Summary
Aiming to identify pleiotropic genomic loci for bone mineral density and bone size, we performed a bivariate GWAS in five discovery samples and replicated in two large-scale samples. We ...identified 2 novel loci at 2q37.1 and 6q26. Our findings provide insight into common genetic architecture underlying both traits.
Introduction
Bone mineral density (BMD) and bone size (BS) are two important factors that contribute to the development of osteoporosis and osteoporotic fracture. Both BMD and BS are highly heritable and they are genetically correlated. In this study, we aim to identify pleiotropic loci associated with BMD and BS.
Methods
We conducted a bivariate genome-wide association (GWA) analysis of hip BMD and hip BS in 6180 participants from 5 samples, followed by in silico replication in the UK Biobank study of BMD (
N
= 426,824) and the deCODE study of BS (
N
= 28,954), respectively.
Results
SNPs from 2 genomic loci were significant at the genome-wide significance (GWS) level (
p
lt; 5 × 10
−8
) in the discovery samples and were successfully replicated in the replication samples (2q37.1, lead SNP rs7575512, discovery
p
= 1.49 × 10
−10
, replication
p
= 0.05; 6q26, lead SNP rs1040724, discovery
p
= 1.95 × 10
−8
, replication
p
= 0.03). Functional annotations suggested functional relevance of the identified variants to bone development.
Conclusion
Our findings provide insight into the common genetic architecture underlying BMD and BS, and enhance our understanding of the potential mechanism of osteoporosis fracture.
The PI3K/Akt/mTOR pathway has a central role in cancer metastasis and radiotherapy. To develop effective therapeutics to improve radiosensitivity, understanding the possible pathways of ...radioresistance involved and the effects of a combination of the PI3K/Akt/mTOR inhibitors with radiotherapy on prostate cancer (CaP) radioresistant cells is needed. We found that compared with parent CaP cells, CaP-radioresistant cells demonstrated G0/G1 and S phase arrest, activation of cell cycle check point, autophagy and DNA repair pathway proteins, and inactivation of apoptotic proteins. We also demonstrated that compared with combination of single PI3K or mTOR inhibitors (BKM120 or Rapamycin) and radiation, low-dose of dual PI3K/mTOR inhibitors (BEZ235 or PI103) combined with radiation greatly improved treatment efficacy by repressing colony formation, inducing more apoptosis, leading to the arrest of the G2/M phase, increased double-strand break levels and less inactivation of cell cycle check point, autophagy and non-homologous end joining (NHEJ)/homologous recombination (HR) repair pathway proteins in CaP-radioresistant cells. This study describes the possible pathways associated with CaP radioresistance and demonstrates the putative mechanisms of the radiosensitization effect in CaP-resistant cells in the combination treatment. The findings from this study suggest that the combination of dual PI3K/Akt/mTOR inhibitors (BEZ235 or PI103) with radiotherapy is a promising modality for the treatment of CaP to overcome radioresistance.
Electrochemical oxidation is a promising technology to treatment of bio-refractory wastewater. Coking wastewater contains high concentration of refractory and toxic compounds and the water quality ...usually cannot meet the discharge standards after conventional biological treatment processes. This paper initially investigated the electrochemical oxidation using boron-doped diamond (BDD) anode for advanced treatment of coking wastewater. Under the experimental conditions (current density 20–60
mA
cm
−2, pH 3–11, and temperature 20–60
°C) using BDD anode, complete mineralization of organic pollutants was almost achieved, and surplus ammonia–nitrogen (NH
3–N) was further removed thoroughly when pH was not adjusted or at alkaline value. Moreover, the TOC and NH
3–N removal rates in BDD anode cell were much greater than those in other common anode systems such as SnO
2 and PbO
2 anodes cells. Given the same target to meet the National Discharge Standard of China, the energy consumption of 64
kWh
kgCOD
−1 observed in BDD anode system was only about 60% as much as those observed in SnO
2 and PbO
2 anode systems. Further investigation revealed that, in BDD anode cell, organic pollutants were mainly degraded by reaction with free hydroxyl radicals and electrogenerated oxidants (S
2O
8
2−, H
2O
2, and other oxidants) played a less important role, while direct electrochemical oxidation and indirect electrochemical oxidation mediated by active chlorine can be negligible. These results showed great potential of BDD anode system in engineering application as a final treatment of coking wastewater.
Although evapotranspiration-induced matric suction for single species has been widely studied, little is known about how mixed-species planting would affect plant growth and induced matric suction. ...This study aims to explore the effects of grass–tree interaction on their growth and induced matric suction during evapotranspiration (ET) and rainfalls. Field monitoring was carried out to measure matric suction responses in compacted soil that was vegetated with (i) single tree species, Schefflera heptaphylla, and (ii) mixed species of the trees and a grass species, Cynodon dactylon. In each condition, three tree spacings (120, 180, and 240 mm) were planted. When tree spacing increased from 120 to 240 mm, the peak tree root area index (RAI, for fine roots with diameter <2 mm) decreased by 16%, but the peak grass RAI increased by 29%. At mixed planting plots, the ET-induced peak matric suction for a tree spacing of 240 mm was 20% higher than that for a spacing of 180 mm because of increased contribution of grass-root water uptake as the trees were more widely spaced. Without grass, a reverse trend was observed as tree–tree interaction reduced at wide spacings. The peak ET-induced matric suction had a significant linear correlation with RAI. During rainfalls, the highest matric suction was preserved for the case of 240 mm spacing due to the greatest reduction of soil hydraulic conductivity by the presence of roots.
One favorable situation for spins to enter the long-sought quantum spin liquid (QSL) state is when they sit on a kagome lattice. No consensus has been reached in theory regarding the true ground ...state of this promising platform. The experimental efforts, relying mostly on one archetypal material ZnCu_{3}(OH)_{6}Cl_{2}, have also led to diverse possibilities. Apart from subtle interactions in the Hamiltonian, there is the additional degree of complexity associated with disorder in the real material ZnCu_{3}(OH)_{6}Cl_{2} that haunts most experimental probes. Here we resort to heat transport measurement, a cleaner probe in which instead of contributing directly, the disorder only impacts the signal from the kagome spins. For ZnCu_{3}(OH)_{6}Cl_{2}, we observed no contribution by any spin excitation nor obvious field-induced change to the thermal conductivity. These results impose strong constraints on various scenarios about the ground state of this kagome compound: while certain quantum paramagnetic states other than a QSL may serve as natural candidates, a QSL state, gapless or gapped, must be dramatically modified by the disorder so that the kagome spin excitations are localized.
Three-dimensional (3D) printing technology has received great attention in the past decades in both academia and industry because of its advantages such as customized fabrication, low manufacturing ...cost, unprecedented capability for complex geometry, and short fabrication period. 3D printing of metals with controllable structures represents a state-of-the-art technology that enables the development of metallic implants for biomedical applications. This review discusses currently existing 3D printing techniques and their applications in developing metallic medical implants and devices. Perspective about the current challenges and future directions for development of this technology is also presented.
Radioresistance is a major challenge in prostate cancer (CaP) radiotherapy (RT). In this study, we investigated the role and association of epithelial-mesenchymal transition (EMT), cancer stem cells ...(CSCs) and the PI3K/Akt/mTOR signaling pathway in CaP radioresistance. We developed three novel CaP radioresistant (RR) cell lines (PC-3RR, DU145RR and LNCaPRR) by radiation treatment and confirmed their radioresistance using a clonogenic survival assay. Compared with untreated CaP-control cells, the CaP-RR cells had increased colony formation, invasion ability and spheroid formation capability (P<0.05). In addition, enhanced EMT/CSC phenotypes and activation of the checkpoint proteins (Chk1 and Chk2) and the PI3K/Akt/mTOR signaling pathway proteins were also found in CaP-RR cells using immunofluorescence, western blotting and quantitative real-time PCR (qRT-PCR). Furthermore, combination of a dual PI3K/mTOR inhibitor (BEZ235) with RT effectively increased radiosensitivity and induced more apoptosis in CaP-RR cells, concomitantly correlated with the reduced expression of EMT/CSC markers and the PI3K/Akt/mTOR signaling pathway proteins compared with RT alone. Our findings indicate that CaP radioresistance is associated with EMT and enhanced CSC phenotypes via activation of the PI3K/Akt/mTOR signaling pathway, and that the combination of BEZ235 with RT is a promising modality to overcome radioresistance in the treatment of CaP. This combination approach warrants future in vivo animal study and clinical trials.
We present the ultralow-temperature specific heat and thermal conductivity measurements on single crystals of triangular-lattice compound EtMe3SbPd(dmit)22, which has long been considered as a ...gapless quantum spin liquid candidate. In specific heat measurements, a finite linear term is observed, consistent with the previous work S. Yamashita et al., Nat. Commun. 2, 275 (2011). However, we do not observe a finite residual linear term in the thermal conductivity measurements, and the thermal conductivity does not change in a magnetic field of 6 T. These results are in sharp contrast to previous thermal conductivity measurements on EtMe3SbPd(dmit)22 M. Yamashita et al., Science 328, 1246 (2010), in which a huge residual linear term was observed and attributed to highly mobile gapless excitations, likely the spinons of a quantum spin liquid. In this context, the true ground state of EtMe3SbPd(dmit)22 has to be reconsidered.
Transversus abdominis plane (TAP) block is an alternative to spinal morphine for analgesia after Caesarean section but there are few data on its comparative efficacy. We compared the analgesic ...efficacy of the TAP block with and without spinal morphine after Caesarean section in a prospective, randomized, double-blinded placebo-controlled trial.
Eighty patients were randomized to one of four groups to receive (in addition to spinal anaesthesia) either spinal morphine 100 µg (SM) or saline (SS) and a postoperative bilateral TAP block with either bupivacaine (TLA) 2 mg kg−1 or saline (TS).
Pain on movement and early morphine consumption were lowest in groups receiving spinal morphine and was not improved by TAP block. The rank order of median pain scores on movement at 6 h was: SMTLA (20 mm)<SMTS (27.5 mm)<SSTS (51.5 mm)<SSTLA (52.0 mm) (P<0.05, highest vs lowest). The rank order of median morphine consumption at 6 h was: SMTS (4.0 mg)<SMTLA (5.0 mg)<SSTLA (8.0 mg)<SSTS (12.0 mg) and at 24 h was: SMTLA (5.0 mg)<SMTS (6.0 mg)<SSTS (9.5 mg)<SSTLA (15.0 mg) (P<0.05, highest vs lowest). Sedation scores and patient satisfaction did not differ between groups. Anti-emetic use and pruritus were highest in the SMTLA group.
Spinal morphine—but not TAP block—improved analgesia after Caesarean section. The addition of TAP block with bupivacaine 2 mg kg−1 to spinal morphine did not further improve analgesia.
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