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Under the background of comprehensively practicing the overall system concept of the "living community" in the new era, incorporating the carbon neutral development goal into the territorial spatial planning and construction and establishing the territorial spatial pattern and optimization strategy in line with the actual development of Gansu Province are of great significance for promoting the comprehensive green low-carbon transformation and high-quality development of regional economy and society. Taking counties in Gansu Province as an example, based on the perspective of carbon neutrality research, the land use carbon budget of 87 counties in Gansu Province in 2010, 2015, and 2021 was calculated and analyzed. GIS spatial analysis and social network analysis were used to further explore their spatial differentiation characteristics and the overall characteristics of the carbon emission spatial correlation network. At last, combined with the main function zoning, the low-carbon oriented land space optimization zoning was carried out, and differentiated low-carbon development strategies were proposed. The results were as followsï¼ â Carbon emissions in Gansu Province showed an upward trend, but the increase rate decreased, showing a spatial distribution of "high in the central and eastern part of the country, low in the southwest." Construction land was the main carbon source. The carbon uptake showed a spatial distribution of "high in the south and low in the north, high in the west and low in the east." Woodlands were the main carbon sinks. The net carbon emissions showed an increasing trend, and approximately 58.62% of the counties in the province were in a carbon imbalance situation. â¡ In 2021, the spatial network of county carbon emissions was closely related, showing a "core-edge" pattern. The Chenguan District and Qilihe District were in the core position of the network and received more correlation relationships in the network. The network contacts in Longzhong area were frequent, followed by the contacts in Longdongnan area. ⢠Based on carbon emissions, carbon sequestration, and ecological carrying capacity coefficients and using the results of spatial correlation of social networks as role positions, the province was divided into four carbon-neutral sub-districts. At the same time, superimposed analysis of the main function zoning, the county area of the province was reconstructed into seven territorial space zones, and the differentiated regional low-carbon optimization development strategy was proposed for each zone.
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BACKGROUND: Osteoporotic vertebral compression fractures (OVCFs) contribute to back pain and functional limitations in older individuals, with percutaneous vertebroplasty (PVP) emerging as a minimally invasive treatment. However, further height loss post-PVP prompts investigation into contributing factors. AIM: To investigate the factors associated with further height loss following PVP with cement augmentation in OVCF patients. METHODS: A total of 200 OVCF patients who underwent successful PVP between January 2021 and December 2022 were included in this study. "Further height loss" during 1 year of follow-up in OVCF patients with bone edema was defined as a vertical height loss of ≥ 4 mm. The study population was divided into two groups for analysis: The "No Further Height Loss group (n = 179)" and the "Further Height Loss group (n = 21)." RESULTS: In comparing two distinct groups of patients, significant differences existed in bone mineral density (BMD), vertebral compression degree, prevalence of intravertebral cleft (IVF), type of bone cement used, and cement distribution patterns. Results from binary univariate regression analysis revealed that lower BMD, the presence of IVF, cleft distribution of bone cement, and higher vertebral compression degree were all significantly associated with further height loss. Notably, the use of mineralized collagen modified-poly(methyl methacrylate) bone cement was associated with a significant reduction in the risk of further height loss. In multivariate regression analysis, lower BMD and the presence of IVF remained significantly associated with further height loss. CONCLUSION: Further height loss following PVP in OVCF patients is influenced by a complex interplay of factors, especially lower BMD and the presence of IVF. These findings underscore the importance of assessing and managing these factors when addressing height loss following PVP in OVCF patients.
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Cerebral ischemia/reperfusion injury (CIRI) is a common feature of ischemic stroke leading to a poor prognosis. Effective treatments targeting I/R injury are still insufficient. The study aimed to investigate the mechanisms, by which glycyrrhizic acid (18ß-GA) in ameliorates CIRI. Our results showed that 18ß-GA significantly decreased the infarct volume, neurological deficit scores, and pathological changes in the brain tissue of rats after middle cerebral artery occlusion. Western blotting showed that 18ß-GA inhibited the expression levels of phosphorylated JAK2 and phosphorylated STAT3. Meanwhile, 18ß-GA increased LC3-II protein levels in a reperfusion duration-dependent manner, which was accompanied by an increase in the Bcl-2/Bax ratio. Inhibition of 18ß-GA-induced autophagy by 3-methyladenine (3-MA) enhanced apoptotic cell death. In addition, 18ß-GA inhibited the JAK2/STAT3 pathway, which was largely activated in response to oxygen-glucose deprivation/reoxygenation. However, the JAK2/STAT3 activator colivelin TFA abolished the inhibitory effect of 18ß-GA, suppressed autophagy, and significantly decreased the Bcl-2/Bax ratio. Taken together, these findings suggested that 18ß-GA pretreatment ameliorated CIRI partly by triggering a protective autophagy via the JAK2/STAT3 pathway. Therefore might be a potential drug candidate for treating ischemic stroke.
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Autofagia , Infarto da Artéria Cerebral Média , Janus Quinase 2 , Fármacos Neuroprotetores , Ratos Sprague-Dawley , Traumatismo por Reperfusão , Fator de Transcrição STAT3 , Transdução de Sinais , Animais , Janus Quinase 2/metabolismo , Janus Quinase 2/antagonistas & inibidores , Fator de Transcrição STAT3/metabolismo , Traumatismo por Reperfusão/metabolismo , Traumatismo por Reperfusão/tratamento farmacológico , Autofagia/efeitos dos fármacos , Autofagia/fisiologia , Masculino , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/fisiologia , Fármacos Neuroprotetores/farmacologia , Infarto da Artéria Cerebral Média/tratamento farmacológico , Infarto da Artéria Cerebral Média/metabolismo , Isquemia Encefálica/metabolismo , Isquemia Encefálica/tratamento farmacológico , Isquemia Encefálica/patologia , Ácido Glicirrízico/farmacologia , Ratos , Apoptose/efeitos dos fármacos , Encéfalo/efeitos dos fármacos , Encéfalo/metabolismo , Encéfalo/patologiaRESUMO
BACKGROUND: Liver transplantations (LTs) with extended criteria have produced surgical results comparable to those obtained with traditional standards. However, it is not sufficient to predict hepatocellular carcinoma (HCC) recurrence after LT according to morphological criteria alone. The present study aimed to construct a nomogram for predicting HCC recurrence after LT using extended selection criteria. METHODS: Retrospective data on patients with HCC, including pathology, serological markers and follow-up data, were collected from January 2015 to April 2020 at Huashan Hospital, Fudan University, Shanghai, China. Logistic least absolute shrinkage and selection operator (LASSO) regression and multivariate Cox regression analyses were performed to identify and construct the prognostic nomogram. Receiver operating characteristic (ROC) curves, Kaplan-Meier curves, decision curve analyses (DCAs), calibration diagrams, net reclassification indices (NRIs) and integrated discrimination improvement (IDI) values were used to assess the prognostic capacity of the nomogram. RESULTS: A total of 301 patients with HCC who underwent LT were enrolled in the study. The nomogram was constructed, and the ROC curve showed good performance in predicting survival in both the development set (2/3) and the validation set (1/3) (the area under the curve reached 0.748 and 0.716, respectively). According to the median value of the risk score, the patients were categorized into the high- and low-risk groups, which had significantly different recurrence-free survival (RFS) rates (P < 0.01). Compared with the Milan criteria and University of California San Francisco (UCSF) criteria, DCA revealed that the new nomogram model had the best net benefit in predicting 1-, 3- and 5-year RFS. The nomogram performed well for calibration, NRI and IDI improvement. CONCLUSIONS: The nomogram, based on the Milan criteria and serological markers, showed good accuracy in predicting the recurrence of HCC after LT using extended selection criteria.
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Phenazines are aromatic compounds with antifungal and cytotoxic activities. Phenazines incorporating phenazine 1-carboxylic acid have widespread applications in agriculture, medicine, and industry. Griseoluteic acid is a cytotoxic compound secreted by Streptomyces griseoluteus P510, displaying potential medical applications. However, the biosynthetic pathway of griseoluteic acid has not been elucidated, limiting its development and application. In this study, a conserved phenazine biosynthetic gene cluster of S. griseoluteus P510 was identified through genomic analysis. Subsequently, its was confirmed that the four essential modification enzymes SgpH, SgpI, SgpK, and SgpL convert phenazine-1,6-dicarboxylic acid into griseoluteic acid by heterologous expression in Escherichia coli. Moreover, the biosynthetic pathway of griseoluteic acid was established in Pseudomonas chlororaphis characterized by a high growth rate and synthesis efficiency of phenazines, laying the foundation for the efficient production of griseoluteic acid.
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Fenazinas , Fenazinas/metabolismo , Fenazinas/química , Estrutura Molecular , Família Multigênica , Vias Biossintéticas , Streptomyces/metabolismo , Streptomyces/genética , Streptomyces griseus/metabolismo , Pseudomonas chlororaphis/metabolismo , Escherichia coli/metabolismoRESUMO
OBJECTIVE: To investigate the association between meteorological data three days before admission and the status of sputum pathogens culture in hospitalized patients with Acute exacerbation of Chronic obstructive pulmonary disease (AECOPD) and respiratory infections. METHODS: Data from 1,370 AECOPD patients (80.66% males, approximately 80% age > 70) with respiratory infections hospitalized in Fujian Provincial Hospital between December 2013 and December 2019 were collected. This cohort comprised, along with concurrent meteorological data from Fuzhou. Group differences were analyzed to compare the meteorological data three days prior to admission between patients with positive sputum pathogen cultures and those without. Logistic regression models were employed to investigate the association between meteorological parameters and the status of sputum pathogen cultures in patients with AECOPD and respiratory infections. Sensitivity analyses was conducted among the hospitalized patients from 2013 to 2016 and 2017-2019. Stratified analysis was performed to explore the factors affecting the effect of temperature differences and their interactions. RESULTS: 578(42.19%) cases had a positive sputum culture report indicating pathogen growth. 323 cases were found with Gram-negative bacteria, 160 with Gram-positive bacteria, and 114 with fungi. Uni-variate analysis revealed statistical differences in DTD three days prior to admission (DTD-3d) between the positive and negative sputum culture groups (p = 0.019). Multivariate analysis indicated that an increase in the risk of positive sputum pathogen cultures was associated with greater DTD three days before admission (DTD-3d), with OR1.657 (95%CI [ 1.328-1.981]). The risk of positive sputum pathogen cultures was higher in groups with greater DTD-3d. The findings were consistent across different admission periods. Stratified analysis showed that patients without respiratory failure were more affected by DTD-3d, and an interaction effect was observed (p < 0.001). CONCLUSION: In coastal areas, the diurnal temperature difference three days prior to admission affects the sputum pathogen status in AECOPD patients with respiratory infections.
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Hospitalização , Doença Pulmonar Obstrutiva Crônica , Escarro , Temperatura , Humanos , Escarro/microbiologia , Masculino , Doença Pulmonar Obstrutiva Crônica/microbiologia , Doença Pulmonar Obstrutiva Crônica/fisiopatologia , Estudos Retrospectivos , Idoso , Feminino , China , Pessoa de Meia-Idade , Infecções Respiratórias/microbiologia , Infecções Respiratórias/diagnóstico , Idoso de 80 Anos ou mais , Progressão da Doença , Bactérias Gram-Negativas/isolamento & purificação , Modelos Logísticos , Bactérias Gram-Positivas/isolamento & purificaçãoRESUMO
This study aims to explore the pharmacological substance basis of Qi Ge Decoction (QG) in antihyperlipidemia through a combination of metabolomics and serum pharmacochemistry. We used ultra-performance liquid chromatography quadrupole-time-of-flight/MS (UPLC Q-TOF/MS) to analyze and identify the chemical constituents of QG in vitro and in blood chemical components. The metabolomics technology was used to analyze serum biomarkers of QG in preventing and treating hyperlipidemia. We constructed a mathematical model of the relationship between constituents absorbed into the blood and endogenous biomarkers and explored the potential therapeutic application of QG for the prevention and treatment of hyperlipidemia. Compared with the model group, the levels of total cholesterol and triglyceride in the QG group were significantly decreased (P < 0.01). A total of 12 chemical components absorbed into the blood were identified, and 48 biomarkers of the hyperlipidemia model were obtained from serum metabolomic analysis, of which 15 metabolites were backregulated after QG intervention. Puerarin, hesperetin, puerarin xyloside, calycosin, and monohydroxy-tetramethoxyflavone had a high correlation with the biomarkers regulated by QG. This study elucidated the material basis of QG in the intervention of hyperlipidemia, thereby facilitating future research aimed at further revealing the pharmacodynamic material basis of QG's antihyperlipidemic effects.
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Medicamentos de Ervas Chinesas , Hiperlipidemias , Hipolipemiantes , Metabolômica , Metabolômica/métodos , Hipolipemiantes/sangue , Hipolipemiantes/farmacocinética , Hipolipemiantes/química , Cromatografia Líquida de Alta Pressão/métodos , Animais , Hiperlipidemias/tratamento farmacológico , Hiperlipidemias/sangue , Masculino , Biomarcadores/sangue , Ratos , Metaboloma/efeitos dos fármacos , Ratos Sprague-Dawley , Espectrometria de Massas/métodosRESUMO
Myocardial infarction (MI), including ST-segment elevation MI (STEMI) and non-ST-segment elevation MI (NSTEMI), is still a leading cause of death worldwide. Metabolomics technology was used to explore differential metabolites (DMs) as potential biomarkers for early diagnosis of STEMI and NSTEMI. In the study, 2531 metabolites, including 1925 DMs, were discovered. In the selected 27 DMs, 14 were successfully verified in a new cohort, and the AUC values were all above 0.8. There were 10 in STEMI group, namely L-aspartic acid, L-acetylcarnitine, acetylglycine, decanoylcarnitine, hydroxyphenyllactic acid, ferulic acid, itaconic acid, lauroylcarnitine, myristoylcarnitine, and cis-4-hydroxy-D-proline, and 5 in NSTEMI group, namely L-aspartic acid, arachidonic acid, palmitoleic acid, D-aspartic acid, and palmitelaidic acid. These 14 DMs may be developed as biomarkers for the early diagnosis of MI with high sensitivity and specificity. These findings have particularly important clinical significance for NSTEMI patients because these patients have no typical ECG changes.
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Biomarcadores , Metabolômica , Infarto do Miocárdio , Biomarcadores/metabolismo , Humanos , Metabolômica/métodos , Masculino , Pessoa de Meia-Idade , Feminino , Infarto do Miocárdio/diagnóstico , Infarto do Miocárdio/metabolismo , Idoso , Infarto do Miocárdio com Supradesnível do Segmento ST/diagnóstico , Infarto do Miocárdio com Supradesnível do Segmento ST/metabolismo , Infarto do Miocárdio sem Supradesnível do Segmento ST/diagnóstico , Infarto do Miocárdio sem Supradesnível do Segmento ST/metabolismo , MetabolomaRESUMO
To investigate the impact of four single nucleotide polymorphisms (SNPs) of the HIF1α gene and its interaction with Helicobacter pylori (H. pylori) infection on susceptibility to gastric cancer (GC).Logistic regression was used to test the relationship between four SNPs of HIF1α gene and the susceptibility of GC. A generalized multifactor dimensionality reduction (GMDR) model was used to assess the HIF1α gene-H. pylori infection interaction.Logistic regression analysis indicated that both the rs11549465-CT genotype and the T allele were associated with an increased risk of GC, adjusted OR (95% CI) were 1.63 (1.09-2.20) (CT vs. CC) and 1.70 (1.13-2.36) (T vs. C), respectively. We also found that both the rs11549467-A allele and rs11549467-GA genotype were associated with an increased risk of GC, and adjusted OR (95% CI) were 2.21 (1.61-2.86) (GA vs. GG), 2.13 (1.65-2.65) (A vs. G), respectively. However, no statistically significant impact of rs2057482 or rs1957757 on risk of GC was found. The GMDR model indicated a statistically significant two-dimensional model combination (including rs11549467 and H. pylori infection). The selected model had testing balanced accuracy of 0.60 and the best cross-validation consistencies of 10/10 (p = 0.0107). Compared with H. pylori infection negative participants with rs11549467-GG genotype, H. pylori positive participants with the rs11549467-GA genotype had the highest GC risk, the OR (95% CI) was 3.04 (1.98-4.12).The rs11549467-A allele and rs11549467-GA genotype was associated with increased GC risk. Additionally, the gene-environment interaction between HIF-1α-rs11549467 and H. pylori infection was also correlated with an increased risk of GC.
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BACKGROUND: Intraductal papillary neoplasm of the bile duct (IPNB) is a premalignant biliary-type epithelial neoplasm with intraductal papillary or villous growth. Currently reported local palliative therapeutic modalities, including endoscopic nasobiliary drainage, stenting and biliary curettage, endoscopic biliary polypectomy, percutaneous biliary drainage, laser ablation, argon plasma coagulation, photodynamic therapy, and radiofrequency ablation to relieve mechanical obstruction are limited with weaknesses and disadvantages. We have applied percutaneous transhepatic cholangioscopy (PTCS)-assisted biliary polypectomy (PTCS-BP) technique for the management of IPNB including mucin-hypersecreting cast-like and polypoid type tumors since 2010. AIM: To assess the technical feasibility, efficacy, and safety of PTCS-BP for local palliative treatment of IPNB. METHODS: Patients with mucin-hypersecreting cast-like or polypoid type IPNB and receiving PTCS-BP between September 2010 and December 2019 were included. PTCS-BP was performed by using a half-moon type snare with a soft stainless-steel wire, and the tumor was snared and resected with electrocautery. The primary outcome was its feasibility, indicated by technical success. The secondary outcomes were efficacy, including therapeutic success, curative resection, and clinical success, and safety. RESULTS: Five patients (four with mucin-hypersecreting cast-like type and one with polypoid type IPNB) were included. Low- and high-grade intraepithelial neoplasia (HGIN) and recurrent IPNB with invasive carcinoma were observed in one, two, and two patients, respectively. Repeated cholangitis and/or obstructive jaundice were presented in all four patients with mucin-hypersecreting cast-like type IPNB. All five patients achieved technical success of PTCS-BP. Four patients (three with mucin-hypersecreting cast-like type and one with polypoid type IPNB) obtained therapeutic success; one with mucin-hypersecreting cast-like type tumors in the intrahepatic small bile duct and HGIN had residual tumors. All four patients with mucin-hypersecreting IPNB achieved clinical success. The patient with polypoid type IPNB achieved curative resection. There were no PTCS-BP-related serious adverse events. CONCLUSION: PTCS-BP appears to be feasible, efficacious, and safe for local palliative treatment of both mucin-hypersecreting cast-like and polypoid type IPNB.
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Leaf senescence is a complex process regulated by developmental and environmental factors, and plays a pivotal role in the development and life cycle of higher plants. Casein kinase 1 (CK1) is a highly conserved serine/threonine protein kinase in eukaryotes and functions in various cellular processes including cell proliferation, light signaling and hormone effects of plants. However, the biological function of CK1 in plant senescence remains unclear. Through systemic genetic and biochemical studies, we here characterized the function of Arabidopsis EL1-like (AEL), a CK1, in promoting leaf senescence by stimulating ethylene biosynthesis through phosphorylating transcription factor WRKY22. Seedlings lacking or overexpressing AELs presented delayed or accelerated leaf senescence, respectively. AELs interact with and phosphorylate WRKY22 at Thr57, Thr60 and Ser69 residues to enhance whose transactivation activity. Being consistent, increased or suppressed phosphorylation of WRKY22 resulted in the promoted or delayed leaf senescence. WRKY22 directly binds to promoter region and stimulates the transcription of 1-amino-cyclopropane-1-carboxylate synthase 7 gene to promote ethylene level and hence leaf senescence. Our studies demonstrated the crucial role of AEL-mediated phosphorylation in regulating ethylene biosynthesis and promoting leaf senescence by enhancing WRKY22 transactivation activity, which helps to elucidate the fine-controlled ethylene biosynthesis and regulatory network of leaf senescence.
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OBJECTIVE: To evaluate the predictive value of PD-1 expression in T lymphocytes for rehospitalization due to acute exacerbations of COPD (AECOPD) in discharged patients. METHODS: 115 participants hospitalized with COPD (average age 71.8 ± 6.0 years) were recruited at Fujian Provincial Hospital. PD1+T lymphocytes proportions (PD1+T%), baseline demographics and clinical data were recorded at hospital discharge. AECOPD re-admission were collected at 1-year follow-up. Kaplan-Meier analysis compared the time to AECOPD readmissions among groups stratified by PD1+T%. Multivariable Cox proportional hazards regression and stratified analysis determined the correlation between PD1+T%, potential confounders, and AECOPD re-admission. ROC and DCA evaluated PD1+T% in enhancing the clinical predictive values of Cox models, BODE and CODEX. RESULTS: 68 participants (59.1%) were AECOPD readmitted, those with AECOPD readmission exhibited significantly elevated baseline PD-1+CD4+T/CD4+T% and PD-1+CD8 + T/CD8 + T% compared to non-readmitted counterparts. PD1+ T lymphocyte levels statistically correlated with BODE and CODEX indices. Kaplan-Meier analysis demonstrated that those in Higher PD1+ T lymphocyte proportions had reduced time to AECOPD readmission (logRank p < 0.05). Cox analysis identified high PD1+CD4+T and PD1+CD8+T ratios as risk factors of AECOPD readmission, with hazard ratios of 1.384(95%CI [1.043-1.725]) and 1.401(95%CI [1.013-1.789]), respectively. Notably, in patients aged < 70 years and with fewer than twice AECOPD episodes in the previous year, high PD1+T lymphocyte counts significantly increased risk for AECOPD readmission(p < 0.05). The AECOPD readmission predictive model, incorporating PD1+T% exhibited superior discrimination to the Cox model, BODE index and CODEX index, AUC of ROC were 0.763(95%CI [0.633-0.893]) and 0.734(95%CI [0.570-0.899]) (DeLong's test p < 0.05).The DCA illustrates that integrating PD1+T% into models significantly enhances the utility in aiding clinical decision-making. CONCLUSION: Evaluation of PD1+ lymphocyte proportions offer a novel perspective for identifying high-risk COPD patients, potentially providing insights for COPD management. TRIAL REGISTRATION: Chinese Clinical Trial Registry (ChiCTR, URL: www.chictr.org.cn/ ), Registration number: ChiCTR2200055611 Date of Registration: 2022-01-14.
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Receptor de Morte Celular Programada 1 , Doença Pulmonar Obstrutiva Crônica , Humanos , Doença Pulmonar Obstrutiva Crônica/sangue , Doença Pulmonar Obstrutiva Crônica/diagnóstico , Doença Pulmonar Obstrutiva Crônica/imunologia , Masculino , Feminino , Idoso , Receptor de Morte Celular Programada 1/metabolismo , Estudos Prospectivos , Pessoa de Meia-Idade , Progressão da Doença , Readmissão do Paciente , Estudos de Coortes , Hospitalização/estatística & dados numéricos , Hospitalização/tendências , Idoso de 80 Anos ou mais , Seguimentos , Linfócitos T/imunologia , Linfócitos T/metabolismoRESUMO
Carbon fiber-reinforced polymer composites (CFRPs) have gained widespread usage due to their promising physiochemical properties, while this causes large amounts of waste CFRPs worldwide. In this study, carbon fibers were successfully recovered from waste CFRPs through the pyrolysis-oxidation method, and the recovered fibers were reused in remanufacturing the secondary generation CFRPs. Moreover, the individual and interactive effects of pyrolysis-oxidation recovering parameters on the mechanical strength of the resulting remanufactured CFRPs (reCFRPs) were investigated. The recovered carbon fibers displayed surface chemical structures similar to virgin fibers but with high contents of oxygen-containing bonds. The tensile strength retention (TSR) of the reCFRPs was primarily influenced by oxidation temperature. Notably, a higher oxidation temperature, especially exceeding 560 °C, amplified the impact of oxidation duration on the TSR value. Similarly, concerning interlaminar shear strength retention (ISSR), the oxidation stage had a more substantial effect compared to the pyrolysis stage. As the oxidation temperature increased from 500 °C to 600 °C, the ISSR value initially increased and then decreased, irrespective of variations in pyrolysis parameters. Additionally, through integrating the response surface methodology (RSM) analysis and multi-island genetic algorithm (MIGA) global optimization, three recovery strategies, along with the corresponding processing parameters, were proposed to meet diverse requirements. The conclusions could provide valuable insights for optimizing the recovery and reuse of carbon fibers from waste CFRPs.
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Fibra de Carbono , Oxirredução , Pirólise , Reciclagem , Fibra de Carbono/química , Reciclagem/métodos , Resistência à Tração , Polímeros/química , Carbono/químicaRESUMO
Background: Osteoporosis is one of the most common bone diseases in middle-aged and elderly populations worldwide. The development of new drugs to treat the disease is a key focus of research. Current treatments for osteoporosis are mainly directed at promoting osteoblasts and inhibiting osteoclasts. However, there is currently no ideal approach for osteoporosis treatment. l-arginine is a semi-essential amino acid involved in a number of cellular processes, including nitric production, protein biosynthesis, and immune responses. We previously reported that l-arginine-derived compounds can play a regulatory role in bone homeostasis. Purpose: To investigate the specific effect of l-arginine on bone homeostasis. Methods: Mildly aged and ovariectomized mouse models were used to study the effects of l-arginine on osteogenesis and angiogenesis, assessed by micro-computed tomography and immunostaining of bone tissue. The effect of l-arginine on osteogenesis, angiogenesis, and adipogenesis was further studied in vitro using osteoblasts obtained from cranial cap bone, endothelial cells, and an adipogenic cell line. Specific methods to assess these processes included lipid staining, cell migration, tube-forming, and wound-healing assays. Protein and mRNA expression was determined for select biomarkers. Results: We found that l-arginine attenuated bone loss and promoted osteogenesis and angiogenesis. l-arginine increased the activity of vascular endothelial cells, whereas it inhibited adipogenesis in vitro. In addition, we found that l-arginine altered the expression of PINK1/Parkin and Bnip3 in the mitochondria of osteoblast-lineage and endothelial cells, thereby promoting mitophagy and protecting cells from ROS. Similarly, l-arginine treatment effectively ameliorated osteoporosis in an ovariectomized mouse model. Conclusion: l-arginine promotes angio-osteogenesis, and inhibits adipogenesis, effects mediated by the PINK1/Parkin- and Bnip3-mediated mitophagy. The Translational Potential of this Article: L-arginine supplementation may be an effective adjunct therapy in the treatment of osteoporosis.
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As a key factor in determining testis size and sperm number, sertoli cells (SCs) play a crucial role in male infertility. Heat stress (HS) reduces SCs counts, negatively impacting nutrient transport and supply to germ cells, and leading to spermatogenesis failure in humans and animals. However, how HS affects the number of SCs remains unclear. We hypothesized that changes in SC metabolism contribute to the adverse effects of HS. In this study, we first observed an upregulation of arachidonic acid (AA), an unsaturated fatty acid after HS exposure by LC-MS/MS metabolome detection. By increasing ROS levels, expression of KEAP1 and NRF2 proteins as well as LC3 and LAMP2, 100 µM AA induced autophagy in SCs by activating oxidative stress (OS). We observed adverse effects of AA on mitochondria under HS with a decrease of mitochondrial number and an increase of mitochondrial membrane potential (MMP). We also found that AA alternated the oxygen transport and absorption function of mitochondria by increasing glycolysis flux and decreasing oxygen consumption rate as well as the expression of mitochondrial electron transport chain (ETC) proteins Complex I, II, V. However, pretreatment with 5 mM NAC (ROS inhibitor) and 2 µM Rotenone (mitochondrial ETC inhibitor) reversed the autophagy induced by AA. In summary, AA modulates autophagy in SCs during HS by disrupting mitochondrial ETC function, inferring that the release of AA is a switch-like response, and providing insight into the underlying mechanism of high temperatures causing male infertility.
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Ácido Araquidônico , Autofagia , Resposta ao Choque Térmico , Mitocôndrias , Células de Sertoli , Regulação para Cima , Masculino , Células de Sertoli/metabolismo , Células de Sertoli/efeitos dos fármacos , Autofagia/efeitos dos fármacos , Animais , Mitocôndrias/metabolismo , Mitocôndrias/efeitos dos fármacos , Resposta ao Choque Térmico/efeitos dos fármacos , Ácido Araquidônico/metabolismo , Regulação para Cima/efeitos dos fármacos , Transporte de Elétrons/efeitos dos fármacos , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Espécies Reativas de Oxigênio/metabolismoRESUMO
AIMS: To investigate the immunology shared mechanisms underlying chronic obstructive pulmonary disease (COPD) and type 2 diabetes mellitus (T2DM) and examine the impact of anti-diabetic drugs on acute exacerbation of COPD (AECOPD). METHODS: We analyzed GSE76925, GSE76894, GSE37768, and GSE25724 to identify differentially expressed genes. Hub-genes were identified through protein-protein interaction network analysis and evaluated by the receiver operating characteristic curve. CXCL12 emerged as a robust biomarker, and its correlation with lung function and CD8+ T cells were further quantified and validated. The activated signaling pathways were inferred through Gene set enrichment analysis (GSEA). The retrospective clinical analysis was executed to identify the influence of dipeptidyl peptidase-4 inhibitors (DPP-4i) on CXCL12 and evaluate the drug's efficacy in AECOPD. RESULTS: The significant up-regulation of CXCL12 expression in patients with two diseases were revealed. CXCL12 exhibited a negative correlation with pulmonary function (r = -0.551, p < 0.05). Consistent with analysis in GSE76925 and GSE76894, the positive correlation between the proportion of CD8+ T cells was demonstrated(r=0.469, p<0.05). GSEA identified "cytokines interaction" as an activated signaling pathway, and the clinical study revealed the correlation between CXCL12 and IL-6 (r=0.668, p<0.05). In patients with COPD and T2DM, DDP-4i treatment exhibited significantly higher serum CXCL12, compared to GLP-1RA. Analysis of 187 COPD patients with T2DM indicated that the DPP-4i group had a higher frequency of AECOPD compared to the GLP-1RA group (OR 1.287, 95%CI [1.018-2.136]). CONCLUSIONS: CXCL12 may represent a therapeutic target for COPD and T2DM. GLP-1RA treatment may be associated with lower CXCL12 levels and a lower risk of AECOPD compared to DPP-4i treatment. CLINICAL TRIAL REGISTRATION: China Clinical Trial Registration Centerï¼ChiCTR2200055611ï¼.
Assuntos
Quimiocina CXCL12 , Biologia Computacional , Diabetes Mellitus Tipo 2 , Inibidores da Dipeptidil Peptidase IV , Doença Pulmonar Obstrutiva Crônica , Humanos , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico , Quimiocina CXCL12/genética , Quimiocina CXCL12/metabolismo , Diabetes Mellitus Tipo 2/tratamento farmacológico , Masculino , Inibidores da Dipeptidil Peptidase IV/uso terapêutico , Inibidores da Dipeptidil Peptidase IV/farmacologia , Feminino , Idoso , Pessoa de Meia-Idade , Estudos Retrospectivos , Linfócitos T CD8-Positivos/imunologia , Linfócitos T CD8-Positivos/efeitos dos fármacos , Progressão da Doença , Mapas de Interação de ProteínasRESUMO
Heat stress reduces the number of Sertoli cells, which is closely related to an imbalanced redox status. Glutamate functions to maintain the equilibrium of redox homeostasis. However, the role of glutamate in heat treated Sertoli cells remains unclear. Herein, Sertoli cells from 3-week-old piglets were treated at 44 °C for 30 min (heat stress). Glutamate levels increased significantly following heat stress treatment, followed by a gradual decrease during recovery, while glutathione (GSH) showed a gradual increase. The addition of exogenous glutamate (700 µM) to Sertoli cells before heat stress significantly reduced the heat stress-induced apoptosis rate, mediated by enhanced levels of antioxidant substances (superoxide dismutase (SOD), total antioxidant capacity (TAC), and GSH) and reduced levels of oxidative substances (reactive oxygen species (ROS) and malondialdehyde (MDA)). Glutamate addition to Sertoli cells before heat stress upregulated the levels of glutamate-cysteine ligase, modifier subunit (Gclm), glutathione synthetase (Gss), thioredoxin (Trx1) and B-cell leukemia/lymphoma 2 (Bcl-2), and the ratio of phosphorylated Akt (protein kinase B)/total Akt. However, it decreased the levels of Bcl2-associated X protein (Bax) and cleaved-caspase 3. Addition of the inhibitor of glutaminase (Gls1), Bptes (Bis-2-(5-phenylacetamido-1,3,4-thiadiazol-2-yl)ethyl sulfide, 30 µM)to Sertoli cells before heat stress reversed these effects. These results inferred that glutamate rescued heat stress-induced apoptosis in Sertoli cells by enhancing activity of antioxidant enzymes and activating the Trx1-Akt pathway. Thus, glutamate supplementation might represent a novel strategy to alleviate the negative effect of heat stress.
Assuntos
Antioxidantes , Apoptose , Ácido Glutâmico , Resposta ao Choque Térmico , Proteínas Proto-Oncogênicas c-akt , Células de Sertoli , Transdução de Sinais , Animais , Células de Sertoli/efeitos dos fármacos , Células de Sertoli/metabolismo , Masculino , Apoptose/efeitos dos fármacos , Ácido Glutâmico/metabolismo , Antioxidantes/farmacologia , Proteínas Proto-Oncogênicas c-akt/metabolismo , Resposta ao Choque Térmico/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos , Suínos , Tiorredoxinas/metabolismo , Células CultivadasRESUMO
Polyhydroxyalkanoates (PHAs) are promising alternatives to petroleum-based plastics, owing to their biodegradability and superior material properties. Here, the controllable biosynthesis of scl-co-mcl PHA containing 3-hydroxybutyrate (3HB) and mcl 3-hydroxyalkanoates was achieved in Pseudomonas chlororaphis HT66. First, key genes involved in fatty acid ß-oxidation, the de novo fatty acid biosynthesis pathway, and the phaC1-phaZ-phaC2 operon were deleted to develop a chassis strain. Subsequently, an acetoacetyl-CoA reductase gene phaB and a PHA synthase gene phaC with broad substrate specificity were heterologously expressed for producing and polymerizing the 3HB monomer with mcl 3-hydroxyalkanoates under the assistance of native ß-ketothiolase gene phaA. Furthermore, the monomer composition of scl-co-mcl PHA was regulated by adjusting the amount of glucose and dodecanoic acid supplemented. Notably, the cell dry weight and scl-co-mcl PHA content reached 14.2 g/L and 60.1 wt %, respectively, when the engineered strain HT11Δ::phaCB was cultured in King's B medium containing 5 g/L glucose and 5 g/L dodecanoic acid. These results demonstrated that P. chlororaphis can be a platform for producing scl-co-mcl PHA and has the potential for industrial application.
Assuntos
Poli-Hidroxialcanoatos , Pseudomonas chlororaphis , Ácido 3-Hidroxibutírico , Pseudomonas chlororaphis/genética , Pseudomonas chlororaphis/metabolismo , Aciltransferases/genética , Aciltransferases/metabolismo , Glucose/metabolismoRESUMO
The aim of this work was to explore the differences between various pharmaceutical processes in combined solutions of a single decoction (QGHBY) and a combined decoction (QGHJY) of Qi-Ge decoction from the perspective of chemical composition changes, so as to further guide the clinical application of drugs. A combined solution of a single decoction and a combined decoction of Astragali Radix, Puerariae Lobatae Radix and Citri Reticulatae Chachiensis Pericarpium was prepared with the same technological parameters. The chemical components of the two were detected and identified based on UPLC-Q-TOF/MS, and the different components were determined by principal component analysis. Eighty-eight compounds were identified in the pharmaceutical solution of Qi-Ge decoction. Principal component analysis revealed 11 different components of QGHBY and QGHJY with the conditions of Variable Importance in Projection (VIP) ≥ 1, fold change ≥ 2 and p < 0.05, among which hesperidin, hesperitin, isosinensetin, sinensetin and 5-demethylnobiletin were the components of Citri Reticulatae Chachiensis Pericarpium. The levels of these 11 different components in QGHJY were higher than those of QGHBY. The combined decoction is beneficial for the dissolution of flavonoids and other chemical components, and there is a significant difference in the content of chemical components between modern herbal concentrate granules and traditional decoctions.