Vascular endothelial growth factor (VEGF) was investigated in the present study to see whether it could provide a therapeutic opportunity for the treatment of Alzheimer's disease (AD). PDGF-hAPP(V717I) transgenic mice were treated with VEGF or PBS by intraperitoneal injection for three consecutive days. The results showed that VEGF ameliorated the memory impairment of mice, accompanied by CD34(+) cells increasing in peripheral blood, vWF(+) vessels increasing in hippocampus, and CD34(+)/VEGFR2(+), vWF(+)/VEGFR2(+) and BrdU(+)/vWF(+) cells expressing in hippocampus. Furthermore, the level of choline acetyltransferase (ChAT) was considerably enhanced and Aβ deposition was decreased in the brains of mice upon VEGF treatment. These observations suggest that VEGF should be pursued as a novel therapeutic agent for treatment of AD.

Mesenchymal stem cells (MSCs) have been used for therapy of type 1 diabetes mellitus. However, the in vivo distribution and therapeutic effects of transplanted MSCs are not clarified well. Herein, we reported that CdSe/ZnS quantum dots-labeled MSCs were prepared for targeted fluorescence imaging and therapy of pancreas tissues in rat models with type 1 diabetes. CdSe/ZnS quantum dots were synthesized, their biocompatibility was evaluated, and then, the appropriate concentration of quantum dots was selected to label MSCs. CdSe/ZnS quantum dots-labeled MSCs were injected into mouse models with type 1 diabetes via tail vessel and then were observed by using the Bruker In-Vivo F PRO system, and the blood glucose levels were monitored for 8 weeks. Results showed that prepared CdSe/ZnS quantum dots owned good biocompatibility. Significant differences existed in distribution of quantum dots-labeled MSCs between normal control rats and diabetic rats (p < 0.05). The ratios of the fluorescence intensity (RFI) analysis showed an accumulation rate of MSCs in the pancreas of rats in the diabetes group which was about 32 %, while that in the normal control group rats was about 18 %. The blood glucose levels were also monitored for 8 weeks after quantum dots-labeled MSC injection. Statistical differences existed between the blood glucose levels of the diabetic rat control group and MSC-injected diabetic rat group (p < 0.01), and the MSC-injected diabetic rat group displayed lower blood glucose levels. In conclusion, CdSe/ZnS-labeled MSCs can target in vivo pancreas tissues in diabetic rats, and significantly reduce the blood glucose levels in diabetic rats, and own potential application in therapy of diabetic patients in the near future.

Perilipin coats lipid droplets in adipocytes and steroidogenic cells. Its major role is in the regulation of intracellular lipolysis in adipocytes. Our aim was to examine the association between common variants at the PLIN1 gene and central obesity in unrelated Chinese adults.

This paper mainly focuses on how to effectively and efficiently measure visual similarity for local feature based representation. Among existing methods, metrics based on Bag of Visual Word (BoV) techniques are efficient and conceptually simple, at the expense of effectiveness. By contrast, kernel based metrics are more effective, but at the cost of greater computational complexity and increased storage requirements. We show that a unified visual matching framework can be developed to encompass both BoV and kernel based metrics, in which local kernel plays an important role between feature pairs or between features and their reconstruction. Generally, local kernels are defined using Euclidean distance or its derivatives, based either explicitly or implicitly on an assumption of Gaussian noise. However, local features such as SIFT and HoG often follow a heavy-tailed distribution which tends to undermine the motivation behind Euclidean metrics. Motivated by recent advances in feature coding techniques, a novel efficient local coding based matching kernel (LCMK) method is proposed. This exploits the manifold structures in Hilbert space derived from local kernels. The proposed method combines advantages of both BoV and kernel based metrics, and achieves a linear computational complexity. This enables efficient and scalable visual matching to be performed on large scale image sets. To evaluate the effectiveness of the proposed LCMK method, we conduct extensive experiments with widely used benchmark datasets, including 15-Scenes, Caltech101/256, PASCAL VOC 2007 and 2011 datasets. Experimental results confirm the effectiveness of the relatively efficient LCMK method.

Prospective studies have shown a strong association between carotid intraplaque hemorrhage (IPH), detected by magnetic resonance imaging (MRI), and cerebrovascular ischemic events. However, IPH is also observed in a substantial number of asymptomatic patients. We hypothesized that there are differences in the characteristics of IPH+ plaques associated with recent symptoms, compared to IPH+ plaques not associated with recent symptoms.

We have previously demonstrated intrinsic anti-HIV activity in cervicovaginal lavage (CVL) from HIV-infected women with high CD4 counts and not on antiretroviral therapy. However, the impact of HIV disease progression on CVL innate immune responses has not been delineated.

The SS18-SSX1 fusion gene has been shown to play important roles in the development of synovial sarcoma (SS), but the underlying molecular mechanisms and its downstream target genes are still not clear. Here SHC SH2-domain binding protein 1 (SHCBP1) was identified and validated to be a novel downstream target gene of SS18-SSX1 by using microarray assay, quantitative real-time (qPCR) and western blot. Expression of SHCBP1 was firstly confirmed in SS cell line and SS tissues. The effects of SHCBP1 overexpression or knockdown on SS cell proliferation and tumorigenicity were then studied by cell proliferation, DNA replication, colony formation, flow cytometric assays, and its in vivo tumorigenesis was determined in the nude mice. Meanwhile, the related signaling pathways of SHCBP1 were also examined in SS cells. The results indicated that SHCBP1 was significantly increased in SS cells and SS tissues compared with adjacent noncancerous tissues. The expression of SHCBP1 was demonstrated to be positively correlated with the SS18-SSX1 level. Overexpression and ablation of SHCBP1 promoted and inhibited, respectively, the proliferation and tumorigenicity of SS cells in vitro. SHCBP1 knockdown also significantly inhibited SS cell growth in nude mice, and lowered the MAPK/ERK and PI3K/AKT/mTOR signaling pathways and cyclin D1 expression. Our findings disclose that SHCBP1 is a novel downstream target gene of SS18-SSX1, and demonstrate that the oncogene SS18-SSX1 promotes tumorigenesis by increasing the expression of SHCBP1, which normally acts as a tumor promoting factor.

The regulatory role of small RNAs (sRNAs) in various biological processes is an active area of investigation; however, there has been limited information available on the role of sRNAs in plant-insect interactions. This study was designed to identify sRNAs in cotton-melon aphid (Aphis gossypii) during the Vat-mediated resistance interaction with melon (Cucumis melo).

Cancer stem cells (CSCs) are postulated to be a small subset of tumor cells with tumor-initiating ability that shares features with normal tissue-specific stem cells. The origin of CSCs and the mechanisms underlying their genesis are poorly understood, and it is uncertain whether it is possible to obliterate CSCs without inadvertently damaging normal stem cells. Here we show that a functional reduction of eukaryotic translation initiation factor 4E (eIF4E) in Drosophila specifically eliminates CSC-like cells in the brain and ovary without having discernable effects on normal stem cells. Brain CSC-like cells can arise from dedifferentiation of transit-amplifying progenitors upon Notch hyperactivation. eIF4E is up-regulated in these dedifferentiating progenitors, where it forms a feedback regulatory loop with the growth regulator dMyc to promote cell growth, particularly nucleolar growth, and subsequent ectopic neural stem cell (NSC) formation. Cell growth regulation is also a critical component of the mechanism by which Notch signaling regulates the self-renewal of normal NSCs. Our findings highlight the importance of Notch-regulated cell growth in stem cell maintenance and reveal a stronger dependence on eIF4E function and cell growth by CSCs, which might be exploited therapeutically.

Asymmetric stem cell division establishes an initial difference between a stem cell and its differentiating sibling, critical for maintaining homeostasis and preventing carcinogenesis. Yet the mechanisms that consolidate and lock in such initial fate bias remain obscure. Here, we use Drosophila neuroblasts to demonstrate that the super elongation complex (SEC) acts as an intrinsic amplifier to drive cell fate commitment. SEC is highly expressed in neuroblasts, where it promotes self-renewal by physically associating with Notch transcription activation complex and enhancing HES (hairy and E(spl)) transcription. HES in turn upregulates SEC activity, forming an unexpected self-reinforcing feedback loop with SEC. SEC inactivation leads to neuroblast loss, whereas its forced activation results in neural progenitor dedifferentiation and tumorigenesis. Our studies unveil an SEC-mediated intracellular amplifier mechanism in ensuring robustness and precision in stem cell fate commitment and provide mechanistic explanation for the highly frequent association of SEC overactivation with human cancers.

The neurotransmitter acetylcholine (ACh) regulates a diverse array of physiological processes throughout the body. Despite its importance, cholinergic transmission in the majority of tissues and organs remains poorly understood owing primarily to the limitations of available ACh-monitoring techniques. We developed a family of ACh sensors (GACh) based on G-protein-coupled receptors that has the sensitivity, specificity, signal-to-noise ratio, kinetics and photostability suitable for monitoring ACh signals in vitro and in vivo. GACh sensors were validated with transfection, viral and/or transgenic expression in a dozen types of neuronal and non-neuronal cells prepared from multiple animal species. In all preparations, GACh sensors selectively responded to exogenous and/or endogenous ACh with robust fluorescence signals that were captured by epifluorescence, confocal, and/or two-photon microscopy. Moreover, analysis of endogenous ACh release revealed firing-pattern-dependent release and restricted volume transmission, resolving two long-standing questions about central cholinergic transmission. Thus, GACh sensors provide a user-friendly, broadly applicable tool for monitoring cholinergic transmission underlying diverse biological processes.

BACKGROUND The aim of this study was to examine the effects of the natural flavonoid, quercetin, in a rat model of adenine-induced chronic kidney disease. MATERIAL AND METHODS Forty male Wister rats were divided into four groups: normal (no adenine or quercetin) (n=10); untreated model (treated withadenine but not quercetin) (n=10); quercetin-treated model (5 mg/kg/day for 21 days) (n=10); quercetin-treated model (10 mg/kg/day for 21 days) (n=10). Urine and blood samples were collected and rat kidneys were examined histologically. RESULTS Comparison of the findings of the model rats treated with quercetin (n=20) with non-treated model rats (n=10) showed reduced levels of fibroblast growth factor 23 (FGF23): normal group, 19.6 pg/ml; untreated group, 73.6 pg/ml; quercetin-treated group (5 mg/kg), 34.25 pg/ml; and quercetin-treated group (10 mg/kg), 21.3 pg/ml. Quercetin-treated model rats had reduced serum levels of parathyroid hormone (PTH), inorganic phosphate, increased urine protein-to-creatinine ratio, increased urine antioxidants, serum lactate dehydrogenase (LDH), and interleukin (IL)-8 when compared with the untreated model group and the control group. Quercetin treatment 10 mg/kg (n=10) reduced the levels of creatinine, blood urea nitrogen (BUN), and urinary uric acid. Renal histopathology in model rats treated with quercetin (n=20) showed reduced inflammation compared with the untreated model rats (n=10). CONCLUSIONS In a rat model of adenine-induced chronic kidney disease, treatment with quercetin improved renal function, reduced oxidative stress factors, serum levels of FGF23, and kidney inflammation.

RNA splicing is a critical mechanism by which to modify transcriptome, and its dysregulation is the underlying cause of many human diseases. It remains challenging, however, to genetically modulate a splicing event in its native context. Here, we demonstrate that a CRISPR-guided cytidine deaminase (i.e., targeted-AID mediated mutagenesis [TAM]) can efficiently modulate various forms of mRNA splicing. By converting invariant guanines to adenines at either 5' or 3' splice sites (SS), TAM induces exon skipping, activation of alternative SS, switching between mutually exclusive exons, or targeted intron retention. Conversely, TAM promotes downstream exon inclusion by mutating cytidines into thymines at the polypyrimidine tract. Applying this approach, we genetically restored the open reading frame and dystrophin function of a mutant DMD gene in patient-derived induced pluripotent stem cells (iPSCs). Thus, the CRISPR-guided cytidine deaminase provides a versatile genetic platform to modulate RNA splicing and to correct mutations associated with aberrant splicing in human diseases.

BACKGROUND Screw penetration into the hip joint is a severe complication during acetabular fracture surgery. The standard fluoroscopic views of the pelvis cannot provide adequate safety during screw insertion. The aim of this research was to determine and evaluate the accuracy of the acetabular lateral view for screw placement. MATERIAL AND METHODS Twenty screws were randomly chosen and intentionally penetrated into the articular surface (1-2 mm), and the remaining 20 screws were extra-articular ones positioned in close proximity to the articular surface. Three surgeons, each evaluating 40 screws, provided a total of 120 rated observations for each screw position. We compared the traditional view or combined with lateral acetabular view with the criterion standard based on unaided visual assessment. A blinded and independent review of each pelvic intraoperative fluoroscopy was made by 3 independent observers. Specificity, sensitivity, positive predictive value, negative predictive value, correct interpretation, intra-class correlation coefficients (ICC), and Youden index were calculated. RESULTS There were significant differences in sensitivity, NPV, correct interpretation, and Youden index between the 2 groups (P<0.05). The ICC was 0.531 when the antero-posterior, iliac, and obturator oblique views were used. The ICC was remarkably increased when using a combination of the ''lateral'' view and the standard views for screw perforation of the joint. CONCLUSIONS Use of the lateral view of the acetabulum can be a complementary method to identify malpositioned screws, and it helps increase the accuracy rate of inserting screws in the treatment of posterior wall fracture.

Toxicological data used for risk assessments must undergo an evaluation of reliability. Nevertheless, a reliability evaluation scheme for such data has yet to be established in China. A method termed TRAM (Toxicological data Reliability Assessment Method) was developed to evaluate toxicological data reliability. A questionnaire survey was performed to identify the most important criteria for reliability, and was divided into three parts: laboratory animal data (LAD), in vitro data (IVD), and human data (HD). The criteria selected from the questionnaire survey and numerical score categorization finally reached a consensus after two conferences. TRAM comprises 22 criteria for LAD, 15 for IVD, and 12 for HD. Furthermore, a combination of a quick and detailed evaluation of approaches for LAD and IVD were proposed to improve evaluation efficiency. Different weights (1-4) were assigned to each criterion, and 0-4 points were allocated according to how well each criterion was met, then a Quality score was calculated. TRAM uses three reliability categories: high (Quality score: 81-100 or met a quick evaluation approach), moderate (60-80) and low(<60). TRAM provides a transparent, easy-to-use, and quantitative method for evaluating toxicological data reliability.

The purpose of this study was to assess the effect of proximal fibular osteotomy (PFO) on ankle joint. 49 patients or 53 lower limbs were included and followed-up with a minimum of one year in the study prospectively. Patients were evaluated radiographically and clinically. The questionnaires of the American Knee Society Score (KSS), the Ankle-Hindfoot Scale of the American Orthopedic Foot and Ankle Society (AOFAS), Visual Analogue Scale/Score (VAS) were used to assess the patients clinically. Radiographic evaluations were measured by the hip-knee-ankle angle (HKA), the femoro-tibial angle (FTA), tibial inclination (TI), distal tibial articural surface (TAS), talar tilt (TT), length of fibular (FL), and hind foot alignment such as hindfoot alignment view angle (HAVA), hindfoot alignment ratio (HAR), and hindfoot moment arm (HMA). Of the 53 subjects, no significant differences were exhibited in AOFAS, VAS scores and FL in ankle joint, but a significant differences were demonstrated in KSS score, HKA, FTA, TI, TT, HAVA, HAR and HMA after PFO. Due to the structural improvements of ankle joint, PFO not only improves joint function but also the alignment of ankle joint radiographically, and is still recommended as a safe surgery in treating medial compartment osteoarthritis of knee.

Patients with chronic inflammatory demyelinating polyneuropathy (CIDP) seropositive for autoantibodies against nodal and paranodal proteins display distinct clinical presentations. We herein tested for autoantibodies against neurofascin (NF) 155, NF186, contactin-associated protein 1 and contactin-1 and investigated the autoantibody-related clinical features in 29 patients with CIDP from China. Six patients with anti-NF155 IgG4 antibodies displayed younger age of onset and poor response to intravenous immunoglobulin than seronegative patients. One patient had anti-NF186 IgG antibody and no patients had anti-contactin-associated protein 1 or anti-contactin-1 antibodies. Clinical features of CIDP patients with anti-NF155 antibodies in China were similar to those reported in other countries.

Pemetrexed combined with platinum complexes can be used as first-line treatment for advanced non-squamous non-small cell lung cancer (NSCLC), however, the efficacy and safety is varying from individuals. There is a need to better understand the genetic variations associated with platinum response.

Our study aimed to determine whether a virus from fecal samples is human rotavirus (HRV), the main pathogen that causes autumn diarrhea. Specimens were obtained from the feces from children with autumn diarrhea treated at Chuiyangliu Hospital and used to infect MA104 cells, subcultured and observed by electron microscopy. RNA was extracted, cDNA was synthesized by reverse transcription, and plaque formation and hemagglutination were assessed. The cytopathic effect (CPE) were associated with the fourth passage in subculture. CPE extracts were examined by electron microscopy, which allowed us to observe the shape of HRV particles. Amplification of the VP4 gene from HRV was used to identify the viruses as group A rotavirus. The virus causes red blood cell aggregation. The virus isolate was designated as HRV CY2017.

The elderly population have a high incidence of cardiovascular disease and are the main users of green spaces, such as city parks. Creating supportive green spaces for exercise for the elderly is of great significance to promote their cardiovascular health. The winter cities have a severely cold climate and high incidence of cardiovascular disease, while the elderly, especially those with cardiovascular disease, face more challenges when participating in exercise in the green spaces. In the context of the winter cities, the kinds of exercise the elderly participate in are more conducive to their cardiovascular health, and determining the factors of the green spaces that are supportive for exercise for cardiovascular health in the winter are of particular interest. Taking Harbin, a typical winter city in China, as an example, this study aims to identify the exercise characteristics of elderly residents in the green spaces in winter, to link them with the principles and contents of exercise prescription for cardiovascular health, to identify the deficient factors of the green spaces in supporting exercise for cardiovascular health, and to put forward optimization design implications. Mixed qualitative methods including interviews, a questionnaire, and field observation were used to identify special behavioral characteristics and spatial factors involving winter exercise in the green spaces among the elderly. The results showed that: (1) about 42.4% of the participants had a gap with the principles of exercise prescription for cardiovascular health. Their exercise items were generally consistent with the principle of low-intensity exercise, but some of them had the problems regarding early exercise time and insufficient exercise duration and frequency. (2) Insufficient supportive factors of the green spaces mainly included facilities allocation, comfort, safety, accessibility, and air quality. Facilities allocation involved walking paths, rehabilitation facilities, auxiliary facilities, and guidance facilities; comfort involved sunlight conditions of the exercise areas; safety involved slippery roads and sites with ice and snow and medical accidents; accessibility involved the proximity, the safety of connecting roads, and the movement of the elderly; air quality involved the planting of evergreen trees. Accordingly, the design implications were given in order to bridge the supportive gap of the green spaces for exercise for cardiovascular health in the elderly population.