CELF4 regulates spine formation and depression-like behaviors of mice.

Chronic social stress is closed related to major depressive disorder, torturing millions of people and may destroy their lives. The prefrontal cortex is one of the core brain areas involved in pathological development and behavior changes in depression. CELF4 is a neuronal RNA-binding protein and plays an essential role in RNA processing. It is closely related to some neurological disorders, including seizures and neuroticism. Most recently, GWAS analysis indicates it is one of the significant genes associated with depression. Nonetheless, we are still unknown whether and how CELF4 gets involved in depression. Here, we reported that the protein and mRNA expression levels of CELF4 in the PFC were decreased in the CSDS depression model, as well as the spine number. Furthermore, we disturbed CELF4 expression in the PFC by using the AAV-shCELF4 virus. Unexpectedly, the spine number showed a decrease in PFC because of the impaired CELF4 expression, and the AAV-shCELF4 mice displayed depression-like behaviors. Our results suggest that CELF4 is critical for spine number and acts a critical role in depression-like behaviors of mice.

Association between the RAGE gene -374T/A, -429T/C polymorphisms and diabetic nephropathy: a meta-analysis.

AIM: The investigations into the association between the receptor for advanced glycation end products (RAGE) gene -374T/A, -429T/C polymorphisms and diabetic nephropathy (DN) in several case-control studies have rendered conflicting results. To shed light on these inconclusive findings, a meta-analysis of all the eligible studies relating these two polymorphisms to the risk of DN was conducted. METHODS: The databases were searched for relevant articles up to July 2014. A pooled estimate of the genetic association, the heterogeneity between studies, and the publication bias were investigated. RESULTS: Eight studies with 1725 cases and 1857 controls were enrolled in -374T/A polymorphism analysis. The main analysis indicated no association for the allele contrast, the recessive model and the dominant model. Subgroup analyses in Caucasians and in type 2 diabetes also showed no association between -374T/A polymorphism and DN. Five studies with 1019 cases and 792 controls were enrolled in -429T/C polymorphism analysis. The main analysis revealed heterogeneity and no association for the allele contrast and the dominant model. However, the recessive model for -429C allele diminished the heterogeneity and showed a marginal association overall [fixed-effects OR = 2.83 (1.33-6.00) and random effects OR = 2.50 (1.00-6.24), respectively]. CONCLUSIONS: Our meta-analysis indicated that the RAGE gene -429CC genotype might be a risk factor for DN in patients with type 2 diabetes.

[Effect of occlusal reconstruction on cerebral blood flow and cerebral oxygen saturation in patients with malocclusion].

OBJECTIVE: To investigate the effect of occlusal reconstruction on blood flow velocity and cerebral oxygen saturation in patients with malocclusion. METHODS: Thirty-three patients with malocclusion treated with occlusal reconstruction in Department of Stomatology, Medical School of Huzhou Normal College from Feb 2011 to Oct 2013 were enrolled in the study. The systolic peak flow velocity (vs), end-diastolic peak flow (vd) , mean peak flow velocity (vm) of middle cerebral artery and the oxygen saturation (rScO2) in the brain were detected at rest or chewing status by using transcranial Doppler color ultrasonography and near-infrared spectroscopy, respectively. RESULTS: In rest state, vm was significantly increased on 3 months after treatment, while vs and vd were significantly increased on 6 months after treatment and rScO2 were increased on 12 months after treatment (P<0.05). In chewing state, vs, vm, and rScO2 were increased on 3 months after treatment, and vd was increased on 6 months after treatment (P<0.05). CONCLUSION: Occlusal reconstruction can increase blood flow velocity of middle cerebral artery and cerebral oxygen saturation and improve oxygen supply of the brain in patients with malocclusion.

Deep Learning-Based Quantitative Blastocyst Assessment.

Selecting the single best blastocyst based on morphological appearance for implantation is a crucial part of in vitro fertilization (IVF). Various deep learning and computer vision-based methods have recently been applied for assessing blastocyst quality. However, to the best of our knowledge, most previous works utilize classification networks to give a qualitative evaluation. It would be challenging to rank blastocyst quality with the same qualitative result. Thus, this paper proposes a regression network combined with a soft attention mechanism for quantitatively evaluating blastocyst quality. The network outputs a continuous score to represent blastocyst quality precisely rather than some categories. As to the soft attention mechanism, the attention module in the network outputs an activation map (attention map) localizing the regions of interest (ROI, i.e., inner cell mass (ICM)) of microscopic blastocyst images. The generated activation map guides the entire network to predict ICM quality more accurately. The experimental results demonstrate that the proposed method is superior to traditional classification-based networks. Moreover, the visualized activation map makes the proposed network decision more reliable.

Association of AGER gene G82S polymorphism with the severity of coronary artery disease in Chinese Han population.

BACKGROUND AND OBJECTIVE: Advanced glycosylation end-product receptor (AGER) plays an important role in the development and progression of atherosclerosis. The G82S polymorphism (rs2070600) is located in the ligand-binding V-domain of AGER suggesting a possible influence of this variant on AGER function. The aim of this study is to evaluate the association of the G82S polymorphism with the severity of coronary artery disease (CAD) in patients with or without type 2 diabetes mellitus (T2DM). DESIGN AND METHODS: The AGER gene G82S polymorphism was analysed in 270 nondiabetic and 270 type 2 diabetic Chinese Han patients with angiographically proven CAD (luminal stenosis ≥ 50%). The number of diseased vessels and Gensini score were used to determine the severity of CAD. Genotyping for the G82S polymorphism was performed by PCR-RFLP using restriction enzymes AluI. RESULTS: The frequency of 82S allele was significantly lower in the diabetic CAD patients with multi-vessel disease than in those with single-vessel disease (P = 0·015). When controlled for confounding variables, the 82S allele was associated with decreased risk of multi-vessel disease [P = 0·038, adjusted OR = 0·565 (0·329-0·972)]. The protective effect of the 82S allele against the severity of CAD was not observed in patients with nondiabetic CAD. CONCLUSIONS: AGER 82S allele showed a protective effect on CAD severity in the presence of T2DM in Chinese Han population.

Tissue distribution of intravenously administrated hydroxyapatite nanoparticles labeled with 125I.

Hydroxyapatite nanoparticles (HANPs) have been developed for biomedical use due to its extraordinary properties. However, the side effects of HANPs on human body have also been concerned, especially in vivo. Now it is still unknown how about the distribution and biobehavior of HANPs in vivo is, though it's very important for application in biosystem. This study was to establish a new method of 125I radiolabeling on HANPs at 80 nm, investigate the long-term tissue distribution of HANPs quantitatively after intravenously administrated HANPs labeled with 125I and the subcellular distribution in liver and spleen by TEM. The results indicated the labeled HANPs had high stability in vitro, and could accumulate mainly in the liver and spleen and decrease in time dependent manner, but still retain in body for more than 28 days. This stagnation most probably attribute to the endocytosis by macrophages in these tissues. The results implied the radioactive iodine labeling was an effective and sensitive method for tracing and analyzing the distribution of NPs in vivo. Liver and spleen should be the main target organ reached when HANPs were injected into circulation system. Because HANPs could stay in vivo for over one month, the biosafety shouldn't be neglected.

Biodistribution and toxicity of intravenously administered silica nanoparticles in mice.

As the biosafety of nanotechnology becomes a growing concern, the in vivo nanotoxicity of NPs has drawn a lot of attention. Silica nanoparticles (SiNPs) have been widely developed for biomedical use, but their biodistribution and toxicology have not been investigated extensively in vivo. Although investigations of in vivo qualitative distribution of SiNPs have been reported, the time-dependent and quantitative informations about the distribution of SiNPs are still lacking. Here we investigated the long-term (30 days) quantitative tissue distribution, and subcellular distribution, as well as potential toxicity of two sizes of intravenously administered SiNPs in mice using radiolabeling, radioactive counting, transmission electron microscopy and histological analysis. The results indicated that SiNPs accumulate mainly in lungs, liver and spleen and are retained for over 30 days in the tissues because of the endocytosis by macrophages, and could potentially cause liver injury when intravenously injected.

Hydroxyapatite nanoparticles as a controlled-release carrier of BMP-2: absorption and release kinetics in vitro.

Recently, nanoparticles have been extensively developed as controlled-release carriers; however, there has been little research on hydroxyapatite nanoparticles (HANPs) and their potential applications. In this study, HANPs were investigated as a controlled-release carrier of bone morphogenetic protein-2 (BMP-2), the absorption and release kinetics of which were analyzed in vitro. Different concentrations of BMP-2 solution were used to evaluate the adsorptive properties of HANPs. It was observed that the amount of BMP-2 adsorbed onto HANPs could be as high as 70 mug/mg and that adsorption rate was highly correlated with the concentration of BMP-2 solution used. After absorption, the suspension of HANPs absorbed BMP-2 (HANPs/BMP-2) was incubated at 37 degrees C for 15 days and the release kinetics of BMP-2 from HANPs/BMP-2 was determined daily. The release profile showed sustained release of BMP-2 over the period of the investigation. Collectively, these results suggest that HANPs has the potential to function as a carrier for drug delivery systems and as a scaffold material in bone tissue engineering.

Penetration of titanium dioxide nanoparticles through slightly damaged skin in vitro and in vivo.

PURPOSE: Titanium dioxide nanoparticles (TiO2-NPs) have been widely developed for versatile use, but the potential risk form their skin exposure is still unclear. To evaluate this risk, the skin penetration of TiO2-NPs is necessary to be understood first. The aims of this study are to investigated the penetration of TiO2-NPs through slightly damaged skin and intact skin in vitro and in vivo. METHODS: TiO2-NPs with a diameter of 20 nm was labeled with 125I.The skin of rat was treated with 2% SLS solution and obtained as slightly damaged skin. The 125I labeled TiO2-NPs (125I-TiO2-NPs)solution and 0.9% PS solution were added into the donor chamber and receptor chamber of static diffusion cells which clamped the skin at the middle of two half-cells, respectively. During 24 hours, samples were extracted from the receptor chamber and counted for 1 min using γ-counter to detect the radioactivity. The skin penetration of TiO2-NPs in vitro was expressed as the percentage of radioactivity of receptor chamber solution compared with total radioactivity in the donor chamber. Thereafter, the 125I-TiO2-NPs was exposed to the rats. After 1 day and 3 days, the blood and tissues of rats were harvested, weighed and counted for 1 min using γ-counter to detect the tissue radioactivity. The skin penetration of TiO2-NPs in vivo was expressed as the percentage dose per gram tissue (% dose/g). RESULTS: In the skin penetration experiment in vitro, the radioactivity of receptor chamber solution through damaged skin was higher than that of through intact skin and was about 2% radioactivity of donor chamber on 24 h. In the skin penetration experiment in vivo, the radioactivity of blood and tissues of rats after exposing to 125I-TiO2-NPs solution though damaged skin or intact skin were less than 0.05% dose/g on 1 d and quickly declined on 3 d. The skin penetration rates of TiO2-NPs through slightly damaged skin and intact skin in vitro and vivo were lower than the rate of free 125I in the TiO2-NPs solution. CONCLUSIONS: The TiO2-NPs could not penetrate through the damaged skin or intact skin both in vitro and in vivo. It suggested that the TiO2-NPs should be safe when it was applied and contacted with skin.

[Effect of schistosomiasis control projects in Hexi Reservoir on Oncomelania snail control].

OBJECTIVE: To evaluate the effect of schistosomiasis control projects in Hexi Reservoir on Oncomelania hupensis snail control. METHODS: The canal hardening + main water system widening + the overflow dam project, the concrete slope protection, the banking and reclamation + concrete slope protection project, the environment reform project, and the comprehensive treatment were implemented in the tail area, the hydro-fluctuation belt, the rainwater harvesting zoon of the upstream area, the dam area, and the downstream area of the reservoir, respectively. The changes of the snail situation were investigated before and after the construction of the reservoir, and the snail control effects of the schistosomiasis control projects in different parts of the reservoir were analyzed. RESULTS: There were no Oncomelania snails found 3 years in the bottom area, dam area, hydro-fluctuation belt, tail region and downstream of the dam after the construction and storage of the reservoir and the implementation of the schistosomiasis control projects. In the rainwater harvesting zoon of the upstream area, the density of living snails decreased from 0.620 4 snails/0.1 m2 in 2009 to 0.113 2 snails/0.1 m2 in 2013, but the snail area still remained. CONCLUSIONS: The schistosomiasis control projects in Hexi Reservoir have effectively prevented the diffusion of Oncomelania snails from the rainwater harvesting zone of the upstream area to the dam area, and they are effective in the snail control.

Tissue distribution and excretion of intravenously administered titanium dioxide nanoparticles.

As the biosafety of nanotechnology becomes a growing concern, the in vivo nanotoxicity of nanoparticles (NPs) has been drawn an increasing attention. Titanium dioxide nanoparticles (TiO(2)-NPs) have been developed for versatile use, but the pharmacokinetics of intravenously administered TiO(2)-NPs have not been investigated extensively. In the present study, the rutile-type TiO(2)-NPs with a size about 20nm were labeled with CF680 and (125)I. The labeled TiO(2)-NPs were injected in mice or rats with the concentration of 1mg/ml and the dose of 10mg/kg body weight and their tissue distribution and excretion were investigated by using ex vivo fluorescent imaging, γ-counter and TEM. The results indicated that the TiO(2)-NPs mainly accumulated in liver and spleen and could be retained for over 30days in these tissues due to the phagocytosis by macrophages. The excretion assay found that the excretory rate of TiO(2)-NPs through urine was higher than that of feces, indicating that renal excretion was the main excretion pathway of TiO(2)-NPs. Overall results of the present study provided important information on distribution and excretion of TiO(2)-NPs in vivo, which would greatly promote the pharmacokinetics and in vivo nanotoxicity research of TiO(2)-NPs.

[Three dimensional finite element analysis of stress distribution of bone tissues around abutments in telescope fixed bridge supported by tooth-implant].

PURPOSE: To study the stress distribution of bone tissues around the abutments in telescope fixed bridge supported by tooth-implant. METHODS: A patient with loss of the left first mandibular molar was used as the subject. Two partial fixed denture models were established. One model (model I) was supported by the second premolar and implant in the second molar, the other model (model II) was supported by the second premolar and implant other than the second molar. Under decentralized vertical and oblique loads, the stress distribution of bone tissues around the tooth and implant was evaluated by three dimensional finite element analysis. RESULTS: Under decentralized vertical load, the max EQVs of the bone tissues around the tooth and implant in model I were 2.58MPa and 43.92MPa, and 2.17MPa and 20.23MPa in model II. Under decentralized oblique load, the max EQVs of the bone tissues around the tooth and implant in model I were 2.23MPa and 46.37MPa, and 1.91MPa and 21.19MPa in model II. CONCLUSIONS: The stress surrounding the implant is declined by the buffer of telescope retainer, and the decline is not different under the two loads. In designing the fixed bridge supported by tooth-implant, we can design telescope retainer on implant to reduce the stress of bone tissues around the implant and to prevent damages to bone tissues.