Exosomes in pathogenesis, diagnosis, and therapy of ischemic stroke

Ischemic stroke is one of the major contributors to death and disability worldwide. Thus, there is an urgent need to develop early brain tissue perfusion therapies following acute stroke and to enhance functional recovery in stroke survivors. The morbidity, therapy, and recovery processes are highly orchestrated interactions involving the brain with other tissues. Exosomes are natural and ideal mediators of intercellular information transfer and recognized as biomarkers for disease diagnosis and prognosis. Changes in exosome contents express throughout the physiological process. Accumulating evidence demonstrates the use of exosomes in exploring unknown cellular and molecular mechanisms of intercellular communication and organ homeostasis and indicates their potential role in ischemic stroke. Inspired by the unique properties of exosomes, this review focuses on the communication, diagnosis, and therapeutic role of various derived exosomes, and their development and challenges for the treatment of cerebral ischemic stroke

Psychometric properties of the Chinese version of the preoperative assessment of readiness tool among surgical patients

BackgroundThe evaluation of the surgical readiness of patients plays an important role in clinical care. Preoperative readiness assessment is needed to identify the inadequacy among surgical patients, which provides guide for interventions to improve patients’ preoperative readiness. However, there is a paucity of high-level, quality tool that evaluate surgical readiness of patients in China. The purpose of this study is to translate the Preoperative Assessment of Readiness Tool (PART) into Chinese and determine the reliability and validity of the Chinese version in the population of surgical patients.MethodsUsing a standard translation-backward method, the original English version of PART was translated into Chinese. A convenient sampling of 210 surgical patients was recruited from 6 hospitals in Zhejiang Province to test the psychometric properties of this scale including internal consistency, split-half reliability, content validity, structure validity, and floor/ceiling effect.ResultsA total of 194 patients (92%) completed questionnaires. The Chinese version of PART achieved Cronbach’s alphas 0.948 and McDonald’s omega coefficient 0.947, respectively, for the full scale. The estimated odd-even split-half reliability was 0.959. The scale-level content validity index was 0.867, and the items content validity index ranged from 0.83 to 1.0.The output of confirmatory factor analysis (CFA) revealed a two-factor model (χ2 = 510.96; df = 86; p < 0.001; root mean square error approximation = 0.08) with no floor/ceiling effect.ConclusionThe Chinese version of PART demonstrated acceptable reliability and validity among surgical patients. It can be used to evaluate patients’ preoperative preparation and help health professionals provide proper preoperative support

CDCA2 Inhibits Apoptosis and Promotes Cell Proliferation in Prostate Cancer and Is Directly Regulated by HIF-1α Pathway.

Prostate cancer (PCa) is a major serious malignant tumor and is commonly diagnosed in older men. Identification of novel cancer-related genes in PCa is important for understanding its tumorigenesis mechanism and developing new therapies against PCa. Here, we used RNA sequencing to identify the specific genes, which are upregulated in PCa cell lines and tissues. The cell division cycle associated protein (CDCA) family, which plays a critical role in cell division and proliferation, is upregulated in the PCa cell lines of our RNA-Sequencing data. Moreover, we found that CDCA2 is overexpressed, and its protein level positively correlates with its histological grade, clinical stage, and Gleason Score. CDCA2 was further found to be upregulated and correlated with poor prognosis and patient survival in multiple cancer types in The Cancer Genome Atlas (TCGA) dataset. The functional study suggests that inhibition of CDCA2 will lead to apoptosis and lower proliferation in vitro. Silencing of CDCA2 also repressed tumor growth in vivo. Loss of CDCA2 affects several oncogenic pathways, including MAPK signaling. In addition, we further demonstrated that CDCA2 was induced in hypoxia and directly regulated by the HIF-1α/Smad3 complex. Thus, our data indicate that CDCA2 could act as an oncogene and is regulated by hypoxia and the HIF-1αpathway. CDCA2 may be a useful prognostic biomarker and potential therapeutic target for PCa

Effects of increased phosphorus fertilizer on C, N, and P stoichiometry in different organs of bluegrass (Poa L.) at different growth stages

IntroductionThe application of phosphorus (P) fertilizer can promote photosynthesis in forage grasses and accelerate their establishment.MethodsTo improve the utilization efficiency of P fertilizer for bluegrass (Poa L.) in alpine regions, the effects of P fertilizer on their growth, and carbon (C), nitrogen (N) and P distribution in their different organs of them are tested at six P fertilization levels (3, 6, 9, 12, 15, 18 g·m−2).Results(1) The nutrient content in each organ of bluegrass varies during different growth stages, with the lowest nutrient content occurring in the wilt stage. (2) The response of the nutrient content and ratio of each organ of bluegrass to different P fertilization levels varies. When the P application rate was 15 g·m−2, the contents of N and P in roots were the highest, and their C/N and C/P ratios were the lowest. When the P application rate was 12 g·m−2, the contents of N and P in the stems were the highest, and their C/N and C/P ratios were the lowest. When the P application rate was 9 g·m−2, the contents of N and P in leaves were the highest, and their C/N and C/P ratios were the lowest. When the P application rate was 6 g·m−2 the contents of N and P in the panicle were the highest, and their C/N and C/P ratios were the lowest.DiscussionThese results provide a better understanding of the effect of P fertilization in the nutrient partitioning pattern of perennial forage plant organs in alpine regions. The information from this study can support a more reasonable P fertilization for the establishment of early grassland. For example, in artificial forage grassland, the application of low-concentration P fertilizer (6~9 g·m−2) can promote the nutrient content in spikes and stems of forage grass; for ecological management, the application of high-concentration P fertilizer (15 g·m−2) can promote the nutrient content in roots and enhance the ecological benefits of forage grassland

Exploring the Role of a Novel Peptide from Allomyrina dichotoma Larvae in Ameliorating Lipid Metabolism in Obesity

The aim of this study was to identify an anti-obesity peptide from Allomyrina dichotoma and investigate the lipid metabolic mechanism. Enzymatically hydrolyzed A. dichotoma larvae were further separated using tangential flow filtration and consecutive chromatographic processes. Finally, an anti-obesity peptide that showed the highest inhibitory effect on lipid accumulation was obtained, and the sequence was Glu-Ile-Ala-Gln-Asp-Phe-Lys-Thr-Asp-Leu (EIA10). EIA10 decreased lipid aggregation in vitro and significantly reduced the accumulation of body weight gain, liver weight, and adipose tissue weight in high-fat-fed mice. Compared with the control group, the levels of total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL), insulin, and homeostasis model assessment of insulin resistance (HOMA-IR) in the high-fat diet (HFD) group increased significantly, and the content of high-density lipoprotein cholesterol (HDL) in the serum decreased significantly. On the contrary, the levels of TC, TG, and insulin in the EIA10 group decreased significantly, and the HDL content increased significantly compared with the HFD group. Additionally, EIA10 dramatically decreased mRNA and protein levels of transcription factors involved in lipid adipogenesis. Taken together, our results suggest that EIA10 could be a promising agent for the treatment and prevention of obesity

Identification of genetically predicted DNA methylation markers associated with non-small cell lung cancer risk among 34,964 cases and 448,579 controls.

BackgroundAlthough the associations between genetic variations and lung cancer risk have been explored, the epigenetic consequences of DNA methylation in lung cancer development are largely unknown. Here, the genetically predicted DNA methylation markers associated with non-small cell lung cancer (NSCLC) risk by a two-stage case-control design were investigated.MethodsThe genetic prediction models for methylation levels based on genetic and methylation data of 1595 subjects from the Framingham Heart Study were established. The prediction models were applied to a fixed-effect meta-analysis of screening data sets with 27,120 NSCLC cases and 27,355 controls to identify the methylation markers, which were then replicated in independent data sets with 7844 lung cancer cases and 421,224 controls. Also performed was a multi-omics functional annotation for the identified CpGs by integrating genomics, epigenomics, and transcriptomics and investigation of the potential regulation pathways.ResultsOf the 29,894 CpG sites passing the quality control, 39 CpGs associated with NSCLC risk (Bonferroni-corrected p ≤ 1.67 × 10-6 ) were originally identified. Of these, 16 CpGs remained significant in the validation stage (Bonferroni-corrected p ≤ 1.28 × 10-3 ), including four novel CpGs. Multi-omics functional annotation showed nine of 16 CpGs were potentially functional biomarkers for NSCLC risk. Thirty-five genes within a 1-Mb window of 12 CpGs that might be involved in regulatory pathways of NSCLC risk were identified.ConclusionsSixteen promising DNA methylation markers associated with NSCLC were identified. Changes of the methylation level at these CpGs might influence the development of NSCLC by regulating the expression of genes nearby.Plain language summaryThe epigenetic consequences of DNA methylation in lung cancer development are still largely unknown. This study used summary data of large-scale genome-wide association studies to investigate the associations between genetically predicted levels of methylation biomarkers and non-small cell lung cancer risk at the first time. This study looked at how well larotrectinib worked in adult patients with sarcomas caused by TRK fusion proteins. These findings will provide a unique insight into the epigenetic susceptibility mechanisms of lung cancer

Integrated Model of Joint Residence-Workplace Location Choice and Commute Behavior Using Latent Class and Mixed Logit Methods

With the rapid development of urbanization and motorization, urban commute trips are becoming increasingly serious due to the unbalanced distribution of residence and workplace land-use types in most Chinese cities. To explore the inherent interrelations among residence location, workplace, and commute trip, an integrated model framework of joint residence-workplace location choice and commute behavior is put forward based on the personal trip survey data of Beijing in 2005. First, to extract households' different choice characteristics, this paper presents a latent class model, clusters all households into several groups, and analyzes the conditional probability of each group. Second, the paper integrates the residence location and workplace together as the joint choice alternative, employs the socioeconomic factors, individual attributes, household attributes, and trip characteristics as explanatory variables, and formulates the joint residence-workplace location choice model using mixed logit method. Estimations of the latent class model show that four latent groups fit the data best. Further results of the joint residence-workplace location choice model indicate that there exist significantly different choice characteristics in each latent group. Generally, the integrated model framework outperforms traditional location choice methods

Integrated Model of Joint Residence-Workplace Location Choice and Commute Behavior Using Latent Class and Mixed Logit Methods

With the rapid development of urbanization and motorization, urban commute trips are becoming increasingly serious due to the unbalanced distribution of residence and workplace land-use types in most Chinese cities. To explore the inherent interrelations among residence location, workplace, and commute trip, an integrated model framework of joint residence-workplace location choice and commute behavior is put forward based on the personal trip survey data of Beijing in 2005. First, to extract households’ different choice characteristics, this paper presents a latent class model, clusters all households into several groups, and analyzes the conditional probability of each group. Second, the paper integrates the residence location and workplace together as the joint choice alternative, employs the socioeconomic factors, individual attributes, household attributes, and trip characteristics as explanatory variables, and formulates the joint residence-workplace location choice model using mixed logit method. Estimations of the latent class model show that four latent groups fit the data best. Further results of the joint residence-workplace location choice model indicate that there exist significantly different choice characteristics in each latent group. Generally, the integrated model framework outperforms traditional location choice methods

Development and validation of fall risk perception scale for patients with Parkinson’s disease

BackgroundPerception assessment plays an important role in fall risk awareness and fall prevention. Parkinson’s disease patients with motor dysfunction are at high risk of falling. Currently, no instrument has been explicitly crafted to assess the risk perception of fall in PD patients. The purpose of this study was to develop and validate the fall risk perception scale for PD patients (FRPS-PD), providing healthcare professionals with a effective assessment tool to enhance proactive fall prevention initiatives.MethodBased on the Proactive Health theory and Risk Perception Attitude (RPA) Framework, the questionnaire was developed through literature review, semi-structure interview, expert consultation and pilot testing. A total of 428 patients with PD from Grade A tertiary hospitals in Shanghai, Hangzhou and Anhui from January 2023 to July 2023 were recruited. The items and dimensions in the scale were explored and confirmed using item-analysis, content validity, exploratory factor analytical (EFA), confirmatory factor analytical (CFA), internal consistency and test–retest reliability analysis.ResultsA total of 16-items, 2-dimensions structure were identified, including 12 items of risk perception and 4 items of self-efficacy dimension. The cumulative variance of EFA model was 73.669%, further CFA showed that acceptable model fit (χ2/df = 2.226, RMSEA = 0.074, NF = 0.928, TLI = 0.951, CFI = 0.959, GFI = 0.887 and AGFI = 0.848). The content validity index was 0.956. The reliability of the scale was 0.952 using Cronbach’s α coefficient method. The test–retest reliability was 0.944.ConclusionThe FRPS-PD is a valid and reliable measurement for evaluating fall risk perception level for individuals with PD in mainland China