined DED was TBUT <10 s, with TBUT ≤5 s also considered (i.e., short TBUT-type DED), either unilateral or bilateral. RESULTS: TBUT-defined DED was present in 81.6 % overall. The highest rates were in those 71 years or older, living in the north, with chronic daily sleep disorder, or daily cosmetic application; or daily digital screen exposure for 5 years, contact lenses 4 h, or 3 months eye drops. Compared with those without TBUT-defined DED, those with TBUT-defined DED showed lower Schirmer I results and more severe meibomian gland plug status (each, P < 0.001). Independent risk factors of DED were: aging; living in the southwest; daily digital screen exposure ≥3 h; and occasional cosmetic use. Risk factors of DED TBUT ≤5 s were: living in the southwest; wearing contact lenses (>3 y); and using eye drops. Rates of unilateral and bilateral DED were comparable. CONCLUSIONS: DED in China is more likely in the aged and those in the north/southwest. DED rates increase with digital screen exposure, and use of cosmetics, contact lenses, or eye drops for asthenopia. Unilateral DED should be treated as promptly as bilateral.
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In paraquat (PQ)induced acute lung injury (ALI)/ acute respiratory distress syndrome, PQ disrupts endothelial cell function and vascular integrity, which leads to increased pulmonary leakage. Anthrahydroquinone2,6disulfonate (AH2QDS) is a reducing agent that attenuates the extent of renal injury and improves survival in PQintoxicated SpragueDawley (SD) rats. The present study aimed to explore the beneficial role of AH2QDS in PQinduced ALI and its related mechanisms. A PQintoxicated ALI model was established using PQ gavage in SD rats. Human pulmonary microvascular endothelial cells (HPMECs) were challenged with PQ. Superoxide dismutase, malondialdehyde, reactive oxygen species and nitric oxide (NO) fluorescence were examined to detect the level of oxidative stress in HPMECs. The levels of TNFα, IL1ß and IL6 were assessed using an ELISA. Transwell and Cell Counting Kit8 assays were performed to detect the migration and proliferation of the cells. The pathological changes in lung tissues and blood vessels were examined by haematoxylin and eosin staining. Evans blue staining was used to detect pulmonary microvascular permeability. Western blotting was performed to detect target protein levels. Immunofluorescence and immunohistochemical staining were used to detect the expression levels of target proteins in HPMECs and lung tissues. AH2QDS inhibited inflammatory responses in lung tissues and HPMECs, and promoted the proliferation and migration of HPMECs. In addition, AH2QDS reduced pulmonary microvascular permeability by upregulating the levels of vascular endothelialcadherin, zonula occludens1 and CD31, thereby attenuating pathological changes in the lungs in rats. Finally, these effects may be related to the suppression of the phosphatidylinositol3kinase (PI3K)/protein kinase B (AKT)/endothelialtype NO synthase (eNOS) signalling pathway in endothelial cells. In conclusion, AH2QDS ameliorated PQinduced ALI by improving alveolar endothelial barrier disruption via modulation of the PI3K/AKT/eNOS signalling pathway, which may be an effective candidate for the treatment of PQinduced ALI.
Subject(s)
Acute Lung Injury , Capillary Permeability , Lung , Nitric Oxide Synthase Type III , Paraquat , Phosphatidylinositol 3-Kinases , Proto-Oncogene Proteins c-akt , Rats, Sprague-Dawley , Signal Transduction , Animals , Acute Lung Injury/metabolism , Acute Lung Injury/drug therapy , Acute Lung Injury/chemically induced , Acute Lung Injury/pathology , Proto-Oncogene Proteins c-akt/metabolism , Nitric Oxide Synthase Type III/metabolism , Capillary Permeability/drug effects , Phosphatidylinositol 3-Kinases/metabolism , Humans , Male , Signal Transduction/drug effects , Lung/pathology , Lung/metabolism , Lung/drug effects , Paraquat/adverse effects , Paraquat/toxicity , Rats , Endothelial Cells/metabolism , Endothelial Cells/drug effects , Oxidative Stress/drug effectsABSTRACT
Glutamate is one of the most important excitatory neurotransmitters within the mammalian central nervous system. The role of glutamate in regulating neural network signaling transmission through both synaptic and extra-synaptic paths highlights the importance of the real-time and continuous monitoring of its concentration and dynamics in living organisms. Progresses in multidisciplinary research have promoted the development of electrochemical glutamate sensors through the co-design of materials, interfaces, electronic devices, and integrated systems. This review summarizes recent works reporting various electrochemical sensor designs and their applicability as miniaturized neural probes to in vivo sensing within biological environments. We start with an overview of the role and physiological significance of glutamate, the metabolic routes, and its presence in various bodily fluids. Next, we discuss the design principles, commonly employed validation models/protocols, and successful demonstrations of multifunctional, compact, and bio-integrated devices in animal models. The final section provides an outlook on the development of the next generation glutamate sensors for neuroscience and neuroengineering, with the aim of offering practical guidance for future research.
Subject(s)
Central Nervous System , Electrochemical Techniques , Glutamic Acid , Glutamic Acid/analysis , Glutamic Acid/metabolism , Electrochemical Techniques/methods , Electrochemical Techniques/instrumentation , Animals , Central Nervous System/metabolism , Humans , Biosensing Techniques/methodsABSTRACT
Our study mainly analyzed the mechanism of C/EBP homologous protein (CHOP) and its interacting protein Nupr1 on endoplasmic reticulum stress (ERS) induced lens epithelial cells (LEC) apoptosis. Cell proliferation was detected by CCK-8. Apoptosis was detected by flow cytometry and TUNEL. Nupr1 expression was detected by RT-qPCR. The expressions of CHOP, Nupr1, apoptosis-related protein, and ERS-related protein were detected by Western blot. DCFH-DA probe was used to detect cell ROS. The SOD, GSH-PX, and MDA contents were detected by the kit. Co-IP was used to detect the interaction between CHOP and Nupr1. The morphology of the lens was detected by HE staining. The result shows that Tunicamycin (TU) can induce endoplasmic reticulum stress and apoptosis in LEC in a concentration-dependent manner. TU induction leads to the occurrence of CHOP nuclear translocation. Overexpression of CHOP can further enhance the inhibitory effect of TU on LEC proliferation and the promotion of apoptosis, while knockdown of CHOP has the opposite effect. CHOP and Nupr1 are interacting proteins, and knockdown of Nupr1 or addition of Nupr1 inhibitor ZZW-115 can reverse the effects of TU and overexpression of CHOP, respectively. It has been observed in animal experiments that treatment with oe-CHOP can further aggravate the pathological lesions of the rat lens, while ZZW-115 can reverse the effect of oe-CHOP to a certain extent and improve the lesions of the rat lens. Overall, CHOP interacts with Nupr1 to regulate apoptosis caused by ERS and mediate cataract progression in rats, and this study provides a new potential therapeutic target for the treatment of cataract.
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BACKGROUND: The escalating complexity of the COVID-19 epidemic underscores the need for heightened attention to booster vaccinations. This study aims to examine the changing trend in the public's intention to receive the second COVID-19 booster vaccination over time and the associated factors following the COVID-19 policy optimization in China. METHOD: Eight cross-sectional surveys utilizing SMS questionnaire links were conducted in Guangzhou, China, from December 2022 to April 2023. The Mann-Kendall test was employed to analyze the trend in intentions to receive the second booster vaccination across the survey time. Adjusted and multivariate logistic analyses were used to analyze the factors associated with vaccination intention. Parallel analyses were performed for two subgroups with different COVID-19 infection statuses. RESULTS: A total of 9860 respondents were surveyed in the eight rounds, of which 8048 completed the first booster vaccination and were included in the analysis. The overall COVID-19 infection rate was 60.0% (4832/8048), while the overall vaccination intention was 72.2% (5810/8048) among respondents. The vaccination intention exhibited a significant declining trend over time, decreasing from 81.5% in December 2022 to 52.2% in April 2023. An adjusted logistic regression analysis revealed that anxiety and depression were negatively associated with an intention to receive the second booster vaccination, while COVID-19-related preventive behaviors and a high engagement in COVID-19-related information were positively associated with an intention to receive the second booster vaccination. A subgroup analysis revealed that the association between psychological and behavioral characteristics and vaccination intention remained relatively stable among individuals with different histories of COVID-19 infections. CONCLUSION: There was a significant decline in the intention to receive the second booster vaccination following the optimization of the COVID policy in China. Our findings emphasize the urgency of the second booster vaccination and provide a foundation for the development of tailored interventions to enhance and sustain vaccination intention among the public.
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CONTEXT: Both physical activity (PA) and sedentary behavior (SB) exert important impact on type 2 diabetes, but it remains unclear how maximum impact on improving the mortality and optimized proportion of the two lifestyles combination exists. OBJECTIVE: To explore the impacts of PA/SB combinations on mortality in patients with diabetes. METHODS: Patients with type 2 diabetes patients samplings were collected from the National Health and Nutrition Examination Survey (NHANES) dataset. Their lifestyles were categorized into eight groups based on combinations of the PA and SB levels. Cox proportional hazards models were used to calculate hazard ratios and 95% confidence intervals. RESULTS: During the follow-up period, 1,148 deaths (18.94%) were recorded. High SB (sedentary time ≥6 hours/day) was significantly associated with higher all-cause mortality (HR 1.65). In participants with low SB (<6 hours/day), low PA was associated with lower all-cause mortality (HR 0.43), while further increase of PA level did not show further reduction in either all-cause or cardiovascular mortality. In contrast, in participants with high SBï¼all levels of PA were associated with lower all-cause mortality (p<0.05), but only moderate PA was associated with lower cardiovascular mortality (HR 0.30). CONCLUSIONS: In patients with type 2 diabetes, different combinations of various levels of PA and SB are associated with different degree of risk for all-cause or cardiovascular mortality.
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BACKGROUND: Type 2 diabetes mellitus (T2DM) increases the risk of liver cancer among people living with hepatitis B virus (HBV). Our study aimed to estimate the global burden and trends of liver cancer attributable to comorbid T2DM among people living with HBV from 1990 to 2019. METHODS: We calculated the population attributable fractions (PAFs) of liver cancer attributable to comorbid T2DM among the burden of HBV-related liver cancer. We applied the PAFs to the burden of HBV-related liver cancer derived from the Global Burden of Disease (GBD) 2019 database to obtain the burden of liver cancer attributable to HBV-T2DM comorbidity. The prevalence, disability-adjusted life year (DALY), and deaths of liver cancer attributable to the comorbidity were assessed at the global, regional, and country levels and then stratified by the sociodemographic index (SDI), sex, and age group. Estimated annual percentage changes (EAPCs) were calculated to quantify the temporal trends. RESULTS: In 2019, the global age-standardized prevalence and DALY rates of liver cancer attributable to HBV-T2DM comorbidity were 9.9 (8.4-11.5) and 182.4 (154.9-212.7) per 10,000,000 individuals, respectively. High-income Asia Pacific and East Asia had the highest age-standardized prevalence and DALY rates of liver cancer attributable to HBV-T2DM comorbidity, respectively. From 1990 to 2019, age-standardized prevalence and DALY rates increased in 16 out of 21 GBD regions. High-income North America had the largest annual increases in both age-standardized prevalence rates (EAPC = 6.07; 95% UI, 5.59 to 6.56) and DALY rates (EAPC = 4.77; 95% UI, 4.35 to 5.20), followed by Australasia and Central Asia. Across all SDI regions, the high SDI region exhibited the most rapid increase in age-standardized prevalence and DALY rates from 1990 to 2019. Additionally, men had consistently higher disease burdens than women across all age groups. The patterns of mortality burden and trends are similar to those of DALYs. CONCLUSIONS: The burden of liver cancer attributable to comorbid T2DM among people living with HBV has exhibited an increasing trend across most regions over the last three decades. Tailored prevention strategies targeting T2DM should be implemented among individuals living with HBV.
Subject(s)
Comorbidity , Diabetes Mellitus, Type 2 , Global Burden of Disease , Liver Neoplasms , Humans , Diabetes Mellitus, Type 2/epidemiology , Liver Neoplasms/epidemiology , Male , Female , Global Burden of Disease/trends , Middle Aged , Prevalence , Adult , Aged , Global Health/statistics & numerical data , Hepatitis B/epidemiology , Disability-Adjusted Life Years/trendsABSTRACT
Non-alcoholic steatohepatitis (NASH) is rapidly surpassing viral hepatitis as the primary cause of hepatocellular carcinoma (HCC). However, understanding of NASH-progressed HCC remains poor, which might impede HCC diagnosis and therapy. In this study, we aim to identify shared transcriptional changes between NASH and HCC, of which we focused on E3 ligase TRIM45. We found TRIM45 exacerbates HCC cells proliferation and metastasis in vitro and in vivo. Further transcriptome analysis revealed TRIM45 predominantly affects fatty acid metabolism and oleic acid restored impaired proliferation and metastasis of TRIM45-deficient HCC cells. IP-tandem mass spectrum and FABP5 depriving experiment indicated that TRIM45 enhance fatty acid synthesis depending on FABP5 presence. Interestingly, we found TRIM45 directly added K33-type and K63-type poly-ubiquitin chains to FABP5 NLS domain, which ultimately promoted FABP5 nuclear translocation. Nuclear FABP5 interacted with PPARγ to facilitate downstream lipid synthesis gene expression. We observed TRIM45 accelerated NASH-to-HCC transition and exacerbated both NASH and NASH-HCC with the enhanced fatty acid production in vivo. Moreover, high concentration of fatty acid increased TRIM45 expression. The established mechanism was substantiated by gene expression correlation in TCGA-LIHC. Collectively, our research revealed a common lipid reprograming process in NASH and HCC and identified the cyclical amplification of the TRIM45-FABP5-PPARγ-fatty acid axis. This signaling pathway offers potential therapeutic targets for therapeutic intervention in NASH and NASH-progressed HCC.
Subject(s)
Carcinoma, Hepatocellular , Fatty Acid-Binding Proteins , Fatty Acids , Liver Neoplasms , Non-alcoholic Fatty Liver Disease , Ubiquitination , Carcinoma, Hepatocellular/pathology , Carcinoma, Hepatocellular/genetics , Carcinoma, Hepatocellular/metabolism , Humans , Liver Neoplasms/pathology , Liver Neoplasms/genetics , Liver Neoplasms/metabolism , Fatty Acid-Binding Proteins/genetics , Fatty Acid-Binding Proteins/metabolism , Non-alcoholic Fatty Liver Disease/metabolism , Non-alcoholic Fatty Liver Disease/pathology , Non-alcoholic Fatty Liver Disease/genetics , Animals , Fatty Acids/metabolism , Mice , Cell Proliferation/genetics , Cell Line, Tumor , Gene Expression Regulation, Neoplastic , Ubiquitin-Protein Ligases/genetics , Ubiquitin-Protein Ligases/metabolism , Disease ProgressionABSTRACT
Gastric cancer (GC) is the second deadliest disease in Asia, so it is crucial to find its promising therapeutic targets. The expression profile data of miR383-5p in the Cancer Genome Atlas (TCGA) were analyzed. The expression levels of miR383-5p in the collected clinical tissue samples and peripheral blood samples were examined by qPCR, and the relationship between its expression and the clinical data of patients was evaluated. MiR383-5p was overexpressed in the AGS cells, and cell biology assays, such as Transwell, were performed to detect the cell proliferation, migration, invasion and other cell biology abilities of miR383-5p. Target prediction and dual luciferase reporter gene assay were performed to find and validate the target genes of miR383-5p. The expression and activity of MMP and related proteins after overexpression of miR383-5p and NCKAP1 were detected by WB and gelatin zymography assay. The expression of miR383-5p was down-regulated in GC tissues, and its low expression was associated with lymph node metastasis. Restoration of miR383-5p expression in GC cells can inhibit the invasion and migration abilities of GC cells. MiR383-5p negatively regulated NCKAP1 through direct interaction with the 3'UTR sequence of NCKAP1. The overexpression of NCKAP1 can improve the migration and invasion abilities of GC cells, whereas overexpression of miR383-5p can inhibit growth of the aforementioned abilities of GC cells induced by NCKAP1 overexpression. The overexpression of NCKAP1 can increase the expression level and activity of MMP2, while the overexpression of miR383-5p can inhibit the increase of MMP2 expression level and activity in GC cells induced by NCKAP1 overexpression. NCKAP1 is a target gene of miR383-5p, and miR383-5p could be a valuable therapeutic target for stomach adenocarcinoma.
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Carnitine acetyltransferase (CAT) and Enoyl-CoA hydratase short-chain 1 (ECHS1) are considered key enzymes that regulate the ß-oxidation of fatty acids. However, very few studies have investigated their full length and expression in genetically improved farmed tilapia (GIFT, Oreochromis niloticus), an important aquaculture species in China. Here, we cloned CAT and ECHS1 full-length cDNA via the rapid amplification of cDNA ends, and the expressions of CAT and ECHS1 in the liver of juvenile GIFT were detected in different fat and carnitine diets, as were the changes in the lipometabolic enzymes and serum biochemical indexes of juvenile GIFT in diets with different fat and carnitine levels. CAT cDNA possesses an open reading frame (ORF) of 2167 bp and encodes 461 amino acids, and the ECHS1 cDNA sequence is 1354 bp in full length, the ORF of which encodes a peptide of 391 amino acids. We found that juvenile GIFT had higher lipometabolic enzyme activity and lower blood CHOL, TG, HDL-C, and LDL-C contents when the dietary fat level was 2% or 6% and when the carnitine level was 500 mg/kg. We also found that the expression of ECHS1 and CAT genes in the liver of juvenile GIFT can be promoted by a 500 mg/kg carnitine level and 6% fat level feeding. These results suggested that CAT and ECHS1 may participate in regulating lipid metabolism, and when 2% or 6% fat and 500 mg/kg carnitine are added to the feed, it is the most beneficial to the liver and lipid metabolism of juvenile GIFT. Our results may provide a theoretical basis for GIFT feeding and treating fatty liver disease.
Subject(s)
Carnitine O-Acetyltransferase , Carnitine , Enoyl-CoA Hydratase , Liver , Animals , Liver/metabolism , Carnitine/metabolism , Carnitine O-Acetyltransferase/genetics , Carnitine O-Acetyltransferase/metabolism , Enoyl-CoA Hydratase/genetics , Enoyl-CoA Hydratase/metabolism , Cichlids/genetics , Cichlids/metabolism , Cichlids/growth & development , Dietary Fats/pharmacology , Dietary Fats/metabolism , Fish Proteins/genetics , Fish Proteins/metabolism , Lipid Metabolism/geneticsABSTRACT
Ambient fine particulate matter (PM2.5) has attracted considerable attention due to its crucial role in the rising global disease burden. Evidence of health risks associated with exposure to PM2.5 and its major constituents is important for advancing hazard assessments and air pollution emission policies. We investigated the relationship between exposure to major constituents of PM2.5 and outpatient visits as well as hospitalizations in Guangdong Province, China, where 127 million residents live in a severe PM2.5 pollution environment. An approach that integrates the generalized weighted quantile sum (gWQS) regression with the difference-in-differences (DID) approach was used to assess the overall mixture effects and relative contributions of each constituent. We observed significant associations between long-term exposure to the mixture of PM2.5 constituents (WQS index) and outpatient visits (IR%, percentage increases in risk per unit WQS index increase:1.73, 95%CI: 1.72, 1.74) as well as hospitalizations (IR%:5.15, 95%CI: 5.11, 5.20). Black carbon (weight: 0.34) and nitrate (weight: 0.60) respectively exhibited the highest contributions to outpatient visits and hospitalizations. The overall mixture effects on outpatient visits and hospitalizations were higher with increased summer air temperatures (IR%: 7.54, 95%CI: 7.33, 7.74 and IR%: 9.55, 95%CI: 8.36, 10.75, respectively) or decreased winter air temperatures (IR%: 1.88, 95%CI: 1.68, 2.08 and IR%: 4.87, 95%CI: 3.73, 6.02, respectively). Furthermore, the overall mixture effects on outpatient visits and hospitalizations were significantly higher in populations with higher socioeconomic status (P < 0.01). It's crucial to address the primary sources of nitrate precursor substances and black carbon (mainly traffic-related and industrial-related air pollutants) and consider the complex interaction effects between air temperature and PM2.5 in the context of climate change. Of particular concern is the need to prioritize healthcare demands in economically disadvantaged regions and to address the health inequalities stemming from the uneven distribution of healthcare resources and PM2.5 pollution.
Subject(s)
Air Pollutants , Air Pollution , Humans , Outpatients , Nitrates , Air Pollutants/analysis , Particulate Matter/analysis , Air Pollution/analysis , China/epidemiology , Hospitalization , Carbon , Environmental Exposure/analysisABSTRACT
Flexible pressure sensors overcome the limitations of traditional rigid sensors on the surface of the measured object, demonstrating broad application prospects in fields such as sports health and vital sign monitoring due to their excellent flexibility and comfort in contact with the body. MXene, as a two-dimensional material, possesses excellent conductivity and abundant surface functional groups. Simultaneously, MXene's unique layered structure and large specific surface area offer a wealth of possibilities for preparing sensing elements in combination with other materials. This article reviews the preparation methods of MXene materials and their performance indicators as sensing elements, discusses the controllable preparation methods of MXene materials and the impact of their physical and chemical properties on their functions, elaborates on the pressure sensing mechanism and evaluation mechanism of MXene materials. Starting from the four specific application directions: aerogel/hydrogel, ink printing, thin film/electronic skin, and fiber fabric, we introduce the research progress of MXene flexible pressure sensors from an overall perspective. Finally, a summary and outlook for developing MXene flexible pressure sensors are provided.
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AIMS: To examine the effectiveness of Self-Help Plus (SH+) as an intervention for alleviating stress levels and mental health problems among healthcare workers. METHODS: This was a prospective, two-arm, unblinded, parallel-designed randomised controlled trial. Participants were recruited at all levels of medical facilities within all municipal districts of Guangzhou. Eligible participants were adult healthcare workers experiencing psychological stress (10-item Perceived Stress Scale scores of ≥15) but without serious mental health problems or active suicidal ideation. A self-help psychological intervention developed by the World Health Organization in alleviating psychological stress and preventing the development of mental health problems. The primary outcome was psychological stress, assessed at the 3-month follow-up. Secondary outcomes were depression symptoms, anxiety symptoms, insomnia, positive affect (PA) and self-kindness assessed at the 3-month follow-up. RESULTS: Between November 2021 and April 2022, 270 participants were enrolled and randomly assigned to either SH+ (n = 135) or the control group (n = 135). The SH+ group had significantly lower stress at the 3-month follow-up (b = -1.23, 95% CI = -2.36, -0.10, p = 0.033) compared to the control group. The interaction effect indicated that the intervention effect in reducing stress differed over time (b = -0.89, 95% CI = -1.50, -0.27, p = 0.005). Analysis of the secondary outcomes suggested that SH+ led to statistically significant improvements in most of the secondary outcomes, including depression, insomnia, PA and self-kindness. CONCLUSIONS: This is the first known randomised controlled trial ever conducted to improve stress and mental health problems among healthcare workers experiencing psychological stress in a low-resource setting. SH+ was found to be an effective strategy for alleviating psychological stress and reducing symptoms of common mental problems. SH+ has the potential to be scaled-up as a public health strategy to reduce the burden of mental health problems in healthcare workers exposed to high levels of stress.
Subject(s)
COVID-19 , Psychological Tests , Sleep Initiation and Maintenance Disorders , Adult , Humans , Prospective Studies , Psychosocial Intervention , Sleep Initiation and Maintenance Disorders/therapy , China , Health Personnel , Self ReportABSTRACT
Background: Lung cancer (LC) is the second-highest incidence and the first-highest mortality cancer worldwide. Early screening and precise treatment of LC have been the research hotspots in this field. Artificial intelligence (AI) technology has advantages in many aspects of LC and widely used such as LC early diagnosis, LC differential classification, treatment and prognosis prediction. Objective: This study aims to analyze and visualize the research history, current status, current hotspots, and development trends of artificial intelligence in the field of lung cancer using bibliometric methods, and predict future research directions and cutting-edge hotspots. Results: A total of 2931 articles published between 2003 and 2023 were included, contributed by 15,848 authors from 92 countries/regions. Among them, China (40%) with 1173 papers,USA (24.80%) with 727 papers and the India(10.2%) with 299 papers have made outstanding contributions in this field, accounting for 75% of the total publications. The primary research institutions were Shanghai Jiaotong University(n=66),Chinese Academy of Sciences (n=63) and Harvard Medical School (n=52).Professor Qian Wei(n=20) from Northeastern University in China were ranked first in the top 10 authors while Armato SG(n=458 citations) was the most co-cited authors. Frontiers in Oncology(121 publications; IF 2022,4.7; Q2) was the most published journal. while Radiology (3003 citations; IF 2022, 19.7; Q1) was the most co-cited journal. different countries and institutions should further strengthen cooperation between each other. The most common keywords were lung cancer, classification, cancer, machine learning and deep learning. Meanwhile, The most cited papers was Nicolas Coudray et al.2018.NAT MED(1196 Total Citations). Conclusions: Research related to AI in lung cancer has significant application prospects, and the number of scholars dedicated to AI-related research on lung cancer is continually growing. It is foreseeable that non-invasive diagnosis and precise minimally invasive treatment through deep learning and machine learning will remain a central focus in the future. Simultaneously, there is a need to enhance collaboration not only among various countries and institutions but also between high-quality medical and industrial entities.