Adenosine A3 receptor stimulation reduces muscle injury following physical trauma and is associated with alterations in the MMP/TIMP response

We have previously demonstrated that in response to traumatic injury in skeletal muscle, there is a dysregulation of the matrix metalloproteases (MMPs) and their inhibitors (TIMPs), a response hypothesized to interfere with proper skeletal muscle regeneration. Moreover, we have shown that pharmacological activation of the adenosine A(3) receptor by Cl-IBMECA in skeletal muscle can protect against ischemia-reperfusion and eccentric exercise injury. However, the mechanism by which Cl-IBMECA protects muscle tissue is poorly defined. This study evaluated the effects of Cl-IBMECA on MMP/TIMP expression in skeletal muscle and tested the hypothesis that adenosine A(3) receptor-stimulated protection of skeletal muscle following traumatic injury is associated with a blunting of MMPs involved in inflammatory processes and collagen degradation, and an increase in MMPs associated with extracellular matrix remodeling. Sixty C57BL/6J male mice were injected with Cl-IBMECA (n = 30) or a vehicle (n = 30), and Evans blue dye. Injury was induced by applying a cold steel probe (-79°C) to the tibialis anterior (TA) muscle for 10 s. TA muscles from uninjured and injured legs were collected 3, 10, and 24 h postinjury for analysis of muscle injury and MMP/TIMP mRNA and protein levels. Twenty-four hours postinjury, 56.8% of the fibers were damaged in vehicle-treated mice vs. 35.4% in Cl-IBMECA-treated mice (P = 0.02). Cl-IBMECA treatment reduced membrane type 1 (MT1)-MMP, MMP-3, MMP-9, and TIMP-1 mRNA expression 2- to 20-fold compared with vehicle-treated mice (P < 0.05). Cl-IBMECA decreased protein levels of latent/shed MT1-MMP 23-2,000%, respectively, 3-10 h postinjury. In Cl-IBMECA-treated mice, latent MMP-2 was decreased 20% 3 h postinjury, active MMP-3 was decreased 64% 3 h postinjury, and latent/active MMP-9 was decreased 417,631% 3 h postinjury and 20% 10 h postinjury. Protein levels of active MMP-2 and latent MMP-3 were increased 25% and 74% 3 h postinjury, respectively. The present study elucidates a new protective role of adenosine A(3) receptor stimulation in posttraumatic skeletal muscle injury.     

Nanoflake‐Assembled Hierarchical Na3V2(PO4)3/C Microflowers: Superior Li Storage Performance and Insertion/Extraction Mechanism

Na₃V₂(PO₄)₃ (NVP) has excellent electrochemical stability and fast ion diffusion coefficient due to the 3D Na⁺ ion superionic conductor framework, which make it an attractive cathode material for lithium ion batteries (LIBs). However, the electrochemical performance of NVP needs to be further improved for applications in electric vehicles and hybrid electric vehicles. Here, nanoflake‐assembled hierarchical NVP/C microflowers are synthesized using a facile method. The structure of as‐synthesized materials enhances the electrochemical performance by improving the electron conductivity, increasing electrode–electrolyte contact area, and shortening the diffusion distance. The as‐synthesized material exhibits a high capacity (230 mAh g^?1), excellent cycling stability (83.6% of the initial capacity is retained after 5000 cycles), and remarkable rate performance (91 C) in hybrid LIBs. Meanwhile, the hybrid LIBs with the structure of NVP || 1 m LiPF₆/EC (ethylene carbonate) + DMC (dimethyl carbonate) || NVP and Li₄Ti₅O₁₂ || 1 m LiPF₆/EC + DMC || NVP are assembled and display capacities of 79 and 73 mAh g^?1, respectively. The insertion/extraction mechanism of NVP is systematically investigated, based on in situ X‐ray diffraction. The superior electrochemical performance, the design of hybrid LIBs, and the insertion/extraction mechanism investigation will have profound implications for developing safe and stable, high‐energy, and high‐power LIBs.     

No‐tillage and fertilization management on crop yields and nitrate leaching in North China Plain

A field experiment was performed from 2003 to 2008 to evaluate the effects of tillage system and nitrogen management regimes on crop yields and nitrate leaching from the fluvo-aquic soil with a winter wheat (Triticum aestivum L.)–maize (Zea mays L.) double-cropping system. The tillage systems consisted of conventional tillage (CT) and no-tillage (NT). Three nitrogen management regimes were included: 270 kg N ha⁻¹ of urea for wheat and 225 kg N ha⁻¹ of urea for maize (U), 180 kg N ha⁻¹ of urea and 90 kg N ha⁻¹ of straw for wheat and 180 kg N of urea and 45 kg N ha⁻¹ of straw for maize (S), 180 kg N ha⁻¹ of urea and 90 kg N ha⁻¹ of manure for wheat and 180 kg N ha⁻¹ of urea and 45 kg N ha⁻¹ of manure for maize (M). An array of tension-free pan lysimeters (50 cm × 75 cm) were installed (1.2 m deep) to measure water flow and -N movement. No significant effect of the N management regime on yields of winter wheat and maize grain was found in the 5-year rotation. Tillage systems had significant influences on -N leaching from the second year and thereafter interacted with N management regimes on -N loads during all maize seasons. The average yield-scaled -N leaching losses were in order of CTS < NTS< CTU < NTU −1 for winter wheat system and from 0.99 (CTS) to 6.27 (NTM) kg N Mg⁻¹ for summer maize system for 5 rotation years. The results showed that CTS decreased the yield-scaled -N leaching losses while sustaining crop grain yields. Considering the lower costs, NTS could be a potential alternative to decrease yield-scaled -N leaching losses and improve soil fertility while maintaining crop yield for the winter wheat–maize double-cropping systems in the North China Plain.     

An TRIM59‐CDK6 axis regulates growth and metastasis of lung cancer

Lung cancer (LC) is a devastating malignancy with no effective treatments, due to its complex genomic profile. Using bioinformatics analysis and immunohistochemical of lung carcinoma tissues, we show that TRIM59 as a critical oncoprotein relating to LC proliferation and metastasis. In this study, high TRIM59 expression was significantly correlated with lymph node metastasis, distant metastasis, and tumour stage. Furthermore, up‐regulation of TRIM59 expression correlated with poorer outcomes in LC patients. Mechanistically, TRIM59 play a key role in promoting LC growth and metastasis through regulation of extracellular‐signal regulated protein kinase (ERK) signalling pathway and epithelial‐to‐mesenchymal transition (EMT)‐markers, as validated by loss‐of‐function studies. In‐depth bioinformatics analysis showed that there is preliminary evidence of co‐expression of TRIM59 and cyclin dependent kinase 6 (CDK6) in LC. Notably, CDK6 expression significantly decreased when TRIM59 was knocked down in the LC cells. In contrast, exogenous up‐regulation of TRIM59 expression also induced significant increases in the expression of CDK6. Moreover, the expression of CDK6 was also inhibited by the ERK signalling inhibitor, U0126. The results of both loss‐ and gain‐of‐function studies showed that TRIM59 could regulate the expression of CDK6. Collectively, these data provide evidence that TRIM59 is involved in lung carcinoma growth and progression possibly through the induction of CDK6 expression and EMT process by activation of ERK pathway.