RNA three-dimensional structure drives the sequence organization of potato spindle tuber viroid quasispecies.

RNA viruses and viroids exist and evolve as quasispecies due to error-prone replication. Quasispecies consist of a few dominant master sequences alongside numerous variants that contribute to genetic diversity. Upon environmental changes, certain variants within quasispecies have the potential to become the dominant sequences, leading to the emergence of novel infectious strains. However, the emergence of new infectious variants remains unpredictable. Using mutant pools prepared by saturation mutagenesis of selected stem and loop regions, our study of potato spindle tuber viroid (PSTVd) demonstrates that mutants forming local three-dimensional (3D) structures similar to the wild type (WT) are more likely to accumulate in PSTVd quasispecies. The selection mechanisms underlying this biased accumulation are likely associated with cell-to-cell movement and long-distance trafficking. Moreover, certain trafficking-defective PSTVd mutants can be spread by functional sister genomes in the quasispecies. Our study reveals that the RNA 3D structure of stems and loops constrains the evolution of viroid quasispecies. Mutants with a structure similar to WT have a higher likelihood of being maintained within the quasispecies and can potentially give rise to novel infectious variants. These findings emphasize the potential of targeting RNA 3D structure as a more robust approach to defend against viroid infections.

Global left ventricular myocardial work: A novel method to assess left ventricular myocardial function and predict major adverse cardiovascular events in maintenance hemodialysis patients.

BACKGROUND: The application value of myocardial work (MW) in evaluating myocardial function and predicting major adverse cardiovascular events (MACE) in maintenance hemodialysis (MHD) patients has not been fully explored. PURPOSE: Comparing noninvasive MW parameters between MHD patients and healthy controls, and further determining its value in predicting MACE in MHD patients. METHODS: A prospective single-institution study included 92 MHD patients without prior cardiovascular disease and 40 age- and sex-matched healthy controls. Conventional echocardiographic data, global longitudinal strain (GLS), and MW parameters (global work index [GWI], global constructive work [GCW], global work efficiency [GWE], global wasted work [GWW]) were derived and compared between MHD and the control. Logistic regression was used to determine the predictive value of these parameters for MACE. The receiver operating characteristic curve was utilized to compare the predictive differences of MACE between GWE and GLS. RESULTS: Compared with healthy individuals, MHD patients had significantly reduced GWE, GLS and elevated LVMI, GWW (all p < 0.001), while there was no significant difference in left ventricular ejection fraction. Twenty eight (30%) MHD patients experienced MACE. Two nested models adding GWE and GLS, respectively, showed that age (p < 0.005), GWE (p = 0.034), and GLS (p = 0.014) were independent predictors of MACE. The AUC derived from GWE for predicting MACE was significantly higher than that derived from GLS (0.836 vs. 0.743, p = 0.039). CONCLUSIONS: Myocardial work is a novel tool for assessing left ventricular myocardial performance in MHD patients. GWE is an independent predictor of MACE.

Unveiling the Role of SlRNC1 in Chloroplast Development and Global Gene Regulation in Tomato Plants.

RNC1, a plant-specific gene, is known for its involvement in splicing group II introns within maize chloroplast. However, its role in chloroplast development and global gene expression remains poorly understood. This study aimed to investigate the role of RNC1 in chloroplast development and identify the genes that mediate its function in the development of entire tomato plants. Consistent with findings in maize, RNC1 silencing induced dwarfism and leaf whitening in tomato plants. Subcellular localization analysis revealed that the RNC1 protein is localized to both the nucleus and cytoplasm, including the stress granule and chloroplasts. Electron microscopic examination of tomato leaf transverse sections exposed significant disruptions in the spatial arrangement of the thylakoid network upon RNC1 silencing, crucial for efficient light energy capture and conversion into chemical energy. Transcriptome analysis suggested that RNC1 silencing potentially impacts tomato plant development through genes associated with all three categories (biological processes, cellular components, and molecular functions). Overall, our findings contribute to a better understanding of the critical role of RNC1 in chloroplast development and its significance in plant physiology.

Relationship between Soluble ST2 and Left Ventricular Geometry in Maintenance Hemodialysis Patients.

INTRODUCTION: Left ventricular hypertrophy (LVH) is a highly prevalent presentation of cardiac structural abnormality and a strong predictor of adverse outcomes in maintenance hemodialysis (MHD) patients. Different left ventricular geometry may provide additional clinical information. Soluble ST2 is a novel cardiac prognostic biomarker in MHD patients and is closely related to cardiac remodeling. OBJECTIVE: This study sought to evaluate the association of sST2 and left ventricular structure in a cohort of MHD patients. METHODS: Two hundred eighty-seven patients were enrolled. Left ventricular structure was assessed via transthoracic echocardiography. Left ventricular geometric patterns were defined according to left ventricular mass index and relative wall thickness (RWT). Serum sST2 levels were measured. RESULTS: Prevalence of LVH was 44.9% in the study population. In univariate analysis, sST2 levels were correlated with interventricular septal wall thickness, posterior wall thickness, and RWT. After multivariate adjustment, sST2 was independently correlated with only RWT (p = 0.028). Comparing sST2 concentrations across different LV geometric patterns, we found sST2 levels were significantly increased in patients with concentric cardiac remodeling and concentric LVH. CONCLUSIONS: The present study found that sST2 were significantly increased in patients with concentric remodeling and concentric LVH. ST2/interleukin (IL)-33 signaling might participate in the process of cardiac remodeling via its pro-fibrotic action. Future studies on the mechanism of ST2/IL-33 pathway are needed.

Neutrophil to Lymphocyte Ratio as a Predictor of Long-Term Outcome in Peritoneal Dialysis Patients: A 5-Year Cohort Study.

INTRODUCTION: The mortality of peritoneal dialysis (PD) patients remains high. The neutrophil to lymphocyte ratio (NLR), as an indicator of systemic inflammation, has been considered to be a predictor of cardiovascular and all-cause mortality in hemodialysis patients. The present study aims to investigate the relationship between NLR and long-term outcome in PD patients. MATERIALS AND METHODS: The study included patients who initiated PD for at least 3 months between January 1, 2013, and December 31, 2015. All the patients were followed up until death, cessation of PD, or to the end of the study (June 31, 2018). NLR was calculated as the ratio of neutrophils to lymphocytes. RESULTS: A total of 140 patients were included in this study. The median NLR reported was 2.87. Patients with lower NLR showed a higher survival rate than patients with higher NLR (log rank 6.886, p = 0.009). Furthermore, patients with higher NLR had a significantly higher cardiovascular mortality (log rank 5.221, p = 0.022). Multivariate Cox proportional hazards model showed that older age (HR 1.054, 95% CI 1.017-1.092, p = 0.004), higher Ca × P (HR 1.689, 95% CI 1.131-2.523, p = 0.010), and higher NLR (HR 2.603, 95% CI 1.037-6.535, p = 0.042) were independent predictors of increased all-cause mortality. NLR was also independently associated with cardiovascular mortality (HR 2.886, 95% CI 1.005-8.283, p = 0.039). Higher NLR (HR 2.667, 95% CI 1.333-5.337, p = 0.006), older age (HR 1.028, 95% CI 1.005-1.052, p = 0.016), and history of cardiovascular disease (HR 1.426, 95% CI 1.195-3.927, p = 0.031) were significantly independently associated with poor peritonitis-free survival in this study. CONCLUSIONS: NLR could be a strong predictor of long-term outcome in PD patients.

Efficacy of Early Goal-Directed Renal Replacement Therapy for the Treatment of Acute Kidney Injury After Heart Transplantation: A Single-Center 10-Year Experience.

OBJECTIVE: Acute kidney injury (AKI) after heart transplantation is a common and serious complication. The present study aimed to evaluate the efficacy of early goal-directed renal replacement therapy (GDRRT) for the treatment of AKI after heart transplantation. DESIGN: Retrospective, observational study. SETTING: Grade A tertiary hospital that performs more than 4,000 cardiac surgery procedures per year. PARTICIPANTS: Patients who underwent heart transplantation with postoperative AKI and received renal replacement therapy from January 2008 to June 2018. INTERVENTIONS: Patients were divided into a late GDRRT group (LGDRRT) (January 2008-September 2012) or an early GDRRT group (EGDRRT) (October 2012-June 2018). RESULTS: The LGDRRT group comprised 30 patients, and the EGDRRT group comprised 46 patients. Duration between surgery to renal replacement therapy (RRT) initiation in the EGDRRT group was significantly shorter than in the LGDRRT group (1 [1-3] d v 2 [2-3] d; p = 0.020). The in-hospital mortality in the EGDRRT group was significantly lower than that of the LGDRRT group (39.1% v 63.3%; p = 0.039). After multivariate adjustment for confounding factors, the hazard ratio for death in the LGDRRT group relative to the EGDRRT group was 2.028 (95% confidence interval 1.072-3.655; p = 0.048). Length of intensive care unit and hospital stays in the EGDRRT group was significantly shorter than that of the LGDRRT group (26 ± 18 d v 38 ± 20 d; p = 0.008 and 38 ± 33 d v 64 ± 45 d; p = 0.005, respectively). The complete renal recovery rate was much greater in the EGDRRT group than that of the LGDRRT group (50.0% v 20.0%; p < 0.001). Serum creatinine at discharge was significantly less in the EGDRRT group than that of the LGDRRT group (134.8 ± 97.3 µmol/L v 220.7 ± 113.6 µmol/L; p < 0.001). Cost of RRT in the EGDRRT group was significantly less than that of the LGDRRT group (0.54 ± 0.10 v. 0.63 ± 0.11 ten thousand USD; p < 0.001). CONCLUSIONS: For heart transplantation recipients with AKI, EGDRRT can reduce the in-hospital mortality and the length of intensive care unit and hospital stays, improve the complete renal recovery rate, and reduce the cost of RRT.

Association of trimethylamine N-Oxide with cardiovascular and all-cause mortality in hemodialysis patients.

BACKGROUND: Trimethylamine-N-Oxide (TMAO) is a proatherogenic and prothrombotic metabolite. Our study examined the association of plasma TMAO level with cardiovascular and all-cause mortality in hemodialysis (HD) patients. METHODS: Patients who were at least 18 years-old and received HD for at least 6 months were enrolled within 6 months. Patients with coronary heart disease, congestive heart failure, arrhythmia, or stroke within 3 months before study onset were excluded. The primary endpoints were cardiovascular and all-cause death, and the secondary endpoint was cerebrovascular death. RESULTS: We recruited 252 patients and divided them into a high-TMAO group (>4.73 µg/mL) and a low-TMAO group (≤4.73 µg/mL). The median follow-up time was 73.4 months (interquartile range: 42.9, 108). A total of 123 patients died, 39 from cardiovascular disease, 19 from cerebrovascular disease, and 65 from other causes. Kaplan-Meier analysis indicated that the high-TMAO group had a greater incidence of cardiovascular death (Log-Rank: p = 0.006) and all-cause death (Log-Rank: p < 0.001). Cox regression analysis showed that high TMAO level was significantly associated with cardiovascular and all-cause mortality. After adjustment for confounding, this association remained significant for cardiovascular mortality (TMAO as a continuous variable: HR: 1.18, 95%CI: 1.07, 1.294, p < 0.001; TMAO as a dichotomous variable: HR: 3.44, 95%CI: 1.68, 7.08, p < 0.001) and all-cause mortality (TMAO as a continuous variable: HR: 1.14, 95%CI: 1.08, 1.21, p < 0.001; TMAO as a dichotomous variable: HR: 2.54, 95%CI: 1.71, 3.76, p < 0.001). CONCLUSIONS: High plasma TMAO level is significantly and independently associated with cardiovascular and all-cause mortality in HD patients.

Increased Soluble Suppression of Tumorigenicity 2 Level Predicts All-Cause and Cardiovascular Mortality in Maintenance Hemodialysis Patients: A Prospective Cohort Study.

BACKGROUND: Soluble suppression of tumorigenicity 2 (sST2) is a novel cardiovascular biomarker. This study aimed to evaluate the prognostic value of sST2 in hemodialysis patients. METHODS: Four hundred and fourteen maintenance hemodialysis (MHD) patients were enrolled and followed up prospectively. Serum sST2 levels were measured. The endpoint was all-cause and cardiovascular mortality. RESULTS: During a median follow-up of 22.3 months, 58 patients died, including 31 cardiovascular deaths. sST2 was an independent predictor of all-cause mortality with a relative risk (RR) of 1.31 (95% CI 1.000-1.717, p = 0.050) and cardiovascular mortality with an RR of 2.10 (95% CI 1.507-2.927, p < 0.001). The prognostic value of sST2 was additive to N-terminal pro-B-type natriuretic peptide (NT-proBNP) and high-sensitivity cardiac troponin T (hs-cTnT), as the combined use of sST2 and NT-proBNP or hs-cTnT better identified higher-risk patients. CONCLUSION: Elevated sST2 is an independent predictor of all-cause and cardiovascular mortality in MHD patients. A combined use of sST2 and NT-proBNP or hs-cTnT helps identify individuals of higher risk.

The Prognostic Value of Red Blood Cell Distribution Width in Patients on Maintenance Hemodialysis.

AIMS: To examine the association between red blood cell distribution width (RDW) and mortality in hemodialysis (HD) patients. METHODS: Three hundred fifty six patients on HD for >3 months were enrolled and followed for 2 years. Patients were divided into 2 groups according to the median RDW value. Patient survival and risk factors for mortality were investigated. RESULTS: The 2-year survival rate was significantly lower in the high-RDW group (>14.9%; log-rank = 10.00, p = 0.0016). RDW (hazard ratio (HR) 1.34, 95% CI 1.04-1.71, p = 0.021), hemoglobin (HR 0.98, 95% CI 0.96-1.00, p = 0.023) and albumin (HR 0.90, 95% CI 0.82-0.99, p = 0.026) were independent predictors of mortality. Receiver operating characteristic curves of RDW to predict 2-year mortality had an area under the curve of 0.6487 (95% CI 0.5714-0.7260). CONCLUSIONS: Abnormal RDW was common in HD patients and significantly related with poor outcomes in these patients.

The conversion of PN-junction influencing the piezoelectric output of a CuO/ZnO nanoarray nanogenerator and its application as a room-temperature self-powered active H2S sensor.

Room-temperature, high H2S sensing has been realized from a CuO/ZnO nanoarray self-powered, active gas sensor. The piezoelectric output of CuO/ZnO nanoarrays can act not only as the power source of the device, but also as the H2S sensing signal at room temperature. Upon exposure to 800 ppm H2S at room temperature, the piezoelectric output of the device greatly decreased from 0.738 V (in air) to 0.101 V. The sensitivity increased to 629.8, much higher than bare ZnO nanoarrays. As the device was exposed to H2S, a CuO/ZnO PN-junction was converted into a CuS/ZnO Ohmic contact, which greatly increased the electron density in the nanowire and enhanced the screen effect on the piezoelectric output. Our results can stimulate a research trend on designing new composite piezoelectric material for high-performance self-powered active gas sensors.

PVDF-PZT nanocomposite film based self-charging power cell.

A novel PVDF-PZT nanocomposite film has been proposed and used as a piezoseparator in self-charging power cells (SCPCs). The structure, composed of poly(vinylidene fluoride) (PVDF) and lead zirconate titanate (PZT), provides a high piezoelectric output, because PZT in this nanocomposite film can improve the piezopotential compared to the pure PVDF film. The SCPC based on this nanocomposite film can be efficiently charged up by the mechanical deformation in the absence of an external power source. The charge capacity of the PVDF-PZT nanocomposite film based SCPC in 240 s is ∼0.010 µA h, higher than that of a pure PVDF film based SCPC (∼0.004 µA h). This is the first demonstration of using PVDF-PZT nanocomposite film as a piezoseparator for SCPC, and is an important step for the practical applications of SCPC for harvesting and storing mechanical energy.

Pt/ZnO nanoarray nanogenerator as self-powered active gas sensor with linear ethanol sensing at room temperature.

A self-powered gas sensor that can actively detect ethanol at room temperature has been realized from a Pt/ZnO nanoarray nanogenerator. Pt nanoparticles are uniformly distributed on the whole surface of ZnO nanowires. The piezoelectric output of Pt/ZnO nanoarrays can act not only as a power source, but also as a response signal to ethanol at room temperature. Upon exposure to dry air and 1500 ppm ethanol at room temperature, the piezoelectric output of the device under the same compressive strain is 0.672 and 0.419 V, respectively. Moreover, a linear dependence of the sensitivity on the ethanol concentration is observed. Such a linear ethanol sensing at room temperature can be attributed to the atmosphere-dependent variety of the screen effect on the piezoelectric output of ZnO nanowires, the catalytic properties of Pt nanoparticles, and the Schottky barriers at Pt/ZnO interfaces. The present results can stimulate research in the direction of designing new material systems for self-powered room-temperature gas sensing.

Synthesis of CdS nanorod arrays and their applications in flexible piezo-driven active H2S sensors.

A flexible piezo-driven active H2S sensor has been fabricated from CdS nanorod arrays. By coupling the piezoelectric and gas sensing properties of CdS nanorods, the piezoelectric output generated by CdS nanorod arrays acts not only as a power source, but also as a response signal to H2S. Under externally applied compressive force, the piezoelectric output of CdS nanorod arrays is very sensitive to H2S. Upon exposure to 600 ppm H2S, the piezoelectric output of the device decreased from 0.32 V (in air) to 0.12 V. Such a flexible device can be driven by the tiny mechanical energy in our living environment, such as human finger pinching. Our research can stimulate a research trend on designing new material systems and device structures for high-performance piezo-driven active gas sensors.

Clinical status of Sagliker syndrome: a case report and literature review.

In a 53-year-old woman, Sagliker syndrome developed during 22 years of treatment with intermittent hemodialysis as a result of severe secondary hyperparathyroidism (SHPT) complicating end-stage renal disease. She failed medical managements and lost her renal graft just after the kidney transplantation due to acute rejection. Although surgical parathyroidectomy was effective, the parathyroid hormone level became extremely high again due to recurrent hyperparathyroidism. It is possible that such patient could survive long-term with dialysis, but prevention of severe SHPT is the most important.

Viroid Replication, Movement, and the Host Factors Involved.

Viroids represent distinctive infectious agents composed solely of short, single-stranded, circular RNA molecules. In contrast to viruses, viroids do not encode for proteins and lack a protective coat protein. Despite their apparent simplicity, viroids have the capacity to induce diseases in plants. Currently, extensive research is being conducted on the replication cycle of viroids within both the Pospiviroidae and Avsunviroidae families, shedding light on the intricacies of the associated host factors. Utilizing the potato spindle tuber viroid as a model, investigations into the RNA structural motifs involved in viroid trafficking between different cell types have been thorough. Nevertheless, our understanding of the host factors responsible for the intra- and inter-cellular movement of viroids remains highly incomplete. This review consolidates our current knowledge of viroid replication and movement within both families, emphasizing the structural basis required and the identified host factors involved. Additionally, we explore potential host factors that may mediate the intra- and inter-cellular movement of viroids, addressing gaps in our understanding. Moreover, the potential application of viroids and the emergence of novel viroid-like cellular parasites are also discussed.

Preliminary Effectiveness of a One-Week Summer Day Camp for Improving Children's Health Behaviors and Psychosocial Well-Being Outcomes.

PURPOSE: Summer day camp offers children opportunities to grow knowledge and skills, be physically active, and have fun. Compared to healthy children, at-risk children (i.e., overweight, or with obesity and chronic health conditions) typically display less optimal health behaviors and psychosocial well-being, especially during summer months. This study examined the preliminary effectiveness of an American-Diabetes-Association-sponsored summer day camp at improving children's health behaviors (i.e., physical activity, screen time, diet, sleep) and psychosocial well-being outcomes (i.e., quality of life [QoL], enjoyment, weight-related self-efficacy). METHOD: The sample consisted of 39 participants, including 19 boys and 20 girls, with majority being overweight (n = 4 or 10%) or with obesity (n = 26 or 67%), who attended the day camp for one week. RESULTS: Significant improvements were observed in screen time, quality of life, and physical function. The results further showed significant time by gender interaction effect for overall QoL (p < 0.05, ηp2 = 0.15), physical health (a dimension of QoL; p < 0.05, ηp2 = 0.18), and significant time by household income for the psychosocial health (another dimension of QoL), favoring boys and those from higher income families. DISCUSSION: The findings indicate a positive preliminary effectiveness of the summer camp at reducing children's screen time and improving their QoL, especially in boys and those from higher-income families. Future research should focus on health disparities and expansion of this camp for the potential of longer-term and more robust effects related to wellness, nutrition literacy, physical activity promotion, and obesity prevention.

Mitochondrial Dysfunction and Ion Imbalance in a Rat Model of Hemodialysis-Induced Myocardial Stunning.

Background/Objectives: Hemodialysis-induced myocardial stunning (HIMS) is a frequent complication in patients undergoing maintenance hemodialysis, characterized by transient left ventricular dysfunction due to ischemic episodes. Mitochondrial dysfunction and fluctuations in key ions such as potassium (K+) and calcium (Ca2+) are implicated in the pathogenesis of HIMS. This study aims to investigate the role of mitochondrial dysfunction and the protective potential of mitochondrial ATP-sensitive potassium channels (mitoKATP) in mitigating HIMS. Methods: A 5/6 nephrectomy rat model was established to mimic chronic kidney disease and the subsequent HIMS. The effects of mitoKATP channel modulators were evaluated by administering diazoxide (DZX), a mitoKATP opener, and 5-hydroxydecanoate (5-HD), a mitoKATP blocker, before hemodialysis. Mitochondrial function was assessed by measuring membrane potential, ATP synthase activity, and intramitochondrial Ca2+ levels. Myocardial function was evaluated using speckle tracking echocardiography. Results: Rats undergoing hemodialysis exhibited significant reductions in left ventricular strain and synchrony. DZX administration significantly improved mitochondrial function and reduced myocardial strain compared to controls. Conversely, 5-HD worsened mitochondrial swelling and disrupted myocardial function. Higher K+ and Ca2+ concentrations in the dialysate were associated with improved mitochondrial energy metabolism and myocardial strain. Conclusions: Mitochondrial dysfunction and ion imbalances during hemodialysis are key contributors to HIMS. The activation of mitoKATP channels provides mitochondrial protection and may serve as a potential therapeutic strategy to mitigate HIMS.

Surface free-carrier screening effect on the output of a ZnO nanowire nanogenerator and its potential as a self-powered active gas sensor.

The output of a piezoelectric nanogenerator (NG) fabricated using ZnO nanowire arrays is largely influenced by the density of the surface charge carriers at the nanowire surfaces. Adsorption of gas molecules could modify the surface carrier density through a screening effect, thus, the output of the NG is sensitive to the gas concentration. Based on such a mechanism, we first studied the responses of an unpackaged NG to oxygen, H2S and water vapor, and demonstrated its sensitivity to H2S to a level as low as 100 ppm. Therefore, the piezoelectric signal generated by a ZnO NWs NG can act not only as a power source, but also as a response signal to the gas, demonstrating a possible approach as a self-powered active gas sensor.

The Secondary Structure of Potato Spindle Tuber Viroid Determines Its Infectivity in Nicotiana benthamiana.

The function of RNAs is determined by their structure. However, studying the relationship between RNA structure and function often requires altering RNA sequences to modify the structures, which leads to the neglect of the importance of RNA sequences themselves. In our research, we utilized potato spindle tuber viroid (PSTVd), a circular-form non-coding infectious RNA, as a model with which to investigate the role of a specific rod-like structure in RNA function. By generating linear RNA transcripts with different start sites, we established 12 PSTVd forms with different secondary structures while maintaining the same sequence. The RNA secondary structures were predicted using the mfold tool and validated through native PAGE gel electrophoresis after in vitro RNA folding. Analysis using plant infection assays revealed that the formation of a correct rod-like structure is crucial for the successful infection of PSTVd. Interestingly, the inability of PSTVd forms with non-rod-like structures to infect plants could be partially compensated by increasing the amount of linear viroid RNA transcripts, suggesting the existence of additional RNA secondary structures, such as the correct rod-like structure, alongside the dominant structure in the RNA inoculum of these forms. Our study demonstrates the critical role of RNA secondary structures in determining the function of infectious RNAs.