GH stimulates growth plate chondrogenesis and longitudinal bone growth directly at the growth plate. However, it is not clear yet whether these effects are entirely mediated by the local expression ...and action of IGF-1 and IGF-2. To determine whether GH has any IGF-independent growth-promoting effects, we generated TamCartIgf1rflox/flox mice. The systemic injection of tamoxifen in these mice postnatally resulted in the excision of the IGF-1 receptor (Igf1r) gene exclusively in the growth plate. TamCartIgf1rflox/flox tamoxifen-treated mice knockout (KO) mice and their Igf1rflox/flox control littermates (C mice) were injected for 4 weeks with GH. At the end of the 4-week period, the tibial growth and growth plate height of GH-treated KO mice were greater than those of untreated C or untreated KO mice. The systemic injection of GH increased the phosphorylation of Janus kinase 2 and signal transducer and activator of transcription 5B in the tibial growth plate of the C and KO mice. In addition, GH increased the mRNA expression of bone morphogenetic protein-2 and the mRNA expression and protein phosphorylation of nuclear factor-κB p65 in both C and KO mice. In cultured chondrocytes transfected with Igf1r small interfering RNA, the addition of GH in the culture medium significantly induced thymidine incorporation and collagen X mRNA expression. In conclusion, our findings demonstrate that GH can promote growth plate chondrogenesis and longitudinal bone growth directly at the growth plate, even when the local effects of IGF-1 and IGF-2 are prevented. Further studies are warranted to elucidate the intracellular molecular mechanisms mediating the IGF-independent, growth-promoting GH effects.
During acidic pretreatment of renewable lignocellulosic biomass, lignin depolymerization/repolymerization reactions often occur, which intensifies lignin inhibition on cellulose hydrolysis generally ...through lignin-derived inhibitors formation, unproductive binding and physical blockage effect. In order to improve the enzymatic digestibility of dilute acid pretreated hardwood, in this work various additives were compared and their inhibition mitigating effects were examined. It was revealed that 2-naphthol addition reduced the formation of inhibitory derivatives from lignin, thus increasing the enzymatic hydrolysis yield of the whole slurry after dilute acid pretreatment. The addition of phenolic acids largely diminished enzyme binding effect of the insoluble lignin. Moreover, the 2-naphthol-7-sulfonate additive led to the most pronounced mitigation on physical blockage effect of lignin, as XPS and SEM results showed the significant removal of surface lignin. This work revealed the different mechanisms of various additives in mitigating lignin inhibition, and provided a better understanding on utilizing proper additives to improve biomass saccharification for biorefinery applications.
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•Proper additives in pretreatment could effectively mitigate lignin inhibition.•Lignin inhibition of cellulose hydrolysis was evaluated and quantified.•Suppression of lignin depolymerization decreased toxic phenolics formation in WSF.•Lignin physical blockage was notably reduced by preventing lignin repolymerization.•Phenolic acids as green additives mostly diminished enzyme binding to lignin.
Sirt1 involved in cellular aging and aging-related diseases, including osteoarthritis (OA). Our previous study showed Sirt1 played a role in the pathogenesis of OA, however, the underlying mechanisms ...are still poorly elicited. In this study, we investigated the role of Sirt1 in epigenetically regulating P53/P21 pathway in a Sirt1 loss model. Sirt1 deletion male mice (n = 10) with destabilization of the medial meniscus (DMM) were used to observe its role on OA development. Then, the relationships between SIRT1 and P53 were detected by Coimmunoprecipitation (CoIP), and the gain-off function of P53 gene was indicated by P53 activators and inhibitors in vitro. Finally, human cartilage samples from patients with OA were collected. Sirt1 deletion mice displayed a spontaneous OA development, manifesting severe chondrocytes hypertrophy markers MMP13 and ADAMTS5, highly expressed P53 and P21. Strikingly, surgery-induced meniscus injury promoted the OA pathogenesis and apoptosis in Sirt1 deficient mice. Ultimately, our CoIP data demonstrated that Sirt1 directly interacted with P53 in vitro. However inhibition of P53 alleviated OA progression. We also observed that chondrocyte apoptosis and P53 increased in osteoarthritis (OA) progression with a declining expression of Sirt1 in human cartilage. Loss of Sirt1 in cartilage led to accelerated OA pathogenesis via aberrant activation of p53/p21 mediated senescence associated secretory phenotype, hypertrophy and apoptosis.
•Sirt1 deletion in cartilage aggravated age-related osteoarthritis in mice.•Disruption of Sirt1 in cartilage exacerbated post-traumatic osteoarthritis (PTOA) in mice by activating P53/P21.•Inhibition of P53 either in chondrocytes or femoral heads improved the OA-like changes.
Solution processable planar heterojunction perovskite solar cell has drawn much attention as a promising low-cost photovoltaic device, and much effort has been made to improve its power conversion ...efficiency by choosing appropriate additives for the perovskite precursor solution. Different to those additives reported, a soluble and thermal stable tert-butyl substituted copper phthalocyanine (CuPc(tBu)4) as additive is first introduced into the perovskite precursor solution of a planar perovskite solar cell that is fabricated via the one-step solution process. It is found that the pristine device without CuPc(tBu)4 additive exhibits a power conversion efficiency of 15.3%, while an extremely low concentration (4.4 × 10−3 mM) of CuPc(tBu)4 in the precursor solution leads to the corresponding device achieving an enhanced power conversion efficiency of 17.3%. CuPc(tBu)4 as an additive can improve the quality of perovskite layer with higher crystallinity and surface coverage, then resulting in enhanced light absorption and reduced charge recombination, and thus the better power conversion efficiency. The finding presented here provides a new choice for improving the quality of perovskite layer and the photovoltaic performance of the planar heterojunction perovskite solar cells.
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•CuPc(tBu)4 as additive is first introduced into the perovskite precursor solution.•The effects of CuPc(tBu)4 additive on the devices' photovoltaic performance are investigated.•CuPc(tBu)4 additive can improve the quality of perovskite layer.•Power conversion efficiency of the planar perovskite solar cell is enhanced from 15.3% to 17.3%.
Autophagy is an essential cellular homeostasis mechanism that was found to be compromised in aging and osteoarthritis (OA) cartilage. Previous studies showed that resveratrol can effectively regulate ...autophagy in other cells. The purpose of this study was to determine whether the chondroprotective effect of resveratrol was related to chondrocyte autophagy and to elucidate underlying mechanisms. OA model was induced by destabilization of the medial meniscus (DMM) in 10-week-old male mice. OA mice were treated with resveratrol with/without 3-MA for 8 weeks beginning 4 weeks after surgery. The local intra-articular injection of resveratrol delayed articular cartilage degradation in DMM-induced OA by OARSI scoring systems and Safranin O-fast green. Resveratrol treatment increased Unc-51-like kinase1, Beclin1, microtubule-associated protein light chain 3, hypoxia inducible factor-1α, phosphorylated AMPK, collagen-2A1, Aggrecan expressions, but decreased hypoxia inducible factor-2α, phosphorylated mTOR, matrix metalloproteinases13 and a disintegrin and metalloproteinase with thrombospondin motifs 5 expressions. The effects of resveratrol were obviously blunted by 3-MA except HIF and AMPK. These findings indicate that resveratrol intra-articular injection delayed articular cartilage degeneration and promoted chondrocyte autophagy in an experimental model of surgical DMM-induced OA, in part via balancing HIF-1α and HIF-2α expressions and thereby regulating AMPK/mTOR signaling pathway.
Biological soil crusts (BSCs, or biocrusts) have important positive ecological functions such as erosion control and soil fertility improvement, and they may also have negative effects on soil ...moisture in some cases. Simultaneous discussions of the two-sided impacts of BSCs are key to the rational use of this resource. This study focused on the contribution of BSCs while combining with specific types of vegetation to erosion reduction and their effects on soil moisture, and it addressed the feasibility of removal or raking disturbance. Twelve plots measuring 4 m × 2 m and six treatments (two plots for each) were established on a 15° slope in a small watershed in the Loess Plateau using BSCs, bare land (as a control, BL), Stipa bungeana Trin. (STBU), Caragana korshinskii Kom. (CAKO), STBU planted with BSCs (STBU+BSCs) and CAKO planted with BSCs (CAKO+BSCs). The runoff, soil loss and soil moisture to a depth of 3 m were measured throughout the rainy season (from June to September) of 2010. The results showed that BSCs significantly reduced runoff by 37.3% and soil loss by 81.0% and increased infiltration by 12.4% in comparison with BL. However, when combined with STBU or CAKO, BSCs only made negligible contributions to erosion control (a runoff reduction of 7.4% and 5.7% and a soil loss reduction of 0.7% and 0.3%). Generally, the soil moisture of the vegetation plots was lower in the upper layer than that of the BL plots, although when accompanied with a higher amount of infiltration, this soil moisture consumption phenomenon was much clearer when combining vegetation with BSCs. Because of the trivial contributions from BSCs to erosion control and the remaining exacerbated consumption of soil water, moderate disturbance by BSCs should be considered in plots with adequate vegetation cover to improve soil moisture levels without a significant erosion increase, which was implied to be necessary and feasible.
•The erosion processes on a convex slope were analyzed by a 3D reconstruction method.•Rill and interrill erosion contributed 60 and 40% to the slope erosion based on DEM.•The differences of slope ...erosion between the convex slope and uniform slope were discussed.•Slope erosion rate was positively correlated with rill density and rill dissection degree.
Rill erosion is one of the main forms of soil erosion on hillslopes in hilly and gully regions of the Loess Plateau. For simplicity, many studies assume hillslopes with a uniform sloping profile. However, the most loess hillslopes are convex shape with variable degrees in this area. Estimating soil losses and planning soil conservation practices on such slopes have required much local judgment. The objective of this study was to clarify soil erosion evolution qualitatively and quantitatively on a convex slope based on a three-dimensional (3D) reconstruction technique and geographic information system (GIS) in simulated rainfall experiments. The results showed that: (1) The erosion processes of the convex slope could be reasonably described with the following stages: splash and sheet erosion – drop pits – head-cut erosion – intermittent rill – continuous rill – rill network development – transition from rill to ephemeral gully. (2) Soil loss rate from the convex slope varied from 0.127 Kg m−2 min−1 in the sheet erosion stage to 0.342 Kg m−2 min−1 in rill network development stage, which was much greater compared with the results of uniform slope erosion reported by others in this area. Once rill erosion evolved into the dominant erosion pattern (after 30 mm of rainfall), rill length, width, and depth enlarged noticeably with headward and lateral erosion. (3) The contribution of sediment from rill and inter-rill erosion to total erosion was accurately depicted, and rill erosion contributed up to 60% of the total sediment amount. (4) Soil erosion rate was significantly correlated with rill morphological parameters—fractal dimension, rill density, and degree of rill dissection (correlation coefficients of 0.978, 0.989, and 0.980, respectively). These results are helpful for the qualitative and quantitative understanding of the erosion processes of hillslopes in Chinese Loess Plateau, and have an important reference for the rational arrangement of erosion control measures.
Background: Evidence suggests that fibroblast growth factor 21 (FGF21) inhibits longitudinal bone growth.
Results: FGF21 antagonizes the growth hormone (GH) stimulatory effects on thymidine ...incorporation and collagen X expression in chondrocytes.
Conclusion: FGF21 inhibits bone growth by antagonizing GH effects on chondrocyte proliferation and differentiation.
Significance: Increased FGF21 during food restriction may contribute to growth failure by directly inhibiting chondrogenesis.
Fibroblast growth factor 21 (FGF21) modulates glucose and lipid metabolism during fasting. In addition, previous evidence indicates that increased expression of FGF21 during chronic food restriction is associated with reduced bone growth and growth hormone (GH) insensitivity. In light of the inhibitory effects on growth plate chondrogenesis mediated by other FGFs, we hypothesized that FGF21 causes growth inhibition by acting directly at the long bones' growth plate. We first demonstrated the expression of FGF21, FGFR1 and FGFR3 (two receptors known to be activated by FGF21) and β-klotho (a co-receptor required for the FGF21-mediated receptor binding and activation) in fetal and 3-week-old mouse growth plate chondrocytes. We then cultured mouse growth plate chondrocytes in the presence of graded concentrations of rhFGF21 (0.01–10 μg/ml). Higher concentrations of FGF21 (5 and 10 μg/ml) inhibited chondrocyte thymidine incorporation and collagen X mRNA expression. 10 ng/ml GH stimulated chondrocyte thymidine incorporation and collagen X mRNA expression, with both effects prevented by the addition in the culture medium of FGF21 in a concentration-dependent manner. In addition, FGF21 reduced GH binding in cultured chondrocytes. In cells transfected with FGFR1 siRNA or ERK 1 siRNA, the antagonistic effects of FGF21 on GH action were all prevented, supporting a specific effect of this growth factor in chondrocytes. Our findings suggest that increased expression of FGF21 during food restriction causes growth attenuation by antagonizing the GH stimulatory effects on chondrogenesis directly at the growth plate. In addition, high concentrations of FGF21 may directly suppress growth plate chondrocyte proliferation and differentiation.
Carboxymethyl cellulose (CMC) and polylactic acid (PLA) are recognized for their environmental friendliness. By merging them into a composite film, packaging solutions can be designed with good ...performance. Nonetheless, the inherent interface disparity between CMC and PLA poses a challenge, and there may be layer separation issues. This study introduces a straightforward approach to mitigate this challenge by incorporating tannin acid and ferric chloride in the fabrication of the CMC−PLA. The interlayer compatibility was improved by the in situ formation of a cohesive interface. The resulting CMC/TA−PLA/Fe multilayer film, devoid of any layer separation, exhibits exceptional mechanical strength, with a tensile strength exceeding 70 MPa, a high contact angle of 105°, and superior thermal stability. Furthermore, the CMC/TA−PLA/Fe film demonstrates remarkable efficacy in blocking ultraviolet light, effectively minimizing the discoloration of various wood surfaces exposed to UV aging.