Development of natural protein-based fibrous scaffolds with tunable physical properties and biocompatibility is highly desirable to construct a three-dimensional (3D), fully cellularized scaffold for wound healing. Herein, we demonstrated a simple and effective technique to construct electrospun 3D fibrous scaffolds for accelerated wound healing using a photocrosslinkable hydrogel based on methacryloylated gelatin (GelMA). We found that the physical properties of the photocrosslinkable hydrogel including water retention, stiffness, strength, elasticity and degradation can be tailored by changing the light exposure time. We further observed that the optimized hydrogel fibrous scaffolds which were soft and elastic could support cell adhesion, proliferation and migration into the whole scaffolds, facilitating regeneration and formation of cutaneous tissues within two weeks. Such tunable characteristics of the fibrous GelMA scaffolds distinguished them from other reported substrates developed for reconstruction of wound defects including glutaraldehyde-crosslinked gelatin or poly (lactic-co-glycolic acid) (PLGA), whose physical and chemical properties were difficult to modify to allow cell infiltration into the 3D scaffolds for tissue regeneration. We anticipate that the ability to become fully cellularized will make the engineered GelMA hydrogel fibrous scaffolds suitable for widespread applications as skin substitutes or wound dressings.
Distal necrosis of random skin flap is always clinical problematic in plastic surgery. The development of 3D functional vascular networks is fundamental for the survival of a local random skin flap. Herein, an effective technique on constructing 3D fibrous scaffolds for accelerated vascularization is demonstrated using a photocrosslinkable natural hydrogel based on gelatin methacryloyl (GelMA) by electrospinning. It is found that the ultraviolet (UV) photocrosslinkable gelatin electrospun hydrogel fibrous membranes exhibit soft adjustable mechanical properties and controllable degradation properties. Furthermore, it is observed that the optimized hydrogel scaffolds can support endothelial cells and dermal fibroblasts adhesion, proliferation, and migration into the scaffolds, which facilitates vascularization. Importantly, a rapid formation of tubes is observed after 3 d seeding of endothelial cells. After GelMA fibrous scaffold implantation below the skin flap in a rat model, it is found that the flap survival rate is higher than the control group, and there is more microvascular formation, which is potentially beneficial for the flap tissue vascularization. These data suggest that GelMA hydrogels can be used for biomedical applications that require the formation of microvascular networks, including the development of complex engineered tissues.
Climate is predicted to change over the 21st century. However, little is known about how climate change can affect soil phosphorus (P) cycle and availability in global terrestrial ecosystems, where P is a key limiting nutrient. With a global database of Hedley P fractions and key-associated physiochemical properties of 760 (seminatural) natural soils compiled from 96 published studies, this study evaluated how climate pattern affected soil P cycle and availability in global terrestrial ecosystems. Overall, soil available P, indexed by Hedley labile inorganic P fraction, significantly decreased with increasing mean annual temperature (MAT) and precipitation (MAP). Hypothesis-oriented path model analysis suggests that MAT negatively affected soil available P mainly by decreasing soil organic P and primary mineral P and increasing soil sand content. MAP negatively affected soil available P both directly and indirectly through decreasing soil primary mineral P; however, these negative effects were offset by the positive effects of MAP on soil organic P and fine soil particles, resulting in a relatively minor total MAP effect on soil available P. As aridity degree was mainly determined by MAP, aridity also had a relatively minor total effect on soil available P. These global patterns generally hold true irrespective of soil depth (≤10 cm or >10 cm) or site aridity index (≤1.0 or >1.0), and were also true for the low-sand (≤50%) soils. In contrast, available P of the high-sand (>50%) soils was positively affected by MAT and aridity and negatively affected by MAP. Our results suggest that temperature and precipitation have contrasting effects on soil P availability and can interact with soil particle size to control soil P availability.
In this paper, we study the behavior of Ricci-flat Kähler metrics on Calabi-Yau manifolds under algebraic geometric surgeries: extremal transitions or flops. We prove a version of Candelas and de la Ossa's conjecture: Ricci-flat Calabi-Yau manifolds related by extremal transitions and flops can be connected by a path consisting of continuous families of Ricci-flat Calabi-Yau manifolds and a compact metric space in the Gromov-Hausdorff topology. In an essential step of the proof of our main result, the convergence of Ricci-flat Kähler metrics on Calabi-Yau manifolds along a smoothing is established, which can be of independent interests.is an extremal transition among Calabi-Yau manifolds, then there exists a family of Ricci-flat Kähler metricsḡ s , s ∈ (0, 1), on M, and a family of Ricci-flat Kähler metricsg t on M t satisfying that {(M,ḡ s )} and {(M t ,g t )} converge to a single compact metric space (X, d X ) in the Gromov-Hausdorff topology,ii) IfM 1 → M 0 M 2 is a flop between two Calabi-Yau manifolds, then there are families of Ricci-flat Kähler metricsḡ i,s , s ∈ (0, 1) onM i (i = 1, 2) such that for a single compact metric space (X, d X ).Furthermore, in both cases X is homeomorphic to M 0 and d X is induced by a Ricci-flat Kähler metric on M 0 \S. In the present paper, we shall prove i) and ii) of the above version of Candelas and de la Ossa's conjecture.Let M 0 be a projective normal Cohen-Macaulay n-dimensional variety with singular set S, and let K M 0 be the canonical sheaf of M 0 ([33]). In this paper, all varieties are assumed to be Cohen-Macaulay. We call M 0 Gorenstein if K M 0 is a rank one locally free sheaf. Assume that M 0 has only canonical singularities, i.e., M 0 is Gorenstein, and for any resolution (M,π),where E are effective exceptional divisors. Consider a resolution (M ,π) of M 0 . If α is an ample class in the Picard group of M 0 ,π * α belongs the boundary of the Kähler cone of M . A resolution (M ,π) of M 0 is called a crepant resolution if KM =π * K M 0 and is called a small resolution if the exceptional subvarietyπ −1 (S) satisfies dim Cπ −1 (S) ≤ n − 2. It is obvious that (M ,π) is crepant if it is a small resolution. If M 0 admits a smoothing (M, π) over a unit disc ∆ ⊂ C with an ample line bundle L on M, then there is an embedding M ֒→ CP N × ∆ such that L m = O ∆ (1)| M for some m ≥ 1, π is a proper surjection given by the restriction of the projection from CP N × ∆ to ∆, and the rank of π * is 1 on M\S. This implies that M t , t ∈ ∆\{0}, have the same underlying differential manifoldM . Moreover, if L is a line bundle on M such that the restriction of L on M 0 is ample, then by Proposition 1.41 in [38] L is ample on π −1 (∆ ′ ) where ∆ ′ ⊆ ∆ is a neighborhood of 0.A Calabi-Yau variety is a simply connected projective normal variety M 0 with trivial canonical sheaf K M 0 ∼ = O M 0 and only canonical singularities. If a Calabi-Yau variety M 0
The snow leopard (Panthera uncia) inhabits the rugged mountains in 12 countries of Central Asia, including the Tibetan Plateau. Due to poaching, decreased abundance of prey, and habitat degradation, it was listed as endangered by the International Union for Conservation of Nature in 1972. Current conservation strategies, including nature reserves and incentive programs, have limited capacities to protect snow leopards. We investigated the role of Tibetan Buddhist monasteries in snow leopard conservation in the Sanjiangyuan region in China's Qinghai Province on the Tibetan Plateau. From 2009 to 2011, we systematically surveyed snow leopards in the Sanjiangyuan region. We used the MaxEnt model to determine the relation of their presence to environmental variables (e.g., elevation, ruggedness) and to predict snow leopard distribution. Model results showed 89,602 km(2) of snow leopard habitat in the Sanjiangyuan region, of which 7674 km(2) lay within Sanjiangyuan Nature Reserve's core zones. We analyzed the spatial relation between snow leopard habitat and Buddhist monasteries and found that 46% of monasteries were located in snow leopard habitat and 90% were within 5 km of snow leopard habitat. The 336 monasteries in the Sanjiangyuan region could protect more snow leopard habitat (8342 km(2) ) through social norms and active patrols than the nature reserve's core zones. We conducted 144 household interviews to identify local herders' attitudes and behavior toward snow leopards and other wildlife. Most local herders claimed that they did not kill wildlife, and 42% said they did not kill wildlife because it was a sin in Buddhism. Our results indicate monasteries play an important role in snow leopard conservation. Monastery-based snow leopard conservation could be extended to other Tibetan Buddhist regions that in total would encompass about 80% of the global range of snow leopards.
Stem mammaliaforms are forerunners to modern mammals, and they achieved considerable ecomorphological diversity in their own right. Recent discoveries suggest that eleutherodontids, a subclade of Haramiyida, were more species-rich during the Jurassic period in Asia than previously recognized. Here we report a new Jurassic eleutherodontid mammaliaform with an unusual mosaic of highly specialized characteristics, and the results of phylogenetic analyses that support the hypothesis that haramiyidans are stem mammaliaforms. The new fossil shows fossilized skin membranes that are interpreted to be for gliding and a mandibular middle ear with a unique character combination previously unknown in mammaliaforms. Incisor replacement is prolonged until well after molars are fully erupted, a timing pattern unique to most other mammaliaforms. In situ molar occlusion and a functional analysis reveal a new mode of dental occlusion: dual mortar-pestle occlusion of opposing upper and lower molars, probably for dual crushing and grinding. This suggests that eleutherodontids are herbivorous, and probably specialized for granivory or feeding on soft plant tissues. The inferred dietary adaptation of eleutherodontid gliders represents a remarkable evolutionary convergence with herbivorous gliders in Theria. These Jurassic fossils represent volant, herbivorous stem mammaliaforms associated with pre-angiosperm plants that appear long before the later, iterative associations between angiosperm plants and volant herbivores in various therian clades.
The fabrication of highly biocompatible hydrogels with multiple unique healing abilities for the whole healing process, for example, multifunctional hydrogels with injectable, degradation, antibacterial, antihypoxic, and wound healing–promoting properties that match the dynamic healing process of skin flap regeneration, is currently a research challenge. Here, a multifunctional and dynamic coordinative polyethylene glycol (PEG) hydrogel with mangiferin liposomes (MF‐Lip@PEG) is developed for clinical applications through Ag–S coordination of four‐arm‐PEG‐SH and Ag+. Compared to MF‐PEG, MF‐Lip@PEG exhibits self‐healing properties, lower swelling percentages, and a longer endurance period. Moreover, the hydrogel exhibits excellent drug dispersibility and release characteristics for slow and persistent drug delivery. In vitro studies show that the hydrogel is biocompatible and nontoxic to cells, and exerts an outstanding neovascularization‐promoting effect. The MF‐Lip@PEG also exhibits a strong cytoprotective effect against hypoxia‐induced apoptosis through regulation of the Bax/Bcl‐2/caspase‐3 pathway. In a random skin flap animal model, the MF‐Lip@PEG is injectable and convenient to deliver into the skin flap, providing excellent anti‐inflammation, anti‐infection, and proneovascularization effects and significantly reducing the skin flap necrosis rate. In general, the MF‐Lip@PEG possesses outstanding multifunctionality for the dynamic healing process of skin flap regeneration.
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