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Kai-Wen Ho,1,2 Yen-Ling Liu,2,3 Tzu-Yi Liao,2,3 En-Shuo Liu,2,3 Tian-Lu Cheng1– 3 1Department of Biomedical Science and Environmental Biology, Kaohsiung Medical University, Kaohsiung, Taiwan; 2Drug Development and Value Creation Research Center, Kaohsiung Medical University, Kaohsiung, Taiwan; 3Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, TaiwanCorrespondence: Tian-Lu Cheng, Department of Biomedical Science and Environmental Biology, Kaohsiung Medical University, No. 100 Shih-Chuan 1st Road, Kaohsiung, 80708, Taiwan, Tel +886 7 3121101 2697, Fax +886 7 3227508, Email tlcheng@kmu.edu.twAbstract: Polyethylene glycol (PEG)-modified nanoparticles (NPs) often struggle with reduced effectiveness against metastasis and liquid tumors due to limited tumor cell uptake and therapeutic efficacy. To address this, actively targeted liposomes with enhanced tumor selectivity and internalization are being developed to improve uptake and treatment outcomes. Using bi-functional proteins to functionalize PEGylated NPs and enhance targeted drug delivery through non-covalent attachment methods has emerged as a promising approach. Among these, the one-step and two-step targeting strategies stand out for their simplicity, efficiency, and versatility. The one-step strategy integrates streptavidin-tagged antibodies or bispecific antibodies (bsAbs: PEG/DIG × marker) directly into PEGylated NPs. This method uses the natural interactions between antibodies and PEG for stable, specific binding, allowing the modification of biotin/Fc-binding molecules like protein A, G, or anti-Fc peptide. Simply mixing bsAbs with PEGylated NPs improves tumor targeting and internalization. The two-step strategy involves first accumulating bsAbs (PEG/biotin × tumor marker) on the tumor cell surface, triggering an initial attack via antibody-dependent and complement-dependent cytotoxicity. These bsAbs then capture PEGylated NPs, initiating a second wave of internalization and cytotoxicity. Both strategies aim to enhance the targeting capabilities of PEGylated NPs by enabling specific recognition and binding to disease-specific markers or receptors. This review provides potential pathways for accelerating clinical translation in the development of targeted nanomedicine.Keywords: PEGylated nanoparticle, monoclonal antibody, antibody-containing nanodrugs, functionalization, targeted cancer therapy

Stiphodon chlorestes sp. nov. is described based on seven specimens collected from Taiwan and Luzon. It is a large-sized Stiphodon species sharing the second dorsal-fin rays 9-10 and pectoral-fin rays 14-16 with similar-sized congeners. However, it differs from them by the wider interorbital width and almost complete lack of scales on the occipital region in males. In addition, the new species can be further distinguished from all congeners by seven to eight oval bands or a black longitudinal band on the lower body, black and white spots on pectoral fins, and a short red or orange line on posterior upper edge of caudal fin. Molecular analysis based on the 680-bp mitochondrial cytochrome oxidase subunit I (COI) fragments also supports it as a distinct species belonging to the "Stiphodon elegans group" and a sister group of the clade consisting of Stiphodon multisquamus and Stiphodon palawanensis., (© 2024 Fisheries Society of the British Isles.)

Background: Weaning outcomes of patients receiving mechanical ventilation (MV) are affected by multiple factors. A clinical feature of critically ill patients is the presence of lymphopenia, however the clinical significance of lymphopenia in patients receiving prolonged MV remains unclear., Methods: We enrolled patients who received at least 21 consecutive days of MV in a medical center in Taiwan between 2007 and 2016. Patients with and without lymphopenia (mean count <1000/μL) were compared after propensity score matching., Results: Of the 3460 patients included in the analysis, 1625 (47.0%) were liberated from MV within 100 days. Lymphopenia and severe lymphopenia (mean count <500/μL) during the first 21 days of MV were common (52.9% and 14.5%, respectively), and restricted cubic spline analysis showed a significant reduction in weaning success when the lymphocyte count dropped below 1000/μL. After propensity score matching, the patients with lymphopenia during the third week had a lower rate of weaning success within 100 days (p = 0.005) and a higher in-hospital mortality rate (p = 0.001) than those without lymphopenia. The lymphopenia group also had significantly reduced platelet (p < 0.001) and albumin (p < 0.001) levels., Conclusions: Our findings suggest that lymphopenia during the first 3 weeks may be a marker of poor weaning outcomes in patients with prolonged MV., Competing Interests: Declaration of competing interest The authors have no conflicts of interest., (Copyright © 2024 The Japanese Respiratory Society. Published by Elsevier B.V. All rights reserved.)

A new species, Luciogobiusopisthoproctus sp. nov. , is described based on 18 specimens collected from Daxi Creek (Yilan) and Babian Creek (Taitung) in Taiwan. The new species is characterized by having a yellowish body with scattered spots on the sides, a black blotch on the caudal fin, the absence of free pectoral-fin rays, and more than 40 vertebrae. The new species can be distinguished from congeners by the following combination of characters: AAA distance (anus to anal-fin origin) shorter than twice the body depth at anus, 4.2-7.2% of standard length (SL); pre-anus length 80.0-92.8% of pre-anal-fin length; snout length 39.7-62.7% of AAA distance; abdominal vertebrae 20-22; caudal vertebrae 20-22; first anal-fin pterygiophore usually inserted behind the second haemal spine., Competing Interests: The authors have declared that no competing interests exist., (Kuan-Hsun Chen, Te-Yu Liao.)

Monitoring the healing progress of diabetic foot ulcers is a challenging process. Accurate segmentation of foot ulcers can help podiatrists to quantitatively measure the size of wound regions to assist prediction of healing status. The main challenge in this field is the lack of publicly available manual delineation, which can be time consuming and laborious. Recently, methods based on deep learning have shown excellent results in automatic segmentation of medical images, however, they require large-scale datasets for training, and there is limited consensus on which methods perform the best. The 2022 Diabetic Foot Ulcers segmentation challenge was held in conjunction with the 2022 International Conference on Medical Image Computing and Computer Assisted Intervention, which sought to address these issues and stimulate progress in this research domain. A training set of 2000 images exhibiting diabetic foot ulcers was released with corresponding segmentation ground truth masks. Of the 72 (approved) requests from 47 countries, 26 teams used this data to develop fully automated systems to predict the true segmentation masks on a test set of 2000 images, with the corresponding ground truth segmentation masks kept private. Predictions from participating teams were scored and ranked according to their average Dice similarity coefficient of the ground truth masks and prediction masks. The winning team achieved a Dice of 0.7287 for diabetic foot ulcer segmentation. This challenge has now entered a live leaderboard stage where it serves as a challenging benchmark for diabetic foot ulcer segmentation., 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 The Author(s). Published by Elsevier B.V. All rights reserved.)

Notch signaling is aberrantly activated in approximately 30% of hepatocellular carcinoma (HCC), significantly contributing to tumorigenesis and disease progression. Expression of the major Notch receptor, NOTCH1, is upregulated in HCC cells and correlates with advanced disease stages, although the molecular mechanisms underlying its overexpression remain unclear. Here, we report that expression of the intracellular domain of NOTCH1 (NICD1) is upregulated in HCC cells due to antagonism between the E3-ubiquitin ligase F-box/WD repeat-containing protein 7 (FBXW7) and the large scaffold protein abnormal spindle-like microcephaly-associated protein (ASPM) isoform 1 (ASPM-i1). Mechanistically, FBXW7-mediated polyubiquitination and the subsequent proteasomal degradation of NICD1 are hampered by the interaction of NICD1 with ASPM-i1, thereby stabilizing NICD1 and rendering HCC cells responsive to stimulation by Notch ligands. Consistently, downregulating ASPM-i1 expression reduced the protein abundance of NICD1 but not its FBXW7-binding-deficient mutant. Reinforcing the oncogenic function of this regulatory module, the forced expression of NICD1 significantly restored the tumorigenic potential of ASPM-i1-deficient HCC cells. Echoing these findings, NICD1 was found to be strongly co-expressed with ASPM-i1 in cancer cells in human HCC tissues (P < 0.001). In conclusion, our study identifies a novel Notch signaling regulatory mechanism mediated by protein-protein interaction between NICD1, FBXW7, and ASPM-i1 in HCC cells, representing a targetable vulnerability in human HCC., (© 2024 The Authors. Molecular Oncology published by John Wiley & Sons Ltd on behalf of Federation of European Biochemical Societies.)

Background: Dihydropteroate synthase (DHPS) mutations may be associated with trimethoprim-sulfamethoxazole resistance in Pneumocystis jirovecii pneumonia (PCP) and worse clinical outcomes. However, the clinical significance of DHPS mutations in PCP among non-human immunodeficiency virus (HIV)-infected patients remains unclear., Methods: Patients with PCP in three tertiary referral hospitals in Taiwan between 2016 and 2020 were retrospectively enrolled. Two point mutations, Thr55Ala and Pro57Ser, in the DHPS protein were analysed. Patients with invalid DHPS mutations in the respiratory specimen, chronic respiratory failure, receiving endotracheal intubation for surgical intervention, HIV infection, Pneumocystis jirovecii colonisation, and no lactate dehydrogenase (LDH) data were excluded. The primary outcome was 30-day survival., Results: A total of 215 patients were analysed. Mutants inside DHPS were found in 78 patients (36.3%) and 68 patients (31.6%) died within 30 days. A total of 214 patients (99.5%) received trimethoprim-sulfamethoxazole as the first-line treatment. The rates of mechanical ventilation, 30-day, and in-hospital mortality were similar between wild-type and mutant DHPS PCP. After adjusting for important confounders, LDH > 500 µ/L (adjusted hazard ratio [aHR] = 2.448, P = 0.001), pneumonia severity index > 135 mg/dL (aHR = 1.689, P = 0.049), and having solid tumours (aHR = 1.832, P = 0.034) were independently associated with higher mortality. In subgroup analysis, mutant DHPS PCP patients had less 30-day mortality among patients aged > 65 years (P = 0.049), with lymphopenia (P = 0.040), and those without solid tumour (P = 0.045)., Conclusions: In non-HIV-infected PCP, point mutants inside DHPS may not be associated with trimethoprim-sulfamethoxazole treatment outcomes. Further prospective large-scale studies are warranted., (Copyright © 2023 Elsevier Ltd and International Society of Antimicrobial Chemotherapy. All rights reserved.)

The utilization of dielectric barrier discharge (DBD) plasma treatment for modifying substrate surfaces constitutes an easy and simple approach with a potential for diverse applications. This technique was used to modify the surface of a commercial porous expanded poly(tetrafluoroethylene) (ePTFE) film with either dimethylaminoethyl methacrylate (DMAEMA) or (trimethylamino)ethyl methacrylate chloride (TMAEMA) monomers, aiming to obtain antibacterial ePTFE. Physicochemical analyses of the membranes revealed that DBD successfully enhanced the surface energy and surface charge of the membranes while maintaining high porosity (>75%) and large pore size (>1.0 μm). Evaluation of the bacteria killing-releasing (K-R) function revealed that both DMAEMA and TMAEMA endowed ePTFE with the ability to kill Escherichia coli bacteria. However, only TMAEMA-grafted ePTFE allowed for the release of dead bacteria from the surface upon washing with sodium hexametaphosphate (SHMP) saline solution, owing to its cationic charge derived from the quaternary amine. Washing with SHMP disturbed the electrostatic force between the polymer brushes and dead bacteria, which caused the release of the dead bacteria. Lastly, dead-end bacteria filtration showed that the TMAEMA-grafted ePTFE was able to kill 99.78% of the bacteria, while approximately 61.55% of bacteria were killed upon contact. The present findings support the feasibility of using DBD plasma treatment for designing surfaces that target bacteria and aid in the containment of disease-causing pathogens.

A morphology-based barcoding library of market teleost fishes (Teleostei) in Cebu is built based on cytochrome c oxidase subunit I (COI) sequences and voucher specimens which aimed to establish a reliable reference of frequently traded fishes in the province, a biodiversity hotspot at the center of the Philippine archipelago. A total of 1721 specimens were collected from 18 fish markets and landing sites around the province, in which 538 specimens were sequenced belonging to 393 species from 229 genera, 86 families, and 37 orders. Most speciose families are coral reef or reef-related shallow-water species. Twelve species from 11 families are newly recorded in the Philippine waters, among which 7 species are deep-sea inhabitants, while 3 species have expanded their distribution range. Only 20 taxa could not be identified to the species level due to the difficulty in morphological examinations, absence of matched reference sequences in online databases, and/or problematic species awaiting further studies. This first comprehensive DNA barcoding survey of Cebu fishes can facilitate further taxonomic research as well as the conservation and management of fisheries in the Philippines., (© 2023. Springer Nature Limited.)

Uropterygius concolor Rüppell, the type species of the genus Uropterygius, is a small, uniformly brown moray considered to be widely distributed in the Indo-Pacific region. However, a recent study indicated that the real U. concolor is currently known only from the type locality in the Red Sea, and species recorded outside the Red Sea may represent a species complex that comprises several species. In this study, we assess the genetic and morphological variations of this species complex based on available data. Analyses of cytochrome c oxidase subunit I sequences revealed at least six distinct genetic lineages recognized under 'U. concolor'. After carefully comparing the morphologies, one of the lineages is described herein as a new species, Uropterygius mactanensis sp. nov., based on 21 specimens collected from Mactan Island, Cebu, Philippines. Another distinct lineage is considered to be a possibly undescribed species based on diagnostic morphological characters. Although the taxonomic status of junior synonyms of U. concolor and some lineages still remain unresolved, this study provides informative morphological characters (i.e., tail length, trunk length, vertebrae number, and arrangement of teeth) that can be used in future studies on this species complex., (© 2023 Fisheries Society of the British Isles.)

Considering the need for versatile surface coatings that can display multiple bioactive signals and chemistries, the use of more novel surface modification methods is starting to emerge. Thiol-mediated conjugation of biomolecules is shown to be quite advantageous for such purposes due to the reactivity and chemoselectivity of thiol functional groups. Herein, the immobilization of poly(ethylene glycol) (PEG) and antimicrobial peptides (AMPs) to silica colloidal particles based on thiol-mediated conjugation techniques, along with an assessment of the antimicrobial potential of the functionalized particles against Pseudomonas aeruginosa and Staphylococcus aureus is investigated. Immobilization of PEG to thiolated Si particles is performed by either a two-step thiol-ene "photo-click" reaction or a "one-pot" thiol-maleimide type conjugation using terminal acrylate or maleimide functional groups, respectively. It is demonstrated that both immobilization methods result in a significant reduction in the number of viable bacterial cells compared to unmodified samples after the designated incubation periods with the PEG-AMP-modified colloidal suspensions. These findings provide a promising outlook for the fabrication of multifunctional surfaces based upon the tethering of PEG and AMPs to colloidal particles through thiol-mediated biocompatible chemistry, which has potential for use as implant coatings or as antibacterial formulations that can be incorporated into wound dressings to prevent or control bacterial infections., (© 2023 Wiley-VCH GmbH.)

The radical-bearing epoxy monomer could be the ideal embodiment of multifunctionality in epoxy-based materials. This study demonstrates the potential of macroradical epoxies as surface coating materials. A diepoxide monomer derivatized with a stable nitroxide radical is polymerized with a diamine hardener under the influence of a magnetic field. The magnetically oriented and stable radicals in the polymer backbone render the coatings antimicrobial. The unconventional use of magnets during polymerization proved crucial in correlating the structure-property relationships with antimicrobial performance inferred from oscillatory rheological technique, polarized macro-attenuated total reflectance - infrared (macro-ATR-IR) spectroscopy and X-ray photoelectron spectroscopy (XPS). The magnetic thermal curing influenced the surface morphology, resulting in a synergy of the coating's radical nature with microbiostatic performance assessed using the Kirby-Bauer test and liquid chromatography - mass spectroscopy (LC-MS). Further, the magnetic curing of blends with a traditional epoxy monomer demonstrates that radical alignment is more critical than radical density in imparting biocidal behavior. This study shows how the systematic use of magnets during polymerization could pave for probing more significant insights into the mechanism of antimicrobial action in radical-bearing polymers., (© 2023 The Authors. Chemistry - An Asian Journal published by Wiley-VCH GmbH.)

Introduction: Nontuberculous mycobacteria (NTM) may be present in the respiratory tract of patients with lung cancer. We investigated the association of pulmonary NTM with the clinical features and outcomes of patients with lung cancer., Methods: Between 2015 and 2019, the data of patients diagnosed with lung cancer at a medical center in northern Taiwan were analyzed. Patients whose respiratory specimens were culture-positive for NTM were identified (NTM group). For each patient in the NTM group, a matched control was selected (control group). The survival of the two groups was compared using the Kaplan-Meier method and Cox proportional hazards regression analysis., Results: Among 8718 patients with lung cancer, 5418 (62.1%) underwent a sputum mycobacterial culture. At least one NTM species was isolated from 138 (2.5%) patients. The median age was 72 years (range: 64-80). In the NTM group, 19.8% fulfilled both the microbiological and radiographic criteria for the diagnosis of NTM lung disease. Compared with the control group, the NTM group exhibited a lower body mass index (22.4 vs. 23.6, p = 0.025) and a higher prevalence of structural lung disease (38.9% vs. 22.2%, p = 0.004). The two-year survival was not significantly different between the two groups (hazard ratio [HR]: 1.110; 95% confidence interval [CI]: 0.702-1.754, p = 0.656). In patients receiving chemotherapy, pulmonary NTM was associated with worse survival (HR: 2.497, 95% CI: 1.262-4.943, p = 0.009)., Conclusions: Except in patients receiving chemotherapy, pulmonary NTM may not be clinically relevant in patients with lung cancer., Competing Interests: Declaration of competing interest None., (Copyright © 2022. Published by Elsevier B.V.)

Small cell lung cancer (SCLC) is among the most aggressive and lethal human malignancies. Most patients with SCLC who initially respond to chemotherapy develop disease relapse. Therefore, there is a pressing need to identify novel driver mechanisms of SCLC progression to unlock treatment strategies to improve patient prognosis. SCLC cells comprise subsets of cells possessing progenitor or stem cell properties, while the underlying regulatory pathways remain elusive. Here, we identified the isoform 1 of the neurogenesis-associated protein ASPM (ASPM-I1) as a prominently upregulated stemness-associated gene during the self-renewal of SCLC cells. The expression of ASPM-I1 was found to be upregulated in SCLC cells and tissues, correlated with poor patient prognosis, and indispensable for SCLC stemness and tumorigenesis. A reporter array screening identified multiple developmental signaling pathways, including Hedgehog (Hh) and Wnt pathways, whose activity in SCLC cells depended upon ASPM-I1 expression. Mechanistically, ASPM-I1 stabilized the Hh transcriptional factor GLI1 at the protein level through a unique exon-18-encoded region by competing with the E3 ligases β-TrCP and CUL3. In parallel, ASPM-I1 sustains the transcription of the Hh pathway transmembrane regulator SMO through the Wnt-DVL3-β-catenin signaling axis. Functional studies verified that the ASPM-I1-regulated Hh and Wnt activities significantly contributed to SCLC aggressiveness in vivo. Consistently, the expression of ASPM-I1 positively correlated with GLI1 and stemness markers in SCLC tissues. This study illuminates an ASPM-I1-mediated regulatory module that drives tumor stemness and progression in SCLC, providing an exploitable diagnostic and therapeutic target., Significance: ASPM promotes SCLC stemness and aggressiveness by stabilizing the expression of GLI1, DVL3, and SMO, representing a novel regulatory hub of Hh and Wnt signaling and targetable vulnerability., (©2023 American Association for Cancer Research.)

A variant of the cold spray (CS) technique was applied for the functionalization of polymer-based materials such as polydimethylsiloxane (PDMS) to improve the extent of mammalian cell interactions with these substrates. This was demonstrated by the embedment of porous titanium (pTi) into PDMS substrates using a single-step CS technique. CS processing parameters such as gas pressure and temperature were optimized to achieve the mechanical interlocking of pTi in the compressed PDMS to fabricate a unique hierarchical morphology possessing micro-roughness. As evidenced by the preserved porous structure, the pTi particles did not undergo any significant plastic deformation upon impact with the polymer substrate. The thickness of the particle embedment layer was determined, by cross-sectional analysis, ranging from 120 μm to over 200 μm. The behavior of osteoblast-like cells MG63 coming into contact with the pTi-embedded PDMS was examined. The results showed that the pTi-embedded PDMS samples promoted 80-96% of cell adhesion and proliferation during the early stages of incubation. The low cytotoxicity of the pTi-embedded PDMS was confirmed, with cell viability of the MG63 cells being above 90%. Furthermore, the pTi-embedded PDMS facilitated the production of alkaline phosphatase and calcium deposition in the MG63 cells, as demonstrated by the higher amount of alkaline phosphatase (2.6 times) and calcium (10.6 times) on the pTi-embedded PDMS sample fabricated at 250 °C, 3 MPa. Overall, the work demonstrated that the CS process provided flexibility in the parameters used for the production of the modified PDMS substrates and is highly efficient for the fabrication of coated polymer products. The results obtained in this study suggest that a tailorable porous and rough architecture could be achieved that promoted osteoblast function, indicating that the method has promise in the design of titanium-polymer composite materials applied to biomaterials used in musculoskeletal applications.

Background: Patients with influenza-associated acute respiratory distress syndrome (ARDS) requiring venovenous extracorporeal membrane oxygenation (vv-ECMO) support have a high mortality rate. Ventilator settings have been known to have a substantial impact on outcomes. However, the optimal settings of mechanical ventilation during vv-ECMO are still unknown., Methods: This multicenter retrospective cohort study was conducted in the intensive care units (ICUs) of three tertiary referral hospitals in Taiwan between July 2009 and December 2019. It aims to describe the effect of ventilator settings during vv-ECMO on patient outcomes., Results: A total of 93 patients with influenza receiving ECMO were screened. Patients were excluded if they: were receiving venoarterial ECMO, died within three days of vv-ECMO initiation, or were transferred to the tertiary referral hospital >24 hours after vv-ECMO initiation. A total of 62 patients were included in the study, and 24 (39%) died within six months. During the first three days of ECMO, there were no differences in tidal volume (5.1 vs. 5.2 mL/kg, p  = 0.833), dynamic driving pressure (15 vs. 14 cmH2O, p  = 0.146), and mechanical power (11.3 vs. 11.8 J/min, p  = 0.352) between survivors and non-survivors. However, respiratory rates were significantly higher in non-survivors compared with survivors (15 vs . 12 breaths/min, p  = 0.013). After adjustment for important confounders, a higher mean respiratory rate of >12 breaths/min was still associated with higher mortality (adjusted hazard ratio = 3.31, 95% confidence interval = 1.10-9.97, p  = 0.034)., Conclusions: In patients with influenza-associated ARDS receiving vv-ECMO support, we found that a higher respiratory rate was associated with higher mortality. Respiratory rate might be a modifiable factor to improve outcomes in this patient population., Competing Interests: The authors declare there are no competing interests., (©2022 Liao et al.)

A new species of scorpionfish, Poseidon's scorpionfish Parascorpaena poseidon , is described on the basis of ten specimens collected from southwestern Taiwanese waters ranging from Penghu to Chufongbi, Pingtung. The morphological and molecular analyses reveal the new species is clearly separated from the two similar species, P. aurita and P. mossambica . Parascorpaena poseidon is distinguished from congeners by the following combination of characters: three equal-sized suborbital spines without ridge; supraocular tentacle absent or very short; pectoral-fin rays 15-16 (usually 16); pored lateral-line scales 22-26 (usually 22-23); longitudinal scale rows 43-47; pre-dorsal-fin scale rows 2-3 (usually 3); 10-12 scale rows between 6th dorsal-fin spine base and lateral line; 10-12 scale rows between the last dorsal-fin spine base and lateral line; total gill rakers 15-16, gill rakers on hypobranchial 2-3; ratio of 11th and 12th dorsal-fin spine 60%-81% (mean 73%); blackish spots randomly distributed on all fins; absence of a distinct black blotch on spinous dorsal fin in male; body size relatively large.

The transformation of tumor cells from an epithelial to a mesenchymal-like phenotype, designated as epithelial-to-mesenchymal transition (EMT), represents a key hallmark of human cancer metastasis, including gastric cancer (GC). However, a large set of non-coding RNAs have been studied for their functions that initiate or inhibit this phenotypic switch in GC cells by regulating oncogenes or tumor suppressors. In this paper, we aimed to identify lncRNA SND1-IT1, miR-124, and COL4A1 gene in the context of GC with a specific focus on their effects on transforming growth factor β1 (TGF-β1)-induced EMT. The study included 52 paired samples of lesion tissues and adjacent lesion-free tissues surgically resected from patients diagnosed with GC. HGC-27 cells were stimulated with exogenous TGF-β1 (2 ng/mL). Expression of lncRNA SND1-IT1, miR-124, and COL4A1 was determined by RT-qPCR. CCK-8 assays, Transwell assays, immunoblotting analysis of EMT-specific markers, and tumor invasion markers were performed to evaluate cell viability, migration, and invasion of cultured HGC-27 cells. Luciferase activity assay was employed to examine miR-124 binding with lncRNA SND1-IT1 and COL4A1, respectively. LncRNA SND1-IT1 was upregulated in GC tissues and cells. TGF-β1-stimulated EMT and regulated lncRNA SND1-IT1, miR-124, and COL4A1 expressions in HGC-27 cells. LncRNA SND1-IT1 knockdown tempered HGC-27 cell viability, migration and invasion. LncRNA SND1-IT1 participated in TGF-β1-stimulated EMT in GC by sponging miR-124. MiR-124 attenuated TGF-β1-stimulated EMT in GC by targeting COL4A1. These results primarily demonstrated TGF-β1 can regulate cancer cell migration, invasion and stimulate EMT through the SND1-IT1/miR-124/COL4A1 axis in GC., (© 2022. The Author(s).)

DNA metabarcoding analysis for gut contents has been shown to compensate the disadvantage of traditionally morphological identification and offer higher resolution of prey items in an efficient way. Holland's carp (Spinibarbus hollandi) is a freshwater fish native to southern and eastern Taiwan. In the past two decades, this species has been introduced as a sport fish into the river basins of northern and western Taiwan. The large body size and active predation make it a potential threat for native fishes, but which native species are preyed by Holland's carp remains unknown. In this study, the diet from the gut contents of Holland's carp from the Zhonggang River, an invaded basin, was examined using DNA metabarcoding from 51 individuals and by morphological examinations on 140 samples. Detritus of plants were found in 83.6% samples (117 individuals). Twenty fish species of seven families were identified by DNA metabarcoding, including species of all water layers. Taiwan torrent carp (Acrossocheilus paradoxus) and Rhinogobius spp. are the most common prey items. Based on the results of this study, Holland's carp is considered an opportunistic omnivore because of its diverse diet items, which is an important trait for successful invasive fish species. The population decline of Opsariichthys pachycephalus may not result from the invasion of Holland's carps. Nonetheless, the time lag between successful invasion and the samplings of this study may be a concern because the population size of O. pachycephalus may have declined and become difficult to prey. The Holland's carps consumed the least species in winter; nonetheless, the occurrence frequencies of preys among seasons were not significantly different probably because of limited temperature fluctuation. The smallest Holland's carps consumed the least prey species compared to other size categories, similar to the relationship of prey species number to size of invasive largemouth bass (Micropterus salmoides)., (© 2021 Fisheries Society of the British Isles.)

Uremic toxins, such as indoxyl sulfate (IS) and kynurenine, accumulate in the blood in the event of kidney failure and contribute to further bone damage. To maintain the homeostasis of the skeletal system, bone remodeling is a persistent process of bone formation and bone resorption that depends on a dynamic balance of osteoblasts and osteoclasts. The aryl hydrocarbon receptor (AhR) is a ligand-activated transcription factor that regulates the toxic effects of uremic toxins. IS is an endogenous AhR ligand and is metabolized from tryptophan. In osteoclastogenesis, IS affects the expression of the osteoclast precursor nuclear factor of activated T cells, cytoplasmic 1 (NFATc1) through AhR signaling. It is possible to increase osteoclast differentiation with short-term and low-dose IS exposure and to decrease differentiation with long-term and/or high-dose IS exposure. Coincidentally, during osteoblastogenesis, through the AhR signaling pathway, IS inhibits the phosphorylation of ERK, and p38 reduces the expression of the transcription factor 2 (Runx2), disturbing osteoblastogenesis. The AhR antagonist resveratrol has a protective effect on the IS/AhR pathway. Therefore, it is necessary to understand the multifaceted role of AhR in CKD, as knowledge of these transcription signals could provide a safe and effective method to prevent and treat CKD mineral bone disease.

Objective: To evaluate the effect of a 12-week breathing-based leg exercises program on quality of life under stabilizing heart rate variability and reducing fatigue in regular hemodialysis patients., Design: Randomized controlled trial., Setting: A 94-bed hemodialysis department at a medical center in northern Taiwan., Participants: Eighty-six patients with end-stage renal disease undergoing hemodialysis were recruited and randomly assigned to the ExBr or control groups., Interventions: The breathing-based leg exercises program comprised abdominal breathing and low-intensity leg exercise, including leg lifts, quadriceps femoris contraction and knee flexion, and lasted for 15 minutes at one time, three times a week for 12 weeks., Main Measure: Data was collected by using the World Health Organization quality of life assessment-brief, physiological signal recorder for heart rate variability and hemodialysis-related fatigue scale at baseline and on Week 4, Week 8, and Week 12., Results: Average (standard deviation) age was 53.70 (10.04) years in the ExBr group and 61.19 (10.19) years in the control group. The linear mixed model with adjusted age, creatinine, heart rate variability and fatigue revealed that the ExBr group had significantly higher quality of life than did the control group ( P  = 0.01), especially on Week 12 ( P  = 0.04). Fatigue was significantly correlated with quality of life ( P <  0.001)., Conclusion: This study supported the benefits of the continued breathing-based leg exercises during hemodialysis for at least 12 weeks, which improved the quality of life of patients with end-stage renal disease and did not affect the stability of their vital signs.

Canakinumab is a fully human monoclonal antibody that specifically neutralizes human interleukin (IL)-1β and has been approved by the US Food and Drug Administration for treating different types of autoinflammatory disorders such as cryopyrin-associated periodic syndrome, tumor necrosis factor receptor-associated periodic syndrome and systemic juvenile idiopathic arthritis. However, long-term systemic neutralization of IL-1β by Canakinumab may cause severe adverse events such as serious upper respiratory tract infections and inflammation, thereby decreasing the quality of life of patients. Here, we used an IgG1 hinge as an Ab lock to cover the IL-1β-binding site of Canakinumab by linking with matrix metalloprotease 9 (MMP-9) substrate to generate pro-Canakinumab that can be specifically activated in the inflamed regions in autoinflammatory diseases to enhance the selectivity and safety of treatment. The Ab lock significantly inhibited the IL-1β-binding by 68-fold compared with Canakinumab, and MMP-9 completely restored the IL-1β neutralizing ability of pro-Canakinumab within 60 min and blocked IL-1β-downstream signaling and IL-1β-regulated genes (i.e., IL-6). It is expected that MMP-9 cleavable and efficient Ab lock will be able to significantly enhance the selective reaction of Canakinumab at the disease site and reduce the on-target toxicities of Canakinumab during systemic circulation, thereby showing potential for development to improve the safety and quality of life of patients with autoinflammatory disorders in the future., (© 2021. The Author(s).)

The on-target toxicity of monoclonal antibodies (Abs) is mainly due to the fact that Abs cannot distinguish target antigens (Ags) expressed in disease regions from those in normal tissues during systemic administration. In order to overcome this issue, we "copied" an autologous Ab hinge as an "Ab lock" and "pasted" it on the binding site of the Ab by connecting a protease substrate and linker in between to generate a pro-Ab, which can be specifically activated in the disease region to enhance Ab selectivity and reduce side effects. Previously, we reported that 70% of pro-Abs can achieve more than 100-fold blocking ability compared to the parental Abs. However, 30% of pro-Abs do not have such efficient blocking ability. This is because the same Ab lock linker cannot be applied to every Ab due to the differences in the complementarity-determining region (CDR) loops. Here we designed a method which uses structure-based computational simulation (MSCS) to optimize the blocking ability of the Ab lock for all Ab drugs. MSCS can precisely adjust the amino acid composition of the linker between the Ab lock and Ab drug with the assistance of molecular simulation. We selected αPD-1, αIL-1β, αCTLA-4 and αTNFα Ab as models and attached the Ab lock with various linkers (L1 to L7) to form pro-Abs by MSCS, respectively. The resulting cover rates of the Ab lock with various linkers compared to the Ab drug were in the range 28.33-42.33%. The recombinant pro-Abs were generated by MSCS prediction in order to verify the application of molecular simulation for pro-Ab development. The binding kinetics effective concentrations (EC-50) for αPD-1 (200-250-fold), αIL-1β (152-186-fold), αCTLA-4 (68-150-fold) and αTNFα Ab (20-123-fold) were presented as the blocking ability of pro-Ab compared to the Ab drug. Further, there was a positive correlation between cover rate and blocking ability of all pro-Ab candidates. The results suggested that MSCS was able to predict the Ab lock linker most suitable for application to αPD-1, αIL-1β, αCTLA-4 and αTNFα Ab to form pro-Abs efficiently. The success of MSCS in optimizing the pro-Ab can aid the development of next-generation pro-Ab drugs to significantly improve Ab-based therapies and thus patients' quality of life., Competing Interests: T.-L. C., C.-H. C. and Y.-C. L. are listed as inventors on patents [U.S. application number: 14/893,509] related to the technology described in this work. The other authors declare that they have no competing interests., (This journal is © The Royal Society of Chemistry.)

Two new moray eels of the genera Diaphenchelys and Gymnothorax from Taiwan and the Philippines are described. Diaphenchelys laimospila sp. nov. is described based on two specimens that represent the third species and a new geographic record of the genus. It can be distinguished from the other two congeners by the number of cephalic sensory pores, vertebral formula, morphometric measurements, and the coloration pattern. Gymnothorax pseudokidako sp. nov. is a muraenid with a dark brown body covered by pale snowflake-like blotches. It differs from the most similar species Gymnothorax kidako (Temminck and Schlegel) by having a relatively short tail (50.5-53.0% vs. 52.9-56.4% of TL), more dentary teeth (17-26 vs. 16-20), fewer total vertebrae (134-139 vs. 137-143), and the absence of white margin on anal fin (vs. prominent white margin). These two new species were also confirmed by molecular analyses, the mitochondrial COI gene (593 bp) for D. laimospila , and the nuclear EGR3 gene (767 bp) for G. pseudokidako .

Introduction: Stem-like cancer cells or cancer stem cells (CSCs) may comprise a phenotypically and functionally heterogeneous subset of cells, whereas the molecular markers reflecting this CSC hierarchy remain elusive. The glycolytic enzyme alpha-enolase (ENO1) present on the surface of malignant tumor cells has been identified as a metastasis-promoting factor through its function of activating plasminogen. The expression pattern of surface ENO1 (sENO1) concerning cell-to-cell or CSC heterogeneity and its functional roles await further investigation., Methods: The cell-to-cell expression heterogeneity of sENO1 was profiled in malignant cells from different types of cancers using flow cytometry. The subcellular localization of sENO1 and its functional roles in the invadopodia formation and cancer cell invasiveness were investigated using a series of imaging, molecular, and in vitro and in vivo functional studies., Results: We showed here that ENO1 is specifically localized to the invadopodial surface of a significant subset (11.1%-63.9%) of CSCs in human gastric and prostate adenocarcinomas. sENO1 + CSCs have stronger mesenchymal properties than their sENO1 - counterparts. The subsequent functional studies confirmed the remarkable pro-invasive and pro-metastatic capacities of sENO1 + CSCs. Mechanistically, inhibiting the surface localization of ENO1 by downregulating caveolin-1 expression compromised invadopodia biogenesis, proteolysis, and CSC invasiveness., Conclusions: Our study identified the specific expression of ENO1 on the invadopodial surface of a subset of highly invasive and pro-metastatic CSCs. sENO1 may provide a diagnostically and/or therapeutically exploitable target to improve the outcome of patients with aggressive and metastatic cancers., 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 © 2021 Huang, Liao, Hsu, Chan, Liao, Yang, Chen, Sung and Tsai.)

Rubi Fructus is a commonly used traditional Chinese medicine. The origin of Rubi Fructus is the dried fruit of Rubus chingii, a plant of the family Rosaceae, according to the 2015 edition of Chinese pharmacopoeia. There are some differences in the plant origin of Rubi Fructus in ancient herbal literature, to trace back its sources, we conducted a textual research on its origin, producing areas, quality evaluation, processing and concocting, properties, tastes and efficacy etc. based on the records of ancient herbal literatures and combined with plant morphology and related investigation. RESULTS:: showed that the variety of Rubi Fructus was more complex among ancient herbal literature, including R. coreanus, R. hirsutus, R. corchorifolius, R. foliolosus and other mixed varieties. Most scholars believe that the R. chingii has not been recorded in ancient herbal literature, while R. chingii was recorded as early as the Ming Dynasty in Compendium of materia medica through our textual research. Ancient Chinese herbs recorded that Rubi Fructus was mostly produced in Hubei, Shandong, Shanxi and Jiangsu provinces, while R. chingii mainly produced in Anhui, Jiangsu, Zhejiang, Jiangxi, Fujian and other provinces nowadays. Also, it was recorded that Rubi Fructus harvested in wheat field during May were the best. Besides, R. chingii with big, full, grain integrate, firm, yellow and green color, sour taste and impurity free possess the best quality in the contemporary. The ancient records of processing and concocting, properties, tastes and efficacy were basically the same as modern ones.These results provide the basis for the correct utilization and further development of Rubi Fructus.

Background: Gastric cancer (GC) is the third leading cause of cancer mortality globally and a molecularly heterogeneous disease. Identifying the driver pathways in GC progression is crucial to improving the clinical outcome. Recent studies identified ASPM (abnormal spindle-like microcephaly-associated) and FOXM1 (Forkhead box protein M1) as novel Wnt and cancer stem cell (CSC) regulators; their pathogenetic roles and potential crosstalks in GC remain unclarified., Methods: The expression patterns of ASPM isoforms and FOXM1 were profiled in normal gastric epithelial and GC tissues. The functional roles of ASPM and FOXM1 in Wnt activity, cancer stemness and GC progression, and the underlying signaling processes were investigated., Results: Approximately one third of GC cells upregulate the expression of ASPM isoform I (ASPMiI) in their cytoplasm; the tumors with a high ASPMiI positive score (≥ 10%) are associated with a poor prognosis of the patients. Mechanistically, the molecular interplay among FOXM1, ASPMiI and DVL3 was found to converge on β-catenin to control the Wnt activity and the stemness property of GC cells. This multi-mode Wnt-regulatory module serves to reinforce Wnt signals in CSCs by transcriptional regulation (FOXM1-ASPM), protein-protein interactions (ASPMiI-DVL3-β-catenin), and nuclear translocation (FOXM1-β-catenin)., Conclusions: This study illuminates a novel Wnt- and stemness-regulatory mechanism in GC cells and identifies a novel subset of FOXM1 high ASPMiI high GC with potential to guide Wnt- and stemness-related diagnostics and therapies.

Rhinogobius gigas is an amphidromous fish endemic to eastern Taiwan. Fishes with the diadromous behavior are expected to have a broader distribution range and higher genetic homogeneity despite that some amphidromous fishes with limited distribution are observed and R. gigas is an additional exception with a limited distribution range. Rhinogobius gigas has been documented to be retained inshore near the river plume with a short pelagic larval duration of 30-40 days, which may account for the endemism of this species. The short marine larval stage of R. gigas may imply a population genetic structure and the aim of the present study is to test whether the population genetic structure is present in R. gigas. To test the population genetic structure, fragments of mitochondrial displacement loop and cytochrome c oxidase subunit I were sequenced to provide molecular inference for genetic structure among populations. Sixty-nine haplotypes were identified among 191 R. gigas from 10 populations of eastern Taiwan and the mean haplotype and nucleotide diversities for all samples were 0.956 and 0.0024, respectively, implying a bottleneck followed by a recent population expansion further supported by Fu's Fs (-26.6; p < 0.001) and Tajima's D (-1.5; p = 0.037) values. The phylogenetic analysis revealed lack of genetic structure and the bush-like median joining network without commonly shared haplotypes supports the same scenario. The genetic homogeneity is probably due to the amphidromous life history providing the opportunity for passive larval transportation among the rivers through coastal currents in eastern Taiwan. The endemism to eastern Taiwan may be a consequence of complicated interactions among short pelagic larval duration, interspecific competition and coastal currents., Competing Interests: The authors have declared that no competing interests exist.

Background: Tumor-targeted nanoparticles hold great promise as new tools for therapy of liquid cancers. Furthermore, the therapeutic efficacy of nanoparticles can be improved by enhancing the cancer cellular internalization., Methods: In this study, we developed a humanized bispecific antibody (BsAbs: CD20 Ab-mPEG scFv) which retains the clinical anti-CD20 whole antibody (Ofatumumab) and is fused with an anti-mPEG single chain antibody (scFv) that can target the systemic liquid tumor cells. This combination achieves the therapeutic function and simultaneously "grabs" Lipo-Dox® (PEGylated liposomal doxorubicin, PLD) to enhance the cellular internalization and anticancer activity of PLD., Results: We successfully constructed the CD20 Ab-mPEG scFv and proved that CD20 Ab-mPEG scFv can target CD20-expressing Raji cells and simultaneously grab PEGylated liposomal DiD increasing the internalization ability up to 60% in 24 h. We further showed that the combination of CD20 Ab-mPEG scFv and PLD successfully led to a ninefold increase in tumor cytotoxicity (LC 50 : 0.38 nM) compared to the CD20 Ab-DNS scFv and PLD (lC 50 : 3.45 nM) in vitro. Importantly, a combination of CD20 Ab-mPEG scFv and PLD had greater anti-liquid tumor efficacy (P = 0.0005) in Raji-bearing mice than CD20 Ab-DNS scFv and PLD., Conclusion: Our results indicate that this "double-attack" strategy using CD20 Ab-mPEG scFv and PLD can retain the tumor targeting (first attack) and confer PLD tumor-selectivity (second attack) to enhance PLD internalization and improve therapeutic efficacy in liquid tumors.

Strophidon McClelland is a muraenid genus with characteristic appearance of a very elongated body, a large mouth cleft and anteriorly placed eyes. The nomenclature and taxonomic history of species within Strophidon are contentious and its members are easily misidentified. In the present study, species of the genus Strophidon are revised based on morphological and molecular data, and five species are considered valid, including S. dawydoffi Prokofiev, S. dorsalis (Seale), S. sathete (Hamilton), S. ui Tanaka and a new species, S. tetraporus. Strophidon tetraporus sp. nov. is described based on 15 specimens from Indonesia, the Philippines, Taiwan and Vietnam with the unique characteristic of the constant presence of the fourth infraorbital pore among species of Strophidon. The intraspecific variation of vertebral formula within S. dorsalis is discussed based on molecular data. Muraena macrurus Bleeker and Thyrsoidea longissima Kaup are synonyms of S. sathete that can be distinguished from the most similar congener S. ui by a longer tail, smaller eyes and more inner maxillary and inner dentary teeth. A key to identify species of Strophidon is provided. The distribution and maximum size of each species are also re-evaluated., (© 2020 Fisheries Society of the British Isles.)

Background: Developing a universal strategy to improve the specificity and sensitivity of PEGylated nanoaparticles (PEG-NPs) for assisting in the diagnosis of tumors is important in multimodality imaging. Here, we developed the anti-methoxypolyethylene glycol (mPEG) bispecific antibody (BsAb; mPEG × HER2), which has dual specificity for mPEG and human epidermal growth factor receptor 2 (HER2), with a diverse array of PEG-NPs to confer nanoparticles with HER2 specificity and stronger intensity., Result: We used a one-step formulation to rapidly modify the nanoprobes with mPEG × HER2 and optimized the modified ratio of BsAbs on several PEG-NPs (Lipo-DiR, SPIO, Qdot and AuNP). The αHER2/PEG-NPs could specifically target MCF7/HER2 cells (HER2 ++ ) but not MCF7/neo1 cells (HER2 +/- ). The αHER2/Lipo-DiR and αHER2/SPIO could enhance the sensitivity of untargeted PEG-NPs on MCF7/HER2 (HER2 ++ ). In in vivo imaging, αHER2/Lipo-DiR and αHER2/SPIO increased the specific targeting and enhanced PEG-NPs accumulation at 175% and 187% on 24 h, respectively, in HER2-overexpressing tumors., Conclusion: mPEG × HER2, therefore, provided a simple one-step formulation to confer HER2-specific targeting and enhanced sensitivity and contrast intensity on HER2 positive tumors for multimodality imaging.

Rhinogobius formosanus Oshima, 1919 has long been considered an amphidromous goby. However, a landlocked population recently found in the Jingualiao Creek upstream of the Feitsui Reservoir in Taipei suggests that R. formosanus may complete its life in the river. This study aims to verify the habitat use of the landlocked population of R. formosanus collected from the Feitsui Reservoir and an amphidromous population collected in Malian Creek using otolith Sr:Ca ratio analysis. The hypothesis that early life history varies between the landlocked and migratory gobies was also tested. Genetic analyses show that the Feitsui Reservoir and Malian Creek populations are not genetically different. Rhinogobius formosanus from Malian Creek showed high-to-low otolith Sr:Ca ratios suggesting that these specimens spent a planktonic larval stage in the sea followed by a freshwater life at later stages. In contrast, R. formosanus from the Feitsui Reservoir showed constant lower otolith Sr:Ca ratios, implying a landlocked life history of fish in the creek upstream of the reservoir. In addition, the analysis of growth increments showed a longer pelagic larval duration for the fish in the Malian Creek (58.8 days) than those in the Feitsui Reservoir (38.8). Variation of pelagic larval duration in two genetically homogenous populations implies acclimatization to the reservoir by the landlocked gobies. This study shows that R. formosanus , like some other congeners, is capable of adapting to a freshwater landlocked environment in its early developmental stage and supports the hypothesis that landlocked populations may have a shorter pelagic larval duration., (Te-Yu Liao, Wen-Chien Huang, Yoshiyuki Iizuka, Ming-Tai Chou, Jen-Chieh Shiao.)

Copper electrocatalysts have been shown to selectively reduce carbon dioxide to hydrocarbons. Nevertheless, the absence of a systematic study based on time-resolved spectroscopy renders the functional agent-either metallic or oxidative Copper-for the selectivity still undecidable. Herein, we develop an operando seconds-resolved X-ray absorption spectroscopy to uncover the chemical state evolution of working catalysts. An oxide-derived Copper electrocatalyst is employed as a model catalyst to offer scientific insights into the roles metal states serve in carbon dioxide reduction reaction (CO 2 RR). Using a potential switching approach, the model catalyst can achieve a steady chemical state of half-Cu(0)-and-half-Cu(I) and selectively produce asymmetric C 2 products - C 2 H 5 OH. Furthermore, a theoretical analysis reveals that a surface composed of Cu-Cu(I) ensembles can have dual carbon monoxide molecules coupled asymmetrically, which potentially enhances the catalyst's CO 2 RR product selectivity toward C 2 products. Our results offer understandings of the fundamental chemical states and insights to the establishment of selective CO 2 RR.

Rhodiola rosea L. ( R. rosea ) is one of the most beneficial medicinal plants and it is studied as an adaptogen. This study aims to evaluate the neuroprotective activity of compounds extracted from the root of R. rosea against methylglyoxal (MG)-induced apoptosis in neuro-2A (N2A) cells. The root of R. rosea was extracted with ethanol and partitioned with water, ethyl acetate, and n -butanol fractions to evaluate acetylcholinesterase (AChE) inhibitory activity and neuroprotective activity. The ethyl acetate fraction exhibited the highest values of AChE inhibitory activity (49.2% ± 3%) and cell viability (50.7% ± 4.8%) for neuroprotection. The structure identification of the most potential fraction (ethyl acetate fraction) revealed 15 compounds, consisting of three tannins, five flavonoids, and seven phenolics by infrared spectroscopy, nuclear magnetic resonance, and mass spectroscopy. All compounds were evaluated for their neuroprotective activity. Salidroside had the most potential neuroprotective activity. Gallic acid and methyl gallate had potential cytotoxicity in N2A cells. This study showed that R. rosea might have potential neuroprotective activities.

Rhodeus flaviventris, a new species, is described from the Le-An River, a tributary flowing into Poyang Lake in the Yangtze River basin, in Jiangxi Province, China. It is distinguished from all congeners by the combination of characters: branched dorsal-fin rays 9 (9-10); branched anal-fin rays 9 (9-10); longest simple rays of dorsal and anal fins thick and stiff; longitudinal scale series 33-34; transverse scale series 11 (10-12); pored scales 4-7; vertebrae 32-34; spindle-shaped eggs with major axis of 3.1-3.7 mm; color pattern of nuptial males (iris yellowish, belly yellow, central part of caudal fin orange, dorsal and anal fins with reddish-orange stripe).

Medical device associated infections remain a significant problem for all classes of devices at this point in time. Here, we have developed a surface modification technique to fabricate multifunctional coatings that combine antifouling and antimicrobial properties. Zwitterionic polymers providing antifouling properties and quaternary ammonium containing polymers providing antimicrobial properties were combined in these coatings. Throughout this study, aminomalononitrile (AMN) was used to achieve one-step coatings incorporating different polymers. The characterization of coatings was carried out using static water contact angle (WCA) measurements, X-ray photoelectron spectroscopy (XPS), profilometry, and scanning electron microscopy (SEM), whereas the biological response in vitro was analyzed using Staphylococcus epidermidis and Escherichia coli as well as L929 fibroblast cells. Zwitterionic polymers synthesized from sulfobetaine methacrylate and 2-aminoethyl methacrylate were demonstrated to reduce bacterial attachment when incorporated in AMN assisted coatings. However, bacteria in suspension were not affected by this approach. On the other hand, alkylated polyethylenimine polymers, synthesized to provide quaternary ammonium groups, were demonstrated to have contact killing properties when incorporated in AMN assisted coatings. However, the high bacterial attachment observed on these surfaces may be detrimental in applications requiring longer-term bactericidal activity. Therefore, AMN-assisted coatings containing both quaternary and zwitterionic polymers were fabricated. These multifunctional coatings were demonstrated to significantly reduce the number of live bacteria not only on the modified surfaces, but also in suspension. This approach is expected to be of interest in a range of biomedical device applications.

Background: To determine the temporal trends of incidence and outcome based on different sources of sepsis using a nationwide administrative database., Methods: From 2002 to 2012, the entire Taiwan's health insurance claims data of emergency-treated and hospital-treated sepsis were analysed for incidence and mortality trends. The information about patients with sepsis and sources of sepsis was identified using a set of validated International Classification of Diseases, ninth revision, clinical modification (ICD-9-CM) codes. The 30-day all-cause mortality was verified by linked death certificate database., Results: A total of 1 259 578 episodes of sepsis were identified during the 11-year study period. Lower respiratory tract infection is the most common source of sepsis in patients, with the highest mortality rate. The incidence of genitourinary tract infection has the fastest growing rate. The sepsis mortality was declining at different rates for each source of sepsis. Co-infections in patients with sepsis are associated with higher mortality rate., Conclusion: The temporal trends of sepsis incidence and mortality varied among different sources of sepsis, with lower respiratory tract being the highest burden among patients with sepsis. Furthermore, sources of sepsis and the presence of co-infection are independent predictors of mortality. Our results support source-specific preventive and treatment strategies for future sepsis management.

Background/aim: A retrospective study of cases with metastatic or advanced solid tumors complicated with AKI (acute kidney injury) with prerenal azotemia., Patients and Methods: Criteria included: (1) advanced or metastatic solid tumors that led to mortality; (2) prerenal azotemia identified upon renal function evaluation and (3) BUN to Cr ratio (BCR)≥15. We also compared the outcomes of patients with BCR>20 with those of patients with BCR=15-20., Results: A total of 218 patients with solid tumors were enrolled. One hundred and forty (64%) and 78 (36%) patients had BCR>20 and 15-20, respectively. Before AKI occurrence, 136 (62%) had thromboembolic complications and 96 (44%) paraneoplastic syndromes. Median survival time was 1 week in all patients. Median survival time was statistically different between the groups with BCR15-20 and BCR>20 (p<0.005, log-rank test)., Conclusion: Cancer patients with concurrent AKI and prerenal azotemia carry a very poor prognosis., (Copyright© 2020, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Based on cascaded Raman scattering, near-infrared (NIR) noise-like pulses (NLPs) were successfully demonstrated using a Yb-doped fiber amplifier system. Through a nonlinear fiber amplifier using a germanium-zirconia-silica Yb 3+ -doped single mode fiber as a gain fiber, the fourth-order Stokes wave (4 th -SW) can be excited to extend the emission peak of approximately 1.2-µm and a 3-dB bandwidth of approximately 130 nm. To further shift the wavelength more efficiently toward 1.3 µm, filtered NLPs with an emission peak at 1075 nm were adopted as seeded pulses to excite the fifth-order Stokes wave (5 th -SW) because of the better conversion efficiency of stimulated Raman scattering without gain competition with Yb-doped fiber. The generated NIR NLPs were shown to be an excellent light source for the photoluminescence emission from three photon absorption of perovskite to illustrate the red shift of the emission peak owing to the reabsorption effect.

A background study is important for the conservation and stock management of a species. Terapon jarbua is a coastal Indo-Pacific species, sourced for human consumption. This study examined 134 samples from the central west and east coasts of Peninsular (West) Malaysia and East Malaysia. A 1446-bp concatenated dataset of mtDNA COI and Cyt b sequences was used in this study and 83 haplotypes were identified, of which 79 are unique haplotypes and four are shared haplotypes. Populations of T. jarbua in Malaysia are genetically heterogenous as shown by the high level of haplotype diversity ranging from 0.9167-0.9952, low nucleotide diversity ranging from 0.0288-0.3434, and high F ST values (within population genetic variation). Population genetic structuring is not distinct as shown by the shared haplotypes between geographic populations and mixtures of haplotypes from different populations within the same genetic cluster. The gene flow patterns and population structuring observed among these regions are likely attributed to geographical distance, past historical events, allopatric speciation, dispersal ability and water currents. For instance, the mixture of haplotypes revealed an extraordinary migration ability of T. jarbua (>1200 km) via ancient river connectivity. The negative overall value of the neutrality test and a non-significant mismatch distribution are consistent with demographic expansion(s) in the past. The median-joining network concurred with the maximum likelihood haplotype tree with three major clades resolved. The scarcity of information on this species is an obstacle for future management and conservation purposes. Hence, this study aims to contribute information on the population structure, genetic diversity, and historical demography of T. jarbua in Malaysia., (Shyama Sundari Devi Chanthran, Phaik-Eem Lim, Yuan Li, Te-Yu Liao, Sze-Wan Poong, Jianguo Du, Muhammad Ali Syed Hussein, Ahemad Sade, Richard Rumpet, Kar-Hoe Loh.)

Many biomedical devices benefit from antibiofouling coatings, which can reduce biointerfacial interactions such as protein adsorption and cell attachment. In this study, we synthesized zwitterionic copolymers consisting of sulfobetaine methacrylate (SB) and 2-aminoethyl methacrylate (AE) via free radical polymerization and combined these copolymers in solution with aminomalononitrile to form zwitterionic coatings in an autopolymerization process. The successful deposition of coatings containing different SB/AE ratios was demonstrated by X-ray photoelectron spectroscopy. The one-step surface modification process was carried out on polydimethylsiloxane (PDMS), tissue culture polystyrene, and gold substrates, demonstrating that this method can be transferred to different substrate materials. The ability of optimized coatings to reduce serum protein adsorption was demonstrated by quartz crystal microbalance measurements while the ability to resist cell attachment for 24 h was demonstrated using L929 mouse fibroblasts. The stability of the coatings under physiological conditions was investigated, and resistance to cell attachment was maintained over a period of 45 days. Furthermore, the resistance of the copolymer coating to cell attachment was maintained after both ethylene oxide sterilization and autoclaving. Finally, copolymer-modified PDMS samples were investigated with regard to their ability to reduce the foreign body response in vivo. Here, a significant reduction in the capsule thickness (approximately 50%) was observed in nude mice after 2 and 4 weeks. It is expected that the one-step, facile, and versatile surface modification strategy discussed here will find applications in biomedical devices.

DNA barcoding based on a fragment of the cytochrome c oxidase subunit I (COI) gene is widely applied in species identification and biodiversity studies. The aim of this study was to establish a comprehensive barcoding database of coastal ray-finned fishes in Vietnam. A total of 3,638 specimens were collected from fish landing sites in northern, central and southern Vietnam. Seven hundred and sixty-five COI sequences of ray-finned fishes were generated, belonging to 458 species, 273 genera, 113 families and 43 orders. A total of 59 species were newly recorded in Vietnam and sequences of six species were new to the Genbank and BOLD online databases. Only 32 species cannot be annotated to species level because difficulty in morphological identifications and their Kimura-2-Parameter (K2P) genetic distances to most similar sequences were more than 2%. Moreover, intra-specific genetic distances in some species are also higher than 2%, implying the existence of putative cryptic species. The mean K2P genetic distances within species, genera, families, orders and classes were 0.34%, 12.14%, 17.39%, 21.42%, and 24.80, respectively. Species compositions are quite different with only 16 common species among northern, central and southern Vietnam. This may attribute to multiple habitats and environmental factors across the 3,260 km Vietnamese coastline. Our results confirmed that DNA barcoding is an efficient and reliable tool for coastal fish identification in Vietnam, and also established a reliable DNA barcode reference library for these fishes. DNA barcodes will contribute to future efforts to achieve better monitoring, conservation, and management of fisheries in Vietnam., Competing Interests: The authors have declared that no competing interests exist.

Background/aim: Chemotherapy is often halted due to abnormal liver function resembling hepatitis. But the cause can be extrahepatic portal venous obstruction (EHPVO) with hepatic enzyme elevation rather than being an adverse effect of chemotherapy. We investigated EHPVO with hepatic enzyme elevation in patients with cancer., Patients and Methods: Data of these hospitalized patients with solid tumors between January 2013 and September 2017 were collected. The criteria for study inclusion were: (i) Extrahepatic malignancy; (ii) computed tomographic scans showing a tumor with external compression of the extrahepatic portal vein; and (iii) serum aminotransferase (AST) or alanine transaminase (ALT) level three times above the normal value., Results: Thirteen out of 377 (3%) patients developed EHPVO with hepatic enzyme elevation, as demonstrated from computed tomographic scan. Four cases (31%) also had vascular thrombosis (three portal vein and one inferior vena cava). Serum AST increased from 34±11 to 169±94 U/l. ALT increased from 9±38 to 177±104 U/l. There was no relationship of EHPVO with viral markers and cirrhosis. Six cases received chemotherapy with liver function improvement., Conclusion: EHPVO occurred in patients with metastatic cancer, leading to hepatic enzyme elevation resembling hepatitis without hepatitis risk factors and cirrhosis. Before withholding chemotherapy due to hepatic enzyme elevation, the possibility of EHPVO should firstly be excluded., (Copyright© 2019, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background/aim: Urothelial carcinoma is a chemo-sensitive cancer. We investigated the contributory factors to survival benefit of metastatic urothelial carcinoma (MUC) patients receiving continuous maintenance chemotherapy., Patients and Methods: Inclusion criteria were: i) pathology-confirmed urothelial carcinoma, ii) metastatic lesions identified mainly on pre-therapy computed tomography (CT) scans, and iii) inpatient-administered chemotherapy of at least three cycles. Chemotherapy regimens included 5-fluorouracil, leucovorin, cisplatin, and gemcitabine., Results: A total of 139 cases were enrolled in this study. The overall objective response rate was 60% and the median survival time was 17 months. Eight-two (59%) patients had inflammation-related symptoms following the course of chemotherapy. Fifty-five (41%) patients survived more than two years. All patients exhibited various fibrosis formations. No patient experienced unfavorable metastatic conditions. Inflammation-related symptoms remained in 28 (51%) patients. We found that surgery, invasive procedures, and infection likely led to a rapid tumor progression., Conclusion: Continuous maintenance chemotherapy targeting chemo-sensitive tumors, administered at metronomic intervals and focus on tumor microenvironment, can increase MUC survival benefits., (Copyright© 2019, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)