MFR-DTA: a multi-functional and robust model for predicting drug-target binding affinity and region.

MOTIVATION: Recently, deep learning has become the mainstream methodology for drug-target binding affinity prediction. However, two deficiencies of the existing methods restrict their practical applications. On the one hand, most existing methods ignore the individual information of sequence elements, resulting in poor sequence feature representations. On the other hand, without prior biological knowledge, the prediction of drug-target binding regions based on attention weights of a deep neural network could be difficult to verify, which may bring adverse interference to biological researchers. RESULTS: We propose a novel Multi-Functional and Robust Drug-Target binding Affinity prediction (MFR-DTA) method to address the above issues. Specifically, we design a new biological sequence feature extraction block, namely BioMLP, that assists the model in extracting individual features of sequence elements. Then, we propose a new Elem-feature fusion block to refine the extracted features. After that, we construct a Mix-Decoder block that extracts drug-target interaction information and predicts their binding regions simultaneously. Last, we evaluate MFR-DTA on two benchmarks consistently with the existing methods and propose a new dataset, sc-PDB, to better measure the accuracy of binding region prediction. We also visualize some samples to demonstrate the locations of their binding sites and the predicted multi-scale interaction regions. The proposed method achieves excellent performance on these datasets, demonstrating its merits and superiority over the state-of-the-art methods. AVAILABILITY AND IMPLEMENTATION: https://github.com/JU-HuaY/MFR.

UVR8-TCP4-LOX2 module regulates UV-B tolerance in Arabidopsis.

The phytohormone jasmonate (JA) coordinates stress and growth responses to increase plant survival in unfavorable environments. Although JA can enhance plant UV-B stress tolerance, the mechanisms underlying the interaction of UV-B and JA in this response remain unknown. In this study, we demonstrate that the UV RESISTANCE LOCUS 8 - TEOSINTE BRANCHED1, Cycloidea and PCF 4 - LIPOXYGENASE2 (UVR8-TCP4-LOX2) module regulates UV-B tolerance dependent on JA signaling pathway in Arabidopsis thaliana. We show that the nucleus-localized UVR8 physically interacts with TCP4 to increase the DNA-binding activity of TCP4 and upregulate the JA biosynthesis gene LOX2. Furthermore, UVR8 activates the expression of LOX2 in a TCP4-dependent manner. Our genetic analysis also provides evidence that TCP4 acts downstream of UVR8 and upstream of LOX2 to mediate plant responses to UV-B stress. Our results illustrate that the UV-B-dependent interaction of UVR8 and TCP4 serves as an important UVR8-TCP4-LOX2 module, which integrates UV-B radiation and JA signaling and represents a new UVR8 signaling mechanism in plants.

The protective effect of sinapic acid in osteoarthritis: In vitro and in vivo studies.

The anti-inflammatory effect of sinapic acid (SA) has been reported in several studies. However, whether SA has the same effect on osteoarthritis (OA) has yet to be clearly elucidated. We designed a series of in vitro and in vivo procedures to verify the above conjecture. Compared with controls, SA-pretreated human chondrocytes showed lower levels of interleukin (IL)-1ß-induced IL-6, prostaglandin E2 (PGE2), nitric oxide (NO) and tumour necrosis factor-α (TNF-α) in vitro. Meanwhile, SA could also reverse the degradation of type II collage and aggrecan, as well as the overproduction of matrix metalloproteinase-9 (MMP-9) and matrix metalloproteinase-13 (MMP-13), inducible nitric oxide synthase (iNOS), cyclooxygenase (COX)-2 and a disintegrin and metalloproteinase thrombospondin motifs (ADAMTS)-5. Furthermore, activation of nuclear factor κB (NF-κB), which was induced by IL-1ß, was also inhibited by SA through the pathway of nuclear factor-erythroid 2-related factor-2 (Nrf2)/heme oxygenase 1. In vivo, SA could delay the progress of mice OA models. We propose that SA may be applied as a potential therapeutic drug in OA treatment.

Inhibition of PI3K/Akt/NF-κB signaling with leonurine for ameliorating the progression of osteoarthritis: In vitro and in vivo studies.

Osteoarthritis (OA) is characterized as the degeneration and destruction of articular cartilage. In recent decades, leonurine (LN), the main active component in medical and edible dual purpose plant Herba Leonuri, has been shown associated with potent anti-inflammatory effects in several diseases. In the current study, we examined the protective effects of LN in the inhibition of OA development as well as its underlying mechanism both in vitro and in vivo experiments. In vitro, interleukin-1 beta (IL-1ß) induced over-production of prostaglandin E2, nitric oxide, inducible nitric oxide synthase, cyclooxygenase-2, interleukin-6 and tumor necrosis factor alpha were all inhibited significantly by the pretreatment of LN at a dose-dependent manner (5, 10, and 20 µM). Moreover, the expression of thrombospondin motifs 5 (ADAMTS5) and metalloproteinase 13 (MMP13) was downregulated by LN. All these changes led to the IL-1ß induced degradation of extracellular matrix. Mechanistically, the LN suppressed IL-1ß induced activation of the PI3K/Akt/NF-κB signaling pathway cascades. Meanwhile, it was also demonstrated in our molecular docking studies that LN had strong binding abilities to PI3K. In addition, LN was observed exerting protective effects in a surgical induced model of OA. To sum up, this study indicated LN could be applied as a promising therapeutic agent in the treatment of OA.

Genome-wide association study identifies novel susceptible loci and highlights Wnt/beta-catenin pathway in the development of adolescent idiopathic scoliosis.

The genetic architecture of adolescent idiopathic scoliosis (AIS) remains poorly understood. Here we present the result of a 4-stage genome-wide association study composed of 5,953 AIS patients and 8,137 controls. Overall, we identified three novel susceptible loci including rs7593846 at 2p14 near MEIS1 (Pcombined = 1.19 × 10-13, OR = 1.21, 95% CI = 1.10-1.32), rs7633294 at 3p14.1 near MAGI1 (Pcombined = 1.85 × 10-12, OR = 1.20, 95% CI = 1.09-1.32), and rs9810566 at 3q26.2 near TNIK (Pcombined = 1.14 × 10-11, OR = 1.19, 95% CI = 1.08-1.32). We also confirmed a recently reported region associated with AIS at 20p11.22 (Pcombined = 1.61 × 10-15, OR = 1.22, 95% CI = 1.12-1.34). Furthermore, we observed significantly asymmetric expression of Wnt/beta-catenin pathway in the bilateral paraspinal muscle of AIS patients, including beta-catenin, TNIK, and LBX1. This is the first study that unveils the potential role of Wnt/beta-catenin pathway in the development of AIS, and our findings may shed new light on the etiopathogenesis of AIS.

A novel oleanolic acid derivative HA-19 ameliorates muscle atrophy via promoting protein synthesis and preventing protein degradation.

Muscle atrophy refers to a decrease in the size of muscles in the body, occurs in certain muscles with inactivity in many diseases and lacks effective therapies up to date. Natural products still play an important role in drug discovery. In the present study, derivatives of a natural product, oleanolic acid, were screened with myoblast differentiation and myotube atrophy assays, respectively. Results revealed that one of the derivatives, HA-19 showed the most potent anti-muscle atrophy activity, and was used for further studies. We demonstrated that HA-19 led to the increase of the protein synthesis by activating mechanistic target of rapamycin complex 1 (mTORC1)/p70 S6K pathways, and also enhanced myoblast proliferation and terminal differentiation via up-regulating of the myogenic transcription factors Pax7, MyoD and Myogenin. The interesting thing was that HA-19 also suppressed protein degradation to prevent myotube atrophy by down-regulating negative growth factors, FoxO1, MuRF1 and Atrogin-1. The results were also supported by puromycin labelling and protein ubiquitination assays. These data revealed that HA-19 possessed a "dual effect" on inhibition of muscle atrophy. In disuse-induced muscle atrophy mice model, HA-19 treatment significantly increased the weights of bilateral tibialis anterior (TA), gastrocnemius (Gastroc.), quadriceps (Quad.), suggesting the effectiveness of HA-19 to remit disuse-induced muscle atrophy. Our finding demonstrated that HA-19 has a great potential as an inhibitor or lead compound for the anti-muscle atrophy drug discovery.

Downregulating STAT1/caspase-3 signaling with fludarabine to alleviate progression in a rat model of steroid-induced avascular necrosis of the femoral head.

Steroid-induced avascular necrosis of the femoral head (SANFH) is mainly induced by glucocorticoids. Fludarabine (Flu) is a specific signal transducer and activator of transcription 1 (STAT1) inhibitor. In this study, we investigated the effect of Flu on SANFH and the role played by the STAT1/caspase-3 signaling pathway. Sprague-Dawley rats were divided into control, SANFH, and Flu-treated SANFH groups. Femoral head tissues were collected for hematoxylin-eosin (H&E) staining and Western blot analysis. The latter was used to measure the levels of stat1, phospho-stat1, caspase-3, cleaved caspase-3, caspase-9, cleaved caspase-9, Bax, cytochrome C, Bak, B-cell lymphoma-extra large, and B-cell lymphoma-2 protein expression. The results showed that Flu regulates protein expression in dexamethasone (Dex)-induced SANFH. H&E staining showed a decrease in the ratio of empty lacunae induced by Dex. Taken together, our study demonstrated the involvement of the STAT1/caspase-3 signaling pathway in SANFH and the potential of Flu as a therapeutic agent for patients with SANFH.

Salidroside attenuates neuroinflammation and improves functional recovery after spinal cord injury through microglia polarization regulation.

Spinal cord injury (SCI) is a severe neurological disease; however, few drugs have been proved to treat SCI effectively. Neuroinflammation is the major pathogenesis of SCI secondary injury and considered to be the therapeutic target of SCI. Salidroside (Sal) has been reported to exert anti-inflammatory effects in airway, adipose and myocardial tissue; however, the role of Sal in SCI therapeutics has not been clarified. In this study, we showed that Sal could improve the functional recovery of spinal cord in rats as revealed by increased BBB locomotor rating scale, angle of incline, and decreased cavity of spinal cord injury and apoptosis of neurons in vivo. Immunofluorescence double staining of microglia marker and M1/M2 marker demonstrated that Sal could suppress M1 microglia polarization and activate M2 microglia polarization in vivo. To verify how Sal exerts its effects on microglia polarization and neuron protection, we performed the mechanism study in vitro in microglia cell line BV-2 and neuron cell line PC12. The results showed that Sal prevents apoptosis of PC12 cells in coculture with LPS-induced M1 BV-2 microglia, also the inflammatory secretion phenotype of M1 BV-2 microglia was suppressed by Sal, and further studies demonstrated that autophagic flux regulation through AMPK/mTOR pathway was involved in Sal regulated microglia polarization after SCI. Overall, our study illustrated that Sal could promote spinal cord injury functional recovery in rats, and the mechanism may relate to its microglia polarization modulation through AMPK-/mTOR-mediated autophagic flux stimulation.

The Protective Effect of Ligustilide in Osteoarthritis: An in Vitro and in Vivo Study.

BACKGROUND/AIMS: Osteoarthritis is a degenerative joint disease characterized by cartilage degeneration and a chondrocyte inflammatory response that induces an inflammatory environment closely linked to extracellular matrix (ECM) degradation. Ligustilide (LIG) is a major component of the herb Radix Angelicae Sinensis, with demonstrated anti-inflammatory effects. To confirm whether LIG has an equally inhibitory effect on inflammation in human osteoarthritis chondrocytes, we performed in vivo and in vitro experiments to validate the above conjectures and determine the relevant mechanisms. METHODS: Quantitative realtime PCR and western blotting were performed to evaluate the expression of MMP-3, MMP-13, ADAMTS-5, iNOS, and COX-2 at both gene and protein levels. An enzyme-linked immunosorbent assay was used to evaluate the levels of other inflammatory factors (PGE2, TNF-α, and IL-6). The PI3K/AKT and nuclear factor kappa B (NF-κB) signaling pathways were also analyzed by western blotting, whereas immunofluorescence was used to assess the expression of collagen II and aggrecan. The in vitro effect of LIG was evaluated by intraperitoneal injection into a mouse osteoarthritis model induced by destabilization of the medial meniscus. RESULTS: LIG lowered the phosphorylation levels of p65, IκBα, and IKKα/ß and suppressed the IL-1ß-induced expression of MMP-3, ADAMTS-5, iNOS, and COX-2 and the inflammatory factors PGE2, TNF-α, and IL-6. LIG markedly decreased IL-1ß-induced degradation of collagen II and aggrecan. In vivo results showed that LIG-treated mouse cartilage showed less damage than the control group; the Osteoarthritis Research Society International (OARSI) score was also lower. LIG further reduced the thickness of the subchondral bone plate and alleviated the synovitis. CONCLUSION: LIG may act as a promising therapeutic agent for osteoarthritis by attenuating IL-1ß-induced inflammation in chondrocytes and ECM degradation via suppression of NF-κB activation by the PI3K/AKT pathway.

Light-controllable fiber interferometer utilizing photoexcitation dynamics in colloidal quantum dot.

The development of highly efficient light-controlled functional fiber elements has become indispensable to optical fiber communication systems. Traditional nonlinearity-based optical fiber devices suffer from the demerits of complex/expensive components, high peak power requirements, and poor efficiency. In this study, we utilize colloidal quantum dots (CQDs) to develop a light-controlled optical fiber interferometer (FI) for the all-optical control of the transmission spectrum. A specially designed exposed-core microstructure fiber (ECMF) is utilized to form the functional structure. Two types of PbS CQDs with absorption wavelengths around 1180 nm and 1580 nm, respectively, are deposited on the ECMF to enable the functional FI. The wavelength and power of control light are key factors for tailoring the FI transmission spectrum. A satisfactory recovery property and linear relationship between the spectrum shift and the power of control light at certain wavelength are achieved. The highest wavelength shift sensitivity of our light-controlled FI is 4.6 pm/mW, corresponding to an effective refractive index (RI) change of 5 × 10-6 /mW. We established a theoretical model to reveal that the RI of the CQD layer is governed by photoexcitation dynamics in CQD with the light absorption at certain wavelength. The concentration of charge carriers in the CQD layer can be relatively high under light illumination owing to their small size-related quantum confinement, which implies that low light power (mW-level in this work) can change the refractive index of the CQDs. Meanwhile, the absorption wavelength of quantum dots can be easily tuned via CQD size control to match specific operating wavelength windows. We further apply the CQD-based FI as a light-controllable fiber filter (LCFF) in a 50-km standard single-mode fiber-based communication system with 12.5-Gbps on-off keying direct modulation. Chirp management and dispersion compensation are successfully achieved by using the developed LCFF to obtain error-free transmission. CQDs possess excellent solution processability, and they can be deposited uniformly and conformally on various substrates such as fibers, silicon chips, and other complex structure surfaces, offering a powerful new degree of freedom to develop light control devices for optical communication.

Effects of combined human parathyroid hormone (1-34) and menaquinone-4 treatment on the interface of hydroxyapatite-coated titanium implants in the femur of osteoporotic rats.

The objective of this study was to investigate the effects of human parathyroid hormone (1-34) (PTH1-34; PTH) plus menaquinone-4 (vitamin K2; MK) on the osseous integration of hydroxyapatite (HA)-coated implants in osteoporotic rats. Ovariectomized female Sprague-Dawley rats were used for the study. Twelve weeks after bilateral ovariectomy, HA-coated titanium implants were inserted bilaterally in the femoral medullary canal of the remaining 40 ovariectomized rats. All animals were then randomly assigned to four groups: Control, MK, PTH and PTH + MK. The rats from groups MK, PTH and PTH + MK received vitamin K2 (30 mg/kg/day), PTH1-34 (60 µg/kg, three times a week), or both for 12 weeks. Thereafter, serum levels of γ-carboxylated osteocalcin (Gla-OC) were quantitated by ELISA and the bilateral femurs of rats were harvested for evaluation. The combination of PTH and MK clearly increased the serum levels of Gla-OC (a specific marker for bone formation) compared to PTH or MK alone. The results of our study indicated that all treated groups had increased new bone formation around the surface of implants and increased push-out force compared to Control. In addition, PTH + MK treatment showed the strongest effects in histological, micro-computed tomography and biomechanical tests. In summary, our results confirm that treatment with PTH1-34 and MK together may have a therapeutic advantage over PTH or MK monotherapy on bone healing around HA-coated implants in osteoporotic rats.

Fludarabine inhibits STAT1-mediated up-regulation of caspase-3 expression in dexamethasone-induced osteoblasts apoptosis and slows the progression of steroid-induced avascular necrosis of the femoral head in rats.

Steroid-induced avascular necrosis of the femoral head (SANFH) is a major limitation of long-term or excessive clinical administration of glucocorticoids. Fludarabine, which is a compound used to treat various hematological malignancies, such as chronic lymphocytic leukemia, acts by down-regulating signal transducer and activator of transcription 1 (STAT1) by inhibiting STAT1 phosphorylation in both normal and cancer cells. This study assessed the effects of fludarabine in vitro (primary murine osteoblasts) and in vivo (rat SANFH model). In vitro, pretreatment with fludarabine significantly inhibited Dexamethasone (Dex)-induced apoptosis in osteoblasts, which was examined by TUNEL staining. Treatment with Dex caused a remarkable decrease in the expression of Bcl-2; an increase in cytochrome c release; activation of BAX, caspase-9, and caspase-3; and an obvious enhancement in STAT1 phosphorylation. However, treatment resulted in the up-regulation of caspase-3 expression. Enhanced P-STAT1 activity and up-regulation of caspase-3 expression were also observed in osteoblasts. In vivo, the subchondral trabeculae in fludarabine-treated rats exhibited less bone loss and a lower ratio of empty lacunae. Taken together, our results suggest that STAT1-mediated up-regulation of caspase-3 is involved in osteoblast apoptosis induced by Dex and indicates that fludarabine may serve as a potential agent for the treatment of SANFH.

Performance enhanced DDO-OFDM system with adaptively partitioned precoding and single sideband modulation.

As a promising solution for short-to-medium transmission systems, direct detection optical orthogonal frequency division multiplexing (DDO-OFDM) or discrete multi-tone (DMT) has been intensively investigated in last decade. Benefitting from the advantages of peak-to-average power (PAPR) reduction and signal-to-noise ratio (SNR) equalization, precoding techniques are widely applied to enhance the performance of DDO-OFDM systems. However, the conventional method of partitioning precoding sets limits the ability of precoding schemes to optimize the SNR variation and the allocation of modulation formats. Thus, the precoding transmission systems are hard to reach the capacity that traditional bit-power loading (BPL) techniques, like the Levin-Campello (LC) algorithm, can achieve. In this paper, we investigate the principle of SNR variation for precoded DDO-OFDM systems and theoretically demonstrate that the SNR equalization effect of precoding techniques is actually determined by the noise equalization process. Based on this fact, we propose an adaptively partitioned precoding (APP) algorithm to unlock the ability to control the SNR of each subcarrier. As demonstrated by the simulation and experimental results, the proposed APP algorithm achieves the transmission capacity as high as the LC algorithm and has nearly 1 dB PAPR reduction. Besides, the look-up table (LUT) operation ensures low complexity of the proposed APP algorithm compared with LC algorithm. To avoid severe chromatic dispersion (CD) induced spectral fading, single sideband (SSB) modulation is also implemented. We find that SSB modulation can reach the capacity of double sideband (DSB) modulation in optical back-to-back (OB2B) configuration by optimizing the modulation index. Therefore, the APP based SSB-DDO-OFDM scheme can sufficiently enhance the performance of cost-sensitive short-to-medium reach optical fiber communication systems.

Ultra-high capacity WDM-SDM optical access network with self-homodyne detection downstream and 32QAM-FBMC upstream.

Towards 100G beyond large-capacity optical access networks, wavelength division multiplexing (WDM) techniques incorporating with space division multiplexing (SDM) and affordable spectrally efficient advanced modulation formats are indispensable. In this paper, we proposed and experimentally demonstrated a cost-efficient multicore fiber (MCF) based hybrid WDM-SDM optical access network with self-homodyne coherent detection (SHCD) based downstream (DS) and direct detection optical filter bank multi carrier (DDO-FBMC) based upstream (US). In the DS experiments, the inner core of the 7-core fiber is used as a dedicated channel to deliver the local oscillator (LO) lights while the other 6 outer cores are used to transmit 4 channels of wavelength multiplexed 200-Gb/s PDM-16QAM-OFDM signals. For US transmission, 4 wavelengths with channel spacing of 100 GHz are intensity modulated with 30 Gb/s 32-QAM-FBMC and directly detected by a ~7 GHz bandwidth receiver after transmission along one of the outer core. The results show that a 4 × 6 × 200-Gb/s DS transmission can be realized over 37 km 7-core fiber without carrier frequency offset (CFO) and phase noise (PN) compensation even using 10 MHz linewidth DFB lasers. The SHCD based on MCF provides a compromise and cost efficient scheme between conventional intradyne coherent detection and intensity modulation and direct detection (IM/DD) schemes. Both US and DS have acceptable BER performance and high spectral efficiency.

Posterior fossa decompression in Chiari I improves denervation of the paraspinal muscles.

OBJECTIVE: To investigate whether posterior fossa decompression (PFD) could improve denervation of the paraspinal muscles in patients with Chiari I malformation (CMI). BACKGROUND: Paraspinal muscle denervation is one of the essential elements in the pathophysiology of CMI/syringomyelia-related scoliosis. Although PFD has been widely used for managing CMI, whether denervation of the paraspinal muscles may benefit from this neurosurgical procedure remains ambiguous. Bax and Bcl-2 are two regulators of apoptosis that are closely related to the innervation status of skeletal muscles, and denervation is associated with upregulated Bax and downregulated Bcl-2. METHODS: Thirty-seven patients who underwent PFD and subsequent deformity correction for CMI-associated scoliosis were enrolled. Biopsy specimens were obtained from bilateral erector spinae muscles during both procedures with an average interval of 6.5 months. The biopsy site was located within the spinal innervation region involved by the syrinx and near the level of upper instrumented vertebra. The expression levels of Bax and Bcl-2 as well as histological features of the muscle fibres were examined at the two time points. RESULTS: After PFD, the mRNA level of antiapoptotic Bcl-2 was elevated by 178% and 260% in the convex and concave muscles, respectively, with a coincident decrease of 69% and 73% for proapoptotic Bax at the corresponding sites (p<0.001). Consistent with the mRNA data, the Bcl-2 protein in the paraspinal muscles was increased by 75% on the convex and by 169% on the concave side following PFD. For Bax protein, decreases of 45% and 52% were detected in the convex and concave muscles, respectively (p<0.001). On average, these changes led to a 60% decrease in the Bax/Bcl-2 ratio, suggesting reduced apoptotic signalling and improved innervation of the paraspinal muscles. Histologically, the specimens demonstrated improvements in denervation-associated changes of the muscle fibres following PFD, with the number of atrophic and necrotic/degenerated fibres decreasing significantly from 6.7 and 8.5 before surgery to 3.2 (p=0.012) and 4.2 (p<0.001) after surgery, respectively. CONCLUSION: In patients with CMI, treatment with PFD led to a decrease in the Bax/Bcl-2 ratio at both the mRNA and protein levels, indicating an attenuated susceptibility to apoptotic cell death. These data, coupled with the observed improvements in histopathological features of the myofibres, suggest that PFD in Chiari I ameliorates denervation of the paraspinal muscles.

Hidden blood loss and the influential factors after percutaneous kyphoplasty surgery.

PURPOSE: Percutaneous kyphoplasty (PKP) is a minimally invasive procedure for the treatment of osteoporotic vertebral compression fractures (OVCFs). It is generally considered that there is little blood loss during the surgery. However, a significant perioperative hidden blood loss (HBL) is neglected. This study was to examine the amount of HBL and determine the influential factors during PKP. METHODS: From January 2015 to January 2016, 115 patients with OVCFs who were scheduled to have a PKP were enrolled in this study. The factors analyzed included gender, age, body mass index (BMI), percentage of vertebral height loss, percentage of vertebral height restoration, number of fracture levels, bone mineral density (BMD), duration of symptom, cement leakage, and other internal diseases (hypertension, diabetes mellitus). According to Gross's formula, each patient's height, weight, and pre-operative and post-operative hematocrit were recorded and used for calculating the blood loss. Influential factors were further analyzed by multivariate linear regression analysis and t test. RESULTS: The mean HBL was 282 ± 162 mL (mL) and the post-operative Hb loss was 8.7 ± 5.4 g per liter (g/L). According to multivariate linear regression analysis, patients with severe vertebral height loss (P = 0.016), better vertebral height restoration (P = 0.038), and multi-segmental vertebral fractures (P = 0.000) had a higher amount of HBL. Fresh fractures (P = 0.008) and cement leakage (P = 0.004) were also important factors to increase HBL, whereas gender (P = 0.642), age (P = 0.203), BMI (P = 0.075), hypertension (P = 0.099), diabetes mellitus (P = 0.905), and BMD (P = 0.521) were not correlate with HBL. When we compared the incidence of anemia between pre-operative and post-operative, we found that the incidence of anemia was significantly associated with HBL (P = 0.000). CONCLUSIONS: HBL cannot be ignored in perioperative period, especially for poor physical condition and multiple fractures patients. Having a correct understanding of HBL can help improve clinical assessment capabilities, ensuring patients' safety.

Lack of association between AKAP2 and the susceptibility of adolescent idiopathic scoliosis in the Chinese population.

BACKGROUND: Adolescent idiopathic scoliosis (AIS) is a well characterized spinal deformity that affects millions of children world-wide. The role of genetic factor in the development of AIS has been of great interest, since obvious hereditary trend has been observed in AIS families. In a recent study of Chinese population, a novel mutation of AKAP2 was observed in a family with AIS, which was believed to play a role in the aetiopathogenesis of AIS. The purpose of this study was to investigate whether genetic variants of AKAP2 are associated with the susceptibility of AIS in Chinese population. METHODS: SNV c.2645A > C of AKAP2 was genotyped in 1254 AIS patients and 1232 normal controls using allelic-specific multiple ligase detection reactions. SNPs located within 5' untranslated regions (UTR) and 3' UTR of AKAP2 gene were selected using Haploview (v2.6). The GWAS database composed of 961 AIS patients and 1499 controls was referred to for the genotyping information. Relative mRNA expression of AKAP2 in peripheral blood was analyzed for 33 patients and 18 age-matched controls. Comparison between the cases and controls were performed using the Student's t test. PLINK (v1.90) was used to calculate the association of each SNP with the disease by Cochran-Armitage trend test. RESULTS: All the patients and the controls presented a genotype of AA in c.2645A > C of AKAP2, and there was no case of mutation in any subject. A total of 116 SNPs covering AKAP2 were analyzed, and none of these SNPs was found to have significantly different allele frequency between the cases and the controls. The mRNA expression of AKAP2 in patients was comparable with that in the controls (1.9 ± 0.8 vs. 1.8 ± 0.7, p = 0.66). CONCLUSIONS: Our large-scale replication study of the variants in AKAP2 gene did not support its association with the susceptibility of AIS in the Chinese population. In future study, functional studies of the previously reported rare variant are warranted to clarify whether the variant can regulate the expression of AKAP2. The whole AKAP2 gene can be sequenced in larger AIS cohorts to identify potentially missing mutations.

Experimental demonstration of large capacity WSDM optical access network with multicore fibers and advanced modulation formats.

Towards the next generation optical access network supporting large capacity data transmission to enormous number of users covering a wider area, we proposed a hybrid wavelength-space division multiplexing (WSDM) optical access network architecture utilizing multicore fibers with advanced modulation formats. As a proof of concept, we experimentally demonstrated a WSDM optical access network with duplex transmission using our developed and fabricated multicore (7-core) fibers with 58.7km distance. As a cost-effective modulation scheme for access network, the optical OFDM-QPSK signal has been intensity modulated on the downstream transmission in the optical line terminal (OLT) and it was directly detected in the optical network unit (ONU) after MCF transmission. 10 wavelengths with 25GHz channel spacing from an optical comb generator are employed and each wavelength is loaded with 5Gb/s OFDM-QPSK signal. After amplification, power splitting, and fan-in multiplexer, 10-wavelength downstream signal was injected into six outer layer cores simultaneously and the aggregation downstream capacity reaches 300 Gb/s. -16 dBm sensitivity has been achieved for 3.8 × 10-3 bit error ratio (BER) with 7% Forward Error Correction (FEC) limit for all wavelengths in every core. Upstream signal from ONU side has also been generated and the bidirectional transmission in the same core causes negligible performance degradation to the downstream signal. As a universal platform for wired/wireless data access, our proposed architecture provides additional dimension for high speed mobile signal transmission and we hence demonstrated an upstream delivery of 20Gb/s per wavelength with QPSK modulation formats using the inner core of MCF emulating a mobile backhaul service. The IQ modulated data was coherently detected in the OLT side. -19 dBm sensitivity has been achieved under the FEC limit and more than 18 dB power budget is guaranteed.

Relative phase noise estimation and mitigation in Raman amplified coherent optical communication system.

The interplay between the stochastic intensity fluctuation of Raman pump laser and cross-phase modulation (XPM) effect in transmission optical fiber leads to additional phase noise, namely, relative phase noise (RPN) of signal in multi-level modulated coherent optical communication system. Both theoretical analysis and quantitative simulation have been performed to investigate the characteristics and impact of RPN. Being low-pass in nature, RPN is different from XPM induced phase noise in PSK/OOK hybrid system, and has not been considered yet. The noise power of RPN can accumulate incoherently along transmission links. With a proper signal model, we study the impact of RPN to the coherent optical communication system through Monte Carlo simulation. RPN will cause more cycle slips in Viterbi-and-Viterbi (V-V) phase estimation (PE), and the quantitative analysis of cycle slip probability is carried out. When using sliding window V-V without any optimization, the Q factor penalty of RPN on DQPSK signal can be as large as around 5 dB in strong RPN condition. However, it can be reduced by over 3 dB when using an optimal block size or optimal averaging weights.

Second trimester amniotic fluid cytokine concentrations, Ureaplasma sp. colonisation status and sexual activity as predictors of preterm birth in Chinese and Australian women.

BACKGROUND: This study tested if second trimester amniotic fluid cytokine levels, Ureaplasma sp. colonisation and sexual activity predict preterm birth and explain the differential preterm birth rates in Chinese compared to Australian women. METHODS: Amniotic fluid was collected by amniocentesis (Chinese 480, Australian 492). Cytokines were measured by multiplex assay and Ureaplasma sp. DNA was detected by PCR analysis. Lifestyle factors, including history of smoking and sexual activity during pregnancy, were obtained through completion of questionnaires upon recruitment to the study. RESULTS: Inflammatory cytokine concentrations were poorly predictive of preterm birth. Ureaplasma sp. was detected in two of the Chinese pregnancies and none from Australia. Sexual activity was less frequent in Chinese, and was not associated with preterm birth or amniotic fluid findings in either population. DISCUSSION: Second trimester amniocentesis for measurement of inflammatory markers and Ureaplasma sp. DNA was not indicative of risk of preterm birth, at least in these populations. The lower rate of preterm birth in China was not explained by differences in amniotic fluid inflammatory markers, Ureaplasma sp. colonisation, or sexual activity.