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1.
Science ; 383(6688): 1204-1209, 2024 Mar 15.
Artículo en Inglés | MEDLINE | ID: mdl-38484057

RESUMEN

Thermoelectric cooling technology has important applications for processes such as precise temperature control in intelligent electronics. The bismuth telluride (Bi2Te3)-based coolers currently in use are limited by the scarcity of Te and less-than-ideal cooling capability. We demonstrate how removing lattice vacancies through a grid-design strategy switched PbSe from being useful as a medium-temperature power generator to a thermoelectric cooler. At room temperature, the seven-pair device based on n-type PbSe and p-type SnSe produced a maximum cooling temperature difference of ~73 kelvin, with a single-leg power generation efficiency approaching 11.2%. We attribute our results to a power factor of >52 microwatts per centimeter per square kelvin, which was achieved by boosting carrier mobility. Our demonstration suggests a path for commercial applications of thermoelectric cooling based on Earth-abundant Te-free selenide-based compounds.

2.
Immun Inflamm Dis ; 12(1): e1133, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-38270319

RESUMEN

INTRODUCTION: Children with atopic dermatitis (AD) bear a significant burden of illness that adversely affects their quality of life. OBJECTIVE: To determine the efficacy of dupilumab and topical corticosteroids for the treatment of pediatric AD. METHODS: A comprehensive literature search was conducted using three prominent databases: Web of Science, PubMed, and Embase. Using a fixed-effects or random-effects model, the standard mean difference or risk ratios with 95% confidence intervals were calculated, and the trial protocol was listed as CRD42023408546. RESULTS: A total of 3 studies were included, and 896 participants met the inclusion criteria. The combined estimate showed that dupilumab plus topical corticosteroids had numerically greater efficacy in terms of Eczema Area and Severity Index (EASI)-50, EASI-75, EASI-90, and Investigator Global Assessment (IGA) score of 0 or 1. Children who received topical corticosteroids and dupilumab achieved significantly higher Children's Dermatological Life Quality Index scores compared to those who received placebo. The number of individuals who achieved IGA 0/1 increased with the use of dupilumab and topical corticosteroids. CONCLUSIONS: Dupilumab and topical corticosteroids can be used to treat symptoms in children with AD. However, given the substantial variation in treatment outcomes among studies, the findings should be interpreted with caution.


Asunto(s)
Anticuerpos Monoclonales Humanizados , Dermatitis Atópica , Niño , Humanos , Corticoesteroides/uso terapéutico , Dermatitis Atópica/tratamiento farmacológico , Inmunoglobulina A , Calidad de Vida , Ensayos Clínicos Controlados Aleatorios como Asunto
3.
J Cell Mol Med ; 28(2): e18047, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-37970991

RESUMEN

Proranolol has long been recommended to prevent variceal bleeding in patients with cirrhosis. However, the mechanisms of propranolol in liver fibrosis have not yet been thoroughly elucidated. Autophagic cell death (ACD) of activated hepatic stellate cells (HSCs) is important in the alleviation of liver fibrosis. Our study aims to assess the mechanisms of propranolol regulating HSC ACD and liver fibrosis. ACD of HSCs was investigated using lentivirus transfection. The molecular mechanism was determined using a PCR profiler array. The role of autophagy-related protein 9b (ATG9b) in HSC ACD was detected using co-immunoprecipitation and co-localization of immunofluorescence. Changes in the signalling pathway were detected by the Phospho Explorer antibody microarray. Propranolol induces ACD and apoptosis in HSCs. ATG9b upregulation was detected in propranolol-treated HSCs. ATG9b upregulation promoted ACD of HSCs and alleviated liver fibrosis in vivo. ATG9b enhanced the P62 recruitment to ATG5-ATG12-LC3 compartments and increased the co-localization of P62 with ubiquitinated proteins. The PI3K/AKT/mTOR pathway is responsible for ATG9b-induced ACD in activated HSCs, whereas the p38/JNK pathway is involved in apoptosis. This study provides evidence for ATG9b as a new target gene and propranolol as an agent to alleviate liver fibrosis by regulating ACD of activated HSCs.


Asunto(s)
Muerte Celular Autofágica , Várices Esofágicas y Gástricas , Humanos , Células Estrelladas Hepáticas/metabolismo , Propranolol/farmacología , Propranolol/metabolismo , Regulación hacia Arriba , Fosfatidilinositol 3-Quinasas/metabolismo , Várices Esofágicas y Gástricas/metabolismo , Várices Esofágicas y Gástricas/patología , Hemorragia Gastrointestinal/metabolismo , Hemorragia Gastrointestinal/patología , Cirrosis Hepática/metabolismo , Hígado/metabolismo , Autofagia
4.
J Orthop Surg Res ; 18(1): 967, 2023 Dec 15.
Artículo en Inglés | MEDLINE | ID: mdl-38098039

RESUMEN

BACKGROUND: Eccentric muscle contraction can cause muscle damage, which reduces the efficiency of exercise. Previous evidence suggested that Sodium salicylate (SS) could improve the repair of aged muscle. This study intends to investigate whether SS can impact skeletal muscle damage caused by eccentric exercise. METHODS: Eccentric treadmill exercise was performed to induce muscle damage in mice. Plasma levels of muscle damage markers were estimated. RT-qPCR was employed for detecting mRNA levels of proinflammatory mediators in murine gastrocnemius muscle. Immunofluorescence staining of laminin/DAPI was utilized for quantifying centrally nucleated myofibers in the gastrocnemius muscle. Western blotting was implemented to examine protein levels of mitsugumin 53 (MG53), matrix metalloproteinase (MMP)-2/9, and NF-κB signaling-related markers. RESULTS: SS administration reduced muscle damage marker production in the plasma and decreased the levels of proinflammatory mediators, MG53 and MMP-2/9 in mice after exercise. SS alleviated the severity of muscle damage in the gastrocnemius of mice after eccentric exercise. SS blocked NF-κB signaling pathway in the gastrocnemius muscle. CONCLUSION: SS administration ameliorates skeletal muscle damage caused by eccentric exercise in the mouse model.


Asunto(s)
FN-kappa B , Salicilato de Sodio , Ratones , Animales , FN-kappa B/metabolismo , Salicilato de Sodio/farmacología , Salicilato de Sodio/metabolismo , Transducción de Señal , Músculo Esquelético/metabolismo , Contracción Muscular/fisiología , Proteínas de la Membrana/metabolismo
5.
J Vis Exp ; (198)2023 08 18.
Artículo en Inglés | MEDLINE | ID: mdl-37607101

RESUMEN

A novel in planta gene transformation method was developed for bamboo, which avoids the need for time-consuming and labor-intensive callus induction and regeneration processes. This method involves Agrobacterium-mediated gene expression via wounding and vacuum for bamboo seedlings. It successfully demonstrated the expression of exogenous genes, such as the RUBY reporter and Cas9 gene, in bamboo leaves. The highest transformation efficiency for the accumulation of betalain in RUBY seedlings was achieved using the GV3101 strain, with a percentage of 85.2% after infection. Although the foreign DNA did not integrate into the bamboo genome, the method was efficient in expressing the exogenous genes. Furthermore, a gene editing system has also been developed with a native reporter using this method, from which an in situ mutant generated by the edited bamboo violaxanthin de-epoxidase gene (PeVDE) in bamboo leaves, with a mutation rate of 17.33%. The mutation of PeVDE resulted in decreased non-photochemical quenching (NPQ) values under high light, which can be accurately detected by a fluorometer. This makes the edited PeVDE a potential native reporter for both exogenous and endogenous genes in bamboo. With the reporter of PeVDE, a cinnamoyl-CoA reductase gene was successfully edited with a mutation rate of 8.3%. This operation avoids the process of tissue culture or callus induction, which is quick and efficient for expressing exogenous genes and endogenous gene editing in bamboo. This method can improve the efficiency of gene function verification and will help reveal the molecular mechanisms of key metabolic pathways in bamboo.


Asunto(s)
Agrobacterium , Edición Génica , Betalaínas , Técnicas Genéticas , Expresión Génica
6.
Altern Ther Health Med ; 29(5): 320-326, 2023 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-37171944

RESUMEN

Objective: Type 2 diabetes poses significant pain, economic burden, and health risks. This meta-analysis evaluates the efficacy and safety of triple therapy with SGLT-2 inhibitor add-on to DPP-4 inhibitor plus metformin for type 2 diabetes treatment. Methods: A comprehensive search was conducted in PubMed, Embase, and the Cochrane Library to identify randomized controlled trials evaluating the efficacy and safety of triple therapy (SGLT-2 inhibitor + DPP-4 inhibitor + metformin) compared to dual therapy (DPP-4 inhibitor + metformin) in type 2 diabetes. The search covered the period from inception to December 2018. Two reviewers independently screened the literature, extracted data, and assessed study quality. Meta-analysis was performed using RevMan 5.3 software. Results: A total of eight randomized controlled trials were included in this meta-analysis. The results showed that compared to dual therapy with DPP-4 inhibitor add-on to metformin, triple therapy with SGLT-2 inhibitor add-on to DPP-4 inhibitor plus metformin was associated with greater reductions in HbA1c, fasting blood glucose, postprandial blood glucose, body weight, and blood pressure (P < .05). However, the risk of genital tract infection was higher in the triple therapy group (OR = 4.43, 95% CI (2.26, 8.70), P < .0001), while there were no statistically significant differences in the incidence of adverse events, hypoglycemia episodes, urinary tract infection, and fractures between the two groups (P > .05). Conclusions: Based on current evidence, triple therapy was found to significantly improve blood glucose, body weight, and blood pressure when compared to dual therapy. Safety indicators did not show significant differences, except for an increased risk of genital tract infection.


Asunto(s)
Diabetes Mellitus Tipo 2 , Inhibidores de la Dipeptidil-Peptidasa IV , Metformina , Infecciones del Sistema Genital , Inhibidores del Cotransportador de Sodio-Glucosa 2 , Humanos , Glucemia , Peso Corporal , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Diabetes Mellitus Tipo 2/complicaciones , Inhibidores de la Dipeptidil-Peptidasa IV/efectos adversos , Inhibidores de la Dipeptidil-Peptidasa IV/uso terapéutico , Quimioterapia Combinada , Hemoglobina Glucada , Hipoglucemiantes/efectos adversos , Hipoglucemiantes/uso terapéutico , Metformina/efectos adversos , Metformina/uso terapéutico , Infecciones del Sistema Genital/inducido químicamente , Infecciones del Sistema Genital/complicaciones , Inhibidores del Cotransportador de Sodio-Glucosa 2/efectos adversos , Inhibidores del Cotransportador de Sodio-Glucosa 2/uso terapéutico , Resultado del Tratamiento
7.
Int J Biol Macromol ; 240: 124406, 2023 Jun 15.
Artículo en Inglés | MEDLINE | ID: mdl-37060976

RESUMEN

Surgical resection of osteosarcoma is always accompanied by residual metastasis of tumor cells and bone tissue defects. In this work, a novel kind of gelatin/polylactic acid (PLA) coaxial fiber membrane with a shell layer containing doxorubicin-loaded hydroxyapatite (DOX@nHAp) nanoparticles and a core layer containing Icariin (ICA) was developed for antitumor and bone enhancement at the defect site. Physical evaluation displayed that the composite membrane provided moderate hydrophilicity, enhanced tensile strength (Dry: 2-3 MPa, wet: 1-2 MPa) and elasticity (70-100 %), as well as increased specific surface area and pore volume (19.39 m2/g and 0.16 cm3/g). In SBF, DOX@nHAp in the fibers promoted biomineralization on the fiber surface. In in vitro evaluation, approximately 80 % of DOX had a short-term release during the first 8 days, followed by long-term release behavior of ICA for up to 40 days. CCK-8 results confirmed that the membrane could actively support MC3T3-E1 cells proliferation and was conductive to high alkaline phosphatase expression, while the viability of MG-63 cells was effectively inhibited to 50 %. Thus, the dual-loaded fibrous membrane with a coaxial structure and nHAp is a promising system for anticancer and defects reconstruction after osteosarcoma surgery.


Asunto(s)
Gelatina , Osteosarcoma , Humanos , Gelatina/química , Durapatita , Andamios del Tejido/química , Poliésteres/química , Huesos , Doxorrubicina/farmacología , Osteosarcoma/tratamiento farmacológico
8.
ACS Biomater Sci Eng ; 9(4): 1976-1990, 2023 04 10.
Artículo en Inglés | MEDLINE | ID: mdl-36881921

RESUMEN

In this study, we developed a poly(ß-amino ester) (PBAE) hydrogel for the double release of vancomycin (VAN) and total flavonoids of Rhizoma Drynariae (TFRD). VAN was covalently bonded to PBAE polymer chains and was released to enhance the antimicrobial effect first. TFRD chitosan (CS) microspheres were physically dispersed in the scaffold, TFRD was released from the microspheres, and osteogenesis was induced subsequently. The scaffold had good porosity (90.12 ± 3.27%), and the cumulative release rate of the two drugs in PBS (pH 7.4) solution exceeded 80%. In vitro antimicrobial assays demonstrated the antibacterial properties of the scaffold against Staphylococcus aureus (S. aureus) and Escherichia coli (E. coli). Besides these, cell viability assays indicated that the scaffold had good biocompatibility. Moreover, alkaline phosphatase and matrix mineralization were expressed more than in the control group. Overall, cell experiments confirmed that the scaffolds have enhanced osteogenic differentiation capabilities. In conclusion, the dual-drug-loaded scaffold with antibacterial and bone regeneration effects is promising in the field of bone repair.


Asunto(s)
Antiinfecciosos , Osteogénesis , Staphylococcus aureus , Hidrogeles/farmacología , Escherichia coli , Andamios del Tejido/química , Antibacterianos/farmacología , Antibacterianos/química , Vancomicina/farmacología , Vancomicina/química , Antiinfecciosos/farmacología
9.
Plant Methods ; 19(1): 20, 2023 Mar 02.
Artículo en Inglés | MEDLINE | ID: mdl-36864483

RESUMEN

BACKGROUND: Bamboo is a perennial and renewable biomass forest resource and its leaf flavonoid is an antioxidant for biological and pharmacological research. The established genetic transformation and gene editing systems in bamboo are significantly limited by the dependence on bamboo regeneration capability. The way to improve the flavonoid content in bamboo leaves through biotechnology is still not feasible. RESULTS: Here, we developed an in-planta, Agrobacterium-mediated gene expression method for exogenous genes via wounding and vacuum in bamboo. We demonstrated that the RUBY served as a reporter efficiently expressed in bamboo leaves and shoots, albeit unable to integrate into the chromosome. We have also developed a gene editing system by creating an in situ mutant of the bamboo violaxanthin de-epoxidase (PeVDE) gene in bamboo leaves, with lower NPQ values under the fluorometer, which can serve as a native reporter for gene editing. Furthermore, the bamboo leaves with increased flavonoid content were achieved by knocking out the cinnamoyl-CoA reductase genes. CONCLUSIONS: Our method can be applied for the functional characterization of novel genes in a short time and is helpful for bamboo leaf flavonoid biotechnology breeding in the future.

10.
Plant J ; 113(5): 1095-1101, 2023 03.
Artículo en Inglés | MEDLINE | ID: mdl-36587294

RESUMEN

The application of DNA-protein interaction reporter assays for relational or ratiometric measurements within an experimental system is popular in biological research. However, the existing reporter-based interaction assays always require special equipment, expensive chemicals, and a complicated operation. Here, we developed a DNA-protein interaction technology integrating two visible reporters, RUBY and UV-visible GFP (eYGFPuv), which allows the expression of the cassette reporter contained cis-acting DNA element (DE) fused upstream of TATA box and RUBY, and a constitutive promoter regulating eYGFPuv in the same construct. The interaction of transcription factor (TF) and the DE can be detected by co-expressed the cassette reporter and TF in tobacco leaves where the cassette reporter alone serves as a control. We also revealed that eight function-unknown bamboo AP2/ERFs interacted with the DE of ANT-AP2R1R2 (ABE), DRE (DBE), GCC-box (EBE), and RAV1 binding element (RBE), respectively, which are consistent with the results by dual-luciferase reporter assays. Thus, the dual-visible reporters offer a convenient, visible, and cost-saving alternative to other existing techniques for DNA-protein interaction in plants.


Asunto(s)
Secuencias Reguladoras de Ácidos Nucleicos , Factores de Transcripción , Factores de Transcripción/genética , Regiones Promotoras Genéticas/genética , Regulación de la Expresión Génica , ADN , Genes Reporteros
11.
Antioxidants (Basel) ; 11(12)2022 Nov 22.
Artículo en Inglés | MEDLINE | ID: mdl-36552517

RESUMEN

Coenzyme Q (CoQ) is a vital lipid that functions as an electron carrier in the mitochondrial electron transport chain and as a membrane-soluble antioxidant. Deficiencies in CoQ lead to metabolic diseases with a wide range of clinical manifestations. There are currently few treatments that can slow or stop disease progression. Primary CoQ10 deficiency can arise from mutations in any of the COQ genes responsible for CoQ biosynthesis. While many mutations in these genes have been identified, the clinical significance of most of them remains unclear. Here we analyzed the structural and functional impact of 429 human missense single nucleotide variants (SNVs) that give rise to amino acid substitutions in the conserved and functional regions of human genes encoding a high molecular weight complex known as the CoQ synthome (or Complex Q), consisting of the COQ3-COQ7 and COQ9 gene products. Using structures of COQ polypeptides, close homologs, and AlphaFold models, we identified 115 SNVs that are potentially pathogenic. Further biochemical characterizations in model organisms such as Saccharomyces cerevisiae are required to validate the pathogenicity of the identified SNVs. Collectively, our results will provide a resource for clinicians during patient diagnosis and guide therapeutic efforts toward combating primary CoQ10 deficiency.

12.
Nat Commun ; 13(1): 6449, 2022 Oct 28.
Artículo en Inglés | MEDLINE | ID: mdl-36307447

RESUMEN

PbSe-based thermoelectric materials exhibit promising ZT values at medium temperature, but its near-room-temperature thermoelectric properties are overlooked, thus restricting its average ZT (ZTave) value at low-medium temperatures. Here, a high ZTave of 0.90 at low temperature (300-573 K) is reported in n-type PbSe-based thermoelectric material (Pb1.02Se0.72Te0.20S0.08-0.3%Cu), resulting in a large ZTave of 0.96 at low-medium temperatures (300-773 K). This high thermoelectric performance stems from its ultralow lattice thermal conductivity caused by dense dislocations through heavy Te/S alloying and Cu interstitial doping. The dislocation density evaluated by modified Williamson-Hall method reaches up to 5.4 × 1016 m-2 in Pb1.02Se0.72Te0.20S0.08-0.3%Cu. Moreover, the microstructure observation further uncloses two kinds of dislocations, namely screw and edge dislocations, with several to hundreds of nanometers scale in length. These dislocations in lattice can strongly intensify phonon scattering to minimize the lattice thermal conductivity and simultaneously maintain high carrier transport. As a result, with the reduced lattice thermal conductivity and optimized power factor in Pb1.02Se0.72Te0.20S0.08-0.3%Cu, its near-room-temperature thermoelectric performance is largely enhanced and exceeds previous PbSe-based thermoelectric materials.

13.
Biomed Res Int ; 2022: 4710993, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36060127

RESUMEN

Aim: In mice with liver fibrosis produced by carbon tetrachloride (CCl4), the effects of olmesartan on intrahepatic angiogenesis and sinusoidal remodeling will be evaluated. Methods: By injecting CCl4 into the peritoneal cavity, we established a mouse model of liver fibrosis. Using Sirius red and Masson trichrome staining, the extent of liver fibrosis in the animals was determined. Using immunohistochemical labeling and western blotting, the level of α-smooth muscle actin (α-SMA) expression, a characteristic of hepatic stellate cell activation, was assessed. Electron microscopy was used to determine the effect of olmesartan on hepatic sinusoidal capillarization, and immunohistochemical labeling was used to determine the expression levels of endothelial and basement membrane proteins in mouse liver tissues. Platelet-derived growth factor (PDGF), IL-10, vascular endothelial growth factor (VEGF), and angiotensin II levels in mouse serum were measured by Luminex multifactor analysis and ELISA. Olmesartan's effect on the angiotensin II type 1 receptor (AT1R) and the VEGF receptor (VEGFR) was evaluated using western blotting. Results: Olmesartan reduced CCl4-induced inflammatory cell infiltration and collagen deposition to alleviate liver fibrosis. α-SMA expression was decreased, and HSC activation was inhibited in mouse liver tissues by olmesartan treatment. In addition, hepatic sinusoidal capillarization was improved under the action of olmesartan. The expression of collagen IV, fibronectin, CD31, and von Willebrand factor (VWF) in the olmesartan group was also markedly downregulated. In fibrotic mice, olmesartan medication decreased the levels of PDGF, VEGF, and angiotensin II, but it increased the level of IL-10. Moreover, olmesartan reduced the expression of VEGFR-1, VEGFR-2, and AT1R relative to CCl4-induced liver fibrosis. Conclusions: In mice with CCl4-induced fibrosis, olmesartan lowers angiogenesis and improves hepatic sinusoidal remodeling, according to our findings. By acting on the angiotensin II-AT1R-VEGF axis, this is achieved.


Asunto(s)
Imidazoles , Cirrosis Hepática , Tetrazoles , Angiotensina II/metabolismo , Animales , Tetracloruro de Carbono/toxicidad , Colágeno/uso terapéutico , Imidazoles/farmacología , Interleucina-10 , Cirrosis Hepática/inducido químicamente , Cirrosis Hepática/tratamiento farmacológico , Cirrosis Hepática/metabolismo , Ratones , Neovascularización Patológica , Tetrazoles/farmacología , Factor A de Crecimiento Endotelial Vascular
14.
Front Immunol ; 13: 830606, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35935985

RESUMEN

Accumulating evidence suggests that regulatory B cells (Bregs) play important roles in inhibiting the immune response in tumors. Programmed death 1 (PD-1) and programmed death ligand 1 (PD-L1) are important molecules that maintain the balance of the immune response and immune tolerance. This study aims to evaluate the soluble form of PD-L1 and its function in inducing the differentiation of B lymphocytes, investigate the relationship between soluble PD-L1 (sPD-L1) and B-cell subsets, and explore the antitumor activity of T lymphocytes after PD-L1 blockade in coculture systems. In an effort to explore the role of sPD-L1 in human breast cancer etiology, we examined the levels of sPD-L1 and interleukin-10 (IL-10) in the serum of breast tumor patients and the proportions of B cells, PD-1+ B cells, Bregs, and PD-1+ Bregs in the peripheral blood of patients with breast tumors and assessed their relationship among sPD-L1, IL-10, and B-cell subsets. The levels of sPD-L1 and IL-10 in serum were found to be significantly higher in invasive breast cancer (IBCa) patients than in breast fibroadenoma (FIBma) patients. Meanwhile, the proportions and absolute numbers of Bregs and PD-1+ Bregs in the peripheral blood of IBCa patients were significantly higher than those of FIBma patients. Notably, they were the highest in triple-negative breast cancer (TNBC) among other subtypes of IBCa. Positive correlations of sPD-L1 and IL-10, IL-10 and PD-1+ Bregs, and also sPD-L1 and PD-1+ Bregs were observed in IBCa. We further demonstrated that sPD-L1 could induce Breg differentiation, IL-10 secretion, and IL-10 mRNA expression in a dose-dependent manner in vitro. Finally, the induction of regulatory T cells (Tregs) by Bregs was further shown to suppress the antitumor response and that PD-L1 blockade therapies could promote the apoptosis of tumor cells. Together, these results indicated that sPD-L1 could mediate the differentiation of Bregs, expand CD4+ Tregs and weaken the antitumor activity of CD4+ T cells. PD-L1/PD-1 blockade therapies might be a powerful therapeutic strategy for IBCa patients, particularly for TNBC patients with high level of PD-1+ Bregs.


Asunto(s)
Linfocitos B Reguladores , Síndromes de Inmunodeficiencia , Neoplasias de la Mama Triple Negativas , Antígeno B7-H1/metabolismo , Humanos , Tolerancia Inmunológica , Terapia de Inmunosupresión , Interleucina-10 , Receptor de Muerte Celular Programada 1/metabolismo
15.
Heliyon ; 8(8): e09982, 2022 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-35965988

RESUMEN

New architectural forms offered by digital design approaches often appear incompatible with the prescribed precision and control in construction, especially in developing regions where advanced implementation means are limited. In response, this paper suggests working with design practice indeterminacy. Named 'anexact architecture', the post-digital design practice strategy presents a convergent diagram of seeking the feasible design solution space. It relies on the procedural parametric modelling to constantly integrate computation and humanisation, so that a rigorous built outcome is capable of accommodating project-specific idiosyncrasies and constraints. The demonstrator projects are discussed based on the combination of the Participatory Action Research method and the idea of anexact architecture. This paper aims to illustrate the peculiarity of anexact architecture and its ideology of treating design delivery uncertainties as essentials rather than negatives when practicing in a volatile construction context.

16.
RSC Adv ; 12(27): 17498, 2022 Jun 07.
Artículo en Inglés | MEDLINE | ID: mdl-35765443

RESUMEN

[This corrects the article DOI: 10.1039/D2RA00311B.].

17.
BMC Complement Med Ther ; 22(1): 115, 2022 Apr 25.
Artículo en Inglés | MEDLINE | ID: mdl-35468773

RESUMEN

BACKGROUND: Trans-cinnamaldehyde (TCA) is one of the main pharmaceutical ingredients of Cinnamomum cassia Presl, which has been shown to have therapeutic effects on a variety of cardiovascular diseases. This study was carried out to characterize and reveal the underlying mechanisms of the protective effects of TCA against cardiac hypertrophy. METHODS: We used phenylephrine (PE) to induce cardiac hypertrophy and treated with TCA in vivo and in vitro. In neonatal rat cardiomyocytes (NRCMs), RNA sequencing and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were carried out to identify potential pathways of TCA. Then, the phosphorylation and nuclear localization of calcium/calmodulin-dependent protein kinase II (CaMKII) and extracellular signal-related kinase (ERK) were detected. In adult mouse cardiomyocytes (AMCMs), calcium transients, calcium sparks, sarcomere shortening and the phosphorylation of several key proteins for calcium handling were evaluated. For mouse in vivo experiments, cardiac hypertrophy was evaluated by assessing morphological changes, echocardiographic parameters, and the expression of hypertrophic genes and proteins. RESULTS: TCA suppressed PE-induced cardiac hypertrophy and the phosphorylation and nuclear localization of CaMKII and ERK in NRCMs. Our data also demonstrate that TCA blocked the hyperphosphorylation of ryanodine receptor type 2 (RyR2) and phospholamban (PLN) and restored Ca2+ handling and sarcomere shortening in AMCMs. Moreover, our data revealed that TCA alleviated PE-induced cardiac hypertrophy in adult mice and downregulated the phosphorylation of CaMKII and ERK. CONCLUSION: TCA has a protective effect against PE-induced cardiac hypertrophy that may be associated with the inhibition of the CaMKII/ERK pathway.


Asunto(s)
Proteína Quinasa Tipo 2 Dependiente de Calcio Calmodulina , Miocitos Cardíacos , Acroleína/análogos & derivados , Animales , Calcio/metabolismo , Proteína Quinasa Tipo 2 Dependiente de Calcio Calmodulina/metabolismo , Cardiomegalia/inducido químicamente , Cardiomegalia/tratamiento farmacológico , Cardiomegalia/metabolismo , Sistema de Señalización de MAP Quinasas , Ratones , Fenilefrina/efectos adversos , Fenilefrina/metabolismo , Ratas , Canal Liberador de Calcio Receptor de Rianodina/genética , Canal Liberador de Calcio Receptor de Rianodina/metabolismo , Canal Liberador de Calcio Receptor de Rianodina/farmacología
18.
RSC Adv ; 12(16): 9524-9533, 2022 Mar 25.
Artículo en Inglés | MEDLINE | ID: mdl-35424939

RESUMEN

The incidence of articular cartilage defects is increasing year by year. In order to repair the cartilage tissue at the defect, scaffolds with nanofiber structure and biocompatibility have become a research hotspot. In this study, we designed and fabricated a bi-layer scaffold prepared from an upper layer of drug-dispersed gelatin methacrylate (GELMA) hydrogel and a lower layer of a drug-encapsulated coaxial fiber scaffold prepared from silk fiber (SF) and polylactic acid (PLA). These bi-layer scaffolds have porosity (91.26 ± 3.94%) sufficient to support material exchange and pore size suitable for cell culture and infiltration, as well as mechanical properties (2.65 ± 0.31 MPa) that meet the requirements of cartilage tissue engineering. The coaxial fiber structure exhibited excellent drug release properties, maintaining drug release for 14 days in PBS. In vitro experiments indicated that the scaffolds were not toxic to cells and were amenable to chondrocyte migration. Notably, the growth of cells in a bi-layer scaffold presented two states. In the hydrogel layer, cells grow through interconnected pores and take on a connective tissue-like shape. In the coaxial fiber layer, cells grow on the surface of the coaxial fiber mats and appeared tablet-like. This is similar to the structure of the functional partitions of natural cartilage tissue. Together, the bi-layer scaffold can play a positive role in cartilage regeneration, which could be a potential therapeutic choice to solve the current problems of clinical cartilage repair.

19.
Science ; 375(6587): 1385-1389, 2022 03 25.
Artículo en Inglés | MEDLINE | ID: mdl-35324303

RESUMEN

Thermoelectric materials allow for direct conversion between heat and electricity, offering the potential for power generation. The average dimensionless figure of merit ZTave determines device efficiency. N-type tin selenide crystals exhibit outstanding three-dimensional charge and two-dimensional phonon transport along the out-of-plane direction, contributing to a high maximum figure of merit Zmax of ~3.6 × 10-3 per kelvin but a moderate ZTave of ~1.1. We found an attractive high Zmax of ~4.1 × 10-3 per kelvin at 748 kelvin and a ZTave of ~1.7 at 300 to 773 kelvin in chlorine-doped and lead-alloyed tin selenide crystals by phonon-electron decoupling. The chlorine-induced low deformation potential improved the carrier mobility. The lead-induced mass and strain fluctuations reduced the lattice thermal conductivity. Phonon-electron decoupling plays a critical role to achieve high-performance thermoelectrics.

20.
BMC Plant Biol ; 22(1): 143, 2022 Mar 25.
Artículo en Inglés | MEDLINE | ID: mdl-35337270

RESUMEN

Aronia is a group of deciduous fruiting shrubs, of the Rosaceae family, native to eastern North America. Interest in Aronia has increased because of the high levels of dietary antioxidants in Aronia fruits. Using Illumina RNA-seq transcriptome analysis, this study investigates the molecular mechanisms of polyphenol biosynthesis during Aronia fruit development. Six A. melanocarpa (diploid) accessions were collected at four fruit developmental stages. De novo assembly was performed with 341 million clean reads from 24 samples and assembled into 90,008 transcripts with an average length of 801 bp. The transcriptome had 96.1% complete according to Benchmarking Universal Single-Copy Orthologs (BUSCOs). The differentially expressed genes (DEGs) were identified in flavonoid biosynthetic and metabolic processes, pigment biosynthesis, carbohydrate metabolic processes, and polysaccharide metabolic processes based on significant Gene Ontology (GO) biological terms. The expression of ten anthocyanin biosynthetic genes showed significant up-regulation during fruit development according to the transcriptomic data, which was further confirmed using qRT-PCR expression analyses. Additionally, transcription factor genes were identified among the DEGs. Using a transient expression assay, we confirmed that AmMYB10 induces anthocyanin biosynthesis. The de novo transcriptome data provides a valuable resource for the understanding the molecular mechanisms of fruit anthocyanin biosynthesis in Aronia and species of the Rosaceae family.


Asunto(s)
Photinia , Transcriptoma , Antocianinas/metabolismo , Frutas , Regulación de la Expresión Génica de las Plantas , Photinia/genética , Photinia/metabolismo , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo
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