Aldehyde dehydrogenase 2 preserves kidney function by countering acrolein-induced metabolic and mitochondrial dysfunction.

The prevalence of chronic kidney diseases (CKD) varies by race due to genetic and environmental factors. The Glu504Lys polymorphism in aldehyde dehydrogenase 2 (ALDH2), commonly observed among East Asians, alters the enzyme's function in detoxifying alcohol-derived aldehydes, impacting kidney function. This study investigated the association between variations in ALDH2 levels within the kidney and the progression of kidney fibrosis. Our clinical data indicates that diminished ALDH2 levels are linked to worse CKD outcomes, with correlations between ALDH2 expression, estimated glomerular filtration rate, urinary levels of acrolein, an aldehyde metabolized by ALDH2, and fibrosis severity. In mouse models of unilateral ureteral obstruction and folic acid nephropathy, reduced ALDH2 levels and elevated acrolein were observed in kidneys, especially in ALDH2 Glu504Lys knock-in mice. Mechanistically, acrolein modifies pyruvate kinase M2, leading to its nuclear translocation and co-activation of HIF-1α, shifting cellular metabolism to glycolysis, disrupting mitochondrial function, contributing to tubular damage and the progression of kidney fibrosis. Enhancing ALDH2 expression through adeno-associated virus vectors reduces acrolein and mitigates fibrosis in both wild-type and Glu504Lys knock-in mice. These findings underscore the potential therapeutic significance of targeting the dynamic interaction between ALDH2 and acrolein in CKD.

Different impacts of physical activity on health in urban and rural older adults.

OBJECTIVE: This study aimed to explore the impact of physical activity on health among older adults in urban and rural areas in Taiwan. METHODS: This study employed a cross-sectional design and data were analyzed from 2015 to 2019 from the Hualien County Health Bureau. Participants were divided into urban (n = 4780) and rural groups (n = 4983), and logistic regression models were employed to examine how physical activity relates to their health condition in urban and rural older adults. RESULTS: Results indicated lower physical activity levels and higher unhealthy behavior rate in rural older adults compared to their urban counterparts. Rural older adults had higher rates of cardiovascular diseases and diabetes but lower rates of mental illness. Physical activity demonstrated greater physical health benefits for urban older adults than rural older people. Conversely, rural individuals who engaged in physical activity 150 min/week exhibited greater mental health benefits than their urban counterparts. CONCLUSIONS: Physical activity offers significant mental health benefits for both urban and rural older adults; however, notable improvements in physical health among urban older adults was found. If in the presence of unhealthy behaviors, regular physical activity may not effectively prevent chronic diseases. It is crucial to promote physical activity and healthy behaviors in rural areas.

Traditional Chinese-version reliability test of the Pieper-Zulkowski pressure ulcer knowledge: Psychometric and assessment.

This study was to translate the Pieper-Zulkowski pressure ulcer knowledge test (PZ-PUKT) into Traditional Chinese and evaluate its psychometric properties as well as identify the predictors of knowledge on pressure injury. The PZ-PUKT was translated into Traditional Chinese (TC-PZ-PUKT), and its content validity was evaluated. A total of 296 nurses participated in this study and completed the 72-item TC-PZ-PUKT online. The reliability of the TC-PZ-PUKT was analysed by evaluating its internal consistency and test-retest reliability. Hierarchical regression was used to determine factors associated with TC-PZ-PUKT scores. Content validity was achieved with a score of 0.986. Internal consistency was observed to be reliable, with a Cronbach's alpha of 0.858. The mean knowledge score on the TC-PZ-PUKT was 72.5%, with a 1-week test-retest reliability of r = 0.849. Education level, certification as a wound specialist and self-learning through reading articles, books or guidelines on pressure injury were significantly associated with TC-PZ-PUKT scores. The TC-PZ-PUKT is a valid and reliable tool. Education level, certification as a wound specialist and self-learning regarding pressure injury are related to knowledge of pressure injury.

Reduced mortality with antimicrobial stewardship guided by BioFire FilmArray Blood Culture Identification 2 panel in critically ill patients with bloodstream infection: a retrospective propensity score-matched study.

OBJECTIVES: To investigate whether using the BioFire® FilmArray® Blood Culture Identification 2 panel (BCID2) leads to timely antimicrobial therapy and improves patient outcomes in critically ill patients with bloodstream infections (BSIs). METHODS: This retrospective observational study included patients with BSIs admitted to the intensive care unit from July 1, 2021, to August 31, 2023. Patients were divided into groups receiving appropriate or inappropriate antimicrobial therapy. Those receiving inappropriate therapy underwent adjustments using standard-of-care (SOC) testing or BCID2. Propensity score matching (PSM) was performed on the original cohort (Model 1) and a time-window bias-adjusted cohort (Model 2). Clinical impact of BCID2-guided antimicrobial adjustment was analyzed in both models. RESULTS: A total of 181 patients received inappropriate antimicrobial therapy, with 33 undergoing BCID2 testing and 148 undergoing SOC testing. Following PSM and time-window bias adjustment, 66 patients were analyzed in Model 1 and 46 patients in Model 2. BCID2 significantly reduced the median time to appropriate antimicrobial therapy (40.8 vs. 74.0 h in Model 1; 42.8 vs. 68.9 h in Model 2) and the day-28 mortality rate (27.8% vs. 77.1%, p < 0.001 in Model 1; 23.5% vs. 58.6%, p = 0.021 in Model 2). In multivariate regression analysis, BCID2-guided antimicrobial adjustment was an independent prognostic factor for day-28 mortality (adjusted odds ratio [aOR] 0.07 in Model 1 and aOR 0.12 in Model 2). CONCLUSION: BCID2-guided antimicrobial stewardship was associated with a shorter time to appropriate antimicrobial therapy and reduced day-28 mortality in critically ill patients with BSIs receiving inappropriate antimicrobial therapy.

Effects of integration interdisciplinary learning on student learning outcomes and healthcare-giving competence: a mixed methods study.

BACKGROUND: Interdisciplinary collaboration is known to foster professional innovation and enhance student learning across different domains. However, the research on the effectiveness of integration of interdisciplinary learning in pediatric nursing education is limited. Therefore, this study aimed to examine the effectiveness of integrating game-based learning, an interdisciplinary approach to teaching, into pediatric nursing education's play courses. METHODS: We used a mixed methods study with pre-test/post-test quantitative analyses and a descriptive qualitative analysis of students' reflection journals. Data were collected between August 2019 and July 2020 to gauge course effectiveness. Quantitative data obtained from the questionnaires were analyzed using a t-test, correlation, and regression analysis. Qualitative data using students' reflective journals were collected and analyzed using content analysis. One hundred and three second-year nursing students enrolled in a four-year nursing program. Nursing students attended classes in university classrooms and served learning in a kindergarten or hospital in Northern Taiwan. RESULTS: The subscales of Students' Learning Outcome in knowledge, abilities, and attitudes showed significantly higher mean post-test scores compared to pre-test scores: 26.15 (SD = 3.35) vs. 16.82 (SD = 4.49), p < .001; 18.03 (SD = 2.13) vs. 11.43 (SD = 2.95), p < .001; and 12.90 (SD = 2.12) vs. 8.72 (SD = 2.52), p < .001. Furthermore, scores on the Service-Learning Abilities Scale indicated a significant increase in communication, problem-solving, knowledge application, and cross-cultural competence. Integrating instruction to improve problem-solving skills and knowledge application predicts student learning outcomes. Qualitative findings revealed nursing students' reflections on integrating different learning areas, communication, problem-solving, and practical knowledge skills. CONCLUSIONS: Integration of interdisciplinary learning effectively stimulates learning among nursing students and enhances their knowledge, abilities, and attitudes toward therapeutic play, benefiting children's health. Our findings demonstrate that integration of interdisciplinary learning significantly enhances nursing students' healthcare-giving competence, particularly in communication, problem-solving, knowledge application, and cross-cultural competence as measured by the Service-Learning Scale. Integrating social service with integration of interdisciplinary learning exposes nursing students to diverse challenges and needs, thereby enhancing their communication skills, knowledge application, and problem-solving abilities. Nursing students can blend knowledge and skills through integrated learning, which is crucial for nursing career preparation. TRIAL REGISTRATION: N/A. It was a survey on educational activities.

Astragalus Polysaccharides and Metformin May Have Synergistic Effects on the Apoptosis and Ferroptosis of Lung Adenocarcinoma A549 Cells.

Astragalus polysaccharides (APSs), the compounds extracted from the common herb Astragalus membranaceus, have been extensively studied for their antitumor properties. In this study, we investigated the effect of APS on lung adenocarcinoma A549 cells. The effects of APS and the anti-diabetic drug metformin on apoptosis and ferroptosis were compared. Furthermore, the combination treatment of APS and metformin was also investigated. We found that APS not only reduced the growth of lung cancer cells but also had a synergistic effect with metformin on A549 cells. The study results showed that it may be promising to use APS and metformin as a combination therapy for the treatment of lung adenocarcinoma.

Advanced Glycation End-Products Acting as Immunomodulators for Chronic Inflammation, Inflammaging and Carcinogenesis in Patients with Diabetes and Immune-Related Diseases.

Increased production of advanced glycation end products (AGEs) among reducing sugars (glucose, fructose, galactose, or ribose) and amino acids/proteins via non-enzymatic Maillard reaction can be found in lifestyle-related disease (LSRD), metabolic syndrome (MetS), and obesity and immune-related diseases. Increased serum levels of AGEs may induce aging, diabetic complications, cardiovascular diseases (CVD), neurodegenerative diseases (NDD), cancer, and inflamm-aging (inflammation with immunosenescence). The Maillard reaction can also occur among reducing sugars and lipoproteins or DNAs to alter their structure and induce immunogenicity/genotoxicity for carcinogenesis. AGEs, as danger-associated molecular pattern molecules (DAMPs), operate via binding to receptor for AGE (RAGE) or other scavenger receptors on cell surface to activate PI3K-Akt-, P38-MAPK-, ERK1/2-JNK-, and MyD88-induced NF-κB signaling pathways to mediate various pathological effects. Recently, the concept of "inflamm-aging" became more defined, and we have unveiled some interesting findings in relation to it. The purpose of the present review is to dissect the potential molecular basis of inflamm-aging in patients with diabetes and immune-mediated diseases caused by different AGEs.

Association Between Coronary Artery Disease and Herpes Zoster: A Cohort Study in Taiwan.

Background: Coronary artery disease (CAD) and herpes zoster represent significant health burdens, and their potential interrelationships remain understudied. This cohort study aimed to address the existing knowledge gap by systematically exploring whether people with CAD are at increased risk for developing herpes zoster. Methods: Using the 2006-2015 claims data of the National Health Insurance Program in Taiwan, we identified participants aged ≥20 years with a new diagnosis of CAD as the CAD group. We selected sex- and age-matched participants without CAD as the non-CAD group. The incidence rate of herpes zoster at the end of follow-up was calculated. A multivariable Cox proportional hazards regression model was used to measure the hazard ratio and 95% CI for herpes zoster associated with covariables. Results: The overall incidence rate of herpes zoster was 1.14-fold greater in the CAD group as compared with the non-CAD group (6.52 vs 5.74 per 1000 person-years; 95% CI, 1.08-1.20). After controlling for covariables, the adjusted hazard ratio of herpes zoster was 1.21 (95% CI, 1.14-1.27) for the CAD group as compared with the non-CAD group. Conclusions: This cohort study provides valuable insights into the potential association between CAD and the risk of developing herpes zoster. The findings may have implications for preventive strategies of herpes zoster in people with CAD. Further research and collaboration with diverse groups will be critical to validate and extend our findings.

Impact of class cancellations on parents' and children' adaptation following an outbreak of the Omicron variant during the COVID-19 pandemic in Taiwan in April 2022.

OBJECTIVE: To explore the impact on Taiwanese parents and children following an outbreak of the Omicron variant during the COVID-19 pandemic. METHODS: Data were collected following class cancellations mandated by the Ministry of Education due to an outbreak of the Omicron variant of COVID-19 in April 2022. A national parent organization developed self-report survey questionnaire, "Impact of the Pandemic-related School Closures/Class Cancellations" (IPRSCCC), assessed parents' perceived impact of school cancellations on their child/children' and on their adaptation. The online survey was available between May 4 and May 9, 2022, in 20 districts throughout Taiwan. RESULTS: A total of 2126 parents representing 2592 children responded. Total scores on the IPRSCCC were significantly higher for parents of children whose classes were cancelled (n = 891) compared with parents whose children continued in-person classes (n = 1053). Parents perceived the class cancellations of the child/children disrupted daily routine, learning loss and impacted academic motivation. They also reported emotional stress and no time for rest, which were associated with parental burnout. However for these parents, there were no significant differences in scores between parents living in low and high socioeconomic areas. Only the subscale score for disrupted daily routine was significantly higher for fathers, and emotional stress was significantly higher for parents with two, or ≥ 3 children. When academic impacts were examined using national examination scores for 12th grade students, the percent of students with scores of ≤ 6 in English, Chinese, and mathematics was higher in 2022 than in 2020. CONCLUSIONS: Higher IPRSCCC scores for parents of children whose classes were cancelled provides additional evidence of the impact of disruptions of in-person classes due to the COVID-19 pandemic. Examination scores confirmed class cancellations impacted academic performance.

Discovery of a mu-opioid receptor modulator that in combination with morphinan antagonists induces analgesia.

Morphinan antagonists, which block opioid effects at mu-opioid receptors, have been studied for their analgesic potential. Previous studies have suggested that these antagonists elicit analgesia with fewer adverse effects in the presence of the mutant mu-opioid receptor (MOR; S196A). However, introducing a mutant receptor for medical applications represents significant challenges. We hypothesize that binding a chemical compound to the MOR may elicit a comparable effect to the S196A mutation. Through high-throughput screening and structure-activity relationship studies, we identified a modulator, 4-(2-(4-fluorophenyl)-4-oxothiazolidin-3-yl)-3-methylbenzoic acid (BPRMU191), which confers agonistic properties to small-molecule morphinan antagonists, which induce G protein-dependent MOR activation. Co-application of BPRMU191 and morphinan antagonists resulted in MOR-dependent analgesia with diminished side effects, including gastrointestinal dysfunction, antinociceptive tolerance, and physical and psychological dependence. Combining BPRMU191 and morphinan antagonists could serve as a potential therapeutic strategy for severe pain with reduced adverse effects and provide an avenue for studying G protein-coupled receptor modulation.

Fluorogenic Aptamer Optimizations on a Massively Parallel Sequencing Platform.

F luorogenic ap tamers (FAPs) have become an increasingly important tool in cellular sensing and pathogen diagnostics. However, fine-tuning FAPs for enhanced performance remains challenging even with the structural details provided by X-ray crystallography. Here we present a novel approach to optimize a DNA-based FAP (D-FAP), Lettuce, on repurposed Illumina next-generation sequencing (NGS) chips. When substituting its cognate chromophore, DFHBI-1T, with TO1-biotin, Lettuce not only shows a red-shifted emission peak by 53 nm (from 505 to 558 nm), but also a 4-fold bulk fluorescence enhancement. After screening 8,821 Lettuce variants complexed with TO1-biotin, the C14T mutation is found to exhibit an improved apparent dissociated constant ( vs. 0.82 µM), an increased quantum yield (QY: 0.62 vs. 0.59) and an elongated fluorescence lifetime (τ: 6.00 vs. 5.77 ns), giving 45% more ensemble fluorescence than the canonical Lettuce/TO1-biotin complex. Molecular dynamic simulations further indicate that the π-π stacking interaction is key to determining the coordination structure of TO1-biotin in Lettuce. Our screening-and-simulation pipeline can effectively optimize FAPs without any prior structural knowledge of the canonical FAP/chromophore complexes, providing not only improved molecular probes for fluorescence sensing but also insights into aptamer-chromophore interactions.

Erratum: Therapeutic potential of EGFR/mTOR/Nf-kb targeting small molecule for the treatment of non-small cell lung cancer.

[This corrects the article on p. 2598 in vol. 13, PMID: 37424807.].

High-fat diet-induced increase in glucocorticoids contributes to adipogenesis in obese mice.

BACKGROUND: This study was designed to examine how glucocorticoids (GCs) induced by a long-term ingestion of high-fat diet (HFD) mediate the HFD-induced adipose expansion and obesity. MATERIAL AND METHODS: To address this goal, we used a unique L/L mouse model that fails to induce its corticosterone (CORT) level, a major type of GCs in rodents, after prolonged exposure to an HFD. RESULTS: We found that, after receiving a 12-week HFD feeding, the L/L mice show less weight gain, milder adipose expansion, and higher plasma levels of triglycerides than the wild-type mice. These changes were reversed by replenishing CORT to L/L mice. When examining the expression levels of various molecules linked to lipid uptake and de novo lipogenesis in CORT-induced adipose expansion, we observed a reduction in the expression of adipose preadipocyte factor 1 (Pref-1), a key regulator in adipogenesis. In 3T3-L1 preadipocyte-like cells, dexamethasone, an agonist of the glucocorticoid receptor, also reduced expressions of Pref-1 and facilitated intracellular accumulation of lipids. CONCLUSIONS: Our results suggest that fat ingestion-induced release of CORT contributes to adipose expansion and development of obesity and highlight the pathogenic role of CORT-mediated downregulation of adipose Pref-1 in diet-induced obesity.

Free Fibular Osteocutaneous Flap Combined With Simultaneous Tendon Reconstruction for Midfoot Restoration After Myoepithelial Carcinoma Resection.

ABSTRACT: Myoepithelial carcinomas of soft tissue are rare, and most are malignant. The optimal treatment is surgical excision. The arches of the foot are a composite structure responsible for weight bearing and pressure distribution, so it is a vast challenge in reconstruction. We report a case of reconstruction of the midfoot with a free fibular bone flap and tendon graft. We review the literature to compare various options in foot reconstructions and sort out the outcomes of different bone flaps. The free fibula osteocutaneous flap is the superior choice for midfoot reconstruction owing to its sufficient length, strength, flexible skin paddles, easy-to-withstand osteotomy, and simultaneous tendon graft harvesting.

One-Step Synthesis of Graphene-Covered Silver Nanowires with Enhanced Stability for Heating and Strain Sensing.

Solution-processed silver nanowire (AgNW) networks have been considered as promising electrode candidates for next-generation electronic devices. However, they suffer from poor thermal and electrical stability and low mechanical properties, hindering their practical applications. In this work, graphene nanosheets are successfully introduced into AgNW via a facile one-step solvothermal process. Benefiting from increased conductive paths, the resultant AgNW/graphene films exhibit high electrical conductivity. More importantly, the interlocking NW morphology can be maintained under high temperature and applied voltage due to suppressed Ag migration, which is enabled by the introduction of graphene. This feature leads to enhanced thermal and electrical stability, making them suitable for use as transparent heaters. Furthermore, the composite films present excellent mechanical performance, and negligible resistance change is observed after 10 000 repeated bending cycles. To demonstrate their feasibility toward sensor applications, sandwiched strain sensors are designed, which can endure larger tensile strains and show higher sensitivity and repeatability compared with pure AgNW-based device. Furthermore, various hand gestures can be easily recognized by the resultant sensors based on unique combinations of sensing response. This work not only provides a low-cost method to realize large-scale synthesis of AgNW/graphene composites but also offers guidance to prepare high-performance electrodes for advanced electronics.

Imbalance in Unc80 RNA Editing Disrupts Dynamic Neuronal Activity and Olfactory Perception.

A-to-I RNA editing, catalyzed by the ADAR protein family, significantly contributes to the diversity and adaptability of mammalian RNA signatures, aligning with developmental and physiological needs. Yet, the functions of many editing sites are still to be defined. The Unc80 gene stands out in this context due to its brain-specific expression and the evolutionary conservation of its codon-altering editing event. The precise biological functions of Unc80 and its editing, however, are still largely undefined. In this study, we first demonstrated that Unc80 editing occurs in an ADAR2-dependent manner and is exclusive to the brain. By employing the CRISPR/Cas9 system to generate Unc80 knock-in mouse models that replicate the natural editing variations, our findings revealed that mice with the "gain-of-editing" variant (Unc80G/G) exhibit heightened basal neuronal activity in critical olfactory regions, compared to the "loss-of-editing" (Unc80S/S) counterparts. Moreover, an increase in glutamate levels was observed in the olfactory bulbs of Unc80G/G mice, indicating altered neurotransmitter dynamics. Behavioral analysis of odor detection revealed distinctive responses to novel odors-both Unc80 deficient (Unc80+/-) and Unc80S/S mice demonstrated prolonged exploration times and heightened dishabituation responses. Further elucidating the olfactory connection of Unc80 editing, transcriptomic analysis of the olfactory bulb identified significant alterations in gene expression that corroborate the behavioral and physiological findings. Collectively, our research advances the understanding of Unc80's neurophysiological functions and the impact of its editing on the olfactory sensory system, shedding light on the intricate molecular underpinnings of olfactory perception and neuronal activity.

Two-photon autofluorescence lifetime assay of rabbit photoreceptors and retinal pigment epithelium during light-dark visual cycles in rabbit retina.

Two-photon excited fluorescence (TPEF) is a powerful technique that enables the examination of intrinsic retinal fluorophores involved in cellular metabolism and the visual cycle. Although previous intensity-based TPEF studies in non-human primates have successfully imaged several classes of retinal cells and elucidated aspects of both rod and cone photoreceptor function, fluorescence lifetime imaging (FLIM) of the retinal cells under light-dark visual cycle has yet to be fully exploited. Here we demonstrate a FLIM assay of photoreceptors and retinal pigment epithelium (RPE) that reveals key insights into retinal physiology and adaptation. We found that photoreceptor fluorescence lifetimes increase and decrease in sync with light and dark exposure, respectively. This is likely due to changes in all-trans-retinol and all-trans-retinal levels in the outer segments, mediated by phototransduction and visual cycle activity. During light exposure, RPE fluorescence lifetime was observed to increase steadily over time, as a result of all-trans-retinol accumulation during the visual cycle and decreasing metabolism caused by the lack of normal perfusion of the sample. Our system can measure the fluorescence lifetime of intrinsic retinal fluorophores on a cellular scale, revealing differences in lifetime between retinal cell classes under different conditions of light and dark exposure.

Evaluating the Margins of Breast Cancer Tumors by Using Digital Breast Tomosynthesis with Deep Learning: A Preliminary Assessment.

BACKGROUND: The assessment information of tumor margins is extremely important for the success of the breast cancer surgery and whether the patient undergoes a second operation. However, conducting surgical margin assessments is a time-consuming task that requires pathology-related skills and equipment, and often cannot be provided in a timely manner. To address this challenge, digital breast tomosynthesis technology was utilized to generate detailed cross-sectional images of the breast tissue and integrate deep learning algorithms for image segmentation, achieving an assessment of tumor margins during surgery. METHODS: this study utilized post-operative tissue samples from 46 patients who underwent breast-conserving treatment, and generated image sets using digital breast tomosynthesis for the training and evaluation of deep learning models. RESULTS: Deep learning algorithms effectively identifying the tumor area. They achieved a Mean Intersection over Union (MIoU) of 0.91, global accuracy of 99%, weighted IoU of 44%, precision of 98%, recall of 83%, F1 score of 89%, and dice coefficient of 93% on the training dataset; for the testing dataset, MIoU was at 83%, global accuracy at 97%, weighted IoU at 38%, precision at 87%, recall rate at 69%, F1 score at 76%, dice coefficient at 86%. CONCLUSIONS: The initial evaluation suggests that the deep learning-based image segmentation method is highly accurate in measuring breast tumor margins. This helps provide information related to tumor margins during surgery, and by using different datasets, this research method can also be applied to the surgical margin assessment of various types of tumors.