Insights into Actin Isoform-Specific Interactions with Myosin via Computational Analysis.

Actin, which plays a crucial role in cellular structure and function, interacts with various binding proteins, notably myosin. In mammals, actin is composed of six isoforms that exhibit high levels of sequence conservation and structural similarity overall. As a result, the selection of actin isoforms was considered unimportant in structural studies of their binding with myosin. However, recent high-resolution structural research discovered subtle structural differences in the N-terminus of actin isoforms, suggesting the possibility that each actin isoform may engage in specific interactions with myosin isoforms. In this study, we aimed to explore this possibility, particularly by understanding the influence of different actin isoforms on the interaction with myosin 7A. First, we compared the reported actomyosin structures utilizing the same type of actin isoforms as the high-resolution filamentous skeletal α-actin (3.5 Å) structure elucidated using cryo-EM. Through this comparison, we confirmed that the diversity of myosin isoforms leads to differences in interaction with the actin N-terminus, and that loop 2 of the myosin actin-binding sites directly interacts with the actin N-terminus. Subsequently, with the aid of multiple sequence alignment, we observed significant variations in the length of loop 2 across different myosin isoforms. We predicted that these length differences in loop 2 would likely result in structural variations that would affect the interaction with the actin N-terminus. For myosin 7A, loop 2 was found to be very short, and protein complex predictions using skeletal α-actin confirmed an interaction between loop 2 and the actin N-terminus. The prediction indicated that the positively charged residues present in loop 2 electrostatically interact with the acidic patch residues D24 and D25 of actin subdomain 1, whereas interaction with the actin N-terminus beyond this was not observed. Additionally, analyses of the actomyosin-7A prediction models generated using various actin isoforms consistently yielded the same results regardless of the type of actin isoform employed. The results of this study suggest that the subtle structural differences in the N-terminus of actin isoforms are unlikely to influence the binding structure with short loop 2 myosin 7A. Our findings are expected to provide a deeper understanding for future high-resolution structural binding studies of actin and myosin.

FPNC Net: A hydrogenation catalyst image recognition algorithm based on deep learning.

The identification research of hydrogenation catalyst information has always been one of the most important businesses in the chemical industry. In order to aid researchers in efficiently screening high-performance catalyst carriers and tackle the pressing challenge at hand, it is imperative to find a solution for the intelligent recognition of hydrogenation catalyst images. To address the issue of low recognition accuracy caused by adhesion and stacking of hydrogenation catalysts, An image recognition algorithm of hydrogenation catalyst based on FPNC Net was proposed in this paper. In the present study, Resnet50 backbone network was used to extract the features, and spatially-separable convolution kernel was used to extract the multi-scale features of catalyst fringe. In addition, to effectively segment the adhesive regions of stripes, FPN (Feature Pyramid Network) is added to the backbone network for deep and shallow feature fusion. Introducing an attention module to adaptively adjust weights can effectively highlight the target features of the catalyst. The experimental results showed that the FPNC Net model achieved an accuracy of 94.2% and an AP value improvement of 19.37% compared to the original CenterNet model. The improved model demonstrates a significant enhancement in detection accuracy, indicating a high capability for detecting hydrogenation catalyst targets.

Adequacy of the examination-based licensing system and a training-based licensing system for midwifery license according to changes in childbirth medical infrastructure in Korea: a surveybased descriptive study

PURPOSE: The number of Korean midwifery licensing examination applicants has steadily decreased due to the low birth rate and lack of training institutions for midwives. This study aimed to evaluate the adequacy of the examination-based licensing system and the possibility of a training-based licensing system. METHODS: A survey questionnaire was developed and dispatched to 230 professionals from December 28, 2022 to January 13, 2023, through an online form using Google Surveys. Descriptive statistics were used to analyze the results. RESULTS: Responses from 217 persons (94.3%) were analyzed after excluding incomplete responses. Out of the 217 participants, 198 (91.2%) agreed with maintaining the current examination-based licensing system; 94 (43.3%) agreed with implementing a training-based licensing system to cover the examination costs due to the decreasing number of applicants; 132 (60.8%) agreed with establishing a midwifery education evaluation center for a training-based licensing system; 163 (75.1%) said that the quality of midwifery might be lowered if midwives were produced only by a training-based licensing system, and 197 (90.8%) said that the training of midwives as birth support personnel should be promoted in Korea. CONCLUSION: Favorable results were reported for the examination-based licensing system; however, if a training-based licensing system is implemented, it will be necessary to establish a midwifery education evaluation center to manage the quality of midwives. As the annual number of candidates for the Korean midwifery licensing examination has been approximately 10 in recent years, it is necessary to consider more actively granting midwifery licenses through a training-based licensing system.

Experiences of Forest Healing Instructors Who Met Cancer Patients in Forest Healing Programs: FGI Research.

BACKGROUND: Demand for urban forest programs for the healing of cancer survivors is increasing. To develop a forest healing program for the integrated care of cancer patients, it is necessary to analyze the experiences of forest healing instructors who have conducted programs for cancer patients. METHODS: This qualitative study applied focus group interviews (FGIs; four interviews with sixteen participants) to describe and understand the experiences of forest healing instructors who run forest healing programs for cancer patients. RESULTS: Four themes were identified: "prepared encounters and unexpected encounters," "yearning for healing," "people who need special care," and "things to prepare for cancer patient programs." CONCLUSION: Forest healing instructors had difficulty facilitating programs for cancer patients owing to prejudice and a lack of knowledge about the characteristics of cancer patients. Moreover, differentiated programs and places that align with the specific needs of cancer patients are needed. It is necessary to develop an integrated care forest healing program for cancer patients and educate forest healing instructors about the needs of cancer patients.

c-Jun N-terminal kinase 1 (JNK1) phosphorylates OTX2 transcription factor that regulates early retinal development.

BACKGROUND: The transcription factor orthodenticle homeobox 2 (OTX2) has critical functions in brain and eye development, and its mutations in humans are related to retinal diseases, such as ocular coloboma and microphthalmia. However, the regulatory mechanisms of OTX2 are poorly identified. OBJECTIVE: The identification of JNK1 as an OTX2 regulatory protein through the protein interaction and phosphorylation. METHODS: To identify the binding partner of OTX2, we performed co-immunoprecipitation and detected with a pooled antibody that targeted effective kinases. The protein interaction between JNK1 and OTX2 was identified with the co-immunoprecipitation and immunocytochemistry. In vivo and in vitro kinase assay of JNK1 was performed to detect the phosphorylation of OTX2 by JNK1. RESULTS: JNK1 directly interacted with OTX2 through the transactivation domain at the c-terminal region. The protein-protein interaction and co-localization between JNK1 and OTX2 were further validated in the developing P0 mouse retina. In addition, we confirmed that the inactivation of JNK1 K55N mutant significantly reduced the JNK1-mediated phosphorylation of OTX2 by performing an immune complex protein kinase assay. CONCLUSION: c-Jun N-terminal kinase 1 (JNK1) phosphorylates OTX2 transcription factor through the protein-protein interaction.

A present from the forest: Focus group interviews on cancer survivors' forest experiences.

Objective: To explore cancer survivors' forest experiences and to understand the relevance of these experiences from their perspectives in the context of the growing interest in nature's impact on health and quality of life. Methods: From July 29 to August 12, 2021, four focus group interviews were conducted with cancer survivors who visited forests in South Korea. The data were analyzed using qualitative content and thematic analysis. Results: The participants were 21 female cancer survivors with a mean age of 58.4 (age range 44-69) years. The focus group interviews revealed three themes and 10 sub-themes regarding subjective perceptions and experiences related to forests. The overarching themes were as follows: (1) awakened bodily senses and fascination with the forest; (2) remedial effect; and (3) a source of inspiration. These three themes capture the impact of forest experiences on participants' lives and the value they derived from these experiences. The participants considered these experiences a gift from forests. In particular, they experienced aesthetic enrichment and restorative effects such as boosted energy levels, reduced fatigue, and a buffer against mood swings. Finally, forests were a source of inspiration that led the participants toward personal growth. Conclusions: By gaining a better understanding of survivors' forest experiences, we identified that forest-based interventions for supportive cancer care can align with patients' values and preferences and serve as a secure space where they can feel cared for. This study can contribute to the development of forest-based interventions for cancer survivorship care.

Effects of a Neonatal Supportive Positioning Training Video Program for Preterm Infants on the Knowledge and Performance of Nurses in Neonatal Intensive Care Units.

PURPOSE: The purpose of this study is to develop and apply a neonatal supportive positioning (NSP) training video program for premature infants, using a position support mat for nurses in neonatal intensive care units (NICUs), and to verify its effect on nurses' performance. METHODS: Thirty-five NICU nurses were included in the study. For the pre-test, preliminary check-ups were conducted, questionnaires about NSP knowledge on preterm infants were distributed, and NSP performance using neonatal dolls were video recorded for each participant. PowerPoint presentations and videos were used to educate participants on NSP. Furthermore, a 20-minute one-on-one training session was conducted using an NPS kit. Two weeks after the training, we repeated the process of distributing questionnaires about NSP knowledge and recording nurses' performance videos using neonatal dolls. Questionnaires and videos collected before and after the training were compared. RESULTS: After NSP training, the mean knowledge score of the participants improved significantly from 23.71 ± 3.62 to 29.51 ± 2.29 (Z = -5.09, p < .001). The performance score for postural supportive positioning was 38.03 ± 7.46 before training and 80.06 ± 9.85 after receiving training, indicating a high-performance score after NSP training (Z = -5.16, p < .001). CONCLUSION: Our NSP training video program increased nurses' NSP knowledge and performance. Continuous training NICU nurses on NSP, using a standardized training video program, can help improve the care of premature infants.

Evaluation of Student Satisfaction with Ubiquitous-Based Tests in Women's Health Nursing Course.

Learning evaluation using ubiquitous-based tests may be essential during a public health crisis, such as the COVID-19 pandemic, during which theoretical classes and clinical practice are conducted online. However, students may not be as familiar with ubiquitous-based tests as they are with paper-based tests. This survey study aimed to evaluate students' satisfaction with ubiquitous-based tests and compare the evaluation results of a paper-based test with that of a ubiquitous-based test in nursing education. For the midterm exam of the Women's Health Nursing course, a paper-based test was conducted, while a ubiquitous-based test using a tablet computer was used for the final exam. The Ubiquitous-Based Test Usefulness and Satisfaction tool, which has a five-point Likert-type response scale, was employed to evaluate the post-test usefulness and satisfaction scores of the ubiquitous-based test. The mean score of the ubiquitous-based test usefulness was 4.01 ± 0.67. There was a significant difference in satisfaction levels between the ubiquitous-based and the paper-based test (t = -3.36, p = 0.001). Specifically, the evaluation scores were not affected by different evaluation methods. Study participants deemed the ubiquitous-based test highly useful and satisfactory, suggesting that such tests may be a future-oriented evaluation method, potentially replacing paper-based tests.

A Fully Human Monoclonal Antibody Targeting cKIT Is a Potent Inhibitor of Pathological Choroidal Neovascularization in Mice.

Stem cell factor (SCF) and its receptor, cKIT, are novel regulators of pathological neovascularization in the eye, which suggests that inhibition of SCF/cKIT signaling may be a novel pharmacological strategy for treating neovascular age-related macular degeneration (AMD). This study evaluated the therapeutic potential of a newly developed fully human monoclonal antibody targeting cKIT, NN2101, in a murine model of neovascular AMD. In hypoxic human endothelial cells, NN2101 substantially inhibited the SCF-induced increase in angiogenesis and activation of the cKIT signaling pathway. In a murine model of neovascular AMD, intravitreal injection of NN2101 substantially inhibited the SCF/cKIT-mediated choroidal neovascularization (CNV), with efficacy comparable to aflibercept, a vascular endothelial growth factor inhibitor. A combined intravitreal injection of NN2101 and aflibercept resulted in an additive therapeutic effect on CNV. NN2101 neither caused ocular toxicity nor interfered with the early retinal vascular development in mice. Ocular pharmacokinetic analysis in rabbits indicated that NN2101 demonstrated a pharmacokinetic profile suitable for intravitreal injection. These findings provide the first evidence of the potential use of the anti-cKIT blocking antibody, NN2101, as an alternative or additive therapeutic for the treatment of neovascular AMD.

Mercury Chloride but Not Lead Acetate Causes Apoptotic Cell Death in Human Lung Fibroblast MRC5 Cells via Regulation of Cell Cycle Progression.

Heavy metals are important for various biological systems, but, in excess, they pose a serious risk to human health. Heavy metals are commonly used in consumer and industrial products. Despite the increasing evidence on the adverse effects of heavy metals, the detailed mechanisms underlying their action on lung cancer progression are still poorly understood. In the present study, we investigated whether heavy metals (mercury chloride and lead acetate) affect cell viability, cell cycle, and apoptotic cell death in human lung fibroblast MRC5 cells. The results showed that mercury chloride arrested the sub-G1 and G2/M phases by inducing cyclin B1 expression. In addition, the exposure to mercury chloride increased apoptosis through the activation of caspase-3. However, lead had no cytotoxic effects on human lung fibroblast MRC5 cells at low concentration. These findings demonstrated that mercury chloride affects the cytotoxicity of MRC5 cells by increasing cell cycle progression and apoptotic cell death.

Bisphenol A Exposure Changes the Transcriptomic and Proteomic Dynamics of Human Retinoblastoma Y79 Cells.

Bisphenol A (BPA) is a xenoestrogen chemical commonly used to manufacture polycarbonate plastics and epoxy resin and might affect various human organs. However, the cellular effects of BPA on the eyes have not been widely investigated. This study aimed to investigate the cellular cytotoxicity by BPA exposure on human retinoblastoma cells. BPA did not show cytotoxic effects, such as apoptosis, alterations to cell viability and cell cycle regulation. Comparative analysis of the transcriptome and proteome profiles were investigated after long-term exposure of Y79 cells to low doses of BPA. Transcriptome analysis using RNA-seq revealed that mRNA expression of the post-transcriptional regulation-associated gene sets was significantly upregulated in the BPA-treated group. Cell cycle regulation-associated gene sets were significantly downregulated by exposure to BPA. Interestingly, RNA-seq analysis at the transcript level indicated that alternative splicing events, particularly retained introns, were noticeably altered by low-dose BPA treatment. Additionally, proteome profiling using MALDI-TOF-MS identified a total of nine differentially expressed proteins. These results suggest that alternative splicing events and altered gene/protein expression patterns are critical phenomena affected by long-term low-dose BPA exposure. This represents a novel marker for the detection of various diseases associated with environmental pollutants such as BPA.

Transcriptome Analysis Reveals HgCl2 Induces Apoptotic Cell Death in Human Lung Carcinoma H1299 Cells through Caspase-3-Independent Pathway.

Mercury is one of the detrimental toxicants that can be found in the environment and exists naturally in different forms; inorganic and organic. Human exposure to inorganic mercury, such as mercury chloride, occurs through air pollution, absorption of food or water, and personal care products. This study aimed to investigate the effect of HgCl2 on cell viability, cell cycle, apoptotic pathway, and alters of the transcriptome profiles in human non-small cell lung cancer cells, H1299. Our data show that HgCl2 treatment causes inhibition of cell growth via cell cycle arrest at G0/G1- and S-phase. In addition, HgCl2 induces apoptotic cell death through the caspase-3-independent pathway. Comprehensive transcriptome analysis using RNA-seq indicated that cellular nitrogen compound metabolic process, cellular metabolism, and translation for biological processes-related gene sets were significantly up- and downregulated by HgCl2 treatment. Interestingly, comparative gene expression patterns by RNA-seq indicated that mitochondrial ribosomal proteins were markedly altered by low-dose of HgCl2 treatment. Altogether, these data show that HgCl2 induces apoptotic cell death through the dysfunction of mitochondria.

Ablation of SMUG1 Reduces Cell Viability and Increases UVC-Mediated Apoptosis in Hepatocarcinoma HepG2 Cells.

Uracil is an unavoidable aberrant base in DNA sequences, the repair of which takes place by a highly efficient base excision repair mechanism. The removal of uracil from the genome requires multiple biochemical steps with conformational changes of DNA that inhibit DNA replication and interfere with transcription. However, the relevance of uracil in DNA for cellular physiology and transcriptional regulation is not fully understood. We investigated the functional roles of SMUG1 using knock-down (KD) and knock-out (KO) models. The proliferation ratio of SMUG1 KD and KO cells was decreased compared to WT control cells, and the cell cycle was arrested in the G2/M phases before the transition to mitosis. The apoptotic cell death was increased in KD and KO cell lines through the increase of BAX and active caspase 3 expression. Phospho-gamma-H2AX expression, which reflected accumulated DNA damage, was also increased in KO cells. Moreover, the apoptotic cells by DNA damage accumulation were markedly increased in SMUG1 KD and KO cells after ultraviolet C irradiation. Transcriptomic analysis using RNA-seq revealed that SMUG1 was involved in gene sets expression including cell cycle transition and chromatin silencing. Together, the results implicate SMUG1 as a critical factor in cell cycle and transcriptional regulation.

Synergistic Effects of Surface Passivation and Charge Separation to Improve Photo-electrochemical Performance of BiOI Nanoflakes by Au Nanoparticle Decoration.

We demonstrate that the photoactivity of bismuth oxyiodide (BiOI) nanoflake (NF) photocathodes in photo-electrochemical (PEC) water splitting can be significantly enhanced by about 24-fold by thermal calcination under an air atmosphere and then surficial decoration of Au nanoparticles (NPs). To understand the key factors affecting the PEC efficiency in Au NP-decorated BiOI NF photoelectrodes, incident photon-to-current conversion efficiency, electrochemical impedance spectroscopy, photovoltage, and electrochemically active surface area measurements were performed. The analytic results presented that thermal calcining could produce mesopores, increasing active sites on the surface of BiOI NFs. In addition, the synergistic effects of surface-state passivation and charge separation were observed for the surficial Au NP decoration on BiOI NFs. Transient absorption spectroscopy coupled with PEC measurements confirmed that the lifetime of photogenerated electrons on the conduction band of BiOI NFs can be prolonged by Au NP decoration, resulting in higher probability to carry out water reduction. The current investigation presents important insights into the mechanism of charge carrier dynamics in metal-semiconductor nano-heterostructures, which is contributive to develop photoelectrode materials in solar fuel production.

Antioxidant and Anti-Inflammatory Effects of Korean Black Ginseng Extract through ER Stress Pathway.

The excessive release of reactive oxygen species (ROS) can result in the development of chronic inflammation. The mechanisms involved in inflammation are various, with endoplasmic reticulum (ER) stress known to be among them. We have previously shown that black ginseng (BG) reduced lipid accumulation in and enhanced the antioxidant function of the liver in vitro and in vivo mostly due to ginsenoside Rb1, Rg3 and Rk1 components. Therefore, this study investigated the antioxidant effect of BG on the intestines and its possible mechanistic pathway through ER stress. The results showed that BG extract decreased ROS and nitric oxide (NO) production and reduced inducible nitric oxide synthase (iNOS) expression levels in vitro, and these results were confirmed by zebrafish embryos in vivo. However, this phenotype was abolished in the absence of inositol-requiring enzyme 1 (IRE1α) but not in the absence of protein kinase RNA (PKR)-like ER-resistant kinase (PERK) or X-box-binding protein 1 (XBP1) in the mouse embryo fibroblast (MEF) knockout (KO) cells, suggesting that BG elicits an antioxidant effect in an IRE1α-dependent manner. Antioxidant and anti-inflammatory effects were assessed in the liver and intestines of the mouse model affected by nonalcoholic fatty liver disease (NAFLD), which was induced by a high-fat/high-fructose diet. In the liver, BG treatment rescued NAFLD-induced glutathione (GSH), catalase (CAT), tumor necrosis factor-α (TNF-α) and interleukin (IL)-6 expression. In the intestines, BG also rescued NAFLD-induced shortened villi, inflammatory immune cell infiltration, upregulated IL-6, cytosine-cytosine-adenosine-adenosine-thymidine (CCAAT)/enhancer-binding homologous protein (CHOP) and binding immunoglobulin protein (BiP) expression. In conclusion, our results show that BG reduces ROS and NO production followed by inflammation in an IRE1α-dependent and XBP1-independent manner. The results suggest that BG provides antioxidant and anti-inflammatory effects through an ER stress mechanism.

Antioxidant Effect of Lycium barbarum Leaf through Inflammatory and Endoplasmic Reticulum Stress Mechanism.

Although the prevalence and incidence of inflammatory bowel disease (IBD), a defective immune response of the gastrointestinal tract, has been increasing in North America and Western Europe, recent studies have shown that this disease is also increasing rapidly in Asia. Several studies have been searching for functional foods that can prevent or reduce IBD symptoms because the drug treatments for IBD are expensive with complications. Genome-Wide Association Study (GWAS), an observational study of a genome-wide set of genetic variants in different individuals, showed that endoplasmic reticulum (ER) stress is one of the causes of IBD. Previously, we reported the effects of Lyciumbarbarum fruit and this study investigated the effects of Lycium barbarum leaf (LL) on inflammation and ER stress of the intestine. The paracellular permeability, antioxidant, and anti-inflammatory response were measured on polarized Caco-2 cells. The ER stress pathway and pro-inflammatory cytokines were evaluated on MEF-knockout cell lines, and on the intestines of the mice fed a high-fat diet with lipopolysaccharide-induced inflammation. Our data showed that the LL pretreatment strengthened the tight junction integrity and reduced NO production both in the presence and in the absence of inflammation. Furthermore, LL inhibited ER stress and inflammation via IRE1α and XBP1 in vitro as well as in the inflamed intestines of mice, highlighting the antioxidant and anti-inflammatory function of LL in an IRE1α-XBP1-dependent manner.

Anti­inflammatory effects of leaf and branch extracts of honeyberry (Lonicera caerulea) on lipopolysaccharide­stimulated RAW264.7 cells through ATF3 and Nrf2/HO­1 activation.

Honeyberry (Lonicera caerulea) has long been used as a traditional medicine in China, Japan and northern Russia. Functional studies of honeyberry have mainly focused on the fruits, which have been reported to exert various pharmacological activities, including anti­inflammatory activity, with limited or no studies on the other parts of the plant, such as the leaves and branches. In the present study, the anti­inflammatory effects of extracts of the leaves (HBL), branches (HBB) and fruit (HBF) of honeyberry plant were evaluated in lipopolysaccharide (LPS)­stimulated RAW264.7 cells. HBL and HBB significantly inhibited the production of pro-inflammatory mediators in LPS­stimulated RAW264.7 cells, and the inhibitory effects of HBL and HBB were stronger than those of HBF. HBL and HBB blocked the nuclear accumulation of p65 independently of IκB­α. HBL did not inhibit the phosphorylation of ERK1/2 or p38; however, HBB effectively inhibited the phosphorylation of p38 but not ERK1/2. HBL and HBB increased the expression of heme oxygenase­1 (HO­1) protein by inducing the nuclear accumulation of nuclear factor erythroid 2­related factor 2 (Nrf2) through the activation of the reactive oxygen species (ROS)/p38 pathway; the reduction in inducible nitric oxide synthase (iNOS) and interleukin­1ß (IL­1ß) expression by HBL and HBB was inhibited by HO­1 knockdown. In addition, HBL and HBB increased the expression of activating transcription factor­3 (ATF3), and the reduction in iNOS and IL­1ß expression by HBL and HBB was inhibited by ATF3 knockdown. Collectively, HBL and HBB inhibited LPS­induced nuclear factor­κB activation by blocking the nuclear accumulation of p65, increasing HO­1 expression through activation of the ROS/p38/Nrf2 pathway, and increasing ATF3 expression. Furthermore, HBB inhibited LPS­induced p38 phosphorylation. These findings suggest that HBL and HBB may have great potential as natural products for the development of anti­inflammatory drugs.

Predicting Functional Outcome Based on Linked Data After Acute Ischemic Stroke: S-SMART Score.

Prediction of outcome after stroke may help clinicians provide effective management and plan long-term care. We aimed to develop and validate a score for predicting good functional outcome available for hospitals after ischemic stroke using linked data. A total of 22,005 patients with acute ischemic stroke from the Clinical Research Center for Stroke Registry between July 2007 and December 2014 were included in the derivation group. We assessed functional outcomes using a modified Rankin scale (mRS) score at 3 months after ischemic stroke. We identified predictors related to good 3-month outcome (mRS score ≤ 2) and developed a score. External validations (geographic and temporal validations) of the developed model were performed. The prediction model performance was assessed using the area under the receiver operating characteristic curve (AUC) and the calibration test. Stroke severity, sex, stroke mechanism, age, pre-stroke mRS, and thrombolysis/thrombectomy treatment were identified as predictors for 3-month good functional outcomes in the S-SMART score (total 34 points). Patients with higher S-SMART scores had an increased likelihood of a good outcome. The AUC of the prediction score was 0.805 (0.798-0.811) in the derivation group and 0.812 (0.795-0.830) in the geographic validation group for good functional outcome. The AUC of the model was 0.812 (0.771-0.854) for the temporal validation group. Moreover, they had good calibration. The S-SMART score is a valid and useful tool to predict good functional outcome following ischemic stroke. This prediction model may assist in the estimation of outcomes to determine care plans after stroke.

Ethylparaben induces apoptotic cell death in human placenta BeWo cells via the Caspase-3 pathway.

Parabens are generally used as preservatives in foods, pharmaceuticals, and various other commercial products. Among them, ethylparaben has weaker estrogenic characteristics than endogenous estrogen. However, growing evidence indicates that ethylparaben has an adverse effect on various human tissues. Here, we investigated whether ethylparaben induces cell death by affecting cell viability, cell proliferation, cell cycle, and apoptosis using the human placenta cell line BeWo. Ethylparaben significantly decreased cell viability in a dose-dependent manner. It caused cell cycle arrest at sub-G1 by reducing the expression of cyclin D1, whereas it decreased the cell proportion at the G0/G1 and S phases. Furthermore, we verified that ethylparaben induces apoptotic cell death by enhancing the activity of Caspase-3. Taken together, our results suggest that ethylparaben exerts cytotoxic effects in human placental BeWo cells via cell cycle arrest and apoptotic pathways.

Dual Binding to Orthosteric and Allosteric Sites Enhances the Anticancer Activity of a TRAP1-Targeting Drug.

The molecular chaperone TRAP1 is the mitochondrial paralog of Hsp90 and is overexpressed in many cancer cells. The orthosteric ATP-binding site of TRAP1 has been considered the primary inhibitor binding location, but TRAP1 allosteric modulators have not yet been investigated. Here, we generated and characterized the Hsp90 inhibitor PU-H71, conjugated to the mitochondrial delivery vehicle triphenylphosphonium (TPP) with a C10 carbon spacer, named SMTIN-C10, to enable dual binding to orthosteric and allosteric sites. In addition to tight binding with the ATP-binding site through the PU-H71 moiety, SMTIN-C10 interacts with the E115 residue in the N-terminal domain through the TPP moiety and subsequently induces structural transition of TRAP1 to a tightly packed closed form. The data indicate the existence of a druggable allosteric site neighboring the orthosteric ATP pocket that can be exploited to develop potent TRAP1 modulators.