Ku80 cooperates with CBP to promote COX-2 expression and tumor growth.

Cyclooxygenase-2 (COX-2) plays an important role in lung cancer development and progression. Using streptavidin-agarose pulldown and proteomics assay, we identified and validated Ku80, a dimer of Ku participating in the repair of broken DNA double strands, as a new binding protein of the COX-2 gene promoter. Overexpression of Ku80 up-regulated COX-2 promoter activation and COX-2 expression in lung cancer cells. Silencing of Ku80 by siRNA down-regulated COX-2 expression and inhibited tumor cell growth in vitro and in a xenograft mouse model. Ku80 knockdown suppressed phosphorylation of ERK, resulting in an inactivation of the MAPK pathway. Moreover, CBP, a transcription co-activator, interacted with and acetylated Ku80 to co-regulate the activation of COX-2 promoter. Overexpression of CBP increased Ku80 acetylation, thereby promoting COX-2 expression and cell growth. Suppression of CBP by a CBP-specific inhibitor or siRNA inhibited COX-2 expression as well as tumor cell growth. Tissue microarray immunohistochemical analysis of lung adenocarcinomas revealed a strong positive correlation between levels of Ku80 and COX-2 and clinicopathologic variables. Overexpression of Ku80 was associated with poor prognosis in patients with lung cancers. We conclude that Ku80 promotes COX-2 expression and tumor growth and is a potential therapeutic target in lung cancer

Rnd3/RhoE Modulates HIF1α/VEGF Signaling by Stabilizing HIF1α and Regulates Responsive Cardiac Angiogenesis

The insufficiency of compensatory angiogenesis in the heart of patients with hypertension contributes to heart failure transition. The hypoxia-inducible factor 1α-vascular endothelial growth factor (HIF1α-VEGF) signaling cascade controls responsive angiogenesis. One of the challenges in reprograming the insufficient angiogenesis is to achieve a sustainable tissue exposure to the proangiogenic factors, such as HIF1α stabilization. In this study, we identified Rnd3, a small Rho GTPase, as a proangiogenic factor participating in the regulation of the HIF1α-VEGF signaling cascade. Rnd3 physically interacted with and stabilized HIF1α, and consequently promoted VEGFA expression and endothelial cell tube formation. To demonstrate this proangiogenic role of Rnd3 in vivo, we generated Rnd3 knockout mice. Rnd3 haploinsufficient (Rnd3(+/-)) mice were viable, yet developed dilated cardiomyopathy with heart failure after transverse aortic constriction stress. The poststress Rnd3(+/-) hearts showed significantly impaired angiogenesis and decreased HIF1α and VEGFA expression. The angiogenesis defect and heart failure phenotype were partially rescued by cobalt chloride treatment, a HIF1α stabilizer, confirming a critical role of Rnd3 in stress-responsive angiogenesis. Furthermore, we generated Rnd3 transgenic mice and demonstrated that Rnd3 overexpression in heart had a cardioprotective effect through reserved cardiac function and preserved responsive angiogenesis after pressure overload. Finally, we assessed the expression levels of Rnd3 in the human heart and detected significant downregulation of Rnd3 in patients with end-stage heart failure. We concluded that Rnd3 acted as a novel proangiogenic factor involved in cardiac responsive angiogenesis through HIF1α-VEGFA signaling promotion. Rnd3 downregulation observed in patients with heart failure may explain the insufficient compensatory angiogenesis involved in the transition to heart failure

Spatiotemporal Variation and Abrupt Change Analysis of Temperature from 1960 to 2012 in the Huang-Huai-Hai Plain, China

Based on a monthly dataset of temperature time series (1960–2012) in the Huang-Huai-Hai Plain of China (HHHPC), spatiotemporal variation and abrupt change analysis of temperature were examined by moving average, linear regression, spline interpolation, Mann-Kendall test, and moving t-test. Major conclusions were listed as follows. (1) Annual and seasonal temperature increased with different rates on the process of fluctuating changes during 1960~2012. The upward trend was 0.22°C 10a−1 for annual temperature, while it was very significant in winter (0.34°C 10a−1) and spring (0.31°C 10a−1), moderately significant in autumn (0.21°C 10a−1), and nonsignificant in summer (0.05°C 10a−1). (2) The spatial changes of annual and seasonal temperature were similar. The temperature increased significantly in Beijing and its adjacent regions, while it was nonsignificant in the central and southern regions. (3) The spring, autumn, winter, and annual temperature had warm abrupt change. The abrupt change time for winter temperature was in the late 1970s, while it was in the late 1980s and early 1990s for spring, autumn, and annual temperature. (4) Macroscopic effects of global and regional climate warming and human activities were probably responsible for the temperature changes. The climate warming would influence the hydrological cycle and agricultural crops in the study area

Overexpression of phyA and appA genes improves soil organic phosphorus utilisation and seed phytase activity in Brassica napus.

Phytate is the major storage form of organic phosphorus in soils and plant seeds, and phosphorus (P) in this form is unavailable to plants or monogastric animals. In the present study, the phytase genes phyA and appA were introduced into Brassica napus cv Westar with a signal peptide sequence and CaMV 35S promoter, respectively. Three independent transgenic lines, P3 and P11 from phyA and a18 from appA, were selected. The three transgenic lines exhibited significantly higher exuded phytase activity when compared to wild-type (WT) controls. A quartz sand culture experiment demonstrated that transgenic Brassica napus had significantly improved P uptake and plant biomass. A soil culture experiment revealed that seed yields of transgenic lines P11 and a18 increased by 20.9% and 59.9%, respectively, when compared to WT. When phytate was used as the sole P source, P accumulation in seeds increased by 20.6% and 46.9% with respect to WT in P11 and a18, respectively. The P3 line accumulated markedly more P in seeds than WT, while no significant difference was observed in seed yields when phytate was used as the sole P source. Phytase activities in transgenic canola seeds ranged from 1,138 to 1,605 U kg(-1) seeds, while no phytase activity was detected in WT seeds. Moreover, phytic acid content in P11 and a18 seeds was significantly lower than in WT. These results introduce an opportunity for improvement of soil and seed phytate-P bioavailability through genetic manipulation of oilseed rape, thereby increasing plant production and P nutrition for monogastric animals

Dynamic Response of UHMW-PE Composite Armors under Ballistic Impact of Blunt Projectiles

To study the dynamic response of UHMW-PE composite armor under ballistic impact, two kinds of UHMW-PE composite armors are designed. Both of them are composed of UHMW-PE laminates and steel face sheets of Q235. The blunt projectile is made of 35CrMnSiA, with a cylinder shape. By numerical simulation, the dynamic response and deformation of composite armors are obtained under the penetration of the projectile. With the increase of impact velocity, the penetration depth increases nearly linearly, with a more severe tendency of swaging in the projectile. Then, experiments are carried out to validate the numerical simulation results. Based on a ballistic gun with a caliber of 14.5 mm, the projectiles are fired with a velocity from 680 m/s to 1300 m/s. The penetration into the composite armor can be divided into an initial shear plugging stage and the following bulging and delamination stage. Based on the theoretical analysis, the shear strength in the shear plugging stage can be estimated. Associated with typical experimental results, numerical simulation is suitable to predict the bulging characteristics of the composite armor. The failure mode of the composite armors under the impact of blunt projectiles is determined, and the failure mechanism is analyzed. The penetration results in the experiment agree well with the numerical simulation results, which validate the correctness of the numerical simulation models. The research results can be significant in the design of composite armor with UHMW-PE laminates

Efficacy and safety of perioperative use of non-steroidal anti-inflammatory drugs for preemptive analgesia in lumbar spine surgery: a systematic review and meta-analysis

Abstract Objective Lumbar spine disorders have become an increasingly common health problem in recent years. Modern clinical studies have shown that perioperative analgesia at certain doses can reduce postoperative pain by inhibiting the process of peripheral sensitization and central sensitization, which is also known as “preemptive analgesia,” Non-steroidal anti-inflammatory drugs (NSAIDs) are a class of drugs that achieve antipyretic and analgesic effects by inhibiting cyclooxygenase (COX) and affecting the production of prostaglandins. Our meta-analysis aimed to assess the efficacy and safety of perioperative preemptive analgesia with non-steroidal anti-inflammatory drugs in patients with lumbar spine surgery. Methods We searched PubMed, ScienceDirect, the Cochrane Library, and the Web of Science for randomized controlled trials (RCTs) that met the inclusion criteria. A total of 12 clinical studies were included to assess the efficacy and safety of perioperative NSAIDs preemptive analgesia for lumbar spine surgery. Result Twelve studies, including 845 patients, met the inclusion criteria. The results showed that perioperative receipt of NSAIDs for preemptive analgesia was effective and safe. Patient’s postoperative morphine consumption (P 0.05). Conclusion Our findings suggest that NSAIDs are effective and safe for preemptive analgesia in the perioperative period of lumbar spine surgery and that more and better quality RCTs and more in-depth studies of pain mechanics are still needed

Deciphering Pharmacological Mechanism of Buyang Huanwu Decoction for Spinal Cord Injury by Network Pharmacology Approach

Objective. The purpose of this study was to investigate the mechanism of action of the Chinese herbal formula Buyang Huanwu Decoction (BYHWD), which is commonly used to treat nerve injuries, in the treatment of spinal cord injury (SCI) using a network pharmacology method. Methods. BYHWD-related targets were obtained by mining the TCMSP and BATMAN-TCM databases, and SCI-related targets were obtained by mining the DisGeNET, TTD, CTD, GeneCards, and MalaCards databases. The overlapping targets of the abovementioned targets may be potential therapeutic targets for BYHWD anti-SCI. Subsequently, we performed protein-protein interaction (PPI) analysis, screened the hub genes using Cytoscape software, performed Gene Ontology (GO) annotation and KEGG pathway enrichment analysis, and finally achieved molecular docking between the hub proteins and key active compounds. Results. The 189 potential therapeutic targets for BYHWD anti-SCI were overlapping targets of 744 BYHWD-related targets and 923 SCI-related targets. The top 10 genes obtained subsequently included AKT1, IL6, MAPK1, TNF, TP53, VEGFA, CASP3, ALB, MAPK8, and JUN. Fifteen signaling pathways were also screened out after enrichment analysis and literature search. The results of molecular docking of key active compounds and hub target proteins showed a good binding affinity for both. Conclusion. This study shows that BYHWD anti-SCI is characterized by a multicomponent, multitarget, and multipathway synergy and provides new insights to explore the specific mechanisms of BYHWD against SCI

Clinical Efficacy and Safety of Zoledronic Acid Combined with PVP/PKP in the Treatment of Osteoporotic Vertebral Compression Fracture: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

Objective. We conducted this meta-analysis to provide better evidence of the efficacy and safety of zoledronic acid (ZA) combined with percutaneous vertebroplasty/kyphoplasty (PVP/PKP) on osteoporotic vertebral compression fracture (OVCF) and proposed a protocol for its application in clinical practice. Methods. All randomized controlled trials (RCTs) of ZA combined with PVP or PKP compared to individual PVP/PKP for the management of patients with OVCFs were included in this study. Electronic database searches were conducted from database inception to November 2020, including the Cochrane Library, PubMed, Web of Science, and Embase. The pooled data were analyzed using RevMan 5.3 software. Results. Seven RCTs with 929 subjects were finally included. All included studies reported visual analog scores (VAS), and no statistically significant differences were identified at follow-ups of 3 d and 1 w (P>0.05). In contrast, significant differences were observed at the 1 mo, 3 mo, 6 mo, and 12 mo follow-ups (P0.05). In addition, significant differences in the bone mineral density (BMD), β-isomerized C-terminal telopeptide of type I collagen (β-CTX), N-terminal propeptide of type I collagen (PINP), and N-terminal molecular fragment (N-MID) levels were observed between the two groups (P0.05). Conclusion. Compared to PVP/PKP alone, an additional ZA injection had advantages of long-term analgesic effects with improved bone metabolism indexes. Moreover, combination therapy significantly prevented complications and drug reactions were well tolerated. Overall, this systematic review revealed that ZA combined with PVP/PKP was an effective, safe, and comprehensive therapy for patients with OVCFs