Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 1.055
Filtrar
1.
Am J Pathol ; 2024 Aug 31.
Artículo en Inglés | MEDLINE | ID: mdl-39222908

RESUMEN

The vaginal epithelium plays pivotal roles in host defense against pathogen invasion, contributing to the maintenance of an acidic microenvironment within the vaginal lumen through the activity of acid-base transport proteins. However, the precise defense mechanisms of the vaginal epithelium after a bacterial infection remain incompletely understood. This study showed that bacterial lipopolysaccharide (LPS) potentiated net proton efflux by up-regulating the expression of Na+-H+ exchanger 1 (NHE1) without affecting other acid-base transport proteins in vaginal epithelial cells. Pharmacologic inhibition or genetic knockdown of Toll-like receptor-4 and the extracellular signal-regulated protein kinase signaling pathway effectively counteracted the up-regulation of NHE1 and the enhanced proton efflux triggered by LPS in vaginal epithelial cells. In vivo studies revealed that LPS administration led to luminal acidification through the up-regulation of NHE1 expression in the rat vagina. Moreover, inhibition of NHE exhibited an impaired defense against acute bacterial infection in the rat vagina. These findings collectively indicate the active involvement of vaginal epithelial cells in facilitating luminal acidification during acute bacterial infection, offering potential insights into the treatment of bacterial vaginosis.

2.
Trends Biotechnol ; 2024 Sep 04.
Artículo en Inglés | MEDLINE | ID: mdl-39237385

RESUMEN

The understanding of cellular energy metabolism activation by engineered scaffolds remains limited, posing challenges for therapeutic applications in tissue regeneration. This study presents biosynthesized poly(3-hydroxybutyrate-co-4-hydroxybutyrate) [P(3HB-co-4HB)] and its major degradation product, 3-hydroxybutyrate (3HB), as endogenous bioenergetic fuels that augment cellular anabolism, thereby facilitating the progression of human bone marrow-derived mesenchymal stem cells (hBMSCs) towards osteoblastogenesis. Our research demonstrated that 3HB markedly boosts in vitro ATP production, elevating mitochondrial membrane potential and capillary-like tube formation. Additionally, it raises citrate levels in the tricarboxylic acid (TCA) cycle, facilitating the synthesis of citrate-containing apatite during hBMSCs osteogenesis. Furthermore, 3HB administration significantly increased bone mass in rats with osteoporosis induced by ovariectomy. The findings also showed that P(3HB-co-4HB) scaffold substantially enhances long-term vascularized bone regeneration in rat cranial defect models. These findings reveal a previously unknown role of 3HB in promoting osteogenesis of hBMSCs and highlight the metabolic activation of P(3HB-co-4HB) scaffold for bone regeneration.

3.
Cell Commun Signal ; 22(1): 409, 2024 Aug 21.
Artículo en Inglés | MEDLINE | ID: mdl-39169379

RESUMEN

BACKGROUND: Melanoma, one of the most lethal forms of skin cancer, has the potential to develop in any area where melanocytes are present. Currently, postoperative recurrence due to the emergence of systemic drug resistance represents a significant challenge in the treatment of melanoma. In this study, terphenyllin (TER), a distinctive inhibitory impact on melanoma cells was identified from the natural p-terphenyl metabolite. This study aimed to elucidate the intrinsic mechanism of this inhibitory effect, which may facilitate the discovery of novel chemotherapeutic agents. METHODS: A transcriptome sequencing and metabolomic analysis of TER-treated A375 cells was conducted to identify potential pathways of action. The key proteins were knocked out and backfilled using CRISPR-Cas9 technology and molecular cloning. Subsequently, the results of cytosolic viability, LDH release, immunofluorescence and flow cytometry were employed to demonstrate the cell death status of the drug-treated cells. RESULTS: The p53 signalling pathway was markedly upregulated following TER treatment, leading to the activation of CASP3 via the intrinsic apoptotic pathway. The activated CASP3 initiated apoptosis, while simultaneously continuing to cleave the GSDME, thereby triggering pyroptosis. The knockout of p53, a key protein situated upstream of this pathway, resulted in a significant rescue of TER-induced cell death, as well as an alleviation of the decrease in cell viability. However, the knockout of key proteins situated downstream of the pathway (CASP3 and GSDME) did not result in a rescue of TER-induced cell death, but rather a transformation of the cells from apoptosis and pyroptosis. CONCLUSIONS: The induction of apoptosis and pyroptosis in A375 cells by TER is mediated via the p53-BAX/FAS-CASP3-GSDME signalling pathway. This lays the foundation for TER as a potential anti-melanoma drug in the future. It should be noted that CASP3 and GSDME in this pathway solely regulate the mode of cell death, rather than determine whether cell death occurs. This distinction may prove valuable in future studies of apoptosis and pyroptosis.


Asunto(s)
Apoptosis , Caspasa 3 , Piroptosis , Proteína p53 Supresora de Tumor , Regulación hacia Arriba , Humanos , Proteína p53 Supresora de Tumor/metabolismo , Proteína p53 Supresora de Tumor/genética , Piroptosis/efectos de los fármacos , Piroptosis/genética , Apoptosis/efectos de los fármacos , Regulación hacia Arriba/efectos de los fármacos , Caspasa 3/metabolismo , Línea Celular Tumoral , Melanoma/metabolismo , Melanoma/genética , Melanoma/patología , Transducción de Señal/efectos de los fármacos , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Gasderminas
4.
Genes (Basel) ; 15(8)2024 Jul 31.
Artículo en Inglés | MEDLINE | ID: mdl-39202363

RESUMEN

Thiacloprid, a neonicotinoid pesticide, is known to affect the gut microbiome of honeybees, yet studies often focus on immediate alternations during exposure, overlooking long-term microbiological impacts post-exposure. This study investigates the influences of sublethal thiacloprid administered during the larval developmental stage of honeybees on physiological changes and gut microbiota of adult honeybees. We found that thiacloprid exposure increased mortality and sugar intake in emerged honeybees. Using 16S rDNA sequencing, we analyzed intestinal microbial diversity of honeybees at one and six days post-emergence. Our findings reveal a significant but transient disruption in gut microbiota on day 1, with recovery from dysbiosis by day 6. This study emphasizes the importance of evaluating chronic sublethal exposure risks of thiacloprid to protect honeybee health.


Asunto(s)
Microbioma Gastrointestinal , Neonicotinoides , Tiazinas , Animales , Abejas/microbiología , Abejas/efectos de los fármacos , Neonicotinoides/toxicidad , Microbioma Gastrointestinal/efectos de los fármacos , Tiazinas/toxicidad , Tiazinas/farmacología , Insecticidas/toxicidad , Larva/efectos de los fármacos , Larva/microbiología , ARN Ribosómico 16S/genética
5.
Environ Pollut ; 360: 124626, 2024 Nov 01.
Artículo en Inglés | MEDLINE | ID: mdl-39084589

RESUMEN

Microplastic (MP) contamination in soil severely impairs plant growth. However, mechanisms underlying the effects of MPs on plant nutrient uptake remain largely unknown. In this study, we revealed that NO3- content was significantly decreased in shoots and roots of wheat plants exposed to high concentrations (50-100 mg L-1) of MPs (1 µm and 0.1 µm; type: polystyrene) in the hydroponic solution. Isotope labeling experiments demonstrated that MP exposure led to a significant inhibition of NO3- uptake in wheat roots. Further analysis indicated that the presence of MPs markedly inhibited root growth and caused oxidative damage to the roots. Additionally, superoxide dismutase and peroxidase activities in wheat roots decreased under all MP treatments, whereas catalase and ascorbate peroxidase activities significantly increased under the 100 mg L-1 MP treatment. The transcription levels of most nitrate transporters (NRTs) in roots were significantly downregulated by MP exposure. Furthermore, exposure to MPs distinctly suppressed the activity of nitrate reductase (NR) and nitrite reductase (NiR), as well as the expression levels of their coding genes in wheat shoots. These findings indicate that a decline in root uptake area and root vitality, as well as in the expression of NRTs, NR, and NiR genes caused by MP exposure may have adverse effects on NO3- uptake and assimilation, consequently impairing normal growth of plants.


Asunto(s)
Microplásticos , Nitratos , Raíces de Plantas , Contaminantes del Suelo , Triticum , Triticum/metabolismo , Triticum/efectos de los fármacos , Triticum/crecimiento & desarrollo , Raíces de Plantas/metabolismo , Raíces de Plantas/efectos de los fármacos , Nitratos/metabolismo , Contaminantes del Suelo/toxicidad , Contaminantes del Suelo/metabolismo , Microplásticos/toxicidad , Nitrato-Reductasa/metabolismo , Brotes de la Planta/metabolismo , Brotes de la Planta/efectos de los fármacos , Brotes de la Planta/crecimiento & desarrollo , Superóxido Dismutasa/metabolismo
6.
Semin Arthritis Rheum ; 68: 152522, 2024 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-39079206

RESUMEN

AIMS: We describe the varied clinical presentations, barriers in diagnosis and outcomes of anti-HMGCR myopathy in a large national cohort. METHODS: Adults found positive for serum anti-HMGCR autoantibodies via line blot or enzyme-immunoassay followed by immunoprecipitation were included in the study. RESULTS: Of 75 patients identified, the records of 72 (96 %) described weakness as the presenting symptom. The records of 65 gave a reliable description of proximal weakness. In 22/65 (33.8 %) the weakness was described as predominantly or solely lower limb weakness. Forty-five of 75 (60 %) presented with a subacute onset (duration of symptoms >4 weeks -≤6 months), whilst 22/75 (29.3 %) presented with a more indolent chronic onset (duration of symptoms >6 months). Eighteen of 75 (24 %) suffered falls and 2/75 (2.7 %) had "general decline". In three patients no weakness was described: two presented with myalgia and one with a skin rash characterized as Jessner lymphocytic skin rash. Median creatine kinase at presentation was 7337 U/L (range 1050-25,500). Muscle biopsy was performed in 38 (50.7 %). Associated malignancy was infrequent. Four patients recovered without immunosuppression. Five-year and 10-year survival was 92.7 % (95 % CI 80.6-97.4 %), and 82.5 % (95 % CI 61.2-92.8 %) respectively. CONCLUSION: Recurrent falls, a long prodrome and dominant lower limb proximal weakness were common in this anti-HMGCR myopathy cohort. These features overlap with frailty syndrome and sporadic inclusion body myositis emphasizing the importance of considering anti-HMGCR myopathy in that clinical context. A minority of patients recover after statin withdrawal alone.


Asunto(s)
Autoanticuerpos , Hidroximetilglutaril-CoA Reductasas , Enfermedades Musculares , Humanos , Masculino , Femenino , Persona de Mediana Edad , Enfermedades Musculares/inmunología , Enfermedades Musculares/diagnóstico , Hidroximetilglutaril-CoA Reductasas/inmunología , Anciano , Nueva Zelanda , Adulto , Autoanticuerpos/sangre , Estudios de Cohortes , Debilidad Muscular , Anciano de 80 o más Años
7.
Sci Rep ; 14(1): 16561, 2024 07 17.
Artículo en Inglés | MEDLINE | ID: mdl-39020066

RESUMEN

Characteristic volatile organic compounds (VOCs) are anticipated to be used for the identification of lung cancer cells. However, to date, consistent biomarkers of VOCs in lung cancer cells have not been obtained through direct comparison between cancer and healthy groups. In this study, we regulated the glycolysis, a common metabolic process in cancer cells, and employed solid phase microextraction gas chromatography mass spectrometry (SPME-GC-MS) combined with untargeted analysis to identify the characteristic VOCs shared by cancer cells. The VOCs released by three types of lung cancer cells (A549, PC-9, NCI-H460) and one normal lung epithelial cell (BEAS-2B) were detected using SPME-GC-MS, both in their resting state and after treatment with glycolysis inhibitors (2-Deoxy-D-glucose, 2-DG/3-Bromopyruvic acid, 3-BrPA). Untargeted analysis methods were employed to compare the VOC profiles between each type of cancer cell and normal cells before and after glycolysis regulation. Our findings revealed that compared to normal cells, the three types of lung cancer cells exhibited three common differential VOCs in their resting state: ethyl propionate, acetoin, and 3-decen-5-one. Furthermore, under glycolysis control, a single common differential VOC-acetoin was identified. Notably, acetoin levels increased by 2.60-3.29-fold in all three lung cancer cell lines upon the application of glycolysis inhibitors while remaining relatively stable in normal cells. To further elucidate the formation mechanism of acetoin, we investigated its production by blocking glutaminolysis. This interdisciplinary approach combining metabolic biochemistry with MS analysis through interventional synthetic VOCs holds great potential for revolutionizing the identification of lung cancer cells and paving the way for novel cytological examination techniques.


Asunto(s)
Cromatografía de Gases y Espectrometría de Masas , Glucólisis , Neoplasias Pulmonares , Compuestos Orgánicos Volátiles , Humanos , Compuestos Orgánicos Volátiles/metabolismo , Compuestos Orgánicos Volátiles/análisis , Glucólisis/efectos de los fármacos , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patología , Neoplasias Pulmonares/tratamiento farmacológico , Línea Celular Tumoral , Células A549 , Microextracción en Fase Sólida
8.
Lipids Health Dis ; 23(1): 212, 2024 Jul 04.
Artículo en Inglés | MEDLINE | ID: mdl-38965560

RESUMEN

BACKGROUND AND AIM: Conflicting results have been reported on the association between Parkinson's disease (PD) and cardiovascular disease (CVD) mortality in different populations. Therefore, studying the relationship between PD and CVD mortality is crucial to reduce mortality caused by the former. METHODS: In this cohort investigation, we enrolled 28,242 participants from the National Health and Nutrition Examination Survey spanning from 2003 to 2018. The 380 cases of PD in the cohort were identified by documenting 'ANTIPARKINSON AGENTS' in their reported prescription medications. Mortality outcomes were ascertained by cross-referencing the cohort database with the National Death Index, which was last updated on 31 December 2019. Cardiovascular disease mortality was categorised according to the 10th revision of the International Classification of Diseases by using a spectrum of diagnostic codes. Weighted multivariable Cox regression analysis was used to examine the association between PD and the risk of CVD mortality. RESULTS: A total of 28,242 adults were included in the study [mean age, 60.156 (12.55) years, 13,766 men (48.74%)], and the median follow-up period was 89 months. Individuals with PD had an adjusted HR of 1.82 (95% CI, 1.24-2.69; p = 0.002) for CVD mortality and 1.84 (95% CI, 1.44-2.33; p < 0.001) for all-cause mortality compared with those without PD. The association between PD and CVD mortality was robust in sensitivity analyses, after excluding participants who died within 2 years of follow-up and those with a history of cancer at baseline [HR,1.82 (95% CI, 1.20-2.75; p = 0.005)]. CONCLUSIONS: PD was associated with a high long-term CVD mortality rate in the US population.


Asunto(s)
Enfermedades Cardiovasculares , Encuestas Nutricionales , Enfermedad de Parkinson , Humanos , Enfermedad de Parkinson/mortalidad , Enfermedad de Parkinson/complicaciones , Enfermedad de Parkinson/epidemiología , Masculino , Femenino , Enfermedades Cardiovasculares/mortalidad , Persona de Mediana Edad , Anciano , Estudios Prospectivos , Factores de Riesgo , Modelos de Riesgos Proporcionales
9.
Intensive Crit Care Nurs ; 84: 103743, 2024 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-38896965

RESUMEN

BACKGROUND: Capillary refill time (CRT) is defined as the time taken for color to return to an external capillary bed after pressure is applied to cause blanching. Recent studies demonstrated the benefits of CRT in guiding fluid therapy for sepsis. However, lack of consistency among physicians in how to perform and interpret CRT has led to a low interobserver agreement for this assessment tool, which prevents its availability in sepsis clinical settings. OBJECTIVE: To give physicians a concise overview of CRT and explore recent evidence on its reliability and value in the management of sepsis. RESEARCH DESIGN: A narrative review. RESULTS: This narrative review summarizes the factors affecting CRT values, for example, age, sex, temperature, light, observation techniques, work experience, training level and differences in CRT measurement methods. The methods of reducing the variability of CRT are synthesized. Based on studies with highly reproducible CRT measurements and an excellent inter-rater concordance, we recommend the standardized CRT assessment method. The threshold of normal CRT values is discussed. The application of CRT in different phases of sepsis management is summarized. CONCLUSIONS: Recent data confirm the value of CRT in critically ill patients. CRT should be detected by trained physicians using standardized methods and reducing the effect of ambient-related factors. Its association with severe infection, microcirculation, tissue perfusion response, organ dysfunction and adverse outcomes makes this approach a very attractive tool in sepsis. Further studies should confirm its value in the management of sepsis. IMPLICATIONS FOR CLINICAL PRACTICE: As a simple assessment, CRT deserves more attention even though it has not been widely applied at the bedside. CRT could provide nursing staff with patient's microcirculatory status, which may help to develop individualized nursing plans and improve the patient's care quality and treatment outcomes.


Asunto(s)
Sepsis , Humanos , Sepsis/fisiopatología , Sepsis/terapia , Sepsis/complicaciones , Microcirculación/fisiología , Fluidoterapia/métodos , Fluidoterapia/normas , Capilares/fisiopatología , Reproducibilidad de los Resultados
10.
Ying Yong Sheng Tai Xue Bao ; 35(5): 1321-1330, 2024 May.
Artículo en Chino | MEDLINE | ID: mdl-38886431

RESUMEN

Rapid acquisition of the data of soil moisture content (SMC) and soil organic matter (SOM) content is crucial for the improvement and utilization of saline alkali farmland soil. Based on field measurements of hyperspectral reflectance and soil properties of farmland soil in the Hetao Plain, we used a competitive adaptive reweighted sampling algorithm (CARS) to screen sensitive bands after transforming the original spectral reflectance (Ref) into a standard normal variable (SNV). Strategies Ⅰ, Ⅱ, and Ⅲ were used to model the input variables of Ref, Ref SNV, Ref-SNV+ soil covariate (SC), and digital elevation model (DEM). We constructed SMC and SOM estimation models based on random forest (RF) and light gradient boosting machine (LightGBM), and then verified and compared the accuracy of the models. The results showed that after CARS screening, the sensitive bands of SMC and SOM were compressed to below 3.3% of the entire band, which effectively optimized band selection and reduced redundant spectral information. Compared with the LightGBM model, the RF model had higher accuracy in SMC and SOM estimation, and the input variable strategy Ⅲ was better than Ⅱ and Ⅰ. The introduction of auxiliary variables effectively improved the estimation ability of the model. Based on comprehensive analysis, the coefficient of determination (Rp2), root mean square error (RMSE), and relative analysis error (RPD) of the SMC estimation model validation based on strategy Ⅲ-RF were 0.63, 3.16, and 2.01, respectively. The SOM estimation models based on strategy Ⅲ-RF had Rp2, RMSE, and RPD of 0.93, 1.15, and 3.52, respectively. The strategy Ⅲ-RF model was an effective method for estimating SMC and SOM. Our results could provide a new method for the rapid estimation of soil moisture and organic matter content in saline alkali farmland.


Asunto(s)
Algoritmos , Compuestos Orgánicos , Suelo , Agua , Suelo/química , Compuestos Orgánicos/análisis , Agua/análisis , Productos Agrícolas/crecimiento & desarrollo , Productos Agrícolas/química , Álcalis/análisis , Álcalis/química , China , Ecosistema
11.
Sci Data ; 11(1): 463, 2024 May 07.
Artículo en Inglés | MEDLINE | ID: mdl-38714688

RESUMEN

Adverse perinatal factors can interfere with the normal development of the brain, potentially resulting in long-term effects on the comprehensive development of children. Presently, the understanding of cognitive and neurodevelopmental processes under conditions of adverse perinatal factors is substantially limited. There is a critical need for an open resource that integrates various perinatal factors with the development of the brain and mental health to facilitate a deeper understanding of these developmental trajectories. In this Data Descriptor, we introduce a multicenter database containing information on perinatal factors that can potentially influence children's brain-mind development, namely, periCBD, that combines neuroimaging and behavioural phenotypes with perinatal factors at county/region/central district hospitals. PeriCBD was designed to establish a platform for the investigation of individual differences in brain-mind development associated with perinatal factors among children aged 3-10 years. Ultimately, our goal is to help understand how different adverse perinatal factors specifically impact cognitive development and neurodevelopment. Herein, we provide a systematic overview of the data acquisition/cleaning/quality control/sharing, processes of periCBD.


Asunto(s)
Encéfalo , Desarrollo Infantil , Niño , Preescolar , Humanos , Encéfalo/crecimiento & desarrollo , Encéfalo/diagnóstico por imagen , China , Cognición , Bases de Datos Factuales , Neuroimagen
12.
Artículo en Inglés | MEDLINE | ID: mdl-38796685

RESUMEN

BACKGROUND: In 2014 the incidence of anti-HMGCR myopathy in New Zealand was ∼1.7 case/million persons/year. OBJECTIVE: Re-estimate the population incidence and assess ethnic variation in those >40-year -olds. SETTING: An incidence cohort was defined by seropositivity for immunoprecipitating anti-HMGCR autoantibodies tested at a national reference laboratory between 1 October 2019-30 September 2021.Separately, ethnicity standardized incidence in > 40-year-olds discharged from New Zealand public hospitals for idiopathic and unspecified myopathy (ICD AM codes M60.8/60.9), was examined for concordance. RESULTS: The forty patients identified in the incidence cohort were all >40-years-old and all had a prior history of statin use. Annual incidence was 4 cases/million/year (95%CI 2.8-5.5). In those >40 years the incidence in Polynesians (Maori and Pacific peoples combined) was 25cases/million/year (95% CI 15.9 -40.1), in Asians 5.7cases/million/year (95% CI 0.7 -20.5) and in Europeans 7cases/million/year (95% CI 3.1 -8.4). The risk in statin users aged > 40 years was ∼1/9000 in Polynesians and ∼1/48000 in Europeans.Ethnic difference in incidence of idiopathic and unspecified myopathy (ICD AM codes M60.8/60.9) was also found in hospital discharges. CONCLUSION: In the past half decade the estimated incidence of anti-HMGCR myopathy in New Zealand has doubled. Polynesian peoples of New Zealand >40-years-old have an estimated 5-fold higher risk compared with European and Asian peoples. The estimated absolute risk in statin users >40-year-olds was 108 cases/million/year in Polynesians vs 21 cases/million/year in Europeans.

13.
World J Gastrointest Surg ; 16(3): 710-716, 2024 Mar 27.
Artículo en Inglés | MEDLINE | ID: mdl-38577097

RESUMEN

BACKGROUND: Laparoscopic colorectal cancer surgery increases the risk of incisional hernia (IH) at the tumor extraction site. AIM: To investigate the incidence of IH at extraction sites following laparoscopic colorectal cancer surgery and identify the risk factors for IH incidence. METHODS: This study retrospectively analyzed the data of 1614 patients who underwent laparoscopic radical colorectal cancer surgery with tumor extraction through the abdominal wall at our center between January 2017 and December 2022. Differences in the incidence of postoperative IH at different extraction sites and the risk factors for IH incidence were investigated. RESULTS: Among the 1614 patients who underwent laparoscopic radical colorectal cancer surgery, 303 (18.8%), 923 (57.2%), 171 (10.6%), and 217 (13.4%) tumors were extracted through supraumbilical midline, infraumbilical midline, umbilical, and off-midline incisions. Of these, 52 patients developed IH in the abdominal wall, with an incidence of 3.2%. The incidence of postoperative IH was significantly higher in the off-midline incision group (8.8%) than in the middle incision groups [the supraumbilical midline (2.6%), infraumbilical midline (2.2%), and umbilical incision (2.9%) groups] (χ2 = 24.985; P < 0.05). Univariate analysis showed that IH occurrence was associated with age, obesity, sex, chronic cough, incision infection, and combined diabetes, anemia, and hypoproteinemia (P < 0.05). Similarly, multivariate analysis showed that off-midline incision, age, sex (female), obesity, incision infection, combined chronic cough, and hypoproteinemia were independent risk factors for IH at the site of laparoscopic colorectal cancer surgery (P < 0.05). CONCLUSION: The incidence of postoperative IH differs between extraction sites for laparoscopic colorectal cancer surgery. The infraumbilical midline incision is associated with a lower hernia rate and is thus a suitable tumor extraction site.

14.
Pestic Biochem Physiol ; 200: 105833, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38582596

RESUMEN

Human skeletal muscle contraction is triggered by activation of Nav1.4 channels. Nav1.4 channels can generate resurgent currents by channel reopening at hyperpolarized potentials through a gating transition dependent on the intracellular Navß4 peptide in the physiological conditions. Tefluthrin (TEF) is a pyrethroid insecticide that can disrupt electrical signaling in nerves and skeletal muscle, resulting in seizures, muscle spasms, fasciculations, and mental confusion. TEF can also induce tail currents through other voltage-gated sodium channels in the absence of Navß4 peptide, suggesting that muscle spasms may be caused by resurgent currents. Further, intracellular Navß4 peptide and extracellular TEF may show competitive or synergistic effects; however, their binding sites are still unknown. To address these issues, electrophysiological recordings were performed on CHO-K1 cells expressing Nav1.4 channels with intracellular Navß4 peptide, extracellular TEF, or both. TEF and Navß4 peptide induced a hyperpolarizing shift of activation and inactivation curves in the Nav1.4 channel. TEF also substantially prolonged the inactivation time constants, while simultaneous application of Navß4 peptide partially reversed this effect. Resurgent currents were enhanced by TEF and Navß4 peptide at negative potentials, but TEF more potently enhances resurgent currents and dampens decay of resurgent currents. With longer depolarization, peak resurgent currents decay was fastest with the TEF alone. Molecular docking suggested that TEF and Navß4 peptide binding site(s) are not in the narrowest part of the channel pore, but rather in the bundle-crossing regions and in the domain linkers, respectively. TEF can induce resurgent currents independently and synergistically with Navß4 peptide, which may explain the muscle spasms observed in TEF intoxication.


Asunto(s)
Ciclopropanos , Hidrocarburos Fluorados , Péptidos , Humanos , Simulación del Acoplamiento Molecular , Péptidos/farmacología , Ciclopropanos/farmacología , Espasmo , Potenciales de Acción
15.
Sci Total Environ ; 930: 172732, 2024 Jun 20.
Artículo en Inglés | MEDLINE | ID: mdl-38663609

RESUMEN

East Asian continental outflows with PM2.5, O3, and other species may determine the baseline conditions and affect the air quality in downwind areas via long-range transport (LRT). To gain insight into the impact and spatiotemporal characteristics of airborne pollutants in East Asian continental outflows, a versatile multicopter drone sounding platform was used to simultaneously observe PM2.5, O3, CO2, and meteorological variables (temperature, specific humidity, pressure, and wind vector) above the northern tip of Taiwan, Cape Fuiguei, which often encounters continental outflows during winter monsoon periods. By coordinating hourly high-spatial-resolution profiles provided by drone soundings, WRF/CMAQ model air quality predictions, HYSPLIT-simulated backward trajectories, and MERRA-2 reanalysis data, we analyzed two prominent phenomena of airborne pollutants in continental outflows to better understand their physical/chemical characteristics. First, we found that pollutants were well mixed within a sounding height of 500 m when continental outflows passed through and completely enveloped Cape Fuiguei. Eddies induced by significant fluctuations in wind speeds coupled with minimal temperature inversion and LRT facilitated vertical mixing, possibly resulting in high homogeneity of pollutants within the outflow layer. Second, the drone soundings indicated exceptionally high O3 concentrations (70-100 ppbv) but relatively low concentrations of PM2.5 (10-20 µg/m3), CO2 (420-425 ppmv), and VOCs in some air masses. The low levels of PM2.5, CO2, and VOCs ruled out photochemistry as the cause of the formation of high-level O3. Further coordination of spatiotemporal data with air mass trajectories and O3 cross sections provided by MERRA-2 suggested that the high O3 concentrations could be attributed to stratospheric intrusion and advection via continental outflows. High-level O3 concentrations persisted in the lower troposphere, even reaching the surface, suggesting that stratospheric intrusion O3 may be involved in the rising trend in O3 concentrations in parts of East Asia in recent years in addition to surface photochemical factors.

16.
Purinergic Signal ; 2024 Apr 27.
Artículo en Inglés | MEDLINE | ID: mdl-38676825

RESUMEN

P2X7 receptor (P2X7R) plays an important role in modulating inflammation and fibrosis, but information is limited whether Zusanli (ST36) can inhibit inflammation and fibrosis by regulating P2X7R. Isoprenaline at 5 mg/kg was subcutaneously injected to wild-type and P2X7R knockout mice for 7 days, while treatment groups received electroacupuncture (EA) stimulation at ST36 for 7 sessions. Following 7-session treatment, Masson's trichrome staining was performed to assess the fibrosis. Morphology, electrocardiogram, and echocardiography were carried out to evaluate the cardiac function and structure. Western blotting, hematoxylin and eosin staining, immunohistochemistry, and biochemical analysis of inflammatory cytokine and transmission electron microscopy were carried out to characterize the effect of ST36 on inflammation. P2X7R was overexpressed in ISO-treated mice. EA at ST36, but not at non-points, reduced ISO-induced cardiac fibrosis, increases in HW/BW, R+S wave relative to mice in ISO groups. In addition, EA at ST36 downregulated ISO-upregulated P2X7R and NLRP3 in ventricle. Moreover, EA reduced cytokines of IL-1ß, IL-6, and IL-18 in serum, and inhibited foam cell gathering, inflammatory cell infiltration, and autophagy. However, EA at ST36 failed to attenuate the cardiac fibrosis and hypertrophy in P2X7R knockout mice. In conclusion, EA at ST36 attenuated ISO-induced fibrosis possibly via P2X7R.

17.
Huan Jing Ke Xue ; 45(2): 1107-1117, 2024 Feb 08.
Artículo en Chino | MEDLINE | ID: mdl-38471948

RESUMEN

Novel Fe-Mn combined graphene oxide (GO-FM) material was produced and tested for its efficacy in remediating agricultural soil co-contaminated by Cd and As. In a 60-day soil incubation experiment, the remediation mechanism and immobilization effects of GO and GO-FM at different addition ratios (0.1%, 0.2%, and 0.3%) were investigated in Shangyu and Foshan soils, which had varying physicochemical properties and contamination degrees. The dynamic changes in pH, DOC concentration, bioavailable Cd and As content, and morphology of Cd and As were explored to determine the remediation efficacy of the materials. The results demonstrated that compared with that in the blank control, GO-FM increased the pH in Shangyu soil but decreased the pH in Foshan soil. After culture, both GO and GO-FM increased the soil DOC content. GO-FM decreased the soluble Cd concentration by 5.08%-19.19% and the bioavailability of Cd by 36.57%-42.8% in Foshan soil, and the main immobilization mechanism was electrostatic adsorption, complexation, and hydroxylated metal ion formation. The immobilization ability of GO-FM on Cd was lower than that of Foshan soil due to the influence of electrostatic repulsion in Shangyu acidic soil. However, with the increase in the amount of GO-FM, the trend of increasing the bioavailability of Cd by graphene oxide was inhibited. The addition of 0.2% and 0.3% GO-FM decreased the bioavailability of Cd by 6.45%-13.56% in Shangyu soil. Additionally, GO-FM decreased the bioavailability of As in Shangyu soil and Foshan soil by 4.34%-9.15% and 0.87%-5.71%, respectively. This was due to the immobilization mechanism of oxidation of As by manganese oxides and inner surface chelate between As and the surface hydroxyl group of iron oxides. In summary, the immobilization effect of GO-FM on Cd in Foshan soil was better than that in Shangyu soil, and the immobilization effect of GO-FM on As in Shangyu soil was better than that in Foshan soil, which can provide a theoretical basis and reference for the prevention and control of Cd and As co-contamination in different types of soil.

18.
Psychol Res Behav Manag ; 17: 1087-1102, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38495087

RESUMEN

Background: The emergence of new technologies, such as artificial intelligence (AI), may manifest as technology panic in some people, including adolescents who may be particularly vulnerable to new technologies (the use of AI can lead to AI dependence, which can threaten mental health). While the relationship between AI dependence and mental health is a growing topic, the few existing studies are mainly cross-sectional and use qualitative approaches, failing to find a longitudinal relationship between them. Based on the framework of technology dependence, this study aimed to determine the prevalence of experiencing AI dependence, to examine the cross-lagged effects between mental health problems (anxiety/depression) and AI dependence and to explore the mediating role of AI use motivations. Methods: A two-wave cohort program with 3843 adolescents (Male = 1848, Mage = 13.21 ± 2.55) was used with a cross-lagged panel model and a half-longitudinal mediation model. Results: 17.14% of the adolescents experienced AI dependence at T1, and 24.19% experienced dependence at T2. Only mental health problems positively predicted subsequent AI dependence, not vice versa. For AI use motivation, escape motivation and social motivation mediated the relationship between mental health problems and AI dependence whereas entertainment motivation and instrumental motivation did not. Discussion: Excessive panic about AI dependence is currently unnecessary, and AI has promising applications in alleviating emotional problems in adolescents. Innovation in AI is rapid, and more research is needed to confirm and evaluate the impact of AI use on adolescents' mental health and the implications and future directions are discussed.

19.
Hum Reprod ; 39(4): 849-855, 2024 Apr 03.
Artículo en Inglés | MEDLINE | ID: mdl-38420683

RESUMEN

Individuals with 46,XX/XY chimerism can display a wide range of characteristics, varying from hermaphroditism to complete male or female, and can display sex chromosome chimerism in multiple tissues, including the gonads. The gonadal tissues of females contain both granulosa and germ cells. However, the specific sex chromosome composition of the granulosa and germ cells in 46,XX/XY chimeric female is currently unknown. Here, we reported a 30-year-old woman with secondary infertility who displayed a 46,XX/46,XY chimerism in the peripheral blood. FISH testing revealed varying degrees of XX/XY chimerism in multiple tissues of the female patient. Subsequently, the patient underwent preimplantation genetic testing (PGT) treatment, and 26 oocytes were retrieved. From the twenty-four biopsied mature oocytes, a total of 23 first polar bodies (PBs) and 10 second PBs were obtained. These PBs and two immature metaphase I (MI) oocytes only displayed X chromosome signals with no presence of the Y, suggesting that all oocytes in this chimeric female were of XX germ cell origin. On the other hand, granulosa cells obtained from individual follicles exhibited varied proportions of XX/XY cell types, and six follicles possessed 100% XX or XY granulosa cells. A total of 24 oocytes were successfully fertilized, and 12 developed into blastocysts, where 5 being XY and 5 were XX. Two blastocysts were transferred with one originating from an oocyte aspirated from a follicle containing 100% XY granulosa cells. This resulted in a twin pregnancy. Subsequent prenatal diagnosis confirmed normal male and female karyotypes. Ultimately, healthy boy-girl twins were delivered at full term. In summary, this 46,XX/XY chimerism with XX germ cells presented complete female, suggesting that germ cells may exert a significant influence on the sexual determination of an individual, which provide valuable insights into the intricate processes associated with sexual development and reproduction.


Asunto(s)
Quimerismo , Células Germinativas , Disgenesia Gonadal 46 XY , Adulto , Femenino , Humanos , Masculino , Embarazo , Gónadas , Oocitos , Cromosoma X
20.
Comput Biol Med ; 171: 108086, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38382383

RESUMEN

Increasing attention is being given to machine learning methods designed to aid clinicians in treatment selection. Therefore, this has aroused a heightened focus on the auto-detect system of epilepsy utilizing electroencephalogram(EEG) data. However, in order for the recognition model to accurately capture a wide range of features related to channel, frequency, and temporal information, it is necessary to have EEG data that is correctly represented. To tackle this challenge, we propose a Residual-based Inception with Hybrid-Attention Network(RIHANet) to achieve automatic seizure detection. Initially, by employing Empirical Mode Decomposition and Short-time Fourier Transform(EMD-STFT) for data processing, it can improve the quality of time-frequency representation of EEG. Additionally, by applying a novel Residual-based Inception to the network architecture, the detection model can learn local and global multiscale spatial-temporal features. Furthermore, the Hybrid Attention model designed is used to obtain relationships between EEG signals from multiple perspectives, including channels, sub-spaces, and global. Using four public datasets, the suggested approach outperforms the results in the most recent scholarly publications.


Asunto(s)
Epilepsia , Procesamiento de Señales Asistido por Computador , Humanos , Convulsiones/diagnóstico , Epilepsia/diagnóstico , Aprendizaje Automático , Electroencefalografía/métodos , Algoritmos
SELECCIÓN DE REFERENCIAS
DETALLE DE LA BÚSQUEDA