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Flemingia stricta Roxb. ex Ait. 1812 belongs to the Phaseoleae tribe within the Fabaceae family and has significant pharmaceutical value. In this study, we reported the complete chloroplast genome of F. stricta using the Illumina DNA sequencing data. The chloroplast genome was 152,940 bp and encoded 111 unique genes, including 77 protein-coding genes (PCGs), 30 transfer RNA (tRNA) genes, and 4 ribosomal RNA (rRNA) genes. The phylogenetic analysis confirmed that F. stricta was closely related to Flemingia prostrata and Flemingia macrophylla. The chloroplast genome of F. stricta could provide critical information for the molecular breeding of F. stricta and be used as a reference genome for other species of Phaseoleae.
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PURPOSE: Chronic Obstructive Pulmonary Disease (COPD) is regarded as an accelerated aging disease. Aging-related genes in COPD are still poorly understood. METHOD: Data set GSE76925 was obtained from the Gene Expression Omnibus (GEO) database. The "limma" package identified the differentially expressed genes. The weighted gene co-expression network analysis (WGCNA) constructes co-expression modules and detect COPD-related modules. The least absolute shrinkage and selection operator (LASSO) and the support vector machine recursive feature elimination (SVM-RFE) algorithms were chosen to identify the hub genes and the diagnostic ability. Three external datasets were used to identify differences in the expression of hub genes. Real-time reverse transcription polymerase chain reaction (RT-qPCR) was used to verify the expression of hub genes. RESULT: We identified 15 differentially expressed genes associated with aging (ARDEGs). The SVM-RFE and LASSO algorithms pinpointed four potential diagnostic biomarkers. Analysis of external datasets confirmed significant differences in PIK3R1 expression. RT-qPCR results indicated decreased expression of hub genes. The ROC curve demonstrated that PIK3R1 exhibited strong diagnostic capability for COPD. CONCLUSION: We identified 15 differentially expressed genes associated with aging. Among them, PIK3R1 showed differences in external data sets and RT-qPCR results. Therefore, PIK3R1 may play an essential role in regulating aging involved in COPD.
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Vieillissement , Broncho-pneumopathie chronique obstructive , Machine à vecteur de support , Humains , Broncho-pneumopathie chronique obstructive/génétique , Vieillissement/génétique , Analyse de profil d'expression de gènes , Phosphatidylinositol 3-kinase de classe Ia/génétique , Algorithmes , Bases de données génétiques , Courbe ROC , Réaction de polymérisation en chaine en temps réel , Marqueurs biologiques/métabolisme , Réseaux de régulation géniqueRÉSUMÉ
BACKGROUND: Amyloid light-chain (AL) amyloidosis is a multisystem disorder, with cardiac amyloid infiltration being a prevalent manifestation. This study aimed to explore the prognostic value of galectin-3 (Gal-3), a soluble marker associated with fibrosis, inflammation, heart failure, and kidney injury, in patients with cardiac AL amyloidosis. METHODS: A total of 60 patients who were diagnosed with cardiac AL amyloidosis from January 2015 to May 2018 were enrolled. The prognostic value of Gal-3 was assessed. Receiver operating characteristic (ROC) curves were used to evaluate the predictive accuracy of Gal-3. A Gal-3 cut-off value was identified to predict survival rates. RESULTS: The ROC curves demonstrated a moderate predictive accuracy of Gal-3 for 0.5- and 5-year survival, with area under the curve (AUC) values of 0.722 and 0.788, respectively. A Gal-3 cut-off value of 15.154 ng/mL was found to predict survival. Kaplan-Meier survival analysis revealed a significant difference in mean overall survival between patients with Gal-3 levels below and above the established cut-off (69.2 months versus 42.1 months, respectively; p = 0.036). Multivariate analysis confirmed that Gal-3 > 15.154 ng/mL remained an independent predictor of survival (HR 2.451, 95% CI 1.017-5.910, p = 0.046). CONCLUSIONS: This study suggests that Gal-3 holds independent prognostic value for survival in patients with cardiac AL amyloidosis. Gal-3 could potentially enhance the prognostic capabilities of the current soluble markers, thereby improving the management of cardiac AL amyloidosis. However, further validation in larger prospective studies is warranted.
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Urolithiasis is one of the most prevalent benign urological disorders globally with a high incidence rate. Male Sprague-Dawley rats were chemically induced to have urolithiasis and treated with triptonide and the standard antiurolithic drug cystone. Kidney weight was measured to detect calculi formation, and urinary parameters such as pH, 24-h urine volume, and protein content were measured to analyze the urolithiasis induction in rats. The inorganic ions, organic solutes, antioxidant levels, and inflammatory cytokines were measured in the experimental rats. Triptonide treatment significantly modulated the urinary pH, decreased the protein concentration, and increased the urinary outflow in urolithiasis induced rats. It also significantly decreased the urinary excretion of calcium and phosphorous and increased the excretion of magnesium, potassium, sodium, creatinine, and uric acid. SOD, CAT, and GPx levels were increased in triptonide-treated rats, and it significantly reduced the MDA levels. Triptonide treatment also decreased the levels of inflammatory cytokines and prevented the renal tissue from inflammation. To conclude, our results prove that triptonide significantly prevents calculi formation and protects renal tissue from urolithiasis-induced damage in rats. Further studies may prove triptonide a potent alternative to currently available antiurolithic drugs.
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Background: For children who are unable to cooperate due to severe dental anxiety (DA), dental treatment of childhood caries under Dental General Anesthesia (DGA) is a safe and high-quality treatment method. This study aims to evaluate the impact on neurocognitive functions and the growth and development of children 2 years after dental procedure based on previous research, and further establish a causal relationship between general anesthesia (GA) and changes in children's neurocognitive functions by incorporating Mendelian Randomization (MR) analysis. Methods: Data were collected and analyzed from 340 cases of S-ECC procedures of preschool children conducted in 2019. This involved comparing the neurocognitive outcomes 2 years post-operation of preschool children receiving dental procedures under general anesthesia or local anesthesia. Physical development indicators such as height, weight, and body mass index (BMI) of children were also compared at baseline, half a year post-operation, and 2 years post-operation. We performed a Mendelian randomization analysis on the causal relationship between children's cognitive development and general anesthesia, drawing on a large-scale meta-analysis of GWAS for anesthesia, including multiple general anesthesia datasets. Results: Outcome data were obtained for 111 children in the general anesthesia group and 121 children in the local anesthesia group. The mean FSIQ score for the general anesthesia group was 106.77 (SD 6.96), while the mean score for the local anesthesia group was 106.36 (SD 5.88). FSIQ scores were equivalent between the two groups. The incidence of malnutrition in children in the general anesthesia group was 27.93% (p < 0.001) before surgery and decreased to 15.32% (p > 0.05) after 2 years, which was not different from the general population. The IVW method suggested that the causal estimate (p = 0.99 > 0.05, OR = 1.04, 95% CI = 5.98 × 10-4-1.82 × 103) was not statistically significant for disease prevalence. This indicates no genetic cause-and-effect relationship between anesthesia and childhood intelligence. Conclusion: There were no adverse outcomes in neurocognitive development in 2 years after severe early childhood caries (S-ECC) procedure under total sevoflurane-inhalation in preschool children. The malnutrition condition in children can be improved after S-ECC procedure under general anesthesia. Limited MR evidence does not support a correlation between genetic susceptibility to anesthesia and an increased risk for intelligence in children.
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INTRODUCTION/AIMS: Previous studies have suggested that treatments targeting the neuromuscular junction (NMJ) may play a role in the treatment of amyotrophic lateral sclerosis (ALS). However, factors impacting repetitive nerve stimulation (RNS), a technique to evaluate NMJ function, have yet to be fully elucidated. We aimed to identify independent factors contributing to the decremental response of the accessory nerve and evaluated its value in ALS clinical practice. METHODS: A total of 626 patients who were diagnosed with ALS and underwent 3 Hz RNS tests on the accessory nerve were enrolled. Data on their clinical and electrophysiological indicators were divided into a training set (collected from June 2016 to December 2022) and a test set (collected from January to August 2023). Stepwise regression was used in independent variable selection and model building. RESULTS: Forty-two percent of patients had a decrement larger than 10% and 24% had a decrement larger than 15%. Onset age, sex, onset site, forced vital capacity (FVC) and motor unit potential (MUP) duration were independent factors contributing to the results of the RNS test. MUP duration had the greatest impact on decremental response, followed by FVC and onset age. The decremental response in females was larger than in males. Upper limb onset was found to contribute more to the decrement than lower limb or bulbar onset. DISCUSSION: In patients with ALS, NMJ safety factor is reduced during re-innervation. Decremental response is affected by multiple factors, which needs to be considered in clinical trials targeting the NMJ in these patients.
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Sclérose latérale amyotrophique , Humains , Sclérose latérale amyotrophique/physiopathologie , Sclérose latérale amyotrophique/diagnostic , Mâle , Femelle , Adulte d'âge moyen , Sujet âgé , Adulte , Stimulation électrique/méthodes , Jonction neuromusculaire/physiopathologie , Électromyographie/méthodesRÉSUMÉ
BACKGROUND: Chylopericardium is a rare condition characterized by the accumulation of chyle in the pericardial space. It is most commonly caused by thoracic duct injury. Chylopericardium following esophagectomy is extremely rare but can cause life-threatening complications. This report presents a case of chylopericardium post-esophagectomy, resulting in cardiac tamponade and cardiac arrest. A systematic literature review was also conducted to facilitate the understanding of this rare condition. CASE PRESENTATION: A 41-year-old male was admitted to our hospital with intermediate to highly differentiated squamous cell carcinoma of the mid-thoracic esophagus (clinical T4NxM0). He underwent thoracoscopic-laparoscopic esophagectomy with cervical anastomosis. On postoperative day 1, patient had a cardiac arrest secondary to cardiac tamponade, requiring emergency ultrasound-guided drainage. The drained fluid was initially serous but became chylous after the administration of enteral nutritional emulsion. As a result of significant daily pericardial drainage, patient subsequently underwent thoracic duct ligation. The amount of drainage was substantially reduced post-thoracic duct ligation. Over a period of 2 years and 7 months, patient recovered well and tolerated full oral diet. A comprehensive literature review was conducted and 4 reported cases were identified. Among these cases, three patients developed pericardial tamponade secondary to chylopericardium post-esophagectomy. CONCLUSION: Chylopericardium is a rare but serious complication post-esophagectomy. Prompt echocardiography and thorough pericardial fluid analysis are crucial for diagnosis. Thoracic duct ligation has been shown to be an effective management approach for this condition.
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Tamponnade cardiaque , Arrêt cardiaque , Épanchement péricardique , Mâle , Humains , Adulte , Épanchement péricardique/diagnostic , Épanchement péricardique/étiologie , Épanchement péricardique/chirurgie , Tamponnade cardiaque/diagnostic , Tamponnade cardiaque/étiologie , Tamponnade cardiaque/chirurgie , Oesophagectomie/effets indésirables , Médiastin , Conduit thoracique/chirurgie , Ligature/effets indésirables , Arrêt cardiaque/chirurgieRÉSUMÉ
Hypertension is the leading risk factor for premature death. The optimal treatment of low-renin hypertension (LRH), present in 30% of hypertensive individuals, is not known. LRH likely reflects a state of excess salt, expanded volume and/or mineralocorticoid receptor (MR) activation. Therefore, targeted treatment with MR antagonists (MRA) may be beneficial. The objective of this systematic review was to assess the efficacy of MRA therapy in LRH. MEDLINE, Embase and Cochrane databases were searched for randomised controlled trials of adults with LRH that compared the efficacy of MRA to placebo or other antihypertensive treatments. Risk of bias was assessed using the Cochrane risk of bias tool. A meta-analysis was performed using a random-effects model to estimate the difference in blood pressure and the certainty of evidence was assessed using the GRADE approach. The protocol is registered on PROSPERO (CRD42022318763). From the 1612 records identified, 17 studies met the inclusion criteria with a total sample size of 1043 participants. Seven studies (n = 345) were assessed as having a high risk of bias. Meta-analysis indicated that MRA reduced systolic blood pressure by -6.8 mmHg (95% confidence interval -9.6 to -4.1) and -4.8 mmHg (95% confidence interval -11.9 to 2.4) compared to angiotensin-converting enzyme inhibitors/angiotensin receptor blockers (ACEi/ARB) and diuretics. The certainty of the evidence was assessed as moderate and very low, respectively. The findings of this systematic review suggest that MRA is effective in lowering blood pressure in LRH and may be better than ACEi/ARB. Translation to clinical practice is limited by the uncertainty of evidence.
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Hypertension artérielle , Antagonistes des récepteurs des minéralocorticoïdes , Humains , Antagonistes des récepteurs des minéralocorticoïdes/usage thérapeutique , Antagonistes des récepteurs des minéralocorticoïdes/effets indésirables , Hypertension artérielle/traitement médicamenteux , Hypertension artérielle/physiopathologie , Résultat thérapeutique , Rénine/antagonistes et inhibiteurs , Pression sanguine/effets des médicaments et des substances chimiques , Antihypertenseurs/usage thérapeutique , Antihypertenseurs/effets indésirablesRÉSUMÉ
BACKGROUND: Primary aldosteronism (PA) has been broadly dichotomized into unilateral and bilateral forms. Adrenal vein sampling (AVS) lateralization indices (LI) ≥2 to 4 are the standard-of-care to recommend unilateral adrenalectomy for presumed unilateral PA. We aimed to assess the rates and characteristics of residual PA after AVS-guided adrenalectomy. METHODS: We conducted an international, retrospective, cohort study of patients with PA from 7 referral centers who underwent unilateral adrenalectomy based on LI≥4 on baseline and/or cosyntropin-stimulated AVS. Aldosterone synthase (CYP11B2) immunohistochemistry and next generation sequencing were performed on available formalin-fixed paraffin-embedded adrenal tissue. RESULTS: The cohort included 283 patients who underwent AVS-guided adrenalectomy, followed for a median of 326 days postoperatively. Lack of PA cure was observed in 16% of consecutive patients, and in 22 patients with lateralized PA on both baseline and cosyntropin-stimulated AVS. Among patients with residual PA postoperatively, 73% had multiple CYP11B2 positive areas within the resected adrenal tissue (versus 23% in those cured), wherein CACNA1D mutations were most prevalent (63% versus 33% in those cured). In adjusted regression models, independent predictors of postoperative residual PA included Black versus White race (odds ratio, 5.10 [95% CI, 1.45-17.86]), AVS lateralization only at baseline (odds ratio, 8.93 [95% CI 3.00-26.32] versus both at baseline and after cosyntropin stimulation), and CT-AVS disagreement (odds ratio, 2.75 [95% CI, 1.20-6.31]). CONCLUSIONS: Multifocal, asymmetrical bilateral PA is relatively common, and it cannot be excluded by robust AVS lateralization. Long-term postoperative monitoring should be routinely pursued, to identify residual PA and afford timely initiation of targeted medical therapy.
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Hyperaldostéronisme , Humains , Hyperaldostéronisme/diagnostic , Hyperaldostéronisme/génétique , Hyperaldostéronisme/chirurgie , Études rétrospectives , Aldostérone , Tétracosactide , Études de cohortes , Cytochrome P-450 CYP11B2 , Glandes surrénales/chirurgie , Glandes surrénales/vascularisation , SurrénalectomieRÉSUMÉ
Endogenous electric fields (EFs) have been demonstrated to facilitate wound healing by directing the migration of epidermal cells. Despite the identification of numerous molecules and signaling pathways that are crucial for the directional migration of keratinocytes under EFs, the underlying molecular mechanisms remain undefined. Previous studies have indicated that microtubule (MT) acetylation is linked to cell migration, while Paxillin exerts a significant influence on cell motility. Therefore, we postulated that Paxillin could enhance EF-induced directional migration of keratinocytes by modulating MT acetylation. In the present study, we observed that EFs (200 mV/mm) induced migration of human immortalized epidermal cells (HaCaT) towards the anode, while upregulating Paxillin, downregulating HDAC6, and increasing the level of microtubule acetylation. Our findings suggested that Paxillin plays a pivotal role in inhibiting HDAC6-mediated microtubule acetylation during directional migration under EF regulation. Conversely, downregulation of Paxillin decreased microtubule acetylation and electrotaxis of epidermal cells by promoting HDAC6 expression, and this effect could be reversed by the addition of tubacin, an HDAC6-specific inhibitor. Furthermore, we observed that EFs also mediated the polarization of Paxillin and acetylated α-tubulin, which is critical for directional migration. In conclusion, our study revealed that MT acetylation in EF-guided keratinocyte migration is regulated by the Paxillin/HDAC6 signaling pathway, providing a novel theoretical foundation for the molecular mechanism of EF-guided directional migration of keratinocytes.
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Kératinocytes , Microtubules , Humains , Paxilline/métabolisme , Histone deacetylase 6/génétique , Histone deacetylase 6/métabolisme , Acétylation , Microtubules/métabolisme , Kératinocytes/métabolismeRÉSUMÉ
Boerhaave syndrome is a rare but potentially life-threatening condition that involves a full-thickness tear of the oesophagus. It accounts for around 15% of all cases of oesophageal perforations and is associated with up to 40% of mortality. Vomiting has been found to be associated with the development of Boerhaave syndrome. However, the aetiology of vomiting varies broadly in the available literatures from alcohol indulgence to marathon running, and from panic attack to radiotherapy for cancer. We present here an unusual case of Boerhaave syndrome where the patient developed spontaneous oesophageal perforation in the setting of renal colic.
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BACKGROUND: Previous studies have assessed the association between antidiabetic drugs and stroke risk, but the results are inconsistent. Mendelian randomization (MR) was used to assess effects of antidiabetic drugs on stroke risk. METHODS: We selected blood glucose-lowering variants in genes encoding antidiabetic drugs targets from genome-wide association studies (GWAS). A two-sample MR and Colocalization analyses were applied to examine associations between antidiabetic drugs and the risk of stroke. For antidiabetic agents that had effect on stroke risk, an independent blood glucose GWAS summary data was used for further verification. RESULTS: Genetic proxies for sulfonylureas targets were associated with reduced risk of any stroke (OR=0.062, 95% CI 0.013-0.295, P=4.65×10ï¼4) and any ischemic stroke (OR=0.055, 95% CI 0.010-0.289, P=6.25×10ï¼4), but not with intracranial hemorrhage. Colocalization supported shared casual variants for blood glucose with any stroke and any ischemic stroke within the encoding genes for sulfonylureas targets (KCNJ11 and ABCC8) (posterior probability>0.7). Furthermore, genetic variants in the targets of insulin/insulin analogues, glucagon-like peptide-1 analogues, thiazolidinediones, and metformin were not associated with the risk of any stroke, any ischemic stroke and intracranial hemorrhage. The association was consistent in the analysis of sulfonylureas with stroke risk using an independent blood glucose GWAS summary data. CONCLUSIONS: Our findings showed that genetic proxies for sulfonylureas targets by lowering blood glucose were associated with a lower risk of any stroke and any ischemic stroke. The study might be of great significance to guide the selection of glucose-lowering drugs in individuals at high risk of stroke.
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Accident vasculaire cérébral ischémique , Accident vasculaire cérébral , Humains , Hypoglycémiants/pharmacologie , Hypoglycémiants/usage thérapeutique , Glycémie , Étude d'association pangénomique , Facteurs de risque , Sulfonylurées/pharmacologie , Sulfonylurées/usage thérapeutique , Insuline , Accident vasculaire cérébral/génétique , Hémorragies intracrâniennesRÉSUMÉ
Lung cancer is the leading cause of cancer-related mortality, and non-small cell lung cancer (NSCLC) accounts for approximately 85% of all lung cancer cases. Our previous study confirmed that synaptotagmin 7 (SYT7) promoted NSCLC metastasis in vivo and in vitro. Studies have shown that SYT7 is an important regulatory molecule of exocytosis in various cells. However, the characteristics of SYT7 across cancers and the function of SYT7 in tumor exosome secretion remain unclear. In this study, we conducted systematic pancancer analyses of SYT7, namely, analyses of expression patterns, diagnostic and prognostic values, genetic alterations, methylation, immune infiltration, and potential biological pathways. Furthermore, we demonstrated that SYT7 increased the secretion of exosomes from A549 and H1299 cells, promoting the migration, proliferation, and tube formation of human umbilical vein endothelial cells (HUVECs). Notably, SYT7 promoted angiogenesis by transferring exosomes containing the molecule centrosomal protein of 55 kDa (CEP55) protein to HUVECs. The CEP55 protein levels was downregulated in STAT1 inhibitor-treating SYT7-overexpresion NSCLC cells. We further found that SYT7 activated the mTOR signaling pathway through the downstream molecule CEP55, thereby promoting the invasion and metastasis of NSCLC cells. SYT7 promoted exosome secretion by NSCLC cells through upregulating syntaxin-1a and syntaxin-3. In vivo, SYT7 promoted the tumorigenesis, angiogenesis and metastasis of A549 cells through the exosome pathway. Our study is of great importance for understanding the mechanism of tumor exosome secretion and the role of exosomes in tumor progression.
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Carcinome pulmonaire non à petites cellules , Exosomes , Tumeurs du poumon , Humains , Carcinome pulmonaire non à petites cellules/anatomopathologie , Tumeurs du poumon/métabolisme , Exosomes/métabolisme , Synaptotagmines/génétique , Synaptotagmines/métabolisme , Cellules endothéliales/métabolisme , Lignée cellulaire tumorale , Prolifération cellulaireRÉSUMÉ
PURPOSE: Tirzepatide, a dual glucose-dependent insulinotropic peptide and glucagon-like peptide 1 receptor agonist, has been approved by the US Food and Drug Administration for the treatment of type 2 diabetes. The purpose of this meta-analysis is to evaluate the impact of tirzepatide on lipid profile and waist circumference (WC), both of which are risk factors of cardiovascular diseases. METHODS: The PubMed, Embase, Cochrane Library, Web of Science, and ClinicalTrials.gov databases were systematically searched for articles published from database inception to July 31, 2022. This meta-analysis included 7 randomized controlled trials with a minimum duration of 12 weeks that compared tirzepatide with placebo or other antidiabetic medications. The random-effects model was used to estimate mean differences in lipid profile and WC from baseline. The Cochrane risk-of-bias tool for randomized trials, version 2 was used to assess the outcome's risk of bias. We evaluated the evidence using the GRADE (Grading of Recommendations Assessment, Development and Evaluation) system. FINDINGS: A total of 8 articles from 7 trials with 7151 participants were included. All 3 eligible maintenance doses of tirzepatide (5, 10, and 15 mg once a week) were effective in increasing total cholesterol (TC) (P < 0.05), HDL-C (P < 0.05), VLDL-C (P < 0.01), triglyceride (TG) (P < 0.01), and WC (P < 0.01) changes from baseline compared with control agents including placebo, semaglutide, dulaglutide, and degludec. Although the evidence for VLDL-C and TGs by GRADE were high or moderate, the evidences for TC, HDL-C, and WC were low or moderate. Only 5mg once-weekly tirzepatide (P < 0.05), not 10 or 15 mg, could induce significant alteration in LDL-C before sensitivity analysis. The evidence by GRADE was moderate. IMPLICATIONS: Tirzepatide had superiority over placebo or other antidiabetic agents in controlling lipid and WC levels. However, the levels of evidence by GRADE varied greatly across different outcome indicators. Limitations of the study include evaluating secondary outcomes of original trials for the meta-analyses, not assessing the effect of baseline lipid-lowering therapy on lipid levels, and not exploring the bias induced by glycemic improvement and weight loss.
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Diabète de type 2 , Peptide gastrointestinal , Humains , Diabète de type 2/traitement médicamenteux , Tour de taille , Peptides/effets indésirables , Hypoglycémiants/effets indésirables , Lipides , Récepteur du peptide-1 similaire au glucagonRÉSUMÉ
Background: Endogenous electric fields (EFs) play an essential role in guiding the coordinated collective migration of epidermal cells to the wound centre during wound healing. Although polarization of leadercells is essential for collective migration, the signal mechanisms responsible for the EF-induced polarization of leader cells under electrotactic collective migration remain unclear. This study aims to determine how the leader cells are polarized and coordinated during EF-guided collective migration of epidermal cell sheets. Methods: Collective migration of the human epidermal monolayer (human immortalized keratinocytes HaCaT) under EFs was observed via time-lapse microscopy. The involvement of tetraspanin-29 (CD9) in EF-induced fibrous actin (F-actin) polarization of leader cells as well as electrotactic migration of the epidermal monolayer was evaluated by genetic manipulation. Blocking, rescue and co-culture experiments were conducted to explore the downstream signalling of CD9. Results: EFs guided the coordinated collective migration of the epithelial monolayer to the anode, with dynamic formation of pseudopodia in leader cells at the front edge of the monolayer along the direction of migration. F-actin polarization, as expected, played an essential role in pseudopod formation in leader cells under EFs. By confocal microscopy, we found that CD9 was colocalized with F-actin on the cell surface and was particularly downregulated in leader cells by EFs. Interestingly, genetic overexpression of CD9 abolished EF-induced F-actin polarization in leader cells as well as collective migration in the epidermal monolayer. Mechanistically, CD9 determined the polarization of F-actin in leader cells by downregulating a disintegrin and metalloprotease 17/heparin-binding epidermal growth factor-like growth factor/epidermal growth factor receptor (ADAM17/HB-EGF/EGFR) signalling. The abolished polarization of leader cells due to CD9 overexpression could be restored in a co-culture monolayer where normal cells and CD9-overexpressing cells were mixed; however, this restoration was eliminated again by the addition of the HB-EGF-neutralizing antibody. Conclusion: CD9 functions as a key regulator in the EF-guided collective migration of the epidermal monolayer by controlling and coordinating the polarization of leader cells through ADAM17/HB-EGF/EGFR signalling.
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BACKGROUND: Currently, miRNAs are involved in the development of amyotrophic lateral sclerosis (ALS), and identifying circulating miRNAs that are causally associated with ALS risk as biomarkers is imperative. METHODS: We performed a two-sample Mendelian randomization study to evaluate the causal relationship between miRNAs and ALS. Our analysis was conducted using summary statistics from miRNA expression quantitative loci (eQTL) data of the Framingham Heart Study and ALS genome-wide association studies data. Another independent miRNA data was used to further validate. RESULTS: We identified eight unique miRNAs that were causally associated with ALS risk. Using expression data of miRNAs from an independent study, we validated three high-confidence miRNAs, namely hsa-miR-27b-3p, hsa-miR-139-5p, and hsa-miR-152-3p, which might have a potential causal effect on ALS risk. CONCLUSION: We suggested that higher levels of hsa-miR-27b-3p and hsa-miR-139-5p had protective effects on ALS, whereas higher levels of hsa-miR-152-3p might act as a risk factor for ALS. The analytical framework presented in this study helps to understand the role of miRNAs in the development of ALS and to identify the biomarkers for ALS risk.
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Sclérose latérale amyotrophique , MicroARN circulant , microARN , Humains , Sclérose latérale amyotrophique/épidémiologie , Sclérose latérale amyotrophique/génétique , Étude d'association pangénomique , microARN/génétique , microARN/métabolisme , MicroARN circulant/génétique , Marqueurs biologiquesRÉSUMÉ
Dansyl chloride fluorophore exhibits typical aggregation induced fluorescence emission behavior in acetone/water solution. To realize the integration of detective and adsorptive functions, dansyl chloride is covalently immobilized on cellulose substrate to fabricate an efficient adsorbent for mercury ions in water. The as-prepared material exhibits excellent fluorescence sensing performance exclusively for Hg (II) with the presence of other metal ions. A sensitive and selective fluorescence quenching across the concentration range of 0.1-8.0 mg/L is observed with a detection limit of 8.33 × 10-9 M as a result of the inhibition of aggregation induced emission caused by the coordination between adsorbent and Hg (II). Besides, the adsorption properties for Hg (II) including the influence of initial concentration and contact time are investigated. Langmuir model and pseudo-second-order kinetics are demonstrated to fit well with the adsorption experiment for the uptake of Hg (II) by the functionalized adsorbent, also, intraparticle diffusion kinetic model is proved to aptly describe the Hg (II) removal in aqueous solution. In addition, the recognition mechanism is considered to originate from the Hg (II) triggered structural reversals of naphthalene ring units which are verified by the X-ray photoelectron spectroscopy and density functional theory calculation. Moreover, the synthesis method used in this work also provides a strategy for the sensing application of organic sensor molecules with AIE properties in which the aggregated behavior could be appropriately realized.
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Mercure , Polluants chimiques de l'eau , Purification de l'eau , Mercure/composition chimique , Cellulose/composition chimique , Polluants chimiques de l'eau/composition chimique , Purification de l'eau/méthodes , Concentration en ions d'hydrogène , Eau/composition chimique , Cinétique , Adsorption , IonsRÉSUMÉ
The 'king of fruits' mango (Mangifera indica) is widely cultivated in tropical areas and has been threatened by frequent extreme cold weather. Cyclic nucleotide-gated ion channel (CNGC) genes have an important function in the calcium-mediated development and cold response of plants. However, few CNGC-related studies are reported in mango, regardless of the mango cold stress response. In this study, we identified 43 CNGC genes in mango showing tissue-specific expression patterns. Five MiCNGCs display more than 3-fold gene expression induction in the fruit peel and leaf under cold stress. Among these, MiCNGC9 and MiCNGC13 are significantly upregulated below 6 °C, suggesting their candidate functions under cold stress. Furthermore, cell membrane integrity was damaged at 2 °C in the mango leaf, as shown by the content of malondialdehyde (MDA), and eight MiCNGCs are positively correlated with MDA contents. The high correlation between MiCNGCs and MDA implies MiCNGCs might regulate cell membrane integrity by regulating MDA content. Together, these findings provide a valuable guideline for the functional characterization of CNGC genes and will benefit future studies related to cold stress and calcium transport in mango.
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Acquired von Willebrand syndrome (AVWS) is caused by an acquired deficiency of von Willebrand factor (VWF), a multimeric protein required for primary hemostasis. For patients with heart valve diseases, high gradient across the malfunctioning valves could cause elevated shear stress and damage the most effective large VWF, eventually resulting in AVWS. However, AVWS has not been reported in association with normally functioning mechanical valves. Herein, we reported a 74-year-old female who suffered from recurrent gastrointestinal bleeding with a history of mechanical aortic and mitral valve replacement. This patient's function/antigen ratio of VWF was decreased and gel electrophoresis revealed the loss of large VWF, which confirmed the diagnosis of AVWS. Echocardiogram showed that the function of the prostheses was normal. However, the gradient across aortic valve was increased due to a high cardiac state which is secondary to chronic anemia, resulting in the disruption of large VWF multimers and exacerbation of gastrointestinal (GI) bleeding. After managing the patient's anemia with transfusion, the gradient across the aortic valve had improved, with the resolution of GI bleeding. This is the first case report of AVWS that is associated with a normally functioning mechanical valve. AVWS should be considered one of the differential diagnoses if patients present with unexplained GI bleeding on the background of having prosthetic heart valves. The management of the underlying condition is essential.