miR-107 reverses the multidrug resistance of gastric cancer by targeting the CGA/EGFR/GATA2 positive feedback circuit.

Chemotherapy is still the main therapeutic strategy for gastric cancer (GC). However, most patients eventually acquire multidrug resistance (MDR). Hyperactivation of the EGFR signaling pathway contributes to MDR by promoting cancer cell proliferation and inhibiting apoptosis. We previously identified the secreted protein CGA as a novel ligand of EGFR and revealed a CGA/EGFR/GATA2 positive feedback circuit that confers MDR in GC. Herein, we outline a microRNA-based treatment approach for MDR reversal that targets both CGA and GATA2. We observed increased expression of CGA and GATA2 and increased activation of EGFR in GC samples. Bioinformatic analysis revealed that miR-107 could simultaneously target CGA and GATA2, and the low expression of miR-107 was correlated with poor prognosis in GC patients. The direct interactions between miR-107 and CGA or GATA2 were validated by luciferase reporter assays and western blot analysis. Overexpression of miR-107 in MDR GC cells increased their susceptibility to chemotherapeutic agents, including fluorouracil, adriamycin and vincristine, in vitro. Notably, intratumor injection of the miR-107 prodrug enhanced MDR xenograft sensitivity to chemotherapies in vivo. Molecularly, targeting CGA and GATA2 with miR-107 inhibited EGFR downstream signaling, as evidenced by the reduced phosphorylation of ERK and AKT. These results suggest that miR-107 may contribute to the development of a promising therapeutic approach for the treatment of MDR in GC.

Design and Synthesis of Low Dielectric Poly(aryl ether ketone) from Incorporation Bulky Fluorene Groups and Regular Hydroquinone Structure.

To decrease the dipole polarization rate and reduce the dielectric constant of poly(aryl ether ketone) (PAEK) resin, 1,4-di(4-fluorobenzoyl) cyclohexane (DFBCH), a weakly polarizing cyclohexane-based monomer, was designed and synthesized as the primary reactant. The bulky fluorene group was incorporated to increase the free volume of the resin, further reducing the dielectric constant. Additionally, hydroquinone with a symmetric and regular structure was utilized to enhance the molecular chain's regularity and reduce dipole relaxation, further lowering the resin's dielectric constant and dielectric loss. The PFQEKs series resins exhibited excellent thermal stability with glass transition temperature (Tg) ranging from 222 to 239 °C and 5% weight loss (Td5%) ranging from 458 to 463 °C, with different monomer ratios. As the hydroquinone content increased, the dielectric constant (Dk) and dielectric loss (Df) of the resin decreased significantly, with Dk ranging from 2.92 to 2.77 and Df ranging from 0.011 to 0.008 at 10 GHz.

GmPTF1 modifies root architecture responses to phosphate starvation primarily through regulating GmEXPB2 expression in soybean.

Though root architecture modifications may be critically important for improving phosphorus (P) efficiency in crops, the regulatory mechanisms triggering these changes remain unclear. In this study, we demonstrate that genotypic variation in GmEXPB2 expression is strongly correlated with root elongation and P acquisition efficiency, and enhancing its transcription significantly improves soybean yield in the field. Promoter deletion analysis was performed using 5' truncation fragments (P1-P6) of GmEXPB2 fused with the GUS gene in soybean transgenic hairy roots, which revealed that the P1 segment containing three E-box elements significantly enhances induction of gene expression in response to phosphate (Pi) starvation. Further experimentation demonstrated that GmPTF1, a basic-helix-loop-helix transcription factor, is the regulatory factor responsible for the induction of GmEXPB2 expression in response to Pi starvation. In short, Pi starvation induced expression of GmPTF1, with the GmPTF1 product directly binding to the E-box motif in the P1 region of the GmEXPB2 promoter. Plus, both GmPTF1 and GmEXPB2 highly expressed in lateral roots, and were significantly enhanced by P deficiency. Further work with soybean stable transgenic plants through RNA sequencing analysis showed that altering GmPTF1 expression significantly impacted the transcription of a series of cell wall genes, including GmEXPB2, and thereby affected root growth, biomass and P uptake. Taken together, this work identifies a novel regulatory factor, GmPTF1, involved in changing soybean root architecture partially through regulation of the expression of GmEXPB2 by binding the E-box motif in its promoter region.

Optimizing selection of the test color sample set for the CIE 2017 color fidelity index.

We have developed a new method for selecting the test color sample set (TCSS) used to calculate CIE 2017 color fidelity index (CIE-Rf). Taking a Large Set as a starting point, a new optimized color sample set (OCSS) is obtained by clustering analysis. Taking metamerism phenomenon into account, spectra clustering is performed within the class obtained from color appearance attributes clustering. The CIE-Rf of 1202 light sources are calculated and analyzed by taking the Large Set, OCSS and CIE color evaluation sample set (CIE CESS-99) as TCSS. Through analyzing CIE-Rf, the performance of the OCSS is further investigated. The results show that the clustering analysis method developed in this paper can be well used in selecting test color samples, and the obtained OCSS can represent Large Set well and be better used for color fidelity metrics of light sources.

Non-Coplanar Diphenyl Fluorene and Weakly Polarized Cyclohexyl Can Effectively Improve the Solubility and Reduce the Dielectric Constant of Poly (Aryl Ether Ketone) Resin.

With the rapid development of high-frequency communication and large-scale integrated circuits, insulating dielectric materials require a low dielectric constant and dielectric loss. Poly (aryl ether ketone) resins (PAEK) have garnered considerable attention as an intriguing class of engineering thermoplastics possessing excellent chemical and thermal properties. However, the high permittivity of PAEK becomes an obstacle to its application in the field of high-frequency communication and large-scale integrated circuits. Therefore, reducing the dielectric constant and dielectric loss of PAEK while maintaining its excellent performance is critical to expanding the PAEK applications mentioned above. This study synthesized a series of poly (aryl ether ketone) resins that are low dielectric, highly thermally resistant, and soluble, containing cyclohexyl and diphenyl fluorene. The effects of cyclohexyl contents on the properties of a PAEK resin were studied systematically. The results showed that weakly-polarized cyclohexyl could reduce the molecular polarization of PAEK, resulting in low permittivity and high transmittance. The permittivity of PAEK is 2.95-3.26@10GHz, and the transmittance is 65-85%. In addition, the resin has excellent solubility and can be dissolved in NMP, DMF, DMAc, and other solvents at room temperature. Furthermore, cyclohexyl provided PAEK with excellent thermal properties, including a glass transition temperature of 239-245 °C and a 5% thermogravimetric temperature, under a nitrogen atmosphere of 469-534 °C. This makes it a promising candidate for use in high-frequency communications and large-scale integrated circuits.

Manufacturing of Porous Glass by Femtosecond Laser Welding.

Based on femtosecond laser glass welding, four different porous structures of welding spots were formed by the manufacturing processes of spatiotemporal beam shaping and alternating high repetition rate transformation. Compared with an ordinary Gaussian beam, the welding spot fabricated by the flattened Gaussian beam had smoother welding edges with little debris, and the bottom of the welding spot pore was flat. Instead of a fixed high repetition rate, periodically alternating high repetition rates were adopted, which induced multiple refractive indices in the welding spot pore. The welding spot pores manufactured by spatiotemporal beam shaping and alternating high repetition rate transformation have a special structure and excellent properties, which correspond to superior functions of porous glass.

Efficient Antibacterial Agent Delivery by Mesoporous Silica Aerogel.

Bacterial infections still cause many health problems for human beings. Silica aerogels with a three-dimensional (3D) porous structure and a large surficial area are promising candidates for drug delivery, but they have rarely been investigated for antibacterial agent delivery. Herein, we study mesoporous silica aerogels as carriers for delivery of three slightly soluble antibacterial agents including cinnamaldehyde (CA, liquid), salicylic acid (SAA, solid), and sorbic acid (SOA, solid) under supercritical fluid carbon dioxide. Notably, all three antibacterial agents form uniform nanocrystals in the mesopores of silica aerogels and the loading efficiency reaches 56 wt %, which assists in overcoming the obstacles of low bioavailability of slightly soluble antibacterial agents. Benefiting from nanocrystallized antibacterial agents, the agent-loaded aerogels exhibit an inhibition rate of 99.99% against Escherichia coli during the initial release; notably, they still have a 95% inhibition rate even after ∼90% of CA is released. Importantly, the agent-loaded silica aerogels demonstrate good biocompatibility in vitro. This work indicates that mesoporous silica aerogels are a promising platform for antibacterial agent delivery.

Protective effects of Salvia miltiorrhiza against cisplatin-induced ototoxicity in guinea pigs.

OBJECTIVE: The aim of the study was to investigate the protective effects of Salvia miltiorrhiza (SM) against cisplatin-induced ototoxicity in guinea pigs. METHODS: Thirty-nine guinea pigs were randomly divided into 3 groups. The first group (control group) received physiologic saline by intraperitoneal (i.p.) injection for 5 days. The second group (cisplatin group) was treated with cisplatin (2 mg/kg per day, i.p. injection) for 5 days. The third group (SM group) was given SM (8 g/kg per day, i.p. injection) for 2 days and then was given SM (8 g/kg per day, i.p. injection) and cisplatin (2 mg/kg per day, i.p. injection) for 5 days. Auditory brain stem response (ABR) and cochlea blood flow measurement were used to evaluate cochlea function. The structures of cochlea were observed by light microscope, scanning electron microscope, transmission electron microscope (TEM), and immunohistochemical examination. RESULTS: Cisplatin could cause severe acoustic damages including significant elevation of ABR threshold, substantial losses of outer hair cells and inner hair cells, and severe damage on the stria vascularis and spiral ganglion cells (SGCs). Although in SM group, the increased tendency of threshold was milder than that in cisplatin group. The damages in cochlea and stria vascularis were also less severe than those in cisplatin group. The expression of induced nitric oxide synthase in the cochlea and SGC in SM group was lower than that in cisplatin group. CONCLUSIONS: Salvia miltiorrhiza can significantly reduce the cisplatin-induced side effects.

Microstructure Evolution and Mechanical Properties of a Wire-Arc Additive Manufactured Austenitic Stainless Steel: Effect of Processing Parameter.

Two single track multi-layer walls with linear energy inputs (LEIs) of 219 and 590 J/mm were deposited by cold metal transfer-based wire arc additive manufacturing system. Combined with the X-ray diffraction technique, scanning electron microscope and uniaxial tensile tests, the influences of LEI and cooling rate (CR) on the microstructure evolution, mechanical properties and fracture mechanisms of the studied steel are analyzed. It is observed that the microstructures of the studied steel are mainly composed of δ-ferrite and austenite dendrites. σ phase is formed on the δferrite-austenite interface under low CR. Meanwhile, the primary dendrites' spacing decreases with the decrease in LEI or the increase in CR, and the maximal primary dendrites' spacing is 32 µm. The values of elongation to fracture roughly decline with the decrease in LEI or the increase in CR, but the variations of ultimate tensile strength and yield stress show an opposite trend. In addition, the mesoscopic damages in the studied steel under low LEI are mainly caused by the coalescence of pores. While under high LEI, the cracks are induced by the dislocations piling up around δ-ferrite.

Study of Grain Growth in a Ni-Based Superalloy by Experiments and Cellular Automaton Model.

The grain growth behavior in a typical Ni-based superalloy was investigated using isothermal heat treatment experiments over a holding temperature range of 1353-1473 K. The experimental results showed that the grain structure continuously coarsened as the holding time and holding temperature increased during heat treatment. A classical parabolic grain growth model was used to explore the mechanism of grain growth under experimental conditions. The grain growth exponent was found to be slightly above 2. This indicates that the current grain growth in the studied superalloy is mainly governed by grain boundary migration with a minor pinning effect from the precipitates. Then, the grain growth in the studied superalloy during isothermal heat treatment was modelled by a cellular automaton (CA) with deterministic state switch rules. The microscale kinetics of grain growth is described by the correlation between the moving velocity and curvature of the grain boundary. The local grain boundary curvature is well evaluated by a template disk method. The grain boundary mobility was found to increase with increasing temperature. The relationship between the grain boundary mobility and temperature has been established. The developed CA model is capable of capturing the dependence of the grain size on the holding time under different holding temperatures.

Inhibition of voltage-gated channel currents in rat auditory cortex neurons by salicylate.

Salicylate is a medicine for anti-inflammation with a side effect of tinnitus. To understand the mechanisms of tinnitus induced by salicylate, we studied the effects of salicylate on voltage-gated ion channels and action potential firing rates in freshly dissociated rat pyramidal neurons in auditory cortex (AC) using the whole-cell patch technique. We found that salicylate reduced the voltage-gated sodium current (I(Na)), the delayed rectifier potassium current (I(K(DR))) and the L-type voltage-gated calcium current (I(Ca,L)) in concentration-dependent manner. An amount of 1mM salicylate shifted the steady-state inactivation curve of I(Na) negatively by about 5mV, shifted the steady-state activation and inactivation curve of I(K(DR)) negatively by approximately 14mV and 17mV, respectively, and shifted the steady-state activation curve of I(Ca,L) negatively by about 10mV. 1mM salicylate significantly increased the action potential firing rates, ultimately. From the results, we speculated that through affecting the voltage-gated ion channels in AC, an important position in auditory system, salicylate increased the firing rate of neurons and enhanced neuronal excitability on the one hand, increased the excitatory transmitters release and reduced the inhibitory transmitter release on the other hand, thus finally induced tinnitus.

Auditory deprivation modifies the expression of brain-derived neurotrophic factor and tropomyosin receptor kinase B in the rat auditory cortex.

The development and plasticity of central auditory system can be influenced by the change of peripheral neuronal activity. However, the molecular mechanism participating in the process remains elusive. Brain-derived neurotrophic factor (BDNF) binding with its functional receptor tropomyosin receptor kinase B (TrkB) has multiple effects on neurons. Here we used a rat model of auditory deprivation by bilateral cochlear ablation, to investigate the changes in expression of BDNF and TrkB in the auditory cortex after auditory deprivation that occurred during the critical period for the development of central auditory system. Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and immunohistochemistry methods were adopted to detect the mRNA and protein expression levels of BDNF and TrkB in the auditory cortex at 2, 4, 6 and 8 weeks after surgery, respectively. The change in the expression of BDNF and TrkB mRNAs and proteins followed similar trend. In the bilateral cochlear ablation groups, the BDNF-TrkB expression level initially decreased at 2 weeks but increased at 4 weeks followed by the reduction at 6 and 8 weeks after cochlear removal, as compared to the age-matched sham control groups. In conclusion, the BDNF-TrkB signaling is involved in the plasticity of auditory cortex in an activity-dependent manner.

Natural occurrence of fumonisins B1 and B2 in maize from eight provinces of China in 2014.

A total of 249 maize kernel samples from 8 maize-producing provinces of China were collected after the harvest season in 2014. All samples were analysed using high-performance liquid chromatography. The incidences of FBs (FB1 + FB2) from Guizhou, Hebei, Inner Mongolia, Shanxi, Chongqing, Liaoning, Heilongjiang, and Henan provinces were 71.4%, 73.8%, 28.0%, 52.6%, 85.0%, 87.5%, 38.1%, and 100.0%, respectively. The average concentration of FBs was 817 µg kg-1 and the concentrations ranged from <6 to 15,252 µg kg-1. Among the 249 maize kernel samples, 28 samples exhibited higher levels as set by the Food and Drug Administration (2000 µg kg-1), whereas 12 samples exhibited higher levels as set by the European Commission (4000 µg kg-1). The average exposure to FBs (0.12 µg kg-1 body weight/day) is within the provisional maximum tolerable daily intake of 2.0 µg kg-1 body weight as set by the Joint FAO/WHO Expert Committee on Food Additives.

Fusarium species identification and fumonisin production in maize kernels from Shandong Province, China, from 2012 to 2014.

A total of 225 maize kernel samples were collected from Shandong Province in China from 2012 to 2014 and analysed for contamination with Fusarium spp. and fumonisins (FBs) using molecular methods and high-performance liquid chromatography with fluorescence detection. The results showed that the average incidences of Fusarium spp. in 2012, 2013 and 2014 were 23.3%, 37.1% and 36.5%, respectively, Fusarium verticillioides being the predominant species. In 2012, the average contamination level of FBs was 3071 ng g(-1), which was higher than that in 2014 (2913 ng g(-1)) and 2013 (2072 ng g(-1)). Of all samples, 13% and 19% had FB contamination levels higher than 2000 and 4000 ng g(-1), which are the maximum limits as set by the Food and Drug Administration of the United States and the European Commission, respectively. Therefore, efforts should be taken to minimise the potential risk of FBs to the health of humans and animals.

Salicylate blocks L-type calcium channels in rat inferior colliculus neurons.

To investigate the effects of the tinnitus inducer sodium salicylate on L-type voltage-gated calcium channels, we studied freshly dissociated inferior colliculus neurons of rats by the whole-cell voltage clamp method. Salicylate's blocking of L-type calcium channels was concentration dependent, and the IC(50) value of salicylate was estimated to be 1.99 mM. An amount of 1 mM salicylate significantly shifted the steady-state inactivation curve of L-type calcium channels about 9 mV in the hyperpolarizing direction and significantly delayed calcium channel recovery. Our results suggest that salicylate's blocking of L-type calcium channels may contribute to salicylate-induced tinnitus by decreasing GABA release in the inferior colliculus.

Effects of salicylate on transient outward and delayed rectifier potassium channels in rat inferior colliculus neurons.

The effects of salicylate (a tinnitus inducer) were studied on the transient outward potassium current (I(K(A))) and the delayed rectifier potassium current (I(K(DR))) in acutely dissociated rat inferior colliculus neurons by the whole-cell voltage-clamp method. Salicylate's inhibition of the amplitude of I(K(A)) and I(K(DR)) was concentration-dependent. The IC(50) values for the blocking action of salicylate on I(K(A)) and I(K(DR)) were 2.27 and 0.80 mM, respectively. At a concentration of 1 mM, salicylate significantly shifted the activation and inactivation curves of I(K(DR)) negatively by approximately 11 and 24 mV, respectively, but did not shift the I(K(A)) curves. In conclusion, salicylate inhibits both I(K(A)) and I(K(DR)) in rat inferior colliculus neurons but only significantly affects the activation and inactivation kinetics of I(K(DR)). Depression of I(K(DR)) by salicylate may play an important role in salicylate-induced tinnitus.

Effects of salicylate on voltage-gated sodium channels in rat inferior colliculus neurons.

To investigate the effects of the tinnitus inducer, sodium salicylate, on voltage-gated sodium channels, we studied freshly dissociated inferior colliculus neurons of rats by the whole-cell voltage clamp method. Salicylate blocked sodium channels in concentration-dependent manner (0.1-10 mM), and the IC50 value of salicylate was estimated to be 1.43 mM after application. The sodium conductance-voltage curve did not shift along the voltage axis with salicylate application. In contrast, the steady-state sodium channel inactivation curve was shifted by about 9 mV in the hyperpolarizing direction. In addition, salicylate delayed the sodium channel recovery from inactivation by increasing the slow time constant. It was concluded that salicylate bound to the resting and inactivated sodium channels to cause blocking, with a higher affinity for the latter state. Our results suggest that salicylate causes a concentration-dependent blockade of voltage-gated sodium channels and shifts the inactivation curve to more hyperpolarized potentials, which could be related to the mechanism of salicylate-induced tinnitus.

[Inhibition of salicylate on voltage-gated sodium channels in rat inferior colliculus neurons].

OBJECTIVE: To investigate the mechanism of the tinnitus inducer, sodium salicylate, on voltage-gated sodium channels. METHOD: The effects of salicylate on voltage-gated sodium channels in freshly dissociated inferior colliculus neurons of rats were studied, using the whole-cell voltage clamp method. RESULT: Salicylate blocked sodium current (INa) in concentration-dependent manner (0.1-10 mmol/L). The IC50 value for the blocking action of salicylate was 1.43 mmol/L. Salicylate did not affect the conductance-voltage curve and the steady-state activation curve of INa. The steady-state INa inactivation curve of INa was shifted by about 9 mV in the hyperpolarizing direction. In addition, salicylate delayed the sodium channel recovery from INa inactivation by increasing the slow time constant. CONCLUSION: Our results suggest that salicylate causes a concentration-dependent blockade of INa and shifts the INa inactivation curve to more hyperpolarized potentials, which could be related to the mechanism of salicylate-induced tinnitus.

Genetic diversity and origin of Chinese cattle revealed by mtDNA D-loop sequence variation.

To determine the origin and genetic diversity of Chinese cattle, we analyzed the complete mtDNA D-loop sequences of 84 cattle from 14 breeds/populations from southwest and west China, together with the available cattle sequences in GenBank. Our results showed that the Chinese cattle samples converged into two main groups, which correspond to the two species Bos taurus and Bos indicus. Although a dominant lineage was clearly discerned in both B. taurus and B. indicus mtDNAs, network analysis of the lineages in each of the two species further revealed multiple clades that presented regional difference. The B. taurus samples in China could be grouped into clades T2, T3, and T4, whereas B. indicus harbored two clades I1 and I2. Age estimation of these discerned clades showed a time range of 14,100-44,500 years before present (YBP). The phylogenetic pattern of Chinese cattle was consistent with the recently described cattle matrilineal pool from northeast Asia, but suggested that B. indicus contributed more to the cattle from south and southwest China. The genetic diversity of Chinese cattle varied among the breeds studied.

[Inhibition of salicylate on potassium channels in rat inferior colliculus neurons].

OBJECTIVE: To understand what role of the transient outward potassium channels and the delayed rectifier potassium channels play in the mechanism of salicylate-induced tinnitus. METHODS: The effects of salicylate on the transient outward potassium channels and the delayed rectifier potassium channels in freshly dissociated inferior colliculus neurons of rats were studied, using the whole-cell voltage clamp method. RESULTS: Salicylate blocked the transient outward potassium current (I(K(A and the delayed rectifier potassium current (I(K(DR in concentration-dependent manner (0.1-1 mmol/L). The IC50 values for the blocking action of salicylate on I(K(A)) and I(K(DR)) were 2.27 and 0.80 mmol/L, respectively. At a concentration of 1 mmol/L, salicylate did not shift the activation and inactivation curves of I(K(A)), but significantly shifted the activation and inactivation curves of I(K(DR)) negatively by approximately 11 mV and 24 mV. CONCLUSIONS: Salicylate inhibits both I(K(A)) and I(K(DR)) in rat inferior colliculus neurons but only significantly affects the activation and inactivation kinetics of I(K(DR)). Effects of I(K(A)) and I(K(DR)), especially I(K(DR)), by salicylate may play an important role in salicylate-induced tinnitus.