Search

We assessed the roles of Smad7 in skin inflammation and wound healing using genetic and pharmacological approaches. In K5.TGFβ1/K5.Smad7 bigenic (double transgenic) mice, Smad7 transgene expression reversed transforming growth factor (TGF)-β1 transgene-induced inflammation, fibrosis, and subsequent epidermal hyperplasia and molecularly abolished TGF-β and NF-κB activation. Next, we produced recombinant human Smad7 protein with a Tat-tag (Tat-Smad7) that rapidly enters cells. Subcutaneous injection of Tat-Smad7 attenuated infiltration of F4/80+ and CD11b+ leukocytes and α-smooth muscle actin+ fibroblasts before attenuating epidermal hyperplasia in K5.TGFβ1 skin. Furthermore, topically applied Tat-Smad7 on K5.TGFβ1 skin wounds accelerated wound closure, with improved re-epithelialization and reductions in inflammation and fibrotic response. A short treatment with Tat-Smad7 was also sufficient to reduce TGF-β and NF-κB signaling in K5.TGFβ1 skin and wounds. Relevant to the clinic, we found that human diabetic wounds had elevated TGF-β and NF-κB signaling compared with normal skin. To assess the oncogenic risk of a potential Smad7-based therapy, we exposed K5.Smad7 skin to chemical carcinogenesis and found reduced myeloid leukocyte infiltration in tumors but not accelerated carcinogenesis compared with wild-type littermates. Our study suggests the feasibility of using exogenous Smad7 below an oncogenic level to alleviate skin inflammation and wound healing defects associated with excessive activation of TGF-β and NF-κB.

Drawing upon the data of China's animal husbandry industry from 2000 to 2020 in 30 provinces, an EBM model incorporating non-desired outputs was employed to gauge the carbon emission efficiency of the animal husbandry industry. Coupling degree models, spatial autocorrelation models, and Markov chain models were utilized to assess the coupling degree between the industrial agglomeration of the animal husbandry sector and its carbon emission efficiency, and to analyze its spatio-temporal distribution and evolution. The outcomes showed that (1) the coupling degree of China's animal husbandry industry agglomeration and carbon emission efficiency exhibited an overall downward inclination. Notably, the diminishing tendency of the coupling degree was more pronounced in the eastern, central, and western parts of the country; (2) the coupling degree of the 30 provinces showed a spatial distribution of "western > central > northeast > eastern"; (3) the coupling degree showed obvious agglomeration distribution characteristics, wherein a substantial quantity of provinces was located in high–high clustering zones and low–low clustering zones; (4) the coupling degree of various provinces remained fairly stable, but after considering the spatial and geographical correlation, the coupling degree of each province would be influenced by the coupling degree of its adjacent provinces. Evidently, there remained a substantial scope for the enhancement of the coupling coordination degree between the industrial agglomeration of China's animal husbandry and the carbon emission efficiency. This research is capable of furnishing a theoretical allusion for promoting regional cooperation, leveraging agglomeration advantages, and implementing carbon emission abatement regimes and directives to enhance the low-carbon development level of animal husbandry industry agglomeration in China. [ABSTRACT FROM AUTHOR]

The resource value of feces and kitchen waste has not been fully emphasized and utilized in rural sanitation management in China. In this paper, we propose a new ecological sanitation model with the core technology of "vacuum toilet and vacuum kitchen waste shredder—vacuum collection—resource treatment", i.e., the modern home–farm cycle sanitation (MHFCS) system. We compared the environmental performance of the MHFCS system with that of a typical end-pipe treatment sanitation (EPTS) system (Johkasou—small onsite wastewater treatment system) in rural China using a life cycle assessment (LCA) approach. The results showed that the main source of environmental impacts of the MHFCS system was the collection and treatment process of domestic organic liquid wastes; the greenhouse gas emissions were 64.543 kg CO2eq·PE−1·year−1, and the MHFCS system indirectly gained a fertilizer substitution benefit of 65.960 kg CO2eq·PE−1·year−1 through nutrient element recycling. The MHFCS system has significant advantages in terms of net GHG emissions. Sensitivity analyses showed that resource consumption of vacuum facilities was a key factor for the MHFCS system. This system offers the potential to break down the barriers of the EPTS system in order to meet environmental sustainability and market demands for systemic diversity. [ABSTRACT FROM AUTHOR]

The endogenous small GTPase, Rac1, plays a critical role during normal skin wound healing. It remains to be determined whether endogenous Rac1 can be appropriately activated in chronic wounds; if not, whether exogenous Rac1 has therapeutic effects on wound healing. Here we show that Rac1 protein levels were lower in wounds of db/db diabetic mice than wounds in wild type mice during the healing process. To assess the therapeutic potential of exogenous Rac1 in wound healing, we produced a Tat-Rac1 fusion protein that enters into cells through protein transduction. Tat-Rac1 increased proliferation and migration of keratinocytes and dermal fibroblasts in vitro. Topical application of Tat-Rac1 accelerated cutaneous wound closure in vivo in db/db mice as well as wild type mice. Further analyses revealed that Tat-Rac1 had faster re-epithelialization, higher keratinocyte proliferation and migration without an earlier onset of myofibroblast activation than vehicle treated wounds. Tat-Rac1 also reduced inflammation in wounds. Our findings revealed the failure of diabetic wounds to elevate Rac1 expression and suggested a therapeutic strategy utilizing a Rac1-based biologic to compensate for this defect thereby promoting wound healing.