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This work is devoted to Poisson stable (including stationary, periodic, quasi-periodic, Bohr almost periodic, Bohr almost automorphic, Birkhoff recurrent, almost recurrent in the sense of Bebutov, Levitan almost periodic, pseudo-periodic, pseudo-recurrent) solutions for stochastic functional evolution equations (SFEEs) with infinite delay. First, we prove the existence of bounded mild solutions for SFEEs with infinite delay. Then, according to the relationship between the solution and (drift and diffusion) coefficients, we obtain such Poisson stable solutions. Because the solutions of the delay equations are not Markov, we employ the solution maps in some phase space as a viable alternative for studying further asymptotic properties, and we also discuss Poisson stable solution maps and their asymptotic stability. [ABSTRACT FROM AUTHOR]

ANKRD11 gene encodes for the large nuclear protein essential for multiple system development including the nervous system. However, the molecular basis for the proper nuclear localization of ANKRD11 has not yet been elucidated. In this study, we have identified a functional bipartite nuclear localization signal (bNLS) between residues 53 and 87 of ANKRD11. Using biochemical approaches, we discovered two major binding sites in this bipartite NLS for Importin α1. Through site-directed mutagenesis and functional analysis, we further found that this bipartite NLS is sufficient for nuclear import of overexpressing GFP in HeLa cells and necessary for nuclear localization of ANKRD11. Importantly, our study provides a possible pathogenic mechanism for certain clinical variants located within the bipartite nuclear localization signal of ANKRD11. • ANKRD11 N-terminus binds to Importin α1 via a bipartite region. • The region is a functional bipartite NLS in ANKRD11 with a long linker. • Disruption of the interaction impairs the nuclear localization of ANKRD11. [ABSTRACT FROM AUTHOR]

We introduce the Q (s) -index ind Γ for a symplectic orthogonal group Q (s) and Q (s) invariant subset Γ of R 2 n and prove that ind S 2 n − 1 = n. Using this fact, we study multiple rotating periodic orbits of Hamiltonian systems. For an orthogonal matrix Q , a Q -rotating periodic solution z (t) has the form z (t + T) = Q z (t) for all t ∈ R and some constant T > 0. According to the structure of Q , it can be periodic, anti-periodic, subharmonic, or just a quasi-periodic one. Under a non-resonant condition, we prove that on each energy surface near the equilibrium, the Hamiltonian system admits at least n Q -rotating periodic orbits, which can be regarded as a Lyapunov type theorem on rotating periodic orbits. [ABSTRACT FROM AUTHOR]

Paraquat (PQ) poisoning leads to irreversible fibrosis in the lungs with high mortality and no known antidote. In this study, we investigated the effect of the SET and MYND domain containing 2 (SMYD2) on PQ-induced pulmonary fibrosis (PF) and its potential mechanisms. We established an in vivo PQ-induced PF mouse model by intraperitoneal injection of PQ (20 mg/kg) and in vitro PQ (25 μM)-injured MLE-12 cell model. On the 15th day of administration, tissue injury, inflammation, and fibrosis in mice were evaluated using various methods including routine blood counts, blood biochemistry, blood gas analysis, western blotting, H&E staining, ELISA, Masson staining, and immunofluorescence. The findings indicated that AZ505 administration mitigated tissue damage, inflammation, and collagen deposition in PQ-poisoned mice. Mechanistically, both in vivo and in vitro experiments revealed that AZ505 treatment suppressed the PQ-induced epithelial-mesenchymal transition (EMT) process by downregulating GLI pathogenesis related 2 (GLIPR2) and ERK/p38 pathway. Further investigations demonstrated that SMYD2 inhibition decreased GLIPR2 methylation and facilitated GLIPR2 ubiquitination, leading to GLIPR2 destabilization in PQ-exposed MLE-12 cells. Moreover, rescue experiments conducted in vitro demonstrated that GLIPR2 overexpression eliminated the inhibitory effect of AZ505 on the ERK/p38 pathway and EMT. Our results reveal that the SMYD2 inhibitor AZ505 may act as a novel therapeutic candidate to suppress the EMT process by modulating the GLIPR2/ERK/p38 axis in PQ-induced PF. [Display omitted] • SMYD2 inhibition ameliorates pulmonary fibrosis in mice after PQ intoxication. • SMYD2 inhibition reverses EMT process in vivo and in vitro. • GLIPR2 is a novel non-histone target of SMYD2. • SMYD2 inhibition alleviates pulmonary fibrosis by inhibiting GLIPR2/ERK/p38 pathway. [ABSTRACT FROM AUTHOR]

Pressure overload induced cardiac remodeling is associated with a complex spectrum of pathophysiological mechanisms. As inflammatory cells, macrophages maintain a critical position in mechanical stress-induced myocardial remodeling. HMGB1 is a highly conserved, ubiquitous protein in various types of cells whose biological roles are closely dependent on subcellular sites. However, whether HMGB1 expressed in macrophages performs the protective or pathological responses in cardiac remodeling is unknown. In this study, we generated the myeloid-specific HMGB1 knockout mice and detected the effects of macrophage HMGB1 in response to pathophysiological stress. Our data showed HMGB1 in macrophages played a protective role against the pressure overload induced cardiac pathophysiology. The deletion of HMGB1 in macrophages gains more differentiation of M1-type pro-inflammatory macrophage during the mechanical stress-induced myocardial remodeling, thereby aggravating the inflammatory response in whole heart, resulting in accelerated deterioration of cardiac function. Moreover, in vitro data also validated HMGB1 got involved in the process of macrophage polarization. Macrophages without HMGB1 are more inclined to differentiate into M1 during the stretch process. In summary, the present results indicated that loss of HMGB1 in macrophages can exacerbate heart failure through increased differentiation of pro-inflammatory macrophages and enhanced inflammatory response. • HMGB1 in macrophage nucleus played a protective role against the pressure overload induced cardiac pathophysiology. • Deleting HMGB1 in macrophages gains more differentiation of M1 macrophage and expression of inflammatory genes after TAC. • Macrophages without nuclear HMGB1 are more inclined to differentiate into M1 macrophage during the in vitro stretch process. [ABSTRACT FROM AUTHOR]

[Display omitted] Enhancing the interfacial dispersion and suspension stability is crucial for magnesium hydroxide (Mg(OH) 2) nanomaterials in the long-term deacidification of paper-based cultural relics. However, because of the low specific surface area and the poor solvent compatibility of as-prepared large-sized Mg(OH) 2 , it often tends to agglomerate and settle down during the usage and storage, that is harmful for paper protection due to its unevenly deacidification and nonuniformly distribution on paper cellulose. Herein, we propose a feasible preparation of colloidal Mg(OH) 2 ultrathin nanoflakes with high dispersion stability via a simple one-step surfactant-assisted strategy. The surfactant acts as both a structure-direct agent to confine the growth of Mg(OH) 2 with rich active sites and a surface modifier to enhance its solvent adaptability and dispersion stability, avoiding the common fussy procedure with additional steric stabilizer. Owing to the evenly interaction with free acid species therein and the uniformly distribution on the paper fiber as alkaline reserve, the as-obtained Mg(OH) 2 presents the superior paper protection performance characterized by its safer pH of 7.29 for the original aged paper (pH = 5.03) and the excellent long-term anti-acidification effect with competitive pH of 5.47 after accelerated-aging at 105 °C for 5 months. Furthermore, Mg(OH) 2 nanoflakes with surfactant-modified structure also endue them as an improved flame retardant for multifunctional paper protection. The protection with Mg(OH) 2 has little effect on the paper surface properties and cellulose crystallinity, in line with the principle of least intervention. This work will put forward a feasible way toward colloidal Mg(OH) 2 nanoflakes with excellent paper protection performance, shedding light on the development of emerging protection materials for paper-based cultural relics. [ABSTRACT FROM AUTHOR]

The laccase mediator system (LMS) with a broad substrate range has attracted much attention as an efficient approach for water remediation. However, the practical application of LMS is limited due to their high solubility, poor stability and low reusability. Herein, the bimetallic Cu/ZIFs encapsulated laccase was in-situ grown in poly(vinyl alcohol) (PVA) polymer matrix. The PVA-Lac@Cu/ZIFs hydrogel was formed via one freeze-thawing cycle, and its catalytic stability was significantly improved. The mediator was further co-immobilized on the hydrogel, and this hierarchically co-immobilized ABTS/PVA-Lac@Cu/ZIFs hydrogel could avoid the continuous oxidation reaction between laccase and redox mediators. The co-immobilized LMS biocatalyst was used to degrade malachite green (MG), and the degradation rate was up to 100 % within 4 h. More importantly, the LMS could be recycled synchronously from the dye solutions and reused to degrade MG multiple times. The degradation rate remained above 69.4 % after five cycles. Furthermore, the intermediate products were detected via liquid chromatography-mass spectrometry, and the potential degradation pathways were proposed. This study demonstrated the significant potential of utilizing the MOF nanocrystals and hydrogel as a carrier for co-immobilized LMS, and the effective reuse of both laccase and mediator was promising for laccase application in wastewater treatment. [Display omitted] • Cu/ZIFs encapsulated laccase was in-situ grown in the PVA polymer matrix. • The LMS was co-immobilized by MOF/hydrogel, enhancing catalytic stability. • PVA-Lac@Cu/ZIFs exhibit over 80 % of initial activity after 8 reaction cycles. • The PVA/ABTS-Lac@Cu/ZIFs was efficient for MG dye degradation practically 100 %. • The co-immobilized LMS could recycle synchronously from dye solutions. [ABSTRACT FROM AUTHOR]

Stoichiometric genome-scale metabolic network models (GEMs) have been widely used to predict metabolic phenotypes. In addition to stoichiometric ratios, other constraints such as enzyme availability and thermodynamic feasibility can also limit the phenotype solution space. Extended GEM models considering either enzymatic or thermodynamic constraints have been shown to improve prediction accuracy. In this paper, we propose a novel method that integrates both enzymatic and thermodynamic constraints in a single Pyomo modeling framework (ETGEMs). We applied this method to construct the EcoETM (E. coli metabolic model with enzymatic and thermodynamic constraints). Using this model, we calculated the optimal pathways for cellular growth and the production of 22 metabolites. When comparing the results with those of i ML1515 and models with one of the two constraints, we observed that many thermodynamically unfavorable and/or high enzyme cost pathways were excluded from EcoETM. For example, the synthesis pathway of carbamoyl-phosphate (Cbp) from i ML1515 is both thermodynamically unfavorable and enzymatically costly. After introducing the new constraints, the production pathways and yields of several Cbp-derived products (e.g. L-arginine, orotate) calculated using EcoETM were more realistic. The results of this study demonstrate the great application potential of metabolic models with multiple constraints for pathway analysis and phenotype prediction. • E. coli metabolic model i ML1515 with enzymatic and thermodynamic constraints. • Pyomo multi-constraints modeling formulation framework and open-source code. • Various variability analysis to identify the bottleneck reactions and key enzymes. • More reliable pathway analysis results due to more favorable arrangement of reactions. [ABSTRACT FROM AUTHOR]

In this paper, we establish an existence and uniqueness result for the system of quasilinear stochastic partial differential equations (SPDEs for short) with reflection in a convex domain in R K by analytical approach. The method is based on the approximation of the penalized systems of SPDEs. [ABSTRACT FROM AUTHOR]

[Display omitted] • The G4 helicase BsPif1 possesses independent binding sites for both ssDNA and G4. • ssDNA translocation driven by ATP hydrolysis, exerts a pulling force on G4 unwinding. • There is a distinct G4 binding region that play a critical role in G4 unwinding. • A novel theoretical framework for the G4 development mechanism within Pif1 helicases. The G-quadruplex (G4) is a distinct geometric and electrophysical structure compared to classical double-stranded DNA, and its stability can impede essential cellular processes such as replication, transcription, and translation. This study focuses on the Bs Pif1 helicase, revealing its ability to bind independently to both single-stranded DNA (ssDNA) and G4 structures. The unfolding activity of Bs Pif1 on G4 relies on the presence of a single tail chain, and the covalent continuity between the single tail chain and the G4′s main chain is necessary for efficient G4 unwinding. This suggests that ATP hydrolysis-driven ssDNA translocation exerts a pull force on G4 unwinding. Molecular dynamics simulations identified a specific region within Bs Pif1 that contains five crucial amino acid sites responsible for G4 binding and unwinding. A "molecular wire stripper" model is proposed to explain Bs Pif1′s mechanism of G4 unwinding. These findings provide a new theoretical foundation for further exploration of the G4 development mechanism in Pif1 family helicases. [ABSTRACT FROM AUTHOR]

Persistent cardiac Ca2+/calmodulin dependent Kinase II (CaMKII) activation plays an essential role in heart failure development. However, the molecular mechanisms underlying CaMKII induced heart failure progression remains incompletely understood. Histone deacetylases (HDACs) are critical for transcriptional responses to stress, and contribute to expression of pathological genes causing adverse ventricular remodeling. Class I HDACs, including HDAC1, HDAC2 and HDAC3, promote pathological cardiac hypertrophy, whereas class IIa HDACs suppress cardiac hypertrophy. While it is known that CaMKII deactivates class IIa HDACs to enhance cardiac hypertrophy, the role of CaMKII in regulating class I HDACs during heart failure progression is unclear. CaMKII increases the deacetylase activity of recombinant HDAC1, HDAC2 and HDAC3 via in vitro phosphorylation assays. Phosphorylation sites on HDAC1 and HDAC3 are identified with mass spectrometry. HDAC1 activity is also increased in cardiac-specific CaMKIIδ C transgenic mice (CaMKIIδ C -tg). Beyond post-translational modifications, CaMKII induces HDAC1 and HDAC3 expression. HDAC1 and HDAC3 expression are significantly increased in CaMKIIδ C -tg mice. Inhibition of CaMKII by overexpression of the inhibitory peptide AC3-I in the heart attenuates the upregulation of HDAC1 after myocardial infarction surgery. Importantly, a potent HDAC1 inhibitor Quisinostat improves downregulated autophagy genes and cardiac dysfunction in CaMKIIδ C -tg mice. In addition to Quisinostat, selective class I HDACs inhibitors, Apicidin and Entinostat, HDAC3 specific inhibitor RGFP966, as well as HDAC1 and HDAC3 siRNA prevent CaMKII overexpression induced cardiac myocyte hypertrophy. CaMKII activates class I HDACs in heart failure, which may be a central mechanism for heart failure progression. Selective class I HDACs inhibition may be a novel therapeutic avenue to alleviate CaMKII hyperactivity induced cardiac dysfunction. Unlabelled Image • CaMKII directly enhances HDAC1 and HDAC3 deacetylase activity. • CaMKII induces HDAC1 and HDAC3 expression in the heart. • CaMKII promotes HDAC1/HDAC2/Sin3a repressive complex formation. • Class I HDAC inhibitors improve CaMKII hyperactivity induced cardiac hypertrophy. • HDAC inhibitor recovers CaMKII hyperactivity induced autophagy genes downregulation. [ABSTRACT FROM AUTHOR]

The utilization of one-carbon (C 1) assimilation pathways to produce chemicals and fuels from low-cost C 1 compounds could greatly reduce the substrate-related production costs, and would also alleviate the pressure of the resource supply for bio-manufacturing. However, the natural C 1 assimilation pathways normally involve ATP consumption or the loss of carbon resources as CO 2 , resulting in low product yields, making the design of novel pathways highly pertinent. Here we present several new ATP-independent and carbon-conserving C 1 assimilation cycles with 100% theoretical carbon yield, which were discovered by computational analysis of metabolic reaction set with 6578 natural reactions from MetaCyc database and 73 computationally predicted aldolase reactions from ATLAS database. Then, kinetic evaluation of these cycles was conducted and the cycles without kinetic traps were chosen for further experimental verification. Finally, we used the two engineered enzymes Gals and TalBF178Y for the artificial reactions to construct a novel C 1 assimilation pathway in vitro and optimized the pathway to achieve 88% carbon yield. These results demonstrate the usefulness of computational design in finding novel metabolic pathways for the efficient utilization of C 1 compounds and shedding light on other promising pathways. • A combinatorial algorithm calculating multiple optimal pathways in metabolic networks. • 59 designed C1 assimilation pathways for AcCoA derived products. • Criteria to choose the most promising C1 assimilation pathways. • In vitro construction of a novel designed pathway reaching 88% carbon yield. [ABSTRACT FROM AUTHOR]

Long noncoding RNAs (lncRNAs) exert crucial roles in hepatocellular carcinoma (HCC) progression. LncRNA EIF3J-AS1 is recently reported to be highly expressed in HCC and correlates with recurrence-free survival. However, the biological function of EIF3J-AS1 and its underlying molecular mechanism are unexplored yet. In the current study, we demonstrated that EIF3J-AS1 expression was obviously upregulated in HCC tissues compared to adjacent noncancerous tissues. Moreover, the elevated levels of EIF3J-AS1 was detected in four HCC cell lines (HepG2, SMMC-7721, MHCC97H, HCCLM3) compared with the normal hepatic cell line LO2. Notably, the expression of EIF3J-AS1 was correlated with prognostic features including tumor size, vascular invasion and tumor stage. TCGA-LIHC data indicated that the upregulated expression of EIF3J-AS1 predicted poor prognosis of HCC. EIF3J-AS1 knockdown remarkably suppressed the proliferation, migration and invasion of HCC cells. Mechanistically, EIF3J-AS1 inversely regulated miR-122–5p expression via acting as a competing endogenous RNA (ceRNA) in HCC cells. Furthermore, catenin delta 2 (CTNND2) was recognized as a novel target of miR-122–5p. CTNND2 restoration partially reversed EIF3J-AS1 knockdown-induced inhibitory effects on HCC cell proliferation, migration and invasion. Importantly, we found that hypoxia induced EIF3J-AS1 and CTNND2 expression, and led to miR-122–5p downregulation in HCC cells. EIF3J-AS1 knockdown partially abolished hypoxia-induced HCC cell proliferation and mobility. In conclusion, our results provide a new insight into the molecular pathogenesis of HCC, and EIF3J-AS1 may be a potential therapeutic target for HCC. • EIF3J-AS1 expression is obviously up-regulated in HCC. • The elevated expression of EIF3J-AS1 indicates poor prognosis of HCC. • EIF3J-AS1 knockdown inhibits HCC cell proliferation, migration and invasion. • EIF3J-AS1 promotes CTNND2 expression via sponging miR-122–5p. • Hypoxia-induced EIF3J-AS1 facilitates HCC progression via regulating CTNND2. [ABSTRACT FROM AUTHOR]

A significant role of MOFs as heterogeneous photocatalysts in enabling organic transformations. • Light harvesting Ru-polypyridyl complexes were incorporated into a semiconductor-like metal-organic framework (MIL-125). • Disclosing photoinduced electron transfer among photocatalysis. • The prepared Ru(bpy) 3 @MIL-125 exhibited good recyclability during reaction. Visible-light-driven selective photocatalytic organic synthesis has recently become a topic of great interest due to its environmental friendliness and sustainability. It is demanding for photocatalysis to utilize the wider range of light, such as visible light, and its performance is often plagued by the sluggish separation of photogenerated charge carriers. An approach is now reported to address these issues by incorporating light harvesting RuII-polypyridyl complexes into a semiconductor-type metal-organic framework (MIL-125). Delightedly, the obtained Ru(bpy) 3 @MIL-125 photocatalyst presents a remarkably stable and high photoactivity toward the selective oxidative coupling of amines under ambient air with visible light irradiation (λ > 440 nm). The mechanistic investigation unveiled that both effectively photoexcited electrons transfer from [Ru(bpy) 3 ]Cl 2 to MIL-125 and the interaction of C H bonds with superoxide radical (O 2 ·−) play a critical role in photo-catalyzing selective aerobic oxidative coupling of amines. This work highlights a significant role of MOFs as heterogeneous photocatalysts in photocatalytic organic transformations. [ABSTRACT FROM AUTHOR]

[Display omitted] • A NIR fluorogenic probe Cy-PITC with mitochondrially-targeted ability has been elaborately developed by the novel analyte-replacement strategy. • NIR probe Cy-PITC showed excellent performances for ClO−/HClO including ultrafast response time (within 5 s) and ultralow LOD (2.28 nM). • NIR probe Cy-PITC was triumphantly applied in the fluorescence imaging of exogenous/endogenous mitochondrial ClO−/HClO inside living cells. • NIR probe Cy-PITC was successfully employed for early diagnosis of ClO−/HClO-related rheumatoid arthritis joint tissues. [ABSTRACT FROM AUTHOR]

The degradation of phenol from wastewater is crucial for environmental protection. Biological enzymes, such as horseradish peroxidase (HRP), have shown great potential in the degradation of phenol. In this research, we prepared a hollow CuO/Cu 2 O octahedron adsorbent with a carambola matrix shape through the hydrothermal method. The surface of the adsorbent was modified by silane emulsion self-assembly, where 3-aminophenyl boric acid (APBA) and polyoxometalate (PW 9) were combined with silanization reagents and grafted onto the surface. The adsorbent was then molecularly imprinted with dopamine to obtain boric acid modified polyoxometalate molecularly imprinted polymer (Cu@B@PW 9 @MIPs). This adsorbent was used to immobilize HRP, which served as a biological enzyme catalyst from horseradish. The adsorbent was characterized, and its synthetic conditions, experimental conditions, selectivity, reproducibility, and reusability were evaluated. The maximum adsorption amount of HRP under optimized conditions was 159.1 mg g−1, as determined using high-performance liquid chromatography (HPLC). At pH 7.0, the immobilized enzyme showed a high efficiency of up to 90.0% in removing phenol, after 20 min of reaction with 25 mmol L−1 H 2 O 2 and 0.20 mg mL−1 Cu@B@PW 9 @HRP. Growth tests of aquatic plants confirmed that the adsorbent reduced harm. Gas chromatography-mass spectrometry (GC-MS) tests revealed that the degraded phenol solution contained about fifteen phenol derivatives intermediates. This adsorbent has the potential to become a promising biological enzyme catalyst for dephenolization. The horseradish peroxidase was immobilized on the boric acid modified polyoxometalate molecularly imprinted polymer to establish a biocatalytic enzyme system. A catalytic oxidation system was constructed using hydrogen peroxide, providing a new method for removing phenol from wastewater (Cu@B: Boric acid modified CuO/Cu 2 O; PW 9 : polyoxometalate; HRP: Horseradish peroxidase; Cu@B@PW 9 : Boric acid and polyoxometalate modified CuO/Cu 2 O; Cu@B@PW 9 @MIPs: boric acid modified polyoxometalate molecularly imprinted polymer). [Display omitted] • A novel boric acid modified polyoxometalate molecularly imprinted polymer have been successfully prepared. • Adsorbent can immobilize horseradish peroxidase (HRP) from plant horseradish. • Measured using high performance liquid chromatography (HPLC), the adsorbent have excellent kinetic properties. • The method has a good removal effect on phenol, which can effectively reduce toxicity. [ABSTRACT FROM AUTHOR]

An oxygen-vacancies-engaged photocatalytic mechanism was proposed to address the poor photo absorption and sluggish electron-hole separation of TiO 2. Electrons and holes are fully utilized for nitrobenzene reduction coupled with benzyl alcohol oxidation under visible light irradiation. • Oxygen vacancies (OVs) were generated through surface complexation under mild condition. • Fully making use of the photogenerated charge carriers rapidly promoted its separation and transfer efficiency. • Disclosing photoinduced electron transfer among photocatalysis. • The prepared TiO 2 exhibited good recyclability. Defects can greatly optimize the solar light harvesting capability and electronic structure of oxide materials. However, it remains challenging to achieve a defect engineering strategy under mild conditions. Meanwhile, the simultaneous exploitation of photogenerated holes (h+) and electrons (e−) to promote both photooxidation and photoreduction in a coupled system has rarely been reported. For the first time, we reveal an oxygen-vacancies-mediated photocatalytic strategy in which the electrons and holes are fully utilized for nitrobenzene reduction coupled with benzyl alcohol oxidation. The oxygen vacancies (OVs) generated in situ on the surface of TiO 2 greatly extend light absorption into the visible region and promote the photogenerated electron transport for efficient photocatalysis. The experimental and theoretical results together indicate that chemisorption on the TiO 2 surface decreases the oxidation potential of benzyl alcohol and causes an upward shift in its HOMO, which facilitates the oxidation reaction of benzyl alcohol to benzaldehyde. The in situ generated surface OVs also act as a bridge to enable the trapping and transferring of the photoinduced electrons to the nitrobenzene. This work provides a new perspective of utilizing the chemisorption between the reactant and catalyst to achieve a defect engineering strategy for synergetic photocatalysis. [ABSTRACT FROM AUTHOR]

The introduction of molybdenum in the form of CoMoO 4 nanoparticles has led to the success of M 0.3 NCP@NF as an excellent multifunctional self-supported electrocatalyst for HER, OER and UOR. [Display omitted] The sluggish kinetics of the hydrogen evolution reaction (HER) and substantial barriers in the oxygen evolution reaction (OER) significantly impede its application in hydrogen production. To address this issue and enhance energy efficiency in hydrogen generation, we explored a high-activity alkaline HER catalyst while concurrently coupling it with the urea oxidation reaction (UOR). In this work, we designed and synthesized porous molybdenum (Mo)-modulated nickel-cobalt bimetallic phosphide nanoarrays (M 0.3 NCP@NF). This multifunctional self-supported electrocatalyst demonstrates superior performance in HER, OER, and UOR. The introduction of Mo, in the form of CoMoO 4 nanoparticles, promotes interfacial electron transfer to reduce the electron density around the cations in phosphides, enhancing the kinetics and intrinsic activity. Furthermore, the morphological changes induced by Mo accelerate both electron and mass transfer processes. Density functional theory and operando electrochemical impedance spectroscopy indicate that Mo introduction optimizes the interaction with HER intermediate H*, facilitating the conversion to a high-valent active intermediate for OER and accelerating UOR kinetics. Benefiting from dual optimization of morphology and structure, the as-prepared M 0.3 NCP@NF electrocatalyst demonstrates outstanding HER, OER, and UOR performances. Notably, a full urea electrolysis device powered by M 0.3 NCP@NF operates with a cell voltage of only 1.53 V to achieve a current density of 100 mA cm−2. which is 240 mV lower than that of conventional water electrolysis, demonstrating the competitive potential of our approach for efficient and energy-saving hydrogen production, along with simultaneous urea wastewater remediation. [ABSTRACT FROM AUTHOR]

Post-MI heart failure is characterized by structural remodeling, in which intramyocardial fibrosis takes a important part. Poly(ADP-ribose) polymerase 1 (PARP-1) is a extensive nuclear enzyme and plays a critical role in various diseases. It was shown that PARP-1 inhibition could alleviate heart failure and dowregulate autophagy, but whether PARP-1 regulates autophagy and thus impacts the activities of CFs remain unknown. We transfected cultured cardiac fibroblasts (CFs) with small interfere RNA-PARP-1 (siPARP-1) to downregulate PARP-1 and analyzed the ability of proliferation, migration, differentiation, and autophagy levels of CFs under different treatments using CCK8 assays, transwell migration assays, immunofluorescence assays detecting expression of α-SMA, western blot assays detecting autophagy-related proteins respectively. Furthermore, rat models of myocardial infarction (MI) were induced by ligation of left anterior descending coronary artery and PARP-1 inhibitor, 4-aminobenzamide (4-AB), was injected intraperitoneally after MI, followed by echocardiography detection, masson assays, immunohistochemistry assays detecting expression of α-SMA and western blot assays detecting autophagy-related proteins to investigate whether PARP-1 inhibition could regulate autophagy, alleviate cardiac fibrosis and improve cardiac function in vivo. In cultured CFs, siPARP-1 repressed TGF-β1-induced proliferation, migration, and differentiation through regulating autophagic levels. The in vitro results was verified by the in vivo study, indicating that PARP-1 inhibition partially decreased autophagy, abrogated cardiac fibrosis and significantly improved cardiac function post-MI. In conclusion, this work demonstrated the vital connection of PARP-1 and autophagy in the activation of CFs, and provided solid evidence supporting PARP-1 inhibition as a feasible strategy for the treatment of post-MI heart failure. [ABSTRACT FROM AUTHOR]

The intrinsically disordered protein β-synuclein is known to inhibit the aggregation of its intrinsically disordered homolog, α-synuclein, which is implicated in Parkinson's disease. While β-synuclein itself does not form fibrils at the cytoplasmic pH 7.4, alteration of pH and other environmental perturbations are known to induce its fibrilization. However, the sequence and structural determinants of β-synuclein inhibition and self-aggregation are not well understood. We have utilized a series of domain-swapped chimeras of α-synuclein and β-synuclein to probe the relative contributions of the N-terminal, C-terminal, and the central non-amyloid-β component domains to the inhibition of α-synuclein aggregation. Changes in the rates of α-synuclein fibril formation in the presence of the chimeras indicate that the non-amyloid-β component domain is the primary determinant of self-association leading to fibril formation, while the N- and C-terminal domains play critical roles in the fibril inhibition process. Our data provide evidence that all three domains of β-synuclein together contribute to providing effective inhibition, and support a model of transient, multi-pronged interactions between IDP chains in both processes. Inclusion of such multi-site inhibitory interactions spread over the length of synuclein chains may be critical for the development of therapeutics that are designed to mimic the inhibitory effects of β-synuclein. [ABSTRACT FROM AUTHOR]

Interleukin (IL)-22 regulates host defense. This study investigated the predominant IL-22-producing cell subsets under HBV associated immune stages. We found circulating IL-22-producing CD3 + CD8- T cells were significantly increased in immune active (IA) stage than those in immunotolerant stage, inactive carrier and healthy controls (HCs). The plasma IL-22 level was higher in IA and HBeAg-negative CHB compared to HCs. Importantly, CD3 + CD8- T cells were identified as the predominant source of plasma IL-22 production. Up-regulated IL-22-producing CD3 + CD8- T cells obviously correlated with the grade of intrahepatic inflammation. The proportions of IL-22-producing CD3 + CD8- T cells were significantly down-regulated after 48 weeks of Peg-interferon treatment, and the differences were of great significance in patients with normalize ALT levels at 48 weeks, rather than those with elevated ALT levels. In conclusion, IL-22 might play a proinflammatory function in. chronic HBV infected patients with active inflammation and Peg-interferon treatment could attenuate the degree of liver inflammation through down-regulating IL-22-producing CD3 + CD8- T cells. [ABSTRACT FROM AUTHOR]

The effects of transglutaminase (TG) and glucose oxidase (GOX) on the water distribution, rheological properties, and microstructure of dough after freeze-thaw cycles were studied. The results showed that, when TG (1%, w/w) and GOX (0.006%, w/w) were added to the dough simultaneously, the syneresis rate of the dough after 8 freeze-thaw cycles reduced by 12.9%, and the extensibility and maximum resistance of the frozen dough increased by 9.6 mm and 14.7 g, respectively. Moreover, the G′ and G″ values of the frozen dough were significantly increased, and the hardness and freezable water content were reduced by 60.1% and 2.9%, respectively. The LF-NMR analysis showed that the tightly bound water content increased by 4.9%, and the semi-bound water content decreased by 4.0%. The number of free sulfhydryl groups in the dough treated with the two enzymes decreased by 16.3 μmol/g. Fourier IR revealed that the content of α-helix increased by 3.1%, β-sheet increased by 5.8%, and β-turn decreased by 4.8%. Scanning electron microscope images indicated that the gluten network of the two enzyme-treated dough remained uniform and dense after multiple freeze-thaw disruptions. [Display omitted] • Enzymes inhibited the migration of water in the frozen dough. • Enzymes mitigated the deterioration of dough quality during freeze-thaw cycles. • The combination of enzymes had a higher effect on delaying the deterioration of frozen dough quality. [ABSTRACT FROM AUTHOR]

Abstract Inflammatory bowel disease (IBD) is a chronic autoimmune disease, and its pathogenesis remains mostly unknown. MicroRNAs (miRs) has drawn much attention as a crucial regulator of autoimmune diseases. In this study, we demonstrated, for the first time, that miR-425 was significantly up-regulated in peripheral blood mononuclear cells (PBMC) and mucosa of patients with IBD. In note, T helper (Th) 17 cells were found to be the major source of miR-425 expression. Using gain-of-function approaches, we demonstrated that miR-425 could facilitate the differentiation of CD4+ T cells into Th17 lineage. In addition, forkhead box O1 (Foxo1) was identified as a novel target gene of miR-425, which was able to inhibit Th17 cell differentiation, and it was observed to be markedly decreased in PBMC and mucosa of patients with IBD. Notably, in vivo inhibition of miR-425 significantly alleviated the disease severity of TNBS-induced colitis in mice, with down-regulated levels of IL-17A. Our data reveal a novel mechanism in which the elevated miR-425 in IBD mediates pathogenic Th17 cell generation through down-regulation of Foxo1. In vivo blockade of miR-425 may serve as a novel therapeutic approach in the treatment of IBD. Highlights • MiR-425 expression is significantly increased in patients with IBD. • MiR-425 promotes pathogenic Th17 cell differentiation. • Foxo1 is a novel target of miR-425. • In vivo inhibition of miR-425 alleviates TNBS-induced colitis in mice. [ABSTRACT FROM AUTHOR]

Despite increasing knowledge of allelochemicals as leads for new herbicides, relatively little is known about the mode of action of allelochemical-based herbicides on herbicide-resistant weeds. In this study, herbicidal activities of a series of allelochemical tricin-derived compounds were evaluated. Subsequently, a benzothiazine derivative 3-(2-chloro-4-methanesulfonyl)-benzoyl-hydroxy-2-methyl-2H-1,2-benzothiazine-1,1-dioxide with 4-hydroxyphenyl-pyruvate dioxygenase (HPPD) inhibiting activity was identified as a target compound on photosynthetic performance of penoxsulam-resistant versus -susceptible barnyardgrass ( Echinochloa crus-galli ). Regardless of barnyardgrass biotype, the benzothiazine derivative greatly affected chlorophyll fluorescence parameters (Fv/Fm, ETR 1 min and NPQ 1 min ), reduced the chloroplast fluorescence levels and expression of HPPD gene. In particular, the benzothiazine derivative interfered with photosynthetic performance of resistant barnyardgrass more effectively than the allelochemical tricin itself. These results showed that the benzothiazine derivative effectively inhibited the growth of resistant barnyardgrass and its mode of action on photosynthesis system was similar to HPPD-inhibiting sulcotrione, making it an ideal lead compound for further development of allelochemical-based herbicide discovery. [ABSTRACT FROM AUTHOR]

This study utilizes the environmental tax reform in China as a quasi-natural experiment to investigate the effect of environmental taxes on income inequality. In January 2018, the Environmental Protection Tax Law (EPTL) came into effect in China, provinces began to collect environmental taxes in accordance with the law. We find that the reform contributes to lower within-firm wage inequality. The reform leads to declines in executive compensation and increases in worker wages. We further find that tax enforcement, environmental regulations, fiscal stress and tax competition vary the relationship between the reform and wage inequality. Heterogeneity analyses show that the effect is greater in non-state-owned firms, small firms, and firms with higher board shareholdings. Extensive robustness tests corroborate our inferences. This paper verifies the effectiveness of environmental regulation in enhancing social welfare, and is beneficial for assessing the welfare effects of environmental regulation more accurately. The findings can also help the government reduce obstacles in the implementation of environmental taxes, and further enhance the effectiveness of the EPTL. [Display omitted] • Environmental taxes contribute to lower income inequality. • The reform results in lower executive compensation and higher worker wages. • Tax enforcement varies the effect of environmental taxes. • Fiscal stress and tax competition influence the effectiveness of the reform. [ABSTRACT FROM AUTHOR]

The zoonotic pathogen avian influenza A H5N8 causes enormous economic losses in the poultry industry and poses a serious threat to the public health. Here, we report the first systematic review and meta-analysis of the worldwide prevalence of birds. We filtered 45 eligible articles from seven databases. A random-effects model was used to analyze the prevalence of H5N8 in birds. The pooled prevalence of H5N8 in birds was 1.6%. In the regions, Africa has the highest prevalence (8.0%). Based on the source, village (8.3%) was the highest. In the sample type, the highest prevalence was organs (79.7%). In seasons, the highest prevalence was autumn (28.1%). The largest prevalence in the sampling time was during 2019 or later (7.0%). Furthermore, geographical factors also were associated with the prevalence. Therefore, we recommend site-specific prevention and control tools for this strain in birds and enhance the surveillance to reduce the spread of H5N8. • Potential risk factors of global transmission of H5N8 in birds were assessed. • Africa was the region with the highest prevalence of H5N8 in birds. • The incidence of H5N8 in birds was also impacted by different geographical and climatic conditions. [ABSTRACT FROM AUTHOR]

In this paper, we consider rotating periodic solutions of the Hamiltonian system x ˙ = J H ′ (t , x) , x ∈ R 2 N , having the form x (t + T) = Q x (t) , ∀ t ∈ R , for some T > 0 and a symplectic orthogonal matrix Q. We study the system under a general twist condition: the nonlinear term H ′ (t , x) is required to be of linear growth but not necessarily to be asymptotically linear at infinity. The twist is reflected in the difference of the generalized Morse index at the origin and at infinity. By combining a finite dimensional reduction method, Morse theory and minimax principle, we establish the existence and multiplicity of nontrivial rotating periodic solutions. [ABSTRACT FROM AUTHOR]

This study demonstrated a dye-sensitized TiO 2 -polyoxometalate system (denoted TiO 2 -(PW 12 -TH) 8 , where PW 12 = PW 12 O 40 3− and TH = thionine) for selective oxidation of alcohols under visible light. The results showed that various substituted alcohols were transformed into their corresponding aldehydes with high selectivity. Due to more efficient electrons transfer, large surface area, and enhanced visible light absorption, the photocatalytic activity of TiO 2 -(PW 12 -TH) 8 was superior to any other dye-sensitized system reported to date. The response in the photocurrent-time curves over several on/off cycles of intermittent irradiation showed good reproducibility. The photocurrent response of TiO 2 -(PW 12 -TH) 8 was much higher than that of TiO 2 /TH (physical mixture of TiO 2 and TH), SiO 2 -(PW 12 -TH) 8 or P25-(PW 12 -TH) 8 (P25 = Degussa P25), attributed to the more efficient transfer and longer lifetime of photoexcited electrons. This photocatalytic process confirmed that efficient electron transfer during photocatalytic oxidation plays a vital role in determining the reaction conversion and obtaining good selectivity. Electron paramagnetic resonance (EPR) spectra and radical scavenging experiments proved that superoxide radicals and electrons were the main reactive species in the proposed system, the absence of hydroxyl radicals and holes is demonstrated to be the key of high reaction selectivity. [ABSTRACT FROM AUTHOR]

Larval zebrafish ( Danio rerio ) have been suggested as a high-throughput experimental animal model for epilepsy-related genetic and developmental studies. The behavioral manifestations in response to the seizure-inducing drugs picrotoxin (PTX) (1, 5, 25, 125, or 625 μM) or pentylenetetrazole (PTZ) (1, 2, 4, 8, or 16 mM) under light-dark conditions were studied using zebrafish larvae at 5 days post-fertilization (dpf). Two behavioral parameters, locomotor activity and thigmotaxis behavior, were analyzed. We conclude that high concentrations of PTX treatment increased locomotion and thigmotaxis in 5 dpf zebrafish larvae under continuous illumination and the locomotion of PTX-treated zebrafish was decreased under the dark condition. High concentrations of PTX treatment also increased thigmotaxis (an indicator of increased anxiety levels) in zebrafish larvae under both continuous illumination and dark condition. PTZ treatment increased the locomotion of 5 dpf zebrafish larvae under continuous illumination. However, 2 mM PTZ decreased locomotion, and high concentrations of PTZ decreased the locomotion of larvae under dark conditions. High concentrations of PTZ treatment also increased thigmotaxis in the zebrafish larvae under both continuous illumination and dark condition. Compared with PTZ, PTX leads to higher levels of movement under light conditions and lower levels of movement under dark condition. However, the level of thigmotaxis in the zebrafish larvae was similar between the two drug treatments. [ABSTRACT FROM AUTHOR]

In this study, the effect of ultrasonic, heating, and enzymatic treatments on the structural and emulsifying attributes of walnut protein isolate (WNPI) was assessed and compared. Ultrasonic, heating, and enzymatic treatments all effectively improved WNPI's emulsifying capacity and stability, especially ultrasonication. Ultrasonication (400 W, 30 min) obviously made WNPI's structure looser and more unfolded, in turn led to 1.57-fold and 2.67-fold increase in EAI and ESI of WNPI, respectively. Besides, the exposure of WNPI′ hydrophobic groups induced by sonication, reflected in a 3.64-fold increase in WNPI's surface hydrophobicity, may also contributes to the increase of WNPI's emulsifying properties. Furthermore, the emulsion stabilized by UT-WNPI exhibited the best lipid and protein oxidative stabilities during storage at 55 °C for 7 days. Compared to emulsion stabilized by the untreated WNPI, hydroperoxide, TBARS, and protein carbonyl contents in the emulsion stabilized by UT-WNPI decreased by 46.92%, 40.74%, and 33.89%, respectively. Our results clarify ultrasonication is the best for improving the emulsifying properties of walnut protein, thereby broadening walnut protein's application in the emulsified food. [Display omitted] • Developing walnut protein as a potential emulsifier in the food industry. • The sonicated walnut protein exhibited the best emulsifying properties. • The sonicated walnut protein stabilized emulsion had the best oxidative stability. • The sonication converted walnut protein's α-helix into random coil. • The sonication improved walnut protein's surface hydrophobicity. [ABSTRACT FROM AUTHOR]

[Display omitted] • Synthesis of ROS-responsive camptothecin prodrugs containing allyl phenyl selenides (CPTSe1-CPTSe7). • CPTSe1-CPTSe7 showed good selectivity for tumor cells over normal cells. • CPTSe1 was more stable than CPT-B. • CPTSe1 enabled real-time monitoring of CPT release and H 2 O 2 detection in tumor cells. Reactive oxygen species (ROS)-responsive prodrugs have received significant attention due to their capacity to target tumors to relieve the side effects caused by chemotherapy. Herein, a series of novel H 2 O 2 -activated theranostic prodrugs (CPTSe1-CPTSe7) were developed containing allyl phenyl selenide moieties as H 2 O 2 acceptors. Compared with conventional boronate ester-based prodrug CPT-B , CPTSe1 was more stable in human plasma and showed a more complete release of camptothecin (CPT) in H 2 O 2 inducing experiment. The selectively activated fluorescence signals of CPTSe1 in tumor cells make it useful for real-time monitoring of CPT release and H 2 O 2 detection. Furthermore, excellent selectivity of CPTSe1 was achieved for tumor cells over normal cells. Our results provide a new platform for the development of H 2 O 2 -responsive theranostic prodrugs. [ABSTRACT FROM AUTHOR]

Diabetic cardiovascular complication is a common systemic disease with high morbidity and mortality worldwide. We hypothesise that exosomes derived from human umbilical cord mesenchymal stem cells (hUCMSCs-exos) can rescue these disorders and alleviate vascular remodeling in diabetes. Morphological, non-targeted metabolomics and 4D label-free proteomics techniques were used to analyze the aortas of db/m mice as normal control group (NCA), saline treated db/db mice (DMA), and hUCMSCs-exos treated db/db mice (DMTA), and to clarify the molecular mechanism of the protection of hUCMSCs-exos in vascular remodeling from a new point of view. The results showed that 74 metabolites were changed significantly in diabetic aortas, of which 15 were almost restored by hUCMSCs-exos. In proteomics, 30 potential targets such as Stromal cell-derived factor 2-like protein 1, Leukemia inhibitory factor receptor, Peroxisomal membrane protein and E3 ubiquitin-protein ligase MYCBP2 were detected. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway-based analysis showed that Central carbon metabolism in cancer and Galactose metabolism pathway were up-regulated to near normal by hUCMSCs-exos in metabolomics, with janus associated kinase-signal transducer and activator of transcription (JAK-STAT) pathway displayed in proteomics. According to bioinformatics and integrated analysis, these targeted molecules of hUCMSCs-exos to attenuate the vascular remodeling were mainly associated with regulation of energy metabolism, oxidative stress, inflammation, and cellular communications. This study provided a reference for the therapy of diabetes-induced cardiovascular complications. [Display omitted] • Diabetic cardiovascular complication is a common systemic disease worldwide. • Metabolomics and proteomics are used to identify potential markers and mechanisms. • Exosomes from mesenchymal stem cells alleviate aortic remodeling in diabetic mice. • JAK-STAT signaling is enriched by proteomics in exosomes interference. [ABSTRACT FROM AUTHOR]

Carboxylesterases (CarEs) are responsible for metabolism of xenobiotics including insecticides in insects. Understanding the expression patterns of a such detoxifying gene and effect of insecticides on its enzyme activity are important to clarify the function of this gene relevant to insecticides-detoxifying process, but little information is available in the codling moth Cydia pomonella (L.). In this study, we investigated the expression profiles of CarE gene CpCE-1 at different developmental stages and in different tissues of C. pomonella , as well as the larvae exposed to chlorpyrifos-ethyl and lambda-cyhalothrin by using absolute real-time quantitative PCR (absolute RT-qPCR). Results indicated that CpCE-1 expression was significantly altered during C. pomonella development stages, and this expression differed between sexes, with a higher transcript in females than males. Meanwhile, CpCE-1 is overexpressed in cuticle, midgut and head than silk gland, fat body and Malpighian tubules. Exposure of third instar larvae to a non-lethal dosage of chlorpyrifos-ethyl and lambda-cyhalothrin resulted in induction of CpCE-1 transcript. The total carboxylesterase enzyme activity was inhibited by chlorpyrifos-ethyl in vivo ; in contrast, the activity of Escherichia coli produced recombinant CpCE-1 was significantly inhibited by both lambda-cyhalothrin and chlorpyrifos-ethyl in vitro . These results suggested that CpCE-1 in C. pomonella is potentially involved in the development and in detoxification of chlorpyrifos-ethyl and lambda-cyhalothrin. [ABSTRACT FROM AUTHOR]

The generation of hydroxyl radicals (HO ) by H 2 O 2 decomposition over solid catalysts (a Fenton-like reaction) will play an important role in the design of new processes for water treatment. More specifically, the understanding of H 2 O 2 decomposition on Au nanoparticles (NPs) is crucial for the optimization of the structure of active sites and the evaluation of cytotoxicity of Au NPs. Here, the kinetic behavior of H 2 O 2 decomposition over supported Au NPs was investigated in a buffer solution at pH ∼ 6.8. Over a range of H 2 O 2 concentrations, the decay of H 2 O 2 followed a pseudo-first-order kinetic rate law with an apparent activation energy of 142 kJ/mol. The observed rate constant was linearly increased from (3.0 ± 1.0) × 10 −3 to (66.7 ± 2.3) × 10 −3 min −1 with the increase in the Au NPs concentration. Further increase in the surface concentration of H 2 O 2 may reduce the HO generation efficiency. A dual intermediate model was proposed for the generation mechanism of HO . [ABSTRACT FROM AUTHOR]

In this work, a simple, low-cost and one-step microwave approach has been demonstrated for the synthesis of water-soluble carbon dots (C-dots). The average size of the resulting C-dots is about 4 nm. From the photoluminescence (PL) measurements, the C-dots exhibit excellent biocompatibility and intense PL with the high quantum yield (QY) at Ca. 25%. Significantly, the C-dots have excellent biocompatibility and the capacity to specifically target the cells overexpressing the folate receptor (FR). These exciting results indicate the as-prepared C-dots are promising biocompatible probe for cancer diagnosis and treatment. [ABSTRACT FROM AUTHOR]

Pine nut oil (PNO) was gelled by solvent exchange and absorption methods through soy protein-tannic acid covalent hydrogel. The current study aimed to compare the in vitro digestion of oleogels prepared by different methods: solvent exchange (network oleogel [SNO] and particulate oleogel [SPO]) and absorption methods (AO), and probe the effect of oleogelation on oxidation. Results showed that the preparation affected the physicochemical properties of oleogels; during in vitro digestion, lipolysis was delayed for the oleogels as compared to that for PNO, and the extent of lipolysis followed the order of AO > SNO > SPO > PNO. The fatty acid profile in the micelle fraction demonstrated enhanced solubilization of unsaturated fatty acids (UFAs), especially pinolenic acid. During storage, oleogels had lower peroxide, thiobarbituric acid, and conjugated diene values than PNO, indicating superior oxidation stability. Thus, this work provides valuable directions for designing a delivery system to facilitate UFAs digestion and improve the oxidation stability of PNO. [Display omitted] • Tannic acid modified-soy protein can structure liquid oil. • Lipolysis kinetic during gastrointestinal tract digestion was affected by oleogel preparation. • Oleogel could increase bioavailability of unsaturated fatty acid. • Oleogel could improve the oxidative stability of pine nut oil. [ABSTRACT FROM AUTHOR]

[Display omitted] • Sixteen male participants were enrolled in a randomized crossover control study involving three sleep-deprivation sessions. • The study investigated the effect of modafinil on working memory decline caused by sleep deprivation, by studying ERPs. • Modafinil may effectively improve the decline in pronunciation-related working memory after sleep deprivation. We aimed to explore whether modafinil mitigates the working memory decline induced by 36 h of acute total sleep deprivation (36-h TSD). Sixteen healthy male participants were enrolled in a randomized double-blind crossover control study involving three sleep-deprivation sessions. Participants were administered 400 mg of placebo, caffeine, or modafinil during these sessions. Behavior and EEG data were recorded while participants performed pronunciation-related working memory tasks. Behavioral indicators showed that, compared with placebo, modafinil improved the accuracy of pronunciation-related working memory tasks and reduced the response time. Compared with before sleep deprivation, the amplitudes of the event-related potentials (ERPs) increased in the N2 component and decreased in the P3 component after sleep deprivation in the placebo condition. In the caffeine condition, the amplitude of the P3 component decreased, the latency of the N2 component was prolonged, and the N2 amplitude remained unchanged. In the modafinil condition, the P3 latency was shortened, and no significant difference was found in the amplitude of the N2 or P3 ERPs; no significant difference was recorded in the N2 latency. Modafinil (400 mg) effectively ameliorated the decline in pronunciation-related working memory after 36-h TSD, suggesting that it may effectively counteract cognitive decline caused by acute sleep deprivation. [ABSTRACT FROM AUTHOR]

[Display omitted] • A NMR method having the multiple-targeting signal selectivity was developed. • Optimal control was used to efficiently prepare singlet order of multiple-spin system. • Several targeted molecules and/or chemical groups were probed simultaneously. Selectively probing specific molecules in complex mixtures with nuclear magnetic resonance promises new insights into molecular structures or molecular interaction. Such a study often can be further facilitated when two or more objects in chemical moieties of interest can be precisely targeted. Herein, we proposed a novel method to implement the multiple-targeting signal selection by optimal control of the spin singlets of two or more targeted spin systems from one or more molecules. This method can endow the conventional nuclear magnetic resonance (NMR), magnetic resonance image (MRI) and magnetic resonance spectrum (MRS) with the multiple-targeting signal selectivity to selectively probe several targeted molecules and/or chemical groups simultaneously. [ABSTRACT FROM AUTHOR]

The solubility of rutaecarpine and evodiamine was measured in (ethanol + water) mixed solvents with different values of mole fraction ethanol from ( φ = 0.30 to 0.80) over the temperature range of ( T = 288.2, 298.2, 308.2, 318.2 and 328.2) K. With increasing temperature and mole fraction ethanol, the solubility of rutaecarpine and evodiamine increased. The experimental solubility values were well correlated by the modified Apelblat equation, simplified thermodynamic equation and semi-empirical Buchowski–Ksiazczak λh equation. The correlated results by the modified Apelblat equation were better than those by other two equations. The enthalpy of dissolution (Δ dis H o ) and entropy of dissolution (Δ dis S o ) of rutaecarpine and evodiamine during the dissolution process in (ethanol + water) mixed solvents were calculated by the van’t Hoff equation. The results indicate that the dissolution process is endothermic and entropy-driven. [ABSTRACT FROM AUTHOR]

Cysteine-rich intestinal protein (CRIP), a Zn 2+ -binding protein, contains a single copy of the highly conserved double-zinc-finger structure known as the LIM (lin-11-isl-1-mec-3) motif. In this paper, a cDNA encoding MmCRIP was isolated from the Asiatic hard clam Meretrix meretrix . The full-length cDNA of MmCRIP consists of a 237-bp open reading frame that encodes a polypeptide of 78 amino acids with a predicted molecular weight (MW) of 8635.8 Da and theoretical isoelectric point (pI) of 9.01. Bioinformatics analysis showed that it belonged to a new member of the CRIP subfamily. Relationship analysis revealed that MmCRIP has high-levels of sequence similarity to many CRIPs reported in other animals, particularly in invertebrates. Real-time PCR analysis showed that the highest level of MmCRIP expression was in hemocyte tissue and at pediveligers stage. To investigate immune function, mature clams were challenged with Aeromonas hydrophila . During A . hydrophila infection, up-regulation of MmCRIP transcript in clam's hemocyte, gill and hepatopancreas was detected. DsRNAi (double-strand RNA interference) approach was employed to study the function of MmCRIP and the data showed that inactivation of the MmCRIP gene blocked larvae development and caused mass mortalities. The probable roles of MmCRIP in clam early development and innate immunity are presented for the first time. [ABSTRACT FROM AUTHOR]

• A novel high birefringence hollow-core anti-resonant THz PCF based on COC is proposed. • The cladding of the fiber is composed of four node-less sector-type tubes. • A high birefringence window from 0.7 to 1.18 THz is obtained. • At 0.83 THz, the lowest transmission loss of 0.172 dB/m and birefringence of 1.06 × 10−3 is realized. • A flatten dispersion and an excellent bending performance are obtained. A novel high birefringence hollow-core anti-resonant terahertz photonic crystal fiber based on cycloolefin copolymer (COC) is proposed. The cladding of the fiber is composed of four sector-type tubes with node-less structure. The properties of birefringence, confinement loss, effective material absorption loss, and power fraction are analyzed by using the finite difference time domain (FDTD) method. The numerical simulation results show that a high birefringence window (B >8×10−4) in the frequency range of 0.7–1.18 THz is obtained when the tube thickness is 0.09 mm. At 0.83 THz, the lowest transmission loss of 0.172 dB/m is attained, and the corresponding birefringence is 1.06×10−3. In addition, the bending loss and dispersion characteristics of the proposed fiber are investigated. It is found that a flatten and low dispersion in the frequency range of 0.7–1.47 THz, and an excellent bending performance in the y -direction with critical bending radius of 22 cm are obtained simultaneously. [ABSTRACT FROM AUTHOR]

In contrast to conventional cancer treatment, in personalized cancer medicine each patient receives a specific treatment. The response to therapy, clinical outcomes, and tumor behavior such as metastases, tumor progression, carcinogenesis can be significantly affected by the heterogeneous tumor microenvironment (TME) and interpersonal differences. Therefore, using native tumor microenvironment mimicking models is necessary to improving personalized cancer therapy. Both in vitro 2D cell culture and in vivo animal models poorly recapitulate the heterogeneous tumor (immune) microenvironments of native tumors. The development of 3D culture models, native tumor microenvironment mimicking models, made it possible to evaluate the chemoresistance of tumor tissue and the functionality of drugs in the presence of cell-extracellular matrix and cell-cell interactions in a 3D construction. Various personalized tumor models have been designed to preserving the native tumor microenvironment, including patient-derived tumor xenografts and organoid culture strategies. In this review, we will discuss the patient-derived organoids as a native tumor microenvironment mimicking model in personalized cancer therapy. In addition, we will also review the potential and the limitations of organoid culture systems for predicting patient outcomes and preclinical drug screening. Finally, we will discuss immunotherapy drug screening in tumor organoids by using microfluidic technology. • In personalized cancer medicine, each patient receives a specific treatment. • The tumor microenvironment and interpersonal differences can affect treatment. • Organoid culture systems fully recapitulate the tumor microenvironments. [ABSTRACT FROM AUTHOR]

Abstract: Massively univariate regression and inference in the form of statistical parametric mapping have transformed the way in which multi-dimensional imaging data are studied. In functional and structural neuroimaging, the de facto standard “design matrix”-based general linear regression model and its multi-level cousins have enabled investigation of the biological basis of the human brain. With modern study designs, it is possible to acquire multi-modal three-dimensional assessments of the same individuals—e.g., structural, functional and quantitative magnetic resonance imaging, alongside functional and ligand binding maps with positron emission tomography. Largely, current statistical methods in the imaging community assume that the regressors are non-random. For more realistic multi-parametric assessment (e.g., voxel-wise modeling), distributional consideration of all observations is appropriate. Herein, we discuss two unified regression and inference approaches, model II regression and regression calibration, for use in massively univariate inference with imaging data. These methods use the design matrix paradigm and account for both random and non-random imaging regressors. We characterize these methods in simulation and illustrate their use on an empirical dataset. Both methods have been made readily available as a toolbox plug-in for the SPM software. [Copyright &y& Elsevier]

Abstract: Mapping the quantitative relationship between structure and function in the human brain is an important and challenging problem. Numerous volumetric, surface, regions of interest and voxelwise image processing techniques have been developed to statistically assess potential correlations between imaging and non-imaging metrices. Recently, biological parametric mapping has extended the widely popular statistical parametric mapping approach to enable application of the general linear model to multiple image modalities (both for regressors and regressands) along with scalar valued observations. This approach offers great promise for direct, voxelwise assessment of structural and functional relationships with multiple imaging modalities. However, as presented, the biological parametric mapping approach is not robust to outliers and may lead to invalid inferences (e.g., artifactual low p-values) due to slight mis-registration or variation in anatomy between subjects. To enable widespread application of this approach, we introduce robust regression and non-parametric regression in the neuroimaging context of application of the general linear model. Through simulation and empirical studies, we demonstrate that our robust approach reduces sensitivity to outliers without substantial degradation in power. The robust approach and associated software package provide a reliable way to quantitatively assess voxelwise correlations between structural and functional neuroimaging modalities. [Copyright &y& Elsevier]

Abstract: Both T-helper 17 cells (Th17) and CD4+CD25+ regulatory T cells (Treg) play important roles in the pathogenesis of psoriasis. However, the relationship between Th17 and Treg cells and their dynamic variations in psoriasis remain unclear. In this study, we found that both Th17 and FoxP3+ Treg cells were increased in psoriasis patients both in the peripheral circulation and skin tissue lesions and were positively correlated with disease severity. The ratio of Th17 to Treg cells in skin tissue lesions was inversely correlated with PASI scores, while it was positively correlated with PASI scores in the circulation. IL-17 secretion by CD4+ T cells was not regulated by Treg cells, even though Treg cells exhibited significant inhibition on CD4+ T cells proliferation and IFN-γ production. These findings provide new information regarding the association between Th17 and Treg cells, which will further our understanding of the pathogenesis of psoriasis. [Copyright &y& Elsevier]

Abstract: GNA1946, a conserved outer membrane lipoprotein from Neisseria meningitidis, has been identified as a candidate antigen for an urgently needed broad-spectrum meningococcal vaccine. It has been predicted to be a periplasmic receptor in the d-methionine uptake ABC transporter system. The crystal structure of GNA1946 was solved by the single-wavelength anomalous dispersion (SAD) method to a resolution of 2.25Å, and it reveals a Venus flytrap-like structure. GNA1946 consists of two globular lobes connected by a hinge region. Surprisingly, the structure showed an l-methionine bound within the cleft between the lobes. A comparison of GNA1946 with two other outer membrane lipoproteins, the l-methionine-binding Tp32 from Treponema pallidum and the dipeptide GlyMet-binding protein Pg110 from Staphylococcus aureus, revealed that although these three proteins share low sequence similarities, there is a high degree of structural conservation and similar substrate-binding frameworks. Our results reveal that GNA1946 is an l-methionine binding lipoprotein in the outer membrane, and should function as an initial receptor for ABC transporters with high affinity and specificity. The GNA1946 structure reported here should provide a valuable starting point for the development of a broad-spectrum meningococcal vaccine. [Copyright &y& Elsevier]

A luminous Zn-MOF(1), formulated as [Zn 2 (3-DBB) (1,4-bib) 1.5 (Ac)]·H 2 O (3-H 3 DBB ​= ​3-(3,5-dicarboxylato benzyloxy) benzoic acid and 1,4-bib ​= ​1,4-bis (1-imidazoly)benzene) has been prepared hydrothermally. Structural analysis shows that Zn ions linked by 3-DBB3- into 2D brick-wall-like double layer-like structure, further assembling 3D framework by 1,4-bib pillared ligands. The Zn-MOF has been discovered to selectively detect Dy3+ by the luminescent enhancement with the detection limit (LOD) of 1.16 ​× ​10−5 ​M, and is highly selective and sensitive to nitrobenzene (LOD:1.40 ​× ​10−6 ​M) and aniline (LOD:2.03 ​× ​10−7 ​M) as well. The theoretical calculation and absorption spectra results verify the correctness of organic solvents detection. Therefore, the material might be used as a multi-response luminescent sensor. [Display omitted] A luminous 3D Zn-MOF is assembled by the 1,4-bib-pillared ligands with 2D brick-wall-like double layer-like structure and prepared hydrothermally. The Zn-MOF has been discovered to high selectively detect Dy3+, and is highly selective and sensitive to nitrobenzene and aniline as well. The theoretical calculation and absorption spectra results verify the correctness of nitrobenzene detection. Therefore, the Zn-MOF might be used as a multi-response luminescent sensor. • A luminous Zn-MOF based on a flexible 3-(3,5-dicarboxylato benzyloxy) benzoic acid and a long N-donor ligand. • The excellent fluorescent properties of Zn-MOFs in solid state or in aqueous solution. • Highly sensitively detection for Dy3+, and to nitrobenzene and aniline as well in aqueous solution. [ABSTRACT FROM AUTHOR]

Abstract: A membrane-bound pyrroloquinoline quinine (PQQ)-dependent d-sorbitol dehydrogenase (mSLDH) in Gluconobacter oxydans participates in the oxidation of d-sorbitol to l-sorbose by transferring electrons to ubiquinone which links to the respiratory chain. To elucidate the kinetic mechanism, the enzyme purified was subjected to two-substrate steady-state kinetic analysis, product and substrate inhibition studies. These kinetic data indicate that the catalytic reaction follows an ordered Bi Bi mechanism, where the substrates bind to the enzyme in a defined order (first ubiquinone followed by d-sorbitol), while products are released in sequence (first l-sorbose followed by ubiquinol). From these findings, we proposed that the native mSLDH bears two different substrate-binding sites, one for ubiquinone and the other for d-sorbitol, in addition to PQQ-binding and Mg2+-binding sites in the catalytic center. [Copyright &y& Elsevier]

Methylmalonic acidemia (MMA) is caused by the deficient activity of l-methylmalonyl-CoA mutase, which is a vitamin B12 (or cobalamin, Cbl)-dependent enzyme. MMA due to the effect of insufficient Cbl metabolism is classified into three forms (cblA, cblB, and cblH). Recently, the genes responsible for cblA and cblB were identified as MMAA and MMAB, respectively. The MMAA protein likely transports Cbl into the mitochondria for adenosylcobalamin synthesis, while the MMAB protein appears to be an adenosyltransferase. We performed a mutation analysis of 10 unrelated Japanese patients with vitamin B12-responsive MMA. Seven patients had mutations in MMAA, whereas the other three patients showed no disease-causing substitutions in either MMAA or MMAB. Five novel mutations were identified in MMAA (R22X, R145X, L217X, R359G, and 503delC). The 503delC mutation was observed in five of the seven MMAA patients, suggesting that the mutation is prevalent in Japanese patients. This finding may facilitate the DNA diagnosis of vitamin B12-responsive MMA within the Japanese population. [Copyright &y& Elsevier]