Search

A steel-concrete-steel sandwich panel with prestressed reinforcement was developed, named prestressed steel-concrete–steel sandwich panel. Nine specimens where the loading mode, top steel plate thickness, spacing of connectors and prestressed reinforcement arrangement were varied were experimentally tested to explore the failure mode, ultimate strength, ductility and deflection of the structure. The results show that prestressing enhanced the ultimate strength and ductility of the structure. Finite element analysis predictions were consistent with test results in terms of crack characteristics, load-displacement curve and ultimate strength. Deflection prediction analysis of the prestressed panels was also developed based on variational theory which provided good agreement with the finite element results.

This paper investigates the secrecy outage performance of a downlink cooperative nonorthogonal multiple access- (NOMA-) assisted hybrid satellite-terrestrial network, where a satellite source communicates with two terrestrial users based on NOMA, in the presence of a terrestrial eavesdropper. We assume that there is no direct link between the satellite source and the far terrestrial user, and the near terrestrial user acts as a relay to forward the information to the far terrestrial user. The near user is assumed to support both half-duplex mode and the full-duplex mode for information relaying. We derive the closed-form exact expressions for the secrecy outage probability (SOP) of the near user, as well as the closed-form approximate expressions for the SOP of the far user based on the Gaussian-Chebyshev quadrature. Theoretical results are validated by conducting simulations. The impacts of various system parameters on the performance comparison between the half-duplex mode and full-duplex mode are investigated. Particularly, the full-duplex mode is shown to outperform the half-duplex mode when the received signal-to-noise ratio (SNR) at the near user is low or the residual self-interference is low.

Therapy of very severe osteoporotic compression fractures (VSOVCF) has been a growing challenge for spine surgeons. Opinions vary regarding the optimal surgical procedure for the treatment of VSOVCF and which internal fixation method is more effective is still under debate, and research on this topic is lacking. This retrospective study was conducted to compare the efficacy and safety of various pedicle screw fixation methods for treating VSOVCF.This single-center retrospective comparative study was conducted between January 2015 and September 2020. Two hundred and one patients were divided into six groups according to different surgical methods: 45 patients underwent long-segment fixation (Group 1); 39 underwent short-segment fixation (Group 2); 30 received long-segment fixation with cement-reinforced screws (Group 3); 32 received short-segment fixation with cement-reinforced screws (Group 4); 29 had long-segment fixation combined with kyphoplasty (PKP) (Group 5); and 26 cases had short-segment fixation combined with PKP (Group 6). The clinical records were reviewed and the visual analogue scale (VAS) score and the Oswestry Disability Index (ODI) score were used for clinical evaluation. The vertebral height (VH), fractured vertebral body height (FVBH), and Cobb's angle were objectively calculated and analyzed on lateral plain radiographs. Student's t-tests and one-way ANOVA among groups were conducted to analyze the continuous, and the chi-squared test was used to compare the dichotomous or categorical variables. The difference was considered statistically significant when the P-value was less than 0.05.The six groups had similar distributions in age, gender, course of the disease, follow-up period, and injured level. In the postoperative assessment of the VAS score, the surgical intervention most likely to rank first in terms of pain relief was the short-segment fixation with cement-reinforced screws (Group 4). For the functional evaluation, the surgical intervention that is most likely to rank first in terms of ODI score was a short-segment fixation with cement-reinforced screws (Group 4), followed by long-segment fixation (Group 1). The long-segment fixation with cement-reinforced screws was the first-ranked surgical intervention for the maintenance of Cobb's angle and vertebral height, whereas the short-segment fixation performed the worst. The highest overall complication rate was in Group 6 with an incidence of 42.3% (11/26), followed by Group 2 with an incidence of 38.5% (15/39).For the treatment of VSOVCF, the short-segment fixation with cement-reinforced screws is the most effective and optimal procedure, and should be used as the preferred surgical method if surgeons are proficient in using cemented screws; otherwise, directly and unquestionably use long-segment fixation to achieve satisfactory clinical results.

This paper presents an experimental research on the composite concrete-filled steel tube roof (C-CFST-R) structure, which is proposed as a new type of tubular-roof structure. The longitudinal large-diameter steel tubes are connected by small-diameter steel tubes in transverse, forming the supporting structure after concrete casting. The mechanical performance and failure mode of the C-CFST-R members are analyzed and following parameters are tested: diameter of the connection tube, eccentricity of the connection tube, the presence of bottom steel plate, and the longitudinal tube spacing. A theoretical formulation for the transverse bending capacity of the cross-section of this structure is also presented. The results show that the failure mode of the test specimens exhibits ductile failure. The transverse stiffness and the bearing capacity increase with the increase of connection tube diameter, while the eccentricity of connection tube has unobvious impact on flexural behavior of the member. Welding the bottom steel plate significantly enhances the bending stiffness and capacity by more than 4 times. The increase of longitudinal tube spacing mainly causes reduction in transverse stiffness. The proposed theoretical calculation method shows a reasonable prediction of the bending capacity in compare with the test results.

Background With the increase in life expectancy, a large number of patients with osteoporosis (OP) are undergoing spine surgery, which may adversely affect the surgical success rate. The prevalence of OP varies in different regions, and no data are available that represent the prevalence of OP among Chinese patients over 50 years of age who are undergoing spine surgery. It was the first multicenter study to assess OP in these patients. Aiming to obtain comprehensive data, this study combined bone mineral density (BMD) measurements and visual radiography assessment (VRA) to analyze the prevalence of OP in patients aged > 50 years who underwent spine surgery. Methods Data from 1,856 patients aged over 50 years undergoing spine surgery who resided in northern, central, and southern China were reviewed between 2018 and 2019. Based on the perioperative BMD and X-ray data, we calculated the prevalence of OP in this special population according to sex, age, and spine degenerative disease. Results A total of 1,245 patients (678 females and 567 males) were included in the study. The prevalence of OP diagnosed by BMD was 52.8 % in females and 18.7 % in males. When we combined with BMD and VRA, the prevalence of OP increased from 52.8 to 65.9 % in females and from 18.7 to 40.6 % in males. Although OP was more severe in females than in males, a significant difference in the rate of vertebral fracture (VF) was not observed between females and males with a normal BMD and osteopenia (females vs. males: aged 50–59 years, P = 0.977; 60–69 years, P = 0.302; >70 years, P = 0.172). Similarly, no significant difference in the vertebral fracture rate was observed within different age groups of patients with a normal BMD and osteopenia (females: P = 0.210; males, P = 0.895). The incidence of OP in patients with degenerative scoliosis was higher than that in the remaining patients (females: 63.6 % vs. 42.4 %, P = 0.018; males: 38.9 % vs. 13.8 %, P = 0.004). Conclusions A high prevalence of OP was identified in patients aged > 50 years undergoing spine surgery, especially in patients whose primary diagnosis was degenerative scoliosis. BMD and VRA evaluations should be included in the clinical routine for these patients prior to surgery.

Background This study aimed to assess the feasibility of using the 3-dimensional (3-D) reconstruction technique based on ultrathin cryomilling to show the lumbar intervertebral foraminal ligaments in situ. Methods Cryomilling was performed on an embalmed human cadaver to acquire successive cross-sectional images. In each of the images, the boundaries of lumbar intervertebral foraminal ligaments and their adjacent structures were outlined, labeled, and reconstructed for 3-D modeling. The morphology, attachments, and spatial orientation of ligaments were described. Results A total of 9 ligaments in 10 lumbar intervertebral foramina (IVFs) were identified and reconstructed. These ligaments can be divided into 5 types. The IVFs were divided into 2 or 3 main portions by the first 4 types of ligaments (transforaminal ligaments, corporotransverse ligaments, “reticular” ligaments, and “Y-shaped” ligaments). The radiating ligaments (the fifth type of ligaments) attached to the surrounding structures of the IVF and were connected directly to the nerve root sleeves. Although there was no indication of neurovascular compromise in this normal specimen, these ligaments limit the space within the bony IVF such that under certain pathologic conditions (e.g., inflammation), their presence would make neurovascular compression more likely than if they were absent. Conclusions The 3-D reconstruction technique based on ultrathin cryomilling can effectively show the lumbar intervertebral foraminal ligaments and their anatomical characteristics in situ, providing a new way to clarify the relationships between these ligaments and their adjacent structures.

Background Osteoporotic vertebral compression fracture (OVCF) is a common disease in elderly population, which could cause serious back pain and has a substantial impact on patients' health-related quality of life (HRQoL). The aim of this study was to identify the effect of Teriparatide as a conservative treatment on reducing back pain, and improving quality of life for postmenopausal women with osteoporotic vertebral fractures. Methods In a 12-month, retrospective study, 112 postmenopausal women with OVCFs were assigned to Teriparatide group (20 µg Teriparatide, subcutaneous, once daily, n=38) or control group (500 mg calcium and 400-800 IU Vitamin D per day, oral administration, n=74) according to patients' choices between January 2016 and October 2018. Patient-reported outcomes scores including the visual analogue score (VAS), Oswestry disability index (ODI), and short form 36 questionnaire (SF-36) were assessed at baseline, the 3rd months, the 6th months and 1 year after treatment. Results Treatments with Teriparatide or calcium plus vitamin D supplements had significant effect on improvement of patients' back pain as well as HRQoL, with significantly reduced VAS and ODI and increased SF-36 physical component summary (PCS) and mental component summary (MCS) scores. At the endpoint, Teriparatide showed better therapeutic effect, with greater reductions in VAS and ODI and more increases in SF-36 PCS and MCS scores. However, more adverse events (AEs) were found in Teriparatide group, but symptoms were relatively mild and of short duration. Conclusions In postmenopausal women with OVCFs, the consequent persistent back pain and impaired HRQoL, treatment with Teriparatide was associated with more profound therapeutic effects and more AEs compared with calcium plus vitamin D supplements.

Background As an irrigant, an antiseptic, and a hemostatic agent, hydrogen peroxide (H2O2) is widely used in surgical treatment, but it has been surrounded by persistent controversy. Fatal or near-fatal embolic events caused by H2O2 have been reported sporadically in spine surgery. Case Description In this report, we present an 87-year-old man who underwent lumbar instrumentation removal and debridement consequent to surgical site infection in a prone position. H2O2 was used to irrigate the infected screw tracks and surrounding tissues during the procedures. Soon after irrigation, the patient suddenly developed tachycardia, hypotension, and rapid oxygen desaturation, followed by bradycardia. Transesophageal echocardiography indicated gas embolism. After prompt first aid treatment, the patient's condition improved and the gas embolus disappeared within a few minutes without any evidence of organ embolism. Conclusions Spine surgeons should reconsider the pending results of using H2O2 during surgery. Prolonged prone positioning and semiclosed cavities may increase the risk of gas embolism. An early diagnosis and timely intervention may be the key measures to prevent the occurrence of fatal consequences caused by gas embolism.

Social recognition and memory are critical for survival. The hippocampus serves as a central neural substrate underlying the dynamic coding and transmission of social information. Yet the molecular mechanisms regulating social memory integrity in hippocampus remain unelucidated. Here we report unexpected roles of Celsr2, an atypical cadherin, in regulating hippocampal synaptic plasticity and social memory in mice. Celsr2-deficient mice exhibited defective social memory, with rather intact levels of sociability. In vivo fiber photometry recordings disclosed decreased neural activity of dorsal CA1 pyramidal neuron in Celsr2 mutants performing social memory task. Celsr2 deficiency led to selective impairment in NMDAR but not AMPAR-mediated synaptic transmission, and to neuronal hypoactivity in dorsal CA1. Those activity changes were accompanied with exuberant apical dendrites and immaturity of spines of CA1 pyramidal neurons. Strikingly, knockdown of Celsr2 in adult hippocampus recapitulated the behavioral and cellular changes observed in knockout mice. Restoring NMDAR transmission or CA1 neuronal activities rescued social memory deficits. Collectively, these results show a critical role of Celsr2 in orchestrating dorsal hippocampal NMDAR function, dendritic and spine homeostasis, and social memory in adulthood.

Currently, microalgae-derived lutein is gaining attention for its potential applications in cosmeceutical, nutraceutical, pharmaceutical, and food industries. Lutein is of commercial interest for a broad variety of health benefits: antioxidant activity, skin health improvement, reducing age-related macular degeneration, and the treatment of cancer. Microalgae are the fastest-growing lutein source, have the highest content in nature, and are a promising sustainable alternative to the current commercial source, marigold flowers. Microalgal cultivation has added environmental benefits over plants with higher carbon sequestration, reduced water footprint, and no pesticide use. To date, no industrial facility exists for the production of lutein from microalgae. This review outlines the existing technologies for bioprocessing of lutein at pilot scale (cultivation, harvesting, extraction, and purification). In addition, lutein encapsulation, a seldom discussed area, is explored in depth. In view of this knowledge, lutein could be anticipated as the next successful sustainable product from microalgae obtained at industrial scale for the circular economy. Graphical abstract: [Figure not available: see fulltext.]

Propranolol (PROP) is a nonselective β-adrenergic receptor antagonist used to treat hypertension and cardiac arrhythmias. Oral administration of PROP has recently emerged as a new treatment modality for hemangiomas. However, the side effects of PROP at the cellular level have not been adequately described. The present study investigates and highlights the mechanisms of coupling of the drugs cyclosporin-A (CyA) and PROP on cell proliferation and the occurrence of apoptosis. It also relays the antioxidant effect of PROP on human umbilical vein endothelial cells (HUVECs). HUVECs were treated with CyA and PROP. At 24 hours after treatment, the levels of reactive oxygen species (ROS), cell proliferation, and apoptosis were determined using the ROS kit, MTT assay, and Annexin V staining. In addition, the related proteins of phospho-p38 mitogen-activated protein kinase were determined by western blotting. Subsequently, HUVECs pretreated with CyA or PROP were treated with the p38 inhibitor (SB203580). Finally, the ROS level, cell proliferation, and apoptosis were measured again in both active HUVECs and HUVECs, in which the p38 proteins were inhibited. The combination of CyA and PROP reversed the effect of CyA on cell viability, reduced the ROS level and the cell apoptosis induced by PROP. Moreover, inhibition of p38 protein catalase activity immediately stopped the effect of CyA–propranolol in HUVECs. The effect of the CyA–propranolol combination on HUVECs is associated with the p38 pathway changes, which is proven to be a potential chemotherapeutic agent that minimizes the side effects of PROP in hemangioma therapy.

A few developmental genes remain persistently expressed in the adult stage, whilst their potential functions in the mature brain remain underappreciated. Here, we report the unexpected importance of Celsr2, a core Planar cell polarity (PCP) component, in maintaining the structural and functional integrity of adult neocortex. Celsr2 is highly expressed during development and remains expressed in adult neocortex. In vivo synaptic imaging in Celsr2 deficient mice revealed alterations in spinogenesis and reduced neuronal calcium activities, which are associated with impaired motor learning. These phenotypes were accompanied with anomalies of both postsynaptic organization and presynaptic vesicles. Knockout of Celsr2 in adult mice recapitulated those features, further supporting the role of Celsr2 in maintaining the integrity of mature cortex. In sum, our data identify previously unrecognized roles of Celsr2 in the maintenance of synaptic function and motor learning in adulthood.

R. esculentum is a popular seafood in Asian countries and an economic marine fishery resource in China. However, the high-resolution genetic map and growth-related molecular markers still lack, hindering the process of the genetic breeding of R. esculentum. Therefore, we firstly used the 2b-RAD method to sequence 152 R. esculentum specimens, identified 9100 single nucleotide polymorphism (SNP) markers and constructed a high-resolution genetic map with a marker interval of 0.58 cM, covering 98.68% of the genome. Then, we separately detected four and three quantitative trait loci (QTLs) associated with umbrella diameter and body weight based on the linkage map, which is located on linkage group (LG) 4, 13, 14 and 15. Finally, 27 genes were found both associated with umbrella diameter and body weight of R. esculentum by genome-wide association study (GWAS), in which one gene named RE13670 containing calcium-binding EGF-like domain may play an important role in controlling the growth. This study will be beneficial for underlying the growth mechanism of R. esculentum and also provide background knowledge for guiding its genetic breeding.

The imbalance between osteogenic and adipogenic differentiation of Bone marrow-derived mesenchymal stem cells (BMSCs) is involved in the occurrence and development of osteoporosis (OP). Previous studies have indicated the potential of phosphatase and actin regulator 1 (Phactr1) in regulating osteogenic and adipogenic differentiation of BMSCs. The present study aims to investigate the function and mechanism of Phactr1 in regulating osteogenic and adipogenic differentiation of BMSCs. Herein, the expression of Phactr1 in bone and adipose tissue of OP rats was determined by immunohistochemical. BMSCs were subjected to osteogenic and adipogenic differentiation, and transfected with Phactr1 overexpression lentivirus, small interference RNA (siRNA) and KD025 (selective ROCK2 inhibitor). The relationship between Phactr1 and ROCK2 was detected by Co-IP experiment. The expression of Phactr1, Runx2, C/EBPα, RhoA and ROCK2 was detected by Western blot. Calcium nodule and lipid droplets were determined by alizarin red and Oil red O staining. Interestingly, Phactr1 increased in both bone and adipose tissue of OP rats. During osteogenic differentiation, Phactr1 decreased and active RhoA, ROCK2 increased, while overexpression Phactr1 inhibits the increase of Runx2. Phactr1 increased and active RhoA decreased, ROCK2 did not changed during adipogenic differentiation. While, Knockdown Phactr1 inhibits the increase of C/EBPα. Phactr1 and ROCK2 were combined in osteogenic differentiation, but not in adipogenic differentiation. By using KD025, the decrease of Phactr1 and increase of Runx2 were inhibited respectively in osteogenic differentiation. Meanwhile, when ROCK2 was inhibited, Phactr1, C/EBPα were significantly increased in adipogenic differentiation. These findings indicated that Phactr1 negatively regulates bone mass by inhibiting osteogenesis and promoting adipogenesis of BMSCs by activating RhoA/ROCK2.

Background The progression of castration-resistant prostate cancer (CRPC) still relies on the function of androgen receptor (AR), achieved by evolving mechanisms to reactivate AR signaling under hormonal therapy. Histone deacetylase inhibitors (HDACis) disrupt cytoplasmic AR chaperone heat shock protein 90 (Hsp90) via HDAC6 inhibition, leading to AR degradation and growth suppression of prostate cancer (PCa) cells. However, current HDACis are not effective in clinical trials treating CRPC. Methods We designed hybrid molecules containing partial chemical scaffolds of AR antagonist enzalutamide (Enz) and HDACi suberoylanilide hydroxamic acid (SAHA) as new anti-PCa agents. We previously demonstrated that Enz-HDACi hybrid drug 2-75 targets both AR and Hsp90, which inhibits the growth of Enz-resistant C4-2 cells. In the current study, we further investigate the molecular and cellular actions of 2-75 and test its anti-PCa effects in vivo. Results Compared with Enz, 2-75 had greater AR antagonistic effects by decreasing the stability, transcriptional activity, and nuclear translocation of intracellular AR. In addition to inhibition of full-length AR (FL AR), 2-75 downregulated the AR-V7 variant in multiple PCa cell lines. Mechanistic studies indicated that the AR affinity of 2-75 retains the drug in the cytoplasm of AR + PCa cells and further directs 2-75 to the AR-associated protein complex, which permits localized effects on AR-associated Hsp90. Further, unlike pan-HDACi SAHA, the cytoplasm-retaining property allows 2-75 to significantly inhibit cytoplasmic HDAC6 with limited impact on nuclear HDACs. These selective cytoplasmic actions of 2-75 overcome the unfavorable resistance and toxicity properties associated with classical AR antagonists, HDACis, and Hsp90 inhibitors. Finally, 2-75 showed greater antitumor activities than Enz in vivo on SQ xenografts derived from LNCaP cells. Conclusions Novel therapeutic strategy using newly designed 2-75 and related AR antagonist-HDACi hybrid drugs has great potential for effective treatment of CRPC.

Background Pedicle screw fixation (PSF) has been considered the preferred surgery for the treatment of severe osteoporotic vertebral compression fracture (sOVCF), and sOVCF was traditionally regarded as a relative contraindication to minimally invasive percutaneous kyphoplasty (PKP). Debate has continued regarding the selection of the best surgical method for sOVCF. In the present study, we compared the efficacy and safety between PKP and PSF. Methods PKP was performed in 376 patients in group 1 and PSF in 121 patients in group 2. The visual analog scale (VAS), Oswestry disability index (ODI), local kyphotic angle, fractured vertebral body height, and complications were evaluated. Results In the immediate postoperative analysis, the mean VAS score for group 1 was 2.4, significantly lower than the VAS score of 4.7 for group 2. The mean ODI score was 44.4% for group 1, lower than the ODI score of 57.1% for group 2. In addition, group 1 had had a significantly better ODI score at 1 year of follow-up. The local kyphotic angle and fractured vertebral body height had recovered better in group 2. In group 1, 113 patients had experienced cement leakage, and 29 patients had undergone PKP for adjacent new vertebral fractures. In group 2, 2 patients had developed wound infections, 4 had developed pneumonia, 2 had developed urinary tract infection, 3 had experienced asymptomatic screw loosening, and 7 had undergone PKP to treat new vertebral fractures and 1 had undergone removal of internal fixation because of back pain. Conclusions The results of the clinical and radiological evaluations showed that PKP is comparable to PSF for the treatment of sOVCF with kyphosis, with PKP having the advantages of minimal invasion, quick postoperative pain relief, and functional recovery.

Background Pyogenic spondylodiscitis (PSD) is challenging to the orthopedist with regards to diagnosis and treatment. The present study was designed to assess and suggest the most indicative diagnostic method and evaluate the effect of surgery comprising of debridement, instrumentation and fusion in treating PSD. Methods Seventy-six patients with PSD who underwent surgical intervention were retrospectively enrolled. Their medical documents, corrections of spinal alignment and improvements in neurological function were assessed. Surgical approaches were compared in lumbar surgeries regarding the improvements in lordotic angle and neurological function. Results Elevated c-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) were found in 77.6 and 71.1% patients respectively. Infectious lesions were found at lumbar (85.5%), cervical (10.5%) and thoracic (3.9%), ascertained with contrast-enhanced MRI. For lumbar patients, surgery was performed through the anterior (26.2%), posterior (49.2%) or combined approach (24.6%), and differences in improvement of lordosis and neurological function between each approach were insignificant. The pathogen was identified in 22.4% of the patients. Postoperative antibiotic therapy was managed against the result of susceptibility test, or empirically given to patients with negative cultures. All antibiotic therapy was initiated intravenously for 4–6 weeks and orally for 6 weeks. Conclusion Elevated CRP and/or ESR, with focal hyper-intensity on contrast-enhanced MRI are suggestive of possible PSD. Surgical intervention comprising of debridement, short-segment instrumentation and fusion that early applied to the PSD patients followed by postoperative antibiotic therapy have demonstrated preferable outcomes, but require further study. The translational potential of this article This article advocates early surgery to enable prompt diagnosis and treatment of PSD, and thus guarantee favorable outcomes for patients, as is shown in our study. In addition, different surgical approaches to the lesions were compared and discussed in this manuscript, but no differences in outcome between approaches were found. This suggests that thorough debridement should be prioritized over selection of surgical approach. In summary, this article has large translational potential to be applied clinically.

Background: Human studies have demonstrated the beneficial effects of soy or isoflavones on bone metabolism. However, conflicting data remain. Equol is the intestinal metabolite of the isoflavone daidzein. The health benefits of soy are more pronounced in equol producers than those not producing equol. This 6-month randomized controlled trial aimed to examine the effect of whole soy (soy flour) and purified daidzein on bone turnover markers (BTMs) in Chinese postmenopausal women who are equol producers. Methods: A total of 270 eligible women were randomized to either one of the three isocaloric supplements as follows: 40 g soy flour (whole soy group), 40 g low-fat milk powder + 63 mg daidzein (daidzein group), or 40 g low-fat milk powder (placebo group) given as a solid beverage daily for 6 months. The following fasting venous samples were collected at the baseline and end of the trial to analyze BTMs: serum cross-linked C-telopeptides of type I collagen, bone-specific alkaline phosphatase, osteocalcin, procollagen type I N-terminal propeptide, and 25(OH)D3. Inflammation-related biomarkers, such as serum interleukin-6, tumor necrosis factor-alpha, C-reactive protein, transferrin, and homocysteine, were also tested to explore potential mechanisms. Results: A total of 253 subjects validly completed the study protocol. Urinary isoflavones suggested a good compliance to the treatments. Intention-to-treat and per-protocol analyses indicated no significant difference in the 6-month or percentage changes in the parameters of bone metabolism and inflammatory markers among the three treatment groups. Conclusions: Whole soy and purified daidzein at provided dosages exhibited no significant effect on the bone metabolism and inflammation levels among Chinese equol-producing postmenopausal women. Trial registration: ClinicalTrials.gov identifier NCT01270737.

The protein kinase TNK2 (ACK1) is an emerging drug target for a variety of indications, in particular for cancer where it plays a key role transmitting cell survival, growth and proliferative signals via modification of multiple downstream effectors by unique tyrosine phosphorylation events. Scaffold morphing based on our previous TNK2 inhibitor XMD8-87 identified urea 17 from which we developed the potent and selective compound 32. A co-crystal structure was obtained showing 32 interacting primarily with the main chain atoms of an alanine residue of the hinge region. Additional H-bonds exist between the urea NHs and the Thr205 and Asp270 residues.

The ability of intermittent parathyroid hormone (1-34) [PTH(1-34)] treatment to enhance bone-implant osseo-integration was recently demonstrated in vivo. However, the mechanisms through which PTH (1-34) regulates bone marrow-derived stromal cells (BMSCs) remain unclear. The present study thus aimed to investigate the effects of PTH(1-34) on the migration and adhesion of, and rictor/mammalian target of rapamycin complex 2 (mTORC2) signaling in BMSCs. In the present study, BMSCs were isolated from Sprague-Dawley rats treated with various concentrations of PTH(1-34) for different periods of time. PTH(1-34) treatment was performed with or without an mTORC1 inhibitor (20 nM rapamycin) and mTORC1/2 inhibitor (10 µM PP242). Cell migration was assessed by Transwell cell migration assays and wound healing assays. Cell adhesion and related mRNA expression were investigated through adhesion assays and reverse transcription-quantitative polymerase chain reaction (RT-qPCR), respectively. The protein expression of chemokine receptors (CXCR4 and CCR2) and adhesion factors [intercellular adhesion molecule 1 (ICAM-1), fibronectin and integrin β1] was examined by western blot analysis. The results revealed that various concentrations (1, 10, 20, 50 and 100 nM) of PTH(1-34) significantly increased the migration and adhesion of BMSCs, as well as the expression of CXCR4, CCR2, ICAM-1, fibronectin and integrin β1. In addition, the p-Akt and p-S6 levels were also upregulated by PTH(1-34). BMSCs subjected to mTORC1/2 signaling pathway inhibition or rictor silencing exhibited a markedly reduced PTH-induced migration and adhesion, while no such effect was observed for the BMSCs subjected to mTORC1 pathway inhibition or raptor silencing. These results indicate that PTH(1-34) promotes BMSC migration and adhesion through rictor/mTORC2 signaling in vitro. Taken together, the results of the present study reveal an important mechanism for the therapeutic effects of PTH(1-34) on bone-implant osseointegration and suggest a potential treatment strategy based on the effect of PTH(1-34) on BMSCs.

The study aims to examine the association of dietary intake of lignans with the risk of hip fractures in Chinese older adults. This was a 1:1 age- and gender- matched case–control study. Dietary survey was conducted by face-to-face interviews using a 79-item validated food frequency questionnaire. Habitual intake of total and individual lignans (matairesinol, secoisolariciresinol, pinoresinol, and lariciresinol) was estimated based on the available lignans databases. Conditional logistic regression was used to examine the relationship of dietary total and individual lignans, lignan-rich foods (vegetables, fruits, nuts, and cereals) and dietary fibers with the risk of hip fracture. A total of 1070 pairs of hip fracture incident cases and controls were recruited. Compared with the lowest quartile, the highest quartile group showed a reduced hip fracture risk by 76.3% (0.237, 95% CI: 0.103–0.544, Ptrend < 0.001) for total lignans, and 62.5% (0.375, 95% CI: 0.194–0.724, Ptrend = 0.001) for dietary fibers. Similar findings were observed for individual lignans, the estimated enterolactone level, as well as lignans from vegetables and nuts. We concluded that greater consumption of total and individual lignans, and lignan-rich foods were significantly associated with decreased risk of hip fracture.

Background The association of dietary sugar intake and skeletal health remains uncertain in the elderly. We aimed to investigate the association of sugar intake with the bone health and mortality of Chinese elderly. Methods An analysis was conducted through an 11-year longitudinal study (Mr. and Ms. OS Hong Kong). Four thousand Chinese elderly aged 65 and older were recruited from the local community between 2001 and 2003. Sugar intake was assessed at baseline by a validated 329-item Food Frequency Questionnaire and a local sugar database. The bone mineral density (BMD) was examined at baseline and the fourth year follow-up by a dual-energy X-ray absorptiometry. Data on the incidence of non-traumatic fractures (total, hip and osteoporotic sites) and all-cause mortality were collected. The multivariable logistic and Cox regression models were used to test the associations of sugar intake with bone health and all-cause mortality. Results No significant association was observed between sugar intakes and BMD changes in the fourth year's follow-up. During a total 34,483 person years' follow-up, we documented 433 non-traumatic fractures and 769 deaths. Although lack of significant association with the incidence of non-traumatic fractures, high added sugar intakes were significantly associated with a low risk of all-cause mortality among the elderly with a hazard ratio of 0.750 (95% CI: 0.590–0.954, P for trend = 0.007) in the highest quintile compared with that in the lowest quintile. Conclusion The amount of sugar consumed by the Chinese elderly did not pose any risk of bone loss and fracture. Moreover, high sugar intake of the elderly was associated with a low rate of all-cause mortality.

Our study aims to investigate the association between dietary acrylamide exposure and cancer mortality among Chinese elderly. A prospective cohort of 4000 elderly men and women aged 65 years and above (Mr. and Ms. OS Hong Kong study) was recruited from local communities from 2001 to 2003. Dietary exposure to acrylamide was evaluated at baseline based on a validated food frequency questionnaire and an acrylamide database from the 1st Hong Kong Total Diet Study. Data on mortality statistics through March 2014 were obtained from the Death Registry of the Department of Health of Hong Kong with a median follow-up of 11.1 years. Cox proportional hazards models were used to examine the association between the acrylamide exposure and cancer mortality. Sex hormones were assessed in men. During a median follow-up of 11.1 years (39,271 person-years), we ascertained 330 cancer deaths. Vegetables (43.7%) and cereals (28.9%) products were the major contributors to dietary acrylamide. Compared with the lowest quartile of acrylamide intake ( 17.1 µg/day) were 1.9 (95% CI 1.3–2.8; P trend

The aim of the study is to explore the longitudinal association of dietary acrylamide exposure with cognitive performance in Chinese elderly. The analysis was conducted among 2534 non-smoking elderly men and women based on a prospective study, Mr. and Ms. OS Hong Kong. Dietary acrylamide intake was assessed by food frequency questionnaires with data on local food contamination, derived from the first Hong Kong Total Diet Study. Global cognitive function was assessed by Cantonese version of Mini-Mental State Exam (MMSE) at the baseline and the 4th year of follow-up. Multivariable-adjusted linear and logistic regression models were used to assess the associations of dietary acrylamide with MMSE score changes or risk of poor cognition. The results indicated that among men with MMSE ≥ 18, each one SD increase of acrylamide decreased MMSE score by 7.698% (95%CI: −14.943%, −0.452%; p = 0.037). Logistic regression revealed an increased risk of poor cognition (MMSE ≤ 26) in men with HR of 3.356 (1.064~10.591, p = 0.039). The association became non-significance after further adjustment for telomere length. No significant association was observed in women. Dietary acrylamide exposure was associated with a mild cognitive decline or increased risk of poor cognition over a 4-year period in non-smoking Chinese elderly men.