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Background: Oxaprozin is labeled as a Class II drug in the biopharmaceutical classification system, and its poor solubility in the entire gastrointestinal tract may be the main reason for its insufficient oral absorption capacity. Objective: The purpose of this study was to develop an oxaprozin formulation to enhance its oral absorption. Method: Oxaprozin-loaded microemulsions were prepared using the titration method and pseudoternary phase diagram. Characterization experiments were performed on microemulsion preparations, including pH, particle size, shape, zeta potential, and stability (thermodynamic, dilution, and differential scanning calorimetry). Then, the in vitro release of the microemulsion and in vivo pharmacokinetics in rats were evaluated. Results: Several microemulsion formulations were prepared. The optimal formulation was 15% oleoyl macrogolglycerides, 35% Tween 20/isopropanol (Km=2), and 50% distilled water. Its particle size met the requirements, and it had a spherical shape with a negatively charged surface. This microemulsion-loaded drug was applied to in vitro release and in vivo pharmacokinetic experiments at 7.47 mg/mL. In vitro release of the oxaprozin-loaded microemulsion best fit the firstorder model, while the microemulsion preparation had a certain sustained-release effect. In vivo pharmacokinetic experiments indicated that the microemulsion formulation significantly delayed the peak time of the blood concentration and simultaneously prolonged the half-life of drug elimination. Conclusions: The obtained data revealed satisfactory results for this novel microemulsion of oxaprozin, which is very meaningful for clinical trials.

In this paper, we study a mathematical model for an infectious disease caused by a virus such as Cholera without lifetime immunity. Due to the different mobility for susceptible, infected human and recovered human hosts, the diffusion coefficients are assumed to be different. The resulting system is governed by a strongly coupled reaction–diffusion system with different diffusion coefficients. Global existence and uniqueness are established under certain assumptions on known data. Moreover, global asymptotic behaviour of the solution is obtained when some parameters satisfy certain conditions. These results extend the existing results in the literature. The main tool used in this paper comes from the delicate theory of elliptic and parabolic equations. Moreover, the energy method and Sobolev embedding are used in derivinga prioriestimates. The analysis developed in this paper can be employed to study other epidemic models in biological, ecological and health sciences.

Extended pluripotent stem (EPS) cells have shown great applicative potentials in generating synthetic embryos, directed differentiation and disease modeling. However, the lack of a xeno-free culture condition has significantly limited their applications. Here, we report a chemically defined and xeno-free culture system for culturing and deriving human EPS cells in vitro. Xeno-free human EPS cells can be long-term and genetically stably maintained in vitro, as well as preserve their embryonic and extraembryonic developmental potentials. Furthermore, the xeno-free culturing system also permits efficient derivation of human EPS cells from human fibroblast through reprogramming. Our study could have broad utility in future applications of human EPS cells in biomedicine., The applications of human extended pluripotent stem cells (which can form both embryonic and extraembryonic lineages) demand a xeno-free culture condition; here, the authors provide a chemically defined and xeno-free culture system to do so.

Hua-Feng Yin,1,2 Chun-Ming Yin,3 Ting Ouyang,4 Shu-Ding Sun,1 Wei-Guo Chen,1 Xiao-Lin Yang,5 Xin He,6 Chun-Feng Zhang1 1School of Traditional Chinese Pharmacy, China Pharmaceutical University, Nanjing, 210009, Jiangsu, People’s Republic of China; 2Jiangxi QingFeng Pharmaceutical Co., Ltd, Ganzhou, 341000, Jiangxi, People’s Republic of China; 3Emergency Department, The First Affiliated Hospital of Gannan Medical University, Ganzhou, 341000, Jiangxi, People’s Republic of China; 4School of Chinese Materia Medical, Beijing University of Chinese Medicine, Beijing, People’s Republic of China; 5Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, People’s Republic of China; 6School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong SAR, People’s Republic of ChinaCorrespondence: Xin HeSchool of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, Hong Kong SAR, People’s Republic of ChinaTel +852-54445989Email xhe06@qub.ac.ukChun-Feng ZhangSchool of Traditional Chinese Pharmacy, China Pharmaceutical University, Nanjing, 210009, People’s Republic of ChinaTel +86-25-86185129Email zhangchunfeng67@163.comPurpose: The aim of the present study was to develop an optimized Genkwanin (GKA)-loaded self-nanoemulsifying drug delivery system (SNEDDS) formulation to enhance the solubility, intestinal permeability, oral bioavailability and anti-colitis-associated colorectal cancer (CAC) activity of GKA.Methods: We designed a SNEDDS comprised oil phase, surfactants and co-surfactants for oral administration of GKA, the best of which were selected by investigating the saturation solubility, constructing pseudo-ternary phase diagrams, followed by optimizing thermodynamic stability, emulsification efficacy, self-nanoemulsification time, droplet size, transmission electron microscopy (TEM), drug release and intestinal permeability. In addition, the physicochemical properties and pharmacokinetics of GKA-SNEDDS were characterized, and its anti-colitis-associated colorectal cancer (CAC) activity and potential mechanisms were evaluated in AOM/DSS-induced C57BL/6J mice model.Results: The optimized nanoemulsion formula (OF) consists of Maisine CC, Labrasol ALF and Transcutol HP in a weight ratio of 20:60:20 (w/w/w), in which ratio the OF shows multiple improvements, specifically small mean droplet size, excellent stability, fast release properties as well as enhanced solubility and permeability. Pharmacokinetic studies demonstrated that compared with GKA suspension, the relative bioavailability of GKA-SNEDDS was increased by 353.28%. Moreover, GKA-SNEDDS not only significantly prevents weight loss and improves disease activity index (DAI) but also reduces the histological scores of inflammatory cytokine levels as well as inhibiting the formation of colon tumors via inducing tumor cell apoptosis in the AOM/DSS-induced CAC mice model.Conclusion: Our results show that the developed GKA-SNEDDS exhibited enhanced oral bioavailability and excellent anti-CAC efficacy. In summary, GKA-SNEDDS, using lipid nanoparticles as the drug delivery carrier, can be applied as a potential drug delivery system for improving the clinical application of GKA.Keywords: insoluble herbal drug, nanoparticle-based drug delivery system, intestinal permeability, pharmacokinetics, anticancer efficacy

Due to its good properties and low cost, melamine formaldehyde foam has been widely used in cars, furniture and construction. However, how to recycle the spent foam still remains challenging for scientists. In this work, a new method was designed to prepare N-doped carbon dot (NCD) materials by calcining sodium lignin sulfonate/melamine formaldehyde foam (LSMF) via one step. TEM, IR and XPS were used to characterize the structure and morphology of newly-synthesized NCDs. It is shown that carbon powder is obtainable by calcination. Since it derives from the collapse of the foam structure of LSMF, the carbon powder can almost completely dissolve in deionized water. The particle size ranges from 5 to 20 nm. The fluorescence properties of NCDs were studied by fluorescence spectroscopy. A strong emission has been detected at 580 nm with the quantum yield of 2.94%. When applying NCDs to detect various metal ions, there is a significant fluorescence quenching effect and good selectivity for Fe3+. The mechanism has been hypothesised. Our study provides a method for productive preparation of NCDs from spent foam.

The rapid growth of ethanol production and its limited blending ratio in gasoline stimulates the conversion of ethanol into value-added chemicals and fuels. Dehydrogenation of ethanol to acetaldehyde provides an elegant option for ethanol conversion in view of versatile applications of acetaldehyde and the high atomic economy of this process. In this review, the recent progress in the catalytic conversion of ethanol to acetaldehyde is summarized and discussed. In particular, the representative catalysts for the oxidative and non-oxidative dehydrogenation of ethanol were highlighted, and reaction mechanisms over typical catalysts were analyzed. Finally, challenges in improving acetaldehyde selectivity and catalyst stability, and opportunities in replacing the fossil route acetaldehyde production were proposed.

To overcome obstacles such as low response and poor selectivity of pure ZnO and SnO2 gas sensors, the ZnO@SnO2 sensor was synthesized by hydrothermal synthesis. The samples were characterized by XRD, XPS, SEM, HRTEM, N2 adsorption–desorption and other techniques. The results show that ZnO@SnO2 forms an n–n-type heterostructure and presents a double-layer capsule with a size of 0.5–4 μm. The results show that compared with pure ZnO and SnO2, the ZnO@SnO2 sensor exhibits a higher response (138.9) to 50 ppm triethylamine (TEA) at 152°C, which is 19.56 times that of the pure ZnO sensor and 21.7 times that of the SnO2 sensor. It has a short response/recovery time (11/11 s), excellent selectivity and cycling stability. Compared with other volatile organic compounds or gases, it has higher selectivity for TEA detection.

The direct C(sp3)-H bond amination has become a hot topic due to its high efficiency in converting the C(sp3)-H bond to the C-N bond. Herein, we report an efficient intramolecular C(sp3)-H bond sulfonamidation under metal-free conditions, which provides a straightforward method for the synthesis of 5-membered cyclic sulfonamides (benzosultams). This protocol avoids the use of metal catalysts, oxidants, and any additives. Mechanistic experiments and the DFT calculations, revealed that the reaction proceeds through a proton transfer coupled with the SN2 (PTSN2) manner, which is different from the other pathways.

In the traditional raw materials used for preparing Sialon ceramics, hydrolytic AlN, cannot easily be used for aqueous gelcasting. To overcome this problem, a new type of gelcasting technique was developed. By introducing 1-methyl-2-pyrrolidinone (NMP) as a solvent, Sialon ceramics were formed using a low-viscosity non-aqueous gel system based on the 2-hydroxyethyl methacrylate (HEMA) gelling agent in this work. Based on this gel system, the rheological properties of the slurry and the solidification and sintering properties of Sialon ceramics were studied. The results show that the best rheological properties of slurry can be obtained with the dispersant dosage of 6 vol%. As the HEMA content increases, the flexural strength of the green bodies increase. When the ratio of HEMA to TMPTA (trimethylolpropane triacrylate) is 10:1 and the HEMA content is 15 wt%, the flexural strength of the green body reaches a maximum of 13.07 MPa. β′-Sialon ceramic has the best comprehensive mechanical properties at the sintering temperature of 1700 °C. Its bulk density, Vickers hardness, fracture toughness and flexural strength were 3.207 g/cm3, 1484 HV, 7.11 MPa m1/2 and 351 MPa, respectively.

The lignin amine (LA) was exploited to prepare dually N/S-doped carbon (NSC), which was endowed with intriguing porous structure by Fe3O4 template. N and S elements, originating from LA, are doped into the materials. NSC possesses diverse-scale 3D pores. The macropores are made by Fe3O4, which facilitate to produce meso and micro pores on their walls by KOH activation. The sample prepared at 700 °C (NSC-700) is found to have the largest specific surface area (1199 cm2 g−1) and specific capacity (241 F g−1 at current density of 1 A g−1). Its capacity is 260% as high as that of lignin amine carbon (LAC) prepared without adding Fe3O4. Excellent rate performance is unraveled because of possessing 82% specific capacity at 20 A g−1 and 27.2 Wh kg−1 energy density at 10000 W kg−1 power density. Moreover, the specific capacity maintains 95.0% after 3000 cycles, indicating good electrochemical stability. The good electrical performance of NSC-700 is attributed to its interesting electronic properties that are induced by special pore structure. Because of having merits such as high rate performance, long life, large specific capacity and low cost, our NSC is anticipated to be a promising capacitor as electrode material.

The effect of super-chilling at -2°C compared with ice storage at 0°C on flavor quality changes of turbot (Psetta maxima) was investigated. Changes in total volatile basic nitrogen (TVB-N), sensory attributes and volatile compounds were periodically examined for 20 days. Results demonstrated that super-chilling retarded the increases of TVB-N values and maintained better sensory quality compared to the ice storage. Additionally, GC-MS analysis showed super-chilling could more effectively maintain the characteristic volatiles responsible for fresh fish flavor and reduce the contents of putrid compounds such as TMA and acetic acid.

ETHNOPHARMACOLOGICAL RELEVANCE Gentiana delavayi Franch. (Gentianaceae) as an ethnomedicinal plant contains a variety of effective active ingredients and exhibits diverse pharmacological actions, such as hepatoprotective, anti-inflammatory and central nervous system effects. In this study we investigated the influence of G. delavayi flower extract on amyloid precursor protein (APP) processing at molecular and cellular levels. APP/PS1 Chinese hamster ovary (CHO) cells were treated with chloroform extract of G. delavayi flower in different concentrations for 24 h. Concentrations of amyloid β (Aβ) 40 and Aβ42 in the cell supernatant and activity of β-site amyloid precursor protein cleaving enzyme 1 (BACE1), BACE2, and cathepsin D were determined. The expression of APP and neprilysin (NEP) within the cell were further determined. Compared with the control group, the levels of Aβ40 and Aβ42 declined notably and the activity of BACE1 was inhibited significantly in the APP/PS1 CHO cells after treatment with the chloroform extract of G. delavayi flower. Although the activities of BACE2 and cathepsin D were not changed, the expression of Aβ degrading enzyme NEP increased remarkably. Our experiments have clearly showed that the chloroform extract of G. delavayi flower inhibits the generation of β-amyloid by specifically inhibiting β-secretase and increases the expression of NEP which fastens the degradation of Aβ, exhibiting the effect of decreasing Aβ accumulation in APP/PS1 CHO cells. These results suggest that the active components from the chloroform extract of G. delavayi flower have a further prospect to be developed as potential anti-Aβ drug.

To advance biomass-metal oxide composite synthesis, develop its interfacial chemistry and raise its performance in applications, specifying local structures and their effects are of great importance. Herein, a facile hydrothermal route was utilized to prepare a composite of renewable cellulose and zinc oxide. Microstructures from nanoscale to atomic level were examined with electron microscopy, spectroscopic technique and relativistic density functional theory. ZnO nanoparticles uniformly grow on linear cellulose nanofiber, affording an orderly hierarchical structure in general. Chemical interfacial coupling is computationally borne out. Three types of local structures with different hydrogen locations are energetically favored; notably the hydrogen-transfer one is most possibly occurring in the composite, whose interfacial interaction is dominated by orbital attractions and interfacial strength reaches − 5.06 eV. Electronic structures of the composite rationalized experimental diffuse reflectance spectra. The influence of different hydrogen positions in composite on various properties was discussed in detail. Experimental and computational characterizations unravel local structures of a typical cellulose–ZnO composite, which show different hydrogen positions. Hydrogen-transfer isomers are found the most possibly occurring, resembling the photoanode in dye-sensitized solar cells. The interfacial nature and interaction strength as well as electronic structures are determined by hydrogen locations.

Identifying the geographic origins of Chinese mitten crabs is important for food safety and fair market competition. In this study, we used strontium (Sr) isotopes as a tool to trace the geographic origins of Chinese mitten crabs. Chinese mitten crabs, water, and different types of crab feed were collected from four different lakes for Sr isotope analyses. The results showed that the Sr isotope compositions of the different parts from one single crab were consistent within error, indicating that any piece of a crab could be used to represent the Sr isotope characteristics of the whole crab. The Sr isotope compositions of Chinese mitten crabs from the same lake were consistent within the analytical error, and the values were similar to the Sr isotope composition of the water from the same lake. However, the Sr isotope compositions of water and crabs from different lakes are significantly different. Therefore, the Sr isotope compositions of Chinese mitten crabs are mainly controlled by lake water composition, while the impact of feed is limited. This study provides an effective method for tracing the geographic origins of Chinese mitten crabs.

The separation of light hydrocarbon mixtures, especially for acetylene-containing mixtures, is in urgent demand to prepare chemical feedstocks and fuels. Here, we have prepared a new 8-connected me...

This study elucidates the discrepancy in gas permeability between bulk films and asymmetric membranes of semi-crystalline cellulose acetates (CAs) from perspectives of thickness-confinement and crystallization suppression. CAs are the workhorse membrane materials for industrial CO2/CH4 separation. Bulk films of CAs often exhibit CO2 permeability values of 1.8–6.6 Barrers at 35 oC, which correspond to permeance values of 36–132 GPU for asymmetric membranes with assumed selective layers of 50 nm. However, commercial CA membranes can have CO2 permeance values as high as 200 GPU with a CO2/CH4 selectivity comparable to the bulk polymers. We hypothesize that as the CA films become thinner, the thickness confinement inhibits crystallization and thus increases gas permeability while retaining gas selectivity. To validate this hypothesis, freestanding cellulose diacetate (CDA) films with thicknesses ranging from 218 nm to 120 μm were prepared, and their crystallinity was determined using Differential Scanning Calorimetry and Wide-angle X-ray Diffraction analysis. Gas solubility and permeability can be satisfactorily correlated with the crystallinity using the empirical equations available in the literature. We demonstrate that the micro- or nano-confinement and dynamics in thin-film polymers are instrumental in understanding gas transport properties of industrial asymmetric membranes.

Background Mitochondria are dynamic organelles that undergo fission and fusion. During cell stress, mitochondrial dynamics shift to fission, leading to mitochondrial fragmentation, membrane leakage, and apoptosis. Mitochondrial fragmentation requires the cleavage of both outer and inner membranes, but the mechanism of inner membrane cleavage is unclear. Bif-1 and prohibitin-2 may regulate mitochondrial dynamics. Methods We used azide-induced ATP depletion to incite cell stress in mouse embryonic fibroblasts and renal proximal tubular cells, and renal ischemia-reperfusion to induce stress in mice. We also used knockout cells and mice to determine the role of Bif-1, and used multiple techniques to analyze the molecular interaction between Bif-1 and prohibitin-2. Results Upon cell stress, Bif-1 translocated to mitochondria to bind prohibitin-2, resulting in the disruption of prohibitin complex and proteolytic inactivation of the inner membrane fusion protein OPA1. Bif-1-deficiency inhibited prohibitin complex disruption, OPA1 proteolysis, mitochondrial fragmentation, and apoptosis. Domain deletion analysis indicated that Bif-1 interacted with prohibitin-2 via its C-terminus. Notably, mutation of Bif-1 at its C-terminal tryptophan-344 not only prevented Bif-1/prohibitin-2 interaction but also reduced prohibitin complex disruption, OPA1 proteolysis, mitochondrial fragmentation, and apoptosis, supporting a pathogenic role of Bif-1/prohibitin-2 interaction. In mice, Bif-1 bound prohibitin-2 during renal ischemia/reperfusion injury, and Bif-1-deficiency protected against OPA1 proteolysis, mitochondrial fragmentation, apoptosis and kidney injury. Conclusions These findings suggest that during cell stress, Bif-1 regulates mitochondrial inner membrane by interacting with prohibitin-2 to disrupt prohibitin complexes and induce OPA1 proteolysis and inactivation.

Although oral formulations of anticancer chemotherapies are clinically available, the therapeutic action relies mostly on drug absorption, being inevitably accompanied with systemic side effects. It is thus desirable to develop oral therapy systems for the local treatment of colon cancers featured with highly selective delivery to cancer cells and minimized systemic drug absorption. The present study demonstrates the effective accumulation and cell uptake of the doxorubicin and superparamagnetic iron oxide nanoparticles-loaded solid lipid nanoparticle (SLN) delivery system for chemo/magnetothermal combination therapy at tumors by hierarchical targeting of folate (FA) and dextran coated on SLN surfaces in a sequential layer-by-layer manner. Both the in vitro and in vivo characterizations strongly confirmed that the dextran shells on SLN surfaces not only retarded the cellular transport of the FA-coated SLNs by the proton-coupled FA transporter on brush border membranes in small intestine, but also enhanced the particle residence in colon by specific association with dextranase. The enzymatic degradation and removal of dextran coating led to the exposure of the FA residues, thereby further facilitating the cellular-level targeting and uptake of the SLNs by the receptor-mediated endocytosis. The evaluation of the in vivo antitumor efficacy of the hierarchically targetable SLN therapy system by oral administration showed the effective inhibition of primary colon tumors and peritoneal metastasis in terms of the ascites volume and tumor nodule number and size, along with the absence of systemic side effects.

A surface imprinting method is presented herein for the development of a highly selective yet highly permeable molecularly imprinted membrane for protein separation and purification. The resultant protein imprinted membrane was shown to exhibit great potential for the efficient separation of the template protein from a binary mixture and a cell lysate solution, while maintaining high transport flux for complementary molecules. Bovine Serum Albumin (BSA) and Lysozyme (Lys) were individually immobilized on a cellulose acetate membrane as template molecules. In situ surface crosslinking polymerization was then used for protein imprinting on the membrane for a controlled duration. Both membranes showed high adsorption capacity towards template proteins in the competitive batch rebinding tests. In addition, the adsorption capacity could be greatly enhanced in a continuous permeation procedure, where the resultant membrane specifically adsorbed the template protein for more than 40 h. Moreover, this is the first report of purification of a specific protein from the cell broth mixture using a molecularly imprinted membrane. The protein imprinted membrane enables the transport of multiple non-template proteins with high permeation rate in a complex system, thus opening the way for high efficiency protein separation at a low cost for the industry.

In this paper, we have developed a new method of accurate detection of retinal blood vessels based on a deep convolutional neural network (CNN) model. This method plays an important role in the observation of many eye diseases. Retinal Images have many issues that make the process of vessels segmentation very hard. We treat each issue of the retina image with the greatest observation to obtain a well-segmented image. The first step is to apply a pre-processing method based on fuzzy logic and image processing tactics. In a second step, in order to generate the segmented images, we propose a strided encoder-decoder CNN model. This network is trained and optimized using the Dice Loss function that supports the class imbalance problem that is in the database. The proposed model has a U-Net shape, but it is deeper and the pooling layers are replaced with strided convolutional layers in the encoder. This modification allows for a more precise segmentation of vessels and accelerates the training process. The last step is post-processing for removing the noisy pixels as well as the shadow of the optic disc. The performance of the proposed method was evaluated on DRIVE and STARE databases. The proposed method gives a sensitivity of 0.802 and 0.801 respectively on DRIVE and STARE, with an accuracy of 0.959 and 0.961 respectively. We focused on sensitivity and accuracy measurements that represent the accuracy of the model, especially tiny vessels. According to the results, the model outperforms many other proposed methods, especially in the above-mentioned measures.

Neural stem/progenitor cell (NSPC) based therapy represents an attractive treatment for Alzheimer's disease (AD), the most common neurodegenerative disorder with no effective treatment to date. This can be achieved by stimulating endogenous NSPCs and/or administrating exogenously produced NSPCs. Successful repair requires the migration of NSPCs to the loci where neuronal loss occurs, differentiation and integration into neural networks. However, the progressive loss of neurons in the brain of AD patients suggests that the repair by endogenous NSPCs in the setting of AD may be defective. The production and deposition of amyloid-β1-42 (Aβ1-42) peptides is thought to be a central event in the pathogenesis of AD. Here we report that Aβ1-42 peptides inhibit the migration of in vitro cultured NSPCs by disturbing the ERK-MAPK signal pathway. We found that the migratory capacity of NSPCs was compromised upon treatment with oligomeric Aβ1-42; the inhibitory effect occurred in a dose-dependent manner. Our previous studies have shown that Aβ1-42 triggers the expression of GRK2 by unknown mechanism. Herein we found that the Aβ1-42 evoked upregulation of GRK2 expression was attenuated upon treatment with the ERK inhibitor SCH772984 at 2.5 μM, but not with inhibitors for p38 or JNK. We detected a dose-dependent increase in levels of phosphorylated ERK1/2 after incubation of cells with oligomeric Aβ1-42 peptides for 3 days. We observed that an increase in the phosphorylation of p38 and JNK coincided with reduced phosphorylation of ERK1/2 upon treatment with Aβ1-42 for 6 and/or 9 days. We hypothesize that the divergence of the activation of the MAPK family of pathways may contribute to the inhibition of NSPCs migration after the long-term incubation with Aβ1-42. Pretreatment with 1 μM MEK inhibitor U0126 reversed the effects of Aβ1-42 on GRK2 expression of and NSPC migration. Together, our results suggest that Aβ1-42 oligomers compromise the migratory capacity of NSPCs through the MEK-ERK pathway.

We demonstrate a broadband and polarization selective terahertz modulator with ultrafast modulation speed, based on the Si grating metasurface on the Sapphire substrate. The Si layer is implanted with B+ and subsequently annealed, which significantly reduces the lifetime of carriers and increases the carrier density, and thus realizes ultrafast and efficient modulation. Our modulator achieves modulation depth up to 60% for the x-polarized THz wave and less than 1% for the y-polarized THz wave in the frequency ranging from 0.5 to 2.5 THz, with switch-on and switch-off time of modulation in 20 ps and around 300 ps, respectively. The carrier dynamics of the fabricated Si grating is also studied to illustrate the ultrafast modulated mechanism. Our results pave the way for ultrafast manipulation of terahertz spectrum and shows great potential in terahertz communication.

Resource-recovered CuOx-CeOx/SiO2 samples were prepared by using rice-husk-derived silica modified with recycled copper ion from panel industry wastewater for controlling Hg0 and NO emissions from simulated flue gases. By using the silicate exfoliation method for sample preparation, the presence of Cu and Ce oxides could increase the specific surface area (SBET) of SiO2. 50%Cu-10%Ce/SiO2 having the largest SBET showed significant NO removal. XRD results indicated that significant CuO diffraction peaks were not detected among all the CuOx/SiO2 samples, suggesting that CuOx was highly dispersed on the surface. SEM and TEM images showed that the uniform spherical SiO2 particles have changed into plate-like structure, further confirming the occurrence of structural rearrangement after incorporated with Cu/Ce oxides via silicate exfoliation. XPS results showed that Cu2+ and Ce4+ were the major valence states presenting in the samples. H2-TPR and NH3-TPD indicated that the 50%Cu/SiO2 and 50%Cu-10%Ce/SiO2 had greater redox ability and stronger acidity as compared to those containing smaller amounts of CuOx and CeOx. Cu and Ce modification was shown to successfully improve the NO removal efficiency. 50%Cu-10%Ce/SiO2 had the best NO conversion efficiency of 70–85% with a broad temperature window of 150–300°C. 50%Cu/SiO2 exhibited the greatest total Hg removal efficiency of 88.2% among all the tested samples at 150°C and remained almost the same removal efficiency at 250°C. These results suggest that the recycled Cu modified rice-husk-derived SiO2 is feasible for not only controlling Hg0 and NO emissions but also recovery of agricultural and industrial wastes.

Backgroud: Heavy metal pollutant, Cadmium (Cd), is an inorganic pollutant in China. Hemp (Cannabis sativa L.) is an important fiber crop to remediate heavy metal-contaminated soils. The MYB family is one of the largest and most important gene families that influences plant growth and produce secondary metabolites. Results: 115 CsMYB genes were identified in the hemp genome. The 1R-MYB subfamily had 17 genes, the 2R-MYB subfamily 88 genes, and the 3R-MYB subfamily 8 genes. The synteny analysis of the CsMYB genes indicated that there were 3 pairs of tandem repeats, 21 pairs of segmental duplication, 6 CsMYB genes present before species differentiation, and 60 genes belonging to the hemp-specific CsMYB genes. 7 CsMYB genes were identified to influence the response to Cd stress by combining the transcriptome data of two hemp species under Cd stress. Based on the changes in the Cannabinoid content of hemp under Cd stress, the expression of different CsMYB genes in hemp with high and low cannabidiol (CBD) contents, and tissue-specific expression, it was inferred that CsMYB024 may be affected by Cd stress and mediate the CBD synthesis pathway.Conclusions: This study provides a comprehensive analysis of the hemp MYB family. These results should be helpful in understanding of their potential functions in Cd-Stress Response and the Regulation of Cannabinoid Biosynthesis in Hemp. In addition, lays the foundation for the further study of biological functions of CsMYBs in hemp.

Receptor-interacting protein 3- (RIPK3-) modulated necroptosis plays a critical role in cardiac remodelling after myocardial infarction (MI). However, the precise regulatory mechanism is not fully elucidated yet. In the present study, we showed that RIPK3 expression was upregulated in myocardial tissue after MI in a mouse model by coronary artery ligation, as well as in the cardiomyocytes following hypoxic injury in vitro. The increase of RIPK3 expression was found to be accompanied by severe cardiac remodelling, cardiac dysfunction, and higher mortality. Elevated RIPK3 expression subsequently abrogated the AMPK pathway that was accompanied by inhibition of Parkin-mediated mitophagy. Loss of mitophagy increased the opening of mitochondrial permeability transition pore (mPTP), which ultimately induced the cardiomyocyte necroptosis. In contrast, genetic ablation of Ripk3 induced the AMPK/Parkin-mitophagy pathway, favouring a prosurvival state that eventually inhibited mPTP opening and induced the necroptosis of cardiomyocytes in the post-MI cardiac remodelling. In conclusion, our results revealed a key mechanism by which necroptosis could be mediated by RIPK3 via the AMPK/Parkin-mitophagy/mPTP opening axis, which provides a potential therapeutic target in the management of heart failure after MI.

Background Enzalutamide, a major antiandrogen indicated for metastatic castration-resistant prostate cancer, has worrisome toxicities in aging patients. Dose reduction might limit toxicity, but potential loss of efficacy is a concern. We compare up-front low-dose versus standard-dose enzalutamide. Patients and Methods Records of prostate cancer patients receiving enzalutamide were retrospectively retrieved. Selection criteria were: age ≥ 75, metastatic disease, surgical or medical castration, and rising prostate-specific antigen (PSA). Data were excluded of those missing follow-up PSA values. Low-dose enzalutamide (≤ 80 mg per day) was compared to standard dose (160 mg per day). Progression-free survival analyzed the time from start of enzalutamide to event, defined as ≥ 25% and ≥ 2 ng/mL PSA increase above nadir, or death from any cause. Results Fifty-nine patients were identified, of whom 16 received low-dose and 43 standard-dose therapy. Patients in the low-dose group were significantly old, with a median (range) age of 84.6 (74.9-93.8) years; median (range) PSA at start of enzalutamide was 59.2 (11.0-1058.3) ng/mL; 11 had bone metastases only, 2 metastatic lymph nodes only, and 3 bone and lymph node localizations. Pain score was > 3/10 in 4 patients (27%), Eastern Cooperative Oncology Group performance status was ≥ 2 in 9 (56%); 3 patients had received prior abiraterone and 3 bicalutamide. None received chemotherapy. PSA decrease of ≥ 50% at 12 weeks was observed in 67% patients (10/15), versus 45.0% with standard dose. Median (range) PSA at last follow-up was 1.6 (0-599.3) ng/mL. Median progression-free survival was 11.2 months, versus 11.9 months for patients receiving the standard dose (P = .612). Conclusion Low-dose enzalutamide in very old, symptomatic, poor-performance patients with metastatic disease was associated with high response rate and survival comparable to standard dose.

Plasma SARS-CoV-2 RNA may represent a viable diagnostic alternative to respiratory RNA levels, which rapidly decline after infection. Quantitative PCR with reverse transcription (RT-qPCR) reference assays exhibit poor performance with plasma, probably reflecting the dilution and degradation of viral RNA released into the circulation, but these issues could be addressed by analysing viral RNA packaged into extracellular vesicles. Here we describe an assay approach in which extracellular vesicles directly captured from plasma are fused with reagent-loaded liposomes to sensitively amplify and detect a SARS-CoV-2 gene target. This approach accurately identified patients with COVID-19, including challenging cases missed by RT-qPCR. SARS-CoV-2-positive extracellular vesicles were detected at day 1 post-infection, and plateaued from day 6 to the day 28 endpoint in a non-human primate model, while signal durations for 20-60 days were observed in young children. This nanotechnology approach uses a non-infectious sample and extends virus detection windows, offering a tool to support COVID-19 diagnosis in patients without SARS-CoV-2 RNA detectable in the respiratory tract.

An isolation-free smartphone-based saliva assay can diagnose COVID-19 cases and quantify viral load within 15 min., Point-of-care COVID-19 assays that are more sensitive than the current RT-PCR (reverse transcription polymerase chain reaction) gold standard assay are needed to improve disease control efforts. We describe the development of a portable, ultrasensitive saliva-based COVID-19 assay with a 15-min sample-to-answer time that does not require RNA isolation or laboratory equipment. This assay uses CRISPR-Cas12a activity to enhance viral amplicon signal, which is stimulated by the laser diode of a smartphone-based fluorescence microscope device. This device robustly quantified viral load over a broad linear range (1 to 105 copies/μl) and exhibited a limit of detection (0.38 copies/μl) below that of the RT-PCR reference assay. CRISPR-read SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) RNA levels were similar in patient saliva and nasal swabs, and viral loads measured by RT-PCR and the smartphone-read CRISPR assay demonstrated good correlation, supporting the potential use of this portable assay for saliva-based point-of-care COVID-19 diagnosis.

Gas chromatography-mass spectrometry (GC-MS) coupled with the acceptance test, partial least-squares regression (PLSR) analysis, validation experiment, and preference test was used to identify the key aroma compounds in dog foods (DFs). Six DFs were evaluated by spraying six palatability enhancers onto a basal DF. The differently flavored palatability enhancers were prepared by the Maillard reaction using different protein sources and reaction conditions. The intake ratios of the six DFs were tested by six adult beagle dogs and were classified into high, medium, and low levels. A total of 55 volatile compounds were identified using headspace solid-phase microextraction (HS-SPME) GC-MS. Correlation analysis of the volatile compounds associated with intake ratios using partial least-squares regression (PLSR) found nine significantly positive and three significantly negative compounds that made a significant contribution to the palatability of DFs. Validation tests undertaken by adding three significantly positive compounds, one significantly negative compound, and one nonsignificant compound into the odorless matrix successfully verified the accuracy prediction of the PLSR model. The nine significantly positive compounds were heptanal, nonanal, octanal, (

• Twenty-four out of 75 patients developed into severe condition in the course of the infection. • The prominent laboratory abnormalities of COVID patients were lymphopenia, elevated C-reactive protein (CRP) and lactate dehydrogenase (LDH). • Elevated interleukin 6 (IL-6) correlated with decrease of LYM%, CD4+ and CD8+ T cell counts, and increase of CRP, LDH and Procalcitonin (PCT) levels.

ObjectiveThe gut microbiota (GM) can have complicated and often undetermined interactions with the function of many organs in the body. GM is altered in a variety of liver diseases, but the significance of such changes on the liver disease is still unclear. Hepatic autophagy deficiency causes liver injury accompanied with cholestasis. Here, we investigated the impact of such hepatic changes on GM and in turn the effect of gut dysbiosis on liver injury.DesignFecal microbiota from mice with liver-specific loss of autophagy-related gene 5 (Atg5), Atg5Δhep mice, were analyzed by 16S sequencing. Antibiotics (ABX) was used to modulate GM in mice. Cholestyramine was used to reduce the enterohepatic bile acid (BA) level. The functional role of fibroblast growth factor 15 (FGF15) and ileal farnesoid X receptor (FXR) was examined in mice over-expressing FGF15 gene, or given a fibroblast growth factor receptor 4 (FGFR4) inhibitor.ResultsThe composition of GM was significantly changed with a notable increase of BA-metabolizing bacteria in Atg5Δhep mice, leading to a lower proportion of tauro-conjugated BAs and a higher proportion of unconjugated BAs in the intestine, which markedly activated ileal FXR with an increased expression of FGF15. ABX or cholestyramine treatment exacerbated liver injury and ductular reaction, and decreased FGF15 expression, whereas modulating FGF15 signaling altered liver phenotypes in the autophagy-deficient mice.ConclusionGut dysbiosis can remedy liver injury in Atg5Δhep mice through the FXR-FGF15 signaling. Antibiotics use in the condition of liver injury may have unexpected adverse consequences via the gut-liver axis.SHORT SUMMARYWhat is already known about this subject?Gut microbiota (GM) can be altered during hepatic pathogenesis.GM are involved in bile acid (BA) metabolism.Autophagy deficiency in the liver disrupts BA homeostasis and causes cholestatic injury.What are the new findings?Deficiency of autophagy in the liver causes alteration of GM, which leads to a higher proportion of BA-metabolizing bacteria.GM contribute to the activation of ileal farnesoid X receptor (FXR) and a higher expression of fibroblast growth factor 15 (FGF15) in autophagy deficient condition in the liver, which is associated with decreased levels of conjugated BAs and increased levels of unconjugated BAs in the intestine.Manipulations that lead to GM alteration, intestinal BA signaling, or FGF15 signaling can all modulate the liver phenotype.BA and GM together can act as a sensor to liver injury to trigger FGF15-mediated protective mechanism.How might it impact on clinical practice in the foreseeable future?These findings indicate that gut dysbiosis in the scenario of liver disease can be beneficial, suggesting cautions should be exercised in the use of antibiotics during specific liver diseases.If antibiotics need to be used in patients with liver diseases it may be beneficial to enhance the FXR-FGF15 feedback signaling to retain the protective effect of GM.

Depression may be associated with reduced monoamine neurotransmission, particularly serotonin and norepinephrine (NE). Reuptake of NE by the norepinephrine transporter (NET) is the primary mechanism by which many of the antidepressants are high-affinity substrates for NET. This study aimed to examine the effect of lentivirus-mediated shRNA targeting NET in locus coeruleus (LC) on depression-like behaviors of rats. We randomly assigned 60 male Wistar rats to 6 experimental groups: (1) Control group: without chronic unpredictable mild stress (CUMS) and without NET-shRNA treatment; (2) shRNA group: without CUMS + NET-shRNA; (3) CUMS group: 3-week CUMS without NET-shRNA; (4) CUMS + nonsense shRNA group; (5) CUMS + amygdala (Amy)-shRNA group; (6) CUMS+ locus coeruleus (LC)-shRNA group. First, recombinant lentiviral vector expressing shRNA (ShRNA-629, ShRNA-330, ShRNA-1222, ShRNA-1146 or ShRNA- negative control) against NET were produced, and their efficiency in knocking down of NET in PC12 cells were assessed by Q-PCR and western blot analysis. Second, shRNA was injected into the rat LC bilaterally to investigate whether it could prevent the depressive-like behavior induced by 3-week CUMS. Third, we tested the depressive-like behavior of the rats in the forced swimming test, the open field test, the sucrose preference test, as well as the body weight gain at the end of the seventh week. Finally, the protein expressions of NET was measured by western blot and the NE levels were measured by high performance liquid chromatography. Q-PCR and western blot showed that the ShRNA-1146 had the best interference efficiency targeting on NET in PC12 cells (p p p p p

Autophagy inhibition has been proposed to be a potential therapeutic strategy for cancer, however, few autophagy inhibitors have been developed. Recent studies have indicated that lysosome and autophagy related 4B cysteine peptidase (ATG4B) are two promising targets in autophagy for cancer therapy. Although some inhibitors of either lysosome or ATG4B were reported, there are limitations in the use of these single target compounds. Considering multi-functional drugs have advantages, such as high efficacy and low toxicity, we first screened and validated a batch of compounds designed and synthesized in our laboratory by combining the screening method of ATG4B inhibitors and the identification method of lysosome inhibitors. ATG4B activity was effectively inhibited in vitro. Moreover, 163N inhibited autophagic flux and caused the accumulation of autolysosomes. Further studies demonstrated that 163N could not affect the autophagosome-lysosome fusion but could cause lysosome dysfunction. In addition, 163N diminished tumor cell viability and impaired the development of colorectal cancer in vivo. The current study findings indicate that the dual effect inhibitor 163N offers an attractive new anti-cancer drug and compounds having a combination of lysosome inhibition and ATG4B inhibition are a promising therapeutic strategy for colorectal cancer therapy.

A cationic lipid-embedded poly(acrylic acid) (PAAc) gel layer coated on chitosan/superparamagnetic iron oxide nanoparticle (SPION) nanohybrid surfaces effectively modulates drug release and MR imaging contrast by pH-responsive morphological transformation and hierarchical alignment of the lipid assemblies.

The outbreak of the novel coronavirus disease 2019 (COVID-19) infection began in December 2019 in Wuhan, and rapidly spread to many provinces in China. The number of cases has increased markedly in Anhui, but information on the clinical characteristics of patients is limited. We reported 75 patients with COVID-19 in the First Affiliated Hospital of USTC from Jan 21 to Feb 16, 2020, Hefei, Anhui Province, China. COVID-19 infection was confirmed by real-time RT-PCR of respiratory nasopharyngeal swab samples. Epidemiological, clinical and laboratory data were collected and analyzed. Of the 75 patients with COVID-19, 61 (81.33%) had a direct or indirect exposure history to Wuhan. Common symptoms at onset included fever (66 [88.0%] of 75 patients) and dry cough (62 [82.67%]). Of the patients without fever, cough could be the only or primary symptom. The most prominent laboratory abnormalities were lymphopenia, decreased percentage of lymphocytes (LYM%), decreased CD4+ and CD8+ T cell counts, elevated C-reactive protein (CRP) and lactate dehydrogenase (LDH). Patients with elevated interleukin 6 (IL-6) showed significant decreases in the LYM%, CD4+ and CD8+ T cell counts. Besides, the percentage of neutrophils, CRP, LDH and Procalcitonin levels increased significantly. We concluded that COVID-19 could cause different degrees of hematological abnormalities and damage of internal organs. Hematological profiles including LYM, LDH, CRP and IL-6 could be indicators of diseases severity and evaluation of treatment effectiveness. Antiviral treatment requires a comprehensive and supportive approach. Further targeted therapy should be determined based on individual clinical manifestations and laboratory indicators.

The rare earth materials have attracted intensive attention due to their strong luminescent characteristic. However, the split fine Stark levels are difficult to be determined. Here we report a room-temperature detection for Stark levels of YNbO4: Er3+ using established laser-induced spectroscopy system with dye laser of superhigh resolution of wavelength at 0.005 nm. From excitation spectra, six split Stark levels of 4G11/2 (Er3+) were directly detected. Moreover, nonradiative relaxations of 4G9/2→4G11/2 and 4G11/2→2H11/2/ 4S3/2 have been observed with weighed lifetimes of 0.70 μs and 6.15 μs, and characteristic green emission of Er3+ (@555 nm) yields lifetime of 31.78 μs.

To remedy the heavy metal ion (HMI) pollution, unravel the relationship of material microstructure and removal performance and clarify relevant mechanism, magnesium-aluminum layered double oxide (MgAl-LDO) has been fabricated via a template method using cellulose. The variously performed characterizations show that ultra-thin flakes of about 5 nm are successfully accessible with the size of 50 ~ 100 nm. They are smaller than the ones prepared without the addition of cellulose. The distinctive structural feature endows the newly-synthesized LDO with large removal capacity for HMIs. Towards Cd2+, Pb2+ and Cu2+, the removal capacity reaches as high as 1422.3, 1336.8 and 1135.4 mg·g−1, respectively. Moreover, the highly achieved durability makes our LDO applicable to treating the polluted water. The mechanism of cation exchange along with deposition has been postulated. The Mg-OH moiety in the sample is found to dominate the HMI removal. The experimental findings are borne out by the first-principle density functional theory calculations on geometries, thermodynamics and electronic structures.

BaFe2As2 superconductors doped with Co or Ni were synthesized by heat treatment of the reactive BaH2 precursor and elemental Fe, Co, Ni, and As in a sealed niobium container. The hydride route prov...

High-performance liquid chromatography (HPLC) was employed to determine drug release rates based on emamectin benzoate concentrations in the medium. Release kinetics equations were used to fit the drug release behavior. The effects of particle size and release medium pH on the release rate were also investigated. The indoor toxicity of emamectin benzoate-loaded polylactic acid microspheres on the diamondback moth larva (Plutella xylostella) was studied to explore drug sustained-release performance. In acidic and neutral media, the drug release behavior of the microspheres was in accord with the first-order kinetics equation. Increasing the spray dosage of emamectin benzoate-loaded polylactic acid microspheres initially resulted in an equivalent insecticidal efficacy with the conventional emamectin benzoate microemulsion. However, the drug persistence period was four-fold longer than that observed using the conventional formulation. The developed emamectin benzoate-loaded polylactic acid microspheres showed dramatic sustained-release performance. A treatment threshold of greater than 35 mg mL−1 was established for an efficient accumulated release concentration of emamectin benzoate-loaded microspheres.

Solvothermal reactions of 1,3-bis(1,2,4-triazol-1-yl)benzene (btb), isophthalic acid (H2ip) with M(NO3)2 (M = Co2+(1), Cu2+(2), Cd2+(3)) afforded three coordination polymers, [M(btb)(ip)]n (Co2+(1), Cu2+(2)) and [Cd2(btb)(ip)2·4H2O]n·4H2O (3), respectively. Both compounds 1 and 2 show 2D networks with binuclear paddle-wheel structures, however 3 is confirmed as 1D double-chain ladder. For complex 1, weak ferromagnetic interactions are detected between CoII ions of Co2 unit without long-range magnetic ordering. Antiferromagnetic interactions are found between the CuII centers in complex 2. In addition, complex 3 shows red-shifted luminescence spectra with obviously higher intensity owning to the more rigid arrangement of the π systems.