Enzyme-free ratiometric fluorescence and colorimetric dual-signal determination of glyphosate based on copper nanoclusters (ZIF/CuNCs) combined with blue carbon dots (bCDs).

A novel ratio fluorescent and colorimetric dual-signal sensing platform for detecting glyphosate based on blue carbon dots (bCDs) combined with ZIF/CuNCs nanomaterials that encapsulate copper nanoclusters (CuNCs) in a metal-organic framework (MOF). In principle, the immobilization of Cu2+ in ZIF/CuNCs results in complexation with imidazole in ZIF, leading to fluorescence quenching of ZIF/CuNCs, while the reference fluorophore bCDs remains unaffected. In addition, the colorimetric sensing strategy was based on the efficient peroxidase-like activity of bCDs binding to Cu2+, catalyzing H2O2 to generate OH. Under this condition, TMB could be oxidized to form blue oxTMB. However, when glyphosate was involved in the system, the fluorescence of ZIF/CuNCs was restored upon due to the strong chelation between Cu2+ and glyphosate, while the peroxidase-like activity of bCDs/Cu2+ decreased and resulted in the generation of fewer oxTMB, accompanied by a lighter blue color. The sensing platform was successfully applied to the determination of glyphosate in real samples of lake water and cabbage, demonstrating reliable and sensitive performance in practical applications.

Enhancing catalytic performance of Fe and Mo co-doped dual single-atom catalysts with dual-enzyme activities for sensitive detection of hydrogen peroxide and uric acid.

Single-atom catalysts (SACs) have attracted much attention due to their excellent catalytic activity, but the improvement of atomic loading which means that weight fraction (wt%) of metal atom was still facing great challenges. In this work, iron and molybdenum co-doped dual single-atom catalysts (Fe/Mo DSACs) was prepared for the first time by using the soft template sacrifice strategy, which improved significantly the atomic load and exhibited both the oxidase-like (OXD) activity and the dominant peroxidase-like (POD) activity. Further experiments reveal that Fe/Mo DSACs can not only catalyze O2 to generate O2•- and 1O2, but also catalyze H2O2 to generate a large number of •OH, which caused 3, 3', 5, 5'-tetramethylbenzidine (TMB) to be oxidized to oxTMB, accompanied by the color changing from colorless to blue. The steady-state kinetic test showed that Michaelis-Menten constant (Km) values and the maximum initial velocity values (Vmax) of the POD activity of Fe/Mo DSACs were 0.0018 mM and 12.6 × 10-8 M s-1, respectively. The corresponding catalytic efficiency was tens of times higher than Fe SACs and Mo SACs, which proves that the synergistic effect between Fe and Mo has significantly improved the catalytic ability. Based on the excellent POD activity of Fe/Mo DSACs, a colorimetric sensing platform combined with TMB was proposed to realize the sensitive detection of H2O2 and uric acid (UA) in a wide range, with limits of detection as low as 0.13 and 0.18 µM, respectively. Finally, accurate and reliable results were obtained in the detection of H2O2 in cells, and of UA in human serum and urine.

Fe-doped carbonized polymer dot-based fluorescent sensor with "turn-on" property for hydrazine hydrate detection.

It has become a significant problem to develop and improve carbonized polymer dot (CPD)-based fluorescence sensors with environmental detection features. In this study, fluorescent "turn on" sensors of CPDs were prepared by a one-step hydrothermal method using o-phenylenediamine (o-PD) and ferric chloride (FeCl3) as raw materials. Fe-doped CPDs exhibited excellent fluorescence properties, stability, and the sensitive and selective "turn on" detection of hydrazine hydrate (N2H4·H2O). In this detection system, Fe3+ acts as an effective fluorescence inhibitor that inhibits the yellow fluorescence emission from CPDs, while Fe3+ is reduced upon the addition of the N2H4·H2O reducing agent. The fluorescence intensity of CPDs gradually increased with the increasing concentration of N2H4·H2O, while the limit of detection (LOD) could reach 0.168 µM. In addition, CPD-based polyvinyl alcohol (CPDs@PVA) films were also prepared, which still maintained excellent sensitivity to N2H4·H2O. The results show that CPDs and their composite films can detect N2H4·H2O with good detection performance.

Presence of diabetes mellitus affects vertigo outcome in vestibular migraine.

OBJECTIVE: To investigate the association of diabetes mellitus (DM) with vertigo outcome in patients with vestibular migraine (VM). METHODS: Two hundred and thirty-four patients with VM were consecutively enrolled between October 2018 and January 2020 in a tertiary teaching medical center. Multivariable linear regression model and stratified analyses were used to explore the relationship between diabetes and vertigo outcome, which was measured by the visual analogue scale (VAS). RESULTS: Patients with diabetes were more likely to have poorer sleep quality and more severe vertigo symptoms measured by VAS at the follow-up than those without diabetes. After adjusting for potential confounders, presence of diabetes was significantly linked with poorer final vertigo VAS score (ß, 95 % confidence interval [CI]: 1.0 [0.1, 2.0]). This association was only significant for female patients with VM (ß, 95%CI: 1.2 [0.2, 2.3], p = 0.0244). CONCLUSIONS: Presence of diabetes was independently and inversely corrected with the vertigo outcome in women with VM. Our findings suggest that diabetes is likely a negative prognosticator of vertigo outcome in VM.

Dual-emission fluorescent nanoprobe based on Ag nanoclusters for sensitive detection of Cu(II).

Noble metal nanoclusters have attracted much attention because of their excellent fluorescence properties. In this work, we demonstrated a dual-emission fluorescent nanocomposite based on silver nanoclusters. First, we synthesized positively charged His-AgNCs, which emits intense blue light, and then Ag nanoclusters with stable red emission were synthesized using DHLA as the ligand. Thus a dual-emission fluorescent nanoprobe was successfully obtained through electrostatic self-assembly, with the advantages of good water solubility and excellent stability. Based on the intensity ratio of the two emission peaks, the nanoprobe can be used for selective and sensitive detection of copper ions, and presents a good linear relationship within a certain concentration range. In addition, we also designed a polymer film, and our dual-emission nanoprobe was successfully loaded onto it, which means that the visual detection of copper ions is possible. This indicates that our dual-emission fluorescent nanoprobe has potential application prospects in environmental analysis, medical diagnosis, biological detection, etc.

New Target of Oxidative Stress Regulation in Cochleae: Alternative Splicing of the p62/Sqstm1 Gene.

We investigated oxidative stress and antioxidant response in the p62/Sqstm1-Keap1-Nrf2 pathway in C57BL/6 mice cochleae during age-related hearing loss (ARHL) and noise-induced hearing loss (NIHL), and the function of full-length and variant p62 in the regulation of Nrf2 activation. Groups of young (2 months), old (13-14 months), control, and acoustic trauma (AT) mice were examined cochlear damage and oxidative stress as follows: auditory brainstem response and hair cell counts; malondialdehyde (MDA) levels measured by assay kit and 7,8-dihydro-8-oxoguanine (8-oxoG) detected by immunohistochemistry. Full-length and variant p62 were examined for expression in cochleae, hippocampus (HIP), and auditory cortex (AC) using immunoblotting. Keap1-Nrf2 pathway activation was based on immunoblotting of nuclear Nrf2 and quantitative real-time PCR of Nrf2 target genes HO-1/NQO-1. The oxidative function of full-length and variant p62 was examined in HEI-OC-1 cells by flow cytometry. The results showed hearing loss, and cochlear hair cell loss was associated with MDA accumulation and 8-oxoG expression during ARHL and NIHL. Nrf2 showed no obvious changes in nuclear protein. Expression levels mRNA for HO-1 and NQO1 were lower in old mice and mildly greater in AT Mice. The expression of p62 splicing variant lacking the Keap1-interacting region was greater than full-length p62 in cochleae. However, the expression of p62 splicing variant was lesser than full-length p62 in HIP and AC. For HEI-OC-1 cells, overexpression of full-length p62 decreased ROS levels induced by H2O2. Oxidative stress is closely related to ARHL and NIHL. Changing the ratio of full-length to variant p62 protein expression may be a new target to reduce the level of oxidative stress in cochleae.

Sleep Deprivation Modifies Noise-Induced Cochlear Injury Related to the Stress Hormone and Autophagy in Female Mice.

A lack of sleep is linked with a range of inner ear diseases, including hearing loss and tinnitus. Here, we used a mouse model to investigate the effects of sleep deprivation (SD) on noise vulnerability, and explored the mechanisms that might be involved in vitro, focusing particularly corticosterone levels and autophagic flux in cells. Female BALB/c mice were divided into six groups [control, acoustic trauma (AT)-alone, 1 day (d) SD-alone, 1d SD pre-AT, 5d SD-alone, and 5d SD pre-AT]. Cochlear damage was then assessed by analyzing auditory brainstem response (ABR), and by counting outer hair cells (OHCs) and the synaptic ribbons of inner hair cells (IHCs). In addition, we measured levels of serum corticosterone and autophagy protein expression in the basilar membranes by ELISA kits, and western blotting, respectively. We found that SD-alone temporarily elevated ABR wave I amplitude, but had no permanent effect on hearing level or IHC ribbon numbers. Combined with AT, the number of synaptic ribbons in the 1d SD pre-AT group was significantly higher than that in the AT-alone group, whereas the 5d SD pre-AT group showed more severe synaptopathy, and a greater loss of OHCs after 2 weeks than the other experimental groups exposed to noise. Correspondingly, the levels of corticosterone in the AT-alone group were higher than those of the 1d SD pre-AT group, but lower than those of the 5d SD pre-AT group. The 1d SD pre-AT group showed a marked elevation in the expression of microtubule-associated protein 1 light chain 3B (LC3B), whereas the AT-alone group exhibited only a mild increase. In contrast, the levels of LC3B did not change in the 5d SD pre-AT group. Experiments with HEI-OC-1 cells and cochlear basilar membrane cultures showed that high-concentrations of dexamethasone, and the inhibition of autophagy, aggravated cellular apoptosis induced by oxidative stress. In conclusion, noise-induced synaptopathy and hair cell loss can be mitigated by preceding 1d SD, but will be aggravated by preceding 5d SD. These findings may be attributable to corticosterone levels and the extent of autophagy.

Down-regulation of Cav1.3 in auditory pathway promotes age-related hearing loss by enhancing calcium-mediated oxidative stress in male mice.

In this study, age related Cav1.3 expression in cochlea and auditory cortex of C57BL/6J male mice was evaluated. It was found that the expression of Cav1.3 in cochlea decreased with aging whereas this phenomenon was not observed in neuron of auditory cortex. The correlation between decreased expression of Cav1.3 and age-related hearing losses was studied in vitro, after Cav1.3 was knocked out, the rate of apoptosis of hair cells increased after being subjected to ROS stresses, accompanied with enhanced senescence. Further, Cav1.3 knock down also interfered with the electrophysiology of hair cells. The effect was further confirmed in vivo, after Cav1.3 knocked down by injection of AAV, hearing impairment was observed in C57BL/6J male mice subjected to senescence and this was accompanied by increased loss of hair cells in cochlea. The effect was further confirmed in 3D organ culture, increased loss of hair cells after Cav1.3 was knocked down under ROS stresses.Mechanistically, Cav1.3 knock out resulted in decreased intracellular calcium which subsequently reduced the inactivation of ROS from complex I, and finally resulted in increased intracellular ROS and enhanced senescence.Collectively, these findings confirmed that Cav1.3 could protect cells in auditory pathway from oxidative stresses, and decreased expression of Cav1.3 in auditory pathway could contribute to hearing losses by enhancement of calcium-mediated oxidative stress.

Expression Patterns and Implications of LaminB1 in Rat Cochleae.

LaminB1, a major component of the nuclear lamina, is a potent regulator of cellular proliferation and senescence and also known to be essential for neuronal migration and brain development. However, the expression patterns of LaminB1 in the rat cochleae are still not fully revealed. Utilizing immunofluorescence, Western blotting, and quantitative real-time PCR, we identified the distribution and expression of LaminB1 in the rat cochleae. Immunofluorescence staining indicated that LaminB1 was mainly localized in the auditory hair cells (HCs), spiral ganglion cells (SGC), stria vascularis (STV, including spiral ligament), Reissner's membrane (RM), and limbus laminae spiralis (LLS). Western blotting analysis illustrated that the distribution of LaminB1 in rat cochleae was characterized by tissue specificity. The LaminB1 protein was expressed more in SGC and basilar membrane (BM) than in STV. Meanwhile, the mRNA expression of LaminB1 displayed difference in cochlear tissues. These observations preliminarily revealed the expression patterns of LaminB1, providing a theoretical basis for further study on the role of LaminB1 in auditory function.

Enhanced degradation of metronidazole by heterogeneous sono-Fenton reaction coupled ultrasound using Fe3O4 magnetic nanoparticles.

Metronidazole (MNZ), one of the most commonly used nitroimidazole antibiotics in the world, poses a serious threat to human life and health. In this study, an enhanced sono-Fenton process for the degradation of MNZ is presented. The catalytic capacity of nano-Fe3O4 in systems comprising ultrasound + Fe3O4 + H2O2, and the influential parameters such as H2O2, nano-Fe3O4 doses and pH for the Sono-Fenton process, was investigated. The results showed that the nano-Fe3O4 particles appeared to be roughly spherical in shape, with an average size of 10-20 nm. It was found that •OH radicals were rapidly generated due to the catalytic activity of the nano-Fe3O4. MNZ could be degraded within a wide pH range, from 3 to 9, and the degradation efficiencies were considerably enhanced by ultrasound. When the MNZ concentration was fixed at 20 mg/L, the nano-Fe3O4 dosage at 500 mg/L, the pH at 3 and the reaction temperature at 30°C, the removal efficiencies of MNZ were above 98% after 5 h. It is indicated that Fe3O4 magnetic nanoparticles were synthesized as heterogeneous catalysts to effectively degrade MNZ, and the observed stability and recyclability demonstrated that nano-Fe3O4 was promising for the treatment of wastewater contaminated with antibiotics.

[A distributed storage architecture for regional medical image sharing and cooperation based on HDFS].

Given the importance of regional centers for medical image sharing and cooperation is important for resource balancing, healthcare service enhancement and medical expense reduction, building such regional medical image sharing and cooperation centers faces huge challenges. In this paper we analyze the advantages and weakness of two storage architectures, and designed a hybrid storage architecture combining FC SAN and Hadoop HDFS. A HDFS suitable medical image file format, called S-DICOM, and a set of S-DICOM operating middleware, SDFO (S-DICOM File Operator), was developed. The results of performance testing indicated that this hybrid storage architecture is suitable for storing and managing large volume of medical images.

[Establishment of Internet-based database of the Virtual Chinese Human dataset].

To establish an Internet-based database for the dataset of Virtual Chinese Human that is accessible to the interested researchers, modifications and compression of the original VCH-format dataset of Virtual Chinese Human were performed before it was uploaded to the server, and RAID0+1 storage technology was adopted with specific download accesses designed for different users. After dataset modification and compression, the data size was considerably reduced to allow convenient data storage and transfer. The RAID0+1 storage technology guarantees the security and high-speed download of data through different means established. Internet-based database provides important accesses for sharing the achievement in virtual human study between world-wide researchers, which has been imperative in the present situation of science development.