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[Display omitted] • A trash to high-value-added material strategy of waste conversion is presented. • Two interactions of polyurethane surface and silica are revealed. • The mechanism of coalescence demulsification of emulsions is revealed. • The obtained materials can separate immiscible and emulsified oil/water mixtures. • The scaling up of the oil/water separator from lab to a factor of 100 was studied. Polyurethane plastic waste (PUPW), a port-abundant solid waste, is difficult to degrade naturally and poses a severe threat to the environment. Hence, the effective recycling of PUPW remains a challenge. Herein, a strategy of converting PUPW into stacked oil/water filtration layer grain through a layer-by-layer (LBL) assembly process is investigated. Notably, such PU-based, grain-stacked, and switchable wettability of the oil/water filter layer is first reported. The grain-stacked filter layers are flexible for separating immiscible oil/water mixtures, water-in-oil emulsions (WOE), and oil-in-water emulsions (OWE) under gravity over 10 cycle-usages. They can withstand strong acid/alkali solutions (pH = 1–14) and salt solutions over 12 h. Besides, 100-times scale-up experiments have indicated that the obtained filter layers exhibit an upper to 98.2 % separation efficiency for 10 L real industrial oil/water emulsion in the 24 h continuous operation. The demulsification mechanism for emulsions is that the electrostatic interaction along with adsorption between emulsion droplets and grains leads to the uneven distribution of surfactants on the interface film of the emulsion droplets, increasing the probability of tiny droplets colliding and coalescing into large droplets to achieve oil/water separation. This work proposes an effective and economical method of abundant plastic waste for industrial-scale oil–water separation rather than just on the laboratory-scale. [ABSTRACT FROM AUTHOR]

Epidermal growth factor receptor (EGFR) is a receptor tyrosine kinase and mutations in EGFR is a major driver force of lung cancer. EGFR tyrosine kinase inhibitors (TKIs) are group of promising agents to treat cancer patients with EGFR mutations. However, the application of TKIs is often hampered by the development of drug-resistance. In the present study, we studied the role of Glutathione peroxidase 4 (GPX4) and mammalian target of rapamycin (mTOR) in regulation of lung cancer cells response to Lapatinib (Lap). Lap resistant NSCLC cells A549/Lap and H1944/Lap were created and GPX4 was knockdown by lentivirus shGPX4. Change of cell viabilities and cell death were measured by MTT and flow cytometry, respectively. ROS, MDA, GSH and Fe2+ were detected by commercial kits. Xenograft mice was used to assay the in vivo effects of GPX4 on the sensitivity of Lap. We found that GPX4 and mTORC1 signalling was upregulated in Lap resistant NSCLC cells when compared to Lap sensitive NSCLC cells. Mechanistically, upregulation of GPX4 was due to enhanced activation of mTORC1 in Lap resistant NSCLC cells. Inhibition of mTORC1 led to the downregulation of GPX4 which promoted Lap induced ferroptosis as evidenced by increase of ROS, MDA, Fe 2+ and decrease of GSH. Rescue experiments confirmed the role of GPX4 in regulation of Lap induced ferroptosis. In vivo experiments also indicated that silencing of GPX4 enhanced the anticancer effect of Lap via promoting ferroptosis. Overall, targeting GPX4 might be a potential strategy to enhance antitumor effects of Lap. • GPX4 and mTOR signalling were upregulated in NSCLC cells that are resistance to Lapatinib. • Inhibition of GPX4 or mTOR could overcome resistance to Lapatinib by promoting ferroptosis in NSCLC cells. • mTOR signalling pathway positively regulate the expression of GPX4. • Knockdown of GPX4 enhanced the anti-tumour effects of Lapatinib in vivo. [ABSTRACT FROM AUTHOR]

Protoporphyrinogen oxidase (PPO, EC 1.3.3.4) is the last common enzyme in the biosynthetic pathway in the synthesis of heme and chlorophyll. The high-frequency use of PPO inhibitor herbicides has led to the gradual exposure of pesticide damage and resistance problems. In order to solve this kind of problem, there is an urgent need to develop new PPO inhibitor herbicides. In this paper, 16 phenylpyrazole derivatives were designed by the principle of active substructure splicing through the electron isosterism of five-membered heterocycles. Greenhouse herbicidal activity experiments and in vitro PPO activity experiments showed that the inhibitory effect of compound 9 on weed growth was comparable to that of pyraflufen-ethyl. Crop safety experiments and cumulative concentration experiments in crops showed that when the spraying concentration was 300 g ai/ha, wheat, corn, rice and other cereal crops were more tolerant to compound 9 , among which wheat showed high tolerance, which was comparable to the crop safety of pyraflufen-ethyl. Herbicidal spectrum experiments showed that compound 9 had inhibitory activity against most weeds. Molecular docking results showed that compound 9 formed one hydrogen bond interaction with amino acid residue ARG-98 and two π-π stacking interactions with amino acid residue PHE-392, indicating that compound 9 had better herbicidal activity than pyraflufen-ethyl. It shows that compound 9 is expected to be a lead compound of phenylpyrazole PPO inhibitor herbicide and used as a herbicide in wheat field. [Display omitted] • The active fragments of target compounds are from different commercial herbicides. • The PPO inhibitory activity (IC 50) of all target compounds were determined. • The herbicidal spectrum experiment of compound 9 was carried out. • The mechanism of action of target compounds was studied by molecular docking. [ABSTRACT FROM AUTHOR]

Soft nanoparticles have attracted increasing attention in biomedical fields because of their unique biological behaviors such as long circulation and high cellular uptake. However, previously reported soft nanoparticles are generally spherical or torispherical in shape, and non-spherical soft nanoparticles are rarely reported because of the shape is thermodynamically unstable for typical soft materials (e.g., liposomes and micelles). Herein, soft mesoporous organosilica nanorods with gold plasmonic core protected with poly-ethylene imine (GNR@SMON/PEI) have been successfully synthesized, for the first time, by a dispersive-protection etching method, in which rod-like solid mesoporous organosilicas with gold nanorod are firstly shielded with PEI (GNR@MON/PEI) and then etched with aqueous NaOH solution. The prepared GNR@SMON/PEI inherits the rod morphology of the mother particle, showing wrinkled morphology and excellent dispersity thanks to the dispersive-protection effect of PEI. In addition, the GNR@SMON/PEI possesses a uniform size (174 × 105 nm), well-defined mesopores (3.9 nm), high surface area (355 m2/g) and large pore volume (0.35 m3/g). Notably, the soft GNR@SMON/PEI exhibits significantly lower Young's modulus (120.2 MPa) in contrast with the hard counterpart (361.4 MPa). Furthermore, after being decorated with hyaluronic acid (HA), the soft GNR@SMON/PEI-HA exhibits excellent in vitro and in vivo biocompatibility. The soft GNR@SMON/PEI-HA has achieved 3-fold cellular uptake efficiency in contrast with the hard one, indicating great potential for biomedical applications. Taken together, this work reports the controllable synthesis of a soft mesoporous nanorod with high cellular uptake efficiency, providing a vital strategy for the synthesis of non-spherical soft nanoparticles and a new nanoplatform for various biomedical applications in future. [ABSTRACT FROM AUTHOR]

Abstract Air pollution exposure has been associated with hypertension, but limited studies have examined the associations in diabetic patients. We aimed to examine the associations of exposure to air pollution with blood pressure in diabetic patients. We identified patients who were previously diagnosed as type-2 diabetes mellitus from hospital records from January 2013 to May 2017. We used generalized linear models to estimate adverse effects of air pollution on systolic/diastolic blood pressure in diabetic patients. A total of 40,125 patients were enrolled in this study. An IQR increase in PM 2.5 , PM 10 , NO 2 , SO 2 , and O 3 exposure was associated with an increased risk of higher systolic blood pressure level (β = 0.628 for PM 2.5 , β = 0.758 for PM 10 , β = 0.766 for NO 2 , β = 0.516 for SO 2 , β = 0.482 for O 3 , all P value < 0.05). Significant associations were observed for some air pollutants and SBP among patients with fasting blood glucose (FBG) ≥ 7.0 mmol/L, normal weight, and younger age. Little evidence was available for the associations between particulate matter (PM) or O 3 exposure and diastolic blood pressure in present study. In our study, diabetic patients were at increased risk of higher blood pressure when exposed to higher residential PM, NO 2 and SO 2. Individuals with lower BMI, younger age, and FBG ≥ 7.0 mmol/L were more susceptible to the adverse effects of ambient air pollution. Highlights • Air pollution has important impact on blood pressure in Diabetic patients in China. • Higher blood pressure occurred in DM patients when exposed to PM, NO 2 and SO 2. • Lower BMI, younger age, and FBG ≥ 7.0 mmol/L were more susceptible to air pollution. [ABSTRACT FROM AUTHOR]

Essential trace elements (ETEs) are essential nutrients for keeping the nervous system functioning. Associations between ETEs and cognitive function are still inconclusive and limited. We aimed to investigate the individual and joint associations between ETEs and cognitive function among older adults. A population (N = 2181) at an average age≥ 65 from Yiwu cohort in China was available for this study. Whole blood chromium (Cr), selenium (Se), manganese (Mn), and copper (Cu) concentrations were measured by inductively coupled plasma mass spectrometry (ICP-MS). Cognitive function was assessed using the Mini-Mental State Examination (MMSE), consisting of five specific cognitive domains: orientation, registry, attention and calculation, recall, and language and praxis. Linear regression, restricted cubic spline (RCS) analysis, and Bayesian kernel machine regression (BKMR) were used to analyze the individual and joint associations between ETEs and cognitive function. The association between Cr and MMSE score presented an inverted-U shape (Q3 versus Q1: β = 0.774, 95 % CI: 0.297, 1.250; Q4 versus Q1: β = 0.481, 95 % CI: 0.006, 0.956); and Cr was especially associated with the registry, recall, and language and praxis. Per IQR (36.32 μg/L) increase of Se was positively associated with the MMSE score (β = 0.497, 95 % CI: 0.277, 0.717) and all five cognitive domains. The BKMR showed that the dose-response association between Se and cognitive function increased initially and then decreased with increasing Se concentration when fixed the other ETEs in median. ETEs mixture was positively associated with cognitive function, and Se (posterior inclusion probabilities, PIPs = 0.915) was the most important contributor within the ETEs mixture. The nonlinear association between Cr and cognitive function suggested further exploration of an appropriate concentration range for ETEs. A positive association between mixed ETEs and cognitive function is a reminder that their joint association should be considered. Further prospective studies or intervention studies are warranted to validate our findings in the future. [Display omitted] • The association between Cr and cognitive function presented an inverted-U shape. • The joint association between ETEs mixture and cognitive function was positive. • Se was the most important contributor to cognitive function within the mixture. [ABSTRACT FROM AUTHOR]

Inference for spatial data is challenging because fitting an appropriate parametric model is often difficult. The penalized likelihood-type approach has been successfully developed for various nonparametric function estimation problems in time series analysis. However, it has not been well developed in spatial analysis. In this paper, a penalized Whittle likelihood approach is developed for nonparametric estimation of spectral density functions for regularly spaced spatial data. In particular, the estimated spectral density is the minimizer of a criterion which is developed based on the Whittle likelihood and a penalty for roughness. This approach aggregates several popular nonparametric density estimation methods into a coherent framework. Asymptotic properties of the proposed estimator are derived under mild assumptions without assuming Gaussianity. In addition, a computationally efficient method is developed to optimize the penalized likelihood function. Simulation results and real data examples are also provided to illustrate the finite sample performances of the methodology. [ABSTRACT FROM AUTHOR]

Type I interferons (IFNs) play essential roles in establishing and modulating host defense against microbial infection via induction of IFN-stimulated genes (ISGs) through Janus kinase (JAK)–signal transducer and activator of transcription (STAT) signaling pathway. However, dysregulation of IFNs production and function could also mediate immune pathogenesis such as inflammatory autoimmune diseases and infectious diseases via aberrantly activating inflammatory responses or improperly suppressing microbial controls. Thus, IFN responses need to be tightly regulated to achieve protective immunity against microbial infection while avoiding harmful toxicity caused by improper or prolonged IFN signaling. Multiple levels of cellular and molecular events act in a cooperated manner to regulate IFN responses, in especial, post-translational modification (PTMs) of signaling molecules and epigenetic modification of gene expression programs are two important mechanisms for regulation of IFN signaling and thus critical for orchestrating IFN-mediated host immune response to the complex pathogenic or environmental stimuli. Conventional PTMs such as phosphorylation and polyubiquitylation, as well as numerous other PTMs including acetylation, ISGylation, SUMOylation and methylation have been shown to potently modulate type I IFN signaling transduction via targeting distinct signaling steps or components. Moreover, epigenetic mechanisms, such as histone modification, DNA methylation, non-coding RNAs play critical roles in regulating chromatin structure and function, leading to flexible and dynamic gene expression patterns downstream type I IFN signaling. Herein, we summarize the recent advances in the PTMs and epigenetic mechanisms in regulation of type I IFN signaling and responses. The involvement of dysregulated IFN signaling in inflammatory and autoimmune diseases are also discussed. [ABSTRACT FROM AUTHOR]

Recently, the use of artificial intelligence based data mining techniques for massive medical data classification and diagnosis has gained its popularity, whereas the effectiveness and efficiency by feature selection is worthy to further investigate. In this paper, we presents a novel method for feature selection with the use of opposite sign test (OST) as a local search for the electromagnetism-like mechanism (EM) algorithm, denoted as improved electromagnetism-like mechanism (IEM) algorithm. Nearest neighbor algorithm is served as a classifier for the wrapper method. The proposed IEM algorithm is compared with nine popular feature selection and classification methods. Forty-six datasets from the UCI repository and eight gene expression microarray datasets are collected for comprehensive evaluation. Non-parametric statistical tests are conducted to justify the performance of the methods in terms of classification accuracy and Kappa index. The results confirm that the proposed IEM method is superior to the common state-of-art methods. Furthermore, we apply IEM to predict the occurrence of Type 2 diabetes mellitus (DM) after a gestational DM. Our research helps identify the risk factors for this disease; accordingly accurate diagnosis and prognosis can be achieved to reduce the morbidity and mortality rate caused by DM. [ABSTRACT FROM AUTHOR]

Abstract: The purpose of this study was to understand the significance of each microorganism in grain formation by evaluating their microbial aggregation and cell surface properties during co-aggregation of LAB and yeasts together with an investigation of biofilm formation. Non-grain forming strains from viili were also evaluated as a comparison. Results indicated that the kefir grain strains, Lactobacillus kefiranofaciens and Saccharomyces turicensis possess strong auto-aggregation ability and that Lactobacillus kefiri shows significant biofilm formation properties. Significant co-aggregation was noted when S. turicensis and kefir LAB strains (Lb. kefiranofaciens and Lb. kefiri) were co-cultured. Most of the tested LAB strains are hydrophilic and had a negative charge on their cell surface. Only the kefir LAB strains, Lb. kefiranofaciens HL1 and Lb. kefiri HL2, possessed very high hydrophobicity and had a positive cell surface charge at pH 4.2. In contrast, the LAB and yeasts in viili did not show any significant self-aggregation or biofilm formation. Based on the above results, we propose that grain formation begins with the self-aggregation of Lb. kefiranofaciens and S. turicensis to form small granules. At this point, the biofilm producer, Lb. kefiri, then begins to attach to the surface of granules and co-aggregates with other organisms and components in the milk to form the grains. On sub-culturing, more organisms attach to the grains resulting in grain growth. When investigated by scanning electron microscopy, it was found that short-chain lactobacilli such as Lb. kefiri occupy the surface, while long-chain lactobacilli such as Lb. kefiranofaciens have aggregated towards the center of the kefir grains. These findings agree with the above hypothesis on the formation of grains. Taken together, this study demonstrates the importance of cell surface properties together with fermentation conditions to the formation of grains in kefir. [Copyright &y& Elsevier]

Abstract: Apoptin, a protein from chicken anemia virus, selectively induces apoptosis of transformed or tumor cells, but not in normal cells. However, the mechanism of action of Apoptin is still not well understood. Using yeast two-hybrid and immunoprecipitation approaches, we found that Apoptin interacted with Heat shock cognate protein 70 (Hsc70). In vivo, Apoptin induced the translocation of endogenous Hsc70 from the cytoplasm to the nucleus, and both were co-localized in the nucleus. In addition, Apoptin induced Akt phosphorylation, which was markedly inhibited by Hsc70 knockdown, suggesting that Hsc70 may play a critical role in Apoptin-induced Akt phosphorylation. These findings help to further understand the molecular mechanism of Apoptin. [Copyright &y& Elsevier]

Abstract: Amyloid-beta peptide (Aβ) and Tau protein are the lead constituents in the pathogenesis of Alzheimer''s disease (AD). However, their inter-relationship in the disease process remains to be established. Tauopathy refers to a characteristic neurodegenerative process in AD. In tauopathy, Tau accumulates as a consequence of altered pre-mRNA splicing of tau exon 10, resulting in 3R (without exon 10)/4R (with exon 10) imbalance. We studied Aβ effects on tau exon 10 pre-mRNA splicing and relevant signaling events. This is the first demonstration of Aβ alteration of tau exon 10 splicing with an increase in 3R/4R ratio caused by reduced 4R expression. This Aβ action is causally related to its activation of GSK-3β which in turn phosphorylates SC35, an enhancer in tau exon 10 splicing. The establishment of the Aβ-GSK-3β-SC35 cascade broadens insight into development of novel strategies to modulate Aβ action on tau exon 10 splicing for possible prevention of tauopathy. [Copyright &y& Elsevier]

Abstract: The present study describes the molecular cloning of a novel cDNA fragment from amphioxus (Branchiostoma belcheri) encoding a 343-amino acid protein that is highly homologous to human uncoupling proteins (UCP), this protein is therefore named amphioxus UCP. This amphioxus UCP shares more homology with and is phylogenetically more related to mammalian UCP2 as compared with UCP1. To further assess the functional similarity of amphioxus UCP to mammalian UCP1 and −2, the amphioxus UCP, rat UCP1, and human UCP2 were separately expressed in Saccharomyces cerevisiae, and the recombinant yeast mitochondria were isolated and assayed for the state 4 respiration rate and proton leak, using pYES2 empty vector as the control. UCP1 increased the state 4 respiration rate by 2.8-fold, and the uncoupling activity was strongly inhibited by GDP, while UCP2 and amphioxus UCP only increased the state 4 respiration rate by 1.5-fold and 1.7-fold in a GDP-insensitive manner, moreover, the proton leak kinetics of amphioxus UCP was very similar to UCP2, but much different from UCP1. In conclusion, the amphioxus UCP has a mild, unregulated uncoupling activity in the yeast system, which resembles mammalian UCP2, but not UCP1. [ABSTRACT FROM AUTHOR]

Abstract: Acquisition and quantitative analysis of high resolution images of dendritic spines are challenging tasks but are necessary for the study of animal models of neurological and psychiatric diseases. Currently available methods for automated dendritic spine detection are for the most part customized for 2D image slices, not volumetric 3D images. In this work, a fully automated method is proposed to detect and segment dendritic spines from 3D confocal microscopy images of medium-sized spiny neurons (MSNs). MSNs constitute a major neuronal population in striatum, and abnormalities in their function are associated with several neurological and psychiatric diseases. Such automated detection is critical for the development of new 3D neuronal assays which can be used for the screening of drugs and the studies of their therapeutic effects. The proposed method utilizes a generalized gradient vector flow (GGVF) with a new smoothing constraint and then detects feature points near the central regions of dendrites and spines. Then, the central regions are refined and separated based on eigen-analysis and multiple shape measurements. Finally, the spines are segmented in 3D space using the fast marching algorithm, taking the detected central regions of spines as initial points. The proposed method is compared with three popular existing methods for centerline extraction and also with manual results for dendritic spine detection in 3D space. The experimental results and comparisons show that the proposed method is able to automatically and accurately detect, segment, and quantitate dendritic spines in 3D images of MSNs. [Copyright &y& Elsevier]

Abstract: Tobacco smoking is an important cause of human oral squamous cell carcinoma (SCC). Tobacco smoke contains multiple carcinogens include polycyclic aromatic hydrocarbons typified by benzo[a]pyrene (B[a]P). Surgery is the conventional treatment approach for SCC, but it remains imperfect. However, chemoprevention is a plausible strategy and we had previously demonstrated that 1,4-phenylenebis(methylene)selenocyanate (p-XSC) significantly inhibited tongue tumors-induced by the synthetic 4-nitroquinoline-N-oxide (not present in tobacco smoke). In this study, we demonstrated that p-XSC is capable of inhibiting B[a]P-DNA adduct formation, cell proliferation, cyclin D1 expression in human oral cells in vitro. In addition, we showed that dietary p-XSC inhibits B[a]P-DNA adduct formation, cell proliferation and cyclin D1 protein expression in the mouse tongue in vivo. The results of this study are encouraging to further evaluate the chemopreventive efficacy of p-XSC initially against B[a]P-induced tongue tumors in mice and ultimately in the clinic. [Copyright &y& Elsevier]

Abstract: Amyloid-β (Aβ) is the core component of senile plaques, which are the pathological markers for Alzheimer’s disease and cerebral amyloid angiopathy. DNA methylation/demethylation plays a crucial role in gene regulation and could also be responsible for presentation of senescence. Oxidative stress, which may be induced by Aβ, is thought to be an important contributor of DNA hyper-methylation; however, contradicting this is the fact that global DNA hypo-methylation has been found in aging brains. It therefore remains largely unknown as to whether Aβ does in fact cause DNA methylation/demethylation. Neprilysin (NEP) is one of the enzymes responsible for Aβ degradation, with its expression decreasing in both Alzheimer and aging brains. Using high-performance liquid chromatography (HPLC), we explore whether Aβ is responsible for alteration of the global DNA methylation status on a murine cerebral endothelial cells model, and also use methylation-specific PCR (MSPCR) to examine whether DNA methylation status is altered on the NEP promoter region. We find that Aβ reduces global DNA methylation whilst increasing NEP DNA methylation and further suppressing the NEP expression in mRNA and protein levels. Our results support that Aβ induces epigenetic effects, implying that DNA methylation may be part of a vicious cycle involving the reduction in NEP expression along with a resultant increase in Aβ accumulation, and that Aβ may induce global DNA hypo-methylation. [Copyright &y& Elsevier]

In this study, we found that UV-B radiation decreased photosynthetic activity and boosted lipid peroxidation of desert Nostoc sp., and exogenous chemicals (ascorbate acid (ASC), N-acetylcysteine (NAC), and sodium nitroprusside (SNP)) had obvious protective effects on photosynthesis and membranes under UV-B radiation. High-concentration SNP boosted the activities of antioxidant enzymes, but low-concentration SNP reduced the activities of antioxidant enzymes. Both NAC and ASC treatments of cells decreased activities of antioxidant enzymes. The results suggested that those chemicals possibly had different mechanisms of protection of algae cells against UV-B radiation. SNP might play double roles as a signal molecule in the formation of algae cell protection of Photosystem II under UV-B radiation and as a (reactive oxygen species) scavenger, while NAC and ASC might function as antioxidant reagents or precursors of other antioxidant molecules, which could protect cells directly against ROS initiated by UV-B radiation. [Copyright &y& Elsevier]

Identification of Epstein-Barr virus (EBV)-infected cells is critical for the diagnosis and clinical management of EBV-associated diseases. EBV-encoded RNA (EBER) located in the nucleus is a reliable marker due to its high levels of expression and inherent stability in tissue specimens. EBER in situ hybridization has long been the gold standard for detecting tumor-associated latent EBV infection and is valuable in determining the primary site and radiation fields of EBV-related malignancies. However, reliable detection is somewhat restricted by diffused signal and time-consuming procedure of this method, especially when proteins and RNA needed to be labeled simultaneously. Here, we optimized and validated our CRISPR-dCas9 mediated in situ RNA imaging tool—RCasFISH that enabled us to detect EBER rapidly and was compatible with IHC methods in fixed cells and tissue sections. Our approach could provide an attractive alternative for the molecular diagnosis of latent EBV infection. Schematic of imaging EBER transcripts by RCasFISH method in fixed cells or FFPE samples. In vitro assembled dCas9 protein, T7-synthesized sgRNA extended with 8 × MS2 aptamers and PAMmer sequence were incubated with fixed cells or tissues. EBER1 complementary to the spacer sequence were targeted by sgRNA-guided hybridization. [Display omitted] • The CRISPR/dCas9 enables sensitive and specific Epstein–Barr virus EBERs detection. • The RCasFISH sensitivity is superior than ISH and comparable to RNAscope. • The RCasFISH can be completed in 30 min, enabling rapid results. • The RCasFISH can be compatible with IHC methods in fixed cells. [ABSTRACT FROM AUTHOR]

PsnWRKY70 is an important transcription factor in plant immunity. In this study, we found that the transcription factor PsnWRKY70 can positively regulate the resistance of poplar to Melampsora laricis-populina. Meanwhile, the PsnWRKY70 gene is involved in the regulation of the composition of the phyllosphere microbiome of the poplar, thereby synergistically relieving the infection of pathogens. In this study, For β diversity analysis, principal coordinate analysis (PCoA) showed that PsnWRKY70 had little effect on phyllosphere bacterial community in healthy leaves of poplar. However, the bacterial community in leaves of transgenic PsnWRKY70 poplars changed significantly when the leaves were infected by Melampsora laricis-populina.The lefse analysis of epiphytic bacteria on infected leaves showed that Rubellimicrobium , Knoellia , Flavisolibacter , Devosia , Dyadobacter , Rhodococcus , Balneimonas , and Sphingobacterium were significantly enriched OE lines. The lefse analysis of endophytic bacteria on infected leaves showed that Erwinia and Ochrobactrum was significantly enriched in the leaves of OE lines. The PsnWRKY70 gene can recruit the strains to improve the ability of the OE lines of the transgenic poplar to resist the invasion of Melampsora laricis-populina. In summary, The results showed that PsnWRKY70 enhanced the resistance of poplar to Melampsora laricis-populina by changing the composition of bacterial community in poplar phyllosphere. • PsnWRKY70 gene is involved in the regulation of the composition of the phyllosphere microbiome of the poplar, thereby synergistically relieving the infection of Melampsora laricis-populina. • The phyllosphere bacterial community of transgenic PsnWRKY70 poplars changed significantly when the leaves were infected by Melampsora laricis-populina. • The phyllosphere bacteria on infected leaves showed that Rubellimicrobium , Knoellia , Flavisolibacter , Devosia Dyadobacter , Rhodococcus , Balneimonas , Sphingobacterium , Erwinia, and Ochrobactrum were significantly enriched OE lines. [ABSTRACT FROM AUTHOR]

It is well known that the dairy cow production is very sensitive to environmental factors, including high temperature, high humidity and radiant heat sources. High temperature-induced heat stress is the main environmental factor that causes oxidative stress and apoptosis, which affects the development of mammary glands in dairy cows. Dihydromyricetin (DMY) is a nature flavonoid compound extracted from Ampelopsis grossedentata; it has been shown to have various pharmacological functions, such as anti-inflammation, antitumor and liver protection. The present study aims to evaluate the protective effect of DMY on heat stress-induced dairy cow mammary epithelial cells (DCMECs) apoptosis and explore the potential mechanisms. The results show that heat stress triggers heat shock response and reduces cell viability in DCMECs; pretreatment of DCMECs with DMY (25 μM) for 12 h significantly alleviates the negative effects of heat stress on cells. DMY can provide cytoprotective effects by suppressing heat stress-caused mitochondrial membrane depolarization and mitochondrial dysfunction, Bax and Caspase 3 activity, and modulation of oxidative enzymes, thereby preventing ROS production and apoptosis in DCMECs. Importantly, DMY treatment could attenuate heat stress-induced mitochondrial fragmentation through mediating the expression of mitochondrial fission and fusion-related genes, including Dynamin related protein 1 (Drp1), Mitochondrial fission 1 protein (Fis1), and Mitofusin1, 2 (Mfn1, 2). Above all, our findings demonstrate that DMY could protect DCMECs against heat stress-induced injury through preventing oxidative stress, the imbalance of mitochondrial fission and fusion, which provides useful evidence that DMY can be a promising therapeutic drug for protecting heat stress-induced mammary glands injury and mastitis. [Display omitted] • Hyperthermal environment causes heat stress and leads to apoptosis in DCMECs. • DMY restores heat stress-induced mitochondrial dysfunction in DCMECs. • DMY attenuated heat stress-induced oxidative injury and apoptosis in DCMECs. [ABSTRACT FROM AUTHOR]

Sleep disorders have been verified to be associated with adverse health outcomes. Recent studies have linked ambient air pollution to sleep disorders. However, evidence with large sample size and especially prospective studies is very limited. We used data from a prospective cohort study established from 2015 to 2018 in Ningbo, China. Participants were followed-up after baseline survey through linkage to the regional Health Information System (HIS). Sleep disorders were defined based on International Classification of Disease 10 (ICD-10). Spatial-temporal land-use regression (LUR) models were used to estimate the annual exposure to particulate matter with diameter ≤ 2.5 µm (PM 2.5), ≤ 10 µm (PM 10) and nitrogen dioxides (NO 2). The associations between long-term exposure to air pollutants and prevalence of sleep disorders were examined using logistic regression models, and Cox regression models for the effects of air pollution on the incidence of sleep disorders. A generalized weighted quantile sum (gWQS) regression was used in the multipollutant analysis. A total of 38,775 participants were included in the final analysis. Based on baseline data, we observed significant positive associations between air pollution exposure and increased odds of prevalent sleep disorders (Odds Ratio (OR) = 1.48, 95% confidence interval (CI): 1.41–1.55 for PM 2.5 ; OR = 1.47,95%CI:1.38–1.57 for PM 10 ; OR = 1.38, 95%CI:1.31–1.46 for NO 2). In the longitudinal analysis, hazard ratios for incident sleep disorders associated with per interquartile range (IQR) increase in PM 2.5 , PM 10 and NO 2 were 1.14 (1.03, 1.25), 1.13 (1.01, 1.27) and 1.13 (1.04, 1.23), respectively. A gWQS regression analysis showed significant association between air pollution mixture and incident sleep disorders (OR = 1.11, 95%CI: 1.03–1.20). Long-term exposure to PM 2.5 , PM 10 and NO 2 were associated with increased risk of sleep disorders in a Chinese population. Our findings could provide evidence for a more general role in the adverse health impact of air pollution. ga1 • Positive associations between air pollution and incident sleep disorder were found. • PM 2.5 , PM 10 and NO 2 contributed similarly to sleep disorders in multipollutant analysis. • Reducing the ambient air pollution level would benefit sleep health. [ABSTRACT FROM AUTHOR]

Residues of the psychoactive drug diazepam (DZP) may pose potential risks to fish in aquatic environments, especially by disrupting their behavioral traits. In this study, female and male zebrafish were subjected to chronic exposure (21 days) to sublethal doses (120 and 12 µg/L) of DZP, aimed to compare the characteristics of their behavioral responses to DZP exposure, and to investigate the possible links between those behavioral responses and variations in their brain γ-aminobutyric acid (GABA) and acetylcholinesterase (AChE) levels. Chronic exposure to DZP significantly decreased the swimming velocity and locomotor activity of both genders, indicating a typical sedative effect. Compared with males, whose locomotor activity was only significantly decreased by exposure to DZP for 21 days, females became hypoactive on day 14 (i.e., more sensitive), and they developed tolerance to the hypoactive effect induced by 120 μg/L DZP by day 21. Exposure to DZP significantly disturbed the behavioral traits related to social interactions in females but not in males. Those results indicate that DZP exhibits sex-dependent effects on the behaviors of fish. Moreover, exposure to DZP for 21 days significantly disturbed almost all of the tested behavioral traits associated with courtship when both genders were put together. Sex-dependent responses in brain GABA and AChE levels due to DZP exposure were also identified. Significant relationships between the brain GABA/AChE levels and some behavioral parameters related to locomotor activity were detected in females, but not in males. • Chronic exposure to DZP exhibited a sedative effect on both genders of zebrafish. • Females were more sensitive and developed tolerance to hypoactive effect of DZP. • DZP disturbed behaviors related to social interactions in females but not in males. • DZP disturbed the behaviors related to courtship when both genders were put together. • Altered brain GABA and AChE may mediate some females' behavioral responses to DZP. [ABSTRACT FROM AUTHOR]

Coronavirus disease 2019 (COVID-19) was first detected in December 2019 in Wuhan, China, with 11,669,259 positive cases and 539,906 deaths globally as of July 8, 2020. The objective of the present study was to determine whether meteorological parameters and air quality affect the transmission of COVID-19, analogous to SARS. We captured data from 29 provinces, including numbers of COVID-19 cases, meteorological parameters, air quality and population flow data, between Jan 21, 2020 and Apr 3, 2020. To evaluate the transmissibility of COVID-19, the basic reproductive ratio (R 0) was calculated with the maximum likelihood "removal" method, which is based on chain-binomial model, and the association between COVID-19 and air pollutants or meteorological parameters was estimated by correlation analyses. The mean estimated value of R 0 was 1.79 ± 0.31 in 29 provinces, ranging from 1.08 to 2.45. The correlation between R 0 and the mean relative humidity was positive, with coefficient of 0.370. In provinces with high flow, indicators such as carbon monoxide (CO) and 24-h average concentration of carbon monoxide (CO_24 h) were positively correlated with R 0 , while nitrogen dioxide (NO 2), 24-h average concentration of nitrogen dioxide (NO 2 _24 h) and daily maximum temperature were inversely correlated to R 0 , with coefficients of 0.644, 0.661, −0.636, −0.657, −0.645, respectively. In provinces with medium flow, only the weather factors were correlated with R 0 , including mean/maximum/minimum air pressure and mean wind speed, with coefficients of −0.697, −0.697, −0.697 and −0.841, respectively. There was no correlation with R 0 and meteorological parameters or air pollutants in provinces with low flow. Our findings suggest that higher ambient CO concentration is a risk factor for increased transmissibility of the novel coronavirus, while higher temperature and air pressure, and efficient ventilation reduce its transmissibility. The effect of meteorological parameters and air pollutants varies in different regions, and requires that these issues be considered in future modeling disease transmissibility. Image 1 • COVID-19 is a worldwide pandemic, with transmission parameters largely remaining unknown. • We provide insight into the role of meteorological factors and air pollutants on COVID-19 transmissibility. • CO is positively while NO 2 is inversely correlated with R 0. • Daily maximal temperature, wind speed and air pressure are inversely correlated with R 0. • Correlations vary by region. [ABSTRACT FROM AUTHOR]

Household consumption activities affect energy and water consumption directly and indirectly. Based on input-output modeling, this paper divided Chinese urban and rural residents into 12 groups, and investigated the impact of the consumption activities of residents with different levels of income on China's energy and water consumption from the perspective of consumers. Two main results were found. 1) In 2012, the energy consumption caused by the consumption activities of the highest-income urban residents accounted for 17.3% of the total energy consumption. For water resources, the per capita water withdrawal and consumption of the highest-income urban residents reached 481.21 m3 and 284.45 thousand m3, 6 times more than that of the low-income rural residents. 2) We identified medium and medium-high income urban residents as the key groups of residents. From the perspective of the industrial sectors, the key sectors for high energy consumption and water usage included the Electricity and Agricultural sectors, and we identified the Electricity sector as the key sector for the water and energy nexus of the residential sectors. The conclusions of this paper have pertinence for policymaking, and they provide an appropriate policy basis for guiding residents' energy and water consumption. • Energy and water usage caused by household consumption in China is investigated. • Chinese urban and rural residents in input-output table are divided into 12 groups. • Energy consumption caused by the highest-income urban residents accounted for 17.3%. • Water usage of the highest-income urban residents is 6 times more than that of the low-income rural residents. • Electricity sector as the key sector for the water and energy nexus of the residential sectors. [ABSTRACT FROM AUTHOR]

Finite mixture models have been widely used for the modeling and analysis of data from a heterogeneous population. Moreover, data of this kind can be subject to some upper and/or lower detection limits because of the restriction of experimental apparatus. Another complication arises when measures of each population depart significantly from normality, for instance, in the presence of heavy tails or atypical observations. For such data structures, we propose a robust model for censored data based on finite mixtures of multivariate Student- t distributions. This approach allows us to model data with great flexibility, accommodating multimodality, heavy tails and also skewness depending on the structure of the mixture components. We develop an analytically simple, yet efficient, EM-type algorithm for conducting maximum likelihood estimation of the parameters. The algorithm has closed-form expressions at the E-step that rely on formulas for the mean and variance of the multivariate truncated Student- t distributions. Further, a general information-based method for approximating the asymptotic covariance matrix of the estimators is also presented. Results obtained from the analysis of both simulated and real datasets are reported to demonstrate the effectiveness of the proposed methodology. The proposed algorithm and methods are implemented in the new R package CensMixReg . [ABSTRACT FROM AUTHOR]

Many modern statistical problems can be cast in the framework of multivariate regression, where the main task is to make statistical inference for a possibly sparse and low-rank coefficient matrix. The low-rank structure in the coefficient matrix is of intrinsic multivariate nature, which, when combined with sparsity, can further lift dimension reduction, conduct variable selection, and facilitate model interpretation. Using a Bayesian approach, we develop a unified sparse and low-rank multivariate regression method to both estimate the coefficient matrix and obtain its credible region for making inference. The newly developed sparse and low-rank prior for the coefficient matrix enables rank reduction, predictor selection and response selection simultaneously. We utilize the marginal likelihood to determine the regularization hyperparameter, so our method maximizes its posterior probability given the data. For theoretical aspect, the posterior consistency is established to discuss an asymptotic behavior of the proposed method. The efficacy of the proposed approach is demonstrated via simulation studies and a real application on yeast cell cycle data. [ABSTRACT FROM AUTHOR]

Podocyte injury induced by sublytic complement attack is the main feature of membranous nephropathy (MN). This study aimed at investigating the impact of sublytic complement attack-related autophagy on podocyte injury in vitro. Here, we show that sublytic complement attack enhances MPC5 podocyte autophagy in vitro. Inhibition of autophagy by treatment with 3-methyladenine (3-MA) significantly increased sublytic complement attack-induced changes in the injury-related morphology, stress fiber, and podocyte apoptosis, but decreased the survival and adhesion of MPC5 podocytes. In contrast, promotion of autophagy by treatment with rapamycin mitigated sublytic complement attack-induced changes in the injury-related morphology, stress fiber, and podocyte apoptosis, but increased the survival and adhesion of MPC5 podocytes. These data suggest that autophagy may protect podocytes from sublytic complement attack-induced injury in vitro. [ABSTRACT FROM AUTHOR]

Herein, we engineered a novel pH-responsive ratiometric assay by virtue of the composite system of Ce3+-enhanced glutathione-encapsulated copper nanoclusters (GSH-CuNCs-Ce3+) and N-doped carbon quantum dots (N-CQDs). The GSH-CuNCs-Ce3+ and N-CQDs were fabricated using one-pot chemical reduction and hydrothermal approaches, respectively, and their morphologies as well as physical and chemical properties were testified in detail by a series of characterization techniques. At 350 nm excitation wavelength, the GSH-CuNCs-Ce3+/N-CQDs system (GCC-NC) featured the 440/650 nm dual-emitting property. The ratios of fluorescence intensities (F 650 /F 440) demonstrated a strong pH-dependence from 3.0 to 5.0 with a coefficient of determination of 0.9982. Consequently, the GCC-NC system was feasible for constructing a pH-responsive dual-emitting fluoroprobe. Based on the catalytic effect of acetylcholinesterase on acetylcholine to yield acetic acid and further trigger varying solution pH, the as-constructed GCC-NC fluoroprobe was satisfactorily applied for detecting malathion. Under optimized conditions, the newly developed GCC-NC fluoroprobe supplied a wider linear range (0.25–200 μM), lower detection limit (0.075 μM), satisfactory recoveries (96.3–106.2%) and higher precision for malathion in several kinds of fruit juice samples. The fortified experiments by malathion's structural analogues and metal ions provided compelling evidence that this fluoroprobe had strong anti-interference capacity and high specificity for malathion. These findings render us to believe that the as-constructed pH-responsive dual-emitting fluoroprobe holds great promise in trace malathion assay in food matrices. • A novel pH-responsive ratiometric fluoroprobe based on GSH-CuNCs-Ce3+ and N-CQDs (GCC-NC) is developed. • Ce3+ can trigger aggregation-induced emission property of CuNCs. • The ratiometric fluorescence probe based on GCC-NC can be used to detect OPs. • The ratiometric fluorescence probe for the detection of malathion shows low LOD, wide LR and high precision. • The ratiometric fluorescence probe possesses wide application prospects for residual monitoring of OPs in food matrices. [ABSTRACT FROM AUTHOR]

A growing body of evidence suggests that metabolic events play essential roles in the development of liver fibrosis. Immune response gene 1 (IRG1) catalyzes the generation of itaconate, which function as a metabolic checkpoint under several pathological circumstances. In the present study, the hepatic level of IRG1 was determined in mice with carbon tetrachloride (CCl 4)-induced liver fibrosis. And then the pathological significance of IRG1 and the pharmacological potential of 4-octyl itaconate (4-OI), a cell-permeable derivate of itaconate, in liver fibrosis were investigated in mice. The results indicated that the hepatic level of IRG1 was upregulated in mice with liver fibrosis. CCl 4 -induced formation of fibrotic septa and deposition of collagen was aggravated in IRG1 KO mice. IRG1 deletion also resulted in increased expression of transforming growth factor beta 1 (TGF-β1), enhanced phosphorylation of Smad3, elevated level of alpha smooth muscle actin (α-SMA) and hydroxyproline, which were associated with compromised activation of nuclear erythroid 2-related factor 2 (Nrf2)-mediated antioxidant system and exacerbated oxidative stress. Interestingly, supplementation with 4-OI activated Nrf2 pathway, suppressed TGF-β1 signaling and attenuated fibrogenesis. Our data indicated that upregulation of IRG1 might function as a protective response during the development of liver fibrosis, and 4-OI might have potential value for the pharmacological intervention of liver fibrosis. • CCl 4 -induced liver fibrosis is associated with upregulation of IRG1. • Deletion of IRG1 aggravated CCl 4 -induced liver fibrosis. • Deletion of IRG1 suppressed Nrf2 pathway but enhanced TGF-β1/Smad3 signaling. • Supplementation with cell-permeable 4-octyl itaconate alleviated liver fibrosis. [ABSTRACT FROM AUTHOR]

A comprehensive overview of the associations between air pollution and the risk of gastrointestinal (GI) diseases has been lacking. We aimed to examine the relationships of long-term exposure to ambient particulate matter (PM) with aerodynamic diameter ≤2.5 μm (PM 2.5), 2.5–10 μm (PM c oarse), ≤10 μm (PM 10), nitrogen dioxide (NO 2), and nitrogen oxides (NO x), with the risk of incident GI diseases, and to explore the interplay between air pollution and genetic susceptibility. A total of 465,703 participants free of GI diseases in the UK Biobank were included at baseline. Land use regression models were employed to calculate the residential air pollutants concentrations. Cox proportional hazard models were used to evaluate the associations of air pollutants with the risk of GI diseases. The dose-response relationships of air pollutants with the risk of GI diseases were evaluated by restricted cubic spline curves. We found that long-term exposure to ambient air pollutants was positively associated with the risk of peptic ulcer (PM 2.5 : Q4 vs. Q1: hazard ratio (HR) 1.272, 95% confidence interval (CI) 1.179–1.372, NO 2 : 1.220, 1.131–1.316, and NO x : 1.277, 1.184–1.376) and chronic gastritis (PM 2.5 : 1.454, 1.309–1.616, PM 10 : 1.232, 1.112–1.366, NO 2 : 1.456, 1.311–1.617, and NO x : 1.419, 1.280–1.574) after Bonferroni correction. Participants with high genetic risk and high air pollution exposure had the highest risk of peptic ulcer, compared to those with low genetic risk and low air pollution exposure (PM 2.5 : HR 1.558, 95%CI 1.384–1.754, NO 2 : 1.762, 1.395–2.227, and NO x : 1.575, 1.403–1.769). However, no significant additive or multiplicative interaction between air pollution and genetic risk was found. In conclusion, long-term exposure to ambient air pollutants was associated with increased risk of peptic ulcer and chronic gastritis. • A comprehensive overview of the associations between air pollution and the risk of GI diseases has been lacking. • Long-term exposure to air pollution was associated with increased risks of peptic ulcer and chronic gastritis. • Our study highlights the importance of controlling air pollution as a preventive measure for GI diseases. [ABSTRACT FROM AUTHOR]

Abstract: Aberrant activation of nuclear factor-kappa B (NF-κB) pathway has been proven to play important roles in the development and progression of cancers. Activation of NF-κB via the classical pathway is modulated by IκBs kinase (IKK-β). However, the mechanism underlying the epigenetic regulation of IKK-β/NF-κB pathway remains largely unknown. In this study, we found that the expression level of miR-218 was markedly downregulated in glioma cell lines and in human primary glioma tissues. Upregulation of miR-218 dramatically reduced the migratory speed and invasive ability of glioma cells. Furthermore, we showed that ectopically expressing miR-218 in glioma cells resulted in downregulation of matrix metalloproteinase-9 (MMP-9) and reduction in NF-κB transactivity at a transcriptional level, but inhibition of miR-218 enhanced the expression of MMP-9 and transcriptional activity of NF-κB. Moreover, we showed that miR-218 inactivated the NF-κB pathway through downregulating IKK-β expression by directly targeting the 3′-untranslated region (3′-UTR) of IKK-β. Taken together, our results suggest that miR-218 plays an important role in preventing the invasiveness of glioma cells, and our results present a novel mechanism of miRNA-mediated direct suppression of IKK-β/NF-κB pathway in gliomas. [ABSTRACT FROM AUTHOR]

Abstract: The dynamic motion of an adaptive visual servoing feedback-controlled punching machine, which is made up by a toggle mechanism driven by a permanent magnet (PM) synchronous servomotor, is studied numerically and experimentally. First, Hamilton''s principle, Lagrange multiplier, geometric constraints and partitioning method are employed to derive its dynamic equations for numerical simulations. To satisfy the demand of the machine performance, adaptive controller by using stability analysis with inertia-related Lyapunov function is designed to control the slider responses. Different from the previous studies, the vision servo system of a non-contact measurement of a charge-coupled device (CCD) camera is employed to measure the shape patterns as output states instead of using the expensive linear scale or encoder of the motor-mechanism system. Finally, the stable and robust control performances of an adaptive controller by the Lyapunov stable theory for a motor-toggle mechanism with external disturbances are proposed. A combination of the visual servoing measurement system and the motion control system are established experimentally for the motor-toggle mechanism system. From the agreements between numerical simulations and experimental results, it is demonstrated that the proposed controller, by use of machine vision, is robust to external disturbances for a punching machine system. [Copyright &y& Elsevier]

Abstract: In this paper, Hamilton''s principle, Lagrange multiplier, geometric constraints and partitioning method are employed to derive the dynamic equations of a slider-crank mechanism driven by a servomotor. The formulation is expressed by only one independent variable and considers the effects of mass, external force and motor electric inputs. Comparing the dynamic responses between the experimental results and numerical simulations, the dynamic modeling gives a wonderful interpretation of a slider-crank mechanism. The parameters of many industrial machines are difficult to obtain if these machines cannot be taken apart. In this paper, a new identification method based on the real-coded genetic algorithm (RGA) is presented to identify the parameters of a slider-crank mechanism. The method promotes the calculation efficiency very much, and is calculated by the real-code without the operations of encoding and decoding. The results of numerical simulations and the experiments prove that the identification method is feasible. Finally, the experimental results by the RGA and the recursive least squares (RLS) are also compared. [Copyright &y& Elsevier]

A polymer-templated raspberry assembly method is developed to generally co-assemble proteins and inorganic clusters on the surface of P4VP. The representative GOX-{Mo 72 Fe 30 }@P4VP co-assemblies can efficiently catalyze the oxidation of o-dianisidine with the presence of glucose, where the color change points out their potential in rapid detection of glucose and biomass conversion. [Display omitted] The hybridization of enzymes and inorganics in controlled manner is challenging, however, critical for the development of chemo-enzymatic cascade catalyst with high efficiency and selectivity. Here, proteins and metal oxide clusters can be facilely co-assembled on the surface of colloid of poly(4-vinylpyridine) (P4VP) via hydrogen bonding, due to their enriched surface hydrogen bonding donors. The co-assembly method can be generally applied for preparing chemo-enzymatic catalyst within the selected database of various proteins and metal oxide clusters while the assembly units retain their structures and activities. Typically, a 2.5 nm metal oxide cluster {Mo 72 Fe 30 }, with peroxidase-like activity, are complexed with glucose oxidase (GOX) on P4VP for the catalysis against the oxidization of o-dianisidine (ODA) with the existence of glucose. Due to the synergistic effects of chemical and enzymatic catalysis, the co-assemblies show even higher ODA oxidation activity compared to GOX/catalase bi-enzymatic system, confirming the effectiveness of the co-assembly protocol for cascade catalysis and enabling its applications in rapid glucose detection and biomass conversion. [ABSTRACT FROM AUTHOR]

• There has been growing interest in the development of e-diaries for use in epilepsy clinical trials. • Overall e-diary compliance in a phase 2 trial of natalizumab in adult patients with focal epilepsy was good (83.6%). • Consideration of e-diary elements such as recall period and reporting of seizure-free days will facilitate accurate data capture in epilepsy clinical trials. • A minority of participants did not achieve good e-diary compliance, and patient-focused strategies should be employed to identify and address any barriers. To analyze electronic diary (e-diary) use in a phase 2, randomized, controlled clinical trial (OPUS; NCT03283371) of natalizumab in adult participants with drug-resistant focal epilepsy. We developed an e-diary, which incorporated an episodic seizure diary and a daily diary reminder, for use as the primary source to record participants' daily seizure activity in the OPUS phase 2 clinical trial. Participants and/or their designated caregivers made e-diary entries by selecting seizure descriptions generated in the participants' and/or caregivers' own words at the time of screening. Seizures and seizure-free days were reported for the current day and for up to 5 and 4 retrospective days, respectively. A record of seizure symptoms entered within the prior 5-day period was displayed on accessing the diary. Changes were not permitted in the e-diary once a seizure record was saved unless a data change request was made. A paper backup diary was available. E-diary entries (N = 15,176) from the 6-week baseline period and subsequent 24-week placebo-controlled period were analyzed for 66 adults who were randomized and dosed in the OPUS trial. The overall e-diary compliance, defined as the total number of days with any entry out of the total number of days in the baseline and placebo-controlled periods for all participants combined, was 83.6%. Caregivers made 190 (1.3%) e-diary entries. Day-of-event e-diary entries totaled 11,248 (74.1%). At least one paper backup diary was used by 36 (54.5%) participants. Our data highlight that good e-diary compliance can be achieved across participants in randomized clinical trials in adult focal epilepsy. In addition to identifying and addressing any barriers that may prevent a minority of participants from achieving good e-diary compliance, consideration of e-diary elements, such as recall period and reporting of seizure-free days, will facilitate the most accurate data capture in epilepsy clinical trials. [ABSTRACT FROM AUTHOR]

Aspartic proteases (APs) are present in both monocotyledonous and dicotyledonous plants. APs consist of nine different families of proteolytic enzymes. APs play important functions in several physiological processes including defense. However, there are limited reports on APs in disease resistance in rice (Oryza sativa). Here, we report that 104 APs were discovered in rice genome. They can be classified into three clades (I, II and III) with APs from Arabidopsis thaliana , and Nymphaea colorata according to phylogenetic relationships. Tandem and segmental duplications were observed to lead to the expansion of OsAP genes in rice. Analysis of gene structure revealed that numerous OsAPs contain multiple exons and introns, however, several OsAPs harbor a single exon and no introns. Synteny analyses demonstrated that four AP genes among O. sativa , A. thaliana , and N. colorata may evolve from a common ancestor of land plants. Ten conserved motifs of amino acids were uncovered from the OsAPs, and two of the motifs are the catalytic sequences, with the conserved Asp-Thr and Ser-Gly amino acids. Within the OsAP promoter sequences, cis -regulatory elements responsive to light, abscisic acid, auxin, gibberellins, methyl jasmonate, and salicylic acid were identified. Stress-responsive elements and tissue-specific expressed elements were also found. Majority of OsAP genes were found to be expressed in diverse tissues and organs. Some of the OsAP genes were observed to be induced by brassinosteroids, jasmonic acid, and salicylic acid. Further, some OsAP genes can be induced by Xanthomonas oryzae pv. oryzae (Xoo), the cause of rice bacterial leaf blight. Among them, OsAP21 was strongly activated by the pathogen, suggesting its potential function in response to the bacterial agent. The results shed light in the potential functions of OsAP genes in rice disease resistance to Xoo. • A total of 104 aspartic proteases were identified in rice. • Many of OsAP genes are induced by brassinosteroids and jasmonic acid. • Some OsAP genes can be induced by Xanthomonas oryzae pv. oryzae. • OsAP21 was strongly activated by Xanthomonas oryzae pv. oryzae. [ABSTRACT FROM AUTHOR]

• Anterior cingulate cortex were negatively associated with IL-6 in the asymptomatic bipolar offspring. • Anterior cingulate cortex mediated the effect of IL-6 on attention function in the asymptomatic offspring. • Two subgroups of 'unaffected' bipolar offspring had distinct cytokine-brain structure-cognition profiles. Neuro-inflammation might impact on clinical manifestations and cognition function via changing the volumes of key brain structures such as the anterior cingulate cortex (ACC) in bipolar disorder (BD). In this study, we investigated the interrelations among interleukin (IL)-6 cytokine level, grey matter (GM) volume of the anterior cingulated cortex (ACC), and attention function among offspring of parents diagnosed with BD. The offspring were categorized as being either asymptomatic or symptomatic based on whether they manifested pre-defined sub-threshold mood symptoms. We found that the symptomatic offspring showed significantly higher serum levels of IL-6 than the asymptomatic offspring (F (1, 59) = 67.65, p < 0.001). On the brain level, we obtained significant interactive effect of group and IL6 level on the ACC GM (P FWE = 0.017). Specifically, the GM volume of the rostral ACC was negatively associated with the levels of IL-6 in the asymptomatic offspring (P FWE = 0.021), but not the symptomatic offspring (P FWE > 0.05). Mediation analyses revealed that the GM volume of the rostral ACC significantly mediated the negative association between the IL-6 levels and attention performance in the asymptomatic offspring (bootstrapping Confidence Interval (CI) = −6.0432 to −0.0731) but not the symptomatic offspring (bootstrapping CI = −0.3197 to 1.3423). Our data suggest that the asymptomatic and symptomatic bipolar offspring may exhibit different neurocognitive-inflammatory profiles, which could be further validated as viable biosignatures for BD risk and resilience. [ABSTRACT FROM AUTHOR]

Sogatella furcifera is a destructive agricultural pest causing large threats to rice production in China and Southeast Asian countries. Despite recent breakthroughs in long-read sequencing, high quality genomic data are very limited in S. furcifera. In present study, a chromosome-level assembly of the S. furcifera genome was completed (0.64 GB), comprising 15 chromosomes covered 95.04% of the estimated genome size, along with other 624 small scaffolds making up the remaining 4.96% of the genome of S. furcifera. A total of 24,669 protein-coding genes, 1211 long noncoding RNA and 7595 circular RNA transcripts were predicted in this study. Comparative genomic analysis revealed rapidly evolved genes were associated with multiple immune-related pathways in S. furcifera. Genome resequencing of 44 individuals from 12 geographic populations revealed frequent gene flow among populations. The systemic genomic analysis will provide more insights into the understanding of the immunity and evolutionary adaptation of S. furcifera. [ABSTRACT FROM AUTHOR]

Graphical abstract Target therapy for TNBC with ICAM-1 antibody mediated mesoporous drug delivery system DOX@PMO-Cy5.5-ICAM. Abstract The development of effective targeted therapies for triple negative breast cancer (TNBC) remains a challenge. This targeted drug delivery system used a near-infrared fluorescence dye cyanine 5.5 (Cy5.5) and an ICAM-1 antibody on thioether-bridged periodic mesoporous organosilica nanoparticles (PMOs). The ICAM-1 antibody and cyanine 5.5-engineered PMOs (PMO-Cy5.5-ICAM) offer excellent in vivo and in vitro biocompatibility. The PMO-Cy5.5-ICAM shows a loading capacity up to 400 mg/g of doxorubicin (DOX). The drug release profile of the DOX-loaded targeted delivery system (DOX@PMO-Cy5.5-ICAM) is pH-sensitive. Confocal microscopy showed that the PMO-Cy5.5-ICAM efficiently targets and enters TNBC cells. In in vivo experiments, the DOX@PMO-Cy5.5-ICAM accumulates more in TNBCs than in the control groups and exhibits better therapeutic effects on TNBC; thus, it is a promising treatment strategy for TNBC. [ABSTRACT FROM AUTHOR]

• A FBG based semicircular sensor architecture with fiber fault monitoring is demonstrated. • There is no optical filter used in the FBG sensor system for wavelength-selection. • Proposed multiple FBG sensor system can sense the temperature and strain simultaneously. • 144 FBG sensors can be employed in the proposed system for sensing. In the investigation, we investigate a fiber Bragg grating (FBG) based semicircular sensor architecture with fiber fault monitoring experimentally. Two erbium-doped fiber amplifiers (EDFAs) are used in the monitoring center to generate a broadband light source for sensing the strain and temperature simultaneously. Here, we utilize six FBG based sensors with different reflected wavelength for proof-of-concept demonstration. There is no optical filter used in the FBG sensor system for wavelength-selection. In addition, the proposed sensor system can monitor one to two fiber faults. In the measurement, the temperature- and strain-induced changes are also analyzed and discussed. Therefore, the proposed multiple FBG based semicircular sensor system not only can sense the temperature and strain simultaneously, but also can be used to monitor where is the fiber fault. [ABSTRACT FROM AUTHOR]

Graphical abstract Highlights • W x C@CS catalysts with controllable phase compositions were successfully prepared. • W 1.25 C@CS displays superior performance for hydrogenolysis of guaiacol to phenol. • The enhanced activity is contributed to structural tuning and surface C-defects. • The connection between phenol space time yield and C/W ratio was established. • Structure–performance relationship was further uncovered by DFT calculations. Abstract Tungsten carbides exhibit excellent performance in many heterogeneous processes because of their distinctive catalytic properties. Preparation of tungsten carbides with controllable phase composition relevant to their catalytic behavior is essential yet challenging. In this study, tungsten carbides embedded in carbon spheres (W x C@CS) were fabricated through carburization of organic–inorganic hybrid precursors. W 1.25 C@CS with rational structure-tuning properties exhibits promising regioselectivity (reaching 91.5%) toward aryl C O bond cleavage, specifically during hydrogenolysis of guaiacol to phenol. A structure reconstruction strategy was adopted to elucidate structure–performance relationship by transforming commercially available bulk WC from inert phase to composition-dependent active catalysts. Combined catalytic and characteristic analyses illustrate that the catalyst performance is dependent on the C-defect structure. The intimate connection between the phenol space time yield and the C/W atomic ratio on the exterior interface of the catalyst was verified. The C/W atomic ratio of 7.2 leads to the optimal catalytic performance. Density functional theory calculations were performed to define the catalytic mechanism at the atomic level. The theoretical analysis suggests an appropriate configuration of surface W and C atoms for activation of hydrogen and guaiacol molecules, rendering the intrinsic active sites for phenol production. This work provides insights into controlling the surface compositions of tungsten carbides to develop efficient C O bond cleavage catalysts, which verifies the importance of hydrogenolysis catalysis in lignin-derived compounds involving complex O-containing guaiacols and phenolics. [ABSTRACT FROM AUTHOR]

Metabolic reprogramming plays a pivotal role in the differentiation and function of immune cells including dendritic cells (DCs). Regulatory DCs can be generated in regional tissue niches like splenic stroma and act as an important part of stromal control of immune response for the maintenance of immune tolerance. However, the metabolic alterations during splenic stroma-driven regulatory DCs differentiation and the metabolic enzyme involved in regulatory DCs function remain poorly understood. By combining metabolomic, transcriptomic, and functional investigations of mature DCs (maDCs) and diffDCs (regulatory DCs differentiated from activated mature DCs through coculturing with splenic stroma), here we identified succinate-CoA ligase subunit beta Suclg2 as a key metabolic enzyme that reprograms the proinflammatory status of mature DCs into a tolerogenic phenotype via preventing NF-κB signaling activation. diffDCs downregulate succinic acid levels and increase the Suclg2 expression along with their differentiation from mature DCs. Suclg2 -interference impaired the tolerogenic function of diffDCs in inducing T cell apoptosis and enhanced activation of NF-κB signaling and expression of inflammatory genes CD40 , Ccl5 , and Il12b in diffDCs. Furthermore, we identified Lactb as a new positive regulator of NF-κB signaling in diffDCs whose succinylation at the lysine 288 residue was inhibited by Suclg2. Our study reveals that the metabolic enzyme Suclg2 is required to maintain the immunoregulatory function of diffDCs, adding mechanistic insights into the metabolic regulation of DC-based immunity and tolerance. • Decreased succinic acid levels and increased Suclg2 expression in spleen stroma-induced regulatory DCs (diffDCs). • Suclg2 inhibits proinflammatory but maintains the tolerogenic function of regulatory DCs. • Suclg2 prevents NF-κB activation and inhibits protein succinylation in diffDCs. • Suclg2 suppresses the succinylation of Lactb protein at the lysine 288 residue. [ABSTRACT FROM AUTHOR]

Multivariate outcomes with multivariate features of possibly high dimension are routinely produced in various fields. In many real-world problems, the collected outcomes are of mixed types, including continuous measurements, binary indicators and counts, and a substantial proportion of values may also be missing. Regardless of their types, these mixed outcomes are often interrelated, representing diverse reflections or views of the same underlying data generation mechanism. As such, an integrative multivariate model can be beneficial. We develop a mixed-outcome reduced-rank regression, which effectively enables information sharing among different prediction tasks. Our approach integrates mixed and partially observed outcomes belonging to the exponential dispersion family, by assuming that all the outcomes are associated through a shared low-dimensional subspace spanned by the features. A general singular value regularized criterion is proposed, and we establish a non-asymptotic performance bound for the proposed estimators in the context of supervised learning with mixed outcomes from an exponential family and under a general sampling scheme of missing data. An iterative singular value thresholding algorithm is developed for optimization with convergence guarantee. The effectiveness of our approach is demonstrated by simulation studies and an application on predicting health-related outcomes in longitudinal studies of aging. [ABSTRACT FROM AUTHOR]

Soil pollution has caused increasingly widespread attention in China. The environmental risk threshold of pollutants is a yardstick to measure soil environmental quality. For decades, plenty of research on soil environmental quality standards (SEQSs) has been carried out, providing scientific basis for the investigation and supervision of soil environmental quality. This paper summaries the development of SEQSs in China, the corresponding influencing factors and methodology of SEQSs derivation. In the current version of SEQSs (GB15618-2018), the thresholds of soil pollutants are derived by the methods of environmental risk assessment, which are more methodologically scientific than geochemical method and ecological effect method used in the previous version (GB15618-1995). Abundant toxicology data on related species is required for risk assessment of soil pollution using extrapolation; however, basic toxicological data is insufficient and few valid data is available at present. Besides, the inadequate consideration on influencing factors for the derivation of soil pollutant threshold would affect the scientificity and rationality of SEQSs, such as biotic factors (species type, test endpoint etc.) and abiotic factors (aging effect, leaching effect, synergistic or antagonistic effects of elements etc.). These problems should be paid close attention in future research on soil environmental quality standards. The contents summarized in this review may provide reference for decision-making on supervision of soil environmental quality and point out important directions for future studies. • The development processes of soil environmental quality standards (SEQSs) in China were reviewed. • The research progresses of derivation methodology of SEQSs were summarized. • At present, few valid data are available for SEQSs derivation using extrapolation. • The influencing factors on SEQSs derivation are taken insufficient account. [ABSTRACT FROM AUTHOR]

Myostatin (MSTN) is a secreted protein belonging to the transforming growth factor-β (TGF-β) family that is primarily expressed in skeletal muscle and also functions in adipocyte maturation. Studies have shown that MSTN can inhibit adipogenesis in muscle satellite cells (MSCs) but not in adipose-derived stem cells (ADSCs). However, the mechanism by which MSTN differently regulates adipogenesis in these two cell types remains unknown. Peroxisome proliferator-activated receptor-γ (PPARγ) and myogenic differentiation factor (MyoD) are two key transcription factors in fat and muscle cell development that influence adipogenesis. To investigate whether MSTN differentially regulates PPARγ and MyoD , we analyzed PPARγ and MyoD expression by assessing mRNA, protein and methylation levels in ADSCs and MSCs after treatment with 100 ng/mL MSTN for 0, 24, and 48 h. PPARγ mRNA levels were downregulated after 24 h and upregulated after 48 h of treatment in ADSCs, whereas in MSCs, PPARγ levels were downregulated at both time points. MyoD expression was significantly increased in ADSCs and decreased in MSCs. PPARγ and MyoD protein levels were upregulated in ADSCs and downregulated in MSCs. The CpG methylation levels of the PPARγ and MyoD promoters were decreased in ADSCs and increased in MSCs. Therefore, this study demonstrated that the different regulatory adipogenic roles of MSTN in ADSCs and MSCs act by differentially regulating PPARγ and MyoD expression. [ABSTRACT FROM AUTHOR]

Highlights: [•] Innovative fabrication of hierarchically structured PSU/TiO2 fibrous membranes. [•] Fractal dimensional analysis confirmed the irregular rough surface features. [•] Correlation between hierarchical roughness and filtration performance was proposed. [•] Two-tier composite medium showed enhanced fine particulate filtration performance. [ABSTRACT FROM AUTHOR]

Abstract: Objective: The purpose of this study is to contribute evidence towards heterogeneity in risk factors for single and recurrent falls. Method: This is a prospective study conducted in Taiwan. Participants were randomly selected from the examinees of the annual health examination in 2010. Participants were interviewed with a detailed questionnaire and followed up one year later. Predictor variables included socio-demographic characteristics, medical conditions, laboratory data, and risk factors for osteoporosis. The outcome was falls in the ensuing 12months. Results: The mean age of the 653 completers was 75.6±6.4. Half (48.7%) were women. Fallers and recurrent fallers comprised 14.5% and 6.0% of the participants, respectively. Blurred vision (adjusted odds ratio (aOR): 1.93, 95% confidence interval (CI): 1.02–3.67), minimal outdoor activities (aOR: 2.28, 95% CI: 1.06–4.88), and overactive thyroid/parathyroid (aOR: 3.49, 95% CI: 1.29–9.50) were associated with single falls. Frailty (aOR: 2.81, 95% CI: 1.11–7.09), decreased body height (aOR: 3.15, 95% CI: 1.52–6.54) and taking sedatives/hypnotics (aOR: 4.23, 95% CI: 2.06–8.67) were associated with recurrent falls. Previous falls (aOR: 2.64, 95% CI: 1.44–4.84 for single falls; aOR: 5.26, 95% CI: 2.61–10.60 for recurrent falls) were associated with all falls. Conclusion: Different intervention strategies should be developed for single and recurrent fallers. [Copyright &y& Elsevier]

Abstract: In yeast, the type 1 protein phosphatase (PP1) catalytic subunit Glc7 is involved in the regulation of multiple cellular processes and thought to achieve specificity through association with different regulatory subunits. Here, we report that the Glc7 regulator Shp1 plays important roles in cell morphogenesis, cell cycle progression and DNA damage response in Candida albicans. SHP1 deletion caused the formation of rod-shaped yeast cells with slow growth. Flow cytometry analysis revealed that shp1Δ cells showed a prolonged G2/M phase, which was rescued by deleting the spindle-checkpoint gene MAD2. Furthermore, shp1Δ cells were hypersensitive to heat and genotoxic stresses. Interestingly, depletion of Glc7 caused defects similar to the shp1Δ mutant such as arrest at G2/M transition; and the GLC7/glc7Δ heterozygous mutant exhibited increased sensitivity to genotoxic stresses, consistent with the recent finding that Saccharomyces cerevisiae Glc7 has a role in DNA damage response. We also show that Shp1 is required for the nuclear accumulation of Glc7, suggesting that Shp1 executes its cellular function partly by regulating Glc7 localization. [Copyright &y& Elsevier]

Compound 10E is a new Nur77 exporter and autophagic death inducer which showed potent antiproliferative activity at micromolar concentrations against three different liver cancer cells. [Display omitted] • New Quinoline-Indole-Schiff base derivatives with naphthalene are potent anti-HCC agents. • 10E greatly inhibits cell migration and promotes cell apoptosis in liver cancer cells. • Molecular docking and MD simulation studies suggest 10E as a valuable small ligand of Nur77. • 10E has a good affinity to Nur77 with K D values of 2.25–4.10 μM. • 10E induces the sub-cellular localization of Nur77 and results in autophagic death. We previously reported 5-((8-methoxy-2-methylquinolin-4-yl)amino)-1 H -indole- 2-carbohydrazide derivatives as new Nur77 modulators. In this study, we explored whether the 8-methoxy-2-methylquinoline moiety and bicyclic aromatic rings at the N '-methylene position were critical for their antitumor activity against hepatocellular carcinoma (HCC). For this purpose, a small library of 5-substituted 1 H -indole-2-carbohydrazide derivatives was designed and synthesized. We found that the 8-methoxy-2-methylquinoline moiety was a fundamental structure for its biological function, while the introduction of the bicyclic aromatic ring into the N '-methylene greatly improved its anti-tumor effect. We found that the representative compound 10E had a high affinity to Nur77. The K D values were in the low micromolar (2.25–4.10 μM), which were coincident with its IC 50 values against the tumor cell lines (IC 50 < 3.78 μM). Compound 10E could induce autophagic cell death of liver cancer cells by targeting Nur77 to mitochondria while knocking down Nur77 greatly impaired anti-tumor effect. These findings provide an insight into the structure–activity relation of Quinoline-Indole-Schiff base derivatives and further demonstrate that antitumor agents targeting Nur77 may be considered as a promising strategy for HCC therapy. [ABSTRACT FROM AUTHOR]

Though growing evidence has linked air pollution to Parkinson's disease (PD), the results remain inconsistent. Less is known about the relevance of road proximity and surrounding green. We aimed to investigate the individual and joint associations of air pollution, road proximity and surrounding green with the incidence of PD in a prospective cohort study. We used data from a prospective cohort of 47,516 participants recruited from July 2015 to January 2018 in Ningbo, China. Long-term exposure to particulate matter with aerodynamic diameter ≤2.5 μm (PM 2.5) and ≤10 μm (PM 10) and nitrogen dioxide (NO 2) estimated by land-use regression models, road proximity and surrounding green assessed by Normalized Difference Vegetation Index (NDVI) were calculated based on the residential address for each participant. Cox proportional hazard models were used to analyze the individual and joint effects of air pollution, road proximity, and surrounding green on PD. In single-exposure models, PM 2.5 , PM 10 , NO 2 and road proximity was associated with increased risk of PD (e.g. Hazard Ratio (HR) = 1.51, 95%CI:1.02, 2.24 per interquartile range (IQR) increase for PM 2.5) while surrounding green was associated with decreased risk of PD (e.g. HR = 0.80, 95%CI:0.65, 0.98 per IQR increase for NDVI in 300 m buffer). In two-exposure models, the associations of PM 2.5 and surrounding green persisted while the associations of NO 2 and road proximity attenuated towards unity. We found that PM 2.5 were associated with increased risk of incident PD while surrounding green was associated with decreased risk of PD. Future studies about PD etiology may benefit from including multiple environmental exposures to address potential joint associations. [Display omitted] • Positive associations between PM 2.5 and incident Parkinson's disease were found. • Negative associations between greenness and incident Parkinson's disease were found. • Improvements in air quality and land use planning might benefit for PD prevention. [ABSTRACT FROM AUTHOR]