RNA‐binding protein QKI (also known as Quaking) belongs to hnRNP K‐homology (KH)‐domain protein family and is implicated a novel regulator in pre‐RNA splicing. As previously shown, the QKI homolog how potentially regulates heart lumen formation and function in fruit fly. However, QKI ’s function in mammalian heart development is largely unknown. We found that Qki specifically expressed in mouse developing hearts as early as E7.0 and this high‐level expression was maintained in the hearts to adulthood. Consistent with this finding, by using human embryonic stem cells (hESCs)‐cardiomyocyte differentiation system, QKI expression was found up‐regulated at Day 6, a critical time frame that cardiogenic progenitor transition into early cardiomyocytes. To determine the biological function of QKI in cardiogenesis, we generated hESCs QKIdef by using CRISPR/Cas9 gene editing technology and analyzed the physiological impact of QKI ‐deficiency to cardiomyocyte differentiation and maturation. As expected, we did not find defect in pluripotency in hESCs QKIdef , but the contractile function was dramatically reduced in hESCs QKIdef ‐derived cardiomyocytes. Based on scRNA‐seq and clustering analyses, there was no significant difference in the distribution of the clusters when compared hESCs QKIdef ‐cardiomyocyte group to normal control group, suggesting that the cardiomyocyte differentiation was largely unaffected in hESCs QKIdef . However, scRNA‐seq demonstrated a handful of genes encoding sarcomere proteins were significantly altered in cardiomyocyte clusters, which included ACTN2, ACTA1, MYH7, and MYL2, etc., indicating a significant defect in cardiomyocyte maturation. Bulk RNA‐seq data not only further confirmed this notion, but also provided additional depth for detailed analysis on the QKI ‐mediated pre‐RNA splicing events. In conjunction with QKI ‐binding motif search and RNA immunoprecipitation (RIP) analysis, we were able to demonstrate that QKI was a key pre‐RNA splicing regulator for sets of genes involved in cardiac myofibrillogenesis and cardiac excitation‐contraction (E‐C) coupling, which ultimately impacted on cardiomyocyte maturation and function. Additional analysis of cardiac developmental defects in Qki bgeo mutant mice further validated that QKI was an indispensable splicing regulator in cardiovascular development. Our results not only revealed a novel mechanism by which QKI regulates pre‐mRNA splicing in cardiogenesis, but also implied that QKI was likely involved in the pathogenesis of certain forms of congenital heart defects and cardiomyopathies. Support or Funding Information This work was supported in part by National Institute of Health P01HL134599
The micro-expression (ME) processing characteristics of patients with depression has been studied but has not been investigated in people with subthreshold depression. Based on this, by adopting the ecological MEs recognition paradigm, this study aimed to explore ME recognition in people with subthreshold depression. A 4 (background expression: happy, neutral, sad and fearful) × 4 (ME: happy, neutral, sad, and fearful) study was designed; two groups of participants (experimental group with subthreshold depression vs. healthy control group, 32 participants in each group) were asked to complete the ecological ME recognition task, and the corresponding accuracy (ACC) and reaction time (RT) were analyzed. Results: (1) Under different background conditions, recognizing happy MEs had the highest ACC and shortest RT. (2) There was no significant difference in the ACC and RT between experimental and control groups. (3)In different contexts, individuals with subthreshold depression tended to misjudge neutral, sad, and fearful MEs as happy, while neutral MEs were misjudged as sad and fearful. (4) The performance of individuals with subthreshold depression in the ecological ME recognition task were influenced by the type of ME; they showed highest ACC and shortest RT when recognizing happy MEs (vs. the other MEs). Conclusions: (1) The performance of individuals' ecological ME recognition were influenced by the background expression, and this embodied the need for ecological ME recognition. (2) Individuals with subthreshold depression showed normal ecological ME recognition ability. (3) In terms of misjudgment, individuals with subthreshold depression showed both positive and negative bias, when completing the ecological ME recognition task. (4) Compared with the other MEs, happy MEs showed an advantage recognition effect for individuals with subthreshold depression who completed the ecological ME recognition task.
42 endophytes were isolated from the heave parts of the phloem and xylem of Jatropha curcas L.Using polymerase chain reaction(PCR) technique,the gene sequence of internal transcribed spacer(ITS) was determined.Through Blast System,the difference of the gene sequences between the isolate and the fungus in European Molecular Biology Laboratory Genbank was compared.The result showed that the isolated fungus and the genera of Pestalotiopsis,Cephalosporium,Acremonium,Fusarium,Trichoderma,Mucor,Penicillium,Rhizopus,Aspergillus and Phoma shared more than 99 % homology sequence.Therefore,the isolated fungus were identified as Pestalotiopsis sp.,Cephalosporium sp.,Acremonium sp.,Fusarium sp.,Trichoderma sp.,Mucor sp.,Penicillium sp.,Rhizopus sp.,Aspergillus sp.Among them,Pesudotiopsis was the dominant genera,Penicillium and Phoma was the second dominant genera.It also indicated that the endophytes from Jatropha curcas L.had the characteristics of diversity.
Population aging is a global concern, with the World Health Organization predicting that by 2030, one in six individuals worldwide will be 60 years or older. Ethylene oxide (EO) is a widely used industrial chemical with potential health risks, including associations with age-related diseases. This study investigates the relationship between EO exposure and biological age acceleration.
744 Background: Pancreatic cancer (PC) is one of the leading causes of cancer death. Identifying molecular residual disease (MRD) with tailored tumor-informed ctDNA-based next-generation sequencing (NGS) assays after curative surgery could facilitate the individualized management of patients with resected pancreatic cancer (PC). Here, we prospectively evaluated the clinical performance of tumor-informed ctDNA mutation analysis using a novel Burning Rock Patient Specific Prognostic and Potential Therapeutic Marker Tracking (brPROPHET) approach for assessing MRD in patients with resected PC. Methods: The prospective cohort study recruited patients (n = 20) diagnosed with resectable stage I-III PC. Plasma samples (n = 63) were collected before surgery (baseline), 7-days after surgery (landmark), 30-days after surgery (before any adjuvant therapy), during the adjuvant therapy and follow-up. Individual tumors and matched white blood cells (WBCs) were whole-exome sequenced and somatic mutations were identified. Serial plasma samples were analyzed by a personalized, tumor-informed ctDNA-based NGS assay (brPROPHET) designed to target up to 50 variants per patient. Results: A total of 20 patients (stage I/II 10 [50%]/9[ 45%]) were analyzed. Patients were followed for a median of 190 days (range: 158 days to 396 days). Preoperative ctDNA was detected in 100% (20/20) of the patients. MRD status was analyzed postoperatively on day 7 and day 30 with a positivity rate of 11% (2/18) and 17% (2/12), respectively. Of the 4 patients with known recurrences, 2 had detectable ctDNA (50%, 2/4) at 7 days after surgery, whereas all disease-free patients were ctDNA-negative (100%, 13/13) at this time point. Detection at the landmark timepoint 7 days after surgery was associated with shorter recurrence-free survival (hazard ratio [HR]: 16.87, p=0.00363). The landmark negative predictive value (NPV) and positive predictive value (PPV) were 87.5% and 100%, respectively. When integrating all timepoints, 100% (4/4) of relapse patients were ctDNA positive before relapse, with the median leading time by brPROPHET assay to radiological recurrence was 126 days, whereas all of the patients with constant ctDNA negative status were disease-free (longitudinal PPV 80%, NPV 100%). In one relapsed patient who had elevated preoperative carbohydrate antigen (CA) 19-9 and constant normal postoperative CA19-9 (<27 U/ml), ctDNA was detected prior to radiological relapse, with a lead time of 211 days. Conclusions: Patient-specific tumor-informed ctDNA-based postoperative monitoring predicts disease recurrence at earlier postoperative settings better than the clinical parameter CA19-9, which paves an alternative strategy in the individualized management of patients with resected PC.
To investigate the effects of cardiotrophin-1 (CT-1) on differentiation of induced rat bone marrow mesenchymal stem cells (BMMSCs) in vitro with 5-azacytidine (5-aza) for the purpose of elucidation of the cellular biological mechanisms.BMMSCs isolated from femur of rats were divided into four groups: untreated group as control (group A); 0.1 nmol/L CT-1 added to medium (Group B); induced with 10 micromol/L 5-aza only (Group C); induced with 10 micromol/L 5-aza combined with 0.1 nmol/L CT-1 added to medium (Group D). After 4 weeks of induced culturing, the differentiation of induced myocyte like cells were estimated, levels of cardiac troponin-T (cTnT) by immunohistochemical staining and ultrastructure of induce-cultured BMMSCs were determined and mRNA expression of alpha-actin, beta-myosin heavy chain (beta-MHC), Nkx2.5, GATA4 were analyzed by real time polymerase chain reaction (RT-PCR).After 4 weeks of induced culturing, morphological characteristics of myocyte like cells with the expression of cTnT were observed in group C and D cells. Higher level expression of GATA4, Nkx2.5, alpha- actin and beta-MHC mRNA in group D was observed by comparing with those of group C and the differentiated BMMSCs with formations of myofilaments distinctly were also existed in 5-aza combined with CT-1 treatment group.This study suggests that induced culturing of BMMSCs in the presence of 5-aza combined with CT-1 can enhance cardiomyocytic characteristics. CT-1 upregulates the expression of GATA4, Nkx2.5, alpha-actin and beta-MHC mRNA, and rapidly promotes the differentiation and maturation of cardiomyocyte-like cells differentiated from BMMSCs induced with 5-aza.
Introduction The neutrophil-percentage-to-albumin ratio (NPAR), a novel inflammatory biomarker, has been used to predict the prognosis of patients with cancer and cardiovascular disease. However, the relationship between NPAR and chronic kidney disease (CKD) remains unknown. The purpose of this study was to investigate the possible association between NPAR and CKD. Methods The cross-sectional study included participants with complete information on NPAR, serum creatinine (Scr), or urinary albumin-to-creatinine ratio (UACR) from the 2009–2018 National Health and Nutrition Examination Survey (NHANES). CKD was defined as the presence of either low estimated glomerular filtration rate (eGFR) or albuminuria. Univariate and multivariate logistic regression and restricted cubic spline regression were used to assess the linear and nonlinear associations between NPAR and renal function. Subgroup and interactive analyses were performed to explore potential interactive effects of covariates. Missing values were imputed using random forest. Results A total of 25,236 participants were enrolled in the study, of whom 4518 (17.9%) were diagnosed with CKD. After adjustment for covariates, the odds ratios (ORs) for prevalent CKD were 1.19 (95% CI = 1.07–1.31, p <0.05) for the Q2 group, 1.53 (95% CI = 1.39–1.69, p < 0.001) for the Q3 group, and 2.78 (95% CI = 2.53–3.05, p < 0.001) for the Q4 group. There was a significant interaction between age and diabetes mellitus on the association between NPAR and CKD (both p for interaction < 0.05). And there was a non-linear association between NPAR levels and CKD in the whole population ( p for non-linear < 0.001). All sensitivity analyses supported the positive association between NPAR and CKD. Conclusions NPAR was positively correlated with increased risk of CKD. The NPAR may serve as an available and cost-effective tool for identifying and intervening the individuals at risk of CKD.
Previous studies have focused on the characteristics of ordinary facial expressions in patients with depression, and have not investigated the processing characteristics of ecological micro-expressions (MEs, i.e., MEs that presented in different background expressions) in these patients. Based on this, adopting the ecological MEs recognition paradigm, this study aimed to comparatively evaluate facial ME recognition in depressed and healthy individuals. The findings of the study are as follows: (1) background expression: the accuracy (ACC) in the neutral background condition tended to be higher than that in the fear background condition, and the reaction time (RT) in the neutral background condition was significantly longer than that in other backgrounds. The type of ME and its interaction with the type of background expression could affect participants' ecological MEs recognition ACC and speed. Depression type: there was no significant difference between the ecological MEs recognition ACC of patients with depression and healthy individuals, but the patients' RT was significantly longer than that of healthy individuals; and (2) patients with depression judged happy MEs that were presented against different backgrounds as neutral and judged neutral MEs that were presented against sad backgrounds as sad. The present study suggested the following: (1) ecological MEs recognition was influenced by background expressions. The ACC of happy MEs was the highest, of neutral ME moderate and of sadness and fear the lowest. The response to the happy MEs was significantly shorter than that of identifying other MEs. It is necessary to conduct research on ecological MEs recognition; (2) the speed of patients with depression in identifying ecological MEs was slower than of healthy individuals; indicating that the patients' cognitive function was impaired; and (3) the patients with depression showed negative bias in the ecological MEs recognition task, reflecting the lack of happy ME recognition ability and the generalized identification of sad MEs in those patients.
Optical coherence elastography (OCE) can quantify the tissue elasticity by measuring the velocities of elastic wave propagation in the tissue. Due to the high sensitivity and micron-level resolution, OCE is especially suitable for biomechanical property measurements of the ocular tissues. Usually, the external excited elastic wave is visualized by optical coherence tomography (OCT). However, the imaging depth of the OCE system is limited by the OCT system and the excitation depth of external force. In this study, we proposed a method extending the OCE imaging depth with an electrically tunable lens (ETL). The method was validated by detecting the propagation of elastic waves in the corneas and retinas of porcine eyes using an acoustic radiation force-based OCE system. Firstly, an acoustic simulation was taken for the ring ultrasound transducer. Secondly, a mathematical model of the ETL was established for dynamic control of the imaging depth. Thirdly, the optical simulation of the sample arm was performed to analyze the critical optical parameters and evaluating the imaging quality of the system. Also, the optimal working depth of the OCT system was discussed. Lastly, an OCE system with a ring ultrasound transducer and an ETL was built. The experimental results on ex vivo porcine eyes showed the imaging depth of the system was 22 mm. This method can extend the depth of elasticity detection and, thus, provides a powerful tool for non-invasive, high-resolution biomechanical analysis of the ocular tissues.
'/%3e%3cuse xlink:href='%23a' transform='rotate(23.036 .093 25.536)'/%3e%3cuse xlink:href='%23a' transform='rotate(45.87 1.273 16.18)'/%3e%3cuse xlink:href='%23a' transform='rotate(69.945 .996 12.078)'/%3e%3cuse xlink:href='%23a' transform='rotate(20.66 -19.689 31.932)'/%3e%3c/svg%3e)