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In this paper, we demonstrate a molecular system for the first active self-assembly linear DNA polymer that exhibits programmable molecular exponential growth in real time, also the first to implement "internal" parallel insertion that does not rely on adding successive layers to "external" edges for growth. Approaches like this can produce enhanced exponential growth behavior that is less limited by volume and external surface interference, for an early step toward efficiently building two and three dimensional shapes in logarithmic time. We experimentally demonstrate the division of these polymers via the addition of a single DNA complex that competes with the insertion mechanism and results in the exponential growth of a population of polymers per unit time. In the supplementary material, we note that an "extension" beyond conventional Turing machine theory is needed to theoretically analyze exponential growth itself in programmable physical systems. Sequential physical Turing Machines that run a roughly constant number of Turing steps per unit time cannot achieve an exponential growth of structure per time. In contrast, the "active" self-assembly model in this paper, computationally equivalent to a Push-Down Automaton, is exponentially fast when implemented in molecules, but is taxonomically less powerful than a Turing machine. In this sense, a physical Push-Down Automaton can be more powerful than a sequential physical Turing Machine, even though the Turing Machine can compute any computable function. A need for an "extended" computational/physical theory arises, described in the supplementary material section S1.
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Background: Resveratrol, a natural antioxidant polyphenol, has the functions of anti-inflammation, anti-cancer, liver protection and cardioprotection. Microorganism biotransformation-produced resveratrol (MBR) product shows higher purity than the natural source of resveratrol and costs less than the chemically synthesized resveratrol. The aim of the present study was to investigate the protective effects of MBR in hamsters treated with a high-fat diet (HFD). Methods: MBR was obtained by the fermentative process of piceid. Hamsters were randomly divided into four groups: HFD plus oral administration of MBR 0 (C), 5 (L), 20 (M) or 50 mg/kg (H), respectively. After six-week of treatment, hamsters were sacrificed, and tissues were collected for further analysis. Results: MBR at these three dosages did not influence the appetite or growth of the hamsters. Liver enzymes, blood glucose, total cholesterol, triglyceride, and liver weight were significantly reduced in the MBR groups than in the control group. Additionally, high-density lipoprotein-cholesterol (HDL-C) was also elevated in all MBR groups. On the other hand, serum low-density lipoprotein-cholesterol (LDL-C) was decreased in the MBR groups. Triglyceride (TG) in liver tissue and fatty liver level were lower in group H. Memory-associated proteins, phosphorylation of calmodulin-dependent protein kinase II (p-CaMK II) and synaptophysin (SYP), were increased in the brains of MBR groups. Conclusion: The high yield- and short procedure-produced MBR has the potential to protect animals fed with HFD from hyperlipidemia, hepatic steatosis, hyperglycemia, and synaptic impairment, which might be beneficial for patients with these types of diseases.
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Hígado Graso , Hiperlipidemias , Animales , Antioxidantes/farmacología , Biotransformación , Glucemia/metabolismo , Proteína Quinasa Tipo 2 Dependiente de Calcio Calmodulina/metabolismo , Proteína Quinasa Tipo 2 Dependiente de Calcio Calmodulina/farmacología , HDL-Colesterol , LDL-Colesterol , Cricetinae , Dieta Alta en Grasa/efectos adversos , Hígado Graso/tratamiento farmacológico , Hígado Graso/etiología , Hígado Graso/metabolismo , Hiperlipidemias/tratamiento farmacológico , Hiperlipidemias/etiología , Hígado , Polifenoles/metabolismo , Polifenoles/farmacología , Resveratrol/farmacología , Sinaptofisina/metabolismo , TriglicéridosRESUMEN
Long-term data of fish assemblages collected in the rocky intertidal zone provides a valuable resource for elucidating the temporal variations in species diversity and intertidal ecosystems. In this study, we describe a long-term time-series dataset of fish collected by counting the number of anesthetized fish at sampling stations in the rocky tidepools on the southern coast of Taiwan. The species assemblages were monitored seasonally at the two stations for 16 y (2000-2008 and 2012-2018). In total, 86 samples containing 5137 individuals belonging to 82 species were recorded. Our data can be used for elucidating the temporal variations in fish assemblages and intertidal ecosystems and as background information for the resilience of the fish community conservation in coastal areas. The current study presents valuable data for researchers to understand the temporal and spatial variations in species abundance, richness, diversity, and composition in relation to climate change, environmental factors, and human activities.
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Ecosistema , Peces , Animales , Humanos , Biodiversidad , Cambio Climático , Taiwán , Factores de TiempoRESUMEN
BACKGROUND: Lineage plasticity in prostate cancer (PCa) has emerged as an important mechanism leading to the onset of therapy- and castration-resistant PCa (t-CRPC), which is closely associated with cancer stem cell (CSC) activity. This study is to identify critical driver(s) with mechanism of action and explore new targeting strategy. METHODS: Various PCa cell lines with different genetic manipulations were subjected to in vitro prostasphere assay, cell viability assay and in vivo stemness potential. In addition, bioinformatic analyses such as Ingenuity pathway and Gene Set Enrichment Analysis were carried out to determine clinical relevance. The in vivo anti-tumour activity of JAK or STAT1 inhibitors was examined in clinically relevant t-CRPC model. RESULTS: We demonstrated the role of interferon-related signalling pathway in promoting PCa stemness, which correlated with significant elevation of interferon related DNA damage resistance signature genes in metastatic PCa. Inhibition of JAK-STAT1 signalling suppresses the in vitro and in vivo CSC capabilities. Mechanistically, IFIT5, a unique downstream effector of JAK-STAT1 pathway, can facilitate the acquisition of stemness properties in PCa by accelerating the turnover of specific microRNAs (such as miR-128 and -101) that can target several CSC genes (such as BMI1, NANOG, and SOX2). Consistently, knocking down IFIT5 in t-CRPC cell can significantly reduce in vitro prostasphere formation as well as decrease in vivo tumour initiating capability. CONCLUSIONS: This study provides a critical role of STAT1-IFIT5 in the acquisition of PCSC and highlights clinical translation of JAK or STAT1 inhibitors to prevent the outgrowth of t-CRPC.
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MicroARNs , Neoplasias de la Próstata Resistentes a la Castración , Humanos , Interferones , Quinasas Janus/metabolismo , Masculino , Neoplasias de la Próstata Resistentes a la Castración/tratamiento farmacológico , Neoplasias de la Próstata Resistentes a la Castración/genética , Neoplasias de la Próstata Resistentes a la Castración/patología , Factores de Transcripción STAT/metabolismo , Transducción de SeñalRESUMEN
Cobalt-doped carbon nitride frameworks (CoNC) were prepared from the calcination of Co-chelated aromatic polyimines (APIM) synthesized from stepwise polymerization of p-phenylene diamine (PDA) and o-phthalaldehyde (OPAl) via Schiff base reactions in the presence of cobalt (II) chloride. The Co-chelated APIM (Co-APIM) precursor converted to CoNC after calcination in two-step heating with the second step performed at 100 °C lower than the first one. The CoNCs demonstrated that its Co, N-co-doped carbonaceous framework contained both graphene and carbon nanotube, as characterized by X-ray diffraction pattern, Raman spectra, and TEM micropictures. CoNCs also revealed a significant ORR peak in the current-voltage polarization cycle and a higher O2 reduction current than that of commercial Pt/C in a linear scanning voltage test in O2-saturated KOH(aq). The calculated e-transferred number even reaches 3.94 in KOH(aq) for the CoNC1000A900 cathode catalyst, which has the highest BET surface area of 393.94 m2 g-1. Single cells of anion exchange membrane fuel cells (AEMFCs) are fabricated using different CoNCs as the cathode catalysts, and CoNC1000A900 demonstrates a peak power density of 374.3 compared to the 334.7 mW cm-2 obtained from the single cell using Pt/C as the cathode catalyst.
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BACKGROUND: One new type of acupuncture and related techniques (ACNRT) is increasingly used by rheumatoid arthritis (RA) patients to control their disease and improve their quality of life. However, the efficacy of using ACNRT in combination with western medicine (WM) for this purpose remains unknown. METHODS: Randomized controlled trials of ACNRT and WM treatments for RA from January 1, 2000, to January 31, 2021, were searched for in the databases PubMed, Embase, Medline, and the Cochrane Central Register of Controlled Trials, as well as in three Chinese databases: China National Knowledge Infrastructure, Wanfang Data, and Airiti Library. The primary outcomes consisted of inflammatory markers including C reactive protein (CRP), erythrocyte sedimentation rate (ESR), and rheumatoid factor. The secondary outcomes were clinical characteristics including pain visual analog scale (VAS) score, Disease Activity Score (DAS-28), swollen joints count (SJC), tender joints count (TJC), morning stiffness, and the results of a health assessment questionnaire. The three types of ACNRT used in the focal trials were acupuncture, moxibustion, and electro-acupuncture. Two qualified researchers extracted data from these trials' results and independently assessed their risk of bias. Statistical analyses were performed using Comprehensive Meta-Analysis V3 software. RESULTS: A total of 12 RCTs with 874 patients met the inclusion criteria. As compared with the patients who received WM treatment alone, those who were given integrated ACNRT/WM treatment showed greater reductions in CRP (weighted mean difference [WMD]: -6.299; 95% CI: -9.082 to -3.517), ESR (WMD: -6.563; 95% CI: -8.604 to -4.522), VAS (WMD: -1.089; 95% CI: -1.575 to -0.602), DAS-28 (WMD: -0.633; 95% CI: -1.006 to -0.259), SJC (WMD: -1.921; 95% CI: -3.635 to -0.207), and TJC (WMD: -1.491; 95% CI: -2.941 to -0.042). CONCLUSION: This meta-analysis of RA provides reliable evidence in favor of ACNRT plus WM. However, longer term, high-quality, repeatable, multicenter randomized controlled trials with larger sample sizes are needed.
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Terapia por Acupuntura , Artritis Reumatoide , Terapia por Acupuntura/métodos , Artritis Reumatoide/terapia , Sedimentación Sanguínea , Proteína C-Reactiva/análisis , Humanos , Estudios Multicéntricos como Asunto , Calidad de VidaRESUMEN
The hydrophilic initiator potassium persulfate (KPS) was converted into a hydrophobic molecule by complexing with cetyltrimethylammonium bromide (CTAB) at both ends of the molecule (CTAPSu). Inverse emulsion polymerization thus proceeded inside micelles dispersed in the affluent toluene with CTAPSu as the initiator. Polyaniline (PANI) formed inside the micelles and entangled with Fe3O4 nanoparticles already esterified with oleic acid (OA). Iron composites consisted of OA-esterified Fe3O4 nanoparticles covered with PANI after de-emulsification. After calcination at 950 °C in an argon atmosphere, the resultant iron compound was a mixture of α-Fe (ferrite) and Fe3C (cementite), as determined by X-ray diffraction. Eventually, the calcined iron compounds (mixtures) demonstrated superparamagnetic properties with a high saturation magnetization (Ms) of 197 emu/g, which decayed to 160 emu/g after exposure to the atmosphere for four months.
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Oleic acid (OA)-modified Fe3O4 nanoparticles were successfully covered with polyanilines (PANIs) via inverse suspension polymerization in accordance with SEM and TEM micrographs. The obtained nanoparticles were able to develop into a ferrite (α-Fe) and αâ³-Fe16N2 mixture with a superparamagnetic property and high saturated magnetization (SM) of 245 emu g-1 at 950 °C calcination under the protection of carbonization materials (calcined PANI) and other iron-compounds (αâ³-Fe16N2). The SM of the calcined iron-composites slightly decreases to 232 emu g-1 after staying in the open air for 3 months. The calcined mixture composite can be ground into homogeneous powders without the segregation of the iron and carbon phases in the mortar without significantly losing magnetic activities.
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Epimedium, is used traditionally in Chinese medicine to treat infertility problems. In this study, we establish the cell model to elucidate the protective effect of epimedium against ES by analyzing the molecular relationship between mitochondrial dynamics and steroidogenesis and to explore the molecular mechanism focusing on mitochondria function relating to fertility. ES induced ROS accumulation in mitochondria and the epimedium treatment significantly reduced the ROS accumulation. Furthermore, mitochondria morphology was restored to elongated shape following epimedium treatment. Epimedium treatment promoted dynamin-associated protein 1 (Drp1)-mediated steroidogenesis pathway by upregulating PKA, CREB, Drp1, and StAR protein expression in response to ES exposure in Leydig cells. Moreover, it was also identified that, CREB plays an important role in epimedium activation in Drp1-mediated steroidogenesis signaling pathway by increasing, phospho-CREB expression in nucleus. Testosterone level is decreased in ES-exposed cells; however, the testosterone level was increased after epimedium treatment. In conclusion, epimedium treatment improved mitochondria function in ES-exposed Leydig cells and activated downstream Drp1-dependent steroidogenesis by CREB mediated signaling pathway.
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Epimedium , Dinámicas Mitocondriales , Dinaminas , Endosulfano , Humanos , Células Intersticiales del Testículo , Masculino , FosfoproteínasRESUMEN
Skin pigmentation is resulted from several processes, such as melanin synthesis transportation and abnormal melanin accumulation in keratinocytes. Various studies have suggested that seven traditional Chinese herbal extracts from Atractylodes macrocephala, Paeonia lactiflora, Bletilla striata, Poria cocos, Dictamnus dasycarpus, Ampelopsis japonica and Tribulus terrestris (which we collectively named ChiBai), show several protective effects toward skin-related diseases. Lactobacillus rhamnosus, a lactic acid bacterium, has been reported to treat skin inflammation and atopic dermatitis. In this study, the broth produced by the cofermentation of ChiBai with Lactobacillus rhamnosus was studied for its effects on skin pigmentation through in vitro and in vitro experiments. In the in vitro experiments, we found that the fermented broth of ChiBai (FB-ChiBai) suppressed alpha-melanocyte stimulating hormone (α-MSH)-induced melanogenesis in B16F0 murine melanoma cells without any cytotoxicity at a concentration of 0.5%. FB-ChiBai significantly attenuated melanin production, tyrosinase activities and melanogenesis-related signaling pathways. Treatment with FB-ChiBai also reduced the nuclear translocation and promoter binding activities of MITF. In the in vivo experiments, FB-ChiBai was topically applied to the dorsal skin of C57BL/6J nude mice and concurrently irradiated with UVB, three times a week for 8 weeks. The results indicated that FB-ChiBai alleviated UVB-induced hyperpigmentation by reducing epidermal hyperplasia and inhibiting the CREB/MITF/tyrosinase pathway. In conclusion, our data indicated that the anti-melanogenic effects of FB-ChiBai are mediated by the inhibition of CREB/MITF/tyrosinase signaling pathway. The findings suggest that FB-ChiBai can protect against UV-B irradiation and that it might be used as an agent in cosmetic products to protect against UVB-induced hyperpigmentation.
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Medicamentos Herbarios Chinos/farmacología , Lacticaseibacillus rhamnosus/metabolismo , Monofenol Monooxigenasa/metabolismo , Pigmentación de la Piel/efectos de los fármacos , Rayos Ultravioleta , Animales , Línea Celular Tumoral , Supervivencia Celular/efectos de los fármacos , Supervivencia Celular/efectos de la radiación , Medicamentos Herbarios Chinos/metabolismo , Fermentación , Humanos , Melaninas/biosíntesis , Ratones , Ratones Endogámicos C57BL , Ratones Desnudos , Factor de Transcripción Asociado a Microftalmía/metabolismo , Transducción de Señal , Piel/efectos de los fármacos , Piel/metabolismo , Piel/patología , Piel/efectos de la radiación , Pigmentación de la Piel/efectos de la radiación , alfa-MSH/antagonistas & inhibidoresRESUMEN
Ultraviolet (UV) irradiation is a crucial factor that leads to skin photoaging and results in increased DNA damage, oxidative stress, and collagen degradation. Jasmine flowers have been utilized as a traditional medicine in Asia to treat various diseases, including dermatitis, diarrhea, and fever. Furthermore, the fermented broth of Lactobacillus rhamnosus has been reported to exert protective effects on the skin. In the present study, jasmine flower extract was fermented with L. rhamnosus. We investigated the antioxidant and collagen-promoting effects on UVB/H2 O2 -induced HS68 dermal fibroblast cell damage. The results indicated that treatment with the fermented flower extracts of Jasminum sambac (F-FEJS) could enhance the viability of HS68 cells. Furthermore, the UVB/H2 O2 -induced excessive production of reactive oxygen species, degradation of collagen, activation of MAPKs, including P38, ERK, and JNK, and premature senescence were remarkably attenuated by F-FEJS in dermal fibroblast cells. The nuclear accumulation of p-c-jun, which is downstream of MAPK, and the inactivation of p-smad2/3, which is one of the crucial transcription factors that enhance collagen synthesis, were reversed in response to F-FEJS treatment in UVB/H2 O2 -exposed cells. Notably, the expression of antioxidant genes, such as HO-1, and the nuclear translocation of Nrf2 were further enhanced by F-FEJS in UVB/H2 O2 -treated cells. Interestingly, the F-FEJS-induced increase in ARE luciferase activity indicated the activation of Nrf2/ARE signaling. In conclusion, our findings demonstrated that F-FEJS can effectively ameliorate UVB/H2 O2 -induced dermal cell aging and may be considered a promising ingredient in skin aging therapy.
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Antioxidantes/farmacología , Senescencia Celular , Fibroblastos/efectos de los fármacos , Jasminum/química , Lacticaseibacillus rhamnosus/metabolismo , Extractos Vegetales/farmacología , Antioxidantes/aislamiento & purificación , Antioxidantes/metabolismo , Línea Celular , Senescencia Celular/efectos de los fármacos , Senescencia Celular/efectos de la radiación , Fermentación , Fibroblastos/metabolismo , Fibroblastos/efectos de la radiación , Flores/química , Humanos , Peróxido de Hidrógeno/toxicidad , Extractos Vegetales/aislamiento & purificación , Extractos Vegetales/metabolismo , Especies Reactivas de Oxígeno/metabolismo , Transducción de Señal , Envejecimiento de la Piel/efectos de los fármacos , Envejecimiento de la Piel/efectos de la radiación , Rayos UltravioletaRESUMEN
Nonalcoholic fatty liver disease (NAFLD) is considered to be a serious clinical complication, which could cause significant liver dysfunction including fibrosis, cirrhosis, and cancer. Obesity could lead to NAFLD and contributes to liver disorder and related complicated liver diseases. Effect of exercise combined with alcalase treatment derived potato protein hydrolysate (APPH) on high-fat diet (HFD)-induced hepatic injury was investigated in senescence accelerated mouse-prone 8 (SAMP8) mice in the present study. Mice were divided into six groups (n = 6): Group I-Control, Group II-HFD, Group III-Exercise, Group IV-HFD + APPH, Group V-HFD + Exercise, and Group VI-HFD + Exercise + APPH. Combined APPH treatment and exercise offer better cytoprotection in HFD-induced histological changes than APPH treatment and exercise alone. Further, APPH and exercise activate the cell survival proteins PI3K/Akt and prevent FasL/FADD-mediated apoptosis in HFD fed SAMP8 mouse. APPH with swimming exercise effectively modulate HFD-induced liver damage and apoptosis in aged mice through activation of PI3K/Akt protein. PRACTICAL APPLICATIONS: Exercise training is proven to reduce the health problems associated with aging and obesity, however, intensity and duration of the exercise differs between individuals. We used integrated pharmacological and nonpharmacological approach as a therapeutic strategy for preventing HFD-induced hepatic injury in aged subjects.
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Dieta Alta en Grasa , Solanum tuberosum , Animales , Apoptosis , Dieta Alta en Grasa/efectos adversos , Hepatocitos , Ratones , Fosfatidilinositol 3-Quinasas , Hidrolisados de Proteína , NataciónRESUMEN
The assemblage of fish species in the rocky intertidal zone is highly affected by the destructive impact of human activities and has an extended impact on land-sea interactions. There are a few long-term research projects that have focused on rocky intertidal ecosystems, especially on the resident fish community. Here, we describe a long-term time series dataset of fish collected by counting the number of anesthetized fishes at sampling stations in rocky tidepools in the intertidal zones on the northern coast of Taiwan. The species assemblages were monitored seasonally at three stations from 1999 to 2018. In total, 144 samples containing 1,577 individuals belonging to 106 species were recorded in the surveys. The resulting data can be used as background information for conservation and resilience studies of the fish community in coastal areas and to establish reasonable conservation strategies. This study presents valuable data to ecologists and fisheries biologists interested in understanding the temporal patterns of species abundance, richness, and composition in relation to environmental factors, climate change, and anthropogenic pressures.
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Conservación de los Recursos Naturales , Ecosistema , Peces/clasificación , Animales , Cambio Climático , Ambiente , TaiwánRESUMEN
[This corrects the article DOI: 10.2196/ijmr.7176.].
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This is the fourth and final study designed to develop International Classification of Functioning, Disability and Health (ICF, and children and youth version, ICF-CY) core sets for attention-deficit hyperactivity disorder (ADHD). To investigate aspects of functioning and environment of individuals with ADHD as documented by the ICF-CY in clinical practice settings. An international cross-sectional multi-centre study was applied, involving nine units from eight countries: Denmark, Germany, India, Italy, Portugal, Saudi Arabia, Sweden and Taiwan. Clinicians and clinical researchers rated the functioning level of 112 children, adolescents and adults with ADHD using the extended ICF-CY checklist version 2.1a. The ratings were based on a variety of information sources, such as medical records, medical history, clinical observations, clinical questionnaires, psychometric tests and structured interviews with participants and family members. In total, 113 ICF-CY categories were identified, of which 50 were related to the activities and participation, 33 to environmental factors and 30 to body functions. The clinical study also yielded strengths related to ADHD, which included temperament and personality functions and recreation and leisure. The study findings endorse the complex nature of ADHD, as evidenced by the many functional and contextual domains impacted in ADHD. ICF-CY based tools can serve as foundation for capturing various functional profiles and environmental facilitators and barriers. The international nature of the ICF-CY makes it possible to develop user-friendly tools that can be applied globally and in multiple settings, ranging from clinical services and policy-making to education and research.
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Trastorno por Déficit de Atención con Hiperactividad/diagnóstico , Clasificación Internacional del Funcionamiento, de la Discapacidad y de la Salud/normas , Psicometría/métodos , Calidad de Vida/psicología , Adolescente , Adulto , Niño , Estudios Transversales , Evaluación de la Discapacidad , Femenino , Humanos , Masculino , Encuestas y Cuestionarios , Adulto JovenRESUMEN
BACKGROUND: Genetic sequencing is critically important to diagnostic health care efforts in the United States today, yet it is still inaccessible to many. Meanwhile, the internet and social networking have made crowdfunding a realistic avenue for individuals and groups hoping to fund medical and research causes, including patients in need of whole exome genetic sequencing (WES). OBJECTIVE: Amplify Hope is an educational program designed to investigate what factors affect the success of medical crowdfunding campaigns. We conducted a needs assessment, a series of 25 interviews concerning crowdfunding, and provided training on best practices identified through our assessment for 11 individuals hoping to run their medical crowdfunding campaigns to raise money for patients to access trio WES to identify the mutated proteins that caused their apparent inherited disease. METHODS: The crowdfunding education was given in a 30-day training period with resources such as webinars, fact sheets and a crowdfunding training guide emailed to each participant. All campaigns were launched on the same date and were given 30 days to raise the same goal amount of US $5000. Reviewing the 4 crowdfunding campaigns that raised the goal amount within the 30-day period, we sought to identify features that made the 4 crowdfunding campaigns successful. In addition, we sought to assess which factors the resulting 75 donors report as influencing their decision to donate to a campaign. Finally, we investigated whether crowdfunding campaigns for exome sequencing had an impact on increasing applicant's and donors' knowledge of genomics. RESULTS: Of the 86 study inquiries, 11 participants submitted the required forms and launched their crowdfunding campaigns. A total of 4 of the 11 campaigns raised their goal amounts within 30 days. CONCLUSIONS: We found that social media played an important role in all campaigns. Specifically, a strong social media network, an active outreach process to networks, as well as engagement within the study all correlated with a higher success rate. Amplify Hope donors were more likely to support projects that were near their fundraising goals, and they found video far more effective for learning about genomics than any other medium.
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3D bioprinting is a technique which enables the direct printing of biodegradable materials with cells into 3D tissue. So far there is no cell reprogramming in situ performed with the 3D bioprinting process. Forkhead box D3 (FoxD3) is a transcription factor and neural crest marker, which was reported to reprogram human fibroblasts into neural crest stem-like cells. In this study, we synthesized a new biodegradable thermo-responsive waterborne polyurethane (PU) gel as a bioink. FoxD3 plasmids and human fibroblasts were co-extruded with the PU hydrogel through the syringe needle tip for cell reprogramming. The rheological properties of the PU hydrogel including the modulus, gelation time, and shear thinning were optimized for the transfection effect of FoxD3 in situ. The corresponding shear rate and shear stress were examined. Results showed that human fibroblasts could be reprogrammed into neural crest stem-like cells with high cell viability during the extrusion process under an average shear stress â¼190â¯Pa. We further translated the method to the extrusion-based 3D bioprinting, and demonstrated that human fibroblasts co-printed with FoxD3 in the thermo-responsive PU hydrogel could be reprogrammed and differentiated into a neural-tissue like construct at 14â¯days after induction. The neural-like tissue construct produced by 3D bioprinting from human fibroblasts may be applied to personalized drug screening or neuroregeneration. STATEMENT OF SIGNIFICANCE: There is no study so far on cell reprogramming in situ with 3D bioprinting. In this manuscript, a new thermoresponsive polyurethane bioink was developed and employed to deliver FoxD3 plasmid into human fibroblasts by the extrusion-based bioprinting. When the polyurethane gel was extruded through the syringe tip, the shear stress generated may have caused the transient membrane permeability for transfection. The shear stress was optimized for transfection in situ by 3D bioprinting. We demonstrated that human fibroblasts could be reprogrammed into neural crest-like stem cells by 3D bioprinting with the gel, and the reprogrammed cells underwent neural differentiation in the printed structure after induction. The neural-like tissue engineering constructs fabricated by 3D bioprinting from human fibroblasts may be applied for neuroregeneration or further developed as mini-brain for basic research and drug screening.
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Bioimpresión , Reprogramación Celular , Fibroblastos/metabolismo , Hidrogeles/química , Neuronas/metabolismo , Poliuretanos/química , Impresión Tridimensional , Adulto , Técnicas de Reprogramación Celular , Fibroblastos/citología , Humanos , Masculino , Neuronas/citologíaRESUMEN
In this study, a rat carotid balloon injury-animal model was used to elucidate the temporal relation of hypertrophy in the progression of cardiac damage and the role of insulin-like growth factor (IGF)-I survival pathway on course of the cardiac damage. Rats were subjected to carotid balloon-injury and examined at different time points. We further studied the heart-weight/body-weight-ratio, histology and protein expression to understand the pathological events associated with percutaneous transluminal coronary angioplasty (PTCA) induced damages. Protein expression analysis showed increased levels of IGF-I signaling pathway and mitogen-activated protein kinase (MAPK) signaling pathway after 2 h and after 2 d of carotid balloon injury. On the other hand, apoptosis signaling pathways were enhanced after 14 d of carotid balloon injury. According to the results, rat carotid balloon injury significantly induced IGF-I survival signaling and compensated hypertrophy pathway during the initial period of injury however after 14 d the proteins involved in apoptotic cell death were elevated and the proteins of the survival pathway and compensatory hypertrophy were significantly reduced.
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Apoptosis/fisiología , Arterias Carótidas/metabolismo , Factor I del Crecimiento Similar a la Insulina/metabolismo , Transducción de Señal/fisiología , Animales , Corazón/fisiología , Hipertrofia/metabolismo , Masculino , Proteínas Quinasas Activadas por Mitógenos/metabolismo , Proteínas/metabolismo , Ratas , Ratas WistarRESUMEN
We have developed a simple route for the preparation of aminophenylboronic acid polymer nanoparticles (APB PNs) from 3-aminophenylboronic acid and formaldehyde under alkaline conditions according to an extended StÓ§ber method. Insulin and R6G have been selected to prepare functional insulin-APB PNs and R6G-APB PNs, respectively. During the formation of APB PNs, the representative molecules are embedded inside the APB PNs. Through specific binding of glucose with boronic acid moieties on the R6G-APB PNs and insulin-APB PNs, glucose induces expansion of the APB PNs, leading to release of R6G and insulin molecules, respectively. As a result of release of R6G molecules, the fluorescence intensity of R6G-APB PN solution increases, allowing quantitation of glucose in PBS solutions (10 mM, pH 7.4) with a linear range over 0-10 mM. Release of insulin from insulin-APB PNs is significant and rapid when the glucose concentration is higher than 7 mM. Having advantages of low cost, simple preparation, biocompatibility, and continuous response to glucose, the insulin-APB PNs hold great potential as an alternative for treating diabetic patients. Graphical Abstract Quantitation of glucose and release of insulin by glucose responsive 3-aminophenylboronic acid polymer nanoparticles.
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Glucemia/análisis , Ácidos Borónicos/química , Colorantes Fluorescentes/química , Insulina/análisis , Nanopartículas/química , Rodaminas/química , Adulto , Femenino , Humanos , Insulina/administración & dosificación , Nanopartículas/ultraestructura , Espectrometría de Fluorescencia/métodosRESUMEN
INTRODUCTION: Denial of smoking status by pregnant women presents a missed opportunity for referral to smoking cessation programmes that are shown to be effective in helping them quit smoking. MATERIALS AND METHODS: A cross-sectional epidemiological survey was conducted to detect the true prevalence of active smoking pregnant patients and the accuracy of self-reporting, investigate the sociodemographic risk factors and test the knowledge of pregnant patients on adverse effects of smoking. This involved 972 antenatal patients of a maternity hospital where participants completed a sociodemographic data survey and answered a knowledge questionnaire. Urine cotinine testing was carried out after informed consent. RESULTS: The prevalence of active smokers was 5.2% (n = 50) with 3% (n = 29) being light smokers and 2.2% (n = 21) being heavy smokers. This was significantly higher than self-reported active smoking status of 3.7% (n = 36; P = 0.02). The Malay race, being aged less than 20 years and not having tertiary level qualifications independently increased the likelihood of being an active smoker. Knowledge of the adverse effects of smoking was generally good with a mean total score of 8.18 out of 10 but there were differences amongst the non-smokers, passive smokers, light smokers and active smokers (P = 0.012). CONCLUSION: While the prevalence of active smoking among pregnant women is low in Singapore compared to other countries, this study substantiated the unreliability of self-reporting of smoking status in the pregnant population which could complicate referral to smoking cessation programmes. The lower awareness of the harms of smoking during pregnancy among smokers highlights a potential area for improvement.