Effects and mechanism of anti-VEGF assisted PPV in the treatment of proliferative retinopathy

AIM: To investigate the effects and mechanism of anti-vascular endothelial growth factor(VEGF)assisted pars plana vitrectomy(PPV)in the treatment of proliferative diabetic retinopathy(PDR).METHODS: A total of 92 patients(92 eyes)with PDR treated by PPV were divided into the simple PPV group(41 patients with 41 affected eyes)and the combined treatment group(51 patients with 51 affected eyes)according to whether the patient underwent intravitreal injection of Ranibizumab(IVR). The combined treatment group was treated with IVR at 5-7d before PPV. The surgical time, times of electrocoagulation, silicone oil filling rate, the incidence of postoperative complications, LogMAR BCVA of affected eyes, levels of VEGF and pigment epithelium derived factor(PEDF)in aqueous humor and vitreous body were compared between the two groups. RESULTS: The surgical time was shorter, the times of electrocoagulation was less, the silicone oil filling rate and the incidence rates of iatrogenic retinal hole and vitreous body hematocele were lower in the combined treatment group than in the simple PPV group(PPPCONCLUSION: IVR combined with PPV can reduce the perioperative levels of VEGF and PEDF, reduce the times of electrocoagulation and the incidence of iatrogenic retinal hole and vitreous body hematocele, and improve the visual acuity of patients with PDR

miR-15a-3p and miR-16-1-3p Negatively Regulate Twist1 to Repress Gastric Cancer Cell Invasion and Metastasis

MicroRNAs are a novel class of gene regulators that function as oncogenes or tumor suppressors. In our current study, we investigated the role of miR-15a-3p and miR-16-1-3p in the regulation of Twist1 expression and EMT process. Our bioinformatics analysis suggested that on the 3' UTR of Twist1, there are two conserved miRNA recognition sites for miR-15a-3p and miR-16-1-3p respectively. Interestingly, overexpression of miR-15a-3p and miR-16-1-3p significantly suppressed the activity of luciferase reporter containing Twist1-3' UTR, reduced mRNA and protein level of EMT related genes such as TWIST1, N-cadherin, α-SMA and Fibronectin, and repressed MMP9 and MMP2 activity, as well as cell migration and invasion. Conversely, inhibition of miR-15a-3p and miR-16-1-3p significantly increased TWIST1, N-cadherin, α-SMA and Fibronectin protein expression. In addition, Twist1 co-transfection significantly ameliorated the loss of cell migration and invasion. Moreover, overexpression of miR-15a-3p and miR-16-1-3p dramatically suppressed the ability of BGC823 cells to form colonies in vitro and develop tumors in vivo in nude mice. Finally, qPCR and Western blot analysis showed that miR-15a-3p and miR-16-1-3p were significantly reduced in clinical gastric cancer tissue, whereas Twist1 mRNA and protein were significantly up-regulated, suggesting that this aberrant down-regulation of miR-15a-3p and miR-16-1-3p might be associated with the abnormal regulation of Twist1 and the EMT process in gastric cancer development. Our results help to elucidate a novel and important mechanism for the regulation of Twist1 in the development of cancer

Near-infrared and mid-infrared semiconductor broadband light emitters

Semiconductor broadband light emitters have emerged as ideal and vital light sources for a range of biomedical sensing/imaging applications, especially for optical coherence tomography systems. Although near-infrared broadband light emitters have found increasingly wide utilization in these imaging applications, the requirement to simultaneously achieve both a high spectral bandwidth and output power is still challenging for such devices. Owing to the relatively weak amplified spontaneous emission, as a consequence of the very short non-radiative carrier lifetime of the inter-subband transitions in quantum cascade structures, it is even more challenging to obtain desirable mid-infrared broadband light emitters. There have been great efforts in the past 20 years to pursue high-efficiency broadband optical gain and very low reflectivity in waveguide structures, which are two key factors determining the performance of broadband light emitters. Here we describe the realization of a high continuous wave light power of >20 mW and broadband width of >130 nm with near-infrared broadband light emitters and the first mid-infrared broadband light emitters operating under continuous wave mode at room temperature by employing a modulation p-doped InGaAs/GaAs quantum dot active region with a ‘J’-shape ridge waveguide structure and a quantum cascade active region with a dual-end analogous monolithic integrated tapered waveguide structure, respectively. This work is of great importance to improve the performance of existing near-infrared optical coherence tomography systems and describes a major advance toward reliable and cost-effective mid-infrared imaging and sensing systems, which do not presently exist due to the lack of appropriate low-coherence mid-infrared semiconductor broadband light sources

Precise determination of seawater calcium using isotope dilution inductively coupled plasma mass spectrometry

NSC, TaiwanWe describe a method for rapid, precise and accurate determination of calcium ion (Ca2+) concentration in seawater using isotope dilution inductively coupled plasma mass spectrometry (ID-ICP-MS). A 10 mu L aliquot of seawater was spiked with an appropriate Ca-43 enriched solution for Ca-44/Ca-43 ID-ICP-MS analyses, using an Element XR (Thermo Fisher Scientific), operated at low resolution in E-scan acquisition mode. A standard-sample bracketing technique was applied to correct for potential mass discrimination and ratio drift at every 5 samples. A precision of better than 0.05% for within-run and 0.10% for duplicate measurements of the IAPSO seawater standard was achieved using 10 mu L solutions with a measuring time less than 3 minutes. Depth profiles of seawater samples collected from the Arctic Ocean basin were processed and compared with results obtained by the classic ethylene glycol tetra-acetic acid (EGTA) titration. Our new ID-ICP-MS data agreed closely with the conventional EGTA data, with the latter consistently displaying 1.5% excess Ca2+ values, possibly due to a contribution of interference from Mg2+ and Sr2+ in the EGTA titration. The newly obtained Sr/Ca profiles reveal sensitive water mass mixing in the upper oceanic column to reflect ice melting in the Arctic region. This novel technique provides a tool for seawater Ca2+ determination with small sample size, high throughput, excellent internal precision and external reproducibility

Ocean internal tides suppress tropical cyclones in the South China Sea

Tropical Cyclones (TCs) are devastating natural disasters. Analyzing four decades of global TC data, here we find that among all global TC-active basins, the South China Sea (SCS) stands out as particularly difficult ocean for TCs to intensify, despite favorable atmosphere and ocean conditions. Over the SCS, TC intensification rate and its probability for a rapid intensification (intensification by ≥ 15.4 m s−1 day−1) are only 1/2 and 1/3, respectively, of those for the rest of the world ocean. Originating from complex interplays between astronomic tides and the SCS topography, gigantic ocean internal tides interact with TC-generated oceanic near-inertial waves and induce a strong ocean cooling effect, suppressing the TC intensification. Inclusion of this interaction between internal tides and TC in operational weather prediction systems is expected to improve forecast of TC intensity in the SCS and in other regions where strong internal tides are present

Spindle Assembly Checkpoint Regulates Mitotic Cell Cycle Progression during Preimplantation Embryo Development

Errors in chromosome segregation or distribution may result in aneuploid embryo formation, which causes implantation failure, spontaneous abortion, genetic diseases, or embryo death. Embryonic aneuploidy occurs when chromosome aberrations are present in gametes or early embryos. To date, it is still unclear whether the spindle assembly checkpoint (SAC) is required for the regulation of mitotic cell cycle progression to ensure mitotic fidelity during preimplantation development. In this study, using overexpression and RNA interference (RNAi) approaches, we analyzed the role of SAC components (Bub3, BubR1 and Mad2) in mouse preimplantation embryos. Our data showed that overexpressed SAC components inhibited metaphase-anaphase transition by preventing sister chromatid segregation. Deletion of SAC components by RNAi accelerated the metaphase-anaphase transition during the first cleavage and caused micronuclei formation, chromosome misalignment and aneuploidy, which caused decreased implantation and delayed development. Furthermore, in the presence of the spindle-depolymerizing drug nocodazole, SAC depleted embryos failed to arrest at metaphase. Our results suggest that SAC is essential for the regulation of mitotic cell cycle progression in cleavage stage mouse embryos

Acid Solution Is a Suitable Medium for Introducing QX-314 into Nociceptors through TRPV1 Channels to Produce Sensory-Specific Analgesic Effects

BACKGROUND: Previous studies have demonstrated that QX-314, an intracellular sodium channel blocker, can enter into nociceptors through capsaicin-activated TRPV1 or permeation of the membrane by chemical enhancers to produce a sensory-selective blockade. However, the obvious side effects of these combinations limit the application of QX-314. A new strategy for targeting delivery of QX-314 into nociceptors needs further investigation. The aim of this study is to test whether acidic QX-314, when dissolves in acidic solution directly, can enter into nociceptors through acid-activated TRPV1 and block sodium channels from the intracellular side to produce a sensory-specific analgesic effect. METHODOLOGY/PRINCIPAL FINDINGS: Acidic solution or noradrenaline was injected intraplantarly to induce acute pain behavior in mice. A chronic constrictive injury model was performed to induce chronic neuropathic pain. A sciatic nerve blockade model was used to evaluate the sensory-specific analgesic effects of acidic QX-314. Thermal and mechanical hyperalgesia were measured by using radiant heat and electronic von Frey filaments test. Spinal Fos protein expression was determined by immunohistochemistry. The expression of p-ERK was detected by western blot assay. Whole cell clamp recording was performed to measure action potentials and total sodium current in rats DRG neurons. We found that pH 5.0 PBS solution induced behavioral hyperalgesia accompanied with the increased expression of spinal Fos protein and p-ERK. Pretreatment with pH 5.0 QX-314, and not pH 7.4 QX-314, alleviated pain behavior, inhibited the increased spinal Fos protein and p-ERK expression induced by pH 5.0 PBS or norepinephrine, blocked sodium currents and abolished the production of action potentials evoked by current injection. The above effects were prevented by TRPV1 channel inhibitor SB366791, but not by ASIC channel inhibitor amiloride. Furthermore, acidic QX-314 employed adjacent to the sciatic nerve selectively blocked the sensory but not the motor functions in naïve and CCI mice. CONCLUSIONS/SIGNIFICANCE: Acid solution is a suitable medium for introducing QX-314 into nociceptors through TRPV1 channels to produce a sensory-specific analgesic effect

Identification of a Functional Genetic Variant at 16q12.1 for Breast Cancer Risk: Results from the Asia Breast Cancer Consortium

Genetic factors play an important role in the etiology of breast cancer. We carried out a multi-stage genome-wide association (GWA) study in over 28,000 cases and controls recruited from 12 studies conducted in Asian and European American women to identify genetic susceptibility loci for breast cancer. After analyzing 684,457 SNPs in 2,073 cases and 2,084 controls in Chinese women, we evaluated 53 SNPs for fast-track replication in an independent set of 4,425 cases and 1,915 controls of Chinese origin. Four replicated SNPs were further investigated in an independent set of 6,173 cases and 6,340 controls from seven other studies conducted in Asian women. SNP rs4784227 was consistently associated with breast cancer risk across all studies with adjusted odds ratios (95% confidence intervals) of 1.25 (1.20−1.31) per allele (P = 3.2×10−25) in the pooled analysis of samples from all Asian samples. This SNP was also associated with breast cancer risk among European Americans (per allele OR  = 1.19, 95% CI  = 1.09−1.31, P = 1.3×10−4, 2,797 cases and 2,662 controls). SNP rs4784227 is located at 16q12.1, a region identified previously for breast cancer risk among Europeans. The association of this SNP with breast cancer risk remained highly statistically significant in Asians after adjusting for previously-reported SNPs in this region. In vitro experiments using both luciferase reporter and electrophoretic mobility shift assays demonstrated functional significance of this SNP. These results provide strong evidence implicating rs4784227 as a functional causal variant for breast cancer in the locus 16q12.1 and demonstrate the utility of conducting genetic association studies in populations with different genetic architectures

Association analyses of East Asian individuals and trans-ancestry analyses with European individuals reveal new loci associated with cholesterol and triglyceride levels

Large-scale meta-analyses of genome-wide association studies (GWAS) have identified >175 loci associated with fasting cholesterol levels, including total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), and triglycerides (TG). With differences in linkage disequilibrium (LD) structure and allele frequencies between ancestry groups, studies in additional large samples may detect new associations. We conducted staged GWAS meta-analyses in up to 69,414 East Asian individuals from 24 studies with participants from Japan, the Philippines, Korea, China, Singapore, and Taiwan. These meta-analyses identified (P < 5 × 10-8) three novel loci associated with HDL-C near CD163-APOBEC1 (P = 7.4 × 10-9), NCOA2 (P = 1.6 × 10-8), and NID2-PTGDR (P = 4.2 × 10-8), and one novel locus associated with TG near WDR11-FGFR2 (P = 2.7 × 10-10). Conditional analyses identified a second signal near CD163-APOBEC1. We then combined results from the East Asian meta-analysis with association results from up to 187,365 European individuals from the Global Lipids Genetics Consortium in a trans-ancestry meta-analysis. This analysis identified (log10Bayes Factor ≥6.1) eight additional novel lipid loci. Among the twelve total loci identified, the index variants at eight loci have demonstrated at least nominal significance with other metabolic traits in prior studies, and two loci exhibited coincident eQTLs (P < 1 × 10-5) in subcutaneous adipose tissue for BPTF and PDGFC. Taken together, these analyses identified multiple novel lipid loci, providing new potential therapeutic targets

Degradation aspects of water formation and transport in Proton Exchange Membrane Fuel Cell: A review

This review paper summarises the key aspects of Proton Exchange Membrane Fuel Cell (PEMFC) degradation that are associated with water formation, retention, accumulation, and transport mechanisms within the cell. Issues related to loss of active surface area of the catalyst, ionomer dissolution, membrane swelling, ice formation, corrosion, and contamination are also addressed and discussed. The impact of each of these water mechanisms on cell performance and durability was found to be different and to vary according to the design of the cell and its operating conditions. For example, the presence of liquid water within Membrane Electrode Assembly (MEA), as a result of water accumulation, can be detrimental if the operating temperature of the cell drops to sub-freezing. The volume expansion of liquid water due to ice formation can damage the morphology of different parts of the cell and may shorten its life-time. This can be more serious, for example, during the water transport mechanism where migration of Pt particles from the catalyst may take place after detachment from the carbon support. Furthermore, the effect of transport mechanism could be augmented if humid reactant gases containing impurities poison the membrane, leading to the same outcome as water retention or accumulation. Overall, the impact of water mechanisms can be classified as aging or catastrophic. Aging has a long-term impact over the duration of the PEMFC life-time whereas in the catastrophic mechanism the impact is immediate. The conversion of cell residual water into ice at sub-freezing temperatures by the water retention/ accumulation mechanism and the access of poisoning contaminants through the water transport mechanism are considered to fall into the catastrophic category. The effect of water mechanisms on PEMFC degradation can be reduced or even eliminated by (a) using advanced materials for improving the electrical, chemical and mechanical stability of the cell components against deterioration, and (b) implementing effective strategies for water management in the cell