Exploring work readiness: A qualitative descriptive study of self-perceptions among new graduate nurses.

Background: Reduced work readiness is associated with elevated turnover rates, necessitating efforts to enhance the positive work readiness of newly graduated nurses to alleviate the shortage in the nursing workforce. Research into the work readiness of recent nursing graduates in China is still in its infancy. Most studies employ quantitative research methods, and further exploration of the self-perception of work readiness among new nurses in China is required. Objectives: This study aimed to investigate genuine experiences and self-perceptions of work readiness among new graduate nurses. Design: A qualitative descriptive study. Methods: Sixteen new nurses from a provincial tertiary hospital in China were included in this study, which adhered to the consolidated criteria for reporting qualitative research (COREQ) checklist for reporting. The data collection process involved conducting semi-structured interviews from September to October 2021. Inductive content analysis was employed to analyze the interview data. Results: The study identified four themes encompassing new nurses' real-life experiences and self-perceptions of work readiness: psychological stress, emotional conflict, empathy fatigue, and ethical dilemmas. Psychological stress comprised three subthemes: knowledge and skill deficits, communication barriers, and fear. Empathy fatigue was primarily characterized by psychological and physical symptoms. Ethical dilemmas involved conflicts over differences in values and between clinical reality and standardized nursing practice. Conclusion: Drawing from the self-perceptions of work readiness among new nurses found in this study, nursing administrators and educators must enhance the existing transition support program for new nurses. Additionally, the establishment of individualized training programs is recommended to further improve the work readiness of new nurses.

The ketogenic diet does not improve cardiac function and blunts glucose oxidation in ischemic heart failure.

AIMS: Cardiac energy metabolism is perturbed in ischemic heart failure and is characterized by a shift from mitochondrial oxidative metabolism to glycolysis. Notably, the failing heart relies more on ketones for energy than a healthy heart, an adaptive mechanism that improves the energy-starved status of the failing heart. However, whether this can be implemented therapeutically remains unknown. Therefore, our aim was to determine if increasing ketone delivery to the heart via a ketogenic diet can improve the outcomes of heart failure. METHODS: C57BL/6J male mice underwent either a sham surgery or permanent left anterior descending (LAD) coronary artery ligation surgery to induce heart failure. After 2 weeks, mice were then treated with either a control diet or a ketogenic diet for 3 weeks. Transthoracic echocardiography was then carried out to assess in vivo cardiac function and structure. Finally, isolated working hearts from these mice were perfused with appropriately 3H or 14C labelled glucose (5 mM), palmitate (0.8 mM), and ß-hydroxybutyrate (0.6 mM) to assess mitochondrial oxidative metabolism and glycolysis. RESULTS: Mice with heart failure exhibited a 56% drop in ejection fraction which was not improved with a ketogenic diet feeding. Interestingly, mice fed a ketogenic diet had marked decreases in cardiac glucose oxidation rates. Despite increasing blood ketone levels, cardiac ketone oxidation rates did not increase, probably due to a decreased expression of key ketone oxidation enzymes. Furthermore, in mice on the ketogenic diet no increase in overall cardiac energy production was observed, and instead there was a shift to an increased reliance on fatty acid oxidation as a source of cardiac energy production. This resulted in a decrease in cardiac efficiency in heart failure mice fed a ketogenic diet. CONCLUSIONS: We conclude that the ketogenic diet does not improve heart function in failing hearts, due to ketogenic diet-induced excessive fatty acid oxidation in the ischemic heart and a decrease in insulin-stimulated glucose oxidation.

Investigation of the Inhibitory Effects of Illicium verum Essential Oil Nanoemulsion on Fusarium proliferatum via Combined Transcriptomics and Metabolomics Analysis.

Fusarium proliferatum is the main pathogen that causes Panax notoginseng root rot. The shortcomings of strong volatility and poor water solubility of Illicium verum essential oil (EO) limit its utilization. In this study, we prepared traditional emulsion (BDT) and nanoemulsion (Bneo) of I. verum EO by ultrasonic method with Tween-80 and absolute ethanol as solvents. The chemical components of EO, BDT, and Bneo were identified by gas chromatography-mass spectrometry (GC-MS) and the antifungal activity and mechanism were compared. The results show that Bneo has good stability and its particle size is 34.86 nm. The contents of (-) -anethole and estragole in Bneo were significantly higher than those in BDT. The antifungal activity against F. proliferatum was 5.8-fold higher than BDT. In the presence of I. verum EO, the occurrence of P. notoginseng root rot was significantly reduced. By combining transcriptome and metabolomics analysis, I. verum EO was found to be involved in the mutual transformation of pentose and glucuronic acid, galactose metabolism, streptomycin biosynthesis, carbon metabolism, and other metabolic pathways of F. proliferatum, and it interfered with the normal growth of F. proliferatum to exert antifungal effects. This study provide a theoretical basis for expanding the practical application of Bneo.

AAV-mediated Gene Cocktails Enhance Supporting Cell Reprogramming and Hair Cell Regeneration.

Mammalian cochlear hair cells (HCs) are essential for hearing, and damage to HCs results in severe hearing impairment. Damaged HCs can be regenerated by neighboring supporting cells (SCs), thus the functional regeneration of HCs is the main goal for the restoration of auditory function in vivo. Here, cochlear SC trans-differentiation into outer and inner HC by the induced expression of the key transcription factors Atoh1 and its co-regulators Gfi1, Pou4f3, and Six1 (GPAS), which are necessary for SCs that are destined for HC development and maturation via the AAV-ie targeting the inner ear stem cells are successfully achieved. Single-cell nuclear sequencing and lineaging tracing results showed that the majority of new Atoh1-derived HCs are in a state of initiating differentiation, while GP (Gfi1, Pou4f3) and GPS (Gfi1, Pou4f3, and Six1) enhanced the Atoh1-induced new HCs into inner and outer HCs. Moreover, the patch-clamp analysis indicated that newborn inner HCs induced by GPAS forced expression have similar electrophysiological characteristics to those of native inner HCs. Also, GPAS can induce HC regeneration in the HC-damaged mice model. In summary, the study demonstrates that AAV-mediated co-regulation of multiple genes, such as GPAS, is an effective means to achieve functional HC regeneration in the mouse cochlea.

Microbiome features in bronchoalveolar lavage fluid of patients with idiopathic inflammatory myopathy-related interstitial lung disease.

Background: Interstitial lung disease (ILD) is a common complication of idiopathic inflammatory myopathy (IIM), which is one of the connective tissue diseases (CTD). It can lead to poor prognosis and increased mortality. However, the distribution and role of the lower respiratory tract (LRT) microbiome in patients with IIM-ILD remains unclear. This study aimed to investigate the microbial diversity and community differences in bronchoalveolar lavage fluid (BALF) in patients with IIM-ILD. Methods: From 28 June 2021 to 26 December 2023, 51 individual BALF samples were enrolled, consisting of 20 patients with IIM-ILD, 16 patients with other CTD-ILD (including 8 patients with SLE and 8 with RA) and 15 patients with CAP. The structure and function of microbiota in BALF were identified by metagenomic next-generation sequencing (mNGS). Results: The community evenness of LRT microbiota within the IIM-ILD group was marginally lower compared to the other CTD-ILD and CAP groups. Nonetheless, there were no noticeable differences. The species community structure was similar among the three groups, based on the Bray-Curtis distance between the samples. At the level of genus, the IIM-ILD group displayed a considerably higher abundance of Pseudomonas and Corynebacterium in comparison to the CAP group (p < 0.01, p < 0.05). At the species level, we found that the relative abundance of Pseudomonas aeruginosa increased significantly in the IIM-ILD group compared to the CAP group (p < 0.05). Additionally, the relative abundance of Prevotella pallens was significantly higher in other CTD-ILD groups compared to that in the IIM-ILD group (p < 0.05). Of all the clinical indicators examined in the correlation analysis, ferritin level demonstrated the strongest association with LRT flora, followed by Serum interleukin-6 level (p < 0.05). Conclusion: Our research has identified particular LRT microorganisms that were found to be altered in the IIM-ILD group and were significantly associated with immune function and inflammatory markers in patients. The lower respiratory tract microbiota has potential in the diagnosis and treatment of IIM-ILD.

Association between dietary zinc intake and asthma in overweight or obese children and adolescents: A cross-sectional analysis of NHANES.

Background: Asthma, characterized by recurrent wheezing, breathlessness, chest tightness, and coughing, is a major health concern among children and adolescents worldwide, currently affecting more than 5 million children. The increasing prevalence of obesity and overweight among the pediatric population has made the issue of childhood respiratory health more complex. Compared with children of healthy weight, the risk of asthma is higher in overweight and obese children. Zinc, a nutrient that regulates the oxidant-antioxidant balance, has been studied for its potential protective effects against asthma in adults and children. However, the results are controversial, with some studies reporting a beneficial effect and others showing no effect. Therefore, our objective was to assess the correlation between zinc intake from diet and asthma occurrence among children and adolescents who are overweight or obese. Methods: The National Health and Nutrition Examination Survey (NHANES) (2011-2020) provided data on individuals aged ≤20 who were overweight or obese, had asthma, and consumed zinc in their diet. The association between dietary zinc and asthma was evaluated using a variety of statistical methods, including multivariate logistic regression, restricted cubic spline analysis, and subgroup analysis. Results: A total of 4597 pediatrics and adolescents were enrolled, with 20.9% (963/4597) suffering from asthma. After adjusting for all covariates in the multivariate logistic regression, compared with the lowest zinc intake group Q1(≤5.68 mg/day), the adjusted OR values for zinc intake and asthma in Q2 (5.69-8.36 mg/day), Q3 (8.37-11.95 mg/day), and Q4 (≥11.96 mg/day) were 0.78 (95% CI: 0.62-0.98, p = 0.03), 0.76 (95% CI: 0.6∼0.98, p = 0.032), 0.71 (95% CI: 0.53∼0.95, p = 0.022), respectively. Stratified analysis showed no interactive role for dietary zinc intake and asthma in overweight or obese children and adolescents. Conclusions: Dietary zinc intake is inversely associated with asthma in overweight or obese children and adolescents.

Disaster literacy in disaster emergency response: a national qualitative study among nurses.

BACKGROUND: As the largest group of healthcare professionals, nurses play an indispensable and crucial role in disaster response. The enhancement of nurses' disaster literacy is imperative for effective disaster emergency management. However, there is currently a lack of knowledge regarding nurses' disaster literacy. This study represents the first attempt to explore the key components and characteristics of disaster literacy among nurses. METHODS: A qualitative descriptive design was employed, and the reporting followed the Consolidated Criteria for Reporting Qualitative Research (COREQ) guidelines (refer to File S1). The purposive sampling method was utilized. Thirty-one rescue nurses from 31 medical institutions across 25 provinces and regions in China were recruited to participate in the study. The respondents were requested to share their experiences and insights regarding disaster rescue operations. Inductive content analysis was employed for data examination. RESULTS: The results indicated that rescue nurses universally recognized that there was a pressing need to enhance the level of disaster literacy among nurses. The disaster literacy of nurses encompasses nine dimensions: physical and mental quality, disaster rescue general knowledge, professional and technical competence, professional ethics, teamwork, emotional ability, information literacy, leadership, and knowledge transformation. CONCLUSIONS: To ensure national sustainability, government departments, healthcare organizations, and hospital administrators can accurately evaluate the disaster literacy of individual clinical nurses, groups, and the workforce as a whole through nine dimensions, which also can provide evidence to support the development of precision strategies to strengthen the disaster literacy of nurses.

Reversal Effect of Phosphorus on Catalytic Performances of Supported Nickel Catalysts in Reductive Amination of 1,6-Hexanediol.

The reductive amination of 1,6-hexanediol with ammonia is one of the most promising green routes for synthesis of 1,6-hexanediamine. Herein, we developed a phosphorous modified Ni catalyst of Ni-P/Al2O3. It presented satisfactory improved selectivity to 1,6-hexanediamine in the reductive amination of 1,6-hexanediol compared to the Ni/Al2O3 catalyst. The phosphorous tended to interact with Al2O3 to form AlPOx species, induced Ni nanoparticle to be flatter, and the decrease of strong acid sites, the new-formed Ni-AlPOx-Al2O3 interface and the flatter Ni nanoparticle were the key to switch the dominating product from hexamethyleneimine to 1,6-hexanediamine. This work develops an efficient catalyst for production of 1,6-hexanediamine from the reductive amination of 1,6-hexanediol, and provides a point of view about designing selective non-noble metal catalysts for producing primary diamines via reductive amination of diols.

Pcolce2 overexpression promotes supporting cell reprogramming in the neonatal mouse cochlea.

Hair cell (HC) damage is a leading cause of sensorineural hearing loss, and in mammals supporting cells (SCs) are unable to divide and regenerate HCs after birth spontaneously. Procollagen C-endopeptidase enhancer 2 (Pcolce2), which encodes a glycoprotein that acts as a functional procollagen C protease enhancer, was screened as a candidate regulator of SC plasticity in our previous study. In the current study, we used adeno-associated virus (AAV)-ie (a newly developed adeno-associated virus that targets SCs) to overexpress Pcolce2 in SCs. AAV-Pcolce2 facilitated SC re-entry into the cell cycle both in cultured cochlear organoids and in the postnatal cochlea. In the neomycin-damaged model, regenerated HCs were detected after overexpression of Pcolce2, and these were derived from SCs that had re-entered the cell cycle. These findings reveal that Pcolce2 may serve as a therapeutic target for the regeneration of HCs to treat hearing loss.

Comparison of clopidogrel and ticagrelor in treating acute coronary syndrome undergoing PCI: A systematic review and meta-analysis.

Objective: The study aims to evaluate and compare the efficacy and safety between ticagrelor and clopidogrel in acute coronary syndrome (ACS) patients undergoing percutaneous coronary intervention (PCI). Methods: We searched MEDLINE (via PubMed), Cochrane, Embase, and the Cochrane library databases for eligible citations (the last search was up to December 2021). Subgroup analyses were performed based on region, study design, dose, and single-center/multicenter. Meta regressions were conducted to explore the source of heterogeneity. A sensitivity analysis was conducted to assess the robustness of the results. Funnel plots and Egger's test were preformed to test publication bias of the meta-analysis. Results: A total of 29 studies were included, totaling 165,981 patients. Ticagrelor reduced the overall incidence rate of major adverse cardiovascular events (MACEs) (HR 0.74; 95% CI, 0.62, 0.89; P = 0.001; I2 = 88.3%, P < 0.001) and all-cause mortality (HR 0.85; 95% CI, 0.75, 0.97; P = 0.019; I2 = 39.7%, P = 0.052) compared with clopidogrel. However, there was a higher risk of major bleeding (HR 1.21; 95% CI, 1.02,1.44; P = 0.026, I2 = 59.3%, P = 0.012) and all bleeding (HR 1.42; 95% CI, 1.24, 1.62; P < 0.001, I2 = 76.4%, P < 0.001) with ticagrelor compared to clopidogrel. The stability of the results was demonstrated by sensitivity analysis. Furthermore, subgroup analyses and meta-regression revealed that the heterogeneity in the study may stem from factors such as whether it was conducted in a single-center or multicenter setting, as well as the geographical region. Conclusion: Ticagrelor has demonstrated superior efficacy compared to clopidogrel in ACS patients undergoing PCI, particularly in Asia and Europe. Nevertheless, it is crucial to acknowledge that the utilization of ticagrelor is linked to a heightened risk of bleeding. To provide guidance for clinical decision-making regarding the use of ticagrelor, future multicenter randomized trials that are relevant and encompass longer follow-up periods are necessary. The category of the manuscript a meta-analysis: PROSPERO registration number CRD42021274198.

Foeniculum vulgare essential oil nanoemulsion inhibits Fusarium oxysporum causing Panax notoginseng root-rot disease.

Background: Fusarium oxysporum (F. oxysporum) is the primary pathogenic fungus that causes Panax notoginseng (P. notoginseng) root rot disease. To control the disease, safe and efficient antifungal pesticides must currently be developed. Methods: In this study, we prepared and characterized a nanoemulsion of Foeniculum vulgare essential oil (Ne-FvEO) using ultrasonic technology and evaluated its stability. Traditional Foeniculum vulgare essential oil (T-FvEO) was prepared simultaneously with 1/1000 Tween-80 and 20/1000 dimethyl sulfoxide (DMSO). The effects and inhibitory mechanism of Ne-FvEO and T-FvEO in F. oxysporum were investigated through combined transcriptome and metabolome analyses. Results: Results showed that the minimum inhibitory concentration (MIC) of Ne-FvEO decreased from 3.65 mg/mL to 0.35 mg/mL, and its bioavailability increased by 10-fold. The results of gas chromatography/mass spectrometry (GC/MS) showed that T-FvEO did not contain a high content of estragole compared to Foeniculum vulgare essential oil (FvEO) and Ne-FvEO. Combined metabolome and transcriptome analysis showed that both emulsions inhibited the growth and development of F. oxysporum through the synthesis of the cell wall and cell membrane, energy metabolism, and genetic information of F. oxysporum mycelium. Ne-FvEO also inhibited the expression of 2-oxoglutarate dehydrogenase and isocitrate dehydrogenase and reduced the content of 2-oxoglutarate, which inhibited the germination of spores. Conclusion: Our findings suggest that Ne-FvEO effectively inhibited the growth of F. oxysporum in P. notoginseng in vivo. The findings contribute to our comprehension of the antifungal mechanism of essential oils (EOs) and lay the groundwork for the creation of plant-derived antifungal medicines.

Recent progress in functional metal-organic frameworks for bio-medical application.

Metal-organic frameworks (MOFs) have a high specific surface area, adjustable pores and can be used to obtain functional porous materials with diverse and well-ordered structures through coordination and self-assembly, which has intrigued wide interest in a broad range of disciplines. In the arena of biomedical engineering, the functionalized modification of MOFs has produced drug carriers with excellent dispersion and functionalities such as target delivery and response release, with promising applications in bio-detection, disease therapy, tissue healing, and other areas. This review summarizes the present state of research on the functionalization of MOFs by physical binding or chemical cross-linking of small molecules, polymers, biomacromolecules, and hydrogels and evaluates the role and approach of MOFs functionalization in boosting the reactivity of materials. On this basis, research on the application of functionalized MOFs composites in biomedical engineering fields such as drug delivery, tissue repair, disease treatment, bio-detection and imaging is surveyed, and the development trend and application prospects of functionalized MOFs as an important new class of biomedical materials in the biomedical field are anticipated, which may provide some inspiration and reference for further development of MOF for bio-medical applications.

Ketones provide an extra source of fuel for the failing heart without impairing glucose oxidation.

BACKGROUND: Cardiac glucose oxidation is decreased in heart failure with reduced ejection fraction (HFrEF), contributing to a decrease in myocardial ATP production. In contrast, circulating ketones and cardiac ketone oxidation are increased in HFrEF. Since ketones compete with glucose as a fuel source, we aimed to determine whether increasing ketone concentration both chronically with the SGLT2 inhibitor, dapagliflozin, or acutely in the perfusate has detrimental effects on cardiac glucose oxidation in HFrEF, and what effect this has on cardiac ATP production. METHODS: 8-week-old male C57BL6/N mice underwent sham or transverse aortic constriction (TAC) surgery to induce HFrEF over 3 weeks, after which TAC mice were randomized to treatment with either vehicle or the SGLT2 inhibitor, dapagliflozin (DAPA), for 4 weeks (raises blood ketones). Cardiac function was assessed by echocardiography. Cardiac energy metabolism was measured in isolated working hearts perfused with 5 mM glucose, 0.8 mM palmitate, and either 0.2 mM or 0.6 mM ß-hydroxybutyrate (ßOHB). RESULTS: TAC hearts had significantly decreased %EF compared to sham hearts, with no effect of DAPA. Glucose oxidation was significantly decreased in TAC hearts compared to sham hearts and did not decrease further in TAC hearts treated with high ßOHB or in TAC DAPA hearts, despite ßOHB oxidation rates increasing in both TAC vehicle and TAC DAPA hearts at high ßOHB concentrations. Rather, increasing ßOHB supply to the heart selectively decreased fatty acid oxidation rates. DAPA significantly increased ATP production at both ßOHB concentrations by increasing the contribution of glucose oxidation to ATP production. CONCLUSION: Therefore, increasing ketone concentration increases energy supply and ATP production in HFrEF without further impairing glucose oxidation.

Helicobacter pylori and immunotherapy for gastrointestinal cancer.

Helicobacter pylori infection is associated with the risk of gastrointestinal (GI) cancers; however, its impact on immunotherapy for GI cancers remains uncertain. In this study, we included 10,122 patients who underwent 13C-urea breath tests. Among 636 patients with Epstein-Barr virus-negative microsatellite-stable gastric cancer (GC) who were treated with anti-PD-1/PD-L1 therapy, H. pylori-positive patients exhibited significantly longer immune-related progression-free survival (irPFS) compared with H. pylori-negative patients (6.97 months versus 5.03 months, p < 0.001, hazard ratio [HR] 0.76, 95% confidence interval [CI] 0.62-0.95, p = 0.015). Moreover, the H. pylori-positive group demonstrated a trend of 4 months longer median immune-related overall survival (irOS) than the H. pylori-negative group. H. pylori-positive GC displayed higher densities of PD-L1+ cells and nonexhausted CD8+ T cells, indicative of a "hot" tumor microenvironment. Transcriptomic analysis revealed that H. pylori-positive GC shared molecular characteristics similar to those of immunotherapy-sensitive GC. However, H. pylori-positive patients with DNA mismatch repair-deficient (dMMR)/microsatellite instability-high (MSI-H) colorectal adenocarcinoma and esophageal squamous cell carcinoma (ESCC) had shorter irPFS compared with H. pylori-negative patients (16.13 months versus not reached, p = 0.042, HR 2.26, 95% CI 1.13-4.50, p = 0.021 and 5.57 months versus 6.97 months, p = 0.029, HR 1.59, 95% CI 1.14-2.23, p = 0.006, respectively). The difference in irOS between H. pylori-positive and -negative patients had the same trend as that between dMMR/MSI-H colorectal adenocarcinoma and ESCC patients. We also identified a trend of shorter irPFS and irOS in H. pylori-positive liver cancer and pancreatic cancer patients. In summary, our findings supported that H. pylori infection is a beneficial factor for GC immunotherapy by shaping hot tumor microenvironments. However, in dMMR/MSI-H colorectal adenocarcinoma and ESCC patients, H. pylori adversely affects the efficacy of immunotherapy.

Genome Sequencing and Analysis of Nigrospora oryzae, a Rice Leaf Disease Fungus.

Nigrospora oryzae is one of several fungal pathogens known to cause brown streaks, leaf spots, and latent infections in rice. In this study, the entire 42.09-Mb genome of N. oryzae was sequenced at a depth of 169× using the Oxford Nanopore Technologies platform. The draft genome sequence was comprised of 26 scaffolds, possessed an average GC content of 58.83%, and contained a total of 10,688 protein-coding genes. Analysis of the complete genome sequence revealed that CAZyme-encoding genes account for 6.11% of all identified genes and that numerous transcription factors (TFs) associated with diverse biological processes belong predominantly to Zn-clus (22.20%) and C2H2 (10.59%) fungal TF classes. In addition, genes encoding 126 transport proteins and 3307 pathogen-host interaction proteins were identified. Comparative analysis of the previously reported N. oryzae reference strain GZL1 genome and the genome of a representative strain ZQ1 obtained here revealed 9722 colinear genes. Collectively, these findings provide valuable insights into N. oryzae genetic mechanisms and phenotypic characteristics.

AAV-mediated Gpm6b expression supports hair cell reprogramming.

Irreversible damage to hair cells (HCs) in the cochlea leads to hearing loss. Cochlear supporting cells (SCs) in the murine cochlea have the potential to differentiate into HCs. Neuron membrane glycoprotein M6B (Gpm6b) as a four-transmembrane protein is a potential regulator of HC regeneration according to our previous research. In this study, we found that AAV-ie-mediated Gpm6b overexpression promoted SC-derived organoid expansion. Enhanced Gpm6b prevented the normal decrease in SC plasticity as the cochlea develops by supporting cells re-entry cell cycle and facilitating the SC-to-HC transformation. Also, overexpression of Gpm6b in the organ of Corti through the round window membrane injection facilitated the trans-differentiation of Lgr5+ SCs into HCs. In conclusion, our results suggest that Gpm6b overexpression promotes HC regeneration and highlights a promising target for hearing repair using the inner ear stem cells combined with AAV.

Virtual Reality-Based Exercise Rehabilitation in Cancer-Related Dysfunctions: Scoping Review.

BACKGROUND: Virtual reality-based exercise rehabilitation (VRER) is a promising intervention for patients with cancer-related dysfunctions (CRDs). However, studies focusing on VRER for CRDs are lacking, and the results are inconsistent. OBJECTIVE: We aimed to review the application of VRER in patients with CRDs. METHODS: This scoping review was conducted following the PRISMA-ScR (Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews) checklist framework. Publications were included from the time of database establishment to October 14, 2023. The databases were PubMed, Embase, Scopus, Cochrane, Web of Science, ProQuest, arXiv, IEEE Xplore, MedRxiv, CNKI, Wanfang Data, VIP, and SinoMed. The population included patients with cancer. A virtual reality (VR) system or device was required to be provided in exercise rehabilitation as an intervention. Eligible studies focused on VRER used for CRDs. Study selection and data extraction were performed by 2 reviewers independently. Extracted data included authors, year, country, study type, groups, sample size, participant age, cancer type, existing or potential CRDs, VR models and devices, intervention programs and durations, effectiveness, compliance, satisfaction, and safety. RESULTS: We identified 25 articles, and among these, 12 (48%) were randomized clinical trials, 11 (44%) were other experimental studies, and 2 (8%) were observational studies. The total sample size was 1174 (range 6-136). Among the 25 studies, 22 (88%), 2 (8%), and 1 (4%) included nonimmersive VR, immersive VR, and augmented reality, respectively, which are models of VRER. Commercial game programs (17/25, 68%) were the most popular interventions of VRER, and their duration ranged from 3 to 12 weeks. Using these models and devices, VRER was mostly applied in patients with breast cancer (14/25, 56%), leukemia (8/25, 32%), and lung cancer (3/25, 12%). Furthermore, 6 CRDs were intervened by VRER, and among these, postmastectomy syndromes were the most common (10/25, 40%). Overall, 74% (17/23) of studies reported positive results, including significant improvements in limb function, joint range of motion, edema rates, cognition, respiratory disturbance index, apnea, activities of daily living, and quality of life. The compliance rate ranged from 56% to 100%. Overall, 32% (8/25) of studies reported on patient satisfaction, and of these, 88% (7/8) reported satisfaction with VRER. Moreover, 13% (1/8) reported mild sickness as an adverse event. CONCLUSIONS: We found that around half of the studies reported using VRER in patients with breast cancer and postmastectomy dysfunctions through nonimmersive models and commercial game programs having durations of 3-12 weeks. In addition, most studies showed that VRER was effective owing to virtualization and interaction. Therefore, VRER may be an alternate intervention for patients with CRDs. However, as the conclusions were drawn from data with acknowledged inconsistencies and limited satisfaction reports, studies with larger sample sizes and more outcome indictors are required.

Mitochondrial fatty acid oxidation is the major source of cardiac adenosine triphosphate production in heart failure with preserved ejection fraction.

AIMS: Heart failure with preserved ejection fraction (HFpEF) is a prevalent disease worldwide. While it is well established that alterations of cardiac energy metabolism contribute to cardiovascular pathology, the precise source of fuel used by the heart in HFpEF remains unclear. The objective of this study was to define the energy metabolic profile of the heart in HFpEF. METHODS AND RESULTS: Eight-week-old C57BL/6 male mice were subjected to a '2-Hit' HFpEF protocol [60% high-fat diet (HFD) + 0.5 g/L of Nω-nitro-L-arginine methyl ester]. Echocardiography and pressure-volume loop analysis were used for assessing cardiac function and cardiac haemodynamics, respectively. Isolated working hearts were perfused with radiolabelled energy substrates to directly measure rates of fatty acid oxidation, glucose oxidation, ketone oxidation, and glycolysis. HFpEF mice exhibited increased body weight, glucose intolerance, elevated blood pressure, diastolic dysfunction, and cardiac hypertrophy. In HFpEF hearts, insulin stimulation of glucose oxidation was significantly suppressed. This was paralleled by an increase in fatty acid oxidation rates, while cardiac ketone oxidation and glycolysis rates were comparable with healthy control hearts. The balance between glucose and fatty acid oxidation contributing to overall adenosine triphosphate (ATP) production was disrupted, where HFpEF hearts were more reliant on fatty acid as the major source of fuel for ATP production, compensating for the decrease of ATP originating from glucose oxidation. Additionally, phosphorylated pyruvate dehydrogenase levels decreased in both HFpEF mice and human patient's heart samples. CONCLUSION: In HFpEF, fatty acid oxidation dominates as the major source of cardiac ATP production at the expense of insulin-stimulated glucose oxidation.

AAV-Mediated Gene Therapy Restores Hearing in Patients with DFNB9 Deafness.

Mutations in OTOFERLIN (OTOF) lead to the autosomal recessive deafness 9 (DFNB9). The efficacy of adeno-associated virus (AAV)-mediated OTOF gene replacement therapy is extensively validated in Otof-deficient mice. However, the clinical safety and efficacy of AAV-OTOF is not reported. Here, AAV-OTOF is generated using good manufacturing practice and validated its efficacy and safety in mouse and non-human primates in order to determine the optimal injection dose, volume, and administration route for clinical trials. Subsequently, AAV-OTOF is delivered into one cochlea of a 5-year-old deaf patient and into the bilateral cochleae of an 8-year-old deaf patient with OTOF mutations. Obvious hearing improvement is detected by the auditory brainstem response (ABR) and the pure-tone audiometry (PTA) in these two patients. Hearing in the injected ear of the 5-year-old patient can be restored to the normal range at 1 month after AAV-OTOF injection, while the 8-year-old patient can hear the conversational sounds. Most importantly, the 5-year-old patient can hear and recognize speech only through the AAV-OTOF-injected ear. This study is the first to demonstrate the safety and efficacy of AAV-OTOF in patients, expands and optimizes current OTOF-related gene therapy and provides valuable information for further application of gene therapies for deafness.