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Environmental antineoplastics such as sorafenib may pose a risk to humans through water recycling, and the increased risk of cardiotoxicity is a clinical issue in sorafenib users. Thus, developing strategies to prevent sorafenib cardiotoxicity is an urgent work. Empagliflozin, as a sodium-glucose co-transporter-2 (SGLT2) inhibitor for type 2 diabetes control, has been approved for heart failure therapy. Still, its cardioprotective effect in the experimental model of sorafenib cardiotoxicity has not yet been reported. Real-time quantitative RT-PCR (qRT-PCR), immunoblot, and immunohistochemical analyses were applied to study the effect of sorafenib exposure on cardiac SGLT2 expression. The impact of empagliflozin on cell viability was investigated in the sorafenib-treated cardiomyocytes using Alamar blue assay. Immunoblot analysis was employed to delineate the effect of sorafenib and empagliflozin on ferroptosis/proinflammatory signaling in cardiomyocytes. Ferroptosis/DNA damage/fibrosis/inflammation of myocardial tissues was studied in mice with a 28-day sorafenib ± empagliflozin treatment using histological analyses. Sorafenib exposure significantly promoted SGLT2 upregulation in cardiomyocytes and mouse hearts. Empagliflozin treatment significantly attenuated the sorafenib-induced cytotoxicity/DNA damage/fibrosis in cardiomyocytes and mouse hearts. Moreover, GPX4/xCT-dependent ferroptosis as an inducer for releasing high mobility group box 1 (HMGB1) was also blocked by empagliflozin administration in the sorafenib-treated cardiomyocytes and myocardial tissues. Furthermore, empagliflozin treatment significantly inhibited the sorafenib-promoted NFκB/HMGB1 axis in cardiomyocytes and myocardial tissues, and sorafenib-stimulated proinflammatory signaling (TNF-α/IL-1β/IL-6) was repressed by empagliflozin administration. Finally, empagliflozin treatment significantly attenuated the sorafenib-promoted macrophage recruitments in mouse hearts. In conclusion, empagliflozin may act as a cardioprotective agent for humans under sorafenib exposure by modulating ferroptosis/DNA damage/fibrosis/inflammation. However, further clinical evidence is required to support this preclinical finding., (© 2024 Wiley Periodicals LLC.)

Background: Human flourishing is an emerging concept, extending beyond the conventional boundaries of subjective well-being and evolving into a comprehensive capture of the diverse dimensions of human life within complex societal structures. Therefore, moving away from traditional approaches centered on the single latent construct, this study aims to explore the multiple aspects of human flourishing and the intricate interplay of their contributing factors., Methods: Data were collected from the Health and Living Environments Survey of Taiwanese Retirees during 2023 (valid sample n = 1,111). Human flourishing was measured using the Secure Flourish Index developed by Harvard University, which includes 12 indicators: (1) life satisfaction, (2) happiness, (3) mental health, (4) physical health, (5) meaning in life, (6) sense of purpose, (7) promoting good, (8) delaying gratification, (9) content relationships, (10) satisfying relationships, (11) financial stability, and (12) material stability. A mixed graphical network analysis was employed to analyze the related determinants, divided into four groups: (a) sociodemographic factors, (b) physical functions and health status, (c) social and family engagement, and (d) community environmental characteristics as nodes., Results: We analyzed 31 variables and identified 133 nonzero edges out of 465 potential connections in the comprehensive network. Results showed that happiness and promoting good were the two most critical indicators influencing retirees' overall flourishing. Different flourishing indicators were also associated with various influential factors. For instance, personal characteristics, especially gender and education, emerged as central factors. Family caregiving negatively affected happiness and financial stability, whereas social engagement was positively associated with life satisfaction and meaning in life. Employment status had mixed effects, negatively associated with life satisfaction but positively associated with mental health. Community environments, such as a sense of community and neighborhood safety, generally enhanced flourishing. However, the accessibility of neighborhood resources was paradoxically associated with material stability, pointing to the complexity of environmental factors in human flourishing., Conclusion: This study provides a comprehensive network analysis that reveals intricate connections between personal, behavioral, and environmental factors, offering profound insights for targeted interventions to foster human flourishing., (© 2024. The Author(s).)

Background: The skin is the largest organ in the human body and serves as a barrier for protective, immune, and sensory functions. Continuous and permanent exposure to the external environment results in different levels of skin and extracellular matrix damage. During skin wound healing, the use of good dressings and addition of growth factors to the wound site can effectively modulate the rate of wound healing. A dressing containing bioactive substances can absorb wound exudates and reduce adhesion between the wound and dressing, whereas growth factors, cytokines, and signaling factors can promote cell motility and proliferation., Aim and Objectives: We prepared a functional wound dressing by combining platelet-rich plasma (PRP) and zwitterionic hydrogels. Functional wound dressings are rich in various naturally occurring growth factors that can effectively promote the healing process in various types of tissues and absorb wound exudates to reduce adhesion between wounds and dressings. Furthermore, PRP-incorporated zwitterionic hydrogels have been used to repair full-thickness wounds in Sprague-Dawley rats with diabetes (DM SD)., Materials and Methods: Fibroblasts and keratinocytes were cultured with PRP, zwitterionic hydrogels, and PRP-incorporated zwitterionic hydrogels to assess cell proliferation and specific gene expression. Furthermore, PRP-incorporated zwitterionic hydrogels were used to repair full-thickness skin defects in DM SD rats., Results: The swelling ratio of hydrogel, hydrogel + PRP1000 (108 platelets/mL), and hydrogel + PRP1000 (109 platelets/mL) groups were similar (~07.71% ± 1.396%, 700.17% ± 1.901%, 687.48% ± 4.661%, respectively) at 144 hours. The tensile strength and Young modulus of the hydrogel and hydrogel + PRP10000 groups were not significantly different. High concentrations of PRP (approximately 108 and 109 platelets/mL) effectively promoted the proliferation of fibroblasts and keratinocytes. The zwitterionic hydrogels were not cytotoxic to any cell type. High PRP concentration-incorporated zwitterionic hydrogels increased the rate of cell proliferation and significantly increased the expression of characteristic genes such as collagen, fibronectin, involucrin, and keratin. Subsequently, zwitterionic hydrogels with high PRP concentrations were used to repair full-thickness skin defects in DM SD rats, and a wound healing rate of more than 90% was recorded on day 12., Conclusions: PRP contains high concentrations of growth factors that promote cell viability, enhance specific gene expression, and have a high medical value in cell therapy. Zwitterionic hydrogels have a 3-dimensional interconnected microporous structure and can resist cell adhesion without causing cytotoxicity. Platelet-rich plasma-incorporated zwitterionic hydrogels further enhance the cellular properties and provide an effective therapeutic option for wound healing., Competing Interests: Conflicts of interest and sources of funding: none declared., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Plants can record external stimuli in mobile mRNAs and systemically deliver them to distal tissues to adjust development. Despite the identification of thousands of mobile mRNAs, the functional relevance of mobile mRNAs remains limited. Many mobile mRNAs are synthesized in the source cells that perceive environmental stimuli, but specifically exert their functions upon transportation to the recipient cells. However, the translation of mobile mRNA-encoded protein in the source cells could locally activate downstream target genes. How plants avoid ectopic functions of mobile mRNAs in the source cells to achieve tissue specificity remains to be elucidated. Here, we show that Arabidopsis AGAMOUS-LIKE 24 (AGL24) is a mobile mRNA whose movement is necessary and sufficient to specify floral organ identity. Although AGL24 mRNA is expressed in vegetative tissues, AGL24 protein exclusively accumulates in the shoot apex. In leaves, AGL24 proteins are degraded to avoid ectopically activating its downstream target genes. Our results reveal how selective protein degradation in source cells provides a strategy to limit the local effects associated with proteins encoded by mobile mRNAs, which ensures that mobile mRNAs specifically trigger systemic responses only in recipient tissues., (© 2023 The Authors New Phytologist © 2023 New Phytologist Foundation.)

Plants convert external cues into mobile mRNAs to synchronize meristematic differentiation with environmental dynamics. These mRNAs are selectively transported to intercellular pores, plasmodesmata (PD), for cell-to-cell movement. However, how plants recognize and deliver mobile mRNAs to PD remains unknown. Here we show that mobile mRNAs hitchhike on organelle trafficking to transport towards PD. Perturbed cytoskeleton organization or organelle trafficking severely disrupts the subcellular distribution of mobile mRNAs. Arabidopsis rotamase cyclophilins (ROCs), which are organelle-localized RNA-binding proteins, specifically bind mobile mRNAs on the surface of organelles to direct intracellular transport. Arabidopsis roc mutants exhibit phenotype alterations and disruptions in the transport of mobile mRNAs. These findings suggest that ROCs play a crucial role in facilitating the systemic delivery of mobile mRNAs. Our results highlight that an RNA-binding protein-mediated hitchhiking system is specifically recruited to orient plant mobile mRNAs for intercellular transport., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)

Objectives: As life expectancy is prolonged, older people may face increased burdens related to supporting multi-generational family members. This study is aimed toward examining the effects of such an emerging type of informal care on the well-being of caregivers., Methods: Participants aged 50 and over from the Taiwan Longitudinal Study on Aging (1996-2007, n  = 4,217) were analyzed. We categorized caregiving status according to different care recipients: 1) older adults only, 2) grandchildren only, 3) both older adults and grandchildren (dual caregiving), and 4) non-caregivers. Well-being was measured based on depressive symptoms and degree of life satisfaction. Generalized Estimation Equation models were used to examine the association between types of caregiving and the caregivers' state of well-being., Results: After adjusting for all covariates, caregivers of older adults had significantly more depressive symptoms and less life satisfaction than non-caregivers, especially when caregiving for adults with ADL problems. In contrast, caregivers of grandchildren were not significantly affect either depression or life satisfaction as compared with non-caregivers. Interestingly, caregiving for both older adults and grandchildren had no significant effect on depression but positively affected the degree of life satisfaction., Conclusion: Our findings highlight that simultaneously taking care of both older adults and grandchildren can buffer negative feelings in caregivers or even improve their mental health.

Limited research has examined the components of retirement planning and the effects on retirees' health behaviors. This study aims to explore whether retirement planning is associated with different types of healthy lifestyles after retirement. We conducted a nationwide Health and Retirement Survey in Taiwan and analyzed the data from 2015 to 2016. A total of 3128 retirees aged 50-74 years were included in the analysis. Twenty items on retirement planning from five categories were administered, and 20 health-related behaviors were used for measuring healthy lifestyles. Results showed that five types of healthy lifestyles were found from the 20 health behaviors by factor analysis. After controlling for all covariates, various components of retirement planning were associated with different types of lifestyles. Retirees having any item of retirement planning would significantly increase the score of 'healthy living'. Those with 1-2 items were also associated with the total score and the type of 'no unhealthy food'. However, those with ≥ 6 items were the only group positively related to the type of 'regular health checkups' but negatively to the type of 'good medication'. In conclusion, retirement planning offers a 'window of opportunity' for promoting healthy lifestyles after retirement. Pre-retirement planning should be advocated in the workplace to improve health-related behaviors, especially for those upcoming retired workers. In addition, a friendly environment and continuous programs should also be incorporated for better retirement life., (© The Author(s) 2023. Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Montmorillonite (MMT) has been frequently utilized as drug vehicles due to its high specific surface area, excellent cation exchange capacity and biocompatibility. However, the significant flocculation of MMT under physiological condition restricted its application to drug delivery. To conquer this problem, the graft-type PEGylated chitosan (PEG-CS) adducts were synthesized as intercalator to stabilize MMT dispersion. Through electrostatic attraction between the chitosan and MMT, the PEG-CS adducts were adsorbed on MMT surfaces and intercalated into MMT. The resulting PEG-CS/MMT nanosheets possessed PEG-rich surfaces, thus showing outstanding dispersion in serum-containing environment. Moreover, the physicochemical characterization revealed that the increased mass ratio of PEG-CS to MMT led to the microstructure transition of PEG-CS/MMT nanosheets from multilayered to exfoliated structure. Interestingly, the PEG-CS/MMT nanosheets with mass ratio of 8.0 in freeze-dried state exhibited a hierarchical lamellar structure organized by the intercalated MMT bundles and unintercalated PEG-CS domains. Notably, the multilayered PEG-CS/MMT nanosheets showed the capability of loading doxorubicin (DOX) superior to the exfoliated counterparts. Importantly, the DOX@PEG-CS/MMT nanosheets endocytosed by TRAMP-C1 cells liberated the drug progressively within acidic organelles, thereby eliciting cell apoptosis. This work provides a new strategy of achieving the controllable dispersion stability of MMT nanoclays towards application potentials in drug delivery., 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 © 2022 Elsevier Ltd. All rights reserved.)

Hyperbaric oxygen therapy (HBOT) is a professional medical regimen with a wide range of clinical applications in various research fields. In addition to treating diving decompression sickness and air embolism, HBOT is used as an adjuvant in the management of various diseases. A large number of studies have been published to confirm its efficacy. Although HBOT has been clinically applied to the treatment of many diseases, the effectiveness of these treatments remains controversial. Exploring and evaluating HBOT will contribute to the future development of research in this field. Through a quantitative analysis of the literature, this paper explores the citation relevance and collaboration map and their impact on research outcomes. This study used bibliometric and cartographic techniques with VOSviewer to identify the most influential countries and scholars using this treatment, based on syndrome differentiation. It also provides continuous quality evaluation and lean management of the medical expenses associated with HBOT.

Abstract: The adipose-derived stromal vascular fraction (SVF) is considered to be an attractive source of stem cells in cell therapy. Besides stem cells, it also contains functional cells, such as macrophages, precursor cells, somatic stem cells, and pericytes. Collagenase digestion is the most frequently used method to isolate SVF, but it is time-consuming and costly and has some problems, such as infectious agents and immune reactions. In this research, we compared the yield, cell population ratios, and cell viability when isolating SVF by the ultrasonic physics (U-SVF) method and traditional enzymatic method (E-SVF). Then, we isolated exosomes from U-SVF and E-SVF, respectively, and cocultured them with fibroblasts to investigate the potential of applying this cell secretion in wound repair. The results showed that there was no significant difference between the ultrasonic method and enzymatic method in terms of cell viability, cell numbers, or the expression of CD markers of stem cells. However, exosome analysis identified a greater number and smaller size of exosome particles obtained by U-SVF. In terms of cell proliferation efficiency, although the proliferation efficiency of U-SVF was lower than that of E-SVF. Trilineage differentiation experiments revealed that both E-SVF and U-SVF had good differentiation ability, owing to high stem cell content. Finally, E-SVF and U-SVF exosomes were cocultured with fibroblasts. The efficiency of fibroblast migration increased in the SVF exosome treated groups, and the expression of related genes (integrin α5β1) was slightly upregulated; however, the expression of FAK, AKT, ERK, and RhoA was significantly upregulated at 24 hours. From the abovementioned experiments, we found that there was no significant difference in stem cell-related characteristics between SVF isolated by ultrasonic cavitation and SVF isolated by the enzymatic method. In addition, exosomes secreted by SVF may have excellent therapeutic effect on skin injuries, which provides a new viewpoint and therapeutic strategy for soft tissue repair., Competing Interests: Conflicts of interest and sources of funding: none declared., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Background: RNA live-cell imaging systems have been used to visualize subcellular mRNA distribution in living cells. The RNA-binding protein (RBP)-based RNA imaging system exploits specific RBP and the corresponding RNA recognition sequences to indirectly label mRNAs. Co-expression of fluorescent protein-fused RBP and target mRNA conjugated with corresponding RNA recognition sequences allows for visualizing mRNAs by confocal microscopy. To minimize the background fluorescence in the cytosol, the nuclear localization sequence has been used to sequester the RBP not bound to mRNA in the nucleus. However, strong fluorescence in the nucleus may limit the visualization of nucleus-localized RNA and sometimes may interfere in detecting fluorescence signals in the cytosol, especially in cells with low signal-to-noise ratio., Results: We eliminated the background fluorescence in the nucleus by using the split fluorescent protein-based approach. We fused two different RBPs with the N- or C-terminus of split fluorescent proteins (FPs). Co-expression of RBPs with the target mRNA conjugated with the corresponding RNA recognition sequences can bring split FPs together to reconstitute functional FPs for visualizing target mRNAs. We optimized the system with minimal background fluorescence and used the imaging system to visualize mRNAs in living plant cells., Conclusions: We established a background-free RNA live-cell imaging system that provides a platform to visualize subcellular mRNA distribution in living plant cells., (© 2022. The Author(s).)

Previous studies have shown an increase of insulin-like growth factor-2 (IGF2) in animal models of neuropathic pain. We aimed to examine the hypothesis that reducing the expression of IGF2 using intrathecal IGF2 small-interfering RNA (siRNA) would attenuate the development of neuropathic pain in rats after spared nerve injury (SNI). Male Wistar rats were divided into three groups: sham-operated group, in which surgery was performed to cut the muscles without injuring the nerves; SNI group, in which SNI surgery was performed to sever the nerves; and SNI + siRNA IGF2 group, in which SNI surgery was performed, and IGF2-siRNA was administered intrathecally 1 day after SNI. The rats were assessed for mechanical allodynia and cold allodynia 1 day before surgery (baseline), and at 2, 4, 6, 8, and 10 days after siRNA treatment. The rat spinal cord was collected for quantitative polymerase chain reaction and western blot analysis. Compared with the SNI group, rats that received IGF2 siRNA showed a significantly increased SNI-induced paw-withdrawal threshold to metal filament stimulation from Day 4 to Day 10 after SNI surgery. IGF2 siRNA significantly decreased the response duration from the acetone test from Day 2 to Day 10 following SNI surgery. SNI increased IGF2 mRNA expression on Day 2 and increased IGF2 protein expression on Day 8 and Day 10 in the spinal cord of the SNI rats. However, the above-mentioned effects of IGF2 mRNA and protein expression were significantly inhibited in the SNI + IGF2 siRNA group. We demonstrated that intrathecal administration of IGF2 siRNA provided significant inhibition of SNI-induced neuropathic pain via inhibition of IGF2 expression in the spinal cord. The analgesic effect lasted for 10 days. Further exploration of intrathecal IGF2 siRNA administration as a potential therapeutic strategy for neuropathic pain is warranted., Competing Interests: The authors have declared that no competing interests exist.

Daunorubicin (DNR) is used clinically to treat acute myeloid leukemia (AML), while the signaling pathways associated with its cytotoxicity are not fully elucidated. Thus, we investigated the DNR-induced death pathway in the human AML cell lines U937 and HL-60. DNR-induced apoptosis in U937 cells accompanied by downregulation of MCL1 and BCL2L1, upregulation of Phorbol-12-myristate-13-acetate-induced protein 1 (NOXA), and mitochondrial depolarization. DNR induced NOX4-mediated reactive reactive oxygen species (ROS) production, which in turn inactivated Akt and simultaneously activated p38 mitogen-activated protein kinase (MAPK). Activated p38 MAPK and inactivated Akt coordinately increased GSK3β-mediated cAMP response element-binding protein (CREB) phosphorylation, which promoted NOXA transcription. NOXA upregulation critically increased the proteasomal degradation of MCL1 and BCL2L1. The same pathway was also responsible for the DNR-induced death of HL-60 cells. Restoration of MCL1 or BCL2L1 expression alleviated DNR-induced mitochondrial depolarization and cell death. Furthermore, ABT-199 (a BCL2 inhibitor) synergistically enhanced the cytotoxicity of DNR in AML cell lines. Notably, DNR-induced DNA damage was not related to NOXA-mediated degradation of MCL1 and BCL2L1. Collectively, these results indicate that the upregulation of NOXA expression through the NOX4-ROS-p38 MAPK-GSK3β-CREB axis results in the degradation of MCL1 and BCL2L1 in DNR-treated U937 and HL-60 cells. This signaling pathway may provide insights into the mechanism underlying DNR-triggered apoptosis in AML cells., (© 2021 Wiley Periodicals LLC.)

Biomarkers are essential tools in osteoarthritis (OA) research, clinical trials, and drug development. Detecting and evaluating biomarkers in OA research can open new avenues for researching and developing new therapeutics. In the present report, we have explored the serological detection of various osteoarthritis-related biomarkers in the preclinical model of OA. In this surgical OA model, we disrupted the medial tibial cartilage's integrity via anterior cruciate ligament transection combined with medial meniscectomy (ACLT+MMx) of a single joint of Wistar rats. The progression of OA was verified, as shown by the microscopic deterioration of cartilage and the increasing cartilage degeneration scoring from 4 to 12 weeks postsurgery. The concentration of serological biomarkers was measured at two timepoints, along with the complete blood count and bone electrolytes, with biochemical analysis further conducted. The panel evaluated inflammatory biomarkers, bone/cartilage biomarkers, and lipid metabolic pathway biomarkers. In chronic OA rats, we found a significant reduction of total vitamin D3 and C-telopeptide fragments of type II (CTX-II) levels in the serum as compared to sham-operated rats. In contrast, the serological levels of adiponectin, leptin, and matrix metallopeptidase (MMP3) were significantly enhanced in chronic OA rats. The inflammatory markers, blood cell composition, and biochemical profile remained unchanged after surgery. In conclusion, we found that a preclinical model of single-joint OA with significant deterioration of the cartilage can lead to serological changes to the cartilage and metabolic-related biomarkers without alteration of the systemic blood and biochemical profile. Thus, this biomarker profile provides a new tool for diagnostic/therapeutic assessment in OA scientific research.

Development of remifentanil-induced hyperalgesia (RIH) postoperatively is an unpleasant experience that requires further treatment. This study assessed the effects of gradual withdrawal combined with drip infusion of remifentanil on postoperative pain and the requirement for rescue analgesics. A total of 559 patients receiving total intravenous anesthesia with propofol and remifentanil were enrolled. All patients either underwent gradual withdrawal of remifentanil (GWR) or gradual withdrawal combined with drip infusion (GWDR) with a dose of 1 mcg·kg -1 for 30 min after extubation. The numeric rating scale (NRS) and the requirement of rescue analgesics were assessed. The requirement for rescue analgesics was significantly lower in the GWDR group than in the GWR group (13.2% vs. 35.7%; p < 0.001). At the post-anesthetic care unit (PACU), patients in the GWDR group had a lower NRS pain score ( p < 0.001). In addition, in the postoperative 2nd hour, patients in the GWDR group had a significantly lower NRS than the GWR group (beta, -0.31; p = 0.003). No remifentanil-related adverse effects were observed. We found that gradual withdrawal combined with drip infusion of remifentanil required less rescue analgesics and reduced pain scores. The new way of remifentanil administration may be effective to prevent RIH.

Hepatocellular carcinoma (HCC) is the most common type of primary liver cancer and accounts for the fourth leading cause of all cancer deaths. Scientific evidence has found that plant extracts seem to be a reliable choice due to their multitarget effects against HCC. Juniperus communis has been used for centuries in traditional medicine and its anticancer properties have been reported. As a result, the purpose of the study was to investigate the anticancer effect and mechanism of J. communis extract (JCo extract) on HCC in vitro and in vivo. In the present study, we found that JCo extract inhibited the growth of human HCC cells by inducing cell cycle arrest at the G0/G1 phase, extensive apoptosis and suppressing metastatic protein expressions in HCC cells. Moreover, the combinational treatment of JCo and VP-16 was found to enhance the anticancer effect, revealing that JCo extract might have the potential to be utilized as an adjuvant to promote HCC treatment. Furthermore, in vivo study, JCo extract significantly suppressed HCC tumor growth and extended the lifespan with no or low systemic and pathological toxicity. JCo extract significantly up-regulated the expression of pro-apoptotic proteins and tumor suppressor p53, suppressed VEGF/VEGFR autocrine signaling, down-regulated cell cycle regulatory proteins and MMP2/MMP9 proteins. Overall, our results provide a basis for exploiting JCo extract as a potential anticancer agent against HCC., (© 2021 The Author(s).)

Most studies have focused on factors associated with depression at the individual level, and evidence on ecological models linking social-economic features with depression is rare in Taiwan. This study aimed to use multi-level analysis to explore the effects of social-economic environments on depressive symptoms among Taiwanese adults. The 2009 National Health Interview Survey (NHIS) and the Age-Friendly Environments database were linked in this study. A total of 6602 adults aged 20 years and older were included in the analysis. A Chinese version of the 10-item CESD was used as the outcome measure. Three social indicators (population density, divorce rate, and crime rate) and three economic indicators (unemployment rate, per capita disposable income, and per capita government expenditures) at the ecological level were examined. Results showed that two social environments and two economic features were significantly associated with depressive symptoms. However, the effects of these factors were different by gender and age groups. The economic environments were critical for males and young adults aged 20-44 years old, whereas the social environments were significant for females and middle-aged and older adults. Intervention efforts for depression prevention should integrate ecological approaches into the effects of social-economic environments on depressive symptoms.

Objective: Divers with a history of decompression sickness may be at high risk for sleep problems. However, limited studies have investigated the relationship between diving exposure and sleep problems of occupational divers. This study investigated the association between diving exposure and sleep quality and quantity among male occupational divers in southern Taiwan., Methods: This descriptive, cross-sectional study included 52 occupational divers and 121 non-divers recruited from southern Taiwan in 2018. Survey data were collected using the Taiwanese version of the Hospital Anxiety and Depression Scale, Pittsburgh Sleep Quality Index, Epworth Sleepiness Scale, and a self-report questionnaire that included demographic variables, diving exposure/protocols, and factors associated with sleep quality., Results: Among all participants examined, occupational divers were significantly more likely to have both poor sleep quality (adjusted odds ratio [OR] = 3.00; 95% confidence interval [CI] = 1.48-6.06; P = 0.002) and excessive daytime sleepiness (adjusted OR = 4.49; 95% CI = 2.12-9.52; P < 0.001). The diving exposure time, depth, ascent rate, and decompression table use showed no significant associations between poor and good sleepers in the divers group. However, a history of decompression sickness was associated with poor sleep quality among divers (adjusted OR = 2.20; 95% CI = 1.07-4.54; P = 0.032)., Conclusions: Our results showed that occupational divers had poor sleep quality and more excessive sleepiness than non-divers. Decompression sickness likely contributes to poor sleep quality. Prevention and early detection of decompression sickness-related sleep problems should be an occupational health priority., (© The Author(s) 2021. Published by Oxford University Press on behalf of the British Occupational Hygiene Society.)

Objectives: Depression in older adults is a growing public health concern. However, limited research has focused on the issues of physical environments and depression in the elderly in Asia. The purpose of the study is to examine the relationship between the built environments and depressive symptoms in older adults using Taiwan as an example., Methods: Two national datasets were used in this study, including the 2009 National Health Interview Survey and the 2006 National Land Use Investigation in Taiwan. A total of 2,155 older adults were recruited, and eight built environments were examined among 161 townships. Depressive symptoms were measured using a 10-item CES-D scale, and four sophisticated models were built using a multi-level analysis., Results: Five types of built environments were found to be significantly associated with depressive symptoms in older adults. Among them, two types of built environments, 'health and medical services' and 'schools' were highly related to a lower CES-D score and lower odds of being depressed, whereas the other three built environments, 'cultural and historical facilities,' 'recreational and amusement areas,' and 'playgrounds and sports venues' were significantly associated with an increasing risk of being depressed., Conclusions: Different built environments had different effects on depression and some even showed a dose-response relationship. These results can help urban planners or city designers reconsider how to facilitate the construction of built environments in neighborhoods that will improve the mental health of older adults.

Health in All Policies (HiAP) is an effective approach to promote population health through addressing comprehensive social determinants of health. In 1997, the World Health Organization designed a 20-step protocol for developing a Healthy Cities (HC) project to build healthy public policies. Taiwan adopted the concept of HC in 2002 and established the first demonstration project in Tainan City in 2003. This study explores the impact of the HC initiative on the development of HiAP, as well as how a window of opportunities for HiAP was opened through the HC movement, using Tainan City as an example. Tainan was selected as the case for this study because of its relative maturity in the development of an HC initiative. A theory-driven thematic analysis was conducted in the study with archived documents between 2003 and 2010. We first adopted a Multiple Streams Approach to examine how the city government opened a window for HiAP through the HC initiative and then drew on the Maturity Model to evaluate the stage of HiAP in the Tainan HC project. After analyzing all related documents, we concluded that HiAP in the Tainan HC project had reached Stage V Institutionalization after 7 years. Key contexts, factors, challenges and strategies were identified. This study suggests that the HC initiative can indeed contribute to the development of HiAP and that the window was opened for HiAP through a concurrence of the three streams of problem, policy and politics along with the HC movement process., (© The Author(s) 2020. Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Introduction: Astragaloside IV (AS-IV) is a natural herb extract and a popular compound used in traditional Chinese medicine because of its effect on multiple biological processes, such as promotion of cell proliferation, improvement in cardiopulmonary and vascular function, and promotion of angiogenesis around wounds, leading to accelerated wound healing. Vascular regeneration primarily results from the differentiation of endothelial progenitor cells (EPCs). Biomedical acceleration of angiogenesis and differentiation of EPCs around the wound remain challenging., Materials and Methods: In this study, we treated human umbilical cord blood-derived EPCs with AS-IV and cultured them on 2-dimensional (tissue culture polystyrene) and 3-dimensional culture plates (3DPs). These cultured cells were then combined with human blood plasma gel and applied on the skin of nude mice in an attempt to repair full-thickness skin defects., Results: The results show that using 3DP culture could increase vascular-related gene expression in EPCs. Furthermore, 12.5 μg/mL AS-IV-treaded EPCs were combined with plasma gels (P-3DP-EPC12.5) and showed enhanced vascular-related protein expression levels after 3 days of culture. Finally, P-3DP-EPC12.5s were used to repair full-thickness skin defects in nude mice, and we could register a wound healing rate greater than 90% by day 14., Conclusions: Based on these results, we concluded that we have developed a potential therapeutic approach for wound healing using plasma gel containing 3-dimensional surface-cultured AS-IV-treated EPCs., Competing Interests: Conflicts of interest and sources of funding: Financial support for this work was provided by the National Defense Medical Center, Tri-Service General Hospital, ROC (TSGH-C107-119), Zouying Branch of Kaohsiung Armed Forces General Hospital, Republic of China (ZBH 107-18), and Chi Mei Medical Center (CMNDMC-10610). Additional financial support was provided by Chunghwa Pharmaceutical Research Foundation, Taiwan, Republic of China., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Mobile signals play pivotal roles in coordinating interorgan communication. Grafting provides an effective strategy to identify and explore the movement of the mobile signals. The mutant collection of Arabidopsis offers background-free living materials for examining the transport of mobile signals in vivo. In the past few years, many grafting methods have been developed to overcome the limitations of rosette-type growth and small size in Arabidopsis. Here we describe a non-sterile grafting method involving an insect pin to secure the scion to the rootstock. The scions can be grafted onto epicotyls or hypocotyls of soil-grown Arabidopsis rootstocks at a wide range of developmental stages. This grafting method provides a useful tool to analyze leaf-derived mobile signals in Arabidopsis.

Focused Clinical Question: With the 2018 AAP/EFP disease classification with the staging and grading systems, does risk assessment for different ethnic group result in a different focus for clinical needs? This comparative analysis aimed to assess two previously reported cohort studies in African-American (Af-A) and Asian-American (As-A) as to the risk for these two populations for clinical attachment loss (CAL) and gingival phenotype., Summary: In comparison of As-A and Af-A cohorts, As-A had higher frequency of thin tissue phenotype, less width of keratinized gingiva (KGW), and more gingival recession (GR). On other hands, Af-A showed higher prevalence of thick phenotype, longer total tooth length and root length (RL). These gingival and dental anatomical patterns suggest there are differential risk for GR, patterns for CAL, and periodontal prognosis between two cohorts., Conclusion(s): Because of nature of dental and gingival anatomy between these two cohorts, As-A are more susceptible in GR and the short RL affords this population less ability to withstand the clinical presentation of periodontal disease. From a therapeutic perspective, clinicians should evaluate patients with different risk assessment based on their dental and gingival characterization. Af-A may have clinical characteristics that makes this population less at risk for mucogingival defects. Conversely, phenotype modification therapy should be considered when treating As-A because of the high prevalence of thin tissue phenotype, inadequate KGW, and GR. Clinicians should also diligently monitor periodontal CAL around the teeth with shorter RL in periodontal or orthodontic therapy for better teeth prognosis., (© 2020 American Academy of Periodontology.)

With the mature technology of wireless communications, the function of estimating the mobile station (MS) position has become essential. Suppressing the bias resulting from non-line-of-sight (NLSO) scenarios is the main issue for a wireless location network. The artificial bee colony (ABC) algorithm, based on the depiction of bee swarm's foraging characteristics, is widely applied to solve optimization problems in several fields. Based on three measurements of time-of-arrival (TOA), an objective function is used to quantify the additional NLOS error on the MS positioning scheme. The ABC algorithm is adopted to locate the most precise MS location by minimizing the objective function value. The performance of the proposed positioning methods is verified under various error distributions through computer simulations. Meanwhile, the localization accuracy achieved by other existing methods is also investigated. According to the simulation results, accurate estimation of the MS position is derived and therefore the efficiency of the localization process is increased.

Background: Physical and social environments may influence cognition health in older adults. However, evidence regarding physical and social environments linked to dementia is lacking, especially in Asia. This study aims to explore the influence of physical and social environments on the incidence of dementia through a population-based case-control design in Taiwan., Methods: We identified 26,206 incident cases with dementia aged≧65 years in 2010, with the same no. of controls from National Health Insurance claims. Environmental measures were collected from government statistics including three physical environments and three social environments. Multilevel logistic regression was used to estimate the odds ratios (ORs) and 95% confidence intervals (CI) of the association between dementia incidence and the environmental measures at the township level., Results: We observed a significant reduction of 12% in the odds ratios of dementia in areas with higher availability of playgrounds and sport venues (OR 0.88, 95% CI 0.81-0.95), after controlling for individual and other environmental characteristics. Community center availability was also significantly associated with an 8% decreased odds for dementia (OR 0.92, 95% CI 0.87-0.99), but the association was not significant after further consideration of individual-level characteristics. Although higher odds of dementia were found in areas with high median annual family income (OR 1.14, 95% CI 1.04-1.25), such a significant relationship did not appear in the full model., Conclusions: Our study suggests that specific physical and social environmental features have different influences on the risk of dementia. Public health interventions may consider these environmental aspects for preventing dementia incidence.

Surgical management of cancer may induce stress and increase the likelihood of cancer metastasis and recurrence. Appropriate surgical and anesthetic techniques may affect the patient's outcome. Although numerous studies have been performed, conflicting results have been obtained regarding the effect of anesthetic techniques on the outcome of patients with cancer. We conducted this study to evaluate the association of anesthetic techniques with overall and recurrence-free survival in patients who had undergone gastric cancer surgery.This retrospective study reviewed the electronic medical records of patients, who had visited our hospital and had been diagnosed with gastric cancer between July 1st, 2006 to June 30th, 2016. Univariate analysis of the potential prognostic factors was performed using the log-rank test for categorical factors, and parameters with a P-value < .05 at the univariate step were included in the multivariate regression analysis. Propensity Score Matching was performed to account for differences in baseline characteristics: propofol or desflurane, in a 1:1 ratio.A total of 408 patients anesthetized with desflurane (218) and propofol (190) were eligible for analysis. After propensity matching, 167 patients remained in each group. The overall mortality rate was significantly higher in the desflurane group (56%) than in the propofol group (34%) during follow-up (P < .001). In addition, a greater percentage of patients in the desflurane group (41%) exhibited postoperative metastasis than those in the propofol group (19%, P < .001).The authors found some association between types of anesthesia used and the long-term prognosis of gastric cancer. Propofol-based total intravenous anesthesia improved survival and reduced the risk of recurrence and metastasis during the 5-year follow-up period after gastric cancer surgery.

Catecholamines have both anti-inflammatory and vasoactive properties. A decreased cardiac response to catecholamines has been associated with a high risk of death in sepsis and septic shock. The aim of this study was to investigate the effects of epinephrine (EPI) on heart rate variability (HRV) and autonomic balance, as well as cytokine levels, in a rat sepsis model. Thirty-six male Sprague-Dawley rats were assigned to 4 experimental groups and 2 control groups of 6 rats each. The rats in the experimental groups were inoculated with a lipopolysaccharide (LPS, endotoxin) to establish a sepsis model. Group A received only LPS; group B received LPS, antecedent EPI and the nonselective β-blocker propranolol; group C received LPS and antecedent EPI; and group D received LPS, antecedent EPI and the selective β1-blocker esmolol. One control group received EPI and the other received saline placebo. Heart rate variability (HRV) was analyzed and tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) and interleukin-1β (IL-1β) levels were measured. Measurements were carried out at baseline, at 0 hour after EPI infusion, and at 0.5, 2, and 4 hours after LPS inoculation. There were significant differences in HRV and cytokine levels between the groups, indicating that LPS infusion caused autonomic imbalance. Antecedent EPI significantly decreased the level of TNF-α in group C compared with group A in which TNF-α level peaked at 2 hours and then declined. Propranolol (group B) but not esmolol (group D) administration resulted in elevated TNF-α levels, comparable to those observed in group A. In conclusion, antecedent administration of EPI in a rat sepsis model inhibits the production of TNF-α possibly via the β2-adrenoceptor.

Background Aims: Combining the use of transfection reagents and physical methods can markedly improve the efficiency of gene delivery; however, such methods often cause cell damage. Additionally, naked plasmids without any vector or physical stimulation are difficult to deliver into stem cells. In this study, we demonstrate a simple and rapid method to simultaneously facilitate efficient in situ naked gene delivery and form a bioactive hydrogel scaffold., Methods: Transfecting naked GATA binding protein 4 (GATA4) plasmids into human umbilical cord-derived mesenchymal stem cells (hUC-MSCs) by co-extruding naked plasmids and hUC-MSCs with a biomimetic and negatively charged water-based biodegradable thermo-responsive polyurethane (PU) hydrogel through a microextrusion-based transient-transfection system can upregulate the other cardiac marker genes., Results: The PU hydrogels with optimized physicochemical properties (such as hard-soft segment composition, size, hardness and thermal gelation) induced GATA4-transfected hUC-MSCs to express the cardiac marker proteins and then differentiated into cardiomyocyte-like cells in 15 days. We further demonstrated that GATA4-transfected hUC-MSCs in PU hydrogel were capable of in situ revival of heart function in zebrafish in 30 days., Conclusions: Our results suggest that hUC-MSCs and naked plasmids encapsulated in PU hydrogels might represent a new strategy for in situ tissue therapy using the microextrusion-based transient-transfection system described here. This transfection system is simple, effective and safer than conventional technologies., (Copyright © 2019 International Society for Cell and Gene Therapy. Published by Elsevier Inc. All rights reserved.)

In this study, a novel antiadhesion membrane made of polycaprolactone, gelatin, and chitosan was fabricated using the electrospinning technique. A series of polycaprolactone/gelatin/chitosan (PGC) electrospun membranes with different amounts of chitosan (0%, 0.5%, 1%, and 2% in weight percentage) was synthesized. The physicochemical properties and biocompatibility of the fabricated membranes were examined and compared with the aim to select an effective antiadhesion membrane. Scanning electron microscopy showed that these 4 electrospun membranes had similar fiber diameter and pore area, with no statistical differences between them. Furthermore, the contact angle decreased with increased chitosan content, indicating that chitosan may contribute to increased hydrophilic properties. The in vitro degradation test revealed that the higher chitosan content corresponded to a lower degradation rate in PGC membranes within 7 days. All PGC membranes exhibited similar cell proliferation; however, cell proliferation was lower than tissue culture polystyrene (P < 0.05). To compare antiadhesion ability, the adhesion between the cecum and abdominal wall was created in a rat model. Assessment after implantation of electrospun membranes revealed that PGCs with higher chitosan content (PGC2) had better antiadhesion effects, as evaluated by an adhesion score at day 14 postsurgery. Thus, PGC2 was effective in reducing the formation of tissue adhesion. Therefore, PGC electrospun membrane may provide a potential peritoneal antiadhesion barrier for clinical use.

Multicellular organisms rely on systemic signals to orchestrate diverse developmental and physiological programs. To transmit environmental stimuli that perceived in the leaves, plants recruit many mobile molecules including mobile mRNAs as systemic signals for interorgan communication. The mobile mRNAs provide an efficient and specific remote control system for plants to cope with environmental dynamics. Upon being transcribed in local tissues, mobile mRNAs are selectively targeted to plasmodesmata for cell-to-cell and long-distance translocation. The mRNA labeling system based on the RNA-binding protein MS2 provides a useful tool to investigate intracellular trafficking of mobile mRNAs in plants. Here we describe the detailed protocol to visualize intracellular trafficking of plant mobile mRNAs by using the MS2 live-cell imaging system.

Purpose: The relationship between built environments and the quality of life (QoL) of the elderly has gained great attention in recent years. However, most QoL studies have been conducted in western countries; thus, limited research was found in Asia, in which the population density, urban forms, narrow roadways, and land use patterns are more compact and highly mixed in terms of use. Therefore, the purpose of this study was an interdisciplinary analysis of two national datasets, the National Land Use Investigation and the National Health Interview Survey, to explore the relationship between built environments and the health-related quality of life of older adults in Taiwan., Methods: Eight types of built environments at the township level were calculated, and 1222 nationally representative older adults aged 65 and older were recruited. The outcome variable was health-related QoL as measured using the EQ-5D, including utility score and the EQ-VAS. Statistical methods included descriptive analysis, bivariate analysis, and mixed-effects logistic regression analysis, which were conducted using SAS 9.4 software., Results: The results showed that a significant relationship exists between cultural and historical facilities and low EQ-VAS; none of the built environments were found to be related to the EQ-5D. Individual factors are the main determinants of the EQ-5D of older adults in Taiwan. Positive relationships were found if older adults were engaging in physical activities and social participation., Conclusions: We suggest that building a supportive environment in which elderly people could consistently engage in physical activities and social participation is another potential approach that might contribute to active aging.

Little is known about the association between environmental features and the risk of Alzheimer's dementia (AD). This study aims to investigate the association of physical and social environments with the incidence of AD. We identified 12,401 newly diagnosed AD cases aged ≥65 years in 2010, with the same no. of matched controls from National Health Insurance claims in Taiwan. Environmental data were collected from government statistics including three physical environments and three social environments. Multilevel logistic regression was conducted to calculate the odds ratios (OR) of AD in association with environmental features at the township level. Results showed that living in the areas with higher availability of playgrounds and sport venues was associated with a 3% decreased odds of AD (95% CI = 0.96-0.99), while higher density of elderly living alone was associated with a 5% increased odds of AD (95% CI = 1.01-1.11), after controlling for individual and other environmental factors. In further examination by urbanization level, the above relationships were found only in rural areas but not in urban areas. This study provides evidence that specific physical and social environmental features have different impacts on the risk of AD.

The Healthy Cities (HC) Project, which was introduced by the World Health Organization (WHO) in 1986, has been recognized as the best setting approach for health promotion. However, very few studies have addressed how to use HC approaches to establish public policies in non-health departments in cities. This paper describes the strategies for the HC Performance Awards used in Taiwan to draw attention from different departments and to sustain intersectoral collaboration for the purpose of establishing Health in All Policies (HiAP). The methods include: (1) setting up the Taiwan Healthy City Alliance; (2) establishing HC Innovation Performance Awards; (3) reviewing the award applications according to seven criteria; and (4) analyzing the topic content of the award applications. We collected 961 HC award applications during 2013⁻2016 to analyze their content. The results showed that the number of applications increased nearly every year while significantly more non-health departments applied for the awards compared to health departments (73.3% vs. 26.7%). The award rates of non-health departments have also increased twice from 13.9% in 2013 to 25.8% in 2016. By examining the topics of the award winners, we concluded that "HC Innovation Performance Awards" indeed provide a role and opportunity for political involvement, intersectoral collaboration, co-opetition and capacity building that is necessary for establishing health in all policies.

The pigment melanin is produced by melanocytes, is primarily responsible for skin color, and protects it against ultraviolet rays that can cause the destruction of genetic material within the keratinocytes. To elucidate the mechanisms of many diseases associated with melanocytes, such as melanoma and albinism, or burns with uneven pigment distribution, the disease model needs to be established first. In this study, we aimed to construct the melanocyte model from patients in a short period.Sandai virus vector containing 4 stemness genes (Oct4, Sox2, Klf4, c-Myc) was transfected into human adipose-derived stem cells to produce induced pluripotent stem cells (iPSCs). Immunofluorescence staining was used to confirm the expression of specific proteins for iPSCs, including Tra-1-60, Tra-1-81, Oct-4, Sox-2, and Nango. polymerase chain reaction results also showed that specific genes of iPSCs with the ability to cause the differentiation of cells into the 3 germ layers were expressed. In our in vivo experiments, iPSCs were subcutaneously injected into nude mice to induce teratoma formation for 2 months. The morphology of the 3 germ layers was confirmed by hematoxylin and eosin staining. Furthermore, melanocytes were purified by serial induction medium, and their presence was confirmed by flow cytometry and the expression of different markers for melanocytes.

Skin substitutes with existing vascularization are in great demand for the repair of full-thickness skin defects. In the present study, we hypothesized that a pre-vascularized skin substitute can potentially promote wound healing. Novel three-dimensional (3D) skin substitutes were prepared by seeding a mixture of human endothelial progenitor cells (EPCs) and fibroblasts into a human plasma/calcium chloride formed gel scaffold, and seeding keratinocytes onto the surface of the plasma gel. The capacity of the EPCs to differentiate into a vascular-like tubular structure was evaluated using immunohistochemistry analysis and WST-8 assay. Experimental studies in mouse full-thickness skin wound models showed that the pre-vascularized gel scaffold significantly accelerated wound healing 7 days after surgery, and resembled normal skin structures after 14 days post-surgery. Histological analysis revealed that pre-vascularized gel scaffolds were well integrated in the host skin, resulting in the vascularization of both the epidermis and dermis in the wound area. Moreover, mechanical strength analysis demonstrated that the healed wound following the implantation of the pre-vascularized gel scaffolds exhibited good tensile strength. Taken together, this novel pre-vascularized human plasma gel scaffold has great potential in skin tissue engineering.

Photoperiodic floral induction is controlled by the leaf-derived and antagonistic mobile signals florigen and antiflorigen. In response to photoperiodic variations, florigen and antiflorigen are produced in leaves and translocated through phloem to the apex, where they counteract floral initiation. Florigen and antiflorigen are encoded by a pair of homologs belonging to FLOWERING LOCUS T ( FT )- or TERMINAL FLOWER1 ( TFL1 )-like clades in the phosphatidylethanolamine-binding domain protein (PEBP) family. The PEBP gene family contains FT -, TFL1 -, and MOTHER OF FT AND TFL1 ( MFT )-like clades. Evolutionary analysis suggests that FT - and TFL1 -like clades arose from an ancient MFT -like clade. The protein movement of the PEBP family is an evolutionarily conserved mechanism in many plants; however, the mRNA movement of the PEBP family remains controversial. Here, we examined the mRNA movement of PEBP genes in different plant species. We identified a tobacco ( Nicotiana sylvestris ) CENTRORADIALIS-like1 gene, denoted NsCET1 , and showed that NsCET1 is an ortholog of the Arabidopsis ( Arabidopsis thaliana ) antiflorigen ATC In tobacco, NsCET1 acts as a mobile molecule that non-cell-autonomously inhibits flowering. Grafting experiments showed that endogenous and ectopically expressed NsCET1 mRNAs move long distances in tobacco and Arabidopsis. Heterografts of tobacco and tomato ( Solanum lycopersicum ) showed that, in addition to NsCET1 , multiple members of the FT -, TFL1 -, and MFT -like clades of tobacco and tomato PEBP gene families are mobile mRNAs. Our results suggest that the mRNA mobility is a common feature of the three clades of PEBP-like genes among different plant species., (© 2018 American Society of Plant Biologists. All rights reserved.)

Many plant mRNAs move from cell to cell or long distance to execute non-cell-autonomous functions. These mobile mRNAs traffic through the phloem to regulate many developmental processes, but despite the burgeoning discovery of mobile mRNAs, little is known about the mechanism underlying the intracellular sorting of these mRNAs. Here, we exploited a fluorescence-based mRNA labeling system, using the bacteriophage coat protein MS2, fused to GFP (MS2-GFP) and an MS2 recognition site in the RNA of interest, to visualize the intracellular trafficking of mobile mRNAs in living plant cells of Nicotiana benthamiana We first improved this system by using the nuclear localization sequence from FD, which substantially reduced the fluorescent background of MS2-GFP in the cytoplasm. The modified system allowed us to observe the cytoplasmic fluorescent foci dependent on MS2-binding sites. Coexpressing the MS2-GFP system with a virus movement protein, which is a plasmodesmata (PD)-localized nonspecific RNA-binding protein, targeted cytoplasmic fluorescent foci to the PD, suggesting that the cytoplasmic fluorescent foci contain mRNA and MS2-GFP. Our ex vivo RNA imaging revealed that mobile but not nonmobile mRNAs were selectively targeted to PD. Real-time images of intracellular translocation revealed that the translocation of mRNA and organelles in the transvacuolar strands may be governed by the same mechanism. Our study suggests that PD targeting of mRNA is a selective step in determining mRNA cell-to-cell movement of mRNAs., (© 2018 American Society of Plant Biologists. All Rights Reserved.)

Urbanization and ageing are global phenomena and offer unique challenges in different countries. A supportive environment plays a critical role in addressing the issue of behavioral change and health promotion among older adults. Many studies in the U.S., EU, and Australia have considered promoting physical activity in the community based on ecological models, whereas very few Asian studies have examined the relationships among urbanization, the built environment and physical activity in elderly at the ecological level, especially from a multi-level perspective. Due to the prevalence of post-war baby boomers and a very low birth-rate, the older population (aged 65 years old and older) in Taiwan has increased rapidly since 2011 and has exceeded the younger generation (0⁻14 years old) in 2017. Hence, the purpose of this study was first to examine the degree of urbanization in townships and the status of related built environments in Taiwan and then to investigate whether the built environment is associated with recommended amounts of physical activity among older adults. Three national datasets and a multi-level design were used in this research. Data at the individual level was obtained from the 2009 National Health Interview Survey (NHIS) which was taken from June 2009 to February 2010. Ecological data was obtained from the 2006 National Land Use Investigation of the National Geographic Information System and the 2010 Population and Housing Census. The analyses included a descriptive analysis, a bivariate analysis, a multiple logistic regression, and a multi-level analysis, utilizing a mostly hierarchical linear model (HLM). The results showed a significant relationship between factors at the environmental levels and physical activity in older adults. Urbanization, the built environment, and the median income of townships were positively correlated to the physical activity of the older adults. After controlling for individual-level factors, urbanization still exhibited this correlation. Parks and green spaces were associated with achieving the recommended amount of physical activity. However, there was no relationship after controlling for factors at the individual level. Detailed discussions were provided.

Significant skin pigmentation changes occur when patients suffer deep burn injuries. These pigmentation disorders may cause not only cosmetic and psychological issues, but more importantly it increases the risk of skin cancer or photoaging. Severe burns significantly effect on the process of repigmentation as the pigmentation is tightly regulated by cell proliferation and differentiation of melanocytes and melanocyte stem cells which are housing in the epidermis and hair follicles of the skin. In the present review, we discuss the possible mechanisms to replenish the melanocytes from the healthy epidermis and hair follicles surrounding burn wounds. The molecular mechanisms of skin repigmentation following healing of burn injuries includes the differentiation of melanoblasts into melanocytes, the distribution and responses of melanocytes and melanocyte stem cells after burn injury, and the regulation of melanin production. We also reviewed advanced therapeutic strategies to treat pigmentation disorders, such as convectional surgery, laser, UV treatment and emerging concepts in skin tissue-engineering., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Paeonol is a key phenolic compound in the root bark of Moutan Cortex Radicis that has been used in traditional Chinese Medicine to ameliorate inflammation. A series of aminothiazole-paeonol derivatives (APDs) were synthesized in this work and subjected to preliminary evaluation in cells followed by verification in animals. Quantification of monocyte chemotactic protein-1 (MCP-1) and interleukin-6 (IL-6) in culture media of LPS-activated A549 cells, a lung epithelial adenocarcinoma cell line, were used to investigate the anti-inflammatory capability of APDs. ALI-bearing rats were employed to verify therapeutic efficacy of APDs according to observations of total cells, protein amounts, MCP-1 and IL-6 in bronchoalveolar lavage fluid (BALF). Histopathological examinations of lung tissues were consequently applied for validation of APDs. Among these compounds, 2-(2-aminothiazol-4-yl)-5-methoxyphenol ( 4 ) had the most potent activity, showing comparable inhibition of MCP-1/IL-6 and superior elimination of neutrophil infiltration and protein exudation in lungs compared to others as well as dexamethasone. This study demonstrated a comprehensive strategy to evaluate APDs through integration of cell-based screening and animal-based verification. In order to fulfill unmet needs of treating acute lung injury (ALI) and acute respiratory distress syndrome (ARDS), APDs introduced in this work could be promising lead compounds to develop high potent anti-inflammation agents., Competing Interests: The authors declare no conflict of interest.

Dengue virus types 1-4 (DENV-1-4) are positive-strand RNA viruses with an envelope that belongs to the Flaviviridae . DENV infection threatens human health worldwide. However, other than supportive treatments, no specific therapy is available for the infection. In order to discover novel medicine against DENV, we tested 59 crude extracts, without cytotoxicity, from 23 plants in vitro ; immunofluorescence assay revealed that the methanol extracts of fruit, heartwood, leaves and stem from Ficus septica Burm. f. had a promising anti-DENV-1 and DENV-2 effect. However, infection with the non-envelope picornavirus , Aichi virus, was not inhibited by treatment with F. septica extracts. F. septica may be a candidate antiviral drug against an enveloped virus such as DENV., Competing Interests: The authors declare there are no competing interests.

Novel therapeutics is urgently needed to prevent cancer-related deaths. MicroRNAs that act as tumor suppressors have been recognized as a next-generation tumor therapy, and the restoration of tumor-suppressive microRNAs using microRNA replacements or mimics may be a less toxic, more effective strategy due to fewer off-target effects. Here, we designed the novel multifunctional oligonucleotide nanocarrier complex composed of a tumor-targeting aptamer sequence specific to mucin 1 (MUC1), poly-cytosine region for fluorescent silver nanocluster (AgNC) synthesis, and complimentary sequence for microRNA miR-34a loading. MiR-34a was employed because of its therapeutic effect of inhibiting oncogene expression and inducing apoptosis in carcinomas. By monitoring the intrinsic fluorescence of AgNC, it was clearly shown that the constructed complex (MUC1-AgNC m -miR-34a) enters MCF-7 cells. To evaluate the efficacy of this nanocarrier for microRNA delivery, we investigated the gene and protein expression levels of downstream miR-34a targets (BCL-2, CDK6, and CCND1) by quantitative PCR and western blotting, respectively, and the results indicated their effective inhibition by miR-34a. This novel multifunctional AgNC-based nanocarrier can aid in improving the efficacy of breast cancer theranostics., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Purpose: Glass fibers were introduced to increase the fracture resistance of resin-based composites restorations; however, the poor polymerization between fibers and resin-based composite were sometimes noted and can cause debonding and failure. The purpose of this study was to investigate the effects of different polymerization methods as well as fiber types on the mechanical behavior of fiber-reinforced resin-based composites., Materials and Methods: Seventy-five specimens were fabricated and divided into one control group and four experimental groups (n = 15), according to the type of glass fiber (strip or mesh) and polymerization methods (one- or two-step). A 0.2-mm-thick fiber layer was fabricated with different polymerization methods, on top of which a 1.8 mm resin-based composite layer was added to make a bar-shape specimen, followed by a final polymerization. Specimens were tested for flexural strength and flexural modulus. The failure modes of specimens were observed by scanning electron microscopy., Results: The fiber types showed significant effect on the flexural strength of test specimens (F = 469.48, p < 0.05), but the polymerization methods had no significant effect (F = 0.05, p = 0.82). The interaction between these two variables was not significant (F = 1.73, p = 0.19). In addition, both fiber type (F = 9.71, p < 0.05) and polymerization method (F = 12.17, p < 0.05) affected the flexural modulus of test specimens; however, the interaction between these two variables was not significant (F = 0.40, p = 0.53)., Conclusions: The strip fibers showed better mechanical behavior than mesh fibers and were suggested for resin-based composites restorations reinforcement; however, different polymerization methods did not have a significant effect on the strength and failure mode of fiber-reinforced resin-based composites., (© 2017 by the American College of Prosthodontists.)

Massive bleeding is the leading cause of battlefield-related deaths and the second leading cause of deaths in civilian trauma centers. One of the challenges of managing severe wounds is the need to promote hemostasis as quickly as possible, which can be achieved by using hemostatic dressings. In this study, we fabricated 2 kinds of gelatin/polycaprolactone composites with 2 ratios of gelatin/polycaprolactone, 1:1 and 2:1 (GP11 and GP21, respectively). Scanning electron microscopy revealed that the GP11 composite exhibited rougher and more porous structure than the GP21 composite did. Furthermore, both composites showed similar biocompatibility as that of tissue culture polystyrene. Moreover, both GP composites tended to show a gradual decrease in contact angle to zero within 40 minutes. The in vitro blood plasma coagulation assay revealed that the prothrombin time was significantly longer for the GP composites than it was for the Quikclot composite, whereas the activated partial thromboplastin time of the GP11 composite was significantly shorter than that of the gauze. Furthermore, the GP11 had the largest platelet adsorption of all the composites. The in vivo coagulation test showed an obvious shortening of the bleeding time with the Quikclot and GP21 compared with gauze sample. In conclusion, the GP composites showed superior biocompatibility and hemostasis to the gauze and comparable effects with the Qickclot composite. Therefore, the GP composites have the potential for development as biodegradable surgical hemostatic agents.

Spongelike porous silica nanosheets, with nanometer thicknesses and pores whose diameters are on the hundreds-of-nanometers scale, have been used as a novel carrier for molecular immobilization of different guests. Enhanced properties of encapsulation were shown for drug molecules of different dimensions due to "softness" caused by the specific nanometric features of the porous structure. The encapsulating effect of the structure results in sustained and stimuli-responsive release behavior of immobilized guest molecules. By studying the adsorption process of DNA molecules on spongelike porous nanosheets or on solid nanoparticles by use of a quartz crystal microbalance, we show that better elasticity of surfaces of the porous nanosheets over that of solid nanoparticles can improve the immobilization of guest molecules. The coating of porous silica nanosheets onto various substrates was also found to effectively mediate DNA delivery to mammalian cells.

To evaluate the associations between exposure to arsenic in drinking water and the progression of chronic kidney disease (CKD), we conducted a study in Taiwan. We recruited 8854 participants from a nationwide health screening program from 2000 to 2009 who were at least 20 years old and had two checkups in a 24-month period with at least 12 months apart. We defined CKD as having an estimated glomerular filtration rate (eGFR)<90ml/min/1.73m 2 or renal dysfunction demonstrated by proteinuria and a rapid progression of CKD as a decline in eGFR>5ml/min/1.73m 2 /year. Arsenic levels were assessed on the basis of a governmental nationwide survey. Of the 8854 participants, 1341 exhibited rapid progression. Participants who lived in areas with arsenic levels≥50μg/L had a higher risk of rapid progression, with an odds ratio of 1.22 (95% confidence interval: 1.05-1.42, p<0.01) after adjusting for hypertension, diabetes mellitus, proteinuria, and anemia. The results showed that a high arsenic level in drinking water was a risk factor for rapid progression of CKD, independent of most of the documented risk factors. Screening and intervention programs should be implemented in endemic areas of exposure to reduce the risk., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Epidemiological studies based on the "hygiene hypothesis" declare that the level of childhood exposure to environmental microbial products is inversely related to the incidence of allergic diseases in later life. Multiple types of immune cell-mediated immune regulation networks support the hygiene hypothesis. Epithelial cells are the first line of response to microbial products in the environment and bridge the innate and adaptive immune systems; however, their role in the hygiene hypothesis is unknown. To demonstrate the hygiene hypothesis in airway epithelial cells, we examined the effect of lipopolysaccharide (LPS; toll-like receptor 4 ligand) on the expression of the proallergic cytokines thymic stromal lymphopoietin (TSLP) and interleukin 33 (IL33) in H292 cells (pulmonary mucoepidermoid carcinoma cells). Stimulation with the TLR ligand polyI:C and human parechovirus type 1 (HPeV1) but not LPS-induced TSLP and IL33 through interferon regulatory factor 3 (IRF3) and NF-κB activity, which was further validated by using inhibitors (dexamethasone and Bay 11-7082) and short hairpin RNA-mediated gene knockdown. Importantly, polyI:C and HPeV1-stimulated TSLP and IL33 induction was reduced by LPS treatment by attenuating TANK-binding kinase 1, IRF3, and NF-κB activation. Interestingly, the basal mRNA levels of TLR signaling proteins were downregulated with long-term LPS treatment of H292 cells, which suggests that such long-term exposure modulates the expression of innate immunity signaling molecules in airway epithelial cells to mitigate the allergic response. In contrast to the effects of LPS treatment, the alarmin high-mobility group protein B1 acts in synergy with polyI:C to promote TSLP and IL33 expression. Our data support part of the hygiene hypothesis in airway epithelia cells in vitro . In addition to therapeutic targeting of TSLP and IL33, local application of non-pathogenic LPS may be a rational strategy to prevent allergies.

Gene delivery into cells can be facilitated by adding plasmid DNA/transfection reagent complexes in culture medium or pre-adsorbing the complexes on the substrate before cell seeding. Using transfection reagents, however, often causes cytotoxicity. Effective delivery of naked plasmid without any transfection reagent remains a challenge. In this study, we cultured human umbilical cord derived mesenchymal stem cells (hMSCs) on different biomaterial substrates with different physico-chemical properties and examined the transfectability of naked plasmid. Specifically, we synthesized a negatively charged polyurethane (PU) to mimic the hyaluronan-modified chitosan (CS-HA) membranes previously found to promote the transfection of naked plasmid. We observed that the PU membranes were as effective as CS-HA membranes in substrate-mediated delivery of naked plasmid into hMSCs. PU membranes with surface microgrooves further increased the gene delivery efficiency to a similar level as the commercial transfection reagent but without the harmful effect. The gene delivery efficiency was associated with the extent of activation of cellular integrins β1 and α5 on different substrates. Moreover, the delivery efficiency was positively correlated with the cell migration rate on various substrates. The substrate-mediated gene delivery by synthetic polymeric substrates supports that integrin activation and cell behavior (e.g. migration and transfectability) changes can be modulated by synthetic polymer surface with microfeatures. The transfection by PU microgrooves is easy, nontoxic, and as effective as the commercial transfection reagent., (Copyright © 2015 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.)