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Auditory neuropathy is a disorder of auditory dysfunction characterized by the normal function of the outer hair cells and malfunction of the inner hair cells, synapses, postsynapses and/or auditory afferent nervous system. This review summarizes the process of discovery and naming of auditory neuropathy and describes the acquired, associated genetic disorders and management available.In the last 40 years, auditory neuropathy has undergone a process of discovery, naming and progressive elucidation of its complex pathological mechanisms. Recent studies have revealed numerous acquired and inherited causative factors associated with auditory neuropathy. Studies have analyzed the pathogenic mechanisms of various genes and the outcomes of cochlear implantation. New therapeutic approaches, such as stem cell therapy and gene therapy are the future trends in the treatment of auditory neuropathy.A comprehensive understanding of the pathogenic mechanisms is crucial in illustrating auditory neuropathy and assist in developing future management strategies.

In this study, the transformation and degradation mechanisms of refractory organic matter in biologically treated leachate from a semi-aerobic aged refuse biofilter (SAARB) in a nano-Fe3O4 enhanced ozonation process (nFe3O4-O3) were investigated in batch experiments. A continuous experiment then confirmed the effectiveness of the process for SAARB effluent treatment. In a batch experiment, the effects of influencing factors, including nFe3O4 dosage, O3 dosage and initial pH on the treatment performance of nFe3O4-O3 process, were comprehensively investigated. The results showed that when the nFe3O4 dosage = 6 g L−1, O3 dosage = 0.15 L minute−1 and initial pH = 7, the total organic carbon, absorbance at 254 nm and colour number removal efficiencies were 40.58%, 62.55% and 89.80%, respectively. In addition, most of the humic- and fulvic-like substances in the SAARB effluent were removed, and the condensation degree, aromaticity and humification degree of the organics were substantially reduced. The morphology and elemental valence state analysis showed that the nFe3O4 in the process was relatively stable and could form an nFe3O4-organic complex. Therefore, the probability of organics reacting with hydroxyl radical increased and the oxidation efficiency was enhanced. In the continuous experiment, both the O3 dosage and hydraulic retention time (HRT) were the key influencing factors. The treatment efficiency of the nFe3O4-O3 process was enhanced at a higher O3 dosage and longer HRT. The electrical energy consumption of the continuous nFe3O3-O3 process was calculated to be 17.72 kW h m−3 in SAARB effluent treatment. This study proved the feasibility of biologically treated landfill leachate treatment by the nFe3O3-O3 process.

Yuyu Huang,1,2,&ast; Haoran Yu,3,&ast; Min Liang,1,2 Shule Hou,1,2 Junmin Chen,1,2 Fan Zhang,1,2 Xiayu Sun,1,2 Huan Jia,2,4,5 Jun Yang1,2,5 1Department of Otorhinolaryngology Head and Neck Surgery, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200092, People’s Republic of China; 2Shanghai Key Laboratory of Translational Medicine on Ear and Nose Diseases (14DZ2260300), Shanghai, 200125, People’s Republic of China; 3ENT Institute and Department of Otorhinolaryngology, Eye & ENT Hospital, Fudan University, Shanghai, 200031, People’s Republic of China; 4Department of Otorhinolaryngology Head and Neck Surgery, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200011, People’s Republic of China; 5Ear Institute, Shanghai Jiao Tong University School of Medicine, Shanghai, 200031, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jun YangENT Ward of Xinhua Hospital, Floor 18, Building 8, 1665 Kongjiang Road, Yangpu District, Shanghai, 200092, People’s Republic of ChinaTel +86 13764981808Email yangjun@xinhuamed.com.cnHuan JiaENT Ward of Ninth People’s Hospital, Floor 2, Building 1, 639 Zhizaoju Road, Huangpu District, Shanghai, 200011, People’s Republic of ChinaTel +86 13601797481Email huan_jia_orl@163.comObjective: To investigate the hearing protection outcomes of different drug-eluting analog electrode arrays implanted into guinea pig cochleae.Methods: Sixty guinea pigs were randomly divided into a negative control group and five experimental groups implanted separately with blank (drug carrier), dexamethasone (DXM), aracytine (Ara-C), Ara-C+DXM, and nicotinamide adenine dinucleotide (NAD+) eluting analog electrode arrays. Micro CT was used to supervise the surgical procedure. Auditory brainstem response (ABR) thresholds of the guinea pigs were measured and analyzed.Results and Conclusions: Compared with the negative control, all other groups showed a significant increase in ABR threshold (p< 0.001) after surgery. Among them, there was no obvious difference between the blank (0 vs 90 days: 59.70± 10.57 vs 64.60± 9.47 dB SPL) and the NAD+ group (0 vs 90 days: 59.90± 9.87 vs 64.70± 8.65 dB SPL). On the other hand, the ABR thresholds in the DXM (0 days: 58.10± 10.73 dB SPL; 90 days: 51.70± 9.07 dB SPL) and the Ara-C group (0 days: 59.00± 10.05 dB SPL; 90 days: 51.60± 8.48 dB SPL) decreased significantly compared with the former two groups (p< 0.001). However, the Ara-C+DXM group showed no further benefit (p> 0.05). In addition, a significantly higher survival rate of spiral ganglion neurons in cochleae was observed in the Ara-C and/or DXM groups.Keywords: guinea pig, cochlear implant, drug-eluting electrode, hearing protection

Cocaine abuse is a serious global public health and social problem, and cocaine detoxification remains a challenge. Benzoylecgonine (BE) is the main toxic metabolite after cocaine consumption, with a longer retention time in the body and environment than cocaine itself. According to many studies, the toxicity of BE to humans is as significant as cocaine itself. Moreover, BE is recognized as an addictive drug contaminant in the environment, especially the freshwater system, leading to worries of its ecotoxicity. Extensive studies on the adverse effects of BE on both humans and ecology have been conducted, showing a marked sub-lethal toxicity of BE to diverse organisms. To eliminate BE in vivo and in vitro, various elimination methods have been developed and their BE removal capacity were evaluated. In this review, we aimed to summarize information in the literature to understand better BE toxicity and elimination that may facilitate the clinical treatment of cocaine abuse. By studying the critical role of BE in cocaine abuse, we propose that the ideal treatment for cocaine abuse should not only detoxify cocaine itself but also remove or degrade BE. Emphasizing the necessity of developing effective BE elimination methods is significant for the development of potential clinical treatments and environmental protections.

We attempted to improve the accuracy of coronary CT angiography (CCTA)-derived fractional flow reserve (FFR) (FFRCT) by expanding the coronary tree in the computational fluid dynamics (CFD) domain. An observational study was performed to evaluate the effects of extending the coronary tree analysis for FFRCT from a minimal diameter of 1.2 to 0.8 mm. Patients who underwent CCTA and interventional FFR were enrolled retrospectively. Seventy-six patients qualified based on the inclusion criteria. The three-dimensional (3D) coronary artery tree was reconstructed to generate a finite element mesh for each subject with different lower limits of luminal diameter (1.2 mm and 0.8 mm). Outlet boundary conditions were defined according to Murray’s law. The Newton–Krylov–Schwarz (NKS) method was applied to solve the governing equations of CFD to derive FFRCT. At the individual patient level, extending the minimal diameter of the coronary tree from 1.2 to 0.8 mm improved the sensitivity of FFRCT by 16.7% (p = 0.022). This led to the conversion of four false-negative cases into true-positive cases. The AUC value of the ROC curve increased from 0.74 to 0.83. Moreover, the NKS method can solve the computational problem of extending the coronary tree to an 0.8-mm luminal diameter in 10.5 min with 2160 processor cores. Extending the reconstructed coronary tree to a smaller luminal diameter can considerably improve the sensitivity of FFRCT. The NKS method can achieve favorable computational times for future clinical applications. • Extending the reconstructed coronary tree to a smaller luminal diameter can considerably improve the sensitivity of FFR CT . • The NKS method applied in our study can effectively reduce the computational time of this process for future clinical applications.

Moisture transport has a great impact on concrete durability. In this study, a hard-pulse one-dimensional frequency coding sequence of low-field nuclear magnetic resonance (LF-NMR) imaging was applied to investigate moisture transport in cement-based materials (CBMs) considering the influences of the water/binder (w/b) ratio, sand/cement (s/c) ratio and contents of silica fume (SF) and super-absorbent polymer (SAP). A weighing method was also applied and the results were compared with the LF-NMR imaging measurements. The results showed that the moisture distribution curves can be divided into three stages by height. In addition, it was found that the moisture absorption height (h) increased with time and the growth rate of water absorption proceeded from fast to slow. Additionally, as the w/b ratio of the sample was increased, h increased. The value of h decreased with increasing s/c ratio and increased with an increase in SF content. When SAP was mixed into the CBMs, the values of h increased with 0·15% SAP addition but decreased with the addition of 0·30% SAP. The LF-NMR imaging measurements were in agreement with the results of the weighing method.

FoxM1 is a transcriptional regulator involved in tumor development, pulmonary fibrosis, and cardiac fibrosis. However, its role in renal interstitial fibrosis (RIF) has yet to be elucidated. We established a TGF-β1-stimulated human proximal tubular epithelial cell (HK-2) model in vitro and a unilateral ureteral obstruction (UUO)-induced rat RIF model in vivo. FoxM1 inhibition was achieved by siRNA interference in vitro and by injecting thiostrepton into UUO-induced RIF rats in vivo. The degree of renal damage and fibrosis were determined by histological assessment via hematoxylin and eosin (H&E) staining. Immunohistochemistry, western blots, and qPCR were used to determine the expression levels of FoxM1, Collagen I, E-cadherin, α-SMA, and Snail1. Our results showed that FoxM1 inhibition could ameliorate RIF and reduce the deposition of Collagen I. H&E staining revealed that renal structural damage, inflammatory cell infiltration, and ECM deposition were significantly attenuated by thiostrepton treatment in the UUO rats. Furthermore, FoxM1 downregulation significantly suppressed epithelial-to-mesenchymal transition, as evidenced by decreased protein and mRNA expression levels of α-SMA and Snail1 and a significant increase in protein and mRNA expression levels of E-cadherin. Collectively, these results suggested that FoxM1 inhibition could be a novel therapeutic strategy for the treatment of RIF.

To develop a drug-eluting polymer film which can be easily personalized and rapidly made on the electrode array of a cochlear implant during surgery.A precursor solution was prepared with poly lactic-co-glycolic acid (PLGA) and trichloromethane. Using a dip-coating method, the silicone electrode array (HiFocus 1J, Advanced Bionics) was coated in polymer film produced from the precursor solution containing one of three drugs: dexamethasone sodium phosphate (DSP), cytosine arabinoside hydrochloride (Ara-C), or nicotinamide adenine dinucleotide (NAD), and the release of these drugs from the polymer film was studied. The drug-eluting film on the electrode array was analyzed by environmental scanning electron microscopy (ESEM). The water contact angle and the impedance of the electrode array were measured before and after coating. Drug release kinetics was evaluated in a quasi-stationary release model, using high performance liquid chromatography every 24 h for 15 days.Five electrode arrays were tested with each of the three drugs in the polymer film coating. Before and after coating, ESEM studies revealed that the drug-loaded PLGA coating yielded a smooth covering with an average thickness of 1.02 ± 0.05 μm. The mass of the coated electrode increased by 1.00 ± 0.03 mg. The water contact angle decreased after coating (102 ± 0.6° vs 77 ± 1.6°, p 0.01) but there was no significant change in the average impedance of the electrodes after coating (0.9 ± 0.22 kΩ vs 1.0 ± 0.18 kΩ, p 0.05). An in vitro drug kinetics study revealed a faster release in the first 24 h (63.4 ± 0.6%) and a sustained release over the following 15 days (78.3 ± 1.7% in 2 days, 95.6 ± 1.0% in 7 days and 99.1 ± 0.4% in 14 days). The release rate was not affected by the drug, dose or the thickness of the coating.The dip-coating method is feasible for rapid casting of a drug-eluting PLGA film on an electrode array during CI surgery. The coated electrode array maintained its original morphology and became more hydrophilic. The loaded drug is released in a sustained manner and is easily regulated, and so the method might represent a potential application for clinical use in cochlear implantation.

The expansion and harvest of stem cells at clinically relevant scales is critical for cell-based therapies. These approaches need to be robust and cost-effective, support the functional maintenance of desired cell behaviors, and allow for simple harvest. Here, we introduce a real-time monitoring 3D printing approach to fabricate scaffolds with quadruple hierarchical structure that meet these design goals for stem cell expansion. Specifically, a versatile strategy was developed to produce scaffolds from alginate and gelatin with approximately 102 μm interconnected macropores, 300 μm microfilaments, 1.3 mm hollow channels, and centimeter-scale overall dimensions. The scaffolds exhibited good pattern fidelity and stable mechanical properties (compressive modulus value was 22-fold that of hydrogels from the same materials), facilitating uniform and efficient cell seeding with high viability (98.9%). The utility of the scaffold was shown with the 3D culture of HepaRG cells and embryonic stem cells (ESCs) with aggregated morphology, and significantly enhanced cell proliferation was observed compared to those of cultures on flat surfaces, obtaining approximately 2 × 108 cells within a single culture. Interestingly, the functional behavior of the cells was dependent on the cell type, as ESCs maintained their pluripotency, while HepaRG cells improved their hepatic differentiation. Cells were harmlessly harvested through chelating the calcium ions in the cross-linked alginate and de-cross-linking the scaffolds, indicating the potential of this study for scalable stem cell culture for numerous downstream applications.

N6-methyladenosine (m6A) has been recognized as a common type of post-transcriptional epigenetic modification. m6A modification and YTHDF1, one of its reader proteins, have been documented to play a pivotal role in numerous human diseases via regulating mRNA splicing, translation, stability, and subcellular localization. The chemotherapeutic drug cisplatin (CDP) can damage sensory hair cells (HCs) and result in permanent sensorineural hearing loss. However, whether YTHDF1-mediated modification of mRNA is potentially involved in CDP-induced injury in sensory hair cells was not fully clarified. This study investigated the potential mechanisms for the modification of YTHDF1 in CDP-induced damage in HCs. Here, we discovered that YTHDF1's expression level statistically increased significantly after treating with CDP. Apoptosis and cell death of HCs induced by CDP were exacerbated after the knockdown of YTHDF1, while overexpression of YTHDF1 in HCs alleviated their injury induced by CDP. Moreover, YTHDF1 expression correlated with cisplatin-induced autophagy with statistical significance in HCs; namely, YTHDF1's overexpression enhanced the activation of autophagy, while its deficiency suppressed autophagy and, at the same time, increased the loss of HCs after CDP damage. WB analysis and qRT-PCR results of autophagy-related genes indicated that YTHDF1 promoted the translation of autophagy-related genes ATG14, thus boosting autophagy. Therefore, CDP-induced YTHDF1 expression protected HCs against CDP-induced apoptosis by upregulating the translation of autophagy-related genes ATG14, along with enhancing autophagy. Based on these findings, it can be inferred that YTHDF1 is potentially a target for ameliorating drug-induced HCs damage through m6A modification.

Myelin undergoes various changes after nerve injury, and c-Jun has a close relationship with Schwann cells (SCs). However, it remains unclear whether c-Jun can be involved in nerve repair by regulating ferroptosis. To explore this, we first set up a facial nerve injury model and detected the changes of ferroptosis-related proteins and c-Jun by immunofluorescence and Western blot. Then, we cultured RSC 96 and pSCs, and studied the potential regulatory relationships by a combination of experimental methods such as CCK-8, ELISA, immunofluorescence, qRT-PCR, Western blot and viral transfection. Finally, we corroborated the role of c-Jun through animal experiments. Our experiments revealed that ferroptosis occurs after facial nerve injury. Erastin decreased GPX4, c-Jun proteins and GSH content, while PTGS2, NRF2, HO-1 proteins, MDA, Fe

A novel fourth-generation nickel-based single crystal superalloy was brazed with Co-based filler alloy. The effects of post-weld heat treatment (PWHT) on the microstructure and mechanical properties of brazed joints were investigated. The experimental and CALPHAD simulation results show that the non-isothermal solidification zone was composed of M3B2, MB-type boride and MC carbide, and the isothermal solidification zone was composed of γ and γ’ phases. After the PWHT, the distribution of borides and the morphology of the γ’ phase were changed. The change of the γ’ phase was mainly attributed to the effect of borides on the diffusion behavior of Al and Ta atoms. In the process of PWHT, stress concentration leads to the nucleation and growth of grains during recrystallization, thus forming high angle grain boundaries in the joint. The microhardness was slightly increased compared to the joint before PWHT. The relationship between microstructure and microhardness during the PWHT of the joint was discussed. In addition, the tensile strength and stress fracture life of the joints were significantly increased after the PWHT. The reasons for the improved mechanical properties of the joints were analyzed and the fracture mechanism of the joints was elucidated. These research results can provide important guidance for the brazing work of fourth-generation nickel-based single crystal superalloy.

Tumor angiogenesis, which may be affected by microenvironmental inflammation and promotes tumor development and metastasis, is one of the key reasons contributing to increased mortality. The goal of this study is to investigate how lignin analogs, specifically honokiol (HNK), block angiogenesis induced by the inflammatory milieu of lung cancer. The human lung cancer cell lines A549 and H460 were treated with HNK. Interleukin-1 was employed to mimic an inflammatory tumor microenvironment. Findings demonstrated that HNK drastically decreased the cell viability of A549 and H460 cells. In A549 and H460 cells, HNK also reduced the production of vascular endothelial growth factor (VEGF), the most important marker of tumor angiogenesis. Signal pathway studies revealed that HNK blocked the NF-κB signaling pathway. This effect, in turn, prevented the expression of VEGF by inhibiting the NF-κB signaling pathway. Human umbilical vein endothelial cells (HUVECs) from A549-conditioned medium cultures were subjected to HNK treatment, which decreased tubulogenesis, horizontal and vertical migration, and cell proliferation in HUVECs. Overall, HNK inhibited the NF-κB pathway. This effect resulted in the downregulation of VEGF, thus reducing the viability and angiogenesis of human lung cancer cell lines. In A549 cell xenografts, HNK decreased VEGF expression, tumor angiogenesis, and tumor development. Our research shows that HNK is a potential antiangiogenic molecule for the treatment of lung cancer.

Mutations in the

In this study, a modified coagulation sludge (MCS) from a real landfill leachate coagulation pretreatment was first prepared with polymerized ferric sulfate (PFS) as the activator for PMS to degrade bisphenol A (BPA). The results showed that 43.34% of BPA was adsorbed by MCS when [BPA]0 = 20 mg/L, [MCS]0 = 0.8 g/L, and time = 80 min. Thereafter, by adding 3000 mg/L PMS to initiate the oxidation process, complete BPA removal, i.e. 100%, was achieved in 60 min. In addition, in tap water and municipal wastewater scenarios, 100% and 90.07% removal of BPA were obtained, respectively, and MCS exhibited outstanding performance after repeated use. MCS displayed an excellent adsorption capacity in which chemical adsorption was the main effect, and hydroxyl radicals were the major contributor to BPA degradation. Characterizations of fresh and reacted MCS were conducted, and the results showed that the MCS structure was stable after repeated use, and the surface functional groups, surface defect sites, and iron oxides participated in PMS activation. Overall, this study demonstrated successful recycling of coagulation sludge from landfill leachate pretreatment to activate PMS for environmental pollution control, which is in accordance with the goal of using waste to control waste.

Parkinson's disease (PD) is the second most common neurodegenerative disorder characterized by the progressive loss of dopaminergic (DA) neurons in the substantia nigra pars compacta (SNpc). Rupture of lysosome is a major cellular stress condition leading to cell death in PD. We have previously shown that environmental oxidative toxins could impair autophagic flux and lysosomal functions in PD. Poloxamer 188 (P188) is an amphipathic polymer which has cytoprotective effect in traumatic brain injury and stroke. But whether Dyrk1A could rescue lysosome malfunction-mediated DA neuron death and α-synuclein aggregation in PD is still unknown. In the present study, MPTP mice models and MPP+-treated SH-SY5Y cells were used for study, and we found that P188 rescued MPP+-induced lysosomal dysfunction and impaired autophagy flux in mild MPP+-treated SH-SY5Y cells. P188 administration significantly restored lysosomal membrane integrity and prevented cathepsins leakage from the lysosomes into the cytoplasm, which triggered caspase-dependent apoptotic cell death in sub-acute MPTP mouse model and MPP+-treated SH-SY5Y cells. Furthermore, P188 ameliorated α-synuclein accumulation and behavioral impairment in chronic MPTP mouse model with MPTP and probenecid treatment. P188 could alleviate MPTP-induced DA neurons damage by restoring lysosome function.

We attempted to improve the accuracy of coronary CT angiography (CCTA)-derived fractional flow reserve (FFR) (FFRPatients who underwent CCTA and interventional FFR were enrolled retrospectively. Seventy-six patients qualified based on the inclusion criteria. The three-dimensional (3D) coronary artery tree was reconstructed to generate a finite element mesh for each subject with different lower limits of luminal diameter (1.2 mm and 0.8 mm). Outlet boundary conditions were defined according to Murray's law. The Newton-Krylov-Schwarz (NKS) method was applied to solve the governing equations of CFD to derive FFRAt the individual patient level, extending the minimal diameter of the coronary tree from 1.2 to 0.8 mm improved the sensitivity of FFRExtending the reconstructed coronary tree to a smaller luminal diameter can considerably improve the sensitivity of FFR• Extending the reconstructed coronary tree to a smaller luminal diameter can considerably improve the sensitivity of FFR

Objective. A previous study has shown that a data-driven approach can significantly improve the discriminative power of transfer function analysis (TFA) used to differentiate between normal and impaired cerebral autoregulation (CA) in two groups of data. The data was collected from both healthy subjects (assumed to have normal CA) and symptomatic patients with severe stenosis (assumed to have impaired CA). However, the sample size of the labeled data was relatively small, owing to the difficulty in data collection. Therefore, in this proof-of-concept study, we investigate the feasibility of using an unsupervised learning model to differentiate between normal and impaired CA on TFA variables without requiring labeled data for learning.Approach. Continuous arterial blood pressure (ABP) and cerebral blood flow velocity (CBFV), which were recorded simultaneously for approximately 10 min, were included from 148 subjects (41 healthy subjects, 31 with mild stenosis, 13 with moderate stenosis, 22 asymptomatic patients with severe stenosis, and 41 symptomatic patients with severe stenosis). Tiecks' model was used to generate surrogate data with normal and impaired CA. A recently proposed unsupervised learning model was optimized and applied to separate the normal and impaired CA for both the surrogate data and real data.Main results. It achieved 98.9% and 74.1% accuracy for the surrogate and real data, respectively.Significance. To our knowledge, this is the first attempt to employ an unsupervised data-driven approach to assess CA using TFA. This method enables the development of a classifier to determine the status of CA, which is currently lacking.

Radiotherapy is an effective treatment for pancreatic cancer. However, radio-resistance often resulted in poor prognostic. Ibrutinib is an orally small molecule drug in B cell malignancies. Here, we investigated for the first time the effect of ibrutinib on radio-sensitivity of human pancreatic cancer cells in vitro and the potential mechanism involved in it. Human BXPC3 and Capan2 cell lines were treated with ibrutinib, and cell viability was conducted with CCK-8 assay. Cell clone formation was observed after treated with ibrutinib and (or) radiation by clone formation assay. The cell cycle and cell apoptosis were measured by flow cytometry. Protein levels was analyzed by western blot. The results revealed that ibrutinib inhibited the proliferation of pancreatic cancer cells. Ibrutinib enhanced the effect of radiation with a sensitization enhancement ratio (SER) of 1.34, 1.68 in BXPC3 and Capan2 cells respectively. Ibrutinib combined with radiation induced G2/M arrest and cell apoptosis. Further investigations revealed that ibrutinib decreased the phosphorylation of EGFR, then reversed the upregulation of p-AKT and downstream genes by radiation. In conclusion, these results suggested that ibrutinib might be an excellent radiosensitizer in pancreatic cancer.

In this research, for the first time, three kinds of landfill leachate (young (YL), mature (ML) and mixed (MYL) leachate) were treated in a semi-aerobic aged refuse biofilter (SAARB) to compare the effectiveness of, and microbial changes in, this biofilter when treating leachates that have significantly different characteristics. The SAARB achieved stable removal of organic matter from all three leachates and reduced the concentrations of aromatic substances. The best treatment was achieved with YL, followed in order by MYL and ML. The removal of nitrogen from all three leachates by the SAARB was particularly significant. The microbial abundance and diversity in the media of the SAARB changed after treatment of the three leachates, and the order of change from small to large was ML# MYL# YL#. The microbial communities were mainly affected by (and negatively correlated to) the relative content of refractory organics in leachate. Proteobacteria was the dominant microorganism. Deinococcus-thermus responded most to the quality of leachate being treated, increasing in relative abundance as the content of refractory organics increased. This was opposite to the response of Chloroflexi. In YL# the dominant species at the genus level was Thauera, and in ML# the dominant species were Truepera and Iodidimonas. The microbial activity and metabolic intensity were enhanced after treatment of the different leachates. The expression of nitrification-related genes was the strongest and the total abundance was the highest when YL was treated. This study promotes the optimization and application of SAARB.

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Face anti-spoofing detection is a crucial procedure in biometric face recognition systems. State-of-the-art approaches, based on Convolutional Neural Networks (CNNs), present good results in this field. However, previous works focus on one single modal data with limited number of subjects. The recently published CASIA-SURF dataset is the largest dataset that consists of 1000 subjects and 21000 video clips with 3 modalities (RGB, Depth and IR). In this paper, we propose a multi-stream CNN architecture called FaceBagNet to make full use of this data. The input of FaceBagNet is patch-level images which contributes to extract spoof-specific discriminative information. In addition, in order to prevent overfitting and for better learning the fusion features, we design a Modal Feature Erasing (MFE) operation on the multi-modal features which erases features from one randomly selected modality during training. As the result, our approach wins the second place in CVPR 2019 ChaLearn Face Anti-spoofing attack detection challenge. Our final submission gets the score of 99.8052% (TPR@FPR = 10e-4) on the test set.

Bruceine D (BD) is the quassinoids isolated from the traditional Chinese herbal medicine Brucea javanica’s fruit, which exhibits anti-cancer activity. Here, we demonstrated that BD inhibited human non-small cell lung cancer (NSCLC) cell lines in vitro that were attributed to the induction of cell apoptosis. Human NSCLC H460 and A549 cell lines were treated with BD, and cell viability was conducted with CCK-8 assay. Cell clone formation was observed by clone formation assay. Cell apoptosis was measured using DAPI staining and flow cytometry. Protein levels was analyzed by western blot. The results showed BD inhibited the cell viability of H460 and A549 cells in a dose-dependent manner with IC50 values of 0.5 and 0.6 μmol/L, respectively, at 48 h of treatment. Treatment with BD (0.125–1.0 μmol/L) dose-dependently promoted chromatin condensation, Annexin V-positive cell population and caspase-dependent apoptosis in H460 and A549 cells. Mechanistically, BD stimulated the phosphorylation of JNK. Furthermore, the anti-cancer effects of BD were alleviated effectively by a specific JNK inhibitor SP600125 in NSCLC cells. In conclusion, the results demonstrated that BD exerted anti-cancer activity against NSCLC cells through JNK activation, which suggests its potent usefulness for prevention and treatment of NSCLC.

An Fe0-participated O3/H2O2 (Fe0-O3/H2O2) process was applied to remove refractory organic matter (OM) in semi-aerobic aged refuse biofilter (SAARB) leachate arising from treating mature landfill leachate. The degradation and transformation characteristics of refractory OM were revealed at molecular level. Removal efficiencies of aromatic substances were 63.55% by the Fe0-O3/H2O2 process (much higher than in other single or binary processes), and fulvic- and humic-like substances were more effectively degraded by this process than by other treatments. According to Fourier transform-ion cyclotron resonance mass spectrometry (FT-ICR MS), 6645 categories of OM in SAARB leachate were identified. Although there was little difference in number of OM categories after treatment using the single-O3 and Fe0-O3/H2O2 processes, Fe0-O3/H2O2 process can better reduce OM relative abundance. It is noteworthy that the Fe0-O3/H2O2 process more effectively degraded CHONS compounds than the single-O3 process, while also producing more CHO compounds having higher bio-availability. The enhanced degradation efficiency of the Fe0-O3/H2O2 process were attributed to the formation of the Fenton process initiated by leached Fe2+ and H2O2. The heterogeneous catalytic effect from iron (hydro) oxides for O3/H2O2 also increased the treatment capacity of the Fe0-O3/H2O2 process, resulting in better total organic carbon removal. The Fe0-O3/H2O2 process is an efficient method for removing refractory OM in SAARB leachate.

Durability is one of the key properties of the cement-based materials (CBMs) and is affected significantly by water migration in CBMs. Sorptivity S and capillarity coefficient k are two of the vital parameters to evaluate the water migration behavior of CBMs and are related closely to its microstructure. In this study, the low-field nuclear magnetic resonance (LF-NMR) was used to measure the pore size distribution and porosity of mortars. Additionally, according to the authors’ previous experimental results using the LF-NMR imaging and gravimetric method, the S and k were calculated, respectively. The results showed that the equivalent pore radius rm of mortar, determined by the pore size distribution, increased with water to binder (w/b) ratio and sand to binder (s/b) ratio, and decreased with silica fume (SF) and super-absorbent polymer (SAP) content. However, the porosity of mortar increased with w/b ratio and SF content, decreased with s/b ratio, while first increased and then decreased with SAP content. Meanwhile, the S was improved with the increasing w/b ratio and SF content, deteriorated with the increase in s/b ratio, while first improved and deteriorated with SAP content. The trend of the k of mortar was similar to that of S. The analytical models for predicting S and k of mortars were proposed, which were based on their microstructure and considered the effects of tortuosity and roundness, and were successfully verified by the test results with the present investigation and the existing literatures. Besides, the relationship between S and k was given and the ratio k/S was approximately between 5.0 and 10.0.

Macromolecular refractory organics in landfill leachate are extremely complex compounds. This study examined the molecular-level transformation characteristics of refractory organics in biologically-treated landfill leachate (i.e., membrane bioreactor (MBR) leachate) during ozonation treatment. Results indicated that higher ozone dosage and longer reaction time enhanced organics removal. When ozone dosage was 32.16 mg/min and reaction time was 30 min, the efficiencies of removing color number, chemical oxygen demand (COD), and dissolved organic carbon (DOC) were 95.16%, 51.13%, and 26.40%, respectively. Furthermore COD / DOC decreased from 3.38 to 2.24, and the content of aromatic substances and macromolecular humic substances (e.g., humic- and fulvic-like substances) substantially decreased. The MBR-treated leachate mainly contained phenolic compounds (82%, aromatic index ≤ 0.50 and H/C1.5), and the major elements within the dissolved organic matter in the MBR-treated leachate were C, H, O, N, and S. The CHOS and CHONS compounds in the leachate indicated that it would have a much greater biorefractory property than the natural organic matter (i.e., technical grade humic acid). After the MBR-treated leachate was treated by ozonation for 10 min, the CHO, CHON, CHOS and CHONS compounds were greatly degraded and removed, and the oxidation degree of dissolved organic matter was significantly increased owing to the strong oxidation ability of ozone. At 30 min of ozonation, CHON, CHOS and CHONS compounds were further degraded, and CHOS and CHONS compounds (as the biorefractory substances) were almost completely removed. It was noteworthy that some CHO compounds that mainly contained phenolic compounds (m/z = 250-300, carbon number 20, and double bond equivalent6) with a higher bioavailability and higher saturation degree accumulated. This study provides beneficial references for practical application of landfill leachate treatment using the ozonation process.

MicroRNAs (miRs) are endogenous substances that act as important diagnostic and treatment targets in renal diseases. miR-146 plays an important role in the development of endotoxin tolerance through NF-κB pathway, but the underlying mechanism is not clearly understood. The aim of this study was to determine the molecular regulation and function of miR-146 and also the expression of miR-146 in an experimental model of renal ischemia reperfusion injury (IRI).IRI was induced in mouse by bilateral IRI for 45 min followed by reperfusion. The male mice were randomized as: sham, I/R, I/R+miR-146, and I/R+antago-miR-146 groups. Renal function, histological damage, and cell apoptosis were evaluated at 24 h after reperfusion.Overexpression of miR-146 protected renal function. Renal cells with upregulated miR-146 had lower plasma levels of blood urea nitrogen (BUN) and creatinine, decreased apoptosis and active caspase-3 protein expressions. miR-146 was shown to have a role in renal IR injury. miR-146 has a protective effect on renal function and plays a significant role in apoptosis. IGSF1 acts as a target of miR-146. IGSF1 rescued the effects of miR-146 on renal IRI. miR-146 protected renal function by activation of PI3K/AKT.These findings suggest that miR-146 might regulate apoptosis and can cause injury in I/R via targeting IGSF1 and also exert renal protection property.

With the incoming of the Internet times, the design pattern of product has been greatly changed. The enterprises have been developing from the past sequential and vertical structures to the parallel and horizontal structures. Design management has become the core of information management and electronic commerce for corporations. The development of design management affects the progress of industry design itself. The article illustrates the necessity of design management system for enterprises' development, researches the techniques and methods for generating the computer aided design management system, and expounds the developing modes and the whole framework of the design management system under the conditions of the high technology, such as network, virtual reality and rapid prototyping.