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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.

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.

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.

Objective Hypertension increases the prevalence of depression to a certain extent and identification and diagnosis of depression frequently pose challenges for clinicians. The study aimed to construct and validate a scoring model predicting the prevalence of depression with hypertension. Methods 6124 individuals with hypertension were utilized from the 2007 to 2020 National Health and Nutrition Examination Survey database (NHANES), including 645 subjects that were assessed to have depressive symptoms, 390 in the development group and 255 in the validation group. Univariable and multivariable analyses were applied to analyze the impact of each parameter on depression with hypertension, resulting in establishment of a predictive model. Finally, the discriminability, calibration ability, and clinical efficacy of the model were verified for both the derivation set and validation set. Results Ten variables comprised this model: age, gender, race, poverty to income ratio (PIR), smoke, sleep hours, exercise, diabetes, congestive heart failure, stroke. The area under the receiver operating characteristic curve for the derivation and validating sets was 0.790 and 0.723, respectively, which showed excellent discriminability. The model also fitted well with the actual prevalence of depression with hypertension in calibration and decision curve analysis (DCA) demonstrated that the depression model was practically useful. Conclusion This scoring model may provide an additional perspective for evaluating the underlying risk factors of depression for hypertensive individuals.

The purpose of this survey study was to comprehensively examine if various types of screen time differed between children with overweight or obesity (OWOB; ≥ 85 th BMI percentile) vs. normal weight (NW: < 85 th BMI percentile) in a largely socioeconomically disadvantaged population. 739 parent proxies of children aged 5–11 years ( M = 9.27, SD = 1.49) mostly enrolled in Medicaid (83.9%) in a United States (US) southern state responded to an online questionnaire called the Movement Behavior Questionnaire – Child (MBQ-C; open version). Eight items of the MBQ-C separately measured passive and interactive screen time on weekdays and weekend days. The survey also gathered parent-reported child weight and height, along with their sociodemographic characteristics. Compared to children with NW ( M = 294.5 ± 7.2 min/day), children with OWOB ( M = 364.3 ± 10.6 min/day) reported greater amount of total screen time ( M Diff = 69.8 min/day, 95% CI = [45.0–94.6], p < 0.001). Of the sample, 24.9% met the sedentary screen time guidelines of no more than 2 hours/day favoring children with NW ( OR = 0.59, 95% CI [0.39, 0.86], p = 0.008). The difference of screen time between weight-status groups was greatest in passive screen time, particularly on weekdays ( M Diff = 63.2 min/day, 95% CI = 47.6–78.7, p < 0.001). Demographic factors did not significantly moderate the relationship between screen time and weight status. Most of the disadvantaged children failed to meet the screen time guidelines. Children with OWOB reported higher screen time, particularly passive screen time on weekdays. These findings suggest the need for tailored interventions to not only curb overall screen time but also mitigate specific types of screen time behaviors on specific days for children with OWOB (i.e., passive screen use on weekdays).

Background The gut microbiota plays a crucial role in regulating host metabolism and producing uremic toxins in patients with end-stage renal disease (ESRD). Our objective is to advance toward a holistic understanding of the gut ecosystem and its functional capacity in such patients, which is still lacking. Results Herein, we explore the gut microbiome of 378 hemodialytic ESRD patients and 290 healthy volunteers from two independent cohorts via deep metagenomic sequencing and metagenome-assembled-genome-based characterization of their feces. Our findings reveal fundamental alterations in the ESRD microbiome, characterized by a panel of 348 differentially abundant species, including ESRD-elevated representatives of Blautia spp., Dorea spp., and Eggerthellaceae, and ESRD-depleted Prevotella and Roseburia species. Through functional annotation of the ESRD-associated species, we uncover various taxon-specific functions linked to the disease, such as antimicrobial resistance, aromatic compound degradation, and biosynthesis of small bioactive molecules. Additionally, we show that the gut microbial composition can be utilized to predict serum uremic toxin concentrations, and based on this, we identify the key toxin-contributing species. Furthermore, our investigation extended to 47 additional non-dialyzed chronic kidney disease (CKD) patients, revealing a significant correlation between the abundance of ESRD-associated microbial signatures and CKD progression. Conclusion This study delineates the taxonomic and functional landscapes and biomarkers of the ESRD microbiome. Understanding the role of gut microbiota in ESRD could open new avenues for therapeutic interventions and personalized treatment approaches in patients with this condition.

The purpose of this pilot study was to test an adapted childhood obesity prevention intervention called Preventing Obesity Using Digital-Assisted Movement and Eating ( ProudMe ) in under-resourced schools. Six schools were cluster-randomized to ProudMe ( n  = 33; at three schools) or waitlist control ( n  = 46; at three schools) conditions. ProudMe aimed to improve participants’ health behaviors and weight status through interventions in the school cafeteria (i.e., ProudMe Cafeteria), physical education (PE) (i.e., ProudMe PE), and through artificial-intelligence- (AI-) assisted behavioral counseling (i.e., ProudMe Tech), and staff professional development (i.e., ProudMe PD). Two implementation outcomes including penetration and fidelity were captured through mixed methods. We drew upon the Consolidated Framework for Implementation Research (CFIR) to identify facilitators and barriers underlying implementation. The intervention only resulted in highly positive implementation outcomes in the cafeterias, which subsequently resulted in improved cafeteria scores. Implementation outcomes were less desirable in ProudMe PE with moderate penetration and fidelity. ProudMe PD was well attended but ProudMe Tech was under-utilized. The pilot intervention as a whole did not show significant effects on student-level outcomes ( p  > 0.05). Multiple facilitators and barriers across CFIR domains emerged as influential factors for the pilot intervention’s implementation and preliminary effectiveness. This study generated mixed evidence concerning the ProudMe intervention. The lessons learned inform future intervention refinement.

Background Hyperkalemia (serum potassium > 5.0 mmol/L) is a common and clinically significant complication in patients with chronic kidney disease (CKD), particularly among those treated with renin-angiotensin-aldosterone system inhibitors (RAASi). Although guideline-directed medical therapy recommends proactive hyperkalemia management to enable continued RAASi use, real-world practice remains suboptimal. Key challenges include inadequate potassium monitoring after RAASi initiation or dose escalation, unnecessary RAASi dose reduction or discontinuation following hyperkalemia episodes, and poor long-term treatment adherence. Moreover, evidence regarding the cardio-renal benefits of RAASi optimization supported by structured hyperkalemia management in Chinese CKD populations is limited. This study aims to bridge the gap between Kidney Disease: Improving Global Outcomes (KDIGO) and Chinese CKD guideline recommendations and routine clinical practice through a nationwide quality improvement program (QIP). Methods This prospective, multicenter, single-arm study will enroll approximately 1,000 adult Chinese patients with non-dialysis CKD and hyperkalemia across 50 sites. The QIP includes comprehensive and reinforcement training for healthcare professionals (HCPs) based on the KDIGO 2024 guidelines, supported by regular quality audits and feedback. Patient-directed interventions comprise structured education delivered by HCPs and self-learning modules. Participants will receive standardized hyperkalemia management over 96 weeks, including protocolized serum potassium monitoring (every 3 months or monthly for high-risk patients), RAASi dose optimization, and long-term potassium control. The primary endpoint is the proportion of patients achieving RAASi optimization with normokalemia (3.5-5.0 mmol/L) at 48 weeks. Secondary endpoints include sustained potassium control, RAASi optimization over time, medication adherence, hyperkalemia recurrence and severity, cardiorenal outcomes, and safety endpoints. Discussion As the first nationwide QIP focusing on hyperkalemia management in CKD patients in China, this study is expected to provide real-world evidence on the effectiveness of standardized hyperkalemia care in facilitating sustained RAASi use. By aligning clinical practice with guideline recommendations, the program has the potential to improve long-term cardio-renal outcomes and inform future CKD care strategies. Trial registration ClinicalTrials.gov, NCT06884267; registered March 13, 2025.

Sudden cardiac death is one of the primary causes of mortality in chronic hemodialysis (HD) patients. Prolonged QTc interval is associated with increased rate of sudden cardiac death. The aim of this article is to assess the abnormalities found in electrocardiograms (ECGs), and to explore factors that can influence the QTc interval. A total of 141 conventional HD patients were enrolled in this study. ECG tests were conducted on each patient before a single dialysis session and 15 minutes before the end of dialysis session (at peak stress). Echocardiography tests were conducted before dialysis session began. Blood samples were drawn by phlebotomy immediately before and after the dialysis session. Before dialysis, 93.62% of the patients were in sinus rhythm, and approximately 65% of the patients showed a prolonged QTc interval (i.e., a QTc interval above 440 ms in males and above 460ms in females). A comparison of ECG parameters before dialysis and at peak stress showed increases in heart rate (77.45±11.92 vs. 80.38±14.65 bpm, p = 0.001) and QTc interval (460.05±24.53 ms vs. 470.93±24.92 ms, p<0.001). After dividing patients into two groups according to the QTc interval, lower pre-dialysis serum concentrations of potassium (K+), calcium (Ca2+), phosphorus, calcium* phosphorus (Ca*P), and higher concentrations of plasma brain natriuretic peptide (BNP) were found in the group with prolonged QTc intervals. Patients in this group also had a larger left atrial diameter (LAD) and a thicker interventricular septum, and they tended to be older than patients in the other group. Then patients were divided into two groups according to ΔQTc (ΔQTc = QTc peak-stress- QTc pre-HD). When analyzing the patients whose QTc intervals were longer at peak stress than before HD, we found that they had higher concentrations of Ca2+ and P5+ and lower concentrations of K+, ferritin, UA, and BNP. They were also more likely to be female. In addition, more cardiac construction abnormalities were found in this group. In multiple regression analyses, serum Ca2+ concentration before HD and LAD were independent variables of QTc interval prolongation. UA, ferritin, and interventricular septum were independent variables of ΔQTc. Prolonged QT interval is very common in HD patients and is associated with several risk factors. An appropriate concentration of dialysate electrolytes should be chosen depending on patients' clinical conditions.

Traditional laboratory teaching of pathogenic cocci faces challenges in biosafety and standardization across medical specialties. While virtual simulation shows promise, evidence from large-scale, multidisciplinary studies remains limited. The study aims to evaluate the effectiveness of integrating virtual simulation with traditional laboratory practice in enhancing medical microbiology education, focusing on the identification of biosafety level 2 pathogenic cocci. The study assessed improvements in student performance, theoretical understanding, laboratory safety, and overall satisfaction, while achieving standardization and cost reduction across multiple medical specialties. This randomized controlled trial involved 1282 medical students from 9 specialties. The experimental group (n=653) received virtual simulation training-featuring interactivity and intelligent feedback-prior to traditional laboratory practice, while the control group (n=629) did not receive such training. Our virtual system focused on biosafety level 2 pathogenic cocci identification with dynamic specimen generation. The experimental group showed significantly improved performance across specialties (P<.05 for each specialty), particularly in clinical medicine, in which the experimental group score was 89.88 (SD 13.09) and the control group score was 68.34 (SD 17.23; P<.001). The students reported that virtual simulation enhanced their theoretical understanding (1268/1282, 98.9%) and laboratory safety (1164/1282, 90.8%) while helping them achieve standardization (790/1282, 61.6%,) and cost reduction (957/1282, 74.6%). Overall student satisfaction reached 97.2% (1246/1282), with distinct learning patterns observed across specialties. The test scores were significantly higher in the experimental group, with a mean of 80.82 (SD 17.10), compared to the control group, with a mean of 67.45 (SD 16.81). This large-scale study demonstrates that integrating virtual simulation with traditional methods effectively enhances medical microbiology education, providing a standardized, safe, and cost-effective approach for teaching high-risk pathogenic experiments.