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Photoionization and dissociative photoionization of acetaldehyde (CH3CHO) in the 10.0-13.7â eV energy range are studied by using synchrotron radiation double imaging photoelectron photoion coincidence spectroscopy (i2PEPICO). The X2A' and A2A" electronic states of CH3CHO+ as well as the Franck-Condon gap region between these two states have been populated with several vibrational sequences and assigned in the high-resolution slow photoelectron spectrum (SPES). The adiabatic ionization energies (AIEs) of the X2A' and A2A" states are measured at 10.228±0.006 and 12.52±0.05â eV, respectively. The present results show that the X2A' state is a stable state while the A2A" state is fully dissociative to produce CH3CO+, CHO+ and CH4 + fragment ions. The 0â K appearance energies (AE0K) of CH3CO+ and CHO+ fragment ions are determined through the modeling of the breakdown diagram, i. e., AE0K(CH3CO+)=10.89±0.01â eV (including a reverse barrier of ~0.19â eV) and AE0K(CHO+)=11.54±0.05â eV. In addition, the dissociation mechanisms of CH3CHO+ including statistical dissociation, direct bond breaking and isomerization are discussed with the support of the calculated dissociation limits and transition state energies.
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OBJECTIVES: To develop and validate a prediction tool for pediatric acute liver failure (PALF) mortality risks that captures the rapid and heterogeneous clinical course for accurate and updated prediction. METHODS: Data included 1144 participants with PALF enrolled during three phases of the PALF registry study over 15 years. Using joint modeling, we built a dynamic prediction tool for mortality by combining longitudinal trajectories of multiple laboratory and clinical variables. The predictive performance for 7-day and 21-day mortality was assessed using the area under curve (AUC) through cross-validation and split-by-time validation. RESULTS: We constructed a prognostic joint model that combines the temporal trajectories of international normalized ratio, total bilirubin, hepatic encephalopathy, platelet count, and serum creatinine. Dynamic prediction using updated information improved predictive performance over static prediction using the information at enrollment (Day 0) only. In cross-validation, AUC increased from 0.784 to 0.887 when measurements obtained between Days 1 and 2 were incorporated. AUC remained similar when we used the earlier subset of the sample for training and the later subset for testing. CONCLUSIONS: Serial measurements of five variables in the first few days of PALF capture the dynamic clinical course of the disease and improve risk prediction for mortality. Continuous disease monitoring and updating risk prognosis are beneficial for timely and judicious medical decisions.
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Encefalopatía Hepática , Fallo Hepático Agudo , Niño , Humanos , Fallo Hepático Agudo/diagnóstico , Pronóstico , Bilirrubina , Progresión de la EnfermedadRESUMEN
Trauma is a common cause of cutaneous surgical disease with an increased risk of secondary infection in cat clinics. Platelet-rich fibrin (PRF), a platelet and leukocyte concentrate containing multiple cytokines and growth factors, is known to accelerate the healing of wounds. However, how PRF affects wound healing in the cat trauma model has not been fully investigated. The study aimed to examine the impact of PRF on skin wound healing in the cat trauma model. In this study, PRF from cats was successfully produced for our investigation. The models of feline trauma were effectively established. A total of 18 cats were randomly divided into 3 groups (n = 6): (1) Control group (CON); (2) PRF group; (3) Manuka honey group (MAN, as a positive control). Experiments were performed separately on days 7, 14, 21, and 28. Our results showed that PRF was a safe and efficient method of wound healing that did not influence the cat's body temperature, respiration rate, and heart rate (HR). PRF accelerated skin wound healing in the cat trauma model based on the rate and histological observation of wound healing. In addition, PRF promoted the production of growth factors and suppressed inflammation during wound healing. PRF accelerated wound healing by increasing the formation of collagen fibers, as shown by Masson-trichrome staining. The outcomes of the PRF and MAN groups were comparable. In conclusion, PRF improves the healing of skin wounds in cats by boosting the synthesis of growth factors, reducing inflammation, and enhancing the synthesis of collagen fibers.
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Fibrina Rica en Plaquetas , Piel , Cicatrización de Heridas , Animales , Gatos/lesiones , Piel/lesiones , Heridas y Lesiones/veterinaria , Heridas y Lesiones/terapia , Masculino , Femenino , Modelos Animales de EnfermedadRESUMEN
Modeling disease risk and survival using longitudinal risk factor trajectories is of interest in various clinical scenarios. The capacity to build a prognostic model using the trajectories of multiple longitudinal risk factors, in the presence of potential dependent censoring, would enable more informed, personalized decision making. A dynamic risk score modeling framework is proposed for multiple longitudinal risk factors and survival in the presence of dependent censoring, where both events depend on participants' post-baseline clinical progression and form a competing risks structure. The model requires relatively few random effects regardless of the number of longitudinal risk factors and can therefore accommodate multiple longitudinal risk factors in a parsimonious manner. The proposed method performed satisfactorily in extensive simulation studies. It is further applied to the motivating registry study on pediatric acute liver failure to model death using the trajectories of multiple clinical and biochemical markers. Once established, the model yields an easily calculable longitudinal risk score that can be used for disease monitoring among future patients.
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Polymer-dispersed liquid crystals (PDLCs) are very attractive due to their electrically switchable properties. However, current PDLC films still have problems such as high driving voltages, low contrast ratio (CR), and poor bending resistance and spacing stability. To solve these problems, a PDLC film with a system of coexisting polymer spacer columns and polymer network was proposed. First, based on the adhesive systems of IBMA and UV6301, the effects of IBMA concentration and LC content on the morphology of the polymer network and the electro-optical properties of PDLC were investigated, respectively. Then, the effects of the process conditions of mask polymerization such as temperature, time, and UV light intensity on the morphology and electro-optical properties of the polymer spacer columns were systematically investigated. It was found that PDLC films with the coexistence system exhibit both excellent electro-optical properties and outstanding bending resistance and spacing stability. Thus, it provides new practical possibilities for the preparation of high-performance PDLC films used in flexible devices.
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BACKGROUND: Certain bacterial infectious diseases are categorized as notifiable infectious diseases in China. Understanding the time-varying epidemiology of bacterial infections diseases can provide scientific evidence to inform prevention and control measures. METHODS: Yearly incidence data for all 17 major notifiable bacterial infectious diseases (BIDs) at the province level were obtained from the National Notifiable Infectious Disease Reporting Information System in China between 2004 and 2019. Of them 16 BIDs are divided into four categories, respiratory transmitted diseases (RTDs, 6 diseases), direct contact/fecal-oral transmitted diseases (DCFTDs, 3 diseases), blood-borne/sexually transmitted diseases (BSTDs, 2 diseases), and zoonotic and vector-borne diseases (ZVDs, 5 diseases), and neonatal tetanus is excluded in the analysis. We characterized the demographic, temporal, and geographical features of the BIDs and examined their changing trends using a joinpoint regression analysis. RESULTS: During 2004â2019, 28 779 thousand cases of BIDs were reported, with an annualized incidence rate of 134.00 per 100 000. RTDs were the most commonly reported BIDs, accounting for 57.02% of the cases (16 410 639/28 779 000). Average annual percent changes (AAPC) in incidence were - 1.98% for RTDs, - 11.66% for DCFTDs, 4.74% for BSTDs, and 4.46% for ZVDs. Females had a higher incidence of syphilis than males, and other BIDs were more commonly reported in males. Among 0-5-year-olds, the diseases with the largest increases in incidence were pertussis (15.17% AAPC) and scarlet fever (12.05%). Children and students had the highest incidence rates of scarlet fever, pertussis, meningococcal meningitis, and bacillary dysentery. Northwest China had the highest incidence of RTDs, while South and East China had the highest incidences of BSTDs. Laboratory confirmation of BIDs increased from 43.80 to 64.04% during the study period. CONCLUSIONS: RTDs and DCFTDs decreased from 2004 to 2019 in China, while BSTDs and ZVDs increased during the same period. Great attention should be paid to BSTDs and ZVDs, active surveillance should be strengthened, and timely control measures should be adopted to reduce the incidence.
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Enfermedades Transmisibles , Escarlatina , Tos Ferina , Masculino , Niño , Femenino , Recién Nacido , Humanos , Preescolar , Incidencia , Escarlatina/epidemiología , Enfermedades Transmisibles/epidemiología , China/epidemiologíaRESUMEN
The cross-reaction of ethyl peroxy radicals (C2H5O2) with methyl peroxy radicals (CH3O2) (R1) has been studied using laser photolysis coupled to time resolved detection of the two different peroxy radicals by continuous wave cavity ring down spectroscopy (cw-CRDS) in their AÃ-XÌ electronic transition in the near-infrared region, C2H5O2 at 7602.25 cm-1, and CH3O2 at 7488.13 cm-1. This detection scheme is not completely selective for both radicals, but it is demonstrated that it has great advantages compared to the widely used, but unselective UV absorption spectroscopy. Peroxy radicals were generated from the reaction of Cl-atoms with the appropriate hydrocarbon (CH4 and C2H6) in the presence of O2, whereby Cl-atoms were generated by 351 nm photolysis of Cl2. For different reasons detailed in the manuscript, all experiments were carried out under excess of C2H5O2 over CH3O2. The experimental results were best reproduced by an appropriate chemical model with a rate constant for the cross-reaction of k = (3.8 ± 1.0) × 10-13 cm3 s-1 and a yield for the radical channel, leading to CH3O and C2H5O, of (Ï1a = 0.40 ± 0.20).
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Organic peroxy radicals (RO2) as key intermediates in tropospheric chemistry exert a controlling influence on the cycling of atmospheric reactive radicals and the production of secondary pollutants, such as ozone and secondary organic aerosols (SOA). Herein, we present a comprehensive study of the self-reaction of ethyl peroxy radicals (C2H5O2) by using advanced vacuum ultraviolet (VUV) photoionization mass spectrometry in combination with theoretical calculations. A VUV discharge lamp in Hefei and synchrotron radiation at the Swiss Light Source (SLS) are employed as the photoionization light sources, combined with a microwave discharge fast flow reactor in Hefei and a laser photolysis reactor at the SLS. The dimeric product, C2H5OOC2H5, as well as other products, CH3CHO, C2H5OH and C2H5O, formed from the self-reaction of C2H5O2 are clearly observed in the photoionization mass spectra. Two kinds of kinetic experiments have been performed in Hefei by either changing the reaction time or the initial concentration of C2H5O2 radicals to confirm the origins of the products and to validate the reaction mechanisms. Based on the fitting of the kinetic data with the theoretically calculated results and the peak area ratios in the photoionization mass spectra, a branching ratio of 10 ± 5% for the pathway leading to the dimeric product C2H5OOC2H5 is measured. In addition, the adiabatic ionization energy (AIE) of C2H5OOC2H5 is determined at 8.75 ± 0.05 eV in the photoionization spectrum with the aid of Franck-Condon calculations and its structure is revealed here for the first time. The potential energy surface of the C2H5O2 self-reaction has also been theoretically calculated with a high-level of theory to understand the reaction processes in detail. This study provides a new insight into the direct measurement of the elusive dimeric product ROOR and demonstrates its non-negligible branching ratio in the self-reaction of small RO2 radicals.
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Ozono , Vacio , Espectrometría de Masas/métodos , FotólisisRESUMEN
We present a vacuum ultraviolet (VUV) photoionization study of the gas-phase sulfuric acid (H2SO4) molecule in the 11-14 eV energy range by using the method of synchrotron radiation-based double imaging photoelectron photoion coincidence (i2PEPICO) spectroscopy complemented with accurate theoretical calculations. The slow photoelectron spectrum (SPES) of H2SO4 has been acquired and the three electronic states of H2SO4+, X2A, A2A and B2A have been populated and assigned. The adiabatic ionization energy of the H2SO4 molecule towards the X2A cationic ground state is measured at 11.684 ± 0.006 eV, in accordance with high-level calculated findings. With increasing photon energies, the H2SO4+ cation dissociates into HSO3+ and OH fragments and their adiabatic appearance energy is measured at 13.498 ± 0.007 eV. Then, the enthalpies of formation for the species involved in the photoionization and dissociative photoionization have been determined through a thermochemical cycle.
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The Cl-initiated oxidation of methacrolein (MACR, C4H6O) under NOx-free conditions has been investigated in a fast flow tube by using a home-made vacuum ultraviolet (VUV) photoionization mass spectrometer complemented by high-level theoretical calculations. The key species such as intermediates and radicals together with products involved in the oxidation are observed online and confirmed in photoionization mass spectra. The reaction potential energy surfaces of the transient C4H5O and C4H6OCl radicals, formed from the hydrogen-abstraction reaction and the addition reaction of MACR with Cl atoms, with oxygen have been theoretically calculated to illuminate the formation of the peroxy radicals of C4H5OO2 and C4H6OClO2. The photoionization processes of these peroxy radicals, whose cations are not stable, and their individual self-reactions as well as bimolecular reactions with HO2 radical are studied and discussed. In addition, kinetic experiments are also performed to get the time evolution of specific products and compared with theoretical models, providing a detailed insight into the reaction mechanism of the Cl-initiated oxidation of MACR.
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BACKGROUND: To investigate deep vein thrombosis (DVT) in hospitalized patients with coronavirus disease 2019 (COVID-19), we performed a single institutional study to evaluate its prevalence, risk factors, prognosis, and potential thromboprophylaxis strategies in a large referral and treatment center. METHODS: We studied a total of 143 patients with COVID-19 from January 29, 2020 to February 29, 2020. Demographic and clinical data, laboratory data, including ultrasound scans of the lower extremities, and outcome variables were obtained, and comparisons were made between groups with and without DVT. RESULTS: Of the 143 patients hospitalized with COVID-19 (age 63±14 years, 74 [51.7%] men), 66 patients developed lower extremity DVT (46.1%: 23 [34.8%] with proximal DVT and 43 [65.2%] with distal DVT). Compared with patients who did not have DVT, patients with DVT were older and had a lower oxygenation index, a higher rate of cardiac injury, and worse prognosis, including an increased proportion of deaths (23 [34.8%] versus 9 [11.7%]; P=0.001) and a decreased proportion of patients discharged (32 [48.5%] versus 60 [77.9%]; P<0.001). Multivariant analysis showed an association only between CURB-65 (confusion status, urea, respiratory rate, and blood pressure) score 3 to 5 (odds ratio, 6.122; P=0.031), Padua prediction score ≥4 (odds ratio, 4.016; P=0.04), D-dimer >1.0 µg/mL (odds ratio, 5.818; P<0.014), and DVT in this cohort, respectively. The combination of a CURB-65 score 3 to 5, a Padua prediction score ≥4, and D-dimer >1.0 µg/mL has a sensitivity of 88.52% and a specificity of 61.43% for screening for DVT. In the subgroup of patients with a Padua prediction score ≥4 and whose ultrasound scans were performed >72 hours after admission, DVT was present in 18 (34.0%) patients in the subgroup receiving venous thromboembolism prophylaxis versus 35 (66.0%) patients in the nonprophylaxis group (P=0.010). CONCLUSIONS: The prevalence of DVT is high and is associated with adverse outcomes in hospitalized patients with COVID-19. Prophylaxis for venous thromboembolism may be protective in patients with a Padua protection score ≥4 after admission. Our data seem to suggest that COVID-19 is probably an additional risk factor for DVT in hospitalized patients.
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Infecciones por Coronavirus/diagnóstico , Neumonía Viral/diagnóstico , Trombosis de la Vena/diagnóstico , Adulto , Anciano , Anticoagulantes/uso terapéutico , Betacoronavirus/aislamiento & purificación , Presión Sanguínea , COVID-19 , China/epidemiología , Infecciones por Coronavirus/complicaciones , Infecciones por Coronavirus/mortalidad , Infecciones por Coronavirus/fisiopatología , Femenino , Productos de Degradación de Fibrina-Fibrinógeno/análisis , Humanos , Estimación de Kaplan-Meier , Extremidad Inferior/diagnóstico por imagen , Masculino , Persona de Mediana Edad , Oportunidad Relativa , Pandemias , Neumonía Viral/complicaciones , Neumonía Viral/mortalidad , Neumonía Viral/fisiopatología , Prevalencia , Pronóstico , Frecuencia Respiratoria , Estudios Retrospectivos , Factores de Riesgo , SARS-CoV-2 , Resultado del Tratamiento , Trombosis de la Vena/complicaciones , Trombosis de la Vena/tratamiento farmacológico , Trombosis de la Vena/epidemiologíaRESUMEN
BACKGROUND: Panic disorder (PD) is thought to be related with deficits in emotion regulation, especially in cognitive reappraisal. According to the cognitive model, PD patients' intrinsic and unconscious misappraisal strategies are the cause of panic attacks. However, no studies have yet been performed to explore the underlying neuromechanism of cognitive reappraisal that occur on an unconscious level in PD patients. METHODS: Twenty-six patients with PD and 25 healthy controls (HC) performed a fully-verified event-block design emotional regulation task aimed at investigating responses of implicit cognitive reappraisal during an fMRI scan. Participants passively viewed negatively valanced pictures that were beforehand neutrally, positively, or adversely portrayed in the task. RESULTS: Whole-brain analysis of fMRI data showed that PD patients exhibited less activation in the right dorsolateral prefrontal cortex (dlPFC) and right dorsomedial prefrontal cortex (dmPFC) compared to HC, but presented greater activation in parietal cortex when negative pictures were preceded by positive/neutral vs negative descriptions. Simultaneously, interactive effects of Group × Condition were observed in the right amygdala across both groups. Furthermore, activation in dlPFC and dmPFC was is negatively correlated to severity of anxiety and panic in PD when negative images were preceded by non-negative vs negative descriptions. CONCLUSIONS: Emotional dysregulation in PD is likely the result of deficient activation in dlPFC and dmPFC during implicit cognitive reappraisal, in line with impaired automatic top-down regulation. Correlations between severity of anxiety and panic attack and activation of right dlPFC and dmPFC suggest that the failure to engage prefrontal region during implicit cognitive reappraisal might be associated wtih the severity of anxiety and panic; such functional patterns might be the target of possible treatments.
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Trastorno de Pánico , Mapeo Encefálico , Cognición , Emociones , Humanos , Imagen por Resonancia Magnética , Trastorno de Pánico/complicaciones , Trastorno de Pánico/diagnóstico por imagenRESUMEN
We study the conformers of the ethyl peroxy radical (C2H5O2), the simplest peroxy radical having more than one conformer, by combining synchrotron radiation vacuum ultraviolet (VUV) photoionization mass spectrometry with theoretical calculations. The ethyl peroxy radical is formed in a microwave discharge flow tube through the reaction of the ethyl radical (C2H5) with oxygen molecules, where C2H5 is generated via the hydrogen-abstraction reaction of ethane with fluorine atoms. Two kinds of C2H5+, originating from photoionization of C2H5 and from dissociative photoionization of C2H5O2, whose cation is not stable, have been identified and separated in photoionization mass spectra. The photoionization spectrum corresponding to C2H5O2 is obtained and assigned with Franck-Condon calculations. The present findings show that the gauche conformer (G-C2H5O2) of C2H5O2 has favorable Franck-Condon factors in the ionization transitions, whereas the contribution of the trans conformer (T-C2H5O2) to the photoionization spectrum is minor or negligible due to its large geometric changes in the photoionization process. Moreover, the reason for the instability of C2H5O2+ and its detailed dissociation mechanisms have been unraveled with the aid of the calculated potential energy curves.
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Brain-derived neurotropic factor (BDNF) deficiency in Schwann cells plays an important role in the pathogenesis of diabetic peripheral neuropathy (DPN). Little is known about the mechanism involved in BDNF downregulation in Schwann cells in DPN. In this study, we first confirmed downregulation of BDNF and neurotrophin 3 expression in the sciatic nerves of diabetic mice, which was accompanied by myelin sheath abnormalities. Moreover, in vitro, high glucose was revealed to cause downregulation of BDNF, but not neurotrophin 3, expression in RSC96â¯cells, which was accompanied by DNA hypermethylation of BDNF promoters I and II. DNMT1 was subsequently revealed to be enhanced at the mRNA and protein levels in high glucose-stimulated RSC96â¯cells, and inhibition of DNMT1 with 5-Aza treatment or shRNA vector transfection reversed high glucose-induced reductions in BDNF expression. Furthermore, the mTOR and upstream Akt pathways were indicated to mediate high glucose-induced DNMT1 and BDNF expression in RSC96â¯cells. Taken together, our results suggest that the Akt/mTOR cascade mediates high glucose-induced reductions in BDNF via DNMT1 in Schwann cells in DPN.
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Factor Neurotrófico Derivado del Encéfalo/metabolismo , Neuropatías Diabéticas/patología , Regulación de la Expresión Génica/efectos de los fármacos , Glucosa/farmacología , Proteínas Proto-Oncogénicas c-akt/metabolismo , Células de Schwann/patología , Serina-Treonina Quinasas TOR/metabolismo , Animales , Factor Neurotrófico Derivado del Encéfalo/genética , Células Cultivadas , Metilación de ADN , Diabetes Mellitus Experimental/complicaciones , Diabetes Mellitus Experimental/metabolismo , Neuropatías Diabéticas/etiología , Neuropatías Diabéticas/metabolismo , Regulación hacia Abajo , Masculino , Ratones , Neurotrofina 3/genética , Neurotrofina 3/metabolismo , Regiones Promotoras Genéticas , Proteínas Proto-Oncogénicas c-akt/genética , Ratas , Células de Schwann/efectos de los fármacos , Células de Schwann/metabolismo , Nervio Ciático/efectos de los fármacos , Nervio Ciático/metabolismo , Nervio Ciático/patología , Edulcorantes/farmacología , Serina-Treonina Quinasas TOR/genéticaRESUMEN
Abnormal lipid metabolism and SREBP-1 downregulation are reported to be involved in the pathogenesis of diabetic peripheral neuropathy (DPN). In the current study, the relationship between PI3K/Akt signaling pathway and SREBP-1 expression was explored in Schwann cells of DPN. The phospho-Akt (Ser 473), phospho-Akt (Thr 308), and SREBP-1 expression were inhibited in the sciatic nerves of diabetic mice versus those of normal mice, accompanied with the atrophy of nerve fiber and the irregular myelin sheath. High concentration glucose suppressed phospho-Akt (Ser 473), phospho-Akt (Thr 308), and SREBP-1 expression in cultured Schwann cell (RSC96 cell) in vitro, and 25 mmol/L glucose was enough to lead to the maximum inhibitory effect. The time-course effect of high glucose showed that Akt phosphorylation gradually decreased with the extension of stimulation time. Somewhat differently, short-term high-glucose exposure enhanced SREBP-1 expression and prolonged high-glucose stimulation reduced the SREBP-1 expression in RSC96 cells. Similarly, prolonged high-glucose stimulation also downregulated FASN messenger RNA (mRNA), ACC mRNA, intracellular triglyceride, and cholesterol. LY294002 suppressed Akt activation followed by the decreased SREBP-1, FASN, ACC, triglyceride, and cholesterol. Contrarily, the PI3K/Akt signaling pathway agonist insulin pretreatment avoided prolonged high-glucose stimulation-blocked Akt activation and increased SREBP-1, FASN, and ACC expression in the levels of protein and mRNA in RSC96 cells. The knockdown of SREBP-1 by shRNA prevented insulin-induced enhanced FASN, ACC mRNA expression, triglyceride, and cholesterol in high-glucose-treated RSC96 cells. In conclusion, prolonged high-glucose exposure inhibits the SREBP-1/FASN/ACC expression in the Schwann cells of DPN via the blockage of the PI3K/Akt signaling pathway.
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Acetil-CoA Carboxilasa/metabolismo , Diabetes Mellitus Experimental/patología , Acido Graso Sintasa Tipo I/metabolismo , Regulación de la Expresión Génica/efectos de los fármacos , Glucosa/farmacología , Células de Schwann/patología , Proteína 1 de Unión a los Elementos Reguladores de Esteroles/metabolismo , Acetil-CoA Carboxilasa/genética , Animales , Células Cultivadas , Diabetes Mellitus Experimental/tratamiento farmacológico , Diabetes Mellitus Experimental/metabolismo , Acido Graso Sintasa Tipo I/genética , Insulina/metabolismo , Masculino , Ratones , Fosfatidilinositol 3-Quinasas/genética , Fosfatidilinositol 3-Quinasas/metabolismo , Proteínas Proto-Oncogénicas c-akt/genética , Proteínas Proto-Oncogénicas c-akt/metabolismo , Ratas , Células de Schwann/efectos de los fármacos , Células de Schwann/metabolismo , Nervio Ciático/efectos de los fármacos , Nervio Ciático/metabolismo , Nervio Ciático/patología , Proteína 1 de Unión a los Elementos Reguladores de Esteroles/genética , Edulcorantes/farmacologíaRESUMEN
Schwann cell apoptosis is one of the characteristics of diabetic peripheral neuropathy (DPN). The mammalian target of rapamycin (mTOR) is a multifunctional signaling pathway that regulates cell apoptosis in various types of tissues and cells. To investigate whether the mTOR pathway is involved in cell apoptosis in the Schwann cells of DPN, diabetic mice and rat Schwann cells (RSC96) were chosen to detect phospho-mTOR (Ser 2448), phospho-S6K1 (Thr 389), phospho-4EBP1 (Thr 37/46), Bcl-2, Bax and cleaved caspase-3 by diverse pathological and biological techniques. The results showed that phospho-mTOR (Ser 2448) was decreased in the sciatic nerves of diabetic mice, concomitant with decreased Bcl-2, increased Bax, cleaved caspase-3 and cell apoptosis. In addition, high glucose treatment for 72â¯h caused a 35.95% decrease in the phospho-mTOR (Ser 2448)/mTOR ratio, a 65.50% decrease in the phospho-S6K1 (Thr 389)/S6K1 ratio, a 3.67-fold increase in the Bax/Bcl-2 ratio and a 1.47-fold increase in the cleaved caspase-3/caspase-3 ratio. Furthermore, mTORC1 inhibition, rather than mTORC2 inhibition, resulted in mitochondrial controlled apoptosis in RSC96 cells by silencing RAPTOR or RICTOR. Again, suppression of the mTORC1 pathway by a chemical inhibitor led to mitochondrial controlled apoptosis in cultured RSC96 cells in vitro. By contrast, activation of the mTORC1 pathway with MHY1485 prevented decreased phospho-S6K1 (Thr 389) levels caused by high glucose and cell apoptosis. Additionally, constitutive activation of S6K1 avoided high glucose-induced cell apoptosis in RSC96 cells. In summary, our findings suggest that activating mTORC1/S6K1 signaling in Schwann cells may be a promising strategy for the prevention and treatment of DPN.
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Apoptosis , Nefropatías Diabéticas/metabolismo , Diana Mecanicista del Complejo 1 de la Rapamicina/metabolismo , Proteínas Quinasas S6 Ribosómicas/metabolismo , Células de Schwann/metabolismo , Animales , Caspasa 3/metabolismo , Línea Celular , Nefropatías Diabéticas/enzimología , Nefropatías Diabéticas/patología , Glucosa/farmacología , Diana Mecanicista del Complejo 1 de la Rapamicina/antagonistas & inhibidores , Ratones , Mitocondrias/efectos de los fármacos , Naftiridinas/farmacología , Proteínas Proto-Oncogénicas c-bcl-2/metabolismo , Proteína Asociada al mTOR Insensible a la Rapamicina/antagonistas & inhibidores , Ratas , Proteína Reguladora Asociada a mTOR/antagonistas & inhibidores , Células de Schwann/efectos de los fármacos , Células de Schwann/enzimología , Nervio Ciático/enzimología , Nervio Ciático/metabolismo , Nervio Ciático/patología , Sirolimus/farmacología , Serina-Treonina Quinasas TOR/antagonistas & inhibidores , Serina-Treonina Quinasas TOR/metabolismo , Proteína X Asociada a bcl-2/metabolismoRESUMEN
OBJECTIVES: The aim of this study was to analyze the diagnostic accuracy of different criteria of pharmaco-penile duplex sonography in venous erectile dysfunction (ED). METHODS: The following parameters were measured after an intracavernous injection test in patients with ED from May 2016 to February 2017 at our hospital: diameter, peak systolic velocity, end-diastolic velocity, and resistance index of the cavernous artery; diameter and peak velocity (if leak occurred) of the deep dorsal vein. Three ultrasonographic diagnostic criteria of venous ED were applied. Criterion A: continuous blood flow signals in the deep dorsal vein, peak velocity greater than 3 cm/s, peak systolic velocity greater than 30 cm/s, end-diastolic velocity greater than 5 cm/s; Criterion B: resistance index less than 0.89 and other parameters corresponding with Criterion A; Criterion C: resistance index less than 0.80 and other parameters corresponding with Criterion A. The diagnostic results of each criterion were compared with the cavernosographic results. RESULTS: Thirty-six patients were diagnosed as venous ED by cavernosography in 54 ED cases. The diagnostic specificity, sensitivity, and accuracy of Criterion A were 70.6%, 91.7%, and 84.9%, respectively. Those of Criterion B were 82.4%, 69.4%, and 73.6%, while the results for Criterion C were 94.1%, 33.3%, and 52.8%, respectively. Criterion A had the highest diagnostic accuracy, the largest area under the receiver operating characteristic curve (area = 0.811), and the highest consistency (kappa = 0.642) with the cavernosographic results in the 3 criteria. The difference was statistically significant (P < .05). CONCLUSIONS: Among the 3 commonly used ultrasonographic criteria, Criterion A is most appropriate in the diagnosis of venous ED.
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Disfunción Eréctil/diagnóstico por imagen , Disfunción Eréctil/fisiopatología , Pene/irrigación sanguínea , Pene/diagnóstico por imagen , Ultrasonografía Doppler Dúplex/métodos , Adolescente , Adulto , Velocidad del Flujo Sanguíneo/fisiología , Humanos , Masculino , Persona de Mediana Edad , Pene/fisiopatología , Estudios Prospectivos , Flujo Sanguíneo Regional/fisiología , Reproducibilidad de los Resultados , Adulto JovenRESUMEN
Taking advantage of the compelling properties of d-penicillamine (d-PA) combined with copper, a method for the sensitive and selective determination of d-PA was established using copper nanocluster (Cu NC)-based fluorescence enhancement. d-PA molecules containing a thiol compound showed a strong tendency to combine with the surface of Cu NCs, causing the re-dispersion of nanoclusters and therefore fluorescence intensity was enhanced. Fluorescence enhancement efficiency of Cu NCs induced by d-PA was linear, with the d-PA concentration varying from 0.6-30 µg ml-1 (R2 = 0.9952) and with a detection limit of 0.54 µg ml-1 . d-PA content in human urine samples was detected with recoveries of 104.8-112.99%. Fluorescence-enhanced determination of d-PA using Cu NCs was established for the first time and this rapid, easy and sensitive method should attract much attention for this application.
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Cobre/química , Colorantes Fluorescentes/química , Nanopartículas del Metal/química , Penicilamina/análisis , Fluorescencia , Humanos , Espectrometría de FluorescenciaRESUMEN
Schwann cells play an important role in maintaining the normal function of peripheral nerves via the secretion of nerve growth factor (NGF). The mTOR signaling pathway is known as a kind of Ser/Thr protein kinase that regulates various cell functions. DNA methyltransferase 1 (DNMT1) is an epigenetic regulator and downstream target of the mTOR pathway. In the present study, we explored the relationship between NGF expression and the mTOR pathway/DNMT1 in RSC96 cells. The results showed that both rapamycin and Torin 1 downregulated NGF expression via the inhibition of phospho-mTOR (Ser 2448) and phospho-S6K1 (Thr 389). Similarly, the silencing of RAPTOR and RICTOR decreased NGF expression by 56.7% and 52.4%, respectively, in RSC96 cells compared with the control siRNA treatment, which was accompanied by reduced phospho-S6K1 (Thr 389). The mTOR/S6K1 activator MHY1485 increased NGF expression by 28.7% and 17.1% 1 day and 2 day after stimulation, respectively, compared to the corresponding control group in RSC96 cells. Furthermore, DNMT1 was enhanced by 94.5% and 42.5% with mTOR pathway inhibitor (rapamycin and Torin 1, respectively) treatment for 3 day compared with the control group. Additionally, the inhibition of DNMT1 with a chemical inhibitor or a specific shRNA plasmid upregulated NGF in RSC96 cells. In summary, our findings suggest that DNMT1 is the downstream target of the mTOR pathway and mediates the mTOR pathway inhibition-induced reduction in NGF expression in Schwann cells. Activation of the mTOR signaling pathway and/or inhibition of DNMT1 increased NGF expression, which may benefit patients suffering from NGF deficiencies, such as diabetic peripheral neuropathy.
Asunto(s)
ADN (Citosina-5-)-Metiltransferasa 1/metabolismo , Diana Mecanicista del Complejo 1 de la Rapamicina/metabolismo , Diana Mecanicista del Complejo 2 de la Rapamicina/metabolismo , Células de Schwann/efectos de los fármacos , Animales , Factor de Crecimiento Nervioso/metabolismo , Fosforilación , Proteínas Proto-Oncogénicas c-akt/metabolismo , Ratas , Proteína Reguladora Asociada a mTOR/metabolismo , Proteína Reguladora Asociada a mTOR/farmacología , Células de Schwann/metabolismo , Transducción de Señal/efectos de los fármacos , Sirolimus/farmacologíaRESUMEN
Poverty and its associated factors put people at risk for depression. The aims of this study were to describe the prevalence of depressive symptoms (DS) of primary caregivers and socioemotional development (SED) delays of young children in poor rural areas of China, and to explore the association between them. Cross-sectional data of 2,664 children aged 3 to 35 months and their primary caregivers were used for analysis. Characteristics of the child, caregiver, and family were collected through face-to-face caregiver interviews. DS were assessed by the Zung Self-Rating Depression Scale (W.W. Zung, 1965, as cited in World Health Organization, ), and SED was evaluated by the Ages and Stage Questionnaires: Social-Emotional (J. Squires, D. Bricker, & L. Potter, 1997). The χ2 test, stratification analysis, and logistic regression analyses were used to explore the association. Among the caregivers, 40.3% (95% confidence interval [CI] [38.4, 42.1]), reported DS. Caregivers who were male, older and ethnic minorities as well as had a low level of education, a low family income, or more children were more likely to have DS. Of the children, 24.4% (95% CI [22.8, 26.0]) were recognized with SED delays. Older children displayed more delays than did younger children, but no significant differences between males and females were found. SED delays were significantly associated with mother outmigrating, male caregivers, older age, ethnic minorities, and low education or families with a single parent, low-income, and having more children. Caregivers having DS, odds ratio (OR) = 2.40, 95% CI [1.99, 2.88], was a significant predictor of increased odds of SED delays; other factors were single-parent family, OR = 1.99, 95% CI [1.37, 2.89], inadequate care, OR = 1.69, 95% CI [1.30, 2.21], physical punishment, OR = 1.61, 95% CI [1.33, 1.95], ethnic minorities, OR = 1.41, 95% CI [1.17, 1.71], and child age in months, OR = 1.03, 95% CI [1.02, 1.04], according to the logistic regression analysis. DS are prevalent among caregivers with young children in poor rural areas. Interventions to improve the mental health of caregivers and their parenting behaviors are needed to improve children's SED.