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Ferroptosis, a mode of cell death characterized by iron-dependent phospholipid peroxidation, has a substantial therapeutic potential for the treatment of various cancers. This study investigated the effects of trifluoperazine (TFP), an FDA-approved drug traditionally utilized for mental health disorder, on oral cancer cells, with a particular focus on the mechanisms involved in its potential anti-tumor properties. Our findings indicate that TFP significantly elevates the levels of lipid-derived reactive oxygen species (ROS) and induces ferroptotic cell death in oral cancer cells through pathways involving autophagy, the SLC7A11/GPX4 axis, and mitochondrial damage. Additionally, molecular docking analyses revealed that TFP acts as an inhibitor of GPX4. The elevated expression level of GPX4 in oral cancer biopsies was also found to correlate with a poor prognosis. Together, these results provide evidence that TFP selectively induces GPX4-mediated, autophagy-dependent ferroptosis, thereby exerting anti-cancer effects against oral cancer and preventable death., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

Aims: To examine the effectiveness of a virtual reality simulation (VRS) triage in improving students' learning motivation, attitudes, satisfaction and learning experiences in an emergency nursing course., Background: VR facilitates the realization of clinical scenarios that are significant for teaching emergency nursing. Triage presents a unique challenge in emergency nursing courses, where practical learning opportunities are seldom available., Design: The study employed a convergent parallel mixed-methods design., Methods: A total of 164 third-year nursing students were recruited from an emergency nursing course. The experimental group of 73 students participated in a VRS triage program and the control group of 91 students received a traditional program based on written case studies. The learning outcomes were evaluated using the Attention, Relevance, Confidence and Satisfaction motivational learning inventory together with questionnaires on learning attitudes and satisfaction. Qualitative data were collected through phenomenographic interviews., Results: The learning outcomes from the experimental group showed significant improvement in motivational learning inventory scores, with the greatest increase in satisfaction, followed by confidence, attention and relevance. Qualitative interviews with 30 students revealed four main themes in their learning experiences: "reflecting a real-world clinical environment," "enabling the internalization of knowledge," "enhancing clinical skills proficiency," and "cultivating a positive attitude toward patient care." The core theme was the establishment of professional core competency., Conclusions: VRS learning shows positive outcomes in enriching students' learning experiences. This study contributes to the literature on the use of VR technology in nursing education by offering insights into the effectiveness of VRS learning., Competing Interests: Declaration of Competing Interest The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Background: To evaluate the association between the pulmonary vein (PV) entry site morphology after total anomalous pulmonary vein repair (TAPVC) and postoperative pulmonary vein stenosis (PVS)., Methods: Computed tomography (CT) examination was performed to determine the PV entry site morphology. The width of the PV confluence was divided by the width of the left atrium (LA) to obtain the cPV/LA index. The cPV/LA index was compared between patients with and without postoperative PVS., Results: Fifty-one patients who had undergone CT after TAPVC repair were included, with a median cPV/LA index of 0.5 (interquartile range (IQR) = 0.349-0.654). Among them, 27 patients developed postoperative PVS. The median cPV/LA index after primary TAPVC repair was significantly lower in patients with PVS compared to those without PVS (0.367, IQR = 0.308-0.433 vs. 0.657, IQR = 0.571-0.783, P < 0.0001). Additionally, the cPV/LA index after surgical re-intervention for PVS was significantly smaller in patients who developed recurrent stenosis compared to those who remained free-from re-stenosis after surgical relief (0.459, IQR = 0.349-0.556; vs. 0.706, IQR = 0.628-0.810, P = 0.0045)., Conclusion: A small PV confluence width is associated with the development of postoperative PVS and recurrent stenosis after surgical relief of PVS. Our results suggest that adequate bilateral pulmonary vein lateralization during TAPVC surgery is crucial., Competing Interests: Declaration of competing interest All the authors reported no conflicts of interest., (Copyright © 2024 Formosan Medical Association. Published by Elsevier B.V. All rights reserved.)

Objective: Microglia in the central nervous system regulate neuroinflammation that leads to a wide range of neuropathological alterations. The present study investigated the anti-neuroinflammatory properties of nobiletin (Nob) derivative, 5-acetoxy-6,7,8,3',4'-pentamethoxyflavone (5-Ac-Nob), in lipopolysaccharide (LPS)-activated BV2 microglia., Materials and Methods: By using the MTT assay, Griess method, flow cytometry, and enzyme-linked immunosorbent assay (ELISA), we determined the cell viability, the levels of nitric oxide (NO), reactive oxygen species (ROS), and pro-inflammatory factors (interleukin 1 beta; IL-1β, interleukin 6; IL-6, tumor necrosis factor alpha; TNF-α and prostaglandin E2; PGE2) in LPS-stimulated BV2 microglia. Toll-like receptor 4 (TLR4)-mediated myeloid differentiation primary response gene 88 (MyD88)/nuclear factor-kappa B (NF-κB), mitogen-activated protein kinase (MAPK) signaling pathway and signal transducer and activator of transcription 3 (STAT3) were measured by western blotting. Analysis of NO generation and mRNA of pro-inflammatory cytokines was confirmed in the zebrafish model., Results: 5-Ac-Nob reduced cell death, the levels of NO, ROS, inducible nitric oxide synthase (iNOS), cyclooxygenase 2 (COX-2), and pro-inflammatory factors in LPS-activated BV-2 microglial cells. TLR4-mediated MyD88/NF-κB and MAPK pathway (p38, ERK and JNK) after exposure to 5-Ac-Nob was also suppressed. Moreover, 5-Ac-Nob inhibited phosphorylated STAT3 proteins expression in LPS-induced BV-2 microglial cells. Furthermore, we confirmed that 5-Ac-Nob decreased LPS-induced NO generation and mRNA of pro-inflammatory cytokines in the zebrafish model., Conclusions: Our findings suggest that 5-Ac-Nob represses neuroinflammatory responses by inhibiting TLR4-mediated signaling pathway and STAT3. As a result of these findings, 5-Ac-Nob has potential as an anti-inflammatory agent against microglia-mediated neuroinflammatory disorders.

Diabetic retinopathy (DR), which can cause vision loss, may progress faster with poor glycemic control and oxidative stress. This study aims to examine how dietary patterns and glycemic control biomarkers relate to retinopathy risk in type 2 diabetes patients. In this study, we enrolled diabetic patients with retinopathy (DR) ( n = 136) and without retinopathy (no DR) ( n = 466) from a cohort of participants in the "Blood Pressure Control to Reduce the Risk of Type 2 Diabetic Nephropathy Study". Hemoglobin A1c (HbA1c) and malondialdehyde were defined as elevated when their levels reached ≥8.5% and ≥2/3 (16.2 μm), respectively. Dietary data were collected by a food frequency questionnaire. Dietary patterns were identified by factor analysis. Elevated HbA1c was significantly correlated with increased risk of DR (OR: 2.12, 95% CI: 1.14-3.93, p = 0.017). In subjects with a high animal protein and processed food dietary pattern (≥highest tertile score) or a low vegetable intake pattern (

Resveratrol, acting as a prebiotic, and propionate, functioning as a postbiotic, hold promise for preventing hypertension in chronic kidney disease (CKD). Previously, we employed propionate to enhance the bioavailability of resveratrol through esterification, resulting in the production of a resveratrol propionate ester (RPE) mixture. In this study, we purified 3-O-propanoylresveratrol (RPE2) and 3,4'-di-O-propanoylresveratrol (RPE4) and investigated their protective effects in a juvenile rat adenine-induced CKD model. To this end, male Sprague Dawley rats aged three weeks ( n = 40) were divided into five groups: control; CKD (rats fed adenine); CKRSV (CKD rats treated with 50 mg/L resveratrol); CDRPE2 (CKD rats treated with 25 mg/L RPE2); and CKRPE4 (CKD rats treated with 25 mg/L RPE 4). RPE2 and PRE4 similarly exhibited blood pressure-lowering effects comparable to those of resveratrol, along with increased nitric oxide (NO) availability. Furthermore, RPE2 and RPE4 positively influenced plasma short-chain fatty acid (SCFA) levels and induced distinct alterations in the gut microbial composition of adenine-fed juvenile rats. The supplementation of RPE2 and RPE4, by restoring NO, elevating SCFAs, and modulating the gut microbiota, holds potential for ameliorating CKD-induced hypertension.

Peptidoglycan (PG) sacculi surround the cytoplasmic membrane, maintaining cell integrity by withstanding internal turgor pressure. During cell growth, PG endopeptidases cleave the crosslinks of the fully closed sacculi, allowing for the incorporation of new glycan strands and expansion of the peptidoglycan mesh. Outer-membrane-anchored NlpI associates with hydrolases and synthases near PG synthesis complexes, facilitating spatially close PG hydrolysis. Here, we present the structure of adaptor NlpI in complex with the endopeptidase MepS, revealing atomic details of how NlpI recruits multiple MepS molecules and subsequently influences PG expansion. NlpI binding elicits a disorder-to-order transition in the intrinsically disordered N-terminal of MepS, concomitantly promoting the dimerization of monomeric MepS. This results in the alignment of two asymmetric MepS dimers respectively located on the two opposite sides of the dimerization interface of NlpI, thus enhancing MepS activity in PG hydrolysis. Notably, the protein level of MepS is primarily modulated by the tail-specific protease Prc, which is known to interact with NlpI. The structure of the Prc-NlpI-MepS complex demonstrates that NlpI brings together MepS and Prc, leading to the efficient MepS degradation by Prc. Collectively, our results provide structural insights into the NlpI-enabled avidity effect of cellular endopeptidases and NlpI-directed MepS degradation by Prc., (© 2024. The Author(s).)

Phytochemical investigation of the bark of Cryptomeria japonica led to the isolation of five new abietane diterpenoids, 5- epi -12-hydroxy-6- nor -5,6-secoabieta-8,11,13-trien-7,5-olide ( 1 ), 12-hydroxy-6β-methoxy-6,7-secoabieta-8,11,13-trien-7,6-olide ( 2 ), 6β,12-dihydroxy-7,8-secoabieta-8,11,13-trien-7,8-olide ( 4 ), 5,12-dihydroxy-7,8-secoabieta-8,11,13-trien-7,8-olide ( 5 ), and 5α,8-epoxy-12-hydroxy-7,8-secoabieta-8,11,13-trien-7-al ( 6 ), together with one known abietane diterpenoid, obtuanhydride ( 3 ). Their structures were elucidated by analysis of spectroscopic data and comparison with the spectral data of known analogs. At the concentration of 100 μg/mL, compounds 4 , 5, and 6 inhibited antifungal activities against wood decay fungi activity by 18.7, 37.2, and 46.7%, respectively.

Angiotensin I-converting enzyme (ACE) inhibition is currently a common method for the treatment and control of hypertension. In this study, four new (1-4) and one known (5) cycloartane triterpenoids were isolated from the leaves of Swietenia macrophylla by chromatographic techniques and identified by their spectroscopic data and a comprehensive comparison of published data. The triterpenoids were evaluated for their ACE inhibitory potential using in vitro inhibition assays and in silico methods. The inhibition assay and enzyme kinetics results showed that the most active triterpenoid, compound 4, inhibited ACE in a mixed-type manner with an IC 50 value of 57.7 ± 6.07 μM. Computer simulations revealed that compound 4 reduces the catalytic efficiency of ACE by competitive insertion into the active pocket blocking the substrate, and the binding activity occurs mainly through hydrogen bonds and hydrophobic interactions. The study showed that S. macrophylla can be a source of bioactive material and the ACE inhibitory triterpenoid could be a potential antihypertensive agent., 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 © 2024 Elsevier B.V. All rights reserved.)

Liver fibrosis occurs due to injury or inflammation, which results in the excessive production of collagen and the formation of fibrotic scar tissue that impairs liver function. Despite the limited treatment options available, freshwater clams may hold promise in the treatment of liver fibrosis. In this study, we demonstrated the effects of ethanol extract of freshwater clam (FCE), ethyl acetate extract of FCE (EA-FCE), and trans-2-nonadecyl-4-(hydroxymethyl)-1,3-dioxolane (TNHD) on liver fibrosis induced by dimethylnitrosamine (DMN). Administration of FCE and TNHD alleviated liver injury, including tissue damage, necrosis, inflammation scores, fibrosis scores, serum enzymes, and triglyceride levels. Furthermore, we analyzed the expression of fibrosis-related proteins, such as α-smooth muscle actin (α-SMA) and transforming growth factor (TGF-β), as well as the hydroxyproline content, which decreased after treatment with FCE and TNHD. Animal experiments revealed that FCE and TNHD can reduce liver fibrosis by inhibiting cytokines that activate stellate cells and decreasing extracellular matrix (ECM) secretion. Cell experiments have shown that TNHD inhibits the MAPK/Smad signaling pathway and TGF-β1 activation, resulting in a reduction in the expression of fibrosis-related proteins. Therefore, freshwater clam extracts, particularly TNHD, may have potential therapeutic and preventive effects for the amelioration of liver fibrosis.

In patients with esophageal cancer undergoing neoadjuvant chemoradiotherapy (nCRT), subsequent restaging with F-18-fluorodeoxyglucose (18F-FDG) positron emission tomography-computed tomography (PET-CT) can reveal the presence of interval metastases, such as liver metastases, in approximately 10% of cases. Nevertheless, it is not uncommon in clinical practice to observe focal FDG uptake in the liver that is not associated with liver metastases but rather with radiation-induced liver injury (RILI), which can result in the overstaging of the disease. Liver radiation damage is also a concern during distal esophageal cancer radiotherapy due to its proximity to the left liver lobe, typically included in the radiation field. Post-CRT, if FDG activity appears in the left or caudate liver lobes, a thorough investigation is needed to confirm or rule out distant metastases. The increased FDG uptake in liver lobes post-CRT often presents a diagnostic dilemma. Distinguishing between radiation-induced liver disease and metastasis is vital for appropriate patient management, necessitating a combination of imaging techniques and an understanding of the factors influencing the radiation response. Diagnosis involves identifying new foci of hepatic FDG avidity on PET/CT scans. Geographic regions of hypoattenuation on CT and well-demarcated regions with specific enhancement patterns on contrast-enhanced CT scans and MRI are characteristic of radiation-induced liver disease (RILD). Lack of mass effect on all three modalities (CT, MRI, PET) indicates RILD. Resolution of abnormalities on subsequent examinations also helps in diagnosing RILD. Moreover, it can also help to rule out occult metastases, thereby excluding those patients from further surgery who will not benefit from esophagectomy with curative intent.

BACKGROUND An aortopulmonary window (APW) is an uncommon congenital defect of the septation between the ascending aorta and pulmonary trunk. The combination of APW and interrupted aortic arch (IAA) is even rarer, with the hallmark characteristics of high peri-operative mortality and postoperative obstruction of the aortic arch, pulmonary artery, and left main bronchus. These complications often need re-interventions. CASE REPORT We present 2 cases with diagnoses of APW and IAA that were treated with single-stage repair. Case 1: A male 32-week premature newborn (weight 1789 g) had APW type I and IAA type A. He had severe postoperative aortic arch obstruction on postoperative day 1, and we re-intervened promptly. He was still asymptomatic after 6 years. Case 2: A male term neonate had APW type III and IAA type A. He had left vocal cord paralysis and left bronchial compression postoperatively. We applied prolonged noninvasive respiratory supports. The complications resolved without re-intervention on postoperative day 66. Progressive arch stenosis at anastomosis after operation required close follow-up with echocardiography. CONCLUSIONS These 2 reports highlight the feasibility of single-stage surgical repair while addressing 2 challenges: (1) Recurrent arch stenosis: Lower body weight and direct end-to-side anastomosis without patch augmentation could be risk factors for re-intervention. (2) Bronchial compression: Presentation of the second reported case implied that bronchial compression may not warrant immediate re-intervention unless there is complete obstruction, persistent atelectasis, or recurrent infection. Further studies on long-term outcomes of different surgical procedure would help us to clarify the proper way to avoid re-intervention.

While the gut microbiota is known to be influenced by habitual food intake, this relationship is seldom explored in type 2 diabetes patients. This study aims to investigate the relationship between dietary patterns and gut microbial species abundance in 113 type 2 diabetes patients (mean age, 58 years; body mass index, 29.1; glycohemoglobin [HbA1c], 8.1%). We analyzed the gut microbiota using 16S amplicon sequencing, and all patients were categorized into either the Bacteroides enterotype (57.5%, n = 65) or the Prevotella enterotype (42.5%, n = 48) using the partitioning around medoids clustering algorithm, based on the most representative genera. Patients with the Bacteroides enterotype showed better glycemic control with a 2.71 odds of HbA1c ≤ 7.0% compared to the Prevotella enterotype (95% confidence interval, 1.02-7.87; P, 0.034). Dietary habits and the nutrient composition of all patients were assessed using a validated food frequency questionnaire. It was observed that the amounts of dietary fiber consumed were suboptimal, with an average intake of 16 g per day. Additionally, we extracted four dietary patterns through factor analysis: eating-out, high-sugar foods, fish-vegetable, and fermented foods patterns. Patients with the Bacteroides enterotype had higher scores for the fish-vegetable pattern compared to the Prevotella enterotype (0.17 ± 0.13 versus -0.23 ± 0.09; P, 0.010). We further investigated the relationship between the microbiota and the four dietary patterns and found that only the fish-vegetable dietary pattern scores were correlated with principal coordinate values. A lower pattern score was associated with the accumulated abundance of the 31 significant microbial features. Among these features, Prevotella copri was identified as the most significant by using a random forest model, with an area under the receiver operating characteristic of 0.93 (95% confidence interval, 0.88-0.98). To validate these results, we conducted a custom quantitative polymerase chain reaction assay. This assay confirmed the presence of P. copri (sensitivity, 0.96; specificity, 0.97) in our cohort, with a prevalence of 47.8%, and a mean relative abundance of 21.0% in subjects harboring P. copri. In summary, type 2 diabetes patients with the Prevotella enterotype demonstrated poorer glycemic control and deviations from a healthy dietary pattern. The abundance of P. copri, as a major contributing microbial feature, was associated with the severity in the deficiency in dietary fish and vegetables. Emphasis should be placed on promoting a healthy dietary pattern and understanding the microbial correlations.

Many AAA+ (ATPases associated with diverse cellular activities) proteins function as protein or DNA remodelers by threading the substrate through the central pore of their hexameric assemblies. In this ATP-dependent translocating state, the substrate is gripped by the pore loops of the ATPase domains arranged in a universal right-handed spiral staircase organization. However, the process by which a AAA+ protein is activated to adopt this substrate-pore-loop arrangement remains unknown. We show here, using cryo-electron microscopy (cryo-EM), that the activation process of the Lon AAA+ protease may involve a pentameric assembly and a substrate-dependent incorporation of the sixth protomer to form the substrate-pore-loop contacts seen in the translocating state. Based on the structural results, we design truncated monomeric mutants that inhibit Lon activity by binding to the native pentamer and demonstrated that expressing these monomeric mutants in Escherichia coli cells containing functional Lon elicits specific phenotypes associated with lon deficiency, including the inhibition of persister cell formation. These findings uncover a substrate-dependent assembly process for the activation of a AAA+ protein and demonstrate a targeted approach to selectively inhibit its function within cells., (© 2023. The Author(s).)

Excessive bone resorption activity of osteoclasts is a common characteristic of osteolytic conditions such as osteoporosis and inflammatory bone diseases. Natural compounds with antiosteoclastogenic function seem to be beneficial for the treatment of osteolytic diseases. In this study, we evaluated the effects of 2,5-dihydroxyacetophenone (DHAP), a phenolic compound in Ganoderma bambusicola, on osteoclastogenesis induced in vitro by the receptor activator of nuclear factor-κB ligand (RANKL). DHAP inhibited the differentiation, actin ring formation, and bone resorption activity of osteoclasts. In particular, DHAP inhibited the transcriptional activity of nuclear factor of activated T-cells cytoplasmic 1 (NFATc1) during osteoclastogenesis. This inhibition resulted in reduced expression levels of cathepsin k (Ctsk), tartrate-resistant acid phosphatase (Trap), and NFATc1 (Nfatc1), thereby reducing the differentiation of osteoclasts. However, DHAP did not affect reactive oxygen species production or activator protein 1 (AP-1) and nuclear factor kappa B (NF-κB) signaling. Our findings suggest that DHAP inhibits RANKL-induced osteoclastogenesis by inhibiting the NFATc1 signaling pathway., 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. Published by Elsevier Ltd.)

Although the incidence of invasive breast cancer (BC) among women in Asian is generally lower than that in Western countries, the incidence of BC has been on the rise in the past three decades in Asian countries. This hospital-based case-control study aimed to explore the relationship between dietary and metabolic factors and BC risk in pre- and post-menopausal women. We enrolled 285 patients with newly diagnosed BC at the National Taiwan University Hospital and 297 controls from the local community and hospital staff. Before receiving anticancer therapy, all patients with BC and control participants completed a 57-question semi-quantitative Food Frequency Questionnaire. For pre-menopausal women, plant-based factor scores rich in seeds and nuts, soy, fruits, and seaweeds correlated significantly with reduced BC risks, whereas menarche occurring at <12 years of age, reduced physical activity, and high-density lipoprotein <40 mg/dL were associated with increased BC risks. For post-menopausal women, plant-based dietary factor scores were also associated with reduced risks, whereas increased body mass index and energy intake levels correlated with increased BC risks. Diets rich in plant-based dietary patterns are protective against BC risk, regardless of menopausal status. Habitual physical activity is protective against BC risk among pre-menopausal Taiwanese women. Maintaining optimal weight and caloric intake is beneficial for reducing post-menopausal BC risk.

Background: Studies comparing the effectiveness of either adjuvant oral uracil-tegafur (UFT) or intravenous chemotherapy on early-stage (stage I and II) non-small cell lung cancer (NSCLC) patients treated with complete surgical treatment remain limited., Methods: From January 2011 to December 2017, patients with early-stage NSCLC (defined as tumor size >3 cm without mediastinal lymph node involvement or any distant metastasis) receiving either adjuvant oral UFT or intravenous chemotherapy after surgical resection were identified from the Taiwan Cancer Registry. Overall survival (OS) and relapse-free survival (RFS) were the primary and secondary outcomes, respectively. Propensity matching was used for controlling confounders., Results: A total of 840 patients receiving adjuvant therapy after surgery (including 595 oral UFT and 245 intravenous chemotherapy) were enrolled. Before matching, patients using oral UFT had significantly longer OS (HR: 0.69, 95% CI: 0.49-0.98, p = 0.0387) and RFS (HR: 0.79, 95% CI: 0.61-0.97, p = 0.0392) than those with intravenous chemotherapy. A matched cohort of 352 patients was created using 1:1 propensity score-matching. In the Cox regression analysis, the UFT and the matched chemotherapy groups had similar OS (HR: 0.80, 95% CI: 0.48-1.32, p = 0.3753) and RFS (HR: 0.98, 95% CI: 0.72-1.34, p = 0.9149). Among subgroup analysis, oral UFT use was associated with longer RFS among the subgroups of non-drinker (HR: 0.66, 95% CI: 0.34-0.99, p = 0.0478) and patients with stage IB disease (HR: 0.67, 95% CI: 0.42-0.97, p = 0.0341)., Conclusions: This population-based study in the real-world setting of Taiwan demonstrates comparable effectiveness between oral UFT and intravenous chemotherapy in terms of clinical outcomes for early-stage NSCLC patients after surgery., (© 2023 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

Background: Prenatal diagnosis of congenital heart disease (CHD) often leads affected families to experience psychological stress. Pediatric cardiology consultation is important in providing parents with sufficient information and reducing their anxiety to make an informed pregnancy decision. Involving a fetal nurse coordinator may optimize fetal anomaly care. Our study aimed to identify factors associated with parental decision-making for choosing to use pediatric cardiology consultations and pregnancy termination., Methods: From September 2017 to December 2018, all fetal CHD cases diagnosed in the second trimester from a primary screening clinic in Taiwan were included (n = 145). Univariate and multivariate logistic regression were performed to analyze maternal, fetal, and medical factors for predictors of parental decisions for consultation use and pregnancy termination., Results: Acceptance for fetal nurse coordinator care and pediatric cardiology consultation were 84.8% (n = 123) and 83.4% (n = 121), respectively. Predictors for termination of pregnancy included the following: multiple anomalies (OR: 10.6; 95% CI: 3.6-35.7), chromosomal/genetic abnormalities (OR: 20.2; 95% CI: 3.1-395.8), severe CHDs (OR: 9.8; 95% CI: 4.3-23.4), CHDs that required surgery (OR: 32.4; 95% CI: 11.4-117.8), and physiological single-ventricle (OR: 47.3; 95% CI: 12.4-312.5). Parents who had pediatric cardiology counseling were less likely to terminate the pregnancy (OR: 0.1; 95% CI: 0.0-0.7). Parents with fetal diagnosis having multiple anomalies (OR: 0.2; 95% CI: 0.1-0.7) or chromosomal/genetic abnormalities (OR: 0.1; 95% CI: 0.03-0.9) were less likely to make use of cardiology consultation. Parents who accepted fetal nurse coordinator care were more likely to have pediatric cardiology consultation before pregnancy decision (OR: 149.5, 95% CI: 37.8-821.5)., Conclusions: Anomaly complexity appeared to be a strong predictor for termination of pregnancy beyond non-acceptability of prenatal cardiology consultation. Prenatal cardiology counseling may help support the parental decision to continue with the pregnancy. Incorporation of a fetal nurse coordinator care into the multidisciplinary fetal medicine team improved the acceptability of prenatal consultation., Competing Interests: Declaration of competing interest The authors state that they do not have any conflict of interests., (Copyright © 2022 Taiwan Pediatric Association. Published by Elsevier B.V. All rights reserved.)

Objectives: To mitigate the shortage of homograft sources, the use of handmade trileaflet expanded polytetrafluoroethylene valves in pulmonary valve replacement has shown excellent results from multicentre studies conducted in Japan. However, world-wide data outside Japan are relatively insufficient. This study presents the long-term results of a single surgeon's use of flipped-back trileaflet method in a 10-year case series., Methods: We have developed an efficient way to make a trileaflet-valved conduit utilizing flipped-back method for pulmonary valve replacement and have employed the technique since 2011. Retrospective data were studied between October 2010 and January 2020. Echocardiography, electrocardiogram, Pro-Brain Natriuretic Peptide and Magnetic Resonance Imaging data were analysed., Results: Fifty-five patients were reviewed and median follow-up duration was 2.9 years. The majority of diagnoses was Tetralogy of Fallot (n = 41), and these patients subsequently underwent secondary pulmonary valve replacement at a median age of 15.6 years. Survival was 92.7% with the longest follow-up period being 10 years. There was no need for reoperation, and freedom from reintervention was 98.0% at 10 years. There were 4 deaths (3 in-hospital and 1 outpatient). One patient eventually received transcatheter pulmonary valve implantation. Postoperative echocardiography showed mild or less pulmonary stenosis and pulmonary regurgitation degree in 92.2% and 92.0% of patients, respectively. Comparable magnetic resonance imaging data (n = 25) showed significant reduction in right ventricular volumes but not in ejection fractions., Conclusions: Our series showed satisfactory long-term function of handmade flipped-back trileaflet-valved conduit used in our patients. The simple design is efficiently reproducible without complex fabrication process., (© The Author(s) 2023. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.)

Background and Aim: In Taiwan, Vitis thunbergii var. taiwaniana (VTT) is used in traditional medicine and as a local tea. VTT rich in resveratrol and resveratrol oligomers have been reported to exhibit anti-obesity and anti-hypertensive activities in animal models; however, no studies have investigated type 2 diabetes mellitus (T2DM) treatments. This study aimed to investigate the anti-T2DM effects of resveratrol tetramers isolated from the VTT in nicotinamide/streptozotocin (STZ)-induced Institute of Cancer Research (ICR) mice., Experimental Procedure: The oral glucose tolerance test (OGTT) was used to imitate postprandial blood glucose (BG) regulations in mice by pre-treatment with VTT extracts, resveratrol tetramers of vitisin A, vitisin B, and hopeaphenol 30 min before glucose loads. Vitisin B (50 mg/kg) was administered to treat T2DM-ICR mice once daily for 28 days to investigate its hypoglycemic activity., Results and Conclusion: Mice pre-treated with VTT-S-95EE, or vitisin B (100 mg/kg) 30-min before glucose loading showed significant reductions ( P  < 0.001) in the area under the curve at 120-min (BG-AUC 0-120 ) than those without pre-treatment with VTT-S-95 E E or vitisin B. Vitisin B-treated T2DM mice showed hypoglycemic activities via a reduction in plasma dipeptidyl peptidase (DPP)-IV activities to maintain insulin actions and differed significantly than those of untreated T2DM mice ( P  < 0.05), and also reduced BG-AUC 0-120 and insulin-AUC 0-120 in the OGTT.These in vivo results showed that VTT containing vitisin B would be beneficial for developing nutraceuticals and/or functional foods for glycemic control in patients with T2DM, which should be investigated further., 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 Center for Food and Biomolecules, National Taiwan University. Production and hosting by Elsevier Taiwan LLC.)

A novel method for near-infrared (NIR) spectroscopy spectra standardization is presented. NIR spectroscopies have been widely used in analytical chemistry, and many methods have been developed for NIR spectra standardization. To establish a robust standardization transformation, most existing methods require spectral data sets from both primal and secondary instruments for 1-1 correspondence validation. However, this limits the usage of standardization methods. This paper investigates an interesting issue, "Can spectra data in sets be arbitrarily order?" and further develops a completely different approach from existing methods in view of statistical signal processing. The key idea is to first compensate for the distortion along the wavelength and intensity of the spectra, and then transfer the second order statistic (2OS) from the primal spectra to the secondary spectra via data sphering and an inverse sphering transform so that the 2OS can be estimated regardless of the sample statistic order. To further demonstrate how the developed method can extend the usage of the NIR spectra standardization, several application-driven experiments on classification and regression are conducted for demonstration, and a comparison to the piecewise direct standardization (PDS) is also studied., 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 Elsevier B.V. All rights reserved.)

Obesity has become a major public health issue which relate to numerous physical problems and highly comorbid with depression and anxiety. Recently, some studies of technology-based interventions for weight reduction emerged to overcome the barriers from time, cost and distance. Mood component and eating behavior related to obesity are less discussed so far with technology-based intervention though. This pilot study was aimed to investigate the effect of telehealth assisted intervention on weight reduction, mood status, and eating behavior change under a smartphone application (app) with novel 3D food picture recognition and incorporated with cognitive behavioral training programs. Adult aged 30-60 years old with overweight were recruited and randomly assigned to control-first group and intervention-first group. In period 1, control-first group had regular life and intervention-first group underwent app intervention; in period 2, two groups went crossover. Body composition and psychological/behavioral questionnaires were collected at baseline, end of period 1, and end of period 2. Nonparametric statistics was performed for data analyzing. A total of 20 participants were enrolled. In control-first group, there were statistically significant reduction in body weight (- 0.55 kg, p = 0.02) and change of body weight percentage (- 0.6%, p = 0.02) after App use. In intervention-first group, the fat percentage decreased by 0.4% after App use in period 1, and increased by 0.05% in period 2. The integrated crossover data revealed that subjects of App group had significant improvements in mindful eating behavior. This pilot study showed the effectiveness in using CogniNU app for weight control and eating behavior. The difference of short-term and long-term effectiveness of technology-based weight control intervention deserves more investigation in the future.Clinical Trial Registration: ISRCTN16082909., (© 2023. The Author(s).)

Competing Interests: The authors have no conflicts of interest relevant to this article.

The current study aimed to investigate comorbidity among symptoms of depression and internet gaming disorder (IGD) utilizing symptom network analysis in a sample of Chinese adolescents. A total of 1,362 Chinese adolescents (Mean age = 15.19 ± 1.67; range 13-21; 39.79% female, 56.02% male, 4.19% not disclosed) were recruited from 11 local secondary schools between June and July 2020. Symptoms of depression and IGD were assessed by the 7-item DASS-21 depression subscale and the 9-item Internet Gaming Disorder Scale. We conducted network analysis to estimate network models and the most central symptoms of depression and IGD and computed a combined network model of both depression and IGD symptoms to find bridge symptoms and illustrate the comorbidity between depression and IGD. We found that feeling 'Worthless', 'Meaningless', and 'Down-hearted' were identified as the most central symptoms of depression, whereas 'Preoccupation' and 'Tolerance' were the two most central symptoms of IGD. The bridge symptoms in the combined network model were 'Gaming for escape or mood relief' from the IGD cluster and 'No initiative' and 'Down-hearted" from the depression cluster. The current study was the first to investigate the relationship between depression and IGD symptoms among adolescents utilizing a symptom network perspective. Also, it highlighted key bridge symptoms in understanding how IGD and depression contribute to each other., Competing Interests: Declaration of Competing Interest None., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Salvinal is a natural lignan isolated from the roots of Salvia mitorrhiza Bunge (Danshen). Previous studies have demonstrated its anti-proliferative activity in both drug-sensitive and -resistant cancer cell lines, with IC 50 values ranging from 4-17 µM. In this study, a series of salvinal derivatives was synthesized and evaluated for the structure-activity relationship. Among the twenty-four salvinal derivatives, six compounds showed better anticancer activity than salvinal. Compound 25 displayed excellent anticancer activity, with IC 50 values of 0.13-0.14 µM against KB, KB-Vin10 (overexpress MDR/Pgp), and KB-7D (overexpress MRP) human carcinoma cell lines. Based on our in vitro microtubule depolymerization assay, compound 25 showed depolymerization activity in a dose-dependent manner. Our findings indicate that compound 25 is a promising anticancer agent with depolymerization activity that has potential for the management of malignance.

In the present work, we take the influences of activated slip systems and the orientation spread into account to predict the cup height using analytical earing models and compare the predicted results with experimental results. The effect of boundary conditions of the various stress states and the work hardening exponents are compared and discussed for profile of single crystals. A stress ratio of -0.3 and a hardening exponent of 0.3 are selected for the prediction of earing profiles. The combination of activation of the single slip systems and orientation spread provides the best prediction of deep-drawing profiles. With further consideration of the orientation spread, an increase in the total orientation leads to peak-broadening, i.e., broad and smooth ears. Furthermore, the difference of the height between the maximum and minimum value of cup profiles is reduced because of the orientation spread. The profile for C is found with single ear at 45°, while the other components individually reveal double ears at 35° and 50° for S, at 15° and 45° for B, at 0° and 90° for Cube, at 5° and 90° for r-Cube, and at 15° and 90° for G. Herein, simple analytical earing models are proposed to understand the effects of slip systems and the orientation spread. The deep-drawing profiles are predicted with six major texture components.

This study investigated the relationship between body composition parameters and changes in future liver remnant volume (FLRV) in hepatocellular carcinoma (HCC) patients undergoing portal vein embolization (PVE) in preparation for right hepatectomy. This retrospective study enrolled 21 patients between May 2013 and October 2020. Body composition parameters, including skeletal muscle attenuation (SMA), skeletal muscle mass index (SMI), intramuscular adipose tissue content (IMAC), and visceral-to-subcutaneous adipose tissue area ratio (VSR), were measured by computed tomography (CT) prior to PVE. Liver volumetry was measured before and at least 5 weeks after PVE. The mean interval between two CT volumetries was 9.1 ± 4.9 weeks, the mean value of increase in FLRV (ΔFLRV) was 236.0 ± 118.3 cm 3 , the ratio of increased FLRV (ΔFLRV%) was 55.7 ± 29.4%, and the rate of increased FLRV was 31.0 ± 18.8 (cm 3 /week). Subjects with high IMAC showed significantly lower (p = 0.044) ΔFLRV% than those with normal IMAC. Furthermore, ΔFLRV% was linearly reduced (p for trend = 0.043) among those with low Ishak fibrosis stage (<3) + normal IMAC (76.1 ± 36.8%), those with low Ishak fibrosis stage (<3) + high IMAC or high Ishak fibrosis stage (>3) + normal IMAC (54.0 ± 24.1%), and those with high Ishak fibrosis stage (>3) + low IMAC (28.7 ± 1.6%) (p for trend = 0.043). Our data indicated that high IMAC with a high Ishak fibrosis stage (>3) had a significant negative effect on ΔFLRV%., (© 2022 The Authors. The Kaohsiung Journal of Medical Sciences published by John Wiley & Sons Australia, Ltd on behalf of Kaohsiung Medical University.)

Purpose: To evaluate the effect of Chan-Chuang qigong with breathing meditation on quality of life (QoL) and interoceptive awareness in patients with breast cancer during chemotherapy., Methods: This was a randomised controlled trial. Participants were randomly assigned to a qigong group (n = 30), which practised Chan-Chuang qigong with breathing meditation for 15 weeks, and a control group (n = 30), which received routine care. Outcomes were measured by using the European Organization for Research and Treatment of Cancer QoL Questionnaire (EORTC QLQ-C30) and Multidimensional Assessment of Interoceptive Awareness (MAIA-C)., Results: The qigong group, when compared with the control group and baseline, exhibited significantly improved emotional function (p = 0.01) and decreased role function (p = 0.04) at week 15. The MAIA-C indicated a significant difference between groups in self-regulation at week 15 (p = 0.04). Within the qigong group, changes were found in attention regulation (p = 0.03), emotional awareness (p = 0.04), self-regulation (p = 0.01), and body listening (p = 0.002)., Conclusions: A 15-week programme of Chan-Chuang qigong with breathing meditation is a simple and safe intervention for patients with breast cancer to improve their emotional function and adjust to their role identity. Participants who practised qigong achieved increased awareness of their own bodies and were able to better regulate their emotion and attention., Trial Register: ClinicalTrials.gov Identifier: NCT05385146., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Chronic kidney disease (CKD) remains a public health problem. Certain dietary supplements can assist in the prevention of CKD progression. In this regard, resveratrol is a polyphenol and has a potential therapeutic role in alleviating CKD. We previously utilized butyrate in order to improve the bioavailability of resveratrol via esterification and generated a resveratrol butyrate monoester (RBM). In this study, the hypothesis that RBM supplementation is able to protect against kidney dysfunction and hypertension was tested by using an adenine-induced CKD model. For this purpose, three-week-old male Sprague Dawley rats (n = 40) were equally categorized into: group 1-CN (sham control); group 2-CKD (adenine-fed rats); group 3-REV (CKD rats treated with 50 mg/L resveratrol); group 4-MEL (CKD rats treated with 25 mg/L RBM); and group 5-MEH (CKD rats treated with 50 mg/L RBM). At the end of a 12-week period, the rats were then euthanized. The adenine-fed rats displayed hypertension and kidney dysfunction, which were attenuated by dietary supplementation with RBM. The CKD-induced hypertension coincided with: decreased nitric oxide (NO) bioavailability; augmented renal protein expression of a (pro)renin receptor and angiotensin II type 1 receptor; and increased oxidative stress damage. Additionally, RBM and resveratrol supplementation shaped distinct gut microbiota profiles in the adenine-treated CKD rats. The positive effect of high-dose RBM was shown together with an increased abundance of the genera Duncaniella , Ligilactobacillus , and Monoglobus , as well as a decrease in Eubacterium and Schaedierella . Importantly, the mechanism of action of the RBM supplementation may be related to the restoration of NO, rebalancing of the RAS, a reduction in oxidative stress, and alterations to the gut microbiota. Moreover, RBM supplementation shows promise for the purposes of improving CKD outcomes and hypertension. As such, further translation to human studies is warranted.

Context: Momordica charantia L. (Cucurbitaceae), known as bitter melon, is an edible fruit cultivated in the tropics. In this study, an active compound, 5β,19-epoxycucurbita-6,23( E )-diene-3β,19( R ),25-triol (ECDT), isolated from M. charantia was investigated in regard to its cytotoxic effect on human hepatocellular carcinoma (HCC) cells., Objective: To examine the mechanisms of ECDT-induced apoptosis in HCC cells., Materials and Methods: The inhibitive activity of ECDT on HA22T HCC cells was examined by MTT assay, colony formation assay, wound healing assay, TUNEL/DAPI staining, annexin V-fluorescein isothiocyanate/propidium iodide (PI) staining and JC-1 dye. HA22T cells were treated with ECDT (5, 10, 15, 20 and 25 μM) for 24 h, and the molecular mechanism of cells apoptosis was examined by Western blot. Cells treated with vehicle DMSO were used as the negative control., Results: ECDT inhibited the cell proliferation of HA22T cells in a dose-dependent manner. Flow cytometry showed that ECDT treatment at 10-20 μM increased early apoptosis by 10-14% and late apoptosis by 2-5%. Western blot revealed that ECDT treatment activated the mitochondrial-dependent apoptotic pathway, and ECDT-induced apoptosis was mediated by the caspase signalling pathway and activation of JNK and p38MAPK. Pre-treatment of cells with MAPK inhibitors (SB203580 or SP600125) reversed the ECDT-induced cell death, which further supported the involvement of the p38MAPK and JNK pathways., Discussion and Conclusions: Our results indicated that ECDT can induce apoptosis through the p38MAPK and JNK pathways in HA22T cells. The findings suggested that ECDT has a valuable anticancer property with the potential to be developed as a new chemotherapeutic agent for the treatment of HCC.

In fish processing, reducing the waste rate and increasing the economic value of products is an important issue for global environmental protection and resource sustainability. It has been discovered that cuttlefish bones can be an excellent resource for producing attractive amounts of chitin and chitosan. Therefore, this study optimized chitosan extraction conditions using response surface methodology (RSM) to establish application conditions suitable for industrial production and reducing environmental impact. In addition, Fourier-transform infrared spectroscopy (FTIR), 1 H NMR and scanning electron microscope (SEM) characteristics of extracted chitosan were evaluated. The optimum extraction conditions for chitosan from cuttlebone chitin were 12.5M NaOH, 6 h and 80 °C, and the highest average yield was 56.47%. FTIR spectroscopy, 1 H NMR, and SEM identification proved that the chitosan prepared from cuttlefish bone has a unique molecular structure, and the degree of deacetylation of chitosan was about 81.3%. In addition, it was also confirmed that chitosan has significant anti-oxidation and oil-absorbing abilities. This research has successfully transformed the by-products of cuttlefish processing into value-added products. The process not only achieved the recycling and utilization of by-products but also enhanced industrial competitiveness and resource sustainability.

Polarized optical microscopy (POM), scanning electron microscopy (SEM), and synchrotron microbeam wide-angle X-ray diffraction (WAXD) were used to investigate the mechanisms of periodic assemblies leading to ring-banded crystal aggregates with light-grating capacity for iridescence in poly (1,4-butylene adipate) (PBA) modulated with poly (ethylene oxide) (PEO). A critical finding is that the PBA crystal assembly on the top surface and in the interior constitutes a grating architecture, with a cross-bar pitch equaling the inter-band spacing. The inner lamellae are arranged perpendicularly to the substrate under the ridge region, where they scroll, bend, and twist 90° to branch out newly spawned lamellae to form the parallel lamellae under the valley region. The cross-hatch grating with a fixed inter-spacing in the PBA aggregated crystals is proved in this work to perfectly act as light-interference entities capable of performing iridescence functions, which can be compared to those widely seen in many of nature's organic bio-species or inorganic minerals such as opals. This is a novel breakthrough finding for PBA or similar polymers, such as photonic crystals, especially when the crystalline morphology could be custom-made and modulated with a second constituent., Competing Interests: The authors declare no conflicts of interest.

A kind of hydroxylated polymethoxyflavone (PMFs) existing in the citrus genus, 5-Demethyltangeretin (5-DTAN), has been reported to possess several bioactivities in vitro and in vivo. The aim of this study was to investigate whether acetylation could enhance the anticancer activity and oral bioavailability of 5-DTAN. PC-3 human prostate cancer cells were treated with tangeretin (TAN), 5-DTAN, and 5-acetylated TAN (5-ATAN), and the results showed that the cytotoxic effect 5-ATAN (IC50 value of 5.1 µM) on the cell viability of PC-3 cells was stronger than that of TAN (IC50 value of 17.2 µM) and 5-DTAN (IC50 value of 11.8 µM). Compared to 5-DTAN, 5-ATAN treatment caused a more pronounced DNA ladder, increased the sub-G1 phase population, and induced G2/M phase arrest in the cell cycle of PC-3 cells. We also found that 5-ATAN triggered the activation of caspase-3 and the progression of the intrinsic mitochondrial pathway in PC-3 cells, suggesting the induction of apoptosis. In a cell wound healing test, 5-ATAN dose-dependently reduced the cell migration, and the expression of matrix metalloproteinase-2 (MMP-2) and matrix metalloproteinase-9 (MMP-9) was decreased after 48 h of 5-ATAN treatment. Moreover, oral administration of 5-ATAN showed a significantly stronger inhibitory effect on tumor size and tumor weight in tumor-bearing nude mice than those of vehicle or the 5-DTAN group (p < 0.05). Furthermore, pharmacokinetic results showed that single-dose oral administration of 5-ATAN exhibited a higher maximum concentration (Cmax) and area under the curve (AUC) of 5-DTAN in plasma than that of 5-DTAN. More extensive distribution of 5-DTAN to most tissues of mice was also observed in mice treated with 5-ATAN for 7 days. In conclusion, acetylation strongly enhances the anticancer activity and oral bioavailability of 5-DTAN and could be a promising strategy to promote the potential bioactivities of natural products.

Hybrid natural products produced via mixed biosynthetic pathways are unique and often surprise one with unexpected medicinal properties in addition to their fascinating structural complexity/diversity. In view of chemical structures, hybridization is a way of diversifying natural products usually through dimerization of two similar or dissimilar subcomponents through a C-C or N-C covalent linkage. Here, we report four structurally attractive diterpene-alkaloid conjugates polyalongarins A-D ( 1 - 4 ), clerodane-containing aporphine and proaporphine alkaloids, the first of its kind from the barks of Taiwanese Polyalthia longifolia (Sonn.) Thwaites var. pendula . In addition to conventional spectroscopic analysis, single crystal X-ray crystallography was employed to determine the chemical structures and stereo-configurations of 1 . Compounds 1 - 4 were subsequently subjected to in vitro antiviral examination against DENV2 by evaluating the expression level of the NS2B protein in DENV2-infected Huh-7 cells. These compounds display encouraging anti-DENV2 activity with superb EC 50 (2.8-6.4 μM) and CC 50 values (50.4-200 μM). The inhibitory mechanism of 1 - 4 on NS2B was further explored drawing on in-silico molecular docking analysis. Based on calculated binding affinities and predicted interactions between the functional groups of 1 - 4 and the allosteric-site residues of the DENV2 NS2B-NS3 protease, our analysis concludes that the clerodane-aporphine/proaporphine-type hybrids are novel and effective DENV NS2B-NS3 protease inhibitors.

The progression of chronic kidney disease (CKD) can be directly or indirectly accelerated by a poor diet and the diet's influence on risk factors for this disease. There have been no food frequency questionnaires (FFQs) developed for the assessment of diet in patients with CKD in Taiwan. This study analyzed the validity of a short FFQ (SFFQ) with 42 items for estimating patient intake of macronutrients, fiber, phosphorus, potassium, and calcium against 3-day dietary records (3-day DRs) in Taiwanese patients with stages 3-5 CKD. In an interview, 107 participants with the help of a dietician filled out an SFFQ and reviewed a 3-day DR the patients had filled out prior to the interview. Partial Pearson correlation coefficients between SFFQ and 3-day DR were 0.722, 0.619, 0.593, 0.572, 0.450, 0.611 and 0.410 for protein, fat, carbohydrate, fiber, phosphorus, potassium, and calcium, respectively, after adjusting for energy intake. Cross-classification analysis revealed 63.5-83.2% similarity in cross-tool estimated intakes of macronutrients, fiber, phosphorus, potassium, and calcium in the same quartiles or adjacent ones. Bland-Altman plots revealed good agreement between the two tools along different intake levels. In conclusion, the newly developed SFFQ had moderate relative validity in estimating the usual intake of key nutrients related to nutrition management of patients with late-stage CKD, suggesting it can be used to assess dietary intakes in a population with CKD, especially in those residing in an Asian region.

Rare skin diseases include more than 800 diseases affecting more than 6.8 million patients worldwide. However, only 100 drugs have been developed for treating rare skin diseases in the past 38 years. To investigate potential treatments through drug repurposing for rare skin diseases, it is necessary to have a well-organized database to link all known disease causes, mechanisms, and related information to accelerate the process. Drug repurposing provides less expensive and faster potential options to develop treatments for known diseases. In this work, we designed and constructed a rare skin disease database (RSDB) as a disease-centered information depository to facilitate repurposing drug candidates for rare skin diseases. We collected and integrated associated genes, chemicals, and phenotypes into a network connected by pairwise relationships between different components for rare skin diseases. The RSDB covers 891 rare skin diseases defined by the Orphanet and GARD databases. The organized network for each rare skin disease comprises associated genes, phenotypes, and chemicals with the corresponding connections. The RSDB is available at https://rsdb.cmdm.tw ., (© 2022. The Author(s).)

Regulation of key digestive enzymes is currently considered an effective remedy for diabetes mellitus. In this study, bioactive constituents were purified from Terminalia boivinii fruits and identified by 1 H-NMR, 13 C-NMR and EI-MS. In vitro and in silico methods were used to evaluate α-glucosidase, α-amylase, and lipase inhibition activities. Compounds 1, 2, and 4-7 with IC 50 values between 89 and 445 μM showed stronger α-glucosidase inhibitory activities than the antihyperglycemic drug acarbose (IC 50 =1463.0±29.5 μM). However, the compounds showed lower inhibitory effects against α-amylase and lipase with IC 50 values above 500 μM than acarbose (IC 50 =16.7±3.5 μM) and ursolic acid (IC 50 =89.5±5.6 μM), respectively. Lineweaver-Burk plots showed that compounds 1, 2, and 7 were non-competitive inhibitors, compounds 4 and 5 were competitive inhibitors and compound 6 was a mixed-type inhibitor. Fluorescence spectroscopic data showed that the compounds altered the microenvironment and conformation of α-glucosidase. Computer simulations indicated that the compounds and enzyme interacted primarily through hydrogen bonding. The findings indicated that the compounds were inhibitors of α-glucosidase and provided significant structural basis for understanding the binding activity of the compounds with α-glucosidase., (© 2022 Wiley-VHCA AG, Zurich, Switzerland.)

Adolescents with comparable personal risk factors may have different lipid profiles because of the school’s context. Lipid determinants in adolescents should be considered using a multilevel perspective. This multilevel study investigated the effects of individual-level and school-level factors on lipid profiles in adolescents and evaluated the cross-level influence of lipid determinants. A representative adolescent cohort (n = 2727) was randomly selected from 36 schools in three diverse economic areas in Taiwan and assessed for their personal dietary patterns, physical parameters, and lipid profiles. For individual-level factors, both low physical activity and high body mass index (BMI) were associated with elevated triglyceride (TG), low-density lipoprotein cholesterol (LDL-C), and total cholesterol (TC) levels, and a sugar-sweetened beverage intake of >500 mL/day was associated with increases of 5.97 and 6.12 mg/dL in LDL-C and TC levels, respectively, compared with abstinence. Regarding school-level factors, students in schools with ≥2 health promotion programs per year had a 5.27 mg/dL lower level of LDL-C than those in schools with 0−1 program, and students in schools with ≥46 food outlets within 600 m of the school had 6.90 and 13.3 mg/dL higher levels of TG and TC, respectively, than those in schools with <46 food outlets. School context modified the individual-level positive correlation between BMI and TG level (the p-value for the random-slope effect was 0.003). In conclusion, individual-level and school-level factors exert a multilevel effect on adolescent lipid profiles. The food environment near the school has a stronger cross-level impact on individual TG levels in adolescents with a high BMI than in those with a normal BMI.

Background: Microglia-related neuroinflammation is associated with a variety of neurodegenerative diseases. Flavonoids have demonstrated different pharmacological effects, such as antioxidation, neuroprotection and anti-inflammation However, the effect of flavonoid 6-methoxyflavone (6-MeOF) on microglia-mediated neuroinflammation remain unknown., Purpose: The current study aim to study the antineuroinflammatory effects of 6-MeOF in lipopolysaccharide- (LPS-) induced microglia in vitro and in vivo., Methods: Pretreatment of BV2 microglia cells with 6-MeOF for 1 h then stimulated with LPS (100 ng/ml) for 24 h. The expression levels of pro-inflammatory factors, NO and reactive oxygen species (ROS) were performed by the enzyme-linked immunosorbent assay (ELISA), Griess assay and flow cytometry. Western blotting was used to assess MAPK, NF-κB signal transducer and antioxidant enzymes-related proteins. Analysis of ROS and microglial morphology was confirmed in the zebrafish and mice brain, respectively., Results: Our results demonstrated that 6-MeOF dose-dependently prevent cell death and decreased the levels of pro-inflammatory mediators in LPS-stimulated BV2 microglia cells. Phosphorylated NF-κB/IκB and TLR4/MyD88/p38 MAPK/JNK proteins after exposure to 6-MeOF was suppressed in LPS-activated BV-2 microglial cells. 6-MeOF also presented antioxidant activity by reduction of NO, ROS, iNOS and COX-2 and the induction of the level of HO-1 and NQO1 expressions in LPS-activated BV2 microglial cells. Furthermore, we demonstrated that 6-MeOF inhibited LPS-induced NO generation in an experimental zebrafish model and prevent the LPS-induced microgliosis in the prefrontal cortex and substantia nigra of mice., Conclusion: These results explored that 6-MeOF possesses potential as anti-inflammatory and anti-oxidant agents against microglia-associated neuroinflammatory disorders., (Copyright © 2022 Elsevier GmbH. All rights reserved.)

The WHO recently included Gaming Disorder as a psychiatric diagnosis. Whether there are distinct groups of adolescents who differ based on severity of gaming disorder and their relationships with other mental health and addictive behavior outcomes, including problematic smartphone use (PSU), remains unclear. The current study explored and identified subtypes of Internet Gaming Disorder (IGD) severity and estimated the association between these subtypes and other disorders. Participants completed online questionnaires assessing the severity of IGD, PSU, depression, and anxiety during COVID-19. We conducted a latent class analysis of IGD symptoms among 1,305 Chinese adolescents (mean age = 15.2; male = 58.5%) from 11 secondary schools in Macao (SAR), China. Multinomial logistic regression estimated correlates of latent class membership and PSU. A 4-class model adequately described the sample subgroups. Classes were labeled as normative gamers (30.9%), occasional gamers (42.4%), problematic gamers (22.7%), and addictive gamers (4.1%). Relative to normative gamers, PSU severity, depression, and being male were significantly higher among problematic gamers, addictive gamers, and occasional gamers. Only problematic gamers showed significant positive associations with anxiety severity compared to the other groups. The study revealed the differences in severity of gaming disorder and its association with psychopathology outcomes. Application in screening for IGD and comorbidity is discussed., Supplementary Information: The online version contains supplementary material available at 10.1007/s12144-022-03133-8., Competing Interests: Conflict of interestPortions of these findings were presented as e-poster in the 20th WPA World Congress of Psychiatry. All other authors declare that they have no conflicts of interest., (© The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature 2022.)

Atopic dermatitis (AD) is a chronic inflammatory and pruritic disease; it can be treated by inhibiting inflammation. Sarcodia suiae sp. is an edible, artificially cultivable red algae with multiple bioactivities. We assessed the anti-inflammatory activity of the ethyl acetate fraction of S. suiae sp. ethanol extract (PD1) on 1-chloro-2,4-dinitrochlorobenzene (DNCB)-induced AD-like lesions. Results show that PD1 alleviated symptoms and significantly decreased clinical dermatitis score. PD1 inhibited serum immunoglobulin E expression and alleviated swelling in the spleen and subiliac lymph nodes. In skin tissues, PD1 alleviated aberrant hyperplasia, decreased epidermal thickness, and decreased the accumulation of mast cells. PD1 mediated the recovery of skin barrier-related proteins, such as claudin-1 and filaggrin. Our study demonstrated that PD1 has anti-inflammatory effects, alleviates AD symptoms, inhibits inflammatory responses in skin tissues, and restores barrier function in DNCB-induced AD mice. These findings reveal that S. suiae sp. extract provides an alternative protective option against AD., (© The Author(s) 2022. Published by Oxford University Press on behalf of Japan Society for Bioscience, Biotechnology, and Agrochemistry.)

Heme oxygenase-1 (HO-1) has been shown to exert antioxidant, anti-inflammatory, and anti-apoptotic effects in various types of cells. Therefore, the induction of HO-1 is an excellent rationale for the development of protective drugs. 15-Deoxy-Δ 12,14 -prostaglandin J 2 (15d-PGJ 2 ) can modulate the expression of antioxidant defense proteins and be beneficial for neuroinflammation. Brain endothelial cells play an important role in the pathophysiology of brain disorders. Whether 15d-PGJ 2 can induce HO-1 expression and protect against the inflammatory responses in mouse brain microvascular endothelial (bEnd.3) cells remains unclear. Here, we reveal that 15d-PGJ 2 stimulated HO-1 protein and mRNA expression in a time- and concentration-dependent manner in bEnd.3 cells, which was attenuated by diphenyleneiodonium chloride (DPI) and MitoTempo. Thus, activation of NADPH oxidase (NOX)- and mitochondria-derived reactive oxygen species (ROS) mediated 15d-PGJ 2 -induced HO-1 expression. ROS generation could cause phosphorylation of protein kinase C (PKC)δ, leading to HO-1 expression, which was suppressed by Rottlerin (selective inhibitor PKCδ), DPI, and MitoTempo. We further demonstrated that phosphorylation of c-Jun N-terminal kinase (JNK)1/2 participated in 15d-PGJ 2 -upregulated HO-1 expression, which was blocked by SP600125 or Rottlerin. Moreover, 15d-PGJ 2 -induced HO-1 expression was mediated through the activation of c-Jun (a subunit of activator protein 1 (AP-1)) and specificity protein 1 (Sp1), leading to their interaction with the HO-1 promoter, revealed by chromatin immunoprecipitation assay, which was attenuated by SP600125, Mithramycin A, or Tanshinone II A. We further verified the anti-inflammatory effect of HO-1 expression. Our results showed that 15d-PGJ 2 -induced HO-1 could mitigate the lipopolysaccharide-triggered interleukin-6 expression and secretion, as measured by an ELISA assay kit. These results suggest that 15d-PGJ 2 -induced HO-1 expression is mediated through the activation of NOX- and mitochondria-derived ROS-dependent PKCδ/JNK1/2/Sp1 and the AP-1 signaling pathway and protects against inflammatory responses in bEnd.3 cells.

(1) Background: The current research intended to obtain functional compounds from agricultural by-products. A functional tea seed flavonoid, kaempferol-3-O-[2-O-β-d-xylopyranosyl-6-O-α-L-rhanmopyranosyl]-β-d-glucopyranoside (KXRG), was isolated from tea seed dregs. We further determined its chemical structure and evaluated the protective effects of KXRG against local and systemic inflammation in vivo; (2) Methods: First, cytotoxicity and proinflammatory cytokine release were examined in a cell-culture system. The biological activities of KXRG were investigated in a mouse model of ear edema, and from inflammatory damage to organs as demonstrated by histologic examination, in addition to brain function evaluation using the Y-maze test. Serum biochemical analysis and western blotting were utilized to explore the related cellular factors; (3) Results: KXRG inhibited IL-6 in RAW264.7 cells at a non-toxic concentration. Further experiments confirmed that KXRG exerted a stronger effect than indomethacin in terms of the prevention of 12-O-tetradecanoylphorbol acetate (TPA)-induced ear inflammation in a mouse model. KXRG feeding significantly prevented LPS-induced small intestine, liver, and kidney inflammatory damage, as demonstrated by histologic examination. KXRG also significantly improved LPS-induced cognitive impairments. Serum biochemical analysis showed that KXRG elevated antioxidant capacity and reduced levels of proinflammatory cytokines. Western blotting revealed that KXRG reduced the COX-2 expression induced by LPS in mouse tissues; (4) Conclusions: KXRG can be purified from agricultural waste, and hence it is inexpensive, with large amounts of raw materials available. Thus, KXRG has strong potential for further development as a wide-use anti-systemic inflammation drug to prevent human disease.

Objective: Although the provision of nutrition helps minimize adverse outcomes in most patients in intensive care units (ICUs), little is known about the relative effect of energy and protein delivered on mortality in ICU patients with different ranges of body mass index (BMI). The aim of this study was to examine the relationships between adequacy of dietary energy and protein intakes separately and simultaneously, and short-term mortality in medical ICU patients across four BMI categories., Methods: We enrolled 1693 patients admitted to a medical center ICU in Taiwan during the period of 2005 to 2011, subcategorizing them by BMI levels: <18.5(n = 418), 18.5-24.9 (n = 889), 25-29.9 (n = 289), and ≥30 kg/m 2 (n = 97). Dietary energy and protein intake (DEI and DPI) were defined by the percent of prescribed dosages that each patient actually received: highly adequate (>80%), moderately adequate (60-80%), and inadequate (<60%), during the first 10 d in the ICU., Results: Mean DEI was 1237 kcal/d and DPI 47 g protein/d. Analyzed separately in our multiple regression models, moderately and highly adequate DEI (P trends  = 0.003-0.026) and DPI (P trends  = 0.001-0.004) were both significantly correlated with reduced mortality in patients with BMI <18.5, 18.5-24.9, and 25-29.9 kg/m 2 but not in those with BMI levels ≥30 kg/m 2 . With DEI and DPI analyzed simultaneously, only APACHE II scores and DPI levels remained significantly related to reduced mortality in patients with BMI <30 kg/m 2 ., Conclusion: Although the adequacy of delivery of prescribed DEI or DPI dosages appeared to be important for reduced risks for mortality in ICU patients with BMI <30 kg/m 2 when analyzed separately, DPI had a stronger effect on decreases in ICU mortality when the two were analyzed simultaneously. Further investigation may be needed to study the role of increased protein in improving clinical outcomes., (Copyright © 2021. Published by Elsevier Inc.)

Resveratrol has been reported to exhibit neuroprotective activities in vitro and in vivo. However, little is known about resveratrol tetramers of hopeaphenol, vitisin A, and vitisin B with the same molecular mass in the improvement of degenerative disorders. In this study, two 95% ethanol extracts (95EE) from stem parts of Vitis thunbergii Sieb. & Zucc. (VT-95EE) and from the root (R) parts of Vitis thunbergii var. taiwaniana (VTT-R-95EE) showed comparable acetylcholinesterase (AChE) inhibitory activities. It was found that VT-95EE and VTT-R-95EE showed different distribution patterns of identified resveratrol and resveratrol tetramers of hopeaphenol, vitisin A, and vitisin B based on the analyses of HPLC chromatographic profiles. The hopeaphenol, vitisin A, and vitisin B, showed AChE and monoamine oxidase-B inhibitions in a dose-dependent manner, among which vitisin B and vitisin A exhibited much better activities than those of resveratrol, and had neuroprotective activities against methylglyoxal-induced SH-SY5Y cell deaths. The scopolamine-induced amnesiac ICR mice treated with VT-95EE and its ethyl acetate-partitioned fraction (VT-95EE-EA) at doses of 200 and 400 mg/kg, or vitisin A at a dose of 40 mg/kg, but not vitisin B (40 mg/kg), were shown significantly to improve the impaired learning behaviors by passive avoidance tests compared to those in the control without drug treatments ( p < 0.05). Compared to mice in the control group, the brain extracts in the vitisin A-treated mice or donepezil-treated mice showed significant reductions in AChE activities and malondialdehyde levels ( p < 0.05), and elevated the reduced protein expressions of brain-derived neurotrophic factor (BDNF) and BDNF receptor, tropomyosin receptor kinase B (TrkB). These results revealed that vitisin A was the active constituent in the VT-95EE and VTT-95EE, and the VT medicinal plant and that the endemic variety of VTT has potential in developing functional foods for an unmet medical need for neurodegenerative disorders.

There are numerous means to improve the tilapia aquaculture industry, and one is to develop disease resistance through selective breeding using molecular markers. In this study, 11 disease-resistance-associated microsatellite markers including 3 markers linked to hamp2 , 4 linked to hamp1 , 1 linked to pgrn2 , 2 linked to pgrn1 , and 1 linked to piscidin 4 ( TP4 ) genes were established for tilapia strains farmed in Taiwan after challenge with Streptococcus inae . The correlation analysis of genotypes and survival revealed a total of 55 genotypes related to survival by the chi-square and Z-test. Although fewer markers were found in B and N2 strains compared with A strain, they performed well in terms of disease resistance. It suggested that this may be due to the low potency of some genotypes and the combinatorial arrangement between them. Therefore, a predictive model was built by the genotypes of the parental generation and the mortality rate of different combinations was calculated. The results show the same trend of predicted mortality in the offspring of three new disease-resistant strains as in the challenge experiment. The present findings is a nonkilling method without requiring the selection by challenge with bacteria or viruses and might increase the possibility of utilization of selective breeding using SSR markers in farms.

Despite recent advances in pharma-nutritional management, chronic kidney disease (CKD) remains an increasingly prevalent disorder. Resveratrol, a pleiotropic phytochemical, has been found to reduce the risk for several chronic diseases. Considering the low bioavailability of resveratrol, we recently synthesized resveratrol butyrate ester (RBE) via the esterification of resveratrol with butyrate. The aim of this study was to examine the effectiveness of RBE as regards protection from hypertension and kidney damage and explore the underlying mechanisms using a young rat adenine-induced CKD model. Three-week-old male Sprague Dawley rats received regular or 0.5% adenine chow for three weeks. Three groups of adenine-fed CKD rats (N = 8/group) received resveratrol (50 mg/L), or a low dose (25 mg/L) or high dose (50 mg/L) of RBE in drinking water from week 6 to week 12. As compared with the controls, adenine-treated rats had markedly increased creatinine levels and blood pressure, which was associated with renal hypertrophy and decreased creatinine clearance. Treatment with resveratrol or a low or high dose of RBE, similarly protected adenine-fed rats against hypertension and kidney damage. CKD-induced hypertension is associated with an altered gut microbiota profile, dysregulated renal short chain fatty acid (SCFA) receptor expression, activation of the aryl hydrocarbon receptor (AhR) signaling pathway, and reduced nitric oxide bioavailability. We found gut microbiota compositions were shaped differentially by resveratrol and RBE treatment in adenine-treated CKD rats. The beneficial effect of high-dose RBE was associated with reduced renal expression of SCFA G protein-coupled receptor 41 (GPR41) and olfactory receptor 78 (Olfr78), antagonizing the AhR signaling pathway, and increased abundance of beneficial bacteria such as genera Akkermansia , Blautia , and Enterococcus . Our study provided the first evidence documenting RBE as a novel phytochemical supplement targeting the gut-kidney axis to protect against adenine-induced kidney damage and hypertension.

Purpose: This study investigated the association between professional quality of life, working context, and mental health outcomes among hospital personnel in Taiwan during the worldwide upsurge in COVID-19 cases., Patients and Methods: We recruited 503 hospital personnel to whom we administered online questionnaires containing items from the Professional Quality of Life (ProQoL) scale, which covers compassion satisfaction (CS), burnout (BO) and compassion fatigue (CF), the Depression, Anxiety and Stress Scale (DASS-21) and questions on work-related variables. Data were collected from 13 July to 19 August 2020., Results: The participants generally reported moderate CS and BO and low CF. Overall prevalence of mild-to-extremely-severe stress, anxiety and depression was 24.5%, 39.6% and 31.2%, respectively. Multiple logistic regression revealed that moderate-to-high BO and CF correlated with increased risks of mild-to-extremely-severe stress (OR = 4.17 and 2.23, respectively), anxiety (OR = 4.86 and 2.81, respectively) and depression (OR = 5.83 and 3.01, respectively), while moderate-to-high CS correlated with reduced risks of stress (OR = 0.53) and depression (OR = 0.45) only. There were CS and BO differences in groups categorized by marital status and profession. Anxiety increased linearly by seniority <10, 10-19 and ≥20 years (p for trend <0.05)., Conclusion: In conclusion, the subscales of ProQOL, BO and CF appeared to be associated with increased risks of stress, anxiety and depression among hospital personnel during the COVID-19 epidemic. A long-term contingency program may be needed to adjust work context variables and support emotional well-being of these workers., Competing Interests: The authors report no conflicts of interest in this work., (© 2021 Su et al.)