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BACKGROUND: Several COVID-19 vaccines are in widespread use in China. Few data exist on comparative immunogenicity of different COVID-19 vaccines given as booster doses. We aimed to assess neutralizing antibody levels raised by injectable and inhaled aerosolized recombinant adenovirus type 5 (Ad5)-vectored COVID-19 vaccine as a heterologous booster after an inactivated COVID-19 vaccine two-dose primary series. METHODS: Using an open-label prospective cohort design, we recruited 136 individuals who had received inactivated vaccine primary series followed by either injectable or inhaled Ad5-vectored vaccine and measured neutralizing antibody titers against ancestral SARS-CoV-2 virus and Omicron BA.1 and BA.5 variants. We also measured neutralizing antibody levels in convalescent sera from 39 patients who recovered from Omicron BA.2 infection. RESULTS: Six months after primary series vaccination, neutralizing immunity against ancestral SARS-CoV-2 was low and neutralizing immunity against Omicron (B.1.1.529) was lower. Boosting with Ad5-vectored vaccines induced a high immune response against ancestral SARS-CoV-2. Neutralizing responses against Omicron BA.5 were ≥ 80% lower than against ancestral SARS-CoV-2 in sera from prime-boost subjects and in convalescent sera from survivors of Omicron BA.2 infection. Inhaled aerosolized Ad5-vectored vaccine was associated with greater neutralizing titers than injectable Ad5-vectored vaccine against ancestral and Omicron SARS-CoV-2 variants. CONCLUSIONS: These findings support the current strategy of heterologous boosting with injectable or inhaled Ad5-vectored SARS-CoV-2 vaccination of individuals primed with inactivated COVID-19 vaccine.
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Vacunas contra la COVID-19 , COVID-19 , Humanos , Anticuerpos Neutralizantes , Anticuerpos Antivirales , Estudios Prospectivos , SARS-CoV-2RESUMEN
Background: Solute carrier organic anion transporter family member 4A1 (SLCO4A1), a member of solute carrier organic anion family, is a key gene regulating bile metabolism, organic anion transport, and ABC transport. However, the association of SLCO4A1 with prognosis and tumor immune infiltration in colon adenocarcinoma (COAD) remains indistinct. Methods: Firstly, we explored the expression level of SLCO4A1 in COAD via GEPIA, Oncomine, and UALCAN databases. Secondly, we used the Kaplan-Meier plotter and PrognoScan databases to investigate the effect of SLCO4A1 on prognosis in COAD patients. In addition, the correlation between SLCO4A1 and tumor immune infiltration was studied by using TIMER and TISIDB databases. Results: Our results showed that SLCO4A1 was overexpressed in COAD tissues. At the same time, our study showed that high expression of SLCO4A1 was associated with poor overall survival, disease-free survival, and disease-specific survival in COAD patients. The expression level of SLCO4A1 was negatively linked to the infiltrating levels of B cells, CD8+ T cells, and dendritic cells in COAD. Moreover, the expression of SLCO4A1 was significantly correlated with numerous immune markers in COAD. Conclusions: These results indicated that SLCO4A1 could be associated with the prognosis of COAD patients and the levels of tumor immune infiltration. Our study suggested that SLCO4A1 could be a valuable biomarker for evaluating prognosis and tumor immune infiltration in COAD patients.
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Neoplasias del Colon , Transportadores de Anión Orgánico , Humanos , Transportadores de Anión Orgánico/antagonistas & inhibidores , Transportadores de Anión Orgánico/genética , Transportadores de Anión Orgánico/metabolismo , Neoplasias del Colon/inmunología , Neoplasias del Colon/patología , Neoplasias del Colon/terapia , Regulación Neoplásica de la Expresión Génica , Biomarcadores , Análisis de Supervivencia , Linfocitos Infiltrantes de Tumor/inmunologíaRESUMEN
Spider venoms are insecticidal mixtures with diverse biological activities, and acylpolyamines are their small molecular active components. However, the mechanism for the insecticidal activity of acylpolyamines remains to be elucidated. Here, the structure and function of two acylpolyamine toxins, AVTX-622 and AVTX-636, from Araneus ventricosus were investigated. Nuclear magnetic resonance (NMR) analysis illustrated that the structure of two toxins was very similar, and compared to AVTX-636, AVTX-622 only missed a methylene group in the linker region between the polyamine head and tail. Both the two toxins did not inhibit on voltage-gated sodium channels in mammalian neuronal cells. Intriguingly, AVTX-622, but not AVTX-636, inhibited voltage-gated sodium channels in DUM neuronal cells of Periplaneta americana. Further animal test displayed that the paralyzing potency of AVTX-622 on insect was over ten-times stronger than that of AVTX-636. These findings indicate that a single methylene deletion from AVTX-636 offered AVTX-622 the insect-selective voltage-gated sodium channel activity, which not only elucidated structure-function of the toxins, but also provided new clues for insect-selective insecticide design.
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Poliaminas/farmacología , Venenos de Araña/farmacología , Canales de Sodio Activados por Voltaje/metabolismo , Animales , Células Cultivadas , Estructura Molecular , Neuronas/efectos de los fármacos , Neuronas/metabolismo , Resonancia Magnética Nuclear Biomolecular , Poliaminas/química , Ratas , Ratas Sprague-Dawley , Venenos de Araña/química , ArañasRESUMEN
The fast progress in research and development of multifunctional, distributed sensor networks has brought challenges in processing data from a large number of sensors. Using deep learning methods such as convolutional neural networks (CNN), it is possible to build smarter systems to forecasting future situations as well as precisely classify large amounts of data from sensors. Multi-sensor data from atmospheric pollutants measurements that involves five criteria, with the underlying analytic model unknown, need to be categorized, so do the Diabetic Retinopathy (DR) fundus images dataset. In this work, we created automatic classifiers based on a deep convolutional neural network (CNN) with two models, a simpler feedforward model with dual modules and an Inception Resnet v2 model, and various structural tweaks for classifying the data from the two tasks. For segregating multi-sensor data, we trained a deep CNN-based classifier on an image dataset extracted from the data by a novel image generating method. We created two deepened and one reductive feedforward network for DR phase classification. The validation accuracies and visualization results show that increasing deep CNN structure depth or kernels number in convolutional layers will not indefinitely improve the classification quality and that a more sophisticated model does not necessarily achieve higher performance when training datasets are quantitatively limited, while increasing training image resolution can induce higher classification accuracies for trained CNNs. The methodology aims at providing support for devising classification networks powering intelligent sensors.
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Aprendizaje Automático , Redes Neurales de la Computación , Retinopatía Diabética/diagnóstico , Retinopatía Diabética/diagnóstico por imagen , Análisis Discriminante , Humanos , Procesamiento de Imagen Asistido por Computador , Análisis de Componente PrincipalRESUMEN
Culex flavivirus (CxFV) is an insect-specific virus of the genus Flavivirus. CxFV strains have been isolated from Cx. pipiens, Cx. quinquefasciatus, and other Cx. species in Asia, Africa, North America, Central America and South America. CxFV was isolated for the first time in China in 2006. As this is a novel flavivirus, we explored the distribution and genetic characteristics of Culex flavivirus in China. A total of 46,649 mosquitoes were collected in seven provinces between 2004 and 2012 and were analysed in 871 pools. 29 CxFV RNAs from Cx. pipiens, Cx. tritaeniorhynchus, Anopheles Sinensis, and Culex spp. tested positive for CxFV in real-time RT-PCR. 6 CxFV strains were isolated from Cx. species collected in Shandong, Henan, and Shaanxi provinces, while no virus or viral RNA was detected in samples from Sichuan, Chongqing, Hubei, and Fujian. Phylogenetic analysis of the envelope gene indicated that Chinese strains formed a robust subgroup of genotype 1, together with viruses from the United States and Japan. This study demonstrates that the geographic distribution of CxFV in China is widespread, but geographical boundaries to spread are apparent. Our findings suggest that CxFV can infect various mosquito species in nature.
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Anopheles/virología , Culex/virología , Flavivirus/aislamiento & purificación , Filogeografía , Animales , China , Análisis por Conglomerados , Femenino , Flavivirus/genética , Genotipo , Reacción en Cadena en Tiempo Real de la Polimerasa , Análisis de Secuencia de ADN , Proteínas del Envoltorio Viral/genéticaRESUMEN
In the present study, we investigated the structure and function of hainantoxin-III (HNTX-III), a 33-residue polypeptide from the venom of the spider Ornithoctonus hainana. It is a selective antagonist of neuronal tetrodotoxin-sensitive voltage-gated sodium channels. HNTX-III suppressed Nav1.7 current amplitude without significantly altering the activation, inactivation, and repriming kinetics. Short extreme depolarizations partially activated the toxin-bound channel, indicating voltage-dependent inhibition of HNTX-III. HNTX-III increased the deactivation of the Nav1.7 current after extreme depolarizations. The HNTX-III·Nav1.7 complex was gradually dissociated upon prolonged strong depolarizations in a voltage-dependent manner, and the unbound toxin rebound to Nav1.7 after a long repolarization. Moreover, analysis of chimeric channels showed that the DIIS3-S4 linker was critical for HNTX-III binding to Nav1.7. These data are consistent with HNTX-III interacting with Nav1.7 site 4 and trapping the domain II voltage sensor in the closed state. The solution structure of HNTX-III was determined by two-dimensional NMR and shown to possess an inhibitor cystine knot motif. Structural analysis indicated that certain basic, hydrophobic, and aromatic residues mainly localized in the C terminus may constitute an amphiphilic surface potentially involved in HNTX-III binding to Nav1.7. Taken together, our results show that HNTX-III is distinct from ß-scorpion toxins and other ß-spider toxins in its mechanism of action and binding specificity and affinity. The present findings contribute to our understanding of the mechanism of toxin-sodium channel interaction and provide a useful tool for the investigation of the structure and function of sodium channel isoforms and for the development of analgesics.
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Venenos de Araña/farmacología , Arañas/metabolismo , Bloqueadores del Canal de Sodio Activado por Voltaje/farmacología , Canales de Sodio Activados por Voltaje/metabolismo , Animales , Células Cultivadas , Ganglios Espinales/citología , Células HEK293 , Humanos , Activación del Canal Iónico/efectos de los fármacos , Cinética , Espectroscopía de Resonancia Magnética , Potenciales de la Membrana/efectos de los fármacos , Ratones , Canal de Sodio Activado por Voltaje NAV1.7/genética , Canal de Sodio Activado por Voltaje NAV1.7/metabolismo , Neuronas/efectos de los fármacos , Neuronas/metabolismo , Neuronas/fisiología , Técnicas de Placa-Clamp , Isoformas de Proteínas/genética , Isoformas de Proteínas/metabolismo , Ratas , Ratas Sprague-Dawley , Venenos de Araña/química , Arañas/genética , Tetrodotoxina/farmacología , Bloqueadores del Canal de Sodio Activado por Voltaje/química , Canales de Sodio Activados por Voltaje/genéticaRESUMEN
BACKGROUND: Black widow spider (L. tredecimguttatus) has toxic components not only in the venomous glands, but also in other parts of the body and its eggs. It is biologically important to investigate the molecular basis of the egg toxicity. RESULTS: In the present work, an aqueous extract was prepared from the eggs of the spider and characterized using multiple physiological and biochemical strategies. Gel electrophoresis and mass spectrometry demonstrated that the eggs are rich in high-molecular-mass proteins and the peptides below 5 kDa. The lyophilized extract of the eggs had a protein content of 34.22% and was shown to have a strong toxicity towards mammals and insects. When applied at a concentration of 0.25 mg/mL, the extract could completely block the neuromuscular transmission in mouse isolated phrenic nerve-hemidiaphragm preparations within 12.0 ± 1.5 min. Using whole-cell patch-clamp technique, the egg extract was demonstrated to be able to inhibit the voltage-activated Na+, K+ and Ca2+ currents in rat DRG neurons. In addition, the extract displayed activities of multiple hydrolases. Finally, the molecular basis of the egg toxicity was discussed. CONCLUSIONS: The eggs of black widow spiders are rich in proteinous compounds particularly the high-molecular-mass proteins with different types of biological activity The neurotoxic and other active compounds in the eggs are believed to play important roles in the eggs' toxic actions.
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Proteínas de Artrópodos/toxicidad , Araña Viuda Negra/química , Óvulo/química , Extractos de Tejidos/química , Exoesqueleto/química , Exoesqueleto/fisiología , Animales , Proteínas de Artrópodos/aislamiento & purificación , Canales de Calcio/efectos de los fármacos , Cucarachas/efectos de los fármacos , Ganglios Espinales/efectos de los fármacos , Ratones , Óvulo/fisiología , Nervio Frénico/efectos de los fármacos , Canales de Potasio con Entrada de Voltaje/efectos de los fármacos , Ratas , Extractos de Tejidos/toxicidad , Canales de Sodio Activados por Voltaje/efectos de los fármacosRESUMEN
Up to now, there have been a few reports on the toxic components purified from black widow spider (Latrodectus tredecimguttatus) eggs. In the present study, a novel neurotoxic protein was purified from the eggs by gel filtration combined with ion-exchange chromatography. Its molecular weight was 23.752 kDa determined by electrospray mass spectrometry. The protein could block the neuromuscular transmission in mouse-isolated phrenic nerve-hemidiaphragm preparations completely in a reversible manner and activate tetrodotoxin-sensitive sodium current in rat dorsal root ganglion cells. The N-terminal sequence of the protein was identified by the Edman degradation to be N-S-I-A-D-D-R-Y-R-W-P-G-Y-P-G-A-G-L-I-P-Y-I-I-D-S-. When the sequence was used to search against protein database with a sequence query in Mascot engine there was no matched sequence or protein whereas the Basic Local Alignment Search Tool (BLAST) analysis indicated that no significant similarity was found. These results demonstrated that the protein (named Latroeggtoxin-I) is a novel neurotoxic protein purified from the eggs of black widow spiders.
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Proteínas de Artrópodos , Araña Viuda Negra/química , Bloqueantes Neuromusculares , Neurotoxinas , Óvulo/química , Transmisión Sináptica/efectos de los fármacos , Secuencia de Aminoácidos , Animales , Proteínas de Artrópodos/química , Proteínas de Artrópodos/aislamiento & purificación , Proteínas de Artrópodos/toxicidad , Ganglios Espinales/citología , Ganglios Espinales/metabolismo , Masculino , Ratones , Datos de Secuencia Molecular , Bloqueantes Neuromusculares/efectos adversos , Bloqueantes Neuromusculares/química , Bloqueantes Neuromusculares/aislamiento & purificación , Bloqueantes Neuromusculares/farmacología , Neurotoxinas/química , Neurotoxinas/aislamiento & purificación , Neurotoxinas/toxicidad , Ratas , Ratas Sprague-DawleyRESUMEN
High staff turnover in certain public sector organizations in Pakistan is a challenging problem, and organizations strive to reduce this issue using different mechanisms. Therefore, this research investigates the parallel mediation impact of perceived organizational support (POS) and organizational citizenship behavior (OCB) on the relationships among perceived supervisor support (PSS), leader-member exchange (LMX), and employee's intention to leave (IL). Data were collected from 482 employees working in public sector museums in Pakistan in three waves. Structural equation modeling (SEM) with a two-step approach was used to evaluate the data. The research found that both POS and OCB mediate the negative relationship between PSS and IL and between LMX and IL in a parallel mediation mechanism. Public sector museums should focus on providing visible supervisory support and develop a healthy work environment where the exchange relationship between supervisors and subordinates strengthens to reduce the possibility of the employee's leave intentions.
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To better understand the impact of COVID-19 epidemic on routine vaccination, a cross-sectional study was carried out during non-pharmaceutical intervention period (2020) and mass COVID-19 vaccination period (2021) in Shaanxi province. Data on NIP (National Immunization Program, Free), nNIP (non-National Immunization Program, Paid), and COVID-19 vaccines inoculated and vaccination clinics were collected. At the beginning of the COVID-19 epidemic, the rate of routine vaccination clinics providing vaccination services was only 20.0%, rabies vaccination clinics was 89.9% and obstetric vaccination clinics was 95.9%. Compared with 2019 (as baseline), NIP vaccines inoculated in 2020 and 2021 decreased by 3.5% and 19.2%, respectively, on the contrary, nNIP vaccines increased by 25.8% and 34.7%, respectively. In 2021, 74.9% of vaccination clinics were involved in mass COVID-19 vaccination, and there was not a significant impact of mass COVID-19 vaccination on the number of other vaccines inoculated. Vaccination coverage of all NIP vaccines was not different from that in previous years. COVID-19 epidemic had a short-term impact on routine vaccination at beginning. The impact of mass COVID-19 vaccination on routine vaccination could even be ignored. The COVID-19 epidemic has once again made people realize the great harm of infectious diseases, and has improved everyone's willingness to receive routine vaccines.
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Vacunas contra la COVID-19 , COVID-19 , Femenino , Embarazo , Humanos , COVID-19/epidemiología , COVID-19/prevención & control , Estudios Transversales , Pandemias , Vacunación , China/epidemiologíaRESUMEN
Background: Hepatitis A (HepA) vaccination and economic factors can change the epidemiology of HepA. In China, the implementation of free vaccination for children under 1.5 years of age in 2008 has resulted in a decline in the overall incidence of HepA. Nevertheless, further investigation is required to comprehensively understand the epidemiological patterns of HepA in economically disadvantaged regions of China. Method: In this study, we evaluated the incidence, seroprevalence, and transmission characteristics of HepA in Shaanxi with less economically developed. We obtained data on reported cases of HepA from 2005 to 2020. Blood samples from 1,559 individuals aged 0 to 60 years were tested for anti-hepatitis A (HAV) antibodies. A questionnaire survey and blood sample collection were conducted in two sentinel sites from 2019 to 2021. Result: Between 2008 to 2020, the number of reported cases of HepA decreased from 3.44/100,000 person-years to 0.65/100,000 person-years, indicating an 81.1% decrease, which was particularly pronounced among younger age groups (0-19 years). From 2015-2020, infections were more likely to occur in people in their 40s and those over the age of 60. Farmers were still the most common occupation of HepA in the last decade. The results of the serological investigation showed the highest anti-HAV seroprevalence was observed in adults aged 39-60 years (94.6%) and those aged 28-38 years (87.8%). The 10-15 years group had the lowest seroprevalence at 49.3%. During the study period, a total of 22 cases were reported by sentinel sites, but the common risk factors (like raw food exposure, travel history, and closed contact with patients) were not identified. Conclusion: Given the greater severity of illness in the adult population and the ambiguous transmission routine, enhanced surveillance for HepA and evaluations that identify feasible approaches to mitigate the risk of HAV transmission are urgent priorities.
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Virus de la Hepatitis A , Hepatitis A , Adulto , Niño , Humanos , Lactante , Hepatitis A/epidemiología , Estudios Seroepidemiológicos , Vacunación , China/epidemiologíaRESUMEN
Mumps is an acute infectious disease, which was well controlled in the past, but recently it has resurged in some areas. This study aimed to evaluate the safety profile of the live attenuated mumps vaccine after large-scale vaccination. We conducted an observational, open-label phase 4 trial in Shaanxi, China from October 2020 to March 2021. Eligible participants were freshmen of junior high school who were not above 14 years old. Adverse events following immunization (AEFI) monitoring was carried out by active and passive surveillance. Safety follow-ups were conducted during the study participation. Overall, 10057 subjects were enrolled in the active surveillance analysis. A total of 214 subjects reported adverse reactions with an incidence of 2.13% (214/10057). Most adverse reactions were grade 1, and the incidence of grade 1 adverse reactions was 1.44% (145/10057); 0.60% for grade 2 (60/10057); and 0.09% for grade 3 (9/10057). The majority of adverse reactions were solicited (1.73%, 174/10057). Injection-site pain was the most frequently reported local adverse reaction (0.71%, 71/10057), followed by redness (0.29%, 29/10057). The most common systemic adverse reactions were nausea (0.19%, 19/10057) and fever (0.16%, 16/10057). For passive AEFI surveillance, 57 AEFI cases were reported, with an incidence of 19.28/100000 (57/287608). And most AEFI cases were common adverse reactions (66.67%, 38/57). In total, the live attenuated mumps vaccine evaluated in this trial has a favorable safety profile and can be used for large-scale inoculation.
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Inmunización , Vacunación , Humanos , Adolescente , Vacunación/efectos adversos , China/epidemiología , Fiebre , Vacuna contra la Parotiditis/efectos adversosRESUMEN
Background: CoronaVac has been authorized worldwide for preventing coronavirus disease 2019. Information on the safety, immunogenicity and consistency of different lots and workshops of CoronaVac is presented here. Methods: In this randomized, double-blind, phase IV clinical trial in healthy children and adolescents aged 3-17 years, we aimed to assess the lot-to-lot and workshop-to-workshop consistency, as well as immunogenicity and safety of seven lots of commercial-scale CoronaVac from three workshops. Eligible participants were enrolled into three age cohorts (3-5, 6-11 and 12-17 years). Within each cohort, participants were randomly assigned to seven groups to receive two doses of CoronaVac, with four weeks apart. Serum samples were collected before the first dose and 28 days after the second dose for neutralizing antibody testing. The primary objective was to evaluate the consistency of immune response among different lots within workshop 2 or 3, as well as among different workshops. The primary endpoint was geometric mean titer (GMT) of neutralizing antibody at 28 days after full-course vaccination. Results: Between July 27th and November 19th, 2021, a total of 2,520 eligible participants were enrolled. Results showed that 95% confidence intervals (CIs) of GMT ratios for all comparative groups among different lots or workshops were within the equivalence criteria of [0.67, 1.5]. The GMT and seroconversion rate for all participants were 126.42 (95%CI: 121.82, 131.19) and 99.86% (95%CI: 99.59%, 99.97%) at 28 days after two-dose vaccination. The incidences of adverse reactions were similar among seven lots, and most adverse reactions were mild in Grade 1, with no serious adverse event. Conclusion: CoronaVac is well-tolerated and can elicit a good immune response among children and adolescents. Lot-to-lot consistency results indicate stable manufacturing of commercial-scale CoronaVac.
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Vacunas contra la COVID-19 , COVID-19 , Niño , Humanos , Adolescente , Vacunas contra la COVID-19/efectos adversos , COVID-19/prevención & control , Anticuerpos Neutralizantes , Método Doble Ciego , SeroconversiónRESUMEN
Phase change materials (PCMs) for the charge and discharge of thermal energy at a nearly constant temperature are of interest for thermal energy storage and management, and porous materials are usually used to support PCMs for preventing the liquid leakage and shape instability during the phase change process. Compared with commonly used polymer matrices and porous carbons, mineral materials with naturally occurring porous structures have obvious advantages such as cost-saving and abundant resources. Attapulgite (ATP) is a clay mineral with natural porous structures, which can be used to contain PCMs for thermal energy storage. However, the poor compatibility between ATP and PCMs is a significant defect that has rarely been studied. Herein, a facile one-step organic modification method of ATP was developed and the chlorosilane-modified ATP (Si-ATP) possesses great hydrophobic and lipophilic properties. Three types of ATP with different compatibility and pore volumes were used as the supports and paraffin as the energy storage units to fabricate a series of form-stable PCMs (FSPCMs). The results showed that the shape-stabilized ability of Si-ATP for paraffin was significantly enhanced, and the Si-ATP supported FSPCM yielded an optimal latent heat of 83.7 J g-1, which was 64.4% higher than that of the pristine ATP based composite. Meanwhile, the thermal energy storage densities of the resulting FSPCMs were gradually increased with an increase in the pore volumes of the three supporting materials. These results may provide a strategy for preparing porous materials as containers to realize the shape stabilization of PCMs and improve the thermal energy storage densities of the resulting FSPCMs.
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The study aims to determine the seroprevalence of antibodies against tetanus among healthy people aged 1−59 years old in Shaanxi province. IgG against tetanus in serum samples were detected by ELISA. 6,439 subjects were enrolled. The positive rate (≥0.01 IU/mL) was 84.39% and GMC was 0.03 IU/mL. There were significant differences in positive rates (χ2 = 308.944, p < 0.01) and GMC (Z = 5,200,000, p < 0.01) among different age groups. The positive rates (χ2 = 304.3, p < 0.01) and GMCs (χ2 = 146.417, p < 0.01) showed regional differences. Both full protection rate (≥0.1 IU/mL) (χ2 = 36.834, p < 0.01) and GMC (Z = 688,000, p < 0.01) increased with the doses of tetanus-toxoid-containing vaccines (TTCVs) administered. The positive rate (χ2 = 54.136, p < 0.01) and GMC (Z = 140,200, p < 0.01) decreased gradually with the time interval after full immunization with TTCVs. The full protection rate (≥0.1 IU/mL) (χ2 = 176.201, p < 0.01) and GMC (Z = 629,900, p < 0.01) decreased with the interval (years) since the last dose of TTCVs. There were significant differences in the positive rates and GMCs for different ages, regions, immunization histories of TTCVs, and doses of TTCVs administered. The full protection rate and GMC decreased with the interval following full immunization with TTCVs and the interval since the last dose of TTCVs. The importance of using tetanus booster doses should be emphasized in adolescents and adults.
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Latroeggtoxin-VI (LETX-VI), a proteinaceous neurotoxin mined from the egg transcriptome of spider L. tredecimguttatus, was previously found to promote the release of dopamine from PC12 cells. However, the relevant molecular mechanism has not been fully clear. Here LETX-VI was demonstrated to rapidly penetrate the plasma membrane of PC12 cells via the vesicle exocytosis/endocytosis cycle, during which vesicular transmembrane protein synaptotagmin 1 (Syt1) functions as a receptor, with its vesicle luminal domain interacting with the C-terminal region of LETX-VI. The C-terminal sequence of LETX-VI is the functional region for both entering cells and promoting dopamine release. After gaining entry into the PC12 cells, LETX-VI down-regulated the phosphorylation levels of Syt1 at T201 and T195, thereby facilitating vesicle fusion with plasma membrane and thus promoting dopamine release. The relevant mechanism analysis indicated that LETX-VI has a protein phosphatase 2A (PP2A) activator activity. The present work has not only probed into the Syt1-mediated action mechanism of LETX-VI, but also revealed the structure-function relationship of the toxin, thus suggesting its potential applications in the drug transmembrane delivery and treatment of the diseases related to dopamine release and PP2A activity deficiency.
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Dopamina , Sinaptotagmina I , Animales , Calcio/metabolismo , Membrana Celular/metabolismo , Endocitosis , Fusión de Membrana , Ratas , Sinaptotagmina I/genética , Sinaptotagmina I/metabolismo , SinaptotagminasRESUMEN
To determine the estimated pertussis incidence in adults and the need for a booster dose by detecting pertussis and diphtheria antibody levels in adults in Shaanxi province, China. Blood samples were collected from healthy individuals aged 18-59 years in Shaanxi province in 2017. Serum immunoglobulin G (IgG) antibodies against pertussis toxin (PT) and diphtheria toxin (DT) were determined using enzyme-linked immunosorbent assay. The data on reported pertussis cases in Shaanxi province were collected from the China Information System for Disease Control and Prevention and compared with the results of this study. A total of 4307 subjects were enrolled. The mean concentration of anti-PT IgG was 19.6 IU/mL (95% CI = 18.9-20.3), and the positive rate (≥40 IU/mL) was 11.0% (474/4307), of which recent infections (≥100 IU/mL) accounted for 1.2% (53/4307). Only one adult case of pertussis was reported in 2017, which is much lower than the results of this study. The mean concentration of anti-DT IgG was 0.04 IU/mL (95% CI = 0.04-0.05), and the positive rate (≥0.01 IU/mL) was 82.3% (3543/4307). The mean concentration of anti-DT IgG decreased from 0.07 IU/mL in the 18-29 year-old group to 0.03 IU/mL in the 50-59 year-old-group, and the positivity rate decreased from 86.7% to 78.7%. Our study suggests that pertussis is not uncommon among adults. The existing surveillance system might have underestimated the true incidence of pertussis. The diphtheria antibody levels decreased with age. Booster vaccination against pertussis should be considered for adolescents and young adults.
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Difteria , Tos Ferina , Adolescente , Adulto Joven , Humanos , Adulto , Persona de Mediana Edad , Tos Ferina/epidemiología , Tos Ferina/prevención & control , Estudios Transversales , Estudios Seroepidemiológicos , Anticuerpos Antibacterianos , Inmunoglobulina G , Difteria/epidemiología , Difteria/prevención & control , Toxina del PertussisRESUMEN
Industry sustainability plays a vital role in shaping the environment for cultural and creative business development. However, considering the influence of the external environment and random factors on the technical efficiency (T.E.) of cultural and creative industries with the inherent defects of the traditional data envelopment analysis (DEA) model; this manuscript analyzed the operating efficiency of 56 cultural and creative enterprises using the three-stage DEA model from 2012 to 2018. An analysis of the results shows that differences in efficiency exist between stage one and stage three DEA. Furthermore, the environmental elements and statistical noise measured by the stochastic frontier analysis (SFA) in stage two reveal positive and negative influences on the creative cultural enterprises at different stages. As a result, the overall efficiency of the listed cultural and creative industries was revealed to be low in China. Finally, this study suggested effective countermeasures and recommendations for better-operating efficiency systems for cultural and creative enterprises.
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Amid the pandemic of COVID-19, the collaborative innovation network of enterprises is conducive to the sharing of innovation resources, knowledge transfer, and technology diffusion, which is closely related to the improvement of corporate technological innovation performance. Based on the patent application data of listed enterprises in Jiangsu, Zhejiang, and Shanghai in China, this study constructs a cooperation matrix, describes the characteristics of collaborative innovation network from two dimensions of network structure and network relationship, introduces the breadth of the knowledge base as a moderating variable, and analyzes the nexus between characteristics of a collaborative innovation network and technological innovation performance. Based on the panel data of 193 listed companies in Jiangsu, Zhejiang, and Shanghai, this study uses a multiple linear regression model for empirical analysis. The results show a U-shaped relationship between clustering coefficient and technological innovation performance. The breadth of knowledge base strengthens the positive relationship between the structural hole and technological innovation performance. In contrast, the breadth of knowledge base weakens the positive relationship between network relationships strength and technological innovation performance. The study findings will enhance enterprises' participation in a suitable collaborative innovation according to their knowledge-based characteristics and improve the technological innovation performance.
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Rubella occurs worldwide, causing approximately 100,000 cases annually of congenital rubella syndrome, leading to severe birth defects. Better targeting of public health interventions is needed to achieve rubella elimination goals. To that end, we measured the epidemiological characteristics and seasonal dynamic patterns of rubella and determined its association with meteorological factors in Shaanxi Province, China. Data on rubella cases in Shaanxi Province from 2005 to 2018 were obtained from the Chinese National Notifiable Disease Reporting System. The Morlet wavelet analysis was used to estimate temporal periodicity of rubella incidence. Mixed generalized additive models were used to measure associations between meteorological variables (temperature and relative humidity) and rubella incidence. A total of 17,185 rubella cases were reported in Shaanxi during the study period, for an annual incidence of 3.27 cases per 100,000 population. Interannual oscillations in rubella incidence of 0.8-1.4 years, 3.8-4.8 years, and 0.5 years were detected. Both temperature and relative humidity exhibited nonlinear associations with the incidence of rubella. The accumulative relative risk of transmission for the overall pooled estimates was maximized at a temperature of 0.23°C and relative humidity of 41.6%. This study found that seasonality and meteorological factors have impact on the transmission of rubella; public health interventions to eliminate rubella must consider periodic and seasonal fluctuations as well as meteorological factors.