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PURPOSE: This study aimed to clarify the characteristics of delaminated rotator cuff tears (RCTs) and evaluate the clinical outcomes of a modified arthroscopic en masse suture bridge repair for delaminated RCTs. METHODS: Patients with full-thickness RCTs, who underwent arthroscopic suture bridge repair with a minimum 2-year follow-up, were retrospectively reviewed. Patients were categorized into two groups based on the presence of delamination. Delaminated RCTs were treated using a modified en masse suture bridge technique, while nondelaminated RCTs received a conventional suture bridge technique. Preoperative and postoperative Constant scores and American Shoulder and Elbow Surgeons (ASES) scores were determined to evaluate clinical outcomes. Postoperative magnetic resonance imaging (MRI) was carried out to identify the integrity and retear of the repaired rotator cuff. RESULTS: A total of 172 patients were included in our study cohort, in which 67 (39%) delaminated RCTs were confirmed intraoperatively. The prevalence of delamination was significantly higher in large tears (53/102, 52%) compared to medium tears (14/70, 20%) (p < 0.001). No significant differences in age (n.s.) or gender (n.s.) were observed between the two groups. Both groups showed significant improvements in Constant and ASES scores postoperatively (both p < 0.001), with no significant differences between the groups (n.s.). The retear rates were 2/67 (3.0%) in the delamination group and 3/105 (2.9%) in the nondelamination group, showing no significant difference (n.s.). CONCLUSIONS: The modified arthroscopic en masse suture bridge technique was effective for repairing delaminated RCTs, yielding favourable clinical outcomes comparable to those of nondelaminated tears. LEVEL OF EVIDENCE: Level IV.
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Objective: To address the research gap in the epidemiology of pediatric respiratory tract infections (RTIs) in Luzhou, Southern Sichuan, China, by analyzing respiratory pathogens in a large pediatric cohort from 2018 to 2021, covering the pre- and during-COVID-19 periods. Methods: This study conducted a retrospective analysis of children with RTIs in Luzhou from July 2018 to January 2021. Strict exclusion criteria were applied to ensure an accurate representation of the pediatric population. Pathogen detection included viruses, bacteria, and atypical agents. Results: Pathogens were identified in 52.8% of 12,546 cases. Viruses accounted for 32.2% of infections, bacteria for 29.8%, and atypical agents for 29.7%, with significant findings of Staphylococcus aureus, Moraxella catarrhalis, and Mycoplasma pneumoniae. Age-related analysis indicated a higher incidence of bacterial infections in infants and viral infections in preschool-aged children, with atypical pathogens being most prevalent in 3-5-year-olds. Gender-based analysis, adjusted for age, revealed similar overall pathogen presence; however, females were more susceptible to viral infections, while males were more prone to Streptococcus pneumoniae. Notably, there was an unusual increase in pathogen cases during spring, potentially influenced by behavioral changes and public health measures related to COVID-19. Co-infections were identified as a significant risk factor for the development of pneumonia. Conclusion: The study provides essential insights into the epidemiology of respiratory pathogens in pediatric populations, emphasizing the need for healthcare strategies tailored to age, gender, and seasonality. The findings highlight the impact of environmental and public health factors, including COVID-19 measures, on respiratory pathogen prevalence, underscoring the importance of targeted diagnostic and treatment protocols in pediatric respiratory infections.
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OBJECTIVES: 45,X/46,XY mosaicism is a rare condition with clinical and genetic heterogeneity and have a greatly increased risk of developing germ cell tumors. We describe a rare 45,X/46,XY Chinese girl with malignant tumors, especially focusing on the molecular genetics of gonadal tumor. CASE PRESENTATION: We report a phenotypically Turner-like Chinese adolescent girl who presented primary amenorrhea and a pelvic mass as the chief complaint, which finally demonstrated dysgerminoma replacing the left gonad and gonadoblastoma arising from right gonad respectively. Her chromosome karyotype was 45,X(4)/46,XY(46); Y-chromosome microdeletions in AZFb regions were found on gonadal DNA rather than peripheral blood lymphocyte (PBL) DNA, while no variants were found in the promoter and coding region of SRY gene in both PBL and gonadal tissues. She underwent bilateral gonadectomy; no recurrence or serious complications were identified after 3 years of follow-up. CONCLUSIONS: This case emphasizes the probable correlation between Y chromosome microdeletions in gonadal tissue and the severity of the phenotype in patients with 45,X/46,XY mosaicism and highlights the importance of clinical genetic testing at the chromosomal and molecular level.
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Dysgerminome , Gonadoblastome , Tumeurs de l'ovaire , Phénotype , Syndrome de Turner , Humains , Femelle , Gonadoblastome/génétique , Gonadoblastome/anatomopathologie , Gonadoblastome/chirurgie , Dysgerminome/génétique , Dysgerminome/anatomopathologie , Dysgerminome/chirurgie , Adolescent , Tumeurs de l'ovaire/génétique , Tumeurs de l'ovaire/anatomopathologie , Syndrome de Turner/génétique , Syndrome de Turner/anatomopathologie , Syndrome de Turner/complications , Mosaïcisme , Pronostic , Caryotype , Protéine de la région déterminant le sexe du chromosome Y/génétique , Peuples d'Asie de l'EstRÉSUMÉ
BACKGROUND: Chronic low-grade inflammation may mediate the relationship between obesity and diabetes, yet clinical research in this area remains scarce. Thus, this study aimed to explore the mediating role of chronic low-grade inflammation in this relationship using the National Health and Nutrition Examination Survey (NHANES). METHODS: This study involved 2,482 participants enrolled in the NHANES between 2005 and 2016. Based on the complex sampling survey weights of NHANES, logistic regression models were fitted, adjusting for various covariates to investigate the relationship between BMI, INFLA score, and diabetes. Moreover, weighted quantile sum (WQS) regression models were fitted to analyze the proportional contribution of individual components within the INFLA score. Finally, mediation analysis was conducted to quantitatively assess the magnitude of the mediating effect of the INFLA score on the relationship between BMI and diabetes. RESULTS: After adjusting for all potential confounding factors, a significant positive correlation was noted between INFLA score and diabetes [OR (95% CI), 1.038(1.003-1.075), p = 0.035]. Additionally, a significant positive correlation was observed between the high INFLA group and diabetes compared to the low INFLA group [OR (95% CI), 1.599(1.031-2.481), p = 0.037]. WQS regression models revealed that the proportional contributions of C-reactive protein, white blood cell count, platelet count, and neutrophil-to-lymphocyte ratio (NLR) were 55.5%, 34.8%, 8.46%, and 1.19%, respectively. Finally, the results of the mediation analysis indicated that the indirect effect of the INFLA score accounted for 10.20%. CONCLUSIONS: Chronic low-grade inflammation was associated with diabetes and partially mediates the relationship between obesity and diabetes.
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Diabète de type 2 , Inflammation , Enquêtes nutritionnelles , Obésité , Humains , Femelle , Mâle , Diabète de type 2/complications , Diabète de type 2/épidémiologie , Obésité/complications , Obésité/épidémiologie , Inflammation/épidémiologie , Adulte d'âge moyen , Adulte , Indice de masse corporelle , Maladie chronique , Sujet âgé , Études transversales , États-Unis/épidémiologie , PronosticRÉSUMÉ
BACKGROUND: Circular RNA (circRNAs) have been found to play major roles in the progression of colorectal cancer (CRC). However, the functions of circ_0008345 (transcribed by PTK2) in regulating CRC development remain undefined. In this study, we aimed to explore the roles and underlying mechanisms of circ_0008345 in CRC. METHODS: RNase R-treated total cellular RNA was used to verify the circular structure of circ_0008345, and a subcellular fractionation assay was performed to detect the subcellular localization of circ_0008345. RNA pull-down and dual-luciferase assays were used to verify the binding relation between microRNA (miR)-182-5p and circ_0008345 and/or CYP1A2. Colony formation assay, EdU, and Transwell assays were performed to detect the biological behavior of CRC cells in vitro, and CRC cells were injected into mice to observe the tumor formation. m6A immunoprecipitation was used to detect the m6A modification of circ_0008345 in CRC cells. RESULTS: Circ_0008345, upregulated in CRC tissues and cells, was mainly present in the cytoplasm. Circ_0008345 bound to miR-182-5p, and miR-182-5p targeted CYP1A2, an oncogene in CRC. The colony formation, mobility, EdU-positive cell rate in vitro, and tumor growth in mice were inhibited after the knockdown of circ_0008345. However, the suppressing effects of sh-circ_0008345 on CRC and CYP1A2 expression were significantly reversed after further knockdown of miR-182-5p. METTL3 was the m6A modifier mediating circ_0008345 expression, and the suppression of METTL3 reduced the expression of circ_0008345. CONCLUSIONS: METTL3-dependent m6A methylation upregulated circ_0008345, which blocked the inhibitory effect of miR-182-5p on CYP1A2, thereby exacerbating the malignant phenotype of CRC cells.
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Tumeurs colorectales , Cytochrome P-450 CYP1A2 , Évolution de la maladie , Methyltransferases , microARN , ARN circulaire , microARN/génétique , microARN/métabolisme , Tumeurs colorectales/génétique , Tumeurs colorectales/anatomopathologie , Tumeurs colorectales/métabolisme , ARN circulaire/génétique , ARN circulaire/métabolisme , Humains , Animaux , Souris , Methyltransferases/métabolisme , Methyltransferases/génétique , Cytochrome P-450 CYP1A2/génétique , Cytochrome P-450 CYP1A2/métabolisme , Régulation de l'expression des gènes tumoraux , Prolifération cellulaire , Lignée cellulaire tumorale , Mâle , Femelle , Transduction du signal , Souris nudeRÉSUMÉ
Metabolic diseases such as obesity and diabetes induce lipotoxic cardiomyopathy, which is characterized by myocardial lipid accumulation, dysfunction, hypertrophy, fibrosis and mitochondrial dysfunction. Here, we identify that mitochondrial glycerol 3-phosphate dehydrogenase (mGPDH) is a pivotal regulator of cardiac fatty acid metabolism and function in the setting of lipotoxic cardiomyopathy. Cardiomyocyte-specific deletion of mGPDH promotes high-fat diet induced cardiac dysfunction, pathological hypertrophy, myocardial fibrosis, and lipid accumulation. Mechanically, mGPDH deficiency inhibits the expression of desuccinylase SIRT5, and in turn, the hypersuccinylates majority of enzymes in the fatty acid oxidation (FAO) cycle and promotes the degradation of these enzymes. Moreover, manipulating SIRT5 abolishes the effects of mGPDH ablation or overexpression on cardiac function. Finally, restoration of mGPDH improves lipid accumulation and cardiomyopathy in both diet-induced and genetic obese mouse models. Thus, our study indicates that targeting mGPDH could be a promising strategy for lipotoxic cardiomyopathy in the context of obesity and diabetes.
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BACKGROUND: Atherosclerotic cardiovascular disease (ASCVD) is a group of clinical diseases based on pathology of atherosclerosis that is the leading cause of mortality worldwide. There is a bidirectional interaction between ASCVD and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Alterations in circulating miRNAs levels are involved in the development of ASCVD in patients infected with SARS-CoV-2, however, the correlation between ASCVD co-infection with SARS-CoV-2 and alterations of cardiac-specific miRNAs is not well understood. HYPOTHESIS: The circulating miR-146a and miR-27a are involved in bidirectional interactions between ASCVD and SARS-CoV-2 infections. METHODS: Circulating miR-146a and miR-27a levels were measured in serum and PBMCs deriving from ASCVD patients and controls after SARS-CoV-2 infection by qRT-PCR analysis. The levels of neutralizing antibodies-resistant SARS-CoV-2 in human serum was determined by competitive magnetic particle chemiluminescence method. Interleukin (IL)-6 levels were detected by automatic biochemical analyzer using electrochemiluminescence. RESULTS: Significant downregulation of circulating miR-146a and upregulation of miR-27a in ASCVD patients after infection with SARS-CoV-2 compared with controls were observed, among which the alterations were more evident in ASCVD patients comorbid with hyperlipidemia and diabetes mellitus. Consistently, correlation analysis revealed that serum miR-146a and miR-27a levels were associated with the levels of lipids and glucose, inflammatory response, and immune function in ASCVD patients. Remarkably, SARS-CoV-2 S protein RBD stimulation of PBMCs derived from both ASCVD and controls significantly downregulated miR-146a, upregulated miR-27a expression levels, and promoted IL-6 release in vitro. CONCLUSIONS: The circulating miR-146a and miR-27a are involved in metabolism, inflammation, and immune levels in patients with ASCVD after SARS-CoV-2 infection, laying the foundation for the development of strategies to prevent the risk of SARS-CoV-2 infection in ASCVD patients.
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Athérosclérose , COVID-19 , microARN , SARS-CoV-2 , Humains , COVID-19/sang , COVID-19/immunologie , COVID-19/complications , microARN/sang , Mâle , Femelle , Adulte d'âge moyen , Athérosclérose/sang , Athérosclérose/épidémiologie , Sujet âgé , Marqueurs biologiques/sang , MicroARN circulant/sangRÉSUMÉ
Glucagon receptor (GCGR) agonism offers potentially greater effects on the mitigation of hepatic steatosis. However, its underlying mechanism is not fully understood. Here, it screened tetraspanin CD9 might medicate hepatic effects of GCGR agonist. CD9 is decreased in the fatty livers of patients and upregulated upon GCGR activation. Deficiency of CD9 in the liver exacerbated diet-induced hepatic steatosis via complement factor D (CFD) regulated fatty acid metabolism. Specifically, CD9 modulated hepatic fatty acid synthesis and oxidation genes through regulating CFD expression via the ubiquitination-proteasomal degradation of FLI1. In addition, CD9 influenced body weight by modulating lipogenesis and thermogenesis of adipose tissue through CFD. Moreover, CD9 reinforcement in the liver alleviated hepatic steatosis, and blockage of CD9 abolished the remission of hepatic steatosis induced by cotadutide treatment. Thus, CD9 medicates the hepatic beneficial effects of GCGR signaling, and may server as a promising therapeutic target for hepatic steatosis.
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Stéatose hépatique , Antigène CD9 , Antigène CD9/métabolisme , Antigène CD9/génétique , Animaux , Souris , Humains , Stéatose hépatique/métabolisme , Stéatose hépatique/traitement médicamenteux , Modèles animaux de maladie humaine , Mâle , Récepteurs au glucagon/agonistes , Récepteurs au glucagon/métabolisme , Récepteurs au glucagon/génétique , Souris de lignée C57BL , Foie/métabolisme , Foie/effets des médicaments et des substances chimiques , Transduction du signal/effets des médicaments et des substances chimiquesRÉSUMÉ
Nicotinamide riboside (NR) is a precursor and exogenous supplement of nicotinamide adenine dinucleotide (NAD+). NR has been shown to play a beneficial role in a variety of neurodegenerative diseases. A phase 1 clinical trial identified NR as a potential neuroprotective therapy for Parkinson's disease (PD). However, the mechanism of action of NR in PD has not been fully elucidated. Therefore, the present study aimed to investigate the potential effects of NR on a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced PD model in zebrafish and its underlying mechanisms. The results showed that NR improved motor dysfunction, survival time, dopamine neurons, and peripheral neurons, as well as the NAD+ levels in the MPTP-affected PD zebrafish model. In addition, transcriptome sequencing analysis revealed that, after NR treatment, differentially expressed genes were significantly enriched in the glucose metabolism and protein processing pathways in the endoplasmic reticulum (ER). Quantitative PCR (qPCR) revealed that the mRNA levels of the glycoheterotrophic enzyme (involved in glucose metabolism) were significantly decreased, and the glycolytic enzyme mRNA expression levels were significantly increased. The results of the non-targeted metabolomic analysis showed that NR treatment significantly increased the levels of metabolites such as nicotinic acid ,nicotinamide, d-glucose (from the gluconeogenesis and glycolysis metabolism pathways) and some glucogenic amino acids, such as glutamine. Importantly, NR ameliorated MPTP-induced endoplasmic reticulum stress (ERS) in the PD zebrafish model through the Perk-Eif2α-Atf4-Chop pathway. These results highlight the neuroprotective effect of NR in the present PD zebrafish model through modulation of glucose metabolism and ERS via the Perk-Eif2α-Atf4-Chop pathway and provide valuable mechanistic insights into the treatment of PD.
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1-Méthyl-4-phényl-1,2,3,6-tétrahydropyridine , Modèles animaux de maladie humaine , Stress du réticulum endoplasmique , Glucose , Nicotinamide , Composés de pyridinium , Danio zébré , Animaux , Stress du réticulum endoplasmique/effets des médicaments et des substances chimiques , Nicotinamide/analogues et dérivés , Nicotinamide/pharmacologie , Nicotinamide/usage thérapeutique , Composés de pyridinium/pharmacologie , Composés de pyridinium/usage thérapeutique , Glucose/métabolisme , Neuroprotecteurs/pharmacologie , Neuroprotecteurs/usage thérapeutique , Maladie de Parkinson/traitement médicamenteux , Maladie de Parkinson/métabolisme , Neurones dopaminergiques/effets des médicaments et des substances chimiques , Neurones dopaminergiques/métabolisme , Protéines de poisson-zèbre/métabolisme , Protéines de poisson-zèbre/génétique , Activité motrice/effets des médicaments et des substances chimiques , MâleRÉSUMÉ
Objective: The coronavirus disease 2019 (COVID-19) spread rapidly and claimed millions of lives worldwide. Acute respiratory distress syndrome (ARDS) is the major cause of COVID-19-associated deaths. Due to the limitations of current drugs, developing effective therapeutic options that can be used rapidly and safely in clinics for treating severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infections is necessary. This study aims to investigate the effects of two food-extracted immunomodulatory agents, ajoene-enriched garlic extract (AGE) and cruciferous vegetables-extracted sulforaphane (SFN), on anti-inflammatory and immune responses in a SARS-CoV-2 acute lung injury mouse model. Methods: In this study, we established a mouse model to mimic the SARS-CoV-2 infection acute lung injury model via intratracheal injection of polyinosinic:polycytidylic acid (poly[I:C]) and SARS-CoV-2 recombinant spike protein (SP). After the different agents treatment, lung sections, bronchoalveolar lavage fluid (BALF) and fresh faeces were harvested. Then, H&E staining was used to examine symptoms of interstitial pneumonia. Flow cytometry was used to examine the change of immune cell populations. Multiplex cytokines assay was used to examine the inflammatory cytokines.16S rDNA high-throughput sequencing was used to examine the change of gut microbiome. Results: Our results showed that AGE and SFN significantly suppressed the symptoms of interstitial pneumonia, effectively inhibited the production of inflammatory cytokines, decreased the percentage of inflammatory cell populations, and elevated T cell populations in the mouse model. Furthermore, we also observed that the gut microbiome of genus Paramuribaculum were enriched in the AGE-treated group. Conclusion: Here, for the first time, we observed that these two novel, safe, and relatively inexpensive immunomodulatory agents exhibited the same effects on anti-inflammatory and immune responses as neutralizing monoclonal antibodies (mAbs) against interleukin 6 receptor (IL-6R), which have been suggested for treating COVID-19 patients. Our results revealed the therapeutic ability of these two immunomodulatory agents in a mouse model of SARS-CoV-2 acute lung injury by promoting anti-inflammatory and immune responses. These results suggest that AGE and SFN are promising candidates for the COVID-19 treatment.
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Lésion pulmonaire aigüe , Angiotensin-converting enzyme 2 , Anti-inflammatoires , Traitements médicamenteux de la COVID-19 , COVID-19 , Modèles animaux de maladie humaine , Agents immunomodulateurs , SARS-CoV-2 , Animaux , Souris , Lésion pulmonaire aigüe/immunologie , Lésion pulmonaire aigüe/traitement médicamenteux , Lésion pulmonaire aigüe/étiologie , COVID-19/immunologie , SARS-CoV-2/immunologie , Agents immunomodulateurs/pharmacologie , Agents immunomodulateurs/usage thérapeutique , Anti-inflammatoires/usage thérapeutique , Anti-inflammatoires/pharmacologie , Angiotensin-converting enzyme 2/métabolisme , Angiotensin-converting enzyme 2/génétique , Isothiocyanates/pharmacologie , Isothiocyanates/usage thérapeutique , Sulfoxydes , Humains , Cytokines/métabolisme , Glycoprotéine de spicule des coronavirus/immunologie , Poumon/immunologie , Poumon/anatomopathologie , Poumon/virologie , Poumon/effets des médicaments et des substances chimiques , Mâle , Poly I-C , Extraits de plantes/pharmacologie , Extraits de plantes/usage thérapeutiqueRÉSUMÉ
Purpose: The isolation rate of carbapenem-resistant Enterobacter cloacae complex (CREC) is continuously increasing. The aims of this study were to investigate the molecular characteristics and risk factors associated with CREC infections. Methods: Bacterial species were identified using the matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS) (Bruker Daltonik GmbH, Bremen, Germany), and the hsp60 gene was utilized for further typing. Antimicrobial susceptibilities were assessed through the MicroScan WalkAway 96 Plus system (Siemens, Germany) and the microbroth dilution method. Antimicrobial resistance genes were screened through polymerase chain reaction (PCR), while the homologous relationship was assessed using multilocus sequence typing (MLST). Conjugation experiments were performed to verify whether the plasmid could be transferred. Additionally, logistic regression model was employed to analyze risk factors for CREC infections. Results: 32 strains of CREC bacteria were isolated during the study, yet only 20 were retained for preservation. While the isolates demonstrated resistance to the majority of antibiotics, they exhibited high sensitivity to polymyxin B and tigecycline. All isolates carried the blaNDM resistance gene, including 13 blaNDM-1 isolates and 7 blaNDM-5 isolates. MLST homology analysis revealed the presence of seven known ST types and one new ST type. Conjugation experiments confirmed that 13 isolates were capable of transferring the blaNDM resistance gene to Escherichia coli strain EC600. Single-factor analysis identified multiple primary risk factors for CREC infection, but multivariate analysis did not reveal independent risk factors. Conclusion: This study investigates the molecular characteristics and risk factors associated with CREC infections. The detection rate of CREC strains in our hospital is continuously rising and homology analysis suggested that strains might spread in our hospital, emphasizing the importance of implementing effective preventive measures to control the horizontal transmission of plasmid-mediated antimicrobial resistance genes.
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OBJECTIVES: The emergence of carbapenem-resistant Pseudomonas putida (CRPP) has raised public awareness. This study investigated two strains from the Pseudomonas putida group that were resistant to carbapenem, tigecycline, and aztreonam-avibactam (ATM-AVI), with a focus on their microbial and genomic characteristics. METHODS: We assessed the antibiotic resistance profile using broth dilution, disk diffusion, and E-test methods. Efflux pump phenotype testing and real-time quantitative PCR were employed to evaluate efflux pump activity in tigecycline resistance, while polymerase chain reaction was utilized to detect common carbapenem genes. Additionally, whole-genome sequencing was performed to analyze genomic characteristics. The transferability of blaIMP-1 and blaAFM-4 was assessed through a conjugation experiment. Furthermore, growth kinetics and biofilm formation were examined using growth curves and crystal violet staining. RESULTS: Both strains demonstrated resistance to carbapenem, tigecycline, and ATM-AVI. Notably, NMP can restore sensitivity to tigecycline. Subsequent analysis revealed that they co-produced blaIMP-1, blaAFM-4, tmexCD-toprJ, and blaOXA-1041, belonging to a novel sequence type ST268. Although they were closely related on the phylogenetic tree, they exhibited different levels of virulence. Genetic environment analysis indicated variations compared to prior studies, particularly regarding the blaIMP-1 and blaAFM-4 genes, which showed limited horizontal transferability. Moreover, it was observed that temperature exerted a specific influence on their biological factors. CONCLUSION: We initially identified two P. putida ST268 strains co-producing blaIMP-1, blaAFM-4, blaOXA-1041, and tmexCD-toprJ. The resistance to tigecycline and ATM-AVI can be attributed to the presence of multiple drug resistance determinants. These findings underscore the significance of P. putida as a reservoir for novel antibiotic resistance genes. Therefore, it is imperative to develop alternative antibiotic therapies and establish effective monitoring of bacterial resistance.
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Antibactériens , Composés azabicycliques , Aztréonam , Tests de sensibilité microbienne , Pseudomonas putida , Tigecycline , bêta-Lactamases , Pseudomonas putida/génétique , Pseudomonas putida/effets des médicaments et des substances chimiques , Tigecycline/pharmacologie , Antibactériens/pharmacologie , Chine , Aztréonam/pharmacologie , Composés azabicycliques/pharmacologie , bêta-Lactamases/génétique , bêta-Lactamases/métabolisme , Multirésistance bactérienne aux médicaments/génétique , Séquençage du génome entier , Humains , Association médicamenteuse , Biofilms/effets des médicaments et des substances chimiques , Biofilms/croissance et développement , Protéines bactériennes/génétique , Protéines bactériennes/métabolisme , Infections à Pseudomonas/microbiologie , Carbapénèmes/pharmacologieRÉSUMÉ
BACKGROUND: Accumulating evidence demonstrates that an increased tumor-associated macrophage abundance is often associated with poor prognosis in colorectal cancer (CRC). The mechanism underlying the effect of tumor-derived exosomes on M2 macrophage polarization remains elusive. RESULTS: The novel circular RNA circPOLQ exhibited significantly higher expression in CRC tissues than in paired normal tissues. Higher circPOLQ expression was associated with poorer prognosis in patients with CRC. In vitro and in vivo experiments showed that tumor-derived exosomal circPOLQ did not directly regulate CRC cell development but promoted CRC metastatic nodule formation by enhancing M2 macrophage polarization. circPOLQ activated the interleukin-10/signal transducer and activator of transcription 3 axis by targeting miR-379-3 p to promote M2 macrophage polarization. CONCLUSION: circPOLQ can enter macrophages via CRC cell-derived exosomes and promote CRC metastatic nodule formation by enhancing M2 macrophage polarization. These findings reveal a tumor-derived exosome-mediated tumor-macrophage interaction potentially affecting CRC metastatic nodule formation.
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Tumeurs colorectales , Exosomes , Interleukine-10 , Macrophages , ARN circulaire , Facteur de transcription STAT-3 , Animaux , Femelle , Humains , Mâle , Souris , Lignée cellulaire tumorale , Tumeurs colorectales/anatomopathologie , Tumeurs colorectales/métabolisme , Tumeurs colorectales/génétique , Exosomes/métabolisme , Interleukine-10/métabolisme , Activation des macrophages , Macrophages/métabolisme , ARN circulaire/génétique , ARN circulaire/métabolisme , Transduction du signal , Facteur de transcription STAT-3/métabolisme , Macrophages associés aux tumeurs/métabolismeRÉSUMÉ
Polymeric vesicles are perspective vehicles for fabricating enzymatic nanoreactors towards diverse biomedical and catalytic applications, yet the design of stable and permeable vesicles remains challenging. Herein, we developed polyion complex (PIC) vesicles featuring high stability and a permeable membrane for adequate enzyme loading and activation. Our design relies on co-assembly of an anionic diblock copolymer (PSS96-b-PEO113) with cationic branched poly(ethylenimine) (PEI). The polymer combination endows strong electrostatic interaction between the PSS and PEI building blocks, so their assembly can be implemented at a high salt concentration (500 mM NaCl), under which the charge interaction of the enzyme-polymer is inhibited. This control realizes the successful and safe loading of enzymes associated with the formation of stable PIC vesicles with an intrinsic permeable membrane that is favourable for enhancing enzymatic activity. The control factors for vesicle formation and enzyme loading were investigated, and the general application of loading different enzymes for cascade reaction was validated as well. Our study reveals that proper design and combination of polyelectrolytes is a facile strategy for fabricating stable and permeable polymeric PIC vesicles, which exhibit clear advantages for loading and activating enzymes, consequently boosting their diverse applications as enzymatic nanoreactors.
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Polyéthylèneimine , Polyéthylèneimine/composition chimique , Perméabilité , Polymères/composition chimique , Polyélectrolytes/composition chimiqueRÉSUMÉ
Spinal cord injury (SCI) constitutes a significant clinical challenge, and there is extensive research focused on identifying molecular activities that can facilitate the repair of spinal cord injuries. Mammalian sterile 20-like kinase 2 (MST2), a core component of the Hippo signaling pathway, plays a key role in apoptosis and cell growth. However, its role in neurite outgrowth after spinal cord injury remains unknown. Through comprehensive in vitro and in vivo experiments, we demonstrated that MST2, predominantly expressed in neurons, actively participated in the natural development of the CNS. Post-SCI, MST2 expression significantly increased, indicating its activation and potential role in the early stages of neural recovery. Detailed analyses showed that MST2 knockdown impaired neurite outgrowth and motor function recovery, whereas MST2 overexpression led to the opposite effects, underscoring MST2's neuroprotective role in enhancing neural repair. Further, we elucidated the mechanism underlying MST2's action, revealing its interaction with AKT and positive regulation of AKT activity, a well-established promoter of neurite outgrowth. Notably, MST2's promotion of neurite outgrowth and motor functional recovery was diminished by AKT inhibitors, highlighting the dependency of MST2's neuroprotective effects on AKT signaling. In conclusion, our findings affirmed MST2's pivotal role in fostering neuronal neurite outgrowth and facilitating functional recovery after SCI, mediated through its positive modulation of AKT activity. In conclusion, our findings confirmed MST2's crucial role in neural protection, promoting neurite outgrowth and functional recovery after SCI through positive AKT activity modulation. These results position MST2 as a potential therapeutic target for SCI, offering new insights into strategies for enhancing neuroregeneration and functional restoration.
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Duchenne muscular dystrophy (DMD MIM#310200) is a degenerative muscle disease caused by mutations in the dystrophin gene located on Xp21.2. The clinical features encompass muscle weakness and markedly elevated serum creatine kinase levels. An 8-year-old Chinese boy was diagnosed with Duchenne muscular dystrophy (DMD). Whole exome gene sequencing was conducted and the Sanger method was used to validate sequencing. A deletion (c.5021del) in exon 35 of the dystrophin gene was identified, which was predicted to generate a frameshift mutation and create an early termination codon (p.Leu1674CysfsTer47). It has a pathogenic effect against dystrophin in the muscle cell membrane of the patient. As such, prednisone treatment at a dose of 0.75 mg/kg.d was administered. After one month, a notable reduction in fall frequency was observed. Our new finding will expand the pathogenic mutation spectrum causing DMD.
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BACKGROUND: The aim of our study was to explore the characteristics of the arterial risk factors and ankle-brachial index (ABI) in patients with lower extremity chronic venous disease (LECVD). METHODS: A total of 2642 subjects were employed in our study. The lifestyle and clinical data were collected. The history of vascular diseases contained coronary artery disease, stroke, hypertension, and diabetes. ABI low than 0.9 was considered as lower extremity artery disease (LEAD). A series of blood indicators were measured. RESULTS: Patients with ABI low than 0.9 belonged to the group of LEAD. Age, smoking, drinking, hypertension, diabetes mellitus, lipid-lowering drug, antidiabetic, total protein, total protein, triglyceride, low-density lipoprotein cholesterol, glycosylated hemoglobin and homocysteine were the common risk factors shared by LEAD and LECVD (P<0.05). The prevalence of LEAD in patients with LECVD was higher than those without LECVD (P<0.05). In Pearson correlation analysis, LECVD was related to LEAD (P<0.05). Before and after adjusted shared factors, as the performance of the logistic regression models, LEAD was an independent risk factor for the prevalence of LECVD (OR=2.937, 95% CI: [1.956, 4.411], P<0.001). CONCLUSIONS: Our study demonstrated that an ABI lower than 0.9 is an independent risk factor for LECVD.
Sujet(s)
Index de pression systolique cheville-bras , Membre inférieur , Maladie artérielle périphérique , Humains , Mâle , Femelle , Adulte d'âge moyen , Facteurs de risque , Maladie chronique , Membre inférieur/vascularisation , Sujet âgé , Maladie artérielle périphérique/épidémiologie , Maladie artérielle périphérique/diagnostic , Maladie artérielle périphérique/physiopathologie , Maladie artérielle périphérique/sang , Prévalence , Adulte , Chine/épidémiologie , Modèles logistiques , Insuffisance veineuse/épidémiologie , Insuffisance veineuse/physiopathologie , Insuffisance veineuse/diagnostic , Insuffisance veineuse/sang , Valeur prédictive des testsRÉSUMÉ
Swarm behaviors are common in nature, where individual organisms collaborate via perception, communication, and adaptation. Emulating these dynamics, large groups of active agents can self-organize through localized interactions, giving rise to complex swarm behaviors, which exhibit potential for applications across various domains. This review presents a comprehensive summary and perspective of synthetic swarms, to bridge the gap between the microscale individual agents and potential applications of synthetic swarms. It is begun by examining active agents, the fundamental units of synthetic swarms, to understand the origins of their motility and functionality in the presence of external stimuli. Then inter-agent communications and agent-environment communications that contribute to the swarm generation are summarized. Furthermore, the swarm behaviors reported to date and the emergence of machine intelligence within these behaviors are reviewed. Eventually, the applications enabled by distinct synthetic swarms are summarized. By discussing the emergent machine intelligence in swarm behaviors, insights are offered into the design and deployment of autonomous synthetic swarms for real-world applications.
RÉSUMÉ
In recent years, breast cancer (BC) has surpassed lung cancer as the most common malignant tumor worldwide and remains the leading cause of cancer death in women. The etiology of BC usually involves dysregulation of epigenetic mechanisms and aberrant expression of certain non-coding RNAs (ncRNAs). N6-methyladenosine (m6A), the most prevalent RNA modification in eukaryotes, widely exists in ncRNAs to affect its biosynthesis and function, and is an important regulator of tumor-related signaling pathways. Interestingly, ncRNAs can also regulate or target m6A modification, playing a key role in cancer progression. However, the m6A-ncRNAs regulatory network in BC has not been fully elucidated, especially the regulation of m6A modification by ncRNAs. Therefore, in this review, we comprehensively summarize the interaction mechanisms and biological significance of m6A modifications and ncRNAs in BC. Meanwhile, we also focused on the clinical application value of m6A modification in BC diagnosis and prognosis, intending to explore new biomarkers and potential therapeutic targets.
Sujet(s)
Tumeurs du sein , Tumeurs du poumon , Femelle , Humains , Tumeurs du sein/génétique , Adénosine/génétique , Épigenèse génétique , ARN non traduit/génétiqueRÉSUMÉ
The aim of this study is to comprehensively investigate the prevalence and distribution patterns of three common genetic variants associated with hearing loss (HL) in Chinese neonatal population. Methods: Prior to June 30, 2023, an extensive search and screening process was conducted across multiple literature databases. R software was utilized for conducting meta-analyses, cartography, and correlation analyses. Results: Firstly, our study identified a total of 99 studies meeting the inclusion criteria. Notably, provinces such as Qinghai, Tibet, Jilin, and Heilongjiang lack large-scale genetic screening data for neonatal deafness. Secondly, in Chinese newborns, the carrier frequencies of GJB2 variants (c.235delC, c.299_300delAT) were 1.63 % (95 %CI 1.52 %-1.76 %) and 0.33 % (95 %CI 0.30 %-0.37 %); While SLC26A4 variants (c.919-2A > G, c.2168A > G) exhibited carrier rates of 0.95 % (95 %CI 0.86 %-1.04 %) and 0.17 % (95 %CI 0.15 %-0.19 %); Additionally, Mt 12S rRNA m.1555 A > G variant was found at a rate of 0.24 % (95 % CI 0.22 %-0.26 %). Thirdly, the mutation rate of GJB2 c.235delC was higher in the east of the Heihe-Tengchong line, whereas the mutation rate of Mt 12S rRNA m.1555 A > G variant exhibited the opposite pattern. Forthly, no significant correlation exhibited the opposite pattern of GJB2 variants, but there was a notable correlation among SLC26A4 variants. Lastly, strong regional distribution correlations were evident between mutation sites from different genes, particularly between SLC26A4 (c.919-2A > G and c.2168A > G) and GJB c.299_300delAT. Conclusions: The most prevalent deafness genes among Chinese neonates were GJB2 c.235delC variant, followed by SLC26A4 c.919-2A > G variant. These gene mutation rates exhibit significant regional distribution characteristics. Consequently, it is imperative to enhance genetic screening efforts to reduce the incidence of deafness in high-risk areas.