Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 511
Filtrar
1.
Ren Fail ; 46(1): 2355354, 2024 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38785302

RESUMO

Serum magnesium levels exceeding 0.9 mmol/L are associated with increased survival rates in patients with CKD. This retrospective study aimed to identify risk factors for cardio-cerebrovascular events among patients receiving continuous ambulatory peritoneal dialysis (CAPD) and to examine their correlations with serum magnesium levels. Sociodemographic data, clinical physiological and biochemical indexes, and cardio-cerebrovascular event data were collected from 189 patients undergoing CAPD. Risk factors associated with cardio-cerebrovascular events were identified by univariate binary logistic regression analysis. Correlations between the risk factors and serum magnesium levels were determined by correlation analysis. Univariate regression analysis identified age, C-reactive protein (CRP), red cell volume distribution width standard deviation, red cell volume distribution width corpuscular volume, serum albumin, serum potassium, serum sodium, serum chlorine, serum magnesium, and serum uric acid as risk factors for cardio-cerebrovascular events. Among them, serum magnesium ≤0.8 mmol/L had the highest odds ratio (3.996). Multivariate regression analysis revealed that serum magnesium was an independent risk factor, while serum UA (<440 µmol/L) was an independent protective factor for cardio-cerebrovascular events. The incidence of cardio-cerebrovascular events differed significantly among patients with different grades of serum magnesium (χ2 = 12.023, p = 0.002), with the highest incidence observed in patients with a serum magnesium concentration <0.8 mmol/L. High serum magnesium levels were correlated with high levels of serum albumin (r = 0.399, p < 0.001), serum potassium (r = 0.423, p < 0.001), and serum uric acid (r = 0.411, p < 0.001), and low levels of CRP (r = -0.279, p < 0.001). In conclusion, low serum magnesium may predict cardio-cerebrovascular events in patients receiving CAPD.


Assuntos
Magnésio , Diálise Peritoneal Ambulatorial Contínua , Humanos , Masculino , Feminino , Diálise Peritoneal Ambulatorial Contínua/efeitos adversos , Pessoa de Meia-Idade , Magnésio/sangue , Estudos Retrospectivos , Fatores de Risco , Adulto , Idoso , Doenças Cardiovasculares/etiologia , Doenças Cardiovasculares/sangue , Doenças Cardiovasculares/epidemiologia , Incidência , Transtornos Cerebrovasculares/etiologia , Transtornos Cerebrovasculares/sangue , Transtornos Cerebrovasculares/epidemiologia , Modelos Logísticos , Proteína C-Reativa/análise , Ácido Úrico/sangue , Falência Renal Crônica/terapia , Falência Renal Crônica/sangue
2.
Angew Chem Int Ed Engl ; : e202405905, 2024 May 21.
Artigo em Inglês | MEDLINE | ID: mdl-38771269

RESUMO

The replacement of a CC unit with an isoelectronic BN unit in aromatic systems can give rise to molecules and materials with fascinating properties. We report here the synthesis, characterization, and reactivity of a 1,4,2,3-diazadiborole species, 2, featuring an unprecedented 6π-aromatic BN-heterocyclic moiety that is isoelectronic to cyclopentadienide (Cp-). Bearing an unsymmetrical B=B entity, 2 exhibits reactivity toward oxidants, protic reagents, electrophiles, and unsaturated substrates. This reactivity facilitates the synthesis of a variety of novel mono- and bicyclic organoboron derivatives through mechanisms including ring retention, cleavage/recombination, annulation, and expansion. These findings reveal innovative synthetic routes to BN-embedded aromatic compounds via desymmetrization, affording unique building blocks for synthetic chemistry.

3.
Metallomics ; 2024 May 21.
Artigo em Inglês | MEDLINE | ID: mdl-38772737

RESUMO

Accumulating evidence indicates that plasma metals levels may associate with Type 2 diabetes mellitus (T2DM) incident risk. Mitochondrial function such as mitochondrial DNA copy number (mtDNA-CN) might be linked metal exposure and physiological metabolism. Mediation analysis was conducted to determine the mediating roles of mtDNA-CN in the associations of plasma metals with diabetes risk. In the present study, we investigated associations between plasma metals levels, mtDNA-CN and T2DM incident in elderly population with 6-year follow-up (2 times) study. Ten plasma metals (i.e. manganese (Mg), aluminium (Al), calcium (Ca), ferrum (Fe), barium (Ba), arsenic (As), copper (Cu), selenium (Se), titanium (Ti) and cesium (Sr) were measured by using inductively coupled plasma mass spectrometry (ICP-MS). Mitochondrial DNA copy number was measured by real-time PCR. Multivariable linear regression and logistic regression models were carried out to estimate the relationship between plasma metal concentrations, mtDNA-CN and T2DM incident risk in the current work. Plasma Ba deficiency and mtDNA-CN decline associated with T2DM incident risk during aging process. Meanwhile plasma Ba found to be positively associated with mtDNA-CN. Mitochondrial function mtDNA-CN demonstrated mediating effects in association between plasma Ba deficiency and T2DM incident risk, and 49.8% of the association was mediated by mtDNA-CN. These findings extend the knowledge of T2DM incident risk factors and highlight the point that mtDNA-CN may be linked metals element and T2DM incident risk.

4.
J Org Chem ; 89(8): 5675-5682, 2024 Apr 19.
Artigo em Inglês | MEDLINE | ID: mdl-38569117

RESUMO

As important π-skeletons, benzosiloles often possess unique electronic and optical properties and have been widely used in semiconductor materials. Therefore, great attention has been drawn to the area of developing novel synthetic methods for various benzosiloles. However, the synthesis of enantioenriched silicon-stereogenic benzosiloles is still at an early stage and remains to be explored. Herein, we performed systematic density functional theory studies on the recently reported nickel-catalyzed asymmetric synthesis of silicon-stereogenic benosiloles, which was enabled by an enantioselective desymmetrization of (2-alkenyl)aryl-substituted silacyclobutanes. Our computational study shows that the reaction mechanism involves ligand exchange, oxidative addition, alkene insertion, and hydrogen-transfer coupled reductive-demetalation steps. The proposed transmetalation and ß-hydride elimination mechanism was not found, which might be due to the unfavorable ring strain of the multicyclic intermediates. The novel hydrogen-transfer coupled reductive-demetalation mechanism was shown to be reasonable for the generation of the silicon-stereogenic benzosilole. Noncovalent interactions (including C-H···π and hydrogen bonding) in the rate-determining alkene insertion transition state account for the origins of the enantioselectivity. Our computational study sheds light on the detailed reaction mechanism and also provides insights for the development of novel approaches for synthesis of high-value silicon-stereogenic compounds.

5.
Angew Chem Int Ed Engl ; : e202400441, 2024 Apr 08.
Artigo em Inglês | MEDLINE | ID: mdl-38587149

RESUMO

Nickel-catalyzed transannulation reactions triggered by the extrusion of small gaseous molecules have emerged as a powerful strategy for the efficient construction of heterocyclic compounds. However, their use in asymmetric synthesis remains challenging because of the difficulty in controlling stereo- and regioselectivity. Herein, we report the first nickel-catalyzed asymmetric synthesis of N-N atropisomers by the denitrogenative transannulation of benzotriazones with alkynes. A broad range of N-N atropisomers was obtained with excellent regio- and enantioselectivity under mild conditions. Moreover, density functional theory (DFT) calculations provided insights into the nickel-catalyzed reaction mechanism and enantioselectivity control.

6.
Clin Immunol ; 263: 110228, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38663494

RESUMO

Asthma is a heterogeneous disease characterized by chronic airway inflammation, reversible airflow limitation, and airway remodeling. Eosinophil peroxidase (EPX) is the most abundant secondary granule protein unique to activated eosinophils. In this study, we aimed to illustrate the effect of EPX on the epithelial-mesenchymal transition (EMT) in BEAS-2B cells. Our research found that both EPX and ADAM33 were negatively correlated with FEV1/FVC and FEV1%pred, and positively correlated with IL-5 levels. Asthma patients had relatively higher levels of ADAM33 and EPX compared to the healthy control group. The expression of TSLP, TGF-ß1 and ADAM33 in the EPX intervention group was significantly higher. Moreover, EPX could promote the proliferation, migration and EMT of BEAS-2B cells, and the effect of EPX on various factors was significantly improved by the PI3K inhibitor LY294002. The findings from this study could potentially offer a novel therapeutic target for addressing airway remodeling in bronchial asthma, particularly focusing on EMT.


Assuntos
Remodelação das Vias Aéreas , Asma , Brônquios , Peroxidase de Eosinófilo , Células Epiteliais , Transição Epitelial-Mesenquimal , Fator de Crescimento Transformador beta1 , Humanos , Asma/metabolismo , Asma/patologia , Asma/fisiopatologia , Asma/imunologia , Masculino , Feminino , Células Epiteliais/metabolismo , Peroxidase de Eosinófilo/metabolismo , Fator de Crescimento Transformador beta1/metabolismo , Pessoa de Meia-Idade , Adulto , Brônquios/patologia , Interleucina-5/metabolismo , Cromonas/farmacologia , Citocinas/metabolismo , Linhagem Celular , Linfopoietina do Estroma do Timo , Proliferação de Células , Movimento Celular , Morfolinas/farmacologia , Proteínas ADAM
7.
Nat Commun ; 15(1): 2028, 2024 Mar 08.
Artigo em Inglês | MEDLINE | ID: mdl-38459051

RESUMO

Copine proteins are highly conserved and ubiquitously found in eukaryotes, and their indispensable roles in different species were proposed. However, their exact function remains unclear. The phytohormone brassinosteroids (BRs) play vital roles in plant growth, development and environmental responses. A key event in effective BR signaling is the formation of functional BRI1-SERK receptor complex and subsequent transphosphorylation upon ligand binding. Here, we demonstrate that BONZAI (BON) proteins, which are plasma membrane-associated copine proteins, are critical components of BR signaling in both the monocot maize and the dicot Arabidopsis. Biochemical and molecular analyses reveal that BON proteins directly interact with SERK kinases, thereby ensuring effective BRI1-SERK interaction and transphosphorylation. This study advances the knowledge on BR signaling and provides an important target for optimizing valuable agronomic traits, it also opens a way to study steroid hormone signaling and copine proteins of eukaryotes in a broader perspective.


Assuntos
Proteínas de Arabidopsis , Arabidopsis , Proteínas de Transporte , Arabidopsis/metabolismo , Brassinosteroides/metabolismo , Zea mays/genética , Zea mays/metabolismo , Proteínas Quinases/metabolismo , Proteínas de Arabidopsis/metabolismo , Proteínas de Membrana/metabolismo
8.
Virology ; 594: 110032, 2024 06.
Artigo em Inglês | MEDLINE | ID: mdl-38467094

RESUMO

Many viruses employ a process known as superinfection exclusion (SIE) to block subsequent entry or replication of the same or closely related viruses in the cells they occupy. SIE is also referred to as Cross-protection refers to the situation where a host plant infected by a mild strain of a virus or viroid gains immunity against a more severe strain closely related to the initial infectant. The mechanisms underlying cross-protection are not fully understood. In this study, we performed a comparative transcriptomic analysis of potato (Solanum tuberosum L.) leaves. The strains PVYN-Wi-HLJ-BDH-2 and PVYNTN-NW-INM-W-369-12 are henceforth designated as BDH and 369, respectively. In total, 806 differentially expressed genes (DEGs) were detected between the Control and JZ (preinfected with BDH and challenge with 369) treatment. Gene Ontology (GO) analysis showed that the response to external biological stimulation, signal transduction, kinase, immunity, redox pathways were significantly enriched. Among these pathways, we identified numerous differentially expressed metabolites related to virus infection. Moreover, our data also identified a small set of genes that likely play important roles in the establishment of cross-protection. Specifically, we observed significant differential expression of the A1-II gamma-like gene, elongation factor 1-alpha-like gene, and subtilisin-like protease StSBT1.7 gene, with StSBT1.7 being the most significant in our transcriptome data. These genes can stimulate the expression of defense plant genes, induce plant chemical defense, and participate in the induction of trauma and pathogenic bacteria. Our findings provided insights into the mechanisms underlying the ability of mild viruses to protect host plants against subsequent closely related virus infection in Solanum tuberosum L.


Assuntos
Potyvirus , Solanum tuberosum , Viroses , Potyvirus/genética , Perfilação da Expressão Gênica , Transcriptoma , Doenças das Plantas
9.
Ren Fail ; 46(1): 2324071, 2024 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38494197

RESUMO

INTRODUCTION: The study presented here aimed to establish a predictive model for heart failure (HF) and all-cause mortality in peritoneal dialysis (PD) patients with machine learning (ML) algorithm. METHODS: We retrospectively included 1006 patients who initiated PD from 2010 to 2016. XGBoost, random forest (RF), and AdaBoost were used to train models for assessing risk for 1-year and 5-year HF hospitalization and mortality. The performance was validated using fivefold cross-validation. The optimal ML algorithm was used to construct the models to predictive the risk of the HF and all-cause mortality. The prediction performance of ML methods and Cox regression was compared. RESULTS: Over a median follow-up of 49 months. Two hundred and ninety-eight patients developed HF required hospitalization; 199 patients died during the follow-up. The RF model (AUC = 0.853) was the best performing model for predicting HF, and the XGBoost model (AUC = 0.871) was the best model for predicting mortality. Baseline moderate or severe renal disease, systolic blood pressure (SBP), body mass index (BMI), age, Charlson Comorbidity Index (CCI) score were strongly associated with HF hospitalization, whereas age, CCI score, creatinine, age, high-density lipoprotein cholesterol (HDL-C), total cholesterol, baseline estimated glomerular filtration rate (eGFR) were the most significant predictors of mortality. For all the above endpoints, the ML models demonstrated better discrimination than Cox regression. CONCLUSIONS: We developed and validated a novel method to predict the risk factors of HF and all-cause mortality that integrates readily available clinical, laboratory, and electrocardiographic variables to predict the risk of HF among PD patients.


Assuntos
Insuficiência Cardíaca , Diálise Peritoneal , Humanos , Nomogramas , Estudos Retrospectivos , Medição de Risco/métodos , Hospitalização , Insuficiência Cardíaca/epidemiologia , Insuficiência Cardíaca/etiologia , Diálise Peritoneal/efeitos adversos , Aprendizado de Máquina , Colesterol
10.
Cell Transplant ; 33: 9636897241236586, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38469823

RESUMO

Systemic lupus erythematosus (SLE) is a multi-organ and systemic autoimmune disease characterized by an imbalance of humoral and cellular immunity. The efficacy and side effects of traditional glucocorticoid and immunosuppressant therapy remain controversial. Recent studies have revealed abnormalities in mesenchymal stem cells (MSCs) in SLE, leading to the application of bone marrow-derived MSCs (BM-MSCs) transplantation technique for SLE treatment. However, autologous transplantation using BM-MSCs from SLE patients has shown suboptimal efficacy due to their dysfunction, while allogeneic mesenchymal stem cell transplantation (MSCT) still faces challenges, such as donor degeneration, genetic instability, and immune rejection. Therefore, exploring new sources of stem cells is crucial for overcoming these limitations in clinical applications. Human amniotic epithelial stem cells (hAESCs), derived from the eighth-day blastocyst, possess strong characteristics including good differentiation potential, immune tolerance with low antigen-presenting ability, and unique immune properties. Hence, hAESCs hold great promise for the treatment of not only SLE but also other autoimmune diseases.


Assuntos
Transplante de Células-Tronco Hematopoéticas , Lúpus Eritematoso Sistêmico , Transplante de Células-Tronco Mesenquimais , Células-Tronco Mesenquimais , Humanos , Âmnio , Lúpus Eritematoso Sistêmico/terapia , Transplante de Células-Tronco Mesenquimais/métodos
11.
J Colloid Interface Sci ; 661: 957-965, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38330667

RESUMO

Constructing in-plane heterojunctions with high interfacial density using two-dimensional materials represents a promising yet challenging avenue for enhancing the hydrogen evolution reaction (HER) in water electrolysis. In this work, we report that three-dimensional porous MoS2-ReS2 in-plane heterojunctions, fabricated via chemical vapor deposition, exhibit robust electrocatalytic activity for the water splitting reaction. The optimized MoS2-ReS2 in-plane heterojunction achieves superior HER performance across a wide pH range, requiring an overpotential of only 200 mV to reach a current density of 10 mA cm-2 in alkaline seawater. Thus, it outperforms standalone MoS2 and ReS2. Furthermore, the catalyst exhibits remarkable stability, enduring up to 200 h in alkaline seawater. Experimental results coupled with density functional theory calculations confirm that electron redistribution at the MoS2-ReS2 heterointerface is likely driven by disparities in in-plane work functions between the two phases. This leads to charge accumulation at the interface, thereby enhancing the adsorptive activity of S atoms toward H* intermediates and facilitating the dissociation of water molecules at the interface. This discovery offers valuable insights into the electrocatalytic mechanisms at the interface and provides a roadmap for designing high-performance, earth-abundant HER electrocatalysts suitable for practical applications.

12.
Heliyon ; 10(3): e25482, 2024 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-38352747

RESUMO

Food has become a crucial factor in attracting tourists to destinations. Providing tourists with satisfying food experiences has become a significant concern for tourist destinations. This study examines how tourists' food experiences contribute to their subjective well-being. After conducting a questionnaire survey of 360 tourists who experienced Zibo barbecue food, and analyzing the data using structural equation modeling, it was found that: tourists' food sensory experience, service experience, and environmental experience positively affect their satisfaction and subjective well-being; The effect of these experiences on tourists' satisfaction is mediated by tourist attitude; Tourist attitude and satisfaction play a chain mediating role in the effect of sensory experience, service experience, and environmental experience on tourists' subjective well-being. The research findings help to deepen the understanding of the relationship between food tourism experience and subjective well-being, enrich the theoretical research on food experience and tourists' well-being, and have insightful significance for the development and construction of other tourist destinations.

13.
Plant Physiol ; 194(4): 2616-2630, 2024 Mar 29.
Artigo em Inglês | MEDLINE | ID: mdl-38206190

RESUMO

The plant cuticle is essential in plant defense against biotic and abiotic stresses. To systematically elucidate the genetic architecture of maize (Zea mays L.) cuticular wax metabolism, 2 cuticular wax-related traits, the chlorophyll extraction rate (CER) and water loss rate (WLR) of 389 maize inbred lines, were investigated and a genome-wide association study (GWAS) was performed using 1.25 million single nucleotide polymorphisms (SNPs). In total, 57 nonredundant quantitative trait loci (QTL) explaining 5.57% to 15.07% of the phenotypic variation for each QTL were identified. These QTLs contained 183 genes, among which 21 strong candidates were identified based on functional annotations and previous publications. Remarkably, 3 candidate genes that express differentially during cuticle development encode ß-ketoacyl-CoA synthase (KCS). While ZmKCS19 was known to be involved in cuticle wax metabolism, ZmKCS12 and ZmKCS3 functions were not reported. The association between ZmKCS12 and WLR was confirmed by resequencing 106 inbred lines, and the variation of WLR was significant between different haplotypes of ZmKCS12. In this study, the loss-of-function mutant of ZmKCS12 exhibited wrinkled leaf morphology, altered wax crystal morphology, and decreased C32 wax monomer levels, causing an increased WLR and sensitivity to drought. These results confirm that ZmKCS12 plays a vital role in maize C32 wax monomer synthesis and is critical for drought tolerance. In sum, through GWAS of 2 cuticular wax-associated traits, this study reveals comprehensively the genetic architecture in maize cuticular wax metabolism and provides a valuable reference for the genetic improvement of stress tolerance in maize.


Assuntos
Estudo de Associação Genômica Ampla , Zea mays , Zea mays/genética , Zea mays/metabolismo , Locos de Características Quantitativas/genética , Fenótipo , Água/metabolismo , Folhas de Planta/genética
14.
Anal Chem ; 96(5): 2217-2226, 2024 02 06.
Artigo em Inglês | MEDLINE | ID: mdl-38262909

RESUMO

Circulating tumor cells (CTCs) have emerged as powerful biomarkers for diagnosis of prostate cancer. However, the effective identification and concurrently accurate imaging of CTCs for early screening of prostate cancer have been rarely explored. Herein, we reported a multifunctional gold nanoprobe-based thermophoretic assay for simultaneous specific distinguishing of prostate cancer CTCs and sensitive imaging of intracellular microRNA (miR-21), achieving the rapid and precise detection of prostate cancer. The multifunctional gold nanoprobe (GNP-DNA/Ab) was modified by two types of prostate-specific antibodies, anti-PSMA and anti-EpCAM, which could effectively recognize the targeting CTCs, and meanwhile linked double-stranded DNA for further visually imaging intracellular miR-21. Upon the specific internalization of GNP-DNA/Ab by PC-3 cells, target aberrant miR-21 could displace the signal strand to recover the fluorescence signal for sensitive detection at the single-cell level, achieving single PC-3 cell imaging benefiting from the thermophoresis-mediated signal amplification procedure. Taking advantage of the sensitive miR-21 imaging performance, GNP-DNA/Ab could be employed to discriminate the PC-3 and Jurkat cells because of the different expression levels of miR-21. Notably, PC-3 cells were efficiently recognized from white blood cells, exhibiting promising potential for the early diagnosis of prostate cancer. Furthermore, GNP-DNA/Ab possessed good biocompatibility and stability. Therefore, this work provides a great tool for aberrant miRNA-related detection and specific discrimination of CTCs, achieving the early and accurate diagnosis of prostate cancer.


Assuntos
MicroRNAs , Células Neoplásicas Circulantes , Neoplasias da Próstata , Masculino , Humanos , Células Neoplásicas Circulantes/patologia , Ouro , Neoplasias da Próstata/patologia , DNA
15.
Int J Mol Sci ; 25(2)2024 Jan 19.
Artigo em Inglês | MEDLINE | ID: mdl-38279212

RESUMO

Animal models of metabolic disorders are essential to studying pathogenic mechanisms and developing therapies for diabetes, but the induction protocols vary, and sexual dimorphism often exists. In a chronic diabetic model of diet-induced obesity (DIO) and low-dose streptozotocin (STZ)-induced hyperglycemia, blood glucose and lipid profiles were measured. The high-fat (HF) diet damaged insulin sensitivity and increased triglycerides, total cholesterol, LDL-cholesterol, HDL-cholesterol, and liver lipid deposition. STZ increased blood glucose and liver fibrosis with less effects on blood lipids or liver lipid deposition. The combination of DIO and STZ treatments led to significant liver lipid deposition and fibrosis. Female mice showed delayed body weight gain on HF diet and resisted STZ-induced hyperglycemia. However, once they developed DIO, which occurs around 26 weeks of HF diet, the female mice were prone to STZ-induced hyperglycemia. In hindlimb ischemia, male mice in the DIO-STZ group showed significantly worse neovascularization compared with DIO or STZ groups. The DIO-STZ females showed significantly worse recovery than the DIO-STZ males. Our observations suggest that DIO-STZ is a plausible model for studying metabolic and cardiovascular disorders in obesity and diabetes. Moreover, the findings in female animals stress the need to assess sexual dimorphism and investigate the underlying mechanisms that contribute to the worse vasculopathy manifestations in females in metabolic models.


Assuntos
Diabetes Mellitus Experimental , Hiperglicemia , Masculino , Feminino , Camundongos , Animais , Glicemia/metabolismo , Insulina/metabolismo , Diabetes Mellitus Experimental/tratamento farmacológico , Obesidade/complicações , Modelos Animais de Doenças , Lipídeos , Hiperglicemia/tratamento farmacológico , Dieta Hiperlipídica/efeitos adversos , Estresse Fisiológico
16.
Phytomedicine ; 123: 155154, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37976696

RESUMO

OBJECTIVE: Alpinia oxyphylla fructus without impurities and shells is called "Yi-Zhi-Ren" (YZR) in Chinese, and traditionally used to alleviate enuresis. The aim of this study was to investigate the effects and underlying mechanisms of YZR in the treatment of overactive bladder (OAB) in spontaneously hypertensive rats (SHR), a vascular disorder-related OAB model. METHODS: A 3-week administration of YZR water extract (p.o.) was done, followed by urodynamics to measure bladder parameters. Changes in bladder structure were observed through H&E staining and Masson's staining. An integrated approach involving network pharmacology, transcriptomics and metabolomics was employed to elucidate the potential mechanisms of YZR, and the key proteins involved in the mechanisms were validated by Western blotting. Additionally, network pharmacology was used to predict the relationship between YZR's active components and validated proteins. RESULTS: YZR treatment significantly improved the bladder storage parameters, tightened the detrusor layer, reduced inflammatory infiltration, and decreased collagen proportion in the SHR bladder. These results indicated that YZR water extract can alleviate OAB symptoms and improve bladder structure. Integrated analysis suggested that YZR may affect extracellular matrix-receptor interaction and calcium signaling pathway. Western blotting results further confirmed that the reduction in key proteins, such as TGFß1, p-SMAD3, collagen III, Gq and PLCß1, involved in collagen synthesis and calcium signaling pathways after YZR treatment. Network pharmacology predicted that sitosterol, chrysin, and nootkatone were potential components responsible for YZR's therapeutic effect on OAB. CONCLUSION: YZR's mechanisms of action in treating OAB involved the TGFß1-SMAD3 signaling pathway-related collagen synthesis and Gq-PLCß1 calcium signaling pathway, which are associated with detrusor contraction frequency and strength, respectively.


Assuntos
Alpinia , Bexiga Urinária Hiperativa , Ratos , Animais , Bexiga Urinária , Ratos Endogâmicos SHR , Alpinia/química , Multiômica , Bexiga Urinária Hiperativa/tratamento farmacológico , Extratos Vegetais/farmacologia , Extratos Vegetais/uso terapêutico , Colágeno
17.
Mol Neurobiol ; 61(1): 519-532, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37644280

RESUMO

Propofol is one of the most used intravenous anesthetic agents, which is widely used in clinical anesthesia induction and maintenance of pediatric patients. Exposure of the developing brain to propofol has been reported to lead to adverse brain changes, which in turn can induce persistent behavioral abnormalities in adulthood. However, the mechanisms by which propofol exposure in the developing brain induces cognitive impairment remain unclear. Here we report that repeated propofol exposure during the second postnatal week impairs spatial learning and memory in young mice. The reduced excitatory synaptic function and synaptogenesis in hippocampal CA1 neurons underlie this cognitive impairment. Propofol exposure specifically activates Toll-like receptor 4 (TLR4)-myeloid differentiation primary response protein 88 (MyD88)-NF-κB signaling pathway. TLR4 deficiency recues propofol exposure-induced synaptic function and cognitive deficits in young mice. Thus, we provide evidence that the activation of the TLR4-mediated pathway by propofol exposure may serve as a crucial trigger for the cognitive impairment in young adulthood caused by repeated exposure to propofol in the developing brain.


Assuntos
Disfunção Cognitiva , Propofol , Animais , Camundongos , Anestésicos Intravenosos/toxicidade , Cognição , Disfunção Cognitiva/induzido quimicamente , Disfunção Cognitiva/metabolismo , Hipocampo/metabolismo , Plasticidade Neuronal , Propofol/farmacologia , Receptor 4 Toll-Like/metabolismo
18.
Nano Lett ; 24(2): 566-575, 2024 Jan 17.
Artigo em Inglês | MEDLINE | ID: mdl-37962055

RESUMO

Optical biosensors based on micro/nanofibers are highly valuable for probing and monitoring liquid environments and bioactivity. Most current optical biosensors, however, are still based on glass, semiconductors, or metallic materials, which might not be fully suitable for biologically relevant environments. Here, we introduce biocompatible and flexible microfibers from lotus silk as microenvironmental monitors that exhibit waveguiding of intrinsic fluorescence as well as of coupled light. These features make single-filament monitors excellent building blocks for a variety of sensing functions, including pH probing and detection of bacterial activity. These results pave the way for the development of new and entirely eco-friendly, potentially multiplexed biosensing platforms.


Assuntos
Técnicas Biossensoriais , Nanofibras , Técnicas Biossensoriais/métodos , Seda , Semicondutores , Bactérias
19.
Pediatr Pulmonol ; 59(2): 399-407, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38014582

RESUMO

OBJECTIVE: Bronchopulmonary dysplasia (BPD) is one of the most serious complications affecting extremely preterm infants. We aimed to evaluate temporal trends in BPD and administration of respiratory support among extremely preterm infants in China over a decade. METHODS: This was a retrospective study using data from a multicenter database, which included infants born less than 28 weeks' gestation discharged from 68 tertiary neonatal care centers in China between 2010 and 2019. Changes in rates and severity of BPD, as well as modalities and duration of respiratory support, were evaluated. RESULTS: Among 4808 eligible infants with gestational age (GA) of 21+6/7  to 27+6/7 weeks and a mean (SD) birth weight of 980 (177) g, no significant change of median GA was found over time. Overall, 780 (16.2%) infants died before 36 weeks' postmenstrual age, 2415 (50.2%) were classified as having no BPD, 917 (19.1%) developed Grade 1 BPD, 578 (12.0%) developed Grade 2 BPD, and 118 (2.5%) developed Grade 3 BPD. The rate of BPD increased from 20.8% in 2010 to 40.7% in 2019 (aRR for trend, 1.081; 95% confidence interval, 1.062-1.099), especially for Grade 1 and Grade 2. Although survival to discharge improved over the decade, the overall survival without BPD did not change during the study period. The use of invasive mechanical ventilation (IMV) remained unchanged. However, the use of noninvasive ventilation (NIV) increased from 71.5% in 2010 to 89.8% in 2019. Moreover, the median duration of NIV increased over time, from 17.0 (4.8, 34.0) days in 2010 to 33.0 (21.0, 44.0) days in 2019, without significant change in the duration of IMV. CONCLUSIONS: Although survival increased over the decade and respiratory support practices changed significantly between 2010 and 2019 in China, with increased use and duration of NIV, there was an increased rate of BPD and survival without BPD has not improved.


Assuntos
Displasia Broncopulmonar , Lactente Extremamente Prematuro , Lactente , Recém-Nascido , Humanos , Displasia Broncopulmonar/etiologia , Estudos Retrospectivos , Respiração Artificial/efeitos adversos , Peso ao Nascer , Idade Gestacional
20.
Food Res Int ; 175: 113746, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38129051

RESUMO

Sojae semen germinatum (SSG) is derived from mature soybean seeds that have been germinated and dried, typically with sprouts measuring approximately 0.5 cm in length. SSG is traditionally known for its properties in clearing heat and moisture. Nevertheless, limited information was reported on the effects and mechanisms of SSG in alleviating urinary symptoms. This study employed urodynamic parameters to investigate the therapeutic effect of SSG water extract on overactive bladder (OAB) in the rat model with benign prostatic hyperplasia. Through a combination of transcriptomic and metabolomic analyses, the pathways and key proteins of the SSG treatment for OAB were identified and validated by ELISA and Western blotting. Furthermore, network pharmacology elucidated the roles of SSG's isoflavones acting on the target which was identified by above-mentioned multi-omics analysis. Our results indicate that SSG water extract significantly mitigated OAB by down-regulating the PGE2/EP1/PLCß2/p-MLC signaling pathway. It was speculated that the active ingredient in the SSG on EP1 was genistein. This study provided valuable insights into the molecular mechanisms of SSG water extract, emphasizing the multi-target characteristics and critical pathways in improving OAB. Furthermore, this study contributes to the potential utilization of SSG as a functional food.


Assuntos
Hiperplasia Prostática , Bexiga Urinária Hiperativa , Humanos , Masculino , Ratos , Animais , Bexiga Urinária Hiperativa/tratamento farmacológico , Bexiga Urinária Hiperativa/metabolismo , Multiômica , Sementes/metabolismo , Hiperplasia Prostática/tratamento farmacológico , Hiperplasia Prostática/metabolismo , Secreções Corporais/metabolismo
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA