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1.
Harmful Algae ; 135: 102633, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38830715

RESUMEN

Nitrogen-fixing cyanobacteria not only cause severe blooms but also play an important role in the nitrogen input processes of lakes. The production of extracellular polymeric substances (EPS) and the ability to fix nitrogen from the atmosphere provide nitrogen-fixing cyanobacteria with a competitive advantage over other organisms. Temperature and nitrogen availability are key environmental factors in regulating the growth of cyanobacteria. In this study, Dolichospermum (formerly known as Anabaena) was cultivated at three different temperatures (10 °C, 20 °C, and 30 °C) to examine the impact of temperature and nitrogen availability on nitrogen fixation capacity and the release of EPS. Initially, confocal laser scanning microscopy (CLSM) and the quantification of heterocysts at different temperatures revealed that lower temperatures (10 °C) hindered the differentiation of heterocysts under nitrogen-deprived conditions. Additionally, while heterocysts inhibited the photosynthetic activity of Dolichospermum, the secretion of EPS was notably affected by nitrogen limitation, particularly at 30 °C. Finally, real-time quantitative polymerase chain reaction (qPCR) was used to measure the expression of nitrogen-utilizing genes (ntcA and nifH) and EPS synthesis-related genes (wzb and wzc). The results indicated that under nitrogen-deprived conditions, the expression of each gene was upregulated, and there was a significant correlation between the upregulation of nitrogen-utilizing and EPS synthesis genes (P < 0.05). Our findings suggested that Dolichospermum responded to temperature variation by affecting the formation of heterocysts, impacting its potential nitrogen fixation capacity. Furthermore, the quantity of EPS released was more influenced by nitrogen availability than temperature. This research enhances our comprehension of interconnections between nitrogen deprivation and EPS production under the different temperatures.


Asunto(s)
Matriz Extracelular de Sustancias Poliméricas , Fijación del Nitrógeno , Nitrógeno , Temperatura , Nitrógeno/metabolismo , Matriz Extracelular de Sustancias Poliméricas/metabolismo , Anabaena/metabolismo , Anabaena/fisiología , Anabaena/genética
2.
Acta Pharmacol Sin ; 2024 Jun 11.
Artículo en Inglés | MEDLINE | ID: mdl-38862818

RESUMEN

Diabetic cardiomyopathy (DCM) is a complication of diabetes mellitus characterized by heart failure and cardiac remodeling. Previous studies show that tetrahydroberberrubine (THBru) retrogrades cardiac aging by promoting PHB2-mediated mitochondrial autophagy and prevents peritoneal adhesion by suppressing inflammation. In this study we investigated whether THBru exerted protective effect against DCM in db/db mice and potential mechanisms. Eight-week-old male db/db mice were administered THBru (25, 50 mg·kg-1·d-1, i.g.) for 12 weeks. Cardiac function was assessed using echocardiography. We showed that THBru administration significantly improved both cardiac systolic and diastolic function, as well as attenuated cardiac remodeling in db/db mice. In primary neonatal mouse cardiomyocytes (NMCMs), THBru (20, 40 µM) dose-dependently ameliorated high glucose (HG)-induced cell damage, hypertrophy, inflammatory cytokines release, and reactive oxygen species (ROS) production. Using Autodock, surface plasmon resonance (SPR) and DARTS analyses, we revealed that THBru bound to the domain of the receptor for advanced glycosylation end products (RAGE), subsequently leading to inactivation of the PI3K/AKT/NF-κB pathway. Importantly, overexpression of RAGE in NMCMs reversed HG-induced inactivation of the PI3K/AKT/NF-κB pathway and subsequently counteracted the beneficial effects mediated by THBru. We conclude that THBru acts as an inhibitor of RAGE, leading to inactivation of the PI3K/AKT/NF-κB pathway. This action effectively alleviates the inflammatory responses and oxidative stress in cardiomyocytes, ultimately leading to ameliorated DCM.

3.
Ann Otol Rhinol Laryngol ; : 34894241261491, 2024 Jun 14.
Artículo en Inglés | MEDLINE | ID: mdl-38877731

RESUMEN

OBJECTIVES: Pendred syndrome, an autosomal recessive disorder, is often associated with pathogenic variants of the SLC26A4 gene that encodes the pendrin protein. Given its autosomal recessive inheritance, tracing the family history and screening siblings become crucial once a diagnosis of Pendred syndrome is confirmed. This case report aims to underscore the variability in inner ear morphology within a family diagnosed with Pendred syndrome, all carrying the same SLC26A4 gene mutation. METHODS: A chart review and a review of the literature. RESULTS: We present a family of 4, all of whom possess sensorineural hearing loss due to the same homozygous SLC26A4 variant c.919-2A>G. Intriguingly, clinical manifestations, especially inner ear deformities, displayed variability among family members. Notably, 1 family member exhibited a normal cochleovestibular structure morphology, which was rarely reported in the literature. CONCLUSIONS: This report highlights the significance of genetic testing and familial consultation when a proband exhibits typical Pendred syndrome symptoms. It also underscores that the inner ear morphology can exhibit variability among family members, even with the same homozygous SLC26A4 variant.

4.
AMIA Jt Summits Transl Sci Proc ; 2024: 478-487, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38827053

RESUMEN

The emerging large language models (LLMs) are actively evaluated in various fields including healthcare. Most studies have focused on established benchmarks and standard parameters; however, the variation and impact of prompt engineering and fine-tuning strategies have not been fully explored. This study benchmarks GPT-3.5 Turbo, GPT-4, and Llama-7B against BERT models and medical fellows' annotations in identifying patients with metastatic cancer from discharge summaries. Results revealed that clear, concise prompts incorporating reasoning steps significantly enhanced performance. GPT-4 exhibited superior performance among all models. Notably, one-shot learning and fine-tuning provided no incremental benefit. The model's accuracy sustained even when keywords for metastatic cancer were removed or when half of the input tokens were randomly discarded. These findings underscore GPT-4's potential to substitute specialized models, such as PubMedBERT, through strategic prompt engineering, and suggest opportunities to improve open-source models, which are better suited to use in clinical settings.

5.
Behav Ecol ; 35(4): arae044, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38903732

RESUMEN

Males often strategically adjust the number of available sperm based on the social context (i.e. sperm priming response), but it remains unclear how environmental and genetic factors shape this adjustment. In freshwater ecosystems, high ambient temperatures often lead to isolated pools of hotter water in which inbreeding occurs. Higher water temperatures and inbreeding can impair fish development, potentially disrupting sperm production. We used guppies (Poecilia reticulata) to investigate how developmental temperature (26 °C, 30 °C) and male inbreeding status (inbred, outbred) influence their sperm priming response. We also tested if sperm priming was affected by whether the female was a relative (sister) and whether she was inbred or outbred. There was no effect of rearing temperature; male inbreeding status alone determined the number of available sperm in response to female presence, her inbreeding status, and her relatedness. Inbred males produced significantly more sperm in the presence of an unrelated, outbred female than when no female was present. Conversely, outbred males did not alter the number of sperm available in response to female presence or relatedness. Moreover, inbred males produced marginally more sperm when exposed to an unrelated female that was outbred rather than inbred, but there was no difference when exposed to an inbred female that was unrelated versus related. Together, a sperm priming response was only observed in inbred males when exposed to an outbred female. Outbred females in our study were larger than inbred females, suggesting that inbred males strategically allocated ejaculate resources toward females in better condition.

6.
Neurochem Res ; 2024 Jun 04.
Artículo en Inglés | MEDLINE | ID: mdl-38834846

RESUMEN

Neuroinflammation and endothelial cell apoptosis are prominent features of blood-brain barrier (BBB) disruption, which have been described in Alzheimer's disease (AD) and can predict cognitive decline. Recent reports revealed vascular ß-amyloid (Aß) deposits, Muller cell degeneration and microglial dysfunction in the retina of AD patients. However, there has been no in-depth research on the roles of inflammation, retinal endothelial cell apoptosis, and blood-retinal barrier (BRB) damage in AD retinopathy. We found that Raddeanin A (RDA) could improve pathological and cognitive deficits in a mouse model of Alzheimer's disease by targeting ß-amyloidosis, However, the effects of RDA on AD retinal function require further study. To clarify whether RDA inhibits inflammation and apoptosis and thus improves BRB function in AD-related retinopathy. In vitro we used Aß-treated HRECs and MIO-M1 cells, and in vivo we used 3×Tg-AD mice to investigate the effect of RDA on BRB in AD-related retinopathy. We found that RDA could improve BRB function in AD-related retinopathy by inhibiting NLRP3-mediated inflammation and suppressing Wnt/ß-catenin pathway-mediated apoptosis, which is expected to improve the pathological changes in AD-related retinopathy and the quality of life of AD patients.

7.
PLoS Biol ; 22(5): e3002519, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38787858

RESUMEN

When males compete, sexual selection favors reproductive traits that increase their mating or fertilization success (pre- and postcopulatory sexual selection). It is assumed that males face a trade-off between these 2 types of sexual traits because they both draw from the same pool of resources. Consequently, allocation into mate acquisition or ejaculation should create similar trade-offs with other key life history traits. Tests of these assumptions are exceedingly rare. Males only ejaculate after they mate, and the costs of ejaculation are therefore highly confounded with those of mating effort. Consequently, little is known about how each component of reproductive allocation affects a male's future performance. Here, we ran an experiment using a novel technique to distinguish the life history costs of mating effort and ejaculation for mosquitofish (Gambusia holbrooki). We compared manipulated males (mate without ejaculation), control males (mate and ejaculate), and naïve males (neither mate nor ejaculate) continuously housed with a female and 2 rival males. We assessed their growth, somatic maintenance, mating and fighting behavior, and sperm traits after 8 and 16 weeks. Past mating effort significantly lowered a male's future mating effort and growth, but not his sperm production, while past sperm release significantly lowered a male's future ejaculate quantity, but not his mating effort. Immune response was the only trait impacted by both past mating effort and past ejaculation. These findings challenge the assumption that male reproductive allocation draws from a common pool of resources to generate similar life history costs later in life. Instead, we provide clear evidence that allocation into traits under pre- and postcopulatory sexual selection have different trait-specific effects on subsequent male reproductive performance.


Asunto(s)
Eyaculación , Reproducción , Conducta Sexual Animal , Masculino , Animales , Eyaculación/fisiología , Femenino , Conducta Sexual Animal/fisiología , Reproducción/fisiología , Preferencia en el Apareamiento Animal/fisiología , Espermatozoides/fisiología , Selección Sexual
8.
Pediatr Neurol ; 156: 59-65, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38733855

RESUMEN

BACKGROUND: Bronchopulmonary dysplasia (BPD) affects the microstructure of white matter in preterm infants, but its influence on the changes of the brain structural network has not been elaborated. This study aims to investigate the connectivity characteristics of the brain structural network of BPD by using diffusion tensor imaging. METHODS: Thirty-three infants with BPD and 26 infants without BPD were enrolled in this study. Brain structural networks were constructed utilizing automated anatomic labeling mapping by tracing the fibers between each pair of regions in individual space. We calculated network metrics such as global efficiency, local efficiency, clustering coefficients, characteristic path length, and small-worldness. Then we compared the network metrics of these infants with those of 57 healthy term infants of comparable postmenstrual age at magnetic resonance imaging scan. Finally, network-based statistics was used to analyze the differences in brain network connectivity between the groups with and without BPD. RESULTS: Preterm infants with BPD had higher local efficiency and clustering coefficient, lower global efficiency, and longer characteristic path length. Also, preterm infants with BPD had decreased strength of limbic connections mainly in four brain regions: the left lingual gyrus, the left calcarine fissure and surrounding cortex, the right parahippocampal gyrus, and the left precuneus. CONCLUSIONS: Our findings suggest that preterm infants with BPD have lower network integration and higher segregation at term-equivalent age, which may reflect a compensatory mechanism. In addition, BPD affects brain regions involved in visual as well as cognitive functions; these findings provide a new approach to diagnose potential brain damage in preterm infants with BPD.


Asunto(s)
Encéfalo , Displasia Broncopulmonar , Imagen de Difusión Tensora , Recien Nacido Prematuro , Red Nerviosa , Humanos , Displasia Broncopulmonar/diagnóstico por imagen , Displasia Broncopulmonar/fisiopatología , Masculino , Femenino , Recién Nacido , Encéfalo/diagnóstico por imagen , Encéfalo/patología , Red Nerviosa/diagnóstico por imagen , Red Nerviosa/fisiopatología , Red Nerviosa/patología , Vías Nerviosas/diagnóstico por imagen , Vías Nerviosas/fisiopatología , Imagen por Resonancia Magnética
9.
Inorg Chem ; 63(24): 10943-10948, 2024 Jun 17.
Artículo en Inglés | MEDLINE | ID: mdl-38818955

RESUMEN

Investigating novel nonlinear optical (NLO) active units serves as a valuable method for broadening the research landscape of NLO materials. This study showcases the potential of the cytosinium cation (C4H6N3O)+ as a novel NLO-active motif through theoretical calculations. The title compound exhibited a wide band gap of 3.85 eV, along with a moderate second harmonic generation (SHG) response of 1.65 times that of KH2PO4 (KDP) and significant birefringence of 0.47. Its exceptional optical properties are primarily attributed to the synergy interaction between cations and anionic groups in the asymmetric unit.

10.
Neural Netw ; 176: 106345, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38733798

RESUMEN

Local Interpretability Model-agnostic Explanations (LIME) is a well-known post-hoc technique for explaining black-box models. While very useful, recent research highlights challenges around the explanations generated. In particular, there is a potential lack of stability, where the explanations provided vary over repeated runs of the algorithm, casting doubt on their reliability. This paper investigates the stability of LIME when applied to multivariate time series classification. We demonstrate that the traditional methods for generating neighbours used in LIME carry a high risk of creating 'fake' neighbours, which are out-of-distribution in respect to the trained model and far away from the input to be explained. This risk is particularly pronounced for time series data because of their substantial temporal dependencies. We discuss how these out-of-distribution neighbours contribute to unstable explanations. Furthermore, LIME weights neighbours based on user-defined hyperparameters which are problem-dependent and hard to tune. We show how unsuitable hyperparameters can impact the stability of explanations. We propose a two-fold approach to address these issues. First, a generative model is employed to approximate the distribution of the training data set, from which within-distribution samples and thus meaningful neighbours can be created for LIME. Second, an adaptive weighting method is designed in which the hyperparameters are easier to tune than those of the traditional method. Experiments on real-world data sets demonstrate the effectiveness of the proposed method in providing more stable explanations using the LIME framework. In addition, in-depth discussions are provided on the reasons behind these results.


Asunto(s)
Algoritmos , Factores de Tiempo , Redes Neurales de la Computación
11.
Nat Commun ; 15(1): 4444, 2024 May 24.
Artículo en Inglés | MEDLINE | ID: mdl-38789421

RESUMEN

Mitochondrial respiration is essential for the survival and function of T cells used in adoptive cellular therapies. However, strategies that specifically enhance mitochondrial respiration to promote T cell function remain limited. Here, we investigate methylation-controlled J protein (MCJ), an endogenous negative regulator of mitochondrial complex I expressed in CD8 cells, as a target for improving the efficacy of adoptive T cell therapies. We demonstrate that MCJ inhibits mitochondrial respiration in murine CD8+ CAR-T cells and that deletion of MCJ increases their in vitro and in vivo efficacy against murine B cell leukaemia. Similarly, MCJ deletion in ovalbumin (OVA)-specific CD8+ T cells also increases their efficacy against established OVA-expressing melanoma tumors in vivo. Furthermore, we show for the first time that MCJ is expressed in human CD8 cells and that the level of MCJ expression correlates with the functional activity of CD8+ CAR-T cells. Silencing MCJ expression in human CD8 CAR-T cells increases their mitochondrial metabolism and enhances their anti-tumor activity. Thus, targeting MCJ may represent a potential therapeutic strategy to increase mitochondrial metabolism and improve the efficacy of adoptive T cell therapies.


Asunto(s)
Linfocitos T CD8-positivos , Inmunoterapia Adoptiva , Mitocondrias , Animales , Linfocitos T CD8-positivos/inmunología , Linfocitos T CD8-positivos/metabolismo , Mitocondrias/metabolismo , Humanos , Inmunoterapia Adoptiva/métodos , Ratones , Ratones Endogámicos C57BL , Proteínas Mitocondriales/metabolismo , Proteínas Mitocondriales/genética , Respiración de la Célula , Línea Celular Tumoral , Femenino , Ovalbúmina/inmunología , Melanoma Experimental/inmunología , Melanoma Experimental/terapia
12.
Behav Ecol ; 35(4): arae037, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38779595

RESUMEN

Male-male contests for access to females or breeding resources are critical in determining male reproductive success. Larger males and those with more effective weaponry are more likely to win fights. However, even after controlling for such predictors of fighting ability, studies have reported a winner-loser effect: previous winners are more likely to win subsequent contests, while losers often suffer repeated defeats. While the effect of winning-losing is well-documented for the outcome of future fights, its effect on other behaviors (e.g. mating) remains poorly investigated. Here, we test whether a winning versus losing experience influenced subsequent behaviors of male mosquitofish (Gambusia holbrooki) toward rivals and potential mates. We housed focal males with either a smaller or larger opponent for 24 h to manipulate their fighting experience to become winners or losers, respectively. The focal males then underwent tests that required them to enter and swim through a narrow corridor to reach females, bypassing a cylinder that contained either a larger rival male (competitive scenario), a juvenile or was empty (non-competitive scenarios). The tests were repeated after 1 wk. Winners were more likely to leave the start area and to reach the females, but only when a larger rival was presented, indicating higher levels of risk-taking behavior in aggressive interactions. This winner-loser effect persisted for at least 1 wk. We suggest that male mosquitofish adjust their assessment of their own and/or their rival's fighting ability following contests in ways whose detection by researchers depends on the social context.

13.
Arch Virol ; 169(5): 114, 2024 May 03.
Artículo en Inglés | MEDLINE | ID: mdl-38700535

RESUMEN

OBJECTIVE: Epstein-Barr virus (EBV)-associated gastric cancer (EBVaGC) is a distinct molecular subtype of gastric cancer (GC). At present, the clinical characteristics and prognostic implications of EBV infection and the potential clinical benefits of immune checkpoint blockade in GC remain to be clarified. Hence, this study was designed to analyze the clinical and pathological characteristics of GC patients with varying EBV infection states and compare their overall survival (OS). METHODS: A retrospective study was performed on 1031 consecutive GC patients who underwent gastrectomy at the Affiliated Hospital of Xuzhou Medical University from February 2018 to November 2022. EBV-encoded RNA (EBER) in situ hybridization (ISH) was used for EBV assessment, and immunohistochemical staining was used for evaluation of human epidermal growth factor receptor 2 (HER2), programmed death ligand 1 (PD-L1), and Ki67 expression. EBVaGC was defined as tumors with EBV positivity. In addition, EBV-negative GC (EBVnGC) patients were matched with EBVaGC patients based on seven clinicopathological parameters (age, gender, anatomic subsite, tumor size, Lauren classification, degree of differentiation, and tumor-node-metastasis [TNM] stage). The correlations of clinical features with HER2, PD-L1, and Ki67 expression were evaluated statistically. The survival of patients was assessed through medical records, telephone, or WeChat communication, and prognostic analysis was performed using the logrank test as well as univariable and multivariable regression analysis. RESULTS: Out of 1031 GC patients tested, 35 (3.4%) were diagnosed with EBVaGC. Notably, the EBVaGC group exhibited a distinct predominance of males and younger patients, significantly higher Ki67 and PD-L1 expression levels, and a lower prevalence of pericancerous nerve invasion than the EBVnGC group (P < 0.01). In the 35 EBVaGC cases, Ki67 expression was negatively correlated with age (P < 0.05), suggesting that a younger onset age was associated with higher Ki67 expression. In addition, PD-L1 expression was correlated with the degree of differentiation, T-stage, and clinical stage of the patient. Furthermore, PD-L1 expression was elevated in tumors with lower differentiation or at later stages (P < 0.05). Using univariate analysis, Ki67, PD-L1, and clinical stage were identified as significant factors influencing the overall survival (OS) of EBVaGC patients (P < 0.05). Moreover, multivariate survival analysis revealed that clinical stage and Ki67 expression were independent risk factors for the OS of the patients (P < 0.05), and the three-year OS rate of EBVaGC patients was 64.2%. CONCLUSION: EBV-ISH is a practical and valuable method to identify EBVaGC. Owing to its unique etiological, pathological, and clinical characteristics, patients with EBVaGC might benefit from immune checkpoint blockade therapy.


Asunto(s)
Infecciones por Virus de Epstein-Barr , Herpesvirus Humano 4 , Neoplasias Gástricas , Humanos , Neoplasias Gástricas/virología , Neoplasias Gástricas/patología , Masculino , Femenino , Infecciones por Virus de Epstein-Barr/virología , Infecciones por Virus de Epstein-Barr/complicaciones , Infecciones por Virus de Epstein-Barr/mortalidad , Persona de Mediana Edad , Herpesvirus Humano 4/genética , Pronóstico , Estudios Retrospectivos , Anciano , Adulto , Antígeno B7-H1/metabolismo , Antígeno B7-H1/genética , Receptor ErbB-2/metabolismo , Receptor ErbB-2/genética , Antígeno Ki-67/metabolismo , ARN Viral/genética , Gastrectomía
14.
World J Gastrointest Surg ; 16(5): 1385-1394, 2024 May 27.
Artículo en Inglés | MEDLINE | ID: mdl-38817293

RESUMEN

BACKGROUND: Previous studies have validated the efficacy of both magnetic compression and surgical techniques in creating rabbit tracheoesophageal fistula (TEF) models. Magnetic compression achieves a 100% success rate but requires more time, while surgery, though less frequently successful, offers rapid model establishment and technical maturity in larger animal models. AIM: To determine the optimal approach for rabbit disease modeling and refine the process. METHODS: TEF models were created in 12 rabbits using both the modified magnetic compression technique and surgery. Comparisons of the time to model establishment, success rate, food and water intake, weight changes, activity levels, bronchoscopy findings, white blood cell counts, and biopsies were performed. In response to the failures encountered during modified magnetic compression modeling, we increased the sample size to 15 rabbit models and assessed the repeatability and stability of the models, comparing them with the original magnetic compression technique. RESULTS: The modified magnetic compression technique achieved a 66.7% success rate, whereas the success rate of the surgery technique was 33.3%. Surviving surgical rabbits might not meet subsequent experimental requirements due to TEF-related inflammation. In the modified magnetic compression group, one rabbit died, possibly due to magnet corrosion, and another died from tracheal magnet obstruction. Similar events occurred during the second round of modified magnetic compression modeling, with one rabbit possibly succumbing to aggravated lung infection. The operation time of the first round of modified magnetic compression was 3.2 ± 0.6 min, which was significantly reduced to 2.1 ± 0.4 min in the second round, compared to both the first round and that of the original technique. CONCLUSION: The modified magnetic compression technique exhibits lower stress responses, a simple procedure, a high success rate, and lower modeling costs, making it a more appropriate choice for constructing TEF models in rabbits.

16.
PLoS One ; 19(5): e0296003, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38787854

RESUMEN

Maintenance of the intestinal epithelium requires constant self-renewal and regeneration. Tight regulation of proliferation and differentiation of intestinal stem cells within the crypt region is critical to maintaining homeostasis. The transcriptional co-factors ß-catenin and YAP are required for proliferation during normal homeostasis as well as intestinal regeneration after injury: aberrant signaling activity results in over proliferation and tumorigenesis. Although both YAP and ß-catenin activity are controlled along canonical pathways, it is becoming increasingly clear that non-canonical regulation of these transcriptional regulators plays a role in fine tuning their activity. We have shown previously that MAMDC4 (Endotubin, AEGP), an integral membrane protein present in endosomes, regulates both YAP and ß-catenin activity in kidney epithelial cells and in the developing intestinal epithelium. Here we show that MAMDC4 interacts with members of the signalosome and mediates cross-talk between YAP and ß-catenin. Interestingly, this cross-talk occurs through a non-canonical pathway involving interactions between AMOT:YAP and AMOT:ß-catenin.


Asunto(s)
Proteínas Adaptadoras Transductoras de Señales , Endosomas , Factores de Transcripción , Vía de Señalización Wnt , beta Catenina , Humanos , beta Catenina/metabolismo , Endosomas/metabolismo , Factores de Transcripción/metabolismo , Factores de Transcripción/genética , Animales , Proteínas Adaptadoras Transductoras de Señales/metabolismo , Proteínas Adaptadoras Transductoras de Señales/genética , Proteínas Señalizadoras YAP/metabolismo , Fosfoproteínas/metabolismo , Fosfoproteínas/genética , Ratones , Proteínas de la Membrana/metabolismo , Proteínas de la Membrana/genética , Células HEK293 , Proteínas de Ciclo Celular/metabolismo , Proteínas de Ciclo Celular/genética , Unión Proteica
18.
Artículo en Inglés | MEDLINE | ID: mdl-38587569

RESUMEN

BACKGROUND: To examine the impact of county-level colorectal cancer (CRC) screening rates on stage at diagnosis of CRC and identify factors associated with stage at diagnosis across different levels of screening rates in rural Georgia. METHODS: We performed a retrospective analysis utilizing data from 2004 to 2010 Surveillance, Epidemiology, and End Results Program. The 2013 United States Department of Agriculture rural-urban continuum codes were used to identify rural Georgia counties. The 2004-2010 National Cancer Institute small area estimates for screening behaviors were applied to link county-level CRC screening rates. Descriptive statistics and multinominal logistic regressions were performed. RESULTS: Among 4,839 CRC patients, most patients diagnosed with localized CRC lived in low screening areas; however, many diagnosed with regionalized and distant CRC lived in high screening areas (p-value = 0.009). In multivariable analysis, rural patients living in high screening areas were 1.2-fold more likely to be diagnosed at a regionalized and distant stage of CRC (both p-value < 0.05). When examining the factors associated with stage at presentation, Black patients who lived in low screening areas were 36% more likely to be diagnosed with distant diseases compared to White patients (95% CI, 1.08-1.71). Among those living in high screening areas, patients with right-sided CRC were 38% more likely to have regionalized disease (95% CI, 1.09-1.74). CONCLUSION: Patients living in high screening areas were more likely to have a later stage of CRC in rural Georgia. IMPACT: Allocating CRC screening/treatment resources and improving CRC risk awareness should be prioritized for rural patients in Georgia.

19.
J Mol Med (Berl) ; 102(6): 819-830, 2024 06.
Artículo en Inglés | MEDLINE | ID: mdl-38568327

RESUMEN

We conducted a comprehensive metabolomic analysis of plasma samples obtained from pregnant women who displayed varying post-vaccination antibody titers after receiving mRNA-1273-SARS-CoV-2 vaccines. The study involved 62 pregnant women, all of whom had been vaccinated after reaching 24 weeks of gestation. To quantify post-vaccination plasma antibody titers, we employed binding antibody units (BAU) in accordance with the World Health Organization International Standard. Subsequently, we classified the study participants into three distinct BAU/mL categories: those with high titers (above 2000), medium titers (ranging from 1000 to 2000), and low titers (below 1000). Plasma metabolomic profiling was conducted using 1H nuclear magnetic resonance spectroscopy, and the obtained data were correlated with the categorized antibody titers. Notably, in pregnant women exhibiting elevated anti-SARS-CoV-2 antibody titers, reduced plasma concentrations of acetate and urea were observed. A significant negative correlation between these compounds and antibody titers was also evident. An analysis of metabolomics pathways revealed significant inverse associations between antibody titers and four distinct amino acid metabolic pathways: (1) biosynthesis of phenylalanine, tyrosine, and tryptophan; (2) biosynthesis of valine, leucine, and isoleucine; (3) phenylalanine metabolism; and (4) degradation of valine, leucine, and isoleucine. Additionally, an association between the synthesis and degradation pathways of ketone bodies was evident. In conclusion, we identified different metabolic pathways that underlie the diverse humoral responses triggered by COVID-19 mRNA vaccines during pregnancy. Our data hold significant implications for refining COVID-19 vaccination approaches in expectant mothers. KEY MESSAGES : Anti-SARS-CoV-2 antibody titers decline as the number of days since COVID-19 vaccination increases. Anti-SARS-CoV-2 antibody titers are inversely associated with acetate, a microbial-derived metabolite, and urea. Amino acid metabolism is significantly associated with SARS-CoV-2 antibody titers.


Asunto(s)
Acetatos , Anticuerpos Antivirales , Vacunas contra la COVID-19 , COVID-19 , Metabolómica , SARS-CoV-2 , Urea , Vacunación , Humanos , Femenino , Embarazo , Anticuerpos Antivirales/sangre , Anticuerpos Antivirales/inmunología , COVID-19/inmunología , COVID-19/prevención & control , COVID-19/sangre , Metabolómica/métodos , SARS-CoV-2/inmunología , Adulto , Urea/sangre , Vacunas contra la COVID-19/inmunología , Metaboloma , Vacuna nCoV-2019 mRNA-1273
20.
Ying Yong Sheng Tai Xue Bao ; 35(3): 759-768, 2024 Mar 18.
Artículo en Inglés | MEDLINE | ID: mdl-38646764

RESUMEN

The increasing carbon emissions is one of the important reasons for global warming. As a key area of carbon emissions, carbon sequestration capacity of cities is urgently needed to be improved. Carbon sequestration ser-vices can be transferred between supply and demand areas due to the circulation of atmosphere. With Linyi City as an example, we used the minimum cumulative resistance model to extract the matching path of supply and demand, and constructed a carbon sequestration ecological network. The results showed that the regions with high supply of carbon sequestration services were located in the north and south of the study area, and that current total supply could solve about 60% of the total demand. Although the spatial distribution of supply and demand was uneven, 54% of the areas that could meet the surrounding carbon sequestration demand were still idle. The optimized supply-demand matching paths could maintain good transmission efficiency of material and energy, with lower costs. Paths with strong potential carbon sequestration capacity were located in the central and northwest part of the research area. In the construction of carbon sequestration ecological network, it is necessary to strengthen the protection and restoration of the supply side of carbon sequestration services, realize carbon reduction and strengthen carbon sequestration on the demand side, and optimize the matching path of supply and demand. This method provided services to the demand areas through the oversupply of ecosystem services, optimized the overall resource allocation, which could advance regional carbon sequestration capacity.


Asunto(s)
Secuestro de Carbono , Ciudades , Ecosistema , China , Conservación de los Recursos Naturales/métodos
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