Effect of perioperative tamsulosin on successful ureteral access sheath placement and stent-related symptom relief: A double-blinded, randomized, placebo-controlled study.

PURPOSE: This study investigated the effect of administering tamsulosin before surgery on the successful insertion of a 12/14 French (F) ureteral access sheath (UAS) during the procedure, as well as the impact of preoperative and postoperative tamsulosin use on symptoms related to the ureteral stent. MATERIALS AND METHODS: This study was a randomized, single-center, double-blinded, placebo-controlled trial involving 200 patients who underwent unilateral retrograde intrarenal surgery. Patients received either tamsulosin (0.4 mg) or placebo 1 week before surgery until stent removal. Patients were randomly assigned to one of four groups. Group 1 received tamsulosin throughout the study period. Group 2 received tamsulosin before surgery and placebo after surgery. Group 3 received placebo before surgery and tamsulosin after surgery. Group 4 received placebo before and after surgery. The USSQ (Ureteral Stent Symptom Questionnaire) was completed between postoperative days 7 and 14 immediately before stent removal. RESULTS: A total of 160 patients were included in this analysis. Their mean age was 55.0±11.0 years, and 48 patients (30.0%) were female. In the group that received preoperative tamsulosin, the success rate of 12/14F UAS deployment was significantly higher than that of the preoperative placebo group (88.0 vs. 75.3%, p=0.038). Preoperative and postoperative tamsulosin did not significantly alleviate symptoms related to the ureteral stent. CONCLUSIONS: Our results revealed that preoperative administration of tamsulosin improved the success of larger-sized UAS, whereas preoperative and postoperative tamsulosin use did not significantly alleviate symptoms related to ureteral stents.

Heat-Dissipation Design and 3D Printing of Ternary Silver Chalcogenide-Based Thermoelectric Legs for Enhancing Power Generation Performance.

Thermoelectric devices have received significant attention because of their potential for sustainable energy recovery. In these devices, a thermal design that optimizes heat transfer and dissipation is crucial for maximizing the power output. Heat dissipation generally requires external active or passive cooling devices, which often suffer from inevitable heat loss and heavy systems. Herein, the design of heat-sink integrated thermoelectric legs is proposed to enhance heat dissipation without external cooling devices, realized by finite element model simulation and 3D printing of ternary silver chalcogenide-based thermoelectric materials. Owing to the self-induced surface charges of the synthesized AgBiSe2 (n-type) and AgSbTe2 (p-type) particles, these particle-based colloidal inks exhibited high viscoelasticity, which enables the creation of complex heat-dissipation architectures via 3D printing. Power generators made from 3D-printed heat-dissipating legs exhibit higher temperature differences and output power than traditional cuboids, offering a new strategy for enhancing thermoelectric power generation.

Triple threat: neutrophil ER stress, NETosis, airway inflammation escalation.

This report aims to propose the novel term 'neutrophil endoplasmic reticulum (ER) stress' (NERS). NERS explores the influence of neutrophil extracellular trap (NET) formation and exacerbation of respiratory ailments. This inquiry aims to advance comprehension in neutrophil biology and respiratory health.

Abnormally High Graphitic Crystallization of Cellulose Nanocrystals.

Cellulose nanocrystals (CNCs) are currently of great interest for many applications, such as energy storage and nanocomposites, because of their natural abundance. A number of carbonization studies have reported abnormal graphitization behavior of CNCs, although cellulose is generally known as a precursor for hard carbon (nongraphitizable carbon). Herein, we report a spray-freeze-drying (SFD) method for CNCs and a subsequent carbonization study to ascertain the difference in the structural development between the amorphous and crystalline phases. The morphological observation by high-resolution transmission electron microscopy of the carbonized SFD-CNC clearly shows that the amorphous and crystalline phases of CNC are attributed to the formation of hard and soft carbon, respectively. The results of a reactive molecular dynamics (RMD) study also show that the amorphous cellulose phase leads to the formation of fewer carbon ring structures, indicative of hard carbon. In contrast, the pristine crystalline cellulose phase has a higher density and thermal stability, resulting in limited molecular relaxation and the formation of a highly crystalline graphitic structure (soft carbon).

Scalable Design of Ru-Embedded Carbon Fabric Using Conventional Carbon Fiber Processing for Robust Electrocatalysts.

Metal-carbon composites are extensively utilized as electrochemical catalysts but face critical challenges in mass production and stability. We report a scalable manufacturing process for ruthenium surface-embedded fabric electrocatalysts (Ru-SFECs) via conventional fiber/fabric manufacturing. Ru-SFECs have excellent catalytic activity and stability toward the hydrogen evolution reaction, exhibiting a low overpotential of 11.9 mV at a current density of 10 mA cm-2 in an alkaline solution (1.0 M aq KOH solution) with only a slight overpotential increment (6.5%) after 10,000 cycles, whereas under identical conditions, that of commercial Pt/C increases 6-fold (from 1.3 to 7.8 mV). Using semipilot-scale equipment, a protocol is optimized for fabricating continuous self-supported electrocatalytic electrodes. Tailoring the fiber processing parameters (tension and temperature) can optimize the structural development, thereby achieving good catalytic performance and mechanical integrity. These findings underscore the significance of self-supporting catalysts, offering a general framework for stable, binder-free electrocatalytic electrode design.

Aging phenotype in AD brain organoids: Track to success and challenges.

Alzheimer's disease (AD) poses a complex challenge, with abnormal protein accumulation in the brain causing memory loss and cognitive decline. Traditional models fall short in AD research, prompting interest in 3D brain organoids (BOs) from human stem cells. These findings hold promise for unveiling the mechanisms of AD, especially in relation to aging. However, an understanding of the aging impact of AD remains elusive. BOs offer insight but face challenges. This review delves into the role of BOs in deciphering aging-related AD and acknowledges limitations. Strategies to enhance BOs for accurate aging modeling in AD brains are suggested. Strengthened by molecular advancements, BOs have the potential to uncover the aging phenotype, advancing AD research.

CLU (clusterin) and PPARGC1A/PGC1α coordinately control mitophagy and mitochondrial biogenesis for oral cancer cell survival.

Mitophagy involves the selective elimination of defective mitochondria during chemotherapeutic stress to maintain mitochondrial homeostasis and sustain cancer growth. Here, we showed that CLU (clusterin) is localized to mitochondria to induce mitophagy controlling mitochondrial damage in oral cancer cells. Moreover, overexpression and knockdown of CLU establish its mitophagy-specific role, where CLU acts as an adaptor protein that coordinately interacts with BAX and LC3 recruiting autophagic machinery around damaged mitochondria in response to cisplatin treatment. Interestingly, CLU triggers class III phosphatidylinositol 3-kinase (PtdIns3K) activity around damaged mitochondria, and inhibition of mitophagic flux causes the accumulation of excessive mitophagosomes resulting in reactive oxygen species (ROS)-dependent apoptosis during cisplatin treatment in oral cancer cells. In parallel, we determined that PPARGC1A/PGC1α (PPARG coactivator 1 alpha) activates mitochondrial biogenesis during CLU-induced mitophagy to maintain the mitochondrial pool. Intriguingly, PPARGC1A inhibition through small interfering RNA (siPPARGC1A) and pharmacological inhibitor (SR-18292) treatment counteracts CLU-dependent cytoprotection leading to mitophagy-associated cell death. Furthermore, co-treatment of SR-18292 with cisplatin synergistically suppresses tumor growth in oral cancer xenograft models. In conclusion, CLU and PPARGC1A are essential for sustained cancer cell growth by activating mitophagy and mitochondrial biogenesis, respectively, and their inhibition could provide better therapeutic benefits against oral cancer.

Ototoxicity of polystyrene nanoplastics in mice, HEI-OC1 cells and zebrafish.

Polystyrene nanoplastics are a novel class of pollutants. They are easily absorbed by living organisms, and their potential toxicity has raised concerns. However, the impact of polystyrene nanoplastics on auditory organs remains unknown. Here, our results showed that polystyrene nanoplastics entered the cochlea of mice, HEI-OC1 cells, and lateral line hair cells of zebrafish, causing cellular injury and increasing apoptosis. Additionally, we found that exposure to polystyrene nanoplastics resulted in a significant elevation in the auditory brainstem response thresholds, a loss of auditory sensory hair cells, stereocilia degeneration and a decrease in expression of Claudin-5 and Occludin proteins at the blood-lymphatic barrier in mice. We also observed a significant decrease in the acoustic alarm response of zebrafish after exposure to polystyrene nanoplastics. Mechanistic analysis revealed that polystyrene nanoplastics induced up-regulation of the Nrf2/HO-1 pathway, increased levels of malondialdehyde, and decreased superoxide dismutase and catalase levels in cochlea and HEI-OC1 cells. Furthermore, we observed that the expression of ferroptosis-related indicators GPX4 and SLC7A11 decreased as well as increased expression of ACLS4 in cochlea and HEI-OC1 cells. This study also revealed that polystyrene nanoplastics exposure led to increased expression of the inflammatory factors TNF-α, IL-1ß and COX2 in cochlea and HEI-OC1 cells. Further research found that the cell apoptosis, ferroptosis and inflammatory reactions induced by polystyrene nanoplastics in HEI-OC1 cells was reversed through the pretreatment with N-acetylcysteine, a reactive oxygen species inhibitor. Overall, our study first discovered and systematically revealed the ototoxicity of polystyrene nanoplastics and its underlying mechanism.

HER2 overexpression predicts pathological T2 stage and improved survival in de novo muscle-invasive bladder cancer after immediate radical cystectomy: a retrospective cohort study.

INTRODUCTION: Human epidermal growth factor receptor type 2 (HER2) overexpression is a prognostic factor and a therapeutic target for breast cancer; however, anti-HER2 therapies are ineffective in patients with bladder cancer. The authors investigated the effect of HER2 overexpression (HER2 + ) on the prognosis of muscle-invasive bladder cancer (MIBC). MATERIALS AND METHODS: This retrospective cohort study included patients who underwent initial transurethral resection of bladder tumors between 2005 and 2013 and were registered in the Korea National Health Insurance Database, which provides data on overall survival (OS). Sixty-one patients with clinically nonmetastatic de novo MIBC were included in this study. As a subgroup, 33 patients who underwent immediate radical cystectomy (RC) were analyzed. Univariate and multivariate Cox proportional hazards models were used to identify prognostic factors for survival. A multivariable binary logistic regression model was used to identify the favorable T stage. RESULTS: Among the 61 patients with d-MIBC, 14 were HER2 + and 47 HER2 - . Age less than 70 years [hazard ratio (HR): 0.312, CI: 0.16-0.59, P <0.001] and HER2 + status (HR: 0.40, CI: 0.19-0.85, P =0.02) were favorable prognostic factors for OS after adjusting for clinical variables. In the RC subgroup, HER2 + status was a significant predictive factor for the pT2 stage (HR): 36.8, CI: 4.83-797.41, P <0.01). Age less than 70 years (HR: 0.15, CI: 0.05-0.42, P <0.001) and HER2 + status (HR: 0.11, CI: 0.02-0.54, P =0.01) were favorable prognostic factors for OS after adjusting for RC pathological variables. CONCLUSIONS: HER2 + status could be a marker for an indolent subset of MIBC and could predict favorable survival regardless of RC status. Moreover, HER2 + status not only consistently predicted a favorable T stage after RC, but also predicted better survival than pathological outcomes.

Angelica gigas extract inhibits acetylation of eNOS via IRE1α sulfonation/RIDD-SIRT1-mediated posttranslational modification in vascular dysfunction.

Angelica gigas NAKAI (AG) is a popular traditional medicinal herb widely used to treat dyslipidemia owing to its antioxidant activity. Vascular disease is intimately linked to obesity-induced metabolic syndrome, and AG extract (AGE) shows beneficial effects on obesity-associated vascular dysfunction. However, the effectiveness of AGE against obesity and its underlying mechanisms have not yet been extensively investigated. In this study, 40 high fat diet (HFD) rats were supplemented with 100-300 mg/kg/day of AGE to determine its efficacy in regulating vascular dysfunction. The vascular relaxation responses to acetylcholine were impaired in HFD rats, while the administration of AGE restored the diminished relaxation pattern. Endothelial dysfunction, including increased plaque area, accumulated reactive oxygen species, and decreased nitric oxide (NO) and endothelial nitric oxide synthase (eNOS) Ser1177 phosphorylation, were observed in HFD rats, whereas AGE reversed endothelial dysfunction and its associated biochemical signaling. Furthermore, AGE regulated endoplasmic reticulum (ER) stress and IRE1α sulfonation and its subsequent sirt1 RNA decay through controlling regulated IRE1α-dependent decay (RIDD) signaling, ultimately promoting NO bioavailability via the SIRT1-eNOS axis in aorta and endothelial cells. Independently, AGE enhanced AMPK phosphorylation, additionally stimulating SIRT1 and eNOS deacetylation and its associated NO bioavailability. Decursin, a prominent constituent of AGE, exhibited a similar effect in alleviating endothelial dysfunctions. These data suggest that AGE regulates dyslipidemia-associated vascular dysfunction by controlling ROS-associated ER stress responses, especially IRE1α-RIDD/sirt1 decay and the AMPK-SIRT1 axis.

HER2 positivity predicts BCG unresponsiveness and adaptive immune cell exhaustion in EORTC risk-stratified cohort of bladder cancer.

Introduction: Predicting the response to Bacillus Calmette-Guérin (BCG) therapy in high-risk patients with non-muscle invasive bladder cancer (NMIBC) is crucial, as failure may necessitate interventions, such as radical cystectomy or salvage therapy. With the recent classification of genetic class 2a (which has HER2 protein abundance as its signature mutation of ERBB2), evaluating its prognostic role and relationship with BCG response could yield important results. Methods: This retrospective study included 160 patients with NMIBC who underwent transurethral resection of bladder tumors at Gangneung Asan Hospital between 2000 and 2013 and were stratified based on the European Organization for Research and Treatment of Cancer (EORTC) risk criteria. In addition, we analyzed a subset of 67 patients who had received BCG induction therapy to identify factors predictive of BCG treatment response. Univariate and multivariate analyses were used to assess the impact of clinicopathological factors, HER2 positivity, and EORTC risk on recurrence, progression, survival, and BCG response. Each variable's prognostic significance was determined using the Kaplan-Meier analysis. The tumor microenvironments (TMEs) were evaluated in relation to HER2 and EORTC risk. Results: Patients with HER2+ had a higher median age, a greater prevalence of high-grade tumors, and more frequent recurrences. The univariate analysis demonstrated that the HER2+, intermediate (vs. low-risk) high (vs. low-risk), and EORTC recurrence risk groups were significantly associated with recurrence. In patients treated with BCG, only the HER2+ status predicted recurrence. In the univariate analysis for progression, age, high EORTC progression risk (vs. low-to-intermediate), HER2+, and programmed death-ligand 1 positive (PD-L1+) were significant factors. In multivariate analyses for progression, age, high EORTC progression risk, and PD-L1+ were significant factors for progression. HER2 expression was associated with the TME, influencing the proportion of PD-L1+ cells, as well as other markers of PD-1, CD8, and Ki67. Conclusion: The HER2+ status may be related to genetic characteristics that appear more frequently in older age, which suggests a potential for predicting the recurrence and response to BCG treatment. Additionally, analyzing TME trends of aggressive adaptive immune response characterized by HER2 expression provides insight into recurrence and BCG response mechanisms.

The Role of Reactive Oxygen Species, Inflammation, and Endoplasmic Reticulum Stress Response in the Finasteride Protective Effect against Benign Prostate Hyperplasia.

PURPOSE: Benign prostate hyperplasia (BPH) is a common age-related chronic condition. Its pathogenesis involves androgen imbalance, inflammation, oxidative stress, and endoplasmic reticulum (ER) stress. This study aims to assess the protective effect of finasteride, a 5α-reductase inhibitor, against testosterone propionate (TP)-induced BPH in rats and explore its potential mechanism of action. MATERIALS AND METHODS: TP-induced BPH rats received either saline or finasteride (1 mg/kg) orally once a day for 7 weeks. Prior to sacrificing the animals, blood samples were collected. After sacrifice, prostate and tissue around the prostate were dissected from seminal vesical for further analysis. Body weight, prostate weight, dihydrotestosterone (DHT), 5α-reductase type 2 (5-AR2), and prostate-specific antigen (PSA) levels were measured. In addition, HIF-1α, VEGF, MMP-2 expressions in prostate, oxidative stress, inflammation, and ER stress responses were analyzed to understand the mechanism of action of finasteride. RESULTS: Finasteride administration inhibited prostate enlargement, DHT, 5-AR2, and PSA levels in BPH rats. Additionally, finasteride inhibited angiogenesis markers such as HIF-1α, VEGF, and MMP-2. Moreover, components of oxidative stress, inflammation, and ER stress responses were significantly regulated by finasteride treatment. CONCLUSIONS: This study suggests that finasteride prevents BPH-associated symptoms by regulating angiogenesis, reactive oxygen species, ER stress responses, and inflammation, another mechanism to explain the effect of the 5α-reductase against BPH.

Combined Treatment of Mori folium and Mori Cortex Radicis Ameliorate Obesity in Mice via UCP-1 in Brown Adipocytes.

Mori Folium (Morus alba leaf, MF) and Mori Cortex Radicis (Morus alba root cortex, MR) have been studied for their anti-obesity effects by enhancing the browning process and inhibiting adipogenesis. However, important aspects of their protective mechanisms have not been thoroughly investigated, which could aid in developing functional food. Thus, this study aims to determine the synergistic effects of MF and MR against obesity and its associated mechanisms. In an in vitro cell culture model of brown adipocytes, a 1:1 mixture of MF and MR showed a synergistic effect on the expression of brown adipocyte-specific genes, including Ucp-1, Ppargc1a, Cbp/p300-interacting transactivator (Cited), Prdm16, Tbx1, and Fgf21 compared with either MF- or MR-treated conditions. Moreover, they demonstrated the involvement of cAMP and Ca2+ in induction of brown adipocyte-specific genes. In an in vivo model using HFD-fed mice, MF/MR significantly inhibited weight gain, plasma cholesterol, LDL, TG content, fat mass, and adipocyte size. Furthermore, MF/MR inhibited morphological alteration and the expressions of fatty acid synthesis genes such as Srebp1 and Fasn in the white adipose tissue. Thermogenesis genes were recovered in the brown adipose tissue with MF/MR supplementation, indicating that MF/MR regulated adipocytic dysmetabolism where AMPK signaling is involved. In conclusion, these results suggested that MF/MR regulates brown and beige adipocyte processes, providing one of the preventive functional food/herbal medicines against obesity and its associated metabolic diseases.

An Artificial Intelligence Exercise Coaching Mobile App: Development and Randomized Controlled Trial to Verify Its Effectiveness in Posture Correction.

BACKGROUND: Insufficient physical activity due to social distancing and suppressed outdoor activities increases vulnerability to diseases like cardiovascular diseases, sarcopenia, and severe COVID-19. While bodyweight exercises, such as squats, effectively boost physical activity, incorrect postures risk abnormal muscle activation joint strain, leading to ineffective sessions or even injuries. Avoiding incorrect postures is challenging for novices without expert guidance. Existing solutions for remote coaching and computer-assisted posture correction often prove costly or inefficient. OBJECTIVE: This study aimed to use deep neural networks to develop a personal workout assistant that offers feedback on squat postures using only mobile devices-smartphones and tablets. Deep learning mimicked experts' visual assessments of proper exercise postures. The effectiveness of the mobile app was evaluated by comparing it with exercise videos, a popular at-home workout choice. METHODS: Twenty participants were recruited without squat exercise experience and divided into an experimental group (EXP) with 10 individuals aged 21.90 (SD 2.18) years and a mean BMI of 20.75 (SD 2.11) and a control group (CTL) with 10 individuals aged 22.60 (SD 1.95) years and a mean BMI of 18.72 (SD 1.23) using randomized controlled trials. A data set with over 20,000 squat videos annotated by experts was created and a deep learning model was trained using pose estimation and video classification to analyze the workout postures. Subsequently, a mobile workout assistant app, Home Alone Exercise, was developed, and a 2-week interventional study, in which the EXP used the app while the CTL only followed workout videos, showed how the app helps people improve squat exercise. RESULTS: The EXP significantly improved their squat postures evaluated by the app after 2 weeks (Pre: 0.20 vs Mid: 4.20 vs Post: 8.00, P=.001), whereas the CTL (without the app) showed no significant change in squat posture (Pre: 0.70 vs Mid: 1.30 vs Post: 3.80, P=.13). Significant differences were observed in the left (Pre: 75.06 vs Mid: 76.24 vs Post: 63.13, P=.02) and right (Pre: 71.99 vs Mid: 76.68 vs Post: 62.82, P=.03) knee joint angles in the EXP before and after exercise, with no significant effect found for the CTL in the left (Pre: 73.27 vs Mid: 74.05 vs Post: 70.70, P=.68) and right (Pre: 70.82 vs Mid: 74.02 vs Post: 70.23, P=.61) knee joint angles. CONCLUSIONS: EXP participants trained with the app experienced faster improvement and learned more nuanced details of the squat exercise. The proposed mobile app, offering cost-effective self-discovery feedback, effectively taught users about squat exercises without expensive in-person trainer sessions. TRIAL REGISTRATION: Clinical Research Information Service KCT0008178 (retrospectively registered); https://cris.nih.go.kr/cris/search/detailSearch.do/24006.

The moderating and mediating effects of personality on the association between morningness and well-being.

Background: Morningness (morning-eveningness preference or chronotypes) and personality can be both associated with well-being, but few studies have directly compared these two constructs as correlates of well-being. Thus, the first purpose of this study was to test the effects of interactions between stable personality traits (temperaments) and morningness on well-being. Furthermore, personality factors are often composed of both stable biological factors (temperament) and socio-cultural factors (character), and little is known about personality interplay of temperament and character factors with respect to morningness and well-being. The second purpose of this study was therefore to examine the sequential mediating effects of temperament and character factors on the relationship between morningness and well-being. Methods: The Composite Scale of Morningness, the Korean version of the Temperament and Character Inventory-Revised Short Version (TCI-RS), and the Satisfaction with Life Scale were used to measure morningness, personality dimensions, and well-being, respectively, in 287 Korean university students. Moderating and sequentially mediating effects of temperament and character traits were determined using Hayes' PROCESS macro in SPSS after controlling for sex and age. Results: First, novelty-seeking (NS) and persistence (PS) temperaments have demonstrated the moderating effect in the association between morningness and well-being. The positive effects of morningness on life satisfaction increased with lower NS and PS, respectively. However, other temperaments such as harm avoidance (HA) and reward dependence (RD) have not shown the moderation in the relationship between morningness on well-being. Second, HA temperament and self-directedness (SD) character sequentially mediated the relationship between morningness and well-being. The combination of low scores of HA and high scores of SD have shown the positive effect on the relationship between morningness and well-being. Discussion: This study demonstrated that both the interactions between temperaments and morningness, and combination of specific TCI-RS temperament and character traits play important roles in influencing the association between morningness and well-being. The significance of the mature SD character and its implications for well-being are discussed with limitation of the present study.

Ixeris dentata and Lactobacillus gasseri media protect against periodontitis through Nrf2-HO-1 signalling pathway.

Periodontitis is an infectious inflammation in the gums characterized by loss of periodontal ligaments and alveolar bone. Its persistent inflammation could result in tooth loss and other health issues. Ixeris dentata (IXD) and Lactobacillus gasseri media (LGM) demonstrated strong antioxidant activity, which may prevent oxidative and inflammatory periodontitis. Here, IXD and LGM extracts were investigated for antioxidative activity against oral discomfort and evaluated for their synergistic effect against oxidative and inflammatory periodontitis in a mouse model. IXD/LGM suppressed pro-inflammatory cytokines like interleukin (IL)-1ß, IL-6, and TNF-α. Additionally, it reduced pro-inflammatory mediators, nitric oxide, iNOS (inducible nitric oxide synthase), and COX-2 (cyclooxygenase-2) and enhanced AKT, Nrf2, and HO-1 activation. Similarly, IXD/LGM treatment elevated osteogenic proteins and mRNAs; alkaline phosphatase, collagen type 1 (COL1), osteopontin (OPN), and runt-related transcription factor 2 (RUNX2). Hematoxylin and Eosin (H&E) staining and micro-CT analysis confirm the positive impact of IXD/LGM on the periodontal structure and its associated inflammation. These findings demonstrate that IXD/LGM inhibits oxidative stress, periodontal inflammation, and its resultant alveolar bone loss in which Akt (also known as protein kinase B)-nuclear factor-erythroid 2-related factor 2 (Nrf2)-hemoxygenase-1 (HO-1) signaling is involved. Thus, IXD/LGM is a potential candidate against oxidative/inflammatory stress-associated periodontitis.