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Cellular senescence is an irreversible state of cell-cycle arrest induced by various stresses, including aberrant oncogene activation, telomere shortening, and DNA damage. Through a genome-wide screen, we discovered a conserved small nucleolar RNA (snoRNA), SNORA13, that is required for multiple forms of senescence in human cells and mice. Although SNORA13 guides the pseudouridylation of a conserved nucleotide in the ribosomal decoding center, loss of this snoRNA minimally impacts translation. Instead, we found that SNORA13 negatively regulates ribosome biogenesis. Senescence-inducing stress perturbs ribosome biogenesis, resulting in the accumulation of free ribosomal proteins (RPs) that trigger p53 activation. SNORA13 interacts directly with RPL23, decreasing its incorporation into maturing 60S subunits and, consequently, increasing the pool of free RPs, thereby promoting p53-mediated senescence. Thus, SNORA13 regulates ribosome biogenesis and the p53 pathway through a non-canonical mechanism distinct from its role in guiding RNA modification. These findings expand our understanding of snoRNA functions and their roles in cellular signaling.
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Senescência Celular , RNA Nucleolar Pequeno , Proteínas Ribossômicas , Ribossomos , Proteína Supressora de Tumor p53 , Humanos , RNA Nucleolar Pequeno/metabolismo , RNA Nucleolar Pequeno/genética , Senescência Celular/genética , Proteína Supressora de Tumor p53/metabolismo , Proteína Supressora de Tumor p53/genética , Ribossomos/metabolismo , Animais , Camundongos , Proteínas Ribossômicas/metabolismo , Proteínas Ribossômicas/genéticaRESUMO
Maternal mortality is unusually high in the United States compared to other wealthy nations and is characterized by major disparities in race/ethnicity, geography, and socioeconomic factors. Similar to other developed nations, the United States has seen a shift in the underlying causes of pregnancy-related death, with a relative increase in mortality resulting from diseases of the cardiovascular system and preexisting medical conditions. Improved continuity of care aimed at identifying reproductive-age women with preexisting conditions that may heighten the risk of maternal death, preconception management of risk factors for major adverse pregnancy outcomes, and primary care visits within the first year after delivery may offer opportunities to address gaps in medical care contributing to the unacceptable rates of maternal mortality in the United States.
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Etnicidade , Mortalidade Materna , Gravidez , Humanos , Feminino , Estados Unidos/epidemiologia , Fatores de RiscoRESUMO
Here, we present the second generation of our bicyclic peptide library (NTB), featuring a stereodiversified structure and a simplified construction strategy. We utilized a tandem ring-opening metathesis and ring-closing metathesis reaction (ROM-RCM) to cyclize the linear peptide library in a single step, representing the first reported instance of this reaction being applied to the preparation of macrocyclic peptides. Moreover, the resulting bicyclic peptide can be easily linearized for MS/MS sequencing with a one-step deallylation process. We employed this library to screen against the E363-R378 epitope of MYC and identified several MYC-targeting bicyclic peptides. Subsequent in vitro cell studies demonstrated that one candidate, NT-B2R, effectively suppressed MYC transcription activities and cell proliferation.
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Biblioteca de Peptídeos , Espectrometria de Massas em Tandem , Peptídeos/farmacologia , Peptídeos/químicaRESUMO
BACKGROUND: Plant-based diets have been associated with a lower risk of cardiovascular disease in nonpregnant adults, but specific evidence for their effects on risk of hypertensive disorders of pregnancy is scarce. OBJECTIVE: This study aimed to evaluate the prospective association between adherence to plant-based diets before pregnancy and the risk for hypertensive disorders of pregnancy. We hypothesized that women with higher adherence to plant-based diets would have a lower risk for hypertensive disorders of pregnancy. STUDY DESIGN: We followed 11,459 parous women (16,780 singleton pregnancies) without chronic diseases, a history of preeclampsia, and cancers who participated in the Nurses' Health Study II (1991-2009), which was a prospective cohort study. Diet was assessed every 4 years using a validated food frequency questionnaire from which we calculated the plant-based diet index (higher score indicates higher adherence) to evaluate the health associations of plant-based diets among participants while accounting for the quality of plant-based foods. Participants self-reported hypertensive disorders of pregnancy, including preeclampsia and gestational hypertension. We estimated the relative risk of hypertensive disorders of pregnancy in relation to plant-based diet index adherence in quintiles using generalized estimating equations log-binomial regression while adjusting for potential confounders and accounting for repeated pregnancies for the same woman. RESULTS: The mean (standard deviation) age at first in-study pregnancy was 35 (4) years. A total of 1033 cases of hypertensive disorders of pregnancy, including 482 cases of preeclampsia (2.9%) and 551 cases of gestational hypertension (3.3%) were reported. Women in the highest quintile of plant-based diet index were significantly associated with a lower risk for hypertensive disorders of pregnancy than women in the lowest quintile (relative risk, 0.76; 95% confidence interval, 0.62-0.93). There was an inverse dose-response relationship between plant-based diet index and risk for hypertensive disorders of pregnancy. The multivariable-adjusted relative risk (95% confidence interval) of hypertensive disorders of pregnancy for women in increasing quintiles of plant-based diet index were 1 (ref), 0.93 (0.78-1.12), 0.86 (0.72-1.03), 0.84 (0.69-1.03), and 0.76 (0.62-0.93) with a significant linear trend across quintiles (P trend=.005). This association was slightly stronger for gestational hypertension (relative risk, 0.77; 95% confidence interval, 0.60-0.99) than for preeclampsia (relative risk, 0.80; 95% confidence interval, 0.61-1.04). Mediation analysis suggested that body mass index evaluation for dietary assessment and pregnancy explained 39% (95% confidence interval, 15%-70%]) of the relation between plant-based diet index and hypertensive disorders of pregnancy and 48% (95% confidence interval, 12%-86%]) of the relation between plant-based diet index and gestational hypertension. CONCLUSION: Higher adherence to plant-based diets was associated with a lower risk of developing hypertensive disorders of pregnancy. Much of the benefit seems to be related to improved weight control.
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Hipertensão Induzida pela Gravidez , Pré-Eclâmpsia , Adulto , Gravidez , Feminino , Humanos , Hipertensão Induzida pela Gravidez/epidemiologia , Pré-Eclâmpsia/epidemiologia , Estudos Prospectivos , Dieta Baseada em Plantas , DietaRESUMO
Long non-coding (lnc)RNAs, once thought to merely represent noise from imprecise transcription initiation, have now emerged as major regulatory entities in all eukaryotes. In contrast to the rapidly expanding identification of individual lncRNAs, mechanistic characterization has lagged behind. Here we provide evidence that the GAL lncRNAs in the budding yeast S. cerevisiae promote transcriptional induction in trans by formation of lncRNA-DNA hybrids or R-loops. The evolutionarily conserved RNA helicase Dbp2 regulates formation of these R-loops as genomic deletion or nuclear depletion results in accumulation of these structures across the GAL cluster gene promoters and coding regions. Enhanced transcriptional induction is manifested by lncRNA-dependent displacement of the Cyc8 co-repressor and subsequent gene looping, suggesting that these lncRNAs promote induction by altering chromatin architecture. Moreover, the GAL lncRNAs confer a competitive fitness advantage to yeast cells because expression of these non-coding molecules correlates with faster adaptation in response to an environmental switch.
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DNA Fúngico/metabolismo , Metabolismo Energético , RNA Fúngico/metabolismo , RNA Longo não Codificante/metabolismo , Saccharomyces cerevisiae/metabolismo , Transcrição Gênica , Ativação Transcricional , Adaptação Fisiológica , Montagem e Desmontagem da Cromatina , RNA Helicases DEAD-box/genética , RNA Helicases DEAD-box/metabolismo , DNA Fúngico/química , DNA Fúngico/genética , Metabolismo Energético/genética , Galactose/metabolismo , Regulação Fúngica da Expressão Gênica , Glucose/metabolismo , Família Multigênica , Proteínas Nucleares/genética , Proteínas Nucleares/metabolismo , Conformação de Ácido Nucleico , RNA Fúngico/química , RNA Fúngico/genética , RNA Longo não Codificante/química , RNA Longo não Codificante/genética , Proteínas Repressoras/genética , Proteínas Repressoras/metabolismo , Ribonuclease H/genética , Ribonuclease H/metabolismo , Saccharomyces cerevisiae/genética , Proteínas de Saccharomyces cerevisiae/genética , Proteínas de Saccharomyces cerevisiae/metabolismo , Fatores de TempoRESUMO
PURPOSE: Research on infertility and risk of breast cancer has been conflicting, potentially because many well-established breast cancer risk factors, such as pregnancy history, are strongly correlated with infertility. METHODS: We followed participants in the Nurses' Health Study II from 1989 to 2015 (n = 103,080) for the development of invasive breast cancer and calculated Hazard Ratios (HR) and 95% confidence intervals (CI) using Cox regression. Participants with a self-reported history of infertility (12 months of trying without conception) were compared to gravid women with no history of infertility. We classified breast cancer by menopausal status and investigated mediation by reproductive factors. RESULTS: Over 26 years of follow-up, 26,208 (25.4%) women reported a history of infertility, and 3,201 women were newly diagnosed with invasive breast cancer. We observed no association between infertility history and risk of overall breast cancer (HR: 1.05, 95% CI: 0.97-1.14) or premenopausal breast cancer (RR: 0.93, 95% CI: 0.83-1.03). However, we observed a modest association between history of infertility and risk of postmenopausal breast cancer (HR: 1.13, 95% CI: 1.00-1.28), approximately 50% of which could be attributed to lower total parity and later age at first birth (95% CI: 8.2%-91.0%). CONCLUSIONS: Women with a history of infertility were at increased risk of postmenopausal breast cancer. Older age at first birth and lower total parity explained approximately half of the association between infertility and risk of postmenopausal breast cancer.
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Neoplasias da Mama , Gravidez , Feminino , Humanos , Masculino , Neoplasias da Mama/epidemiologia , Neoplasias da Mama/diagnóstico , Estudos Prospectivos , Paridade , História Reprodutiva , Fatores de RiscoRESUMO
Increasing evidences showed that ovulatory dysfunction, possibly caused by luteinized unruptured follicular follicle syndrome (LUFS), is one of the reasons for endometriosis-related infertility. The present study was conducted to explore the potential effect of elevated progesterone in follicular fluid (FF) on ovulation in endometriosis. A prospective study including 50 ovarian endometriosis patients and 50 control patients with matched pairs design was conducted with alterations in FF and peritoneal fluid (PF) components identified by metabolomics analyses and differentially expressed genes in granulosa cells (GCs) identified by transcriptome analysis. Patients with endometriosis exhibited a significantly higher progesterone level in serum, FF, and PF. Granulosa cells from endometriosis patients revealed decreased expression of HPGD, COX-2, and suppressed NF-ĸB signaling. Similarly, progesterone treatment in vitro downregulated HPGD and COX2 expression and suppressed NF-ĸB signaling in granulosa tumor-like cell line KGN (Bena Culture Collection, China) and primarily cultured GCs, as manifested by decreased expressions of IL1R1, IRAK3, reduced pIĸBα/IĸBα ratio, and nucleus translocation of p65. On the contrary, TNF-α treatment increased expression of IL1R1, IRAK3, pIĸBα, p65, and HPGD in GCs. One potential p65 binding site was identified in the promoter region of HPGD by chromatin immunoprecipitation. In conclusion, we found that intrafollicular progesterone might downregulate HPGD and COX-2 in GCs via suppressing the NF-ĸB signaling pathway, shedding light on the mechanism underlying the endometriosis-related ovulatory dysfunction.
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Endometriose , Infertilidade Feminina , Feminino , Humanos , Progesterona/farmacologia , Progesterona/metabolismo , Líquido Folicular/metabolismo , Endometriose/genética , Endometriose/metabolismo , Ciclo-Oxigenase 2/genética , Ciclo-Oxigenase 2/metabolismo , NF-kappa B/genética , NF-kappa B/metabolismo , Estudos Prospectivos , Células da Granulosa/metabolismo , Infertilidade Feminina/metabolismoRESUMO
BACKGROUND: Pre-pandemic psychological distress is associated with increased susceptibility to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, but associations with the coronavirus disease 2019 (COVID-19) severity are not established. The authors examined the associations between distress prior to SARS-CoV-2 infection and subsequent risk of hospitalization. METHODS: Between April 2020 (baseline) and April 2021, we followed 54 781 participants from three ongoing cohorts: Nurses' Health Study II (NHSII), Nurses' Health Study 3 (NHS3), and the Growing Up Today Study (GUTS) who reported no current or prior SARS-CoV-2 infection at baseline. Chronic depression was assessed during 2010-2019. Depression, anxiety, worry about COVID-19, perceived stress, and loneliness were measured at baseline. SARS-CoV-2 infection and hospitalization due to COVID-19 was self-reported. Relative risks (RRs) were calculated by Poisson regression. RESULTS: 3663 participants reported a positive SARS-CoV-2 test (mean age = 55.0 years, standard deviation = 13.8) during follow-up. Among these participants, chronic depression prior to the pandemic [RR = 1.72; 95% confidence interval (CI) 1.20-2.46], and probable depression (RR = 1.81, 95% CI 1.08-3.03), being very worried about COVID-19 (RR = 1.79; 95% CI 1.12-2.86), and loneliness (RR = 1.81, 95% CI 1.02-3.20) reported at baseline were each associated with subsequent COVID-19 hospitalization, adjusting for demographic factors and healthcare worker status. Anxiety and perceived stress were not associated with hospitalization. Depression, worry about COVID-19, and loneliness were as strongly associated with hospitalization as were high cholesterol and hypertension, established risk factors for COVID-19 severity. CONCLUSIONS: Psychological distress may be a risk factor for hospitalization in patients with SARS-CoV-2 infection. Assessment of psychological distress may identify patients at greater risk of hospitalization. Future work should examine whether addressing distress improves physical health outcomes.
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COVID-19 , Humanos , Pessoa de Meia-Idade , COVID-19/epidemiologia , SARS-CoV-2 , Estudos Prospectivos , Solidão/psicologia , Depressão/epidemiologia , Depressão/psicologia , Ansiedade/epidemiologia , Ansiedade/psicologia , HospitalizaçãoRESUMO
BACKGROUND: Avian influenza (AI) is a disease caused by the avian influenza virus (AIV). These viruses spread naturally among wild aquatic birds worldwide and infect domestic poultry, other birds, and other animal species. Currently, real-time reverse transcription polymerase chain reaction (rRT-PCR) is mainly used to detect the presence of pathogens and has good sensitivity and specificity. However, the diagnosis requires sophisticated instruments under laboratory conditions, which significantly limits point-of-care testing (POCT). Rapid, reliable, non-lab-equipment-reliant, sensitive, and specific diagnostic tests are urgently needed for rapid clinical detection and diagnosis. Our study aimed to develop a reverse transcription recombinase polymerase amplification (RT-RPA)/CRISPR method which improves on these limitations. METHODS: The Cas12a protein was purified by affinity chromatography with Ni-agarose resin and observed using sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE). Specific CRISPR RNA (crRNA) and primers targeting the M and NP genes of the AIV were designed and screened. By combining RT-RPA with the Cas12a/crRNA trans-cleavage system, a detection system that uses fluorescence readouts under blue light or lateral flow strips was established. Sensitivity assays were performed using a tenfold dilution series of plasmids and RNA of the M and NP genes as templates. The specificity of this method was determined using H1-H16 subtype AIVs and other avian pathogens, such as newcastle disease virus (NDV), infectious bursal disease virus (IBDV), and infectious bronchitis virus (IBV). RESULTS: The results showed that the method was able to detect AIV and that the detection limit can reach 6.7 copies/µL and 12 copies/µL for the M and NP gene, respectively. In addition, this assay showed no cross-reactivity with other avian-derived RNA viruses such as NDV, IBDV, and IBV. Moreover, the detection system presented 97.5% consistency and agreement with rRT-PCR and virus isolation for detecting samples from poultry. This portable and accurate method has great potential for AIV detection in the field. CONCLUSION: An RT-RPA/CRISPR method was developed for rapid, sensitive detection of AIV. The new system presents a good potential as an accurate, user-friendly, and inexpensive platform for point-of-care testing applications.
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Vírus da Influenza A , Influenza Aviária , Animais , Influenza Aviária/diagnóstico , Sistemas CRISPR-Cas , Aves , Aves Domésticas , Sensibilidade e Especificidade , Reação em Cadeia da Polimerase em Tempo Real/métodos , Vírus da Doença de Newcastle/genética , RNARESUMO
Drug delivery systems (DDSs) play an important role in delivering active pharmaceutical ingredients (APIs) to targeted sites with a predesigned release pattern. The chemical and biological properties of APIs and excipients have been extensively studied for their contribution to DDS quality and effectiveness; however, the structural characteristics of DDSs have not been adequately explored. Structure pharmaceutics involves the study of the structure of DDSs, especially the three-dimensional (3D) structures, and its interaction with the physiological and pathological structure of organisms, possibly influencing their release kinetics and targeting abilities. A systematic overview of the structures of a variety of dosage forms, such as tablets, granules, pellets, microspheres, powders, and nanoparticles, is presented. Moreover, the influence of structures on the release and targeting capability of DDSs has also been discussed, especially the in vitro and in vivo release correlation and the structure-based organ- and tumor-targeting capabilities of particles with different structures. Additionally, an in-depth discussion is provided regarding the application of structural strategies in the DDSs design and evaluation. Furthermore, some of the most frequently used characterization techniques in structure pharmaceutics are briefly described along with their potential future applications.
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Biofarmácia , Neoplasias , Humanos , Sistemas de Liberação de Medicamentos , Preparações Farmacêuticas , ExcipientesRESUMO
To understand the suppressing actions of inorganic compound flame retardant (CFR) on the pyrolysis behavior of asphalt, five halogen-free flame retardants, such as expanded graphite, aluminum hydroxide, magnesium hydrate, calcium hydroxide, and microencapsulated red phosphorus, were selected to match the pyrolysis temperature ranges of four asphalt components, respectively. The pyrolysis behaviors, volatile emissions, and pyrolysis residues from asphalt and CFR-modified asphalt (FR asphalt) were compared. Also, the effects of CFR on the microscopic morphology, microstructures, and micromechanical performance of asphalt were analyzed. The high-temperature stability of asphalt is increased by the presence of CFR, and there is a flame-retardant constituent in CFR that suppresses the pyrolysis of each component in the overall asphalt pyrolysis process. Additionally, the FR asphalt pyrolysis process is endothermic. The added CFR retards the asphalt pyrolysis process. The formation of the surface carbon layer impedes heat transfer. Also, the volatile emissions during asphalt pyrolysis are reduced by the presence of CFR. The added CFR promotes an increase in the size of the asphalt microstructure. The surface of FR asphalt becomes rougher and more rugged than that of asphalt. Finally, the elastic modulus, deformation resistance, and micromechanical performance of asphalt are increased as the level of FR presence is increased. FR asphalt has a higher adhesive force, which is conducive to increasing the adhesivity of FR asphalt with mineral aggregate in the FR asphalt mixture.
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BACKGROUND: Women are at greater risk than men of developing chronic inflammatory conditions and "long COVID." However, few gynecologic health risk factors for long COVID-19 have been identified. Endometriosis is a common gynecologic disorder associated with chronic inflammation, immune dysregulation, and comorbid presentation with autoimmune and clotting disorders, all of which are pathophysiological mechanisms proposed for long COVID-19. Therefore, we hypothesized that women with a history of endometriosis may be at greater risk of developing long COVID-19. OBJECTIVE: This study aimed to investigate the association between history of endometriosis before SARS-CoV-2 infection and risk of long COVID-19. STUDY DESIGN: We followed 46,579 women from 2 ongoing prospective cohort studies-the Nurses' Health Study II and the Nurses' Health Study 3-who participated in a series of COVID-19-related surveys administered from April 2020 to November 2022. Laparoscopic diagnosis of endometriosis was documented prospectively in main cohort questionnaires before the pandemic (1993-2020) with high validity. SARS-CoV-2 infection (confirmed by antigen, polymerase chain reaction, or antibody test) and long-term COVID-19 symptoms (≥4 weeks) defined by the Centers for Disease Control and Prevention were self-reported during follow-up. Among individuals with SARS-CoV-2 infection, we fit Poisson regression models to assess the associations between endometriosis and risk of long COVID-19 symptoms, with adjustment for potential confounding variables (demographics, body mass index, smoking status, history of infertility, and history of chronic diseases). RESULTS: Among 3650 women in our sample with self-reported SARS-CoV-2 infections during follow-up, 386 (10.6%) had a history of endometriosis with laparoscopic confirmation, and 1598 (43.8%) reported experiencing long COVID-19 symptoms. Most women were non-Hispanic White (95.4%), with a median age of 59 years (interquartile range, 44-65). Women with a history of laparoscopically-confirmed endometriosis had a 22% greater risk of developing long COVID-19 (adjusted risk ratio, 1.22; 95% confidence interval, 1.05-1.42) compared with those who had never been diagnosed with endometriosis. The association was stronger when we defined long COVID-19 as having symptoms for ≥8 weeks (risk ratio, 1.28; 95% confidence interval, 1.09-1.50). We observed no statistically significant differences in the relationship between endometriosis and long COVID-19 by age, infertility history, or comorbidity with uterine fibroids, although there was a suggestive trend indicating that the association may be stronger in women aged <50 years (<50 years: risk ratio, 1.37; 95% confidence interval, 1.00-1.88; ≥50 years: risk ratio, 1.19; 95% confidence interval, 1.01-1.41). Among persons who developed long COVID-19, women with endometriosis reported on average 1 additional long-term symptom compared with women without endometriosis. CONCLUSION: Our findings suggest that those with a history of endometriosis may be at modestly increased risk for long COVID-19. Healthcare providers should be aware of endometriosis history when treating patients for signs of persisting symptoms after SARS-CoV-2 infection. Future studies should investigate the potential biological pathways underlying these associations.
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COVID-19 , Endometriose , Infertilidade , Masculino , Humanos , Feminino , Pessoa de Meia-Idade , Endometriose/diagnóstico , Estudos Prospectivos , Síndrome de COVID-19 Pós-Aguda , SARS-CoV-2RESUMO
BACKGROUND: Deep learning (DL) is more and more widely used in children's medical treatment. In this study, we have developed a computed tomography (CT)-based DL model for identifying undiagnosed non-Wilms tumors (nWTs) from pediatric renal tumors. METHODS: This study collected and analyzed the preoperative clinical data and CT images of pediatric renal tumor patients diagnosed by our center from 2008 to 2020, and established a DL model to identify nWTs noninvasively. RESULTS: A total of 364 children who had been confirmed by histopathology with renal tumors from our center were enrolled, including 269 Wilms tumors (WTs) and 95 nWTs. For DL model development, all cases were randomly allocated to training set (218 cases), validation set (73 cases), and test set (73 cases). In the test set, the DL model achieved area under the curve of 0.831 (95% CI: 0.712-0.951) in discriminating WTs from nWTs, with the accuracy, sensitivity, and specificity of 0.781, 0.563, and 0.842, respectively. The sensitivity of our model was higher than a radiologist with 15 years of experience. CONCLUSIONS: We presented a DL model for identifying undiagnosed nWTs from pediatric renal tumors, with the potential to improve the image-based diagnosis. IMPACT: Deep learning model was used for the first time to identify pediatric renal tumors in this study. Deep learning model can identify non-Wilms tumors from pediatric renal tumors. Deep learning model based on computed tomography images can improve tumor diagnosis rate.
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Neoplasias Renais , Tumor de Wilms , Criança , Humanos , Tumor de Wilms/diagnóstico por imagem , Tumor de Wilms/patologia , Neoplasias Renais/diagnóstico por imagem , Neoplasias Renais/tratamento farmacológico , Neoplasias Renais/patologia , Redes Neurais de Computação , Tomografia Computadorizada por Raios X/métodos , Estudos RetrospectivosRESUMO
H2S was deemed as a toxic gradient in the realm of food and environment but plays pivotal pathophysiological roles in organisms. H2S instabilities and disturbances are always responsible for multiple disorders. We fabricated a H2S-responsive NIR fluorescent probe (HT) for H2S detection and evaluation both in vitro and in vivo. HT exhibited rapid H2S response within 5 min, accompanied with visible color change and NIR fluorescence generation, and the fluorescent intensities were linearly correlated with corresponding H2S concentrations. When HT was incubated with A549 cells, the intracellular H2S and H2S fluctuations could be monitored ore rotundo via the responsive fluorescence. Meanwhile, when HT was co-administrated with H2S prodrug ADT-OH, the H2S release from ADT-OH could be visualized and monitored to evaluate its release efficacy.
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Sulfeto de Hidrogênio , Pró-Fármacos , Humanos , Corantes Fluorescentes , Tionas , Células HeLaRESUMO
High-throughput photofragmentation studies of thymine and guanine were performed at 257 and 343 nm and for a wide range of ionisation laser intensities. Combining a continuous laser-based thermal desorption source with femtosecond multiphoton ionisation using a 50 kHz repetition rate laser allowed us to produce detailed 2D maps of fragmentation as a function of incident laser intensity. The fragmentation was distinctly soft, the parent ions being at least an order of magnitude more abundant than fragment ions. For thymine there was a single dominant fragmentation channel, which involves consecutive HNCO and CO losses. In contrast, for guanine there were several competing ones, the most probable channel corresponding to CH2N2 loss through opening of the pyrimidine ring. The dependence of parent ion abundance on the ionisation laser intensity showed that at 257 nm the ionisation of thymine is a 1 + 1 resonance enhanced process through its open-shell singlet state.
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We study the vacuum ultraviolet (VUV) photodissociation dynamics of carbonyl sulfide (OCS) by using the time sliced velocity map ion imaging technique. Experimental images of the dissociative O (3PJ=0,1,2) products were acquired at five VUV photolysis wavelengths from 133.26 to 139.96 nm that correspond to the F Rydberg state of OCS. High vibrational states of the carbon monosulfide (CS) co-products are partially resolved in the images. The product total kinetic energy releases, angular distributions, and the product state branching ratios were derived from the experimental images. Notably, it is found that the anisotropic parameters change systematically with the photolysis wavelength. The anisotropic parameters and the product state branching ratios are significantly sensitive to the J quantum number of the O (3PJ) products. The phenomenon indicates that multiple nonadiabatic pathways are strongly involved in the photodissociation processes.
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Atorvastatin, an effective lipid-lowering drug, could reduce the risks of morbidity and mortality of cardiovascular diseases. Patients with cardiovascular diseases often use atorvastatin along with berberine. Atorvastatin is the substrate of CYP3A4 and P-gp. However, berberine is the inhibitor. The combination might lead to DDIs. The aim of this study was to assess the effect of berberine on pharmacokinetics and pharmacodynamics of atorvastatin in rats.Plasma concentrations of atorvastatin with or without berberine were determined by HPLC. Pharmacokinetics parameters were calculated and used to evaluate pharmacokinetics interactions. The effect of berberine on pharmacodynamics of atorvastatin was investigated by detecting blood lipid, SOD, MDA, GSH-Px, AST, ALT, and liver histopathology.Cmax, tmax, and AUC0-t of atorvastatin in combination group significantly increased both in normal and model rats (p < 0.01). The increase of t1/2, AUC0-t in model rats was more significant than that in normal rats (p < 0.05). Pharmacodynamics indexes in treatment groups were significantly improved, especially combination group (p < 0.05). Moreover, it could be found that there is a significant recovery in liver histopathology.In conclusion, berberine could affect pharmacokinetics of atorvastatin, enhance lipid-lowering effect and improve liver injury in rats. More attention should be paid to plasma exposure in clinical to avoid adverse reactions.
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Berberina , Doenças Cardiovasculares , Hiperlipidemias , Humanos , Ratos , Animais , Atorvastatina/farmacologia , Berberina/farmacologia , Hiperlipidemias/tratamento farmacológico , LipídeosRESUMO
BACKGROUND: The unclarified treatment strategy for acute and subacute ndSMA-TE limits the therapeutic efficacy and worsens the prognosis. This study aimed to determine the predictive factors impacting the treatment strategy for acute and subacute ndSMA-TE. METHOD: A database of 116 patients with nonchronic ndSMA-TE admitted between January 2001 and December 2021 was retrospectively analyzed. Univariate/multivariate logistic regression and the predictive models constructed by stepwise backward regression were used to explore the influencing factors of the treatment decisions and the risk factors for failed conservative treatment. The EuroQol-5 Dimension questionnaire was used to evaluate the long-term quality of life. RESULTS: Only the white blood cell (WBC) levels were significantly different between the conservative group and the surgical group (P = 0.013 < 0 .05, odds ratio (OR) = 1.153, 95% confidence interval (CI) [1.038, 1.306]). The WBC levels (P < 0.001, OR = 1.169, 95% CI [1.080, 1.286]) and heart diseases (except atrial fibrillation) (P = 0.011 < 0 .05, OR = 5.116, 95% CI [1.541, 20.452]) were included in the predictive model of the treatment decision. The hemoglobin levels (P = 0.005 < 0 .05, OR = 1.095, 95% CI [1.040, 1.187]) and no flatus or stool (P = 0.007 < 0 .05, OR = 0.031, 95% CI [0.002, 0.296]) were significant risk factors for the conservative treatment outcome. The EuroQol-5 Dimension evaluation demonstrated a fairly high long-term quality of life in both treatment strategies. CONCLUSIONS: Elevated WBC levels, decreased hemoglobin levels, and no flatus or stool can be used as predictive indicators for the surgical treatment of nonchronic ndSMA-TE to avoid a misdiagnosis and an inappropriate treatment.
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Artéria Mesentérica Superior , Tromboembolia , Humanos , Prognóstico , Estudos Retrospectivos , Resultado do Tratamento , Qualidade de Vida , HemoglobinasRESUMO
BACKGROUND: Spontaneous jugular venous ectasia (SJVE) is characterized by dilation of the internal jugular vein (IJV) and external jugular vein. It is generally considered a benign anomaly. There is no accepted categorization for this disorder. METHODS: We conducted a case series study and a systematic review of available articles on SJVE to understand the main characteristics, clinicopathologic classifications, and therapeutic approaches. RESULTS: From January 2001 to December 2021, 14 patients in our hospital were analyzed. A total of 110 original articles (295 cases/311 lesions) were included in the systematic review. We proposed a classification and categorized SJVE into 4 main types (type I-IV) plus one (type V) in which the specific ectasia was located around the jugular bulb at the IJV. CONCLUSIONS: Conservative treatment is preferred for patients with type I (without thrombus) SJVE and asymptomatic patients who can be treated without anticoagulants. The therapeutic efficiency of surgery was high, and the best surgical modalities were chosen according to the type of SJVE.
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Trombose , Doenças Vasculares , Humanos , Dilatação Patológica , Resultado do Tratamento , Veia Subclávia , Veias Jugulares/cirurgiaRESUMO
Central catadioptric cameras with a single effective viewpoint can easily transform the original image into a perspective image. In this study, we proposed a calibration algorithm for central catadioptric cameras. A vanishing line was recovered by the images of two sphere images (or line images) and mirror contour based on the properties of right and oblique cones. Subsequently, the intrinsic parameters were solved by the image of circular points and the orthogonal vanishing points. Finally, the distortion coefficient was estimated based on the geometric properties of the right cone. The simulation and real-time experiments conducted proved the effectiveness and feasibility of the proposed algorithm.