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Potassium voltage‑gated channel subfamily A member 5 (KCNA5) is a voltage‑gated potassium channel protein encoded by the KCNA5 gene. A large number of studies have shown that KCNA5 is associated with the survival of malignant tumors, including breast cancer, but the detailed mechanism remains inconclusive. Our previous study found that KCNA5 is co‑expressed with a scaffolding protein, caveolin‑1 in MCF‑10A‑neoT non‑tumorigenic epithelial cell. In the present study, KCNA5 and caveolin‑1 were expressed in breast cancer tissues and cell lines. Exposing MCF‑10A‑neoT to 2 mM of methyl‑β‑cyclodextrin, an agent to disrupt caveolae and lipid rafts led to a downregulation of caveolin‑1 that reduced the expression of KCNA5. Furthermore, following caveolin‑1 knockdown, the expression of KCNA5 was decreased in MDA‑MB‑231 human breast cancer and MCF‑10A‑neoT non‑tumorigenic epithelial cell lines. In subsequent experiments, the MTT assay showed that increased caveolin‑1 and KCNA5 expression promoted the survival of MCF‑7 human breast cancer cells, but cell survival was not affected following KCNA5 overexpression alone. Using small interfering RNA technology, KCNA5‑silenced MCF‑10A‑neoT cells were established and a decreased level of phosphorylated‑AKT serine/threonine kinase (AKT) was observed in the cells compared with the parental cells. Overall, these results suggested that caveolin‑1 facilitated KCNA5 expression and may be associated with AKT activation. [ABSTRACT FROM AUTHOR]

We investigated the minimum inhibitory concentration (MIC), antibacterial activity, and preservation ability of four molar masses of γ-polyglutamic acid (PGA) against Escherichia coli , Bacillus subtilis , and yeast. The antibacterial mechanism was determined based on the cell structure, membrane permeability, and microscopic morphology of the microorganisms. We then measured the weight loss, decay rate, total acid, catalase activity, peroxidase activity, and malondialdehyde content toward the possible use of PGA as a preservative coating for cherries. When the molar mass was greater than 700 kDa, the MIC for Escherichia coli and Bacillus subtilis was less than 2.5 mg/mL. The mechanism of action of the four molar masses of PGA was different with respect to the three microbial species, but a higher molar mass of PGA corresponded to stronger inhibition against the microbes. PGA of 2000 kDa molar mass damaged the microbial cellular structure, resulting in excretion of alkaline phosphatase, but PGA of 1.5 kDa molar mass affected the membrane permeability and the amount of soluble sugar. Scanning electron microscopy indicated the inhibitory effect of PGA. The antibacterial mechanism of PGA was related to the molar mass of PGA and the microbial membrane structure. Compared with the control, a PGA coating effectively inhibit the spoilage rate, delay the ripening, and prolong the shelf life of cherries. [Display omitted] • Four molar masses of PGA have different MICs for three bacteria. • The antibacterial mechanism of γ-polyglutamic acid (PGA) is preliminarily discussed. • The preservation of PGA has prospective application for fruits and vegetables. [ABSTRACT FROM AUTHOR]

Traditional Chinese medicines (TCMs) are undoubtedly treasured natural resources for discovering effective medicines in treating and preventing various diseases. However, it is still extremely difficult for screening the bioactive compounds due to the tremendous constituents in TCMs. In this work, the chemical composition of toad venom was comprehensively analyzed using ultra-high performance liquid chromatography (UPLC) coupled with high-resolution LTQ-Orbitrap mass spectrometry and 93 compounds were detected. Among them, 17 constituents were confirmed by standard substances and 8 constituents were detected in toad venom for the first time. Further, a compound database of toad venom containing the fullest compounds was further constructed using UPLC coupled with high-sensitivity Qtrap MS. Then a target cell-based approach for screening potential bioactive compounds from toad venom was developed by analyzing the target cell extracts. The reliability of this method was validated by negative controls and positive controls. In total, 17 components in toad venom were discovered to interact with the target cancer cells. Further, in vitro pharmacological trials were performed to confirm the anti-cancer activity of four of them. The results showed that the six bufogenins and seven bufotoxins detected in our research represented a promising resource to explore bufogenins/bufotoxins-based anticancer agents with low cardiotoxic effect. The target cell-based screening method coupled with the compound database of toad venom constructed by UPLC-Qtrap-MS with high sensitivity provide us a new strategy to rapidly screen and identify the potential bioactive constituents with low content in natural products, which was beneficial for drug discovery from other TCMs.ᅟGraphical abstract [ABSTRACT FROM AUTHOR]

Dechlorane Plus (DP) is a chlorinated flame retardant that is currently in intensive use and has been detected extensively in the environment. In China, the temporal and spatial distribution of DP is characterized by sources of point emissions in the south and diffusion to the north and west, including to remote, high-elevation areas, which are characterized by different climatic conditions and topographies. Thus, relatively high and low concentrations of DP have been observed in areas without significant nearby pollution sources. High DP concentrations have been observed in South China because of the recycling of large amounts of electronic waste and the presence of a DP factory. DP in urban areas is not influenced by atmospheric transportation, whereas DP in rural areas originates from atmospheric transmission from specific sources, such as e-waste recycling areas, which vary seasonally. Furthermore, DP in Chinese forest soils has been observed to preferentially accumulate in the mineral horizon due to leaching by precipitation as well as erosion by weathering in the organic horizon. Although the hazard quotient (HQ) has been estimated to be far from 1 for DP manufacturing operators, the HQ might not reveal deleterious effects on humans. Extremely high DP concentrations have been observed in serum samples from DP manufacturing operators in China. Moreover, different isomer-specific accumulation in terrestrial species, except for aquatic biota, shows that syn-DP is preferentially accumulated. Finally, to achieve better understanding of the mechanisms of DP degradation both in nature and in organisms, further laboratory study is needed. [ABSTRACT FROM AUTHOR]

Low-cost ceramic floor tiles were successfully produced from recycling red mud with addition of kaolin. (NH 4 ) 6 Mo 7 O 24 were used as catalyst to alter the mullitization reaction pathway and promote the growth of mullite crystals. The effects of molybdate content and sintering temperature on morphologies and performances of resultant specimens were characterized in detail. The phase evolution and microstructure observation were conducted by X-ray powder diffraction (XRD) and scanning electron microscopy (SEM). The results indicate the ceramic floor tile with 6 wt% (NH 4 ) 6 Mo 7 O 24 addition exhibits a flexural strength of 185.6 MPa, bulk density of 1.45 g/cm 3 and water absorption 5.5%, an intergrown microstructure composed of anisotropically grown mullite at 1180 °C. This work opens up the possibilities of the sintered ceramic as a building material since the ceramic system has good performances in flexural strength and bulk density. [ABSTRACT FROM AUTHOR]

In this study, we present detrital zircon U-Pb ages and Hf isotopic data and whole-rock geochemical data from meta-sedimentary rocks of the Jiangyu Group in eastern Jilin Province (Northeast China) to constrain the late Silurian - Early Devonian tectonic evolution of the southeastern Xing'an-Mongolia Orogenic Belt. Two samples of the meta-sedimentary rocks from the Jiangyu Group yielded concordant ages ranging from 2926 to 415 Ma, and the youngest zircon populations of the two samples yielded weighted mean ages of 427 ± 3 and 426 ± 3 Ma, respectively. Combined with reliable published muscovite 40Ar-39Ar ages of 408 Ma from the overlying metamorphic ophiolitic mélange, these data indicate that the protoliths of the Jiangyu Group were deposited during the late Silurian - Early Devonian Era. A comparison of the U-Pb ages and Hf isotopic data for detrital zircons from northeastern Gondwana and the Jiangyu Group indicates a probable tectonic affinity. The whole-rock geochemical data indicate that the protoliths of the meta-sedimentary rocks from the Jiangyu Group were graywackes deposited in a continental arc setting. Based on the recognition of the early to middle Paleozoic subduction-accretion events along the eastern segment of the northern margin of the North China Craton (NCC), we infer that the subduction-accretion events may have occurred in the Yanbian area followed by one or more arc-continent collisions after the Early Devonian. [ABSTRACT FROM AUTHOR]

Malignant glioma are linked to a high mortality rate. Therefore, it is necessary to explore and develop effective therapeutic strategy. Oroxyloside is a metabolite of oroxylin A. However, its inhibitory effects on cancer are little to be known. In the present study, we investigated the effects of oroxyloside on cell proliferation, migration, and apoptosis in vitro and in vivo in human glioma. The results indicated that oroxyloside significantly suppressed the proliferation of human glioma cells through inducing cell cycle arrest at G0/G1 phase through reducing Cyclin D1 and cyclin-dependent kinase 2 (CDK2) while enhancing p53 and p21 expressions. In addition, the migration of glioma cells was dramatically inhibited by oroxyloside in a dose-dependent manner, which was related to its modulation on extracellular matrix (ECM), as evidenced by up-regulated E-cadherin, and metastasis-associated protein 3 (MTA3), whereas down-regulated N-cadherin, Vimentin, Twist, alpha-smooth muscle actin (α-SMA) and Syndecan-2. Furthermore, oroxyloside treatment markedly induced apoptosis in glioma cells through improving Caspase-9, Caspase-3 and PARP cleavage, accompanied with high release of cytochrome c (Cyto-c) into cytoplasm and subsequently increase of apoptotic protease-activating factor 1 (Apaf-1). In vivo, oroxyloside administration significantly inhibited the glioma cell xenograft tumorigenesis through various signaling pathways, including suppression of Cyclin D1/CDK2 and ECM pathways, as well as potentiation of p53/p21 and Caspases pathways. Together, the findings above illustrated that oroxyloside, for the first time, was used as a promising candidate against human glioma. [ABSTRACT FROM AUTHOR]

Aims Several population pharmacokinetic (popPK) models for ciclosporin (CsA) in adult renal transplant recipients have been constructed to optimize the therapeutic regimen of CsA. However, little is known about their predictabilities when extrapolated to different clinical centres. Therefore, this study aimed to externally evaluate the predictive ability of CsA popPK models and determine the potential influencing factors. Methods A literature search was conducted and the predictive performance was determined for each selected model using an independent data set of 62 patients (471 predose and 500 2-h postdose concentrations) from our hospital. Prediction-based diagnostics and simulation-based normalized prediction distribution error were used to evaluate model predictability. The influence of prior information was assessed using Bayesian forecasting. Additionally, potential factors influencing model predictability were investigated. Results Seventeen models extracted from 17 published popPK studies were assessed. Prediction-based diagnostics showed that ethnicity potentially influenced model transferability. Simulation-based normalized prediction distribution error analyses indicated misspecification in most of the models, especially regarding variance. Bayesian forecasting demonstrated that the predictive performance of the models substantially improved with 2-3 prior observations. The predictability of nonlinear Michaelis-Menten models was superior to that of linear compartmental models when evaluating the impact of structural models, indicating the underlying nonlinear kinetics of CsA. Structural model, ethnicity, covariates and prior observations potentially affected model predictability. Conclusions Structural model is the predominant factor influencing model predictability. Incorporation of nonlinear kinetics in CsA popPK modelling should be considered. Moreover, Bayesian forecasting substantially improved model predictability. [ABSTRACT FROM AUTHOR]

A novel thermostable endoglucanase (CTendo45) encoding gene was cloned from Chaetomium thermophilum and heterologously expressed in Pichia pastoris . Sequence alignment indicated that the CTendo45 enzyme belonged to glycoside hydrolase family 45. The recombinant enzyme was purified by Ni 2+ affinity chromatography, and its apparent molecular mass was estimated to be 32 kDa by SDS-PAGE. The purified enzyme displayed maximum activity at 70°C and pH 4. CTendo45 was stable at 60°C for 1 h, and residual activities of 78.9% and 65.6% were estimated after 1 h at 70°C and 80°C, respectively. Ca 2+ , Zn 2+ , Mg 2+ , Cu 2+ and Mn 2+ were found to have beneficial effects on the enzyme activity to different degrees. The specific activity of purified CTendo45 was 1.52 IU mg −1 and the K m value was 59.6 μg ml −1 with a sodium carboxymethyl cellulose substrate. Moreover, CTendo45 exhibited high hydrolysis activity towards pectin, and the hydrolysis products were mainly galacturonic acid oligosaccharides. CTendo45 is the first reported bifunctional enzyme in glycoside hydrolase family 45 from C . thermophilum that is able to hydrolyze both cellulose and pectin. The biochemical properties of this recombinant CTendo45 make it a potentially effective glycoside hydrolase for industrial applications. [ABSTRACT FROM AUTHOR]

Understanding various biogeochemical processes, especially in eutrophic sediments, necessitates fine-scale phosphorus (P) measurements in pore waters. To the best of our knowledge, the fine-scale distributions of P across the sediment profiles of Lake Nansi have rarely been investigated. Herein we evaluated the dynamic distributions of labile P and Fe across the sediment-water interface (SWI) of Lake Nansi at two-dimensional (2D) and sub-millimeter resolution, using well-established colorimetric diffusive gradients in thin films (DGT) methodology. The concentrations of labile P in all investigated sediment profiles exhibited strong spatial variations, ranging from 0 to 1.50 mg/L with a considerable number of hotspots. Lake Nanyang (0.55 ± 0.21 mg/L) had the highest mean concentration of labile P, followed by Lake Dushan (0.38 ± 0.19 mg/L), Lake Weishan (0.28 ± 0.21 mg/L), and Lake Zhaoyang (0.18 ± 0.09 mg/L). The highest concentrations of labile P were always detected in Lake Dushan, which had been subjected to excessive exogenous P pollution. The co-distributions of labile P and Fe in the majority of the sediment of Lake Nansi confirmed highly positive correlations (P < 0.01), suggesting that the mobility of labile P throughout the SWI was likely governed by iron redox processes. The apparent diffusion fluxes of P across the SWI ranged from −7.7 to 33.6 μg/m2·d, with a mean value of 5.26 ± 7.80 μg/m2·d. Positive apparent fluxes for labile P were recorded in most sediment cores, demonstrating the strong upward mobility of P from the sediment to the overlying water. Our results provided accurate and extensive information regarding the micro-distribution and dynamic exchange of labile P across the SWI. This allows for a better understanding of eutrophication processes and the implementation of P management strategies in Lake Nansi. [Display omitted] • The spatial variation and mobility of P in Lake Nansi were characterized using DGT. • 2D, heterogeneously micro-distribution of P in the sediment profile was observed. • Labile P had a northward and downward spatial gradient, related to human activity. • The mobility of P across the SWI was likely governed by iron redox processes. • Fine-scale measurement improves the accuracy P-cycle depiction for eutrophic lake. [ABSTRACT FROM AUTHOR]

Background: Currently, there is limited data on the risk factors associated with treatment delay in tuberculous meningitis (TBM). This study aimed to assess the duration of delay in the treatment TBM and to investigate its determinants.Methods: During the period from September 2009 to February 2016, a retrospective cohort study of consecutive TBM patients admitted to our hospital was conducted to determine the risk factors associated with treatment delay in TBM. Treatment delay duration was defined as the time interval from onset of symptoms (by patient recall) to initiation of treatment and was stratified into two categories: ≤ 20 days, >20 days (median delay day is 20 days). Data collected included demography, comorbidity, cerebrospinal fluid (CSF) examinations and others. Univariable and multivariable logistic regression analysis was used to evaluate the determinants of treatment delay.Results: A total of 161 TBM patients were included in our study, all were confirmed by CSF mycobacterial culture. The median treatment delay for all patients included in the study was 20 days [interquartile range, 14-60 days]. Multivariate analysis revealed that age (≤21 years old, OR = 0.202, 95% CI: 0.079, 0.521), fever (OR = 0.414, 95% CI: 0.180, 0.952), and headache (OR = 0.204, 95% CI: 0.095, 0.442) had significantly lower risk for treatment delay, while multiple healthcare contact (>3 times) (OR = 3.938, 95% CI: 1.326, 11.691) as well as CSF chloride (>111 mmol/L) (OR = 2.479, 95% CI: 1.143, 5.377) had significantly higher risk of the delay.Conclusions: Our findings indicate that multiple healthcare contact and high CSF chloride predict the risk of long delay, while young age, fever and headache are associated with short delay. Maintained focus on awareness of TBM in the population and in healthcare systems, and continuous implementation of diagnostic methods for TBM to detect the disease early, may reduce the mortality and morbidity. [ABSTRACT FROM AUTHOR]

Background: Prior studies evaluating the impact of hysteroscopy on outcomes in endometrial cancer have predominantly evaluated type I tumors. We sought to evaluate whether hysteroscopy worsens prognosis in type II endometrial cancer. Methods: A retrospective cohort analysis of 140 patients from two institutions with type II endometrial cancer was performed. Women who underwent either diagnostic hysteroscopy (HSC) or dilation and curettage (D&C) for cancer diagnosis from June 2001 until June 2010 were included. The clinical and pathologic characteristics, including peritoneal cytology results were reviewed. The primary endpoint was disease-specific survival (DSS). The exposure of interest was hysteroscopy. Survival curves were projected using the Kaplan-Meier method and compared using the log-rank test. Results: There was no difference in age, histology, stage, depth of myometrial invasion, adnexal involvement, or nodal metastasis between HSC and D&C patients. Positive cytology was found in 16/54 (30%) patients following HSC and in 10/86 (12%) following D&C (p = 0.008). Fourteen patients with stage I and II disease had positive peritoneal cytology, with 11/40 (27.5%) patients in the HSC group and 3/59 (5%) patients in the D&C group(p = 0.002). Median DSS was clinically different for the HSC and D&C groups, but statistical significance was not reached (53 versus 63.5 months, p = 0.34). For stage I and II patients, 18/99 (18%) were dead of EC, with a median DSS of 60 months for HSC and 71 months for D&C (p = 0.82). Overall 46 (33%) patients developed a recurrence, with 18/54 (33%) in the HSC group compared to 28/86 (32%) in the D&C group (p = 0.92). There was no difference in recurrence location between groups. Conclusions: Diagnostic hysteroscopy significantly increased the rate of positive peritoneal cytology at the time of surgical staging in this cohort of patients with type II EC. However, we were unable to detect a difference in prognosis as measured by DSS. [ABSTRACT FROM AUTHOR]

Electrocatalytic decomposition of water using bifunctional catalysts is a potential method for clean hydrogen energy production. In order to solve the weakness of present catalysts, this study rationally designed a novel iron-nickel bifunctional electrocatalyst of Fe x Ni 1−x @C, P composites prepared by pyrolysis and phosphorus doping of a FeNi-bimetal-organic framework (FeNi-MOF). The innovative combination of FeNi bimetallic co-doping, low-temperature curing and phosphating has bred an excellent electrocatalyst for the hydrogen evolution reaction (HER) in alkaline solution. When the mass ratio of phosphate to Fe x Ni 1−x @C 250–800 was 10:1, Fe x Ni 1−x @C 250–800 , P (10:1) showed the highest hydrogen evolution activity, obtaining a low 189 mV hydrogen evolution overpotential with a Tafel slope of 91.9 mV·dec−1 at 10 mA·cm−2 current density. Meanwhile, Fe x Ni 1−x @C 250–800 , P exhibited good stability during HER process. This work would open up a novel pathway for designing efficient and stable bifunctional electrocatalysts for water electrolysis as well as sustainable chemistry applications. • A novel electrocatalyst of P-doped carbon-supported FeNi alloys (Fe x Ni 1−x @C, P) was first designed for HER. • Fe x Ni 1−x @C, P has bred an excellent electrocatalyst for the hydrogen evolution reaction in alkaline media. • P-doped carbon-supported FeNi alloys offer numerous effective active sites and accelerate electrons transfer. [ABSTRACT FROM AUTHOR]

Dynamitin (Dmn) is a major component of dynactin, a multiprotein complex playing important roles in a variety of intracellular motile events. We previously found that Wolbachia bacterial infection resulted in a reduction of Dmn protein. As Wolbachia may modify sperm in male hosts, we speculate that Dmn may have a function in male fertility. Here we used nosGal4 to drive Dmn knock down in testes of Drosophila melanogaster to investigate the functions of Dmn in spermatogenesis. We found that knockdown of Dmn in testes dramatically decreased male fertility, overexpression of Dmn in Wolbachia -infected males significantly rescued male fertility, indicating an important role of Dmn in inducing male fertility defects following Wolbachia infection. Some scattered immature sperm with late canoe-shaped head distributed in the end of Dmn knockdown testis and only about half mature sperm were observed in the Dmn knockdown testis relative to those in the control. Transmission electron microscopy (TEM) exhibited fused spermatids in cysts and abnormal mitochondrial derivatives. Immunofluorescence staining showed significantly less abundance of tubulin around the nucleus of spermatid and scattered F-actin cones to different extents in the individualization complex (IC) during spermiogenesis in Dmn knockdown testes, which may disrupt the nuclear condensation and sperm individualization. Since dynein-dynactin complex has been shown to mediate transport of many cellular components, including mRNAs and organelles, these results suggest that Dmn may play an important role in Drosophila spermiogenesis by affecting transport of many important cytoplasmic materials. [ABSTRACT FROM AUTHOR]

The wide application of polyelectrolyte complex (PEC) nanofibers has been restrained by their unsatisfactory mechanical properties due to high porosity. In this study, we proposed a strategy for improving the mechanical properties of PEC nanofibers using graphene oxide (GO) fillers pretreated by polycation. Chitosan/gelatin (CS/GE) was adopted as the PEC model system. Through the proposed preparation procedure, GO/CS/GE nanofibers can be obtained successfully by electrospinning. Fourier transform infrared spectroscopy (FITR) and differential scanning calorimetry (DSC) results revealed the strong interactions between GO and PEC matrix, which resulted from the synergistic effect of electrostatic attraction and hydrogen bonding. The effective dispersion of GO in CS/GE matrix was verified through TEM and XRD analysis. As demonstrated by the results of tensile testing, mechanical properties of CS/GE can be effectively enhanced with the addition of GO fillers. At 1.5 wt% filler content, GO/CS/GE nanofiber membranes achieved 358% augment of tensile strength, 175% improvement of Young's modulus and 460% boost of toughness compared with neat CS/GE, which were attributed to effective filler-matrix interactions and good dispersion of fillers. Therefore, the inclusion of GO fillers into PEC through the procedure proposed in this study is a promising strategy for mechanical enhancement of PEC nanofibers. [ABSTRACT FROM AUTHOR]

Spaceborne gravity gradients are proposed in this paper to provide autonomous orbit determination capabilities for near Earth satellites. The gravity gradients contain useful position information, which can be extracted by matching the observations with a precise gravity model. The extended Kalman filter (EKF) is investigated as the principal estimator. The stochastic model of orbital motion, the measurement equation, and the model configuration are discussed for the filter design. An augmented state filter is also developed to deal with unknown significant measurement biases. Simulations are conducted to analyze the effects of initial errors, data-sampling periods, orbital heights, attitude and gradiometer noise levels, and measurement biases. Results show that the filter performs well with additive white noise observation errors. Degraded observability for the along-track position is found for the augmented state filter. Real flight data from the GOCE (gravity field and steady-state ocean circulation explorer) satellite are used to test the algorithm. Radial and cross-track position errors of less than 100 m have been achieved. [ABSTRACT FROM AUTHOR]

An innovative orbit determination method which makes use of gravity gradients for Low-Earth-Orbiting satellites is proposed. The measurement principle of gravity gradiometry is briefly reviewed and the sources of measurement error are analyzed. An adaptive hybrid least squares batch filter based on linearization of the orbital equation and unscented transformation of the measurement equation is developed to estimate the orbital states and the measurement biases. The algorithm is tested with the actual flight data from the European Space Agency’s Gravity field and steady-state Ocean Circulation Explorer (GOCE). The orbit determination results are compared with the GPS-derived orbits. The radial and cross-track position errors are on the order of tens of meters, whereas the along-track position error is over one order of magnitude larger. The gravity gradient based orbit determination method is promising for potential use in GPS-denied spacecraft navigation. [ABSTRACT FROM AUTHOR]

Polycrystalline Na 0.81−x Bi x Co 1−y Mn y O 2 (0 ≤ x ≤ 0.15, 0 ≤ y ≤ 0.05) thermoelectric materials have been synthesized by solid-state reaction method using Bi and Mn as the property-manipulated substitution elements. The thermoelectric ceramics were characterized by X-ray diffraction (XRD) for phase composition, field emission scanning electron microscopy (FE-SEM) for grain morphology and cross section of sintered samples, and inductive-coupled plasma atomic emission spectroscopy (ICP-AES) for stoichiometric composition. The bulk density and average grain size of the system were also examined. The effects of partial substitution of Bi for Na and/or Mn for Co on the thermoelectric properties of Na 0.81 CoO 2 have been systematically investigated. The power factor was substantially improved by Bi and Mn co-substitution in Na 0.81 CoO 2 , and the power factor value of Na 0.66 Bi 0.15 Co 0.99 Mn 0.01 O 2 was about three times as large as that of Na 0.81 CoO 2 in the whole measured temperature range. It is evident that the Bi and Mn co-substitution is effective for optimizing thermoelectric properties of Na 0.81 CoO 2 . [ABSTRACT FROM AUTHOR]

Many neurodegenerative disorders, such as Parkinson's disease ( PD), are characterized by progressive neuronal loss in different regions of the central nervous system, contributing to brain dysfunction in the relevant patients. Stem cell therapy holds great promise for PD patients, including with foetal ventral mesencephalic cells, human embryonic stem cells ( hESCs) and human induced pluripotent stem cells (hi PSCs). Moreover, stem cells can be used to model neurodegenerative diseases in order to screen potential medication and explore their mechanisms of disease. However, related ethical issues, immunological rejection and lack of canonical grafting protocols limit common clinical use of stem cells. iPSCs, derived from reprogrammed somatic cells, provide new hope for cell replacement therapy. In this review, recent development in stem cell treatment for PD, using hi PSCs, as well as the potential value of hi PSCs in modelling for PD, have been summarized for application of iPSCs technology to clinical translation for PD treatment. [ABSTRACT FROM AUTHOR]

Background: Previous studies have indicated that enhancement of autophagy lysosome pathway may be beneficial for Parkinson's disease (PD), in which aberrant accumulation of aggregated/misfolded proteins and mitochondrial dysfunction are considered as crucial pathogenesis. Recently, a number of studies have suggested the neuroprotective effects of lithium in models of several neurodegenerative diseases including PD. However, the exact mechanisms underlying this neuroprotection remain unclear. In our study, rotenone-exposed SH-SY5Y cells were used as an in vitro parkinsonian model to assess the autophagy-enhancing effect of lithium and the underlying mechanisms were further investigated.Results: Similar to the common used autophagy enhancer rapamycin (Rap, 0.2 μM), lithium (LiCl, 10 mM) significantly recovered the shrinkage of SH-SY5Y cells, and alleviated rotenone-induced cell apoptosis, mitochondrial membrane potential reduction and reactive oxygen species accumulation. Furthermore, the protective effects induced by LiCl were partially blocked by the co-treatment of autophagy inhibitors such as 3-methyladenine (3-MA, 10 mM) or chloroquine (CHL, 10 μM). Moreover, 3-MA or Chl suppressed LiCl-induced autophagy in the immunoblot assay. In addition, the co-localization of LC3 and mitochondria and the preservation of mitochondrial function within LiCl-treated cells were observed, confirming that the damaged mitochondria were cleared through autophagy (mitophagy).Conclusions: These findings suggested that lithium exerted neuroprotection against rotenone-induced injuries partially through the autophagy pathway. Pharmacologically induction of autophagy by lithium may represent a novel therapeutic strategy as a disease-modifier in PD. [ABSTRACT FROM AUTHOR]

The neuroprotection by estrogen (E2) and tamoxifen is well documented in experimental stroke models; however, the exact mechanism is unclear. A membrane-based estrogen receptor, ER-α36, has been identified. Postmenopausal-levels of E2 act through ER-α36 to induce osteoclast apoptosis due to a prolonged activation of the mitogen-activated protein kinase (MAPK)/extracellular signal-related kinase (ERK) signaling. We hypothesized that ER-α36 may play a role in the neuroprotective activities of estrogen and tamoxifen. Here, we studied ER-α36 expression in the brain, as well as its neuroprotective effects against oxygen and glucose deprivation (OGD) in PC12 cells. We found that ER-α36 was expressed in both rat and human brain. In addition, OGD-induced cell death was prevented by l nmol/L 17β-estradiol (E2β). E2β activates the MAPK/ERK signaling pathway in PC12 cells under basal and OGD conditions by interacting with ER-α36 and also induces ER-α36 expression. Low-dose of tamoxifen up-regulated ER-α36 expression and enhanced neuronal survival in an ovariectomized ischemic stroke model. Furthermore, low-dose of tamoxifen enhanced neuroprotective effects by modulating activates or suppress ER-α36. Our results thus demonstrated that ER-α36 is involved in neuroprotective activities mediated by both estrogen and tamoxifen. [ABSTRACT FROM AUTHOR]

The effects of crystal size on the mechanical properties and meso-mechanical behavior of octahydro-1,3,5,7-tetranitro-1,3,5,7-tetrazocine (HMX) based polymer bonded explosives (PBX) during die pressing were systematically studied based on experiments and Discrete Element Method (DEM) simulations. The experimental results show that under the same pressure, larger crystal size will show higher relative breakage (B r), and further lead to the increase of density and the decrease of mechanical strength. By using DEM simulations which considered the realistic particle shape and microstructure of component crystals and binder, a comprehensive understanding of meso-mechanical behavior of PBX powder during die pressing has been achieved. Under the same stress, the maximum contact force between particles increases along with the crystal size. Tensile micro-cracks dominated the crystal breakage during the loading process. Energy dissipation results indicate crystal breakage plays a key role in promoting crystal displacement and enhancing the interparticle friction dissipation. Particularly, at small strains, crystal breakage disrupts the strain energy build-up. At large strains, particle breakage is greatly reduced, steady energy dissipation by elastic potential energy build-up and interparticle friction can be observed. [Display omitted] • A discrete element model was developed to simulate the meso-mechanical behavior of PBX powder during die pressing. • The force chains, cracks propagation and energy dissipation of PBX powder during die pressing are investigated. • Mechanism of the effect of crystal size on the moldability of PBX is illustrated. [ABSTRACT FROM AUTHOR]

Background: We investigated the reliability of core needle biopsy (CNB) in evaluating the status of hormone receptor (HR),human epidermal growth factor receptor (HER)-2, and Ki-67 status, and the effect of neoadjuvant chemotherapy (NAC) on the expression of these immunohistochemical markers. Methods: Among 177 patients with breast adenocarcinoma, 95 patients underwent NACand the remaining 82 patients made up the control group. Immunohistochemistry (IHC) was used to evaluate the expression status of estrogen receptor (ER), progesterone receptor (PR), HER-2, and Ki-67 in the specimens obtained by surgical excision or CNB. Results: In the control group, the expression of ER, PR, HER-2, and Ki-67 was highly consistent between samples from surgical excision or CNB (all r > 0.8, P < 0.05). In theNACgroup, the proportions of sampleswith changes in ER, PR, HER-2, and Ki-67 expression were 12.7%, 24.1%, 5.1%, and 38.0%, respectively; the figures in the control group were 2.4%, 4.9%, 2.4%, and 7.3%, respectively, which significantly differed in ER, PR, and Ki-67 (P < 0.05), but not HER-2 (P > 0.05). In theNAC group, pre- and post-treatment ER+ rates did not significantly differ (P > 0.05), although PR+ and high Ki-67 expression rates did significantly differ (P < 0.05). Conclusion: Neither CNB nor surgical excision samples gave highly consistent results in HR, HER-2, and Ki-67 status.NAC can alter HR and Ki-67 status in breast adenocarcinoma patients.NAC decreased PR+ rate and Ki-67 expression. The mean ER+ rate exhibited a decreasing, but insignificant trend after NAC treatment. NAC had no significant effect on HER-2 expression. [ABSTRACT FROM AUTHOR]

Background The aim of this study was to investigate the feasibility of sentinel lymph node biopsy ( SLNB) after neoadjuant chemotherapy ( NAC) in breast cancer patients with confirmed axillary nodal metastases. Methods We enrolled 51 patients with breast cancer who received NAC. All patients were proven to have axillary nodal metastases by histopathology biopsy prior to NAC. They all underwent SLNB before breast surgery, and complete axillary lymph node dissection immediately followed. Results The identification rate for SLNB was 87.5% (84/96); the false negative rate was 24.5% (12/49). The clinicopathological factors were not significantly correlated with the identification and false negative rate of the SLNB. Lymphatic mapping, blue dye or radionuclide methods tended to decrease the identification rate of SLNB ( P = 0.073). Clinical nodal status before NAC has a trend to increase the false-negative rates of the SLNB ( P = 0.059). For patients with N1 clinical axillary lymph nodal status, the identification rate was 93.9%, and the false negative rate was 5.9%, compared with N2-3 patients with 73.9% and 38.9%, respectively. Conclusions SLNB is feasible for the patients whose axillary lymph nodal status before NAC is N1. However, for N2-3 patients, SLNB cannot be used as an infallible indicator of non- SLN status. [ABSTRACT FROM AUTHOR]

[Display omitted] • A strategy to enhanced performance by adding hybrid semiconductive nanofillers. • Achieve U e of 7.2 J/cm3 with high η of 83% at low field (300 MV/m). • Investigate the underlying mechanism of high energy storage performance. Polymer-based nanocomposites with hybrid fillers are expected to possess high energy storage density taking advantage of different morphologies and electric properties of the nanofillers. In this article, hybrid semi-conductive nanofillers with MoS 2 two-dimensional (2-D) nanosheets and ZnO zero-dimensional (0-D) nanoparticles in different ratios were fabricated by the wet chemical route and ultrasonic mixing. The ZnO nanoparticles have a good distribution on MoS 2 nanosheets confirmed by TEM, XRD, and XPS results. The P(VDF-CTFE-DB)/ZnO@MoS 2 composites with different weight percent of fillers were prepared by solution cast, and the influence of hybrid fillers on polymer matrix was systematically investigated. P(VDF-CTFE-DB) with hybrid filler exhibits optimized discharged energy density of 7.2 J/cm3 and efficiency of 83% at 300 MV/m, both of which are higher than those reported in polymer nanocomposites at the same electric field. Moreover, the distribution of polarization and electric field of the distribution of 2D fillers in four different models for composite P(VDF-CE-DB)/ZnO@MoS 2 with 2 mol% of fillers were investigated by the finite element simulation analysis (COMSOL). In addition, the nanocomposite also possesses high power density and excellent fatigue reliability, demonstrating it can be a good candidate for energy storage device that requires high energy density at a low electric field for safer working conditions. [ABSTRACT FROM AUTHOR]

Electrospinning is a special fiber manufacturing process, which has the advantages of simple equipment, low cost, and controllable process conditions. Cr 2 O 3 is grown in situ on carbon nanofibers by electrospinning technology. The effects of different contents of Cr 2 O 3 on the morphology and physicochemical properties of carbon nanofibers are systematically studied. The in-situ Cr 2 O 3 nanoparticles were distributed evenly on the carbon nanofibers, which increase the defect degree of the carbon nanofibers. The carbon fiber electrode modified by Cr 2 O 3 has good electrochemical reversibility and activity for vanadium ion redox reaction. At 150 mA·cm−2, compared with pristine cell, the discharge capacity and energy efficiency of modified battery are increased by 77.2% and 6%, respectively. The energy storage performance of modified battery has been significantly improved. The synergistic effect of carbon nanofibers and second phase catalyst Cr 2 O 3 with high catalytic performance can effectively enhance the performance of VRFB. [Display omitted] [ABSTRACT FROM AUTHOR]

Summary: In the primate visual system, area V4 is located in the ventral pathway and is traditionally thought to be involved in processing color and form information. However, little is known about its functional role in processing motion information. Using intrinsic signal optical imaging over large fields of view in V1, V2, and V4, we mapped the direction of motion responses in anesthetized macaques. We found that V4 contains direction-preferring domains that are preferentially activated by stimuli moving in one direction. These direction-preferring domains normally occupy several restricted regions of V4 and tend to overlap with orientation- and color-preferring domains. Single-cell recordings targeting these direction-preferring domains also showed a clustering, as well as a columnar organization of V4 direction-selective neurons. These data suggest that, in contrast to the classical view, motion information is also processed in ventral pathway regions such as area V4. [Copyright &y& Elsevier]

A simple and efficient solid-phase extraction - spectrofluorimetric method has been developed to determine glutathione (GSH). Fluorescent probe N-(4,4-difluoro-5,7-dimethyl-4-bora-3a,4a-diaza-s-indacene-3-yl)methyl)iodoacetamide (BODIPY Fl-C1-IA) was used as the derivatization reagent. The procedure was based on a BODIPY Fl-C1-IA selective reaction with GSH to form the highly fluorescent product BODIPY Fl-C1-IA-GSH, using a solid-phase extraction column and spectrofluorimetric determination. The variables affecting analytical performance were studied and optimized. The calibration graph using the preconcentration system for GSH was linear over the range of 1-200 nmol/L with a limit of detection of 0.05 nmol/L (signal-to-noise ratio = 3). The relative standard deviation for six replicate determinations of GSH at the 100 nmol/L concentration level was 3.9%. The method was applied to water samples and average recoveries between 87.5% and 111.5% were obtained for spiked samples. On a développé une méthode simple et efficace d'extractoin spectrofluorimétrique en phase solide pour déterminer le glutathion (GSH). On a utilisé la sonde fluorescente N-(4,4-difluoro-5,7-diméthyl-4-bora-3a,4a-diaza-s-indacène-3-yl)méthyl)iodoacétamide (BODIPY F1-C1-1A) comme réactif pour obtenir des dérivés. La méthode repose sur le fait que le BODIPY F1-C1-1A donne une réaction sélective avec le GSH conduisant à la formation du produit hautement fluorescent BODIPY F1-C1-1A-GSH qui peut être isolé par extraction en phase solide sur colonne et soumis à une détermination spectrofluorimétrique. On a étudié et optimisé les variables qui affectent la performance analytique. Le graphique de calibration à l'aide du système de préconcentration du GSH est linéaire sur la plage de 1 à 200 nmol/L, avec une limite de détection de 0,05 nmol/L (rapport signal à bruit = 3). La déviation relative standard pour six déterminations de GSH en duplicata, à un niveau de concentration de 100 nmol/L, est de 3,9 %. On a appliqué la méthode à des échantillons d'eau et on a obtenu des taux de récupérations moyens variant de 87,5 % à 111,5 % pour les échantillons ensemencés. [ABSTRACT FROM AUTHOR]

Abstract: Most proteins are hydrophilic and poorly encapsulated into the hydrophobic matrix of solid lipid nanoparticles (SLN). To solve this problem, poly (lactic-co-glycolic acid) (PLGA) was utilized as a lipophilic polymeric emulsifier to prepare hydrophilic protein-loaded SLN by w/o/w double emulsion and solvent evaporation techniques. Hydrogenated castor oil (HCO) was used as a lipid matrix and bovine serum albumin (BSA), lysozyme and insulin were used as model proteins to investigate the effect of PLGA on the formulation of the SLN. The results showed that PLGA was essential for the primary w/o emulsification. In addition, the stability of the w/o emulsion, the encapsulation efficiency and loading capacity of the nanoparticles were enhanced with the increase of PLGA concentration. Furthermore, increasing PLGA concentration decreased zeta potential significantly but had no influence on particle size of the SLN. In vitro release study showed that PLGA significantly affected the initial burst release, i.e. the higher the content of PLGA, the lower the burst release. The released proteins maintained their integrity and bioactivity as confirmed by sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE) and biological assay. These results demonstrated that PLGA was an effective emulsifier for the preparation of hydrophilic protein-loaded SLN. [Copyright &y& Elsevier]

As sessile organisms, the precise development phase transitions are very important for the success of plant adaptability, survival and reproduction. The transition from juvenile to the adult phase—referred to as the vegetative phase change—is significantly influenced by numbers of endogenous and environmental signals. Here, we showed that brassinosteroid (BR), a major growth-promoting steroid hormone, positively regulates the vegetative phase change in Arabidopsis thaliana. The BR-deficient mutant det2-1 and BR-insensitive mutant bri1-301 displayed the increased ratio of leaf width to length and reduced blade base angle. The plant specific transcription factors SQUAMOSA PROMOTER BINDING PROTEIN-LIKE (SPL) are key masters for the vegetative phase transition in plants. The expression levels of SPL9, SPL10 and SPL15 were significantly induced by BR treatment, but reduced in bri1-116 mutant compared to wild-type plants. The gain-of-function pSPL9:rSPL9 transgenic plants displayed the BR hypersensitivity on hypocotyl elongation and partially suppressed the delayed vegetative phase change of det2-1 and bri1-301. Furthermore, we showed that BRASSINAZOLE-RESISTANT 1 (BZR1), the master transcription factor of BR signaling pathway, interacted with SPL9 to cooperatively regulate the expression of downstream genes. Our findings reveal an important role for BRs in promoting vegetative phase transition through regulating the activity of SPL9 at transcriptional and post-transcriptional levels. [ABSTRACT FROM AUTHOR]

Soybean protein isolate (SPI) and its four fractionated products (7S globulin, 11S globulin, upper soybean residue, and lower soybean residue) were compared by fabricating films and film liquids. The separation and grading effects, rheological properties of the film liquids, and difficulty in uncovering the films, in addition to the mechanical properties, water vapor permeability, oil permeability, and surface morphology of the films, were investigated. Results showed that the centrifugal precipitation method could be used to produce fractionated products. The 7S and 11S globulin films exhibited better hydrogels at lower shear rates than the other SPIs; however, they were more difficult to uncover. The tensile strength of the graded films decreased by varying degrees. However, the elongation at the break of the upper soybean residue film considerably increased, reaching 70.47%. Moreover, the permeability and surface morphology of the film were enhanced or weakened. The fractionated products, 7S and 11S globulin films, exhibited better performance. Overall, this study provides a basis for the improved development and use of fractioned SPI products. [ABSTRACT FROM AUTHOR]

• Metal boride was firstly proposed as a novel catalyst for VRFB. • TiB 2 nanoparticles has low cost, large surface area and good electrical conductivity. • TiB 2 displays excellent electrocatalytic performance toward V3+/V2+ couple. • TiB 2 modified cell exhibits superior VRFB energy storage performance. [Display omitted] Transition metal borides have broad application prospects in the field of electrochemistry due to their excellent physicochemical stability and electrical conductivity. In this study, metal boride (titanium boride, TiB 2) was first proposed as a novel catalyst for V3+/V2+ in vanadium redox flow battery. Nano-TiB 2 exhibits large specific surface area and great electrical conductivity, and shows excellent catalytic performance in V3+/V2+ redox reaction. The performance of TiB 2 as negative catalyst for cell was further investigated. Compared with pristine cell, TiB 2 modified cell displays much higher discharge capacity (16.9 mA h) after 50 cycles and the incipient energy efficiency increases by 6.5%. The cell with TiB 2 as the negative electrode catalyst exhibits excellent rate performance at 50–150 mA cm−2. Voltage efficiency and energy efficiency of modified cell are 8.7% and 7.5% higher than those of pristine cell at 150 mA cm−2, respectively. In conclusion, this work reveals that nano-TiB 2 is a promising catalyst for enhancing the electrochemical performance toward V3+/V2+ redox reaction for vanadium redox flow battery. [ABSTRACT FROM AUTHOR]

[Display omitted] • Ultrasonic vibration was applied on the compaction process of PBX powder. • By application of ultrasonic increase in the compressive modulus and the tensile fracture and strength was measured. • Enhanced homogeneity and microstructure evolution were reported by applying ultrasonic vibration. • The ultrasound assistance can effectively improve the densification level of samples and lower internal total particle surface area. Improving the density of parts, structural homogeneity, and mechanical properties are the most challenging issues in the PBX compaction process. In this study, the ultrasonic-assisted PBX compaction technique and equipment were introduced and designed. With this equipment, it is found that the density of compacted PBX parts increases, and the diameter expansion and density differences decrease by applying ultrasonic vibration. The influences of compaction pressure, hold time and particle size on the compaction were also analyzed. The results indicate that increasing the pressure and time, while decreasing the particle size, results in a higher density and strength of PBX parts. Then, the microstructures were analyzed to show the mechanism of density distributions. It is found that the density increase is due to the particle's rearrangement leading to a "dense" structure and smaller particle sizes with ultrasonic vibration. Finally, the compressive modulus and strength, and the tensile fracture and strength were found to increase by applying ultrasonic vibration. These mechanical properties decrease along the radial and axial direction, indicating the surface effect of the ultrasonic vibration. [ABSTRACT FROM AUTHOR]

• Providing a new method for the preparation of Al-Ti-C grain refiner. • The contact angle θ of aluminum-carbon interface is reduced under ultrasonic field. • TiC particles are detached from the interface driven by sound pressure, which results that the wetting interface is updated in real time. • The wetting and spreading of the aluminum melt on the graphite surface under ultrasonic field are simulated. In the preparation of an Al-Ti-C grain refiner under an ultrasonic field, the mechanism of the wetting behaviour between Al and C was systematically investigated. The results demonstrated that the wetting behaviour was mainly dependent on the wetting of the Al melt on graphite under the ultrasonic field (physical wetting) and the formation and mass transfer of TiC (reactive wetting). The diffusion of Ti atoms and their adsorption around the graphite could contribute to the wetting of Al-C. TiC particles were formed under the high temperature caused by the cavitation effect, and they detached from the interface due to the sound pressure, which resulted in consistently sufficient contact on the wetting interface. Moreover, the wetting and spreading behaviour of the Al melt on graphite under an ultrasonic field were numerically simulated, strongly manifesting that the ultrasonic field could facilitate the wetting of the Al-C interface. [ABSTRACT FROM AUTHOR]

The composite system composed of polymer, conductive and dielectric filler has excellent dielectric properties. Herein, by studying the effect of filler distribution on the composite system's performance, the graphene nanoplatelets/Polystyrene (GNP/PS)/Barium titanate/Polyvinylidene Fluoride (BT/PVDF) selective composite system is prepared. When the conductivity and dielectric loss change little, the dielectric constant and breakdown field strength of the selective composite system are improved obviously. In the selective composite system, as the dielectric constant is between 12 and 13, the characteristic breakdown field strength is as high as 25.8 kV/mm, which is over three times higher than it of the pure composite system. It is because the addition of BT and GNP particles enhances the establishment of polarization. Besides, the blending of PVDF and PS improves the breakdown field strength of the material. Comprehensive properties of the material are enhanced. Therefore, this study provides a basis for the subsequent study of dielectric materials. • The selective composite system of (graphene plate/polystyrene)/(barium titanate/polyvinylidene fluoride) is prepared. • In the selective composite system, the characteristic breakdown field strength is as high as 25.8 kV/mm, which is over three times higher than it of the pure composite system. • The dielectric constant of the blend system which has continuous matrix and selective distribution of fillers is predicted by the mixed dielectric model. • The theoretical predicted value of the dielectric constant is in good agreement with the measured value. [ABSTRACT FROM AUTHOR]

As a novel type of proton conductor, BaHfO 3 -based proton conductor has a promising application potential, but its poor sinterability and low conductivity limit its application as hydrogen separation membrane materials. In this paper, In and Sn co-doping BaHfO 3 strategy was adopted to further optimize its sinterability and electrical conductivity. BaHf 0.9−x In x Sn 0.1 O 3−δ (x = 0.05–0.25) proton conductors were prepared by high temperature solid state method. The results of X-ray diffraction show that In3+ and Sn4+ have been successfully doped into the lattice to form a cubic perovskite structure. BaHf 0.7 In 0.2 Sn 0.1 O 3−δ (BHSI) was facilely sintered and reached a relative density above 96.25% at 1600 °C. The scanning electron microscope observation shows that the introduction of In3+ and Sn4+ can effectively improve the sinterability and increase the grain size of the sample. High relative density and big grain size allow reducing the volume fraction of grain boundaries and increasing the electrical conductivity of BHSI. The total conductivity of BHSI in wet air reaches 5.69 × 10−3 S cm−1 at 700 °C. In addition, BHSI also shows excellent chemical stability in pure H 2 and CO 2 , 200 ppm H 2 S and water steam, and boiling water. The obtained BHSI membranes were evaluated for hydrogen separation under a mode-pure protonic conductor with external short circuit. The hydrogen separation performance of BHSI membrane was tested systematically. Gas humidification on the feed side and sweep side can obviously increase the hydrogen permeation fluxes. BHSI membrane still maintains a stable hydrogen permeation performance, even 3% CO 2 and 100 ppm H 2 S was introduced into the feed gas, respectively. • The sinterability of barium hafnate-based proton conductors is improved by In and Sn co-doping. • BaHf 0.7 In 0.2 Sn 0.1 O 3−δ exhibits the improved conductivity due to decreasing bulk and grain boundary resistances. • The BaHf 0.7 In 0.2 Sn 0.1 O 3−δ membrane shows high performance for hydrogen separation. [ABSTRACT FROM AUTHOR]

The COVID-19 pandemic has been disastrous to society and effective drugs are urgently needed. The papain-like protease domain (PLpro) of SARS-CoV-2 (SCoV2) is indispensable for viral replication and represents a putative target for pharmacological intervention. In this work, we describe the development of a potent and selective SCoV2 PLpro inhibitor, 19. The inhibitor not only effectively blocks substrate cleavage and immunosuppressive function imparted by PLpro, but also markedly mitigates SCoV2 replication in human cells, with a submicromolar IC 50. We further present a convenient and sensitive activity probe, 7 , and complementary assays to readily evaluate SCoV2 PLpro inhibitors in vitro or in cells. In addition, we disclose the co-crystal structure of SCoV2 PLpro in complex with a prototype inhibitor, which illuminates their detailed binding mode. Overall, these findings provide promising leads and important tools for drug discovery aiming to target SCoV2 PLpro. [Display omitted] • Development of a sensitive and affordable PLpro activity probe • Identification of potential SCoV2 PLpro inhibitors through HTS • Co-crystal structure determination and lead optimization • Characterization of a submicromolar inhibitor of SCoV2 PLpro represents a putative druggable target for SCoV2. Utilizing multiple approaches, including fluorogenic activity probes, HTS, co-crystallization, structure-based design, and other optimized cellular assays, Shan et al. successfully develop a potent and selective inhibitor of SCoV2 PLpro. [ABSTRACT FROM AUTHOR]

Simple Summary: Cancer, a major public health issue worldwide, is the second most common cause of death. Initiatives such as the Human Genome Project (HGP) and Human Proteome Project (HPP) have greatly advanced the understanding of human health and disease, including cancer, and are supporting the current trend towards personalized/precision medicine. In this review, we will overview recent technological achievements, the key hallmarks of cancer, and unmet clinical needs. We will specifically detail the importance of cancer biomarkers in diagnosis and treatment, the role of the microbiome in health and disease, the potential of emerging omics technologies and the goals of personalized/precision medicine. Finally, we will discuss future perspectives, both from the standpoint of perceived advances in treatment, but also from the hurdles that have to be overcome. As of 2020 the human genome and proteome are both at >90% completion based on high stringency analyses. This has been largely achieved by major technological advances over the last 20 years and has enlarged our understanding of human health and disease, including cancer, and is supporting the current trend towards personalized/precision medicine. This is due to improved screening, novel therapeutic approaches and an increased understanding of underlying cancer biology. However, cancer is a complex, heterogeneous disease modulated by genetic, molecular, cellular, tissue, population, environmental and socioeconomic factors, which evolve with time. In spite of recent advances in treatment that have resulted in improved patient outcomes, prognosis is still poor for many patients with certain cancers (e.g., mesothelioma, pancreatic and brain cancer) with a high death rate associated with late diagnosis. In this review we overview key hallmarks of cancer (e.g., autophagy, the role of redox signaling), current unmet clinical needs, the requirement for sensitive and specific biomarkers for early detection, surveillance, prognosis and drug monitoring, the role of the microbiome and the goals of personalized/precision medicine, discussing how emerging omics technologies can further inform on these areas. Exemplars from recent onco-proteogenomic-related publications will be given. Finally, we will address future perspectives, not only from the standpoint of perceived advances in treatment, but also from the hurdles that have to be overcome. [ABSTRACT FROM AUTHOR]

• We established a target separation counter-current chromatography technique. • The technique was used to separate components of zedoary turmeric oil. • Four lysine-specific demethylase 1 (LSD1) inhibitors were efficiently separated. • These are the first sesquiterpene-based natural LSD1 inhibitors characterized. • One of the compounds inhibited tumor cell migration and evasion. Lysine-specific histone demethylase 1 (LSD1) was the first histone demethylase identified in epigenetics and has recently emerged as an attractive therapeutic target for treating tumors. To date, almost all reported LSD1 inhibitors have been chemosynthesized; however, natural products possess pharmacological and biological activity and can be sources for drug development. Here, we established a target separation countercurrent chromatography technique to isolate LSD1 inhibitors from zedoary turmeric oil. Four sesquiterpene-based LSD1 inhibitors were efficiently obtained with an inhibition ratio equal to or less than that of the positive control drug. Compound 2 showed the most potent inhibitory activity, with a half-maximal inhibitory concentration of 3.97 μM, and was further tested to determine its ability to inhibit LSD1 and its antitumor metastatic effects in MDA-MB-231 cells. These four compounds are the first sesquiterpene-based natural LSD1 inhibitors to be characterized. Our findings provide a new molecular framework for studying LSD1 inhibitors and offer a template for designing more sesquiterpene-based LSD1 inhibitors with potential antitumor activity. [ABSTRACT FROM AUTHOR]

Rapid, reliable and easy-to-implement diagnostics that can be adapted in early severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) diagnosis are critical to combat the epidemic. SARS-CoV-2 nucleocapsid protein (NP) is an ideal target for viral antigen-based detection. A rapid and convenient method was developed based on fluorescence immunochromatographic (FIC) assay to detect the SARS-CoV-2 NP antigen. However, the accuracy of this diagnostic method needs to be examined. This prospective study was carried out between 10 and 15 February 2020 in seven hospitals in Wuhan and one hospital in Chongqing, China. Participants with clinically suspected SARS-CoV-2 infection were enrolled. NP antigen testing by FIC assay and nucleic acid (NA) testing by real-time reverse transcriptase PCR (RT-PCR) were performed simultaneously in a blinded manner with the same nasopharyngeal swab sample. The diagnostic accuracy of NP antigen testing was calculated by taking NA testing of RT-PCR as the reference standard, in which samples with a cycle threshold (C t) value of ≤40 were interpreted as positive for SARS-CoV-2. A total of 253 participants were enrolled; two participants were excluded from the analyses because of invalid NP testing results. Of 251 participants (99.2%) included in the diagnostic accuracy analysis, 201 (80.1%) had a C t value of ≤40. With C t value 40 as the cutoff of NA testing, the sensitivity, specificity and percentage agreement of the FIC assay was 75.6% (95% confidence interval, 69.0–81.3), 100% (95% confidence interval, 91.1–100) and 80.5% (95% confidence interval, 75.1–84.9) respectively. With RT-PCR assay as the reference standard, NP antigen testing by FIC assay shows high specificity and relatively high sensitivity in SARS-CoV-2 diagnosis in the early phase of infection. [ABSTRACT FROM AUTHOR]

Platycodin D (PD) is a triterpenoid saponin that exists in the roots of Platycodonis. It exhibits evident growth inhibitory effects and potent cytotoxicity against multiple types of cancer. Gallbladder cancer (GBC) is the most common malignant disease of the biliary tract system. Patients with GBC usually have limited available treatment strategies and a poor prognosis. The present study investigated the antitumor effects of PD on human GBC cells in vitro and its underlying molecular mechanisms of action. The results indicated that PD, as assessed using MTT and colony forming assays, induced evident growth inhibition. Flow cytometry indicated that PD robustly induced apoptosis and blocked GBC cells at the G2/M phase. Cell migration and invasion assays demonstrated that PD effectively inhibited the migratory and invasive abilities of GBC cell lines. Western blotting indicated that PD may initiate mitochondrial destruction in GBC cells through the JNK signaling pathway, thereby inducing apoptosis. The present results indicated that PD may exhibit antitumor effects by inducing apoptosis; inhibiting migration and invasion; and affecting the cell cycle in GBC cells. Therefore, PD has the potential to become a novel antitumor drug for GBC therapy. [ABSTRACT FROM AUTHOR]

Background: Breast cancer is a worldwide health concern. For early stage breast cancer patients, choosing the surgical method after diagnosis is always a dilemma. Decision aids designed for use by patients are tools which may help with surgical decision making for these patients.Methods: We screened through MEDLINE, EMBASE, PubMed and Web of Science using the inclusion criteria which included (1) newly diagnosed patients with early stage breast cancer, (2) outcomes/results involving surgical options including breast conserving surgery. The search strategy used these key words or the combination of these words: "breast cancer", "decision aid", "decision making", "decision support", "breast conserving surgery", "breast conserving therapy".Results: A total of 621 studies were identified, but only seven studies were included. Results were synthesized into narrative format. Various patterns of decision aids designed for use by patients were implemented. Mostly were educational materials via booklet, video or CDROM with or without assistance from surgeons. After decision aids, four studies showed that patients were more likely to change their original choices into mastectomy or modified radical instead of sticking to breast conserving surgery. Other results such as knowledge of breast cancer and treatments, decisional conflict and satisfaction, psychological changes after surgery and quality of life were all showed with a better trend in patients with decision aids in most studies.Conclusion: Decision aids on breast conserving surgery made it easier for patient involvement in surgical decision making and improved decision-related outcomes in most early stage breast cancer patients. With more attention, improving procedures, and better interdisciplinary cooperation, more research is necessary for the improvement of decision aids. And we believe decision aids with agreed objective information are needed. [ABSTRACT FROM AUTHOR]

Background: Cancer stem cells (CSCs) play an important role in tumor invasion and metastasis. CD44 is the most commonly used marker of CSCs, with the potential to act as a determinant against the invasion and migration of CSCs and as the key factor in epithelial–mesenchymal transition (EMT)-like changes that occur in colorectal cancer (CRC). Runt-related transcription factor-2 (RUNX2) is a mesenchymal stem marker for cancer that is involved in stem cell biology and tumorigenesis. However, whether RUNX2 is involved in CSC and in inducing EMT-like changes in CRC remains uncertain, warranting further investigation. Methods: We evaluated the role of RUNX2 in the invasion and migration of CRC cells as a promoter of CD44-induced stem cell- and EMT-like modifications. For this purpose, western blotting was employed to analyze the expression of differential proteins in CRC cells. We conducted sphere formation, wound healing, and transwell assays to investigate the biological functions of RUNX2 in CRC cells. Cellular immunofluorescence and coimmunoprecipitation (co-IP) assays were performed to study the relationship between RUNX2 and BRG1. Real-time quantitative PCR (RT-qPCR) and immunohistochemistry (IHC) were performed to analyze the expressions of RUNX2, BRG1, and CD44 in the CRC tissues. Results: We found that RUNX2 could markedly induce the CRC cell sphere-forming ability and EMT. Interestingly, the RUNX2-mediated EMT in CRC cell may be associated with the activation of CD44. Furthermore, RUNX2 was found to interact with BRG1 to promote the recruitment of RUNX2 to the CD44 promoter. Conclusions: Our cumulative findings suggest that RUNX2 and BRG1 can form a compact complex to regulate the transcription and expression of CD44, which has possible involvement in the invasion and migration of CRC cells. [ABSTRACT FROM AUTHOR]

In this work, a novel combined forward osmosis (FO)-extraction process is applied for resource recovery and dye wastewater treatment simultaneously. FO process is utilized to concentrate the dye wastewater, to achieve a higher concentration factor and lower energy consumption compared with NF process. The FO pre-treatment can increase the dye concentration and reduce the stream volume, thereby reducing the reagent consumption in the subsequent extraction process and lowering the processing cost. In the extraction process, the compositions of the extractant and stripping agent are also optimized, and the recovery rates for congo red, fuchsin acid, orange acid and methyl blue are 97.8%, 82.1%, 80.1% and 76.1%, respectively. In addition, the FO process is driven by the simulated seawater (0.6 M NaCl) draw solution, which can avoid the energy-intensive operation for the draw solution regeneration. Therefore, this study provides a sustainable strategy for the dye wastewater treatment in the coastal areas. Image 1 • FO pre-treatment can reduces the reagent consumption in extraction process. • Hybrid process achieves high dye recovery from dye wastewater. • FO shows a higher concentration factor and lower energy consumption compare to NF. • Seawater-driven FO avoids energy-intensive regeneration of draw solution. [ABSTRACT FROM AUTHOR]

Forward osmosis (FO) is a promising membrane-based technology for water treatment and desalination. But, internal concentration polarization (ICP), a unique phenomenon in FO, generally leads to the sharp performance decline. In this study, a novel polyacrylonitrile (PAN) substrate with low polymer concentration (4 wt%) of the thin-film composite (TFC) membrane with a low membrane structural parameter (S) is developed with sodium chloride (NaCl) aqueous solution as the coagulation bath, and exhibits high performance for FO applications. The existence of NaCl in the coagulation bath not only affects the phase inversion process significantly, resulting in the formation of a thin substrate with finely tuned morphology structure, but also benefits the formation of a uniform and defect-free top polyamide (PA) layer. Effects of NaCl content in the coagulation bath on the morphology and intrinsic properties of resulting PAN substrates, the formed PA layer, as well as the morphology and FO performance of resulting TFC membranes, are investigated systematically. Moreover, an extended study on cellulose acetate (CA) substrate is also conducted to study the universality of this salt induction method to fabricate high-performance TFC membranes. Compared to the control TFC membrane, modified TFC membranes show much lower S parameters and superior separation performance with the higher water flux (324% increment) and lower reverse salt flux (58% reduction). Image 1 • Substrates with low ICP were fabricated using salt-containing coagulation bath. • Modified substrates exhibit higher porosity, smaller thickness and large pore size. • TFC membranes with a modified substrate have rougher and thicker PA layers. • Modified TFC membrane possesses much higher water flux and lower reverse salt flux. • Modified TFC membrane has significantly lower structural parameter. [ABSTRACT FROM AUTHOR]

The aerobic granular sludge with larger size and more compact spherical structure generally shows excellent performance in antibiotic removal, yet little is known about the long-term effect of environmentally-relevant concentration (μg/L) of antibiotics on the proliferation of antibiotic resistance genes (ARGs) and microbial community in aerobic granules. Herein, a sequencing batch reactor (SBR) was set up with dosing different concentrations (0–500 μg/L) of tetracycline to investigate its influences on microbial communities and ARG levels in aerobic granular sludge. Results show that the bioreactor could effectively remove chemical oxygen demand (COD), nitrogen, and tetracycline during the long-term operation. The quantitative polymerase chain reaction (qPCR) analysis shows that tetracycline at μg/L level could greatly enhance the absolute and relative abundances of tetA , sulII , and bla TEM - 1 in the effluent and aerobic granules, indicating tetracycline could serve as a selection pressure on the development of ARGs corresponding to different types of antibiotics in aerobic granules. Pearson's correlation analysis also implies that sulII and bla TEM - 1 were correlated strongly with tetA. Moreover, the presence of tetracycline altered the microbial communities and diversity of the effluent and aerobic granules in the bioreactor. These findings would advance our understanding of the proliferation and development of ARGs in aerobic granules under tetracycline pressure and serve as a foundation to guide the application of aerobic granular sludge for treatment of antibiotic-containing wastewater. Unlabelled Image • Tetracycline did not inhibit the performance of bioreactor in pollutant removal. • Tetracycline altered microbial community and diversity of aerobic granular sludge. • Long-term pressure of tetracycline could co-enrich tetA , sulII , and bla TEM - 1. • sulII and bla TEM - 1 were strongly correlated with tetA in aerobic granular sludge. [ABSTRACT FROM AUTHOR]

Signal transducer and activator of transcription 3 (STAT3) is a well-known antitumor target. Exogenous ROS insult can lead to selective cytotoxicity against cancer cells. A combination of STAT3 inhibition and 'oxidation therapy' may be a new strategy to address the multidrug-resistance issue due to their important roles in the survival and drug resistance of cancer cells. Here, a series of novel curcumin-BTP hybrids were designed and evaluated as STAT3 inhibitors with ROS production activity. Compound 6b exerted the best antitumor activity and selectivity for MCF-7 and MCF-7/DOX cells (IC50 = 0.52 μM and 0.40 μM, respectively), while its IC50 value for MCF-10A breast epithelial cells was 7.72 μM. Furthermore, compound 6b suppressed STAT3 phosphorylation, nuclear translocation and DNA-binding activity and the expression of STAT3 specific oncogenes. Increases in the level of IL-6-induced p-STAT3 were also inhibited by 6b without influencing IFN-γ-induced p-STAT1 expression. Additionally, 6b effectively promoted intracellular ROS accumulation, induced cancer cell apoptosis and cell cycle arrest, abolished the colony formation ability of breast cancer cells, and inhibited P-gp expression in MCF-7/DOX cells. Finally, 6b suppressed the growth of implanted human breast cancer in vivo. Our findings highlight that 6b may be a promising therapeutic agent for drug-sensitive and drug-resistant breast cancers. [ABSTRACT FROM AUTHOR]