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Hyun Ho Shin,1,* Junyoung Park,2,* Yeo-Jin Kim,3 Donghyeon Kim,2 Eun-Jung Jin,2,4 Ji Hyun Ryu1,3,4 1Department of Chemical Engineering, Wonkwang, University, Iksan, Jeonbuk, 54538, Republic of Korea; 2Department of Biological Sciences, College of Natural Sciences, Wonkwang University, Iksan, Jeonbuk, 54538, Republic of Korea; 3Department of Carbon Convergence Engineering, Smart Convergence Materials Analysis Center, Wonkwang University, Iksan, Jeonbuk, 54538, Republic of Korea; 4Integrated Omics Institute, Wonkwang University, Iksan, Jeonbuk, 54538, Republic of Korea*These authors contributed equally to this workCorrespondence: Ji Hyun Ryu, Department of Carbon Convergence Engineering, Iksan, Jeonbuk, 54538, Republic of Korea, Email jhryu4816@wku.ac.kr Eun-Jung Jin, Department of Biological Sciences, Wonkwang University, Iksan, Jeonbuk, 54538, Republic of Korea, Email jineunjung@wku.ac.krIntroduction: Cartilage regeneration is a challenging issue due to poor regenerative properties of tissues. Electrospun nanofibers hold enormous potentials for treatments of cartilage defects. However, nanofibrous materials used for the treatment of cartilage defects often require physical and/or chemical modifications to promote the adhesion, proliferation, and differentiation of cells. Thus, it is highly desirable to improve their surface properties with functionality. We aim to design hydrophilic, adhesive, and compound K-loaded nanofibers for treatments of cartilage defects.Methods: Hydrophilic and adhesive compound K-containing polycaprolactone nanofibers (CK/PCL NFs) were prepared by coatings of gallic acid-conjugated chitosan (CHI-GA). Therapeutic effects of CHI-GA/CK/PCL NFs were assessed by the expression level of genes involved in the cartilage matrix degradation, inflammatory response, and lipid accumulations in the chondrocytes. In addition, Cartilage damage was evaluated by safranin O staining and immunohistochemistry of interleukin-1β (IL-1β) using OA animal models. To explore the pathway associated with therapeutic effects of CHI-GA/CK/PCL NFs, cell adhesion, phalloidin staining, and the expression level of integrins and peroxisome proliferator-activated receptor (PPARs) were evaluated.Results: CHI-GA-coated side of the PCL NFs showed hydrophilic and adhesive properties, whereas the unmodified opposite side remained hydrophobic. The expression levels of genes involved in the degradation of the cartilage matrix, inflammation, and lipogenesis were decreased in CHI-GA/CK/PCL NFs owing to the release of CK. In vivo implantation of CHI-GA/CK/PCL NFs into the cartilage reduced cartilage degradation induced by destabilization of the medial meniscus (DMM) surgery. Furthermore, the accumulation of lipid deposition and expression levels of IL-1β was reduced through the upregulation of PPAR.Conclusion: CHI-GA/CK/PCL NFs were effective in the treatments of cartilage defects by inhibiting the expression levels of genes involved in cartilage degradation, inflammation, and lipogenesis as well as reducing lipid accumulation and the expression level of IL-1β via increasing PPAR. Keywords: polycaprolactone nanofibers, gallic acid-conjugated chitosan, compound K, hydrophilic coating, adhesive material, cartilage regeneration

Considerable evidence has been accumulated on serious acute health outcomes associated with short-term exposure to ambient fine particulate matter (PM 2.5 ). Modifying factors of those associations, however, have been less explored and need further analyses. In this national study, we investigated whether short-term effects of PM 2.5 are modified according to region, cause of mortality/hospitalization, season, age, and sex. PM 2.5 -related adverse health effects were estimated by an ecological time-series study, covering about 80 % of the Canadian population for 18 years (2001-2018). We estimated city-specific associations using daily averages of PM 2.5 and temperature, and daily counts of hospitalizations and mortality (non-accidental all-cause, circulatory, and respiratory). National and regional associations were then estimated with a 2-stage model. We considered potential modifying factors of PM 2.5 -related adverse health effects, and examined linear trends in the annual associations. Nationally, PM 2.5 exposure was associated with both hospitalizations and mortality, and there was evidence of differences by the modifying factors. Of the various causes, circulatory mortality and respiratory hospitalization were more attributable to PM 2.5 exposure. We found regional differences for both all-cause hospitalization and all-cause mortality, and seasonal differences for respiratory hospitalization (warm season) and circulatory hospitalization (cold season). Circulatory mortality risk was significant for seniors and females. All-cause hospitalizations appeared to gradually decrease over time, but annual all-cause mortality remained constant at 0.6 % of the population. Adverse health effects of PM 2.5 exposures may depend on not only PM 2.5 concentration, but also other factors (region, cause, season, age, sex). National estimates for the baseline (age ≥ 1 year, both sexes) risk cannot be interpreted without consideration of the differences by modifying factors. Study findings can be used by seniors, women, and those who have pre-existing health conditions to make informed decisions regarding their health risks from daily exposure to ambient PM 2.5 ., Competing Interests: Declaration of competing interest The study sponsor (Health Canada) had no role in study design, collection, analysis, interpretation of data, or writing of the manuscript. The authors also declare that they have no actual or potential competing financial interests, and that this study did not have any relationships or support that might be perceived as constituting a conflict of interest., (Crown Copyright © 2024. Published by Elsevier B.V. All rights reserved.)

The direction and magnitude of association between maternal exposure to ambient air pollutants across gestational windows and offspring risk of autism spectrum disorders (ASD) remains unclear. We sought to evaluate the time-varying effects of prenatal air pollutant exposure on ASD. We conducted a matched case-control study of singleton term children born in Ontario, Canada from 1-Apr-2012 to 31-Dec-2016. Provincial birth registry data were linked with applied behavioural analysis services and ambient air pollutant datasets to ascertain prenatal exposure to nitrogen dioxide (NO 2 ), ground-level ozone (O 3 ), fine particulate matter (PM 2.5 ), and ASD diagnoses. Covariate balance between cases and controls was established using coarsened exact matching. Conditional logistic regression was used to assess the association between prenatal air pollutant exposure and ASD. Distributed lag non-linear models (DLNM) were used to examine the effects of single-pollutant exposure by prenatal week. Sensitivity analyses were conducted to assess the impact of exposure period on the observed findings. The final sample included 1589 ASD cases and 7563 controls. Compared to controls, cases were more likely to be born to mothers living in urban areas, delivered by Caesarean section, and assigned male sex at birth. NO 2 was a consistent and significant contributor to ASD risk after accounting for co-exposure to O 3 , PM 2.5 and covariates. The odds ratio per interquartile range increase was 2.1 (95%CI 1.8-2.3) pre-conception, 2.2 (2.0-2.5) for the 1st trimester, 2.2 (1.9-2.5) for the 2nd trimester, and 2.1 (1.9-2.4) for the 3rd trimester. In contrast, findings for O 3 and PM 2.5 with ASD were inconsistent. Findings from DLNM and sensitivity analyses were similar. Exposure to NO 2 before and during pregnancy was significantly associated with ASD in offspring. The relationship between prenatal O 3 and PM 2.5 exposure and ASD remains unclear. Further investigation into the combined effects of multi-pollutant exposure on child neurodevelopment is warranted., 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., (Crown Copyright © 2024. Published by Elsevier Inc. All rights reserved.)

Specific bacterial species induce algal blooms by producing growth-promoting substances, such as siderophores, under iron-limited conditions. However, the molecular mechanisms underlying these effects remain poorly understood. This study investigates the interactions between the harmful dinoflagellate Alexandrium pacificum (Group IV) and siderophore-producing bacteria, with a focus on iron acquisition facilitated by bacterial siderophores. During algal bloom seasons in the South Sea of Korea, Photobacterium sp. TY1-4 was isolated, which enhances A. pacificum cell density under iron-deficient conditions, TY1-4 can use the sterile exudates from A. pacificum as the sole source of carbon, suggesting a mutualistic relationship. Transcriptomic and genomic analyses revealed siderophore-mediated redox-based signaling and non-reductive pathways enhancing iron bioavailability. Photobacterium sp. TY1-4 initiates siderophore production through quorum sensing, whereas A. pacificum utilizes specific receptors and transporters for hydroxamate-type siderophores (ApFHUA and ApFHUC) to uptake iron. Three redox key iron-uptake genes were also identified in A. pacificum: membrane-bound ferroxidase ApFET3, high-affinity iron permease ApFTR1, and ferric-chelate reductases/oxidoreductases ApFRE1, with transcription levels inversely related to bioavailable iron. Increased iron bioavailability mediated by siderophores alleviates iron stress in A. pacificum, supporting its growth in iron-scarce environments. Additionally, A. pacificum co-cultured with Photobacterium sp. TY1-4 synthesized high-toxicity STXs, including GTX4, GTX2, and STX. These findings highlight the critical role of bacterial siderophores in iron binding and their potential impact on harmful algal bloom dynamics., 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.)

Objectives: Oral biofilms, including pathogens such as Porphyromonas gingivalis, are involved in the initiation and progression of various periodontal diseases. However, the treatment of these diseases is hindered by the limited efficacy of many antimicrobial materials in removing biofilms under the harsh conditions of the oral cavity. Our objective is to develop a gel-type antimicrobial agent with optimal physicochemical properties, strong tissue adhesion, prolonged antimicrobial activity, and biocompatibility to serve as an adjunctive treatment for periodontal diseases., Methods: Phenylboronic acid-conjugated alginate (Alg-PBA) was synthesized using a carbodiimide coupling agent. Alg-PBA was then combined with tannic acid (TA) to create an Alg-PBA/TA hydrogel. The composition of the hydrogel was optimized to enhance its mechanical strength and tissue adhesiveness. Additionally, the hydrogel's self-healing ability, erosion and release profile, biocompatibility, and antimicrobial activity against P. gingivalis were thoroughly characterized., Results: The Alg-PBA/TA hydrogels, with a final concentration of 5 wt% TA, exhibited both mechanical properties comparable to conventional Minocycline gel and strong tissue adhesiveness. In contrast, the Minocycline gel demonstrated negligible tissue adhesion. The Alg-PBA/TA hydrogel also retained its rheological properties under repeated 5 kPa stress owing to its self-healing capability, whereas the Minocycline gel showed irreversible changes in rheology after just one stress cycle. Additionally, Alg-PBA/TA hydrogels displayed a sustained erosion and TA release profile with minimal impact on the surrounding pH. Additionally, the hydrogels exhibited potent antimicrobial activity against P. gingivalis, effectively eliminating its biofilm without compromising the viability of MG-63 cells., Significance: The Alg-PBA/TA hydrogel demonstrates an optimal combination of mechanical strength, self-healing ability, tissue adhesiveness, excellent biocompatibility, and sustained antimicrobial activity against P. gingivalis. These attributes make it superior to conventional Minocycline gel. Thus, the Alg-PBA/TA hydrogel is a promising antiseptic candidate for adjunctive treatment of various periodontal diseases., 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 Authors. Published by Elsevier Inc. All rights reserved.)

Background/objectives: Hormonal alterations during menopause result in substantial physiological changes. Although hormone replacement therapy (HRT) is widely used as a treatment strategy for these changes, its use remains controversial due to its associated risks. Plant isoflavones are phytoestrogens that are considered a potential alternative therapy for postmenopausal syndrome. We aimed to investigate the efficacy of ethanolic extracts from Styphnolobium japonicum fruit (SJF) and germinated soybean embryo (GSE) in alleviating prominent menopausal symptoms., Methods: A cell model (MCF7 human breast cancer cells) was used to investigate estrogen-like activity. A rat ovariectomy model was used to simulate estrogen depletion after menopause and to evaluate the efficacy of the SJF-GSE complex extract at ratios of 1:1, 1:2, and 2:1., Results: Treatment with the SJF-GSE extract elicited estrogen-like effects, raising pS2 and estrogen receptor α expression in MCF7 cells. The extract was found to contain 48-72 mg/g sophoricoside and 8-12 mg/g soyasaponin 1, identified as active compounds. In ovariectomized rats, the extract effectively reduced body weight and fat content, alleviated vasomotor symptoms, improved vaginal mucosal health, and exerted osteoprotective effects by enhancing bone density and structure, reducing bone-resorption markers and positively altering estradiol levels and lipid profiles., Conclusions: The SJF-GSE extract, working synergistically, provides a safe and effective alternative to HRT for managing postmenopausal symptoms and enhancing bone health, without adverse effects. These findings support the inclusion of SJF and GSE in health-functional foods and underscore the importance of further research into plant-based therapies for menopause.

Metabolic dysfunction-associated fatty liver disease (MAFLD) is a common liver disease associated with obesity and is caused by the accumulation of ectopic fat without alcohol consumption. Coxsackievirus and adenovirus receptor (CAR) are vital for cardiac myocyte-intercalated discs and endothelial cell-to-cell tight junctions. CAR has also been reported to be associated with obesity and high blood pressure. However, its function in the liver is still not well understood. The liver of obese mice exhibit elevated CAR mRNA and protein levels. Furthermore, in the liver of patients with non-alcoholic steatohepatitis, CAR is reduced in hepatocyte cell-cell junctions compared to normal levels. We generated liver-specific CAR knockout (KO) mice to investigate the role of CAR in the liver. Body and liver weights were not different between wild-type (WT) and KO mice fed a paired or high-fat diet (HFD). However, HFD induced significant liver damage and lipid accumulation in CAR KO mice compared with WT mice. Additionally, inflammatory cytokines transcription, hepatic permeability, and macrophage recruitment considerably increased in CAR KO mice. We identified a new interaction partner of CAR using a protein pull-down assay and mass spectrometry. Apolipoprotein B mRNA editing enzyme catalytic polypeptide-like 3C (APOBEC3C) demonstrated a complex relationship with CAR, and hepatic CAR expression tightly regulated its level. Moreover, Apolipoprotein B (ApoB) and Low-density lipoprotein receptor (LDLR) levels correlated with APOBEC3C expression in the liver of CAR KO mice, suggesting that CAR may regulate lipid accumulation by controlling APOBEC3C activity. In this study, we showed that hepatic CAR deficiency increased cell-to-cell permeability. In addition, CAR deletion significantly increased hepatic lipid accumulation by inducing ApoB and LDLR expression. Although the underlying mechanism is unclear, CARs may be a target for the development of novel therapies for MAFLD., (© 2024. The Author(s).)

Plasmon photocatalysis reactions are thought to occur through vibrationally activated reactants, driven by nonthermal energy transfer from plasmon-induced hot carriers. However, a detailed quantum-state-level understanding and quantification of the activation have been lacking. Using anti-Stokes surface-enhanced Raman scattering (SERS) spectroscopy, we mapped the vibrational population distributions of reactants on plasmon-excited nanostructures. Our results reveal a highly nonthermal distribution with an anomalously enhanced population of multiquantum excited states  ( v ≥ 2). The shape of the distribution and its dependence on local field intensity and excitation wavelength cannot be explained by photothermal heating or vibronic optical transitions of the metal-molecule complex. Instead, it can be modeled by hot electron-molecule energy transfer mediated by the transient negative ions, establishing direct links among nonthermal reactant activation, plasmon-induced hot electrons, and negative ion resonances. Moreover, the presence of multiquantum excited reactants, which are far more reactive than those in the ground state or first excited state, presents opportunities for vibrationally controlling chemical selectivities.

Background: Increasing evidence links early life residential exposure to natural urban environmental attributes and positive health outcomes in children. However, few studies have focused on their protective effects on the risk of autism spectrum disorder (ASD). The aim of this study was to investigate the associations of neighborhood greenspace, and active living environments during pregnancy with ASD in young children (≤6 years)., Methods: We conducted a population-based matched case-control study of singleton term births in Ontario, Canada for 2012-2016. The ASD and environmental data was generated using the Ontario Autism Spectrum Profile, the Better Outcomes Registry & Network Ontario, and Canadian Urban Environmental Health Research Consortium. We employed conditional logistic regressions to estimate the odds ratio (OR) between ASD and environmental factors characterizing selected greenspace metrics and neighborhoods conducive to active living (i.e., green view index (GVI), normalized difference vegetation index (NDVI), tree canopy, park proximity and active living environments index (ALE))., Results: We linked 8643 mother-child pairs, including 1554 cases (18%). NDVI (OR 1.034, 0.944-1.024, per Inter Quartile Range [IQR] = 0.08), GVI (OR 1.025, 95% CI 0.953-1.087, per IQR = 9.45%), tree canopy (OR 0.992, 95% CI 0.903-1.089, per IQR = 6.24%) and the different categories of ALE were not associated with ASD in adjusted models for air pollution. In contrast, living closer to a park was protective (OR 0.888, 0.833-0.948, per 0.06 increase in park proximity index), when adjusted for air pollution., Conclusions: This study reported mixed findings showing both null and beneficial effects of green spaces and active living environments on ASD. Further investigations are warranted to elucidate the role of exposure to greenspaces and active living environments on the development of ASD., 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., (Crown Copyright © 2024. Published by Elsevier Inc. All rights reserved.)

Bacteriophages, also known as phages, are viruses that replicate in bacteria and archaea. Phages were initially discovered as antimicrobial agents, and they have been used as therapeutic agents for bacterial infection in a process known as "phage therapy." Recently, phages have been investigated as functional nanomaterials in a variety of areas, as they can function not only as therapeutic agents but also as biosensors and tissue regenerative materials. Phages are nontoxic to humans, and they possess self-assembled nanostructures and functional properties. Additionally, phages can be easily genetically modified to display specific peptides or to screen for functional peptides via phage display. Here, we demonstrated the application of phage nanomaterials in the context of tissue engineering, sensing, and probing., 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 © 2024 Kim, Heo, Kim and Shin.)

Background: Although high tibial osteotomy (HTO) is an established treatment option for medial compartment osteoarthritis, predictive factors for HTO treatment success remain unclear. This study aimed to identify informative variables associated with HTO treatment success and to develop and internally validate machine learning algorithms to predict which patients will achieve HTO treatment success for medial compartmental osteoarthritis., Methods: This study retrospectively reviewed patients who underwent medial opening-wedge HTO (MOWHTO) at our center between March 2010 and December 2015. The primary outcomes were a lack of conversion to total knee arthroplasty (TKA) and achievement of a minimal clinically important difference of improvement in the Knee Injury and Osteoarthritis Outcome Score (KOOS) at a minimum of five years postoperatively. Recursive feature selection was used to identify the combination of variables from an initial pool of 25 features that optimized model performance. Five machine learning algorithms (XGBoost, multilayer perception, support vector machine, elastic-net penalized logistic regression, and random forest) were trained using five-fold cross-validation three times and applied to an independent test set of patients. The performance of the model was evaluated by the area under the receiver operating characteristic curve (AUC)., Results: A total of 231 patients were included, and 200 patients (86.6%) achieved treatment success at the mean of 9 years of follow-up. A combination of seven variables optimized algorithm performance, and the following specific cutoffs increased the likelihood of MOWHTO treatment success: body mass index (BMI) ≤ 26.8 kg/m 2 , preoperative KOOS for pain ≤ 46.0, preoperative KOOS for quality of life ≤ 33.0, preoperative International Knee Documentation Committee score ≤ 42.0, preoperative Short-Form 36 questionnaire (SF-36) score > 42.25, three-month postoperative hip-knee-ankle angle > 1.0°, and three-month postoperative medial proximal tibial angle (MPTA) > 91.5° and ≤ 94.7°. The random forest model demonstrated the best performance (F1 score: 0.93; AUC: 0.81) and was transformed into an online application as an educational tool to demonstrate the capabilities of machine learning., Conclusions: The random forest machine learning algorithm best predicted MOWHTO treatment success. Patients with a lower BMI, poor clinical status, slight valgus overcorrection, and postoperative MPTA < 94.7 more frequently achieved a greater likelihood of treatment success., Level of Evidence: Level III, retrospective cohort study., (© 2024. The Author(s).)

Recently, interest in polyphenol-containing composite adhesives for various biomedical applications has been growing. Tannic acid (TA) is a polyphenolic compound with advantageous properties, including antioxidant and antimicrobial properties. Additionally, TA contains multiple hydroxyl groups that exhibit biological activity by forming hydrogen bonds with proteins and biomacromolecules. Furthermore, TA-containing polymer composites exhibit excellent tissue adhesion properties. In this study, the gelation behavior and adhesion forces of TA/Pluronic F127 (TA/PluF) composite hydrogels were investigated by varying the TA and PluF concentrations. PluF (above 16 wt%) alone showed temperature-responsive gelation behavior because of the closely packed micelle aggregates. After the addition of a small amount of TA, the TA/PluF hydrogels showed thermosensitive behavior similar to that of PluF hydrogels. However, the TA/PluF hydrogels containing more than 10 wt% TA completely suppressed the thermo-responsive gelation kinetics of PluF, which may have been due to the hydrogen bonds between TA and PluF. In addition, TA/PluF hydrogels with 40 wt% TA showed excellent tissue adhesion properties and bursting pressure in porcine intestinal tissues. These results are expected to aid in understanding the use of mixtures of TA and thermosensitive block copolymers to fabricate adhesive hydrogels for versatile biomedical applications.

Customizable bioadhesives for individual organ requirements, including tissue type and motion, are essential, especially given the rise in implantable medical device applications demanding adequate underwater adhesion. While synthetic bioadhesives are widely used, their toxicity upon degradation shifts focus to biocompatible natural biomaterials. However, enhancing the adhesive strengths of these biomaterials presents ongoing challenges while accommodating the unique properties of specific organs. To address these issues, three types of customized underwater bioadhesive patches (CUBAPs) with strong, water-responsive adhesion and controllable biodegradability and stretchability based on bioengineered mussel adhesive proteins conjugated with acrylic acid and/or methacrylic acid are proposed. The CUBAP system, although initially nonadhesive, shows strong underwater adhesion upon hydration, adjustable biodegradation, and adequate physical properties by adjusting the ratio of poly(acrylic acid) and poly(methacrylic acid). Through ex vivo and in vivo evaluations using defective organs and the implantation of electronic devices, the suitability of using CUBAPs for effective wound healing in diverse internal organs is demonstrated. Thus, this innovative CUBAP system offers strong underwater adhesiveness with tailored biodegradation timing and physical properties, giving it great potential in various biomedical applications., (© 2023 Wiley‐VCH GmbH.)

Attention toward the preventive effects of postbiotics on metabolic diseases has increased because of greater stability and safety over probiotics. However, studies regarding the bioactive effects of postbiotics, especially from probiotic Bacillus strains, are relatively limited. The anti-obesity effects of the cell-free culture supernatant of Bacillus velezensis KMU01 (CFS- B.vele ) were evaluated using high-fat-diet (HFD)-induced mice. HFD-induced mice (n = 8 per group) received equal volumes of (1) CFS- B.vele (114 mg/kg) in PBS, (2) Xenical in PBS, or (3) PBS alone by oral gavage daily for 13 weeks. The results demonstrated that CFS- B.vele changed the gut microbiota and showed anti-obesity effects in HFD-induced obese mice. The elevated Firmicutes/Bacteroidota ratio induced by HFD was decreased in the CFS- B.vele group compared to the other groups ( p  < 0.05). The CFS- B.vele intervention led to the enrichment of SCFA-producers, such as Roseburia and Eubacterium , in the cecum, suggesting their potential involvement in the amelioration of obesity. Due to these changes, the various obesity-related biomarkers (body weight, fat in tissue, white adipose tissue weight and size, serum LDL-cholesterol level, hepatic lipid accumulation, and adipogenesis/lipogenesis-related gene/protein expression) were improved. Our findings suggest that CFS- B.vele has potential as a novel anti-obesity agent through modulation of the gut microbiota., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests:Moon-Hee Sung reports financial support was provided by Korea Ministry of Small and Medium Enterprises and Startups. Moon Hee Sung reports financial support was provided by Korea 10.13039/501100003624Ministry of Agriculture, Food and Rural Affairs., (© 2024 The Authors. Published by Elsevier Ltd.)

Copper (Cu) is a widely used catalyst for the nitrate reduction reaction (NO 3 RR), but its susceptibility to surface oxidation and complex electrochemical conditions hinders the identification of active sites. Here, we employed electropolished metallic Cu with a predominant (100) surface and compared it to native oxide-covered Cu. The electropolished Cu surface rapidly oxidized after exposure to either air or electrolyte solutions. However, this oxide was reduced below 0.1 V vs. RHE, thus returning to the metallic Cu before NO 3 RR. It was distinguished from the native oxide on Cu, which remained during NO 3 RR. Fast NO 3 - and NO reduction on the metallic Cu delivered 91.5 ± 3.7% faradaic efficiency for NH 3 at -0.4 V vs. RHE. In contrast, the native oxide on Cu formed undesired products and low NH 3 yield. Operando shell-isolated nanoparticle-enhanced Raman spectroscopy (SHINERS) analysis revealed the adsorbed NO 3 - , NO 2 , and NO species on the electropolished Cu as the intermediates of NH 3 . Low overpotential NO 3 - and NO adsorptions and favorable NO reduction are key to increased NH 3 productivity over Cu samples, which was consistent with the DFT calculation on Cu(100)., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

To understand environmental effects affecting paralytic shellfish toxin production of Centrodinium punctatum, this study examined the growth responses, and toxin contents and profiles of a C. punctatum culture exposed to drastic changes of temperature (5-30 °C) and salinity (15-40). C. punctatum grew over a temperature range of 15-25 °C, with an optimum of 20 °C., and over a salinity range of 25-40, with optimum salinities of 30-35. This suggests that C. punctatum prefers relatively warm waters and an oceanic habitat for its growth and can adapt to significant changes of salinity levels. When C. punctatum was cultivated at different temperature and salinity levels, the PST profile included four major analogs (STX, neoSTX, GTX1 and GTX4, constituted >80 % of the profile), while low amounts of doSTX and traces of dc-STX and dc-GTX2 were also observed. Interestingly, though overall toxin contents did not change significantly with temperature, increases in the proportion of STX, and decreases in proportions in GTX1 and GTX4 were observed with higher temperatures. Salinity did not affect either toxin contents or profile from 25 to 35. However, the total toxin content dropped to approximately half at salinity 40, suggesting this salinity may induce metabolic changes in C. punctatum., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Saxitoxin (STX) is a highly toxic small-molecule cyanotoxin that is water-soluble, stable in acidic media, and thermostable. STX is hazardous to human health and the environment in ocean, thus it is an important to detect it at very low concentrations. Herein, we developed an electrochemical peptide-based biosensor for the trace detection of STX in different sample matrix utilizing differential pulse voltammetry (DPV) signal. We synthesized the nanocomposite of zeolitic imidazolate framework-67 (ZIF-67) decorated bimetallic platinum (Pt) and ruthenium (Ru) nanoparticles (Pt-Ru@C/ZIF-67) using impregnation method. The nanocomposite modified with screen-printed electrode (SPE) was subsequently used to detect STX in the range of 1-1,000 ng mL -1 , with a detection limit (LOD) of 26.7 pg mL -1 . The developed peptide-based biosensor is highly selective and sensitive towards STX detection, thus it represents a promising strategy for the development of novel portable bioassay for monitoring various hazardous molecules in aquatic food chains., 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 Ltd. All rights reserved.)

The occurrence of leakage from anastomotic sites is a significant issue given its potential undesirable complications. The management of anastomotic leakage after gastrointestinal surgery is particularly crucial because it is directly associated with mortality and morbidity in patients. If adhesive materials could be used to support suturing in surgical procedures, many complications caused by leakage from the anastomosis sites could be prevented. In this study, we have developed self-healing, shear-thinning, tissue-adhesive, carbon-black-containing, gallic acid-conjugated chitosan (CB/Chi-gallol) hydrogels as sealing materials to be used with suturing. The addition of CB into Chi-gallol solution resulted in the formation of a crosslinked hydrogel with instantaneous solidification. In addition, these CB/Chi-gallol hydrogels showed enhancement of the elastic modulus (G') values with increased CB concentration. Furthermore, these hydrogels exhibited excellent self-healing, shear-thinning, and tissue-adhesive properties. Notably, the hydrogels successfully sealed the incision site with suturing, resulting in a significant increase in the bursting pressure. The proposed self-healing and adhesive hydrogels are potentially useful in versatile biomedical applications, particularly as suture support materials for surgical procedures.

Purpose: To demonstrate the clinical outcomes of patients with fungal periprosthetic joint infections (PJIs) after two-stage exchange arthroplasty combined with antifungal therapy., Methods: We retrospectively reviewed the outcomes of 41 patients with fungal PJIs after primary total knee arthroplasty (TKA) in a single centre from January 1999 to October 2017. During the first stage of resection arthroplasty, antifungal-impregnated cement spacers (AICSs) were implanted in all patients. After systemic antifungal treatment during the interval between the two surgeries, delayed reimplantation as part of a two-stage exchange protocol was performed when patients were clinically stable. We defined treatment success as a well-functioning arthroplasty without any signs of PJI after a minimum follow-up of two years without antimicrobial suppression. Successful treatment was confirmed by repeat negative cultures as well as a return of inflammatory markers to normal levels., Results: The treatment success rate was 63.4% at the final follow-up. Thirty-six of 41 patients (87.8%) met the criteria for second-stage revision after confirmation of complete infection control. The mean prosthesis-free interval was 6.6 months (range, 2.0-30.0 months). During follow-up after two-stage exchange arthroplasty, ten patients (27.7% of 36 patients) unfortunately experienced recurrence or relapse of infection after an average of 31.3 months (range, 2.7-135.6 months). The rate of survivorship free from reinfection was 94.4% at six months, 84.8% at one year, and 73.6% at two years. Cox proportional hazard regression analysis demonstrated that the prosthesis-free interval (HR = 1.016, p = 0.037) and mean length of antifungal treatment (HR = 0.226, p = 0.046) were potential risk factors for failure., Conclusion: Fungal PJIs led to devastating clinical outcomes despite even two-stage revision arthroplasty with the use of AICSs and antifungal medications., (© 2023. The Author(s) under exclusive licence to SICOT aisbl.)

In biology and chemistry, the ultimate goal is to monitor single molecules without labels. However, long-term monitoring of label-free molecules remains a challenge. Here, on the basis of the photothermal effect of gold nanorods (GNRs), we developed a platform for monitoring of a single molecule employing surface-enhanced Raman spectroscopy (SERS). Laser re-irradiation forms 1.0 nm gaps between GNRs, allowing us to observe single crystal violet (CV) molecules blinking for up to 4 min with dynamic surface-enhanced Raman spectroscopy (D-SERS). Bianalyte experiments confirm single-molecule features at CV concentrations of 10 -14 M. Combining density functional theory (DFT) calculations with a free CV molecule observed in millisecond D-SERS, we propose that CV molecules can be confined to sub-nanometer space and the orientation of an individual CV moving in the range of 50-90° can be dynamically captured by D-SERS. This will provide a novel idea for effective exploration of the temporal and spatial dynamic processes of different reactions.

Preventing anastomotic leakage (AL) and postoperative adhesions after gastrointestinal surgery is crucial for ensuring a favorable surgical prognosis. However, AL prevention using tissue adhesives can unintentionally lead to undesirable adhesion formation, while anti-adhesive agents may interfere with wound healing and contribute to AL. In this study, we have developed a double-layer patch, consisting of an adhesive layer on one side, utilizing gallic acid-conjugated chitosan (CHI-G), and an anti-adhesive layer on the opposite side, employing crosslinked hyaluronic acid (cHA). These CHI-G/cHA double-layer adhesives significantly prevented AL by forming physical barriers of CHI-G and reduced post-surgical adhesion at the anastomosis sites by the anti-adhesive layers of cHA. The bursting pressure (161.1 ± 21.6 mmHg) of double-layer adhesives-applied rat intestine at postoperative day 21 was far higher than those of the control (129.4 ± 5.7 mmHg) and the commercial anti-adhesives-applied group (120.8 ± 5.2 mmHg). In addition, adhesion score of double-layer adhesives-applied rat intestine was 3.6 ± 0.3 at postoperative day 21, which was similar to that of the commercial anti-adhesives-applied group (3.6 ± 0.3) and lower than that of the control group (4.9 ± 0.5). These findings indicate that the double-layer patch (CHI-G/cHA) has the potential to effectively prevent both postoperative adhesions and anastomotic leakage, offering a promising solution for gastrointestinal surgery., Competing Interests: The authors declare that there is no conflict of interest., (© 2023 The Authors.)

Biomaterial-based drug delivery systems have been developed to expedite cartilage regeneration; however, challenges related to drug recovery, validation, and efficient drug delivery remain. For instance, compound K (CK) is a major metabolite of ginsenosides that is known to protect against joint degeneration by inhibiting the production of inflammatory cytokines and the activation of immune cells. However, its effects on cartilage degradation and tissue regeneration remain unclear. Additionally, tissue-adhesive drug delivery depots that stably adhere to cartilage defects are required for CK delivery. In this study, CK-loaded adhesive patches were reported to seal cartilage defects and deliver CK to defect sites, preventing cartilage degradation and accelerating cartilage tissue regeneration. Adhesive patches are stable and suitable for application in surgical procedures under physiological conditions and show excellent adhesiveness to cartilage surfaces. In addition, there were no significant differences in the adhesive polymeric networks before and after CK loading. CK-loaded hydrocaffeic acid-conjugated chitosan patches significantly inhibited the stimulation of cartilage-degrading enzymes and apoptosis in osteoarthritic cartilage by releasing CK in cartilage defects. Additionally, the NFkB signaling pathway of released CK from the adhesive patches in the treatment of osteoarthritis is revealed. Thus, the CK-loaded adhesive patches are expected to significantly contribute to cartilage regeneration., (© The Author(s) 2023. Published by Oxford University Press.)

Recent studies on plasmon-assisted chemical reactions postulate that the hot electrons of plasmon-excited nanostructures may induce a non-thermal vibrational activation of metal-bound reactants. However, the postulate has not been fully validated at the level of molecular quantum states. We directly and quantitatively prove that such activation occurs on plasmon-excited nanostructures: The anti-Stokes Raman spectra of reactants undergoing a plasmon-assisted reaction reveal that a particular vibrational mode of the reactant is selectively excited, such that the reactants possess >10 times more energy in the mode than is expected from the fully thermalized molecules at the given local temperature. Furthermore, a significant portion (∼20%) of the excited reactant is in vibrational overtone states with energies exceeding 0.5 eV. Such mode-selective multi-quantum excitation could be fully modeled by the resonant electron-molecule scattering theory. Such observations suggest that the vibrationally hot reactants are created by non-thermal hot electrons, not by thermally heated electrons or phonons of metals. The result validates the mechanism of plasmon-assisted chemical reactions and further offers a new method to explore the vibrational reaction control on metal surfaces.

To better understand the role of resting cysts in the outbreak of paralytic shellfish poisoning and bloom dynamics in Jinhae-Masan Bay, Korea, this study investigated the germination features of ellipsoidal Alexandrium cysts isolated from sediments collected in winter and summer under different combinations of temperature and salinity. Morphology and phylogeny of germling cells revealed that the ellipsoidal Alexandrium cysts belong to Alexandrium catenella (Group I). The cysts could germinate across a wide range of temperature (5-25 °C) with germination success within 5 days, indicating that continuous seeding for the maintenance of vegetative cells in the water column may occur through the year without an endogenous clock to regulate germination timing. In addition, the cyst germination of A. catenella (Group I) was not controlled by seasonal salinity changes. Based on the results, this study provides a schematic scenario of the bloom development of A. catenella (Group I) in Jinhae-Masan Bay, Korea., 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 Ltd. All rights reserved.)

Most of the existing epidemiological studies have investigated adverse health effects of multiple air pollutants for a limited number of cities, thus the evidence of the health impacts is limited and it is challenging to compare these results because of different modeling approaches and potential publication bias. In this paper, we expand the number of Canadian cities, with the use of the most recent available health data. A multi-pollutant model in a case-crossover design is used to investigate the short-term impacts of air pollution on various health outcomes in 47 Canadian main cities, comparing three age groups (all-age, senior (age 66+), non-senior). The main findings are that a 14 ppb increase of O 3 was associated with a 0.17%-2.78% (0.62%-1.46%) increase in the odds of all-age respiratory mortality (hospitalization). A 12.8 ppb increase of NO 2 was associated with a 0.57%-1.47% (0.68%-1.86%) increase in the odds of all-age (non-senior) respiratory hospitalization. A 7.6 μgm -3 increase of PM 2.5 was associated with a 0.19%-0.69% (0.33%-1.1%) increase in the odds of all-age (non-senior) respiratory hospitalization., 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., (Crown Copyright © 2023. Published by Elsevier Inc. All rights reserved.)

The coxsackievirus and adenovirus receptor (CAR) is very well known as an epithelial tight junction and cardiac intercalated disc protein; it mediates attachment and infection via the coxsackievirus B3 (CVB3) and type 5 adenovirus. Macrophages play important roles in early immunity during viral infections. However, the role of CAR in macrophages is not well studied in relation to CVB3 infection. In this study, the function of CAR was observed in the Raw264.7 mouse macrophage cell line. CAR expression was stimulated by treatment with lipopolysaccharide (LPS) and tumor necrosis factor-α (TNF-α). In thioglycollate-induced peritonitis, the peritoneal macrophage was activated and CAR expression was increased. The macrophage-specific CAR conditional knockout mice (KO) were generated from lysozyme Cre mice. The expression of inflammatory cytokine (IL-1β and TNF-α) was attenuated in the KO mice's peritoneal macrophage after LPS treatment. In addition, the virus was not replicated in CAR-deleted macrophages. The organ virus replication was not significantly different in both wild-type (WT) and KO mice at days three and seven post-infection (p.i). However, the inflammatory M1 polarity genes (IL-1β, IL-6, TNF-α and MCP-1) were significantly increased, with increased rates of myocarditis in the heart of KO mice compared to those of WT mice. In contrast, type1 interferon (IFN-α and β) was significantly decreased in the heart of KO mice. Serum chemokine CXCL-11 was increased in the KO mice at day three p.i. compared to the WT mice. The attenuation of IFN-α and β in macrophage CAR deletion induced higher levels of CXCL-11 and more increased CD4 and CD8 T cells in KO mice hearts compared to those of WT mice at day seven p.i. These results demonstrate that macrophage-specific CAR deletion increased the macrophage M1 polarity and myocarditis in CVB3 infection. In addition, chemokine CXCL-11 expression was increased, and stimulated CD4 and CD8 T cell activity. Macrophage CAR may be important for the regulation of innate-immunity-induced local inflammation in CVB3 infection.

Endoscopic tattooing with India ink is a popular method for identifying colonic lesions during minimally invasive surgery because it is highly challenging to localize lesions during laparoscopy. However, there is a perceived unmet need for the injection of India ink and carbon particle suspension due to various complications and inconstant durability during the perioperative period. In this study, carbon black-containing self-healing adhesive alginate/polyvinyl alcohol composite hydrogels were synthesized as endoscopic tattooing inks. Alginate (Alg) conjugated with phenylboronic acid (PBA) groups in the backbone was crosslinked with polyvinyl alcohol (PVA) because of the dynamic bonds between the phenylboronic acid in alginate and the cis-diol groups of PVA. The carbon black-incorporated Alg-PBA/PVA hydrogels exhibited self-healing and re-shapable properties, indicating that improved intraoperative localization could be achieved. In addition, the adhesive tattooing hydrogels were stably immobilized on the target regions in the intraperitoneal spaces. These carbon black-containing self-healing adhesive hydrogels are expected to be useful in various surgical procedures, including endoscopic tattooing., (© 2023. The Author(s).)

Numerous studies have reported adverse health effects of ambient air pollution on circulatory health outcomes mainly based on single-pollutant models. However, limited studies have focused on adjusted effect of multi-pollutant exposures on public health. This study aimed to examine short-term effects of three common air pollutants-ground-level ozone (ozone), nitrogen dioxide (NO 2 ), and fine particulate matter (PM 2.5 )-through multi-pollutant models for mixed effect of adjustment. Daily data (circulatory hospitalization and mortality) and hourly data (air pollutants and temperature) were collected for 24 Canadian cities for 2001-2012. We applied generalized additive over-dispersion Poisson regression models with 1, 2, or 3 pollutants for city-specific risks, and Bayesian hierarchical models for national risks. This study found little mixed effect of adjustment through multi-pollutant models (ozone and/or NO 2 and/or PM 2.5 ) for circulatory hospitalization or mortality in Canada for 2001-2012, indicating that the 1-pollutant model did not result in considerable under- or over-estimates. It seemed weak-to-moderate correlations among air pollutants did not change the significant effect of one air pollutant after accounting for others. Inconsistent findings between other previous studies and this study indicate the need of comparable study design for multi-pollutant effect analysis., (© 2022. Crown Copyright as represented by the Minister of Health Canada.)

Upconverting nanoparticles (UCNPs) have been extensively investigated for nanophotonics and biomedical applications. However, establishing a unified view of their emission characteristics to elucidate the underlying photophysics and expand the application fields of these materials is a great challenge due to their sophisticated internal energy transfer and lack of standardized single-particle spectroscopy (SPS) platform. Here, we present an SPS technique called multiband single-particle irradiance-dependent imaging (multiband SPIDI). We demonstrate that the emission characteristics of Yb 3+ ,Tm 3+ -doped UCNPs are universal for three emission bands over a wide range of irradiance and dependent on the Tm 3+ doping concentration, indicating that the number of emitted photons of each band is proportional to the number of activator ions and is dependent on the number of absorbed photons and the activator interionic distance. We also suggest a cooperative energy transfer upconversion (CETU) mechanism for transition to a higher-energy state through photon accumulation. For a single UCNP, the emission at 800 nm is detectable at an ultralow irradiance of 4.9 W cm -2 ; moreover, that at 450 nm is measurable at 98 W cm -2 , based on the optimal concentration. These findings based on the multiband SPIDI platform can provide insights into the interionic energy transfer by studying irradiance-dependent steady-state dynamics to achieve brighter UCNPs and their broader applications.

Background: A total of 8,303 individuals (4.3%) with adverse reactions (n=191,860) after vaccination developed serious conditions or died. Such health developments could cause people not vaccinated yet or waiting for a booster shot to become fearful of the vaccination., Methods: The 3-month (July-September 2021) clinical data of 41 patients from the family medicine department of a single medical center were analyzed retrospectively to determine risk factors and to investigate the clinical course to identify the cause of symptoms in detail., Results: A significant number of older adults aged over 50 years reported experiencing general weakness (P=0.026) but fewer incidences of fever than patients aged 50 years or younger (P=0.011). Eighteen of the 41 patients were requested to visit more than twice or consult a specialist. In 14 patients, the symptoms were explained by other medical causes., Conclusion: The primary physician has a pivotal role in thoroughly evaluating patients who complain of adverse effects after vaccination, considering the broad multitude of symptoms and medical conditions presented. To thoroughly evaluate and appropriately advise patients with adverse reactions to their chosen vaccine, taking detailed medical history and nutritional counseling are required to identify possible underlying causes, resolve symptoms, and educate them on self-care and regarding vaccines.

Micropatterning is considered a promising strategy for improving the performance of electrochemical devices. However, micropatterning on ceramic is limited by its mechanically fragile properties. This paper reports a novel imprinting-assisted transfer technique to fabricate an interlayer structure in a protonic ceramic electrochemical cell with a micropatterned electrolyte. A dense proton-conducting electrolyte, BaCe 0.7 Zr 0.1 Y 0.1 Yb 0.1 O 3-δ , is micropatterned in a chevron shape with the highest aspect ratio of patterns in electrode-supported cells to the best of our knowledge, increasing surface areas of both electrode sides more than 40%. The distribution of relaxation time analysis reveals that the chevron-patterned electrolyte layer significantly increases the electrode contact areas and active electrochemical reaction sites at the vicinity of the interfaces, contributing to enhanced performances of both the fuel cell and electrolysis operations. The patterned cell demonstrates improved fuel cell performance (>45%) and enhances electrolysis cell performance (30%) at 500 °C. This novel micropatterning technique is promising for the facile production of layered electrochemical cells, further opening a new route for the performance enhancement of ceramic-based electrochemical cells.

The taxonomy of the extant dinoflagellate genus Gonyaulax is challenging since its thecate morphology is rather conservative. In contrast, cysts of Gonyaulax are varied in morphology and have been related with the fossil-based genera Spiniferites and Impagidinium. To better understand the systematics of Gonyaulax species, we performed germination experiments on cysts that can be identified as S. ristingensis, an unidentified Spiniferites with petaloid processes here described as Spiniferites pseudodelicatus sp. nov. and Impagidinium variaseptum from Chinese and Portuguese waters. Despite marked differences in cyst morphology, motile cells of S. pseudodelicatus and I. variaseptum are indistinguishable from Gonyaulax baltica. Motile cells hatched from S. ristingensis are morphologically similar to G. baltica as well but differ in the presence of one pronounced antapical spine. Three new species, Gonyaulax amoyensis (cyst equivalent S. pseudodelicatus), Gonyaulax bohaiensis (cyst equivalent I. variaseptum), and Gonyaulax portimonensis (cyst equivalent S. ristingensis), were erected. In addition, a new ribotype (B) of G. baltica was reported from South Korea and a bloom of G. baltica ribotype B is reported from New Zealand. Molecular phylogeny based on LSU and SSU rRNA gene sequences revealed that Gonyaulax species with minute or short antapical spines formed a well-resolved clade, whereas species with two pronounced antapical spines or lack of antapical spines formed the sister clade. Six strains of four above species were examined for yessotoxin production by liquid chromatography coupled with tandem mass spectrometry, and very low concentrations of yessotoxin were detected for one G. bohaiensis strain., (© 2022 Phycological Society of America.)

The demand to visualize the spatial distribution of chemical species based on vibrational spectra is rapidly increasing. Driven by such a need, various Raman and infrared spectro-microscopies with a nanometric spatial resolution have been developed over the last two decades. Despite rapid progress, a large gap still exists between the general needs and what these techniques can achieve. This Perspective highlights the key challenges and recent breakthroughs of the two vibrational nano-imaging techniques, scattering-type scanning near-field optical microscopy and tip-enhanced Raman scattering.

PBL plays a critical role in the atmosphere by transferring heat, moisture, and momentum. The warm PBL has a distinct diurnal cycle including daytime convective mixing layer (ML) and nighttime residual layer developments. Thus, for PBL characterization and process study, simultaneous determinations of PBL height (PBLH) and ML height (MLH) are necessary. Here, new approaches are developed to provide reliable PBLH and MLH to characterize warm PBL evolution. The approaches use Raman lidar (RL) water vapor mixing ratio (WVMR) and Doppler lidar (DL) vertical velocity measurements at the Southern Great Plains (SGP) atmospheric observatory, which was established by the Atmospheric Radiation Measurement (ARM) user facility. Compared with widely used lidar aerosol measurements for PBLH, WVMR is a better trace for PBL vertical mixing. For PBLH, the approach classifies PBL water vapor structures into a few general patterns, then uses a slope method and dynamic threshold method to determine PBLH. For MLH, wavelet analysis is used to re-construct 2-D variance from DL vertical wind velocity measurements according to the turbulence eddy size to minimize the impacts of gravity wave and eddy size on variance calculations; then, a dynamic threshold method is used to determine MLH. Remotely-sensed PBLHs and MLHs are compared with radiosonde measurements based on the Richardson number method. Good agreements between them confirm that the proposed new algorithms are reliable for PBLH and MLH characterization. The algorithms are applied to warm seasons' RL and ML measurements at the SGP site for five years to study warm season PBL structure and processes. The weekly composited diurnal evolutions of PBLHs and MLHs in warm climate were provided to illustrate diurnal and seasonal PBL evolutions. This reliable PBLH and MLH dataset will be valuable for PBL process study, model evolution, and PBL parameterization improvement.

A bacterial strain, designated J12C1-MA-4 T , was isolated from liquid culture of the dinoflagellate Ceratoperidinium margalefii. The bacterium was Gram-negative, aerobic, and rod-shaped. Oxidase and catalase were positive. Optimal growth was observed at 30 °C, pH 7.0, in the presence of 1% (w/v) NaCl. Phylogenetic analyses based on 16S rRNA gene and a 92 core gene set suggested that the strain J12C1-MA-4 T belongs to the family Rhodobacteraceae in the class Alphaproteobacteria and represents a taxon separated from other genera. 16S rRNA gene sequence of the strain J12C1-MA-4 T showed high similarities to Loktanella ponticola KCTC 42133 T (95.7%), Pseudooctadecabacter jejudonensis KCTC 32525 T (95.5%) and Jannaschia helgolandensis KCTC 12191 T (95.3%). The genome length of strain J12C1-MA-4 T was 3,621,968 bp with a DNA G + C content of 64.48 mol%. The major cellular fatty acids of strain J12C1-MA-4 T were summed feature 8 (comprising C 18:1 ω7c and/or C 18:1 ω6c) (> 10%). Phosphatidylglycerol (PG), phosphatidylcholine (PC), phospholipids (PL), lipids 1 (L1) and aminolipid (AL) were shown to be the major polar lipids. The sole predominant isoprenoid quinone was Q-10. Based on phylogenetic, phenotypic, chemotaxonomic and genomic features, we propose that strain J12C1-MA-4 T represent a novel species in the novel genus of the family Rhodobacteraceae, with the proposed name Gymnodinialimonas ceratoperidinii gen. nov., sp. nov.. The type strain is J12C1-MA-4 T (=KCTC 82770 T  =GDMCC 1.2729 T )., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Numerous studies have estimated adverse effects of short-term exposure to ambient air pollution on public health. Few have focused on sex-differences, and results have been inconsistent. The purpose of this study was three-fold: to identify sex-differences in air pollution-related health outcomes; to examine sex-differences by cause and season; and to examine time trends in sex-differences., Methods: Daily data were collected on circulatory- and respiratory-related mortality (for 29 years) and cause-specific hospitalization (for 17 years) with hourly concentrations of ozone (O3), nitrogen dioxide (NO2), and fine particulate matter (PM2.5). For hospitalization, more specific causes were examined: ischemic heart disease (IHD), other heart disease (OHD), cerebrovascular disease (CEV), chronic lower respiratory diseases (CLRD), and Influenza/Pneumonia (InfPn). Generalized Poisson models were applied to 24 Canadian cities, and the city-specific estimates were combined for nationwide estimates for each sex using Bayesian hierarchical models. Finally, sex-differences were tested statistically based on their interval estimates, considering the correlation between sex-specific national estimates., Results: Sex-differences were more frequently observed for hospitalization than mortality, respiratory than circulatory health outcomes, and warm than cold season. For hospitalization, males were at higher risk (M > F) for warm season (OHD and InfPn from O3; IHD from NO2; and InfPn from PM2.5), but F > M for cold season (CEV from O3 and OHD from NO2). For mortality, we found F > M only for circulatory diseases from ozone during the warm season. Among the above-mentioned sex-differences, three cases showed consistent time trends over the years: while M > F for OHD from O3 and IHD from NO2, F > M for OHD from NO2., Conclusions: We found that sex-differences in effect of ambient air pollution varied over health outcome, cause, season and time. In particular, the consistent trends (either F > M or M > F) across 17 years provide stronger evidence of sex-differences in hospitalizations, and warrant investigation in other populations., 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., (Crown Copyright © 2021. Published by Elsevier B.V. All rights reserved.)

Protein kinase B2 (AKT2) is involved in various cardiomyocyte signaling processes, including those important for survival and metabolism. Coxsackievirus B3 (CVB3) is one of the most common pathogens that cause myocarditis in humans. The role of AKT2 in CVB3 infection is not yet well understood. We used a cardiac-specific AKT2 knockout (KO) mouse to determine the role of AKT2 in CVB3-mediated myocarditis. CVB3 was injected intraperitoneally into wild-type (WT) and KO mice. The mice's survival rate was recorded: survival in KO mice was significantly decreased compared with WT mice (WT vs. KO: 73.3 vs. 27.1%). Myocardial damage and inflammation were significantly increased in the hearts of KO mice compared with those of WT mice. Moreover, from surface ECG, AKT2 KO mice showed a prolonged atria and ventricle conduction time (PR interval, WT vs. KO: 47.27 ± 1.17 vs. 64.79 ± 7.17 ms). AKT2 deletion induced severe myocarditis and cardiac dysfunction due to CVB3 infection. According to real-time PCR, the mRNA level of IL-1, IL-6, and TNF-α decreased significantly in KO mice compared with WT mice on Days 5 after infection. In addition, innate immune response antiviral effectors, Type I interferon (interferon-α and β), and p62, were dramatically suppressed in the heart of KO mice. In particular, the adult cardiac myocytes isolated from the heart showed high induction of TLR4 protein in KO mice in comparison with WT. AKT2 deletion suppressed the activation of Type I interferon and p62 transcription in CVB3 infection. In cardiac myocytes, AKT2 is a key signaling molecule for the heart from damage through the activation of innate immunity during acute myocarditis.

Background: Maternal prenatal exposure to air pollution has been associated with adverse birth outcomes. However, previous studies focused on a priori time intervals such as trimesters reported inconsistent associations., Objectives: We investigated time-varying vulnerability of birth weight to fine particulate matter (PM2.5) and nitrogen dioxide (NO2) using flexible time intervals., Methods: We analyzed 1,300 live, full-term births from Maternal-Infant Research on Environmental Chemicals, a Canadian prospective pregnancy cohort spanning 10 cities (2008-2011). Daily PM2.5 and NO2 concentrations were estimated from ground-level monitoring, satellite models, and land-use regression, and assigned to participants from pre-pregnancy through delivery. We developed a flexible two-stage modeling method-using a Bayesian Metropolis-Hastings algorithm and empirical density threshold-to identify time-dependent vulnerability to air pollution without specifying exposure periods a priori. This approach identified critical windows with varying lengths (2-363 days) and critical windows that fell within, or straddled, predetermined time periods (i.e., trimesters). We adjusted the models for detailed infant and maternal covariates., Results: Critical windows associated with reduced birth weight were identified during mid- to late-pregnancy for both PM2.5 and NO2: -6 g (95% credible interval: -11, -1 g) and -5 g (-10, -0.1 g) per µg/m3 PM2.5 during gestational days 91-139 and 249-272, respectively; and -3 g (-5, -1 g) per ppb NO2 during days 55-145., Discussion: We used a novel, flexible selection method to identify critical windows when maternal exposures to air pollution were associated with decrements in birth weight. Our results suggest that air pollution impacts on fetal development may not be adequately captured by trimester-based analyses., Competing Interests: The authors report no conflicts of interest., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

To better understand the outbreaks of paralytic shellfish poisoning and bloom dynamics caused by Alexandrium species in Jinhae-Masan Bay, Korea, the germination and distributions of ellipsoidal Alexandrium cysts were investigated, and paralytic shellfish toxins (PSTs) profiles and contents were determined using strains established from germling cells. The phylogeny and morphological observations revealed that the germinated vegetative cells from ellipsoidal cysts collected from the surface sediments in Jinhae-Masan Bay belong to Alexandrium catenella (Group I) and A. pacificum (Group IV) nested within A. tamarense species complex. Cyst germinations of A. catenella (Group I) were observed at only 10 °C, whereas cysts of A. pacificum (Group IV) could germinate at temperature ranges of 10 to 25 °C. Maximum germination success (85%) for isolated cysts occurred at 15 °C, and the germling cells were A. pacificum (Group IV). The results indicate that the variation in water temperature in Jinhae-Masan Bay can control the seasonal variations in germination of cysts of A. catenella (Group I) and A. pacificum (Group IV). The germination rates of ellipsoidal Alexandrium cysts were different among sampling sites in Jinhae-Masan Bay, probably because of differences in distribution and abundance of A. catenella (Group I) and A. pacificum (Group IV) in the sediments. The ellipsoidal Alexandrium cyst concentrations were much higher in February than in August, however the distributions were similar. Gonyautoxins 3 and 4 (GTX-3 and GTX-4) contributed a large proportion (>90%) of the toxins produced by strains A. catenella (Group I) and A. pacificum (Group IV) established from germling cells, and the total cellular contents were higher in A. catenella (Group I) than in A. pacificum (Group IV)., (Copyright © 2021. Published by Elsevier B.V.)

To understand the effects of the toxic marine dinoflagellate, Gymnodinium catenatum, on the brine shrimp, Artemia franciscana, we examined the acute toxicity and swimming behavior parameters such as swimming speed, swimming distance, and swimming path trajectory with transcriptional regulation of heat shock protein (hsp) genes in response to G. catenatum exposure. Mortality was not observed in response to G. catenatum. In the case of swimming behavior parameters, swimming speed and swimming distance were significantly decreased (P < 0.05) for 5 min at three concentrations (240, 360, and 600 cells/mL) of G. catenatum, whereas no significant change in swimming path trajectory was observed, suggesting that G. catenatum has potential adverse effects on the swimming behavior of A. franciscana. Additionally, the four A. franciscana-hsp genes (hsp26, hsp40, hsp70, and hsp90) were upregulated in response to G. catenatum. In particular, A. franciscana-hsp40 was significantly upregulated in response to 600 cells/mL G. catenatum, suggesting that A. franciscana-hsp genes are highly associated with cellular defense mechanisms and that A. franciscana-hsp40 is a potential biomarker for G. catenatum exposure. Overall, this study improves our understanding of the effects of G. catenatum on the swimming behavior and cellular defense mechanisms of A. franciscana., (Copyright © 2021 Elsevier B.V. All rights reserved.)

To clarify an unspecified toxic Gambierdiscus-like species isolated from seawaters off Jeju Island, Korea, its morphology and molecular phylogeny based on the small subunit (SSU) and partial large subunit (LSU) rRNA gene sequences were examined. Cells were narrow in ventral view and broad in lateral view with a smooth surface. The round thecal pores were evenly distributed, with an average diameter of 0.41 µm. Cell depth, width and height were 51.7 ± 4.5 μm, 43.0 ± 4.2 μm and 55.0 ± 4.7 μm, respectively, and depth-to-width (D/W) and height-to-width (H/W) ratios were 1.1 ± 0.2 μm and 1.3 ± 0.02 μm, respectively. The nucleus was located in the hypotheca. Scanning electron microscope observations revealed that the cells displayed a plate formula of Po, 4', 6'', 6c, 6s, 5''' and 2''', and transmission electron microscope observation demonstrated that the cells contained crystal-like particles. Morphological features indicated that the unspecified Korean isolate belonged to the genus Fukuyoa, and based on the H/W and D/W ratios, the apical pore H/W ratio and thecal pore size, it could be differentiated from other Fukuyoa species. The phylogenetic analyses based on the SSU and LSU rRNA sequences revealed that the Korean isolate was nested within the genus Fukuyoa with high support, and it grouped with F. cf. yasumotoi isolated from Japan. Based on the morpho-molecular data, a new species, Fukuyoa koreansis sp. nov. is proposed. The maximum growth rate (0.254 d -1 ) of F. koreansis was observed at 25°C and a salinity of 25. The required levels of temperature and salinity for growth distinguished Fukuyoa koreansis from Gambierdiscus species., (Copyright © 2021. Published by Elsevier B.V.)

A Gram-stain-negative, aerobic, rod-shaped strain (R2A-3 T ) was isolated from the toxin-producing dinoflagellate Centrodinium punctatum and identified as a novel genus and new species based on a polyphasic taxonomic approach. The optimum conditions for growth of the strain were at 25 °C, pH 8.0 and in the presence of 3 % (w/v) NaCl. Phylogenetic analyses based on 16S rRNA genes and 92 core genes sets revealed that strain R2A-3 T belongs to the family Nevskiaceae in the class Gammaproteobacteria and represented an independent taxon separated from other genera. The 16S rRNA gene of strain R2A-3 T showed the highest sequence similarity to Polycyclovorans algicola TG408 T (95.2%), Fontimonas thermophila HA-01 T (94.1%) and Sinimarinibacterium flocculans NH6-24 T (93.2%), and less than 92.8 % similarity to other genera in the family Nevskiaceae . The genome length of strain R2A-3 T was 3608892 bp with 65.2 mol% G+C content. Summed feature 8 (comprising C 18 : 1  ω 7 c and/or C 18 : 1  ω 6 c ) was the major fatty acid (>10 %). Diphosphatidylglycerol, phosphatidylglycerol and phosphatidylethanolamine were detected as the major polar lipids. The major respiratory quinone was ubiquinone-8. According to its phylogenetic, phenotypic, chemotaxonomic and genomic features, strain R2A-3 T represents a new species in the new genus of the family Nevskiaceae . It is recommended to name it Flagellatimonas centrodinii gen. nov., sp. nov. The type strain is R2A-3 T (=KCTC 82469 T =GDMCC 1.2523 T ).

Federated learning (FL) is a method used for training artificial intelligence models with data from multiple sources while maintaining data anonymity, thus removing many barriers to data sharing. Here we used data from 20 institutes across the globe to train a FL model, called EXAM (electronic medical record (EMR) chest X-ray AI model), that predicts the future oxygen requirements of symptomatic patients with COVID-19 using inputs of vital signs, laboratory data and chest X-rays. EXAM achieved an average area under the curve (AUC) >0.92 for predicting outcomes at 24 and 72 h from the time of initial presentation to the emergency room, and it provided 16% improvement in average AUC measured across all participating sites and an average increase in generalizability of 38% when compared with models trained at a single site using that site's data. For prediction of mechanical ventilation treatment or death at 24 h at the largest independent test site, EXAM achieved a sensitivity of 0.950 and specificity of 0.882. In this study, FL facilitated rapid data science collaboration without data exchange and generated a model that generalized across heterogeneous, unharmonized datasets for prediction of clinical outcomes in patients with COVID-19, setting the stage for the broader use of FL in healthcare., (© 2021. The Author(s), under exclusive licence to Springer Nature America, Inc.)

Establishing an appropriate disease model that mimics the complexities of human cardiovascular disease is critical for evaluating the clinical efficacy and translation success. The multifaceted and complex nature of human ischemic heart disease is difficult to recapitulate in animal models. This difficulty is often compounded by the methodological biases introduced in animal studies. Considerable variations across animal species, modifications made in surgical procedures, and inadequate randomization, sample size calculation, blinding, and heterogeneity of animal models used often produce preclinical cardiovascular research that looks promising but is irreproducible and not translatable. Moreover, many published papers are not transparent enough for other investigators to verify the feasibility of the studies and the therapeutics' efficacy. Unfortunately, successful translation of these innovative therapies in such a closed and biased research is difficult. This review discusses some challenges in current preclinical myocardial infarction research, focusing on the following three major inhibitors for its successful translation: Inappropriate disease model, frequent modifications to surgical procedures, and insufficient reporting transparency., 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 Shin, Shin and Shudo.)