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1.
Lab Invest ; 104(7): 102087, 2024 May 24.
Artículo en Inglés | MEDLINE | ID: mdl-38797344

RESUMEN

Addressing the existing gaps in our understanding of sex- and strain-dependent disparities in renal microhemodynamics, this study conducted an investigation into the variations in renal function and related biological oscillators. Using the genetically diverse mouse models BALB/c, C57BL/6, and Kunming, which serve as established proxies for the study of renal pathophysiology, we implemented laser Doppler flowmetry conjoined with wavelet transform analyses to interrogate dynamic renal microcirculation. Creatinine, urea, uric acid, glucose, and cystatin C levels were quantified to investigate potential divergences attributable to sex and genetic lineage. Our findings reveal marked sexual dimorphism in metabolite concentrations, as well as strain-specific variances, particularly in creatinine and cystatin C levels. Through the combination of Mantel tests and Pearson correlation coefficients, we delineated the associations between renal functional metrics and microhemodynamics, uncovering interactions in female BALB/c mice for creatinine and uric acid, and in male C57BL/6 mice for cystatin C. Histopathologic examination confirmed an augmented microvascular density in female mice and elucidating variations in the expression of estrogen receptor ß among the strains. These data collectively highlight the influence of both sex and genetic constitution on renal microcirculation, providing an understanding that may inform the etiologic exploration of renal ailments.

2.
Microvasc Res ; 151: 104617, 2024 01.
Artículo en Inglés | MEDLINE | ID: mdl-37918522

RESUMEN

Type 1 diabetes mellitus (T1DM) is predominantly managed using insulin replacement therapy, however, pancreatic microcirculatory disturbances play a critical role in T1DM pathogenesis, necessitating alternative therapies. This study aimed to investigate the protective effects of glycine supplementation on pancreatic microcirculation in T1DM. Streptozotocin-induced T1DM and glycine-supplemented mice (n = 6 per group) were used alongside control mice. Pancreatic microcirculatory profiles were determined using a laser Doppler blood perfusion monitoring system and wavelet transform spectral analysis. The T1DM group exhibited disorganized pancreatic microcirculatory oscillation. Glycine supplementation significantly restored regular biorhythmic contraction and relaxation, improving blood distribution patterns. Further-more, glycine reversed the lower amplitudes of endothelial oscillators in T1DM mice. Ultrastructural deterioration of islet microvascular endothelial cells (IMECs) and islet microvascular pericytes, including membrane and organelle damage, collagenous fiber proliferation, and reduced edema, was substantially reversed by glycine supplementation. Additionally, glycine supplementation inhibited the production of IL-6, TNF-α, IFN-γ, pro-MMP-9, and VEGF-A in T1DM, with no significant changes in energetic metabolism observed in glycine-supplemented IMECs. A statistically significant decrease in MDA levels accompanied by an increase in SOD levels was also observed with glycine supplementation. Notably, negative correlations emerged between inflammatory cytokines and microhemodynamic profiles. These findings suggest that glycine supplementation may offer a promising therapeutic approach for protecting against pancreatic microcirculatory dysfunction in T1DM.


Asunto(s)
Diabetes Mellitus Tipo 1 , Islotes Pancreáticos , Ratones , Animales , Microcirculación , Células Endoteliales , Islotes Pancreáticos/irrigación sanguínea , Islotes Pancreáticos/metabolismo , Suplementos Dietéticos
3.
Vet Res ; 55(1): 78, 2024 Jun 14.
Artículo en Inglés | MEDLINE | ID: mdl-38877574

RESUMEN

Endoplasmic reticulum stress (ERS) and oxidative stress (OS) are adaptive responses of the body to stressor stimulation. Although it has been verified that Trichinella spiralis (T. spiralis) can induce ERS and OS in the host, their association is still unclear. Therefore, this study explored whether T. spiralis-secreted serpin-type serine protease inhibitor (TsAdSPI) is involved in regulating the relationship between ERS and OS in the host intestine. In this study, mice jejunum and porcine small intestinal epithelial cells (IECs) were detected using qPCR, western blotting, immunohistochemistry (IHC), immunofluorescence (IF), and detection kits. The results showed that ERS- and OS-related indexes changed significantly after TsAdSPI stimulation, and Bip was located in IECs, indicating that TsAdSPI could induce ERS and OS in IECs. After the use of an ERS inhibitor, OS-related indexes were inhibited, suggesting that TsAdSPI-induced OS depends on ERS. When the three ERS signalling pathways, ATF6, IRE1, and PERK, were sequentially suppressed, OS was only regulated by the PERK pathway, and the PERK-eif2α-CHOP-ERO1α axis played a key role. Similarly, the expression of ERS-related indexes and the level of intracellular Ca2+ were inhibited after adding the OS inhibitor, and the expression of ERS-related indexes decreased significantly after inhibiting calcium transfer. This finding indicated that TsAdSPI-induced OS could affect ERS by promoting Ca2+ efflux from the endoplasmic reticulum. The detection of the ERS and OS sequences revealed that OS occurred before ERS. Finally, changes in apoptosis-related indexes were detected, and the results indicated that TsAdSPI-induced ERS and OS could regulate IEC apoptosis. In conclusion, TsAdSPI induced OS after entering IECs, OS promoted ERS by enhancing Ca2+ efflux, and ERS subsequently strengthened OS by activating the PERK-eif2α-CHOP-ERO1α axis. ERS and OS induced by TsAdSPI synergistically promoted IEC apoptosis. This study provides a foundation for exploring the invasion mechanism of T. spiralis and the pathogenesis of host intestinal dysfunction after invasion.


Asunto(s)
Estrés del Retículo Endoplásmico , Células Epiteliales , Estrés Oxidativo , Serpinas , Trichinella spiralis , Animales , Estrés del Retículo Endoplásmico/efectos de los fármacos , Trichinella spiralis/fisiología , Ratones , Estrés Oxidativo/efectos de los fármacos , Porcinos , Serpinas/metabolismo , Serpinas/genética , Inhibidores de Serina Proteinasa/farmacología , Proteínas del Helminto/metabolismo , Proteínas del Helminto/genética , Yeyuno/efectos de los fármacos
4.
BMC Infect Dis ; 24(1): 653, 2024 Jun 28.
Artículo en Inglés | MEDLINE | ID: mdl-38944667

RESUMEN

BACKGROUND: An improper host immune response to Mycoplasma pneumoniae generates excessive inflammation, which leads to the impairment of pulmonary ventilation function (PVF). Azithromycin plus inhaled terbutaline has been used in the treatment of Mycoplasma pneumoniae pneumonia (MPP) in children with impaired pulmonary function, but previous randomized controlled trials (RCTs) showed inconsistent efficacy and safety. This study is aimed to firstly provide a systematic review of the combined therapy. METHODS: This study was registered at the International Prospective Register of Systematic Reviews (PROSPERO CRD42023452139). A PRISMA-compliant systematic review and meta-analysis was performed. Six English and four Chinese databases were comprehensively searched up to June, 2023. RCTs of azithromycin sequential therapy plus inhaled terbutaline were selected. The revised Cochrane risk of bias tool for randomized trials (RoB2) was used to evaluate the methodological quality of all studies, and meta-analysis was performed using Stata 15.0 with planned subgroup and sensitivity analyses. Publication bias was evaluated by a funnel plot and the Harbord' test. Certainty of evidence was assessed using the Grading of Recommendations, Assessment, Development and Evaluation recommendations. RESULTS: A total of 1,938 pediatric patients from 20 RCTs were eventually included. The results of meta-analysis showed that combined therapy was able to significantly increase total effectiveness rate (RR = 1.20, 95%CI 1.15 to 1.25), forced expiratory volume in one second (SMD = 1.14, 95%CIs, 0.98 to 1.29), the ratio of forced expiratory volume in one second/forced vital capacity (SMD = 2.16, 95%CIs, 1.46 to 2.86), peak expiratory flow (SMD = 1.17, 95%CIs, 0.91 to 1.43). The combined therapy was associated with a 23% increased risk of adverse reactions compared to azithromycin therapy alone, but no significant differences were found. Harbord regression showed no publication bias (P = 0.148). The overall quality of the evidence ranged from moderate to very low. CONCLUSIONS: This first systematic review and meta-analysis suggested that azithromycin sequential therapy plus inhaled terbutaline was safe and beneficial for children with MPP. In addition, the combined therapy represented significant improvement of PVF. Due to lack of high-quality evidence, our results should be confirmed by adequately powered RCTs in the future.


Asunto(s)
Antibacterianos , Azitromicina , Mycoplasma pneumoniae , Neumonía por Mycoplasma , Terbutalina , Humanos , Azitromicina/administración & dosificación , Azitromicina/uso terapéutico , Terbutalina/administración & dosificación , Terbutalina/uso terapéutico , Neumonía por Mycoplasma/tratamiento farmacológico , Niño , Antibacterianos/administración & dosificación , Antibacterianos/uso terapéutico , Mycoplasma pneumoniae/efectos de los fármacos , Quimioterapia Combinada , Administración por Inhalación , Resultado del Tratamiento , Ensayos Clínicos Controlados Aleatorios como Asunto , Preescolar
5.
Environ Res ; 252(Pt 1): 118827, 2024 Jul 01.
Artículo en Inglés | MEDLINE | ID: mdl-38580006

RESUMEN

BACKGROUND: PM2.5 is a harmful mixture of various chemical components that pose a challenge in determining their individual and combined health effects due to multicollinearity issues with traditional linear regression models. This study aimed to develop an analytical methodology combining traditional and novel machine learning models to evaluate PM2.5's combined effects on blood pressure (BP) and identify the most toxic components. METHODS: We measured late-pregnancy BP of 1138 women from the Heshan cohort while simultaneously analyzing 31 PM2.5 components. We utilized multiple linear regression modeling to establish the relationship between PM2.5 components and late-pregnancy BP and applied Random Forest (RF) and generalized Weighted Quantile Sum (gWQS) regression to identify the most toxic components contributing to elevated BP and to quantitatively evaluate the cumulative effect of the PM2.5 component mixtures. RESULTS: The results revealed that 16 PM2.5 components, such as EC, OC, Ti, Fe, Mn, Cu, Cd, Mg, K, Pb, Se, Na+, K+, Cl-, NO3-, and F-, contributed to elevated systolic blood pressure (SBP), while 26 components, including two carbon components (EC, OC), fourteen metallics (Ti, Fe, Mn, Cr, Mo, Co, Cu, Zn, Cd, Na, Mg, Al, K, Pb), one metalloid (Se), and nine water-soluble ions (Na+, K+, Mg2+, Ca2+, NH4+, Cl-, NO3-, SO42-, F-), contributed to elevated diastolic blood pressure (DBP). Mn and Cr were the most toxic components for elevated SBP and DBP, respectively, as analyzed by RF and gWQS models and verified against each other. Exposure to PM2.5 component mixtures increased SBP by 1.04 mmHg (95% CI: 0.33-1.76) and DBP by 1.13 mmHg (95% CI: 0.47-1.78). CONCLUSIONS: Our study highlights the effectiveness of combining traditional and novel models as an analytical strategy to quantify the health effects of PM2.5 constituent mixtures.


Asunto(s)
Contaminantes Atmosféricos , Presión Sanguínea , Aprendizaje Automático , Material Particulado , Femenino , Material Particulado/análisis , Material Particulado/toxicidad , Humanos , Embarazo , Presión Sanguínea/efectos de los fármacos , Adulto , Contaminantes Atmosféricos/análisis , Contaminantes Atmosféricos/toxicidad , China
6.
Nutr Metab Cardiovasc Dis ; 34(7): 1590-1600, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38499451

RESUMEN

BACKGROUND AND AIMS: Obesity and insulin resistance are associated with left ventricular diastolic dysfunction (LVDD) and increased risk of heart failure. Cardiometabolic index (CMI) and triglyceride glucose (TyG) are new indexes to assess visceral obesity and insulin resistance, respectively. The study aimed to investigate the clinical usefulness of these indexes for identifying LVDD individuals. METHODS AND RESULTS: Overall, 1898 asymptomatic individuals were included in this cross-sectional study. Participants underwent anthropometrics, serum biochemical evaluation, and echocardiography. Multiple linear regression analysis revealed that both indexes were independent determinants of diastolic parameters among females; while for males, CMI and TyG were not associated with A velocity. In the multivariate logistic analysis, the proportion of LVDD in the third and fourth quartiles of CMI remained significantly greater than that in the lowest quartile in females (Q3 vs. Q1: odds ratio (OR) = 2.032, 95% confidence interval (CI): 1.181-3.496; Q4 vs. Q1: OR = 2.393, 95% CI: 1.347-4.249); while in males, the incidence of LVDD was significantly greater only in the fourth quartile. For TyG, the presence of LVDD in the fourth quartile was significantly greater in both genders. The discriminant values between the CMI (AUC: 0.704, 95% CI: 0.668-0.739) and TyG (AUC: 0.717, 95% CI: 0.682-0.752) were similar in females. Both indexes performed better in females than in males to identify LVDD. CONCLUSION: The CMI and TyG might both serve as effective tools to identify LVDD in routine health check-ups in primary care, mainly in females. With simpler parameters, the CMI could be utilized in medically resource-limited areas.


Asunto(s)
Enfermedades Asintomáticas , Biomarcadores , Glucemia , Factores de Riesgo Cardiometabólico , Diástole , Resistencia a la Insulina , Valor Predictivo de las Pruebas , Triglicéridos , Disfunción Ventricular Izquierda , Función Ventricular Izquierda , Humanos , Femenino , Masculino , Estudios Transversales , Triglicéridos/sangre , Persona de Mediana Edad , Glucemia/metabolismo , Disfunción Ventricular Izquierda/epidemiología , Disfunción Ventricular Izquierda/fisiopatología , Disfunción Ventricular Izquierda/sangre , Disfunción Ventricular Izquierda/diagnóstico , Disfunción Ventricular Izquierda/diagnóstico por imagen , Biomarcadores/sangre , Adulto , Medición de Riesgo , Obesidad Abdominal/diagnóstico , Obesidad Abdominal/epidemiología , Obesidad Abdominal/fisiopatología , Obesidad Abdominal/sangre , Factores Sexuales , Incidencia
7.
Nucleic Acids Res ; 50(6): 3581-3592, 2022 04 08.
Artículo en Inglés | MEDLINE | ID: mdl-35323947

RESUMEN

Direct cloning of biosynthetic gene clusters (BGCs) from microbial genomes facilitates natural product-based drug discovery. Here, by combining Cas12a and the advanced features of bacterial artificial chromosome library construction, we developed a fast yet efficient in vitro platform for directly capturing large BGCs, named CAT-FISHING (CRISPR/Cas12a-mediated fast direct biosynthetic gene cluster cloning). As demonstrations, several large BGCs from different actinomycetal genomic DNA samples were efficiently captured by CAT-FISHING, the largest of which was 145 kb with 75% GC content. Furthermore, the directly cloned, 110 kb long, cryptic polyketide encoding BGC from Micromonospora sp. 181 was then heterologously expressed in a Streptomyces chassis. It turned out to be a new macrolactam compound, marinolactam A, which showed promising anticancer activity. Our results indicate that CAT-FISHING is a powerful method for complicated BGC cloning, and we believe that it would be an important asset to the entire community of natural product-based drug discovery.


Asunto(s)
Productos Biológicos , Streptomyces , Sistemas CRISPR-Cas , Clonación Molecular , Familia de Multigenes , Streptomyces/genética
8.
Ren Fail ; 46(1): 2329249, 2024 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-38482598

RESUMEN

BACKGROUND: Renal microcirculation plays a pivotal role in kidney function by maintaining structural and functional integrity, facilitating oxygen and nutrient delivery, and waste removal. However, a thorough bibliometric analysis in this area remains lacking. Therefore, we aim to provide valuable insights through a bibliometric analysis of renal microcirculation literature using the Web of Science database. METHODS: We collected renal microcirculation-related publications from the Web of Science database from January 01, 1990, to December 31, 2022. The co-authorship of authors, organizations, and countries/regions was analyzed with VOSviewer1.6.18. The co-occurrence of keywords and co-cited references were analyzed using CiteSpace6.1.R6 software to generate visualization maps. Additionally, burst detection was applied to keywords and cited references to forecast research hotspots and future trends. RESULTS: Our search yielded 7462 publications, with the American Journal of Physiology-Renal Physiology contributing the most articles. The United States, Mayo Clinic, and Lerman Lilach O emerged with the highest publication count, indicating their active collaborations. 'Type 2 diabetes' was the most significant keyword cluster, and 'diabetic kidney disease' was the largest cluster of cited references. 'Cardiovascular outcome' and 'diabetic kidney diseases' were identified as keywords in their burst period over the past three years. CONCLUSION: Our bibliometric analysis illuminates the contours of nephrology and microcirculation research, revealing a landscape ripe for challenges and the seeds of future scientific innovation. While the trends discerned from the literature emerging opportunities in diagnostic innovation, renal microcirculation research, and precision medicine interventions, their translation to clinical practice is anticipated to be a deliberate process.


Asunto(s)
Nefropatías Diabéticas , Riñón , Humanos , Microcirculación , Bibliometría , Bases de Datos Factuales
9.
BMC Nurs ; 23(1): 53, 2024 Jan 19.
Artículo en Inglés | MEDLINE | ID: mdl-38238711

RESUMEN

BACKGROUND: One factor that influences nursing students' decision to engage in volunteer activities is volunteer motivation. It is important to understand the motivations of nursing students to volunteer. However, the majority of current studies have concentrated on the present level of nursing students' motivation to volunteer. OBJECTIVES: To identify subgroups of nursing students' volunteer motivation and its influential factors. METHODS: From January to February 2022, a cross-sectional online study was conducted, and 2569 nursing students from 10 provinces in China were recruited. Participants completed the General Information Questionnaire, Volunteer Functional Inventory (VFI), Perceived Stress Scale (PSS) and Perceived Social Support Scale (PSSS). We explore the categories and characteristics of volunteer motivation using latent profile analysis. Then, we determined factors that affect undergraduate nursing students' volunteer motivation using multinomial logistic regression. RESULTS: The volunteer motivation score of the nursing students was 77.65 (15.22). The study found that volunteer motivation could be divided into three categories: low-low protective volunteer motivation group (9.3%), general-high career values volunteer motivation group (37.5%), and high volunteer motivation group (53.2%). Perceived social support scale score, perceived stress scale score, gender, and grade significantly influenced the volunteer motivation of nursing students in different categories (both P < 0.05). Women were more likely to have higher motivation to volunteer than men, and fourth-year nursing students were more likely to be in general-high career values volunteer motivation group. CONCLUSIONS: The study highlights the significant heterogeneity in volunteer motivation among nursing students. Higher volunteer motivation was associated with higher perceived social support and lower perceived stress. In addition, gender and academic year were significant influencing factors. Nursing educators should develop targeted volunteer management plans based on the typological characteristics of the population to motivate nursing students to volunteer and promote the development of individual physical and mental health and social well-being. TRIAL REGISTRATION: The survey was approved by the Biomedical Ethics Committee of the Department of Medicine, Xi'an Jiaotong University (No. 2022-0006).

10.
Pharm Biol ; 62(1): 472-479, 2024 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-38769628

RESUMEN

CONTEXT: The Xihuang pill (XHP) is a traditional Chinese medicine formulation that has been historically used in the prevention and treatment of proliferative breast diseases. However, there is a lack of guidelines that offer recommendations for its clinical use. OBJECTIVE: The task force from the Chinese Guangdong Pharmaceutical Association aims to develop evidence-based guidelines for XHP to prevent and treat proliferative breast diseases. METHODS: We searched six Chinese and English electronic databases, including the China National Knowledge Infrastructure, the Chinese Scientific Journal Database, the Wanfang Medical Database, PubMed, and Embase, up to November 1, 2022. Publications (case reports, clinical observation, clinical trials, reviews) on using XHP to treat proliferative breast diseases were manually searched. The search terms were Xihuang pill, hyperplasia of the mammary gland, breast lump, and mastalgia. The writing team developed recommendations based on the best available evidence. RESULTS: Treatment should be customized based on syndrome identification. We recommend using XHP for the prevention and treatment of breast hyperplasia disease when a patient presents the following syndromes: concurrent blood stasis syndrome, concurrent phlegm-stasis syndrome, and concurrent liver fire syndrome. Safety indicators, including blood analysis and liver and kidney function monitoring, should be performed regularly during treatment. CONCLUSIONS: Current clinical evidence suggests that XHP can be used as a standalone treatment or in conjunction with other medications to prevent and manage breast hyperplasia diseases. More randomized controlled studies are warranted to establish high-quality evidence of its use.


Asunto(s)
Enfermedades de la Mama , Medicamentos Herbarios Chinos , Hiperplasia , Medicina Tradicional China , Humanos , Femenino , Medicamentos Herbarios Chinos/uso terapéutico , Medicamentos Herbarios Chinos/administración & dosificación , Enfermedades de la Mama/tratamiento farmacológico , Medicina Tradicional China/métodos , China
11.
Angew Chem Int Ed Engl ; : e202406246, 2024 Jun 27.
Artículo en Inglés | MEDLINE | ID: mdl-38934471

RESUMEN

Terpene synthases (TPSs) play pivotal roles in generating diverse terpenoids through complex cyclization pathways. Protein engineering of TPSs offers a crucial approach to expanding terpene diversity. However, significant potential remains untapped due to limited understanding of the structure-function relationships of TPSs. In this investigation, using a joint approach of molecular dynamics simulations-assisted engineering and site-directed mutagenesis, we manipulated the aromatic residue cluster (ARC) of a bifunctional terpene synthase (BFTPS), Pestalotiopsisfici nigtetraene synthase (PfNS). This led to the discovery of previously unreported catalytic functions yielding different cyclization patterns of sesterterpenes. Specifically, a quadruple variant (F89A/Y113F/W193L/T194W) completely altered PfNS's function, converting it from producing the bicyclic sesterterpene nigtetraene to the tricyclic ophiobolin F. Additionally, analysis of catalytic profiles by double, triple, and quadruple variants demonstrated that the ARC functions as a switch, unprecedently redirecting the production of 5/11 bicyclic (Type B) sesterterpenes to 5/15 bicyclic (Type A) ones. Molecular dynamics simulations and theozyme calculations further elucidated that, in addition to cation-π interactions, C-H∙∙∙π interactions also play a key role in the cyclization patterns. This study offers a feasible strategy in protein engineering of TPSs for various industrial applications.

12.
Plant Cell ; 32(2): 470-485, 2020 02.
Artículo en Inglés | MEDLINE | ID: mdl-31852774

RESUMEN

Among many glycoproteins within the plant secretory system, KORRIGAN1 (KOR1), a membrane-anchored endo-ß-1,4-glucanase involved in cellulose biosynthesis, provides a link between N-glycosylation, cell wall biosynthesis, and abiotic stress tolerance. After insertion into the endoplasmic reticulum, KOR1 cycles between the trans-Golgi network (TGN) and the plasma membrane (PM). From the TGN, the protein is targeted to growing cell plates during cell division. These processes are governed by multiple sequence motifs and also host genotypes. Here, we investigated the interaction and hierarchy of known and newly identified sorting signals in KOR1 and how they affect KOR1 transport at various stages in the secretory pathway. Conventional steady-state localization showed that structurally compromised KOR1 variants were directed to tonoplasts. In addition, a tandem fluorescent timer technology allowed for differential visualization of young versus aged KOR1 proteins, enabling the analysis of single-pass transport through the secretory pathway. Observations suggest the presence of multiple checkpoints/branches during KOR1 trafficking, where the destination is determined based on KOR1's sequence motifs and folding status. Moreover, growth analyses of dominant PM-confined KOR1-L48L49→A48A49 variants revealed the importance of active removal of KOR1 from the PM during salt stress, which otherwise interfered with stress acclimation.


Asunto(s)
Proteínas de Arabidopsis/metabolismo , Arabidopsis/metabolismo , Celulasa/metabolismo , Retículo Endoplásmico/metabolismo , Proteínas de la Membrana/metabolismo , Estrés Salino/fisiología , Tolerancia a la Sal/fisiología , Red trans-Golgi/metabolismo , Arabidopsis/genética , Proteínas de Arabidopsis/genética , Membrana Celular/metabolismo , Pared Celular/metabolismo , Celulasa/genética , Celulosa/metabolismo , Regulación de la Expresión Génica de las Plantas , Glicosilación , Aparato de Golgi/metabolismo , Proteínas de la Membrana/genética , Mutación , Raíces de Plantas/crecimiento & desarrollo , Plantas Modificadas Genéticamente , Transporte de Proteínas , Control de Calidad , Estrés Salino/genética , Tolerancia a la Sal/genética , Sales (Química)/metabolismo , Alineación de Secuencia , Transcriptoma
13.
Allergy ; 78(6): 1570-1584, 2023 06.
Artículo en Inglés | MEDLINE | ID: mdl-36876522

RESUMEN

BACKGROUND: Spinal astrocytes contribute to chronic itch via sensitization of itch-specific neurons expressing gastrin-releasing peptide receptor (GRPR). However, whether microglia-neuron interactions contribute to itch remains unclear. In this study, we aimed to explore how microglia interact with GRPR+ neurons and promote chronic itch. METHODS: RNA sequencing, quantitative real-time PCR, western blot, immunohistochemistry, RNAscope ISH, pharmacologic and genetic approaches were performed to examine the roles of spinal NLRP3 (The NOD-like receptor family, pyrin-containing domain 3) inflammasome activation and IL-1ß-IL1R1 signaling in chronic itch. Grpr-eGFP and Grpr KO mice were used to investigate microglia-GRPR+ neuron interactions. RESULTS: We observed NLRP3 inflammasome activation and IL-1ß production in spinal microglia under chronic itch conditions. Blockade of microglial activation and the NLRP3/caspase-1/IL-1ß axis attenuated chronic itch and neuronal activation. Type 1 IL-1 receptor (IL-1R1) was expressed in GRPR+ neurons, which are essential for the development of chronic itch. Our studies also find that IL-1ß+ microglia are localized in close proximity to GRPR+ neurons. Consistently, intrathecal injection of IL1R1 antagonist or exogenous IL-1ß indicate that the IL-1ß-IL-1R1 signaling pathway enhanced the activation of GRPR+ neurons. Furthermore, our results demonstrate that the microglial NLRP3/caspase-1/IL-1ß axis contributes to several different chronic itches triggered by small molecules and protein allergens from the environment and drugs. CONCLUSION: Our findings reveal a previously unknown mechanism in which microglia enhances the activation of GRPR+ neurons through the NLRP3/caspase-1/IL-1ß/IL1R1 axis. These results will provide new insights into the pathophysiology of pruritus and novel therapeutic strategies for patients with chronic itch.


Asunto(s)
Inflamasomas , Proteína con Dominio Pirina 3 de la Familia NLR , Ratones , Animales , Inflamasomas/metabolismo , Proteína con Dominio Pirina 3 de la Familia NLR/genética , Proteína con Dominio Pirina 3 de la Familia NLR/metabolismo , Microglía/metabolismo , Receptores de Bombesina/metabolismo , Prurito/genética , Prurito/metabolismo , Enfermedad Crónica , Interleucina-1beta/metabolismo , Neuronas/metabolismo , Caspasas , Ratones Endogámicos C57BL
14.
Brain Behav Immun ; 108: 98-117, 2023 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-36427810

RESUMEN

Growing evidence suggests the involvement of the microbiota-gut-brain axis in cognitive impairment induced by sleep deprivation (SD), however how the microbiota-gut-brain axis work remains elusive. Here, we discovered that chronic SD induced intestinal dysbiosis, activated NLRP3 inflammasome in the colon and brain, destructed intestinal/blood-brain barrier, and impaired cognitive function in mice. Transplantation of "SD microbiota" could almost mimic the pathological and behavioral changes caused by chronic SD. Furthermore, all the behavioral and pathological abnormalities were practically reversed in chronic sleep-deprived NLRP3-/- mice. Regional knockdown NLRP3 expression in the gut and hippocampus, respectively. We observed that down-regulation of NLRP3 in the hippocampus inhibited neuroinflammation, and ameliorated synaptic dysfunction and cognitive impairment induced by chronic SD. More intriguingly, the down-regulation of NLRP3 in the gut protected the intestinal barrier, attenuated the levels of peripheral inflammatory factors, down-regulated the expression of NLRP3 in the brain, and improved cognitive function in chronic SD mice. Our results identified gut microbiota as a driver in chronic SD and highlighted the NLRP3 inflammasome as a key regulator within the microbiota-gut-brain axis.


Asunto(s)
Disfunción Cognitiva , Inflamasomas , Ratones , Animales , Inflamasomas/metabolismo , Proteína con Dominio Pirina 3 de la Familia NLR/metabolismo , Privación de Sueño/complicaciones , Disbiosis/inducido químicamente , Hipocampo/metabolismo , Disfunción Cognitiva/metabolismo , Intestinos
15.
Chemphyschem ; 24(6): e202200845, 2023 Mar 14.
Artículo en Inglés | MEDLINE | ID: mdl-36426857

RESUMEN

Extensive efforts to enhance the oxygen evolution reaction (OER) catalytic performance of transition metal oxides mainly concentrate on the extrinsic morphology tailoring, lattice doping, and electrode interface optimizing. Nevertheless, little room is left for performance improvement using these methods and an obvious gap still exists compared to the precious metal catalysts. In this work, a novel "mixed-valent cobalt modulation" strategy is presented to enhance the electrocatalytic OER of perovskite LaCoO3 (LCO) oxide. The valence transition of cobalt is realized by ethylenediamine post reduction procedure at room temperature, which further induces the variation of magnetic properties for LCO catalyst. The optimized LCO catalyst with Co2+ /Co3+ of 1.98 % exhibits the best OER activity, and the overpotential at 10 mA cm-2 current density is decreased by 170 mV compared pristine LCO. Impressively, the ferromagnetic LCO catalyst can perform magnetic OER enhancement. By application of an external magnetic field, the overpotential of LCO at 10 mA cm-2 can be further decreased by 20 mV compared to that of under zero magnetic field, which arises from the enhanced energy states of electrons and accelerated electron transfer process driven by magnetic field. Our findings may provide a promising strategy to break the bottleneck for further enhancement of OER performance.

16.
Fish Shellfish Immunol ; 141: 109025, 2023 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-37625733

RESUMEN

Zinc plays a crucial role in the antioxidant capacity, and inflammatory response of aquatic species, but its impact on largemouth bass Micropterus salmoides is rarely reported. Therefore, this paper aimed to investigate the effects of different levels of zinc on the growth performance, histopathology, antioxidant capacity, and inflammatory cytokines of largemouth bass Micropterus salmoides. Fish with an initial weight of 7.84 ± 0.06 g were cultured for 10 weeks. Five experimental diets were prepared with supplemented proteinate Zn (Bioplex Zn, Alltech) (0, 30, 60, 90, and 120 mg/kg), which were named the Zn-42, Zn-73, Zn-103, Zn-133, and Zn-164 groups. No evident difference was found between the dietary zinc level and the survival rate, the crude lipid content of the whole fish, or the visceral somatic index. Weight gain, condition factor, whole-body crude protein content, interleukin-10, and transforming growth factor beta gene expression were gradually enhanced with up to 102.68 mg/kg zinc and decreased at higher levels. The hepatosomatic index, feed conversion ratio, malondialdehyde level in the liver, aspartate aminotransferase, and alanine transaminase activity in the serum, gradually decreased up to 102.68 mg/kg zinc, and gradually increased beyond this. Activation of the nuclear factor erythroid-derived 2-like 2/Kelch-like ECH-associated protein 1 signaling pathway gradually up-regulated the mRNA levels and activities of glutathione peroxidase, total antioxidant capacity, catalase, and superoxide dismutase in the liver, this antioxidant ability was lower when the zinc was greater than 102.68 mg/kg. The gene expressions of nuclear factor-k-gene binding and pro-inflammation cytokines (interleukin-1ß, interleukin-15, tumor necrosis factor alpha, and interleukin-8) were up-regulated up to 102.68 mg/kg zinc and then gradually repressed. In conclusion, using broken line analysis to estimate weight gain and Zn proteinate as the zinc source, the recommended dietary zinc for largemouth bass is 66.57 mg/kg zinc.


Asunto(s)
Antioxidantes , Lubina , Animales , Antioxidantes/metabolismo , Suplementos Dietéticos/análisis , Dieta/veterinaria , Citocinas/genética , Zinc , Alimentación Animal/análisis
17.
Eur J Nutr ; 62(1): 175-184, 2023 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-35931834

RESUMEN

PURPOSE: We aimed to investigate whether parental and siblings' sugar-sweetened beverage (SSB) intake had prospective impact on children's SSB consumption, and the potential sex difference in these associations. METHODS: This study included a total of 904 children and their parents enrolled from 2004 to 2011 China Health and Nutrition Survey (CHNS) cohort study. SSB consumption information was estimated using a short dietary questionnaire and total energy intake was assessed with three-day 24-h dietary assessments at recruitment and follow-up surveys. Multivariate logistic or linear regression analyses were used to assess the association for SSB consumption between parents, siblings and children after adjusting for age, body mass index (BMI) z-score, household income and parental educational level. RESULTS: In this study, a majority (87.6%) of children consumed SSB. Among them, the median consumption of SSB was 70.3 ml/day per capita and 205.4 ml/day per consumer. Parental SSB consumption was relevant to children's SSB consumption, and this association was more pronounced in boys than in girls. Meanwhile, fathers seemed to have a stronger impact on whether children consume SSB than mothers which was reflected by lower P and higher OR. Additionally, children's SSB intake was prospectively associated with their older siblings' SSB consumption (P for trend < 0.03). CONCLUSIONS: Parental and older siblings' SSB consumption was relevant to children's SSB intake. Particularly, boys were more susceptible to parental impact than girls, and fathers seemed to have a greater influence on children than mothers.


Asunto(s)
Bebidas Azucaradas , Humanos , Masculino , Niño , Femenino , Bebidas , Estudios de Cohortes , Padres , China
18.
Phys Chem Chem Phys ; 25(32): 21730-21735, 2023 Aug 16.
Artículo en Inglés | MEDLINE | ID: mdl-37552090

RESUMEN

An ultrasonic method for lithium-ion battery (LIB) state of charge (SoC) estimation is a promising emerging technology which may largely improve the SoC estimation accuracy. Previously, it was unknown whether the SoC change induced ultrasonic signal change originated from the anode or the cathode, because the thicknesses of cathodes, anodes and separators are much smaller than the ultrasonic wavelength, which makes it impossible to decouple the anodic and cathodic influence. To quantitatively solve the above problem, we have designed a special half-cell architecture with an extra-thick separator (675 µm) to study the reflected ultrasonic signal. The thickened separator would significantly delay the reflection of ultrasonic waves from the counter-electrode (Li), so that the influence of the working electrode (LiFePO4 or graphite) on the ultrasonic wave can be studied separately. As a result, in the Gr anode, the time of flight (ToF) of the ultrasonic wave decreases with SoC, the changing rate coefficient of which is in the range of -110 to -70 ps µmGr thickness-1, depending on the compact density. A lower compact density electrode leads to a more significant ultrasonic ToF decrease and intensity increase while in the LFP cathode, the ToF increases with SoC, the changing rate coefficient of which is in the range of 15-43 ps µmLFP thickness-1. The ToF change of the transmitted ultrasound through multilayered LIB matches very well with the sum of the ToF change in each electrode measured with our half-cells.

19.
Phys Chem Chem Phys ; 25(25): 16952-16961, 2023 Jun 28.
Artículo en Inglés | MEDLINE | ID: mdl-37326588

RESUMEN

Two-dimensional carbon-based materials have great potential for electrocatalysis. Herein, we screen 12 defective and doped C3N nanosheets by evaluating their CO2RR and NRR activity and selectivity vs. the HER based on density functional theory calculations. The calculation results suggest that all 12 C3Ns can enhance CO2 adsorption and activation. And PN-VC-C3N is the best electrocatalyst for the CO2RR towards HCOOH with UL = -0.17 V, which is much more positive than most of the reported values. BN-C3N and PN-C3N are also good electrocatalysts that promote the CO2RR towards HCOOH (UL = -0.38 V and -0.46 V). Moreover, we find that SiC-C3N can reduce CO2 to CH3OH, adding an alternative option to the limited catalysts available for the CO2RR to CH3OH. Furthermore, BC-VC-C3N, BC-VN-C3N, and SiC-VN-C3N are promising electrocatalysts for the HER with |ΔGH*| ≤ 0.30 eV. However, only three C3Ns of BC-VC-C3N, SiC-VN-C3N, and SiC-VC-C3N can slightly improve N2 adsorption. And none of the 12 C3Ns are found to be suitable for the electrocatalytic NRR because all the ΔeNNH* values are larger than the corresponding ΔGH* values. The high performance of C3Ns in the CO2RR stems from the altered structure and electronic properties, which result from the introduction of vacancies and doping elements into C3N. This work identifies suitable defective and doped C3Ns for excellent performance in the electrocatalytic CO2RR, which will inspire relevant experimental studies to further explore C3Ns for electrocatalysis.

20.
Appl Opt ; 62(26): 7036-7043, 2023 Sep 10.
Artículo en Inglés | MEDLINE | ID: mdl-37707044

RESUMEN

We propose and experimentally demonstrate a tunable and switchable multi-wavelength erbium-doped fiber ring pulsed laser based on a nonlinear optical loop mirror (NOLM) and an improved Sagnac filter. To achieve multi-wavelength pulsed laser output, we adopt a NOLM as a quasi-saturable absorber and an improved Sagnac loop as a wavelength selected filter. The constructed laser has a maximum output wavelength number of five with a pulse repetition frequency of 40.45 kHz and pulse duration of 108 ns. The laser can output single-wavelength and dual-wavelength pulsed lasers within a certain wavelength tuning range and a five-wavelength pulsed laser with a constant wavelength interval of 3 nm by adjusting the polarization controller. Dual-wavelength, three-wavelength, and four-wavelength pulsed lasers with various wavelength intervals are also obtained. The output performance of the constructed laser is tested with a maximum average output power of 127.45 µW and minimum pulse duration of 52 ns, and the stability of the laser output is also tested with a maximum power fluctuation of 0.62 dB and minimum wavelength drift of 0.51 nm with pump power of 350 mW.

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