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Multiple regulatory mechanisms are in place to ensure the normal processes of bone metabolism, encompassing both bone formation and absorption. This study has identified chaperone-mediated autophagy (CMA) as a critical regulator that safeguards bone formation from the detrimental effects of excessive inflammation. By silencing LAMP2A or HSCA8, we observed a hindrance in the osteoblast differentiation of human bone marrow mesenchymal stem cells (hBMSCs) in vitro. To further elucidate the role of LAMP2A, we generated LAMP2A gene knockdown and overexpression of mouse BMSCs (mBMSCs) using adenovirus. Our results showed that LAMP2A knockdown led to a decrease in osteogenic-specific proteins, while LAMP2A overexpression favored the osteogenesis of mBMSCs. Notably, active-ß-catenin levels were upregulated by LAMP2A overexpression. Furthermore, we found that LAMP2A overexpression effectively protected the osteogenesis of mBMSCs from TNF-α, through the PI3K/AKT/GSK3ß/ß-catenin pathway. Additionally, LAMP2A overexpression significantly inhibited osteoclast hyperactivity induced by TNF-α. Finally, in a murine bone defect model, we demonstrated that controlled release of LAMP2A overexpression adenovirus by alginate sodium capsule efficiently protected bone healing from inflammation, as confirmed by imaging and histological analyses. Collectively, our findings suggest that enhancing CMA has the potential to safeguard bone formation while mitigating hyperactivity in bone absorption.
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Autofagia Mediada por Chaperonas , Glicogênio Sintase Quinase 3 beta , Inflamação , Proteína 2 de Membrana Associada ao Lisossomo , Células-Tronco Mesenquimais , Osteogênese , Fosfatidilinositol 3-Quinases , Proteínas Proto-Oncogênicas c-akt , beta Catenina , Animais , Osteogênese/fisiologia , Glicogênio Sintase Quinase 3 beta/metabolismo , Glicogênio Sintase Quinase 3 beta/genética , Proteínas Proto-Oncogênicas c-akt/metabolismo , Camundongos , Fosfatidilinositol 3-Quinases/metabolismo , beta Catenina/metabolismo , Humanos , Células-Tronco Mesenquimais/metabolismo , Inflamação/metabolismo , Proteína 2 de Membrana Associada ao Lisossomo/metabolismo , Proteína 2 de Membrana Associada ao Lisossomo/genética , Transdução de Sinais , Masculino , Camundongos Endogâmicos C57BL , Osteoblastos/metabolismo , Diferenciação Celular , Osteoclastos/metabolismoRESUMO
The mortality rate linked with nephrotic syndrome (NS) is quite high. The renal tubular injury influences the response of NS patients to steroid treatment. KN motif and ankyrin repeat domains 2 (KANK2) regulates actin polymerization, which is required for renal tubular cells to maintain their function. In this study, we found that the levels of KANK2 in patients with NS were considerably lower than those in healthy controls, especially in NS patients with acute kidney injury (AKI). To get a deeper understanding of the KANK2 transcriptional control mechanism, the core promoter region of the KANK2 gene was identified. KANK2 was further found to be positively regulated by E2F Transcription Factor 1 (E2F1), Transcription Factor AP-2 Gamma (TFAP2C), and Nuclear Respiratory Factor 1 (NRF1), both at mRNA and protein levels. Knocking down E2F1, TFAP2C, or NRF1 deformed the cytoskeleton of renal tubular cells and reduced F-actin content. EMSA and ChIP assays confirmed that all three transcription factors could bind to the upstream promoter transcription site of KANK2 to transactivate KANK2 in renal tubular epithelial cells. Our study suggests that E2F1, TFAP2C, and NRF1 play essential roles in regulating the KANK2 transcription, therefore shedding fresh light on the development of putative therapeutic options for the treatment of NS patients.
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Síndrome Nefrótica , Fator 1 Nuclear Respiratório , Humanos , Fator 1 Nuclear Respiratório/metabolismo , Síndrome Nefrótica/genética , Fatores de Transcrição/metabolismo , Regulação da Expressão Gênica , Regiões Promotoras Genéticas/genética , Fator de Transcrição E2F1/genética , Fator de Transcrição AP-2/genéticaRESUMO
Recent work indicates that killing of bacteria by diverse antimicrobial classes can involve reactive oxygen species (ROS), as if a common, self-destructive response to antibiotics occurs. However, the ROS-bacterial death theory has been challenged. To better understand stress-mediated bacterial death, we enriched spontaneous antideath mutants of Escherichia coli that survive treatment by diverse bactericidal agents that include antibiotics, disinfectants, and environmental stressors, without a priori consideration of ROS. The mutants retained bacteriostatic susceptibility, thereby ruling out resistance. Surprisingly, pan-tolerance arose from carbohydrate metabolism deficiencies in ptsI (phosphotransferase) and cyaA (adenyl cyclase); these genes displayed the activity of upstream regulators of a widely shared, stress-mediated death pathway. The antideath effect was reversed by genetic complementation, exogenous cAMP, or a Crp variant that bypasses cAMP binding for activation. Downstream events comprised a metabolic shift from the TCA cycle to glycolysis and to the pentose phosphate pathway, suppression of stress-mediated ATP surges, and reduced accumulation of ROS. These observations reveal how upstream signals from diverse stress-mediated lesions stimulate shared, late-stage, ROS-mediated events. Cultures of these stable, pan-tolerant mutants grew normally and were therefore distinct from tolerance derived from growth defects described previously. Pan-tolerance raises the potential for unrestricted disinfectant use to contribute to antibiotic tolerance and resistance. It also weakens host defenses, because three agents (hypochlorite, hydrogen peroxide, and low pH) affected by pan-tolerance are used by the immune system to fight infections. Understanding and manipulating the PtsI-CyaA-Crpmediated death process can help better control pathogens and maintain beneficial microbiota during antimicrobial treatment.
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Anti-Infecciosos , Colicinas , Proteína Receptora de AMP Cíclico , Proteínas de Escherichia coli , Escherichia coli , Proteínas de Transporte de Monossacarídeos , Estresse Oxidativo , Sistema Fosfotransferase de Açúcar do Fosfoenolpiruvato , Anti-Infecciosos/farmacologia , Colicinas/metabolismo , AMP Cíclico/metabolismo , Proteína Receptora de AMP Cíclico/metabolismo , Tolerância a Medicamentos , Escherichia coli/efeitos dos fármacos , Escherichia coli/genética , Escherichia coli/fisiologia , Proteínas de Escherichia coli/metabolismo , Proteínas de Transporte de Monossacarídeos/metabolismo , Sistema Fosfotransferase de Açúcar do Fosfoenolpiruvato/metabolismo , Espécies Reativas de Oxigênio/metabolismoRESUMO
Electron-donating/-withdrawing groups (EDGs/EWGs) substitution is widely used to regulate the catalytic performance of transition-metal phthalocyanine (MPc) toward electrochemical CO2 reduction, but the corresponding structure-activity relationships and regulation mechanisms are still ambiguous. Herein, by investigating a series of substitution-functionalized MPc (MPc-X), this work reveals a double-volcano-like relationship between the electron-donating/-withdrawing abilities of the substituents and the catalytic activities of MPc-X. The weak-EDG/-EWG substitution enhances whereas the strong-EDG/-EWG substitution mostly lowers the CO selectivity of MPc. Experimental and calculation results demonstrate that the electronic properties of the substituents influence the symmetry and energy of the highest occupied molecular orbitals of MPc-X, which in turn determine the CO2 adsorption/activation and lead to diverse CO2 reduction pathways on the EWG or EDG substituted MPc via different CO2 adsorption modes. This work provides mechanism insights that could be guidance for the design and regulation of molecular catalysts.
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Novel binder designs are shown to be fruitful in improving the electrochemical performance of silicon (Si)-based anodes. However, issues with mechanical damage from dramatic volume change and poor lithium-ion (Li+) diffusion kinetics in Si-based materials still need to be addressed. Herein, an aqueous self-repairing borate-type binder (SBG) with a web-like architecture and high ionic conductivity is designed for Si and SiO electrodes. The 3D web-like architecture of the SBG binder enables uniform stress distribution, while its self-repairing ability promotes effective stress dissipation and mechanical damage repair, thereby enhancing the damage tolerance of the electrode. The tetracoordinate boron ions ( - BO 4 - $ - {\mathrm{BO}}_4^ - $ ) in the SBG binder boosts the Li transportation kinetics of Si-based electrodes. Based on dynamic covalent and ionic conductive boronic ester bonds, the diverse requirements of the binder, including uniform stress distribution, self-repairing ability, and high ionic conductivity, can be met by simple components. Consequently, the proposed straightforward multifunction design strategy for binders based on dynamic boron chemistry provides valuable insights into fabricating high-performance Si-based anodes.
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Oral submucous fibrosis (OSF) is a potentially malignant disorder of the oral mucosa; however, whether and how the fibrotic matrix of OSF is involved in the malignant transformation of epithelial cells remains unknown. Herein, oral mucosa tissue from patients with OSF, OSF rat models, and their controls were used to observe the extracellular matrix changes and epithelial-mesenchymal transformation (EMT) in fibrotic lesions. Compared with controls, oral mucous tissues from patients with OSF showed an increased number of myofibroblasts, a decreased number of blood vessels, and increased type I and type III collagen levels. In addition, the oral mucous tissues from humans and OSF rats showed increased stiffness, accompanied by increased EMT activities of epithelial cells. The EMT activities of stiff construct-cultured epithelial cells were increased significantly by exogenous piezo-type mechanosensitive ion channel component 1 (Piezo1) activation, and decreased by yes-associated protein (YAP) inhibition. During ex vivo implantation, oral mucosal epithelial cells of the stiff group showed increased EMT activities and increased levels of Piezo1 and YAP compared with those in the sham and soft groups. These results indicate that increased stiffness of the fibrotic matrix in OSF led to increased proliferation and EMT of mucosal epithelial cells, in which the Piezo1-YAP signal transduction is important.
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Fibrose Oral Submucosa , Humanos , Ratos , Animais , Fibrose Oral Submucosa/metabolismo , Fibrose Oral Submucosa/patologia , Mucosa Bucal/metabolismo , Mucosa Bucal/patologia , Transição Epitelial-Mesenquimal , Miofibroblastos/metabolismo , Células Epiteliais/metabolismoRESUMO
OBJECTIVE: Prostate hyperplasia and cancer are more prevalent in middle-aged and elderly men. Previous studies have linked both disorders to androgen receptors. Herein, efforts were made to identify factors associated with prostate cancer in patients ≥60 years, aiming to enhance their health management. METHODS: An analytical framework was established utilizing the "Prostate Cancer Early Warning Dataset" from the National Clinical Medical Science Data Center. Variables selection was conducted through LASSO regression, followed by multifactorial logistic stepwise regression to construct a predictive model. RESULTS: A total of 1,502 patients with BPH and 294 with combined PCa were hereby included. Multivariate regression delineated several independent predictors of PCa coexistence, including age (OR [95% CI]: 1.06 [1.04-1.09], p < 0.001), fPSA/tPSA ratio (OR [95% CI]: 0.01 [0.002-0.05], p < 0.001), serum inorganic phosphorus (OR [95% CI]: 5.85 [2.61-13.15], p < 0.001), globulin levels (OR [95% CI]: 1.06 [1.02-1.11], p = 0.005), serum potassium (OR [95% CI]: 0.58 [0.40-0.86], p = 0.006), low-density lipoprotein (LDL) cholesterol (OR [95% CI]: 1.28 [1.06-1.54], p = 0.009), among others. CONCLUSION: The analysis revealed connections between PCa occurrence in men aged over 60 and BPH, along with specific serum biomarkers such as inorganic phosphorus, globulin, LDL cholesterol, lower fPSA/tPSA ratios and serum potassium.
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Hiperplasia Prostática , Neoplasias da Próstata , Humanos , Masculino , Hiperplasia Prostática/sangue , Hiperplasia Prostática/epidemiologia , Neoplasias da Próstata/sangue , Neoplasias da Próstata/epidemiologia , Idoso , Pessoa de Meia-Idade , Fatores de Risco , Antígeno Prostático Específico/sangue , Fatores Etários , Idoso de 80 Anos ou mais , Modelos LogísticosRESUMO
Fe has been reported to play a crucial role in improving the catalytic activity and stability of Ni/Co-based electrocatalysts for the oxygen evolution reaction (OER), while the Fe effect remains intangible. Here, we design several experiments to identify the activity and stability improvement using porous anodized nickel foam (ANF) as the electrode and 1.0 M KOH containing 1000 µM Fe(III) ions as the electrolyte. Systematic investigations reveal that Ni sites serve as hosts to capture Fe ions to create active FeNi-based intermediates on the surface of ANF to improve the OER activity significantly, and Fe ions regulate catalytic equilibrium and maintain the stability for a long time. The system exhibits 242 and 343 mV overpotentials to reach 10 and 1000 mA cm-2 current densities and a robust stability of 360 h at an industrially suitable current density (1000 mA cm-2). This work expands insights into the Fe(III) catalysis effect on the OER efficiency of Ni-based catalysts and provides an economical and practical way to commercial application.
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INTRODUCTION: The objective of this study was to evaluate the abnormal myocardial function in HFpEF patients with renal dysfunction (RD) and investigate the relationship between renal function and myocardial mechanical characteristics in patients with HFpEF. METHODS: 134 patients with HFpEF and 32 control subjects were enrolled in our study. Clinical and echocardiography data were collected for offline analysis. Global work index (GWI), global constructive work (GCW), global waste work (GWW), and global work efficiency (GWE) were measured after noninvasive pressure-strain loop analysis. Univariate and multivariate analyses were used to determine the correlation between renal function and myocardial function in patients with HFpEF. RESULTS: In comparison to control subjects, patients with HFpEF tend to have higher GWW (78 [50-115] vs. 108 [65-160] mm Hg%, p < 0.05) and lower GWE (96 [95-97] vs. 95 [92-96] %, p < 0.05), while left ventricular ejection fraction (65.5 ± 3.3 vs. 64.3 ± 4.6%, p < 0.05) was comparable between them. Besides, increased GWW (86 [58-152] vs. 125 [94-187] mm Hg%, p < 0.05) and decreased GWE (96 [93-97] vs. 94 [92-96] %, p < 0.05) were detected in patients with RD compared to those with normal renal function. An independent correlation was found between estimated glomerular filtration rate and GWW after multivariate analysis. DISCUSSION/CONCLUSION: More severely impaired myocardial function was detected in HFpEF patients with RD compared to those with normal renal function. Estimated glomerular filtration rate was independently correlated to GWW in patients with HFpEF.
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Insuficiência Cardíaca , Humanos , Insuficiência Cardíaca/complicações , Volume Sistólico , Função Ventricular Esquerda , Miocárdio , Rim/diagnóstico por imagemRESUMO
OBJECTIVE: To investigate the predictive ability of global longitudinal strain (GLS) and mechanical dispersion for coronary stenosis and provide a more reliable noninvasive method for diagnosis of obstructive coronary artery disease(OCAD). METHODS: Sixty-seven patients diagnosed with suspected CAD were included in the study. Patients with coronary stenosis greater than 50% were assigned as OCAD, while the others were assigned as non obstructive coronary artery disease(NOCAD). General information was collected and patients underwent speckle tracking echocardiogram(STE). RESULTS: Spearman's correlation analysis showed that GLS and mechanical dispersion were positively correlated with the degree of coronary stenosis (r = 0.383, 0.342, p < 0.05), and there was also a positive correlation between GLS and mechanical dispersion (r = 0.327, p < 0.05). GLS, longitudinal strain (LS) of each chamber, and mechanical dispersion were higher in the OCAD group than in the NOCAD group (p < 0.05). Univariate regression analysis showed that GLS, each lumen LS and mechanical dispersion were statistically significant (p < 0.05). Multifactorial regression analysis showed that elevated GLS (p = 0.007) and elevated mechanical dispersion (p = 0.030) were independent risk factors for OCAD. The ROC curves showed that GLS predicted OCAD (AUC area 0.745, 95% CI 0.624 to 0.865) versus mechanical discrete prediction of OCAD (AUC area 0.702, 95% CI 0.569 to 0.834) were more diagnostic than conventional cardiac ultrasound observations of ventricular wall motion abnormalities (AUC area 0.566, 95% CI 0.463 to 0.669). CONCLUSIONS: Combining GLS with mechanical dispersion can rapidly assess OCAD in a very short period, which has strong promotion value and in-depth research value.
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Doença da Artéria Coronariana , Estenose Coronária , Humanos , Doença da Artéria Coronariana/complicações , Doença da Artéria Coronariana/diagnóstico por imagem , Ecocardiografia/métodos , Coração , Curva ROC , Função Ventricular Esquerda , Reprodutibilidade dos Testes , Valor Preditivo dos TestesRESUMO
OBJECTIVES: The application of a growing rod technique can retain the growth and development potential of the spine and thorax while controlling the progression of scoliosis deformity. Theoretically, convex side short fusion combined with a concave side single growing rod technique can significantly reduce the asymmetric growth of the spine in the vertex region in most patients. However, the final clinical outcome of various techniques is yet to be clearly determined and compared between studies. Therefore, we compared the efficacy of these two growing rod techniques in treating early onset scoliosis. METHODS: In a retrospective study of 152 EOS patients seen between 2013.1 and 2019.12, 36 cases of EOS patients were selected for inclusion. Among the 36 cases, 11 cases were treated with convex side short fusion combined with a concave side single growing rod technique, group (A) The remaining 25 cases were treated with traditional bilateral growing rod technique, group (B) Age, gender, etiology, follow-up time, Cobb angle of main curve, T1-S1 height, coronal trunk shift, sagittal vertical axis (SVA), Cobb angle of thoracic kyphosis at last follow-up, and Cobb angle at proximal junction kyphosis of the first and last post-operation follow-up were recorded. In addition, internal fixation related complications, infection, nervous system complications were recorded as well. RESULTS: There was no statistically significant difference between group A and group B in preoperative age, Cobb angle of main curve, coronal trunk shift, T1-S1 height, SVA, Cobb angle of thoracic kyphosis (p > 0.05). However, at the last follow-up (Group A, mean 4.4 ± 1.01 years; Group B, mean 3.6 ± 0.01 years) the Cobb angle of the main curve was less and T1-S1 height greater in group A compared with group B (p < 0.05). There was no statistically significant difference between group A and group B in the correction rate of the Cobb angle of the main curve or the growth rate of T1-S1 height (p > 0.05). There was no statistically significant difference in the coronal imbalance ratio, thoracic kyphosis abnormality ratio, or the occurrence PJK ratio between group A and group B at the last follow-up (p > 0.05), but the sagittal imbalance ratio and internal fixation abnormality ratio were higher in group A than in the group B (p < 0.05). CONCLUSIONS: During the treatment of EOS, both the convex side short fusion combined with concave side single growing rod technique and traditional bilateral growing rod technique can correct the Cobb angle of main curve with no significant hindering of the spinal growth observed. The traditional bilateral growing rod technique has advantages in control of the sagittal balance of the spine, and the complications associated with internal fixation were lower.
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Escoliose , Fusão Vertebral , Humanos , Escoliose/cirurgia , Escoliose/diagnóstico por imagem , Feminino , Estudos Retrospectivos , Masculino , Fusão Vertebral/métodos , Fusão Vertebral/efeitos adversos , Fusão Vertebral/instrumentação , Criança , Resultado do Tratamento , Vértebras Torácicas/cirurgia , Vértebras Torácicas/diagnóstico por imagem , Pré-Escolar , Seguimentos , Idade de InícioRESUMO
Chemical oxidation processes are widely used for the remediation of organically contaminated soils, but their potential impact on variable-valence and toxic metals such as chromium (Cr) is often overlooked. In this study, we investigated the risk of Cr(â ¢) oxidation in soils during the remediation of 2-chlorophenol (2-CP) contaminated soils using four different processes: Potassium permanganate (KMnO4), Modified Fenton (Fe2+/H2O2), Alkali-activated persulfate (S2O82-/OH-), and Fe2+-activated persulfate (S2O82-/Fe2+). Our results indicated that the KMnO4, Fe2+/H2O2, and S2O82-/Fe2+ processes progressively oxidized Cr(III) to Cr(â ¥) during the 2-CP degradation. The KMnO4 process likely involved direct electron transfer, while the Fe2+/H2O2 and S2O82-/Fe2+ processes primarily relied on HO⢠and/or SO4â¢- for the Cr(III) oxidation. Notably, after 4 h of 2-CP degradation, the Cr(VI) content in the KMnO4 process surpassed China's 3.0 mg kg-1 risk screening threshold for Class I construction sites, and further exceeded the 5.7 mg kg-1 limit for Class II construction sites after 8 h. Conversely, the S2O82-/OH- process exhibited negligible oxidation of Cr(III), maintaining a low oxidation ratio of 0.13%, as highly alkaline conditions induced Cr(III) precipitation, reducing its exposure to free radicals. Cr(III) oxidation ratio was directly proportional to oxidant dosage, whereas the Fe2+/H2O2 process showed a different trend, influenced by the concentration of reductants. This study provides insights into the selection and optimization of chemical oxidation processes for soil remediation, emphasizing the imperative for thorough risk evaluation of Cr(III) oxidation before their application.
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Clorofenóis , Cromo , Recuperação e Remediação Ambiental , Oxirredução , Poluentes do Solo , Solo , Cromo/química , Poluentes do Solo/química , Clorofenóis/química , Solo/química , Peróxido de Hidrogênio/química , Permanganato de Potássio/químicaRESUMO
Thoracic aortic dissection (TAD) is an important cause of sudden cardiac death and is characterized by high morbidity, mortality, and a poor prognosis. Patent ductus arteriosus (PDA) is a common congenital heart disease. The pathogenesis of both TAD and PDA has been reported to be related to genetic factors. The MYH11 gene, which encodes myosin heavy chain 11, has been reported in individuals with both TAD and PDA. Herein, we first detected a harmful MYH11 missense variant (c. T3728C, p. L1243P) in a TAD and PDA family. This missense variant co-segregated with the TAD/PDA phenotype in this family of four individuals, providing evidence of its harmfulness. Histopathological examinations revealed the presence of fragmented, broken, and lessened elastic fibers and the deposition of proteoglycans in the median of aortic dissection. Moreover, the immunofluorescence results showed that the labeled MYH11 protein in the tissue of the aortic dissection was weaker than that in the normal aorta. We present this familial case to stress the necessity of postmortem genetic testing in such cases among forensic practices. Identifying those culprit gene variants can direct effective genetic counseling and personalized health management in family members (especially first-degree relatives) with high-risk genotypes.
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Dissecção Aórtica , Dissecção da Aorta Torácica , Permeabilidade do Canal Arterial , Humanos , Permeabilidade do Canal Arterial/genética , Permeabilidade do Canal Arterial/patologia , Testes Genéticos , Dissecção Aórtica/genética , Aorta/patologia , Cadeias Pesadas de Miosina/genéticaRESUMO
The concept of topological energy bands and their manifestations have been demonstrated in condensed matter systems as a fantastic paradigm toward unprecedented physical phenomena and properties that are robust against disorders. Recent years, this paradigm was extended to phononic metamaterials (including mechanical and acoustic metamaterials), giving rise to the discovery of remarkable phenomena that were not observed elsewhere thanks to the extraordinary controllability and tunability of phononic metamaterials as well as versatile measuring techniques. These phenomena include, but not limited to, topological negative refraction, topological 'sasers' (i.e. the phononic analog of lasers), higher-order topological insulating states, non-Abelian topological phases, higher-order Weyl semimetal phases, Majorana-like modes in Dirac vortex structures and fragile topological phases with spectral flows. Here we review the developments in the field of topological phononic metamaterials from both theoretical and experimental perspectives with emphasis on the underlying physics principles. To give a broad view of topological phononics, we also discuss the synergy with non-Hermitian effects and cover topics including synthetic dimensions, artificial gauge fields, Floquet topological acoustics, bulk topological transport, topological pumping, and topological active matters as well as potential applications, materials fabrications and measurements of topological phononic metamaterials. Finally, we discuss the challenges, opportunities and future developments in this intriguing field and its potential impact on physics and materials science.
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This study aimed to investigate the effects of mitochondrial homeostasis on lipopolysaccharide (LPS)-induced endothelial cell barrier function and the mechanisms that underlie these effects. Cells were treated with LPS or oligomycin (mitochondrial adenosine triphosphate synthase inhibitor) and the mitochondrial morphology, mitochondrial reactive oxygen species (mtROS), and mitochondrial membrane potential (ΔΨm) were evaluated. Moreover, the shedding of glycocalyx-heparan sulphate (HS), the levels of HS-specific degrading enzyme heparanase (HPA), and the expression of occludin and zonula occludens (ZO-1) of Tight Junctions (TJ)s, which are mediated by myosin light chain phosphorylation (p-MLC), were assessed. Examining the changes in mitochondrial homeostasis showed that adding heparinase III, which is an exogenous HPA, can destroy the integrity of glycocalyx. LPS simultaneously increased mitochondrial swelling, mtROS, and ΔΨm. Without oligomycin effects, HS, HPA levels, and p-MLC were found to be elevated, and the destruction of occludin and ZO-1 increased. Heparinase III not only damaged the glycocalyx by increasing HS shedding but also increased mitochondrial swelling and mtROS and decreased ΔΨm. Mitochondrial homeostasis is involved in LPS-induced endothelial cell barrier dysfunction by aggravating HPA and p-MLC levels. In turn, the integrated glycocalyx protects mitochondrial homeostasis.
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Células Endoteliais , Lipopolissacarídeos , Lipopolissacarídeos/farmacologia , Ocludina/metabolismo , Ocludina/farmacologia , Células Endoteliais/metabolismo , Junções Íntimas/metabolismo , Oligomicinas/farmacologia , Oligomicinas/metabolismoRESUMO
Pod dehiscence facilitates seed dispersal in wild legumes but results in yield loss in cultivated legumes. The evolutionary genetics of the legume pod dehiscence trait remain largely elusive. We characterized the pod dehiscence of chromosome segment substitution lines of Glycine max crossed with Glycine soja and found that the gene underlying the predominant quantitative trait locus (QTL) of soybean pod-shattering trait was Pod dehiscence 1 (Pdh1). A few rare loss-of-function (LoF) Pdh1 alleles were identified in G. soja, while only an allele featuring a premature stop codon was selected for pod indehiscence in cultivated soybean and spread to low-precipitation regions with increased frequency. Moreover, correlated interactions among Pdh1's haplotype, gene expression, and environmental changes for the developmental plasticity of the pod dehiscence trait were revealed in G. max. We found that orthologous Pdh1 genes specifically originated in warm-season legumes and their LoF alleles were then parallel-selected during the domestication of legume crops. Our results provide insights into the convergent evolution of pod dehiscence in warm-season legumes, facilitate an understanding of the intricate interactions between genetic robustness and environmental adaptation for developmental plasticity, and guide the breeding of new legume varieties with pod indehiscence.
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Fabaceae , Fabaceae/genética , Alelos , Estações do Ano , Melhoramento Vegetal , Locos de Características Quantitativas/genética , Glycine max/genética , Sementes/genéticaRESUMO
This corrects the article DOI: 10.1103/PhysRevLett.129.254301.
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Herein, hypervalent iodine-catalyzed halogenation of aryl-activated alkenes using BX3 (X = Cl, Br) as the halogen source and activating reagents was reported. Various halogenated 1,3-oxazine/2-oxazoline derivatives were obtained in good-to-high yields. Using BF3 resulted in different substitute sites from BBr3 and BCl3 of the products, indicating different reactive intermediates and reaction pathways. The reaction underwent a "ligand coupling/oxidative addition/intermolecular nucleophilic attack/1,2-aryl migration/reductive elimination/intramolecular nucleophilic attack" cascade when BF3 was applied as the halogen source, while 1,2-aryl migration has "disappeared" when the halogen source was BBr3 or BCl3. Possible catalytic cycles were proposed, and DFT calculations were conducted to demonstrate the differences among BX3 (X = F, Cl, Br) in the hypervalent iodine-catalyzed halogenations.
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BACKGROUND: Childhood asthma is a major global health concern. ADP-ribosylation factor 6 (ARF6) is a low-molecular-weight GTPase; however, its role in childhood asthma remains unclear. METHODS: Ovalbumin (OVA)-challenged neonatal mice and transforming growth factor-ß1 (TGF-ß1)-induced BEAS-2B cells were used as in vivo and in vitro models of childhood asthma, respectively. RESULTS: Upon OVA stimulation, ARF6 expression was upregulated in the lung tissue. Neonatal mice administered SehinH3 (an ARF6 inhibitor) exhibited improved pulmonary pathological injury, along with reduced inflammatory cell infiltration in the lungs and cytokine release in bronchial alveolar lavage fluid and serum (interleukin [IL]-3, IL-5, IL-13, IgE, and OVA-specific IgE). SehinH3 treatment restrained epithelial - mesenchymal transition (EMT) in the lungs of asthmatic mice, as evidenced by increased E-cadherin and decreased N-cadherin and α-smooth muscle actin expression. Different TGF-ß1 exposures to BEAS-2B cells induced a time- and dose-dependent increase in ARF6 expression in vitro. Upon TGF-ß1 stimulation, ARF6 knockdown repressed EMT and SehinH3 treatment caused similar results in BEAS-2B cells. The transcription factor E2F8 is involved in diverse biological functions and its increased expression was confirmed in vivo and in vitro. Dual-luciferase assays confirmed that E2F8 binds to the ARF6 promoter and promotes its transcriptional activity. In vitro results revealed that E2F8 silencing suppressed EMT, whereas rescue experiments showed that ARF6 overexpression partly reversed these phenomena. CONCLUSION: Our study showed that ARF6 is associated with childhood asthma progression and may be positively regulated by E2F8. These results provide insight into the pathogenesis and treatment of childhood asthma.
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Asma , Fator de Crescimento Transformador beta1 , Camundongos , Animais , Fator de Crescimento Transformador beta1/metabolismo , Ovalbumina , Fator 6 de Ribosilação do ADP , Transição Epitelial-Mesenquimal , Asma/metabolismo , Inflamação , Imunoglobulina E , Fatores de Transcrição E2F/metabolismo , Camundongos Endogâmicos BALB C , Modelos Animais de DoençasRESUMO
PURPOSE: Diabetic cardiomyopathy (DCM) is a common and severe complication of diabetes. Inflammation and oxidative stress play important roles in DCM development. Bicyclol is a hepatoprotective drug in China that exerts anti-inflammatory effects by inhibiting the MAPK and NF-κB pathways to prevent obesity-induced cardiomyopathy. Our purpose was to explore the effect and mechanism of bicyclol on DCM. METHODS: A type 1 diabetes mouse model was established using C57BL/6 mice by intraperitoneal injection of STZ. The therapeutic effect of bicyclol was evaluated in both heart tissues of diabetic mice and high concentration of glucose (HG)-stimulated H9c2 cells. RESULTS: We showed that bicyclol significantly attenuated diabetes-induced cardiac hypertrophy and fibrosis, which is accompanied by the preservation of cardiac function in mice. In addition, bicyclol exhibited anti-inflammatory and anti-oxidative effects both in vitro and in vivo. Furthermore, bicyclol inhibited the hyperglycemia-induced activation of MAPKs and NF-κB pathways, while upregulating the Nrf-2/HO-1 pathway to exhibit protective effects. CONCLUSION: Our data indicate that bicyclol could be a promising cardioprotective agent in the treatment of DCM.