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During early pregnancy in mice, the establishment of uterine receptivity and endometrial decidualization require the extensive proliferation and differentiation of endometrial epithelial cells or stromal cells. Pin1 has been suggested to act as a molecular 'timer' of the cell cycle and is involved in the regulation of cellular proliferation and differentiation by binding many cell-cycle regulatory proteins. However, its physiological role during early pregnancy is still not fully understood. Here, we employed immunohistochemistry to determine the spatiotemporal pattern of Pin1 expression during early pregnancy. We found that Pin1 was mainly localized in subluminal stromal cells on day 4, in the decidual zone on days 5 to 8 of pregnancy and in artificial decidualization. Using a uterine stromal cell culture system, we found that progesterone, but not estrogen, induced the expression of Pin1 in a progesterone receptor-dependent manner. Inhibition of Pin1 in the uterus leads to impaired embryo implantation and decidualization in mice. Notably, a decrease in Pin1 activation affected the functional execution of several implantation- or decidualization-related factors. These findings provide new evidence for a previously unknown function of Pin1 in mediating embryo implantation and decidualization during successful pregnancy establishment and maintenance.
Assuntos
Decídua , Implantação do Embrião , Peptidilprolil Isomerase de Interação com NIMA , Útero , Animais , Feminino , Peptidilprolil Isomerase de Interação com NIMA/metabolismo , Peptidilprolil Isomerase de Interação com NIMA/genética , Implantação do Embrião/fisiologia , Camundongos , Gravidez , Decídua/metabolismo , Decídua/citologia , Útero/metabolismo , Útero/citologia , Progesterona/metabolismo , Células Estromais/metabolismo , Receptores de Progesterona/metabolismo , Células Cultivadas , Endométrio/metabolismo , Endométrio/citologiaRESUMO
OBJECTIVE: To explore adverse event (AE) signals of Ceftazidime/avibactam (CZA) based on the FDA Adverse Event Reporting System (FAERS) database. METHODS: AE reports primarily associated with CZA were retrieved from the FAERS database from the second quarter of 2015 to the second quarter of 2023. Signal detection was conducted using the reporting odds ratio (ROR), proportional reporting ratio (PRR), Bayesian Confidence Propagation Neural Network (BCPNN), and Multi-item Gamma Poisson Shrinker (MGPS) methods. RESULTS: A total of 750 AEs reports with CZA as the preferred suspected drug were obtained, identifying 66 preferred terms (PTs) involving 24 system organ classes (SOCs). Besides, the AEs already mentioned in the drug label, this study also revealed some new, clinically valuable potential AEsignals, such as Cholestasis (n = 14, ROR 29.39, PRR 29.15, IC 3.34, EBGM 29.11), Drug-induced liver injury (n = 8, ROR 9.05, PRR 9.01, IC 2.25, EBGM 9.01), Hepatocellular injury (n = 7, ROR 13.90, PRR 13.84, IC 2.41, EBGM 13.63), Haemolytic anaemia (n = 5, ROR 24.29, PRR 24.22, IC 2.42, EBGM 40.53), etc. Additionally, AE signals with higher intensity were identified, such as Hypernatraemia (n = 5, ROR 40.73, PRR 40.61, IC 2.31, EBGM 24.19), Toxic epidermal necrolysis (n = 4, ROR 11.58, PRR 11.55, IC 1.89, EBGM 11.54). Therefore, special vigilance for these potential AEs is warranted when using CZA clinically. CONCLUSION: This study highlights the potential AEs and risks associated with the clinical use of CZA, particularly the risks related to Cholestasis, Drug-induced liver injury, Haemolytic anaemia, Hypernatraemia, and Toxic epidermal necrolysis.
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The therapeutic outcomes for bladder cancer (BLCA) remain suboptimal. Concurrently, there is a growing appreciation for the role of neoantigens in tumors. In this study, we explored the mechanisms underlying the involvement of neoantigen-associated genes in BLCA and their impact on prognosis. Our analysis incorporated both single-cell sequencing and bulk sequencing data sourced from publicly available databases. By employing a comprehensive set of 10 machine learning algorithms, we generated 101 algorithm combinations. The optimal combination, determined based on consistency indices, was utilized to construct a prognostic model comprising nine genes (CAPG, ACTA2, PDIA6, AKNA, PTMS, SNAP23, ID2, CD3G, SP140). Subsequently, we validated this model in an independent cohort, demonstrating its robust testing efficacy. Moreover, we explored the correlations between various clinical traits, model scores, and genes. Leveraging extensive public data resources, we conducted a drug sensitivity analysis to provide insights for targeted drug screening. Additionally, consensus clustering analysis and immune infiltration analysis were performed on bulk sequencing datasets and immunotherapy cohorts. These analyses yield valuable insights into the role of neoantigens in BLCA, guiding future research endeavors.
Assuntos
Neoplasias da Bexiga Urinária , Humanos , Neoplasias da Bexiga Urinária/genética , Algoritmos , Avaliação Pré-Clínica de Medicamentos , Proteínas de Ligação a DNA , Proteínas Nucleares , Fatores de TranscriçãoRESUMO
OBJECTIVE: To explore the frequency and effect of extreme temperature on the non-accidental death rate in Hulunbuir, a Chinese ice city. METHODS: From 2014 to 2018, mortality data of residents residing in Hulunbuir City were collected. The lag and cumulative effects of extreme temperature conditions on non-accidental death and respiratory and circulatory diseases were analyzed by distributed lag non-linear models (DLNM). RESULTS: The risk of death was the highest during high-temperature conditions, the RR value was 1.111 (95% CI 1.031 ~ 1.198). The effect was severe and acute. The risk of death during extreme low-temperature conditions peaked on the fifth day, (RR 1.057; 95% CI 1.012 ~ 1.112), then decreased and was maintained for 12 days. The cumulative RR value was 1.289 (95% CI 1.045 ~ 1.589). Heat significantly influenced the incidence of non-accidental death in both men (RR 1.187; 95% CI 1.059-1.331) and women (RR 1.252; 95% CI 1.085-1.445). CONCLUSIONS: Regardless of the temperature effect, the risk of death in the elderly group (≥ 65 years) was significantly higher than that of the young group (0-64 years). High-temperature and low-temperature conditions can contribute to the increased number of deaths in Hulunbei. While high-temperature has an acute effect, low-temperature has a lagging effect. Elderly and women, as well as people with circulatory diseases, are more sensitive to extreme temperatures.
Assuntos
Doenças Cardiovasculares , Dinâmica não Linear , Masculino , Humanos , Feminino , Idoso , Temperatura , Estudos Longitudinais , Temperatura Baixa , Temperatura Alta , China/epidemiologiaRESUMO
High carbonate alkalinity is one of the major stress factors for survival of aquatic animals in saline-alkaline water. Exopalaemon carinicauda is a good model for studying the saline-alkaline adaption mechanism in crustacean because of its great adaptive capacity to alkalinity stress. In this study, non-targeted liquid chromatography-mass spectrometry (LC-MS) metabolomics analyses based on high-throughput RNA sequencing (RNA-Seq) were used to study the metabolomic responses of hepatopancreas in E. carinicauda at 12 h and 36 h after acute carbonate alkalinity stress. The results revealed that most of the significantly differential metabolites were related to the lipid metabolism. In particular, the sphingolipid metabolism was observed at 12 h, the glycerophospholipid metabolism was detected at 36 h, and the linoleic acid metabolic pathway was significantly enriched at both 12 h and 36 h. The combined transcriptome and metabolome analysis showed that energy consumption increased at 12 h, resulting in significant enrichment of AMPK signaling pathways, which contributed to maintain energy homeostasis. Subsequently, the hepatopancreas provided sufficient energy supply through cAMP signaling pathway and glycerophosphate metabolism to maintain normal metabolic function at 36 h. These findings might help to understand the molecular mechanisms of the E. carinicauda under carbonate alkalinity stress, thereby promote the research and development of saline-alkaline resistant shrimp.
Assuntos
Palaemonidae , Transcriptoma , Animais , Hepatopâncreas , Palaemonidae/genética , Palaemonidae/metabolismo , Carbonatos/metabolismoRESUMO
Tigecycline is a tetracycline-class antibacterial indicated for the treatment of complicated skin and skin-structure infections, complicated intra-abdominal infections, and community-acquired bacterial pneumonia. It has a broad-spectrum antibacterial activity. It has identified gastrointestinal side-effects, particularly nausea and vomiting. With the increasing clinical use of tigecycline, its associated acute pancreatitis has been frequently reported in adults. However, cases of tigecycline-induced acute pancreatitis have rarely been described in children. In this study, we report a case of acute pancreatitis caused by the use of tigecycline in a child with pulmonary cystic fibrosis. In this case, abdominal pain, nausea, and vomiting occurred on the 5th day after the use of tigecycline. Elevated pancreatic enzymes occurred, and abdominal computed tomography findings were compatible with pancreatitis. After 2 weeks of discontinuation of tigecycline, the pancreatic enzyme level decreased to normal, and the symptoms of abdominal pain, nausea, and vomiting disappeared completely. In conclusion, we hope to improve the clinical awareness of children with tigecycline-associated pancreatitis, so as to reduce the probability of adverse reactions through the analysis of this case.
Assuntos
Fibrose Cística , Pancreatite , Doença Aguda , Adulto , Antibacterianos/efeitos adversos , Criança , Fibrose Cística/tratamento farmacológico , Humanos , Minociclina/efeitos adversos , Pancreatite/induzido quimicamente , Pancreatite/diagnóstico , Pancreatite/tratamento farmacológico , TigeciclinaRESUMO
Imipenem cilastatin sodium, as a member of a new generation of ß-lactam antibiotics, has a broad spectrum of antibacterial activity and a very wide range of application. Thrombocytopenia has been reported as a rare adverse event in several studies of patients treated with imipenem cilastatin sodium. In this study, we present a case of thrombocytopenia associated with imipenem cilastatin sodium in an older patient. The 78-year-old male patient with pulmonary infection was initiated on anti-infection therapy with imipenem cilastatin sodium. On the 9th day after imipenem cilastatin sodium administration, the patient experienced a sudden and dramatic decrease in platelet count. Similarly, on the 4th day after the re-administration of imipenem cilastatin sodium for anti-infection therapy, the patient's platelet count showed a remarkable downward trend again. A time correlation between the drug therapy and the occurrence of platelet reaction was found. The patient's platelet count gradually returned to the normal level on the 6th day after the first drug withdrawal and the 13th day after the second drug withdrawal, respectively. Considering the widespread use of imipenem cilastatin sodium, healthcare providers should improve the notification of thrombocytopenia associated with imipenem cilastatin sodium.
Assuntos
Infecções Bacterianas , Trombocitopenia , Idoso , Antibacterianos/efeitos adversos , Infecções Bacterianas/tratamento farmacológico , Cilastatina/efeitos adversos , Combinação Imipenem e Cilastatina/uso terapêutico , Combinação de Medicamentos , Humanos , Imipenem/efeitos adversos , Masculino , Tienamicinas/uso terapêutico , Trombocitopenia/induzido quimicamente , Trombocitopenia/diagnóstico , Trombocitopenia/tratamento farmacológicoRESUMO
Embryo implantation is a crucial step for the successful establishment of mammalian pregnancy. Cyclophilin A (CYPA) is a ubiquitously expressed intracellular protein and is secreted in response to inflammatory stimuli to regulate diverse cellular functions. However, there are currently no reports about the role of CYPA in embryo implantation. Here, we examine the expression pattern of CYPA during mouse early pregnancy and explore the potential role of CYPA during implantation. CYPA is expressed in the subluminal stroma surrounding the implanting blastocyst on day 5 of pregnancy, but not at inter-implantation sites. In ovariectomized mice, estrogen and progesterone significantly stimulate CYPA expression. When pregnant mice are injected intraperitoneally with CYPA inhibitor, the numbers of implantation sites are significantly reduced. Using an in vitro stromal cell culture system, Ppia siRNA knockdown of CYPA and CYPA-specific inhibitor treatment partially inhibits levels of CD147, MMP3 and MMP9. Decreased CYPA expression also significantly inhibits Stat3 activity and expands estrogen responsiveness. Taken together, CYPA may play an important role during mouse embryo implantation.
Assuntos
Ciclofilina A/metabolismo , Implantação do Embrião , Regulação da Expressão Gênica no Desenvolvimento , Fator de Transcrição STAT3/metabolismo , Animais , Ciclofilina A/genética , Feminino , Hormônios Esteroides Gonadais/metabolismo , Camundongos , Gravidez , Fator de Transcrição STAT3/genética , Células Estromais/citologia , Células Estromais/metabolismo , Útero/citologia , Útero/metabolismoRESUMO
OBJECTIVE: To investigate a simple, cost-effective and eco-friendly method for colorimetric detection of Hg2+ using gold nanoparticles (AuNPs) synthesized by Trichosporon montevideense WIN. RESULTS: Hg2+ induced more visible blue shift of SPR band of the AuNPs than other heavy metal ions including Pb2+, Cd2+, Fe3+, Mn2+, Co2+ and Cu2+. The λmax of SPR band exhibited a gradual blue shift from 548 to 537 nm with concentration of Hg2+ increasing (0-200 µM), and the absorbance ratio (A537/A548) showed a positive linear correlation with Hg2+ concentration (R2 = 0.96). AuNPs synthesized at pH 6 showed more obvious blue shift than at pH 5 and pH 7. Through Fourier transform infrared (FTIR) spectroscopy and transmission electron microscopy (TEM) analysis, biomolecules coated on the AuNPs were speculated to dominate the formation of a core (Au)-shell (Hg) structure, which resulted in the colorimetric response. CONCLUSION: A sensitive and selective approach to detect Hg2+ using AuNPs synthesized by Trichosporon montevideense WIN is reported for the first time, which can provide a new potential candidate for detecting Hg2+ in the future.
Assuntos
Basidiomycota/metabolismo , Colorimetria/métodos , Ouro/química , Mercúrio/análise , Nanopartículas Metálicas/química , Concentração de Íons de Hidrogênio , Poluentes Químicos da Água/análiseRESUMO
Rapid and accurate detection and identification of microbial pathogens causing urinary tract infections allow prompt and specific treatment. We optimized specimen processing to maximize the limit of detection (LOD) by matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS) and evaluated the capacity of combination of MALDI-TOF MS and urine analysis (UA) for direct detection and identification of bacterial pathogens from urine samples. The optimal volumes of processed urine, formic acid/acetonitrile, and supernatant spotted onto the target plate were 15 ml, 3 µl, and 3 µl, respectively, yielding a LOD of 1.0 × 105 CFU/ml. Among a total of 1,167 urine specimens collected from three hospital centers, 612 (52.4%) and 351 (30.1%) were, respectively, positive by UA and urine culture. Compared with a reference method comprised of urine culture and 16S rRNA gene sequencing, the sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of MALDI-TOF MS alone and MALDI-TOF MS coupled with UA were 86.6% versus 93.4% (χ2 = 8.93; P < 0.01), 91.5% versus 96.3% (χ2 = 7.06; P < 0.01), 81.5% versus 96.4% (χ2 = 37.32; P < 0.01), and 94.1% versus 93.1% (χ2 = 0.40; P > 0.05), respectively. No significant performance differences were revealed among the three sites, while specificity and NPV of MALDI-TOF MS for males were significantly higher than those for females (specificity, 94.3% versus 77.3%, χ2 = 44.90, P < 0.01; NPV, 95.5% versus 86.1%, χ2 = 18.85, P < 0.01). Our results indicated that the optimization of specimen processing significantly enhanced analytical sensitivity and that the combination of UA and MALDI-TOF MS provided an accurate and rapid detection and identification of bacterial pathogens directly from urine.
Assuntos
Bactérias/classificação , Bactérias/isolamento & purificação , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz/métodos , Infecções Urinárias/diagnóstico , Urina/microbiologia , Algoritmos , Bactérias/genética , Técnicas Bacteriológicas/métodos , Enterococcus faecalis/genética , Enterococcus faecalis/isolamento & purificação , Escherichia coli/genética , Escherichia coli/isolamento & purificação , Feminino , Humanos , Klebsiella pneumoniae/genética , Klebsiella pneumoniae/isolamento & purificação , Limite de Detecção , Masculino , RNA Ribossômico 16S/genética , Sensibilidade e Especificidade , Urinálise/métodos , Infecções Urinárias/microbiologiaRESUMO
BACKGROUND/AIMS: Cardiac fibrosis after myocardial infarction (MI) has been identified as a key factor in the development of heart failure, but the mechanisms undelying cardiac fibrosis remained unknown. microRNAs (miRNAs) are novel mechanisms leading to fibrotic diseases, including cardiac fibrosis. Previous studies revealed that miR-22 might be a potential target. However, the roles and mechanisms of miR-22 in cardiac fibrosis remained ill defined. The present study thus addressed the impact of miR-22 in cardiac fibrosis. METHODS: After seven days following coronary artery occlusion in mice, tissues used for histology were collected and processed for Masson's Trichrome staining. In addition, cardiac fibroblasts were transfected with mimics and inhibitors of miR-22 using Lipofectamin 2000, and luciferase activity was measured in cell lysates using a luciferase assay kit. Western blotting was used to detect the expression of collagen1, α-SMA and TGFßRI proteins levels, and real time-PCR was employed to measure the Col1α1, Col3α1, miR-22 and TGFßRI mRNA levels. RESULTS: In this study, we found that miR-22 was dynamically downregulated following MI induced by permanent ligation of the left anterior descending coronary artery for 7 days, an effect paralleled by significant collagen deposition. Inhibition of miR-22 with AMO-22 resulted in increased expression of Col1α1, Col3α1 and fibrogenesis in cultured cardiac fibroblasts. Conversely, overexpression of miR-22 in cultured cardiac fibroblasts significantly abrogated angiotensin II-induced collagen formation and fibrogenesis. Furthermore, we found that TGFßRI is a direct target for miR-22, and downregulation of TGFßR may have mediated the antifibrotic effect of miR-22. CONCLUSION: Our data clearly demonstrate that miR-22 acts as a novel negative regulator of angiotensin II-induced cardiac fibrosis by suppressing the expression of TGFßRI in the heart and may represent a new potential therapeutic target for treating cardiac fibrosis.
Assuntos
Fibroblastos/metabolismo , Fibroblastos/patologia , MicroRNAs/metabolismo , Miocárdio/patologia , Proteínas Serina-Treonina Quinases/genética , Receptores de Fatores de Crescimento Transformadores beta/genética , Angiotensina II/farmacologia , Animais , Sequência de Bases , Células Cultivadas , Colágeno/metabolismo , Regulação para Baixo/efeitos dos fármacos , Regulação para Baixo/genética , Fibrose , Inativação Gênica/efeitos dos fármacos , Masculino , Camundongos Endogâmicos C57BL , MicroRNAs/genética , Infarto do Miocárdio/genética , Infarto do Miocárdio/patologia , Proteínas Serina-Treonina Quinases/metabolismo , Ratos Sprague-Dawley , Receptor do Fator de Crescimento Transformador beta Tipo I , Receptores de Fatores de Crescimento Transformadores beta/metabolismoRESUMO
Bone loss is a critical pathology responsible for the functional disability in patients with rheumatoid arthritis (RA). It is well known that receptor activator of nuclear factor kappa-B (NF-κB) ligand (RANKL) plays a crucial role in bone loss in RA. The purpose of this study was to determine whether recombinant human endostatin (rh-endostatin) mediates bone erosion in RA by regulation of RANKL expression in an experimental model of RA, consisting of mice with adjuvant-induced arthritis (AA). Cultured AA fibroblast-like synoviocytes (FLSs) obtained from these mice were induced by tumor necrosis factor-α (TNF-α) combined with or without rh-endostatin. The levels of RANKL and osteoprotegerin (OPG) mRNA, soluble and membrane-bound proteins were assessed by real-time PCR, ELISA, and Western blotting. Western blotting and the luciferase reporter assay were used to study related signaling pathways. Rh-endostatin inhibited RANKL mRNA expression, soluble and membrane-bound protein expression in AA FLSs but not in CD4+ T cells. However, OPG expression and secretion was not affected by rh-endostatin in AA FLSs. Molecular analysis demonstrated that rh-endostatin significantly inhibited TNF-α-induced MAPK and AP-1 signaling pathways. Moreover, rh-endostatin attenuated TNF-α-induced NF-κB signaling by suppressing the phosphorylation level of inhibitor kappaBα (IκBα) and nuclear translocation of NF-κB p65 in FLSs from mice with AA. These results provide the first evidence that rh-endostatin inhibits TNF-α-induced RANKL expression in AA FLSs.
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Artrite Experimental/tratamento farmacológico , Endostatinas/uso terapêutico , Fibroblastos/patologia , Ligante RANK/metabolismo , Proteínas Recombinantes/uso terapêutico , Sinoviócitos/patologia , Fator de Necrose Tumoral alfa/farmacologia , Animais , Artrite Experimental/metabolismo , Artrite Experimental/patologia , Linfócitos T CD4-Positivos/efeitos dos fármacos , Linfócitos T CD4-Positivos/metabolismo , Núcleo Celular/efeitos dos fármacos , Núcleo Celular/metabolismo , Células Cultivadas , Endostatinas/farmacologia , Fibroblastos/efeitos dos fármacos , Fibroblastos/metabolismo , Humanos , Proteínas I-kappa B/metabolismo , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Modelos Biológicos , Osteoprotegerina/metabolismo , Fosforilação/efeitos dos fármacos , Transporte Proteico/efeitos dos fármacos , Proteínas Recombinantes/farmacologia , Sinoviócitos/efeitos dos fármacos , Sinoviócitos/metabolismo , Fator de Transcrição AP-1/metabolismo , Fator de Transcrição RelA/metabolismoRESUMO
Collagenous fibroma (desmoplastic fibroblastoma) is a rare benign tumor. This type of tumor mostly occurs in the subcutaneous tissues or skeletal muscle, and to the best of our knowledge, there is no unique case report of it occurring in the cardiac valves. This is the first description of collagenous fibroma in a human heart.
Assuntos
Fibroma Desmoplásico/diagnóstico por imagem , Neoplasias Cardíacas/diagnóstico por imagem , Doenças das Valvas Cardíacas/diagnóstico por imagem , Idoso , Ecocardiografia Tridimensional , Ecocardiografia Transesofagiana , Feminino , Fibroma Desmoplásico/cirurgia , Neoplasias Cardíacas/cirurgia , Doenças das Valvas Cardíacas/cirurgia , Valvas Cardíacas/diagnóstico por imagem , Valvas Cardíacas/cirurgia , Humanos , Tomografia Computadorizada por Raios XRESUMO
Fibrous cyst of the chordae tendineae of the mitral valve (MV) is defined as a fibrous cyst arising from the chordae tendineae of the MV. It is extremely rare and its etiology is not clear. We present a case of a cystic structure within the left ventricle. This structure is connected to the anterior MV leaflet and the posterior chordae tendineae. It moves freely, resulting in stenosis of inflow tract and outflow tract of the left ventricle. Intraoperative assessment and histopathologic examination revealed it as a fibrous cyst. Its echocardiographic appearance is unique and it must be resected immediately.
Assuntos
Cordas Tendinosas/diagnóstico por imagem , Cistos/diagnóstico por imagem , Ecocardiografia/métodos , Insuficiência da Valva Mitral/diagnóstico por imagem , Obstrução do Fluxo Ventricular Externo/diagnóstico por imagem , Adolescente , Cistos/complicações , Cistos/cirurgia , Humanos , Masculino , Valva Mitral/diagnóstico por imagem , Insuficiência da Valva Mitral/complicações , Insuficiência da Valva Mitral/cirurgia , Resultado do Tratamento , Obstrução do Fluxo Ventricular Externo/etiologia , Obstrução do Fluxo Ventricular Externo/cirurgiaRESUMO
OBJECTIVE: To investigate the feasibility and application value of AR-Vol measured by GI3DQ method directly. METHODS: One hundred and two patients with aortic regurgitation who underwent echocardiographic examination in Tianjin Chest Hospital from February 2014 to October 2014 were selected randomly and divided into two groups: the eccentric group included forty cases with eccentric aortic regurgitation; the central group included sixty and two cases with central aortic regurgitation. AR-Vol were directly measured by GI3DQ method, and then it was calculated by PISA method as the reference standard. RESULTS: (1) In the eccentric group, the AR-Vol measured by GI3DQ method and PISA method were respectively (44±11) ml and (48±10) ml. In the central group, the AR-Vol measured by GI3DQ method and PISA method were respectively (34±13) ml and (33±13) ml. (2) Paired t test analysis showed significant difference in two methods of the eccentric group (P<0.01); no significant difference was found in two methods of the central group (P=0.202). (3) The correlation coefficients of the AR-Vol measurement by GI3DQ method and PISA method are relatively in two groups: r=0.835, r=0.913; consistency analysis showed differences between the two methods of the eccentric group had statistical significance, and differences between the two methods of the central group had no statistical significance. CONCLUSION: In the central aortic regurgitation, AR-Vol measured by GI3DQ method is feasible and accurate compared with the PISA method, which can be used for routine application.
Assuntos
Insuficiência da Valva Aórtica , Ecocardiografia , Humanos , Imageamento TridimensionalRESUMO
Prostate cancer remains a complex and challenging disease, necessitating innovative approaches for prognosis and therapeutic guidance. This study integrates machine learning techniques to develop a novel mitophagy-related long non-coding RNA (lncRNA) signature for predicting the progression of prostate cancer. Leveraging the TCGA-PRAD dataset, we identify a set of four key lncRNAs and formulate a riskscore, revealing its potential as a prognostic indicator. Subsequent analyses unravel the intricate connections between riskscore, immune cell infiltration, mutational landscapes, and treatment outcomes. Notably, the pan-cancer exploration of YEATS2-AS1 highlights its pervasive impact, demonstrating elevated expression across various malignancies. Furthermore, drug sensitivity predictions based on riskscore guide personalized chemotherapy strategies, with drugs like Carmustine and Entinostat showing distinct suitability for high and low-risk group patients. Regression analysis exposes significant correlations between the mitophagy-related lncRNAs, riskscore, and key mitophagy-related genes. Molecular docking analyses reveal promising interactions between Cyclophosphamide and proteins encoded by these genes, suggesting potential therapeutic avenues. This comprehensive study not only introduces a robust prognostic tool but also provides valuable insights into the molecular intricacies and potential therapeutic interventions in prostate cancer, paving the way for more personalized and effective clinical approaches.
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Domoic acid (DA)-producing algal blooms are a global marine environmental issue. However, there has been no previous research addressing the question regarding the fate of DA in marine benthic environments. In this work, we investigated the DA fate in the water-sediment microcosm via the integrative analysis of a top-down metabolic model, metagenome, and metabolome. Results demonstrated that biodegradation is the leading mechanism for the nonconservative attenuation of DA. Specifically, DA degradation was prominently completed by the sediment aerobic community, with a degradation rate of 0.0681 ± 0.00954 d-1. The DA degradation pathway included hydration, dehydrogenation, hydrolysis, decarboxylation, automatic ring opening of hydration, and ß oxidation reactions. Moreover, the reverse ecological analysis demonstrated that the microbial community transitioned from nutrient competition to metabolic cross-feeding during DA degradation, further enhancing the cooperation between DA degraders and other taxa. Finally, we reconstructed the metabolic process of microbial communities during DA degradation and confirmed that the metabolism of amino acid and organic acid drove the degradation of DA. Overall, our work not only elucidated the fate of DA in marine environments but also provided crucial insights for applying metabolic models and multi-omics to investigate the biotransformation of other contaminants.
Assuntos
Biotransformação , Sedimentos Geológicos , Ácido Caínico , Toxinas Marinhas , Ácido Caínico/análogos & derivados , Ácido Caínico/metabolismo , Sedimentos Geológicos/microbiologia , Toxinas Marinhas/metabolismo , Microbiota , Metaboloma , Biodegradação Ambiental , Metagenoma , Poluentes Químicos da Água/metabolismo , MultiômicaRESUMO
BACKGROUND: Although long-term exposures to air pollutants have been linked to mental disorders, existing studies remain limited and inconsistent. We investigated the relationship between exposure to particulate matter (PM) and depressive symptoms, as well as the potential role of sleep duration and physical activity. METHOD: Using the surveillance data (2019 to 2022) of common diseases and risk factors among 312,390 students aged 10-25 years, logistic regression, generalized liner model (GLM) and restricted cubic spline (RCS) were employed to investigate the relationship between long-term exposure to PM and depressive symptoms. RESULT: Significant associations were found between PM1 (OR = 1.21, 95 % CI: 1.12-1.32), PM2.5 (OR = 1.24, 95 % CI: 1.19-1.38), and PM10 (OR = 1.87, 95 % CI: 1.69-2.07) and increased risks of depressive symptoms. Sleep duration and physical activity relieved these associations. The odds ratios (ORs) of PM1, PM2.5, and PM10 on depressive symptoms were lower in group with sufficient sleep (1.02 vs. 1.49, 1.20 vs. 1.80, 2.15 vs. 2.23), lower in group with high level MVPA (1.13 vs. 1.48, 1.14 vs. 1.58, 1.85 vs. 2.38), and lower in group with high level outdoor activity (1.19 vs. 1.55, 1.23 vs. 1.63, 1.83 vs. 2.72). LIMITATIONS: Conclusions about causality remain speculative because of the cross-sectional design. CONCLUSION: Sufficient sleep duration and outdoor activity may mitigate the decline in mental health among adults in developing countries caused by long-term exposure to PM. This contribution enhanced our understanding of the mechanisms linking air pollution to mental health.
Assuntos
Depressão , Exercício Físico , Material Particulado , Sono , Humanos , Material Particulado/efeitos adversos , Adolescente , China/epidemiologia , Masculino , Feminino , Criança , Depressão/epidemiologia , Adulto Jovem , Adulto , Poluição do Ar/estatística & dados numéricos , Poluição do Ar/efeitos adversos , Exposição Ambiental/efeitos adversos , Exposição Ambiental/estatística & dados numéricos , Poluentes Atmosféricos/efeitos adversos , Fatores de RiscoRESUMO
Coronavirus disease 2019 (COVID-19) has ravaged the world since December 2019. Up to now, it is still prevalent around the world. Vaccines are an important means to prevent the spread of COVID-19 and reduce severe disease and mortality. Currently, different types of novel coronavirus vaccines are still being developed and improved, and the relevant vaccines that have been approved for marketing have been widely vaccinated around the world. As vaccination coverage continues to grow, concerns about the efficacy and safety of vaccines after real-world use have grown. Some clinical studies have shown that vaccine effectiveness is closely related to antibody response after vaccination. Among them, the advantages of COVID-19 messenger ribonucleic acid (mRNA) vaccine, such as better adaptability to variant strains and better immune response ability, have attracted great attention. However, different populations with different genders, ages, previous COVID-19 infection history, underlying diseases and treatments will show different antibody responses after mRNA vaccination, which will affect the protection of the vaccine. Based on this, this paper reviews the reports related severe acute respiratory syndrome Coronavirus 2 mRNA vaccines, and summarizes the effectiveness of vaccines in different populations and different disease states and looked forward to the precise vaccination strategy of the vaccine in the future.
Assuntos
Vacinas contra COVID-19 , COVID-19 , Feminino , Masculino , Humanos , SARS-CoV-2 , COVID-19/prevenção & controle , RNA Mensageiro , Vacinas de mRNARESUMO
Ganoderma lucidum is a mushroom widely used for its edible and medicinal properties. Primary bioactive constituents of G. lucidum are ganoderic triterpenoids (GTs), which exhibit important pharmacological activity. Abscisic acid (ABA), a plant hormone, is associated with plant growth, development, and stress responses. ABA can also affect the growth, metabolism, and physiological activities of different fungi and participates in the regulation of the tetracyclic triterpenes of some plants. Our findings indicated that ABA treatment promoted GT accumulation by regulating the gene expression levels (squalene synthase (sqs), 3-hydroxy-3-methylglutaryl-CoA reductase (hmgr), and lanosterol synthase (ls)), and also activated cytosolic Ca2+ channels. Furthermore, under ABA mediation, exogenous Ca2+ donors and inhibitors directly affected the cytosolic Ca2+ concentration and related gene expression in Ca2+ signaling. Our study also revealed that ABA-mediated cytosolic Ca2+ played a crucial regulatory role in GT biosynthesis, accompanied by antioxidant defense modulation with increasing superoxide dismutase (SOD) activity and ascorbate peroxidase (APX) activity, and the resistance ability of O2â¢- and glutathione (GSH) contents.