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To investigate the contamination characteristics and potential ecological risks of pharmaceuticals and personal care products (PPCPs) in the Third Drain of Ningxia, 14 PPCPs were detected and analyzed using solid-phase extraction coupled with ultra-high performance liquid chromatography-tandem mass spectrometry. The results showed that these 14 PPCPs were detected in the Third Drain and its confluent streams, with total concentrations of 117.74-1947.64 ng·L

In this paper, it is found that the preferential growth of secondary {117} facets of Bi24O31Br10 into dominant facets would lead to higher photocatalytic activity, although the original main {213} facet has a stronger molecular oxygen adsorption ability, which illustrates that the charge separation efficiency induced by dominant/secondary facet control plays a more important role than that of O2 adsorptive performance in improving activity.

Solid-phase extraction and ultra-high performance liquid chromatography-electrostatic field orbit hydrazine mass spectrometry were used to detect and analyze the contamination of nine antibiotics including sulfonamides, tetracyclines, macrolides, quinolones, and lincomycin in the third drain of Ningxia. Correlations between the antibiotic concentration and water quality indexes were explored, and the ecological risks were evaluated. The results showed that seven antibiotics were detected in the third drain and its confluent stream, with the total concentrations of 14.91-153.48 ng·L

In this paper, it is found that the preferential growth of secondary {117} facets of Bi

3d-4f heterometallic supertetrahedral clusters with the formula of Ln

Retinal organoids (ROs) derived from human inducible pluripotent stem cells (hiPSCs) exhibit considerable therapeutic potential. However, current quality control of ROs during in vitro differentiation is largely limited to the detection of molecular markers, often by immunostaining, polymerase chain reaction (PCR) assays and sequencing, often without proper functional assessments. As such, in the current study, we systemically characterized the physiological maturation of photoreceptor-like cells in hiPSC-derived ROs. By performing patch-clamp recordings from photoreceptor-like cells in ROs at distinct differentiation stages (ie, Differentiation Day [D]90, D150, and D200), we determined the electrophysiological properties of the plasma membrane and several characteristic ion channels closely associated with the physiological functions of the photoreceptors. Ionic hallmarks, such as hyperpolarization-activated cyclic nucleotide-gated (HCN) channels and cyclic nucleotide-gated (CNG) channels, matured progressively during differentiation. After D200 in culture, these characteristic currents closely resembled those in macaque or human native photoreceptors. Furthermore, we demonstrated that the hyperpolarization-activated inward current/depolarization-activated outward current ratio (I−120/I+40), termed as the inward-outward current (IOC) ratio hereon, accurately represented the maturity of photoreceptors and could serve as a sensitive indicator of pathological state. Thus, this study provides a comprehensive dataset describing the electrophysiological maturation of photoreceptor-like cells in hiPSC-derived ROs for precise and sensitive quality control during RO differentiation.

Persistent neural activity in cortical, hippocampal, and motor networks has been described as mediating working memory for transiently encountered stimuli. Internal emotional states, such as fear, also persist following exposure to an inciting stimulus, but it is unclear whether slow neural dynamics are involved in this process. Neurons in the dorsomedial and central subdivisions of the ventromedial hypothalamus (VMHdm/c) that express the nuclear receptor protein NR5A1 (also known as SF1) are necessary for defensive responses to predators in mice. Optogenetic activation of these neurons, referred to here as VMHdm^(SF1) neurons, elicits defensive behaviours that outlast stimulation, which suggests the induction of a persistent internal state of fear or anxiety. Here we show that in response to naturalistic threatening stimuli, VMHdm^(SF1) neurons in mice exhibit activity that lasts for many tens of seconds. This persistent activity was correlated with, and required for, persistent defensive behaviour in an open-field assay, and depended on neurotransmitter release from VMHdm^(SF1) neurons. Stimulation and calcium imaging in acute slices showed that there is local excitatory connectivity between VMHdm^(SF1) neurons. Microendoscopic calcium imaging of VMHdm^(SF1) neurons revealed that persistent activity at the population level reflects heterogeneous dynamics among individual cells. Unexpectedly, distinct but overlapping VMHdm^(SF1) subpopulations were persistently activated by different modalities of threatening stimulus. Computational modelling suggests that neither recurrent excitation nor slow-acting neuromodulators alone can account for persistent activity that maintains stimulus identity. Our results show that stimulus-specific slow neural dynamics in the hypothalamus, on a time scale orders of magnitude longer than that of working memory in the cortex, contribute to a persistent emotional state.

A series of POM-based all-inorganic open frameworks, H

Thymocyte-expressed, positive selection-associated 1 (Tespa1) is a critical signaling molecule in thymocyte development. This study demonstrates the negative regulatory effect of Tespa1 on mast cells. This effect is associated with the interleukin (IL)-4 /signal transducers and activators of transcription 6 (STAT6) signaling pathway. Experimental results showed the decreased Tespa1 mRNA expression level in the sputum of patients with asthma compared with that of healthy individuals. In addition, animal experiments showed that Tespa1 knockout (Tespa1-/-) mice exhibited more severe inflammation, higher quantity of goblet cells and mast cells in the bronchium, and greater activity of mast cell tryptase, which is induced by ovalbumin, than the wild-type (WT) mice. Enzymelinked immunosorbent assay and Western blot results showed that IL-4, IL13, phospho-Janus kinase 1, and P-STAT6 expressions presented a higher increase in the i>Tespa1-/- mouse model than in the WT mouse model. Further in vitro studies confirmed that IL-4 could more significantly promote tryptase and P-STAT6 activities in i>Tespa1-/- mast cells than their WT counterparts. Correlation analysis results showed a negative correlation between Tespa1 and P-STAT6. Immunoprecipitation results showed a direct link between Tespa1 and STAT6. Altogether, our results indicate that Tespa1 can negatively regulate mast cell activity, and this event is related to the mast cell IL-4/STAT6 signaling pathway and could be therapeutically exploited to treat asthma attacks. Funding Statement: This work was supported by grants from the National Natural Science Foundation of China (No. 81570013), Application Project of Lishui (NO. 2016GYX33), Natural Science Foundation of Zhejiang province, China (NO. LY17H100001) and Zhejiang University Student Science and Technology Innovation Activity Plan (New Talent Program) (NO. 2019R434018). Declaration of Interests: The authors declare no competing financial interests. Ethics Approval Statement: This study was conducted in strict accordance with the recommendations of the Guide for the Care and Use of Laboratory Animals of the National Institutes of Health, and its protocol was approved by the Animal Research Ethics Board of the Lishui University (Lishui, Zhejiang Province, China. Permit Number: 0901-2018).

Background Thymocyte-expressed, positive selection-associated 1 (Tespa1) is a critical signaling molecule in thymocyte development. This study aimed to investigate the regulatory effect of Tespa1 on mast cells in the pathogenesis of asthma and its relationship with the interleukin (IL)-4/signal transducers and activators of transcription 6 (STAT6) signaling pathway. Methods Tespa1 mRNA expression analysis and IgE levels were carried out using the induced sputum of 33 adults with stable asthma and 36 healthy controls. Tespa1-knockout mice (Tespa1−/−, KO) and C57BL/6 background (wild-type, WT) mice were sensitized and treated with ovalbumin (OVA) to establish an asthma model. Pathological changes, number and activity of mast cells, and changes in activation of the IL-4/STAT6 pathway in lung tissue were detected. The changes of tryptase expression and STAT6 activation after mast cell gene knockout were analyzed in vitro. The changes of enzyme expression and STAT6 activation after mast cell gene knockout were analyzed in vitro. The association between the Tespa1 and p-STAT6 was analyzed by co-immunoprecipitation method. Results Compared with the healthy controls, Tespa1 expression was decreased, and IgE levels were elevated in the sputum of asthmatic patients. Animal experiments showed that Tespa1−/− mice exhibited more severe inflammation, higher quantity of goblet cells and mast cells in the bronchium, and greater expression of mast cell tryptase, which is induced by ovalbumin, than WT mice. And IL-4, IL-13, phospho-Janus kinase 1, and p-STAT6 expressions presented a higher increase in the Tespa1−/− mouse model than in the WT mouse model. Further in vitro studies confirmed that IL-4 could more significantly promote tryptase and p-STAT6 activities in Tespa1−/− mast cells than their WT counterparts. Correlation analysis results showed a negative correlation between Tespa1 and p-STAT6. Co-immunoprecipitation results demonstrated an association between Tespa1 and p-STAT6. Conclusions Altogether, our results indicate that Tespa1 can negatively regulate mast cell activity, and this event is related to the mast cell IL-4/STAT6 signaling pathway and could be therapeutically exploited to treat asthma attacks.

Liquid-phase adsorption of Cu2+ ions onto magnetic Fe3O4@graphene oxide (GO) composites, prepared by a co-precipitation approach, has been investigated. This synthesis method is capable of depositing highly crystalline Fe3O4 nanoparticles onto GO sheets. The adsorption temperature and the weight ratio of Fe3O4 nanoparticles to GO sheets are found to be crucial factors affecting the adsorption performance. The pH value of the aqueous solution has a strong influence on the adsorption capacity of Cu2+ ions. The Langmuir, Freundlich, and Dubinin-Radushkevich (D-R) adsorption models were adopted to fit the adsorption isotherms. The deposition of magnetite enhances the equilibrium rate constant (Langmuir model) and the adsorption energy (D-R model). The analysis of thermodynamic parameters reveals that the adsorption of Cu2+ ions is a favorable and spontaneous process. However, a moderate density of magnetite onto GO substrate is essential for the design of Fe3O4@GO adsorbents for efficient removal of metal ions from an aqueous solution.

The removal of copper ions by magnetic Fe3O4/carbon nanotube (CNT) composite adsorbents, prepared by co-precipitation method, in aqueous solution has been investigated. The influence of magnetite loading (35.5‒64.1 wt.%) onto oxidized CNT support on the adsorption capacity and regeneration efficiency is investigated. The adsorption isotherms of Cu2+ ions are well characterized by Langmuir, Freundlich, and Dubinin–Radushkevich models within the temperature range of 303‒323 K. The decoration of magnetic Fe3O4 significantly enhances the removal efficiency, equilibrium rate constant, and adsorption capacity, as analyzed by these models. The appropriate loading of magnetite nanoparticles on the CNT supports not only increases adsorption capacity but also facilitates regeneration efficiency. Accordingly, the Fe3O4/CNT composite can be used as an effective adsorbent for rapid removal of Cu2+ ions from aqueous solution.

Autophagy and apoptosis are common responses to pathological damage in the process of Parkinson's disease (PD), and lysosome dysfunction may contribute to the etiology of PD's neurodegenerative process. In this study, we demonstrated that the neurotoxin 6-hydroxydopamine (6-OHDA) increased autophagy in SH-SY5Y cells, as determined by detection of the lysosome marker lysosomal-associated membrane protein1, the autophagy protein light chain 3 (LC3)-II and the autophagy substrate P62 protein. Meanwhile, autophagy repression with 3-methyladenine accelerated the activation of caspase-3 and PARP and aggravated the cell apoptotic death induced by 6-OHDA. Furthermore, we found that 6-OHDA treatment resulted in a transient increase in the intracellular and nuclear expression of cathepsin L (CTSL). The CTSL inhibitor, Z-FY-CHO, could promote autophagy, decrease accumulation of P62, and block activation of caspase-3 and PARP. Taken together, these results suggest that activation of autophagy may primarily be a protective process in SH-SY5Y cell death induced by 6-OHDA, and the nuclear translocation of CTSL could enhance the cell apoptotic cascade via disturbing autophagy-apoptotic systems in SH-SY5Y cells. Our findings highlight the potential role of CTSL in the cross talk between autophagy and apoptosis, which might be considered a therapeutic strategy for treatment of pathologic conditions associated with neurodegeneration.

An HDR-based Cas9/RecA system was developed to precisely correct the Pde6b mutation in rods of rd1 mice to restore their vision., Although Cas9-mediated genome editing has been widely used to engineer alleles in animal models of human inherited diseases, very few homology-directed repair (HDR)–based genetic editing systems have been established in postnatal mouse models for effective and lasting phenotypic rescue. Here, we developed an HDR-based Cas9/RecA system to precisely correct Pde6b mutation with increased HDR efficiency in postnatal rodless (rd1) mice, a retinitis pigmentosa (RP) mutant model characterized by photoreceptor degeneration and loss of vision. The Cas9/RecA system incorporated Cas9 endonuclease enzyme to generate double-strand breaks (DSBs) and bacterial recombinase A (RecA) to increase homologous recombination. Our data revealed that Cas9/RecA treatment significantly promoted the survival of both rod and cone photoreceptors, restored the expression of PDE6B in rod photoreceptors, and enhanced the visual functions of rd1 mice. Thus, this study provides a precise therapeutic strategy for RP and other genetic diseases.

The pharmaceuticals and personal care products (PPCPs) released into urban rivers are triggering certain ecological risks. The current study investigated the removal efficiencies of 30 frequently detected PPCPs by two river water bypass treatment processes (CS-BAF-UF-Ozone and CS-MBR-Ozone), and investigated the removal mechanism and eco-toxicological risk variation of target compounds via section-removal investigation and risk quotient model, respectively. Results indicated that both processes could efficiently remove the target PPCPs; the removal rates of tetracyclines and caffeine were90% in the biological sections, while sulfonamides, fluoroquinolones, and other pharmaceuticals could only be efficiently removed when the COD of the influent and the water temperature were comparatively higher; the ozone process had particular effect on removing these compounds. The cumulative removal rate of all PPCPs during the whole process was higher than 92.5%. The total risk quotient (RQ

Ovarian cancer (OC) is the leading cause of death among all gynecological malignancies in the world and its underlying mechanism is still unclear. Compared with research on microRNAs, research on long non-coding RNAs (lncRNAs) is still in its infancy. Studies in recent years have demonstrated that lncRNAs exhibit multiple biological functions in various stages of OC development. In this review, we conclude that lncRNAs are closely involved in the pathogenesis of OC. The expression of lncRNAs indicates the early diagnosis, prognosis, and response to chemotherapy of OC. An attractive approach to treatment of OC is lncRNA small interfering RNA or acting as a plasmid targeting the expression of toxic genes, which is a novel step toward a major breakthrough in the treatment of human OC. E2-regulated lncRNA and its polymorphism, methylation, are also involved in OC. Further research efforts are needed before fully identifying, characterizing, and elucidating the actual functions of lncRNAs in OC at the molecular level and putting them into clinical practice.

Metastasis is a multistep process by which tumor cells disseminate from their primary site and form secondary tumors at a distant site. The pathophysiological course of metastasis is mediated by the dynamic plasticity of cancer cells, which enables them to shift between epithelial and mesenchymal phenotypes through a transcriptionally regulated program termed epithelial-to-mesenchymal transition (EMT) and its reverse process, mesenchymal-to-epithelial transition (MET). Using a mouse model of spontaneous metastatic breast cancer, we investigated the molecular mediators of metastatic competence within a heterogeneous primary tumor and how these cells then manipulated their epithelial-mesenchymal plasticity during the metastatic process. We isolated cells from the primary mammary tumor, the circulation, and metastatic lesions in the lung in TA2 mice and found that the long noncoding RNA (lncRNA) H19 mediated EMT and MET by differentially acting as a sponge for the microRNAs miR-200b/c and let-7b. We found that this ability enabled H19 to modulate the expression of the microRNA targets Git2 and Cyth3 , respectively, which encode regulators of the RAS superfamily member adenosine 5′-diphosphate (ADP) ribosylation factor (ARF), a guanosine triphosphatase (GTPase) that promotes cell migration associated with EMT and disseminating tumor cells. Decreasing the abundance of H19 or manipulating that of members in its axis prevented metastasis from grafts in syngeneic mice. Abundance of H19, GIT2, and CYTH3 in patient samples further suggests that H19 might be exploited as a biomarker for metastatic cells within breast tumors and perhaps as a therapeutic target to prevent metastasis.

The zero-valent iron (ZVI) particles were synthesized by the aqueous phase reduction, and the tapping mode image of atomic force microscope (AFM) showed that the diameter of the ZVI particles was in the range of 90 nm - 400 nm. By comparison of the debromination of BDE-47 by sunlight, ZVI, ZVI impregnated activated carbon (ZVI/AC) and ZVI impregnated ion exchange resin (ZVI/IER), the debromination effect was found to descend in the following order: ZVI/IER > ZVI/AC > ZVI > sunlight. Second order and first order kinetic models were used for the fitting of the debromination data of BDE-47. Results show that the debromination data of BDE-47 by the sunlight, ZVI, ZVI/AC and ZVI/IER in the current study are generally best described by the pseudo first order equation. Meanwhile, the debromination data of BDE-47 by the ZVI and ZVI/IER can also be described by the pseudo second order equation.

Heavy metals (Hg, As, Pb, Cd, Cr, Cu) pollution in soil samples of Rosa sterilis planting areas located in Wudang District in Guiyang and Pingba County in Anshun was studied using a new evaluation theory of pollution loss rate, and following a series of methods for Rosa sterilis leaf including over standard rate, enrichment coefficient, single pollution index and comprehensive pollution index, the heavy metals pollution of the two Rosa sterilis planting areas was analyzed and evaluated. The results showed that the soil comprehensive pollution loss rate ranged from 12.73% to 28.26% in Wudang District samples, most of which belong to light pollution level. The comprehensive soil pollution loss rate of the sampling points in Pingba County varied from 9.68% to 16.10%, which belong to fairly clean level. Meanwhile, the experimental results for the Rosa sterilis leaf showed that the contents of Cr and Pb in both planting areas exceeded the permissible limit, while other elements were below the safe limit. The six heavy metal elements in Rosa sterilis leaf did not accumulate.

Chili powder-enriched dough was sandwiched between two dough layers prepared from (a) wheat flour, (b) wheat flour plus resistant starch flour and (c) wheat flour plus soy protein isolate (SPI) and microbial transglutaminase (MTGase), and these were used for preparing wheat flour control (LN-C), wheat flour-resistant starch (LN-F) and wheat flour-SPI-MTGase (LN-S) noodles, respectively. All cooked noodles were assessed for physical properties, starch digestibility and capsaicin-retaining abilities. Compared to other noodles, the LN-S noodles exhibited the highest tensile strength and elasticity, and the highest capsaicin retaining ability at pH 7.4. However, at pH 1.2 the capsaicin-retaining ability of all noodles was similar. The predicted glycemic indices (pGIs) of LN-F and LN-S noodles were similar ( P > 0.05), and were significantly ( P

This paper reports a study on vertical distribution characteristics of phosphorus speciation in samples collected at four sites from Baihua Lake, based on the Standards, Measurements and Testing (SMT) programme. In this study, the total phosphorus (TP) concentrations of these sediments samples varied from 944.86 to 2591.56 mg/kg and inorganic phosphorus (IP) was the main phosphorus fraction. For this heavily contaminated sediment, the IP mainly consisted of the Fe/Al-P. The vertical variation of the phosphorus had a tendency to decrease with the depth at sites JYS and YPZ. Since the concentrations of the TP in sediments were high and the phosphorus release potential and bioavailability were significant, the lake is still facing an ecological risk.

The quantitative structure property relationship (QSPR) study was performed in this work to develop models to predict the normalized reaction rate constants for the reductive debromination of polybrominated diphenyl ethers (PBDEs) by zero-valent iron (ZVI). In order to consider the solvent effect, conductor-like polarizable continuum model (CPCM) was applied to optimize the geometries and obtain the molecular descriptors using the pseudopotential basis set. The prediction results with the inclusion of solvent effect are slightly better than that of the corresponding gas-phase calculations. The artificial neural network (ANN) model could be more satisfactory to predict the rate constants than the partial least squares regression (PLSR) and principal component analysis-multiple linear regression analysis (PCA-MLR) models.

Neutral PBDEs congeners and their corresponding radical anions were studied with the pseudopotential method of stuttgart group (SDD) effective-core potentials basis set for the bromine atoms and the all-electron basis set for all other atoms. The pseudopotential method can be used for compounds containing heavy elements with relativistic effects and can reduce the computational time. The quantitative structure property relationship (QSPR) study was also performed in this work to develop models to predict the normolized reaction rate constants for the reductive debromination of polybrominated diphenyl ethers (PBDEs) by zero-valent iron (ZVI). The partial least squares regression (PLSR), principal component analysis-multiple linear regression analysis (PCA-MLR), and back propagation artificial neural network (BP-ANN) approaches were employed for the QSPR study between the molecular descriptors and the logarithm of normalized reaction rate constants of fourteen selected BDE congeners. The results show that the ANN models could be more satisfactorily to predict the rate constants than the PLSR and PCA-MLR models.

The modified Tessier method was used in the present study to analyze the antimony (Sb) speciation in suspended solids in mining wastewater from Ban-po Antimony Mine in Guizhou province. It was found that the residual fraction and the soluble fraction are the highest and the lowest in the five Sb fractions, accounting for 62.5% and 3% of the total respectively. The order of the five Sb fractions is: the residual fraction > the reduced fraction > the oxidation fraction > the acid-extractable fraction > the soluble fraction. The antimony soluble form in aqueous solution is mainly Sb (V), about 90% of the total. The results from the analysis by X-ray diffraction and scanning electron microscopy showed that the major crystalline forms of suspended solids are K-Mg-Fe-Al-Si-O-H2O, Cu3SbS4, 3CaO·2Sb2O5·8H2O, SiO2 and the content of antimony element is approximately 2.55%.

The concentration of ammonia nitrogen in a slaughterhouse wastewater sample was determined using Nessler's reagent spectrophotometry with four different pretreatment approaches. Comparison of the results shows that the concentrations increased in the following order: coagulation sedimentation < boric acid absorption < filtration < acidifying filtration. Boric acid absorption method is more favorable, and standard curve method (SCM) should be considered superior to standard addition method (SAM) in the present research.

Cortical inhibitory circuits play important roles in shaping sensory processing. In auditory cortex, however, functional properties of genetically identified inhibitory neurons are poorly characterized. By two-photon imaging-guided recordings, we specifically targeted 2 major types of cortical inhibitory neuron, parvalbumin (PV) and somatostatin (SOM) expressing neurons, in superficial layers of mouse auditory cortex. We found that PV cells exhibited broader tonal receptive fields with lower intensity thresholds and stronger tone-evoked spike responses compared with SOM neurons. The latter exhibited similar frequency selectivity as excitatory neurons. The broader/weaker frequency tuning of PV neurons was attributed to a broader range of synaptic inputs and stronger subthreshold responses elicited, which resulted in a higher efficiency in the conversion of input to output. In addition, onsets of both the input and spike responses of SOM neurons were significantly delayed compared with PV and excitatory cells. Our results suggest that PV and SOM neurons engage in auditory cortical circuits in different manners: while PV neurons may provide broadly tuned feedforward inhibition for a rapid control of ascending inputs to excitatory neurons, the delayed and more selective inhibition from SOM neurons may provide a specific modulation of feedback inputs on their distal dendrites.

Objective: To study the effect of microRna-21 (miRna-21) on the regulation of the interleukin 12 (iL-12)/signal transducer and activator of transcription 4 (STaT4) pathway in the lung tissue of asthmatic mice. Material and methods: Forty five male C57BL/6 mice were randomly divided into three groups of 15 mice each: normal control, asthmatic model, and dexamethasone. our mouse model of allergic asathma was established using oVa sensitization and challenge. Hematoxylin and eosin staining was performed to observe the pathological changes in lung tissue morphology. Both the total cell number and the amount of eosinophils (EoS) in the bronchoalveolar lavage fluid (BaLF) were manually counted. The expression of miRna-21 was detected by real time quantitative PCR. The expression levels of iL-12 and STaT4 in lung tissue were assayed via western blot, and immunohistochemistry was used to observe the distribution of their expression. Results: The expression levels of miRna-21 as well as the total number of BaLF cells and EoS were significantly higher in the asthmatic model group than in the control or dexamethasone groups, with significantly higher amounts found in the dexamethasone group than in the control group. The expression levels of iL-12 and STaT4 proteins were lower in the asthmatic model group than in the control and dexamethasone groups, with a significantly lower expression of iL-12 and STaT4 in the dexamethasone group than in the control group. Conclusions: The expression level of miRna-21 was significantly increased and the expression level of iL-12 and STaT4 proteins was significantly decreased in allergic asthmatic mice compared with normal control mice. These findings suggest a role for miRna-21 and the iL-12/STaT4 pathway in the development of allergic asthma.

This paper makes a detailed analysis on the natural conditions, flood disasters and watercourse conditions and evolution in Yibin, and conducts an analytical study on the flood control in Yibin Reach based on the needs of social and economic development in Yibin City. Based on hydrologic and hydraulic calculations as well as the layout of the project, it puts forward the recommendations for urban flood control in Yibin Reach, which is of great importance to improve the regional ecological environment and promote the development of regional economy in Yibin, and can bring considerable social benefits and economic benefits.

Specialty layered noodles (LN) were prepared by sandwiching a capsaicin-enriched dough (CED) between two gastro-resistant dough layers made up of wheat flour, soy protein isolate (SPI) and microbial transglutaminase (MTG) at 0.5 (0.5MTG LN), 1.0 (1.0MTG LN) and 1.5 (1.5MYG LN) g/100 g of wheat-SPI flour. The textural, tensile and structural breakdown properties, capsaicin retention, microstructures and the sensory characteristics of cooked LN were evaluated. Compared to other LN, 1.5MTG LN exhibited the highest textural and tensile parameters, highest capsaicin retention, densest structure and was the most difficult to breakdown. The sensory quality of all LN was acceptable, even though it was the Control LN (prepared without SPI and MTG) that scored the highest acceptability. In general, increasing the level of MTG in the sandwiching dough layers of MTG LN reduced the release of capsaicin in simulated mouth, gastric and intestinal conditions, and these results could be due to increased protein cross-linking.

The qualitative analysis method of ultra performance liquid chromatography tandem quadrupole time of flight mass spectrometry (UPLC-Q-TOF-MS/MS) was established for the chemical constituents in Sanhuang tablets. Waters ACQUITY BEH C₁₈ (2.1 mm×100 mm, 1.7 μm) column was used with 0.1% formic acid solution (A)-0.1% formic acid acetonitrile (B) as the mobile phase for gradient elution. The flow rate was 0.2 mL•min⁻¹; the sample volume was 1 μL and the column temperature was 30 ℃. The high-resolution quadrupole time-flight mass spectrometry was used as detector with electrospray ion source in both positive and negative models, and the dry gas temperature was 325 ℃. Based on the analysis of mass spectrometry and literature reports, 38 compounds were confirmed, including 1 alkaloid, 1 dianthrone compound, 6 tannins, 7 anthraquinone glycosides, 6 anthraquinones and 17 flavonoids. Liquid chromatography-mass spectrometry method is simple, reliable and rapid to identify the chemical compositions of Sanhuang tablets, and it is helpful to reveal its chemical constituents and pharmacodynamic substances.

Orientation selectivity (OS) in the visual cortex has been found to be invariant to increases in stimulus contrast, a finding that cannot be accounted for by the original, purely excitatory Hubel and Wiesel model. This property of OS may be important for preserving the quality of perceived stimulus across a range of stimulus intensity. The synaptic mechanisms that can prevent a broadening of OS caused by contrast-dependent strengthening of excitatory inputs to cortical neurons remain unknown. Usingin vivoloose-patch recordings, we found in excitatory neurons in layer 4 of mouse primary visual cortex (V1) that the spike response to the preferred orientation was elevated as contrast increased while that to the orthogonal orientation remained unchanged, resulting in an overall sharpening rather than a weakening of OS. Whole-cell voltage-clamp recordings further revealed that contrast increases resulted in a scaling up of excitatory conductance at all stimulus orientations. Inhibitory conductance was enhanced at a similar level as excitation for the preferred orientation, but at a significantly higher level for the orthogonal orientation. Modeling revealed that the resulting broadening of inhibitory tuning is critical for maintaining and sharpening OS at high contrast. Finally, two-photon imaging guided recordings from parvalbumin-positive (PV) inhibitory neurons revealed that the broadening of inhibition can be attributed to a contrast-dependent broadening of spike-response tuning of PV neurons. Together our results suggest that modulation of synaptic inhibition in the mouse V1 cortical circuit preserves the sharpness of response selectivity during changes of stimulus strength.

In this paper, conducted a systematic study of thermal performance of steel mesh frame sandwich insulation board. The thermal performance of steel mesh frame sandwich insulation board was determined under different conditions. Proposed the insulation effect on oblique inserting wire in the steel mesh frame sandwich insulation board and provided the basis for engineering design and application.

Overproduction and accumulation of amyloid-β (Aβ) have been proposed to be an initiating factor of neuron loss in Alzheimer's disease (AD). AKT is a pivotal molecule in regulating neuronal survival, however, it is still not known whether upregulation of AKT can protect the cells from the Aβ-induced apoptosis. By using cell viability assay and flow cytometry, we demonstrated in the present study that overexpression of AKT could significantly attenuate the cell apoptosis induced by Aβ1-42, whereas simultaneous inhibition of PI3 K, the immediate upstream stimulator of AKT, abolished the protective effect of AKT in HEK293 cells. Upregulation of AKT restored the Aβ-induced alterations of the mitochondria-related Bcl-2 family members (including Bcl-xL, Bcl-w, Bad, and Bax) and suppressed the activation of caspase-3 and JNK. Our data suggest that upregulation of AKT could be a promising therapeutic strategy for arresting Aβ toxicity in AD patients.

In this paper, a new type lithium hexafluorophosphate (LiPF6) complex was prepared with a new method using phosphorus pentachlorine (PCl5), lithium fluoride (LiF) and 1,2-dimethoxyethane (C4H10O2). The structure of the complex was carefully characterized by FTIR, TG-DTG,1H NMR and31P NMR. FTIR results indicate that the synthesized complex is consisted of LiPF6and C4H10O2. Chemical analysis shows that the content of LiPF6in the complex is about 45%, which could infer that the mole ratio of LiPF6and LiPF6(C4H10O2)2in the complex is 1:2. The results of1H NMR and31P NMR further confirm the composition of the complex and determine the structure. The molecular formula of the LiPF6complex is LiPF6(C4H10O2)2. Thermal analysis shows that the strong decomposition peaks of the complex appear at 75°C and 175°C. LiPF6(C4H10O2)2may be used in the electrolyte of the lithium ion battery which 1,2-dimethoxyethane is permitted or broke down into LiPF6after further preparation.

Accumulating evidences suggest that the related autophagy-lysosomal mechanism plays a critical role in many neurodegenerative disorders. In this study, we examined postmortem Parkinson's disease (PD) substantia nigra for evidence of cathepsin L by immunofluorescent staining, and found increased expression of cathepsin L in dopamine neurons of PD patients. We confirmed 6-OHDA induced nuclear translocation of cathepsin L in rat substantia nigral neurons as well. Furthermore, we observed autophagic vacuoles and lysosomes were accumulated in the 6-hydroxydopamine (6-OHDA) injured rat substantia nigra neurons with electron microscopy. Immunofluorescent staining showed that LC3 was enriched in dopamine neurons after 6-OHDA treatment. When pretreated with 3-methyladenine (3-MA), dopaminergic neurons were protected from cell death induced by 6-OHDA, associated with the suppression of LC3 and cathepsin L. Our results demonstrate that activation of autophagy and abnormal distribution of cathepsin L may be responsible for dopamine neuron death, involved in the pathogenic cascade event for the development of Parkinson's disease.

Summary Retinitis pigmentosa (RP) is an irreversible, inherited retinopathy in which early-onset nyctalopia is observed. Despite the genetic heterogeneity of RP, RPGR mutations are the most common causes of this disease. Here, we generated induced pluripotent stem cells (iPSCs) from three RP patients with different frameshift mutations in the RPGR gene, which were then differentiated into retinal pigment epithelium (RPE) cells and well-structured retinal organoids possessing electrophysiological properties. We observed significant defects in photoreceptor in terms of morphology, localization, transcriptional profiling, and electrophysiological activity. Furthermore, shorted cilium was found in patient iPSCs, RPE cells, and three-dimensional retinal organoids. CRISPR-Cas9-mediated correction of RPGR mutation rescued photoreceptor structure and electrophysiological property, reversed the observed ciliopathy, and restored gene expression to a level in accordance with that in the control using transcriptome-based analysis. This study recapitulated the pathogenesis of RPGR using patient-specific organoids and achieved targeted gene therapy of RPGR mutations in a dish as proof-of-concept evidence., Graphical Abstract, Highlights • HiPSC-derived 3D retinae with outer segments and electrophysiological properties • RPGR mutation results in diseased photoreceptor in patient iPSC-derived 3D retinae • Mutation correction rescues defects in photoreceptor morphology and electrophysiology • Ciliogenesis defects appear in RPGR patient-specific iPSCs, iPSC-RPE, and 3D retinae, Jin and colleagues demonstrate that patient-specific iPSC-derived 3D retinae can recapitulate disease progress of retinitis pigmentosa through presenting defects in photoreceptor morphology, gene profile, and electrophysiology, as well as the defective ciliogenesis in iPSCs, iPSC-RPE, and 3D retinae. CRISPR/Cas9-mediated gene correction can rescue not only photoreceptor structure and electrophysiological property but also observed ciliopathy.

The finding of nuclear translocation of cathepsin L and its ability to process the CDP/Cux transcription factor uncovers an important role of cathepsin L in control of cell cycle progression. As the expression of certain cell cycle regulators is associated with nigral neuronal death, the present study was sought to investigate if nuclear translocation of cathepsin L and expression of certain cyclins were induced in DA neurons by 6-hydroxydopamine (6-OHDA). The neuroprotective effects of the cell cycle inhibitor olomoucine against 6-OHDA-induced death of nigral neurons were examined. Using immunocytochemistry and real-time PCR we demonstrated that cyclin D1, cyclin B1 and proliferating cell nuclear antigen (PCNA) were aberrantly expressed in some dopaminergic neurons after 6-OHDA infusion. The nuclear translocation of cathepsin L and up-regulation of LC3, a protein involved in autophagy, were observed in nigral DA neurons. Olomoucine, a cyclin dependent kinase (CDK) inhibitor, reduced contralateral rotations and the loss of TH-positive neurons in substantia nigra induced by lesion with 6-OHDA. Pretreatment of rats or primary DA neurons with olomoucine resulted in a partial blockade of nuclear translocation of cathepsin L. Olomoucine also increased the expression of punctate LC3 immunoreactivity, indicating activation of autophagy. These findings suggest that olomoucine may exert neuroprotective effects through inhibiting cathepsin L nuclear translocation and activating autophagy.

We have previously shown that fenofibrate, a peroxisome proliferator-activated receptor-α activator, increases renal cytochrome P450 (CYP)-derived eicosanoids and improves endothelial function in pre-diabetic obese rats. The present study was designed to explore the efficacy of fenofibrate on blood pressure and renal injury in the advanced stage of type-2 diabetes. 26-week-old male Zucker diabetic fatty rats (ZDF) were fed fenofibrate (100 mg/kg/day) for 6 weeks. Chronic treatment with fenofibrate normalized systolic blood pressure and reduced glomerular size by 19% in diabetic rats. Western blot and fluorescent immunostaining revealed that the over-expression of collagen type IV and α-smooth muscle actin was significantly attenuated in the kidney of fenofibrate-treated ZDF (F-ZDF) rats. In addition, fenofibrate administration dramatically decreased the cyclin D1 protein level in the kidney of diabetic rats. In contrast, renal CYP2C23 and CYP4A proteins were significantly increased in F-ZDF rats. These fenofibrate effects were observed in the absence of significant changes in glucose, insulin or lipid levels. Taken together, our results demonstrate that fenofibrate may lower blood pressure and attenuate glomerular hypertrophy and collagen accumulation through the downregulation of cyclin D1 and upregulation of CYP monooxygenases in the late stage of type-2 diabetes.

Cell cycle reentry has been found during apoptosis of postmitotic neurons under certain pathological conditions. To evaluate whether nuclear factor-kappaB (NF-kappaB) activation promotes cell cycle entry and neuronal apoptosis, we studied the relation among NF-kappaB-mediated cyclin induction, bromodeoxyuridine (BrdU) incorporation, and apoptosis initiation in rat striatal neurons following excitotoxic insult. Intrastriatally injected N-methyl-D-aspartate receptor agonist quinolinic acid (QA, 60 nmol) elicited a rise in cyclin D1 mRNA and protein levels (P

To evaluate the efficacy of splenectomy plus selective pericardial devascularization under endoscope in the treatment of advanced schistosomiasis patients with portal hypertension and hypersplenism so as to explore the minimally invasive and safer surgical treatment.A secure splenectomy was performed with laparoscope and its supporting devices, and at the same time, the ligation of the left gastric vein and the ligation of esophageal vein perforating vertically into the esophagus were also performed in 14 advanced schistosomiasis patients with portal hypertension and hypersplenism.Among the 14 patients, the splenic artery was separated and clipped before the treatment of splenic pedicle. One patient was of conversion to open laparotomy for the splenic vein rupture bleeding in the separation. There was no death.The operation of splenectomy plus selective pericardial devascularization under endoscope is effective, truly minimally invasive, and safe in the treatment of advanced schistosomiasis patients with portal hypertension and hypersplenism.

Pemphigus is an autoimmune disease in which autoantibodies play a pathogenic role, causing loss of epithelial cell adhesion with resulting blister formation. In the present study, the distribution patterns of desmocollin 3 (Dsc 3), desmocollin 1 (Dsc 1) and desmoglein 1 and 2 (Dsg 1,2) in pemphigus vulgaris (PV) and pemphigus erythematosus (PE) were investigated by immunohistochemistry. Dsc 3 was distributed at the cell membrane of the basal and suprabasal layers of the normal oral mucosa and skin epithelium. Dsc 1 was distributed only at the cell membrane of the upper spinous layers of normal skin, and was not visible in normal oral mucosa epithelium. Dsg 1,2 was distributed at the cell membrane of the suprabasal layers of normal oral mucosa and skin epithelium. The distribution of Dsc 3 and Dsg 1,2 was obviously sparser in the oral PV and cutaneous PV than in normal control epithelium. Internalization of Dsc 3, Dsc 1 and Dsg 1,2 occurred specifically in PV and PE, giving staining patterns resembling cytoplasmic patchy granules, rings and dense clumps. Internalization of Dsc 3 was more frequent in cutaneous PV (60%) and PE (60%) than in oral PV (30%). These findings suggest that internalization of Dsc 3 is closely associated with disease duration (P

To examine the protein and mRNA levels of interleukin-9(IL-9) and the frequencies of CD4(+)IL-9(+)T-cells in peripheral blood of patients with systemic lupus erythematosus (SLE) and explore the roles of double positive T cells and IL-9 in the pathogenesis of SLE and the effects of glucocorticoid.Twenty-eight hospitalized SLE patients were recruited and 12 healthy volunteers selected as normal controls. The mRNA levels of IL-9 in peripheral blood were measured by real time-polymerase chain reaction (RT-PCR), plasma protein of IL-9 by enzyme-linked immunosorbent assay (ELISA) and frequencies of CD4(+)IL-9(+)T-cells by flow cytometry. And the differences between two groups and the effects of glucocorticoid were analyzed.(1) The mRNA levels of IL-9 were significantly elevated in SLE patients as compared with normal controls (P0.01). The serum levels of IL-9 were significantly higher in active and inactive SLE patients than those in healthy individuals (68 ± 11 vs 26 ± 6 ng/L, P0.01; 56 ± 14 vs 26 ± 6 ng/L, P0.05). The percentages of CD4(+)IL-9(+)T-cells increased in active SLE patients (1.96% ± 0.31%) versus inactive SLE patients (0.89% ± 0.13%, P0.01) and healthy controls (0.28% ± 0.05%, P0.001). And it was higher in inactive SLE patients than that in controls (P0.05). (2) The serum levels of IL-9 and the frequencies of CD4(+)IL-9(+)T-cells were positively correlated with SLE disease activity index (SLEDAI). (3) The frequencies of CD4(+)IL-9(+)T-cells and the serum levels of IL-9 in 8 untreated active SLE patients decreased at weeks 1, 2 and 3 after the therapy of methylprednisolone (0.8 mg×kg(-1)×d(-1)) versus those at pre-treatment.The abnormalities of IL-9 and CD4(+)IL-9(+)T-cells may play an important role in the pathogenesis of SLE. And the frequencies of CD4(+)IL-9(+)T-cells and the levels of IL-9 are evaluative parameters of SLE activity and severity.