BRD4 promotes the migration and invasion of bladder cancer through the Sonic hedgehog signaling pathway and enhances cisplatin resistance

Platinum-based chemotherapy is a widely used strategy in bladder cancer (BCa) treatments. However, the clinical efficacy is affected by chemotherapy resistance with complex molecular mechanisms. Therefore, it is urgent to explore new targets for BCa therapy. Here, we showed that bromodomain-4 protein (BRD4) expression was obviously upregulated in BCa tissues and cells. Inhibition of BRD4 attenuated the migration and invasion of BCa cells, which was rescued by the Sonic hedgehog (SHH) pathway activator recombinant human Sonic hedgehog peptide (rhSHH). We further found that cisplatin (DDP) suppressed the migration and invasion of BCa cells in vitro and inhibited tumor growth in vivo; however overexpression of BRD4 weakened the pharmacological effects of DDP. In brief, our research reveals that BRD4 promotes migration and invasion by positively regulating the SHH pathway, drives DDP resistance in BCa and is a novel therapeutic target for the treatment of BCa.The accepted manuscript in pdf format is listed with the files at the bottom of this page. The presentation of the authors' names and (or) special characters in the title of the manuscript may differ slightly between what is listed on this page and what is listed in the pdf file of the accepted manuscript; that in the pdf file of the accepted manuscript is what was submitted by the author

Quantification of Plasma Cell-Free DNA1 in Predicting Therapeutic Efficacy of Sorafenib on Metastatic Clear Cell Renal Cell Carcinoma

PURPOSE: The objective of this study is to determine whether or not plasma cfDNA levels can predict efficacy of sorafenib in patient with metastatic cRCC

Should exotic Eucalyptus be planted in subtropical China : insights from understory plant diversity in two contrasting Eucalyptus chronosequences

Although Eucalyptus is widely planted in South China, whose effects on native biodiversity are unclear. The objective of this study was to quantify the richness and composition of understory plants in two contrasting Eucalyptus chronosequences in South China. One was in Zhangzhou City with plantation age of 2, 4, and 6 years after clear-cutting Chinese fir forests, while the other was in Heshan City with plantation age of 2, 3, and 24 years that reforested on barren lands. Results showed that the richness of understory plants and functional groups was not significantly altered in the Zhangzhou chronosequence, while increased in the 24-year-old plantations, with a significantly larger proportion of woody plants than the younger plantations for the Heshan chronosequence. Moreover, a higher richness of woody plants accompanied by a lower richness of herbaceous species was detected in the Zhangzhou chronosequence compared with the Heshan one. To balance the need for pulp production and plant diversity conservation, we suggest that intercropping approaches between exotic Eucalyptus plantations and native forests should be considered in the fast rotation Eucalyptus plantations. However, Eucalyptus plantations may be used as pioneer species to sustain ecosystem functioning for the degraded lands

Attenuation Effect of Recovery Sleep for Impaired Reproductive Function in Male Rats by Sleep Deprivation

Purpose: The aim of the present study was to test the hypothesis that recovery sleep could counteract the detrimental effects of sleep deprivation (SD) on male rats’ fertility. Materials and Methods: Twenty-two rats were housed in groups of six per cage with unrestricted access to food and water in a room. The modified multiple platform method was used to induce SD in rats over a 96-hour period. We examined the effect of SD on semen quality, reproductive hormones, and testicular histology in adult male rats. Then, we investigated the effect of 7 days recovery sleep on impaired reproductive function induced by SD. Results: After the acclimation period, 22 rats were randomly separated into three experimental groups (SD, recovery sleep, and the control groups). Ninety-six hours of SD resulted in a significant decrease in sperm motility (24.33±10.93 vs . 48.20±8.55, p<0.001) and the number of morphologically normal sperm (9.68±2.77 vs. 26.21±14.60, p<0.01) in rats, accompanied by a decrease in testosterone levels (1.53±0.55 vs. 4.44±0.56, p<0.001) and destruction of testicular tissue structure compared with control group. After 7 days of recovery sleep, semen quality, especially sperm motility, was improved and testosterone levels were significantly higher compared to post-SD (3.70±0.53 vs. 1.53±0.55, p<0.05), but remained low compared to the control group. Conclusions: In conclusion, 96 hours of SD deteriorated the parameters of sperm motility and the number of morphologically normal sperm in rats, probably due to the decrease in serum testosterone levels and the disruption of testicular tissue structure when compared to the control group. After 7 days of recovery sleep, semen parameter, especially sperm motility and testosterone levels did not return to baseline levels compared to the control group

Asynchronous responses of soil microbial community and understory plant community to simulated nitrogen deposition in a subtropical forest

Atmospheric nitrogen (N) deposition greatly affects ecosystem processes and properties. However, few studies have simultaneously examined the responses of both the above- and belowground communities to N deposition. Here, we investigated the effects of 8 years of simulated N deposition on soil microbial communities and plant diversity in a subtropical forest. The quantities of experimental N added (g of N m(−2) year(−1)) and treatment codes were 0 (N0, control), 6 (N1), 12 (N2), and 24 (N3). Phospholipid fatty acids (PLFAs) analysis was used to characterize the soil microbial community while plant diversity and coverage were determined in the permanent field plots. Microbial abundance was reduced by the N3 treatment, and plant species richness and coverage were reduced by both N2 and N3 treatments. Declines in plant species richness were associated with decreased abundance of arbuscular mycorrhizal fungi, increased bacterial stress index, and reduced soil pH. The plasticity of soil microbial community would be more related to the different responses among treatments when compared with plant community. These results indicate that long-term N deposition has greater effects on the understory plant community than on the soil microbial community and different conservation strategies should be considered

Asynchronous responses of soil microbial community and understory plant community to simulated nitrogen deposition in a subtropical forest

Atmospheric nitrogen (N) deposition greatly affects ecosystem processes and properties. However, few studies have simultaneously examined the responses of both the above- and belowground communities to N deposition. Here, we investigated the effects of 8 years of simulated N deposition on soil microbial communities and plant diversity in a subtropical forest. The quantities of experimental N added (g of N m-2 year-1) and treatment codes were 0 (N0, control), 6 (N1), 12 (N2), and 24 (N3). Phospholipid fatty acids (PLFAs) analysis was used to characterize the soil microbial community while plant diversity and coverage were determined in the permanent field plots. Microbial abundance was reduced by the N3 treatment, and plant species richness and coverage were reduced by both N2 and N3 treatments. Declines in plant species richness were associated with decreased abundance of arbuscular mycorrhizal fungi, increased bacterial stress index, and reduced soil pH. The plasticity of soil microbial community would be more related to the different responses among treatments when compared with plant community. These results indicate that long-term N deposition has greater effects on the understory plant community than on the soil microbial community and different conservation strategies should be considered. Nitrogen deposition may change above- and belowground biological communities. Our results indicate that N deposition has greater effects on the understory plant community than on the soil microbial community and different conservation strategies should be considered

CircHIPK3 negatively regulates autophagy by blocking VCP binding to the Beclin 1 complex in bladder cancer

Abstract Circular RNA HIPK3 (circHIPK3) mediates the progression of multiple cancers, including bladder cancer, by regulating cell migration, autophagy and epithelial mesenchymal transition. However, the mechanism by which circHIPK3 regulates autophagy in bladder cancer cells remains unclear. Autophagy is a common self-protection mechanism in eukaryotic cells and is essential for cell survival and death regulation. However, it is unclear whether circHIPK3 affects the level of autophagy in bladder cancer through binding proteins, and the potential regulatory mechanism is unknown. Here, we found that circHIPK3 levels were significantly lower and autophagy-related proteins were significantly upregulated in bladder cancer cells and tissues compared to normal controls. CircHIPK3 downregulation promoted bladder cancer cell proliferation, while circHIPK3 overexpression inhibited proliferation. CircHIPK3 overexpression significantly suppressed autophagy in bladder cancer cells. Overexpression of circHIPK3 did not affect VCP protein expression but inhibited the VCP/Beclin 1 interaction. VCP also stabilized Beclin 1 and promoted autophagy in bladder cancer cells by downregulating ataxin-3. Thus, circHIPK3 may play an important role in bladder cancer by inhibiting VCP-mediated autophagy

The decoupling between gas exchange and water potential of Cinnamomum camphora seedlings during drought recovery and its relation to ABA accumulation in leaves

Aims Drought stress and the degree of drought severity are predicted to rise under highly variable patterns of precipitation due to climate change, while the capacity of trees to cope with drought recovery through physiological and biochemical adjustment remains unclear. We aimed to examine the coupling of physiology and biochemistry in trees during drought and the following recovery. Methods Potted seedlings of Cinnamomum camphora were grown under well watered conditions prior to the experimental drought stress, which was initiated by withholding water. Seedlings were rewatered following attainment of two drought severities: mild drought (stomatal closure) and moderate drought (ψxylem = −1.5 MPa). We measured leaf-level water potential, gas exchange (photosynthesis and stomatal conductance), abscisic acid (ABA), proline and non-structural carbohydrates (NSCs) concentrations in seedlings of C. camphora during drought and a 4-day recovery. Important Findings We found that drought severity largely determined physiological and biochemical responses and affected the rate of recovery. Stomatal closure occurred at the mild drought stress, accompanied with ABA accumulation in leaves and decline in water potential, while leaf proline accumulation and variable NSC were evident at the moderate drought stress. More severe drought stress led to delayed recovery of gas exchange, but it did not have significant effect on water potential recovery. The relationships of water potential and gas exchange differed during drought stress and post-drought recovery. There was tight coupling between water potential and gas exchange during drought, but not during rewatering due to high ABA accumulation in leaves, thereby delaying recovery of stomatal conductance. Our results demonstrate that ABA could be an important factor in delaying the recovery of stomatal conductance following rewatering and after water potential recovery of C. camphora. Furthermore, greater drought severity had significant impacts on the rate of recovery of tree physiology and biochemistry