Growth differentiation factor 11 is a circulating factor that reverses age-related cardiac hypertrophy.

The most common form of heart failure occurs with normal systolic function and often involves cardiac hypertrophy in the elderly. To clarify the biological mechanisms that drive cardiac hypertrophy in aging, we tested the influence of circulating factors using heterochronic parabiosis, a surgical technique in which joining of animals of different ages leads to a shared circulation. After 4 weeks of exposure to the circulation of young mice, cardiac hypertrophy in old mice dramatically regressed, accompanied by reduced cardiomyocyte size and molecular remodeling. Reversal of age-related hypertrophy was not attributable to hemodynamic or behavioral effects of parabiosis, implicating a blood-borne factor. Using modified aptamer-based proteomics, we identified the TGF-ß superfamily member GDF11 as a circulating factor in young mice that declines with age. Treatment of old mice to restore GDF11 to youthful levels recapitulated the effects of parabiosis and reversed age-related hypertrophy, revealing a therapeutic opportunity for cardiac aging.

The Autoimmunity-Associated Gene CLEC16A Modulates Thymic Epithelial Cell Autophagy and Alters T Cell Selection.

CLEC16A variation has been associated with multiple immune-mediated diseases, including type 1 diabetes, multiple sclerosis, systemic lupus erythematosus, celiac disease, Crohn's disease, Addison's disease, primary biliary cirrhosis, rheumatoid arthritis, juvenile idiopathic arthritis, and alopecia areata. Despite strong genetic evidence implicating CLEC16A in autoimmunity, this gene's broad association with disease remains unexplained. We generated Clec16a knock-down (KD) mice in the nonobese diabetic (NOD) model for type 1 diabetes and found that Clec16a silencing protected against autoimmunity. Disease protection was attributable to T cell hyporeactivity, which was secondary to changes in thymic epithelial cell (TEC) stimuli that drive thymocyte selection. Our data indicate that T cell selection and reactivity were impacted by Clec16a variation in thymic epithelium owing to Clec16a's role in TEC autophagy. These findings provide a functional link between human CLEC16A variation and the immune dysregulation that underlies the risk of autoimmunity.

Fish By-Product Collagen Extraction Using Different Methods and Their Application.

The processing of fishery resources results in the production of a growing quantity of byproducts, including heads, skins, viscera, intestines, frames, and fillet cutoffs. These byproducts are either wasted or utilized for the production of low-value items and fish oil. Typically, fish processing industries use only 25%, while the remaining 75% is considered as waste by-products. This review presents a comprehensive review on the extraction of collagen from fish byproducts, highlighting numerous techniques including acid-soluble collagen (ASC), enzyme-soluble collagen (ESC), ultrasound extraction, deep eutectic solvent (DES) extraction, and supercritical fluid extraction (SFE). A detailed explanation of various extraction parameters such as time, temperature, solid to liquid (S/L) ratio, and solvent/pepsin concentration is provided, which needs to be considered to optimize the collagen yield. Moreover, this review extends its focus to a detailed investigation of fish collagen applications in the biomedical sector, food sector, and in cosmetics. The comprehensive review explaining the extraction methods, extraction parameters, and the diverse applications of fish collagen provides a basis for the complete understanding of the potential of fish-derived collagen. The review concludes with a discussion of the current research and a perspective on the future development in this research field.

Check-all-that-apply (CATA)- and rate-all-that-apply (RATA)-based sensometric assessment of germinated-wheat beverages.

Sensometrics assesses sensory perspectives in consumer research using statistics and various methodologies. This study evaluated consumer responses to hot and cold germinated-wheat beverages in check-all-that-apply (CATA) and rate-all-that-apply (RATA) assessments using sensometric statistical approaches, including Cochran's Q test, penalty-lift analysis, and multiple factor analysis. Hot beverages (HB) were prepared by infusion using different amounts of germinated wheat (HB_1: 0.8 g/100 mL, HB_2: 2 g/100 mL, and HB_3: 4 g/100 mL), while cold beverages (CB) were made using cooled boiled germinated wheat with varying concentrations (CB_1: 25 g/L, CB_2: 50 g/L, and CB_3: 75 g/L). Results of the CATA study suggested that consumers preferred HB_1 and CB_1 because they expressed the sensory characteristics associated with liking, including "barley tea flavor", "neat taste", and "nutty taste", while "bitterish taste", "stuffy taste", and "astringent taste" were undesirable attributes. "Browning index", "barley tea odor", and "nutty taste" showed significant differences (p < 0.05) in both favorable and unfavorable rating scores. Overall, CB_1 elicited a clear taste and odor with fewer negative emotions. These findings demonstrate the usefulness of the sensometric approach combined with CATA and RATA analyses to obtain more easily interpretable results on the sensory perception of consumers to new food products. Supplementary Information: The online version contains supplementary material available at 10.1007/s13197-023-05884-z.

MEK1/2 inhibition rescues neurodegeneration by TFEB-mediated activation of autophagic lysosomal function in a model of Alzheimer's Disease.

Alzheimer's Disease (AD) is a progressive neurodegenerative disorder, which is characterized by cognitive deficit due to synaptic loss and neuronal death. Extracellular amyloid ß plaques are one of the pathological hallmarks of AD. The autophagic lysosomal pathway is the essential mechanism to maintain cellular homeostasis by driving clearance of protein aggregates and is dysfunctional in AD. Here, we showed that inhibiting MEK/ERK signaling using a clinically available MEK1/2 inhibitor, trametinib (GSK1120212, SNR1611), induces the protection of neurons through autophagic lysosomal activation mediated by transcription factor EB (TFEB) in a model of AD. Orally administered trametinib recovered impaired neural structures, cognitive functions, and hippocampal long-term potentiation (LTP) in 5XFAD mice. Trametinib also reduced Aß deposition via induction of autophagic lysosomal activation. RNA-sequencing analysis revealed upregulation of autophagic lysosomal genes by trametinib administration. In addition, trametinib inhibited TFEB phosphorylation at Ser142 and promoted its nuclear translocation, which in turn induced autophagic lysosomal related genes, indicating that trametinib activates the autophagic lysosomal process through TFEB activation. From these observations, we concluded that MEK inhibition provides neuronal protection from the Aß burden by increasing autophagic lysosomal activity. Thus, MEK inhibition may be an effective therapeutic strategy for AD.

TLR7 activation by miR-21 promotes renal fibrosis by activating the pro-inflammatory signaling pathway in tubule epithelial cells.

BACKGROUND: Toll-like receptor 7 (TLR7) is an endosomal TLR activated by single-stranded RNA, including endogenous microRNAs. Although TLR7 is known to promote inflammatory responses in pathophysiological conditions, its role in renal fibrosis has not been investigated. Here, we aim to investigate the inflammatory roles of TLR7 in kidney inflammation and fibrosis. METHODS: TLR7 knockout mice (Tlr7 -/-) subjected to AD-induced kidney injury were utilized to examine the role of TLR7 in kidney fibrosis. To elucidate the role of TLR7 in renal epithelial cells, NRK52E rat renal tubule epithelial cells were employed. RESULTS: Under fibrotic conditions induced by an adenine diet (AD), TLR7 was significantly increased in damaged tubule epithelial cells, where macrophages were highly infiltrated. TLR7 deficiency protected against AD-induced tubular damage, inflammation, and renal fibrosis. Under in vitro conditions, TLR7 activation increased NF-κB activity and induced chemokine expression, whereas TLR7 inhibition effectively blocked NF-κB activation. Furthermore, among the known TLR7 endogenous ligands, miR-21 was significantly upregulated in the tubular epithelial regions. In NRK52E cells, miR-21 treatment induced pro-inflammatory responses, which could be blocked by a TLR7 inhibitor. When the TLR7 inhibitor, M5049, was administered to the AD-induced renal fibrosis model, TLR7 inhibition significantly attenuated AD-induced renal inflammation and fibrosis. CONCLUSIONS: Overall, activation of TLR7 by endogenous miR-21 in renal epithelial cells contributes to inflammatory responses in a renal fibrosis model, suggesting a possible therapeutic target for the treatment of renal fibrosis. Video Abstract.

Risk analysis of metformin use in prostate cancer: a national population-based study.

INTRODUCTION: Various approaches are required to prevent and treat heterogeneity-based prostate cancer. Here, we analyzed the anticancer effects of metformin, which has a good toxicity profile and is inexpensive. METHOD: From January 2010 to December 2019, analysis was conducted retrospectively in a cohort from the National Health Insurance Service database. The wash-out period was set for cancer diagnosis in 2010 and 2011, and subjects (105,279) diagnosed with prostate cancer (ICD C61) from 2012 to 2014 were excluded The final subjects (105,216) were defined as the metformin administration group when they took metformin for 180 days or more from January 2012 to December 2019. The non-metformin group was defined as those who took less than 180 days from January 2012 to December 2019. The prevalence of prostate cancer according to metformin administration and the risk according to the cumulative duration of metformin were analyzed. RESULTS: A total of 105,216 people were included in this study, with 59,844 in the metformin group and 45,372 in the metformin non-administration group. When calculating HRs (Hazard Rate) according to the cumulative period of metformin administration, metformin administration period length was inversely associated with prostate cancer risk (Q2 HR = 0.791 95% CI: 0.773-0.81, Q3 HR = 0.634 95% CI: 0.62-0.649, Q4 HR = 0.571 95% CI: 0.558-0.585). HRs tended to decrease with the cumulative duration of metformin administration. CONCLUSION: This study confirmed that prostate cancer risk decreased with increasing duration of metformin administration. Metformin should be considered as a new strategy in the treatment and prevention of prostate cancer characterized by heterogeneity.

NIR band-pass filters for CMOS image sensors constructed with NIR absorbing dyes and plasmonic nanoparticles.

Two NIR band-pass filters for CMOS image sensors are developed by incorporating NIR absorption dye and silver nanodisks simultaneously in a transparent polymer, one of which blocks the NIR near the wavelength of 750 nm and the other near 950 nm. They offer low NIR transmittance while maintaining high visible light transparency even at a thin film thickness of 500 nm. By superimposing the proposed NIR band-pass filters, an NIR cutoff filter with a thickness of 1 µm is formed that shields the NIR at wavelengths longer than 680 nm while remaining transparent in the visible range.

Intelligence Sensors and Sensing Spaces for Smart Home and Environment.

Practitioners in the domains of architecture, engineering, and construction have conducted considerable research on smart homes and smart environments [...].

Smart Homes Supporting the Wellness of One or Two-Person Households.

The reduction in face-to-face contact and the increase in time spent at home during the ongoing coronavirus disease pandemic have resulted in increasing interest and demand for smart homes. Further, the rapid increase in the number of one-person and two-person households in Korea recently has led to these becoming representative household types. This study identifies the wellness characteristics of such households and proposes a direction for smart home development to help them lead healthy, happy lives. It focuses on mapping residents' perceptions and experiences to scenarios and on identifying the functions required in smart homes and the technologies needed to provide these functions. It uses data from a survey to investigate and analyze the wellness characteristics of one- and two-person households in five dimensions and develops five scenarios of representative household types. By analyzing the developed scenarios, this study proposes smart homes that support the wellness of such households in six categories: exercise/sports, hobby/entertainment, social communications, occupation/work, self-development/education, and energy conservation. These households are exposed to digital environments from an early age and are familiar with the internet and technologies. Therefore, they are likely to adopt innovative technologies in housing. Thus, the smart home development proposed in this study is a promising strategic approach to housing planning.

A User-Centered Approach to the Application of BIM in Smart Working Environments.

Considerable research has been performed on smart working environments in the architecture, engineering, and construction industry, with building information modeling considered as a critical element for implementing intelligent working systems. Although much software has been developed, a lack of understanding inhibits a user-centered approach to the application of building information modeling in architectural design offices. This study focuses on usability factors for the development of software and proposes a direction for the adoption of building information modeling in architectural design offices. This study adopts a persona method that focuses on user experience, starting with a survey conducted in two large domestic architectural offices. For developing the persona scenarios, this study provides a conceptual framework of usability, identifies user demands, and characterizes user experience. Four representative personas were developed for the representative types of users in smart working environments. The persona scenarios provide a basis that directly reflects user needs and experiences regarding the use of building information modeling software in architectural design offices. Two implications of the application of building information modeling are proposed based on the scenarios: a user-friendly working environment for smart workflows and a customized training program focusing on user experience for the use of building information modeling software.

Canavalia gladiata Pod Extract Mitigates Ovalbumin-Induced Asthma Onset in Male BALB/c Mice via Suppression of MAPK.

Asthma is one of the most common inflammatory diseases of the lung worldwide. There has been considerable progress in recent studies to treat and prevent allergic asthma, however, various side effects are still observed in clinical practice. Six-week-old male BALB/c mice were orally administered with either sword bean pod extracts (SBP; 100 or 300 mg/kg) or dexamethasone (DEX; 5 mg/kg) once daily over 3 weeks, followed by ovalbumin sensitization (OVA/Alum.; intraperitoneal administration, 50 µg/2 mg/per mouse). Scoring of lung inflammation was performed to observe pathological changes in response to SBP treatment compared to OVA/Alum.-induced lung injury. Additionally, inflammatory cytokines were quantified in serum, bronchoalveolar lavage fluid (BALF), and lung tissue using ELISA and Western blot analyses. SBP treatment significantly reduced the infiltration of inflammatory cells, and release of histamine, immunoglobulin E, and leukotriene in serum and BALF. Moreover, the therapeutic effect of SBP was also assessed to analyze the inflammatory changes in the lung tissues. SBP markedly suppressed the activation of the MAPK signaling pathway and the expression of key inflammatory proteins (e.g., TNF-α) and Th2 type cytokines (IL-5 and IL-13). SBP was effective in ameliorating the allergic inflammation against OVA/Alum.-induced asthma by suppressing pulmonary inflammation.

Development of an experimental model for ocular toxicity screening in Zebrafish.

BACKGROUND: To investigate the efficacy of a novel experimental model for exploring visual function using a contrast-optomotor response (C-OMR) assay made by applying the contrast sensitivity test to the OMR assay in zebrafish. METHODS: Zebrafish larvae were treated with 0 (control), 5, 10, or 15 µM gentamicin and digoxin for 24 h at four days post-fertilization (dpf). Zebrafish larvae were assessed using the C-OMR assay with graded contrast gray-white stripes at 5 dpf, and the results were expressed as the percentage of larvae that finished swimming for 30 s (n = 20 per each group). The same C-OMR assay was repeated four times using different larvae. RESULTS: The percentage of larvae that finished swimming within 30 s was significantly reduced in larvae treated with 5, 10, and 15 µM gentamicin and 10 and 15 µM digoxin as compared to the Control groups. The C-OMR assay could distinguish that the decrease in visual function was different depending on the concentration of gentamicin and digoxin (5, 10, and 15 µM), whereas the OMR test with one contrast gray-white stripe could not. CONCLUSIONS: The method of analyzing zebrafish OMR using graded contrast gray-white stripes is more sensitive than the OMR assay alone and may be more useful for assessing the drug toxicity and eye-related diseases to improve the understanding of drug-induced ocular side effects in the clinic.

Foamy macrophages and the progression of the human tuberculosis granuloma.

The progression of tuberculosis from a latent, subclinical infection to active disease that culminates in the transmission of infectious bacilli is determined locally at the level of the granuloma. This progression takes place even in the face of a robust immune response that, although it contains infection, is unable to eliminate the bacterium. The factors or environmental conditions that influence this progression remain to be determined. Recent advances have indicated that pathogen-induced dysregulation of host lipid synthesis and sequestration serves a critical role in this transition. The foamy macrophage seems to be a key participant in both sustaining persistent bacteria and contributing to the tissue pathology that leads to cavitation and the release of infectious bacilli.

Programmed cell death 5 suppresses AKT-mediated cytoprotection of endothelium.

Programmed cell death 5 (PDCD5) has been associated with human cancers as a regulator of cell death; however, the role of PDCD5 in the endothelium has not been revealed. Thus, we investigated whether PDCD5 regulates protein kinase B (PKB/AKT)-endothelial nitric oxide synthase (eNOS)-dependent signal transduction in the endothelium and affects atherosclerosis. Endothelial-specific PDCD5 knockout mice showed significantly reduced vascular remodeling compared with wild-type (WT) mice after partial carotid ligation. WT PDCD5 competitively inhibited interaction between histone deacetylase 3 (HDAC3) and AKT, but PDCD5L6R, an HDAC3-binding-deficient mutant, did not. Knockdown of PDCD5 accelerated HDAC3-AKT interaction, AKT and eNOS phosphorylation, and nitric oxide (NO) production in human umbilical vein endothelial cells. Moreover, we found that serum PDCD5 levels reflect endothelial NO production and are correlated with diabetes mellitus, high-density lipoprotein cholesterol, and coronary calcium in human samples obtained from the cardiovascular high-risk cohort. Therefore, we conclude that PDCD5 is associated with endothelial dysfunction and may be a novel therapeutic target in atherosclerosis.

Characterizing Smart Environments as Interactive and Collective Platforms: A Review of the Key Behaviors of Responsive Architecture.

Since architect Nicholas Negroponte first proposed a vision of responsive architecture smart environments have been widely investigated, especially in the fields of computer science and engineering. Despite growing interest in the topic, a comprehensive review of research about smart environments from the architectural perspective is largely missing. In order to provide a formal understanding of smart environments in architecture, this paper conducts a systematic literature review of scholarly sources over the last decade, focusing on four related subjects: (1) responsive architecture, (2) kinetic architecture, (3) adaptive architecture and (4) intelligent buildings. Through this review, the paper identifies and examines interactive and collective behaviors in smart environments, thereby contributing to defining the properties of creative, smart spaces in the contemporary digital ecosystem. In addition, this research offers a means of systematically characterizing and constructing smart environments as interactive and collective platforms, enabling occupants to sense, experience and understand smart spaces.

Soluble neprilysin and long-term clinical outcomes in patients with coronary artery disease undergoing percutaneous coronary intervention: a retrospective cohort study.

BACKGROUND: Neprilysin has an essential role in regulating fluid balance and vascular resistance, and neprilysin inhibitors have shown beneficial effects in patients with heart failure. However, the potential predictive value of neprilysin levels as a biomarker for cardiovascular risk remains unclear. The aim of this study was to assess the prognostic value of soluble neprilysin (sNEP) levels in patients with ischemic heart disease. METHODS: Neprilysin levels were measured in 694 consecutive patients with coronary artery disease (CAD) undergoing percutaneous coronary intervention (PCI). These patients were classified into two groups according to their serum levels of neprilysin and categorized into the lower neprilysin group (n = 348) and the higher neprilysin group (n = 346). The primary clinical endpoint was all-cause mortality, and the secondary endpoint was a composite of major adverse cardiac events (MACE). RESULTS: The median sNEP level was 76.0 pg/ml. The median sNEP levels were higher in patients with left ventricular ejection fraction (LVEF) ≥40% (77.6 pg/ml, interquartile range 46.6-141.3) than in those with LVEF < 40% (70.0 pg/ml, interquartile range 47.1-100.6; P = 0.032). Among all patients, each clinical outcome and MACE did not differ significantly according to the groups divided into median, tertile, or quartile of sNEP levels during a median follow-up of 28.4 months. We did not find a significant relationship between sNEP levels and clinical outcomes in multivariate Cox regression analysis. Among patients with LVEF < 40%, an increased sNEP level was associated with a higher rate of all-cause death (adjusted hazard ratio 2.630, 95% confidence interval 1.049-6.595, P = 0.039). CONCLUSION: Serum sNEP levels are not associated with long-term mortality or cardiovascular outcomes after PCI in patients with CAD. In the LVEF < 40% group, increased sNEP levels may be associated with a higher risk of all-cause death.

Subacute dermal toxicity of perfluoroalkyl carboxylic acids: comparison with different carbon-chain lengths in human skin equivalents and systemic effects of perfluoroheptanoic acid in Sprague Dawley rats.

Perfluoroalkyl and polyfluoroalkyl substances (PFASs) are used in various fields but raise concerns regarding human health and environmental consequences. Among PFASs, perfluorooctanoic acid (PFOA) and short-chain perfluoroalkyl carboxylic acids (SC PFCAs) are detectable in skin-contact consumer products and have dermal absorption potential. Here, we investigated the effects of dermal exposure to PFOA and SC PFCAs using in vitro and in vivo models. Human skin equivalents were topically treated with 0.25 mM and 2.5 mM PFOA and SC PFCAs (perfluoropentanoic acid, PFPeA; perfluorohexanoic acid, PFHxA; and perfluoroheptanoic acid, PFHpA) for 6 days, and cell viability, interleukin (IL)-1α, oxidative stress markers (malondialdehyde, MDA; and 8-hydroxydeoxyguanosine, 8-OHdG), and histopathology were examined. MDA levels were significantly higher in the PFASs groups than in controls. Compared with SC PFCAs, 2.5 mM PFOA caused more IL-1α (p < 0.001) release, decreased skin thickness and microscopic abnormalities. To evaluate systemic effects, Sprague Dawley (SD) rats were dermally treated with 250 and 1000 mg/kg PFHpA for 2 weeks and clinical and anatomic pathology were assessed. At 1000 mg/kg, 83% of the rats died, with severe ulcerative dermatitis at the application site. Adverse PFHpA-treated systemic changes were observed in the kidney, liver and testes, and histopathologic lesions such as renal tubular necrosis, hepatocellular necrosis, and germ cell degeneration were seen at 250 and 1000 mg/kg. Our study suggests that SC PFCAs have fewer effects on the skin than PFOA, but SC PFCAs can have adverse effects on major organs with systemic exposure at high concentrations.

TXNIP Regulates Natural Killer Cell-Mediated Innate Immunity by Inhibiting IFN-γ Production during Bacterial Infection.

The function of natural killer (NK) cell-derived interferon-γ (IFN-γ) expands to remove pathogens by increasing the ability of innate immune cells. Here, we identified the critical role of thioredoxin-interacting protein (TXNIP) in the production of IFN-γ in NK cells during bacterial infection. TXNIP inhibited the production of IFN-γ and the activation of transforming growth factor ß-activated kinase 1 (TAK1) activity in primary mouse and human NK cells. TXNIP directly interacted with TAK1 and inhibited TAK1 activity by interfering with the complex formation between TAK1 and TAK1 binding protein 1 (TAB1). Txnip-/- (KO) NK cells enhanced the activation of macrophages by inducing IFN-γ production during Pam3CSK4 stimulation or Staphylococcus aureus (S. aureus) infection and contributed to expedite the bacterial clearance. Our findings suggest that NK cell-derived IFN-γ is critical for host defense and that TXNIP plays an important role as an inhibitor of NK cell-mediated macrophage activation by inhibiting the production of IFN-γ during bacterial infection.

Magma Seawater Inhibits Hepatic Lipid Accumulation through Suppression of Lipogenic Enzymes Regulated by SREBPs in Thioacetamide-Injected Rats.

Thioacetamide (TAA) is known to induce lipid accumulation in the liver. In the present study, we investigated the effects of magma seawater (MS) rich in minerals on hepatic lipid metabolism by evaluating lipogenic enzymes regulated by sterol regulatory element-binding proteins (SREBPs). Rats (n = 10 per group) were intraperitoneally injected with TAA (200 mg/kg bw) thrice a week for seven weeks in combination with a respective experimental diet. Rats in the TAA-treated group received either a chow diet (Control group) or a chow diet containing MS (TMS group, 2.05%) or silymarin (TSM group, 0.05%). Rats in the normal group were injected with PBS as a vehicle and received a chow diet. Rats in the TMS group showed significantly lower hepatic lipid concentrations than rats in the control group (p < 0.05). Hepatic protein expression levels of fatty acid synthase, SREBP-1, 3-hydroxy-3-methylglutaryl-coenzyme A reductase, and SREBP-2 were significantly downregulated in the TMS group, whereas carnitine palmitoyltransferase 1 levels were upregulated (p < 0.05). Hepatic thiobarbituric acid reactive substances levels were lower in the TMS group, whereas protein levels of glutathione peroxidase and catalase were elevated (p < 0.05). The effects of MS were comparable to those of silymarin. Our results evidently showed that MS inhibits hepatic lipid accumulation by suppressing lipid synthesis, accompanied by lipid oxidation and elevation of antioxidative status.