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Wastewater-based epidemiology (WBE) has emerged as a promising tool for monitoring the spread of COVID-19, as SARS-CoV-2 can be shed in the faeces of infected individuals, even in the absence of symptoms. This study aimed to optimize a prediction model for estimating COVID-19 infection rates based on SARS-CoV-2 RNA concentrations in wastewater, and reveal the infection trends and variant diversification in Shenzhen, China following the lifting of a strict COVID-19 strategy. Faecal samples (n = 4337) from 1204 SARS-CoV-2 infected individuals hospitalized in a designated hospital were analysed to obtain Omicron variant-specific faecal shedding dynamics. Wastewater samples from 6 wastewater treatment plants (WWTPs) and 9 pump stations, covering 3.55 million people, were monitored for SARS-CoV-2 RNA concentrations and variant abundance. We found that the viral load in wastewater increased rapidly in December 2022 in the two districts, demonstrating a sharp peak in COVID-19 infections in late-December 2022, mainly caused by Omicron subvariants BA.5.2.48 and BF.7.14. The prediction model, based on the mass balance between total viral load in wastewater and individual faecal viral shedding, revealed a surge in the cumulative infection rate from <0.1 % to over 70 % within three weeks after the strict COVID-19 strategy was lifted. Additionally, 39 cryptic SARS-CoV-2 variants were identified in wastewater, in addition to those detected through clinical surveillance. These findings demonstrate the effectiveness of WBE in providing comprehensive and efficient assessments of COVID-19 infection rates and identifying cryptic variants, highlighting its potential for monitoring emerging pathogens with faecal shedding.
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COVID-19 , SARS-CoV-2 , Aguas Residuales , COVID-19/epidemiología , China/epidemiología , Aguas Residuales/virología , Humanos , Heces/virología , Betacoronavirus , Pandemias , Monitoreo Epidemiológico Basado en Aguas Residuales , ARN Viral/análisis , Esparcimiento de Virus , Carga ViralRESUMEN
Avian influenza viruses (AIVs) are the origin of multiple mammal influenza viruses. The genetic determinants of AIVs adapted to humans have been widely elucidated, however, the molecular mechanism of cross-species transmission and adaptation of AIVs to canines are still poorly understood. In this study, two H3N2 influenza viruses isolated from a live poultry market (A/environment/Guangxi/13431/2018, GX13431) and a swab sample from a canine (A/canine/Guangdong/0601/2019, GD0601) were used to investigate the possible molecular basis that determined H3N2 AIV adapting to canine. We found that GD0601 exhibited more robust polymerase activity in cells and higher pathogenicity in mice compared with its evolution ancestor H3N2 AIV GX13431. A series of reassortments of the ribonucleoprotein (RNP) complex showed that the PB2 subunit was the crucial factor that conferred high polymerase activity of GD0601, and the substitution of I714S in the PB2 subunit of GD0601 attenuated the replication and pathogenicity in mammal cells and the mouse model. Mechanistically, the reverse mutation of I714S in the PB2 polymerase subunit which was identified in AIV GX13431 reduced the nuclear import efficiency of PB2 protein and interfered with the interactions of PB2-PA/NP that affected the assembly of the viral RNP complex. Our study reveals amino acid mutation at the position of 714 in the nuclear localization signal (NLS) area in PB2 plays an important role in overcoming the barrier from poultry to mammals of the H3N2 canine influenza virus and provides clues for further study of mammalian adaptation mechanism of AIVs.
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Subtipo H3N2 del Virus de la Influenza A , Infecciones por Orthomyxoviridae , ARN Polimerasa Dependiente del ARN , Ribonucleoproteínas , Proteínas Virales , Animales , Perros , Subtipo H3N2 del Virus de la Influenza A/genética , Subtipo H3N2 del Virus de la Influenza A/fisiología , Ratones , Proteínas Virales/genética , Proteínas Virales/metabolismo , ARN Polimerasa Dependiente del ARN/genética , ARN Polimerasa Dependiente del ARN/metabolismo , Infecciones por Orthomyxoviridae/virología , Humanos , Ribonucleoproteínas/genética , Ribonucleoproteínas/metabolismo , Transporte Activo de Núcleo Celular , Replicación Viral , Mutación , Células de Riñón Canino Madin Darby , Enfermedades de los Perros/virología , Ratones Endogámicos BALB C , Células HEK293 , Virus Reordenados/genéticaRESUMEN
China has been continuously improving its monitoring methods and strategies to address key infectious diseases (KIDs). After the severe acute respiratory syndrome epidemic in 2003, China established a comprehensive reporting system for infectious diseases (IDs) and public health emergencies. The relatively lagging warning thresholds, limited warning information, and outdated warning technology are insufficient to meet the needs of comprehensive monitoring for modern KIDs. Strengthening early monitoring and warning capabilities to enhance the public health system has become a top priority, with increasing demand for early warning thresholds, information, and techniques, thanks to constant innovation and development in molecular biology, bioinformatics, artificial intelligence, and other identification and analysis technologies. A panel of 31 experts has recommended a fourth-generation comprehensive surveillance system targeting KIDs (41 notifiable diseases and emerging IDs). The aim of this surveillance system is to systematically monitor the epidemiology and causal pathogens of KIDs in hosts such as humans, animals, and vectors, along with associated environmental pathogens. By integrating factors influencing epidemic spread and risk assessment, the surveillance system can serve to detect, predict, and provide early warnings for the occurrence, development, variation, and spread of known or novel KIDs. Moreover, we recommend comprehensive ID monitoring based on the fourth-generation surveillance system, along with a data-integrated monitoring and early warning platform and a consortium pathogen detection technology system. This series of considerations is based on systematic and comprehensive monitoring across multiple sectors, dimensions, factors, and pathogens that is supported by data integration and connectivity. This expert consensus will provides an opportunity for collaboration in various fields and relies on interdisciplinary application to enhance comprehensive monitoring, prediction, and early warning capabilities for the next generation of ID surveillance. This expert consensus will serve as a reference for ID prevention and control as well as other related activities.
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Addressing marine oil spills and industrial water pollution necessitates the development of eco-efficient oil-absorbing materials. With increasing concern for the environment, there is a consensus to decrease the use of petroleum-based polymers. Herein, lightweight poly(lactic acid) (PLA) blend foams with varying thermoplastic polyurethane (TPU) content were fabricated via a solvent-free, eco-friendly supercritical carbon dioxide (scCO2) extrusion foaming technology. The incorporation of TPU significantly enhanced the crystallization rate of PLA, with the semi-crystallization time of PT30 and PT50 blends at 105 °C exhibiting a reduction of 77.2 % and 47.9 %, respectively, compared to neat PLA. The resulting foams exhibited an open-cell structure with excellent selective oil adsorption capabilities. Notably, the PT30 foam achieved a remarkable maximum expansion ratio of 36.0, while the PT50 foam attained the highest open-cell content of 96.2 %. The PT50 foam demonstrated an outstanding adsorption capacity, spanning from 4.7 to 18.8 g/g for diverse oils and solvents, with rapid adsorption kinetics, reaching 94.9 % of the equilibrium adsorption capacity for CCl4 within just 1 min. Furthermore, the PT50 foam retained 95.2 % of its adsorption capacity for CCl4 over 10 adsorption-desorption cycles. This study presents a scalable and sustainable approach for large-scale production of high-performance, bio-based foams, facilitating efficient oil-water separation.
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Dióxido de Carbono , Poliésteres , Poliésteres/química , Adsorción , Dióxido de Carbono/química , Aceites/química , Poliuretanos/química , CinéticaRESUMEN
Objective To investigate the effect of 3-deazaadenosine (3-DAA), an N6-methyladenosine (m6A) methylation modification inhibitor, on the replication of the Japanese encephalitis virus (JEV). Methods Neuro2a mouse neuroblastoma cells, N9 mouse microglial cells, and BHK baby hamster kidney cells were exposed to JEV and then treated with 3-DAA. JEV was also injected into the footpad of adult C57BL/6 mice, which were then administered 3-DAA intraperitoneally. Real-time quantitative PCR was utilized to measure mRNA expression levels of JEV, interleukin 1ß (IL-1ß), IL-6, tumor necrosis factor α (TNF-α), monocyte chemoattractant protein 1 (MCP-1), inducible nitric oxide synthase (iNOS), arginase 1 (Arg1), interferon (IFN)-α, IFN-ß, IFN-γ, and C-X-C motif chemokine ligand 10 (CXCL10) in the cells and mouse brain tissues. Western blot analysis was used to detect JEV protein expression in the cells and mouse brain tissues. Furthermore, the survival of the mice was monitored and pathological changes in mouse brains were observed via hematoxylin and eosin (HE) staining. Results 3-DAA had a dose-dependent effect on the replication of RNA and protein expression of JEV in both BHK, N9, Neuro 2α cells and mouse brain tissues, which resulted in rapid progression of JEV infection in mice and a decrease in their survival rate. Furthermore, 3-DAA suppressed the expression of inflammatory factors such as IL-6, TNF-α, CXCL10, IL-1ß and iNOS, thus weakening the immune response. Conclusion 3-DAA promotes JEV infection and hastens death of infected cells and mice, indicating that m6A modification may negatively regulate JEV replication.
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Virus de la Encefalitis Japonesa (Especie) , Tubercidina , Cricetinae , Animales , Ratones , Ratones Endogámicos C57BL , Antivirales/farmacología , Interleucina-6 , Factor de Necrosis Tumoral alfa/genética , Interferón-alfa , Interleucina-1beta/genéticaRESUMEN
N6-methyladenosine (m6A) is present in diverse viral RNA and plays important regulatory roles in virus replication and host antiviral innate immunity. However, the role of m6A in regulating JEV replication has not been investigated. Here, we show that the JEV genome contains m6A modification upon infection of mouse neuroblast cells (neuro2a). JEV infection results in a decrease in the expression of m6A writer METTL3 in mouse brain tissue. METTL3 knockdown by siRNA leads to a substantial decrease in JEV replication and the production of progeny viruses at 48 hpi. Mechanically, JEV triggered a considerable increase in the innate immune response of METTL3 knockdown neuro2a cells compared to the control cells. Our study has revealed the distinctive m6A signatures of both the virus and host in neuro2a cells infected with JEV, illustrating the positive role of m6A modification in JEV infection. Our study further enhances understanding of the role of m6A modification in Flaviviridae viruses.
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Virus de la Encefalitis Japonesa (Especie) , Encefalitis Japonesa , Animales , Ratones , Virus de la Encefalitis Japonesa (Especie)/genética , Metiltransferasas/genética , Metiltransferasas/metabolismo , ARN Interferente Pequeño/genética , ARN Interferente Pequeño/metabolismo , Inmunidad Innata , Replicación Viral/genéticaRESUMEN
PURPOSE: To investigate the prevalence, characteristics, causes, consequences, and predictors of and responses to disruptive behavior toward nurses in the perioperative arena. DESIGN: A cross-sectional design using a network questionnaire platform. METHODS: Nurses in the perioperative arena were recruited online in March 2020. Data on disruptive behavior toward nurses in the past 6 months and nurses' sociodemographic and environmental factors were collected. FINDINGS: Nurses (N = 496) responded validly to the survey. In total, 82.1% of participants experienced disruptive behavior. Assignment of overwhelming workloads and verbal aggression were the most common behaviors, and surgeons were the major perpetrators. Perpetrators' intrapersonal issues were the most commonly perceived causes. A positive strategy was the most common strategy adopted by participants. Further, 80.8% of participants recounted their negative experiences, and more than half of respondents (59.9%) talked with their nursing colleagues. Nearly half of respondents (45.9%) did not report disruptive behavior. Negative emotions as an immediate effect were reported by 53.1% of the participants, and the most common long-term impact was decreased passion for work. Middle age, job position, practice environment, and system help were risk factors for experiencing disruptive behavior. CONCLUSIONS: The prevalence of disruptive behavior toward nurses in the perioperative arena is high, and its ramifications should not be ignored. Health care institutions should urgently implement intervention strategies to reduce disruptive behavior toward nurses.
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Problema de Conducta , Humanos , Masculino , Estudios Transversales , Femenino , Adulto , Problema de Conducta/psicología , Encuestas y Cuestionarios , Persona de Mediana Edad , Enfermería Perioperatoria/métodos , Factores de Riesgo , Personal de Enfermería en Hospital/psicología , Personal de Enfermería en Hospital/estadística & datos numéricos , PrevalenciaRESUMEN
To address the challenges posed by spilled oil and oily wastewater, the development of clean oil-adsorption materials is crucial. However, traditional oil-adsorption materials suffer from the issue of secondary pollution. Herein, fully biodegradable nanofibrillated poly(butylene succinate)/poly(lactic acid) (PBS/PLA) foams with outstanding selective oil-adsorption performance were successfully fabricated via an eco-friendly supercritical CO2 foaming technology. The PBS/PLA composites, featuring nanofibrils with a diameter of approximately 100 nm, were prepared through a hot-stretching method subsequent to extrusion. Substantial improvements were observed in the crystallization rate and rheological properties of the fibrillated PBS/PLA composites. Furthermore, PLA nanofibrils enhanced foamability of the composite, achieving an impressive expansion ratio of up to 38.0, resulting in an outstanding oil-absorption performance (19.2-50.4 g/g) of the F-1 %-95 foam. Additionally, 20 adsorption-desorption cycles illustrated the prepared F-1 %-95 foam displayed recyclable oil-absorption characteristics. This work provides an eco-friendly strategy for preparing fully biodegradable foams intended for application as oil-adsorption materials.
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Poliésteres , Temperatura , Poliésteres/química , Fenómenos Químicos , CristalizaciónRESUMEN
Achieving a high-strength piezoresistive foam with high sensitivity and a large workable range remains a major challenge. To realize these goals, we developed a facile, novel, and eco-friendly strategy for constructing segregated microcellular structures fabricated using coating, heat compression molding, and supercritical CO2 (ScCO2) foaming. The segregated poly(ether block amide) (PEBA)/carbon nanostructure (CNS) composites were fabricated via compression molding. This effectively improved the foamability and cell morphology of PEBA/CNS composites. Moreover, compared with the randomly distributed structure, the segregated structure also endowed the foams with better conductivity and sensing capability. Subsequently, the ScCO2 foaming was employed to fabricate segregated PEBA/CNS composite foams. The foaming gave composites a large compressibility and reduced their percolation threshold. Under 1 wt % CNS loading, via tuning the expansion ratio of foam from â¼2.1 to 4.1, the compression stress at 50% compression strain of foam varied from â¼3.3 to 0.5 MPa, and the conductivity changed from 4.89 × 10-3 to 1.93 × 10-6 s/m, implying a tunable conductivity. Additionally, the adjustable conductivity enabled the sensitivity of segregated composite foams to be regulated. The segregated PEBA/CNS foam (FCNS1-4.1) exhibited a good combination of high sensitivity (GF = 3.5), large work range (80% strain), and high compression strength (â¼0.5 MPa at 50% strain) as well as a stable, reproducible, and durable sensing response under a low CNS content (â¼0.11 vol %). Furthermore, the ΔI/I0 of FCNS1-4.1 (75.6% porosity) reached a high value of â¼810 and exhibited an ultrahigh sensitivity of â¼3706 (ΔI/I0ε) from 60 to 80% strain. Moreover, the foam sensor could be used as a sensing function sole for monitoring diverse human motions. Therefore, the segregated PEBA/CNS composite foams with outstanding piezoresistive performances show promising potential applications in monitoring human motions as wearable electronics and provides a new design strategy for a new generation of foam sensors with high performance.
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Background: In recent years, mobile health (mHealth) has gradually developed in China, and intelligent medicine has become an important research topic. However, there are still significant problems in mHealth applications (apps). Although healthcare professionals and patients are the main users, few studies have focused on their perceptions of the quality of mHealth apps. Objective: This study aimed to (1) understand the respective perceptions of healthcare professionals and patients regarding mHealth apps, (2) assess what barriers exist that influence the user experience, and (3) explore how to improve the quality of mHealth apps and the development of the mHealth market in China. The study aims to promote the standardization of mHealth apps and provide effective information for the improvement and development of mHealth apps in the future. Methods: Semistructured interviews with 9 patients and 14 healthcare professionals were conducted from January 2022 to April 2022 in the Affiliated Hospital of Xuzhou Medical University. The participants used mHealth apps for more than 3 months, including the "Good Mood" and "Peace and Safe Doctors" apps and apps developed by the hospital that were popular in China. Interview transcripts were analysed using thematic analysis. Results: The following five themes were extracted: different concerns, hidden medical dangers, distance and insecurity, barriers for older people, and having positive perceptions of mHealth apps. Healthcare professionals prioritized simplicity in regard to mHealth apps, whereas patients rated effectiveness as the most crucial factor. The study also revealed several problems with mHealth apps, including insufficient information about physician qualifications, inaccurate medical content, nonstandard treatment processes, and unclear accountability, which led to a sense of distance and insecurity among participants. Older individuals faced additional obstacles when using mHealth apps. Despite these issues, the participants remained optimistic about the future of mHealth app development. Conclusion: The utilization, advantages, and obstacles of mHealth applications for healthcare professionals and patients were explored through semistructured interviews. Despite the promising prospects for mHealth apps in China, numerous issues still need to be addressed. Enhancing the safety monitoring system and developing user-friendly mHealth apps for older adult patients are essential steps to bridge the gap between healthcare providers and patients.
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Actitud del Personal de Salud , Actitud Frente a la Salud , Personal de Salud , Aplicaciones Móviles , Telemedicina , Anciano , Humanos , China , Aplicaciones Móviles/normas , Investigación Cualitativa , Telemedicina/normas , Calidad de la Atención de SaludRESUMEN
An integrated way to generate and manipulate higher-order Poincaré sphere beams (HOPBs) is a sought-after goal in photonic integrated circuits for high-capacity communication systems. Here, we demonstrate a novel method for on-chip generation and manipulation of HOPBs through combining metasurface with optical waveguides on lithium niobate on insulator platform. With phase modulation by a diatomic geometric metasurface, guided waves are extracted into free space with a high signal-to-noise ratio in the form of two orthogonal circularly polarized optical vortices which are linearly superposed into HOPBs. Meanwhile, a dual-port waveguide crossing is established to reconfigure the output states into an arbitrary point on a higher-order Poincaré sphere based on in-plane interference of two guided waves. Our approach provides a promising solution to generate and manipulate the HOPBs in a compact manner, which would be further enhanced by employing the electro-optical modulation on a lithium niobate waveguide to access a fully tunable scheme.
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Citrinin, a mycotoxin existing in fruits, has nephrotoxicity, hepatotoxicity and embryotoxicity. The effects of citrinin on Leydig cell development in prepuberty remains unclear. Male Sprague-Dawley rats were gavaged with 0, 1, 2.5, and 5 mg/kg citrinin from postnatal days 21-28. Citrinin at 5 mg/kg significantly decreased serum testosterone levels, while increasing serum LH and FSH levels. Citrinin at 1-5 mg/kg markedly downregulated Hsd17b3 and HSD17B3 expression, while upregulating Srd5a1 (SRD5A1) and Akr1c14 (AKR1C14) expression at 2.5 and/or 5 mg/kg. Citrinin at 5 mg/kg also significantly increased PCNA-labeling index in Leydig cells. Citrinin at 5 mg/kg significantly raised testicular MDA amount, whiling at 2.5 and 5 mg/kg downregulating SOD1 and SOD2 expression. Citrinin at 5 mg/kg markedly decreased the ratio of Bcl2 to Bax, in consistent with the increased apoptosis in Leydig cells judged by TUNEL assay. Enzymatic assay revealed that citrinin inhibited rat testicular HSD3B1 activity at 100 µM and HSD17B3 activity at 10-100 µM. Citrinin at 50 µM and higher also induced reactive oxygen species (ROS) and apoptosis of R2C cell line. In conclusion, citrinin inhibits Leydig cell development at multiple levels via different mechanisms and oxidative stress partially plays a role.
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Citrinina , Células Intersticiales del Testículo , Ratas , Masculino , Animales , Células Intersticiales del Testículo/metabolismo , Ratas Sprague-Dawley , Citrinina/toxicidad , Citrinina/metabolismo , Testículo , Diferenciación Celular , TestosteronaRESUMEN
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection causes asymptomatic or mild symptoms, even rare hospitalization in children. A major concern is whether the pre-existing antibodies induced by low pathogenic human coronaviruses (LPH-CoVs) in children can cross-react with SARS-CoV-2. To address this unresolved question, we analyzed the pre-existing spike (S)-specific immunoglobin (Ig) G antibodies against LPH-CoVs and the cross-reactive antibodies against SARS-CoV-2 in 658 serum samples collected from children prior to SARS-CoV-2 outbreak. We found that the seroprevalence of these four LPH-CoVs reached 75.84%, and about 24.64% of the seropositive samples had cross-reactive IgG antibodies against the nucleocapsid, S, and receptor binding domain antigens of SARS-CoV-2. Additionally, the re-infections with different LPH-CoVs occurred frequently in children and tended to increase the cross-reactive antibodies against SARS-CoV-2. From the forty-nine serum samples with cross-reactive anti-S IgG antibodies against SARS-CoV-2, we found that seven samples with a median age of 1.4 years old had detected neutralizing activity for the wild-type or mutant SARS-CoV-2 S pseudotypes. Interestingly, all of the seven samples contained anti-S IgG antibodies against HCoV-OC43. Together, these data suggest that children's pre-existing antibodies to LPH-CoVs have limited cross-reactive neutralizing antibodies against SRAS-CoV-2.
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COVID-19 , Coronaviridae , Niño , Humanos , Lactante , SARS-CoV-2 , Inmunidad Humoral , Estudios Seroepidemiológicos , Anticuerpos Antivirales , Inmunoglobulina GRESUMEN
Tetramethyl bisphenol A (TMBPA) is a widely used flame retardant. TMBPA has been a toxic to Leydig cells in puberty, but it remains unclear whether TMBPA has a similar inhibitor effect on fetal Leydig cells (FLCs). This study reported morphological and functional alterations of FLCs in the testes of male offspring at birth after in utero exposure to TMBPA. Pregnant Sprague Dawley rats were dosed via continuous gavage of TMBPA (0, 10, 50, and 200 mg/kg/day) from gestational day 14 to 21. TMBPA markedly raised serum total testosterone level, testicular volume, and FLC number of male offspring at 200 mg/kg dose. The up-regulation of Insl3, Star, and Cyp11a1 mRNAs was observed after 200 mg/kg TMBPA exposure. After normalization to the number of FLCs, TMBPA significantly reduced Lhcgr and Hsd3b1 expressions at 10 mg/kg, and Cyp17a1 at 200 mg/kg paralleling with their protein levels. TMBPA compromised the expression of Esr1, while increased the expression of Cdk2 and Cdk4 as well as their protein levels. TMBPA particularly increased the phosphorylation of AKT1 and AKT2 at 200 mg/kg. In conclusion, the present study suggests that TMBPA may promote FLC proliferation via ESR1-CDK2/4-AKT pathway, while inhibits the function of FLCs by reducing steroidogenic enzyme activity.
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Retardadores de Llama , Células Intersticiales del Testículo , Animales , Compuestos de Bencidrilo , Proliferación Celular , Enzima de Desdoblamiento de la Cadena Lateral del Colesterol/metabolismo , Receptor alfa de Estrógeno/genética , Receptor alfa de Estrógeno/metabolismo , Femenino , Fluorenos , Masculino , Complejos Multienzimáticos/metabolismo , Complejos Multienzimáticos/farmacología , Fenoles , Embarazo , Proteínas Proto-Oncogénicas c-akt/metabolismo , Ratas , Ratas Sprague-Dawley , Receptores del Activador de Plasminógeno Tipo Uroquinasa/metabolismo , Maduración Sexual , Testículo , TestosteronaRESUMEN
OBJECTIVE: Although the serine active site containing 1 (SERAC1) protein is essential for cardiolipin remodeling and cholesterol transfer, its physiological role in whole-body energy metabolism remains unclear. Thus, we investigated the role of SERAC1 in lipid distribution and metabolism in mice. METHODS: CRISPR/Cas9 was used to create homozygous Serac1 knockout mice. A range of methods, including electron microscopy, histological analysis, DNA sequencing, glucose and insulin tolerance tests, and biochemical analysis of serum lipid levels, were used to assess lipid distribution and rates of lipid synthesis in mice. RESULTS: We found that Serac1 depletion in mice prevented high-fat diet-induced obesity but did not affect energy expenditure. The liver was affected by Serac1 depletion, but adipose tissues were not. Serac1 depletion was shown to impair cholesterol transfer from the liver to the serum and led to an imbalance in cholesterol distribution. The livers from mice with Serac1 depletion showed increased cholesterol synthesis because the levels of cholesterol synthesis enzymes were upregulated. Moreover, the accumulation of hepatic lipid droplets in mice with Serac1 depletion were decreased, suggesting that SERAC1 depletion may decrease the risk for hepatic steatosis in high fat diet-induced mice. CONCLUSION: Our findings demonstrate that SERAC1 can serve as a potential target for the treatment or prevention of diet-induced hepatic lipid metabolic disorders.
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Dieta Alta en Grasa , Resistencia a la Insulina , Animales , Dominio Catalítico , Colesterol , Dieta Alta en Grasa/efectos adversos , Metabolismo de los Lípidos/genética , Hígado/metabolismo , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Obesidad/etiología , Obesidad/metabolismo , Obesidad/prevención & control , Serina/metabolismoRESUMEN
Fluornen-9-bisphenol (BPFL) is used as one of the alternatives for bisphenol A. However, whether BPFL has deleterious effects to the male reproductive system and the underlying mechanism remain unknown. Here, we report the effects of BPFL on Leydig cell development in male rats in puberty. Male Sprague-Dawley (28 days old) rats were dosed with 0, 10, 100, 200 mg/kg/day BPFL via gavage for 28 days. BPFL significantly decreased serum testosterone levels at 200 mg/kg while increasing serum luteinizing hormone and follicle-stimulating hormone levels at 200 mg/kg. BPFL markedly increased Leydig cell number but down-regulated the expression of Cyp17a1 and its protein level in Leydig cells at 200 mg/kg. Further study showed that BPFL significantly increased Pcna and Cdk2 expression and increased Leydig cell proliferation at 200 mg/kg. BPFL treatment to immature Leydig cells isolated from 28-day-old male rats for 24 h significantly inhibited testosterone biosynthesis at 50 µM, which was completely reversed by the androgen receptor agonist 7α-methyl-nortestosterone and estrogen receptor α antagonist ICI 182,780. In conclusion, BPFL increases Leydig cell proliferation but inhibits its maturation in male rats in puberty by blocking androgen receptor and activating estrogen receptor α.
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Células Intersticiales del Testículo , Receptores Androgénicos , Animales , Compuestos de Bencidrilo , Proliferación Celular , Receptor alfa de Estrógeno/metabolismo , Masculino , Fenoles , Ratas , Ratas Sprague-Dawley , Receptores Androgénicos/metabolismo , Maduración Sexual , TestosteronaRESUMEN
Tetramethyl bisphenol A (TMBPA) is a commonly used bisphenol analog, used as a fire retardant. However, whether it inhibits the function of Leydig cells in late puberty remains unclear. In this study, 35-day-old male Sprague-Dawley rats were gavaged with 0, 10, 100, and 200 mg/kg body weight TMBPA for 21 days. TMBPA significantly reduced serum testosterone levels at 10 mg/kg and higher doses without altering serum luteinizing hormone and follicle-stimulating hormone levels. TMBPA significantly increased serum iron concentraion while reducing the ratio of serum glutathione (GSH) and GSH/GSSG (oxidized glutathione disulfide). In addition, TMBPA significantly increased testicular iron amount at 10 mg/kg and higher doses and malondialdehyde level at 200 mg/kg. TMBPA down-regulated the expression of Leydig cell genes, including Nr5a1, Star, Scarb1, Insl3, Cyp11a1, Cyp17a1, Hsd17b3, and Hsd11b1, and their proteins. In addition, TMBPA markedly down-regulated the expression of genes in the ferroptosis pathway (Tp53, Slc7a11, Sod1, Sod2, Cat, Sqstm1, Keap1, and Hmox1). TMBPA significantly reduced the levels of ferroptosis pathway proteins (TP53, SLC7A11, GPX4, SQSTM1, KEAP1, NRF2, and HMOX1) in Leydig cells in vivo. Immature and adult Leydig cell culture in vitro also showed that TMBPA significantly reduced testosterone concentrations in the medium, which can be reversed by a ferroptosis inhibitor. After 24 h of culture in primary Leydig cells at 10 and 50 µM, TMBPA significantly induced reactive oxygen species and lowered the mitochondrial membrane potential. TMBPA also altered protein levels in the ferroptosis pathway in Leydig cells in vitro. In conclusion, TMBPA directly inhibits the activity of rat Leydig cell steroidogenic enzymes and induces the ferroptosis of Leydig cells, thereby inhibiting the testosterone synthesis of Leydig cells in the late puberty.