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Li-Ting Kao,1 Shian-Chin Ko,2 Ping-Jen Chen,3,4 Yu-Cih Wu,5 Kuang-Ming Liao,6 Yi-Shan Liang,1 Chung-Han Ho,5,7,8 Fu-Wen Liang9– 11 1Department of Respiratory Therapy, Chi Mei Medical Center, Tainan, Taiwan; 2Center for Palliative Care, Chi Mei Medical Center, Tainan, Taiwan; 3Department of Family Medicine and Division of Geriatrics and Gerontology, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan; 4School of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan; 5Department of Medical Research, Chi Mei Medical Center, Tainan City, Taiwan; 6Department of Internal Medicine, Chi Mei Medical Center, Chiali, Tainan, Taiwan; 7Department of Information Management, Southern Taiwan University of Science and Technology, Tainan City, Taiwan; 8Cancer Center, Taipei Municipal Wanfang Hospital, Taipei Medical University, Taipei, Taiwan; 9Department of Public Health, College of Health Sciences, Kaohsiung Medical University, Kaohsiung, Taiwan; 10Department of Medical Research, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan; 11Center for Big Data Research, Kaohsiung Medical University, Kaohsiung, TaiwanCorrespondence: Chung-Han Ho, Department of Medical Research, Chi Mei Medical Center, No. 901, Zhonghua Road Yongkang District, Tainan City, 71004, Taiwan, Tel +886-6-281-2811, Email ho.c.hank@gmail.com Fu-Wen Liang, Department of Public Health, College of Health Sciences, Kaohsiung Medical University, No. 100, Shih-Chuan 1st Road, Sanmin District, Kaohsiung, 807, Taiwan, Tel +886-7-312-1101 Ext 2786, Fax +886-7-311-0811, Email fwliang@kmu.edu.twPurpose: Palliative care utilization among hospitalized patients with advanced chronic obstructive pulmonary disease (COPD) in Taiwan remains low despite its costs making it eligible for reimbursement since 2009. Few studies have examined the trends of palliative care utilization. We analyzed the annual rate, associated factors, and timing of the inpatient palliative care utilization by hospitalized patients with COPD.Patients and Methods: We conducted a cross-sectional observational study between 1 January 2007 and 31 December 2018. Population-based claims data were extracted from Taiwan’s National Health Insurance Research Database to identify patients aged ≧40 years with COPD five years before the first instance of inpatient palliative care utilization.Results: There were 24,502 patients with COPD receiving inpatient palliative care. Our results indicated that older age, concomitant chronic conditions—especially cancer—and severity of comorbidities were associated with a higher rate of palliative care utilization by hospitalized patients with chronic obstructive pulmonary disease. In our study, the proportion of hospitalized patients with COPD receiving inpatient palliative care and having a Charlson comorbidity index score of 1– 2 was lower than that of patients with cancer and a Charlson comorbidity index score ≧3 during the 12-year study-observation period. In addition, approximately 50% of hospitalized patients with COPD received palliative care within 18 months after their initial admission for COPD during the study period. However, individuals with a CCI score of 1– 2 exhibited a slower entry into palliative care, with nearly 50% initiating it within the first two years.Conclusion: Inpatient palliative care utilization by hospitalized patients with advanced COPD remains low due to various causes. Our findings highlight that palliative care may be considered by professional care providers as routine care and as a way to manage problematic symptoms during hospitalization.Keywords: cancer comorbidity, inpatient care, joinpoint regression, Taiwan’s health insurance database

Kuo-Chen Cheng,1,* Chih-Cheng Lai,2,* Cheng-Yi Wang,3 Ching-Min Wang,4 Chung-Han Ho,5– 7 Mei-I Sung,1 Shu-Chen Hsing,1 Kuang-Ming Liao,8 Shian-Chin Ko1 1Department of Internal Medicine, Chi Mei Medical Center, Tainan, Taiwan; 2Department of Internal Medicine, Kaohsiung Veterans General Hospital Tainan Branch, Tainan, Taiwan; 3Department of Internal Medicine, Cardinal Tien Hospital, New Taipei City, Taiwan; 4Department of Internal Medicine, Chi Mei Medical Center, Liouying, Taiwan; 5Department of Medical Research, Chi Mei Medical Center, Tainan, Taiwan; 6Cancer Center, Wan Fang Hospital, Taipei Medical University, Taipei, 11695, Taiwan; 7Department of Information Management, Southern Taiwan University of Science and Technology, Tainan, Taiwan; 8Department of Internal Medicine, Chi Mei Medical Center, Chiali, Taiwan*These authors contributed equally to this workCorrespondence: Kuang-Ming Liao, Department of Internal Medicine, Chi Mei Medical Center, Chiali, Taiwan, Email abc8870@yahoo.com.tw Shian-Chin Ko, Department of Internal Medicine, Chi Mei Medical Center, Tainan, Taiwan, Email 737005@mail.chimei.org.twObjective: To investigate the impact of a multidisciplinary intervention on the clinical outcomes of patients with COPD.Methods: This study retrospectively extracted the data of patients enrolled in the national pay-for-performance (P4P) program for COPD in four hospitals. Only COPD patients who received regular follow-up for at least one year in the P4P program between September 2018 and December 2020 were included.Results: A total of 1081 patients were included in this study. Among them, 424 (39.2%), 287 (26.5%), 179 (16.6%), and 191 (17.7%) patients were classified as COPD Groups A, B, C, and D, respectively. Dual therapy with long-acting β 2-agonist (LABA)/long-acting muscarinic antagonist (LAMA) was the most used inhaled bronchodilator at baseline (n = 477, 44.1%) patients, followed by LAMA monotherapy (n = 195, 18.0%), triple therapy with inhaled corticosteroid (ICS)/LABA/LAMA (n = 184, 17.0%), and ICS/LABA combination (n = 165, 15.3%). After one year of intervention, 374 (34.6%) and 323 (29.9%) patients had their pre- and post-bronchodilator-forced expiratory volume in one second (FEV1) increase of more than 100 mL. Both the COPD Assessment Test (CAT) and modified British Medical Research Council (mMRC) scores had a mean change of − 2.2 ± 5.5 and − 0.3 ± 0.9, respectively. The improvement in pulmonary function and symptom score were observed across four groups. The decreased number of exacerbations was only observed in Groups C and D, and not in Groups A and B.Conclusion: This real-world study demonstrated that the intervention in the P4P program could help improve the clinical outcome of COPD patients. It also showed us a different view on the use of dual therapy, which has a lower cost in Taiwan.Keywords: chronic obstructive pulmonary disease, COPD, dual therapy, Disease-Specific Care – Chronic Obstructive Pulmonary Disease, DSC-COPD, certification program, Joint Commission of Taiwan, pay-for-performance, quality-improvement

Objectives: To pioneer the first artificial intelligence system integrating radiological and objective clinical data, simulating the clinical reasoning process, for the early prediction of high-risk influenza patients., Materials and Methods: Our system was developed using a cohort from National Taiwan University Hospital in Taiwan, with external validation data from ASST Grande Ospedale Metropolitano Niguarda in Italy. Convolutional neural networks pretrained on ImageNet were regressively trained using a 5-point scale to develop the influenza chest X-ray (CXR) severity scoring model, FluDeep-XR. Early, late, and joint fusion structures, incorporating varying weights of CXR severity with clinical data, were designed to predict 30-day mortality and compared with models using only CXR or clinical data. The best-performing model was designated as FluDeep. The explainability of FluDeep-XR and FluDeep was illustrated through activation maps and SHapley Additive exPlanations (SHAP)., Results: The Xception-based model, FluDeep-XR, achieved a mean square error of 0.738 in the external validation dataset. The Random Forest-based late fusion model, FluDeep, outperformed all the other models, achieving an area under the receiver operating curve of 0.818 and a sensitivity of 0.706 in the external dataset. Activation maps highlighted clear lung fields. Shapley additive explanations identified age, C-reactive protein, hematocrit, heart rate, and respiratory rate as the top 5 important clinical features., Discussion: The integration of medical imaging with objective clinical data outperformed single-modality models to predict 30-day mortality in influenza patients. We ensured the explainability of our models aligned with clinical knowledge and validated its applicability across foreign institutions., Conclusion: FluDeep highlights the potential of combining radiological and clinical information in late fusion design, enhancing diagnostic accuracy and offering an explainable, and generalizable decision support system., (© The Author(s) 2024. Published by Oxford University Press on behalf of the American Medical Informatics Association. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Saxidomus purpurata extract (SPE) is a highly consumable seafood worldwide with known health-related benefits. However, there are no reports of its' anti-obesity effect. This study explores the potential of SPE for anti-obesity effects by modulating adipogenesis and lipolysis. SPE reduced intracellular lipid and triglyceride accumulation while increasing free glycerol release in adipocytes. SPE inhibited lipogenesis protein expressions and increased the phosphorylation of hormone-sensitive lipase and Adenosine monophosphate-activated protein kinase (AMPK) to promote lipolysis. In addition, SPE suppressed adipogenesis by downregulating protein expression of key adipogenic markers, peroxisome proliferator-activated receptor gamma (PPARγ), CCAAT/enhancer-binding protein α (C/EBPα), and sterol regulatory element-binding protein 1 (SREBP1) via Wnt/β-catenin signaling. SPE augmented the heme oxygenase-1 (HO-1) expression. Thus, pharmacological intervention with Zinc protoporphyrin (ZnPP-HO-1 antagonist) was employed to validate the HO-1 role. The presence of ZnPP increased the lipid accumulation and reduced the free glycerol release. At the molecular level, adipogenic transcription factors (PPARγ, C/EBPα, and SREBP1) expressions were restored in the presence of ZnPP. GC-MS analysis revealed that SPE was comprised of several fatty acids, contributing to its anti-obesity activity. SPE is an effective nutraceutical that can be used to reduce the progression of obesity. HO-1 expression during adipogenesis might be the mechanism of action for the anti-obesity effect of SPE.

To reveal potent ACE inhibitors, researchers screen various bioactive peptides from several sources, and more attention has been given to aquatic sources. This review summarizes the recent research achievements on marine peptides with ACE-inhibitory action and application. Marine peptides are considered excellent bioactives due to their large structural diversity and unusual bioactivities. The mechanisms by which these marine peptides inhibit ACE include competitive binding to ACEs' active site, interfering with ACE conformational changes, and avoiding the identification of substrates. The unique 3D attributes of marine peptides confer inhibition advantages toward ACE activity. Because IC 50 values of marine peptides' interaction with ACE are low, structure-based research assumes that the interaction between ACE and peptides increased the therapeutic application. Numerous studies on marine peptides focused on the sustainable extraction of ACE-inhibitory peptides produced from several fish, mollusks, algae, and sponges. Meanwhile, their potential applications and medical benefits are worth investigating and considering. Due to these peptides exhibiting antioxidant, antihypertensive, and even antimicrobial properties simultaneously, their therapeutic potential for cardiovascular disease and other illnesses only increases. In addition, as marine peptides show better pharmacological benefits, they have increased absorption rates and low toxicity and could perhaps be modified for better stability and bioefficacy. Biotechnological advances in peptide synthesis and formulation have greatly facilitated the generation of peptide-based ACE inhibitors from marine sources, which subsequently offer new treatment models. This article gives a complete assessment of the present state of knowledge about marine organism peptides as ACE inhibitors. In addition, it emphasizes the relevance of additional investigation into their mechanisms of action, the optimization of manufacturing processes, and assessment in in vivo, preclinical, and clinical settings, underlining the urgency and value of this study. Using marine peptides for ACE inhibition not only broadens the repertory of bioactive compounds but also shows promise for tackling the global health burden caused by cardiovascular diseases.

Background: Vertebral artery (VA) stump syndrome (VASS) is an embolic source for cerebral infarction (CI) in the posterior circulation after VA occlusion., Case Description: A 63-year-old patient with a history of hypertension presented to our emergent department with dizziness, vomiting, and gait disturbance. Head magnetic resonance imaging (MRI) showed acute CIs in the bilateral cerebellar hemispheres and the vermis. Magnetic resonance angiography revealed patency of the VA and basilar artery. Left subclavian artery digital subtraction angiography (DSA) revealed severe left VA orifice stenosis and collateral flow from the deep cervical artery into the left V2 segment. Right VA angiography showed retrograde flow to the left V4 segment, branching bihemispheric posterior inferior cerebellar artery (PICA), and to-and-flow appearance in the proximal PICA segment and VA. VASS was diagnosed, and conservative treatment with aspirin was administered. Worsened nausea and gait disturbance had developed during hospitalization. MRI revealed an enlarged posterior circulation CI. Follow-up DSA revealed proximal to-and-flow appearance translocation to the proximal V4 segment and poor PICA flow. We performed proximal V4 segment parent artery occlusion (PAO) by endovascular therapy. No recurrence of symptoms or CI was observed. The patient was discharged on day 32 of hospitalization with 1 on the modified Rankin scale., Conclusion: We reported a rare case of VASS involving bihemispheric PICA. No CI recurrence was observed after performing PAO of the proximal V4 segment. When treating acute cases of bilateral cerebellar CI due to VASS, the contribution of PICA variations should be considered., Competing Interests: There are no conflicts of interest., (Copyright: © 2024 Surgical Neurology International.)

Background: Central giant cell granuloma (CGCG) is an uncommon, benign intraosseous lesion that most frequently occurs in the mandible and maxilla., Case Description: A 31-year-old female with a medical history of Kawasaki disease presented to our hospital complaining of a clogged right ear. Head computed tomography revealed a mass in the squamous part of the right temporal bone, with osteolytic changes and invasion of the external auditory canal, middle ear, temporomandibular joint, and mastoid air cells. Enhanced magnetic resonance imaging (MRI) showed a strong signal in the intraosseous lesion. Digital subtraction angiography revealed tumor staining from multiple feeders, including the middle meningeal, posterior deep temporal, and posterior auricular arteries. Preoperative feeder embolization using a detachable coil and Embosphere Microspheres were performed for the middle meningeal artery under general anesthesia. After the endovascular treatment, we operated on the temporal bone lesion. Postoperative enhanced MRI showed subtotal resection and residual tumor near the external auditory canal, which was left in place to prevent opening the external auditory canal. The histopathological examination showed proliferation of mononuclear cells intermingled with osteoclast-like multinucleated giant cells. A diagnosis of CGCG was made. The postoperative course was uncomplicated, and the patient was discharged on day 10 of hospitalization., Conclusion: We reported a rare case of CGCG in the temporal bone, managed by endovascular therapy and surgical resection. This combination therapy resulted in subtotal resection, preserving surrounding normal structures, such as the external auditory canal and tympanic cavity., Competing Interests: There are no conflicts of interest., (Copyright: © 2024 Surgical Neurology International.)

The current study aimed to determine whether Strongylocentrotus intermedius ( S. intermedius ) extract (SIE) exerts anti-obesity potentials employing 3T3-L1 cells as in vitro model. Herein we reported that treatment of SIE for 6 days reduced lipid accretion and triglyceride content whereas it increased the release of free glycerol. The inhibited lipid accumulation and induced lipolysis were evidenced by the downregulation of lipogenesis proteins, such as fatty acid synthase and lipoprotein lipase, and the upregulation of hormone-sensitive lipase expression. Furthermore, the downregulation of adipogenic transcription factors, including peroxisome proliferator-activated receptor gamma, CCAAT/enhancer-binding protein α, and sterol regulatory element-binding protein 1, highlights that reduced lipid accumulation is supported by lowering adipocyte differentiation. Additionally, treatment activates brown adipocyte phenotype in 3T3-L1 cells by inducing expression of brown adipose tissue-specific proteins, such as uncoupling protein 1 and peroxisome proliferator-activated receptor-γ coactivator 1α. Moreover, SIE induced the phosphorylation of AMP-activated protein kinase (AMPK). The pharmacological approach using AMPK inhibitor revealed that the restraining effect of SIE on adipogenesis and promotion of adipocyte browning were blocked. In GC-MS analysis, SIE was mainly composed of cholest-5-en-3-ol (36.71%) along with saturated and unsaturated fatty acids which have favorable anti-obesity potentials. These results reveal that SIE has the possibility as a lipid-lowering agent for the intervention of obesity.

In this research, we aimed to harness machine learning to predict the imminent risk of acute exacerbation in chronic obstructive pulmonary disease (AECOPD) patients. Utilizing retrospective data from electronic medical records of two Taiwanese hospitals, we identified 26 critical features. To predict 3- and 6-month AECOPD occurrences, we deployed five distinct machine learning algorithms alongside ensemble learning. The 3-month risk prediction was best realized by the XGBoost model, achieving an AUC of 0.795, whereas the XGBoost was superior for the 6-month prediction with an AUC of 0.813. We conducted an explainability analysis and found that the episode of AECOPD, mMRC score, CAT score, respiratory rate, and the use of inhaled corticosteroids were the most impactful features. Notably, our approach surpassed predictions that relied solely on CAT or mMRC scores. Accordingly, we designed an interactive prediction system that provides physicians with a practical tool to predict near-term AECOPD risk in outpatients., Competing Interests: The authors declare no conflict of interest., (© 2024 The Author(s).)

A biocompatible, heterogeneous, fucose-rich, sulfated polysaccharide (fucoidan) is biosynthesized in brown seaweed. In this study, fucoidan was isolated from Padina arborescens (PAC) using celluclast-assisted extraction, purified, and evaluated for its anti-inflammatory potential in lipopolysaccharide (LPS)-induced RAW 264.7 cells. Structural analyses were performed using Fourier transform infrared (FTIR) and scanning electron microscopy. Among the purified fucoidans, fucoidan fraction 5 (F5) exhibited strong inhibitory activity against LPS-induced nitric oxide (NO) production and pro-inflammatory cytokine generation through the regulation of iNOS/COX-2, MAPK, and NF-κB signaling in LPS-induced RAW 264.7 cells. Determination of the structural characteristics indicated that purified F5 exhibited characteristics similar to those of commercial fucoidan. In addition, further analyses suggested that F5 inhibits LPS-induced toxicity, cell death, and NO generation in zebrafish models. Taken together, these findings imply that P. arborescens fucoidans have exceptional anti-inflammatory action, both in vitro and in vivo, and that they may have prospective uses in the functional food sector.

The present study aims to explore the probable anti-adipogenesis effect of Dictyopteris divaricata ( D. divaricata ) in 3T3-L1 preadipocytes by regulating heme oxygenase-1 (HO-1). The extract of D. divaricata retarded lipid accretion and decreased triglyceride (TG) content in 3T3-L1 adipocytes but increased free glycerol levels. Treatment with the extract inhibited lipogenesis by inhibiting protein expressions of fatty acid synthase (FAS) and lipoprotein lipase (LPL), whereas lipolysis increased by activating phosphorylation of hormone-sensitive lipase (p-HSL) and AMP-activated protein kinase (p-AMPK). The extract inhibited adipocyte differentiation of 3T3-L1 preadipocytes through down-regulating adipogenic transcription factors, including peroxisome proliferator-activated receptor gamma (PPARγ) and CCAAT/enhancer-binding protein α (C/EBPα), and sterol regulatory element-binding protein 1 (SREBP1). This is attributed to the triggering of Wnt/β-catenin signaling. In addition, this study found that treatment with the extract activated HO-1 expression. Pharmacological approaches revealed that treatment with Zinc Protoporphyrin (ZnPP), an HO-1 inhibitor, resulted in an increase in lipid accumulation and a decrease in free glycerol levels. Finally, three adipogenic transcription factors, such as PPARγ, C/EBPα, and SREBP1, restored their expression in the presence of ZnPP. Analysis of chemical constituents revealed that the extract of D. divaricata is rich in 1,4-benzenediol, 7-tetradecenal, fucosterol, and n-hexadecanoic acid, which are known to have multiple pharmacological properties.

Bacterial small RNAs (sRNAs) function in post-transcriptional regulatory responses to environmental changes. However, the lack of eukaryotic RNA interference-like machinery in bacteria has limited the systematic engineering of RNA repression. Here, we report the development of clustered regularly interspaced short palindromic repeats (CRISPR)-guided dead CRIPSR-associated protein 13a (dCas13a) ribonucleoprotein that utilizes programmable CRISPR RNAs (crRNAs) to repress trans-acting and cis-acting sRNA as the target, altering regulatory mechanisms and stress-related phenotypes. In addition, we implemented a modular loop engineering of the crRNA to promote modular repression of the target gene with 92% knockdown efficiency and a single base-pair mismatch specificity. With the engineered crRNAs, we achieved targetable single-gene repression in the polycistronic operon. For metabolic application, 102 crRNAs were constructed in the biofoundry and used for screening novel knockdown sRNA targets to improve lycopene (colored antioxidant) production in Escherichia coli. The CRISPR-dCas13a system will assist as a valuable systematic tool for the discovery of novel sRNAs and the fine-tuning of bacterial RNA repression in both scientific and industrial applications., (© The Author(s) 2023. Published by Oxford University Press on behalf of Nucleic Acids Research.)

The design and development of wound dressing with antioxidant and antibacterial properties to accelerate wound healing remain challenging. In this study, we synthesize a chitooligosaccharide-gentisic acid (COS-GSA) conjugate using the free-radical grafting method, and fabricate a poly(vinyl alcohol) (PVA)/chitosan (CH)/COS-GSA (PVA/CH/CG) hydrogel using a freeze-thaw method. We characterize the synthesized COS-GSA conjugates using through polyphenol assay, absorbance, and 1 H NMR spectroscopy and evaluate their antioxidant properties. The COS-GSA conjugates are successfully synthesized and exhibit better antioxidant properties than pristine COSs. Subsequently, the fabricated hydrogel is characterized based on its morphological analysis, rheological properties, water contact angle, swelling, degradation, water retention properties, and COS-GSA release profiles. Finally, the biocompatibility of the fabricated hydrogel is evaluated on HDF and HaCaT cells through indirect and direct cytotoxicity. The PVA/CH/CG hydrogel exhibited significantly higher antioxidant properties (DPPH, 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS), and hydrogen peroxide (H 2 O 2 ) scavenging activities) and antibacterial activities (Staphylococcus aureus and Pseudomonas aeruginosa) compared to other fabricated hydrogels such as PVA, PVA/CH, and PVA/CH/COS (PVA/CH/C). These results provide evidence that PVA/CH/CG hydrogels with antioxidant, antibacterial, and non-cytotoxic properties have great potential for wound-dressing applications., 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.)

Angiotensin I-converting enzyme (ACE) is an important blood pressure regulator. In this study, we aimed to investigate the ACE-inhibitory effects of meroterpenoids isolated from the brown alga, Sargassum macrocarpum , and the molecular mechanisms underlying ACE inhibition. Four fractions of S. macrocarpum were prepared using hexane, chloroform, ethyl acetate, and water as solvents and analyzed for their potential ACE-inhibitory effects. The chloroform fraction showed the strongest ACE-inhibitory effect, with an IC 50 value of 0.18 mg/mL. Three meroterpenoids, sargachromenol, 7-methyl sargachromenol, and sargaquinoic acid, were isolated from the chloroform fraction. Meroterpenoids isolated from S. macrocarpum had IC 50 values of 0.44, 0.37, and 0.14 mM. The molecular docking study revealed that the ACE-inhibitory effect of the isolated meroterpenoids was mainly attributed to Zn-ion, hydrogen bonds, pi-anion, and pi-alkyl interactions between the meroterpenoids and ACE. These results suggest that S. macrocarpum could be a potential raw material for manufacturing antihypertensive nutraceutical ingredients.

In this study, seahorse peptide (SHP) was isolated from an alcalase-treated hydrolysate from Hippocampus abdominalis and assessed for its antioxidant potential against AAPH-induced oxidative stress damage. AAPH stimulation significantly decreased cell viability and increased intracellular reactive oxygen species (ROS) production in Vero cells. SHP treatment increased cell viability and remarkably lowered ROS production under AAPH-induced oxidative stress. Furthermore, it protected against AAPH-induced apoptotic DNA damage. Western blot analysis demonstrated that SHP treatment remarkably increased the protein expression levels of catalase and SOD in AAPH-induced Vero cells. A zebrafish study revealed that SHP-treated zebrafish embryos resulted in lower cell death, ROS generation, and lipid peroxidation than the AAPH-treated group. These results suggest that SHP is a potent functional antioxidant that could be developed as a natural antioxidant in the food and functional food industries., 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 © 2022 Elsevier Ltd. All rights reserved.)

Sargassum horneri is a seaweed species with diverse bioactivities. However, its antifibrotic effects during nasal polyp (NP) formation are not clearly understood. Therefore, we investigated the inhibitory effect of S. horneri on fibrosis progression in NP-derived fibroblasts (NPDFs) and NP tissues ex vivo. NPDFs were stimulated with TGF-β1 in the presence or absence of S. horneri ethanol extract (SHE). The extracellular matrix (ECM) protein production levels, myofibroblast differentiation (α-smooth muscle actin, α-SMA), and phosphorylation of Smad 2/3 and -ERK in TGF-β1-stimulated NPDFs were investigated using western blotting. Further, the contractile activity of SHE was assessed by performing a collagen gel contraction assay. The expression levels of collagen-1, fibronectin, and α-SMA were investigated in NP organ cultures treated with SHE. TGF-β1 stimulated ECM protein expression, myofibroblast differentiation, and collagen contractile activity while these were attenuated by pretreatment with SHE. We also found antifibrotic effect of SHE on ex vivo NP tissues. The antifibrotic effects of SHE were modulated through the attenuation of Smad 2/3 and ERK signaling pathways in TGF-β1-stimulated NPDFs. In conclusion, SHE inhibited ECM protein accumulation and myofibroblast differentiation during NP remodeling. Thus, SHE may be helpful as a treatment for NP recurrence after endoscopic sinus surgery.

Background: For the intensivists, accurate assessment of the ideal timing for successful weaning from the mechanical ventilation (MV) in the intensive care unit (ICU) is very challenging., Purpose: Using artificial intelligence (AI) approach to build two-stage predictive models, namely, the try-weaning stage and weaning MV stage to determine the optimal timing of weaning from MV for ICU intubated patients, and implement into practice for assisting clinical decision making., Methods: AI and machine learning (ML) technologies were used to establish the predictive models in the stages. Each stage comprised 11 prediction time points with 11 prediction models. Twenty-five features were used for the first-stage models while 20 features were used for the second-stage models. The optimal models for each time point were selected for further practical implementation in a digital dashboard style. Seven machine learning algorithms including Logistic Regression (LR), Random Forest (RF), Support Vector Machines (SVM), K Nearest Neighbor (KNN), lightGBM, XGBoost, and Multilayer Perception (MLP) were used. The electronic medical records of the intubated ICU patients of Chi Mei Medical Center (CMMC) from 2016 to 2019 were included for modeling. Models with the highest area under the receiver operating characteristic curve (AUC) were regarded as optimal models and used to develop the prediction system accordingly., Results: A total of 5,873 cases were included in machine learning modeling for Stage 1 with the AUCs of optimal models ranging from 0.843 to 0.953. Further, 4,172 cases were included for Stage 2 with the AUCs of optimal models ranging from 0.889 to 0.944. A prediction system (dashboard) with the optimal models of the two stages was developed and deployed in the ICU setting. Respiratory care members expressed high recognition of the AI dashboard assisting ventilator weaning decisions. Also, the impact analysis of with- and without-AI assistance revealed that our AI models could shorten the patients' intubation time by 21 hours, besides gaining the benefit of substantial consistency between these two decision-making strategies., Conclusion: We noticed that the two-stage AI prediction models could effectively and precisely predict the optimal timing to wean intubated patients in the ICU from ventilator use. This could reduce patient discomfort, improve medical quality, and lower medical costs. This AI-assisted prediction system is beneficial for clinicians to cope with a high demand for ventilators during the COVID-19 pandemic., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Liu, Hung, Ko, Cheng, Chao, Sung, Hsing, Wang, Chen, Lai, Chen and Chiu.)

Fibroblast growth factor 11 (FGF11) is one of intracrine FGFs (iFGFs), which function within cells. Unlike canonical FGFs, FGF11 remains intracellularly and plays biological roles in FGF receptor (FGFR)-independent manner. Here, we established an expression system of recombinant FGF11 proteins in E. coli and investigated whether the extracellular administration of FGF11 can activate cellular signaling. Human FGF11 has two isoforms, FGF11a and FGF11b, depending on the presence of nuclear localization sequences (NLSs) in the N-terminus. Because these two isoforms are unstable, we prepared an FGF11a-Mut by substituting three cysteine residues in the NLS with serine and FGF11b-ΔC with C-terminal truncation. The introduction of mutation in the NLS improved the solubility of FGF11 prepared from E. coli. Exogenous addition of FGF11b and FGF11b-ΔC to BALB3T3 increased cell proliferation, while FGF11a-Mut exerted no effect. FGF11b-ΔC showed higher cell proliferation activity and FGFR signaling than FGF11b. The cell-proliferating activities of FGF11b and FGF11b-ΔC were blocked by an FGFR1 inhibitor or a recombinant FGFR1, confirming the FGFR1-dependent extracellular activity of FGF11b. The analysis of circular dichroism suggested that the C-terminus of FGF11 has an α-helical structure, which may affect its interaction with FGFR1. These results suggest that the N-and C-terminus of recombinant FGF11 are involved in the activation of FGFR1. The above results provide novel insights into the function and mechanism of FGF11 that may aid the development of useful ligands for FGFR regulation., (© 2022. Author(s).)

Lab automation has facilitated synthetic biology applications in an automated workflow, and biofoundry facilities have enabled automated high-throughput experiments of gene cloning and genome engineering to be conducted following a precise experimental design and protocol. However, before-experiment procedures in biofoundry applications have been underdetermined. We aimed to develop a Python-based planning-assistant software, namely Biofoundry Palette, for liquid handler-based experimentation and operation in the biofoundry workflow. Depending on the synthetic biology project, variable information and content information may vary; the Biofoundry Palette provides precise information for the before-experiment units for each process module in the biofoundry workflow. As a demonstration, more than 200 unique information sets, generated by Biofoundry Palette, were used in automated gene cloning or pathway construction. The information on planning and management can potentially help the operator faithfully execute the biofoundry workflow after securing the before-experiment unit, thereby lowering the risk of human errors and performing successful biofoundry operations for synthetic biology applications.

Ecklonia maxima is a brown seaweed, which is abundantly distributed in South Africa. This study investigated an efficient approach using high-performance centrifugal partition chromatography (HPCPC), which has been successfully developed for the isolation and purification of phlorotannins, eckmaxol, and dieckol from the ethyl acetate fraction of E. maxima (EEM). We evaluated EEM for its inhibitory effect against lipopolysaccharide (LPS)-induced inflammatory responses in zebrafish embryos. The separation of eckmaxol and dieckol from samples of EEM using HPCPC was found to be of high purity and yield under an optimal solvent system composed of n-hexane:ethyl acetate:methanol:water (2:7:3:7, v / v / v / v ). To evaluate the anti-inflammatory efficacy of EEM containing active compounds, zebrafish embryos exposed to LPS were compared with and without EEM treatment for nitric oxide (NO) production, reactive oxygen species (ROS) generation, and cell death two days after fertilization. These evaluations indicate that EEM alleviated inflammation by inhibiting cell death, ROS, and NO generation induced by LPS treatment. According to these results, eckmaxol and dieckol isolated from brown seaweed E. maxima could be considered effective anti-inflammatory agents as pharmaceutical and functional food ingredients.

The aim of this study was to assess the potential hypertensive effects of the IGTGIPGIW peptide purified from Hippocampus abdominalis alcalase hydrolysate (HA) for application in the functional food industry. We investigated the antihypertensive effects of IGTGIPGIW in vitro by assessing nitric oxide production in EA.hy926 endothelial cells, which is a major factor affecting vasorelaxation. The potential vasorelaxation effect was evaluated using 4-amino-5-methylamino-2',7'-difluorofluorescein diacetate, a fluorescent stain. IGTGIPGIW significantly increased the expression of endothelial-derived relaxing factors, including endothelial nitric oxide synthase and protein kinase B, in EA.hy926 cells. Furthermore, oral administration of IGTGIPGIW significantly lowered the systolic blood pressure (183.60 ± 1.34 mmHg) and rapidly recovered the diastolic blood pressure (143.50 ± 5.55 mmHg) in the spontaneously hypertensive rat model in vivo. Our results demonstrate the antihypertensive activity of the IGTGIPGIW peptide purified from H. abdominalis and indicate its suitability for application in the functional food industry.

Successful weaning from prolonged mechanical ventilation (MV) is an important issue in respiratory care centers (RCCs). Delayed or premature extubation increases both the risk of adverse outcomes and healthcare costs. However, the accurate evaluation of the timing of successful weaning from MV is very challenging in RCCs. This study aims to utilize artificial intelligence algorithms to build predictive models for the successful timing of the weaning of patients from MV in RCCs and to implement a dashboard with the best model in RCC settings. A total of 670 intubated patients in the RCC in Chi Mei Medical Center were included in the study. Twenty-six feature variables were selected to build the predictive models with artificial intelligence (AI)/machine-learning (ML) algorithms. An interactive dashboard with the best model was developed and deployed. A preliminary impact analysis was then conducted. Our results showed that all seven predictive models had a high area under the receiver operating characteristic curve (AUC), which ranged from 0.792 to 0.868. The preliminary impact analysis revealed that the mean number of ventilator days required for the successful weaning of the patients was reduced by 0.5 after AI intervention. The development of an AI prediction dashboard is a promising method to assist in the prediction of the optimal timing of weaning from MV in RCC settings. However, a systematic prospective study of AI intervention is still needed.

Background: Myasthenia gravis (MG) is an autoimmune disease, and early thymectomy is recommended. Since the introduction of video-assisted thoracoscopic surgery, the safety and effectiveness of carbon dioxide insufflation in the thoracic cavity (capnothorax) has been controversial. This study aimed to compare the safety and effectiveness of ventilation methods in bilateral video-assisted thoracoscopic extended thymectomy (BVET) with capnothorax., Methods: We retrospectively investigated the medical records of patients with MG who underwent BVET between August 2016 and January 2018. Patients were divided into two groups: group D (n = 26) for one-lung ventilation and group S (n = 28) for two-lung ventilation. We set nine anesthesia time points (T0-T8) and collected respiratory and hemodynamic variables, including arterial O2 index (PaO2/FiO2)., Results: SpO2 at T1-T3 and T8 was significantly lower in group D than in group S. The FiO2 in group S was lower than that in group D at all time points. The number of PaO2/FiO2 ≤ 300 and PaO2/FiO2 ≤ 200 events was significantly higher in group D than in group S. Hemodynamic variables were not significantly different between the two groups at any time point. The duration of surgery and anesthesia was shorter in group S than in group D., Conclusions: This retrospective study suggests that anesthesia using two-lung ventilation during BVET with capnothorax is a safe and effective method to improve lung oxygenation and reduce anesthesia time.

Efficient and versatile DNA assembly frameworks have had an impact on promoting synthetic biology to build complex biological systems. To accelerate system development, laboratory automation (or biofoundry) provides an opportunity to construct organisms and DNA assemblies via computer-aided design. However, a modular cloning (MoClo) system for multiple DNA assemblies limits the biofoundry workflow in terms of simplicity and feasibility by preparing the number of cloning materials such as destination vectors prior to the automation process. Herein, we propose robot-assisted MoClo (RoboMoClo) to accelerate a synthetic biology project with multiple gene expressions at the biofoundry. The architecture of the RoboMoClo framework provides a hybrid strategy of hierarchical gene assembly and iterative gene assembly, and fewer destination vectors compared with other MoClo systems. An industrial bacterium, Corynebacterium glutamicum , was used as a model host for RoboMoClo. After building a biopart library (promoter and terminator; level 0) and evaluating its features (level 1), various transcriptional directions in multiple gene assemblies (level 2) were studied using the RoboMoClo vectors. Among the constructs, the convergent construct exhibited potential transcriptional interference through the collision of RNA polymerases. To study design of experiment-guided lycopene biosynthesis in C. glutamicum (levels 1, 2, and 3), the biofoundry-assisted multiple gene assembly was demonstrated as a proof-of-concept by constructing various sub-pathway units (level 2) and pathway units (level 3) for C. glutamicum . The RoboMoClo framework provides an improved MoClo toolkit for laboratory automation in a synthetic biology application.

Introduction: According to data released by the Korea National Statistical Office, the number of accidents has been decreasing since 2012. However, a considerable number of deaths related to safety accidents (23-46 deaths) are still reported annually. This study aimed to observe the correlation between accident prevention activities in the Republic of Korea (ROK) military and the incidence of safety accidents., Methods: The study used data from the 2014-2015 Military Health Survey and included 13 618 responses (Army: 8414 (61.8%); Navy/Marine: 2262 (16.6%); Air Force: 2942 (21.6%)) from the ROK military personnel. Accident experiences and thoughts on accident prevention activities were self-reported. Multiple logistic regression analysis was used to examine the validity of accident prevention activity and accident experience., Results: Of the 13 618 military personnel who responded, 12.0% reported experiencing safety accidents in the military and 1020 (7.5%) felt that accident prevention activities in the military were insufficient. On logistic regression analysis, we found a significant difference (insufficiency OR=1.56, CI 1.31 to 1.86). In particular, military personnel who belong to the Army and Navy were more likely to think that accident prevention activities were insufficient. In addition, military personnel who experienced falls/slips, crash, and laceration/puncture wound/amputation/penetrating wound accidents were more likely to think accident prevention activities were insufficient., Conclusions: Our study found that accident prevention activities in the military and accident experiences were related. It is necessary for the ROK Ministry of Defense, Army, Navy and Air Force headquarters to re-evaluate their accident prevention systems., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Protocatechuic aldehyde (PA) is a naturally occurring phenolic compound that is a potent inhibitor of mushroom tyrosinase. However, the molecular mechanisms of the anti-melanogenesis activity of PA have not yet been reported. The aim of the current study was to clarify the melanogenesis inhibitory effects of PA and its molecular mechanisms in murine melanoma cells (B16F10). We first predicted the 3D structure of tyrosinase and used a molecular docking algorithm to simulate binding between tyrosinase and PA. These molecular modeling studies calculated a binding energy of -527.42 kcal/mol and indicated that PA interacts with Cu400 and 401, Val283, and His263. Furthermore, PA significantly decreased α-MSH-induced intracellular tyrosinase activity and melanin content in a dose-dependent manner. PA also inhibited key melanogenic proteins such as tyrosinase, tyrosinase-related protein 1 (TRP-1), and TRP-2 in α-MSH-stimulated B16F10 cells. In addition, PA decreased MITF expression levels by inhibiting phosphorylation of cAMP response element-binding protein (CREB) and cAMP-dependent protein kinase A (PKA). These results demonstrate that PA can effectively suppress melanin synthesis in melanoma cells. Taken together, our results show that PA could serve as a potential inhibitor of melanogenesis, and hence could be explored as a possible skin-lightening agent.

Three-dimensional (3 D) printing is an effective technology that has shown considerable potential for use in tissue regeneration. Of the many materials that have been proposed for this purpose, poly (ε-caprolactone) (PCL) 3 D scaffolds have been received significant attention in the bone tissue engineering field due to its advantageous mechanical properties and biocompatibility. In this study, a novel method was developed for tissue-engineered bone that combines PCL 3 D scaffolds with fish collagen (Col) and the osteogenic abalone intestine gastro-intestinal digests (AIGIDs) from Haliotis discus hannai . And then, mouse mesenchymal stem cells (MSCs) were seeded onto the fabricated scaffolds. After in vitro culturing, the proliferation of the MSCs on the scaffolds, alkaline phosphatase (ALP) activity, and the amount of deposited calcium were investigated. The results indicated that the ALP activity and mineralization in PCL/AIGIDs/Col was higher than that of the other scaffolds. In an in vivo experiment, the two fabricated scaffolds were implanted in a rabbit tibia. PCL/AIGIDs/Col group exhibited strong osteoinduction capability in the rabbit tibia defect model. These stimulated biological responses in vitro and in vivo suggest that the PCL/AIGIDs/Col scaffold are promising material for use in tissue implants and bone regeneration.

To supply the sustainable calorie-free sweetener stevioside, synthetic photosynthetic bacteria were developed to produce ent -kaurenoic acid as a precursor of stevioside directly from CO 2 . By the use of a combinatorial and modular approach for gene expression, including a cytochrome P450 and the corresponding reductase, engineered Synechoccous elongatus PCC 7942 as a model cyanobacterium enabled the biosynthesis of ent -kaurenoic acid at 2.9 ± 0.01 mg L -1 from CO 2 . We found that the order of genes for expression was critical, producing ent -kaurenoic acid by balancing gene expressions and accumulation of the toxic intermediate in a cell. The engineered bacteria allowed the complete biosynthesis of ent -kaurenoic acid, and it will be used for stevioside biosynthesis from CO 2 as a controlled fermentation.

Economically feasible photosynthetic cultivation of microalgal and cyanobacterial strains is crucial for the biological conversion of CO 2 and potential CO 2 mitigation to challenge global warming. To overcome the economic barriers, the production of value-added chemicals was desired by compensating for the overall processing cost. Here, we engineered cyanobacteria for photosynthetic squalene production and cultivated them in a scalable photobioreactor using industrial flue gas. First, an inducer-free gene expression system was developed for the cyanobacteria to lower production const. Then, the recombinant cyanobacteria were cultivated in a closed photobioreactor (100 L) using flue gas (5% CO 2 ) as the sole carbon source under natural sunlight as the only energy source. Seasonal light intensities and temperatures were analyzed along with cyanobacterial cell growth and squalene production in August and October 2019. As a result, the effective irradiation hours were the most critical factor for the large-scale cultivation of cyanobacteria. Thus, an automated photobioprocess system will be developed based on the regional light sources.

Introduction: The National Statistical Yearbook of Defense 2018 issued by the Republic of Korea (ROK) Ministry of National Defense reported that the number of patients using military hospitals steadily increased from 2008 to 2017. However, in the outpatient clinic statistics for years 2015-2017 from the ROK Armed Forces Medical Command, the amount of medical care received from some medical departments, such as the infection medicine, surgery, and anesthesiology departments, decreased. Therefore, the purpose of this study was to observe the differences in incidence of military personnel's unmet healthcare needs according to number of diseases by type., Materials and Methods: The study used data from the Military Health Survey, which was conducted from 2014 to 2015 and included 5162 responses from ROK military personnel. The number of diseases by type and unmet healthcare needs were self-reported. A multiple logistic regression analysis was used to examine the validity of the annual disease experience by type and correlations with unmet healthcare needs., Results: Of the 5162 military personnel, 25.2% experienced unmet healthcare needs, and the more people with the number of disease by type, the more likely they were to experience unmet healthcare needs (1: 13.4%, 2: 22.9%, 3: 29.2%, 4: 34.5%, 5: 41.4%). The logistic regression analysis also revealed significant differences (1 = REF, 2 odds ratio (OR) = 1.83, 95% confidence interval (CI): 1.50-2.24; 3 OR = 2.53, 95% CI: 2.05-3.11, 4 OR = 3.10, 95% CI = 2.49-3.85; ≥5 OR = 3.85, 95% CI = 3.08-4.81). In addition, subgroup analysis showed that female military personnel are more likely to experience unmet healthcare needs than are male military personnel. We have also confirmed that working areas and private insurance can affect unmet healthcare needs., Conclusion: This study suggests that unmet healthcare needs are influenced by the number of disease by the type of ROK military personnel. It is therefore necessary to strive to reduce the number of military personnel who experience unmet healthcare needs through this data., (© The Author(s) 2020. Published by Oxford University Press on behalf of the Association of Military Surgeons of the United States.)

Purposes: To compare hearing recovery levels after initial treatment or salvage intratympanic dexamethasone injection (ITDI), and to find the prognostic factor on salvage ITDI therapy in profound ISSNHL., Methods: We retrospectively reviewed 115 patients with profound ISSNHL. All patients were treated with combination or systemic steroid therapy as the initial treatment. Next, we used salvage ITDI therapy on patients who showed slight or no improvement according to Siegel's criteria. To find the prognostic factors for the effectiveness of salvage ITDI therapy, we analyzed clinical data, such as, age, sex, vertigo, symptom duration, diabetes, hypertension, initial PTA, pre-salvage PTA, and treatment methods, using multiple regression analyses., Results: The rate of serviceable hearing recovery were 10.4% (12/115) in the initial-treatment group and 20.4% (21/103) in the salvage group. The difference was statistically significant (p = 0.041). Pre-salvage PTA, diabetes mellitus, and symptom duration were affective factors for the effectiveness of salvage ITDI therapy in profound ISSNHL refractory to initial treatment, with odds ratios of 1.169 (95% confidence interval, 1.088-1.256), 0.069 (95% confidence interval, 0.005-0.889), and 9.242 (95% confidence interval, 1.079-79.146)., Conclusions: Salvage therapy should be considered for profound ISSNHL, which is expected to result in poor prognosis or hearing recovery: ITSI therapy might be an effective treatment as salvage therapy.

Chronic obstructive pulmonary disease (COPD) is a chronic disease that burdens patients worldwide. This study aims to discover the burdens of health services among COPD patients who received palliative care (PC). Study subjects were identified as COPD patients with ICU and PC records between 2009 and 2013 in Taiwan's National Health Insurance Research Database. The burdens of healthcare utilization were analyzed using logistic regression to estimate the difference between those with and without cancer. Of all 1215 COPD patients receiving PC, patients without cancer were older and had more comorbidities, higher rates of ICU admissions, and longer ICU stays than those with cancer. COPD patients with cancer received significantly more blood transfusions (Odds Ratio, OR: 1.66; 95% C.I.: 1.11-2.49) and computed tomography scans (OR: 1.88; 95% C.I.: 1.10-3.22) compared with those without cancer. Bronchoscopic interventions (OR: 0.26; 95% C.I.: 0.07-0.97) and inpatient physical restraints (OR: 0.24; 95% C.I.: 0.08-0.72) were significantly more utilized in patients without cancer. COPD patients without cancer appeared to receive more invasive healthcare interventions than those without cancer. The unmet needs and preferences of patients in the life-limiting stage should be taken into consideration for the quality of care in the ICU environment.

Prolonged endotracheal intubation is the most common cause of tracheal stenosis, which may lead to serious airway obstruction. Development of an endotracheal tube coated with biomaterials that exhibit anti-inflammatory or anti-fibrogenic effects may prevent tracheal stenosis. This study demonstrates that an endotracheal tube coated with phlorotannin, which is present in extracts of the brown alga Ecklonia cava, can prevent tracheal stenosis in a rabbit model. An in vitro study shows that phlorotannin inhibits proliferation of human tracheal fibroblasts treated with transforming growth factor β1. Phlorotannin-coated endotracheal tubes show steady release of phlorotannin for up to 7 days, and removal of the tube 1 week after insertion reveals a reduction in both fibrogenesis and thickening of tracheal submucosa. Western blot analysis of tracheal tissues after removal of the phlorotannin-coated tube shows decreased protein expression levels of phenotypic markers of fibrosis such as collagen type I and α-smooth muscle actin. The ability of phlorotannin-coated endotracheal tube to prevent tracheal stenosis caused by endotracheal intubation indicates that phlorotannin may be considered as a candidate biomaterial for coating the cuff of endotracheal tubes to prevent tracheal stenosis., (© 2019 Wiley Periodicals, Inc.)

In this study, we fabricated polyvinyl alcohol hydrogels containing diphlorethohydroxycarmalol (DPHC) from Ishige okamurae for its anti-bacterial effect in wound-dressing applications. First, the minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) of DPHC against Staphylococcus aureus and Pseudomonas aeruginosa were investigated, and these were found to be about 128 μg/mL and 512 μg/mL, respectively. Polyvinyl alcohol hydrogels loaded with different concentrations of DPHC were then produced for the dressing of wounds to assist in the healing process and to provide an antibacterial effect. To investigate the characteristics of the proposed PVA/DPHC hydrogels, we conducted SEM analysis, rheological analysis, thermogravimetric analysis, water swelling analysis, drug release testing, and gel fraction assessment. The antibacterial activity of the PVA/DPHC hydrogels was also tested against the gram-positive bacterium S. aureus and the gram-negative bacterium P. aeruginosa using ASTM E2149 tests. The biocompatibility of the PVA/DPHC hydrogels was assessed using in vitro indirect and direct contact tests and in vivo tests on ICR mice. The PVA/DPHC hydrogels exhibited the ability to reduce the viability of S. aureus and P. aeruginosa by about 99% in ASTM E2149 testing, while not producing any toxic effect on NHDF-Neo or HaCaT cells as shown in MTT assays and in vitro FDA fluorescence analysis. In addition, the PVA/DPHC hydrogels had a strong wound healing effect when compared to non-treated groups of ICR mice in vivo. Based on the characterization of the PVA/DPHC hydrogels in vitro and in vivo, this study suggests that the proposed hydrogel has significant potential for use in wound dressing., (Copyright © 2019 Elsevier B.V. All rights reserved.)

This study investigated the antihypertensive effects of an antioxidant peptide, Leu-Trp-His-Thr-His (LWHTH), purified from Styela clava peptic hydrolysate, to assess the bioactivity of the peptide and verify the value of S. clava as a health-promoting food. Also, the study presented structural evidence for the effects of LWHTH. The inhibitory effect of LWHTH on angiotensin I-converting enzyme (ACE) was assessed using enzyme reaction methods and the simulation methods in computational space. LWHTH inhibited ACE with an IC 50 value of 16.42 ± 0.45  μ M. The LWHTH structure was stable, and its ACE inhibitory effect was retained under simulated gastrointestinal conditions. In silico simulations revealed that LWHTH binds the active site of ACE, with residues LW making the ACE-LWHTH complex stable and residues HTH making the complex strong. Furthermore, LWHTH significantly reduced blood pressure in spontaneously hypertensive rats. These results demonstrate that LWHTH has the potential to be a healthy functional food with antihypertensive effects. Therefore, S. clava consumption may be beneficial for human health.

Sargassum thunbergii is a brown alga from which various bioactive compounds can be extracted. Among these, the activities of indole derivatives, particularly as potential inhibitors of matrix metalloproteinases (MMPs), and their underlying mechanisms have been rarely investigated. Therefore, we evaluated the inhibitory effects of indole‑6‑carboxaldehyde (I6CA) on MMP‑9 by gelatin zymography and western blot anlaysis. We used phorbol 12‑myristate 13‑acetate (PMA), which is known to induce MMP‑9 expression and secretion, to stimulate HT1080 cells. Our results revealed that I6CA significantly inhibited MMP‑9 expression and secretion, without significantly affecting the viability of PMA‑stimulated HT1080 cells. Our mechanistic studies indicated that I6CA suppressed the phosphorylation and activation of two mitogen‑activated protein kinases (MAPKs), c‑Jun N‑terminal kinase (JNK) and extracellular signal‑regulated kinase 1/2 (ERK). Furthermore, I6CA inhibited the phosphorylation of inhibitor of κBα (IκBα) in response to PMA stimulation, which suppressed nuclear factor‑κB (NF‑κB) p65 subunit nuclear translocation. Collectively, I6CA was determined to suppress MMP‑9 expression and secretion, and effects were proposed to be mediated via the inhibition of the MAPK and NF‑κB p65 pathways. Therefore, we suggested I6CA to be a potential therapeutic agent for MMP‑9‑related processes, including tumor invasion and metastasis; however, further investigation is required.

Velvet antler has a long history in traditional medicine. It is also an important healthy ingredient in food as it is rich in protein. However, there has been no report about antioxidant peptides extracted from velvet antler by enzymatic hydrolysis. Thus, the objective of this study was to hydrolyze velvet antler using different commercial proteases (Acalase, Neutrase, trypsin, pepsin, and α-chymotrypsin). Antioxidant activities of different hydrolysates were investigated using peroxyl radical scavenging assay by electron spin resonance spectrometry. Among all enzymatic hydrolysates, Alcalase hydrolysate exhibited the highest peroxyl radical scavenging activity. Alcalase hydrolysate was then purified using ultrafiltration, gel filtration, and reverse-phase high performance liquid chromatography. The purified peptide was identified to be Trp-Asp-Val-Lys (tetrapeptide) with molecular weight of 547.29 Da by Q-TOF ESI mass spectroscopy. This purified peptide exhibited strong scavenging activity against peroxyl radical (IC 50 value, 0.028 mg/mL). In addition, this tetrapeptide showed significant protection ability against AAPH-induced oxidative stress by inhibiting of reactive oxygen species (ROS) generation in Chang liver cells in vitro and in a zebrafish model in vivo. This research suggests that the tetrapeptide derived from Alcalase-proteolytic hydrolysate of velvet antler are excellent antioxidants and could be effectively applied as functional food ingredients and pharmaceuticals., Competing Interests: The authors declare no conflict of interest.

Fish bone extract (FBE) containing a trioligopeptide (FBP-KSA, Lys-Ser-Ala) isolated from Johnius belengerii could induce osteogenic activities on MC3T3-E1 pre-osteoblasts in our previous study. Regarding the osteogenic effect of FBE, in the present study, we fabricated the three-dimensional (3D) interconnected polycaprolactone (PCL)/FBE scaffolds for bone tissue regeneration. After fabrication of PCL scaffolds using 3D printing, FBE was coated on the surface of PCL scaffolds by self-assembly process. In the physical characteristic and mechanical property tests, the results demonstrated that the fabricated scaffolds have the strut diameter (between 340 and 345 μm), pore size (between 470 and 480 μm), porosity (between 50% and 55%), and tensile properties (Young's modulus: 9.18-9.42 MPa; max tensile strengths 82.3-87.4 MPa) were similar to those of PCL scaffold. In the cell proliferation and osteogenic assay, the results showed that PCL/FBE scaffolds could significantly induce cell proliferation, calcium deposition, and the expression of osteogenic phenotype markers such as alkaline phosphatase, osteopontin, osteocalcin, and bone morphogenetic protein-2 in the osteoblasts. These results suggest that FBE-coated PCL scaffolds are promising materials for use in biomedical application to promote bone tissue regeneration. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater 107B: 1937-1944, 2019., (© 2018 Wiley Periodicals, Inc.)

Seahorses, Hippocampus abdominalis, have a long history in traditional Chinese medicine as an important healthy ingredient in foods. This study evaluated the antioxidant activity of an enzymatic hydrolysate prepared from a seahorse bred in Jeju, South Korea. Experiments were performed in vitro using electron spin resonance spectrometry (ESR) to determine the free radical scavenging activity and in vivo using a zebrafish model to determine the protective effects against 2,2-azobis hydrochloride (AAPH)-induced oxidative damage. H. abdominalis protein hydrolysate (HPH) exhibited peroxyl radical scavenging activity (IC 50  = 0.58 mg/ml) generated by the water-soluble AAPH (azo initiator of peroxyl radicals). HPH reduced dose-dependently both intracellular reactive oxygen species (ROS) levels in AAPH-induced cells and cell death in AAPH-induced zebrafish embryos. The antioxidant peptide purified from HPH was identified as a tripeptide (alanine-glycine-aspartic acid) using Q-TOF ESI mass spectroscopy. Thus, this study demonstrated that HPH contains antioxidant peptides that exhibit a strong antioxidant activity. PRACTICAL APPLICATIONS: Hippocampus abdominalis is one of the largest seahorse species and cultivated in many countries. Because of its large body size compared to other seahorse species, H. abdominalis has acquired considerable consumer attraction in the global market. Owing to its biologically useful properties, it recently gained attention as the natural products obtained from H. abdominalis have varied applications in the field of medicine, health care products, and functional foods. Thus, commercial products of this particular seahorse species are popular among customers, especially in China. The purpose of this study was to evaluate the antioxidant property of H. abdominalism, cultured in a commercial seahorse farm in Jeju Island. Owing to its prominent antioxidant activity, it could be used as an ingredient in medicinal preparations, nutraceuticals, and functional foods., (© 2019 Wiley Periodicals, Inc.)

The aim of the present study was to investigate the effect of 5-bromo-3,4-dihydroxybenzaldehyde (BD) isolated from Polysiphonia morrowii on adipogenesis and differentiation of 3T3-L1 preadipocytes into mature adipocytes and its possible mechanism of action. Levels of lipid accumulation and triglyceride were significantly lower in BD treated cells than those in untreated cells. In addition, BD treatment reduced protein expression levels of peroxisome proliferator-activated receptor-γ, CCAAT/enhancer-binding proteins α, and sterol regulatory element-binding protein 1 compared with control (no treatment). It also reduced expression levels of adiponectin, leptin, fatty acid synthase, and fatty acid binding protein 4. AMP-activated protein kinase activation was found to be one specific mechanism involved in the effect of BD. These results demonstrate that BD possesses inhibitory effect on adipogenesis through activating AMP-activated protein kinase signal pathway., (© 2018 John Wiley & Sons, Ltd.)

Main Conclusion: Photosynthetic production of isoprenoids in cyanobacteria is considered in terms of metabolic engineering and biological importance. Metabolic engineering of photosynthetic bacteria (cyanobacteria) has been performed to construct bio-solar cell factories that convert carbon dioxide to various value-added chemicals. Isoprenoids, which are found in nature and range from essential cell components to defensive molecules, have great value in cosmetics, pharmaceutics, and biofuels. In this review, we summarize the recent engineering of cyanobacteria for photosynthetic isoprenoids production as well as carbon molar basis comparisons with heterotrophic isoprenoids production in engineered Escherichia coli.

Propionibacterium acnes plays a key role in the onset of inflammation leading to acne and in downregulation of the defense system against oxidative stress. Therefore, antibiotics such as macrolides, tetracyclines, azelaic acid, and erythromycin are used to reduce microbial proliferation and resulting inflammation. Nonetheless, antibiotic treatment has side effects including cytotoxicity, allergy, and diarrhea. Therefore, recent studies were focused on the development of alternative antimicrobial materials. We conjugated chitooligosaccharide (COS) with gallic acid (GA) by the hydrogen peroxide-mediated method and evaluated antioxidant and antimicrobial activities. Then, we fabricated a polyvinyl alcohol (PVA) hydrogel containing COS conjugated with GA (GA-COS) for acne treatment. GA-COS at 5-10 kDa showed an excellent antioxidant activity and a better antimicrobial activity against P. acnes as compared with COS. In addition, the PVA hydrogel with GA-COS inhibited intracellular formation of reactive oxygen species and exerted antimicrobial action better than controls did., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Herein, we successfully developed a novel three dimensional (3D) opened networks based on nitrogen doped graphene‑carbon nanotubes attaching with gold nanoparticles (N-GR-CNTs/AuNPs) to apply for non-enzymatic glucose determination. It was demonstrated that the N-GR-CNTs/AuNPs modified electrode exhibited good behavior for glucose detection with a long linear range of 2 μM to 19.6 mM, high sensitivity of 0.9824 μA·mM -1 ·cm -2 , low detection limit of 500 nM, and negligible interference effect. The high performance of the N-GR-CNTs/AuNPs based sensor was assumed due to the outstanding catalytic activity of AuNPs well dispersing on N-GR-CNTs networks, which exhibited as a perfect supporting scaffold due to the enhanced electrical conductivity and large surface area. The obtained results indicated that the N-GR-CNTs/AuNPs hybrid is highly promising for sensitive and selective detection of glucose in sensor application., (Copyright © 2018 Elsevier B.V. All rights reserved.)