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This study aimed to establish optimal criteria for evaluation of moderate (50%-69%) and severe (70%-99%) middle cerebral artery (MCA) stenosis with transcranial color-coded sonography (TCCS). A total of 375 cases provided 409 TCCS/digital subtraction angiography vessel pairs. Peak systolic velocity (PSV), end-diastolic velocity (EDV) and mean flow velocity (MFV) of the MCA were measured. The stenotic/distal MFV ratios (SDRs) were calculated. With digital subtraction angiography as a reference, for 50%-69% MCA stenosis, the optimal combined criteria were PSV ≥180 cm/s (sensitivity 95.7%, specificity 64.9% and overall accuracy 69.7%); EDV ≥75 cm/s (90.0%, 66.4% and 68.7%); MFV ≥110 cm/s (95.7%, 64.0% and 69.4%); and SDR ≥2.5 (88.6%, 71.3% and 76.3%). Criteria for 70%-99% MCA stenosis were PSV ≥240 cm/s (93.5%, 89.9% and 85.5%); EDV ≥100 cm/s (96.8%, 89.0% and 87.3%); MFV≥160 cm/s (91.9%, 92.8% and 92.2%); and SDR ≥4 (87.1%, 92.2% and 91.4%). Parameters of the MCA detected by TCCS, especially SDR, may increase accuracy in diagnosis of 50%-69% and 70%-99% MCA stenosis. [ABSTRACT FROM AUTHOR]

Rationale and Objectives: To explore the influence of data parsing (either selection of frames at set time intervals or by an experienced sonographer) of contrast-enhanced ultrasound (CEUS) exams on physician diagnoses and confidence levels.Materials and Methods: Forty consecutive CEUS exams consisting of 10 cases each of indeterminate liver lesions, indeterminate renal lesions, renal cell carcinoma postablation follow-up, and hepatocellular carcinoma postchemoembolization follow-up were selected for analysis. Exams were parsed into sets consisting of five images selected by the performing sonographer and sets containing systematically stored frames every 10, 30, and 60 seconds. Three blinded physicians then reviewed the cine loop and each set of images in randomized order and provided a diagnosis and confidence level.Results: For all clinical applications investigated, no statistically significant differences in diagnostic performance measures or reader confidence were observed between review of the entire cine loop and images selected by the performing sonographer (p > 0.42). Diagnostic performance at 10-second intervals did not show statically significant changes compared to the full cine loop review for all applications (p > 0.18), although reader confidence decreased. At 30-60-second intervals, both diagnostic performance and reader confidence showed statistically significant reduction compared to review of the full cine loop (p < 0.045).Conclusions: Transfer and review of large cine loops from CEUS exams represent a potential barrier to adoption within the United States workflows. This study demonstrates that images selected by a performing trained sonographer may provide the same value without the review time and data storage costs needed for full cine loop review. Parsing by time points reduced reader confidence and diagnostic performance. [ABSTRACT FROM AUTHOR]

To explore the effects of transforming growth factor-β2 (TGF-β2) and TGF-β1 on the odontogenic and osteogenic differentiation of mesenchymal stem cells (MSCs). We used lentiviral transduction to knock down TGF-β1 or TGF-β2 in stem cells from dental apical papilla (SCAPs), and to generate bone marrow mesenchymal stem cells (BMSCs) with overexpression of TGF-β1 or TGF-β2. We investigated the odontogenic and osteogenic differentiation abilities of these transductants in vitro and in vivo. In vitro , TGF-β2 knockdown in SCAPs reduced the expression of odontoblast-related markers DSPP and DMP-1, and increased the expression of osteoblast-related markers OCN and RUNX-2. Conversely, TGF-β1 knockdown had the opposite effects. TGF-β2 overexpression promoted expression of odontoblast-related markers in BMSCs at early differentiation, but inhibited the expression of odontoblast-related markers at later stages. TGF-β2 overexpression attenuated expression of osteogenic-related markers in BMSCs, while TGF-β1 overexpression enhanced odontoblast-related and osteoblast-related markers. SCAP or BMSC transductants were transplanted underneath kidneys in vivo. Masson staining showed that knockdown of TGF-β1, but not TGF-β2 promoted the expression of type I collagen in SCAPs. Immunohistochemical staining showed that TGF-β2 knockdown inhibited DSPP expression in SCAPs, but TGF-β1 knockdown had no obvious effect on DSPP expression. In vivo , TGF-β1 overexpression and TGF-β2 overexpression had no effect on the expression of type I collagen and DSPP in BMSCs. TGF-β2 promotes odontogenic differentiation of SCAPs and attenuates osteogenic differentiation of SCAPs and BMSCs. TGF-β1 promotes osteogenic differentiation of BMSCs and plays a complex role in regulating odontogenic differentiation of MSCs. • TGF-β2 promoted the odontogenic differentiation of SCAPs. • TGF-β2 attenuated osteogenic differentiation of SCAPs and BMSCs. • TGF-β1 promoted the osteogenic differentiation of BMSCs. [ABSTRACT FROM AUTHOR]

The deepening research and development of micro currents/potentials has made the tiny electrical signals very common in many applicable fields, such as radio frequency identification (RFID), smart chip cards, cosmetics, low-power wearable electronics, etc. A typical alternative energy source from water vapor/moisture, which is prevalent in nature, moisture power (MP) has not been heavily developed and it is usually applied only as a power supply side, without being assigned new tasks and missions leading to the sharpness being covered up. Here, we designed a flexible antibacterial MP membrane by electrospinning and in situ synthesis of AgNPs. The electrospun membrane containing Oxi-silk fibroin with AgNPs (AgNPs@Oxi-SF) in an asymmetric humid environment can generate MP by the presence of directionally migrating charged ions, which can trigger the release of more free Ag+ from AgNPs and allow AgNPs@Oxi-SF to exhibit better antibacterial activity. The continuous and moderate MP generated by AgNPs@Oxi-SF electrospun membrane (AOSFEM) in a humid environment (RH = 99%, 2 h) allowed it to exhibit nearly 100% bactericidal rate compared to 36.7–56.3% in a non-MP environment. [Display omitted] Moisture power is designed in flexible natural biopolymer electrospinning membrane with AgNPs attached to its surfaces. The MP is generated by the unidirectional transport and vertical gradient distribution of charged ions within the membrane in an asymmetric humid atmosphere, which triggers the release of more free Ag+ from the AgNPs, thus further effectively inactivating the bacteria. • MP electrospun membrane composed of natural SF nanofibers achieves magnitude modulation of the MP signal after oxidation. • MP participates in the oxidative dissolution of AgNPs to Ag+, releasing more Ag+ to inactivate typical bacteria. • The flexible AOSFEM was used as an antibacterial face mask, which greatly expands the breadth and depth of MP applications. [ABSTRACT FROM AUTHOR]

Abstract: We analyze higher order finite elements applied to second order elliptic interface problems. Our a priori error estimates in the - and -norm are expressed in terms of the approximation order p and a parameter δ that quantifies how well the interface is resolved by the finite element mesh. The optimal p-th order convergence in the -norm is only achieved under stringent assumptions on δ, namely, . Under weaker conditions on δ, optimal a priori estimates can be established in the - and in the -norm, where is a subdomain that excludes a tubular neighborhood of the interface of width . In particular, if the interface is approximated by an interpolation spline of order p and if full regularity is assumed, then optimal convergence orders and p for the approximation in the - and the -norm can be expected but not order p for the approximation in the -norm. Numerical examples in 2D and 3D illustrate and confirm our theoretical results. [Copyright &y& Elsevier]

The mechanisms by which Hsp40 functions as a molecular chaperone to recognize and bind nonnative polypeptides is not understood. We have identified a peptide substrate for Ydj1, a member of the type I Hsp40 from yeast. The structure of the Ydj1 peptide binding fragment and its peptide substrate complex was determined to 2.7 A˚ resolution. The complex structure reveals that Ydj1 peptide binding fragment forms an L-shaped molecule constituted by three domains. The domain I exhibits a similar protein folds as domain III while the domain II contains two Zinc finger motifs. The peptide substrate binds Ydj1 by forming an extra β strand with domain I of Ydj1. The Leucine residue in the middle of the peptide substrate GWLYEIS inserts its side chain into a hydrophobic pocket formed on the molecular surface of Ydj1 domain I. The Zinc finger motifs located in the Ydj1 domain II are not in the vicinity of peptide substrate binding site. [Copyright &y& Elsevier]

E. coli Hsp100 ClpB can disaggregate denatured polypeptides by employing ATP hydrolysis. The ClpB N-terminal domain (ClpBN) has been proposed to play important roles in ClpB molecular chaperone activities. We have determined the crystal structure of ClpBN to 1.95 A˚ resolution by MAD methods. The ClpBN monomer contains two subdomains that have similar folds. The crystal structure revealed a hydrophobic groove on the molecular surface. We have constructed ClpB mutants in which the hydrophobic residues within the putative peptide binding groove were replaced by glutamine. These ClpB mutants exhibited severe defects in molecular chaperone activity but retained the wild-type ATPase activity. [Copyright &y& Elsevier]

• Ecological impact coefficients and land use protection coefficients are proposed. • The system dynamic model was developed to analyze land space changes under different scenarios. • The coordinated symbiotic scenario would be in a better state compared with the other development scenarios. Simulation of future land space changes in urban agglomerations is a powerful means to optimize regional spatial structure and improve human well-being. This study highlights the equilibrium between urban development and ecological protection and introduces ecological impact coefficient and land use protection coefficient to measure the degree of sustainable land development. The system dynamic model was used to simulate the dynamics of urban development space, ecological space, and urban agricultural space in the Changsha-Zhuzhou-Xiangtan urban agglomeration from 2019 to 2035. Four development scenarios were used in the simulation, namely, status-quo, economic-centric, environment-centric, and coordinated equilibrium. Simulation results show that for the year 2035, urban development space scale would increase by 678.91 km2 under the status quo, increase by 870.12 km2 under the economic-centric scenario, increase by 740.98 km2 under an environment-centric setting, and increase by 775.54 km2 with coordinated equilibrium. The various scenarios would have significant differences in ecological impact and land use protection coefficients, with the environment-centric scenario yielding the highest values for these indicators. The approach presented in this study shows that the needs for urban development can be achieved while also protecting ecological and urban agricultural spaces and that allocation of production, living, and ecological spaces can be optimized using multi-scenario simulation. The development of ecological impact coefficients and land use protection coefficients, as well as the use of different development scenarios, can be used as reference for the more efficient use of land resources areas and the formulation of land-use and spatial planning. [ABSTRACT FROM AUTHOR]

Objective: The influence of atherosclerotic cardiovascular disease (ASCVD) on cerebral blood flow control is not well known. The aim of this study was to investigate the association between cardiovascular function and dynamic cerebral autoregulation (dCA) in patients with preclinical ASCVD.Methods: A total of 44 participants aged 26-76 years were divided into low- and high-risk groups according to the China assessment of ASCVD risk. The cardiac function was assessed by echocardiography. The beat-to-beat blood pressure and cerebral blood flow velocity were measured at rest. Spectral and transfer function analyses were used to calculate cerebral and systemic hemodynamic variability and to estimate dCA metrics.Results: There were no group differences in beat-to-beat heart rate, blood pressure, and cerebral blood flow velocity variability nor the ejection fraction, E/A and E'/A'. The dCA phase at very low frequency was reduced in the high-risk group (P = .03). Moreover, the dCA phase and E'/A' were negatively correlated with age, and dCA phase was positively correlated with E'/A' within the high-risk group (r2 = .517, P < .01).Conclusions: These findings suggest that advancing age, particularly in the high-risk ASCVD group, impairs cerebral blood flow control and cardiac diastolic function which are correlated with each other and may interplay under the effects of ASCVD risk factors. [ABSTRACT FROM AUTHOR]

Objective: To evaluate efficacy of using 2D and 3D contrast enhanced ultrasound (CEUS) for surveillance of RCC recurrence in patients post-ablation and identify imaging hallmarks of recurrence.Methods: 53 patients >8 months post ablation of RCC provided informed consent for this IRB approved study. Patients received 2D and 3D CEUS examinations with Optison (GE Healthcare). Three radiologists of varying CEUS experience described enhancement characteristics, made a diagnosis of recurrence/no-recurrence, and quantified their diagnostic confidence levels.Results: Cases of RCC recurrence showed full ablation cavity enhancement with equal arrival times and intensity compared to the renal cortex. Lack of recurrence was characterized as a complete lack of enhancement within the cavity, or delayed enhancement stemming from the periphery of the ablation cavity. Sensitivity for detecting RCC recurrence was 100% for all readers and specificity was 90%-94%. Reader agreement ranged from 88% to 96%. No significant improvements were achieved with the addition of 3D CEUS, and its inclusion resulted in decreased reader confidence.Conclusion: Contrast-enhanced ultrasound successfully identified all cases of RCC recurrence in this study. Importantly, some patients with complete response to treatment developed delayed enhancement at the periphery of the ablation cavity over time, corresponding to fat necrosis, scarring or granulation tissue within the ablation cavity. [ABSTRACT FROM AUTHOR]

Cerebral hyperperfusion syndrome (CHS) is a rare but serious complication following carotid endarterectomy (CEA). The aim of this study was to identify intraoperative transcranial Doppler (TCD) hemodynamic predictors of CHS after CEA. Between January 2013 and December 2018, intraoperative TCD monitoring was performed for 969 patients who underwent CEA. The percentage increase in the mean velocity of the middle cerebral artery (MCAV%) at 3 postdeclamping time points (immediately after declamping, 5 minutes after declamping, and after suturing the skin) over baseline was compared between CHS and non-CHS patients. CHS was diagnosed in 31 patients (3.2%), including 11 with intracranial hemorrhage. The MCAV% values at the 3 postdeclamping time points over baseline were 177% (81%–275%), 90% (41%–175%), and 107% (55%–191%) in the CHS group, significantly higher than those in the non-CHS group (40% [14%–75%], 15% [1%–36%], and 18% [3%–41%], respectively, all P < 0.001). Receiver operating characteristic curve analysis showed that the 3 intraoperative MCAV% parameters all had excellent accuracy in identifying CHS (areas under the curve: 0.854, 0.839, and 0.858, respectively, all P < 0.001). The predictive value of the model consisting only of preoperative parameters was significantly increased by adding the intraoperative TCD hemodynamic parameters (area under the curve: 0.747 vs. 0.858, P = 0.006). Multivariate analyses identified the intraoperative MCAV% immediately after declamping (odds ratio: 9.840, 95% confidence interval: 2.638–36.696, P < 0.001) as an independent predictor of CHS. Our results indicate that intraoperative TCD monitoring helps predict CHS after CEA at an early stage. [ABSTRACT FROM AUTHOR]

The aim of the study described here was to establish ultrasound criteria for defining the severity of vertebral artery in-stent restenosis. A total of 197 patients with vertebral artery stents were enrolled in this study. Color Doppler ultrasonography was performed after stenting. Peak systolic velocity and end-diastolic velocity within the stent (PSV stent , EDV stent ) and at the intervertebral segments were recorded. The ratio of the PSV at the origin to that at the intervertebral segment was calculated. With digital subtraction angiography as the reference standard, the optimal cutoff values of hemodynamic parameters identifying 50%–69% and 70%–99% restenosis were determined by receiver operating characteristic analysis. The optimal cutoff values of hemodynamic parameters identifying 50%–69% restenosis were PSV stent ≥ 170 cm/s, EDV stent ≥45 cm/s and PSV ratio ≥2.7, and those for 70%–99% restenosis were PSV stent ≥220 cm/s, EDV stent ≥55 cm/s and PSV ratio ≥4.2. In conclusion, color Doppler ultrasonography is a reliable method for monitoring patients with avertebral artery stents. [ABSTRACT FROM AUTHOR]

We present and analyze a first order least squares method for convection dominated diffusion problems, which provides robust L 2 a priori error estimate for the scalar variable even if the given data f ∈ L 2 ( Ω ) . The novel theoretical approach is to rewrite the method in the framework of discontinuous Petrov–Galerkin (DPG) method, and then show numerical stability by using a key equation discovered by Gopalakrishnan and Qiu (2014). This new approach gives an alternative way to do numerical analysis for least squares methods for a large class of differential equations. We also show that the condition number of the global matrix is independent of the diffusion coefficient. A key feature of the method is that there is no stabilization parameter chosen empirically. In addition, Dirichlet boundary condition is weakly imposed. Numerical experiments verify our theoretical results and, in particular, show our way of weakly imposing Dirichlet boundary condition is essential to the design of least squares methods—numerical solutions on subdomains away from interior layers or boundary layers have remarkable accuracy even on coarse meshes, which are unstructured quasi-uniform. [ABSTRACT FROM AUTHOR]

T-2 toxin is a class A trichothecene mycotoxin produced by Fusarium , which exhibits genotoxic, cytotoxic, and immunotoxic effects in animals and humans. In this study, we developed an aptasensor for the sensitive detection of T-2 toxin, which was based on fluorescence resonance energy transfer (FRET), and acted by adjusting the electric potential on the surface of upconversion nanoparticles (UCNPs) and MIL-101(Cr). In addition, it combined the excellent spectral properties of UCNPs with the good adsorption quenching abilities of metal organic frameworks (MOFs). Under the action of π-π stacking interactions, the UCNPs-aptamer was adsorbed onto the surface of MIL-101, leading to fluorescence quenching due to the occurrence of FRET. After the addition of T-2 toxin, owing to its selective binding to the UCNPs-aptamer, the UCNPs-aptamer moved away from MIL-101(Cr), resulting in fluorescence recovery. Moreover, the extent of fluorescence recovery was positively correlated with the concentration of T-2 toxin. The limit of detection (LOD) of this sensor was 0.087 ng mL−1 (S/N = 3), and a good linear correlation was observed between the fluorescence intensity and the T-2 toxin concentration in the range of 0.1–100 ng mL−1. Moreover, the recovery of this method was 97.52–109.53% for corn meal samples (relative standard deviation, RSD = 1.7–2.4%) and 90.81–100.02% for beer samples (RSD = 2.4–2.7%). By adjusting the surface electric potentials, the efficient fluorescence aptasensor combined the advantages of UCNPs and MIL-101(Cr) and allowed the first application of such a system in toxin detection, thereby indicating its potential food sample analysis and biochemical sensing. [Display omitted] • An upconversion fluorescent aptasensor was constructed by adjusting the electric potentials. • The functional modification of UCNPs also regulated the surface potential. • The aptasensor combined the advantages of UCNPs and MIL-101 and was applicable to the real sample. [ABSTRACT FROM AUTHOR]

The aim of this study was to identify the ultrasound-based carotid plaque characteristics associated with new cerebral ischemic lesions after carotid endarterectomy (CEA). Between January 2013 and December 2018, carotid duplex ultrasound was performed in 1061 patients who underwent CEA. Brain magnetic resonance diffusion-weighted imaging (DWI) was performed pre-operatively and within 30 d after CEA. New cerebral ischemic lesions on DWI were observed in 169 patients. The cutoff value gray-scale median (GSM) used to distinguish DWI-positive from DWI-negative patients was 30.5, with an area under the receiver operating characteristic curve of 0.837. A larger proportion of multiple DWI lesions were observed in the GSM ≤30.5 group (59.5% vs. 41.5%, p = 0.030). Univariate and multivariate analyses identified GSM ≤30.5, ulcerated carotid plaques and pre-operative ischemic symptoms as predictors of post-operative cerebral DWI lesions. Our results indicate that ultrasound-based carotid plaque characteristics help predict new cerebral ischemic lesions after CEA. [ABSTRACT FROM AUTHOR]

Abstract Tungsten-copper composites of network structure are increasingly being studied because of their unique mechanical, thermal and electrical properties. Chemical plating and mechanical alloying were used to prepare tungsten-copper alloys with different compositions in this investigation. Samples obtained through mechanical alloying method and sintered by spark plasma sintering (SPS) technique at 1030 °C, 60 MPa exhibited excellent performance. Ni element and Cr element were added to the composite as activating elements to improve the interface wettability of tungsten‑copper. The experimental results showed the Cr element contributes more to the densities, tensile strength, flexural strength and thermal properties of the composites than Ni element. Besides, the effect of two different ball milling ways on the properties of the composites was also studied. The sample W 20Cu (15Cr), which was prepared by Cu(Cr) ball milling, showing a network structure, has the best performance. Highlights • A combined process of SPS and activated sintering were used in the fabrication. • The W Cu composite showed a network structure with continuous copper phase. • Two different ways of mechanical alloying were compared. • The resulting composites show excellent mechanical and thermal properties. [ABSTRACT FROM AUTHOR]

Background Two recent genome-wide association studies (GWASs) reported that the FAM13A gene at the 4q22 locus associated with pulmonary fibrosis (defined by rs2609255) overlapping with COPD (defined by rs6837671). We hypothesized that single-nucleotide polymorphisms (SNPs) related to lung disease (especially pulmonary fibrosis) identified in this region are also associated with the risk of silicosis. Methods To test this hypothesis, we genotyped these two SNPs (rs2609255 and rs6837671) in a case-control study including 177 silicosis cases and 204 controls with silica dust exposure years similar to the levels for cases in a Chinese population. Results We found that rs2609255 was significantly associated with increased silicosis risk (dominant model: OR = 1.71; 95% CI = 1.01–2.92; P  = 0.047). Additionally, eQTL analysis based on the GTEx database indicated that the rs2609255 polymorphism may alter the expression level of FAM13A in lung tissues ( P  = 1.8 × 10 −4 ). Furthermore, interaction analyses showed that rs2609255 interacts multiplicatively with years of silica dust exposure to contribute to silicosis risk (interaction P  = 0.040). Conclusions These results indicate that rs2609255 may modify silicosis susceptibility in the Chinese population. [ABSTRACT FROM AUTHOR]

Purpose: Much of the volume of solid tumors typically exists in a chronically hypoxic microenvironment that has been shown to result in both chemotherapy and radiation therapy resistance. The purpose of this study was to use localized microbubble delivery to overcome hypoxia prior to therapy.Materials and Methods: In this study, surfactant-shelled oxygen microbubbles were fabricated and injected intravenously to locally elevate tumor oxygen levels when triggered by noninvasive ultrasound in mice with human breast cancer tumors. Changes in oxygen and sensitivity to radiation therapy were then measured.Results: In this work, we show that oxygen-filled microbubbles successfully and consistently increase breast tumor oxygenation levels in a murine model by 20 mmHg, significantly more than control injections of saline solution or untriggered oxygen microbubbles (P < .001). Using photoacoustic imaging, we also show that oxygen delivery is independent of hemoglobin transport, enabling oxygen delivery to avascular regions of the tumor. Finally, we show that overcoming hypoxia by this method immediately prior to radiation therapy nearly triples radiosensitivity. This improvement in radiosensitivity results in roughly 30 days of improved tumor control, providing statistically significant improvements in tumor growth and animal survival (P < .03).Conclusions: Our findings demonstrate the potential advantages of ultrasound-triggered oxygen delivery to solid tumors and warrant future efforts into clinical translation of the microbubble platform. [ABSTRACT FROM AUTHOR]

To explore the methylation status, function, and underlying mechanism of the imprinted gene Neuronatin (NNAT) in hepatocellular carcinoma (HCC) progression. Immunohistochemistry (IHC) was performed to evaluate the expression of NNAT in HCC samples. Bisulfite genomic sequencing PCR (BSP) was applied to examine the methylation status of the NNAT promoter. In addition, colony formation, 5-Ethynyl-20-deoxyuridine (EdU) assays and subcutaneous xenograft nude models were used to explore the roles of NNAT in HCC cell proliferation. Furthermore, RNA-seq and phospho-specific protein microarray assays were conducted to illustrate the underlying mechanism by which NNAT regulates HCC progression. NNAT was obviously downregulated in HCC tissues, and its expression level was closely associated with tumor growth and patient prognosis. The downregulation of NNAT in HCC was induced by hypermethylation of CpG islands in the promoter region, and hypermethylation was correlated with overall survival of HCC. Moreover, the enforced expression of NNAT significantly inhibited HCC cell proliferation in vitro and in vivo. Transcriptome analysis showed that the alteration of NNAT expression was mainly related to dysregulation of the PI3K-Akt signaling pathway. Finally, phospho-specific antibody microarray detection further revealed that overexpressed NNAT can increase the phosphorylation levels of LKB1, Met, and elF4E and decrease the phosphorylation levels of PTEN, which are all involved in the PI3K-Akt signaling pathway. Our research provides new insights into the epigenetic regulation of imprinted genes in tumorigenesis and implies that the imprinted gene NNAT may act as a prognostic biomarker and tumor suppressor in HCC. [ABSTRACT FROM AUTHOR]

Benzene is a globally occurring environmental and occupational pollutant that causes leukemia. To better understand telomere length (TL) as a function of benzene toxicity, we recruited 294 shoe-making workers and 102 controls from Wenzhou, China in 2011. Biomarkers of TL, cytokinesis-block micronucleus (MN) frequency, and white blood cells (WBC) were measured. In total, 18 polymorphic sites in environmental response genes, including metabolic and DNA repair genes, were analyzed. Results indicate that benzene exposure led to a longer TL at a threshold of 32 mg/m3-year of cumulative exposure dose (CED). Furthermore, the TL was longer in members of the damaged group, when evaluated for MN frequency (P < 0.001) and reduced WBC (P < 0.001), than in those of the normal group. Workers carrying genotype TT (β = 0.32, P = 0.042) in rs3212986 of ERCC1 and genotype TC (β = 0.24, P = 0.082) in rs1051740 of mEH exon3 were associated with a longer TL as compared to the wild-type group. TA (β = −0.53, P < 0.001) in rs6413432 of CYP2E1 was associated with a shorter TL. Benzene exposure interacted with the TA type in rs6413432 (β = 0.003, 95% CI: 0, 0.006, P = 0.042) and the CC type in rs1051740 (β = 0.007, 95% CI: 0.001, 0.013, P = 0.015) after adjusting for confounding factors. Our results indicate that benzene induces an increase in TL at a threshold of CED ≥32mg/m3-year. Rs1051740, rs3212986, and rs6413432 were found to be involved in benzene-induced telomere growth; in particular, rs1051740 and rs6413432 interacted with the benzene exposure, resulting in an extended TL. Image 1 • Benzene induces longer telomere length with a dose-response relationship. • The telomere length in the damaged group was longer than that in the normal group. • Rs1051740, rs3212986, and rs6413432 were associated with telomere length increase. •Benzene can interact with rs1051740 and rs6413432 to aggravate longer telomere length. [ABSTRACT FROM AUTHOR]

Abstract: Strong evidence has shown that a defect in the Parkin gene is known to be a common, genetic cause of Parkinson disease (PD). The E3 ubiquitin ligase Nrdp1 is shown to interact with the N terminal of Parkin (the first 76 amino acids) and catalyze degradation of Parkin via the ubiquitin–proteasome pathway, suggesting that Nrdp1 may be involved in the development of PD via the regulation of Parkin, We believe we are the first to have screened PD patients for mutations in the Nrdp1 gene to determine the association between these variants and PD. By direct sequencing, we analysed the entire coding regions and 5′ UTR of Nrdp1 in 209 Chinese PD patients and 302 unrelated healthy individuals. No variant was detected in the coding regions (exons 3–7); only 2 variants (c.−206 T > A and c.−208–8 A > G) were identified in the 5′ UTR (exon 2) and intron 1. Furthermore, a study of the allelic and genotypic association between patients and controls showed no significant association between the c.−206 T > A polymorphism and PD; c.−208–8 A > G was identified in one PD patient and not in controls. Our data do not support the hypothesis of a major role for the Nrdp1 gene in PD development in the Chinese population. [Copyright &y& Elsevier]