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Based on the joint HCPMMP parcellation method we developed before, which divides the cortical brain into 360 regions, the concept of ordered core features (OCF) is first proposed to reveal the functional brain connectivity relationship among different cohorts of Alzheimer's disease (AD), late mild cognitive impairment (LMCI), early mild cognitive impairment (EMCI) and healthy controls (HC). A set of core network features that change significantly under the specifically progressive relationship were extracted and used as supervised machine learning classifiers. The network nodes in this set mainly locate in the frontal lobe and insular, forming a narrow band, which are responsible for cognitive impairment as suggested by previous finding. By using these features, the accuracy ranged from 86.0% to 95.5% in binary classification between any pair of cohorts, higher than 70.1%–91.0% when using all network features. In multi-group classification, the average accuracy was 75% or 78% for HC, EMCI, LMCI or EMCI, LMCI, AD against baseline of 33%, and 53.3% for HC, EMCI, LMCI and AD against baseline of 25%. In addition, the recognition rate was lower when combining EMCI and LMCI patients into one group of mild cognitive impairment (MCI) for classification, suggesting that there exists a big difference between early and late MCI patients. This finding supports the EMCI/LMCI inclusion criteria introduced by ADNI based on neuropsychological assessments.

Cardiovascular disease (CVD) is the leading cause of death among persons aged 65 and older in the United States and many other developed countries. Tissue engineered vascular systems (TEVS) can serve as grafts for CVD treatment and be used as in vitro model systems to examine the role of various genetic factors during the CVD progressions. Current focus in the field is to fabricate TEVS that more closely resembles the mechanical properties and extracellular matrix environment of native vessels, which depends heavily on the advance in biofabrication techniques and discovery of novel biomaterials. In this review, we outline the mechanical and biological design requirements of TEVS and explore the history and recent advances in biofabrication methods and biomaterials for tissue engineered blood vessels and microvascular systems with special focus on in vitro applications. In vitro applications of TEVS for disease modeling are discussed.

BackgroundUniversal salt iodization (USI) was implemented in mainland China in 1996. The prevalence of hyperthyroidism and its risk factors now require examination.MethodsData were acquired from a nationwide Thyroid, Iodine, and Diabetes Epidemiological survey (TIDE 2015–2017) of 78,470 subjects from 31 provinces. Iodine status, and thyroid hormones and antibodies were measured. ResultsAfter two decades of USI, the prevalence of overt hyperthyroidism (OH), Graves’ disease (GD), severe subclinical hyperthyroidism (severe SCH), and mild subclinical hyperthyroidism (mild SCH) in mainland China was 0.78%, 0.53%, 0.22%, and 0.22%, respectively. OH and GD prevalence were higher in women than in men (OH: 1.16% vs. 0.64%, P

Objective This study evaluated the association of serum irisin level with thyroid autoantibody (TAA) positivity and subclinical hypothyroidism (SH). Methods In this cross-sectional study, 334 participants were assigned to one of the following four age- and sex-matched groups: TAA plus SH (84 patients), isolated TAA (83 patients), isolated SH (83 patients), or healthy controls (84 individuals). Irisin and creatine kinase (CK) were measured in serum samples. Results Patients with TAA plus SH, isolated TAA, and isolated SH had higher irisin levels compared with the controls. There was a significant increase in the irisin level in the TAA plus SH group compared with the control group. Among all participants, the irisin levels were positively associated with thyroglobulin and thyroid peroxidase antibody titers and high-density lipoprotein cholesterol levels, but negatively associated with waist circumference, glycated hemoglobin levels, and fasting plasma glucose levels. The irisin level was not associated with the thyroid-stimulating hormone, free thyroxine, or CK levels. Irisin levels were independently associated with TAA, with or without SH, but they were not associated with SH alone. Conclusions Irisin level may help to predict the risk of developing TAA with or without SH.

Laser has become a well-accepted technique for surgical procedures. To fit the physically irradiated area to the clinically planned target area, a multifibre laser system can be used. This paper theoretically investigated the temperature distribution in a three-dimensional biological tissue when irradiated by multifibre lasers with the aids of the dual-phase-lag (DPL) bio-heat conduction model. First, four laser beams located on the corners of a square are used as the heat sources. The method of separation of variables is adopted to obtain the analytical expression of temperature. The characteristics of DPL bio-heat transfer model and the difference with Pennes model were checked graphically. It is found that the effect of multiple laser beams on temperature response differs from those of single laser beam distinctly. A second heating phenomenon occurs and the contour of a square with curved corners are obtained. Then the laser beams are located to form a triangle and a trapezoid and the corresponding temperature responses are studied. Different irradiated zone can be obtained and accomplished by changing the spot size, the arrangement layout and the interval distance of the laser beams.

The introduction of hydrophobic units into crown ethers can dramatically decrease the critical transition temperature of LCST and realize macroscopic phase separation at low to moderate temperature and concentration. Minor modifications in the chemical structure of crown ethers (benzo-21-crown-7, B21C7s) can effectively control the thermo-responsive properties.

Identification of vulnerable lines in power systems has great meaning to predict cascading failures and prevent the blackouts. A novel approach to identify the vulnerable lines in power systems based on the weighted H-index is proposed. Firstly, to remove the Kirchhoff's law constraint in power system, a second-level correlation network is constructed considering the secondary cascading failure. Then, the relative node strength is defined in the second-level correlation network to improve the identification effectiveness. Secondly, a weighted H-index is proposed, aiming at the disadvantages of the classic H-index only suited for unweighted networks. The improved indicator is applied in the second-level correlation network to identify the vulnerable lines of the power grid. The proposed method is verified in the IEEE-39 bus system and a real-life regional power grid in China. The experimental results show that the proposed method has higher precision compared with other methods. Specifically, the identification accuracy is improved by at least 8.33% than existing methods in the IEEE-39 bus system. In addition, the weighted H-index has higher discrimination and robustness than the classic H-index.

Background: The anti-tumor properties of Alpinia oxyphylla Miquel (A. oxyphylla) extracts and their petroleum ether (PE) fractions have long attracted scientific attention. These extracts’ anti-tumor activity and mechanisms in vivo are still unclear. This study was designed to investigate the anti-tumor activity and the underlying mechanism of PE’s effect on hepatocellular carcinoma (HCC) in vitro and in vivo. Materials and method: The anti-tumor activity of PE was evaluated by MTT assay and xenograft study. Mechanistic studies of PE were analyzed by Hoechst 33342 staining, Annexin V-FITC/PI double-staining assay, immunohistochemical staining and western blot assay. The toxicity of the PE treatment was verified by the levels of liver and kidney function in nude mice and the H&E staining of their liver and kidney tissues. Result: PE significantly inhibited the growth of HepG2, BEL-7402, SMMC-7721 and Hep3B cells in a concentration- and time-dependent manner. Specifically, PE inhibited the growth of Hep3B cells by inducing apoptosis. PE treatment at the doses of 0.25, 0.5 and 1 g/kg for 21 days caused a respective 35.7 percent, 49.3 percent and 58.8 percent inhibition of the tumor volume, and a 14.8 percent, 40.2 percent and 55.6 percent decrease in the tumor weight, respectively, as compared with the vehicle group in tumor-loaded mice in vivo. PE promoted the release of cytochrome c from mitochondria to cytosol in a concentration-dependent manner. The expression levels of BAX (p

Abstract Background Inflammatory micro-environment has been proposed to play a critical role in lung tumorigenesis. NLRP3 is known as an intracellular receptor involving inflammation and has been reported which is increasingly associated with tumor development, but the role in inflammation-driven lung cancer has not been fully clarified. In this study, we investigated whether lipopolysaccharide (LPS)-induced pulmonary inflammation could contribute to lung tumorigenesis induced by benzo(a)pyrene [B(a)p] in C57BL/6J mice and the role of NLRP3 in the pathogenesis. Methods NLRP3−/− mice and C57BL/6J mice (wide-type, WT) were instilled intratracheally with B(a)p (1 mg/mouse) once a week for 4 times [the week of the last time of B(a)p treatment named Week 0], and mice were then instilled intratracheally with LPS at Week 3, 2.5 μg/mouse, once every three weeks for 5 times. At Week 30, the incidence, number, size and histopathology of lung tumor were analyzed. Results Mice exposed to B(a)p or B(a)p plus LPS could induce lung tumors, whereas LPS or vehicles treatment could not induce lung tumorigenesis. In WT mice, B(a)p plus LPS exposure significantly increased tumor incidence, mean tumor count and tumor size of visible tumors of lungs compared with B(a)p treatment alone, and NLRP3 deletion inhibited lung tumorigenesis induced by B(a)p or B(a)p plus LPS. Histopathological examination found LPS-induced pulmonary inflammatory changes enhanced lung tumorigenesis induced by B(a)p in WT mice, deletion of NLRP3 improved the inflammatory changes induced by LPS and the number and size of pathological tumor nests induced by B(a)p or B(a)p plus LPS. In addition, we found B(a)p treatment and B(a)p plus LPS treatment predominately induced the development of adenoma. Conclusion LPS enhanced B(a)p-induced lung tumorigenesis in WT and NLRP3−/− mice of C57BL/6J strain, and NLRP3 deletion inhibits lung tumorigenesis induced by B(a)p or B(a)p plus LPS.

In the present work, the ultrafine-grained W-25 wt.%Cu composites doped with multi-walled carbon nanotubes (CNTs) have been prepared through combined processes of high-energy ball-milling, liquid-phase sintering and infiltration. Furthermore, the microstructure, hardness and electrical conductivity of the ultrafine-grained W-Cu composites doped with different contents of CNTs were investigated. Meanwhile, the wear resistance, compressive performance at different temperatures and arc erosion resistance were evaluated in comparison with the W-Cu composite without CNTs. The results revealed that the hardness, wear resistance, compressive performance and arc erosion resistance of the W-Cu composites doped with CNTs were enhanced dramatically due to the introduction of tungsten carbide phases after sintering and infiltration. Keywords: W-Cu composite, CNTs, Tungsten carbide, Wear resistance, Compressive performance

Traumatic brain injury (TBI) is a common neurological disease. Netrin-1 and deleted in colorectal cancer (DCC) receptor are potential biomarkers associated with nerve regeneration and immune regulation. We aimed to investigate the ability of the DCC receptor and Netrin-1 to predict a high ICP level after operation in severe traumatic brain injury and their prognostic significance. This study is a prospective observational study. We selected 23 patients with traumatic brain injury who had undergone surgical operations as subjects. Immunohistochemical staining was performed on the contusion tissue that was removed by the operation to determine the expression of DCC receptor. At the same time, enzyme-linked immunosorbent assay (ELISA) kits were used to detect the serum Netrin-1 content. Determination of intracranial pressure (ICP) value was measured by intraventricular catheter. The Glasgow Outcome Scale (GOS) score at six months after trauma was defined as the main study endpoint. The results showed that serum Netrin-1 concentrations of patients in the critical TBI group (GCS 3–5 points) was significantly lower than that in the severe TBI group (GCS 6–8 points). The ICP peak and average mannitol consumption in the high Netrin-1 group were significantly lower than those in the low Netrin-1 group. DCC receptor-positive patients had a significantly lower ICP peak. There was no significant difference in six month-GOS scores between patients in the high and low Netrin-1 groups, while DCC receptor concentrations below 3.82 ng/mL predicted poor prognosis (GOS 1–3 points). In conclusion, the expression level of the DCC receptor can better evaluate the postoperative high ICP level and prognosis than the level of serum Netrin-1 in severe traumatic brain injury.

Objective: To explore the influence by not performing an oral glucose tolerance test (OGTT) in Han Chinese over 40 years. Design: Overall, 6682 participants were included in the prospective cohort study and were followed up for 3 years. Methods: Fasting plasma glucose (FPG), 2-h post-load plasma glucose (2h-PG), FPG and 2h-PG (OGTT), and HbA1c testing using World Health Organization (WHO) or American Diabetes Association (ADA) criteria were employed for strategy analysis. Results: The prevalence of diabetes is 12.4% (95% CI: 11.6–13.3), while the prevalence of prediabetes is 34.1% (95% CI: 32.9–35.3) and 56.5% (95% CI: 55.2–57.8) using WHO and ADA criteria, respectively. 2h-PG determined more diabetes individuals than FPG and HbA1c. The testing cost per true positive case of OGTT is close to FPG and less than 2h-PG or HbA1c. FPG, 2h-PG and HbA1c strategies would increase costs from complications for false-positive (FP) or false-negative (FN) results compared with OGTT. Moreover, the least individuals identified as normal by OGTT at baseline developed (pre)diabetes, and the most prediabetes individuals identified by HbA1c or FPG using ADA criteria developed diabetes. Conclusions: The prevalence of isolated impaired glucose tolerance and isolated 2-h post-load diabetes were high, and the majority of individuals with (pre)diabetes were undetected in Chinese Han population. Not performing an OGTT results in underdiagnosis, inadequate developing risk assessment and probable cost increases of (pre)diabetes in Han Chinese over 40 years and great consideration should be given to OGTT in detecting (pre)diabetes in this population. Further population-based prospective cohort study of longer-term effects is necessary to investigate the risk assessment and cost of (pre)diabetes.

The global spread of the novel coronavirus SARS-CoV-2 urgently requires discovery of effective therapeutics for the treatment of COVID-19. The spike (S) protein of SARS-CoV-2 plays a key role in receptor recognition, virus-cell membrane fusion and virus entry. Our previous studies have reported that 3-hydroxyphthalic anhydride-modified chicken ovalbumin (HP-OVA) serves as a viral entry inhibitor to prevent several kinds of virus infection. Here, our results reveal that HP-OVA can effectively inhibit SARS-CoV-2 replication and S protein-mediated cell-cell fusion in a dose-dependent manner without obvious cytopathic effects. Further analysis suggests that HP-OVA can bind to both the S protein of SARS-CoV-2 and host angiotensin-converting enzyme 2 (ACE2), the functional receptor of SARS-CoV-2, and disrupt the S protein-ACE2 interaction, thereby exhibiting inhibitory activity against SARS-CoV-2 infection. In summary, our findings suggest that HP-OVA can serve as a potential therapeutic agent for the treatment of deadly COVID-19.

Coal is the primary source of energy in China’s energy structure system. With the large-scale mining of mineral resources, a large amount of mine water will be produced in the process of development, construction, and production, which will pollute and damage the ecological environment of mine water. At present, China vigorously advocates coal revolution, implements low-carbon economy, and carries out clean production of energy development and utilization. Green mining, precision mining, and other strategic ideas have been applied to mine development to guide production practice. This paper does an in-depth analysis of the physical, chemical, biological, and environmental characteristics of mine water, puts forward the basic classification of mine water, and points out the characteristics of environmental hazards of mine water. Aiming at different types of mine water, such as mine wastewater, drainage water, goaf water, mine water with suspended solids, high salinity mine water, acid mine water, and mine water with special pollution, the paper puts forward the mine water treatment and resource utilization technology with different characteristics and strong pertinence. On this basis, the comprehensive treatment and development direction of mine water in the future are prospected.

The linker of nucleoskeleton and cytoskeleton (LINC) complex is responsible for tethering the nucleus to the cytoskeleton, providing a pathway for the cell’s nucleus to sense mechanical signals from the environment. Recently, we explored the role of the LINC complex in the development of glandular epithelial acini, such as those found in kidneys, breasts, and other organs. Acini developed with disrupted LINC complexes exhibited a loss of structural integrity, including filling of the lumen structures. As part of our investigation, we performed a mechanical indentation assay of LINC disrupted and undisrupted MDCK II cells using a micro-indentation instrument mounted above a laser-scanning confocal microscope. Through a combination of force measurements acquired from the micro-indentation instrument and contact area measurements taken from fluorescence images, we determined the average contact pressure at which the acini structure ruptured. Here, we provide a detailed description of the design of the micro-indentation instrument, as well as the experimental steps developed to perform these bio-indentation measurements. Furthermore, we discuss the data analysis steps necessary to determine the rupture pressure of the acini structures. While this protocol is focused on the indentation of individual glandular acini, the methods presented here can be adapted to perform a variety of mechanical indentation experiments for both 2D and 3D biological systems.

Objective To investigate the relationship between thyroid stimulating hormone (TSH) concentration and the risks of developing metabolic syndrome and its components. Methods A total of 10,140 residents of the Yunyan district of Guiyang (Guizhou, China) who were ≥40 years old were selected by cluster random sampling between May and August 2011, of whom 5692 were eligible. TSH concentration and indices of metabolic syndrome were documented at baseline and 3 years later. Participants were allocated to a euthyroid (TSH 0.55–4.78 mIU/L) or high TSH concentration (TSH >4.78 mIU/L) group. Patients with overt hypothyroidism or were undergoing treatment for hypothyroidism were excluded. Results The crude and adjusted prevalences of metabolic syndrome were 39.9% and 33.9% in the euthyroid group and 44.3% and 37.5% in the high TSH group, respectively. Binary logistic regression analysis revealed a positive correlation between a high TSH concentration at baseline and the cumulative incidence of metabolic syndrome during follow up. Conclusions High TSH is associated with a higher risk of developing metabolic syndrome or one of its components; therefore, people with a high TSH concentration should be screened regularly to permit the early identification of metabolic syndrome and followed up thoroughly.

Immune checkpoint inhibitors (ICIs) have shown potential to improve the prognosis of patients with brain metastasis (BM) caused by advanced cancers. However, controversies still exist in regard to its survival benefits. In the present work, a time series-based meta-analysis based on the phase I/II/III trials and observational studies were performed to investigate the differences in mortality of ICI-treated BM patients. A number of public library databases, including MEDLINE, EMBASE, OVID, and COCHRANE, were systemically searched by March 2019. The quality of included studies was evaluated by the Newcastle-Ottawa Scale (NOS) scoring. Outcome measures here established were mortality and progression-free survival (PFS) at different follow-up endpoints. Survival rates and curve data were pooled for further analysis. To detect the data heterogeneity, subgroup analyses were conducted according to tumor and ICI types. Eighteen studies, 6 trials, and 12 controlled cohorts were assessed, involving a total of 1330 ICI-treated BM patients. The 6-month survival rate and PFS were 0.67 (95%CI: 0.59–0.74) and 0.36 (95%CI: 0.24–0.49), respectively. According to the tumor type (melanoma, NSCLC, and RCC), subgroup analyses indicated that melanoma presented the lowest survival rates among the three groups here selected. In regard to the type of ICIs, the anti-CTLA-4 combined with the anti-PD-1/PD-L1 showed the best survival outcome among these groups. The 12-month survival rate and PFS showed a consistent pattern of findings. In the long-term, the 24-month survival rate and PFS were 0.20 (95%CI: 0.12–0.31) and 0.18 (0.05–0.46) in BM patients. Hence, ICI therapy may be associated with an improved prognosis of BM patients. Nevertheless, current research presented a limited study design. Multicenter randomized trials may later assist in validating ICI-based therapies for a better outcome of BM patients.

In this study, the W (10–20%)–Cu composites were simultaneously fabricated using commercial, graded commercial, and graded jet-milled W powder. The results show that the W–Cu composites prepared with the graded jet-milled W powders have the highest density and best comprehensive performance due to the combined effect of the particle gradation and jet-milling treatment. Particle gradation is employed to increase the packing density of powders, thereby increasing the relative density of the compressed W skeleton, and the rounded powder with narrow particle size distribution after jet-milling treatment is used to reduce the enclosed pores formed during the process of compacting and infiltration. W–Cu composites with a high density of 16.25 g/cm3 can be directly obtained by conventional compacting at a low pressure of 300 MPa and following infiltration.

Au–Pt–Sn alloys are a novel class of materials with promising catalytic properties. This study provides updated information on phase equilibrium structures and thermodynamics of the Au–Pt–Sn ternary system. The formation enthalpies of Au–Sn and Pt–Sn binary subsystems were predicted by first principles calculations and these values were further refined by CALPHAD method. The results obtained accurately reproduced the experimental data. The reassessed phase diagram of the Au–Pt–Sn ternary system accurately described the phase composition of several Au–Pt–Sn alloys, which is essential for further modifications of these materials.

Coal is the main energy source in China, and coal chemistry wastewater treatment has always been a research hotspot. For the large amount of concentrated organic wastewater, high cost caused by complex treatment process is the key issue. In this paper, the fixed bed Lurgi gasifier wastewater coupled with solid oxide cells (SOCs) system is employed for its treatment. Based on Aspen Plus software, the purified methane from marsh gas is sent to solid oxide fuel cell (SOFC) for electricity generation. While carbon dioxide separated from biogas purification and acid gas removal enters solid oxide electrolysis cell (SOEC) to produce syngas by co-electrolysis with steam.The simulation results show that the efficiency of SOFC is 48.5 %. The generated electric energy can be used for auxiliary equipment in wastewater treatment and SOEC to produce syngas, recycling of carbon dioxide. SOEC with wind power of 12.84 MW is enough to treat the waste gas generated by the 1,100 t/h Lurgi gasification wastewater treatment process. Economically, the cost of producing syngas, with high purity and fewer contaminant contents, is about 0.126 $/Nm3. It can be used to produce various chemicals, so as to further improve the economic benefit of wastewater treatment.

Purpose: The expressions of antibodies against thyroid peroxidase (TPOAb) and thyroglobulin (TgAb) are very common in the sera of patients with autoimmune thyroid diseases (AITD). The relationship between thyroid autoantibodies and the occurrence of glucose and lipid metabolic disorders remains unclear. This study was performed to investigate the correlation between the presence of serum TPOAb/TgAb and those metabolic disorders in euthyroid general population.Methods: The data of this study were derived from the Thyroid Disease, Iodine status, and Diabetes National epidemiological (TIDE) survey from all 31 provinces of mainland China. A total of 17,964 euthyroid subjects including 5,802 males (4,000 with TPOAb−TgAb− and 1,802 with TPOAb+/TgAb+) and 12,162 females (8,000 with TPOAb−TgAb− and 4,162 with TPOAb+/TgAb+) were enrolled in this study. The blood glucose and lipid levels were compared between individuals with TPOAb−TgAb− and those with TPOAb+TgAb−, TPOAb−TgAb+, TPOAb+TgAb+.Results: Both fasting blood glucose (FBG) concentration and the proportion of individuals with impaired FBG (IFG) showed the decreased trends in TPOAb−TgAb+ males as compared with TPOAb−TgAb− men. There were significantly lower FBG and higher HDL-C levels as well as tendencies toward decreased incidences of IGT and hypertriglyceridemia in TPOAb−TgAb+ females when compared with TPOAb−TgAb− women. Binary logistic regression analysis further showed that serum TgAb single positivity in males was an independent protective factor for IFG with an OR of 0.691 (95% CI, 0.503–0.949). For females, serum TgAb single positivity was an independent protective factor for hypertriglyceridemia with an OR of 0.859 (95% CI, 0.748–0.987). Trend test showed that with the increase of serum TgAb level, there were significant decreases in the prevalence of IFG among the men with TSH ≤ 2.5 mIU/L and that of hypertriglyceridemia in the women, especially among non-obese females.Conclusion: Serum TgAb single positivity may imply a reduced risk of IFG in euthyroid men and that of hypertriglyceridemia in euthyroid women. The mechanisms for the independent protective roles of TgAb await further investigation.

A simple, rapid, and sensitive liquid chromatography (LC)/mass spectrometry (MS) method was established and validated for simultaneous quantitation of pyrazinamide, isoniazid, rifampicin, and ethambutol in human blood sample. Samples were pretreated by a single-step precipitation with acetonitrile. Chromatographic separation was achieved on XSelecT HSS T3 column by gradient elution with a total run time of 5.0 min. MS detection was performed by a triple quadrupole tandem mass spectrometer in the multiple reaction monitoring mode with a positive electrospray ionization source. Isotope-labeled internal standard, especially rifampicin-D8, was applied to adjust for the loss during sample treatment. The established LC-MS/MS method showed a wide analytical range (pyrazinamide: 1.02∼60.0 μg/mL, isoniazid: 0.152∼10.0 μg/mL, rifampicin: 0.500∼30.0 μg/mL, and ethambutol: 0.0998∼5.99 μg/mL) and a good linearity (r > 0.99 for the four analytes) with acceptable accuracy and precision (90.15%∼104.62% and 94.00%∼104.02% for intra- and interaccuracy, respectively; RSD%:

Abstract Background Previous studies have shown that patients with mental illnesses such as schizophrenia have a higher risk for syphilis infection. However, the clinical characteristics of psychotic patients who are infected with syphilis remain unknown. The aim of this study was to investigate the prevalence of syphilis in psychotic patients in Xiamen and to compare the social function and serum biochemical markers between schizophrenia patients with and without syphilis. Methods There were a total of 1586 psychotic patients screened for syphilis from May 2016 to August 2017 in Xiamen Mental Health Center. We retrospectively studied 87 schizophrenia patients in this study. The NOSIE-30 score and serum biochemical markers were analyzed for all schizophrenia patients. Results The seroprevalence of syphilis was 3.3% (52/1586) in our study. Schizophrenia patients infected with syphilis (SCZ-S) showed a higher irritability score compared with patients without syphilis (SCZ-C) (p

In this study, we mainly aimed at developing the Ifosfamide-loaded-lipid-core nanocapsules (IFS-LNC) to increase the therapeutic efficacy in osteosarcoma. The nanoparticle was prepared and evaluated in terms of physical, chemical and biological parameters. The lipid-core-nanocapsules were nanosized with narrow particle size distribution and exhibited a high loading capacity. The LNC displayed a sustained release profile of the drug suggesting its potential application in biomedical field and prolonged anticancer therapy. The LNC showed an endocytosis-mediated cellular uptake in MG63 cancer cells which may lead to an accelerated disruption of the acidic endolysosomal vesicles with release of IFS into the cytoplasm. Specifically, IFS-LNC exhibited a significantly higher cytotoxicity than free IFS used at the same concentration. The indiscriminate ability of the drug-loaded formulation increased the apoptosis of cancer cells by increasing the expression levels of caspase-3 and caspase-9 in MG63 cells. Overall, nanoparticulate formulations of Ifosfamide enhanced the therapeutic efficacy in osteosarcoma. Keywords: Osteosarcoma, Nanocapsules, Ifosfamide, Apoptosis, Chemotherapy

Abstract Background Over the last two or three decades, the pace of development of treatments for osteosarcoma tends has been slow. Novel effective therapies for osteosarcoma are still lacking. Previously, we reported that tumor-suppressing STF cDNA 3 (TSSC3) functions as an imprinted tumor suppressor gene in osteosarcoma; however, the underlying mechanism by which TSSC3 suppresses the tumorigenesis and metastasis remain unclear. Methods We investigated the dynamic expression patterns of TSSC3 and autophagy-related proteins (autophagy related 5 (ATG5) and P62) in 33 human benign bone tumors and 58 osteosarcoma tissues using immunohistochemistry. We further investigated the correlations between TSSC3 and autophagy in osteosarcoma using western blotting and transmission electronic microscopy. CCK-8, Edu, and clone formation assays; wound healing and Transwell assays; PCR; immunohistochemistry; immunofluorescence; and western blotting were used to investigated the responses in TSSC3-overexpressing osteosarcoma cell lines, and in xenografts and metastasis in vivo models, with or without autophagy deficiency caused by chloroquine or ATG5 silencing. Results We found that ATG5 expression correlated positively with TSSC3 expression in human osteosarcoma tissues. We demonstrated that TSSC3 was an independent prognostic marker for overall survival in osteosarcoma, and positive ATG5 expression associated with positive TSSC3 expression suggested a favorable prognosis for patients. Then, we showed that TSSC3 overexpression enhanced autophagy via inactivating the Src-mediated PI3K/Akt/mTOR pathway in osteosarcoma. Further results suggested autophagy contributed to TSSC3-induced suppression of tumorigenesis and metastasis in osteosarcoma in vitro and in vivo models. Conclusions Our findings highlighted, for the first time, the importance of autophagy as an underlying mechanism in TSSC3-induced antitumor effects in osteosarcoma. We also revealed that TSSC3-associated positive ATG5 expression might be a potential predictor of favorable prognosis in patients with osteosarcoma.

PM machine or Permanent magnet synchronous motor (PMSM) is a nonlinear system with multivariable couplings. To achieve the sensorless control of a PMSM with high inertial load, a modified current observer, using PI regulator instead of sliding mode switching function, is proposed in this paper. The modified current observer can solve the chattering and phase delay problem while still maintaining the robust advantages of sliding mode system in position estimation. In addition, a new phase-locked loop (PLL) based angle switching strategy is designed to ensure the motor can smoothly switch from I-F control to closed-loop sensorless vector control in startup stage with a high inertial load. The simulation and experimental results show that the control system of PMSM with proposed ideas has fast response speed, accurate rotor position estimation, stable state switching and good system robustness under high inertia load.

Insulin-like growth factor 1 (IGF-1) is a potential nutrient for nerve repair. However, it is impractical as a therapy because of its limited half-life, rapid clearance, and limited target specificity. To achieve targeted and long-lasting treatment, we investigated the addition of a binding structure by fusing a collagen-binding domain to IGF-1. After confirming its affinity for collagen, the biological activity of this construct was examined by measuring cell proliferation after transfection into PC12 and Schwann cells using a 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide assay. Immunofluorescence staining was conducted to detect neurofilament and microtubule-associated protein 2 expression, while real time-polymerase chain reaction was utilized to determine IGF-1 receptor and nerve growth factor mRNA expression. Our results demonstrate a significant increase in collagen-binding activity of the recombinant protein compared with IGF-1. Moreover, the recombinant protein promoted proliferation of PC12 and Schwann cells, and increased the expression of neurofilament and microtubule-associated protein 2. Importantly, the recombinant protein also stimulated sustained expression of IGF-1 receptor and nerve growth factor mRNA for days. These results show that the recombinant protein achieved the goal of targeting and long-lasting treatment, and thus could become a clinically used factor for promoting nerve regeneration with a prolonged therapeutic effect.

A balanced bandpass filter with high common‐mode (CM) suppression using isosceles right‐angled triangular (RAT) resonator is proposed in this Letter. The two high order orthogonal modes (TM210Z and TM200Z) are generated in the two overlapped isosceles RAT resonators under differential‐mode (DM) and CM excitation, respectively. In this structure, TM210Z mode will be transmitted and TM200Z mode will be blocked. Furthermore, four via‐holes are introduced to disturb TM210Z mode while TM200Z mode is unaffected, in order to shift the DM passband to the position of CM suppression. The designed balanced bandpass filter operating at 6.12 GHz with 3 dB fractional bandwidth of 5% is fabricated and measured. The measured and simulated results match very well with each other validating the feasibility of the proposed design concept.

Antarctic geothermal heat flux is a basic input variable for ice sheet dynamics simulation. It greatly affects the temperature and mechanical properties at the bottom of the ice sheet, influencing sliding, melting, and internal deformation. Due to the fact that the Antarctica is covered by a thick ice sheet, direct measurements of heat flux are very limited. This study was carried out to estimate the regional heat flux in the Antarctic continent through geophysical inversion. Princess Elizabeth Land, East Antarctica is one of the areas in which we have a weak understanding of geothermal heat flux. Through the latest airborne geomagnetic data, we inverted the Curie depth, obtaining the heat flux of bedrock based on the one-dimensional steady-state heat conduction equation. The results indicated that the Curie depth of the Princess Elizabeth Land is shallower than previously estimated, and the heat flux is consequently higher. Thus, the contribution of subglacial heat flux to the melting at the bottom of the ice sheet is likely greater than previously expected in this region. It further provides research clues for the formation of the developed subglacial water system in Princess Elizabeth Land.

Intracellular nicotinamide phosphoribosyltransferase (iNAMPT) is the rate-limiting enzyme of the mammalian NAD+ biosynthesis salvage pathway. Using inducible and conditional knockout (cKO) mice, we show that Nampt gene deletion in adult projection neurons leads to a progressive loss of body weight, hypothermia, motor neuron (MN) degeneration, motor function deficits, paralysis, and death. Nampt deletion causes mitochondrial dysfunction, muscle fiber type conversion, and atrophy, as well as defective synaptic function at neuromuscular junctions (NMJs). When treated with nicotinamide mononucleotide (NMN), Nampt cKO mice exhibit reduced motor function deficits and prolonged lifespan. iNAMPT protein levels are significantly reduced in the spinal cord of amyotrophic lateral sclerosis (ALS) patients, indicating the involvement of NAMPT in ALS pathology. Our findings reveal that neuronal NAMPT plays an essential role in mitochondrial bioenergetics, motor function, and survival. Our study suggests that the NAMPT-mediated NAD+ biosynthesis pathway is a potential therapeutic target for degenerative MN diseases.

Abstract Jumonji (JmjC) domain proteins influence gene expression and chromatin organization by way of histone demethylation, which provides a means to regulate the activity of genes across the genome. JmjC proteins have been associated with many human diseases including various cancers, developmental and neurological disorders, however, the shared biology and possible common contribution to organismal development and tissue homeostasis of all JmjC proteins remains unclear. Here, we systematically tested the function of all 13 Drosophila JmjC genes. Generation of molecularly defined null mutants revealed that loss of 8 out of 13 JmjC genes modify position effect variegation (PEV) phenotypes, consistent with their ascribed role in regulating chromatin organization. However, most JmjC genes do not critically regulate development, as 10 members are viable and fertile with no obvious developmental defects. Rather, we find that different JmjC mutants specifically alter the phenotypic outcomes in various sensitized genetic backgrounds. Our data demonstrate that, rather than controlling essential gene expression programs, Drosophila JmjC proteins generally act to “fine-tune” different biological processes.

Cellular fusion is essential for skeletal muscle development. Here the authors identify Minion as a microprotein required for myoblast fusion and skeletal muscle formation, and show that co-expression of Minion and Myomaker is sufficient to induce cytoskeletal rearrangement and cell fusion even in non-muscle cells.

To investigate whether probiotic supplementation could reduce the risk of fungal infection in preterm neonates in neonatal intensive care units (NICUs), we systematically searched PubMed, EMBASE, and the Cochrane Central Register of Controlled Trials databases for randomized controlled trials (RCTs) focusing on the effect of probiotics on fungal infection in preterm neonates. The outcomes of interest were Candida colonization and invasive fungal sepsis. Seven trials involving 1371 preterm neonates were included. Meta-analysis (fixed-effects model) showed that probiotic supplementation was significantly associated with a lower risk of Candida colonization (2 RCTs, n = 329; relative risk (RR), 0.43; 95% confidence interval (CI), 0.27–0.67; p = 0.0002; I2 = 0%), and invasive fungal sepsis (7 RCTs, n = 1371; RR, 0.64; 95% CI, 0.46–0.88; p = 0.006; I2 = 13%). After excluding one study with a high baseline incidence (75%) of fungal sepsis, the effect of probiotics on invasive fungal sepsis became statistically insignificant (RR, 0.88; 95% CI, 0.44–1.78; p = 0.72; I2 = 15%). When using the random-effects model, the effect of probiotics remained favorable for Candida colonization (RR, 0.43; 95% CI 0.27–0.68; p = 0.0002; I2 = 0%) but not for fungal sepsis (RR, 0.64; 95% CI 0.38–1.08; p = 0.10; I2 = 13%). Current evidence indicates that probiotics can reduce the risk of Candida colonization in preterm neonates in NICUs. Limited data support that probiotic supplementation prevents invasive fungal sepsis in preterm neonates. High-quality and adequately powered RCTs are warranted.

Background/Aims: Atherosclerosis is a multifactorial chronic disease and is the main cause of death and impairment in the world. Endothelial injury and apoptosis play a crucial role in the onset and development of atherosclerosis. MicroRNAs (miRNAs) have been proven to be involved in the pathogenesis of atherosclerosis. However, studies of the functional role of apoptosis-related miRNAs in the endothelium during atherogenesis are limited. Methods: Cell injury and apoptosis were measured in five types of cells transfected with miR-1185 or co-transfected with miR-1185 and its inhibitor. Bioinformatics analysis and a luciferase reporter assay were used to confirm the targets of miR-1185. The effects of the targets of miR-1185 on endothelial apoptosis were determined using small-interfering RNA. Results: In this study, we first report that miR-1185 significantly promoted apoptosis in endothelial cells but not in vascular smooth muscle cells and macrophages. A mechanistic analysis showed that ultraviolet irradiation resistance-associated gene (UVRAG) and krev1 interaction trapped gene 1 (KRIT1), targets of miR-1185, mediated miR-1185-induced endothelial cell apoptosis. Conclusion: The results revealed the impact of miR-1185 on endothelial apoptosis, suggesting that miR-1185 may be a potential target for the prevention and treatment of atherosclerosis.

Background/Aims: Atherosclerosis is the primary cause of cardiovascular ischaemic events; arterial stiffness is a characteristic of the atherosclerotic process. MicroRNAs (miRNAs) have been revealed as crucial modulators of atherosclerosis. However, the role of arterial stiffness-related miRNAs in the atherosclerotic process is still unclear. Methods: Four hundred six participants from Northern China were enrolled in this study. Circulating miR-1185 and adhesion molecule levels were measured. Multiple linear regression models were used to evaluate the association of miR-1185 levels with brachial-ankle pulse wave velocity (baPWV) and adhesion molecule levels. A mediation analysis was also performed to examine the mediating effect. Cell adhesion molecule levels were measured in primary human umbilical vein endothelial cells (pHUVECs) and human umbilical vein smooth cells (HUVSMCs) transfected with miR-1185 or co-transfected with a miR-1185 inhibitor. Results: miR-1185 was independently correlated with arterial stiffness. A positive relationship between miR-1185 and vascular cell adhesion molecule-1 (VCAM-1) and E-selectin levels was observed. VCAM- 1 and E-selectin partially mediated the correlation between miR-1185 and arterial stiffness. miR-1185 induced a significant increase in the VCAM-1 and E-selectin levels in pHUVECs and HUVSMCs in vitro. According to our mechanistic analysis, VCAM-1 and E-selectin mediated miR-1185-induced arterial stiffening. Conclusions: miR-1185 modulated the expression of VCAM-1 and E-selectin to promote arterial stiffening, suggesting that miR-1185 plays a crucial role in the development of atherosclerosis and may serve as a novel therapeutic target for atherosclerosis.

Extreme meteorological disaster effects on grain production is mainly determined by the interaction between danger degree of hazard-induced factors and vulnerability degree of hazard-affected bodies. This paper treats physical exposure, sensitivity of the response to the impact, and capabilities of disaster prevention and mitigation as a complex system for vulnerability degree of hazard-affected bodies, which included the external shocks and internal stability mechanism. Hazard-induced factors generate external shocks on grain production systems though exposure and sensitivity of hazard-affected body, and the result can be represented as affected area of grain. By quantile regression model, this paper depicts the quantitative relationship between hazard-induced factors of extreme meteorological disaster and the affected area in the tail of the distribution. Moreover, the model of production function have also been utilized to expound and prove the quantitative relationship between the affected area and final grain output under the internal stability mechanism of the agricultural natural resources endowment, the input factors of agricultural production, and the capacity of defending disaster. The empirical study of this paper finds that impact effects of drought disaster to grain production system presents the basic law of “diminishing marginal loss”, namely, with the constant improvement of the grade of drought, marginal affected area produced by hazard-induced factors will be diminishing. Scenario simulation of extreme drought impact shows that by every 1% reduction in summer average rainfall, grain production of Jilin Province will fell 0.2549% and cut production of grain 14.69% eventually. In response to ensure China's grain security, the construction of the long-term mechanism of agricultural disaster prevention and mitigation, and the innovation of agricultural risk management tools should be also included in the agricultural policy agenda.

In this paper, we propose a new hotspot ranking-based indoor mapping and mobility analysis approach based on the sporadically collected crowdsourced Wi-Fi received signal strength (RSS) data. This approach aims to construct the indoor mapping, as well as achieve the mobility analysis of the users following their daily motion patterns in target environment. First, we perform the wavelet analysis with respect to each RSS sequence to mitigate the noise interference to some extent. Second, we develop a new multidimensional scaling approach to map each RSS data into a linear one in the 2-D signal space, which is followed by the density clustering approach to merge the linear ones into different clusters based on the spatial correlation property. Finally, we construct the indoor mapping from the signal into physical spaces by the concept of hotspot ranking order, as well as the transfer relations among different RSS clusters and different physical sub-areas. The experimental results demonstrate that the proposed approach can achieve the superior performance in terms of indoor mapping and mobility analysis in an unknown indoor environment.

β-site amyloid precursor protein cleaving enzyme 1 (BACE1) is the rate-limiting enzyme in the formation of β-amyloid peptides (Aβ), which are important in the development of Alzheimer's disease. It has been demonstrated that albiflorin can alleviate Aβ aggregation. However, the mechanism behind this effect is unknown. In our previous work, albiflorin and its four analogues were isolated from Paeonia lactiflora Pall. This study aims to investigate the relationship of these four compounds with BACE1. Our results show that the albiflorin analogue 4-O-galloylalbiflorin (4-O-GA) had the strongest BACE1 inhibitory effect and was also selective for BACE1. Furthermore, docking study of BACE1 with these analogues yielded similar results, whereby 4-O-GA treatment caused the greatest decreases in both the generation of Aβ1–42 and Aβ1–40 and in the expression of BACE1 and HIF-1α. Our findings indicate that 4-O-GA exerted significant and selective inhibitory activities against BACE1, potentially providing a useful agent for developing BACE1 inhibitor drugs.

Objective: Explicating the property and action of traditional Chinese medicine (TCM) in the perspectives of modern science deepens the insight into the property of TCM, and provides the basis for new drug discovery and clinical therapy. In this study, we investigated the relationship between transient receptor potential melastatin 8 (TRPM8) and pungent flavor using three-dimensional pharmacophores based on virtual screening methods. Methods: Firstly, an inhouse database was established to identify the related pharmacological action according to the traditional Chinese herbs expressing an action of promoting blood circulation. Then, several therapeutic targets, 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMG-CoAR), cholesteryl ester transfer protein (CETP), Niemann-Pick C1-Like 1 (NPC1L1) and platelet-activating factor receptor (PAFR), were selected to screen traditional Chinese herbs, and the common virtual screening hits with various hit scores providing data to reveal the correlation among TRPM8 and therapeutic targets. Results: According to the screening results, TRPM8 agonists were able to identify the effective components of pungent herbs and TRPM8, which shares the common virtual screening hits with the therapeutic targets, was considered to be related to the action of pungent taste. Conclusion: The novel ideas and methods in this study are beneficial to unveil the scientific relationship between a TCM property and its action.

ObjectivesAlthough several studies have shown that cigarette smoking is associated with thyroid stimulating hormone (TSH), thyroid peroxidase antibody (TPOAb) and thyroglobulin antibody (TgAb), the exact relationship between smoking and thyroid function is controversial. As little is known about the effects of smoking on TSH, TPOAb and TgAb in Chinese residents. This study aimed to evaluate the association between cigarette smoking and TSH, TPOAb and TgAb in ten-city residents of China.Study designThis was a population-based cross-sectional study.MethodsIn this cross-sectional study, 15,181 subjects from ten major cities of China were investigated. Data regarding demographic characteristics, smoking status and consumption of iodine status were collected using in-person interviews based on a self-designed structured questionnaire. Serum concentrations of TSH, TPOAb and TgAb were measured using electrochemiluminescence immunoassays. Univariate analysis and multivariate linear stepwise regression analyses were used to analyze the data.ResultsThe regular smokers had lower concentrations of TSH, TPOAb and TgAb than occasional smokers, former smokers and never smokers. Multivariate analysis demonstrated that regular smoking was associated with the decreased concentrations of TSH (β = -0.178), TPOAb (β = -0.287) and TGAb (β = -0.453) after adjusting other factors. Furthermore, daily smoking number was significantly associated with the decreased level of TSH (β = -0.045) and TPOAb(β = -0.080), and smoking duration was associated with the decreased TSH level (β = -0.030).ConclusionsOur findings suggest that cigarette smoking is related to a significant decline in the concentrations of TSH, TPOAb and TgAb. In addition, daily smoking number and long-term smoking decrease serum TSH and TPOAb levels. Cigarette smoking plays a significant role in the development of thyroid dysfunction.

In this study, the effect of ionizing radiation on 8-hydroxy-2′-deoxyguanosine (8-OHdG) in human peripheral blood was investigated. Blood samples were collected from 230 radiation workers and 8 patients who underwent radiotherapy for population study. Blood samples from 2 healthy individuals were irradiated with different X-ray doses for in vitro experiment, and levels of 8-OHdG in serum and cell culture supernatants were assessed by enzyme-linked immunosorbent assay. Observations demonstrated the positive relationships between serum 8-OHdG level and radiation dose and working period were observed, and serum 8-OHdG levels were higher among interventional radiation workers than among other hospital radiation workers. In addition, 8-OHdG yields in supernatants increased, peaked at 3 Gy of radiation dose, and then decreased with further increases in radiation; the dose–response curve obtained fitted a polynomial function. By contrast, a similar trend was not found in radiotherapy patients. The present study suggests that 8-OHdG may be a useful biomarker reflecting oxidative damage among workers occupationally exposed to low-dose radiation.

Elevated free fatty acid (FFA) is a key risk factor for insulin resistance (IR). Our previous studies found that mangiferin could decrease serum FFA levels in obese rats induced by a high-fat diet. Our research was to determine the effects and mechanism of mangiferin on improving IR by regulating FFA metabolism in HepG2 and C2C12 cells. The model was used to quantify PA-induced lipid accumulation in the two cell lines treated with various concentrations of mangiferin simultaneously for 24 h. We found that mangiferin significantly increased insulin-stimulated glucose uptake, via phosphorylation of protein kinase B (P-AKT), glucose transporter 2 (GLUT2), and glucose transporter 4 (GLUT4) protein expressions, and markedly decreased glucose content, respectively, in HepG2 and C2C12 cells induced by PA. Mangiferin significantly increased FFA uptake and decreased intracellular FFA and triglyceride (TG) accumulations. The activity of the peroxisome proliferator-activated receptor α (PPARα) protein and its downstream proteins involved in fatty acid translocase (CD36) and carnitine palmitoyltransferase 1 (CPT1) and the fatty acid β-oxidation rate corresponding to FFA metabolism were also markedly increased by mangiferin in HepG2 and C2C12 cells. Furthermore, the effects were reversed by siRNA-mediated knockdown of PPARα. Mangiferin ameliorated IR by increasing the consumption of glucose and promoting the FFA oxidation via the PPARα pathway in HepG2 and C2C12 cells.

In the study, an expected revenue model was built for the farmers and insurance institutes in China, with the aim of researching the realization conditions of the target price insurance market equilibrium; analysing the reasons and consequences of the moral hazards; obtaining a paradox and elaborating the reason; measuring the moral hazard premium and researching positions, as well as the role of government in the target price premium; and also discussing the relationship between the target price and the cost price. The conclusions found were that the market risk was the major risk in agriculture; the target price insurance implementation relies on the government subsidy, which shall be equivalent to the sum of the farmers' moral hazard premium and social costs; the moral hazard premium has a negative externality; the insurance companies are also the beneficiaries of the farmers' moral hazard; and the best target price should be smaller than the total cost price of the agricultural products.

Objective: Lipid droplet (LD) deposition in adipose tissue is a critical factor leading to metabolic dysfunction. Various herbal medicines in traditional Chinese medicine (TCM) are used to treat hyperlipidemia, type 2 diabetes, obesity, and other diseases. The objective of this study was to identify potential anti-adipogenic agents from TCM herbal compounds. Methods: One hundred and twenty compounds were evaluated in terms of their effect on adipocyte differentiation through image-based high content screening. Anti-adipogenic effects of identified hits were further confirmed at various concentrations. In addition, drug-induced liver injury assay was performed with HepG2 cells to test the hepatotoxicity of hit compounds. Results: Berbamine (BBM), a chemical isolated from barberry, and a derivative of BBM, berbamine dihydrochloride (BBMD), reduced LDs formation by more than 50%. Dose-dependent effects were observed and the IC50 values of the two hits, BBM and BBMD, were determined as 1.88 μM and 0.95 μM, respectively. Moreover, BBM induced mild HepG2 cell injury, while its dihydrochloride—BBMD did not exhibit hepatotoxicity within 40 μM. Conclusion: This study demonstrates that BBMD may be a potential therapeutic candidate for disorders associated with elevated LDs accumulation.

UHRF1 is involved in the maintenance of DNA methylation, but the regulatory mechanism of this epigenetic regulator is unclear. Here, the authors show that it has a closed conformation and are able to make conclusions about the mechanism of recognition of epigenetic marks.

Purpose: Drug resistance has been recognized to be a major obstacle to the chemotherapy for osteosarcoma. And the potential importance of hypoxia as a target to reverse drug resistance in osteosarcoma has been indicated, though the mechanism underlining such role is not clarified. The present study aims to investigate the role of hypoxia in the drug resistance in osteosarcoma cells via activating AMP-activated protein kinase (AMPK) signaling. Experimental design: We investigated the promotion of the resistance to doxorubicin of osteosarcoma MG-63 and U2-os cells in vitro, and then determined the role of hypoxia-inducible factor-1 (HIF-1)α and HIF-1β, the activation and regulatory role of AMPK in the osteosarcoma U2-os cells which were treated with doxorubicin under hypoxia. Results: It was demonstrated that hypoxia significantly reduced the sensitivity of MG-63 and U2-os cells to doxorubicin, indicating an inhibited viability reduction and a reduced apoptosis promotion. And such reduced sensitivity was not associated with HIF-1α, though it was promoted by hypoxia in U2-os cells. Interestingly, the AMPK signaling was significantly promoted by hypoxia in the doxorubicin-treated U2-os cells, with a marked upregulation of phosphorylated AMPK (Thr 172) and phosphorylated acetyl-CoA carboxylase (ACC) (Ser 79), which were sensitive to the AMPK activator, AICAR and the AMPK inhibitor, Compound C. Moreover, the promoted AMPK activity by AICAR or the downregulated AMPK activity by Compound C significantly reduced or promoted the sensitivity of U2-os cells to doxorubicin. Conclusion: The present study confirmed the AMPK signaling activation in the doxorubicin-treated osteosarcoma cells, in response to hypoxia, and the chemical upregulation or downregulation of AMPK signaling reduced or increased the chemo-sensitivity of osteosarcoma U2-os cells in vitro. Our study implies that AMPK inhibition might be a effective strategy to sensitize osteocarcoma cells to chemotherapy.

In this paper, we proposed a novel information-based approach to precision analysis of indoor wireless local area network (WLAN) localization using location fingerprint. First of all, by using the Fisher information matrix (FIM), we derive the fundamental limit of WLAN fingerprint-based localization precision considering different signal distributions in characterizing the variation of received signal strengths (RSSs) in the target environment. After that, we explore the relationship between the localization precision and access point (AP) placement, which can provide valuable suggestions for the design of the highly-precise localization system. Second, we adopt the heuristic simulated annealing (SA) algorithm to optimize the AP locations for the sake of approaching the fundamental limit of localization precision. Finally, the extensive simulations and experiments are conducted in both regular line-of-sight (LOS) and irregular non-line-of-sight (NLOS) environments to demonstrate that the proposed approach can not only effectively improve the WLAN fingerprint-based localization precision, but also reduce the time overhead.