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Ferns native to Korea, such as Davallia mariesii, Dicranopteris pedata, and Gleichenia japonica, possess antioxidant and antibacterial properties. However, their inhibitory effects on skin photoaging have not been demonstrated. Measurement and comparison of the antioxidant activity of three types of ferns revealed that the extract from G. japonica had the best effect. This study evaluates the potential of G. japonica extract as a new functional material for preventing skin damage caused by ultraviolet radiation. G. japonica extracts showed protective effects against ultraviolet B (UVB) radiation in human epidermal keratinocyte cells; the extracts inhibited intracellular reactive oxygen species production. In addition, collagen biosynthesis increased, and matrix metalloproteinase-1 activity and protein expression level decreased in human primary dermal fibroblast irradiated with UVB. The main peak (compound 1) of the extract was separated through high-performance liquid chromatography analysis and preparative liquid chromatography. Compound 1 is strongly inferred to be the main active ingredient because it showed better antioxidant activity and UVB protection effect than G. japonica extract. These results demonstrate the physiological effects of G. japonica extract and suggest its applicability as a new functional substance for preventing skin damage caused by ultraviolet radiation.

In this study, we focused on reducing the molecular weight of purified red okra pectin using various hydrolytic enzymes and evaluating its physicochemical properties or characterization. The enzyme treatments targeted both the main pectin chain and the side-chain sugars, resulting in a reduction in the molecular weight by approximately 10% (from 647 kDa) to 60% (down to 252 kDa). Both the purified red okra pectin and enzyme-treated pectins exhibited a homogalacturonan (HG)-type backbone. Fourier transform infrared (FT-IR) spectroscopy revealed a decrease in the absorbance peak for the pectin backbone (1200–1000 cm−1) in the low-molecular-weight (LMW) pectin. The most significant decrease was observed at 3300 cm−1 in pectin treated with both RGH+RGAE enzymes, indicating reduced sugar bonds. These results demonstrate the physicochemical changes in LMW red okra pectin following enzyme treatment and confirm its potential applications due to its unique characteristics.

ABSTRACT The coronavirus disease 2019 (COVID-19) pandemic has highlighted the need for safe and effective vaccines to be rapidly developed and distributed worldwide, especially considering the emergence of new severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants. Protein subunit vaccines have emerged as a promising approach due to their proven safety record and ability to elicit robust immune responses. In this study, we evaluated the immunogenicity and efficacy of an adjuvanted tetravalent S1 subunit protein COVID-19 vaccine candidate composed of the Wuhan, B.1.1.7 variant, B.1.351 variant, and P.1 variant spike proteins in a nonhuman primate model with controlled SIVsab infection. The vaccine candidate induced both humoral and cellular immune responses, with T and B cell responses mainly peaking post boost immunization. The vaccine also elicited neutralizing and cross-reactive antibodies, angiotensin-converting enzyme 2 (ACE2)-blocking antibodies, and T cell responses, including spike-specific CD4+ T cells. Importantly, the vaccine candidate was able to generate Omicron variant spike-binding and ACE2-blocking antibodies without specifically vaccinating with Omicron, suggesting potential broad protection against emerging variants. The tetravalent composition of the vaccine candidate has significant implications for COVID-19 vaccine development and implementation, providing broad antibody responses against numerous SARS-CoV-2 variants. IMPORTANCE The study provides important insights into the immunogenicity and efficacy of a tetravalent protein subunit vaccine candidate against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The vaccine induced both humoral and cellular immune responses in nonhuman primates with controlled SIVagm infection and was able to generate Omicron variant-specific antibodies without specifically vaccinating with Omicron. These findings suggest that the tetravalent composition of the vaccine candidate could provide broad protection against multiple SARS-CoV-2 variants while minimizing the risk of immune escape and the emergence of new variants. Additionally, the use of rhesus macaques with controlled SIVsab infection may better represent vaccine immunogenicity in humans with chronic viral diseases, highlighting the importance of preclinical animal models in vaccine development. Overall, the study provides valuable information for the development and implementation of coronavirus disease 2019 vaccines, particularly for achieving global vaccine equity and addressing emerging variants.

ABSTRACT The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants has raised concerns about reduced vaccine effectiveness and the increased risk of infection, and while repeated homologous booster shots are recommended for elderly and immunocompromised individuals, they cannot completely protect against breakthrough infections. In our previous study, we assessed the immunogenicity of an adenovirus-based vaccine expressing SARS-CoV-2 S1 (Ad5.S1) in mice, which induced robust humoral and cellular immune responses (E. Kim, F. J. Weisel, S. C. Balmert, M. S. Khan, et al., Eur J Immunol 51:1774–1784, 2021, https://doi.org/10.1002/eji.202149167). In this follow-up study, we found that the mice had high titers of anti-S1 antibodies 1 year after vaccination, and one booster dose of the nonadjuvanted rS1Beta (recombinant S1 protein of SARS-CoV-2 Beta [B.1.351]) subunit vaccine was effective at stimulating strong long-lived S1-specific immune responses and inducing significantly high neutralizing antibodies against Wuhan, Beta, and Delta strains, with 3.6- to 19.5-fold increases. Importantly, the booster dose also elicited cross-reactive antibodies, resulting in angiotensin-converting enzyme 2 (ACE2) binding inhibition against spikes of SARS-CoV-2, including Omicron variants, persisting for >28 weeks after booster vaccination. Interestingly, the levels of neutralizing antibodies were correlated not only with the level of S1 binding IgG but also with ACE2 inhibition. Our findings suggest that the rS1Beta subunit vaccine candidate as a booster has the potential to offer cross-neutralization against broad variants and has important implications for the vaccine control of newly emerging breakthrough SARS-CoV-2 variants in elderly individuals primed with adenovirus-based vaccines like AZD1222 and Ad26.COV2.S. IMPORTANCE Vaccines have significantly reduced the incidences of severe coronavirus disease 2019 (COVID-19) cases and deaths. However, the emergence of SARS-CoV-2 variants has raised concerns about their increased transmissibility and ability to evade neutralizing antibodies, especially among elderly individuals who are at higher risks of mortality and reductions of vaccine effectiveness. To address this, a heterologous booster vaccination strategy has been considered as a solution to protect the elderly population against breakthrough infections caused by emerging variants. This study evaluated the booster effect of an S1 subunit vaccine in aged mice that had been previously primed with adenoviral vaccines, providing valuable preclinical evidence for elderly people vaccinated with the currently approved COVID-19 vaccines. This study confirms the potential for using the S1 subunit vaccine as a booster to enhance cross-neutralizing antibodies against emerging variants of concern.

Abstract Background We previously showed that enzymatically hydrolyzed Dendropanax morbiferus H. Lév. leaf (Hy-DP) and unripe Rubus coreanus Miq. (5-uRCK) extracts exhibit potent vasodilator effects on isolated aortic rings from rats partly through endothelium-dependent and endothelium-independent mechanisms. These two extracts have different mechanisms of action; however, their combined effect on antihypertensive activity has not been explored. Methods The present study aims to investigate the effect of a chronic optimized mixture (HDR-2, composed of Hy-DP and 5-uRCK in a 2:1 mass ratio) on vascular tension and blood pressure in two different hypertensive rat models. Results The results showed that HDR-2 concentration-dependently relaxed endothelium-intact and endothelium-denuded aortic rings precontracted with phenylephrine. Antihypertensive effects were assessed in vivo on a 1 kidney-1 clip (1 K-1C) rat model of hypertension and spontaneously hypertensive rats (SHRs). Acute HDR-2 treatment significantly decreased systolic blood pressure (SBP) 3 h posttreatment in both models. Chronic HDR-2 administration also significantly decreased SBP in the hypertensive rat models. Moreover, HDR-2 increased eNOS protein expression and phosphorylation levels in the aorta. Conclusion Chronic HDR-2 administration may effectively improve vascular function by decreasing plasma angiotensin-converting enzyme (ACE) activity and AngII levels. HDR-2 significantly improved acetylcholine (ACh)-induced aortic endothelium-dependent relaxation and affected sodium nitroprusside (SNP)-induced endothelium-independent relaxation in SHRs.

Blue light is reported to be harmful to eyes by inducing reactive oxygen species (ROS). Herein, the roles of Peucedanum japonicum Thunb. leaf extract (PJE) in corneal wound healing under blue light irradiation are investigated. Blue-light-irradiated human corneal epithelial cells (HCECs) show increased intracellular ROS levels and delayed wound healing without a change in survival, and these effects are reversed by PJE treatment. In acute toxicity tests, a single oral administration of PJE (5000 mg/kg) does not induce any signs of clinical toxicity or body weight changes for 15 days post-administration. Rats with OD (oculus dexter, right eye) corneal wounds are divided into seven treatment groups: NL (nonwounded OS (oculus sinister, left eye)), NR (wounded OD), BL (wounded OD + blue light (BL)), and PJE (BL + 25, 50, 100, 200 mg/kg). Blue-light-induced delayed wound healing is dose-dependently recovered by orally administering PJE once daily starting 5 days before wound generation. The reduced tear volume in both eyes in the BL group is also restored by PJE. Forty-eight hours after wound generation, the numbers of inflammatory and apoptotic cells and the expression levels of interleukin-6 (IL-6) largely increase in the BL group, but these values return to almost normal after PJE treatment. The key components of PJE, identified by high-performance liquid chromatography (HPLC) fractionation, are CA, neochlorogenic acid (NCA), and cryptochlorogenic acid (CCA). Each CA isomer effectively reverses the delayed wound healing and excessive ROS production, and their mixture synergistically enhances these effects. The expression of messenger RNAs (mRNAs) related to ROS, such as SOD1, CAT, GPX1, GSTM1, GSTP1, HO-1, and TRXR1, is significantly upregulated by PJE, its components, and the component mixture. Therefore, PJE protects against blue-light-induced delayed corneal wound healing via its antioxidative, anti-inflammatory, and antiapoptotic effects mechanistically related to ROS production.

This paper presents a novel approach for improving the efficacy of COVID-19 vaccines against emergent SARS-CoV-2 variants. We have evaluated the immunogenicity of unadjuvanted wild-type (WU S1-RS09cg) and variant-specific (Delta S1-RS09cg and OM S1-RS09cg) S1 subunit protein vaccines delivered either as a monovalent or a trivalent antigen in BALB/c mice. Our results show that a trivalent approach induced a broader humoral response with more coverage against antigenically distinct variants, especially when compared to monovalent Omicron-specific S1. This trivalent approach was also found to have increased or equivalent ACE2 binding inhibition, and increased S1 IgG endpoint titer at early timepoints, against SARS-CoV-2 spike variants when compared monovalent Wuhan, Delta, or Omicron S1. Our results demonstrate the utility of protein subunit vaccines against COVID-19 and provide insights into the impact of variant-specific COVID-19 vaccine approaches on the immune response in the current SARS-CoV-2 variant landscape. Particularly, our study provides insight into effects of further increasing valency of currently approved SARS-CoV-2 vaccines, a promising approach for improving protection to curtail emerging viral variants.

RNA granules (RGs) are membraneless intracellular compartments that play important roles in the post-transcriptional control of gene expression. Stress granules (SGs) are a type of RGs that form under environmental challenges and/or internal cellular stresses. Stress treatments lead to strong mRNAs translational inhibition and storage in SGs until the normal growth conditions are restored. Intriguingly, we recently showed that plant stress granules are associated with siRNA bodies, where the RDR6-mediated and transposon-derived siRNA biogenesis occurs (Kim et al., 2021). This protocol provides a technical workflow for the enrichment of cytoplasmic RGs from Arabidopsis seedlings. We used the DNA methylation-deficient ddm1 mutant in our study, but the method can be applied to any other plant samples with strong RG formation. The resulting RG fractions can be further tested for either RNAs or proteins using RNA-seq and mass spectrometry-based proteomics.

Purpose Previously, we demonstrated that the specific ratio of Korean multi-herbal formula (SR-5) exhibits hepatoprotective properties against ethanol-induced hepatic damage in rats. Chronic and excessive alcohol consumption is a major etiological factor involved in gastric disease and ulcer development induced by the inflammatory response and oxidative stress. Methods The present study evaluated the gastroprotective effects of SR-5 (100, 150, and 200 mg/kg) against hydrochloride acid/ethanol (HCl/EtOH)-induced and indomethacin/hydrochloride acid (INDO/HCl)-induced gastritis in a mouse model and the mechanisms involved. Results All the tested doses of SR-5 significantly inhibited gastric lesions in the HCl/EtOH-induced ulcer model mice. Similarly, all the tested doses of SR-5 significantly inhibited gastric lesions in the INDO/HCl-induced ulcer model mice. Furthermore, mice pretreated with SR-5 had significantly increased gastric levels of enzymatic and nonenzymatic antioxidants, namely, catalase (CAT) and glutathione (GSH), with concomitant reductions in malondialdehyde (MDA) and reactive oxygen species (ROS) levels compared with those in the HCl/EtOH or INDO/HCl group. SR-5 suppressed the expression of nuclear factor-kappa B (NF-κB)/p65, inducible nitric oxide synthase (iNOS), tumor necrosis factor-α (TNF-α), and cyclooxygenase-2 (COX-2) to their normal values. Conclusion These findings are the first to demonstrate the powerful protective effect of SR-5 against gastric injury development and provide hope for clinical application.

Motivational regulation, or the way learners purposefully initiate, maintain, or supplement their willingness for task engagement and completion, has been an important area of research in educational psychology. However, despite the surge of research on this topic, it remains unclear how specific motivational regulation strategies relate to learners' academic performance, motivation, and other forms of self-regulation. Based on findings from 55 studies (67 unique samples), we found a range of positive correlations among 10 types and subtypes of motivational regulation strategies and the following variables: academic achievement (rs = 0.01-0.15), motivation (effort, rs = 0.11-0.52; value perceptions, rs = 0.21-0.35; and competence beliefs, rs = 0.22-0.40), and self-regulation (cognitive, rs = 0.28-0.51; behavioral, rs = 0.10-0.33). Moderator results indicated that the magnitudes of associations among motivational regulation strategies and achievement and self-regulation varied by grade level and geographic region. Intercorrelations among motivational regulation strategies indicated wide-ranging degrees of overlap across strategies. Using meta-analytic structural equation modeling, we explored how motivational regulation strategies indirectly related to achievement through motivational beliefs and how self-regulatory factors were precursors to motivational regulation. Our meta-analytic findings shed light upon which motivational regulation strategies might be most adaptive for academic achievement, motivation, and self-regulation, and identified for whom and under what circumstances specific strategies can be most adaptively used.

Abstract In patients with back or scapular pain, if there is evidence of neurological symptoms, fever, chills, malaise, or other signs of infection, the work‐up should consider the possibility of a spinal‐esophageal fistula.

Background: Coronaviruses pose a serious threat to global health as evidenced by Severe Acute Respiratory Syndrome (SARS), Middle East Respiratory Syndrome (MERS), and COVID-19. SARS Coronavirus (SARS-CoV), MERS Coronavirus (MERS-CoV), and the novel coronavirus, previously dubbed 2019-nCoV, and now officially named SARS-CoV-2, are the causative agents of the SARS, MERS, and COVID-19 disease outbreaks, respectively. Safe vaccines that rapidly induce potent and long-lasting virus-specific immune responses against these infectious agents are urgently needed. The coronavirus spike (S) protein, a characteristic structural component of the viral envelope, is considered a key target for vaccines for the prevention of coronavirus infection. Methods: We first generated codon optimized MERS-S1 subunit vaccines fused with a foldon trimerization domain to mimic the native viral structure. In variant constructs, we engineered immune stimulants (RS09 or flagellin, as TLR4 or TLR5 agonists, respectively) into this trimeric design. We comprehensively tested the pre-clinical immunogenicity of MERS-CoV vaccines in mice when delivered subcutaneously by traditional needle injection, or intracutaneously by dissolving microneedle arrays (MNAs) by evaluating virus specific IgG antibodies in the serum of vaccinated mice by ELISA and using virus neutralization assays. Driven by the urgent need for COVID-19 vaccines, we utilized this strategy to rapidly develop MNA SARS-CoV-2 subunit vaccines and tested their pre-clinical immunogenicity in vivo by exploiting our substantial experience with MNA MERS-CoV vaccines. Findings: Here we describe the development of MNA delivered MERS-CoV vaccines and their pre-clinical immunogenicity. Specifically, MNA delivered MERS-S1 subunit vaccines elicited strong and long-lasting antigen-specific antibody responses. Building on our ongoing efforts to develop MERS-CoV vaccines, promising immunogenicity of MNA-delivered MERS-CoV vaccines, and our experience with MNA fabrication and delivery, including clinical trials, we rapidly designed and produced clinically-translatable MNA SARS-CoV-2 subunit vaccines within 4 weeks of the identification of the SARS-CoV-2 S1 sequence. Most importantly, these MNA delivered SARS-CoV-2 S1 subunit vaccines elicited potent antigen-specific antibody responses that were evident beginning 2 weeks after immunization. Interpretation: MNA delivery of coronaviruses-S1 subunit vaccines is a promising immunization strategy against coronavirus infection. Progressive scientific and technological efforts enable quicker responses to emerging pandemics. Our ongoing efforts to develop MNA-MERS-S1 subunit vaccines enabled us to rapidly design and produce MNA SARS-CoV-2 subunit vaccines capable of inducing potent virus-specific antibody responses. Collectively, our results support the clinical development of MNA delivered recombinant protein subunit vaccines against SARS, MERS, COVID-19, and other emerging infectious diseases.

Background: Suicide is a major health concern, especially in South Korea. The probability of dying by suicide and the fatality rate differ between men and women. The present study compared the suicide characteristics of women and men and analyzed the choice of suicide methods. Methods: This study retrospectively analyzed patients who visited the emergency department after a suicide attempt in the period from 2016 to 2018, which had been obtained from the National Emergency Department Information System. Variables included suicide methods, Korean Triage and Acuity Scale level, vital signs, and disposition following emergency care. Results: A total of 88,495 (54.7% women vs. 45.3% men) cases were investigated. Significant gender differences were observed in clinical outcomes. In total, 10.3% of the men (n = 3811) and 4.0% of the women (n = 1852) died in the hospital. Women were proportionately more likely to use poisoning (62.3% vs. 51.0% in men) and piercing and cutting (24.9% vs. 22.9% in men) compared with men, whereas men were more likely to use hanging (9.5% vs. 4.6% in women) and being struck (7.9% vs. 1.1% in women). Conclusions: Women chose less lethal suicide methods, whereas men chose more violent methods. The fatalities among men were higher, even when the same method was used. In establishing a suicide prevention policy, it is important to consider gender differences.

We previously demonstrated that urban particulate matter (UPM) exposure decreases the migration activity and survival of human corneal epithelial cells (HCECs). Herein, we investigated the potential to improve the corneal wound-healing ability of Peucedanum japonicum Thunb. leaf extract (PJE) and its active components on UPM-induced ocular surface damage in vitro and in vivo. PJE effectively assisted wound healing without altering HCEC survival and enhanced catalase (CAT), heme oxygenase 1 (HO1) and glutathione peroxidase 1 (GPX1) antioxidant gene expression. A corneal wound was uniformly induced on the right eye in all experimental animals and divided into eight groups such as two control groups (wounded right eye group—NR and non-wounded left eye group—NL), UPM treated group and PJEs (25, 50, 100, 200, 400 mg/kg) treated groups. Corneal abrasion model rats exposed to UPM showed delayed wound healing compared to unexposed rats, but wound healing was dose-dependently enhanced by PJE oral administration. Seventy-two hours after wound generation, inflammatory cells, apoptotic cells and interleukin-6 (IL-6) expression were increased substantially after UPM exposure, but PJE treatment significantly reduced the wound to an almost normal level while enhancing re-epithelialization without changing corneal thickness. Next, we tried to identify the key molecules for enhancing wound healing through fractionation. The major compounds in the fraction, confirmed by high-performance liquid chromatography (HPLC), were chlorogenic acid (CA), neochlorogenic acid (NCA) and cryptochlorogenic acid (CCA). Each type of CA isomers showed slightly different half maximal effective (EC50) and maximal effective (ECmax) concentrations, and their mixtures synergistically enhanced HCEC migration. Thus, corneal abrasion wound recovery after UPM exposure improved after PJE treatment, and the active PJE components were identified, providing an important basis to develop therapeutics for ocular surface damage using PJE.

Background and Objectives: This study aimed at investigating the laxative effects of a standardized aqueous extract of Dendropanax morbiferus H. Lév. on two different constipation rat models. Materials and Methods: Animal studies were conducted with low-fiber diet-induced and loperamide-induced constipation animal models, and isolated colons were used in ex vivo analysis to determine the changes in colonic motility caused by D. morbiferus H. Lév. leaf extract (DPL). Results: The results showed that DPL administration significantly improved certain reduced fecal parameters (number, weight, and water content of the stools) in a both low-fiber diet and loperamide-induced constipation models without adverse effects of diarrhea. The laxative effect of DPL was confirmed to improve the charcoal excretion time upon DPL treatment in a low-fiber diet or loperamide-induced constipation model through gastrointestinal (GI) motility evaluation using the charcoal meal test. In addition, when DPL was administered to RAW264.7 cells and loperamide-induced constipation model rats, the production of prostaglandin E2 (PGE2) increased significantly in cells and tissue. Furthermore, DPL dose-dependently stimulated the spontaneous contractile amplitude and frequency of the isolated rat colon. Conclusion: Although our study did not provide information on the acute or chronic toxicity of DPL, our results demonstrated that DPL can effectively promote defecation frequency and rat colon contraction, providing scientific evidence to support the use of DPL as a therapeutic application. However, further toxicity studies of DPL are needed prior to the initiation of clinical trials and clinical applications.

Recombinant poxviruses, utilized as vaccine vectors and oncolytic viruses, often require manipulation at multiple genetic loci in the viral genome. It is essential for viral vectors to possess no adventitious mutations and no (antibiotic) selection marker in the final product for human patients in order to comply with the guidance from the regulatory agencies. Rintoul et al. have previously developed a selectable and excisable marker (SEM) system for the rapid generation of recombinant vaccinia virus. In the current study, we describe an improved methodology for rapid creation and selection of recombinant poxviruses with multiple genetic manipulations solely based on expression of a fluorescent protein and with no requirement for drug selection that can lead to cellular stress and the risk of adventitious mutations throughout the viral genome. Using this improved procedure combined with the SEM system, we have constructed multiple marker-free oncolytic poxviruses expressing different cytokines and other therapeutic genes. The high fidelity of inserted DNA sequences validates the utility of this improved procedure for generation of therapeutic viruses for human patients. We have created an oncolytic poxvirus expressing human chemokine CCL5, designated as vvDD-A34R-hCCL5, with manipulations at two genetic loci in a single virus. Finally, we have produced and purified this virus in clinical grade for its use in a phase I clinical trial and presented data on initial in vitro characterization of the virus.

Abstract Background Lac color, a natural red dye derived from the larvae of laccifer lacca kerr, is one of the most commonly used substances in food. To date, no studies have reported on the antigenicity of lac color and the other biomarkers that can determine anaphylactic reactions. To address this, we evaluated the antigenicity of lac color through active systemic anaphylaxis (ASA) in addition to identifying potential biomarkers performing exploratory studies. For ASA test, Guinea pigs (n = 5) were sensitized with 0(negative control), 4 mg/kg of lac color, 4 mg/kg of lac color + FCA, and 5 mg/kg of ovalbumin + FCA (positive control) 3 times a week for three weeks. Fourteen days after the last sensitization, animals were challenged intravenously weekly for two weeks. Hematological and histopathological analyses were performed and compared to control groups. Results In the ASA test, all lac color groups showed mild symptoms such as nose rubbing, urination, and evacuation, which are insufficient indicators of anaphylaxis. Exploratory studies identified several biomarkers: decreased platelet count, and increased basophil count; distention in the lung, and redness on the inner wall of trachea; mononuclear inflammatory cell infiltration (MICI) in the ear, and heart hemorrhage. When these biomarkers were applied to the ASA test of lac color, in comparison to the negative control group, the positive control group (ovalbumin + FCA) showed a significant over 60-fold reduction in platelet count and nearly threefold higher basophil count compared to other groups. Furthermore, only positive control group exhibited full lung distention and severe redness on the inner wall of the trachea. Mononuclear inflammatory cell infiltration (MICI) in the ear was about three times higher, and heart hemorrhage was only present in the positive control group compared to others. None of the lac color groups were different from the negative control group (p > 0.05), whereas the positive control group was significantly different (p

Abstract Background Preoperative templating is an important step for total knee arthroplasty (TKA), facilitating hospital personnel in the anticipation and preparation of necessary surgical resources. Despite its importance, this process currently lacks automation. This study aimed to develop an artificial intelligence (AI) model to automate implant size prediction. Methods A total of 13,281 (2938 anteroposterior, 10,343 lateral) knee radiographs obtained from the authors’ institute were utilized for model training, with 2302 (1034 anteroposterior, 1268 lateral) images set apart for validation and testing. The templating AI model integrates a pipeline composed of multiple steps for automated implant size estimation. To predict implant size, anterioposterior (AP) and lateral radiograph predictions were merged, selecting the smaller of the predicted sizes to prevent implant overhang. The model’s size predictions were validated with 81 real TKA data set apart from the training data, and its accuracy was compared to that of manual templating by an orthopedic specialist. Predictions matching the actual implanted sizes were labeled “exact” and those within one size, “accurate.” The influence of patient characteristics on the model’s prediction accuracy was also analyzed. The measurement time elapsed for implant sizing was recorded for both the AI model and the orthopedic specialist. Implant position predicted by the model was validated by comparing insert locations with postoperative images. Results Compared with data from 81 actual TKA procedures, the model provided exact predictions for 39.5% of femoral and 43.2% of tibial components. Allowing a one-size margin of error, 88.9% of predictions were deemed “accurate” for both components. Interobserver reliability (Cohen’s kappa) were 0.60 and 0.70 for femoral and tibial implants, respectively, both classified as “substantial.” The orthopedic specialist produced results accurate within one-size margin of error in 95.1% and 100% of cases for femoral and tibial components, respectively. Interobserver reliability between the orthopedic specialist and ground truth was 0.76 and 0.8 for femoral and tibial components, respectively. The measurement time per case was 48.7 s for the AI model, compared with 97.5 s for the orthopedic specialist. Compared with postoperative radiographs, predicted implant position had an error of less than 4 mm on average. Conclusions An AI-based templating tool for TKA was successfully developed, demonstrating satisfactory accuracy and efficiency. Its application could significantly reduce the clinical workload in TKA preparation.

Since it emerged in Brazil in May 2015, the mosquito-borne Zika virus (ZIKV) has raised global concern due to its association with a significant rise in the number of infants born with microcephaly and neurological disorders such as Guillain-Barré syndrome. We developed prototype subunit and adenoviral-based Zika vaccines encoding the extracellular portion of the ZIKV envelope gene (E) fused to the T4 fibritin foldon trimerization domain (Efl). The subunit vaccine was delivered intradermally through carboxymethyl cellulose microneedle array (MNA). The immunogenicity of these two vaccines, named Ad5.ZIKV-Efl and ZIKV-rEfl, was tested in C57BL/6 mice. Prime/boost immunization regimen was associated with induction of a ZIKV-specific antibody response, which provided neutralizing immunity. Moreover, protection was evaluated in seven-day-old pups after virulent ZIKV intraperitoneal challenge. Pups born to mice immunized with Ad5.ZIKV-Efl were all protected against lethal challenge infection without weight loss or neurological signs, while pups born to dams immunized with MNA-ZIKV-rEfl were partially protected (50%). No protection was seen in pups born to phosphate buffered saline-immunized mice. This study illustrates the preliminary efficacy of the E ZIKV antigen vaccination in controlling ZIKV infectivity, providing a promising candidate vaccine and antigen format for the prevention of Zika virus disease.

The purpose of this study was to explore classroom choir teachers' perceptions of choral methods topics in secondary choral teaching preparedness. Members of the American Choral Directors Association Facebook Group who had classroom choir teaching experiences and responded to a survey (N = 100) participated in this study. I employed two procedures. First, participants rated 16 choral methods topics on their importance to classroom choral teaching preparedness using a 7-point Likert-type scale (1 = not very important to 7 = very important). I then arranged participants' mean ratings of the 16 items in order of importance. The five most important participants-rated items were choral rehearsal techniques, choral classroom management, vocal techniques, choral repertoire and literature, and choral student recruitment/retention. The five least important participants-rated items were choral microteaching, choral class administrative tasks, choral music student assessment, choral conducting techniques, and diction. Additionally, participants selected their five most important choral methods topics using the same 16 choral methods topics. The five most important participants-selected topics were choral rehearsal techniques, vocal techniques, choral classroom management, choral repertoire and literature, and sight-singing skills. The findings of this study could be helpful for choral methods instructors in prioritizing instructional and learning activities for preservice music teachers' classroom choral instruction.

This study explores how Korean-to-English machine translation (MT) systems (e.g., Google Translator, NAVER Papago) deal with Korean passive structures. Cross-linguistically, Korean and English passives show different ways to construct passive-voice sentences from active structure. English passives including with [to be + past participle] may have a "by phrase" after the verb, which perform the agent of the action. However, Korean has three different passive structures and a rich repertoire of affixes, including case markers, which play critical roles in the production and comprehension of passives, complicating translation to English. Moreover, the grammatical constructions that express passive voice in Korean and English differ in terms of frequency in both written and spoken contexts. To explore production accuracy by two MTs, 213 Korean passive sentences were translated into English passives. This finding shows that current Korean-to-English MTs almost always produce translations that are correct in meaning when they generally translate Korean passives into English passives. They also translate Korean passives into English active voice constructions at significant rates.

Octacalcium phosphate (OCP) is a precursor of biological apatite minerals that can be used in synthetic bone grafts. In this work, a new type of synthetic bone grafts was developed by adding water glass to OCP (W-OCP). The OCP phase is generally known to be thermodynamically unstable and rapidly hydrolyzes to apatite. However, X-ray diffraction confirmed that OCP can remain stable even in the presence of water glass. In a rabbit calvarial defect model, W-OCP increased the bone area by 22.4 %, which was significantly higher than that of defects only at week 4 (p

Incorporating β-glucan-rich oat bran (OB) can attenuate postprandial glycemic response (PPGR) in solid foods, but its effect in liquid matrices is unclear. This study investigated the ability of differently processed low-dose-β-glucan-containing beverages to lower PPGR, and the mechanisms of action. Twenty participants consumed five malt beverages made from cocoa powder: intact OB (Intact), OB treated with enzymatic hydrolysis (EnzymA, EnzymB) or extrusion (Extr), or no OB (Ctrl). Four-hour postprandial incremental areas under the curve (iAUC) and peak incremental concentrations (iCmax) of glucose, insulin, glucagon-like peptide 1 (GLP-1), gastric inhibitory polypeptide (GIP), and paracetamol were evaluated. The molecular weight (MW) and extractability of the β-glucan in all the test products were also assessed. The three-hour glucose iAUC significantly decreased by −26%, −28%, −32%, and −38% in Intact, EnzymA, EnzymB, and Extr, respectively, and the insulin levels of the oat-containing products were also significantly lower compared to Ctrl. Intact and Extr elicited a lower insulin iCmax and GLP-1 3 h iAUC compared to Ctrl. However, the GIP and paracetamol levels were not changed. All the processed OBs improved β-glucan extractability and lowered the MW of β-glucan compared to Intact. In conclusion, low-dose oat β-glucan in a beverage significantly reduced PPGR, with effects maintained across different oat processing methods.

Studies on organotellurium compounds have not been extensively conducted due to a lack of tolerable synthetic methods, difficult isolation processes, and their chemical instabilities. Overcoming these hurdles, we developed an efficient and mild method for the selective synthesis of symmetrical diorganyl tellurides 1, a representative class of organotellurium compounds, using a proper reducing reagent. The reaction condition was optimized for the selective formation of 1 by forming the telluride dianion (Te2−) using a reducing reagent, sodium borohydride (NaBH4), and then followed by the addition of organyl halides. The optimized reaction condition was as follows: (1) Te (1.0 eq), NaBH4 (2.5 eq) in DMF for 1 h at 80 °C; (2) organyl halides (2.0 eq) for 3–5 h at 25–153 °C. Using this condition, 18 various diorganyl tellurides 1 were selectively and efficiently synthesized in reasonable yields (37–93%). The reaction pathways for the formation of diorganyl tellurides 1 were also investigated. Consequently, we established a practical and efficient method for the selective synthesis of diorganyl tellurides 1 as a representative class of organotellurium compounds.

Breathing is the process of exchanging gases between the human body and the surrounding environment. It plays a vital role in maintaining human health, sustaining life, and supporting various bodily functions. Unfortunately, current methods for monitoring respiration are impractical for medical applications because of their high costs and need for bulky equipment. When measuring changes in moisture during respiration, we observed a slow response time for 2D nanomaterial-based resistance measurement methods used in respiration sensors. Through thermal annealing, the crystal structure of MoS2 is transformed from 1T@2H to 2H, allowing the measurement of respiration at more than 30 cycles per minute and enabling analysis of the response. This study highlights the potential of two-dimensional nanomaterials for the development of low-cost and highly sensitive humidity and respiration sensors for various applications.

We developed inverted red quantum dot light-emitting diodes (QLEDs) with ZnO nanoparticles synthesized in open and closed systems. Wurtzite-structured ZnO nanoparticles were synthesized using potassium hydroxide and zinc acetate dihydrate at various temperatures in the open and closed systems. The particle size increases with increasing synthesis temperature. The ZnO nanoparticles synthesized at 50, 60, and 70 °C in the closed system have an average particle size of 3.2, 4.0, and 5.4 nm, respectively. The particle size is larger in the open system compared to the closed system as the methanol solvent evaporates during the synthesis process. The surface defect-induced emission in ZnO nanoparticles shifts to a longer wavelength and the emission intensity decreases as the synthesis temperature increases. The inverted red QLEDs were fabricated with a synthesized ZnO nanoparticle electron transport layer. The driving voltage of the inverted QLEDs decreases as the synthesis temperature increases. The current efficiency is higher in the inverted red QLEDs with the ZnO nanoparticles synthesized in the closed system compared to the devices with the nanoparticles synthesized in the open system. The device with the ZnO nanoparticles synthesized at 60 °C in the closed system exhibits the maximum current efficiency of 5.8 cd/A.

Chlamys farreri is primarily cultivated in Japan, China, and South Korea. Although mass mortality of scallops has been occurring recently, likely caused by high temperatures or infectious diseases, the underlying cause remains unclear. Little is known regarding the viral diseases affecting them. Therefore, we explored DNA virus diversity in the mid-gut gland of C. farreri and compared it with that of seawater. C. farreri was cultivated at depths below 5 m from the sea surface in the coastal waters of South Korea and sampled from May to August 2018. Different DNA viral communities were observed in both C. farreri and seawater. In C. farreri, prevalent groups included Mimiviridae (7%), Poxviridae (6%), and Phycodnaviridae (5%). Conversely, the dominant groups in seawater were Autographiviridae (20%), Kyanoviridae (12%), and Zobellviridae (10%). We identified C. farreri-specific viral communities and potentially infectious viruses, such as Ostreid herpesvirus 1 and Abalone herpesvirus Victoria/AUS/2009. Furthermore, C. farreri acts as a reservoir for various viruses, which impact microbial community dynamics and disease transmission in marine ecosystems. Understanding these viral communities is crucial to protecting and restoring coastal ecosystems by highlighting their role in the transmission of potential avian- and bivalve-specific viruses.

Background/Objectives: Beeswax alcohol (BWA; Raydel®) is a blend of six long-chain aliphatic alcohols extracted from honeybee wax and is well known for its diverse functionality and health benefits. Herein, the efficacy of a BWA dietary intervention for 20 weeks was assessed to ameliorate high-cholesterol diet (HCD)-induced dyslipidemia and adverse effects on the vital organs of adult zebrafish. Methods: Adult zebrafish were fed different high-cholesterol diets (HCDs; final concentration of 4%, w/w) supplemented with BWA (final concentrations of 0.1%, 0.5% and 1.0%, w/w) or CoQ10 (final concentration of 1.0%). Following 20 weeks of supplementation, blood and different organs (liver, kidney, testes and ovaries) were collected, and biochemical, histological and immunohistochemical analyses were performed. Results: The results demonstrate a dose-dependent effect of BWA of mitigating HCD-induced mortality in zebrafish over the 20-week supplementation period, which was noticeably better than the effect exerted by coenzyme Q10 (CoQ10). Consistently, a dose-dependent effect of BWA consumption of curtailing HCD-induced total cholesterol (TC) and triglyceride (TG) levels and increasing high-density-lipoprotein cholesterol (HDL-C) levels was noticed. Compared with CoQ10 (final concentration of 1.0%, w/w), BWA (final concentration of 1.0%, w/w) displayed a significantly better effect of mitigating HCD-induced dyslipidemia, as evidenced by 1.2-fold (p < 0.05) and 2.0-fold (p < 0.05) lower TC and TG levels and 2.4-fold (p < 0.01) higher HDL-C levels. The histological analysis revealed substantial prevention of fatty liver changes, reactive oxygen species (ROS) generation, cellular senescence and interleukin (IL)-6 production in the hepatic tissue of BWA zebrafish, which was significantly better than the effect exerted by CoQ10. Consistently, compared with CoQ10, significant 25% (p < 0.05) and 35% (p < 0.01) reductions in the HCD-induced elevated levels of the hepatic function biomarkers aspartate aminotransferase and alanine aminotransferase was observed in the BWA group. Likewise, BWA consumption efficiently ameliorated HCD-induced kidney, ovary and testis damage by inhibiting ROS generation, cellular senescence and lipid accumulation. Conclusion: Supplementation with BWA demonstrated higher therapeutic potential than that with CoQ10 to prevent dyslipidemia and organ damage associated with long-term consumption of HCDs.

Given the various motivational challenges that students experience when engaging in academic tasks, there is an emerging interest in investigating students' cost perceptions and how to reduce them. However, most of the research has investigated general cost perceptions with a one-time assessment, often divorced from context in which cost is experienced. Centreing the situatedness of students' motivational processes, we conducted an experience sampling study (57 undergraduates; 1,504 responses) to examine the link between general and "in-situ" momentary cost perceptions in students' daily lives, as well as the potential moderating role of motivational regulation. Results showed that certain dimensions of momentary cost perceptions (outside effort cost and emotional cost) were positively associated with their corresponding general cost perceptions. Other dimensions of momentary cost (task effort cost and loss of valued alternatives cost) showed nonsignificant associations, suggesting higher sensitivity to context than others. Moreover, motivational regulation moderated the relationship between general and momentary cost for the majority of the dimensions, suggesting that interventions designed to improve students' motivational regulation may reduce their momentary cost perceptions and increase the positivity of learning experiences.

In 2009 a new pandemic disease appeared and spread globally. The recent emergence of the pandemic influenza virus H1N1 first isolated in Mexico and USA raised concerns about vaccine availability. We here report our development of an adenovirus-based influenza H1N1 vaccine tested for immunogenicity and efficacy to confer protection in animal model.We generated two adenovirus(Ad5)-based influenza vaccine candidates encoding the wildtype or a codon-optimized hemagglutinin antigen (HA) from the recently emerged swine influenza isolate A/California/04/2009 (H1N1)pdm. After verification of antigen expression, immunogenicity of the vaccine candidates were tested in a mouse model using dose escalations for subcutaneous immunization. Sera of immunized animals were tested in microneutalization and hemagglutination inhibition assays for the presence of HA-specific antibodies. HA-specific T-cells were measured in IFNgamma Elispot assays. The efficiency of the influenza vaccine candidates were evaluated in a challenge model by measuring viral titer in lung and nasal turbinate 3 days after inoculation of a homologous H1N1 virus.A single immunization resulted in robust cellular and humoral immune response. Remarkably, the intensity of the immune response was substantially enhanced with codon-optimized antigen, indicating the benefit of manipulating the genetic code of HA antigens in the context of recombinant influenza vaccine design. These results highlight the value of advanced technologies in vaccine development and deployment in response to infections with pandemic potential. Our study emphasizes the potential of an adenoviral-based influenza vaccine platform with the benefits of speed of manufacture and efficacy of a single dose immunization.