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Chuan-Chou Tu,1,* Shih-Yen Weng,2– 4,* Nan-Chen Hsieh,2,3 Wen-Chang Cheng,5 Javad Alizargar,3,6 Ko-Shih Chang7 1Department of Internal Medicine, Yuan Rung Hospital, Changhua, 510, Taiwan, Republic of China; 2College of Health Technology, National Taipei University of Nursing and Health Sciences, Taipei City, 112, Taiwan, Republic of China; 3Research Center for Healthcare Industry Innovation, National Taipei University of Nursing and Health Sciences, Taipei City, 112, Taiwan, Republic of China; 4Smart Healthcare Interdisciplinary College, National Taipei University of Nursing and Health Sciences, Taipei City, 112, Taiwan, Republic of China; 5Hyperbaric Oxygen Therapy and Wound Treatment Centre, Yuan Rung Hospital, Changhua, 510, Taiwan, Republic of China; 6College of Nursing, School of Nursing, National Taipei University of Nursing and Health Sciences, Taipei, 112, Taiwan, Republic of China; 7Department of Cardiology, Yuan Rung Hospital, Changhua, 510, Taiwan, Republic of China*These authors contributed equally to this workCorrespondence: Ko-Shih Chang, Department of Cardiology, Yuan Rung Hospital, No. 201, Zhongzheng Road, Yuanlin, Changhua, 510, Taiwan, Republic of China, Tel +886 4 8326161 ext 2702, Fax +886 4 8317776, Email yrh2702@gmail.comAbstract: Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is a highly contagious viral infection. In addition to its association with common pulmonary and gastrointestinal complications, COVID-19 is also associated with numerous neurological and neuropsychiatric conditions. This minireview aims to cover current literature addressing the application of telemedicine in neurological disorders and neuropsychiatric conditions, especially in response to the COVID-19 pandemic. This article revealed that quarantine, masking, and social distancing policies practiced during the COVID-19 pandemic involved restrictions and challenges to providing medical services, especially for patients with neurological disorders with or without COVID-19 infection. During the pandemic, both healthcare administrators and clinicians, including neurologists, have rapidly adapted or introduced telemedicine technologies for delivering specialty care. In some areas in the world, telemedicine has been successfully applied to reduce the impact imposed by COVID-19. Conclusively, this article supports the idea that telemedicine is an effective tool for providing specialized healthcare for patients with neurological conditions while adhering to social distancing or lockdown policies instituted during the COVID-19 pandemic. Government and medical/healthcare authorities, physicians and healthcare providers need to work together to expand the adoption of telemedicine applications, even after the COVID-19 crisis.Keywords: COVID-19 infection, neurological disorders, social distancing, telemedicine

Background: The authors evaluated the utility of immunofluorescence staining with an antipromyelocytic leukemia (anti-PML) antibody for patients with a suspected diagnosis of new or relapsed acute promyelocytic leukemia (APL) and correlated the findings with the results of other established diagnostic modalities.Methods: Bone marrow (BM) and/or peripheral blood (PB) smears from 349 patients in whom the diagnosis of APL was considered were assessed with the anti-PML antibody using immunofluorescence. The study group included 199 patients with confirmed APL and 150 with other conditions. The results of conventional cytogenetics, reverse transcription polymerase chain reaction (RT-PCR), and fluorescence in situ hybridization (FISH) performed on these patients were correlated with the PML results.Results: Among patients with confirmed APL, anti-PML antibody was positive in 182 of 184 BM and 32 of 33 PB smears. Conventional cytogenetics demonstrated t(15;17)(q22;q12) in 166 of 182 (91%) patients; 10 had a normal karyotype, 4 had insufficient mitoses to grow in culture, 1 was inconclusive, and 1 was 48, XX, +8, +8. Anti-PML staining was positive in 9 of 10 with a normal karyotype and in all 4 cases with insufficient mitoses. RT-PCR and FISH were positive for PML-retinoic acid receptor-alpha in 169 of 172 (98%) and 90 of 94 (96%) cases, respectively. Among the patients without APL, 148 of 150 (98.6%) were negative with anti-PML antibody. The sensitivity and specificity of the test were 98.9% and 98.7%, respectively.Conclusions: PML immunofluorescence staining is a rapid (<4 hours turnaround time) and reliable frontline diagnostic approach that can facilitate initiation of targeted therapy, particularly in clinical settings where cytogenetic and molecular testing are not readily available. [ABSTRACT FROM AUTHOR]

Introduction: Herein, we explore whether coil embolization (CE) is effective in treating veno-occlusive dysfunction (VOD). We present five cases with seven CE episodes and a narrative literature review. Methods: From 2013 to 2018, refractory impotence prompted five men to seek penile vascular stripping (PVS), although seven CE episodes were included. All received dual cavernosography in which erection-related veins and VOD were documented. PVS entailed the venous stripping of one deep dorsal vein and two cavernosal veins. The abridged five-item version of the International Index of Erectile Function (IIEF-5) score system and the erection hardness scale (EHS) were used, and yearly postoperative follow-ups were conducted via the Internet. Using Pub Med, a narrative literature review was performed on CE treatment for VOD or varicocele. Results: Inserted coils were scattered along the erection-related veins, including the deep dorsal veins (n = 4), periprostatic plexus (n = 5), iliac vein (n = 5), right pulmonary artery (n = 2), left pulmonary artery (n = 2), and right ventricle (n = 1). PVS resulted in some improvements in the IIEF-5 score and EHS scale. Six articles highly recommend CE treatment for VOD. All claimed it is a minimally invasive effective treatment for varicocele. Conclusions: CE is not justified as a VOD treatment, regardless of its viability in the treatment of varicocele.

Background: The functions of activating transcription factor 3 (ATF3) within the human bladder remain unexplored. This study delves into the expressions, functions, and regulatory mechanisms of ATF3 in human bladder cancer., Material and Methods: Gene expressions were determined by immunoblot, RT-qPCR, and reporter assays. Assays of Ki67, colony formation, Matrigel invasion, and the xenograft animal study were used to assess the cell proliferation, invasion, and tumorigenesis in vitro and in vivo. Silico analysis from TCGA database examined the correlations between GDF15 and ATF3 expressions, clinicopathologic features, and progression-free survival rates., Results: Silico analysis confirmed that ATF3 is an antitumor gene, and the expression positively correlates with GDF15 in bladder cancer tissues. Multivariate analysis revealed that low ATF3/GDF15 but not a single low expression of ATF3 is an independent prognostic factor for progression-free survival of bladder cancer patients. Ectopic overexpression of ATF3 downregulated cell proliferation and invasion in bladder cancer cells in vitro, while ATF3-knockdown reversed these results. Knockdown of ATF3 upregulated EMT markers to enhance cell invasion in vitro and downregulated GDF15, NDRG1, and KAI-1 to elevate tumor growth in vivo. The activation of metformin on ATF3 and GDF15 in bladder cancer cells was blocked by SB431542, a TGFβ receptor inhibitor. ATF3 positively regulated GDF15 expression in bladder cancer cells through a feedback loop., Conclusions: Our results identify that ATF3 is a metformin-upregulated antitumor gene. Results of Silico analysis align with cell-based studies suggesting that low ATF3/GDF15 could be a negative prognostic marker for bladder cancer., Competing Interests: Declaration of Competing Interest The authors have no conflicts of interest to declare., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Toloese, a bed composition, is formulated with a combination of minerals of various wavelengths by utilizing a specific ratio and particle size. A maturation mixing technique is used without additional compression processes, resulting in the natural formation of numerous fine pores in the bed structure. At 40 °C, far infrared radiation in the range of 5-20 μm is emitted with a 0.916 radiant ratio, and the measured emitted radiant energy is 3.69 × 10 2 W/m 2 ·μm. This study aimed to investigate the influence of far infrared radiation emitted from a Toloese bed on endogenous nitric oxide production. Clinical trials were conducted with 20 healthy adults aged 20 years. Blood samples were collected before and after Toloese bed usage for 1 h daily for 3 weeks. Nitric oxide levels in the saliva and blood of men and women significant increased after they used the Toloese bed for 1 h. Additionally, sweating sharply increased in the upper and lower body regions after Toloese bed usage. No hematological changes or adverse effects were observed, but blood glucose, cholesterol, and triglycerides decreased after Toloese bed usage compared with those before Toloese bed usage. These findings demonstrated that far infrared radiation emitted by the Toloese bed induced endogenous nitric oxide production and contributed to significant reductions in blood glucose, cholesterol, and triglyceride levels.

Introduction: Traditional anatomy-based penile venous surgery is deemed inadequate. Based on revolutionary insights into penile vasculature, penile venous stripping (PVS) shows promise in treating adolescent erectile dysfunction (AED). We aimed to report on this novel approach., Methods: We conducted a retrospective analysis of 223 individuals under 30 diagnosed with veno-occlusive dysfunction (VOD) between 2009 and 2023. Among them, 83 were diagnosed with AED and divided into the PVS ( n = 37) and no-surgery (NS, n = 46) groups. All participants had been dissatisfied with conventional therapeutic options. Dual pharmaco-cavernosography was the primary diagnostic modality. PVS involved stripping the deep dorsal vein and two cavernosal veins after securing each emissary's vein with a 6-0 nylon suture. Erection restoration was accessed using the abridged five-item version of the International Index of Erectile Function (IIEF-5) score system and the erection hardness scale (EHS). Statistical analysis was performed using IBM SPSS 21.0., Results: There were significant differences (both p < 0.001) between the preoperative and postoperative IIEF-5 scores in the PVS and NS groups (9.8 ± 3.0 vs. 20.4 ± 2.2; 9.9 ± 2.5 vs. 9.5 ± 2.1), as well as in the EHS scores (1.7 ± 0.7 vs. 3.5 ± 0.6 and 1.8 ± 0.5 vs. 1.3 ± 0.4). The satisfaction rate was 87.9% (29/33) in the PVS group and 16.7% (17/41) in the NS group., Conclusions: AED can be effectively treated using physiological methods, although larger patient cohorts are needed for validation.

Hepatitis delta virus (HDV), an RNA virus with two forms of the delta antigen (HDAg), relies on hepatitis B virus (HBV) for envelope proteins essential for hepatocyte entry. Hepatocellular carcinoma (HCC) ranks third in global cancer deaths, yet HDV's involvement remains uncertain. Among 300 HBV-associated HCC serum samples from Taiwan's National Health Research Institutes, 2.7% (8/300) tested anti-HDV positive, with 62.7% (5/8) of these also HDV RNA positive. Genotyping revealed HDV-2 in one sample, HDV-4 in two, and two samples showed mixed HDV-2/HDV-4 infection with RNA recombination. A mixed-genotype infection revealed novel mutations at the polyadenylation signal, coinciding with the ochre termination codon for the L-HDAg. To delve deeper into the possible oncogenic properties of HDV-2, the predominant genotype in Taiwan, which was previously thought to be less associated with severe disease outcomes, an HDV-2 cDNA clone was isolated from HCC for study. It demonstrated a replication level reaching up to 74% of that observed for a widely used HDV-1 strain in transfected cultured cells. Surprisingly, both forms of HDV-2 HDAg promoted cell migration and invasion, affecting the rearrangement of actin cytoskeleton and the expression of epithelial-mesenchymal transition markers. In summary, this study underscores the prevalence of HDV-2, HDV-4, and their mixed infections in HCC, highlighting the genetic diversity in HCC as well as the potential role of both forms of the HDAg in HCC oncogenesis.

This study examines the predictive value of elevated N-terminal-pro brain natriuretic peptide (NT-pro BNP) levels for mortality among patients with end-stage renal disease (ESRD). Data from 768 ESRD patients, excluding those with cancer or lost follow-up, were analyzed using Kaplan-Meier curves and Cox proportional hazards models over three years. Results indicated that patients with very high NT-pro BNP levels had shorter average survival times and a significantly higher risk of mortality (hazard ratio 1.43). Advanced age, ICU admission, and comorbidities like cerebrovascular diseases and chronic obstructive pulmonary disease also contributed to increased mortality risks. Thus, elevated NT-pro BNP is an independent risk factor for mortality in ESRD patients., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors. Published by Elsevier Ltd.)

Sophora koreensis Nakai, an endemic species distributed only in the Korean Peninsula, is of great geographical, economic, and taxonomic importance. Although its complete chloroplast (cp) genome sequence has been reported, its mitochondrial (mt) genome sequence has not yet been studied. Therefore, in this study, we aimed to investigate its mt genome sequence and compare it with those reported for other Fabaceae species. Total genomic DNA was extracted from fresh S. koreensis leaves collected from natural habitats in Gangwon-do Province, South Korea. This was followed by polymerase chain reaction (PCR) amplification of cpDNA insertions in the mt genome and the detection of microsatellites and dispersed repeats in the cp and mt genomes. Finally, the cp and mt genomes of S. koreensis were compared with those reported for other Fabaceae species. The cp sequence of S. koreensis showed identical gene orders and contents as those previously reported. Only six substitutions and one deletion were detected with 99 % homology. Conversely, the complete mt genome sequence, which was 517,845 bp in length and encoded 61 genes, including 43 protein-coding, 15 transfer RNAs, and 3 ribosomal RNA genes, was considerably different from that of S. japonica in terms of gene order and composition. Further, the mt genome of S. koreensis included ca. 7 and 3 kb insertions, representing an intracellular gene transfer (IGT) event, and the regions with these insertions were determined to be originally present in the cp genome. This IGT event was also confirmed via PCR amplification. IGT events can be induced via biological gene expression control or the use of repetitive sequences, and they provide important insights into the evolutionary lineage of S. koreensis. However, further studies are needed to clarify the gene transfer mechanisms between the two organelles., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Author(s). Published by Elsevier B.V. All rights reserved.)

Phaeodactylum tricornutum is a model diatom with significant biotechnological applications, including enhancing biomass, biofuel, and carotenoid production. Specifically, owing to the capacity of this organism to serve as a valuable source of essential raw materials for pharmaceuticals and nutraceuticals, ongoing research is actively focused on enhancing its productivity. One of the genes involved in various stages of fucoxanthin (Fx) biosynthesis, violaxanthin de-epoxidase like 1 (VDL1), has recently been identified. To validate the intracellular function of this gene and boost Fx production through overexpression, we established and examined three transgenic P. tricornutum lines characterized by elevated P. tricortunum VDL1 ( PtVDL1) expression and evaluate their cell growth and Fx productivity. These transgenic lines exhibited substantially increased PtVDL1 mRNA and protein levels compared to the wild type (WT). Notably, the enzyme substrate violaxanthin was entirely depleted and could not be detected in the transformants, whereas it remained at constant levels in the WT. Interestingly, under standard white light conditions, Fx productivity in the transformants remained unchanged; however, but after 48 h of exposure to red light, it increased by up to 15%. These results indicate that PtVDL1-overexpressing P. tricornutum has industrial potential, particularly for enhancing Fx production under red light conditions.

Purpose: To test the efficacy of a self-management program based on acceptance and commitment therapy on quality of life, emotional distress, fatigue, physical activity, and fruit and vegetable intake in patients with colorectal cancer., Methods: The study was a randomized controlled trial. A sample of 156 patients with colorectal cancer (stage I-III) was recruited by convenience sampling and participants were allocated randomly assigned to control or intervention groups. The intervention included a colorectal cancer self-management information booklet, two personal skills training sessions, and 12 follow-up telephone calls. The control group received health education leaflets. Outcome variables were assessed in both groups at baseline and every two months thereafter during the six-month follow-up period., Result: The mean age of participants was 62 years (range: 30-89 years). Generalized estimation equations analyses revealed significant differences over time in changes in anxiety (β = -2.22, p = 0.001), depression (β = -1.48, p = 0.033), fatigue (β = 4.46, p = 0.001), physical and functional measures (β = 6.16, p = 0.005), and colorectal-cancer-specific quality of life (β = 7.45, p = 0.012). However, there were no significant differences in changes in physical activity or fruit and vegetable intake over time., Conclusion: The self-management skills provided by oncology nurses, including symptom management, psychological adjustment, and relaxation exercises, help colorectal cancer patients to overcome the challenges of cancer survivorship, accelerate their recovery, and improve their quality of life., The Trial Number: NCT03853278 registered on ClinicalTrials.gov., Competing Interests: Declaration of competing interest None declared., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Spiral-phase-contrast imaging, which utilizes a spiral phase optical element, has proven to be effective in enhancing various aspects of imaging, such as edge contrast and shadow imaging. Typically, the implementation of spiral-phase-contrast imaging requires the formation of a Fourier plane through a 4f optical configuration in addition to an existing optical microscope. In this study, we present what we believe to be a novel single spiral-phase-objective, integrating a spiral phase plate, which can be easily and simply applied to a standard microscope, such as a conventional objective. Using a new hybrid design approach that combines ray-tracing and field-tracing simulations, we theoretically realized a well-defined and high-quality vortex beam through the spiral-phase-objective. The spiral-phase-objective was designed to have conditions that are practically manufacturable while providing predictable performance. To evaluate its capabilities, we utilized the designed spiral-phase-objective to investigate isotropic spiral phase contrast and anisotropic shadow imaging through field-tracing simulations, and explored the variation of edge contrast caused by changes in the thickness of the imaging object.

Sargassum horneri (SH) and Ulva australis (UA) are marine waste resources that cause environmental and economic problems when entering or multiplying the coastal waters of Jeju Island. We analyzed their anti-diabetic efficacy to assess their reusability as functional additives. The alpha-glucosidase inhibitory activity of SH and UA extracts was confirmed, and the effect of UA extract was higher than that of SH. After the induction of insulin-resistant HepG2 cells, the effects of the two marine extracts on oxidative stress, intracellular glucose uptake, and glycogen content were compared to the positive control, metformin. Treatment of insulin-resistant HepG2 cells with SH and UA resulted in a concentration-dependent decrease in oxidative stress and increased intracellular glucose uptake and glycogen content. Moreover, SH and UA treatment upregulated the expression of IRS-1 , AKT , and GLUT4 , which are suppressed in insulin resistance, to a similar degree to metformin, and suppressed the expression of FoxO1 , PEPCK involved in gluconeogenesis, and GSK-3β involved in glycogen metabolism. The oral administration of these extracts to rats with streptozotocin-induced diabetes led to a higher weight gain than that in the diabetic group. Insulin resistance and oral glucose tolerance are alleviated by the regulation of blood glucose. Thus, the SH and UA extracts may be used in the development of therapeutic agents or supplements to improve insulin resistance.

Sleeve gastrectomy achieves long-term weight control by reducing gastric volume. However, postoperative gastrointestinal symptoms and insufficient nutritional intake are likely to occur, which are not conducive to physical health. A retrospective study aimed to investigate changes in nutritional status and associated factors in patients after sleeve gastrectomy. Data were collected from the medical records of patients who underwent sleeve gastrectomy at a teaching hospital in Taiwan. Data from 120 patients who met the eligibility criteria were included in the analysis. The results show that sleeve gastrectomy has a strong weight loss effect. Within 12 months, the average body mass index of the patients decreased by 13.47 kg/m 2 . The number of morbidly obese patients decreased from 62 (51.7%) to 3 (2.5%). However, surgery is also associated with gastrointestinal symptoms and the threat of malnutrition. The number of patients with moderate to severe nutritional risk increased from 4 (3.3%) before surgery to 24 (20%) at 12-month follow-up. Likewise, the number of patients with anemia increased from 11 (9.2%) to 29 (24.17%). Gender, constipation, and diarrhea affected postoperative nutritional status. These findings suggest that patients after sleeve gastrectomy are at risk of malnutrition and require regular monitoring. Special attention should be given to women and patients with constipation or diarrhea, as they are at a particularly high risk of malnutrition.

Most (90%) vitamin D synthesis occurs in the skin using sunlight (ultraviolet rays), and 10% is obtained through food. Vitamin D is an essential nutrient for skeletal growth and maintenance, cell proliferation and differentiation, and immune function. This study investigated whether maternal serum vitamin D concentrations induce maternofetal effects. Hematological analysis, serological changes, and precision fetal ultrasound findings were analyzed by maternal vitamin D concentration in gestational weeks 22-25 to ascertain direct effects on fetal growth. Bone density-vitamin D concentration correlation was analyzed. No hematologic or serological effect of maternal vitamin D concentration was detected; however, the sexually transmitted infection and cross-infection rates were inversely proportional to maternal vitamin D concentration. No significant correlation between vitamin D concentration and vertebral and femoral BMD was detected. For fetal growth, biparietal diameter, head circumference, abdominal circumference, femur length, and humerus length were analyzed. Humerus ( p < 0.05) and femur ( p < 0.001) lengths were higher in the vitamin D-sufficient group than in the vitamin D-deficient group. Vitamin D concentration did not positively affect hematologic changes and bone density; maternal vitamin D concentration essentially affected fetal bone growth. Vitamin D inhibits sexually transmitted infections in mothers and promotes fetal bone growth. Prevention of vitamin D deficiency, supplementation, or outdoor activities is recommended.

Patients with the sleep disorder narcolepsy suffer from excessive daytime sleepiness, disrupted nighttime sleep, and cataplexy-the abrupt loss of postural muscle tone during wakefulness, often triggered by strong emotion. The dopamine (DA) system is implicated in both sleep-wake states and cataplexy, but little is known about the function of DA release in the striatum and sleep disorders. Recording DA release in the ventral striatum revealed orexin-independent changes across sleep-wake states as well as striking increases in DA release in the ventral, but not dorsal, striatum prior to cataplexy onset. Tonic low-frequency stimulation of ventral tegmental efferents in the ventral striatum suppressed both cataplexy and rapid eye movement (REM) sleep, while phasic high-frequency stimulation increased cataplexy propensity and decreased the latency to REM sleep. Together, our findings demonstrate a functional role of DA release in the striatum in regulating cataplexy and REM sleep., Competing Interests: The authors declare no competing interests., (© 2023 The Authors.)

Objective: This article aims to provide the experiences of mindfulness treatments from the perspectives of patients with a history of substance abuse., Data Source: Peer-reviewed articles on 5 databases, namely, PubMed, PsychINFO, Medline, CINAHL and the Cochrane Library, between the year of 2000 and 2023., Study Inclusion and Exclusion Criteria: Studies were included if they were published in the English language and reported on qualitative studies that directly engaged patients with experiences of substance abuse and mindfulness treatments., Data Extraction: After our initial search, 5355 studies were reviewed by title and abstract, consequently, 10 studies were included., Data Synthesis: Meta-ethnography were used in this study. Data were obtained from the quotations from participants and text under the heading "results" or "findings" from the included 10 studies., Results: Effective mindfulness-based interventions (MBI) influence recovery from substance abuse. Four themes were identified as factors influencing the MBI treatment effect. They were (1) engaging in mindfulness: entry and retention, (2) perceived benefits of MBIs, (3) implementation of treatment group and (4) maintenance of treatment effect., Conclusion: This article examines the scientific literature to date and presents the evidence on the factors that influentially impact the effect of MBIs in patients with substance abuse. The findings of this study should be helpful in guiding clinical practice, policy, and future research focused on the treatment effect of MBIs for person with substance use., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 The Authors.)

Background: Lower extremity venous disease (LEVD) is a complex disorder, and determining the etiology of LEVD is paramount for treatment selection. Two-dimensional phase-contrast magnetic resonance imaging (2D PC-MRI) can provide an objective measure of hemodynamic status and may help differentiate between different etiologies of LEVD. A total of 271 participants, including 256 symptomatic patients with venous lower extremity disease and 15 healthy volunteers, were collected in this cohort study., Methods: It is a single-center prospective observational study using 2D PC-MRI analysis to assess the hemodynamic characteristics of patients with LEVD among participants recruited between April 2017 and October 2021 at a tertiary hospital. The approval institutional review board number for this study were 201802137B0, 201901058B0, 202100938B0, and 202102344B0. Participants were classified as venous reflux (VR) and venous obstruction (VO) by standard ultrasonography. 2D PC-MRI by 1.5 T scanner revealed stroke volume (SV), forward flow volume (FFV), absolute stroke volume (ASV), mean flux (MF), velocity time integral (VTI), and mean velocity (MV) for each selected venous segments., Results: 2D PC-MRI assessed 167 diseased legs from the 116 VR patients [mean age ± standard deviation (SD): 57.9±12.8 years; 39 males] and 113 diseased legs from the 95 VO patients (mean age ± SD: 66.4±12.8 years; 42 males). 2D PC-MRI analysis demonstrated discrimination ability to differentiate from VR to VO [SV, FFV, ASV, MF, VTI, and MV in the various venous segments, respectively, P≤0.001; area under the curve (AUC) =62-68.8%, P≤0.001 by Mann-Whitney U test]. The ratio data (morbid limb to normal limb) in the same individual with single-leg disease revealed differences between VR and VO (SV, FFV, ASV, and MF in the various venous segments, respectively; P<0.05; AUC =60.2-68.7%, P≤0.05 by Mann-Whitney U test). The most favorable differentiating variables of ratios were FFV in the great saphenous veins [AUC =68.7%, 95% confidence interval (CI): 59.8-77.6%] and ASV in the external iliac veins (AUC =67.4%, 95% CI: 58.7-76.2%)., Conclusions: Quantitative 2D PC-MRI analysis is capable of differentiating VR from VO. It also provides an important diagnostic capability for preoperative evaluation., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://qims.amegroups.com/article/view/10.21037/qims-22-1194/coif). The authors have no conflicts of interest to declare., (2023 Quantitative Imaging in Medicine and Surgery. All rights reserved.)

Despite the recent progress in public health measures, malaria remains a troublesome disease that needs to be eradicated. It is essential to develop new antimalarial medications that are reliable and secure. This report evaluated the pharmacokinetics and antimalarial activity of 1,2,6,7-tetraoxaspiro[7.11]nonadecane (N-89) using the rodent malaria parasite Plasmodium berghei in vivo. After a single oral dose (75 mg /kg) of N-89, its pharmacokinetic parameters were measured, and t1/2 was 0.97 h, Tmax was 0.75 h, and bioavailability was 7.01%. A plasma concentration of 8.1 ng/ml of N-89 was maintained for 8 h but could not be detected at 10 h. The dose inhibiting 50% of parasite growth (ED50) and ED90 values of oral N-89 obtained following a 4-day suppressive test were 20 and 40 mg/kg, respectively. Based on the plasma concentration of N-89, we evaluated the antimalarial activity and cure effects of oral N-89 at a dose of 75 mg/kg 3 times daily for 3 consecutive days in mice harboring more than 0.5% parasitemia. In all the N-89- treated groups, the parasites were eliminated on day 5 post-treatment, and all mice recovered without a parasite recurrence for 30 days. Additionally, administering oral N-89 at a low dose of 50 mg/kg was sufficient to cure mice from day 6 without parasite recurrence. This work was the first to investigate the pharmacokinetic characteristics and antimalarial activity of N-89 as an oral drug. In the future, the following steps should be focused on developing N-89 for malaria treatments; its administration schedule and metabolic pathways should be investigated.

Cerebral Small Vessel Disease (CSVD) frequently affects the elderly, with inflammation playing a crucial role in related health complications, including dementia, stroke, and SVD. Studies, including animal experiments, indicate a strong link between inflammation and SVD progression. The Neutrophil-Lymphocyte Ratio (NLR) serves as a possible biomarker for ongoing inflammatory risks. A total of 720 adults aged 50 years or older from the community-based I-Lan Longitudinal Aging Study were included in this study. General linear regression and ordinally logistic regression analyses were performed to evaluate the association between NLR and CSVD. We further examined the presence of lacune, microbleed, and white matter hyperintensity (WMH) on brain MRI, which were used to construct a combined CSVD score. The NLR was positively associated with WMH (adjusted r = 0.109, p = 0.003), microbleed (adjusted r = 0.102, p = 0.006), and lacune (adjusted r = 0.100, p = 0.008). After adjustments for smoking, drinking, and physical activity in the ordinal logistic regression analysis, age, gender, brachial Systolic Blood Pressure (SBP), fasting glucose, LDL-cholesterol, and Hs-CRP were compared among subjects with low tertile (T1), medium tertile (T2) and high tertile (T3) NLR. The results showed that T2 vs. T1 had an odds ratio of 1.23 (0.86-1.77); and T3 vs. T1 had an odds ratio of 1.87 (1.29-2.71) of CSVD scores in four groups (zero (reference group), one, two, and three or more). NLR could be used to assess the state of inflammation in cerebral vessels. A significant and positive correlation between NLR and CSVD was verified in this study. However, the practical clinical application of NLR in CSVD patients and prognosis prediction should be validated through more scientific attempts.

Photoactivated gas sensors that are fully integrated with micro light-emitting diodes (µLED) have shown great potential to substitute conventional micro/nano-electromechanical (M/NEMS) gas sensors owing to their low power consumption, high mechanical stability, and mass-producibility. Previous photoactivated gas sensors mostly have utilized ultra-violet (UV) light (250-400 nm) for activating high-bandgap metal oxides, although energy conversion efficiencies of gallium nitride (GaN) LEDs are maximized in the blue range (430-470 nm). This study presents a more advanced monolithic photoactivated gas sensor based on a nanowatt-level, ultra-low-power blue (λ peak  = 435 nm) µLED platform (µLP). To promote the blue light absorbance of the sensing material, plasmonic silver (Ag) nanoparticles (NPs) are uniformly coated on porous indium oxide (In 2 O 3 ) thin films. By the plasmonic effect, Ag NPs absorb the blue light and spontaneously transfer excited hot electrons to the surface of In 2 O 3 . Consequently, high external quantum efficiency (EQE, ≈17.3%) and sensor response (ΔR/R 0 (%) = 1319%) to 1 ppm NO 2 gas can be achieved with a small power consumption of 63 nW. Therefore, it is highly expected to realize various practical applications of mobile gas sensors such as personal environmental monitoring devices, smart factories, farms, and home appliances., (© 2023 Wiley-VCH GmbH.)

New psychoactive substances (NPS) are emerging illegal substances or synthetic drugs that pose public health threats worldwide. This study was aimed at reporting the clinical characteristics of NPS and classical illicit substances used by patients who presented to the emergency room. We conducted a retrospective cohort study on patients with suspected illicit substance use who visited the emergency department (ED) with the suspicion of illicit substance use. We divided the patients into 4 groups based on the NPS testing results: NPS positive, NPS negative, NPS combined with classical illicit drugs (INPS), and subjects with negative testing results. The majority of patients in all groups were male. The NPS users were significantly younger than those with negative results on toxic testing (26.4 vs 37.5, P = .005 < 0.05). The heart rate of NPS users was significantly faster than that of the group with negative results of toxic testing (111.1 vs 93.5 beats per minute, P = .046). The heartbeats of INPS group were also significantly faster than those with a negative result in toxicology screen (119.6 vs 93.5 beats per minute, P = .024). Those who used classical illicit drugs combined with NPS had significantly higher palpitation than those with negative results of toxic testing (27.3% vs 3.1%, P = .017). Patients who were highly suspicious of NPS use were younger, had tachycardia, felt palpitations, and had fair oxygen saturation compared to patients who were negative for urine toxicity screening., Competing Interests: The authors have no funding and conflicts of interest to disclose., (Copyright © 2023 the Author(s). Published by Wolters Kluwer Health, Inc.)

Submerged plasma-assisted discharge direct patterning of diamond-like carbon (DLC) onto the silicon substrate in ambient conditions has succeeded as a new and novel soft solution process. In this environmentally benign technique, a copious amount of pure ethanol (ca. 4 mL) was locally activated with a maximum of ca. 0.23 mkWh by an as-electrochemically synthesized ultrasharp tungsten tip. With the assisted submerged plasma, the decomposed ethanol molecules are anodically patterned directly onto the silicon substrate in ambient conditions. The physical nature of DLC patterns was accessed by profilometry, atomic force microscopy, scanning electron microscopy, and transmission electron microscopy analysis. Furthermore, Fourier-transform infrared, Raman, and X-ray photoelectron spectra were analyzed for chemical compositions and structures, such as surface functionalization, carbon-carbon bonding, and sp 2 -sp 3 ratio, respectively. From a Berkovich-configured nanoindentation analysis, Young's modulus and hardness have shown increasing trend with increasing sp 3 -sp 2 ratio in DLC patterns of 68.5 and 2.8 GPa, respectively. From the electrochemical cyclovoltammetry analysis, a maximum areal specific capacitance of 205.5 μF/cm 2 has been achieved at a scan rate of 5 mV/s. The one-step, green, and environmentally sustainable approach of rapid formation of DLC patterns is thus a promising technique for various carbon-based electrode fabrication processes., Competing Interests: The authors declare no competing financial interest., (© 2023 The Authors. Published by American Chemical Society.)

The discovery of new effective and safe antimalarial drugs is mandatory. In this report, we formulate and evaluate transdermal (td) 1,2,6,7-tetraoxaspiro[7.11]nonadecane (N-89) using the Plasmodium berghei rodent malaria parasite in vivo model. The selected solvent for the ointment type of td N-89 was polyethylene glycol (PEG) [PEG400:PEG 4000 = 8:1 (v/w)]. We tested different application areas of 4, 6, and 8 cm 2 on the shaved backs of mice. Pharmacokinetic (PK) analysis of N-89 parameters after a single 4 cm 2 transdermal application revealed that the T max was 2 h, the T 1/2 was 1.9 h, and the AUC was 1951.1 ng . h/mL. More than 10 ng/mL of plasma concentration was maintained for 12 h. The ED 50 values for the 4, 6, and 8 cm 2 application areas in a 4-day suppressive test were 18.9, 25.1, and 26.8 mg/kg, respectively. We additionally tested the cure effect of td N-89 in mice at a dose of 60 mg/kg, twice daily for 4 days at 0.2% parasitemia. Parasites disappeared following day 7 post-treatment in all td N-89 treated groups. Mice were cured without any parasite recurrence or dermal irritation. In conclusion, this study determined for the first time the PK parameters and effect of a new ointment type of td N-89. This suggests that transdermal treatment with N-89 is an effective and safe alternative route for the treatment of malaria, especially in children., Competing Interests: Declaration of Competing Interest The authors have no conflict of interest., (Copyright © 2022 Elsevier B.V. All rights reserved.)

The androgen-dependent or -independent pathways are regarded as primary therapeutic targets for the neoplasm of the prostate. Mucosa-associated lymphoid tissue 1 (MALT1) acting as a paracaspase in the regulation of nuclear factor κB (NF-κB) signal transduction plays a central role in inflammation and oncogenesis in cancers. This study confirmed the potential linkages between androgen and NF-κB activation by inducing MALT1 in the androgen receptor-full length (ARFL)-positive LNCaP and 22Rv1 prostate cancer cells. Although androgen did not stimulate MALT1 expression in AR-null or ectopic ARFL-overexpressed PC-3 cells, the ectopic overexpression of the AR splicing variant 7 (ARv7) upregulated MALT1 to activate NF-κB activities in 22Rv1 and PC-3 cells. Since the nuclear translocation of p50 and p65 was facilitated by ARv7 to motivate NF-κB activity, the expressions of MALT1, prostate-specific antigen (PSA), and N-myc downstream regulated 1 (NDRG1) were therefore induced in ectopic ARv7-overexpressed prostate cancer cells. Ectopic ARv7 overexpression not only enhanced 22Rv1 or PC-3 cell growth and invasion in vitro but also the tumor growth of PC-3 cells in vivo. These results indicate that an androgen receptor induces MALT1 expression androgen-dependently and -independently in ARFL- or ARv7-overexpressed prostate cancer cells, suggesting a novel ARv7/MALT1/NF-κB-signaling pathway may exist in the cells of prostate cancer.

Spectrally encoded confocal microscopy (SECM) is a high-speed reflectance confocal microscopy technique. Here, we present a method to integrate optical coherence tomography (OCT) and SECM for complementary imaging by adding orthogonal scanning to the SECM configuration. The co-registration of SECM and OCT is automatic, as all system components are shared in the same order, eliminating the need for additional optical alignment. The proposed multimode imaging system is compact and cost-effective while providing the benefits of imaging aiming and guidance. Furthermore, speckle noise can be suppressed by averaging the speckles generated by shifting the spectral-encoded field in the direction of dispersion. Using a near infrared (NIR) card and a biological sample, we demonstrated the capability of the proposed system by showing SECM imaging at depths of interest guided by the OCT in real time and speckle noise reduction. Interfaced multimodal imaging of SECM and OCT was implemented at a speed of approximately 7 frames/s using fast-switching technology and GPU processing.

Biochip-based research is currently evolving into a three-dimensional and large-scale basis similar to the in vivo microenvironment. For the long-term live and high-resolution imaging in these specimens, nonlinear microscopy capable of label-free and multiscale imaging is becoming increasingly important. Combination with non-destructive contrast imaging will be useful for effectively locating regions of interest (ROI) in large specimens and consequently minimizing photodamage. In this study, a label-free photothermal optical coherence microscopy (OCM) serves as a new approach to locate the desired ROI within biological samples which are under investigation by multiphoton microscopy (MPM). The weak photothermal perturbation in sample by the MPM laser with reduced power was detected at the endogenous photothermal particles within the ROI using the highly sensitive phase-differentiated photothermal (PD-PT) OCM. By monitoring the temporal change of the photothermal response signal of the PD-PT OCM, the hotspot generated within the sample focused by the MPM laser was located on the ROI. Combined with automated sample movement in the x-y axis, the focal plane of MPM could be effectively navigated to the desired portion of a volumetric sample for high-resolution targeted MPM imaging. We demonstrated the feasibility of the proposed method in second harmonic generation microscopy using two phantom samples and a biological sample, a fixed insect on microscope slide, with dimensions of 4 mm wide, 4 mm long, and 1 mm thick., (© 2023. The Author(s).)

We have previously reported 1,2,6,7-tetraoxaspiro [7.11]nonadecane (N-89) as a promising antimalarial compound. In this study, we evaluated the effect of transdermal therapy (tdt) of N-89 in combination (tdct) with other antimalarials as an application for children. We prepared ointment formulas containing N-89 plus another antimalarial drug, specifically, mefloquine, pyrimethamine, or chloroquine. In a 4-day suppressive test, the ED 50 values for N-89 alone or combined with either mefloquine, pyrimethamine, or chloroquine were 18, 3, 0.1, and 3 mg/kg, respectively. Interaction assays revealed that N-89 combination therapy showed a synergistic effect with mefloquine and pyrimethamine, but chloroquine provoked an antagonistic effect. Antimalarial activity and cure effect were compared for single-drug application and combination therapy. Low doses of tdct N-89 (35 mg/kg) combined with mefloquine (4 mg/kg) or pyrimethamine (1 mg/kg) gave an antimalarial effect but not a cure effect. In contrast, with high doses of N-89 (60 mg/kg) combined with mefloquine (8 mg/kg) or pyrimethamine (1 mg/kg), parasites disappeared on day 4 of treatment, and mice were completely cured without any parasite recurrence. Our results indicated that transdermal N-89 with mefloquine and pyrimethamine provides a promising antimalarial form for application to children.

Objective: Sacroiliac joint (SIJ) pain is a common cause of chronic low back pain. Full-endoscopic rhizotomy of lateral branches of dorsal rami innervating SIJ is a potential option for patients' refractory to medical treatment. The full-endoscopic rhizotomy is sometimes challenging under fluoroscopic guidance. This study is to evaluate the effectiveness of the navigation-assisted full-endoscopic rhizotomy for SIJ pain., Methods: The study was a retrospective match-paired study that enrolled consecutive patients undergoing navigation-assisted full-endoscopic rhizotomy for SIJ pain. The patient demographics, clinical outcomes, and operative parameters of endoscopic rhizotomy were compared with conventional cooled radiofrequency ablation (RFA) treatment., Results: The study enrolled 72 patients, including 36 patients in the endoscopic group. Thirty-six patients in the cooled RFA group were matched by age as the control. The follow-up time was at least 1 year. Patient characteristics were similar between the groups. The navigation-assisted endoscopic rhizotomy operation time was significantly longer than the cooled RFA. The visual analogue scale (VAS) for pain and Oswestry Disability Index (ODI) significantly decreased after each treatment. However, the between-group comparison revealed that the VAS and ODI of the patients after endoscopic rhizotomy were significantly lower than those after the cooled RFA group. There were no postoperative complications in the study., Conclusion: Navigation-assisted full-endoscopic rhizotomy is an alternative to SIJ pain treatment. Integrating intraoperative navigation can ensure accurate full-endoscopic rhizotomy to provide better durability of pain relief than the cooled RFA.

The discovery of new antimalarial drugs can be developed using asynchronized Plasmodium berghei malaria parasites in vivo in mice. Studies on a particular stage are also required to assess the effectiveness and mode of action of drugs. In this report, we used endoperoxide 6-(1,2,6,7-tetraoxaspiro [7.11] nonadec-4-yl) hexan-1-ol (N-251) as a model antimalarial compound on P. chabaudi parasites. We examined the antimalarial effect of N-251 against ring-stage- and trophozoite-stage-rich P. chabaudi parasites and asynchronized P. berghei parasites using the 4-day suppressive test. The ED50 values were 27, 22, and 22 mg/kg, respectively, and the antimalarial activity of N-251 was verified in both rodent malaria parasites. To assess the stage-specific effect of N-251 in vivo, we evaluated the change of parasitemia and distribution of parasite stages using ring-stage- and trophozoite-stage-rich P. chabaudi parasites with one-day drug administration for one life cycle. We discovered that the parasitemias decreased after 13 and 9 hours post-treatment in the ring-stage- and trophozoite-stage-rich groups, respectively. Additionally, in the ring-stage-rich N-251 treated group, the ring-stage parasites hindered trophozoite parasite development. For the trophozoite-stage-rich N-251 treated group, the distribution of the trophozoite stage was maintained without a change in parasitemia until 9 hours. Because of these findings, it can be concluded that N-251 suppressed the trophozoite stage but not the ring stage. We report for the first time that N-251 specifically suppresses the trophozoite stage using P. chabaudi in mice. The results show that P. chabaudi is a reliable model for the characterization of stage-specific antimalarial effects.

Background: The diagnosis of acute mountain sickness, which lacks a reliable and objective diagnostic tool, still depends on the clinical symptoms and signs and remains a major threat and unpredictable disease affecting millions of mountaineers., Objectives: To record electroencephalography signals with small, convenient, wireless equipment and to test whether electroencephalography parameters, which are more sensitive and reliable markers, could predict the symptoms of acute mountain sickness., Methods: Twenty-five participants were enrolled and separated into two groups to climb Mount Jade in Taiwan. We collected electrocardiography signals and arterial oxygen saturation data at ground, moderate (2,400 m), and high altitude (3,400 m). A spectral analysis of the electrocardiography was performed to assess the study subjects' electroencephalography activity at different frequencies (α, β, θ, δ) and the mean power frequency of electrocardiography. The clinical symptoms and Lake Louise Acute Mountain Sickness scores of the subjects were recorded for comparison., Results: A significant change in the δ power of electroencephalography was recorded in subjects ascending from the ground to a high altitude of 3,400 m in a 4-day itinerary. In addition, between the two groups of subjects with and without acute mountain sickness (Lake Louise Acute Mountain Sickness scores < 3 and ≥ 3), the δ power of electroencephalography at the fronto-parietal 1 and parietal 3 electrodes at moderate altitude as well as the changes of δ power and mean power frequency of electrocardiography over parietal 4 at high altitude showed a significant difference. At moderate altitude, the increasing δ power of electroencephalography at the parietal 4 electrode was related to the headache symptom of acute mountain sickness before ascending to high altitude., Conclusion: At moderate altitude, the δ power increase of electroencephalography at the P4 electrode could be a predictor of acute mountain sickness symptoms before ascending to high altitude. Thus, electroencephalography had the potential to identify the risk of acute mountain sickness., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2022 Chang et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Caffeic acid phenethyl ester (CAPE), a bioactive component of propolis, has beneficial effects on cancer prevention. Growth differentiation factor 15 (GDF15) is an antitumor gene of bladder cancer. Therefore, this study investigated the anti-cancer effect of CAPE on bladder carcinoma cells and related mechanisms., Methods: The expressions of GDF15, N-myc downstream-regulated gene 1 (NDRG1), and maspin, and the activations of extracellular signal regulated kinase (ERK), c-jun Nterminal kinase (JNK), p38, and 50 adenosine monophosphate-activated protein kinase (AMPK) α1/2 in human bladder cells after gene transfection or knockdown were determined by immunoblot, real-time reverse transcriptase-polymerase chain reaction (RT-qPCR), and reporter assays. The assays of 5-ethynyl-2'-deoxyuridine (EdU), CyQUANT cell proliferation, and Matrigel invasion, and the xenograft animal study were used to assess the cell proliferation, invasion, and tumorigenesis., Results: GDF15 expression in epithelial cells was negatively correlated with neoplasia in vitro. Also, GDF15 exhibits in bladder fibroblasts and smooth muscle cells. CAPE-induced expressions of NDRG1 and maspin decreased cell proliferation and invasion of bladder carcinoma cells in a GDF15-dependent manner in vitro. The xenograft animal study suggesting CAPE attenuated tumor growth in vivo. CAPE increased phosphorylation of ERK, JNK, p38, and AMPKα1/2 to modulate the GDF15 expressions. Pretreatments with ERK, JNK, or p38 inhibitors partially inhibited the CAPE effects on the inductions of GDF15, NDRG1, or maspin. Knockdown of AMPKα1/2 attenuated the CAPE-induced GDF15 expression and cell proliferation in bladder carcinoma cells., Conclusions: Our findings indicate that CAPE is a promising agent for anti-tumor growth in human bladder carcinoma cells via the upregulation of GDF15., Competing Interests: Declaration of competing interest The authors declare no conflicts of interest., (Copyright © 2021 Chang Gung University. Published by Elsevier B.V. All rights reserved.)

The WNT1 inducible signaling pathway protein 1 (WISP1), a member of the connective tissue growth factor family, plays a crucial role in several important cellular functions in a highly tissue-specific manner. Results of a RT-qPCR indicated that WISP1 expressed only in cells of the human prostate fibroblasts, HPrF and WPMY-1, but not the prostate carcinoma cells in vitro. Two major isoforms (WISP1v1 and WISP1v2) were identified in the HPrF cells determined by RT-PCR and immunoblot assays. The knock-down of a WISP1 blocked cell proliferation and contraction, while treating respectively with the conditioned medium from the ectopic WISP1v1- and WISPv2-overexpressed 293T cells enhanced the migration of HPrF cells. The TNFα induced WISP1 secretion and cell contraction while the knock-down of WISP1 attenuated these effects, although TNFα did not affect the proliferation of the HPrF cells. The ectopic overexpression of WISP1v1 but not WISP1v2 downregulated the N-myc downstream regulated 1 (NDRG1) while upregulating N-cadherin, slug, snail, and vimentin gene expressions which induced not only the cell proliferation and invasion in vitro but also tumor growth of prostate carcinoma cells in vivo. The results confirmed that WISP1 is a stroma-specific secreting protein, enhancing the cell migration and contraction of prostate fibroblasts, as well as the proliferation, invasion, and tumor growth of prostate carcinoma cells.

Thin film catalysts, giving a different morphology, provide a significant advantage over catalyst particles for the gas evolution reaction. Taking the advantages of sputter deposition, a high entropy alloy (HEA) thin film electrocatalyst is hereby reported for the oxygen evolution reaction (OER). The catalyst characteristics are investigated not only in its as-deposited state, but also during and after the OER. For comparison, unary, binary, ternary, and quaternary thin film catalysts are prepared and characterized. The surface electronic structure modification due to the addition of a metal is studied experimentally and theoretically using density functional theory calculation. It is demonstrated that sputtered FeNiMoCrAl HEA thin film exhibits OER performance superior to all the reported HEA catalysts with robust electrocatalytic activity having a low overpotential of 220 mV at 10 mA cm -2 , and excellent electrochemical stability at different constant current densities of 10 and 100 mA cm -2 for 50 h. Furthermore, the microstructure transformation is investigated during the OER, which is important for the understanding of the OER mechanism provided by HEA electrocatalyst. Such a finding will contribute to future catalyst design., (© 2022 Wiley-VCH GmbH.)

Functions of metallothionein 2A (MT2A) in bladder cancer have not been extensively explored even though metallothioneins are regarded as modulators in several biological regulations including oxidation and cancerous development. We evaluated MT2A in bladder carcinoma cells in terms of the mechanisms of regulation and the underlying functions. MT2A overexpression not only downregulated endogenous ROS but also blocked ROS induced by H 2 O 2 . We used the annexin V-FITC apoptosis assay to determine the modulation of H 2 O 2 -induced cell apoptosis by MT2A expression. Results of immunoblot and reporter assays indicated that caffeic acid phenethyl ester (CAPE) treatment induced MT2A and heme oxygenase-1 (HO-1) expressions; moreover, the involvement of CAPE in either upregulation of the HO-1 expression or downregulation of endogenous ROS is MT2A dependent in bladder carcinoma cells. Knockdown of MT2A increased invasion and cell growth in vitro and in vivo, whereas ectopic overexpression of MT2A had the reverse effect in bladder carcinoma cells. Unlike bladder cancer tissues, the real-time reverse transcriptase-polymerase chain reaction (RT-qPCR) analysis showed a significant level of MT2A mRNA in the normal bladder tissues. Collectively, our results indicated that MT2A is acting as an antioxidant and also a tumor suppressor in human bladder carcinoma cells.