The sensitive interfacial interaction of liquid crystals (LC) holds potential for precision biosensors. In the past, the developments of LC biosensors were limited by the complicated manufacturing ...process, which hinders commercialization and wider applications of such devices. In this report, we demonstrate the first nano-structural polymeric stabilized-cholesteric LC (PSCLC) thin films to be a new label-free biosensing technology.
The transmission spectra of PSCLC devices were measured by the fiber-optic spectrometer with high-resolution. In addition, a smartphone was set on the stage, and the camera of smartphone was placed and aligned with a set of lenses embedded in the designed stage. To decrease the chromatic and spherical aberrations, an achromatic lens set composition, consisting of both dual-convex lens and concave-plane lens, was applied for measuring and imaging the PSCLC texture. The average and the estimated standard deviation (SD) were used to present quantitative experimental results. The test BSA was immobilized and fulfilled by the ceramic silicon-constructed DMOAP-coated glass in aqueous BSA solutions at 1 mg/mL, 1 µg/mL, and 1 ng/mL.
The fabrication process of PSCLC is much simplified compared to previous LC biosensors. The color of PSCLC biosensor altered with the BSA concentration, making detection result easy to read. The detection limit of 1 ng/mL is achieved for label-free PSCLC biosensor. The PSCLC biosensor was able to successfully detect due to the albumin concentration's alteration, with a linear range of 1 ng/mL-2 mg/mL. Thus, the label-free-proposed design-integrated nanoscale PSCLCs smartphone-based biosensor could successfully detect BSA in a preclinical urine sample.
Finally, we propose a design to integrate the PSCLC biosensor with a smartphone. The PSCLC owns potential for high performance, low cost for detecting various disease biomarkers in home use. Owing to its great potential for high performance and low cost, the PSCLC biosensors can be used as a label-free point-of-care for detecting various disease biomarkers for patients in care homes.
•The bulk-equivalent hardness values and their increments of tungsten irradiated with 200keV He+ at 800°C were investigated.•Vacancy like defects in tungsten induced by 200keV He+ at 800°C were ...investigated.•The irradiation induced hardening behavior in tungsten could be explained by the dispersed barrier hardening model.•The irradiation induced hardening in tungsten was consistent with the vacancy like defects.
The irradiation induced hardening and vacancy like defects are investigated as a function of irradiation fluences with 200keV He ion implantation at 800°C in this work. Nano-indentation tests show the irradiation induces hardening and the hardness values increase with increasing irradiation fluences. Doppler broadening spectroscopy analyses of slow positron annihilation find that a large amount of vacancy like defects are produced under irradiation. When the He/dpa ratio is less than about 2.2%He/dpa, the vacancy like defects include mainly empty vacancy clusters and loops, and HenVm complexes. When the He/dpa ratio is more than about 2.2%He/dpa, the vacancy like defects become mainly HenVm complexes with increasing irradiation fluences. Meanwhile, these complexes increase in size and He/V ratio while the irradiation fluences increase. Based on the Orowan hardening mechanism, we discuss the relationship between irradiation induced hardening and defects under indentation, especially the contribution of HenVm complexes to the hardening.
Classical swine fever (CSF) is one of the most epidemic viral diseases in swine industry. The causative pathogen is CSF virus (CSFV), a small enveloped RNA virus of Flaviviridae family. Claudin-1 was ...reported to be involved in the infections of a number of viruses, including many from Flaviviridae family, but no studies have investigated the role of porcine claudin-1 during CSFV infection in PK-15 cells. In this study, on the one hand, we demonstrated that CSFV infection reduced the claudin-1 expression at both mRNA and protein levels; on the other hand, CSFV infection was enhanced after claudin-1 knockdown, but inhibited by claudin-1 overexpression in a dose-dependent manner. Furthermore, negative correlation was demonstrated between the claudin-1 expression and CSFV titer. In conclusion, claudin-1 might be a barrier for CSFV infection in PK-15 cells, while CSFV bypasses the barrier through lysosome mediated degradation of claudin-1, which could be repressed by bafilomycin A1. Although the elaborate mechanisms how claudin-1 plays its roles in CSFV infection require further investigations, this study may advance our understanding of the molecular host–pathogen interaction mechanisms underlying CSFV infection and suggests enhancement of porcine claudin-1 as a potential preventive or therapeutic strategy for CSF control.
•Amino acid sequences of claudin-1 are conserved across the 14 selected mammalians.•CSFV infection in PK-15 cells induced lysosome mediated degradation of claudin-1.•Knockdown of claudin-1 enhanced CSFV infection.•Overexpression of claudin-1 inhibited CSFV infection.•Enhancement of claudin-1expression could be a potential therapeutic strategy for CSF control.
As a top ambient pollutant in urban area, fine particulate matter (PM2.5) has been associated with the occurrence and deterioration of many medical conditions, while limited studies have observed the ...association with psychiatric conditions. This study aimed to investigate the association between short-term PM2.5 exposure and psychiatric emergency events, and further explored the variation by age, sex and seasonal patterns, which have been suggested to be associated with both psychiatric risk and pollutant toxicity.
We used time-series analysis to investigate the association between short-term exposure of PM2.5 and emergency ambulance dispatches for psychiatric emergencies (EPE) (n = 158634) in Beijing, one of the top polluted cities in China during the study period between 2008 and 2014. Stratified analyses were conducted to examine the effects of age, sex and seasonal pattern.
Every 10 μg/m3 increase of the PM2.5 concentration was associated with a 0.12% increase of the same-day overall EPE (95% CI: 0.03–0.22%, p = 0.013) and a 0.12% increase of the suicide-related EPE at lag 2 (95%CI: 0.01–0.24%, p = 0.041). The associations remained when adjusted for sunlight duration. An age effect was observed where children (age <18) showed a higher risk of suicide-related EPE after PM2.5 exposure compared to adults (18 ≤ age≤64). We did not observe evidence of effect modification by sex and season based on the results of stratified analysis.
We found a positive association between acute PM2.5 exposure and increased psychiatric emergency presentations indicated by emergency ambulance dispatches data. Children were more vulnerable and might develop psychiatric problems including those leading to suicide. Public awareness of the health risks of PM2.5 is important to strengthen current efforts to reduce emissions.
•Increased PM2.5 is associated with increased number of ambulance dispatches for psychiatric emergencies.•Children showed a higher risk of suicide-related emergency associated with PM2.5 concentration compared to adults.•Intervention strategy should be developed to reduce PM2.5 level and exposure particularly in the younger population.
Tivantinib has been described as a highly selective inhibitor of MET and is currently in a phase III clinical trial for the treatment of hepatocellular carcinoma (HCC). However, the mechanism of ...tivantinib anti-tumor effect has been questioned by recent studies.
We show that tivantinib indiscriminately inhibited MET dependent and independent HCC cells proliferation. In contrast, other MET inhibitors, JNJ-38877605 and PHA-665752, just specifically inhibited the growth of MET dependent HCC cells. Tivantinib neither inhibit constitutive MET phosphorylation nor HGF-induced MET phosphorylation in HCC cells. In the microtubule polymerization analysis, tivantinib affected microtubule dynamics by a mechanism as a microtubule depolymerizer. Interesting, unlike other microtubule-targeting agents, paclitaxel and vincristine, tivantinib showed similar anti-proliferative activity in parental and multidrug-resistant cells. Further studies demonstrated that tivantinib induced a G2/M arrest and promoted apoptosis by both intrinsic and extrinsic pathway. The in vivo efficacy evaluation showed that tivantinib exhibited a good anti-tumor growth activity with anti-proliferative and pro-apoptotic effects.
The potent anti-tumor activity of tivantinib in HCC was achieved by targeting microtubule. Tivantinib treatment for patients with HCC should not be selected based on MET status.
We used colloidal Au to enhance the amount of antibody immobilized on a gold electrode and ultimately monitored the interaction of antigen–antibody by impedance measurement. Self-assembly of 6
nm ...(diameter) colloidal Au onto the self-assembled monolayers (SAMs) of 4-aminothiophenol modified gold electrode resulted in an easier attachment of antibody. The redox reactions of Fe(CN)
6
4−/Fe(CN)
6
3− on the gold surface were blocked due to the procedures of self-assembly of 4-aminothiophenol and antibody immobilization, which were investigated by cyclic voltammetry and impedance spectroscopy. The interaction of antigen with grafted antibody recognition layers was carried out by soaking the modified electrode into a phosphate buffer at pH 7.4 with various concentrations of antigen at 37
°C for 30
min. The antibody recognition layers and their interactions with various concentrations of antigen could be detected by measurements of the impedance change. The results show that this method has good correlation for detection of Hepatitis B virus surface antigen in the range of 0.5–200
μg/l and a detection limit of about 50
ng/l.
Disulfiram (DSF) is an FDA approved anti-alcoholism drug in use for more than 60 years. Recently, antitumor activity of the DSF/copper (DSF/Cu) complex has been identified. Its anti-multiple myeloma ...activity, however, has barely been investigated. In the present study, our results demonstrated that the DSF/Cu complex induced apoptosis of MM cells and MM primary cells. The results indicated that DSF/Cu significantly induced cell cycle arrest at the G2/M phase in MM.1S and RPMI8226 cells. Moreover, JC-1 and Western blot results showed that DSF/Cu disrupted mitochondrial membrane integrity and cleaved caspase-8 in MM cells, respectively, suggesting that it induced activation of extrinsic and intrinsic apoptosis pathways. Interestingly, DSF/Cu induced caspase-3 activation was partly blocked by Z-VAD-FMK (zVAD), a pan-caspase inhibitor, indicating at caspase-dependent and -independent paths involved in DSF/Cu induced myeloma cell apoptosis machinery. Additionally, activation of the c-Jun N-terminal kinase (JNK) signaling pathway was observed in DSF/Cu treated MM cells. More importantly, our results demonstrated that DSF/Cu significantly reduced tumor volumes and prolonged overall survival of MM bearing mice when compared with the controls. Taken together, our novel findings showed that DSF/Cu has potent anti-myeloma activity in vitro and in vivo highlighting valuable clinical potential of DSF/Cu in MM treatment.
•ITGB3 was identified as a RACK1 interacting protein.•Abrogation of ITGB3 inhibited PRRSV replication and NF-κB activation.•Overexpression of ITGB3 enhanced PRRSV replication and NF-κB ...activation.•Inhibition of ITGB3 alleviated cytopathic effects and reduced the viral titer.•RACK1 and ITGB3 are NF-κB target genes, while indirectly regulating each other.
Porcine reproductive and respiratory syndrome virus (PRRSV) is the pathogen of porcine reproductive and respiratory syndrome (PRRS), which is one of the most economically harmful diseases in modern pig production worldwide. Receptor of activated protein C kinase 1 (RACK1) was previously shown to be indispensable for the PRRSV replication and NF-κB activation in Marc-145 cells. Here we identified a membrane protein, integrin β3 (ITGB3), as a RACK1-interacting protein. PRRSV infection in Marc-145 cells upregulated the ITGB3 expression. Abrogation of ITGB3 by siRNA knockdown or antibody blocking inhibited PRRSV infection and NF-κB activation, while on the other hand, overexpression of ITGB3 enhanced PRRSV infection and NF-κB activation. Furthermore, inhibition of ITGB3 alleviated the cytopathic effects and reduced the TCID50 titer in Marc-145 cells. We also showed that RACK1 and ITGB3 were NF-κB target genes during PRRSV infection, and that they regulated each other. Our data indicated that ITGB3, presumably as a co-receptor, played an imperative role during PRRSV infection and NF-κB activation in Marc-145 cells. PRRSV infection activates a positive feedback loop involving the activation of NF-κB and upregulation of ITGB3 and RACK1 in Marc-145 cells. The findings would advance our elaborated understanding of the molecular host–pathogen interaction mechanisms underlying PRRSV infection in swine and suggest ITGB3 and NF-κB signaling pathway as potential therapeutic targets for PRRS control.
Porous perovskite lanthanum ferrites (LaFeO3) powders were synthesized under the different pH value by sol-gel technique and self-propagating combustion method. After the characterization with XRD, ...SEM, VSM, nitrogen adsorption-desorption isotherm and UV–Vis spectroscopy, the magnetic properties, photocatalytic activity and gas-sensing performance are discussed in detail. All LaFeO3 samples exhibit ferromagnetism for the spin mismatch due to oxygen vacancies. LaFeO3 powders present the good photocatalytic performance to MB and could be easily separated by magnetic separation technique after photocatalysis. Furthermore, the LaFeO3 gas sensors exhibited the considerable sensitivity to ethanol gas. Among all samples, LF-1 (LaFeO3 powders prepared at pH = 1) present the highest removal rate of MB (68%), the largest saturation magnetization (4.57 emu/g) and the best gas response to ethanol. The highest response for LF-1 sensor reaches (263.4) at the optimized operating temperature of 250 °C to 100 ppm ethanol gas, which should be attributed to the higher oxygen vacancies.
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•Porous LaFeO3 powders were prepared by sol-gel method.•Samples present the high surface area due to porous microstructures.•Ferromagnetism of LaFeO3 powders results from oxygen vacancies.•The lower bandgap lead to the highest photocatalytic activity of LF-1 to MB.•Surface area, bandgap and oxygen vacancies greatly affects the gas-sensing performance.
Environmental phenols, bisphenol A (BPA), triclosan (TCS), and benzophenone-3 (BP-3), are known as emerging endocrine-disrupting chemicals; however, their impacts on thyroid hormones and children's ...neurobehaviors are still unclear.
We aimed to examine the associations of prenatal and childhood exposure to phenols with neonatal thyroid function and childhood behavioral problems aged 10 years.
A total of 386 mother-singleton pairs were included from Sheyang Mini Birth Cohort Study (SMBCS), a longitudinal birth cohort in China. We quantified urinary BPA, TCS and BP-3 concentrations in maternal and 10-year-old children's urine samples using gas chromatography tandem mass spectrometry and thyroid function parameters in cord serum samples. Caregivers completed the Strength and Difficulties Questionnaire (SDQ) for their children at 10 years of age. Multivariable linear regression models and logistic regression models were applied to estimate associations of urinary phenol concentrations with thyroid hormones and risks of children's behavioral problems, respectively.
The median values of urinary BPA, TCS and BP-3 concentrations for pregnant women were 1.75 μg/L, 0.54 μg/L and 0.37 μg/L, while 1.29 μg/L, 6.64 μg/L and 1.39 μg/L for children, respectively. Maternal urinary BPA concentrations were in associations with 1.00% 95% confidence interval (CI): 0.20%, 1.92% increases in cord serum FT4 concentrations and significantly associated with increased risks of total difficulties odds ratio (OR): 1.45, 95% CI: 1.07, 1.97, while maternal urinary levels of BP-3 were significantly related to poorer prosocial behaviors (OR: 1.58, 95% CI: 1.04, 2.39) of children at 10 years of age. In sex-stratified analyses, maternal urinary BPA concentrations were related to increased total difficulty subscales only in boys.
The findings indicated that higher prenatal urinary BPA concentrations were associated with increased risks of total difficulties, especially in boys and maternal urinary BP-3 concentrations were related to poorer prosocial behaviors at 10 years.
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•BPA, TCS and BP-3 are ubiquitous in participants' urinary samples.•Maternal urinary BPA concentrations were positively related to serum FT4 levels.•Prenatal BPA exposure may increase risks of total difficulties at 10 years.•Higher BP-3 concentration during pregnancy predicted poorer prosocial behaviors.•The observed associations were stronger in boys than those in girls.
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