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Germ cells are vital for transmitting genetic information from one generation to the next and for maintaining the continuation of species. Here, we analyze the transcriptome of human primordial germ cells (PGCs) from the migrating stage to the gonadal stage at single-cell and single-base resolutions. Human PGCs show unique transcription patterns involving the simultaneous expression of both pluripotency genes and germline-specific genes, with a subset of them displaying developmental-stage-specific features. Furthermore, we analyze the DNA methylome of human PGCs and find global demethylation of their genomes. Approximately 10 to 11 weeks after gestation, the PGCs are nearly devoid of any DNA methylation, with only 7.8% and 6.0% of the median methylation levels in male and female PGCs, respectively. Our work paves the way toward deciphering the complex epigenetic reprogramming of the germline with the aim of restoring totipotency in fertilized oocytes.
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Metilación de ADN , Células Germinativas/metabolismo , Transcriptoma , Movimiento Celular , Cromosomas Humanos X , Análisis por Conglomerados , Embrión de Mamíferos/metabolismo , Femenino , Histonas/metabolismo , Humanos , Masculino , Análisis de Componente Principal , Factores de Transcripción SOX/metabolismoRESUMEN
Polymer semiconductors composed of a carbon-based π conjugated backbone have been studied for several decades as active layers of multifarious organic electronic devices. They combine the advantages of the electrical conductivity of metals and semiconductors and the mechanical behavior of plastics, which are going to become one of the futures of modulable electronic materials. The performance of conjugated materials depends both on their chemical structures and the multilevel microstructures in solid states. Despite the great efforts that have been made, they are still far from producing a clear picture among intrinsic molecular structures, microstructures, and device performances. This review summarizes the development of polymer semiconductors in recent decades from the aspects of material design and the related synthetic strategies, multilevel microstructures, processing technologies, and functional applications. The multilevel microstructures of polymer semiconductors are especially emphasized, which plays a decisive role in determining the device performance. The discussion shows the panorama of polymer semiconductors research and sets up a bridge across chemical structures, microstructures, and finally devices performances. Finally, this review discusses the grand challenges and future opportunities for the research and development of polymer semiconductors.
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This study investigated the use of intravoxel incoherent motion imaging (IVIM) to compare skeletal muscle perfusion during and after high-intensity interval training (HIIT) and moderate-intensity continuous training (MICT) to determine the impact on fat oxidation outcomes. Twenty overweight volunteers were recruited for the study. Each participant received one HIIT intervention and one MICT intervention using a cycling ergometer. Participants underwent a magnetic resonance imaging scan before, immediately after, and 1 and 2 h after each intervention. The IVIM parameters (D, fD*) of the rectus femoris, vastus lateralis, and biceps femoris long head were obtained. Changes in IVIM parameters of these muscles after both exercise interventions were compared using a two-factor repeated measures analysis of variance. In the rectus femoris, the fD* increased immediately after exercise intervention (d = 0.69 × 10-3 mm2 /s, p < 0.0083) and 2 h after exercise intervention (d = 0.64 × 10-3 mm2 /s, p < 0.0083) compared with before exercise. The increase in the fD* in the HIIT group was greater than that in the MICT group (d = 0.32, p = 0.023). In the vastus lateralis, the fD* increased immediately after the exercise intervention (d = 0.53 × 10-3 mm2 /s, p < 0.001) and returned to the pre-exercise level 1 h after exercising. The increase in the fD* in the HIIT group was lower than that in the MICT group (d = -0.21, p = 0.015). For the biceps femoris long head, the fD* was not significantly different between the two exercise interventions before and after exercise. Furthermore, the fD* 60 min after the HIIT intervention correlated with maximal oxygen consumption (VO2max), whereas fD* immediately after the MICT intervention correlated with VO2max. In summary, IVIM parameters can be used to evaluate differences in muscle perfusion between HIIT and MICT, and show a correlation with VO2max.
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Entrenamiento de Intervalos de Alta Intensidad , Humanos , Entrenamiento de Intervalos de Alta Intensidad/métodos , Muslo/diagnóstico por imagen , Ejercicio Físico/fisiología , Músculo Esquelético/diagnóstico por imagen , Imagen por Resonancia MagnéticaRESUMEN
To investigate the metabolic difference among tissue layers of the rabbits' eye during the development of myopia using metabolomic techniques and explore any metabolic links or cascades within the ocular wall. Ultra Performance Liquid Chromatography - Mass Spectrometry (UPLC-MS) was utilized for untargeted metabolite screening (UMS) to identify the significant differential metabolites produced between myopia (MY) and control (CT) (horizontal). Subsequently, we compared those key metabolites among tissues (Sclera, Choroid, Retina) of MY for distribution and variation (longitudinal). A total of 6285 metabolites were detected in the three tissues. The differential metabolites were screened and the metabolic pathways of these metabolites in each myopic tissue were labeled, including tryptophan and its metabolites, pyruvate, taurine, caffeine metabolites, as well as neurotransmitters like glutamate and dopamine. Our study suggests that multiple metabolic pathways or different metabolites under the same pathway, might act on different parts of the eyeball and contribute to the occurrence and development of myopia by affecting the energy supply to the ocular tissues, preventing antioxidant stress, affecting scleral collagen synthesis, and regulating various neurotransmitters mutually.
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Miopía , Espectrometría de Masas en Tándem , Animales , Conejos , Cromatografía Liquida , Modelos Animales de Enfermedad , Miopía/metabolismo , Retina/metabolismo , Esclerótica/metabolismo , Neurotransmisores/metabolismoRESUMEN
INTRODUCTION: Since the discovery of gonadotropin-inhibitory hormone (GnIH), it has been found to play a critical role in reproduction in vertebrates. Recently, a regulatory role of GnIH in appetite and energy metabolism has emerged, although its precise physiological mechanisms remain unknown. METHODS: Thus, the present study evaluated the effects of a single or long-term intraperitoneal GnIH treatment on the food intake, weight, and glucolipid metabolism of chickens, as well as investigating the possible neuroendocrinology factors and mechanisms involved in GnIH-induced obesity and glucolipid metabolism disorder. RESULTS: Our results show that the intraperitoneal administration of GnIH to chickens resulted in a marked body mass increase, hyperlipidemia, hyperglycemia, and glucose intolerance. Subsequently, the results of metabolomics studies and the pharmacological inhibition of the 5-HT2C receptor revealed that blocking the 5-HT2C receptor reinforced the effects of GnIH on food intake, body weight, and blood glucose and lipid levels, resulting in even worse cases of GnIH-induced hyperglycemia, hyperlipidemia, and hepatic lipid deposition. This suggests that, via the 5-HT2C receptor, peripheral 5-HT may act as a negative feedback regulator to interplay with GnIH and jointly control energy balance homeostasis in chickens. DISCUSSION: Our present study provides evidence of cross-talk between GnIH and 5-HT in food intake and energy metabolism at the in vivo pharmacological level, and it proposes a molecular basis for these interactions, suggesting that functional interactions between GnIH and 5-HT may open new avenues for understanding the mechanism of the neuroendocrine network involved in appetite and energy metabolism, as well as providing a new therapeutic strategy to prevent obesity, diabetes, and metabolic disorders.
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Pollos , Metabolismo Energético , Conducta Alimentaria , Receptor de Serotonina 5-HT2C , Serotonina , Animales , Metabolismo Energético/efectos de los fármacos , Receptor de Serotonina 5-HT2C/metabolismo , Serotonina/metabolismo , Conducta Alimentaria/efectos de los fármacos , Conducta Alimentaria/fisiología , Hormonas Hipotalámicas/metabolismo , Masculino , Glucemia/metabolismo , Glucemia/efectos de los fármacos , Hiperlipidemias/metabolismo , Hiperlipidemias/inducido químicamenteRESUMEN
BACKGROUND: PCSK9 inhibitors are a novel class of lipid-lowering drugs that have demonstrated favorable efficacy and safety. Evolocumab and alirocumab have been added to China's National Reimbursement Drug List through the National Drug Price Negotiation (NDPN) policy. This study aims to evaluate the impact of the NDPN policy on the utilization and accessibility of these two PCSK9 inhibitors. METHODS: The procurement data of evolocumab and alirocumab were collected from 1,519 hospitals between January 2021 and December 2022. We determined the monthly availability, utilization, cost per daily defined dose (DDDc), and affordability of the two medicines. Single-group interrupted time series (ITS) analysis was performed to assess the impact of the NDPN policy on each drug, and multiple-group ITS analysis was performed to compare the differences between them. RESULTS: The NDPN policy led to a significant and sudden increase in the availability and utilization of PCSK9 inhibitors, along with a decrease in their DDDc. In the year following the policy implementation, there was an increase in the availability, utilization, and spending, and the DDDc remained stable. The affordability of PCSK9 inhibitors in China have been significantly improved, with a 92.97% reduction in out-of-pocket costs. The availability of both PCSK9 inhibitors was similar, and the DDDc of alirocumab was only $0.23 higher after the intervention. The market share of evolocumab consistently exceeded that of alirocumab. Regional disparities in utilization were observed, with higher utilization in the eastern region and a correlation with per capita disposable income. CONCLUSIONS: The NDPN policy has successfully improved the accessibility and utilization of PCSK9 inhibitors in China. However, regional disparities in utilization indicate the need for further interventions to ensure equitable medicine access.
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Anticuerpos Monoclonales Humanizados , Costos de los Medicamentos , Análisis de Series de Tiempo Interrumpido , Inhibidores de PCSK9 , Humanos , China , Anticuerpos Monoclonales Humanizados/uso terapéutico , Anticuerpos Monoclonales Humanizados/economía , Accesibilidad a los Servicios de Salud/estadística & datos numéricos , Anticolesterolemiantes/uso terapéutico , Anticolesterolemiantes/economía , Política de SaludRESUMEN
Rare earth elements (REEs) exposure during pregnancy may increase the risk of unexplained spontaneous abortion. However, the association between REEs intrauterine exposure and unexplained spontaneous abortion had yet to be studied. In order to conduct this large case-control study, we thus collected chorionic villus from 641 unexplained spontaneous abortion and 299 control pregnant women and detected the concentrations of 15 REEs by inductively coupled plasma mass spectrometer (ICP-MS). Because the detection rates of 10 REEs were less than 80%, the remaining 5 REEs, which were lanthanum (La), cerium (Ce), praseodymium (Pr), neodymium (Nd) and yttrium (Y), underwent to further analysis. The association between 5 REEs and unexplained spontaneous abortion was assessed by using the logistic regression, bayesian kernel regression (BKMR) and weighted quantile sum regression (WQS) models. In the adjusted logistic regression model, Pr, Nd and Y enhanced the incidence of unexplained spontaneous abortion in a dose-dependent way and Ce increased the risk only at high concentration group. The result of BKMR model demonstrated that the risk of unexplained spontaneous abortion increased as the percentile of five mixed REEs increased. Y and Nd were both significantly associated with an increased incidence of unexplained spontaneous abortion, but La was correlated with a decrease in the risk of unexplained spontaneous abortion. Pr was substantially associated with an increase in the risk of unexplained spontaneous abortion when other REEs concentrations were fixed at the 25th and 50th percentiles. According to WQS regression analysis, the WQS index was significantly associated with unexplained spontaneous abortion (OR = 3.75, 95% CI:2.40-5.86). Y had the highest weight, followed by Nd and Pr, which was consistent with the analysis results of our other two models. In short, intrauterine exposure to REEs was associated with an increased risk of unexplained spontaneous abortion, with Y, Nd and Pr perhaps playing an essential role.
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Aborto Espontáneo , Metales de Tierras Raras , Aborto Espontáneo/epidemiología , Aborto Espontáneo/inducido químicamente , Femenino , Humanos , Embarazo , Metales de Tierras Raras/análisis , Estudios de Casos y Controles , Adulto , Vellosidades Coriónicas , Adulto Joven , Modelos LogísticosRESUMEN
To analyse the imaging findings of papillary glioneuronal tumors (PGNTs), in order to improve the accuracy of preoperative diagnosis of this tumor. The clinical and imaging manifestations of 36 cases of PGNT confirmed by pathology were analyzed retrospectively. A total of 17 males and 19 females, averaging 22.47 (± 11.23) years. Initial symptoms included epilepsy in ten, headache in seven, and others in 19 cases. 97.2% (35/36) of the lesions were located in the supratentorial area, and 80.5% (29/36) in the intraventricular or deep white matter adjacent to the lateral ventricles. Twenty-four of the lesions (66.7%) were mixed cystic and solid, four (11.1%) were cystic with mural nodules, four (11.1%) were cystic, and four (11.1%) were solid. Four cases of PGNT of cystic imaging showed a "T2-FLAIR mismatch" sign. 69.4% (25/36) had septations. Nine lesions (25%) were accompanied by edema, and 9 (25%) of the mixed cystic and solid lesions were accompanied by hemorrhage. Among the 18 patients who underwent computed tomography (CT) or susceptibility-weighted imaging (SWI), nine had lesions with calcification. PGNTs mostly manifest as cystic mass with mural nodules or mixed cystic and solid mass in the white matter around the supratentorial ventricle, and the cystic part of the lesion is mostly accompanied by septations. Pure cystic lesions may exhibit the sign of "T2-FLAIR mismatch". PGNT is rarely accompanied by edema but sometimes by calcification and hemorrhage. Patients often present with seizures, headaches, and mass effect symptoms.
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Neoplasias Encefálicas , Imagen por Resonancia Magnética , Humanos , Masculino , Femenino , Adulto , Adolescente , Adulto Joven , Niño , Estudios Retrospectivos , Neoplasias Encefálicas/diagnóstico por imagen , Neoplasias Encefálicas/patología , Neoplasias Encefálicas/cirugía , Tomografía Computarizada por Rayos X , Persona de Mediana Edad , Ganglioglioma/cirugía , Ganglioglioma/patología , Ganglioglioma/diagnóstico por imagen , PreescolarRESUMEN
Nasopharyngeal carcinoma (NPC) is a malignant tumor with high metastatic features originating from the nasopharynx. However, the underlying mechanism of Suppressor of variegation 3-9 homolog 2 (SUV39H2) in NPC remains poorly understood. RT-qPCR was carried out to examine SUV39H2 and SIRT1 expression in NPC tissues and cells. Kaplan-Meier method was utilized to evaluate the association between SUV39H2 level and overall survival. The function of SUV39H2 and SIRT1 in NPC cell viability, metastasis, and apoptosis was tested through CCK-8, transwell, and flow cytometry experiments. Here, it was uncovered that SUV39H2 level was augmented in NPC tissues and cells. Moreover, SUV39H2 expedited NPC cell viability, metastasis, and inhibited apoptosis, while SIRT1 addition reversed these impacts. Besides, SUV39H2 induced H3K9me3 enhancement to repress SIRT1 transcription via binding to SIRT1 promoter. Collectively, our results demonstrated upregulated SUV39H2 aggravated NPC tumorigenesis through SIRT1, which may offer a potential therapeutic target for NPC.
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N-Metiltransferasa de Histona-Lisina , Carcinoma Nasofaríngeo , Neoplasias Nasofaríngeas , Sirtuina 1 , Sirtuina 1/metabolismo , Sirtuina 1/genética , Humanos , Carcinoma Nasofaríngeo/patología , Carcinoma Nasofaríngeo/genética , Carcinoma Nasofaríngeo/metabolismo , Línea Celular Tumoral , Neoplasias Nasofaríngeas/patología , Neoplasias Nasofaríngeas/genética , Neoplasias Nasofaríngeas/mortalidad , N-Metiltransferasa de Histona-Lisina/genética , N-Metiltransferasa de Histona-Lisina/metabolismo , Apoptosis , Supervivencia Celular , Regulación Neoplásica de la Expresión Génica , Metástasis de la NeoplasiaRESUMEN
Bottom-up synthesized graphene nanoribbons (GNRs) are increasingly attracting interest due to their atomically controlled structure and customizable physical properties. In recent years, a range of GNR-based field-effect transistors (FETs) has been fabricated, with several demonstrating quantum-dot (QD) behavior at cryogenic temperatures. However, understanding the relationship between the cryogenic charge-transport characteristics and the number of the GNRs in the device is challenging, as the length and location of the GNRs in the junction are not precisely controlled. Here, we present a methodology based on a dual-gate FET that allows us to identify different scenarios, such as single GNRs, double or multiple GNRs in parallel, and a single GNR interacting with charge traps. Our dual-gate FET architecture therefore offers a quantitative approach for comprehending charge transport in atomically precise GNRs.
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Human movement trajectories can reveal useful insights regarding the underlying mechanisms of human behaviors. Extracting information from movement trajectories, however, can be challenging because of their complex and dynamic nature. The current paper presents a Python toolkit developed to help users analyze and extract meaningful information from the trajectories of discrete rapid aiming movements executed by humans. This toolkit uses various open-source Python libraries, such as NumPy and SciPy, and offers a collection of common functionalities to analyze movement trajectory data. To ensure flexibility and ease of use, the toolkit offers two approaches: an automated approach that processes raw data and generates relevant measures automatically, and a manual approach that allows users to selectively use different functions based on their specific needs. A behavioral experiment based on the spatial cueing paradigm was conducted to illustrate how one can use this toolkit in practice. Readers are encouraged to access the publicly available data and relevant analysis scripts as an opportunity to learn about kinematic analysis for human movements.
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Movimiento , Programas Informáticos , Humanos , Movimiento/fisiología , Fenómenos Biomecánicos , Lenguajes de Programación , MasculinoRESUMEN
Embedding both boron and nitrogen into the backbone of acenes to generate their isoelectronic structures has significantly enriched the acene chemistry to offer appealing properties. However, only small BN-heteroacenes have been extensively investigated, with BN-heptacenes as the hitherto longest homologue. Herein, we report the synthesis of three new nonacene BN-isosteres via incorporating a pair of antiaromatic B2 C4 and N2 C4 heterocycles, representing a new length record for BN-heteroacenes. The distance between the B2 C4 and N2 C4 rings affects the contribution of the charge-separated resonance forms, leading to tunable antiaromaticity of the two heterocycles. The adjusted local antiaromaticity manifests substantial influence on the molecular orbital arrangement, and consequently, the radiative transition rate of BN-3 is greatly enhanced compared with BN-1 and BN-2, realizing a high fluorescence quantum yield of 92 %. This work provides a novel design concept of large acene BN-isosteres and reveals the importance of BN/CC isosterism on their luminescent properties.
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Mixed reality technologies, such as virtual (VR) and augmented (AR) reality, present promising opportunities to advance education and professional training due to their adaptability to diverse contexts. Distortions in the perceived distance in such mediated conditions, however, are well documented and have imposed nontrivial challenges that complicate and limit transferring task performance in a virtual setting to the unmediated reality (UR). One potential source of the distance distortion is the vergence-accommodation conflict-the discrepancy between the depth specified by the eyes' accommodative state and the angle at which the eyes converge to fixate on a target. The present study involved the use of a manual pointing task in UR, VR, and AR to quantify the magnitude of the potential depth distortion in each modality. Conceptualizing the effect of vergence-accommodation offset as a constant offset to the vergence angle, a model was developed based on the stereoscopic viewing geometry. Different versions of the model were used to fit and predict the behavioral data for all modalities. Results confirmed the validity of the conceptualization of vergence-accommodation as a device-specific vergence offset, which predicted up to 66% of the variance in the data. The fitted parameters indicate that, due to the vergence-accommodation conflict, participants' vergence angle was driven outwards by approximately 0.2°, which disrupted the stereoscopic viewing geometry and produced distance distortion in VR and AR. The implications of this finding are discussed in the context of developing virtual environments that minimize the effect of depth distortion.
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Prolonged exposure of the peritoneum to high glucose dialysate leads to the development of peritoneal fibrosis (PF), and apoptosis of peritoneal mesothelial cells (PMCs) is a major cause of PF. The aim of this study is to investigate whether Astragaloside IV could protect PMCs from apoptosis and alleviate PF. PMCs and rats PF models were induced by high glucose peritoneal fluid. We examined the pathology of rat peritoneal tissue by HE staining, the thickness of rat peritoneal tissue by Masson's staining, the number of mitochondria and oxidative stress levels in peritoneal tissue by JC-1 and DHE fluorescence staining, and mitochondria-related proteins and apoptosis-related proteins such as PGC-1α, NRF1, TFAM, Caspase3, Bcl2 smad2 were measured. We used hoechst staining and flow cytometry to assess the apoptotic rate of PMCs in the PF model, and further validated the observed changes in the expressions of PGC-1α, NRF1, TFAM, Caspase3, Bcl2 smad2 in PMCs. We further incubated PMCs with MG-132 (proteasome inhibitor) and Cyclohexylamine (protein synthesis inhibitor). The results demonstrated that Astragaloside IV increased the expression of PGC-1α by reducing the ubiquitination of PGC-1α. It was further found that the protective effects of Astragaloside IV on PMCs were blocked when PGC-1α was inhibited. In conclusion, Astragaloside IV effectively alleviated PF both in vitro and in vivo, possibly by promoting PGC-1α to enhance mitochondrial synthesis to reduce apoptotic effects.
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Fibrosis Peritoneal , Ratas , Animales , Fibrosis Peritoneal/patología , Peritoneo/patología , Apoptosis , Glucosa/metabolismo , Coactivador 1-alfa del Receptor Activado por Proliferadores de Peroxisomas gamma/genética , Coactivador 1-alfa del Receptor Activado por Proliferadores de Peroxisomas gamma/metabolismoRESUMEN
Ferroptosis is an iron-dependent and phospholipid peroxidation-mediated cell death, which has been identified to be involved in sepsis-induced injury. However, the in-depth molecular mechanisms of N6-methyladenosine (m6A) and ferroptosis on sepsis-induced myocardial injury are still unclear. Here, in the septic myocardial injury, m6A methyltransferase METTL3 level and methylation level high-expressed in lipopolysaccharide (LPS)-induced cardiomyocytes (H9C2). Functionally, METTL3 silencing repressed the ferroptosis phenotype induced by LPS. Mechanistically, METTL3-mediated m6A methylation on solute carrier family 7 member 11 (SLC7A11) empowered its mRNA with high methylation level. Moreover, YTHDF2 directly bound to the m6A modification sites of SLC7A11 to mediate the mRNA degradation. The m6A modified SLC7A11 mRNA was recognized by YTHDF2, which promoted the decay of SLC7A11 mRNA, consequently up-regulating ferroptosis in sepsis-induced myocardial injury. Together, these findings establish a role of METTL3 in the ferroptosis of LPS-induced cardiomyocytes, and provide potential therapeutic target to treat the sepsis-induced myocardial injury.
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Ferroptosis , Sepsis , Humanos , Apoptosis , Ferroptosis/genética , Lipopolisacáridos/farmacología , Metiltransferasas/genética , Metiltransferasas/metabolismo , ARN Mensajero/genética , ARN Mensajero/metabolismo , Sepsis/complicaciones , Sepsis/genética , Factores de TranscripciónRESUMEN
BACKGROUND: The initial cases of novel coronavirus (2019-nCoV)-infected pneumonia (NCIP) occurred in Wuhan, Hubei Province, China, in December 2019 and January 2020. We analyzed data on the first 425 confirmed cases in Wuhan to determine the epidemiologic characteristics of NCIP. METHODS: We collected information on demographic characteristics, exposure history, and illness timelines of laboratory-confirmed cases of NCIP that had been reported by January 22, 2020. We described characteristics of the cases and estimated the key epidemiologic time-delay distributions. In the early period of exponential growth, we estimated the epidemic doubling time and the basic reproductive number. RESULTS: Among the first 425 patients with confirmed NCIP, the median age was 59 years and 56% were male. The majority of cases (55%) with onset before January 1, 2020, were linked to the Huanan Seafood Wholesale Market, as compared with 8.6% of the subsequent cases. The mean incubation period was 5.2 days (95% confidence interval [CI], 4.1 to 7.0), with the 95th percentile of the distribution at 12.5 days. In its early stages, the epidemic doubled in size every 7.4 days. With a mean serial interval of 7.5 days (95% CI, 5.3 to 19), the basic reproductive number was estimated to be 2.2 (95% CI, 1.4 to 3.9). CONCLUSIONS: On the basis of this information, there is evidence that human-to-human transmission has occurred among close contacts since the middle of December 2019. Considerable efforts to reduce transmission will be required to control outbreaks if similar dynamics apply elsewhere. Measures to prevent or reduce transmission should be implemented in populations at risk. (Funded by the Ministry of Science and Technology of China and others.).
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Betacoronavirus , Infecciones por Coronavirus/epidemiología , Infecciones por Coronavirus/transmisión , Transmisión de Enfermedad Infecciosa/estadística & datos numéricos , Epidemias , Periodo de Incubación de Enfermedades Infecciosas , Neumonía Viral/epidemiología , Neumonía Viral/transmisión , Adolescente , Adulto , Anciano , Betacoronavirus/genética , COVID-19 , China/epidemiología , Control de Enfermedades Transmisibles/métodos , Infecciones por Coronavirus/virología , Transmisión de Enfermedad Infecciosa/prevención & control , Epidemias/prevención & control , Femenino , Humanos , Incidencia , Masculino , Persona de Mediana Edad , Pandemias , Neumonía Viral/virología , Reacción en Cadena de la Polimerasa , SARS-CoV-2 , Adulto JovenRESUMEN
Escherichia coli is a common conditional pathogen, for which antibiotic therapy is considered an effective treatment. The imprudent use of antibiotics has led to the increase of multiple-antibiotic-resistant E. coli species. With the incidence of antibiotic resistance reaching a crisis point, it is imperative to find alternative treatments for multidrug-resistant infections. Using phage for pathogen control is a promising treatment option to combat bacterial resistance. In this study, a novel virulent Podoviridae phage Kayfunavirus TM1 infecting Escherichia coli was isolated from pig farm sewage in Guangxi, China. The one-step growth curve with the optimal multiplicity of infection of 0.01 revealed a latent period of 10 min and a burst size of 50 plaque-forming units per cell. The stability test reveals that it is stable from 4 to 60 °C and pH from 3 to 11. The double-stranded DNA genome of phage Kayfunavirus TM1 is composed of 39,948 base pairs with a GC content of 50.03%.
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Bacteriófagos , Porcinos , Animales , Bacteriófagos/genética , Escherichia coli/genética , Genoma Viral , ADN Viral/genética , China , AntibacterianosRESUMEN
BACKGROUND: Escherichia coli (E. coli) is a common pathogen that often causes diarrhea in piglets. Since bacteria are becoming more and more resistant to antibiotics, phages have become a promising alternative therapy. However, the therapy of oral phage often fails to achieve the desired effect. A novel phage named A221 was isolated by using E. coli GXXW-1103 as host strain, characterized by electron microscopy, genomic sequencing and analyzed by measuring lysis ability in vitro. RESULTS: Phage A221 was identified as a member of Ackermannviridae, Aglimvirinae, Agtrevirus with 153297 bp genome and effectively inhibited bacterial growth in vitro for 16 h. This study was conducted to evaluate the therapeutic effect of oral microencapsulated phage A221 on E. coli GXXW-1103 infections in weaned piglets. The protective effect of phage was evaluated by body weight analysis, bacterial load and histopathological changes. The results showed that with the treatment of phage A221, the body weight of piglets increased, the percentage of Enterobacteriaceae in duodenum decreased to 0.64%, the lesions in cecum and duodenum were alleviated, and the bacterial load in the jejunal lymph nodes, cecum and spleen were also significantly different with infected group (P < 0.001). CONCLUSIONS: The results showed that phage A221 significantly increased the daily weight gain of piglets, reduced the bacterial load of tissues and the intestinal lesions, achieved the same therapeutic effect as antibiotic Florfenicol. Taken together, oral microencapsulated phage A221 has a good therapeutic effect on bacterial diarrhea of weaned piglets, which provides guidance for the clinical application of phage therapy in the future.
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Bacteriófagos , Infecciones por Escherichia coli , Terapia de Fagos , Enfermedades de los Porcinos , Animales , Porcinos , Escherichia coli , Terapia de Fagos/veterinaria , Infecciones por Escherichia coli/terapia , Infecciones por Escherichia coli/veterinaria , Diarrea/terapia , Diarrea/veterinaria , Antibacterianos/uso terapéutico , Peso Corporal , Enfermedades de los Porcinos/terapiaRESUMEN
Depression is a highly prevalent and heterogeneous disorder that requires new strategies to overcome depression. In this study, we aimed to investigate whether leonurine modulated hippocampal nerve regeneration in chronic and unpredictable mild stress (CUMS) rats through the SHH/GLI signaling pathway and restoring gut microbiota and microbial metabolic homeostasis. The CUMS rat model was constructed and treated with leonurine. The body weight of rats was recorded, and a series of tests were performed. Western blot was utilized to measure the expression of BDNF and 5-HT in the hippocampus. Then the expression of SHH, GLI, PTCH, and SMO were measured by qRT-PCR and western blot. The colocalization of BrdU+DCX and BrdU+NeuN was evaluated by IF. 16S rDNA high-throughput sequencing was applied to detect the composition and distribution of gut microbiota. The differential metabolites were analyzed by untargeted metabolomics. The correlation between gut microbiota and microbial metabolites was analyzed by Pearson correlation coefficient. After CUMS modeling, the body weight of rats was decreased, and the expression of BDNF and 5-HT were decreased, while the body weight was recovered, and the expression of BDNF and 5-HT were increased after leonurine treatment. Leonurine reversed the reduction in the colocalization of BrdU+DCX and BrdU+NeuN and the reduction in the levels of SHH, GLI, PTCH, and SMO induced by CUMS modeling. Leonurine also restored gut microbiota and microbial metabolites homeostasis in CUMS rats. Furthermore, Prevotellaceae_Ga6A1_group was negatively correlated with 3-Oxocholic acid, nutriacholic acid, and cholic acid. Collectively, leonurine regulated hippocampal nerve regeneration in CUMS rats by activating the SHH/GLI signaling pathway and restoring gut microbiota and microbial metabolic homeostasis.
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Depresión , Microbioma Gastrointestinal , Ratas , Animales , Depresión/metabolismo , Factor Neurotrófico Derivado del Encéfalo/metabolismo , Serotonina/metabolismo , Bromodesoxiuridina/metabolismo , Regeneración Nerviosa , Homeostasis , Transducción de Señal , Hipocampo/metabolismo , Peso Corporal , Estrés Psicológico/metabolismo , Modelos Animales de EnfermedadRESUMEN
The design of an integrated sensing and communication (ISAC) waveform compatible with the 5G new radio (NR) system is crucial in enabling ISAC by utilizing the hardware of existing base stations (BSs). In this paper, we design an inner-frame time division multiplexed sensing waveform in the frame structure of 5G NR to achieve ISAC. The designed waveform is computed by the simulated annealing algorithm on an optimization cost function of a constrained combination of the peak-to-sidelobe ratio (PSLR) and the integrated sidelobe ratio (ISLR) of the velocity ambiguity function. Specifically, the constraints are the 5G communication protocol and 5G NR frame structure. In addition, we conducted corresponding signal detection and estimation methods to illustrate the performance of the sensing waveform. Both theoretical analysis and simulation experiments show that the designed waveform can effectively achieve target detection and parameter estimation under low sensing cost conditions.