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Osteoarthritis (OA) is the most common joint disease. Currently there are no effective methods that simultaneously prevent joint degeneration and reduce pain1. Although limited evidence suggests the existence of voltage-gated sodium channels (VGSCs) in chondrocytes2, their expression and function in chondrocytes and in OA remain essentially unknown. Here we identify Nav1.7 as an OA-associated VGSC and demonstrate that human OA chondrocytes express functional Nav1.7 channels, with a density of 0.1 to 0.15 channels per µm2 and 350 to 525 channels per cell. Serial genetic ablation of Nav1.7 in multiple mouse models demonstrates that Nav1.7 expressed in dorsal root ganglia neurons is involved in pain, whereas Nav1.7 in chondrocytes regulates OA progression. Pharmacological blockade of Nav1.7 with selective or clinically used pan-Nav channel blockers significantly ameliorates the progression of structural joint damage, and reduces OA pain behaviour. Mechanistically, Nav1.7 blockers regulate intracellular Ca2+ signalling and the chondrocyte secretome, which in turn affects chondrocyte biology and OA progression. Identification of Nav1.7 as a novel chondrocyte-expressed, OA-associated channel uncovers a dual target for the development of disease-modifying and non-opioid pain relief treatment for OA.
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Condrócitos , Canal de Sódio Disparado por Voltagem NAV1.7 , Osteoartrite , Bloqueadores do Canal de Sódio Disparado por Voltagem , Animais , Humanos , Camundongos , Cálcio/metabolismo , Sinalização do Cálcio/efeitos dos fármacos , Condrócitos/efeitos dos fármacos , Condrócitos/metabolismo , Progressão da Doença , Gânglios Espinais/citologia , Gânglios Espinais/metabolismo , Canal de Sódio Disparado por Voltagem NAV1.7/deficiência , Canal de Sódio Disparado por Voltagem NAV1.7/genética , Canal de Sódio Disparado por Voltagem NAV1.7/metabolismo , Neurônios/metabolismo , Osteoartrite/complicações , Osteoartrite/tratamento farmacológico , Osteoartrite/genética , Osteoartrite/metabolismo , Dor/complicações , Dor/tratamento farmacológico , Dor/metabolismo , Bloqueadores do Canal de Sódio Disparado por Voltagem/farmacologia , Bloqueadores do Canal de Sódio Disparado por Voltagem/uso terapêuticoRESUMO
Nitrophenols present on the surface of particulates are ubiquitous in the atmosphere. However, its atmospheric photochemical transformation pathway remains unknown, for which the crucial effect of visible light is largely overlooked, resulting in an incomplete understanding of the effects of nitrophenols in the atmospheric environment. This study delves into the photolysis mechanism of 4-nitrophenol (4NP), one of the most abundant atmospheric nitrophenol compounds, on the surface of photoactive particulates under visible light irradiation. Unexpectedly, the nonradical species (singlet oxygen, 1O2) was identified as a dominant factor in driving the visible photolysis of 4NP. The pathways of HONO and p-benzoquinone (C6H4O2) generation were clarified by acquiring direct evidence of C-N and O-H bond breakage in the nitro (-NO2) and hydroxyl (-OH) groups of 4NP. The further decomposition of HONO results in the generation of NO and hydroxyl radicals, which could directly contribute to atmospheric oxidizing capacity and complicate the PM2.5 composition. Significantly, the behavior of 1O2-induced visible photolysis of 4NP was universal on the surface of common particulates in the atmosphere, such as A1 dust and Fe2O3. This work advances the understanding of the photochemical transformation mechanism of particulate-phase atmospheric nitrophenols, which is indispensable in elucidating the role of nitrophenols in atmospheric chemistry.
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The carboxysome is a natural proteinaceous organelle for carbon fixation in cyanobacteria and chemoautotrophs. It comprises hundreds of protein homologs that self-assemble to form a polyhedral shell structure to sequester cargo enzymes, ribulose 1,5-bisphosphate carboxylase/oxygenase (Rubisco) and carbonic anhydrases. How these protein components assemble to construct a functional carboxysome is a central question in not only understanding carboxysome structure and function but also synthetic engineering of carboxysomes for biotechnological applications. Here, we determined the structure of the chaperone protein CcmS, which has recently been identified to be involved in ß-carboxysome assembly, and its interactions with ß-carboxysome proteins. The crystal structure at 1.99 Å resolution reveals CcmS from Nostoc sp. PCC 7120 forms a homodimer, and each CcmS monomer consists of five α-helices and four ß-sheets. Biochemical assays indicate that CcmS specifically interacts with the C-terminal extension of the carboxysome shell protein CcmK1, but not the shell protein homolog CcmK2 or the carboxysome scaffolding protein CcmM. Moreover, we solved the structure of a stable complex of CcmS and the C-terminus of CcmK1 at 1.67 Å resolution and unveiled how the CcmS dimer interacts with the C-terminus of CcmK1. These findings allowed us to propose a model to illustrate CcmS-mediated ß-carboxysome assembly by interacting with CcmK1 at the outer shell surface. Collectively, our study provides detailed insights into the accessory factors that drive and regulate carboxysome assembly, thereby improving our knowledge of carboxysome structure, function, and bioengineering.
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Bladder cancer ranks as the 10th most common cancer worldwide, with deteriorating prognosis as the disease advances. While immune checkpoint inhibitors (ICIs) have shown promise in clinical therapy in both operable and advanced bladder cancer, identifying patients who will respond is challenging. Anoikis, a specialized form of cell death that occurs when cells detach from the extracellular matrix, is closely linked to tumor progression. Here, we aimed to explore the anoikis-based biomarkers for bladder cancer prognosis and immunotherapeutic decisions. Through consensus clustering, we categorized patients from the TCGA-BLCA cohort into two clusters based on anoikis-related genes (ARGs). Significant differences in survival outcome, clinical features, tumor immune environment (TIME), and potential ICIs response were observed between clusters. We then formulated a four-gene signature, termed "Ascore", to encapsulate this gene expression pattern. The Ascore was found to be closely associated with survival outcome and served as an independent prognosticator in both the TCGA-BLCA cohort and the IMvigor210 cohort. It also demonstrated superior predictive capacity (AUC = 0.717) for bladder cancer immunotherapy response compared to biomarkers like TMB and PD-L1. Finally, we evaluated Ascore's independent prognostic performance as a non-invasive biomarker in our clinical cohort (Gulou-Cohort1) using circulating tumor cells detection, achieving an AUC of 0.803. Another clinical cohort (Gulou-Cohort2) consisted of 40 patients undergoing neoadjuvant anti-PD-1 treatment was also examined. Immunohistochemistry of Ascore in these patients revealed its correlation with the pathological response to bladder cancer immunotherapy (P = 0.004). Impressively, Ascore (AUC = 0.913) surpassed PD-L1 (AUC = 0.662) in forecasting immunotherapy response and indicated better net benefit. In conclusion, our study introduces Ascore as a novel, robust prognostic biomarker for bladder cancer, offering a new tool for enhancing immunotherapy decisions and contributing to the tailored treatment approaches in this field.
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Antígeno B7-H1 , Neoplasias da Bexiga Urinária , Humanos , Prognóstico , Antígeno B7-H1/genética , Anoikis/genética , Progressão da Doença , Neoplasias da Bexiga Urinária/genética , Neoplasias da Bexiga Urinária/terapia , Imunoterapia , Biomarcadores , Microambiente TumoralRESUMO
Nitrogen doping has been recognized as an important strategy to enhance the oxygen reduction reaction (ORR) activity of carbon-encapsulated transition metal catalysts (TM@C). However, previous reports on nitrogen doping have tended to result in a random distribution of nitrogen atoms, which leads to disordered electrostatic potential differences on the surface of carbon layers, limiting further control over the materials' electronic structure. Herein, a gradient nitrogen doping strategy to prepare nitrogen-deficient graphene and nitrogen-rich carbon nanotubes encapsulated cobalt nanoparticles catalysts (Co@CNTs@NG) is proposed. The unique gradient nitrogen doping leads to a gradual increase in the electrostatic potential of the carbon layer from the nitrogen-rich region to the nitrogen-deficient region, facilitating the directed electron transfer within these layers and ultimately optimizing the charge distribution of the material. Therefore, this strategy effectively regulates the density of state and work function of the material, further optimizing the adsorption of oxygen-containing intermediates and enhancing ORR activity. Theoretical and experimental results show that under controlled gradient nitrogen doping, Co@CNTs@NG exhibits significantly ORR performance (Eonset = 0.96 V, E1/2 = 0.86 V). At the same time, Co@CNTs@NG also displays excellent performance as a cathode material for Zn-air batteries, with peak power density of 132.65 mA cm-2 and open-circuit voltage (OCV) of 1.51 V. This work provides an effective gradient nitrogen doping strategy to optimize the ORR performance.
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BACKGROUND: The assessment of human papillomavirus (HPV) genotype distribution in terms of age and cervical lesions could contribute to the adoption of more targeted preventive approaches to specific populations against cervical cancer. The current study was conducted in Ordos City, China, with the aim of analyzing the HPV genotypes prevalence and infection patterns within a hospital-based population. METHODS: The analysis included a total of 26,692 women aged 25-64 who underwent cervical cancer screening between January 1st, 2019, and June 30th, 2022, in Ordos City. These women had valid results for both the polymerase chain reaction (PCR)-reverse dot blot (RDB) HPV test and the liquid-based cytology (thinprep cytologic test/TCT). Data were extracted from the database of KingMed Diagnostics laboratories. The prevalence of HPV genotypes within different age groups and cytology diagnoses were calculated. RESULTS: Among 26,692 women, 7136 (26.73%) women were HPV positive, 5696 (21.34%) women were high-risk HPV (HR-HPV) positive, and 2102 (7.88%) women had multiple HPV infections. The most frequently detected HPV genotypes were HPV16 (4.72%) and HPV52 (4.15%), ranking as the first and second most prevalent genotypes, respectively. The prevalence of HR-HPV increased with age groups and severity of cervical lesions. Notably, the positive rate of HR-HPV among women aged 35-64 years showed a decreasing trend over the respective years, ranging from 26.00 to 19.70% (Ptrend < 0.001). CONCLUSION: In conclusion, the epidemiology of HPV genotypes partly reflects the effectiveness of regional cervical cancer prevention and control efforts in the past. These findings can inform future initiatives concerning HPV vaccination and screening in the region.
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Infecções por Papillomavirus , Neoplasias do Colo do Útero , Feminino , Humanos , Papillomavirus Humano , Neoplasias do Colo do Útero/diagnóstico , Neoplasias do Colo do Útero/epidemiologia , Infecções por Papillomavirus/diagnóstico , Infecções por Papillomavirus/epidemiologia , Detecção Precoce de Câncer , Prevalência , China/epidemiologiaRESUMO
Dissecting the photochemical reactivity of metal ions is a significant contribution to understanding secondary pollutant formation, as they have a role to be reckoned with atmospheric chemistry. However, their photochemical reactivity has received limited attention within the active nitrogen cycle, particularly at the gas-solid interface. In this study, we delve into the contribution of magnesium ion (Mg2+) and ferric ion (Fe3+) to nitrate decomposition on the surface of photoactive mineral dust. Under simulated sunlight irradiation, the observed NOX production rate differs by an order of magnitude in the presence of Mg2+ (6.02 × 10-10 mol s-1) and Fe3+ (2.07 × 10-11 mol s-1). The markedly decreased fluorescence lifetime induced by Mg2+ and the change in the valence of Fe3+ revealed that Mg2+ and Fe3+ significantly affect the concentration of nitrate decomposition products by distinct photochemical reactivity with photogenerated electrons. Mg2+ promotes NOX production by accelerating charge transfer, while Fe3+ hinders nitrate decomposition by engaging in a redox cyclic reaction with Fe2+ to consume photogenerated carriers continuously. Furthermore, when Fe3+ coexists with other metal ions (e.g., Mg2+, Ca2+, Na+, and K+) and surpasses a proportion of approximately 12%, the photochemical reactivity of Fe3+ tends to be dominant in depleting photogenerated electrons and suppressing nitrate decomposition. Conversely, below this threshold, the released NOX concentration increases sharply as the proportion of Fe3+ decreases. This research offers valuable insights into the role of metal ions in nitrate transformation and the generation of reactive nitrogen species, contributing to a deep understanding of atmospheric photochemical reactions.
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Metais , Nitratos , Nitratos/química , Metais/química , Minerais/química , Poeira , Atmosfera/química , Íons , Processos FotoquímicosRESUMO
BACKGROUND: Human papillomavirus (HPV) vaccination is a promising step toward cervical cancer elimination. This study was conducted to investigate the knowledge, attitude, and HPV vaccine uptake among female adults in mainland China based on a large e-commerce platform. METHODS: We conducted a cross-sectional online survey of female adults between March 4 to April 20, 2022. The survey consisted of sociodemographic information, related knowledge, vaccination uptake, and attitudes toward vaccination. We included women aged 18-45 years in the final analysis. Logistic regressions were conducted to explore influencing factors associated with related knowledge, HPV vaccination uptake, and willingness to be vaccinated. RESULTS: In total, 3,572 female adults (34 years, IQR 30-39) were included in the analysis. The majority of the participants were highly educated (78.7%) with a high monthly family income (79.0%). The median HPV knowledge score was 8.25 out of 11. More than 75% of respondents were unvaccinated, while 95.8% of unvaccinated female adults are willing to be vaccinated. Variables such as age, insurance, vaccination history, and whether one had heard of the HPV vaccine influence HPV vaccination practice (all p-values < 0.05). The main barriers to vaccination were vaccine inaccessibility and the high cost of the vaccine. CONCLUSION: The findings of our study highlight a moderate knowledge level, poor vaccination rate, and strong willingness to be vaccinated among Chinese female adults who were better educated and wealthier. Targeted health education and practical support should be provided in the future, to reduce gaps between vaccine uptake and vaccine acceptance.
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Infecções por Papillomavirus , Vacinas contra Papillomavirus , Neoplasias do Colo do Útero , Adulto , Humanos , Feminino , Infecções por Papillomavirus/prevenção & controle , Estudos Transversais , Conhecimentos, Atitudes e Prática em Saúde , Vacinação , Inquéritos e Questionários , Aceitação pelo Paciente de Cuidados de Saúde , Papillomavirus Humano , Neoplasias do Colo do Útero/prevenção & controle , InternetRESUMO
BACKGROUND AND OBJECTIVE: Chronic kidney disease (CKD) is a global health concern that is frequently associated with hypertension. Inflammation is an important factor in the development of both illnesses. The Dietary Inflammation Index (DII) has evolved as a way to measure how much a diet can cause inflammation, which may impact CKD, especially in hypertensive persons. The study's goal is to investigate the link between DII and the occurrence of CKD in hypertensive individuals. METHODS: This study examined data from 22940 hypertensive patients from 1999 to 2018 of the National Health and Nutrition Examination Survey (NHANES). The DII was computed using 28 dietary components. CKD was diagnosed based on the estimated glomerular filtration rate and urine albumin-to-creatinine ratio. The link between DII and CKD was explored using sampling-weighted logistic regression and restricted cubic splines. RESULTS: Higher DII scores were shown to be strongly related with an increased risk of CKD. In the fully adjusted model, this connection remained consistent across demographic and clinical categories. CONCLUSIONS: The study found a strong association between a pro-inflammatory diet and an elevated risk of CKD in hypertensive individuals, emphasizing the potential of dietary changes in CKD management.
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Dieta , Hipertensão , Inflamação , Inquéritos Nutricionais , Insuficiência Renal Crônica , Humanos , Insuficiência Renal Crônica/epidemiologia , Insuficiência Renal Crônica/complicações , Masculino , Feminino , Hipertensão/epidemiologia , Hipertensão/complicações , Pessoa de Meia-Idade , Inflamação/epidemiologia , Prevalência , Dieta/efeitos adversos , Taxa de Filtração Glomerular , Adulto , Fatores de Risco , Idoso , Estudos Transversais , Estados Unidos/epidemiologia , Modelos LogísticosRESUMO
Colorectal cancer (CRC) is one of the most common cancers, with a high mortality rate worldwide. Mounting evidence indicates that mRNA modifications are crucial in RNA metabolism, transcription, processing, splicing, degradation, and translation. Studies show that N6-methyladenosine (m6A) is mammalians' most common epi-transcriptomic modification. It has been demonstrated that m6A is involved in cancer formation, progression, invasion, and metastasis, suggesting it could be a potential biomarker for CRC diagnosis and developing therapeutics. Cytokines, growth factors, and hormones function in JAK/STAT3/5 signaling pathway, and they could regulate the intestinal response to infection, inflammation, and tumorigenesis. Reports show that the JAK/STAT3/5 pathway is involved in CRC development. However, the underlying mechanism is still unclear. Signal Transducer and Activator of Transcription 3/5 (STAT3, STAT5) can act as oncogenes or tumor suppressors in the context of tissue types. Also, epigenetic modifications and mutations could alter the balance between pro-oncogenic and tumor suppressor activities of the STAT3/5 signaling pathway. Thus, exploring the interaction of cytokines-JAKs-STAT3 and/or STAT5 with mRNA m6A is of great interest. This review provides a comprehensive overview of the characteristics and functions of m6A and JAKs-STAT3/5 and their relationship with gastrointestinal (GI) cancers.
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Understanding the interactions between fish gut microbiota and the aquatic environment is a key issue for understanding aquatic microorganisms. Environmental microorganisms enter fish intestines through feeding, and the amount of invasion varies due to different feeding habits. Traditional fish feeding habitat preferences are determined by fish morphology or behavior. However, little is known about how the feeding behavior of fish relative to the vertical structure in a shallow lake influences gut microbiota. In our study, we used nitrogen isotopes to measure the trophic levels of fish. Then high-throughput sequencing was used to describe the composition of environmental microbiota and fish gut microbiota, and FEAST (fast expectation-maximization for microbial source tracking) method was used to trace the source of fish gut microbiota. We investigated the microbial diversity of fish guts and their habitats in Lake Sanjiao and verified that the sediments indeed played an important role in the assembly of fish gut microbiota. Then, the FEAST analysis indicated that microbiota in water and sediments acted as the primary sources in half of the fish gut microbiota respectively. Furthermore, we classified the vertical habitat preferences using microbial data and significant differences in both composition and function of fish gut microbiota were observed between groups with distinct habitat preferences. The performance of supervised and unsupervised machine learning in classifying fish gut microbiota by habitat preferences actually exceeded classification by fish species taxonomy and fish trophic level. Finally, we described the stability of fish co-occurrence networks with different habitat preferences. Interestingly, the co-occurrence network seemed more stable in pelagic fish than in benthic fish. Our results show that the preferences of fish in the vertical structure of habitat was the main factor affecting their gut microbiota. We advocated the use of microbial interactions between fish gut and their surrounding environment to reflect fish preferences in vertical habitat structure. This approach not only offers a novel perspective for understanding the interactions between fish gut microbiota and environmental factors, but also provides new methods and ideas for studying fish habitat selection in aquatic ecosystems.
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Cellulose acetate film, as a biodegradable and biomass-derived material, has great potential applications in food packaging. However, the poor mechanical and antibacterial properties limit its applications. Herein, a highly flexible carbon nitride-polyethylene glycol-cellulose acetate (CN-PEG-CA) film was successfully prepared by combining graphitic carbon nitride (g-C3N4) photocatalyst with cellulose acetate (CA). The g-C3N4 enables the film with antibacterial activity, as a green photocatalyst. PEG softens the rigid polymer CA and crosslinks CA, PEG, and g-C3N4 together by hydrogen bonding, as a flexible crosslinker. X-ray diffractometer (XRD), scanning electron microscope (SEM), and Fourier transform infrared spectrum (FT-IR) characterizations confirmed the successful preparation of the CN-PEG-CA film. The mechanical property tests demonstrated that adding PEG increased the elongation at break of the film by about 4 times. The composite film had high antibacterial activity, and the bactericidal rates on Escherichia coli and Staphylococcus aureus were 99.98 % and 99.89 %, respectively. It effectively extended the shelf life of strawberries to 96 h and effectively maintained the quality of strawberries during storage. After 96 h, the weight loss rate of strawberries packaged with 15 % CN-PEG-CA film was 21.83 %, vitamin C content was 45.47 %, titratable acidity content was 0.89 %, and color, hardness and total soluble solids were well maintained. And biocompatibility test results showed that the film was safe and nontoxic. From the ecological and economic point of view, the highly flexible and biodegradable films with efficient photocatalytic antibacterial activity synthesized in this paper have great potential in the field of food packaging.
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Antibacterianos , Celulose , Celulose/análogos & derivados , Escherichia coli , Nitrilas , Polietilenoglicóis , Staphylococcus aureus , Celulose/química , Celulose/farmacologia , Antibacterianos/farmacologia , Antibacterianos/química , Polietilenoglicóis/química , Nitrilas/química , Nitrilas/farmacologia , Catálise , Escherichia coli/efeitos dos fármacos , Staphylococcus aureus/efeitos dos fármacos , Embalagem de Alimentos/métodos , Frutas/química , Conservação de Alimentos/métodos , Testes de Sensibilidade Microbiana , Fragaria , Processos FotoquímicosRESUMO
Previous studies mainly focused on individual-level factors that influence the adoption and usage of mobile technology and social networking sites, with little emphasis paid to the influences of household situations. Using multilevel modelling approach, this study merges household- (n1 = 1,455) and individual-level (n2 = 2,570) data in the U.K. context to investigate (a) whether a household economic capital (HEC) can affect its members' Twitter adoption, (b) whether the influences are mediated by the member's activity variety and self-reported efficacy with mobile technology, and (c) whether the members' traits, including educational level, gross income and residential area, moderate the relationship between HEC and Twitter adoption. Significant direct and indirect associations were discovered between HEC and its members' Twitter adoption. The educational level and gross income of household members moderated the influence of HEC on individuals' Twitter adoption.
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Mídias Sociais , Humanos , Análise Multinível , Características da Família , Renda , EscolaridadeRESUMO
Oxidized low density lipoprotein (oxLDL)-induced endothelial oxidative damage promotes the development of atherosclerosis. Caveolae play an essential role in maintaining the survival and function of vascular endothelial cell (VEC). It is reported that the long coiled-coil protein NECC2 is localized in caveolae and is associated with neural cell differentiation and adipocyte formation, but its role in VECs needs to be clarified. Our results showed NECC2 expression increased in the endothelium of plaque-loaded aortas and oxLDL-treated HUVECs. Down-regulation of NECC2 by NECC2 siRNA or compound YF-307 significantly inhibited oxLDL-induced VEC apoptosis and the adhesion factors expression. Remarkably, inhibition of NECC2 expression in the endothelium of apoE-/- mice by adeno-associated virus (AAV)-carrying NECC2 shRNA or compound YF-307 alleviated endothelium injury and restricted atherosclerosis development. The immunoprecipitation results confirmed that NECC2 interacted with Tyk2 and caveolin-1(Cav-1) in VECs, and NECC2 further promoted the phosphorylation of Cav-1 at Tyr14 b y activating Tyk2 phosphorylation. On the other hand, inhibiting NECC2 levels suppressed oxLDL-induced phosphorylation of Cav-1, uptake of oxLDL by VECs, accumulation of intracellular reactive oxygen species and activation of NF-κB. Our findings suggest that NECC2 may contribute to oxLDL-induced VEC injury and atherosclerosis via modulating Cav-1 phosphorylation through Tyk2. This work provides a new concept and drug target for treating atherosclerosis.
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Aterosclerose , Animais , Camundongos , Apolipoproteínas/efeitos adversos , Apolipoproteínas/metabolismo , Apolipoproteínas E/genética , Apolipoproteínas E/metabolismo , Aterosclerose/metabolismo , Endotélio/metabolismo , Lipoproteínas LDL/metabolismo , Estresse OxidativoRESUMO
BACKGROUND: Patients with polycystic ovary syndrome (PCOS) have a higher risk of obstetric complications. The association between anti-Müllerian hormone (AMH) and gestational hypertension in these patients is poorly understood. OBJECTIVE: To determine the association between serum AMH levels and gestational hypertension in patients with PCOS undergoing fresh embryo transfer. METHODS: This retrospective study included 649 patients with PCOS who had singleton live births after undergoing fresh embryo transfers. The association of AMH with gestational hypertension in these patients was estimated before and after propensity score matching (PSM). RESULTS: Patients with gestational hypertension had higher AMH levels than those without gestational hypertension. In single-factor logistic regression, the odds of gestational hypertension increased by 11.7% and 18.6% for every 1â ng/mL increase in AMH before and after adjusting for confounding factors [OR 1.117, 95% CI(1.025, 1.217), P = 0.012; adjusted OR 1.186, 95% CI(1.061, 1.327), adjusted P = 0.003], respectively. The odds of gestational hypertension increased more than 100% [adjusted OR 2.635, 95% CI(1.132, 6.137), adjusted P = 0.025] in the 75th percentile group (>9.30â ng/ml) and more than thrice [adjusted OR 4.75, 95% CI(1.672, 13.495), adjusted P = 0.003] in the 90th percentile group (>12.31â ng/ml) as compared to the without-gestational hypertension group. AMH level was still associated with gestational hypertension after PSM. The area under the curve of AMH predicting gestational hypertension was 0.654 [95% CI (0.532, 0.776), P = 0.011] with an optimal cutoff value of 11.975â ng/mL. CONCLUSIONS: High serum AMH level pre-pregnancy (especially at levels > 9.30â ng/mL) indicates a high odds of gestational hypertension in patients with PCOS undergoing fresh embryo transfer.
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The construction of neuronal membranes is a dynamic process involving the biogenesis, vesicular packaging, transport, insertion and recycling of membrane proteins. Optical imaging is well suited for the study of protein spatial organization and transport. However, various shortcomings of existing imaging techniques have prevented the study of specific types of proteins and cellular processes. Here we describe strategies for protein tagging and labeling, cell culture and microscopy that enable the real-time imaging of axonal membrane protein trafficking and subcellular distribution as they progress through some stages of their life cycle. First, we describe a process for engineering membrane proteins with extracellular self-labeling tags (either HaloTag or SNAPTag), which can be labeled with fluorescent ligands of various colors and cell permeability, providing flexibility for investigating the trafficking and spatiotemporal regulation of multiple membrane proteins in neuronal compartments. Next, we detail the dissection, transfection and culture of dorsal root ganglion sensory neurons in microfluidic chambers, which physically compartmentalizes cell bodies and distal axons. Finally, we describe four labeling and imaging procedures that utilize these enzymatically tagged proteins, flexible fluorescent labels and compartmentalized neuronal cultures to study axonal membrane protein anterograde and retrograde transport, the cotransport of multiple proteins, protein subcellular localization, exocytosis and endocytosis. Additionally, we generated open-source software for analyzing the imaging data in a high throughput manner. The experimental and analysis workflows provide an approach for studying the dynamics of neuronal membrane protein homeostasis, addressing longstanding challenges in this area. The protocol requires 5-7 days and expertise in cell culture and microscopy.
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Nanoparticles-loaded bio-based polymers have emerged as a sustainable substitute to traditional oil-based packaging materials, addressing the challenges of limited recyclability and significant environmental impact. However, the functionality and efficiency of nanoparticles have a significant impact on the application of bio-based composite films. Herein, graphitic carbon nitride (g-C3N4) and titanium dioxide (TiO2) coupled photocatalyst (g-C3N4-TiO2) was prepared by one-step calcination and introduced into chitosan (CS) and polyvinyl alcohol (PVA) solution to fabricate g-C3N4-TiO2/CS/PVA green renewable composite film via solution casting method. The results demonstrated the successful preparation of a Z-scheme heterojunction g-C3N4-TiO2 with exceptional photocatalytic activity. Furthermore, the incorporation of heterojunction enhanced mechanical properties, water barrier, and ultraviolet (UV) resistance properties of the fresh-keeping film. The g-C3N4-TiO2/CS/PVA composite film exhibited superior photocatalytic antibacterial preservation efficacy on strawberries under LED light, with a prolonged preservation time of up to 120 h, when compared to other films such as polyethylene (PE), CS/PVA, g-C3N4/CS/PVA, and TiO2/CS/PVA. In addition, the composite film has good recyclability and renewability. This work is expected to have great potential for low-cost fruit preservation and sustainable packaging, which also contributes to environmental protection.
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Quitosana , Embalagem de Alimentos , Grafite , Álcool de Polivinil , Titânio , Titânio/química , Quitosana/química , Álcool de Polivinil/química , Embalagem de Alimentos/métodos , Grafite/química , Frutas/química , Catálise , Compostos de Nitrogênio/química , Antibacterianos/química , Antibacterianos/farmacologiaRESUMO
Importance: Limited evidence supports the performance of human papillomavirus (HPV) DNA testing as a primary screening method, followed by triage with visual inspection with acetic acid, in areas with limited health care resources, as suggested by the 2021 World Health Organization guidelines. Objective: To evaluate the performance of visual inspection with acetic acid and Lugol iodine as a triage method for detecting cervical precancerous lesions among HPV-positive women in 1 visit. Design, Setting, and Participants: This cohort study examined the implementation of a government-led cervical cancer screening program conducted from January 1, 2016, to December 31, 2020, in Ordos City, China. Female residents, aged 35 to 64 years, who understood the screening procedures and voluntarily participated were included in the study. Women were excluded if they reported never having had sexual intercourse, were pregnant, had a hysterectomy, or had ever undergone treatment for cervical lesions. Statistical analysis was conducted from December 2022 to December 2023. Exposures: The program used the careHPV DNA assay as the primary screening method, and immediate triage was performed by visual inspection if HPV screening results were positive, with a 5-year screening interval. A colposcopy was performed for the women who had suspected cancer on visual inspection results or who were HPV positive and had abnormal visual inspection results, all in 1 visit. Main Outcomes and Measures: The rate of compliance with colposcopy and the detection rate of cervical intraepithelial neoplasia grade 2 or higher (CIN2+). Results: The study included 187â¯863 women (median age, 46 years [IQR, 40-52 years]) who participated in the program and had valid HPV test results. The overall prevalence of HPV positivity was 12.8% (24â¯070 of 187â¯863), and the adherence to triage with visual inspection among HPV-positive women was 93.9% (22â¯592 of 24â¯070). Among HPV-positive women, the rate of compliance with colposcopy was 65.6% (2714 of 4137), and the CIN2+ detection rate was 2.8% (643 of 22â¯592). Conclusions and Relevance: The findings of this cohort study suggest that the implementation of HPV testing, visual inspection, and colposcopy within 1 visit may mitigate losses to follow-up, detect precancerous lesions, and hold significant implications for screening in comparable areas with limited health care resources.
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Iodo , Infecções por Papillomavirus , Lesões Pré-Cancerosas , Displasia do Colo do Útero , Neoplasias do Colo do Útero , Gravidez , Feminino , Humanos , Pessoa de Meia-Idade , Neoplasias do Colo do Útero/diagnóstico , Neoplasias do Colo do Útero/epidemiologia , Neoplasias do Colo do Útero/patologia , Ácido Acético , Estudos de Coortes , Detecção Precoce de Câncer/métodos , Triagem , Infecções por Papillomavirus/epidemiologia , Displasia do Colo do Útero/patologia , Lesões Pré-Cancerosas/diagnóstico , DNA ViralRESUMO
Tumor necrosis factor α (TNF-α) is a major pro-inflammatory cytokine, important in many diseases, that sensitizes nociceptors through its action on a variety of ion channels, including voltage-gated sodium (NaV) channels. We show here that TNF-α acutely upregulates sensory neuron excitability and current density of threshold channel NaV1.7. Using electrophysiological recordings and live imaging, we demonstrate that this effect on NaV1.7 is mediated by p38 MAPK and identify serine 110 in the channel's N terminus as the phospho-acceptor site, which triggers NaV1.7 channel insertion into the somatic membrane. We also show that the N terminus of NaV1.7 is sufficient to mediate this effect. Although acute TNF-α treatment increases NaV1.7-carrying vesicle accumulation at axonal endings, we did not observe increased channel insertion into the axonal membrane. These results identify molecular determinants of TNF-α-mediated regulation of NaV1.7 in sensory neurons and demonstrate compartment-specific effects of TNF-α on channel insertion in the neuronal plasma membrane.
Assuntos
Células Receptoras Sensoriais , Fator de Necrose Tumoral alfa , Fator de Necrose Tumoral alfa/farmacologia , Fator de Necrose Tumoral alfa/metabolismo , Células Receptoras Sensoriais/metabolismo , Axônios/metabolismo , Nociceptores/metabolismo , Membrana Celular/metabolismoRESUMO
Dimethylsulfoniopropionate (DMSP) is a ubiquitous organosulfur molecule in marine environments with important roles in stress tolerance, global carbon and sulfur cycling, and chemotaxis. It is the main precursor of the climate active gas dimethyl sulfide (DMS), which is the greatest natural source of biosulfur transferred from ocean to atmosphere. Alteromonas sp. M12, a Gram-negative and aerobic bacterium, was isolated from the seawater samples collected from the Mariana Trench at the depth of 2500 m. Here, we report the complete genome sequence of strain M12 and its genomic characteristics to import and utilize DMSP. The genome of strain M12 contains one circular chromosome (5,012,782 bp) with the GC content of 40.88%. Alteromonas sp. M12 can grow with DMSP as a sole carbon source, and produced DMS with DMSP as a precursor. Genomic analysis showed that strain M12 contained a set of genes involved in the downstream steps of DMSP cleavage, but no known genes encoding DMSP transporters or DMSP lyases. The results indicated that this strain contained novel DMSP transport and cleavage genes in its genome which warrants further investigation. The import of DMSP into cells may be a strategy of strain M12 to adapt the hydrostatic pressure environment in the Mariana Trench, as DMSP can be used as a hydrostatic pressure protectant. This study sheds light on the catabolism of DMSP by deep-sea bacteria.