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1.
J Inflamm Res ; 17: 5923-5942, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39247837

RESUMO

Background: Despite ongoing interventions, SARS-CoV-2 continues to cause significant global morbidity and mortality. Early diagnosis and intervention are crucial for effective clinical management. However, prognostic features based on transcriptional data have shown limited effectiveness, highlighting the need for more precise biomarkers to improve COVID-19 treatment outcomes. Methods: We retrospectively analyzed 149 clinical features from 189 COVID-19 patients, identifying prognostic features via univariate Cox regression. The cohort was split into training and validation sets, and 77 prognostic models were developed using seven machine learning algorithms. Among these, the least absolute shrinkage and selection operator (Lasso) method was employed to refine the selection of prognostic variables by ten-fold cross-validation strategy, which were then integrated with random survival forests (RSF) to build a robust COVID-19-related prognostic model (CRM). Model accuracy was evaluated across training, validation, and entire cohorts. The diagnostic relevance of interleukin-10 (IL-10) was confirmed in bulk transcriptional data and validated at the single-cell level, where we also examined changes in cellular communication between mononuclear cells with differing IL-10 expression and other immune cells. Results: Univariate Cox regression identified 43 prognostic features. Among the 77 machine learning models, the combination of Lasso and RSF produced the most robust CRM. This model consistently performed well across training, validation, and entire cohorts. IL-10 emerged as a key prognostic feature within the CRM, validated by single-cell transcriptional data. Transcriptome analysis confirmed the stable diagnostic value of IL-10, with mononuclear cells identified as the primary IL-10 source. Moreover, differential IL-10 expression in these cells was linked to altered cellular communication in the COVID-19 immune microenvironment. Conclusion: The CRM provides accurate prognostic predictions for COVID-19 patients. Additionally, the study underscores the importance of early IL-10 level testing upon hospital admission, which could inform therapeutic strategies.

3.
Healthcare (Basel) ; 12(17)2024 Aug 23.
Artigo em Inglês | MEDLINE | ID: mdl-39273710

RESUMO

As numerous nations transition into digital and aging societies, the digital divide has emerged as a significant impediment to older adults' autonomous engagement in the digital society. Enhancing the well-being of elderly individuals through remote medical technology represents a prevailing and prospective trend. Nevertheless, remote medical technology extends beyond the realm of healthcare, offering promise for narrowing the digital divide through the deployment of digital devices and provision of intergenerational support. Therefore, this study investigates the role of trust and expectations in the use of telemedicine, indicating potential pathways for how these products can improve older adults' daily living abilities. Through the construction of a theoretical model, we collected the relevant data of 661 elderly people who use telemedicine technology in China and analyzed the data with SmartPLS4 to obtain the research results. The study discovered that, among older people using telemedicine technology, (1) healthcare expectations promote the breadth of telemedicine product use; (2) trust in product safety increases the depth of telemedicine product use; (3) trust in the service provider promotes the breadth of telemedicine product use; and (4) when compared to the depth of product use, the breadth of telemedicine product use increases older adults' sense of control over their digital lives. The findings provide new empirical data to support growing beliefs about how expectations and trust can increase a sense of control over one's life. They also provide practical contributions on how to boost older adults' usage of telemedicine products, promote their digital literacy and competency, and enhance their sense of control over their digital lives.

4.
J Hazard Mater ; 480: 135839, 2024 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-39298965

RESUMO

A precious metal catalyst with loaded Pt single atoms was prepared and used for the complete oxidation of C3H6O. Detailed results show that the T100 of the 1.5Pt SA/γ-Al2O3 catalyst in the oxidation process of acetone is 250 °C, the TOF of Pt is 1.09 × 10-2 s-1, and the catalyst exhibits good stability. Characterization reveals that the high dispersion of Pt single atoms and strong interaction with the carrier improve the redox properties of the catalyst, enhancing the adsorption and dissociation capability of gaseous oxygen. DFT calculations show that after the introduction of Pt, the oxygen vacancy formation energy on the catalyst surface is reduced to 1.2 eV, and PDOS calculations prove that electrons on Pt atoms can be quickly transferred to O atoms, increasing the number of electrons on the σp * bond and promoting the escape of lattice oxygen. In addition, in situ DRIFTS and adsorption experiments indicate that the C3H6O oxidation process follows the Mars-van Krevelen reaction mechanism, and CH2 =C(CH3)=O(ads), O* (O2-), formate, acetate, and carbonate are considered as the main intermediate species and/or transients in the reaction process. Particularly, the activation rate of O2 and the cleavage of the -C-C- bond are the main rate-determining steps in the oxidation of C3H6O. This work will further enhance the study of the oxidation mechanism of oxygenated volatile organic pollutants over loaded noble metal catalysts.

5.
Nat Cancer ; 5(9): 1427-1447, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-39242942

RESUMO

Prostate cancer (PCa) exhibits significant geoethnic disparities as reflected by distinct variations in the cancer genome and disease progression. Here, we perform a comprehensive proteogenomic characterization of localized high-risk PCa utilizing paired tumors and nearby tissues from 125 Chinese male patients, with the primary objectives of identifying potential biomarkers, unraveling critical oncogenic events and delineating molecular subtypes with poor prognosis. Our integrated analysis highlights the utility of GOLM1 as a noninvasive serum biomarker. Phosphoproteomics analysis reveals the crucial role of Ser331 phosphorylation on FOXA1 in regulating FOXA1-AR-dependent cistrome. Notably, our proteomic profiling identifies three distinct subtypes, with metabolic immune-desert tumors (S-III) emerging as a particularly aggressive subtype linked to poor prognosis and BCAT2 catabolism-driven PCa progression. In summary, our study provides a comprehensive resource detailing the unique proteomic and phosphoproteomic characteristics of PCa molecular pathogenesis and offering valuable insights for the development of diagnostic and therapeutic strategies.


Assuntos
Biomarcadores Tumorais , Fator 3-alfa Nuclear de Hepatócito , Neoplasias da Próstata , Proteogenômica , Idoso , Humanos , Masculino , Pessoa de Meia-Idade , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/sangue , China , População do Leste Asiático/genética , Regulação Neoplásica da Expressão Gênica , Fator 3-alfa Nuclear de Hepatócito/genética , Fator 3-alfa Nuclear de Hepatócito/metabolismo , Fosforilação , Prognóstico , Neoplasias da Próstata/genética , Neoplasias da Próstata/diagnóstico , Neoplasias da Próstata/metabolismo , Proteogenômica/métodos , Receptores Androgênicos/genética , Receptores Androgênicos/metabolismo
6.
Transfus Clin Biol ; 2024 Sep 26.
Artigo em Inglês | MEDLINE | ID: mdl-39341351

RESUMO

OBJECTIVE: To detect the differentially expressed regulatory miRNAs in the late stage of red blood cell (RBC) preservation and predict their roles. METHODS: Suspended RBCs with different storage periods of 35 day, 42 day, and 50 day were collected for routine blood tests, RNA extraction, and preparation of small RNA sequencing libraries. The constructed libraries were sequenced and the biological functions of differential miRNAs in RBCs in the late storage were analyzed by bioinformatics. RESULTS: Routine indicators of RBCs in the late stage were not significantly affected by preservation time. The Pearson correlation analysis performing on RBC miRNAs with different storage days revealed that RBC miRNAs changed with the increase of storage days. RBC miRNAs from day 35 (D35), day 42 (D42) and day 50 (D50) showed significant differences (P<0.05). Compared RBC miRNAs from D42 with these from D35, there were 690 up-regulated miRNAs and 82 down-regulated miRNAs; compared RBC miRNAs from D50 with these from D35, there were 638 up-regulated miRNAs and 123 down-regulated miRNAs; compared RBC miRNAs from D42 with these from D50, there were 271 up-regulated miRNAs and 515 down-regulated miRNAs. GO enrichment analysis of target genes of differential miRNAs were mainly involved in cell metabolism, biosynthesis, protein modification, gene expression and transcriptional regulation of biological processes. KEGG pathway enrichment analysis of miRNA target genes showed that differential miRNA target genes were closely related to pathways in cancer. CONCLUSION: MiRNAs were differentially expressed in the late stage of RBC preservation, and may be involved in various biological processes, especially cancer.

7.
J Plant Res ; 2024 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-39198337

RESUMO

Soil salinization has been considered as a major environmental threat to plant growth. Different types of salt in saline soil have different effects on germination and seedling growth. Effect of NaCl on germination and seedling establishment in Suaeda liaotungensis have been reported, but its response to alkali stress remains unclear. Our results showed that brown seeds had higher germination rate, however, black seeds had higher germination recovery percentage under alkali stress. Na2CO3 had stronger inhibitory effect on germination and seedling growth than NaHCO3. As the concentration of alkali stress increased, the ROS level of brown seeds gradually ascended, while that of black seeds decreased first and then ascended. MDA content of dimorphic seeds significantly increased under alkali stress. The trend of SOD, POD and CAT activity between dimorphic seeds was similar under the same type of alkali stress. Alkali stress enhanced proline content of dimorphic seeds, and dimorphic seeds in NaHCO3 solution had higher proline content than Na2CO3 solution. Moreover, radicle and shoot tolerance indexes of seedlings in NaHCO3 solution were significantly higher than that of Na2CO3 solution. Under strong alkali stress, seedlings in NaHCO3 solution had significantly lower ROS level and MDA content as well as higher antioxidant enzyme activity than Na2CO3 solution. This study comprehensively compared the morphological and physiological characteristics in germination and seedlings to better reveal the saline-alkali tolerance mechanisms in S. liaotungensis.

8.
J Nutr Biochem ; 134: 109733, 2024 Aug 09.
Artigo em Inglês | MEDLINE | ID: mdl-39127309

RESUMO

To investigate the effects of vitamin D status on cutaneous wound healing, C57BL/6J mice were fed diets with different vitamin D levels or injected intraperitoneally with 1α,25(OH)2D3. Dorsal skin wounds were created and wound edge tissues were collected on days 4, 7, 11, and 14 postwounding. The proliferation and migration of HaCaT cells treated with shVDR or 1α,25(OH)2D3 were assessed. Vitamin D deficiency (VDD) decreased wound closure and might delay inflammatory response, shown by slower inflammatory cell infiltration, decreased IL6 and TNF expression in early phase followed by an increase later. VDD might postpone epithelial-mesenchymal transition (EMT), initially characterized by higher epithelial markers and lower mesenchymal markers, followed by opposite appearance later. Dietary vitamin D supplementation and 1α,25(OH)2D3 intervention tended to accelerate EMT. Regarding extracellular matrix (ECM), VDD appeared to reduce collagen deposition on day 4 and downregulated fibronectin, COL3A1, and MMP9 expression early, followed by an increase later, together with an initial increase and subsequent decrease in Timp1 mRNA expression. Dietary vitamin D intervention promoted fibronectin and MMP9 expression on day 4 and then downregulated their expression on day 14. TGFb1/SMAD2/3 signaling seemed to be downregulated by VDD and upregulated by 1α,25(OH)2D3. In vitro, partial inhibition of VDR by shVDR tended to inhibit HaCaT cell proliferation and migration, EMT, and TGFb1/SMAD2/3 signaling, whereas 1α,25(OH)2D3 appeared to generate opposite effects. In conclusion, VDD hindered cutaneous wound healing, potentially due to impaired inflammatory response, delayed EMT, decreased ECM, and inhibited TGFb1/SMAD2/3 pathway. Vitamin D and 1α,25(OH)2D3 tended to enhance EMT and ECM.

9.
J Clin Neurosci ; 128: 110801, 2024 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-39168063

RESUMO

PURPOSE: There are currently no models for predicting hip fractures after stroke. This study wanted to investigate the risk factors leading to hip fracture in stroke patients and to establish a risk prediction model to visualize this risk. PATIENTS AND METHODS: We reviewed 439 stroke patients with or without hip fractures admitted to the Affiliated Hospital of Xuzhou Medical University from June 2014 to June 2017 as the training set, and collected 83 patients of the same type from the First Affiliated Hospital of Harbin Medical University and the Affiliated Hospital of Xuzhou Medical University from June 2020 to June 2023 as the testing set. Patients were divided into fracture group and non-fracture group based on the presence of hip fractures. Multivariate logistic regression analysis was used to screen for meaningful factors. Nomogram predicting the risk of hip fracture occurrence were created based on the multifactor analysis, and performance was evaluated using receiver operating characteristic curve (ROC), calibration curves, and decision curve analysis (DCA). A web calculator was created to facilitate a more convenient interactive experience for clinicians. RESULTS: In training set, there were 35 cases (7.9 %) of hip fractures after stroke, while in testing set, this data was 13 cases (15.6 %). In training set, univariate analysis showed significant differences between the two groups in the number of falls, smoking, hypertension, glucocorticoids, number of strokes, Mini-Mental State Examination (MMSE), visual acuity level, National Institute of Health stroke scale (NIHSS), Berg Balance Scale (BBS), and Stop Walking When Talking (SWWT) (P<0.05). Multivariate analysis showed that number of falls [OR=17.104, 95 % CI (3.727-78.489), P = 0.000], NIHSS [OR=1.565, 95 % CI (1.193-2.052), P = 0.001], SWWT [OR=12.080, 95 % CI (2.398-60.851), P = 0.003] were independent risk factors positively associated with new fractures. BMD [OR = 0.155, 95 % CI (0.044-0.546), P = 0.012] and BBS [OR = 0.840, 95 % CI (0.739-0.954), P = 0.007] were negatively associated with new fractures. The area under the curve (AUC) of nomogram were 0.939 (95 % CI: 0.748-0.943) and 0.980 (95 % CI: 0.886-1.000) in training and testing sets, respectively, and the calibration curves showed a high agreement between predicted and actual status with an area under the decision curve of 0.034 and 0.109, respectively. CONCLUSIONS: The number of falls, fracture history, low BBS score, high NIHSS score, and positive SWWT are risk factors for hip fracture after stroke. Based on this, a nomogram with high accuracy was developed and a web calculator (https://stroke.shinyapps.io/DynNomapp/) was created.


Assuntos
Fraturas do Quadril , Nomogramas , Acidente Vascular Cerebral , Humanos , Feminino , Masculino , Fraturas do Quadril/epidemiologia , Estudos Retrospectivos , Idoso , Acidente Vascular Cerebral/epidemiologia , Acidente Vascular Cerebral/diagnóstico , Acidente Vascular Cerebral/complicações , Acidente Vascular Cerebral/etiologia , Pessoa de Meia-Idade , Fatores de Risco , Idoso de 80 Anos ou mais , Medição de Risco/métodos
10.
Acta Biomater ; 186: 275-285, 2024 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-39097124

RESUMO

Hypothermic preservation (HP) is highly desired for the maintenance of the viability of living cell specimens, e.g. rare cells in whole-blood samples or therapeutic cells, in an unfrozen state. However, the extension of the viable preservation time is a challenge because of the multiple injuries suffered by hypothermically preserved cells. Here, based on a dynamic bond crosslinked zwitterionic hydrogel, we established a sensing preservation system that could monitor the levels of reactive oxygen species (ROS) via real-time electronic signals and intelligent control of antioxidant addition, to completely prevent an excess of ROS in the whole-cell specimen. Furthermore, the hydrogel-based system can counter the extracellular-matrix-loss-induced anoikis of living cells. Based on the design aimed at affording protection against two primary HP injuries (i.e. ROS overproduction and anoikis) to cells, this system extended the preservation time of cell specimens under refrigerated conditions to 24 days. After preservation, the use of a mild cell retrieval process guaranteed the activity of the preserved living cells. This work not only possesses the potential to facilitate intelligent cell-based clinical applications, but also paves the way for the preparation of living materials that can host programmed cells with long-term survival. STATEMENT OF SIGNIFICANCE: An intelligent system based on a zwitterionic sensing hydrogel is established, which can afford ultra-long hypothermic cell-preservation times of up to 24 days. The system enables the real-time monitoring of ROS overproduction and intelligent antioxidant addition, because of the merging of the smart hydrogel with a computer intelligent detection and control system. Furthermore, the automatic addition of an antioxidant according to the ROS-signal changes produced by the ZBA hydrogel effectively prevented HP lesions, including ROS over-production and ECM loss, in the preserved living cells. Subsequently, the system could also be gently dissociated, to retrieve the preserved cells. This work provides a solution for the real-time monitoring and long-term HP of living specimens, which holds the promise of benefiting cell-based medicine and the development of genetically programmed cell-based living materials.


Assuntos
Hidrogéis , Espécies Reativas de Oxigênio , Espécies Reativas de Oxigênio/metabolismo , Humanos , Hidrogéis/química , Sobrevivência Celular/efeitos dos fármacos , Antioxidantes/farmacologia , Antioxidantes/química , Animais , Anoikis/efeitos dos fármacos , Técnicas Biossensoriais/métodos
11.
Int Immunopharmacol ; 140: 112826, 2024 Oct 25.
Artigo em Inglês | MEDLINE | ID: mdl-39128416

RESUMO

Chronic airway inflammation induced by cigarette smoke (CS) plays an essential role in the pathogenesis of chronic obstructive pulmonary disease (COPD). MALAT1 is involved in a variety of inflammatory disorders. However, studies focusing on the interaction between MALAT1 and CS-induced airway inflammation remain unknown. The present study investigated the effects and mechanisms of MALAT1 in CS-induced airway inflammation in the pathogenesis of COPD. RT-qPCR was employed to determine the mRNA levels of MALAT1, miR-30a-5p and inflammatory cytokines. Protein concentrations of IL-1ß and IL-6 in cell culture supernatant and mouse bronchoalveolar lavage fluid (BALF) were assessed by ELISA assay kits. Dual-luciferase reporter assay was conducted to verify the interaction between MALAT1 and miR-30a-5p. The protein expression of JNK and p-JNK was determined by western blot (WB). MALAT1 was highly expressed in cigarette smoke extract (CSE)-treated human bronchial epithelial cells (HBECs) and COPD mice lung tissues. Knockdown of MALAT1 significantly alleviate CS-induced inflammatory response. MALAT1 directly interacted with miR-30a-5p and knockdown of miR-30a-5p significantly inhibit the protective effects of MALAT1 silencing after CS exposure. Additionally, our results showed that miR-30a-5p could regulate inflammation via modulating the activation of JNK signaling pathway. Moreover, our results demonstrated MALAT1 could activate JNK signaling pathway by sponging miR-30a-5p. Our results demonstrated MALAT1 promotes CS-induced airway inflammation by inhibiting the activation of JNK signaling pathway via sponging miR-30a-5p.


Assuntos
Camundongos Endogâmicos C57BL , MicroRNAs , Doença Pulmonar Obstrutiva Crônica , RNA Longo não Codificante , MicroRNAs/genética , MicroRNAs/metabolismo , Animais , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , Humanos , Doença Pulmonar Obstrutiva Crônica/genética , Doença Pulmonar Obstrutiva Crônica/metabolismo , Doença Pulmonar Obstrutiva Crônica/imunologia , Camundongos , Sistema de Sinalização das MAP Quinases , Fumaça/efeitos adversos , Masculino , Linhagem Celular , Citocinas/metabolismo , Citocinas/genética , Fumar Cigarros/efeitos adversos , Células Epiteliais/metabolismo , Pulmão/patologia , Pulmão/imunologia , Pulmão/metabolismo , Modelos Animais de Doenças , Nicotiana/efeitos adversos
12.
Lipids Health Dis ; 23(1): 249, 2024 Aug 16.
Artigo em Inglês | MEDLINE | ID: mdl-39148061

RESUMO

BACKGROUND: Existing studies have presented limited and disparate findings on the nexus between immune cells, plasma metabolites, and metabolic dysfunction-associated steatotic liver disease (MASLD). The aim of this study was to investigate the causal relationship between immune cells and MASLD. Additionally, we aimed to identify and quantify the potential mediating role of metabolites. METHODS: A Mendelian randomization (MR) analysis was conducted using two samples of pooled data from genome-wide association studies on MASLD that included 2568 patients and 409,613 control individuals. Additionally, a mediated MR study was employed to quantify the metabolite-mediated immune cell effects on MASLD. RESULTS: In this study, eight immunophenotypes were linked to the risk of MASLD, and thirty-five metabolites/metabolite ratios were linked to the occurrence of MASLD. Furthermore, a total of six combinations of immunophenotypic and metabolic factors demonstrated effects on the occurrence of MASLD, although the mediating effects of metabolites were not significant. CONCLUSION: Our study demonstrated that certain immunophenotypes and metabolite/metabolite ratios have independent causal relationships with MASLD. Furthermore, we identified specific metabolites/metabolite ratios that are associated with an increased risk of MASLD. However, their mediating role in the causal association between immunophenotypes and MASLD was not significant. It is important to consider immune and metabolic disorders among patients with MASLD in clinical practice.


Assuntos
Estudo de Associação Genômica Ampla , Análise da Randomização Mendeliana , Humanos , Polimorfismo de Nucleotídeo Único , Fígado Gorduroso/genética , Fígado Gorduroso/metabolismo , Fígado Gorduroso/patologia , Fígado Gorduroso/imunologia , Imunofenotipagem , Masculino
13.
J Inflamm Res ; 17: 5113-5127, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39099665

RESUMO

Background: Progress in research on expression profiles in osteoarthritis (OA) has been limited to individual tissues within the joint, such as the synovium, cartilage, or meniscus. This study aimed to comprehensively analyze the common gene expression characteristics of various structures in OA and construct a diagnostic model. Methods: Three datasets were selected: synovium, meniscus, and knee joint cartilage. Modular clustering and differential analysis of genes were used for further functional analyses and the construction of protein networks. Signature genes with the highest diagnostic potential were identified and verified using external gene datasets. The expression of these genes was validated in clinical samples by Real-time (RT)-qPCR and immunohistochemistry (IHC) staining. This study investigated the status of immune cells in OA by examining their infiltration. Results: The merged OA dataset included 438 DEGs clustered into seven modules using WGCNA. The intersection of these DEGs with WGCNA modules identified 190 genes. Using Least Absolute Shrinkage and Selection Operator (LASSO) and Random Forest algorithms, nine signature genes were identified (CDADC1, PPFIBP1, ENO2, NOM1, SLC25A14, METTL2A, LINC01089, L3HYPDH, NPHP3), each demonstrating substantial diagnostic potential (areas under the curve from 0.701 to 0.925). Furthermore, dysregulation of various immune cells has also been observed. Conclusion: CDADC1, PPFIBP1, ENO2, NOM1, SLC25A14, METTL2A, LINC01089, L3HYPDH, NPHP3 demonstrated significant diagnostic efficacy in OA and are involved in immune cell infiltration.

14.
Diabetes Metab Syndr Obes ; 17: 2855-2867, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39100967

RESUMO

Purpose: Luteolin is a promising candidate for diabetic nephropathy due to its potential anti-inflammatory and anti-fibrotic properties. This study explored the molecular mechanisms through which luteolin combats fibrosis in DN. Methods: Potential targets affected by luteolin and genes associated with DN were collected from databases. Overlapping targets between luteolin and diabetic nephropathy were identified through Venn analysis. A protein-protein interaction network was constructed using these common targets, and critical pathways and targets were elucidated through GO and KEGG analysis. These pathways and targets were confirmed using a streptozotocin-induced mouse model. Luteolin was administered at 45 mg/kg and 90 mg/kg. Various parameters were evaluated, including body weight, blood glucose levels, and histopathological examinations. Protein levels related to energy metabolism, inflammation, and fibrosis were quantified. Results: Fifty-three targets associated with luteolin and 36 genes related to diabetic nephropathy were extracted. The AGE-RAGE signaling pathway was the key pathway impacted by luteolin in diabetic nephropathy. Key molecular targets include TGF-ß, IL-1ß, and PPARG. Luteolin reduced body weight and blood glucose levels, lowered the left kidney index, and improved insulin and glucose tolerance. Furthermore, luteolin mitigated inflammatory cell infiltration, basement membrane thickening, and collagen deposition in the kidney. Luteolin up-regulated the protein expression of p-AMPKα (Th172) while simultaneously down-regulated the protein expression of p-NF-ĸB (p65), NLRP3, TGF-ß1, α-SMA, and Collagen I. Conclusion: Luteolin mitigated renal fibrosis by alleviating energy metabolism disruptions and inflammation by modulating the AMPK/NLRP3/TGF-ß signaling pathway.

15.
Angew Chem Int Ed Engl ; : e202407215, 2024 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-39082673

RESUMO

Kalmanol, the flagship member of the kalmane diterpene family, possesses a complex and highly oxidized 5/5/8/5 tetracyclic skeleton with nine contiguous stereocenters and exhibits significant analgesic effects and cardiotoxic properties. We have achieved the efficient total synthesis of (+)-kalmanol in 22 steps with 2.3% yield. The synthesis featured a Rh-catalyzed [5+2+1] cycloaddition reaction to construct 5/5/8 tricyclic skeleton, and a meticulously designed sequence of stereoselective oxidations of the 5/5/8/5 tetracyclic skeleton.

16.
Toxicol Lett ; 400: 49-57, 2024 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-39084329

RESUMO

OBJECTIVE: This study evaluated the effects of long-term polystyrene microplastics (PS-MPs) exposure on hepatic lipid metabolism in vivo by lipidomics. RESULTS: H&E staining showed long-term PS-MPs exposure could trigger the hepatic inflammatory cell infiltration and hepatic steatosis in SD rats, indicating long-term PS-MPs exposure caused hepatoxicity. Lipidomics revealed that the concentrations of 8 lipid metabolites in the liver were altered after exposure to PS-MPs for both 6 and 12 months, namely LdMePE (16:0), LPC (18:1), LPC (18:2), LPC (20:4), PC (17:0_20:4), PC (18:2_22:6), PC (22:6_13:0) and SM (d18:1_24:0), which were all statistically different from the control groups detected at both time points after PS-MPs exposure, suggesting the mainly metabolic pathway was glycerolipid metabolism. CONCLUSION: This study showed chronic exposure to PS-MPs could cause hepatotoxicity and induce hepatic lipidomics alterations in vivo, which could provide an essential clue for the safety assessment of PS-MPs.


Assuntos
Metabolismo dos Lipídeos , Lipidômica , Fígado , Microplásticos , Poliestirenos , Ratos Sprague-Dawley , Animais , Poliestirenos/toxicidade , Fígado/efeitos dos fármacos , Fígado/metabolismo , Microplásticos/toxicidade , Metabolismo dos Lipídeos/efeitos dos fármacos , Masculino , Ratos , Lipídeos , Fatores de Tempo , Doença Hepática Induzida por Substâncias e Drogas/etiologia , Doença Hepática Induzida por Substâncias e Drogas/metabolismo , Doença Hepática Induzida por Substâncias e Drogas/patologia , Fígado Gorduroso/induzido quimicamente , Fígado Gorduroso/metabolismo
18.
Water Res ; 262: 122123, 2024 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-39067271

RESUMO

Identifying the sources and cycling of phosphorus (P) is particularly important for formulating effective P management strategies in inland water. The oxygen isotopic compositions of phosphate (δ18OP) are recognized as a promising tool to solve this problem. However, the application of δ18OP in freshwater sediment is currently constrained by multiple difficulties. In this study, we presented a novel pretreatment method for δ18OP analysis of sediment inorganic P pools. Our results showed that the new method has advantages of simple operation, less time-consuming, and high P recovery rates. Specifically, we replaced the traditional Mg-induced co-precipitation (MAGIC) method by introducing Zr-Oxides gels with high selective adsorption function for phosphate. This made subsequent processing simpler and reduced the time consumption to ∼10 days, and the range of P recovery rates were from 88 % to 104 %. Furthermore, we emphasized the necessity of vacuum roasting following lyophilized Ag3PO4 to eliminate residual oxygen-containing impurities (e.g., NO3-, Ag2O, and organic matter). Additionally, evidences from microscopy and spectroscopy confirmed that this method ultimately yielded high-purity Ag3PO4 with the Ag:P molar ratios of 3.35:1. Importantly, combining direct synthesis Ag3PO4 between KH2PO4 and AgNO3 with the Ag3PO4 obtained by the method revealed no stark oxygen isotopic fractionation of phosphate during the pretreatment processes. The newly established δ18OP pretreatment methods here can also be extended to broader studies of the biogeochemical cycling of P in aquatic ecosystems, potentially advancing the understanding of the global P cycle.


Assuntos
Água Doce , Sedimentos Geológicos , Isótopos de Oxigênio , Fósforo , Sedimentos Geológicos/química , Água Doce/química , Fosfatos/química
19.
Int J Pharm ; 662: 124515, 2024 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-39074649

RESUMO

Spherical agglomeration (SA) is a processing technique that enhances the physical properties of particles, reduces the number of unit operations in pharmaceutical manufacturing, and improves process efficiency. However, one of the limitations of SA is its high nonlinearity, which makes scalability a challenge. This prospective study was designed to realize the optimization of SA process parameters of aspirin, the world's first and most widely used nonsteroidal anti-inflammatory drug, by developing a green SA model through response surface methodology. First, Plackett-Burman experiments were conducted to identify the key operating variables affecting SA, and Sustainability Index (STI) was defined to evaluate the effects of these operating variables on the SA and the energy input to the environment during the post-processing process. Furthermore, the effects of three independent variables on mean size, yield, and STI were investigated based on Box-Behnken design. A second-order regression equation with response values was developed to optimize the above three objectives. As a result, the spherical products were obtained with excellent powder properties, including anti-caking property, filtration property, and tableting performance compared to the raw materials. This work provides an experimental and modelling basis for the further application of this environmentally-friendly SA technology.


Assuntos
Anti-Inflamatórios não Esteroides , Aspirina , Tamanho da Partícula , Tecnologia Farmacêutica , Aspirina/química , Tecnologia Farmacêutica/métodos , Anti-Inflamatórios não Esteroides/química , Pós/química , Comprimidos/química , Química Verde/métodos , Química Farmacêutica/métodos , Composição de Medicamentos/métodos , Estudos Prospectivos
20.
Opt Express ; 32(9): 15053-15064, 2024 Apr 22.
Artigo em Inglês | MEDLINE | ID: mdl-38859165

RESUMO

The purpose of this study is to present a physical layer security scheme for key concealment and distribution based on carrier scrambling. The three-dimensional (3D) Lorenz system is used to generate independent chaotic sequences that encrypt the information with bit, constellation and subcarrier. In order to realize the flexible distribution of the key and ensure its security, the key information is loaded into a specific subcarrier. While key subcarrier and the ciphertext subcarrier are scrambled simultaneously. The encrypted key position information is processed and transmitted in conjunction with the training sequence (TS) to facilitate demodulation by the legitimate receiver. The processed TS can accommodate up to 10 key position information, thereby demonstrating the scheme's exceptional scalability. Experimental results show that the proposed scheme can safely transmit 131.80 Gb/s Orthogonal frequency division multiplexing (OFDM) signals across 2 km 7-core fiber. Meanwhile, the scheme enables simultaneous flexible distribution and concealment of the key, thereby offering a promising solution for physical layer security.

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