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The centre of the highest region of muscle spindle abundance (CHRMSA) in the intramuscular nerve-dense region has been suggested as the optimal target location for injecting botulinum toxin A to block muscle spasms. The anterior forearm muscles have a high incidence of spasticity. However, the CHRMSA in the intramuscular nerve-dense region of the forearm anterior muscle group has not been defined. This study aimed to accurately define the body surface position and the depth of CHRMSA in an intramuscular nerve-dense region of the anterior forearm muscles. Twenty-four adult cadavers (57.7 ± 11.5 years) were included in this study. The curved line close to the skin connecting the medial and lateral epicondyles of the humerus was designated as the horizontal reference line (H line), and the line connecting the medial epicondyle of the humerus and the ulnar styloid was defined as the longitudinal reference line (L line). Modified Sihler's staining, haematoxylin-eosin staining and computed tomography scanning were employed to determine the projection points (P and P') of the CHRMSAs on the anterior and posterior surfaces of the forearm. The positions (PH and PL) of point P projected onto the H and L lines, and the depth of each CHRMSA, were determined using the Syngo system. The PH of the CHRMSA of the ulnar head of pronator teres, humeral head of pronator teres, flexor carpi radialis, palmaris longus, flexor carpi ulnaris, ulnar part of flexor digitorum superficialis, radial part of flexor digitorum superficialis, flexor pollicis longus, ulnar part of flexor digitorum profundus, radial portion of flexor digitorum profundus and pronator quadratus muscles were located at 42.48%, 45.52%, 41.20%, 19.70%, 7.77%, 25.65%, 47.42%, 53.47%, 12.28%, 38.41% and 51.68% of the H line, respectively; the PL were located at 18.38%, 12.54%, 28.83%, 13.43%, 17.65%, 32.76%, 57.32%, 64.12%, 20.05%, 45.94% and 88.71% of the L line, respectively; the puncture depths were located at 21.92%, 27.25%, 23.76%, 18.04%, 15.49%, 31.36%, 26.59%, 41.28%, 38.72%, 45.14% and 53.58% of the PP' line, respectively. The percentage values are the means of individual values. We recommend that the body surface puncture position and depth of the CHRMSA are the preferred locations for the intramuscular injection of botulinum toxin A to block anterior forearm muscle spasms.
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Toxinas Botulínicas Tipo A , Antebraço , Adulto , Humanos , Fusos Musculares , Músculo Esquelético , Cadáver , EspasmoRESUMO
Dysregulated autophagy is associated with cardiovascular and metabolic diseases, where impaired flow-mediated endothelial cell responses promote cardiovascular risk. The mechanism by which the autophagy machinery regulates endothelial functions is complex. We applied multi-omics approaches and in vitro and in vivo functional assays to decipher the diverse roles of autophagy in endothelial cells. We demonstrate that autophagy regulates VEGF-dependent VEGFR signaling and VEGFR-mediated and flow-mediated eNOS activation. Endothelial ATG5 deficiency in vivo results in selective loss of flow-induced vasodilation in mesenteric arteries and kidneys and increased cerebral and renal vascular resistance in vivo. We found a crucial pathophysiological role for autophagy in endothelial cells in flow-mediated outward arterial remodeling, prevention of neointima formation following wire injury, and recovery after myocardial infarction. Together, these findings unravel a fundamental role of autophagy in endothelial function, linking cell proteostasis to mechanosensing.
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Células Endoteliais , Infarto do Miocárdio , Humanos , Autofagia , Proteína 5 Relacionada à Autofagia/genética , Proteína 5 Relacionada à Autofagia/metabolismo , Células Endoteliais/metabolismo , Endotélio Vascular/metabolismo , Artérias Mesentéricas/metabolismo , Infarto do Miocárdio/metabolismo , Óxido Nítrico Sintase Tipo III/metabolismo , Transdução de Sinais , Vasodilatação , Animais , CamundongosRESUMO
Climate change and human activities have significantly influenced soil loss and the soil conservation service, posed threats to regional ecological sustainability. However, the relationships and underlying driving forces between potential soil loss, actual soil loss, and soil conservation service have not been well understood. Utilizing the Integrated Valuation of Ecosystem Services and Trade-offs (InVEST) model, we evaluated the soil conservation service on the Tibetan plateau from 1990 to 2020. We analyzed the spatial and temporal trends and examined the driving factors using linear regression, Pearson correlation, and random forest regression. The soil conservation service exhibited a complex pattern of increase followed by a decrease, with a turning point around 2010. Soil conservation service and soil loss demonstrated non-trade-off changes. The potential soil loss dominated the spatiotemporal patterns of soil conservation service on the Tibetan Plateau. Climatic factors significantly influenced the spatiotemporal patterns of soil conservation service, with annual precipitation emerging as the dominant driving factor, contributing approximately 20%. However, the impacts of human activities became more pronounced since 2010, and the contribution of vegetation to changes in soil conservation service was increased. The impact of the Normalized Difference Vegetation Index (NDVI) on soil conservation service for the grades I, II, and III increased by 13.19%, 3.08%, and 3.41%, respectively. Conversely, in northern Tibet before 2010 and eastern Three-River-Source after 2010, soil conservation service exhibited an increasing trend driven by both climate factors and human activities. Which indicates that the implementation of ecological restoration measures facilitated vegetation improvement and subsequently reduced actual soil loss. This study provides a scientific basis for resource management, land development strategies, and the formulation of ecological restoration measures on the Tibetan Plateau.
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Remolding the reactivity of metal active sites is critical to facilitate renewable electricity-powered water electrolysis. Doping heteroatoms, such as Se, into a metal crystal lattice has been considered an effective approach, yet usually suffers from loss of functional heteroatoms during harsh electrocatalytic conditions, thus leading to the gradual inactivation of the catalysts. Here, we report a new heteroatom-containing molecule-enhanced strategy toward sustainable oxygen evolution improvement. An organoselenium ligand, bis(3,5-dimethyl-1H-pyrazol-4-yl)selenide containing robust C-Se-C covalent bonds equipped in the precatalyst of ultrathin metal-organic nanosheets Co-SeMON, is revealed to significantly enhance the catalytic mass activity of the cobalt site by 25 times, as well as extend the catalyst operation time in alkaline conditions by 1 or 2 orders of magnitude compared with these reported metal selenides. A combination of various in situ/ex situ spectroscopic techniques, ab initio molecular dynamics, and density functional theory calculations unveiled the organoselenium intensified mechanism, in which the nonclassical bonding of Se to O-containing intermediates endows adsorption-energy regulation beyond the conventional scaling relationship. Our results showcase the great potential of molecule-enhanced catalysts for highly efficient and economical water oxidation.
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Cobalto , Metais , Adsorção , Oxigênio , ÁguaRESUMO
Advances in single-atom (-site) catalysts (SACs) provide a new solution of atomic economy and accuracy for designing efficient electrocatalysts. In addition to a precise local coordination environment, controllable spatial active structure and tolerance under harsh operating conditions remain great challenges in the development of SACs. Here, we show a series of molecule-spaced SACs (msSACs) using different acid anhydrides to regulate the spatial density of discrete metal phthalocyanines with single Co sites, which significantly improve the effective active-site numbers and mass transfer, enabling one of the msSACs connected by pyromellitic dianhydride to exhibit an outstanding mass activity of (1.63 ± 0.01) × 105 A·g-1 and TOFbulk of 27.66 ± 1.59 s-1 at 1.58 V (vs RHE) and long-term durability at an ultrahigh current density of 2.0 A·cm-2 under industrial conditions for oxygen evolution reaction. This study demonstrates that the accessible spatial density of single atom sites can be another important parameter to enhance the overall performance of catalysts.
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Cu-based metal-organic frameworks have attracted much attention for electrocatalytic CO2 reduction, but they are generally instable and difficult to control the product selectivity. We report flexible Cu(I) triazolate frameworks as efficient, stable, and tunable electrocatalysts for CO2 reduction to C2 H4 /CH4 . By changing the size of ligand side groups, the C2 H4 /CH4 selectivity ratio can be gradually tuned and inversed from 11.8 : 1 to 1 : 2.6, giving C2 H4 , CH4 , and hydrocarbon selectivities up to 51 %, 56 %, and 77 %, respectively. After long-term electrocatalysis, they can retain the structures/morphologies without formation of Cu-based inorganic species. Computational simulations showed that the coordination geometry of Cu(I) changed from triangular to tetrahedral to bind the reaction intermediates, and two adjacent Cu(I) cooperated for C-C coupling to form C2 H4 . Importantly, the ligand side groups controlled the catalyst flexibility by the steric hindrance mechanism, and the C2 H4 pathway is more sensitive than the CH4 one.
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Cobalt imidazolate frameworks are classical electrocatalysts for the oxygen evolution reaction (OER) but suffer from the relatively low activity. Here, a non-3d metal modulation strategy is presented for enhancing the OER activity of cobalt imidazolate frameworks. Two isomorphous frameworks [Co4 (MO4 )(eim)6 ] (M=Mo or W, Heim=2-ethylimidazole) having Co(eim)3 (MO4 ) units and high water stabilities were designed and synthesized. In different neutral media, the Mo-modulated framework coated on a glassy carbon electrode shows the best OER performances (1â mA cm-2 at an overpotential of 210â mV in CO2 -saturated 0.5 m KHCO3 electrolyte and 2/10/22â mA cm-2 at overpotential of 388/490/570â mV in phosphate buffer solution) among non-precious metal catalysts and even outperforms RuO2 . Spectroscopic measurements and computational simulations revealed that the non-3d metals modulate the electronic structure of Co for optimum reactant/product adsorption and tailor the energy of rate-determining step to a more moderate value.
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Anthropogenic activities have induced profound changes across the globe. Human appropriation of net primary production (HANPP) is a useful indicator for quantifying anthropogenic influences on natural ecosystems. We applied a detailed HANPP framework to the Tibet Autonomous Region of China for the period 1989-2015 and performed clustering analysis to explore county-level dynamics of HANPP components. The results indicated a continuous increase in HANPP per unit area from 10.3â¯gâ¯C/m2/yr in 1989 to 18.5â¯gâ¯C/m2/yr in 2008, with some fluctuation and a decline to 16.8â¯C/m2/yr in 2015. As a percentage of potential net primary production (NPPpot), HANPP increased from 6.9% to 13.5%. This rise was mainly driven by the commercialization of animal husbandry and by ecological conservation policies. Animal stocks dominated HANPP in Tibet in 1989, and by 2015 beef or crop production had become predominant in 30 of 73 counties. However, HANPP did not change uniformly across all locations. Changes were mainly concentrated in the south-central river valley area because of the growth in beef and crop production there. While in almost half of the 73 counties located in the northwestern regions, HANPP was dominated by sheep stocks and changed only slightly over the study period. These findings indicate that a comprehensive spatiotemporal analysis of HANPP components in Tibet provides deeper insights into changes in production and livelihood strategies of local residents, aligned with ecological conservation policies and economic development. Moreover, it unravels the complex impacts of human activities on alpine ecosystems, and indicates the need to optimize local ecosystem management and conservation policies.
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Ecossistema , Atividades Humanas , Animais , China , Monitoramento Ambiental , Humanos , Rios , Ovinos , TibetRESUMO
The paddle-wheel type cluster Co2(RCOO)4(LT)2 (R = substituent group, LT = terminal ligand), possessing unusual metal coordination geometry compared with other cobalt compounds, may display high catalytic activity but is highly unstable especially in water. Here, we show that with judicious considerations of the host/guest geometries and modular synthetic strategies, the labile dicobalt clusters can be immobilized and stabilized in a metal-organic framework (MOF) as coordinative guests. The Fe(na)4(LT) fragment in the MOF [{Fe3(µ3-O)(bdc)3}4{Fe(na)4(LT)}3] (H2bdc = 1,4-benzenedicaboxylic acid, Hna = nicotinic acid) can be removed to give [{Fe3(µ3-O)(bdc)3}4] with a unique framework connectivity possessing suitable distribution of open metal sites for binding the dicobalt cluster in the form of Co2(na)4(LT)2. After two-step, single-crystal to single-crystal, postsynthetic modifications, a thermal-, water-, and alkaline-stable MOF [{Fe3(µ3-O)(bdc)3}4{Co2(na)4(LT)2}3] containing the desired dicobalt cluster was obtained, giving extraordinarily high electrocatalytic oxygen evolution activity in water at pH = 13 with overpotential as low as 225 mV at 10.0 mA cm-2.
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Developing sustainable use patterns for alpine grassland in Tibet is the primary challenge related to conserving these vulnerable ecosystems of the 'world's third pole' and guaranteeing the well-being of local inhabitants. This challenge requires researchers to think beyond the methods of most current studies that are limited to a single aspect of conservation or productivity, and focus on balancing various needs. An analysis of trade-offs involving ecosystem services provides a framework that can be used to quantify the type of balancing needed. In this study, we measured variations in four types of ecosystem services under five types of grassland management including grazing exclusion, sowing, combined plowing and grazing exclusion, combined plowing and sowing, and natural grassland, from 2013 to 2015. In addition, we accessed the existence and changing patterns of ecosystem service trade-offs using Spearman coefficients and a trade-off index. The results revealed the existence of trade-offs among provisioning and regulating services. Plowing and sowing could convert the trade-off relationships into synergies immediately. Grazing exclusion reduced the level of trade-offs gradually over time. Thus, the combined plowing and sowing treatment promoted the total supply of multiple ecosystem services when compared with natural grassland. We argue that the variations in dry matter allocation to above- and belowground serve as one cause of the variation in trade-off relationships. Another cause for variation in trade-offs is the varied species competition between selection effects and niche complementarity. Our study provides empirical evidence that the effects of trade-offs among ecosystem services could be reduced and even converted into synergies by optimizing management techniques.
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Ecossistema , Pradaria , China , TibetRESUMO
Postsynthetic ion exchange of [Co2(µ-Cl)2(btta)] (MAF-X27-Cl, H2bbta =1H,5H-benzo(1,2-d:4,5-d')bistriazole) possessing open metal sites on its pore surface yields a material [Co2(µ-OH)2(bbta)] (MAF-X27-OH) functionalized by both open metal sites and hydroxide ligands, giving drastically improved electrocatalytic activities for the oxygen evolution reaction (an overpotential of 292 mV at 10.0 mA cm(-2) in 1.0 M KOH solution). Isotope tracing experiments further confirm that the hydroxide ligands are involved in the OER process to provide a low-energy intraframework coupling pathway.
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AIMS: The long-term failure of autologous saphenous vein bypass grafts due to neointimal thickening is a major clinical burden. Identifying novel strategies to prevent neointimal thickening is important. Thus, this study aimed to identify microRNAs (miRNAs) that are dysregulated during neointimal formation and determine their pathophysiological relevance following miRNA manipulation. METHODS AND RESULTS: We undertook a microarray approach to identify dysregulated miRNAs following engraftment in an interpositional porcine graft model. These profiling experiments identified a number of miRNAs which were dysregulated following engraftment. miR-21 levels were substantially elevated following engraftment and these results were confirmed by quantitative real-time PCR in mouse, pig, and human models of vein graft neointimal formation. Genetic ablation of miR-21 in mice or grafted veins dramatically reduced neointimal formation in a mouse model of vein grafting. Furthermore, pharmacological knockdown of miR-21 in human veins resulted in target gene de-repression and a significant reduction in neointimal formation. CONCLUSION: This is the first report demonstrating that miR-21 plays a pathological role in vein graft failure. Furthermore, we also provided evidence that knockdown of miR-21 has therapeutic potential for the prevention of pathological vein graft remodelling.
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MicroRNAs/genética , Neointima/genética , Veia Safena/metabolismo , Enxerto Vascular , Animais , Artéria Carótida Primitiva/metabolismo , Células Cultivadas , Técnicas de Silenciamento de Genes , Rejeição de Enxerto/genética , Rejeição de Enxerto/metabolismo , Humanos , Camundongos , Camundongos Knockout , MicroRNAs/metabolismo , Análise em Microsséries , Veia Safena/transplante , Suínos , Veias Cavas/metabolismoRESUMO
Purpose: The overall distribution pattern of intramuscular nerves and the regions with the highest spindle abundance in deep cervical muscles have not been revealed. This study aimed to reveal neuromuscular compartmentalization and localize the body surface position and depth of the center of the region of highest muscle spindle abundance (CRHMSA) in the deep cervical muscles. Methods: This study included 36 adult cadavers (57.7 ± 11.5 years). The curved line joining the lowest point of the jugular notch and chin tip was designated as the longitudinal reference line (line L), and the curved line connecting the lowest point of the jugular notch and acromion was designated as the horizontal reference line (line H). Modified Sihler's staining, hematoxylin-eosin staining and computed tomography scanning were employed to determine the projection points (P) of the CRHMSAs on the anterior surfaces of the neck. The positions (PH and PL) of point P projected onto the H and L lines, and the depth of each CRHMSA, and puncture angle were determined using the Syngo system. Results: The scalenus posterior and longus capitis muscles were divided into two neuromuscular compartments, while the scalenus anterior and longus colli muscles were divided into three neuromuscular compartments. The scalenus medius muscle can be divided into five neuromuscular compartments. The PH of the CRHMSA of the scalenus muscles (anterior, medius, and posterior), and longus capitis and longus colli muscles, were located at 36.27, 39.18, 47.31, 35.67, and 42.71% of the H line, respectively. The PL positions were at 26.53, 32.65, 32.73, 68.32, and 51.15% of the L line, respectively. The depths of the CRHMSAs were 2.47 cm, 2.96 cm, 2.99 cm, 3.93 cm, and 3.17 cm, respectively, and the puncture angles were 87.13°, 85.92°, 88.21°, 58.08°, and 77.75°, respectively. Conclusion: Present research suggests that the deep cervical muscles can be divided into neuromuscular compartments; we recommend the locations of these CRHMSA as the optimal target for administering botulinum toxin A injections to treat deep cervical muscle dystonia.
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Wintergrazer-70 and Ganyin No1 are high-yield forage varieties suitable for cultivation in high-altitude areas of Tibet (4300 m above sea level). Ganyin No1 was developed from Wintergrazer-70, with the latter serving as its parent variety. Ganyin No1 was identified as a spring variety, and subsequent RNA sequencing was conducted. RNA sequencing analysis identified 4 differentially expressed genes related to vernalization and 28 genes related to photoperiod regulation. The Sc7296g5-i1G3 gene is related to the flowering inhibition of rye, which may be related to the phenotypic difference in the Ganyin No1 variety in winter and spring. This finding provides valuable insights for future research on Ganyin No1, especially in addressing feed shortages in Tibet during winter and spring.
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Altitude , Estações do Ano , Secale , Secale/genética , Regulação da Expressão Gênica de Plantas , Análise de Sequência de RNA/métodos , Mutação , Tibet , Proteínas de Plantas/genéticaRESUMO
Alpine grassland of Tibet is a frangible ecosystem in terms of carbon (C) emission. Yak dung is an important resident energy with about 80 % of yak dung combusted for energy in the north Tibetan plateau. This paper investigated the impact of dung combustion on the C cycle of the alpine grassland ecosystem in north Tibet, China. During the growing season of 2011, from a field survey and household questionnaires, the main impacts of dung collection for fuel on the C cycle of the ecosystem were identified. (1) The C sequestration and storage capacity, including the dung-derived C stored in soil and C captured by vegetation, decreased. The net primary production decreased remarkably because of the reduction of dung returned to soil. (2) In a given period, more C was emitted to the atmosphere in the dung combustion situation than that in the dung returned to soil situation. (3) The energy grazing alpine meadow ecosystem changed into a net C source, and the net biome production of the ecosystem dropped to -15.18 g C/m2 year in the dung combustion situation, 42.95 g C/m2 year less than that in the dung returned situation. To reduce the CO2 emission derived from dung use, the proportion of dung combustion should be reduced and alternative renewable energy such as solar, wind, or hydro energy should be advocated, which is suitable for, and accessible to, the north Tibetan plateau.
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Ciclo do Carbono , Fontes Geradoras de Energia , Esterco , Animais , Carbono/análise , Bovinos , Ingestão de Alimentos , Humanos , Poaceae , Solo/química , Inquéritos e Questionários , TibetRESUMO
The real structure and in situ evolution of catalysts under working conditions are of paramount importance, especially for bifunctional electrocatalysis. Here, we report asymmetric structural evolution and dynamic hydrogen-bonding promotion mechanism of an atomically dispersed electrocatalyst. Pyrolysis of Co/Ni-doped MAF-4/ZIF-8 yielded nitrogen-doped porous carbons functionalized by atomically dispersed Co-Ni dual-metal sites with an unprecedented N8V4 structure, which can serve as an efficient bifunctional electrocatalyst for overall water splitting. More importantly, the electrocatalyst showed remarkable activation behavior due to the in situ oxidation of the carbon substrate to form C-OH groups. Density functional theory calculations suggested that the flexible C-OH groups can form reversible hydrogen bonds with the oxygen evolution reaction intermediates, giving a bridge between elementary reactions to break the conventional scaling relationship.
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The critical factor determining the in vivo effect of bone repair materials is the microenvironment, which greatly depends on their abilities to promote vascularization and bone formation. However, implant materials are far from ideal candidates for guiding bone regeneration due to their deficient angiogenic and osteogenic microenvironments. Herein, a double-network composite hydrogel combining vascular endothelial growth factor (VEGF)-mimetic peptide with hydroxyapatite (HA) precursor was developed to build an osteogenic microenvironment for bone repair. The hydrogel was prepared by mixing acrylated ß-cyclodextrins and octacalcium phosphate (OCP), an HA precursor, with gelatin solution, followed by ultraviolet photo-crosslinking. To improve the angiogenic potential of the hydrogel, QK, a VEGF-mimicking peptide, was loaded in acrylated ß-cyclodextrins. The QK-loaded hydrogel promoted tube formation of human umbilical vein endothelial cells and upregulated the expression of angiogenesis-related genes, such as Flt1, Kdr, and VEGF, in bone marrow mesenchymal stem cells. Moreover, QK could recruit bone marrow mesenchymal stem cells. Furthermore, OCP in the composite hydrogel could be transformed into HA and release calcium ions facilitating bone regeneration. The double-network composite hydrogel integrated QK and OCP showed obvious osteoinductive activity. The results of animal experiments showed that the composite hydrogel enhanced bone regeneration in skull defects of rats, due to perfect synergistic effects of QK and OCP on vascularized bone regeneration. In summary, improving the angiogenic and osteogenic microenvironments by our double-network composite hydrogel shows promising prospects for bone repair.
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There is a high demand for bespoke grafts to replace damaged or malformed bone and cartilage tissue. Three-dimensional (3D) printing offers a method of fabricating complex anatomical features of clinically relevant sizes. However, the construction of a scaffold to replicate the complex hierarchical structure of natural tissues remains challenging. This paper reports a novel biofabrication method that is capable of creating intricately designed structures of anatomically relevant dimensions. The beneficial properties of the electrospun fibre meshes can finally be realised in 3D rather than the current promising breakthroughs in two-dimensional (2D). The 3D model was created from commercially available computer-aided design software packages in order to slice the model down into many layers of slices, which were arrayed. These 2D slices with each layer of a defined pattern were laser cut, and then successfully assembled with varying thicknesses of 100 µm or 200 µm. It is demonstrated in this study that this new biofabrication technique can be used to reproduce very complex computer-aided design models into hierarchical constructs with micro and nano resolutions, where the clinically relevant sizes ranging from a simple cube of 20 mm dimension, to a more complex, 50 mm-tall human ears were created. In-vitro cell-contact studies were also carried out to investigate the biocompatibility of this hierarchal structure. The cell viability on a micromachined electrospun polylactic-co-glycolic acid fibre mesh slice, where a range of hole diameters from 200 µm to 500 µm were laser cut in an array where cell confluence values of at least 85% were found at three weeks. Cells were also seeded onto a simpler stacked construct, albeit made with micromachined poly fibre mesh, where cells can be found to migrate through the stack better with collagen as bioadhesives. This new method for biofabricating hierarchical constructs can be further developed for tissue repair applications such as maxillofacial bone injury or nose/ear cartilage replacement in the future.
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NiCo metal-organic framework (MOF) electrodes were prepared by a simple hydrothermal method. The flower-like NiCo MOF electrode exhibited an exciting potential window of 1.2 V and an excellent specific capacitance of 927.1 F g-1 at 1 A g-1. The flower-like NiCo MOF//activated carbon (AC) device delivered a high energy density of 28.5 W hkg-1 at a power density of 400.5 W kg-1 and good cycle stability (95.4% after 5000 cycles at 10 A g-1). Based on the flower-like NiCo MOF electrode, the asymmetric quasi-solid-state flexible supercapacitor (AFSC) was prepared and exhibited good capacitance retention after bending (79% after 100 bends and 64.4% after 200 bends). Furthermore, two AFSCs in series successfully lit up ten parallel red LED lights, showing great application potential in flexible and wearable energy storage devices.