Explore the vast range of titles available.

Background Heart failure (HF) is a major public health concern in China, but there is a lack of epidemiological data on the prevalence of early-stage HF in the elderly. Objectives This study aimed to evaluate the prevalence of different stages of HF in individuals aged ≥ 60 years in a community-based survey. Methods This cross-sectional study enrolled 7,640 participants from a community. Basic demographic information, NT-proBNP, troponin T (TnT) levels, and echocardiographic data were collected. Participants were classified into four stages: Healthy, Stage A, Stage B, and Stage C. Prevalence and associated risk factors were analyzed. Results The mean age was 70.2 years, with 54.5% being female. The prevalence of Stage A and B was 44.0% and 27.8%, respectively. In Stage A, hypertension was the most common risk factor (80.89%), followed by diabetes (29.75%) and obesity (18.08%). In Stage B and C, 97.2% and 88.2% had an ejection fraction ≥ 50%. The prevalence of Stage B increased with age ( P  < 0.001), and women had higher prevalence of Stage B compared to men (29.69% vs. 25.65%, P  < 0.001). Female gender (OR 1.352, P  < 0.001), older age (OR 1.096, P  < 0.001), atrial fibrillation/flutter (OR 2.853, P  < 0.001), and coronary artery disease (OR 1.473, P  < 0.001) were identified as significant risk factors for Stage B. Conclusions This survey revealed a high prevalence of Stage A and B HF in the elderly, with most Stage B individuals having an ejection fraction ≥ 50%, emphasizing the need for targeted prevention and management strategies for at-risk groups.

Background Human umbilical cord-derived mesenchymal stem cells (HucMSCs) have been recognized as a promising cell for treating myocardial infarction (MI). Inflammatory response post MI is critical in determining the cardiac function and subsequent adverse left ventricular remodeling. However, the local inflammatory effect of HucMSCs after intramyocardial injection in murine remains unclear. Methods HucMSCs were cultured and transplanted into the mice after MI surgery. Cardiac function of mice were analyzed among MI-N.S, MI-HucMSC and MI-HucMSC-C–C Motif Chemokine receptor 5 (CCR5) antagonist groups, and angiogenesis, fibrosis and hypertrophy, and immune cells infiltration of murine hearts were evaluated between MI-N.S and MI-HucMSC groups. We detected the expression of inflammatory cytokines and their effects on CD4 + T cells migration . Results HucMSCs treatment can significantly improve the cardiac function and some cells can survive at least 28 days after MI. Intramyocardial administration of HucMSCs also improved angiogenesis and alleviated cardiac fibrosis and hypertrophy. Moreover, we found the much higher numbers of CD4 + T cells and CD4 + FoxP3 + regulatory T cells (Tregs) in the heart with HucMSCs than that with N.S treatment on day 7 post MI. In addition, the protein level of C–C Motif Chemokine Ligand 5 (CCL5) greatly increased in HucMSCs treated heart compared to MI-N.S group. In vitro, HucMSCs inhibited CD4 + T cells migration and addition of CCL5 antibody or CCR5 antagonist significantly reversed this effect. In vivo results further showed that addition of CCR5 antagonist can reduce the cardioprotective effect of HucMSCs administration on day 7 post MI injury. Conclusion These findings indicated that HucMSCs contributed to cardiac functional recovery and attenuated cardiac remodeling post MI. Intramyocardial injection of HucMSCs upregulated the CD4 + FoxP3 + Tregs and contributed to the migration of CD4 + T cells into the injured heart via CCL5/CCR5 pathway.

Microwave remote sensing is one of the most useful methods for observing the ocean parameters. The Doppler frequency or interferometric phase of the radar echoes can be used for an ocean surface current speed retrieval,which is widely used in spaceborne and airborne radars. While the effect of the ocean currents and waves is interactional. It is impossible to retrieve the ocean surface current speed from Doppler frequency shift directly. In order to study the relationship between the ocean surface current speed and the Doppler frequency shift, a numerical ocean surface Doppler spectrum model is established and validated with a reference. The input parameters of ocean Doppler spectrum include an ocean wave elevation model, a directional distribution function, and wind speed and direction. The suitable ocean wave elevation spectrum and the directional distribution function are selected by comparing the ocean Doppler spectrum in C band with an empirical geophysical model function（CDOP）. What is more, the error sensitivities of ocean surface current speed to the wind speed and direction are analyzed. All these simulations are in Ku band. The simulation results show that the ocean surface current speed error is sensitive to the wind speed and direction errors. With VV polarization, the ocean surface current speed error is about 0.15 m/s when the wind speed error is 2 m/s, and the ocean surface current speed error is smaller than 0.3 m/s when the wind direction error is within 20° in the cross wind direction.

In order to examine the phylogeny and evolutionary history of the subfamily Notodontinae (Noctuoidea: Notodontidae), a molecular systematic study was conducted, mainly based on mitochondrial protein-coding genes (PCGs) generated by high-throughput sequencing, including 57 species belonging to 37 genera, together with 64 other species within Notodontidae and 14 outgroups, with the dataset comprising 10,980 bp of nucleotide sequences. An individual dataset of orthologous genes (OGs) comprising 589 loci (919,493 bp in total) was utilized as a supporting analysis for the result from the mitochodrial dataset. In this study, the monophyly of Notodontinae was well supported, with the internal clades consisting of three tribes—Stauropini, Notodontini, and Fentoniini—and supporting evidence found in the male genital characteristics. Furthermore, Neodrymoniaini Kobayashi, 2016 syn. nov. was synonymized with Fentoniini Matsumura, 1929. Divergence time estimation for Notodontinae, conducted using phylogenetic results across five fossil calibration points, suggested that Notodontinae originated around 22.71 Ma, and the most recent common ancestor of Stauropini and Fentoniini diverged between 24.44 and 20.23 Ma, followed by the emergence of Stauropini between 23.83 and 19.53 Ma. Then, Notodontini diverged around 23.60–19.10 Ma, with the youngest tribe, Fentoniini, dividing in 21.70–16.63 Ma. In summary, this study provided a robust foundation for classification within the terminal clades of Notodontidae and laid the groundwork for further research on phylogenetic relationships across the whole family.

Background The tumor microenvironment (TME) is integral to tumor progression. However, its prognostic implications and underlying mechanisms in clear cell renal cell carcinoma (ccRCC) are not yet fully elucidated. This study aims to examine the prognostic significance of genes associated with immune-stromal scores and to explore their underlying mechanisms in ccRCC. Methods Data from the Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) were subjected to analysis to compute immune and stromal scores utilizing the ESTIMATE algorithm. The weighted gene co-expression network analysis (WGCNA) was employed to identify gene modules associated with these scores. Differentially expressed genes were assessed using the limma package. Prognostic biomarkers were subsequently identified through univariate, LASSO, and multivariate Cox regression analyses, culminating in the development of a risk score model. Gene expression was confirmed in ccRCC cell lines (786-O, Caki-1) and tumor tissues. Functional assays, such as wound healing and Transwell assays, were employed to evaluate tumor invasion and migration. The prognostic accuracy was assessed through ROC curve analysis, and a nomogram integrating risk scores with clinical variables was constructed. Analyses of immune infiltration, human leukocyte antigen (HLA) expression, immune checkpoint expression, immunophenoscore (IPS), tumor immune dysfunction and exclusion (TIDE) scores, and responses to six targeted therapies were conducted across different risk groups. Results Twelve critical prognostic markers, including CAPRIN1, CXCR3, FERMT3, HAPLN3, HBP1, MACF1, MPEG1, OSCAR, STAT1, UBA7, VAMP1, and VSIG4, were identified. The risk score model exhibited a high degree of predictive accuracy for survival outcomes in ccRCC. Immune profiling revealed significant differences in the TME between risk groups, with high-risk patients displaying elevated expression of HLA and immune checkpoints. Drug sensitivity analyses suggested that high-risk patients had a better response to erlotinib, temsirolimus, axitinib, and sunitinib, whereas low-risk patients demonstrated greater sensitivity to pazopanib. Variability in immunotherapy responsiveness between groups was observed based on IPS and TIDE analyses. Conclusion This study highlights the prognostic value and TME-related mechanisms of immune-stromal score signatures in ccRCC, developing a risk score model and nomogram for predicting patient prognosis. Highlights 1. Identified prognostic genes related to immune and stromal scores in clear cell renal cell carcinoma (ccRCC). 2. Constructed a risk score model and nomogram to predict survival outcomes in ccRCC patients. 3. Analyzed immune infiltration, HLA, and immune checkpoint expression, along with IPA and TIDE scores. 4. Evaluated differential responses to six targeted therapies between high- and low-risk patient groups. 5. Demonstrated the role of identified biomarkers in ccRCC invasion and migration through qRT-PCR, Western blot, wound-healing, and Transwell assays. 6. Employed flow cytometry to assess the impact of biomarkers on ccRCC cell lines' responsiveness to targeted therapies. 7. Addressed the significant yet unresolved impact of the tumor microenvironment on ccRCC prognosis and treatment response.

Our previous studies showed that MAN3-mediated mannose plays an important role in plant responses to cadmium (Cd) stress. However, the underlying mechanisms and signaling pathways involved are poorly understood. In this study, we showed that an Arabidopsis MYB4-MAN3-Mannose-MNB1 signaling cascade is involved in the regulation of plant Cd tolerance. Loss-of-function of MNB1 ( m an n ose- b inding-lectin 1) led to decreased Cd accumulation and tolerance, whereas overexpression of MNB1 significantly enhanced Cd accumulation and tolerance. Consistently, expression of the genes involved in the GSH-dependent phytochelatin (PC) synthesis pathway (such as GSH1 , GSH2 , PCS1 , and PCS2 ) was significantly reduced in the mnb1 mutants but markedly increased in the MNB1-OE lines in the absence or presence of Cd stress, which was positively correlated with Cd-activated PC synthesis. Moreover, we found that mannose is able to bind to the GNA-related domain of MNB1, and that mannose binding to the GNA-related domain of MNB1 is required for MAN3-mediated Cd tolerance in Arabidopsis . Further analysis showed that MYB4 directly binds to the promoter of MAN3 to positively regulate the transcript of MAN3 and thus Cd tolerance via the GSH-dependent PC synthesis pathway. Consistent with these findings, overexpression of MAN3 rescued the Cd-sensitive phenotype of the myb4 mutant but not the mnb1 mutant, whereas overexpression of MNB1 rescued the Cd-sensitive phenotype of the myb4 mutant. Taken together, our results provide compelling evidence that a MYB4-MAN3-Mannose-MNB1 signaling cascade regulates cadmium tolerance in Arabidopsis through the GSH-dependent PC synthesis pathway.

A series of novel inflammation-related indexes has been confirmed to be efficient indicators of human immune and inflammatory status, with great potential as predictors for a variety of diseases. However, the association between inflammation-related indexes and sex hormones in the general population remained uncertain. We incorporated data from the NHANES 2013-2016 survey of American adults. On the basis of distribution and comparison analysis, we chose to undertake separate analyses of men and women (including premenopausal and postmenopausal groups). Multivariable weighted linear regression models, eXtreme Gradient Boosting (XGBoost) models, generalized linear analysis, stratified models, logistic regression models and sensitivity analysis were utilized to assess the relationships between inflammation-related indexes and sex hormones. Total 9372 participants out of 20146 were fitted into our research. We conducted separate gender analysis due to different distribution. Multivariable weighted linear regression indicated every component of the inflammation-related index was negatively correlated with at least one component of the male hormone indexes. However, SII, NLR, PPN, and NC were associated positively with female estradiol. XGBoost identify SII, PLR and NLR were the critical indexes on sex hormones. Inflammation-related indexes was associated with Testosterone deficiency in male and postmenstrual group and associated with Excessive Estradiol in premenstrual group. Finally, the subgroup analysis revealed that the association between sex hormones and inflammatory indicators was prominent in American adults over the age of 60 or those with BMI (>28 kg/m ). In all, inflammation-related indexes act as independent risks associated with sex hormone alterations and metabolic disorder in both genders. Using multiple models, we revealed the relative importance of inflammation-related indexes. Subgroup analysis also identified the high-risk population. More prospective and experimental research should be conducted to validate the results.

Background Primary carnitine deficiency (PCD) is an autosomal recessive disorder of carnitine transportation that leads to impaired fatty acid oxidation. Large-scale studies on newborn screening (NBS) for PCD are limited. This study aimed to investigate the biochemical and genetic characteristics of patients with PCD detected through NBS. Results A total of 548 247 newborns were screened for PCD between January 2014 and June 2021; 1714 newborns with low free carnitine (C0) levels were called back and 49 patients were diagnosed with PCD. The latest incidence rate in Quanzhou, China, was estimated to be 1 in 11 189 newborns. NBS results showed that the 49 patients had varying degrees of decreased C0 levels, whereas seven patients exhibited normal C0 levels during the recall review. All patients harbored biallelic pathogenic variants of the SLC22A5 gene. Nineteen distinct SLC22A5 variants were detected in these 49 patients, and most of the detected variants were clustered in exons 1, 4, and 7. The top eight variants had an allele frequency of 86.73%. The most common variant was c.760C > T (p.R254*) with an allele frequency of 31.63%, followed by c.51C > G (p.F17L) (17.35%) and c.1400C > G (p.S467C) (16.33%). The C0 level of patients with the N/N genotype was significantly lower than that of the M/M group. The C0 levels of patients with genotypes of R254*/R254* and R254*/F17L were far lower than those of patients with the R254*/S467C genotype. Conclusions This study presented more than 500,000 NBS data with the latest incidence of 1:11 189 in the Quanzhou area. The SLC22A5 variant spectrum in the selected southern Chinese population has been updated. Patients with null variants were associated with low C0 levels. Combining NBS with genetic testing is critical to improve screening efficiency because patients with PCD may have normal C0 levels during NBS and recall review.

Background Prostatic cancer (PCa) is one of the most common malignant tumors in men worldwide. Emerging evidence indicates significance of hypoxia and immunity in PCa invasion and metastasis. This study aimed to develop a hypoxia- and immune-related gene risk signature and explore the molecular mechanisms to formulate a better prognostic tool for PCa patients. Methods The hypoxia and immune scores of all PCa patients in The Cancer Genome Atlas (TCGA) dataset were calculated via the maximally selected rank statistics method and the ESTIMATE algorithm. From common genes identified overlapping hypoxia- and immune-related differentially expressed genes (DE-HRGs and DE-IRGs), a hypoxia- and immune-related gene risk signature was developed utilizing univariate and multivariate Cox regression analyses, and validated in the Memorial Sloan Kettering Cancer Centre (MSKCC) database. The immune cell infiltration level of PCa samples were evaluated with ssGSEA algorithm. Differential expression of prognostic genes was evidenced by immunohistochemistry and western blot (WB) in paired PCa samples. Expression levels of these genes and their variations under regular and hypoxic conditions were examined in cell lines. The functional effects of the prognostic gene on PCa cells were examined by wound healing and transwell assays. Results A hypoxia- and immune-related gene risk signature constructed by ISG15 and ZFP36 displays significant predictive potency, with higher risk score representing worse survival. A nomogram based on independent prognostic factors including the risk score and Gleason score exhibited excellent clinical value in the survival prediction of PCa. Infiltration levels of eosinophils, neutrophils, Tcm, Tem, TFH, Th1 cells, and Th17 cells were significantly lower in the high-risk group. Conversely, aDC, pDC, T helper cells, and Tregs were significantly higher. Additionally, the two prognostic genes were closely correlated with the tumor-infiltrating immune cell subset in PCa progression. RT-qPCR and WB presented higher and lower expression of ISG15 and ZFP36 in PCa cells, respectively. They were correspondingly increased and decreased in PCa cells under hypoxic conditions. Wound healing and transwell assays showed that over-expression of ISG15 promoted the migration and invasion of PCa cells. Conclusion Our study identified a novel hypoxia- and immune-related gene signature, contributing a new perspective to the treatment of PCa