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Ming-Hua Ho,1 Hao-Chieh Chang,2,3 Yu-Chia Chang,3 Jeiannete Claudia,1 Tzu-Chiao Lin,2 Po-Chun Chang2,3 1Department of Chemical Engineering, College of Engineering, National Taiwan University of Science and Technology, Taipei, Taiwan; 2Graduate Institute of Clinical Dentistry, School of Dentistry, National Taiwan University, Taipei, Taiwan; 3Department of Dentistry, National Taiwan University Hospital, Taipei, Taiwan Abstract: This study aimed to develop a functionally graded membrane (FGM) to prevent infection and promote tissue regeneration. Poly(L-lactide-co-D,L-lactide) encapsulating platelet-derived growth factor (PDLLA-PDGF) or metronidazole (PDLLA-MTZ) was electrospun to form a nanofibrous layer on the inner or outer surface of a clinically available collagen membrane, respectively. The membrane was characterized for the morphology, molecule release profile, in vitro and in vivo biocompatibility, and preclinical efficiency for alveolar ridge regeneration. The PDLLA-MTZ and PDLLA-PDGF nanofibers were 800–900 nm in diameter, and the thicknesses of the functional layers were 20–30 µm, with sustained molecule release over 28 days. All of the membranes tested were compatible with cell survival in vitro and showed good tissue integration with minimal fibrous capsule formation or inflammation. Cell proliferation was especially prominent on the PDLLA-PDGF layer in vivo. On the alveolar ridge, all FGMs reduced wound dehiscence compared with the control collagen membrane, and the FGM with PDLLA-PDGF promoted osteogenesis significantly. In conclusion, the FGMs with PDLLA-PDGF and PDLLA-MTZ showed high biocompatibility and facilitated wound healing compared with conventional membrane, and the FGM with PDLLA-PDGF enhanced alveolar ridge regeneration in vivo. The design represents a beneficial modification, which may be easily adapted for future clinical use. Keywords: tissue engineering, platelet-derived growth factor, metronidazole, alveolar process, animal models

Ming-Hua Ho,1,2 Chih-Jung Yao,3 Mei-Hsiu Liao,4 Pei-I Lin,4 Shing-Hwa Liu,5 Ruei-Ming Chen2,4,6 1Department of Chemical Engineering, National Taiwan University of Science and Technology, 2Cell Physiology and Molecular Image Research Center, Taipei Medical University-Wan Fang Hospital, 3Department of Internal Medicine, School of Medicine, 4Graduate Institute of Medical Sciences, College of Medicine, Taipei Medical University, 5Institute of Toxicology, College of Medicine, National Taiwan University, 6Anesthetics and Toxicology Research Center, Taipei Medical University Hospital, Taipei, Taiwan Abstract: Osteoblasts play critical roles in bone formation. Our previous study showed that chitosan nanofibers can stimulate osteoblast proliferation and maturation. This translational study used an animal model of bone defects to evaluate the effects of chitosan nanofiber scaffolds on bone healing and the possible mechanisms. In this study, we produced uniform chitosan nanofibers with fiber diameters of approximately 200 nm. A bone defect was surgically created in the proximal femurs of male C57LB/6 mice, and then the left femur was implanted with chitosan nanofiber scaffolds for 21 days and compared with the right femur, which served as a control. Histological analyses revealed that implantation of chitosan nanofiber scaffolds did not lead to hepatotoxicity or nephrotoxicity. Instead, imaging analyses by X-ray transmission and microcomputed tomography showed that implantation of chitosan nanofiber scaffolds improved bone healing compared with the control group. In parallel, microcomputed tomography and bone histomorphometric assays further demonstrated augmentation of the production of new trabecular bone in the chitosan nanofiber-treated group. Furthermore, implantation of chitosan nanofiber scaffolds led to a significant increase in the trabecular bone thickness but a reduction in the trabecular parameter factor. As to the mechanisms, analysis by confocal microscopy showed that implantation of chitosan nanofiber scaffolds increased levels of Runt-related transcription factor 2 (Runx2), a key transcription factor that regulates osteogenesis, in the bone defect sites. Successively, amounts of alkaline phosphatase and osteocalcin, two typical biomarkers that can simulate bone maturation, were augmented following implantation of chitosan nanofiber scaffolds. Taken together, this translational study showed a beneficial effect of chitosan nanofiber scaffolds on bone healing through stimulating trabecular bone production due to upregulation of Runx2-mediated alkaline phosphatase and osteocalcin gene expressions. Our results suggest the potential of chitosan nanofiber scaffolds for therapy of bone diseases, including bone defects and bone fractures. Keywords: chitosan nanofibers, bone healing, micro-computed tomography, bone histomorphometry, Runx2/OCN/ALP

Ming-Hua Ho,1,2 Mei-Hsiu Liao,3 Yi-Ling Lin,2 Chien-Hao Lai,3 Pei-I Lin,3 Ruei-Ming Chen2–4 1Department of Chemical Engineering, National Taiwan University of Science and Technology, Taipei, Taiwan; 2Cell Physiology and Molecular Image Research Center and Department of Anesthesiology, Wan Fang Hospital, 3Graduate Institute of Medical Sciences, Taipei Medical University, Taipei, Taiwan; 4Anesthetics and Toxicology Research Center, Taipei Medical University Hospital, Taipei, Taiwan Abstract: Osteoblast maturation plays a key role in regulating osteogenesis. Electrospun nanofibrous products were reported to possess a high surface area and porosity. In this study, we developed chitosan nanofibers and examined the effects of nanofibrous scaffolds on osteoblast maturation and the possible mechanisms. Macro- and micro observations of the chitosan nanofibers revealed that these nanoproducts had a flat surface and well-distributed fibers with nanoscale diameters. Mouse osteoblasts were able to attach onto the chitosan nanofiber scaffolds, and the scaffolds degraded in a time-dependent manner. Analysis by scanning electron microscopy further showed mouse osteoblasts adhered onto the scaffolds along the nanofibers, and cell–cell communication was also detected. Mouse osteoblasts grew much better on chitosan nanofiber scaffolds than on chitosan films. In addition, human osteoblasts were able to adhere and grow on the chitosan nanofiber scaffolds. Interestingly, culturing human osteoblasts on chitosan nanofiber scaffolds time-dependently increased DNA replication and cell proliferation. In parallel, administration of human osteoblasts onto chitosan nanofibers significantly induced osteopontin, osteocalcin, and alkaline phosphatase (ALP) messenger (m)RNA expression. As to the mechanism, chitosan nanofibers triggered runt-related transcription factor 2 mRNA and protein syntheses. Consequently, results of ALP-, alizarin red-, and von Kossa-staining analyses showed that chitosan nanofibers improved osteoblast mineralization. Taken together, results of this study demonstrate that chitosan nanofibers can stimulate osteoblast proliferation and maturation via runt-related transcription factor 2-mediated regulation of osteoblast-associated osteopontin, osteocalcin, and ALP gene expression. Keywords: chitosan nanofibers, osteoblast-associated gene expression, osteoblast maturation, Runx2

This paper describes a new and facile method, ‘solvent capillary contact printing(SCCP)’, that fabricates micro-patterned hydrophilic/hydrophobic surface causedby the selective manipulation of nanometre-scale block copolymer micelles. Themethod is based on using capillary injection and evaporation of a solvent, which ispreferential to a core block of micelles, through poly(dimethylsiloxane) (PDMS)microchannels placed on a pre-formed block copolymer micelle monolayer. Weproduced well-defined surface micropatterns where a nanostructure consistingof core-opened micelles gave rise to hydrophilic surface property in the regionsin contact with solvent while one consisting of hemispherical micelles remainedhydrophobic in the regions contacted by the PDMS mould. Our method allows repetitivemicropatterning; a surface micropattern previously formed is simply erased byexposure of preferential solvent vapour due to reversible structure modificationof micelles. Furthermore, SCCP with various metal salts, precursors of metalnanoparticles, enables us to fabricate micropatterned arrays of well-separated metalnanoparticles which can be used as a catalyst for synthesizing nanowires. Themicropatterned arrays of GaN nanowires are demonstrated, fabricated by SCCP. [ABSTRACT FROM AUTHOR]

J Ian Spark,1 Christopher L Delaney,1 Richard B Allan,1 Melissa HL Ho,2 Michelle D Miller21Department of Vascular Surgery, Flinders Medical Centre and Flinders University, 2Department of Nutrition and Dietetics, Flinders University, Bedford Park, Adelaide, South Australia, AustraliaBackground: Peripheral arterial disease affects 10%–25% of adults aged .55 years, and while a multitude of risk factors exist, one key influence is genetics. Rather than awaiting the onset of debilitating symptoms, interventions that target high-risk individuals and prevent or delay the onset of symptoms would have widespread impact. The aim of this study is to implement a 12-week fish oil intervention (10 mL/day containing approximately 1.5 g of eicosapentaenoic acid and 1 g of docosahexaenoic acid), with the intention of improving endothelial function, inflammation, and lipid status in a high-risk population, ie, those with impaired endothelial function and a parent with symptomatic peripheral arterial disease.Methods: This is a parallel-group, double-blind, randomized controlled trial involving administration of fish oil containing either about 1.5 g of docosahexaenoic acid and 1 g of docosahexaenoic acid (intervention) or about 0.15 g of eicosapentaenoic acid and about 0.1 g of docosahexaenoic acid for 12 consecutive weeks (control). The participants are 100 offspring of adults with diagnosed peripheral arterial disease who themselves have an ankle-brachial pressure index ≥0.9 but impaired endothelial function according to peripheral arterial tonometry. Measures performed at baseline and at 6 and 12 weeks include flow-mediated dilatation, C-reactive protein, absolute neutrophil and lymphocyte counts, tumor necrosis factor-α, interleukin-1ß, and interleukin-6 levels, thromboxane and prostacyclin, lipid status, and homocysteine, nitrite, and nitrate levels. Participants will be phoned fortnightly to monitor adherence and side effects, while participants will maintain a diary of fish oil consumption on a daily basis, and fish oil returned will be measured to confirm adherence. Participants will complete validated surveys to determine background diet and physical activity levels.Discussion: This study will examine the effectiveness of a moderate-dose fish oil intervention in reversing endothelial dysfunction in asymptomatic offspring of patients with peripheral arterial disease. It provides the opportunity to delay the progression of peripheral arterial disease using a cheap and readily available dietary supplement that has minimal side effects compared with synthetic vasoactive pharmacological medications.Keywords: omega 3 fatty acids, endothelial function, peripheral arterial disease

Background: Despite increasing evidence on the benefits of statin therapy for acute myocardial infarction (AMI), differential outcomes in accordance with statin intensity have not been evaluated in patients with AMI and low-density lipoprotein cholesterol (LDL-C) levels < 55 mg/dL. Therefore, this study aimed to compare the clinical outcomes of high- and moderate-intensity statin therapy in this population., Methods: A total of 752 participants with AMI and LDL-C levels < 55 mg/dL from a Korean nationwide multicenter observational cohort (2016-2020) were included and categorized into two groups: high-intensity statin group (n = 384) and moderate-intensity statin group (n = 368). The primary outcome was 1-year major adverse cardiac and cerebrovascular events (MACCEs). Propensity score matching (PSM) and Cox models were used to determine whether statin intensity independently influenced the primary outcome., Results: Compared to the moderate-intensity statin group, the high-intensity statin group had a comparable risk of MACCE in all Cox models and PSM-adjusted analyses. The cumulative incidence of MACCE was comparable between the two groups., Conclusions: Statin intensity appeared to have no significant impact on clinical outcomes in AMI patients with LDL-C levels < 55 mg/dL. These results underscore the need for further investigations aimed at refining treatment strategies for this specific patient cohort, potentially reducing treatment-related burdens without compromising clinical effectiveness.

Background: Mounting evidence suggests an associated between myocardial bridging (MB) and coronary vasospasm (CVS); however, no consensus has been established on whether CVS worsens clinical outcomes in patients with MB. Therefore, this retrospective study aimed to compare the long-term clinical outcomes in patients with MB based on CVS presence., Methods: This retrospective study enrolled 254 consecutive patients with MB undergoing provocative testing for coronary reactivity between January 1, 2009 and December 30, 2015, and stratified them into 2 groups: (a) group A (with CVS, n = 168); and (b) group B (without CVS, n = 86). The primary endpoints were major adverse cardiovascular events (MACEs), a composite of cardiac death, cardiac arrest, non-fatal myocardial infarction, ischemia-driven revascularization, ischemia-driven coronary angiography, and ischemia-related hospitalization. Diverse Cox models were used to determine whether CVS independently influenced MACE., Results: The mean age of study participants was 50.8 years, and 60.2% of them were male. The median follow-up period was 8.15 years. The rate of MACE was 35.1% and 26.7% in groups A and B, respectively. Group A had a significantly higher risk of MACE than group B (the reference group) in model 3 (hazard ratio [HR]:1.92; 95% confidence interval [CI]:1.12-3.29) and model 4 (adjusted HR: 1.94; 95% CI: 1.04-3.59)., Conclusions: The presence of CVS adversely affects clinical outcomes in patients with MB. Further prospective clinical studies are required to confirm this association.

This study investigates the effect of silicon carbon nitride (SiCN) as an interlayer for ZnO-based resistive random access memory (RRAM). SiCN was deposited using plasma-enhanced chemical vapor deposition with controlled carbon content, achieved by varying the partial pressure of tetramethylsilane (4MS). Our results indicate that increasing the carbon concentration enhances the endurance of RRAM devices but reduces the on/off ratio. Devices with SiCN exhibited lower operating voltages and more uniform resistive switching behavior. Oxygen migration from ZnO to SiCN is examined by x-ray diffraction and x-ray photoelectron spectroscopy analyses, promoting the formation of conductive filaments and lowering set voltages. Additionally, we examined the impact of top electrode oxidation on RRAM performance. The oxidation of the Ti top electrode was found to reduce endurance and increase low resistive state resistance, potentially leading to device failure through the formation of an insulating layer between the electrode and resistive switching material. The oxygen storage capability of SiCN was further confirmed through high-temperature stress tests, demonstrating its potential as an oxygen reservoir. Devices with a 20 nm SiCN interlayer showed significantly improved endurance, with over 500 switching cycles, compared to 62 cycles in those with a 5 nm SiCN layer. However, the thicker SiCN layer resulted in a notably lower on/off ratio due to reduced capacitance. These findings suggest that SiCN interlayers can effectively enhance the performance and endurance of ZnO-based RRAM devices by acting as an oxygen reservoir and mitigating the top electrode oxidation effect., (© 2024 IOP Publishing Ltd. All rights, including for text and data mining, AI training, and similar technologies, are reserved.)

Dopaminergic neurotransmission plays a crucial role in motor function through the coordination of dopamine receptor (DRD) subtypes, such as DRD1 and DRD2, thus the functional imbalance of these receptors can lead to Parkinson's disease. However, due to the complexity of dopaminergic circuits in the brain, it is limited to investigating the individual functions of each DRD subtype in specific brain regions. Here, we developed a light-responsive chimeric DRD2, OptoDRD2, which can selectively activate DRD2-like signaling pathways with spatiotemporal resolution. OptoDRD2 was designed to include the light-sensitive component of rhodopsin and the intracellular signaling domain of DRD2. Upon illumination with blue light, OptoDRD2 triggered DRD2-like signaling pathways, such as Gαi/o subtype recruitment, a decrease in cAMP levels, and ERK phosphorylation. To explore unknown roles of DRD2 in glutamatergic cell populations of basal ganglia circuitry, OptoDRD2 was genetically expressed in excitatory neurons in lateral globus pallidus (LGP) of the male mouse brain. The optogenetic stimulation of OptoDRD2 in the LGP region affected a wide range of locomotion-related parameters, such as increased frequency of movement and decreased immobility time, resulting in the facilitation of motor function of living male mice. Therefore, our findings indicate a potential novel role for DRD2 in the excitatory neurons of the LGP region, suggesting that OptoDRD2 can be a valuable tool enabling the investigation of unknown roles of DRD2 at specific cell types or brain regions. Significance Statement We developed a light-responsive chimeric dopamine receptor type 2, OptoDRD2, by combining the blue-light sensing part of rhodopsin and intracellular functional regions of DRD2. OptoDRD2 can selectively trigger DRD2-like downstream signaling pathways upon illumination of blue light. To explore unknown roles of DRD2 in glutamatergic cell populations of basal ganglia circuitry, OptoDRD2 was genetically expressed in excitatory neurons at lateral globus pallidus (LGP) in the mouse brain. Optogenetic stimulation of OptoDRD2 in living mice suggested a potential novel function of DRD2 in the LGP that enhances motor outputs. Therefore, OptoDRD2 enabled the precise control of DRD2-like signaling in specific cell types and brain regions, allowing the exploration of potential novel DRD2 functions in living mice., (Copyright © 2024 Kim et al.)

Purpose: Population attributable fractions (PAFs) for hormone and reproductive factors have been estimated in several countries. IARC designated as Group 1 and Group 2A carcinogen for hormone factors in breast, ovarian, endometrial and uterine cervix cancer. This study aimed to estimate the PAFs of hormone/reproductive factor attributed to cancer incidence and deaths in Korean women and projected trends from 2015 to 2030., Materials and Methods: The PAF was estimated with using the 2005 standardized prevalence rates and 2020 incidence and deaths with a 15-year latency. Based on the Levin's formula, prevalence rates were calculated using the Korea National Health and Nutrition Examination Survey (KNHANES) and the relative risks (RRs), which were the risk of selected female cancer associated with oral contraceptive, hormone replacement therapy and duration of breastfeeding, were estimated from the meta-analysis of studies performed in Korean women population. Studies based on the Asian and Global populations were calculated as a sensitivity analysis., Results: The estimation PAFs for hormone was 1.02% with 1,192 cases and reproductive was 2.67% with 3,112 cases. Moreover, 0.40% (125 deaths) and 1.09% (342 deaths) in female-related cancer deaths in order. EP combined HRT accounted the most proportion in hormone factors and breastfeeding in reproductive factors. Also, the breast cancer had the highest percent in both hormone and reproductive factors., Conclusion: Through this study, 1.02% and 2.67% of female-related cancer incidence will be reduced by encouraging avoiding the use of oral contraceptives (OCs) and hormone replacement therapy (HRT) and breastfeeding for more than 6 months in reproductive factors. Additionally, among four selected female cancers in this study, breast cancer was observed to be a significant level of prevention.

Limited data exists regarding the time-point risk stratification model after acute coronary syndrome. This study aimed to investigate time-point mortality rates in patients with acute myocardial infarction, focusing on comparison by type of myocardial infarction, in a real-world cohort. A total of 12,836 patients from a nationwide Korean registry were analyzed. Mortality rates were calculated at yearly, monthly, and weekly time points after admission in patients with ST-elevation myocardial infarction (STEMI) and non-ST-elevation myocardial infarction (NSTEMI), dividing the number of deaths during a specific period by the number of patients at risk in the same period. In the first week after admission, patients with STEMI had a significantly higher mortality rate than NSTEMI patients (4.62% vs. 1.79%, P <0.001). However, this trend had been inverted since the second week. The higher mortality rate in patients with STEMI versus NSTEMI was inverted since the second week for male but not for female patients, where the inversion occurred since the tenth week. Temporal assessment of correlates of mortality revealed that several baseline variables, including Killip class, systolic blood pressure, total cholesterol, and STEMI diagnosis, had significantly different impacts on deaths over time. In conclusion, temporal assessment of time-point outcomes from the Korean registry revealed that an initially higher mortality rate in patients with STEMI versus NSTEMI had been inverted at second week. This outcome assessment could be one step toward advanced risk prediction model for time-course personalized medicine. Further studies are needed to clarify this issue., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Myung Ho Jeong reports financial support was provided by Korea Disease Control and Prevention Agency. If there are other authors, they 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. Published by Elsevier Inc.)

Background: It has been suggested that the association between body mass index and breast cancer risk differs between Asian women and Western women. We aimed to assess the associations between body mass index and breast cancer incidence in East Asian women., Methods: Pooled analyses were performed using individual participant data of 319,189 women from 13 cohort studies in Japan, Korea, and China. Participants' height and weight were obtained by measurement or self-reports at cohort baseline. Breast cancer was defined as code C50.0-C50.9 according to the International Classification. Using a Cox proportional hazards model, hazard ratios of breast cancer were estimated for each body mass index category, with the reference group set as the group with a body mass index of 21 to < 23 kg/m 2 . The hazard ratio for a 5 kg/m 2 increase in body mass index was also calculated., Results: During a mean 16.6 years of follow-up, 4819 women developed breast cancer. Similar to Westerners, a steady increase in breast cancer risk with increasing body mass index was observed in postmenopausal women, but the slope of the risk increase appeared to slow at a body mass index of 26-28 kg/m 2 . In premenopausal women, the inverse association seen in Westerners was not observed. The risk of developing breast cancer after 50 years of age increased slightly with increasing body mass index, which was more pronounced in the older birth cohort. There was no significant association between body mass index and the risk of developing breast cancer before 50 years of age, but the risk estimates changed from positive to negative as the birth cohort got younger., Conclusions: In East Asia, the role of body mass index in breast cancer in premenopausal women may be changing along with the increase in obesity and breast cancer. The increased risk of postmenopausal breast cancer with a higher body mass index was as robust as that of Western women., Competing Interests: Declarations Ethics approval and consent to participate This study was performed in accordance with the Declaration of Helsinki. Each participating study was approved by the relevant institutional ethical review boards. The protocol for the ACC analysis was approved by the institutional review board of the National Cancer Center, Japan. The requirement for consent from several cohort studies was waived due to the justification for lack of consent at the time of the survey, the difficulty in obtaining new consent, and the public necessity of the research. Consent for publication All authors reviewed and approved the final version for submission. Competing interests The authors declare no competing interests., (© 2024. The Author(s).)

A viscoelastic flow focusing device is presented that enables simple and robust focusing of submicron-sized particles in the channel center by optimizing operating conditions such as channel length, flow rate and poly(ethylene oxide) (PEO) concentration. Submicron-sized particles (up to 100 nm) can be easily focused to the channel center under viscoelastic fluid flow without any external force via a simply fabricated microchannel with a long channel length and a large square cross-section. The device was fabricated using a common soft lithography technique for the polydimethylsiloxane (PDMS) channel, which has a width of 50 μm, a height of 50 μm and a channel length of 27 cm. The extralong channel enabled submicron-sized particle focusing, even in a channel of a relatively large size with high flow rate, which can realize flow cytometric applications. The focusing performance was first demonstrated using submicron-sized polystyrene (PS) beads ranging from 870 nm to 50 nm and then using biological particles such as E. coli bacteria to demonstrate the biological feasibility of the device. The PS beads, which ranged in diameter from 870 nm to 100 nm, were focused to the center of the channel, achieving over 90% focusing efficiency for beads as small as 510 nm and 62% focusing efficiency for 100-nm beads. The device could also align a bacterial suspension in the center of the channel at flow rates up to 30 µL/min, demonstrating its biological importance. The ability of the developed device to align submicron-sized particles within a narrow flow stream in a highly robust manner is promising for various biological and clinical applications, such as distinguishing pathogenic bacteria and evaluating individual antibiotic responses in a single experiment., Competing Interests: Declarations Ethical approval Not applicable. Competing interests The authors declare no competing interests., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Austria, part of Springer Nature.)

Local coordination environment (LCE) manipulation has emerged as a significant approach for modulating the electrocatalytic behavior of low-dimensional nanomaterials. However, challenges persist in accurately identifying active sites and understanding dynamic changes during operation. Here, we underscore the influence of LCE on the electrochemical production of H 2 O 2 , utilizing the Pd cluster as a model catalyst. Density functional theory (DFT) calculations illustrate the role of first- and second-coordinated sulfur and oxygen in modulating the binding strength of HOO*. Guided by DFT screening, the as-prepared Pd cluster (Pd x /HMCS) catalyst presents exceptional catalytic performance with a high mass activity of 4.06 A mg -1 at 0.45 V and selectivity above 94%. The Pd x /HMCS catalyst also delivers promising potential for industrial practices with a production rate of 16.3 mol g cat -1 h -1 in flow cell evaluation. Elaborated in situ characterizations confirm that under operation, oxygen migrates from the second coordination sphere (CS) to the first CS to achieve oxygen coverage on the catalyst surface. Such an oxygen migration phenomenon and the optimized first and second coordination environment give rise to the outstanding performance.

Calcific aortic valve disease (CAVD) is a considerable health burden with a lack of effective therapeutic options. There is an urgent need to develop interventions that inhibit the osteogenic transformation of valvular interstitial cells (VICs) and delay the calcification process. Niclosamide, an FDA-approved anti-helminthic drug, has emerged as a promising candidate that demonstrates a negative regulatory effect on porcine VICs calcification. However, its molecular mechanism in human VICs (hVICs) remains to be investigated. In this study, high-resolution mass spectrometry-based proteomics and phosphoproteomics were employed, and 8373 proteins and 3697 phosphosites were identified in hVICs treated with a pro-calcifying medium and niclosamide. The quantitative proteomic and phosphoproteomic analysis resulted in the identification of calcification markers and osteogenesis-associated proteins. Bioinformatic analysis of the protein-protein interaction network and affected kinase prediction revealed that the AMPK/mTOR/p70S6K signaling cascade was altered upon calcific induction and niclosamide treatment. Further validation indicated that niclosamide inhibited the calcification of hVICs by targeting the mammalian target of the rapamycin (mTOR) signaling pathway. This study provides the first evidence that niclosamide could prevent osteoblastic differentiation in hVICs partially through the inhibition of the AMPK/mTOR/p70S6k signaling pathway, thereby mitigating hVICs calcification. These findings present a foundation for potential therapeutic strategies to impede the progression of CAVD and provide valuable insights into the pharmacological effects of niclosamide on human VICs., 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 Elsevier Inc. All rights reserved.)

Polygenic risk scores (PRSs) are promising for risk stratification but have mainly been developed in European populations. This study developed single- and multi-ancestry PRSs for lung adenocarcinoma (LUAD) in East Asian (EAS) never-smokers using genome-wide association study summary statistics from EAS (8,002 cases; 20,782 controls) and European (2,058 cases; 5,575 controls) populations. A multi-ancestry PRS, developed using CT-SLEB, was strongly associated with LUAD risk (odds ratio=1.71, 95% confidence interval (CI):1.61,1.82), with an area under the receiver operating curve value of 0.640 (95% CI:0.629,0.653). Individuals in the highest 20% of the PRS had nearly four times the risk compared to the lowest 20%. Individuals in the 95 th percentile of the PRS had an estimated 6.69% lifetime absolute risk. Notably, this group reached the average population 10-year LUAD risk at age 50 (0.42%) by age 41. Our study underscores the potential of multi-ancestry PRS approaches to enhance LUAD risk stratification in EAS never-smokers.

Background: Chemo-endocrine therapy can lead to various side effects associated with ovarian dysfunction. Predicting menstrual recovery is necessary to discuss the treatment-related issues regarding fertility and premature menopause with patients., Methods: In the ASTRRA trial, patients who resumed ovarian function within 2 years after chemotherapy were randomized to receive tamoxifen for 5 years or OFS with tamoxifen for 2 years. With these 1298 patients, we developed a model that predicts when menstrual recovery will occur within a 3-year period after chemotherapy using variables including age, body mass index, chemotherapy regimen and duration, and serum estradiol and follicle-stimulating hormone levels., Results: The data of 957 patients were used to develop the prediction model, and those of 341 patients were used for validation. In the development group, menstruation resumed in 450 patients (47.0%) within 5 years. In multivariable analysis, younger age (< 35 vs. 45, HR 7.85, 95% CI 4.63-13.30, p < 0.0001), anthracycline-based chemotherapy without taxane (vs. with taxane, HR 1.81, 95% CI 1.37-2.38, p < 0.0001), and chemotherapy duration (≤ 90 days vs. > 90 days, HR 1.32, 95% CI 1.01-1.72, p = 0.045) correlated with menstrual recovery. Using combined age, regimen, and duration of chemotherapy, we developed a simplified scoring system to estimate recovery chances and used a concordance index of 0.679 overall and 0.744 at 3 years for validation., Conclusion: This model predicted timing and probability of menstrual recovery, based on their individual age, type and duration of chemotherapy in premenopausal women diagnosed with breast cancer who received tamoxifen after chemotherapy., (© 2024. The Author(s).)

Background: Smart wearable technology has potential benefits for promoting physical activity and preventing sarcopenia., Objective: The purpose of this study was to explore the efficacy of a wearable activity tracker with 2-stage goal-setting for daily steps on older adults' physical activity and sarcopenia indicators., Methods: The study used a clustered trial design and was conducted in March to June 2022. Participants were community-dwelling adults older than 60 years who were recruited from 4 community centers in Taipei City. The intervention was designed with 2-stage goals set to 5000 steps/day in the first 4 weeks and 7500 steps/day in the final 4 weeks while wearing a commercial wearable activity tracker. Data were collected by self-reported questionnaires, a body composition analyzer, a handle grip tester, and 5 sit-to-stand tests., Results: All 27 participants in the experimental group and 31 participants in the control group completed the 8-week intervention. Total and light-intensity physical activities, skeletal muscle index, and muscle strength increased, while sedentary time, BMI, and the waist circumference of participants decreased in the experimental group, with significant group-by-time interactions compared to the control group., Conclusions: A wearable activity tracker with gradual goal-setting is an efficient approach to improve older adults' physical activity and sarcopenia indicators. Smart wearable products with behavioral change techniques are recommended to prevent sarcopenia in older adult populations., (©Mu-Hsing Ho, Chi-Yuan Peng, Yung Liao, Hsin-Yen Yen. Originally published in the Journal of Medical Internet Research (https://www.jmir.org), 01.11.2024.)

Background and Objectives: Familial hypercholesterolemia (FH) increases the risk of premature cardiovascular disease through disrupted low-density lipoprotein cholesterol (LDL-C) metabolism. Although FH is a severe condition, it remains widely underdiagnosed, which can be attributed to barriers in genetic testing and a lack of awareness. This study aims to propose and evaluate a targeted screening program for FH in South Korea by integrating the General Health Screening Program (GHSP) with cascade genetic screening., Methods: The study included individuals with LDL-C levels ≥190 mg/dL identified during the 2021 GHSP (primary participants). Data on demographics, lifestyle, medical history, and family history were collected through questionnaires. Targeted next-generation sequencing was used to identify pathogenic mutations in the PCSK9 , APOB , LDLRAP1 , and LDLR genes associated with FH. Pathogenic mutations found in primary participants were confirmed in their relatives (secondary participants) using Sanger sequencing. Participant characteristics were analyzed based on the presence of pathogenic mutations., Results: Among 83 individuals with severe hypercholesterolemia identified through the GHSP, 7 primary participants (8.4%) carried pathogenic mutations in the LDLR and PCSK9 genes. In secondary participants, pathogenic mutations were identified in 61.1% of the relatives of 4 patients with pathogenic mutations. The prevalence of pathogenic mutations was significantly higher in primary participants compared to secondary participants., Conclusions: Integrating community resources with FH screening can enhance the early detection and treatment of FH. By utilizing GHSP data and adding genetic screening, the proposed model provides a strategy to reduce the cardiovascular risks associated with FH, supporting its wider adoption at the national level., Competing Interests: Conceptualization: Kim HY, Shin MH; Formal analysis: Yang JH, Shin MH; Investigation: Yang JH, Shin MH; Methodology: Shin MH; Supervision: Shin MH; Writing - original draft: Yang JH, Kim HY, Shin MH; Writing - review & editing: Yang JH, Cho KH, Hong YJ, Kim JH, Kim HY, Shin MH., (Copyright © 2024. The Korean Society of Cardiology.)

Purpose: To investigate the long-term efficacy and safety of intravitreal brolucizumab (BRZ) injections in patients with typical neovascular age-related macular degeneration (typical nAMD) and polypoidal choroidal vasculopathy (PCV)., Methods: This multicentre retrospective study included 401 eyes of 398 patients with nAMD who received BRZ injection(s), with a follow-up duration of ≥12 months. Changes in best-corrected visual acuity (BCVA), retinal fluid evaluation and central subfield thickness (CST) on optical coherence tomography were assessed. The efficacy of BRZ was compared between typical nAMD and PCV groups., Results: Analyses were conducted with 280 eyes of 278 patients with typical nAMD and 121 eyes of 120 patients with PCV (mean age, 71.1 ± 8.6 years). 29 eyes (7.2%) were treatment naïve. The mean follow-up period was 15.3 ± 2.8 months; the mean number of BRZ injections within 1 year was 4.5 ± 1.7. BCVA was maintained during the follow-up period, and CST significantly improved from the first injection month and was maintained for 12 months in both the typical nAMD and PCV groups. The dry macula proportion increased from 2.7% at baseline to 56.1% at 1 month and 42.9% at 12 months. Among the 18 eyes that underwent indocyanine green angiography both before and after treatment, 10 (55.6%) showed polyp regression. Overall, the incidence of intraocular inflammation (IOI), retinal vasculitis and occlusive retinal vasculitis was 9.4% (38 eyes), 1.2% (5 eyes) and 0.5% (2 eyes), respectively. IOI occurred from the first to the sixth injections, with an average IOI onset of 28.5 ± 1.4 days. All eyes achieved IOI resolution, although the two eyes with occlusive retinal vasculitis showed a severe visual decline after IOI resolution., Conclusion: Brolucizumab was effective in maintaining BCVA and managing fluid in eyes with nAMD for up to 1 year, exhibiting a high polyp regression rate. However, the not uncommon incidence of IOI and the severe visual decline caused by the rare occlusive retinal vasculitis following BRZ treatment underscore the importance of careful monitoring and timely management., (© 2024 Acta Ophthalmologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.)

Background and Objectives: Real-world evidence on the relationship between delayed hospitalization and outcomes in myocardial infarction with nonobstructive coronary arteries (MINOCA) is lacking. Hence, we aimed to evaluate the clinical characteristics of patients with MINOCA and the 2-year mortality outcomes in this patient population according to the symptom-to-door time (SDT)., Methods: Overall, 861 patients with MINOCA from 2 Korean nationwide observational registries (2011-2020) were included and categorized as early or late presenters. Late presentation was defined as SDT ≥12 hours in patients with ST-segment elevation myocardial infarction (STEMI) and SDT ≥24 hours in patients with non-STEMI. The primary outcome was 2-year all-cause mortality. Propensity score matching (PSM) and age-sex adjusted analysis were used to determine whether late presentation independently affected mortality. Multivariate logistic regression analysis was used to examine the independent factors correlated with late presentation., Results: In unadjusted data, late presenters had a notably higher risk of 2-year all-cause mortality than early presenters (hazard ratio [HR], 2.44; 95% confidence interval [CI], 1.47-4.08). This trend persisted in age-sex adjusted analysis (adjusted HR, 2.29; 95% CI, 1.36-3.84) and PSM-adjusted analysis (adjusted HR, 2.18; 95% CI, 1.05-4.53). The positive independent factors for late presentation included female sex, no emergency medical service use and high creatinine level, whereas the negative independent factor was a dyslipidemia., Conclusions: Late presentation is associated with higher mortality in patients with MINOCA. Multidisciplinary efforts are needed to reduce pre-hospital delay, thereby improving the clinical outcomes in these patients., Competing Interests: The authors have no financial conflicts of interest., (Copyright © 2024. The Korean Society of Cardiology.)

Despite clinical data stretching over millennia, the neurobiological basis of the effectiveness of acupuncture in treating diseases of the central nervous system has remained elusive. Here, using an established model of acupuncture treatment in Parkinson's disease (PD) model mice, we show that peripheral acupuncture stimulation activates hypothalamic melanin-concentrating hormone (MCH) neurons via nerve conduction. We further identify two separate neural pathways originating from anatomically and electrophysiologically distinct MCH neuronal subpopulations, projecting to the substantia nigra and hippocampus, respectively. Through chemogenetic manipulation specifically targeting these MCH projections, their respective roles in mediating the acupuncture-induced motor recovery and memory improvements following PD onset are demonstrated, as well as the underlying mechanisms mediating recovery from dopaminergic neurodegeneration, reactive gliosis, and impaired hippocampal synaptic plasticity. Collectively, these MCH neurons constitute not only a circuit-based explanation for the therapeutic effectiveness of traditional acupuncture, but also a potential cellular target for treating both motor and non-motor PD symptoms., (© 2024 The Author(s). Advanced Science published by Wiley‐VCH GmbH.)

Background: Proteinuria is considered as a predictor for cardiovascular complications in diabetes mellitus (DM). However, no study has examined the association between changes in proteinuria and the risk of diabetic microvascular complications., Methods: Study participants were 71,825 DM patients who received urine dipstick test for proteinuria both in 2003-2004 and 2006-2007. They were categorized into four groups according to changes in proteinuria over 3 years (negative: negative → negative, resolved: proteinuria ≥ 1+ → negative, incident: negative → proteinuria ≥ 1+, persistent: proteinuria ≥ 1+ → proteinuria ≥ 1+). Cox-proportional hazard model was used in assessing the adjusted hazard ratios (HR) and 95% confidence interval (CI) for incidence of retinopathy, and neuropathy (adjusted HR [95% CI])., Result: In all of DM patients, risk for comprehensive incidence of retinopathy and neuropathy increased in all types of proteinuria changes. In type 1 DM, HR for retinopathy and neuropathy generally increased in order of negative (reference), resolved (2.175 [1.150-4.114] and 1.335 [0.909-1.961]), incident (2.088 [1.185-3.680] and 1.753 [1.275-2.409]), and persistent proteinuria (1.314 [0.418-4.134] and 2.098 [1.274-3.455]). This pattern of relationship was similarly observed in type 2 DM for retinopathy and neuropathy: negative (reference), resolved (1.490 [1.082-2.051] and 1.164 [0.988-1.371]), incident (1.570 [1.161-2.123] and 1.291 [1.112-1.500]), and persistent proteinuria (2.309 [1.407-3.788] and 1.272 [0.945-1.712])., Conclusion: Risk for diabetic retinopathy and neuropathy generally increased in order of negative, resolved, incident, and persistent proteinuria. Once manifested proteinuria was associated with the increased risk of diabetic retinopathy and neuropathy even after remission of proteinuria., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Evidence has suggested an increased risk of psychiatric manifestations following viral infections including coronavirus disease-2019 (COVID-19). However, psychiatric adverse events (AEs) after COVID-19 vaccination, which were documented in case reports and case series, remain unclear. This study is aimed to investigate the psychiatric AEs after COVID-19 vaccination from a large population-based cohort in Seoul, South Korea. We recruited 50% of the Seoul-resident population randomly selected from the Korean National Health Insurance Service (KNHIS) claims database on 1, January, 2021. The included participants (n = 2,027,353) from the Korean National Health Insurance Service claims database were divided into two groups according to COVID-19 vaccination. The cumulative incidences per 10,000 of psychiatric AEs were assessed on one week, two weeks, one month, and three months after COVID-19 vaccination. Hazard ratios (HRs) and 95% Confidence interval (CIs) of psychiatric AEs were measured for the vaccinated population. The cumulative incidence of depression, anxiety, dissociative, stress-related, and somatoform disorders, sleep disorders, and sexual disorders at three months following COVID-19 vaccination were higher in the vaccination group than no vaccination group. However, schizophrenia and bipolar disorders showed lower cumulative incidence in the vaccination group than in the non-vaccinated group. Depression (HR [95% CI] = 1.683 [1.520-1.863]), anxiety, dissociative, stress-related, and somatoform disorders (HR [95% CI] = 1.439 [1.322-1.568]), and sleep disorders (HR [95% CI] = 1.934 [1.738-2.152]) showed increased risks after COVID-19 vaccination, whereas the risks of schizophrenia (HR [95% CI] = 0.231 [0.164-0.326]) and bipolar disorder (HR [95% CI] = 0.672 [0.470-0.962]). COVID-19 vaccination increased the risks of depression, anxiety, dissociative, stress-related, and somatoform disorders, and sleep disorders while reducing the risk of schizophrenia and bipolar disorder. Therefore, special cautions are necessary for administering additional COVID-19 vaccinations to populations vulnerable to psychiatric AEs., (© 2024. The Author(s).)

Purpose: To evaluate the feasibility of intraoperative neurophysiological monitoring (IONM) during magnetic resonance (MR) imaging-guided ablations and identify strategies to reduce IONM electrode radiofrequency (RF) heating during MR imaging., Materials and Methods: Ex vivo experiments with a porcine tissue phantom simulating a typical high RF heating risk IONM setup during an MR imaging-guided ablation procedure on the shoulder were performed using a 1.5-T scanner. Mutual interference between MR imaging and IONM was evaluated. To assess RF heating risks, 4 pairs of IONM electrodes were inserted into the phantom at regions corresponding to the shoulders, midarm, and wrist. MR imaging of the "shoulder" was performed at 3 different specific absorption rates (SARs) with electrode wires positioned in various geometric configurations. Different combinations of electrode connections to the IONM system were investigated. Temperatures of each electrode were recorded using fiber-optic sensors., Results: Simultaneous IONM readout and MR imaging resulted in distortion of the IONM signal, but interleaving MR imaging and IONM without moving electrodes was feasible. During MR imaging, temperature elevations greater than 60°C at the electrode insertion sites were observed. Temperature reductions were achieved by routing electrode wires along the scanner central axis, reducing the wire length within the scanner bore, or lowering the SAR of the imaging sequence. Altering the electrode connection with the IONM system did not result in consistent changes in RF heating., Conclusions: With electrodes in the scanner bore, interleaving IONM and MR imaging is desired to avoid signal interference, and several strategies identified herein can reduce risk of electrode RF heating during MR imaging-guided ablation., (Copyright © 2024 SIR. Published by Elsevier Inc. All rights reserved.)

Nanoplastics (NPs), plastic particles ranging from 1 to 100 nm are ubiquitous environmental pollutants infiltrating ecosystems. Their small size and widespread use in various products raise concerns for human health, particularly their association with cardiovascular diseases (CVD). NPs can enter the human body through multiple routes, causing oxidative stress, and leading to the senescence and dysfunction of endothelial cells (ECs). Although there are potential natural compounds for treating CVD, there is limited research on preventing CVD induced by NPs. This study investigates the efficacy of Ecklonia cava extract (ECE) in preventing NPs-induced premature vascular senescence and dysfunction. Exposure of porcine coronary arteries (PCAs) and porcine coronary ECs to NPs, either alone or in combination with ECE, demonstrated that ECE mitigates senescence-associated β-galactosidase (SA-β-gal) activity induced by NPs, thus preventing premature endothelial senescence. ECE also improved NPs-induced vascular dysfunction. The identified active ingredient in Ecklonia cava, 2,7'-Phloroglucinol-6,6'-bieckol (PHB), a phlorotannin, proved to be pivotal in these protective effects. PHB treatment ameliorated SA-β-gal activity, reduced oxidative stress, restored cell proliferation, and decreased the expression of cell cycle regulatory proteins such as p53, p21, p16, and angiotensin type 1 receptor (AT1), well known triggers for EC senescence. Moreover, PHB also improved NPs-induced vascular dysfunction by upregulating endothelial nitric oxide synthase (eNOS) expression and restoring endothelium-dependent vasorelaxation. In conclusion, Ecklonia cava and its active ingredient, PHB, exhibit potential as therapeutic agents against NPs-induced premature EC senescence and dysfunction, indicating a protective effect against environmental pollutants-induced CVDs associated with vascular dysfunction., 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 Elsevier B.V. All rights reserved.)

Background: Minimally invasive procedures are increasingly implemented in aortic valve replacement (AVR) surgeries to minimize surgical trauma and achieve early patient recovery. We aimed to compare between short- and mid-term outcomes for isolated AVR using the representative minimally invasive approaches of right anterior mini-thoracotomy (RAMT) and partial upper sternotomy [J-sternotomy (JS)]., Methods: Patients (n=832) who had undergone surgical AVR between March 2009 and September 2022 were included. We retrospectively examined and compared data from these two minimally invasive approaches, and performed propensity score matching to account for differences in patient baseline characteristics. Early outcomes and late mortality were compared between the matched groups., Results: After applying exclusion criteria, the study comprised 315 patients who underwent RAMT and 92 who underwent JS. Patients who underwent JS had more comorbidities, compared with those who underwent RAMT. Propensity score matching of 16 variables yielded similar groups for comparison (n=90). Thirty-day mortality was similar between the two groups (0% vs. 1%, respectively; P>0.99). In the RAMT group, the rate of on-table extubation was significantly higher (P<0.001), whereas the blood transfusion rate was lower and length of stay was shorter, compared with the JS group. The 5-year survival rate was higher in the RAMT group than in the JS group (95.0% vs. 85.6%, respectively; P=0.03)., Conclusions: AVR via RAMT was associated with improved early clinical outcomes, shorter length of stay, and increased survival, compared with JS. Despite the technical challenges associated with RAMT, this procedure can be considered a primary strategy for isolated AVR., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://jtd.amegroups.com/article/view/10.21037/jtd-24-928/coif). The authors have no conflicts of interest to declare., (2024 AME Publishing Company. All rights reserved.)

This study presents the impact of the side chains in 1-n-alkylimidazolium ionomers with varying side chain lengths (C n H 2n+1 where n = 1, 4, 10, 16) on Cu-catalyzed electrochemical CO 2 reduction reaction (CO 2 RR). Longer side chains suppress the H 2 and CH 4 formation, with the n-hexadecyl ionomer (n = 16) showing the greatest reduction in kinetics by up to 56.5% and 60.0%, respectively. On the other hand, C 2 H 4 production demonstrates optimal Faradaic efficiency with the n-decyl ionomer (n = 10), a substantial increase of 59.9% compared to its methyl analog (n = 1). Through a combination of density functional theory calculations and material characterization, it is revealed that the engineering of the side chains effectively modulates the thermodynamic stability of key intermediates, thus influencing the selectivity of both CO 2 RR and hydrogen evolution reaction. Moreover, ionomer engineering enables industrially relevant partial current density of -209.5 mA cm -2 and a Faradaic efficiency of 52.4% for C 2 H 4 production at 3.95 V, even with a moderately active Cu catalyst, outperforming previous benchmarks and allowing for further improvement through catalyst engineering. This study underscores the critical role of ionomers in CO 2 RR, providing insights into their optimal design for sustainable chemical synthesis., (© 2024 The Author(s). Advanced Science published by Wiley‐VCH GmbH.)

Background: Hemoplasma infections in cattle are caused by Mycoplasma wenyonii and Candidatus Mycoplasma haemobos and induce asymptomatic or chronic infections but occasionally lead to life-threatening hemolytic anemia. Despite the global distribution of bovine hemoplasmas, information regarding their transmission vectors and prevalence is still lacking in the Republic of Korea. Therefore, this study aims to investigate the infection rate of bovine hemoplasma in cattle and houseflies and to assess the risk factors associated with hemoplasma infection in cattle., Methods: Overall, 376 blood samples were collected from Korean indigenous cattle (male, 10-13 months old), along with 2,690 houseflies (Musca domestica) from the same farm where the cattle were raised. PCR assays targeting the 16S rRNA gene were performed to detect hemoplasmas, and positive samples were sequenced., Results: The infection rate of bovine hemoplasmas was 50.8% (191/376) in cattle and 7.4% in pooled houseflies. Among cattle, 18.6% (70/376) and 20.0% (75/376) tested positive for M. wenyonii and Candidatus M. haemobos, respectively. Conversely, in houseflies, Candidatus M. haemobos was more frequently detected (5.9%) than M. wenyonii (0.7%). Co-infection was 12.2% (46/376) in cattle and 0.7% in flies. Furthermore, hemoplasma infection was significantly associated with the grazing experience of their dams. Cattle born to cows with grazing experience exhibited a higher risk for M. wenyonii infection (odds ratio [OR] = 1.62; 95% confidence interval [CI]: 1.03-2.55; P = 0.045), whereas these cattle had a lower risk for Candidatus M. haemobos infection (OR = 0.32, 95% CI: 0.19-0.74; P = 0.000) than animals born to cows without grazing experience. The sequences obtained from houseflies were confirmed as Candidatus M. haemobos, which displayed high similarity (98.2-100%) to those from cattle obtained in this study., Conclusions: To our knowledge, this study represents the first report of bovine hemoplasmas identified in houseflies. This molecular evidence suggests that houseflies may be possible vectors for Candidatus M. haemobos., (© 2024. The Author(s).)

Oxidative stress and excitotoxicity are the major causes of neuronal death/loss in the brain following ischemia and reperfusion (IR). Hyperthermia is known to exacerbate ischemic neuronal damage; however, the underlying mechanisms remain unclear. This study investigated the mechanisms underlying neuronal damage caused by IR injury (IRI) under hyperthermic conditions in the gerbil hippocampal CA1 region. Gerbils were controlled at normothermia (37.5±0.2°C) or hyperthermia (39.5±0.2°C). After temperature control for 30 min, the animals received IRI (following 5 min of transient forebrain ischemia) or sham ischemia, and were subsequently sacrificed at 0, 3, 6, 12, 24, 48, and 120h after IRI. Neuronal death was examined using neuronal nuclear antigen immunohistochemistry and Fluoro-Jade B histofluorescence. Oxidative stress was analyzed by immunohistochemistry for 8-Hydroxy-2'-deoxyguanosine (8OHdG) and superoxide dismutase 2 (SOD2). Excitotoxicity was investigated by immunohistochemistry and western blotting for glutamate transporter 1 (GLT1). Immunohistochemical staining for glial fibrillary acidic proteins (GFAP) was performed to detect reactive astrogliosis. Loss of pyramidal neurons was detected earlier (48h post-IRI) in the hyperthermia-IRI group than in the normothermia-IRI group (120h post-IRI). Further, 8OHdG and SOD2 immunoreactivity in the hyperthermia-IRI group was significantly higher than that in the normothermia-IRI group. Changes in GLT1 immunoreactivity in both groups were biphasic, indicating that the immunoreactivity and protein levels were significantly lower in the hyperthermia-IRI group. GFAP immunoreactivity was enhanced following neuronal loss, indicating that the immunoreactivity was significantly higher in the hyperthermia-IRI group. Taken together, these results suggest that brain IR under hyperthermic conditions can aggravate neuronal damage in the hippocampal CA1 region through severe oxidative stress and excitotoxicity., (©The Author(s) 2024. Open Access. This article is licensed under a Creative Commons CC-BY International License.)

Periodontitis is associated with elevated C-reactive protein (CRP) levels. Although the coexistence of periodontitis and elevated CRP levels may heighten the risk of mortality, previous studies have not confirmed their synergistic effect. Understanding this interaction is crucial for identifying potential interventions to reduce mortality risk in individuals with periodontitis. This study aimed to assess the synergistic effects of periodontitis and elevated CRP levels on mortality in 7,938 adult individuals who participated in the National Health and Nutrition Examination Study 2001-2004. The association of periodontitis status and CRP levels with mortality was assessed using a survey-weighted Cox model. The interactive effect was estimated; the synergistic effect of CRP levels and periodontitis status on mortality was assessed using the relative excess risk due to interaction (RERI). Periodontitis was diagnosed in 1,065 (13.4%) participants. Compared with the participants without periodontitis and possessing CRP levels of ≤ 0.5 mg/dL, those with periodontitis (hazard ratio [HR], 1.38) or CRP levels of > 0.5 mg/dL (HR 1.23) had higher HRs. The participants with both periodontitis and CRP levels of > 0.5 mg/dL had the highest HR of 2.01. The additive scale interactive effect of the periodontal status and CRP levels, measured using RERI 0.41 (-0.07, 0.95), was positive and nearly significant in the total population. The synergy between the periodontal status and CRP levels was more prominent in the participants aged ≥60 years than that in younger individuals. Periodontitis with high CRP levels may indicate a high mortality rate, indicating the importance of active monitoring and intensive management of periodontitis and inflammatory markers., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Han et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

The precise characterization and control of single-electron wave functions emitted from a single-electron source are essential for advancing electron quantum optics. Here, we introduce a method for tailoring a single-electron emission distribution using energy filtering, enabling selective control of the distribution under various energy barrier conditions of the filter. The tailored electron is studied by reconstructing its Wigner distribution in the time-energy phase space using the continuous-variable tomography method. Our results reveal that the filtering cuts the portion of the distribution below the energy-barrier height of the filter in the time-energy space. While the filtering is demonstrated in a classical regime of the emitted electrons, we expect that this study significantly contributes to the design and implementation of advanced experiments toward quantum information processing based on single electrons.

Competing Interests: Declaration of competing interest Dr. Mu-Hsing Benjamin Ho, a co-author of this paper, holds the position of associate editor for Intensive and Critical Care Nursing. Dr. Ho did not participate in the editorial review or the decision to publish this article.

Defects in wide bandgap materials have emerged as promising candidates for solid-state quantum optical technologies. Electrical excitation of single emitters may lead to scalable on-chip devices and therefore is highly sought after. However, most wide bandgap materials are not amenable to efficient doping, posing challenges for electrical excitation and on-chip integration. Here, we demonstrate narrowband electroluminescence from visible and near-infrared color centers in hexagonal boron nitride (hBN). We harness van der Waals tunnel junctions of graphene-hBN-graphene. Charge carriers are electrically injected into hBN, exciting localized defects that emit nonclassical light, as characterized by the second order correlation measurement. Remarkably, the devices operate at room temperature and produce robust, narrowband emission spanning from visible to the near-infrared. Our work marks an important milestone in vdW materials and their promising attributes for integrated quantum technologies and on-chip photonic circuits.

Objectives: Dietary soy, known for its high phytoestrogen content, has been suggested to exhibit a sex-specific association with type 2 diabetes. However, evidence regarding the sex-specific associations of different legume subtypes with type 2 diabetes remains scarce. We aimed to evaluate whether habitual consumption of soy and non-soy legumes (beans and peanuts) was prospectively and sex-specifically associated with the risk of type 2 diabetes incidence, taking into considering significant sex-specific genetic factors beyond legume consumption., Methods: A total of 16,666 participants (96,945 person-years) were followed and 945 incident cases were observed. Cumulative intake of legume subtypes was calculated using a food frequency questionnaire administered at baseline and during the revisit surveys., Results: Non-soy legumes are inversely associated with type 2 diabetes in both men and women. Dietary soy intake, however, demonstrated a unilaterally interacting sex-specific association with type 2 diabetes risk (pinteraction for sex=0.0173). Specifically, there was a significant inverse association with type 2 diabetes risk in women (incidence rate ratio, 0.66; 95% confidence interval, 0.48 to 0.80; ptrend=0.0066), but no such association was observed in men. This sex-specific association persisted and even appeared antagonistic in minor allele carriers of 2 novel single nucleotide polymorphisms, rs10196939 (LRRTM4) and rs11750158 (near GFPT2) (pinteraction for sex=0.0014 and 0.0112, respectively)., Conclusion: Habitual consumption of legumes shows protective impacts against type 2 diabetes, although these benefits vary by sex. Non-soy legumes provide health advantages for both men and women, whereas soy consumption seems to be beneficial exclusively for women.