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The COVID-19 pandemic has fostered major advances in vaccination technologies1-4; however, there are urgent needs for vaccines that induce mucosal immune responses and for single-dose, non-invasive administration4-6. Here we develop an inhalable, single-dose, dry powder aerosol SARS-CoV-2 vaccine that induces potent systemic and mucosal immune responses. The vaccine encapsulates assembled nanoparticles comprising proteinaceous cholera toxin B subunits displaying the SARS-CoV-2 RBD antigen within microcapsules of optimal aerodynamic size, and this unique nano-micro coupled structure supports efficient alveoli delivery, sustained antigen release and antigen-presenting cell uptake, which are favourable features for the induction of immune responses. Moreover, this vaccine induces strong production of IgG and IgA, as well as a local T cell response, collectively conferring effective protection against SARS-CoV-2 in mice, hamsters and nonhuman primates. Finally, we also demonstrate a mosaic iteration of the vaccine that co-displays ancestral and Omicron antigens, extending the breadth of antibody response against co-circulating strains and transmission of the Omicron variant. These findings support the use of this inhaled vaccine as a promising multivalent platform for fighting COVID-19 and other respiratory infectious diseases.
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Vacinas contra COVID-19 , Imunidade nas Mucosas , Animais , Cricetinae , Humanos , Camundongos , Administração por Inalação , Aerossóis , Anticorpos Antivirais/imunologia , Células Apresentadoras de Antígenos/imunologia , Células Apresentadoras de Antígenos/metabolismo , Antígenos Virais/imunologia , Toxina da Cólera , COVID-19/imunologia , COVID-19/prevenção & controle , Vacinas contra COVID-19/administração & dosagem , Imunidade nas Mucosas/imunologia , Imunoglobulina A/imunologia , Imunoglobulina G/imunologia , Nanopartículas , Pós , Primatas/virologia , SARS-CoV-2/classificação , SARS-CoV-2/imunologia , Linfócitos T/imunologia , Vacinação , CápsulasRESUMO
BACKGROUND: Cervical cancer (CC) causes more than 311,000 deaths annually worldwide. The integration of human papillomavirus (HPV) is a crucial genetic event that contributes to cervical carcinogenesis. Despite HPV DNA integration is known to disrupt the genomic architecture of both the host and viral genomes in CC, the complexity of this process remains largely unexplored. RESULTS: In this study, we conducted whole-genome sequencing (WGS) at 55-65X coverage utilizing the PacBio long-read sequencing platform in SiHa and HeLa cells, followed by comprehensive analyses of the sequence data to elucidate the complexity of HPV integration. Firstly, our results demonstrated that PacBio long-read sequencing effectively identifies HPV integration breakpoints with comparable accuracy to targeted-capture Next-generation sequencing (NGS) methods. Secondly, we constructed detailed models of complex integrated genome structures that included both the HPV genome and nearby regions of the human genome by utilizing PacBio long-read WGS. Thirdly, our sequencing results revealed the occurrence of a wide variety of genome-wide structural variations (SVs) in SiHa and HeLa cells. Additionally, our analysis further revealed a potential correlation between changes in gene expression levels and SVs on chromosome 13 in the genome of SiHa cells. CONCLUSIONS: Using PacBio long-read sequencing, we have successfully constructed complex models illustrating HPV integrated genome structures in SiHa and HeLa cells. This accomplishment serves as a compelling demonstration of the valuable capabilities of long-read sequencing in detecting and characterizing HPV genomic integration structures within human cells. Furthermore, these findings offer critical insights into the complex process of HPV16 and HPV18 integration and their potential contribution to the development of cervical cancer.
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Infecções por Papillomavirus , Neoplasias do Colo do Útero , Feminino , Humanos , Neoplasias do Colo do Útero/genética , Células HeLa , Infecções por Papillomavirus/genética , DNA , Genômica , Integração Viral/genéticaRESUMO
BACKGROUND: Head and neck squamous cell carcinoma (HNSCC) typically present with a complex anatomical distribution, often accompanied by insidious symptoms. This combination contributes to its high incidence and poor prognosis. It is now understood that the immune features of cellular components within the tumor ecosystem and their complex interactions are critical factors influencing both tumor progression and the effective immune response. METHODS: We obtained single-cell RNA sequencing data of 26,496 cells from three tumor tissues and five normal tissues and performed subsequent analyses. Immunohistochemical staining on tumor sections was used to validate the presence of malignant cells. Additionally, we included bulk RNA sequencing data from 502 HNSCC patients. Kaplan-Meier analysis and the log-rank test were employed to assess predictors of patient outcomes. RESULTS: We identified three epithelial subclusters exhibiting immune-related features. These subclusters promoted the infiltration of T cells, dendritic cells, and monocytes into the tumor microenvironment. Additionally, cancer-associated fibroblasts displayed tumor-promoting and angiogenesis characteristics, contrasting with the predominant antigen-presenting and inflammatory roles observed in fibroblasts from normal tissues. Furthermore, tumor endothelial subsets exhibited a double-sided effect, promoting tumor progression and enhancing the effectiveness of immune response. Finally, follicular helper T cells and T helper 17 cells were found to be significantly correlated with improved outcomes in HNSCC patients. These CD4+ T cell subpopulations could promote the anti-tumor immune response by recruiting and activating B and T cells. CONCLUSION: Our findings provide deeper insights into the immune features of the tumor ecosystem and reveal the prognostic significance of follicular helper T cells and T helper 17 cells. These findings may pave the way for the development of therapeutic approaches.
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Neoplasias de Cabeça e Pescoço , Linfócitos do Interstício Tumoral , Análise da Expressão Gênica de Célula Única , Carcinoma de Células Escamosas de Cabeça e Pescoço , Células Th17 , Microambiente Tumoral , Feminino , Humanos , Masculino , Neoplasias de Cabeça e Pescoço/imunologia , Neoplasias de Cabeça e Pescoço/genética , Neoplasias de Cabeça e Pescoço/patologia , Linfócitos do Interstício Tumoral/imunologia , Prognóstico , RNA-Seq/métodos , Análise da Expressão Gênica de Célula Única/métodos , Carcinoma de Células Escamosas de Cabeça e Pescoço/imunologia , Carcinoma de Células Escamosas de Cabeça e Pescoço/genética , Carcinoma de Células Escamosas de Cabeça e Pescoço/patologia , Células T Auxiliares Foliculares/imunologia , Células Th17/imunologia , Microambiente Tumoral/imunologiaRESUMO
OBJECTIVE: Conventional single-target field control for matrix gradient coils will add control complexity in MRI spatial encoding, such as designing specialized fields and sequences. This complexity can be reduced by multi-target field control, which is realized by optimizing the coil structure according to target fields. METHODS: Based on the principle of multi-target field control, the X, Y and Z gradient fields can be set as target fields, and all coil elements can then be divided into three groups to generate these fields. An improved simulated annealing algorithm is proposed to optimize the coil element distribution of each group to generate the corresponding target field. In the improved simulated annealing process, two swapping modes are presented, and randomly selected with certain probabilities that are set to 0.25, 0.5 and 0.75, respectively. The flexibility of the final designed structure is demonstrated by a spherical harmonic basis up to the full second order with single-target field control. An experimental platform is built to measure the gradient fields generated by the designed structure with multi-target target control. RESULTS: With three probabilities of swapping modes, three similar coil element distributions are optimized, and their maximum magnetic field errors for generating X, Y and Z gradients are all below 5%. The structure selected for the final design is the one with a probability of 0.75, considering the coil performance and structural symmetry. The maximum error for all target fields generated by single-target field control is also below 5%. The experimental results show that the measured gradient fields along the axes have enough strength and high linearity. CONCLUSIONS: With the proposed improved simulated annealing algorithm and swapping modes, multi-target field control for matrix gradient coils is verified and achieved in this study by optimizing the coil element distribution. Moreover, this study provides a solution to simplify the complexity of controlling the matrix gradient coil in spatial encoding.
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Campos Magnéticos , Imageamento por Ressonância Magnética , Desenho de Equipamento , Imageamento por Ressonância Magnética/métodos , AlgoritmosRESUMO
OBJECTIVE: To propose a deep learning-based low-field mobile MRI strategy for fast, high-quality, unshielded imaging using minimal hardware resources. METHODS: Firstly, we analyze the correlation of EMI signals between the sensing coil and the MRI coil to preliminarily verify the feasibility of active EMI shielding using a single sensing coil. Then, a powerful deep learning EMI elimination model is proposed, which can accurately predict the EMI components in the MRI coil signals using EMI signals from at least one sensing coil. Further, deep learning models with different task objectives (super-resolution and denoising) are strategically stacked for multi-level post-processing to enable fast and high-quality low-field MRI. Finally, extensive phantom and brain experiments were conducted on a home-built 0.2 T mobile brain scanner for the evaluation of the proposed strategy. RESULTS: 20 healthy volunteers were recruited to participate in the experiment. The results show that the proposed strategy enables the 0.2 T scanner to generate images with sufficient anatomical information and diagnostic value under unshielded conditions using a single sensing coil. In particular, the EMI elimination outperforms the state-of-the-art deep learning methods and numerical computation methods. In addition, 2 × super-resolution (DDSRNet) and denoising (SwinIR) techniques enable further improvements in imaging speed and quality. DISCUSSION: The proposed strategy enables low-field mobile MRI scanners to achieve fast, high-quality imaging under unshielded conditions using minimal hardware resources, which has great significance for the widespread deployment of low-field mobile MRI scanners.
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Cellular ionic concentrations are a central factor orchestrating host innate immunity, but no pathogenic mechanism that perturbs host innate immunity by directly targeting metal ions has yet been described. Here, we report a unique virulence strategy of Yersinia pseudotuberculosis (Yptb) involving modulation of the availability of Mn2+, an immunostimulatory metal ion in host cells. We showed that the Yptb type VI secretion system (T6SS) delivered a micropeptide, TssS, into host cells to enhance its virulence. The mutant strain lacking TssS (ΔtssS) showed substantially reduced virulence but induced a significantly stronger host innate immune response, indicating an antagonistic role of this effector in host antimicrobial immunity. Subsequent studies revealed that TssS is a Mn2+-chelating protein and that its Mn2+-chelating ability is essential for the disruption of host innate immunity. Moreover, we showed that Mn2+ enhances the host innate immune response to Yptb infection by activating the stimulator of interferon genes (STING)-mediated immune response. Furthermore, we demonstrated that TssS counteracted the cytoplasmic Mn2+ increase to inhibit the STING-mediated innate immune response by sequestering Mn2+ Finally, TssS-mediated STING inhibition sabotaged bacterial clearance in vivo. These results reveal a previously unrecognized bacterial immune evasion strategy involving modulation of the bioavailability of intracellular metal ions and provide a perspective on the role of the T6SS in pathogenesis.
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Imunidade Inata , Manganês/metabolismo , Proteínas de Membrana/metabolismo , Sistemas de Secreção Tipo VI , Animais , Camundongos , Camundongos Endogâmicos C57BL , Ligação Proteica , Transporte Proteico , Yersinia pseudotuberculosis/metabolismo , Yersinia pseudotuberculosis/patogenicidadeRESUMO
The classic chemical Mitsunobu reaction suffers from the need of excess alcohol activation reagents and the generation of significant by-products. Efforts to overcome these limitations have resulted in numerous creative solutions, but the substrate scope of these catalytic processes remains limited. Here we report an electrochemical Mitsunobu-type reaction, which features azo-free alcohol activation and broad substrate scope. This user-friendly technology allows a vast collection of heterocycles as the nucleophile, which can couple with a series of chiral cyclic and acyclic alcohols in moderate to high yields and excellent ee's. This practical reaction is scalable, chemoselective, uses simple Electrasyn setup with inexpensive electrodes and requires no precaution to exclude air and moisture. The synthetic utility is further demonstrated on the structural modification of diverse bioactive natural products and pharmaceutical derivatives and its straightforward application in a multiple-step synthesis of a drug candidate.
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MET amplification and exon 14 skipping are well known as oncogenic drivers in multiple cancer types. However, MET fusions in most cancer types are poorly defined. To explore the profile and analyze the characteristics of MET fusions, a large-cohort study was conducted to screen MET fusions in clinical samples (n = 10 882) using DNA-based NGS. A total of 37 potentially functional MET fusions containing the intact tyrosine kinase domain (TKD) of MET were identified in 36 samples. Further, 15 novel MET fusions were identified in five cancer types, and the incidence of novel MET fusions accounted for 40.5% (15/37). Brain cancer had the highest incidence of MET fusion, with PTPRZ1-MET as the most common fusion (37.0%). All MET breakpoints in brain cancer (n = 27) were also located in intron 1, while those in lung cancer (n = 4) occurred in intron 1, intron 11, intron 14 and exon 14, respectively. The positive consistency of the common fusion group was 100% (11/11), while that of the rare fusion group was 53.8% (7/13). In conclusion, we provided a comprehensive genomic landscape of MET rearrangement and updated the MET fusions database for clinical test. In addition, we revealed that DNA-based NGS might serve as the clinical test for common MET fusions; however, rare MET fusions must be validated by both DNA-based NGS and RNA-based NGS. Prospective trials are necessary to confirm the treatment efficacy of MET inhibitors.
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Neoplasias Encefálicas , Neoplasias Pulmonares , Humanos , Neoplasias Encefálicas/genética , Estudos de Coortes , Neoplasias Pulmonares/genética , Proteínas de Fusão Oncogênica/genética , Estudos Prospectivos , Proteínas Tirosina Fosfatases Classe 5 Semelhantes a Receptores/genéticaRESUMO
Vibrio parahaemolyticus produces dual flagellar systems, i.e., the sheathed polar flagellum (Pof) and numerous lateral flagella (Laf), both of which are strictly regulated by numerous factors. QsvR is an AraC-type regulator that controls biofilm formation and virulence of V. parahaemolyticus. In the present study, we showed that deletion of qsvR significantly enhanced swimming motility of V. parahaemolyticus, while the swarming motility was not affected by QsvR. QsvR bound to the regulatory DNA regions of flgAMN and flgMN within the Pof gene loci to repress their transcription, whereas it negatively controls the transcription of flgBCDEFGHIJ and flgKL-flaC in an indirect manner. However, over-produced QsvR was also likely to possess the binding activity to the regulatory DNA regions of flgBCDEFGHIJ and flgKL-flaC in a heterologous host. In summary, this work demonstrated that QsvR negatively regulated the swimming motility of V. parahaemolyticus via directly action on the transcription of Pof genes.
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Vibrio parahaemolyticus , Vibrio parahaemolyticus/genética , Vibrio parahaemolyticus/metabolismo , Flagelos/genética , Flagelos/metabolismo , Genes Bacterianos , Regulação Bacteriana da Expressão Gênica , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismoRESUMO
Chemodivergent tandem radical cyclization offers exciting possibilities for the synthesis of structurally diverse cyclic compounds. Herein, we revealed a chemodivergent tandem cyclization of alkene-substituted quinazolinones under metal- and base-free conditions, this transformation is initiated by alkyl radicals produced from oxidant-induced α-C(sp3 )-H functionalization of alkyl nitriles or esters. The reaction resulted in the selective synthesis of a series of mono- and di-alkylated ring-fused quinazolinones by modulating the loading of oxidant, reaction temperature, and reaction time. Mechanistic investigations show that the mono-alkylated ring-fused quinazolinones is constructed by the key process of 1,2-hydrogen shift, whereas the di-alkylated ring-fused quinazolinones is mainly achieved through crucial steps of resonance and proton transfer. This protocol is the first example of remote second alkylation on the aromatic ring via α-C(sp3 )-H functionalization and difunctionalization achieved by association of two unsaturated bonds in radical cyclization.
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BACKGROUND: The novel coronavirus disease 2019 (COVID-19) has spread rapidly around the world since December 8, 2019. However, the key factors affecting the duration of recovery from COVID-19 remain unclear. OBJECTIVE: To investigate the associations of long recovery duration of COVID-19 patients with ambient air pollution, temperature, and diurnal temperature range (DTR) exposure. METHODS: A total of 427 confirmed cases in Changsha during the first wave of the epidemic in January 2020 were selected. We used inverse distance weighting (IDW) method to estimate personal exposure to seven ambient air pollutants (PM2.5, PM2.5-10, PM10, SO2, NO2, CO, and O3) at each subject's home address. Meteorological conditions included temperature and DTR. Multiple logistic regression model was used to investigate the relationship of air pollution exposure during short-term (past week and past month) and long-term (past three months) with recovery duration among COVID-19 patients. RESULTS: We found that long recovery duration among COVID-19 patients was positively associated with short-term exposure to CO during past week with OR (95% CI) = 1.42 (1.01-2.00) and PM2.5, NO2, and CO during past month with ORs (95% CI) = 2.00 (1.30-3.07) and 1.95 (1.30-2.93), and was negatively related with short-term exposure to O3 during past week and past month with ORs (95% CI) = 0.68 (0.46-0.99) and 0.41 (0.27-0.62), respectively. No association was observed for long-term exposure to air pollution during past three months. Furthermore, increased temperature during past three months elevated risk of long recovery duration in VOCID-19 patients, while DTR exposure during past week and past month decreased the risk. Male and younger patients were more susceptible to the effect of air pollution on long recovery duration, while female and older patients were more affected by exposure to temperature and DTR. CONCLUSION: Our findings suggest that both TRAP exposure and temperature indicators play important roles in prolonged recovery among COVID-19 patients, especially for the sensitive populations, which provide potential strategies for effective reduction and early prevention of long recovery duration of COVID-19.
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Poluentes Atmosféricos , Poluição do Ar , COVID-19 , Feminino , Humanos , Masculino , Poluentes Atmosféricos/análise , Poluição do Ar/efeitos adversos , China/epidemiologia , COVID-19/epidemiologia , Exposição Ambiental , Dióxido de Nitrogênio/análise , Material Particulado/análise , TemperaturaRESUMO
Mounting evidence have linked ambient air pollution and temperature with childhood pneumonia, but it is unclear whether there is an interaction between air pollution and temperature on childhood pneumonia. We aim to assess the combined effect of ambient air pollution and temperature exposure during preconception and pregnancy on pneumonia by a case-control study of 1510 children aged 0-14 years in Changsha, China. We obtained the data of childhood pneumonia from XiangYa Hospital electrical records. We estimated personal exposure to outdoor air pollution (PM10, SO2 and NO2) by inverse distance weighted (IDW) method and temperature indicators. Multiple logistic regression models were used to evaluate associations of childhood pneumonia with air pollution, temperature (T), and diurnal temperature variation (DTV). We found that exposure to industry-related air pollution (PM10 and SO2) during preconception and pregnancy were associated with childhood pneumonia, with ORs (95% CI) of 1.72 (1.48-1.98) and 2.96 (2.50-3.51) during 1 year before pregnancy and 1.83 (1.59-2.11) and 3.43 (2.83-4.17) in pregnancy. Childhood pneumonia was negatively associated with T exposure during 1 year before pregnancy and pregnancy, with ORs (95% CI) of 0.57 (0.41-0.80) and 0.85 (0.74-0.98). DTV exposure during pregnancy especially during the 1st and 2nd trimesters significantly increased pneumonia risk, with ORS (95% CI) of 1.77 (1.19-2.64), 1.47 (1.18-1.83), and 1.37 (1.07-1.76) respectively. We further observed interactions of PM10 and SO2 exposure with low T and high DTV during conception and pregnancy in relation to childhood pneumonia. This study suggests that there were interactions air pollution with temperature and DTV on pneumonia development.
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Poluentes Atmosféricos , Poluição do Ar , Pneumonia , Efeitos Tardios da Exposição Pré-Natal , Criança , Feminino , Humanos , Gravidez , Poluentes Atmosféricos/toxicidade , Poluentes Atmosféricos/análise , Poluição do Ar/efeitos adversos , Estudos de Casos e Controles , Pneumonia/induzido quimicamente , Pneumonia/epidemiologia , Efeitos Tardios da Exposição Pré-Natal/induzido quimicamente , Efeitos Tardios da Exposição Pré-Natal/epidemiologia , TemperaturaRESUMO
BACKGROUND: The prevalence of childhood allergies has increased during past decades leading to serious hospitalization and heavy burden worldwide, yet the key factors responsible for the onset of early symptoms and development of diagnosed diseases are unclear. OBJECTIVE: To explore the role of early life exposure to ambient air pollution and indoor environmental factors on early allergic symptoms and doctor diagnosed allergic diseases. METHODS: A retrospective cohort study of 2598 preschool children was conducted at 36 kindergartens in Changsha, China from September of 2011 to February of 2012. A questionnaire was developed to survey each child's early onset of allergic symptoms (wheeze and rhinitis-like symptoms) and doctor diagnosis of allergic diseases (asthma and rhinitis) as well as home environments. Each mother's and child's exposures to ambient air pollutants (PM10, SO2, and NO2) and temperature were estimated for in utero and postnatal periods. The associations of early symptoms and diagnosed diseases with outdoor air pollution and indoor environmental variables were examined by logistic regression models. RESULTS: Childhood early allergic symptoms (33.9%) including wheeze (14.7%) and rhinitis-like symptoms (25.4%) before 2 years old were not associated with outdoor air pollution exposure but was significantly associated with maternal exposure of window condensation at home in pregnancy with ORs (95% CI) of 1.33 (1.11-1.59), 1.30 (1.01-1.67) and 1.27 (1.04-1.55) respectively, and was associated with new furniture during first year after birth with OR (95% CI) of 1.43 (1.02-2.02) for early wheeze. Childhood diagnosed allergic diseases (28.4%) containing asthma (6.7%) and allergic rhinitis (AR) (7.2%) were significantly associated with both outdoor air pollutants (mainly for SO2 and NO2) during first 3 years and indoor new furniture, redecoration, and window condensation. We found that sex, age, parental atopy, maternal productive age, environmental tobacco smoke (ETS), antibiotics use, economic stress, early and late introduction of complementary foods, and outdoor air pollution modified the effects of home environmental exposure in early life on early allergic symptoms and diagnosed allergic diseases. CONCLUSION: Our study indicates that early life exposure to indoor environmental factors plays a key role in early onset of allergic symptoms in children, and further exposure to ambient air pollution and indoor environmental factors contribute to the later development of asthma and allergic rhinitis.
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Poluentes Atmosféricos , Poluição do Ar em Ambientes Fechados , Poluição do Ar , Asma , Rinite Alérgica , Rinite , Pré-Escolar , Gravidez , Feminino , Humanos , Dióxido de Nitrogênio/análise , Poluição do Ar em Ambientes Fechados/análise , Rinite/epidemiologia , Estudos Retrospectivos , Poluentes Atmosféricos/toxicidade , Poluentes Atmosféricos/análise , Exposição Ambiental , Asma/epidemiologia , Asma/etiologia , Sons Respiratórios , Rinite Alérgica/epidemiologia , Rinite Alérgica/etiologia , China/epidemiologiaRESUMO
Epidemiological and animal studies have shown that maternal fine particulate matters (PM2.5) exposure correlates with various adverse pregnancy outcomes such as low birth weight (LBW) of offspring. However, the underlying biological mechanisms have not been fully understood. In this study, female C57Bl/6 J mice were exposed to filtered air (FA) or concentrated ambient PM2.5 (CAP) during pregestational and gestational periods, and metabolomics was performed to analyze the metabolic features in maternal serum and placenta by liquid chromatography-mass spectrometry (LC-MS). The partial least squares discriminate analysis (PLS-DA) displayed evident clustering of FA- and CAP-exposed samples for both maternal serum and placenta. In addition, pathway analysis identified that vitamin digestion and absorption was perturbed in maternal serum, while metabolic pathways including arachidonic acid metabolism, serotonergic synapse, 2-oxocarboxylic acid metabolism and cAMP signaling pathway were perturbed in placenta. Further analysis indicated that CAP exposure influenced the nutrient transportation capacity of placenta, by not only changing the ratios of some critical metabolites in placenta to maternal serum but also significantly altering the expressions of nutrition transporters in placenta. These findings reaffirm the importance of protecting women from PM2.5 exposure, and also advance our understanding of the toxic actions of ambient PM2.5.
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Poluentes Atmosféricos , Exposição Materna , Gravidez , Humanos , Feminino , Camundongos , Animais , Exposição Materna/efeitos adversos , Poluentes Atmosféricos/análise , Material Particulado/análise , Placenta/química , Camundongos Endogâmicos C57BL , HomeostaseRESUMO
BACKGROUND: Given the serious consequences of depression and the lack of information about it during the crucially developmental period from the National College Entrance Exam (CEE, i.e., Chinese gaokao) to college, this study aimed to estimate the cumulative incidence, prevalence, age of onset, correlates, and service use of depressive disorders (DDs) among youth who passed the CEE and were enrolled at Hunan Normal University in China. METHODS: A two-stage cross-sectional epidemiological survey of DDs was conducted from October to December, 2017 among 6,922 incoming college students (98.5% effective response, N = 6,818, 71.4% female, age range: 16-25 years, mean age = 18.6). Using a stratified sampling method based on the risk of depression, 926 participants (mean age = 18.5, 75.2% female) were selected and subsequently interviewed with the Kiddie-Schedule for Affective Disorders and Schizophrenia-Present and lifetime version (K-SADS-PL). RESULTS: The sex-adjusted 9-month (i.e., 3 months pre-CEE, 3 months after CEE, and 3 months post-matriculation) incidence of new-onset DDs was 2.3% (standard error [S.E.] 0.3%), and the sex-adjusted 1-month, 6-month and lifetime prevalence were 0.7 (S.E. 0.3%), 1.7 (S.E. 0.2%) and 7.5% (S.E. 1.3%), respectively. The median age of onset was 17 (interquartile range: 16-18) years. Critically, over one-third (36.5%, S.E. 0.6) of depressed youth had their new onset during the 9-month period. The risk factors for depression included having mothers with higher education, experiencing major life events, being female, and experiencing parental divorce or death. The adjusted lifetime treatment rate was 8.7%. CONCLUSION: The 9-month incidence of new-onset depression from gaokao to college among the youth sample in China is similar to the global annual incidence (3.0%), but the 1-month and lifetime prevalence are significantly lower than the global point (7.2%) and lifetime prevalence (19%). These findings suggest a high proportion of new-onset depression during the CEE to college among the sample youth in China. The risk of depression is associated with familial and stress correlates. Low treatment is a serious concern. Emphasis on early prevention and available treatment for adolescent and young adult depression is a critical need in China.
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Transtorno Depressivo , Adulto Jovem , Humanos , Adolescente , Feminino , Adulto , Masculino , Universidades , Estudos Transversais , China/epidemiologia , Transtorno Depressivo/epidemiologia , Inquéritos EpidemiológicosRESUMO
OBJECTIVE: To compare the efficacy of dienogest and GnRH-a after endometriosis surgery. METHODS: Patients with endometriosis who were admitted to our hospital from December 2020 to March 2022 were randomly collected. A total of 81 patients were collected and divided into 40 cases in the control group and 41 cases in the observation group. Among them, the control group was treated with GnRH-a drug, and the observation group was treated with dienogest (DNG). RESULTS: The study found that the therapeutic effects of the two drugs were basically the same in patients with endometriosis. The VAS and Kupperman scores of the control group were 0.78 ± 0.8, 3.9 ± 1.84, P < 0.05, respectively; the VAS and Kupperman scores of the observation group were 0.73 ± 0.78, 1.55, respectively ± 1.24, P < 0.05, the difference was statistically significant.In the case of postoperative recurrence, the observation group was better than the control group, with 8 cases of recurrence in the control group and 2 cases of recurrence in the observation group, P < 0.05. CONCLUSION: In the comparison of postoperative efficacy of the two drugs on patients with endometriosis, dienogest is better than GnRH-a adjuvant drug in postoperative recurrence, and has a good improvement and application, which is worthy of further promotion in clinical practice.
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Endometriose , Nandrolona , Feminino , Humanos , Endometriose/cirurgia , Hormônio Liberador de Gonadotropina/uso terapêutico , Antagonistas de Hormônios/uso terapêutico , Nandrolona/uso terapêuticoRESUMO
OBJECTIVE: To design a lightweight permanent magnet for a lowfield movable head imaging MRI system. MATERIALS AND METHODS: To reduce the weight of the magnet, the pole pieces, anti-eddy current plates, and shimming rings were removed, and the distance between the two vertical yokes was shortened as much as possible. To compensate for the magnetic field deformation caused by the shortened distance between two vertical iron yokes, two side magnetic poles were added to the vertical yokes. The magnetic field distributions in magnetic poles, the iron yoke, and the spherical imaging region were simulated. Phantom and in vivo head imaging were conducted with a lowfield movable MRI prototype scanner equipped with the proposed permanent magnet. RESULTS: A permanent magnet with a center field of 0.19815 T, a homogeneity of 46 ppm over the 20 cm spherical imaging region, and a weight of 654 kg have been achieved. Acceptable images of a phantom and a human brain have been acquired with the prototype MRI scanner. DISCUSSION: The proposed permanent magnet design significantly reduces the magnet's weight compared with the conventional magnet structure and shows promise in promoting the development of lowfield compact MRI systems.
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Imageamento por Ressonância Magnética , Imãs , Humanos , Imageamento por Ressonância Magnética/métodos , Campos Magnéticos , Magnetismo , FerroRESUMO
Vibrio parahaemolyticus, the leading cause of bacterial seafood-associated gastroenteritis, can form biofilms. In this work, the gene expression profiles of V. parahaemolyticus during biofilm formation were investigated by transcriptome sequencing. A total of 183, 503, and 729 genes were significantly differentially expressed in the bacterial cells at 12, 24 and 48 h, respectively, compared with that at 6 h. Of these, 92 genes were consistently activated or repressed from 6 to 48 h. The genes involved in polar flagellum, chemotaxis, mannose-sensitive haemagglutinin type IV pili, capsular polysaccharide, type III secretion system 1 (T3SS1), T3SS2, thermostable direct hemolysin (TDH), type VI secretion system 1 (T6SS1) and T6SS2 were downregulated, whereas those involved in V. parahaemolyticus pathogenicity island (Vp-PAI) (except for T3SS2 and TDH) and membrane fusion proteins were upregulated. Three extracellular protease genes (vppC, prtA and VPA1071) and a dozen of outer membrane protein encoding genes were also significantly differentially expressed during biofilm formation. In addition, five putative c-di-GMP metabolism-associated genes were significantly differentially expressed, which may account for the drop in c-di-GMP levels after the beginning of biofilm formation. Moreover, many putative regulatory genes were significantly differentially expressed, and more than 1000 putative small non-coding RNAs were detected, suggesting that biofilm formation was tightly regulated by complex regulatory networks. The data provided a global view of gene expression profiles during biofilm formation, showing that the significantly differentially expressed genes were involved in multiple cellular pathways, including virulence, biofilm formation, metabolism, and regulation.
Assuntos
Vibrioses , Vibrio parahaemolyticus , Humanos , Transcriptoma , Vibrio parahaemolyticus/genética , Virulência/genética , Fatores de Virulência/genética , Biofilmes , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo , Vibrioses/microbiologia , Regulação Bacteriana da Expressão GênicaRESUMO
The cysteine-rich polycomb-like protein (CPP) gene family is a class of transcription factors containing conserved cysteine-rich CRC structural domains that is involved in the regulation of plant growth and stress tolerance to adversity. Relative to other gene families, the CPP gene family has not received sufficient attention. In this study, six SlCPPs were identified for the first time using the most recent genome-wide identification data of tomato. Subsequently, a phylogenetic analysis classified SlCPPs into four subfamilies. The analysis of cis-acting elements in the promoter indicates that SlCPPs are involved in plant growth and development and also stress response. We present for the first time the prediction of the tertiary structure of these SlCPPs proteins using the AlphaFold2 artificial intelligence system developed by the DeepMind team. Transcriptome data analysis showed that SlCPPs were differentially expressed in different tissues. Gene expression profiling showed that all SlCPPs except SlCPP5 were up-regulated under drought stress; SlCPP2, SlCPP3 and SlCPP4 were up-regulated under cold stress; SlCPP2 and SlCPP5 were up-regulated under salt stress; all SlCPPs were up-regulated under inoculation with Cladosporium fulvum; and SlCPP1, SlCPP3, and SlCPP4 were up-regulated under inoculation with Stemphylium lycopersici. We performed a virus-induced gene silencing experiment on SlCPP3, and the results indicated that SlCPP3 was involved in the response to drought stress. Finally, we predicted the interaction network of the key gene SlCPP3, and there was an interaction relationship between SlCPP3 and 10 genes, such as RBR1 and MSI1. The positive outcome showed that SlCPPs responded to environmental stress. This study provides a theoretical and empirical basis for the response mechanisms of tomato in abiotic stresses.
Assuntos
Solanum lycopersicum , Solanum lycopersicum/genética , Cisteína/metabolismo , Filogenia , Inteligência Artificial , Fatores de Transcrição/metabolismo , Perfilação da Expressão Gênica , Estresse Fisiológico/genética , Proteínas de Plantas/metabolismo , Regulação da Expressão Gênica de Plantas , Família MultigênicaRESUMO
Phloroglucinol is commonly used to alleviate dysmenorrhoea and stomach cramps. However, there is little evidence of phloroglucinol in the mechanism of primary dysmenorrhoea (PD) development. In this study, a PD rat model was established. The effects of phloroglucinol on the contraction of rat gastric circular muscle and uterine smooth muscle induced by oxytocin (OT) were investigated. The writhing response, and levels of oestradiol (E2), prostaglandin e2 (PGE2), and prostaglandin f2α (PGF2α) were determined. The protein and mRNA levels of OT receptor (OTR) were detected. OT showed a significant promoting effect on gastric circular muscle and uterine smooth muscle contraction. However, phloroglucinol strongly inhibited the contraction induced by 10-6 mol/L of OT. We also found that phloroglucinol reduced writhing response and attenuated uterine damage. Compared to the blank group, E2 and PGF2α were significantly increased, but PGE2 was significantly decreased in the PD model group. Phloroglucinol was found to reverse the changes of E2, PGF2α and PGE2. Moreover, phloroglucinol reduced the protein and mRNA levels of OTR. In conclusion, phloroglucinol could attenuate PD and inhibit the contraction of rat gastric circular muscle and uterine smooth muscle induced by OT. The mechanism might be related with the regulation of OTR expression.IMPACT STATEMENTWhat is already known on this subject? Phloroglucinol is commonly used to alleviate dysmenorrhoea and stomach cramps. However, there is little evidence of phloroglucinol in the mechanism of primary dysmenorrhoea (PD) development.What do the results of this study add? Phloroglucinol could attenuate PD and inhibit the contraction of rat gastric circular muscle and uterine smooth muscle induced by OT. The underlying mechanisms of phloroglucinol for PD treatment may be associated with OTR.What are the implications of these findings for clinical practice and/or further research? These findings provide novel ideas for the role of phloroglucinol in PD development.