Autophagy mediated CoCrMo particle-induced peri-implant osteolysis by promoting osteoblast apoptosis

Wear particle-induced osteolysis is the leading cause of aseptic loosening, which is the most common reason for THA (total hip arthroplasty) failure and revision surgery. Although existing studies suggest that osteoblast apoptosis induced by wear debris is involved in aseptic loosening, the underlying mechanism linking wear particles to osteoblast apoptosis remains almost totally unknown. In the present study, we investigated the effect of autophagy on osteoblast apoptosis induced by CoCrMo metal particles (CoPs) in vitro and in a calvarial resorption animal model. Our study demonstrated that CoPs stimulated autophagy in osteoblasts and PIO (particle-induced osteolysis) animal models. Both autophagy inhibitor 3-MA (3-methyladenine) and siRNA of Atg5 could dramatically reduce CoPs-induced apoptosis in osteoblasts. Further, inhibition of autophagy with 3-MA ameliorated the severity of osteolysis in PIO animal models. Moreover, 3-MA also prevented osteoblast apoptosis in an antiautophagic way when tested in PIO model. Collectively, these results suggest that autophagy plays a key role in CoPs-induced osteolysis and that targeting autophagy-related pathways may represent a potential therapeutic approach for treating particle-induced peri-implant osteolysis.     

Low Goiter Rate Associated with Small Average Thyroid Volume in Schoolchildren after the Elimination of Iodine Deficiency Disorders

Background

After the implementation of the universal salt iodization (USI) program in 1996, seven cross-sectional school-based surveys have been conducted to monitor iodine deficiency disorders (IDD) among children in eastern China.

Objectives

This study aimed to examine the correlation of total goiter rate (TGR) with average thyroid volume (Tvol) and urinary iodine concentration (UIC) in Jiangsu province after IDD elimination.

Design

Probability-proportional-to-size sampling was applied to select 1,200 children aged 8–10 years old in 30 clusters for each survey in 1995, 1997, 1999, 2001, 2002, 2005, 2009 and 2011. We measured Tvol using ultrasonography in 8,314 children and measured UIC (4,767 subjects) and salt iodine (10,184 samples) using methods recommended by the World Health Organization. Tvol was used to calculate TGR based on the reference criteria specified for sex and body surface area (BSA).

Results

TGR decreased from 55.2% in 1997 to 1.0% in 2009, and geometric means of Tvol decreased from 3.63 mL to 1.33 mL, along with the UIC increasing from 83 μg/L in 1995 to 407 μg/L in 1999, then decreasing to 243 μg/L in 2005, and then increasing to 345 μg/L in 2011. In the low goiter population (TGR < 3.9%), TGR was positively associated with average Tvol (r = 0.99); UIC showed a non-linear association with average Tvol, and UIC > 300 μg/L was associated with a smaller average Tvol in children.

Conclusions

After IDD elimination in Jiangsu province in 2001, lower TGR was associated with smaller average Tvol. Average Tvol was more sensitive than TGR in detecting the fluctuation of UIC. A UIC of 300 μg/L may be defined as a critical value for population level iodine status monitoring.     

Impact of Cardiovascular Risk Factors on Carotid Intima-Media Thickness and Degree of Severity: A Cross-Sectional Study

Objective

Age, hypertension, dyslipidemia and diabetes are common cardiovascular risk factors (CVRFs) that contribute to the development of atherosclerosis in cardiovascular system including carotid artery disease. However, the impact of these risk factors on the increased carotid intima-media thickness (cIMT) and degree of carotid severity remains to be further clarified. This study aims to evaluate the relationship between CVRFs and degree of carotid severity and cIMT in high-risk subjects.

Methods

Four thousand and three hundred ninety-four subjects with one or more risk factors were retrospectively reviewed in this study. Patients were divided into different groups based on age, the type and quantity of CVRFs. cIMT and degree of carotid artery stenosis were measured and analyzed based on carotid ultrasound imaging with findings compared to the CVRFs to determine the correlation between these variables.

Results

Aging was significantly associated with degree of severity (P < 0.05) and cIMT was significantly increased with age (P < 0.05). Individual CVRF analysis shows that hypertension was more related to the degree of severity than dyslipidemia and diabetes with corresponding abnormal cIMT rates being 79.39%, 72.98% and 32.37%, respectively. The prevalence of carotid atherosclerosis were 20.06%, 22.88% and 28.63%, respectively corresponding to patients with zero, one and more than one chronic diseases. The percentage of abnormal cIMT in hypertensive patient group with dyslipidemia is significantly higher than the other groups (P< 0.05).

Conclusions

This study shows a direct correlation between the degree of carotid severity and cIMT and cardiovascular risk factors, especially with age and hypertension. Carotid atherosclerosis is closely related to the number of cardiovascular risk factors.     

Recoverin depletion accelerates cone photoresponse recovery

The neuronal Ca²⁺-binding protein Recoverin has been shown to regulate phototransduction termination in mammalian rods. Here we identify four recoverin genes in the zebrafish genome, rcv1a, rcv1b, rcv2a and rcv2b, and investigate their role in modulating the cone phototransduction cascade. While Recoverin-1b is only found in the adult retina, the other Recoverins are expressed throughout development in all four cone types, except Recoverin-1a, which is expressed only in rods and UV cones. Applying a double flash electroretinogram (ERG) paradigm, downregulation of Recoverin-2a or 2b accelerates cone photoresponse recovery, albeit at different light intensities. Exclusive recording from UV cones via spectral ERG reveals that knockdown of Recoverin-1a alone has no effect, but Recoverin-1a/2a double-knockdowns showed an even shorter recovery time than Recoverin-2a-deficient larvae. We also showed that UV cone photoresponse kinetics depend on Recoverin-2a function via cone-specific kinase Grk7a. This is the first in vivo study demonstrating that cone opsin deactivation kinetics determine overall photoresponse shut off kinetics.     

Effect of Er,Cr:YSGG Laser at Different Output Powers on the Micromorphology and the Bond Property of Non-Carious Sclerotic Dentin to Resin Composites

Background

The objective of this study was to investigate the influence of Er,Cr:YSGG laser irradiated at different powers on the micromorphology and the bonding property of non-carious sclerotic dentin to resin composites.

Methods

Two hundred bovine incisors characterized by non-carious sclerotic dentin were selected, and the seventy-two teeth of which for surface morphological analysis were divided into nine groups according to various treatments (A: the control group, B: only treated with the adhesive Adper Easy One, C: diamond bur polishing followed by Adper Easy One, D-I: Er,Cr:YSGG laser irradiating at 1W, 2W, 3W, 4W, 5W, 6W output power, respectively, followed by Adper Easy One). The surface roughness values were measured by the non-contact three-dimensional morphology scanner, then the surface micromorphologies of surfaces in all groups were assessed by scanning electron microscopy (SEM); meanwhile, Image Pro-Plus 6.0 software was used to measure the relative percentage of open tubules on SEM images. The rest, one hundred twenty-eight teeth for bond strength test, were divided into eight groups according to the different treatments (A: only treated with the adhesive Adper Easy One, B: diamond bur polishing followed by the above adhesive, C-H: Er,Cr:YSGG laser irradiating at 1 W, 2 W, 3 W, 4 W, 5 W, 6 W output power, respectively, followed by the above adhesive), and each group was subsequently divided into two subgroups according to whether aging is performed (immediately tested and after thermocycling). Micro-shear bond strength test was used to evaluate the bond strength.

Results

The 4W laser group showed the highest roughness value (30.84±1.93μm), which was statistically higher than the control group and the diamond bur groups (p<0.05). The mean percentages ((27.8±1.8)%, (28.0±2.2)%, (30.0±1.9)%) of open tubules area in the 4W, 5W, 6W group were higher than other groups (p<0.05). The 4W laser group showed the highest micro-shear bond strength not only in immediately tested (17.60±2.55 PMa) but after thermocycling (14.35±2.08MPa).

Conclusion

The Er,Cr:YSGG laser at 4W power can effectively improve the bonding property between non-carious sclerotic dentin and resin composites by increasing the roughness and mean percentage area of open tubules.     

MicroRNA-141 promotes the proliferation of non-small cell lung cancer cells by regulating expression of PHLPP1 and PHLPP2

The dysregulation of microRNAs (miRNAs) is crucially implicated in the development of various cancers. In this study, we explored the biological role of miR-141 in non-small cell lung cancer (NSCLC). miR-141 expression was significantly up-regulated in NSCLC tissues, and its overexpression accelerated NSCLC cell proliferation in vitro and tumor growth in vivo. We subsequently identified the antagonists of PI3K/AKT signaling, PH domain leucine-rich-repeats protein phosphatase 1 (PHLPP1) and PHLPP2, as direct targets of miR-141. Re-introduction of PHLPP1 and PHLPP2 abrogated miR-141-induced proliferation of NSCLC cells. Together, the results of this study suggest that miR-141 and its targets PHLPP1 and PHLPP2 play critical roles in NSCLC tumorigenesis, and provide potential therapeutic targets for NSCLC treatment.     

Construction of a Bacillus thuringiensis engineered strain with high toxicity and broad pesticidal spectrum against coleopteran insects

A newly engineered strain, denominated BIOT185, was constructed through integrating the cry8Ca2 gene into the endogenous plasmid of BT185 (contains cry8Ea1) by homologous recombination. The thermosensitive plasmid vector was eliminated by the rising temperature of recombinant cultures. No antibiotic gene or other unnecessary genes were introduced to the new strain. Sodium dodecyl sulfate–polyacrylamide gel electrophoresis and Western blot analysis demonstrated that the cry8Ca2 gene was expressed normally and produced a 130-kDa protein in the BIOT185 strain. Bioassay results showed that the new strain had high toxicity to the pests Anomala corpulenta and Holotrichia parallela, which often damage the same fields.     

Identification of an anticoagulant peptide that inhibits both fXIa and fVIIa/tissue factor from the blood-feeding nematode Ancylostoma caninum

Factor VIIa-tissue factor complex (fVIIa/TF) and factor XIa (fXIa) play important roles in the initiation and amplification of coagulation, respectively. They may be good targets for the development of novel anticoagulants to treat and prevent thromboembolic disease. In this study, we cloned, expressed and identified a novel anticoagulant peptide, AcaNAP10, from the blood-feeding nematode Ancylostoma caninum. AcaNAP10 showed potent anticoagulant activity and doubled the activated partial thromboplastin and prothrombin times at estimated concentrations of 92.9 nM and 28.8 nM, respectively. AcaNAP10 demonstrated distinct mechanisms of action compared with known anticoagulants. It inhibited fXIa and fVIIa/TF with IC₅₀ values of 25.76 ± 1.06 nM and 123.9 ± 1.71 nM, respectively. This is the first report on an anticoagulant that can inhibit both fXIa and fVIIa/TF. This anticoagulant peptide may be an alternative molecule for the development of novel anticoagulants.     

鄂西大蓟根的化学成分的研究

本题对菊科蓟属植物鄂西大蓟根Cirsium henryi的化学成分进行系统研究。采用硅胶柱色谱法分离了五个单体成分并以光谱分析法鉴定它们的结构:乙酰丁香酸(p-Hydroxycinnamic acid,1),原儿茶酸(protocate-chuic acid,2),香草酸(vanillic acid,3),二羟丙基软脂酸酯(2,3-dihydroxypropyl hexadecanoate,4)和胡萝卜苷(glucoraphenin,5)。这些化合物均为首次从该植物中分离得到。     

Gene Expression Variability within and between Human Populations and Implications toward Disease Susceptibility

Variations in gene expression level might lead to phenotypic diversity across individuals or populations. Although many human genes are found to have differential mRNA levels between populations, the extent of gene expression that could vary within and between populations largely remains elusive. To investigate the dynamic range of gene expression, we analyzed the expression variability of ∼18, 000 human genes across individuals within HapMap populations. Although ∼20% of human genes show differentiated mRNA levels between populations, our results show that expression variability of most human genes in one population is not significantly deviant from another population, except for a small fraction that do show substantially higher expression variability in a particular population. By associating expression variability with sequence polymorphism, intriguingly, we found SNPs in the untranslated regions (5′ and 3′UTRs) of these variable genes show consistently elevated population heterozygosity. We performed differential expression analysis on a genome-wide scale, and found substantially reduced expression variability for a large number of genes, prohibiting them from being differentially expressed between populations. Functional analysis revealed that genes with the greatest within-population expression variability are significantly enriched for chemokine signaling in HIV-1 infection, and for HIV-interacting proteins that control viral entry, replication, and propagation. This observation combined with the finding that known human HIV host factors show substantially elevated expression variability, collectively suggest that gene expression variability might explain differential HIV susceptibility across individuals.