Search

Previous work comparing safety and effectiveness outcomes for new initiators of angiotensin converting‐enzyme inhibitors (ACEi) and thiazides demonstrated more favorable outcomes for thiazides, although cohort definitions allowed for addition of a second antihypertensive medication after a week of monotherapy. Here, we modify the monotherapy definition, imposing exit from cohorts upon addition of another antihypertensive medication. We determine hazard ratios (HR) for 55 safety and effectiveness outcomes over six databases and compare results to earlier findings. We find, for all primary outcomes, statistically significant differences in effectiveness between ACEi and thiazides were not replicated (HRs: 1.11, 1.06, 1.12 for acute myocardial infarction, hospitalization with heart failure and stroke, respectively). While statistical significance is similarly lost for several safety outcomes, the safety profile of thiazides remains more favorable. Our results indicate a less striking difference in effectiveness of thiazides compared to ACEi and reflect some sensitivity to the monotherapy cohort definition modification. [ABSTRACT FROM AUTHOR]

Viral deep-sequencing data play a crucial role toward understanding disease transmission network flows, providing higher resolution compared to standard Sanger sequencing. To more fully utilize these rich data and account for the uncertainties in outcomes from phylogenetic analyses, we propose a spatial Poisson process model to uncover human immunodeficiency virus (HIV) transmission flow patterns at the population level. We represent pairings of individuals with viral sequence data as typed points, with coordinates representing covariates such as gender and age and point types representing the unobserved transmission statuses (linkage and direction). Points are associated with observed scores on the strength of evidence for each transmission status that are obtained through standard deep-sequence phylogenetic analysis. Our method is able to jointly infer the latent transmission statuses for all pairings and the transmission flow surface on the source-recipient covariate space. In contrast to existing methods, our framework does not require preclassification of the transmission statuses of data points, and instead learns them probabilistically through a fully Bayesian inference scheme. By directly modeling continuous spatial processes with smooth densities, our method enjoys significant computational advantages compared to previous methods that rely on discretization of the covariate space. We demonstrate that our framework can capture age structures in HIV transmission at high resolution, bringing valuable insights in a case study on viral deep-sequencing data from Southern Uganda. [ABSTRACT FROM AUTHOR]

High‐rate and stable Zn‐ion batteries working at low temperatures are highly desirable for practical applications, but are challenged by sluggish kinetics and severe corrosion. Herein, inspired by frost‐resistant plants, we report trace hydroxyl‐rich electrolyte additives that implement a dual remodeling effect for high‐performance low‐temperature Zn‐ion batteries. The additive with high Zn absorbability not only remodels Zn2+ primary solvent shell by alternating H2O molecules, but also forms a shielding layer thus remodeling the Zn surface, which effectively enhances fast Zn2+ de‐solvation reaction kinetics and prohibits Zn anode corrosion. Taking trace α‐D‐glucose (αDG) as a demonstration, the electrolyte obtains a low freezing point of −55.3 °C, and the Zn//Zn cell can stably cycle for 2000 h at 5 mA cm−2 under −25 °C, with a high cumulative capacity of 5000 mAh cm−2. A full battery that stably operates for 10000 cycles at −50 °C is also demonstrated. [ABSTRACT FROM AUTHOR]

High‐rate and stable Zn‐ion batteries working at low temperatures are highly desirable for practical applications, but are challenged by sluggish kinetics and severe corrosion. Herein, inspired by frost‐resistant plants, we report trace hydroxyl‐rich electrolyte additives that implement a dual remodeling effect for high‐performance low‐temperature Zn‐ion batteries. The additive with high Zn absorbability not only remodels Zn2+ primary solvent shell by alternating H2O molecules, but also forms a shielding layer thus remodeling the Zn surface, which effectively enhances fast Zn2+ de‐solvation reaction kinetics and prohibits Zn anode corrosion. Taking trace α‐D‐glucose (αDG) as a demonstration, the electrolyte obtains a low freezing point of −55.3 °C, and the Zn//Zn cell can stably cycle for 2000 h at 5 mA cm−2 under −25 °C, with a high cumulative capacity of 5000 mAh cm−2. A full battery that stably operates for 10000 cycles at −50 °C is also demonstrated. [ABSTRACT FROM AUTHOR]

Postmarket safety surveillance is an integral part of mass vaccination programs. Typically relying on sequential analysis of real‐world health data as they accrue, safety surveillance is challenged by sequential multiple testing and by biases induced by residual confounding in observational data. The current standard approach based on the maximized sequential probability ratio test (MaxSPRT) fails to satisfactorily address these practical challenges and it remains a rigid framework that requires prespecification of the surveillance schedule. We develop an alternative Bayesian surveillance procedure that addresses both aforementioned challenges using a more flexible framework. To mitigate bias, we jointly analyze a large set of negative control outcomes that are adverse events with no known association with the vaccines in order to inform an empirical bias distribution, which we then incorporate into estimating the effect of vaccine exposure on the adverse event of interest through a Bayesian hierarchical model. To address multiple testing and improve on flexibility, at each analysis timepoint, we update a posterior probability in favor of the alternative hypothesis that vaccination induces higher risks of adverse events, and then use it for sequential detection of safety signals. Through an empirical evaluation using six US observational healthcare databases covering more than 360 million patients, we benchmark the proposed procedure against MaxSPRT on testing errors and estimation accuracy, under two epidemiological designs, the historical comparator and the self‐controlled case series. We demonstrate that our procedure substantially reduces Type 1 error rates, maintains high statistical power and fast signal detection, and provides considerably more accurate estimation than MaxSPRT. Given the extensiveness of the empirical study which yields more than 7 million sets of results, we present all results in a public R ShinyApp. As an effort to promote open science, we provide full implementation of our method in the open‐source R package EvidenceSynthesis. [ABSTRACT FROM AUTHOR]

Grassland is not only an important part of the terrestrial ecosystem with multiple ecological functions, but also an important base for Chinese herdsmen to produce and live. However, the occurrence and spread of rodent infestation reduces the biodiversity and productivity of grassland ecosystems. It also severely threatens human life, health, and biosecurity through disease transmission. In this study, we explored the ability of the nanocomposite sterilant ND-1 to control grassland rodent populations. Semi-closed experimental and control plots were established in the desert area of Alashan, Inner Mongolia, China. In spring 2018, the nanocomposite sterile ND-1 (Nongda-1) was introduced once, and the control effect of ND-1 on the growth of the wild population of midday gerbils was measured for two years. We show that ND-1 significantly reduced the population of midday gerbils in the experimental area, with a negative population growth rate. In addition, in the second year, the ratio of female midday gerbils to sub-adults in the experimental area was significantly lower than that in the control area, which resulted in a significant difference in the sex ratio of midday gerbils. There were significantly fewer females than males, and the population growth of midday gerbils in the experimental area was significantly inhibited. ND-1 had no significant effect on the home range of midday gerbils, and sterile individuals continued to occupy the home range and consume resources. Therefore, ND-1 reduced the number of female midday gerbils during the breeding period and the sex ratio and population density and altered the age structure of the wild population. Additionally, competition between sterile and normal individuals had a significant control effect on the growth of wild populations. Our studies demonstrate the significance of ND-1 in the sustainable control of grassland rodent pests, with the potential for limiting grassland rodent damage in the future. [ABSTRACT FROM AUTHOR]

The goal of the present work is to elucidate the ability of protocatechuic acid (PCA) in downregulating the dissolubility property and gain an innovative insights into conquering adverse reactions of the antifungal drug 5-fluorocytosine (FYT) by a salification strategy. The strategy highlights the feature of adjacent 3,4-substituted phenolic groups on PCA molecule that establishes the helical morphology to attain the hydrophobic molecular salt by facilitating proton exchange reaction between PCA and FTY, thus decreasing FYT's dissolution capacity; moreover, it can also play to PCA's strengths with hepatoprotective effect and antifungal potential as a phenolic acid nutrient, all of which benefit in overcoming the adverse drug reactions caused by the fast and inappropriate absorption of FYT. Taking the strategy as a guideline, the first FTY's molecular salt, FTY–PCA, with hydrophobic characteristics has been successfully synthesized and thoroughly characterized by multiple analytical approaches. The single-crystal X-ray diffraction technology verifies that the newly obtained FTY–PCA consists of an unusual hydrophobic triple helix structure (THS) that is dexterously wound by three strands single helix structure (SHS) via robust hydrogen-bonding interplays and electrostatic forces, which endows the ability of concurrent downregulation of the solubility and dissolution rate, with the maximum reduction being, respectively, 31.23% and 60.49% relative to the parent drug FYT. The experimental outcomes are strongly confirmed by relevant theoretical studies. The molecular electrostatic potential confirms that the THS motif constructed by the SHS forms serves a crucial role in reducing the polarity of the molecular salt and complies with the abatement in polarity, attributable to the reinforced hydrogen-bonding energy as per the electron density difference as well as topology analysis of atoms in molecules, thereby clarifying the hydrophobic property of the molecular salt at theoretical levels. Thereby, the current contribution not only exemplifies the first hydrophobic molecular salt of FYT with a rare triple-helical structure, filling the gaps in the application of hydrophobic molecular salt in antifungal drugs, but also supplies some novel insights into the salinization strategy aiming at overcoming the adverse effects caused by the fast and almost entire absorption of some drugs by ameliorating the dissolubility behaviors. [ABSTRACT FROM AUTHOR]

This document is a response to a comment made by Huang et al. regarding a previous article on vaccine safety surveillance. The authors thank Huang et al. for their support and address two issues raised by them. They argue that using a single reliable method from the start is more effective than dividing detection into two stages. They also acknowledge the importance of data quality in observational health studies and suggest using high-quality statistical methods for signal discovery, followed by validation methods like chart reviews. The authors express interest in future research and collaboration to develop alternative approaches and tools for improving case validation accuracy. [Extracted from the article]

Post‐approval safety surveillance of medical products using observational healthcare data can help identify safety issues beyond those found in pre‐approval trials. When testing sequentially as data accrue, maximum sequential probability ratio testing (MaxSPRT) is a common approach to maintaining nominal type 1 error. However, the true type 1 error may still deviate from the specified one because of systematic error due to the observational nature of the analysis. This systematic error may persist even after controlling for known confounders. Here we propose to address this issue by combing MaxSPRT with empirical calibration. In empirical calibration, we assume uncertainty about the systematic error in our analysis, the source of uncertainty commonly overlooked in practice. We infer a probability distribution of systematic error by relying on a large set of negative controls: exposure‐outcome pairs where no causal effect is believed to exist. Integrating this distribution into our test statistics has previously been shown to restore type 1 error to nominal. Here we show how we can calibrate the critical value central to MaxSPRT. We evaluate this novel approach using simulations and real electronic health records, using H1N1 vaccinations during the 2009–2010 season as an example. Results show that combining empirical calibration with MaxSPRT restores nominal type 1 error. In our real‐world example, adjusting for systematic error using empirical calibration has a larger impact than, and hence is just as essential as, adjusting for sequential testing using MaxSPRT. We recommend performing both, using the method described here. [ABSTRACT FROM AUTHOR]

The current work aims to take full advantage of the structural superiority and hepatoprotective effect of the nutrient trans-p-coumaric acid (TPCA) to decrease the solubility and dissolution rate of the antimycotic agent 5-fluorocytosine (FLCY) by using a co-crystallization strategy, thereby giving a novel understanding into conquering the dose-limiting hepatotoxicity induced by the quick and almost complete absorption of FLCY. To that end, FLCY–TPCA, as the first cocrystal of FLCY and phenolic acid (a nutrient of the hydroxycinnamic acid type), is orientationally self-assembled and fully characterized. The single crystal structure shows that TPCA molecules in the crystal lattice locate at the polar sites in situ of FLCY via robust hydrogen bond interaction, thus creating a vital planar construction (VPC) possessing hydrophobicity, which results in the simultaneous down-regulation for the cocrystal of solubility and dissolution rate versus the parent FLCY. The outcomes of the experiment are strongly supported by related theory research. Molecular electrostatic potential (MEP) calculation showed that the VPC polarity in the cocrystal is lower than that of free FLCY, which conforms with the reduction in polarity due to intensifying hydrogen-bond energy based on topology analysis with atoms in molecules (AIM) theory, hence conferring a conspicuous improvement in hydrophobicity on the cocrystal. Furthermore, the molecular planarity analysis based on Multiwfn's wave function calculation module confirms the convergence in planarity at a two-dimensional infinite level, which undoubtedly contributes to forming a tight three-dimensional supramolecular superposition landscape, corresponding with the coinstantaneous reinforcement of π–π stacking interaction evidenced by the reduced density gradient (RDG), and all these results further support the fact that the hydrophobicity of the FLCY–TPCA cocrystal is significantly enhanced. As a result, the current contribution exemplifies a feasible cocrystallization strategy using integrated experimental and systematic theoretical approaches to overcome the intractable toxicity issues of antifungal agents. [ABSTRACT FROM AUTHOR]

Radiative cooling materials (RCMs) possess the capability of passively transferring heat from surfaces to the outer space through the atmospheric window via long-wavelength radiation and cool the surfaces to below the ambient temperature, showing excellent potentials for building energy efficiency. To adequately embody this passive cooling effect, especially for the spectra selective RCMs, quantitative spectrum integral is generally needed in building simulations. Nevertheless, the current integral process for hourly simulations may introduce massive computational time requirements when applied to large buildings or a cluster of buildings in cities, hindering its engineering applications. This study proposed four algorithms to simplify the integral process with evaluated accuracy and time-saving: the threshold algorithm, greedy algorithm, hierarchical clustering algorithm, and polynomial approximation algorithm. As a result, approximately 50–98% of the computational time consumption has been saved for the four RCMs. The polynomial approximation performs best compared with other three algorithms with an acceptable error in net long-wavelength radiation transfer of 0.16–4.33 W / m 2. The optimized incorporation algorithm in this study could promote the simulation of RCMs in large city-scale application scenarios, such as urban heat island mitigation and heat wave impact. [ABSTRACT FROM AUTHOR]

Aims: Meropenem is increasingly used to treat neonatal sepsis. There are several guidelines recommending different dosing regimens of meropenem in neonates. Furthermore, deviations from these guidelines regularly occur in daily clinical practice. Therefore, the current study aimed to evaluate the variations of meropenem dosing guidelines and compare the difference between guideline and clinical practice in terms of the probability of target attainment. Methods: This study is based on a population pharmacokinetic model. After defining the predictive performance of the model, Monte Carlo simulations were used to calculate the probability of target attainment of the currently existing dosing guidelines of meropenem and their use in daily clinical practice. Results: Two guidelines and two labels were included in the Monte Carlo simulations. For 70% fT>MIC (fraction of time when the free meropenem concentration exceeded the minimum inhibitory concentration during the dosing interval), the probability of target attainment of four recommended doses ranged from 59% to 88% (MIC = 2 mg·L−1) and from 17% to 47% (MIC = 8 mg·L−1). At the clinical practice evaluation, only 20% of patients attained target exposure for the MIC of 8 mg·L−1 with 70% fT>MIC, which was much less than those found in the Food and Drug Administration labels (40%). Conclusion: This model‐based population pharmacokinetics simulation showed that improper guidelines and/or clinical practice deviations will result in low probability of target attainment for patients infected with resistant bacteria and critically ill patients. It is important to develop and adhere to evidence‐based and clinically pragmatic guidelines. [ABSTRACT FROM AUTHOR]

Background and Objective: Vancomycin is frequently used to treat Gram-positive bacterial infections in neonates. However, there is still no consensus on the optimal initial dosing regimen. This study aimed to assess the performance of pharmacokinetic model-based virtual trials to predict the dose–exposure relationship of vancomycin in neonates. Methods: The PubMed database was searched for clinical trials of vancomycin in neonates that reported the percentage of target attainment. Monte Carlo simulations were performed using nonlinear mixed-effect modeling to predict the dose–exposure relationship, and the differences in outcomes between virtual trials and real-world data in clinical studies were calculated. Results: A total of 11 studies with 14 dosing groups were identified from the literature to evaluate dose–exposure relationships. For the ten dosing groups where the surrogate marker for exposure was the trough concentration, the mean ± standard deviation (SD) for the target attainment between original studies and virtual trials was 3.0 ± 7.3%. Deviations between − 10 and 10% accounted for 80% of the included dosing groups. For the other four dosing groups where the surrogate marker for exposure was concentration during continuous infusion, all deviations were between − 10 and 10%, and the mean ± SD value was 2.9 ± 4.5%. Conclusion: The pharmacokinetic model-based virtual trials of vancomycin exhibited good predictive performance for dose–exposure relationships in neonates. These results might be used to assist the optimization of dosing regimens in neonatal practice, avoiding the need for trial and error. [ABSTRACT FROM AUTHOR]

[Display omitted] • First P. gingivalis RNAP structure at 3.5 Å resolution revealed new features. • P. gingivalis RNAP obtained is active and physiologically relevant. • The new orientation of its RNAP SI2 is ∼90° rotated from the one in E. coli. • Inserted region in its RNAP β' shelf may influence transcription complex assembly. • α2 in P. gingivalis RNAP ω subunit is twice as long, suggesting ω-σ interaction. Porphyromonas gingivalis , an anaerobic CFB (Cytophaga , Fusobacterium , and Bacteroides) group bacterium, is the keystone pathogen of periodontitis and has been implicated in various systemic diseases. Increased antibiotic resistance and lack of effective antibiotics necessitate a search for new intervention strategies. Here we report a 3.5 Å resolution cryo-EM structure of P. gingivalis RNA polymerase (RNAP). The structure displays new structural features in its ω subunit and multiple domains in β and β' subunits, which differ from their counterparts in other bacterial RNAPs. Superimpositions with E. coli RNAP holoenzyme and initiation complex further suggest that its ω subunit may contact the σ4 domain, thereby possibly contributing to the assembly and stabilization of initiation complexes. In addition to revealing the unique features of P. gingivalis RNAP, our work offers a framework for future studies of transcription regulation in this important pathogen, as well as for structure-based drug development. [ABSTRACT FROM AUTHOR]

• The ternary salt cocrystal of milrinone with 3,5-dinitrobenzoic acid and gallic acid was reported. • The systematic DFT-based theoretical calculations and investigations were implemented. • The simultaneous increase of dissolving and permeability was verified by experimental test. • The ternary salt cocrystal offer a new cocrystalline model for MIL with synchronously optimizing dissolubility and permeability. • The validity and feasibility were exemplified by combining theoretical with experimental approaches in elucidating the properties of multi-drug cocrystal systems. For the sake of fully laying stress on the advantages of multi-component cocrystals in ameliorating limitations of poor pharmaceutical peculiarities, and further offering fresh insights for the application of salt-type cocrystals in the optimization of anti-heart failure medication milrinone (MIL), the present project exploits the structural characteristic and property preponderance of gallic acid (GLC) and 3,5-dinitrobenzoic acid (HBA) to design and assemble MIL ternary salt cocrystal via a combination tactic of cocrystallization and salification. This strategy organizes the ternary salt-cocrystal by fashioning a salt portion to foster solubility enhancement and shaping a cocrystal moiety to achieve permeability advancement. Following this thread, the MIL ternary salt-cocrystal, namely [HMIL+-BA−]-GLC H 2 O (indicated as TSC there-in-after), is accurately authenticated by comprehensive characterization means. Single-crystal X-ray diffraction affirms that the asymmetric unit of TSC comprises a [HMIL+-BA−] salt, one neutral GLC molecule along with three water molecules, all of which build a three-dimensional hydrogen-bonding network containing electrostatic forces and π-π stacking interactions. Such unique structural feature and aggregation motif make MIL in TSC achieve a coinstantaneous elevation of 10.59 times in permeability and 4.76−5.15 folds in solubility versus the parent medicine itself at different physiological pH, which supports well agreement with the DFT-based theoretical investigations including reduced density gradient, molecular electrostatic potential surface, topology, Hirshfeld surface analysis, together with Gibbs free energy of solvation. All of these not only contribute a completely new cocrystalline model for MIL with synchronously optimizing dissolubility and permeability, but demonstrate the feasibility and effectiveness of ternary salt cocrystals in modifying the properties of anti-heart failure medicines. [ABSTRACT FROM AUTHOR]

The extraction of keratin from discarded feathers for the preparation of poly (vinyl alcohol) (PVA) ionic conductive hydrogels with enhanced mechanical properties shows promise for applications in green flexible electronics. Here, we first extracted feather keratin (FK) from duck feather fibers using the lactic acid/ l -cysteine deep eutectic solvents. Subsequently, the composite ionic conductive hydrogel composed of FK, PVA, and CaCl 2 was constructed by a one-pot freeze-thawing strategy. The introduction of FK resulted in a denser structure of the fabricated hydrogel, which significantly enhanced its mechanical properties, including high elongation at break of 639.3%, high breaking strength of 270 kPa, and durable fatigue resistance. Impressively, the hydrogel-based wearable strain sensor demonstrated high strain sensing sensitivity (GF = 1.26), wide strain detection range (5%–200%), fast response, and stable reliability, enabling it to accurately monitor and distinguish the difference in electrical signals generated by large and tiny human motions. This work provides a reliable method for the green extraction of FK and the design of high-performance PVA hydrogel-based flexible electrical devices. [Display omitted] • FK was extracted from feathers using a novel deep eutectic solvent. • PVA based ionic conductive hydrogels were constructed by a one-pot freeze-thawing strategy. • FK enhanced mechanical properties and ionic conductivity of hydrogels. • The hydrogel demonstrated superior strain sensing performance. • The hydrogel sensors are suitable for human motion monitoring. [ABSTRACT FROM AUTHOR]

We propose a generative model and an inference scheme for epidemic processes on dynamic, adaptive contact networks. Network evolution is formulated as a link-Markovian process, which is then coupled to an individual-level stochastic susceptible-infectious-recovered model, to describe the interplay between the dynamics of the disease spread and the contact network underlying the epidemic. A Markov chain Monte Carlo framework is developed for likelihood-based inference from partial epidemic observations, with a novel data augmentation algorithm specifically designed to deal with missing individual recovery times under the dynamic network setting. Through a series of simulation experiments, we demonstrate the validity and flexibility of the model as well as the efficacy and efficiency of the data augmentation inference scheme. The model is also applied to a recent real-world dataset on influenza-like-illness transmission with high-resolution social contact tracking records. for this article are available online. [ABSTRACT FROM AUTHOR]

Synopsis: Molecular adduct of antifungal medication bifonazole (BIF) and caffeic acid, as the first BIF's molecular salt featured with the lipid-water amphiphilic structure, was directionally synthesized and fully characterized. The integrated theoretical and experimental investigations revealed that the in vitro physicochemical property and antifungal efficacy of the molecular salt were improved simultaneously. [Display omitted] • Bifonazole caffeate as the first molecular salt was reported. • The systematic DFT-based theoretical investigations were implemented. • The simultaneous increase of dissolution and permeability was found experimentally. • The antifungal activity for molecular salt was significantly enhanced. • The validity and feasibility were exemplified by combining theory with experiment. In order to make novel breakthroughs in molecular salt studies of BCS class-IV antifungal medication bifonazole (BIF), a salification-driven strategy towards ameliorating attributes and aiding augment efficiency is raised. This strategy fully harnesses structural characters together attributes and benefits of caffeic acid (CAF) to concurrently enhance dissolvability and permeability of BIF by introducing the two ingredients into the identical molecular salt lattice through the salification reaction, which, coupled with the aroused potential activity of CAF significantly amplifies the antifungal efficacy of BIF. Guided by this route, the first BIF-organic molecular salt, BIF-CAF, is directionally designed and synthesized with satisfactorily structural characterizations and integrated theoretical and experimental explorations on the pharmaceutical properties. Single-crystal X-ray diffraction resolving confirms that there is a lipid-water amphiphilic sandwich structure constructed by robust charge-assistant hydrogen bonds in the salt crystal, endowing the molecular salt with the potential to enhance both dissolvability and permeability relative to the parent drug, which is validated by experimental evaluations. Remarkably, the comprehensive DFT-based theoretical investigations covering frontier molecular orbital, molecular electrostatic potential, Hirshfeld surface analysis, reduced density gradient, topology, sphericity and planarity analysis strongly support these observations, thereby allowing some positive relationships between macroscopic properties and microstructures of the molecular salt can be made. Intriguingly, the optimal properties, together with the stimulated activity of CAF markedly augment in vitro antifungal ability of the molecular salt, with magnifying inhibition zones and reducing minimum inhibitory concentrations. These findings fill in the gaps on researches of BIF-organic molecular salt, and adequately exemplify the feasibility and validity by integrating theoretical and experimental approaches to resolve BIF's problems via the salification-driven tactic. [ABSTRACT FROM AUTHOR]

Passive radiative cooling materials (RCM) can cool surfaces by radiating heat to outer space via long-wave radiation. In simulation application, co-simulation of the thermal process between RCMs and building structures is generally required; however, the high computing time cost and low integration level have hindered the integrated whole-building simulation in architectural design. Traditional building energy simulations utilize the effective sky temperature to numerically approximate the effect of sky radiation. However, given the limitations of effective sky temperature concept, it is more suitable to evaluate diffusive gray surfaces while not fully capturing the characteristics of radiative heat transfer for spectrum-selective surfaces. In this study, an innovative equivalent-sky-radiative temperature was introduced as a new equivalent parameter to accurately simulate the thermal performance of RCMs in buildings. Embedding this new parameter into whole-building energy simulation tools such as EnergyPlus and DeST is expected to significantly improve the calculation accuracy and reduce the computational cost. Case studies in this work have shown an average error of 5.47 W/m2. The generation of the new parameter for 50 cities worldwide also demonstrated the technical feasibility of applying the equivalent-sky-radiative temperatures to evaluate the thermal performance and energy savings of real-world RCMs in buildings. [ABSTRACT FROM AUTHOR]

Major depressive disorder (MDD) is a neurasthenic disease, which is the second-largest burden of disease globally. Increasing studies have revealed that depression is associated with abnormalities in gut microbiota and metabolites. Several species of bacteria have been classified as psychobiotics, which confer mental health benefits through interactions with commensal gut microbiota. Therefore, it is essential to identify new psychobiotics and elucidate their mechanisms in the treatment of depression. This study aims to evaluate the antidepressant effect of Akkermansia muciniphila (AKK) in a mouse model of depression induced by chronic restraint stress (CRS). C57BL/6 male mice were divided into three groups: mice subjected to CRS, mice not subjected to CRS, and mice treated with AKK for 3 weeks. Behavioral tests were performed, and hormone, neurotransmitter, and brain-derived neurotrophic factor (BDNF) levels were measured. Cecal microbiota was analyzed using 16S rRNA gene sequencing, and serum metabolites were detected using untargeted metabolomics. In addition, correlations between altered gut microbiota and metabolites with significant variations in serum associated with AKK ameliorating depression were analyzed using Pearson's correlation coefficient. The results revealed that AKK significantly ameliorated depressive-like behavior and restored abnormal variations in depression-related molecular (corticosterone, dopamine, and BDNF). Moreover, AKK altered chronic stress–induced gut microbial abnormalities. Untargeted metabolomics analysis revealed 23 potential biomarkers in serum that could be associated with the mechanisms underlying CRS-induced depression and the therapeutic effects of AKK. Pearson's correlation coefficient analysis revealed that AKK predominantly upregulated β-alanyl-3-methyl-l-histidine and edaravone to relieve depression. Furthermore, β-alanyl-3-methyl-l-histidine and edaravone exhibited the antidepressant phenotype in mice subjected to CRS. In conclusion, the study demonstrated that AKK ameliorates chronic stress–induced depressive symptoms in mice by regulating gut microbiota and metabolites. Key points: • AKK reduces depressive-like behaviors induced by chronic stress. • AKK regulates the gut microbial structure and metabolomics of serum under the chronic stress. • Antidepressant effect of AKK correlates with the increase of β-alanyl-3-methyl-l-histidine and edaravone. [ABSTRACT FROM AUTHOR]

The total flavone of Abelmoschus manihot (TFA), a compound extracted from the flowers of Abelmoschus manihot (L.) Medic, has been widely used for the treatment of Crohn's disease, chronic glomerulonephritis and other diseases. The aim of this study was to investigate the effect of TFA on the gut microbiota and intestinal barrier in dextran sulfate sodium (DSS)-induced experimental colitis. C57BL/6J mice were treated with 2.5% DSS in drinking water to induce colitis. Mice were orally administered TFA (62.5 mg/kg, 125 mg/kg) or prednisone acetate (PAT, 2.5 mg/kg) once daily for 7 days. Biological samples were collected for analysis of inflammatory cytokines, gut microbiota and intestinal barrier integrity. TFA-H (125 mg/kg) markedly attenuated DSS-induced colon shortening and histological injury in experimental colitis. The therapeutic effect was similar to that of PAT administration. TFA-H notably modulated the dysbiosis of gut microbiota induced by DSS and greatly enriched Akkermansia muciniphila (A. muciniphila). Moreover, TFA-H remarkably ameliorated the colonic inflammatory response and intestinal epithelial barrier dysfunction. Interestingly, TFA directly promotes the growth of A. muciniphila in vitro. Taken together, the results revealed for the first time that TFA, as a prebiotic of A. muciniphila, improved DSS-induced experimental colitis, at least partly by modulating the gut microflora profile to maintain colonic integrity and inhibit the inflammatory response. [ABSTRACT FROM AUTHOR]

Long‐term disability after stroke is common but the mechanisms of post‐stroke recovery remain unclear. Cerebral Ras‐related C3 botulinum toxin substrate (Rac) 1 contributes to functional recovery after ischemic stroke in mice. As Rac1 plays divergent roles in individual cell types after central neural system injury, we herein examined the specific role of neuronal Rac1 in post‐stroke recovery and axonal regeneration. Young male mice were subjected to 60‐min of middle cerebral artery occlusion (MCAO). Inducible deletion of neuronal Rac1 by daily intraperitoneal injection of tamoxifen (2 mg/40 g) into Thy1‐creER/Rac1‐floxed mice day 7–11 after MCAO worsened cognitive (assayed by novel object recognition test) and sensorimotor (assayed by adhesive removal and pellet reaching tests) recovery day 14–28 accompanied with the reduction of neurofilament‐L (NFL) and myelin basic protein (MBP) and the elevation of glial fibrillary acidic protein (GFAP) in the peri‐infarct zone assessed by immunostaining. Whereas the brain tissue loss was not altered assayed by cresyl violet staining. In another approach, delayed overexpression of neuronal Rac1 by injection of lentivirus encoding Rac1 with neuronal promotor into both the cortex and striatum (total 4 μl at 1 × 109 transducing units/mL) of stroke side in C57BL/6J mice day 7 promoted stroke outcome, NFL and MBP regrowth and alleviated GFAP invasion. Furthermore, neuronal Rac1 over‐expression led to the activation of p21 activating kinases (PAK) 1, mitogen‐activated protein kinase kinase (MEK) 1/2 and extracellular signal‐regulated kinase (ERK) 1/2, and the elevation of brain‐derived neurotrophic factor (BDNF) day 14 after stroke. Finally, we observed higher counts of neuronal Rac1 in the peri‐infarct zone of subacute/old ischemic stroke subjects. This work identified a neuronal Rac1 signaling in improving functional recovery and axonal regeneration after stroke, suggesting a potential therapeutic target in the recovery stage of stroke. [ABSTRACT FROM AUTHOR]

• The simulation model evaluates the container shipping performance of a seaport. • Implementing Container-on-Barge (COB) can effectively mitigate port congestion. • Congestion relief becomes more significant as the COB modal share increases. • The case study demonstrates how COB helps U.S. seaports reduce congestions. Port congestion has become a big challenge for many seaports in the United States (U.S.). There are multiple factors contributing to port congestion, such as the booming market of international container trading, limited space and capacity at a seaport, labor shortages, equipment failures, and supply chain disruptions (e.g., COVID-19 pandemic). Without appropriate management, port congestion will increase transportation costs, cause delays in goods movement and cargo delivery, reduce port operation efficiency, and lead to supply chain disruptions. Traditional strategies, such as infrastructure investment, truck appointments optimization, and party cooperation enhancement, have been implemented by ports for years, but the results are often unsatisfactory. To learn the needs of U.S. seaports and seek an efficient method for congestion relief, we develop a discrete event simulation model incorporating Container-on-Barge (COB) as an alternative transportation mode in this study. The simulation model mimics port operations involving COB and investigates congestion times at berth, yard, and gates. A case study on the Port of New Orleans (Port NOLA) is conducted to demonstrate the implementation of the simulation model and to evaluate the potential of COB for seaport congestion relief. The simulation results suggest that with a good level of COB development, the congestion at berth, yard and entrances of a seaport can be decreased significantly. [ABSTRACT FROM AUTHOR]

• We synthesized semi-amorphous Ti-BDC using an acid-conditioned approach. • By optimizing synthesis conditions, we enhanced photocatalytic efficiency. • High surface area, oxygens vacancies, and active sites enhance photocatalysis. • Active species such as ·O2-, ·OH can be produced during the photocatalytic process. Ti-based Metal–organic frameworks (MOFs) are considered one of the most charming research due to the remarkable optoelectronic and photocatalytic properties. However, the complexity of controlling the chemical changes in Ti makes the synthesis of Ti-MOFs complex. Here we simply adjusted the synthesis conditions with acetic acid (AA) to obtained a semi-amorphous structure (Ti-BDC). The introduction of AA changed the morphology of the original typical MIL-125(Ti), and enhanced its photocatalytic performance. By adding excess of AA, the grains are refined and Ti-BDC is formed, thus changing the surface state of materials, increasing the light absorption, and reducing the photogenerated charge, which eventually improve the photocatalytic performance. Besides, the samples showed good stability and cycling performance. This method paves the way for stable and economical preparation of Ti-based photocatalytic materials. [Display omitted] [ABSTRACT FROM AUTHOR]

Cobalt-boride (Co-B) alloys, as promising wear resistant materials, can form different intermetallic compounds. In this work, supercooling treatment is applied to control the microstructures and compounds in the alloys, and the related mechanical and tribological properties have been investigated systematically. The results suggest that besides FCC-Co and HCP-Co, it forms Co 3 B and minor Co 2 B in the as-cast samples, Co 3 B, Co 2 B and Co 23 B 6 under different supercooling degree. Tribological experiments of these alloys under distilled water environment demonstrate that the Co-B alloy containing Co 23 B 6 has the best tribological performance, followed by Co 2 B and Co 3 B. The coefficient of friction and wear rate of alloy containing Co 23 B 6 are about 0.2 and 1.6 × 10−6 mm3/Nm, respectively, which are reduced by 60 % and one magnitude lower compared to the as-cast sample containing Co 2 B and Co 3 B. The promising tribological result of Co 23 B 6 is attributed to the formation of tribolayer, which is rich in Co(OH) 2 , silicate, SiO 2 and possibly H 3 BO 3. This work provides guideline for tuning phases of Co-B alloys when using as rubbing parts in moisture environment. [ABSTRACT FROM AUTHOR]

Building thermal process simulation is an effective technique for quantitatively analyzing building energy consumption. The finite difference method is commonly used for structuring heat transfer equations due to its generality. However, the state-space method is preferred in BPS tools due to its computational efficiency. As building simulation analysis evolves, there is a need for high-performance computation to simulate large-scale constructions. This study proposes a new computing architecture for optimizing the state-space method in BPS tools, focusing on both personal computers and server clusters. The simulation procedure is parallelized at different stages while maintaining accuracy. Two case studies validate the feasibility of the proposed computing architectures. Compared to the original serial architecture, the parallel architecture achieves an acceleration of 2.12–2.33 times on a PC and 5.68–17.24 times on a server cluster. This significant acceleration potential demonstrates the power of parallelization in maximizing computing power. [ABSTRACT FROM AUTHOR]

A considerable number of engineering hazards are caused by loose internal structure of sands. Thus, many researchers have explored a variety of reinforcement methods. A new reinforcement technique was experimentally evaluated in this study. In particular, a hybrid method with a combination of fiber and polymer was studied. Three different types of fibers (sisal, polypropylene, and palm) in combination with varying concentrations of polymers were experimented to improve the internal structure and strength of sand samples reconstituted at different densities. Through a series of laboratory tests, the compressive and tensile strength variations of different combinations were obtained, and the interaction between fibers and polymer inside the sand was evaluated by scanning electron microscopy (SEM). The experimental results show that the tensile and compressive strength of the reinforced sand increases with the increase of the polymer concentration, sample density, and different fiber combinations. This provides some references for future practical engineering applications. [ABSTRACT FROM AUTHOR]

Background: For a long time, the relationship between caffeine consumption and infertility in the general population is unclear, this study is aimed to systematically review the evidence from any type of controlled clinical studies to explore whether caffeine intake is a risk factor for human infertility.Methods: Seven databases were searched from inception to May 2019. We included women/men without a history of infertility but were willing to have children in prospective studies and women/men who were diagnosed with infertility in retrospective studies. The observed exposure factor should be caffeine or caffeine containing beverage. Diagnosis of infertility or not for participants was the key outcome. The Newcastle-Ottawa scale (NOS) or Cochrane risk of bias tool were used to assess the methodological quality of included studies. Meta-analysis was conducted if there were acceptable clinical and statistical heterogeneity among studies. The GRADE method was used to assess the certainty of the evidence.Results: Four studies (one cohort study and three case-control studies) involving 12,912 participants were included. According NOS, the average score of case-control studies was 6, and the cohort study achieved 9. Meta-analysis and subgroup analysis were conducted. The results showed that low (OR 0.95, 95%CI 0.78-1.16), medium (OR 1.14, 95%CI 0.69-1.86) and high doses (OR 1.86, 95%CI 0.28-12.22) of caffeine intake may not increase the risk of infertility. The quality of the current evidence bodies were all low.Conclusion: Our study provides low quality evidence that regardless of low, medium and high doses of caffeine intake do not appear increase the risk of infertility. But the conclusion should be treated with caution. [ABSTRACT FROM AUTHOR]

• A new KF roughening and alkali washing strategy is proposed as a surface pretreatment. • The damage ratio of HGMs decreases by 10% compared to that by HF roughening. • NaOH has a better washing effect on roughened HGMs than KOH. • Metal nanoparticles distribute more uniformly and tightly on the surface of HGMs by using NaOH instead of KOH. • The metallized HGMs have a competitive absorbing ability in X-band and Ku-band. Surface roughening of hollow glass microspheres (HGMs) is a necessary step determining their adhesion ability with the following electroless plated metallization coating. In this paper, a new KF roughening and alkali washing strategy was proposed to replace HF roughening as a surface pretreatment for the following electroless plating metallization. In order to remove the byproduct of K 2 SiF 6 from the roughening reaction of KF with HGMs, NaOH washing and KOH washing were conducted, the former of which was found to dissolve K 2 SiF 6 effectively. The effects of KF roughening temperature, alkali concentration and HGMs loading on the recovery ratio, phase composition, surface morphology and performance of HGMs were investigated, through which such a pretreating strategy was found to not only decrease the damage ratio of HGMs compared to that by HF roughening, but also render the metallized HGMs a competitive absorbing ability for the electromagnetic wave in X-band and Ku-band. Finally, the related surface treatment and electroless plating mechanism were discussed. This paper illustrates successfully a new pretreatment strategy for development of lightweight HGMs-supported functional materials. [ABSTRACT FROM AUTHOR]

Ultrafiltration (UF) technology is considered an efficient water treatment method. In recent years, researchers have been committed to enhancing the treatment efficiency of UF and alleviating membrane fouling. An effective method is to achieve this is through the use of coagulation as a pre-treatment to UF; however, during a long term operation, membrane fouling can occur due to the residual organic matters and the generation of microorganisms. In this study, we combine coagulation and ozonation as a pre-treatment of UF and compare four types of pre-treatment: coagulation, ozonation, coagulation followed by ozonation (C–O) and ozonation followed by coagulation (O–C). Results showed that ozonation alone did not perform well. Both combinations of coagulation and ozonation enhanced the organic matter removal efficiency, although membrane fouling was lowest following the C–O pre-treatment as the microbial load was reduced. While a slight increase in the yield of disinfection by-products was observed with the addition of ozonation, the concentration remained below the Chinese standard for tap water quality (100 μg/L). • Using coagulation and ozonation as pre-treatments has been investigated. • The addition of ozone after coagulation achieved better UV 254 removal. • Ozone decrease the EPS concentration to alleviate membrane fouling. • Ozone may cause slight increase of disinfection by-products. [ABSTRACT FROM AUTHOR]

[Display omitted] To emphasize the superiority of uracil (UR) in ameliorating biopharmaceutical characteristics of marine antitumor medicine cytarabine (ARA), thus gaining some innovative opinions for the exploitation of nanococrystal formulation, a cocrystal nanonization strategy is proposed by integrating cocrystallization and nanosize preparation techniques. For one thing, based on UR's unique structural features and natures together with advantages of preferential uptake by tumor cells, cocrystallizing ARA with UR is expected to improve the in vitro / vivo performances. For another, the nanonization procedure is oriented towards maintaining the long-term effective drug level. Along this route, a cocrystal of ARA with UR, viz., ARA-UR, is successfully synthesized and then transformed into nano-cocrystal. The cocrystal structure is precisely confirmed by various methods, demonstrating that a 1:1 ARA and UR in the crystal forms cytosine-UR hydrogen-bonding interactions, thus constructing supramolecular frameworks by strong π-π stacking interplays; while the nano-cocrystal is block-shaped particles of 562.70 nm with zeta potential −33.40 mV. The properties of cocrystal ARA-UR and its nano-cocrystal in vitro / vivo are comparatively explored by theoretical calculations and experimental analyses, revealing that permeability of both is significantly increased than ARA per se. Notably, the meliorative natures of both the cocrystal and nano-cocrystal in vitro bring excellent antitumor activity, but the latter has greater strengths over the former. More notably, the nano-cocrystal can sustain effective concentration for a relatively longer time, causing lengthened retention time and better absorption in vivo. The contribution offers a fire-new dosage form of ARA for long-lasting delivery, thus filling the vacancy in nanococrystal studies about marine drugs. [ABSTRACT FROM AUTHOR]

The aberrant proliferation and migration of vascular smooth muscle cells (VSMCs) play an essential role in the pathogenesis of atherosclerosis (AS). Long noncoding RNAs (lncRNAs) have been reported as important regulators in a number of diseases. However, very little is known regarding the functional role of lncRNAs in governing proliferation and migration of VSMCs and AS development. Both in vitro and in vivo assays were performed to investigate the role of lncRNA in the pathophysiology of AS. Our previous lncRNA arrays revealed that lncRNA RP4-639F20.1 was significantly decreased in atherosclerotic plaques. Lentivirus overexpressing RP4-639F20.1 and lncRNA RP4-639F20.1 silencing vectors (Si-lnc-RP4-639F20.1) were constructed and transfected in VSMCs. The in vitro functions of lncRNA were analyzed by CCK-8 assays, EdU assays, scratch wound assays, transwell assays, qRT-PCR and Western blot analyses. RNA fluorescence in situ hybridization, immunoprecipitation and mRNA microarrays were used to explore the underlying mechanism. Adeno-associated-virus-9 (AAV9) overexpressing RP4-639F20.1 was constructed and injected intravenously into ApoE −/− mice to explore the role of lncRNA in vivo. In vitro experiments showed that lncRNA RP4-639F20.1 interacted with THRAP3 and downregulated c-FOS expression. Both increase of lncRNA RP4-639F20.1 expression and knockdown of c-FOS inhibited the expression of MMP10 and VEGF-α in VSMCs and suppressed VSMCs proliferation and migration. In vivo experiments using ApoE −/− mice fed a high-fat diet demonstrated that lncRNA RP4-639F20.1 overexpression deterred atherosclerosis and decreased lipid levels in atherosclerotic lesions. Patients with coronary artery disease were found to have higher c-FOS levels than healthy individuals and c-FOS expression was positively correlated with the SYNTAX score of patients. Overall, these data indicated that lncRNA RP4-639F20.1/THRAP3/c-FOS pathway protects against the development of atherosclerosis by suppressing VSMCs proliferation and migration. LncRNA RP4-639F20.1 and c-FOS could represent potential therapeutic targets to ameliorate atherosclerosis-related diseases. [Display omitted] • Expression of lncRNA RP4-639F20.1 is decreased in human atherosclerotic plaques. • LncRNA RP4-639F20.1 inhibits VSMCs proliferation and migration and inhibits atherosclerotic lesion formation in ApoE −/− mice. • LncRNA RP4-639F20.1 interacts with THRAP3 to regulate c-FOS in VSMCs. • C-FOS levels are higher in human plaques. [ABSTRACT FROM AUTHOR]

• A codrug molecular salt of pyrimethamine with fenbufen was designed and prepared. • The accurate structure of the salt was resolved by various techniques. • The dissolubility behavior of the salt was studied theoretically and experimentally. • Both solubility and dissolution rate of pyrimethamine were optimized by the salt formation approach. An approach of dual-drug salt formation assisted increase efficacy has been put forward with the aim of fully exploiting the benefits of NSAID fenbufen (HFB) in enhancing the dissolubility and efficacy of antimalarial drug pyrimethamine (PYR). The approach features the acidic property of HFB and PYR's alkalinity to generate the designed molecular salt via the neutralization reaction, thus making the solubility capacity of the two bulk drugs be concurrently heightened due to the salt formation effect, which, in turn, not only makes for enhancing PYR's bioavailability, but contributes to playing the fast and efficient antipyretic function of HFB serving as a fever-relieving medicine, thereby, conducing to increasing the therapeutic effect of PYR on malaria. Based on this approach, the objective dual-drug molecular salt PYR-HFB has been successfully attained and structurally authenticated by single-crystal X-ray diffraction and diversified analytical techniques. The single-crystal structure analysis demonstrates that the resulting heterodimer entity in the asymmetric unit of the molecular salt comprises a HFB anion and a PYR cation linked by robust charge-assisted hydrogen-bonds to construct an integral 3D supramolecular network, endowing the present molecular salt with the ability to respectively raise solubility and intrinsic dissolution rate up to 2.3- and 4.6-fold relative to parent drug PYR, which fulfills positive connections with theoretical forecasts involving Hirshfeld surface analysis, molecular electrostatic potential, theory of atoms in molecules and frontier molecular orbit. Therefore, this investigation not only affords a fire-new crystalline style with developing foreground for PYR, but supplies an insightful salt formation approach for perfecting both dissolubility and efficiency of antimalarial medicines at the molecular level by playing the characteristic and function of NSAIDs in treating malaria. A dual-drug molecular salt of pyrimethamine (PYR) and fenbufen (HFB) is successfully synthesized and fully characterized. The dissolubility behaviors of the molecular salt are comprehensively investigated by means of theory and experiment approaches, revealing that the solubility and dissolution rate of pyrimethamine have been enhanced simultaneously through the codrug salt formation approach. [Display omitted] [ABSTRACT FROM AUTHOR]

Brain microvascular endothelial cells play an essential role in maintaining blood–brain barrier (BBB) integrity, and disruption of the BBB aggravates the ischemic injury. CaMKK (α and β) is a major kinase activated by elevated intracellular calcium. Previously, we demonstrated that inhibition of CaMKK exacerbated outcomes, conversely, overexpression reduced brain injury after stroke in mice. Interestingly, CaMKK has been shown to activate a key endothelial protector, sirtuin 1 (SIRT1). We hypothesized that CaMKK protects brain endothelial cells via SIRT1 activation after stroke. In this study, Oxygen‐Glucose Deprivation (OGD) was performed in human brain microvascular endothelial cells. Stroke was induced by middle cerebral artery occlusion (MCAO) in male mice. Knockdown of CaMKK β using siRNA increased cell death following OGD. Inhibition of CaMKK β by STO‐609 significantly and selectively down‐regulated levels of phosphorylated SIRT1 after OGD. Changes in the downstream targets of SIRT1 were observed following STO‐609 treatment. The effect of STO‐609 on cell viability after OGD was absent, when SIRT1 was concurrently inhibited. We also demonstrated that STO‐609 increased endothelial expression of the pro‐inflammatory proteins ICAM‐1 and VCAM‐1 and inhibition of CaMKK exacerbated OGD‐induced leukocyte‐endothelial adhesion. Finally, intracerebroventricular injection of STO‐609 exacerbated endothelial apoptosis and reduced BBB integrity after 24‐hr reperfusion following MCAO in vivo. Collectively, these results demonstrated that CaMKK inhibition reduced endothelial cell viability, exacerbated inflammatory responses and aggravated BBB impairment after ischemia. CaMKK activation may attenuate ischemic brain injury via protection of the microvascular system and a reduction in the infiltration of pro‐inflammatory factors. In brain endothelial cells after stroke, CaMKK β activates SIRT1 by phosphorylation, which subsequently produces anti‐oxidative effect and enhances eNOS signaling. eNOS signaling then produces pleiotropic effects including endothelial cell protection and inhibiting inflammation by reducing VCAM‐1, ICAM‐1, E‐selectins, and leukocytes extravasation. STO‐609 and EX‐527 are pharmacological inhibitors of CaMKK and SIRT1, respectively. [ABSTRACT FROM AUTHOR]

Abstract Coagulation–ultrafiltration (C–UF) is widely used for surface water treatment. With the removal of pollutants, the characteristics of organic matter change and affect the final treatment efficiency and the development of membrane fouling. In this study, we built a dynamic C–UF set-up to carry out the treatment of micro-polluted surface water, to investigate the characteristics of dissolved organic matter from different units. The influences of poly aluminum chloride and poly dimethyldiallylammonium chloride (PDMDAAC) on removal efficiency and membrane fouling were also investigated. Results showed that the dosage of PDMDAAC evidently increased the UV 254 and dissolved organic carbon removal efficiencies, and thereby alleviated membrane fouling in the C–UF process. Most hydrophobic bases (HoB) and hydrophobic neutral fractions could be removed by coagulation. Similarly, UF was good at removing HoB compared to hydrophilic substances (HiS) and hydrophobic acid (HoA) fractions. HiS and HoA fractions with low molecule weight accumulated on the surface of the membrane, causing the increase of transmembrane pressure (TMP). Membrane fouling was mainly caused by a removable cake layer, and mechanical cleaning was an efficient way to decrease the TMP. Graphical abstract Unlabelled Image [ABSTRACT FROM AUTHOR]

Coke oven gas is considered as a potential hydrogen source for biogas bio-upgrading. In this study, the effects of CO on biomethanation performance and microbial community structure of hydrogenotrophic mixed cultures were investigated under thermophilic (55 °C) and extreme-thermophilic (70 °C) conditions. 5% (v/v) CO did not inhibit hydrogenotrophic methanogenesis during semi-continuous operation, and 83–97% CO conversion to CH 4 was achieved. Methanothermobacter thermoautotrophicus was the dominant methanogen at both temperatures and was the main functional archaea associated with CO biomethanation. Specific methanogenic activity test results showed that long-term 5% CO acclimation shortened the lag phase from 5 h to 1 h at 55 °C and 15 h to 3 h at 70 °C. CO 2 was the preferred carbon source over CO for hydrogenotrophic methanogens and CO consumption only started when CO 2 was completely depleted. M. thermoautotrophicus dominated mixed cultures showed a great potential in simultaneous hydrogenotrophic methanogenesis and CO biomethanation. [ABSTRACT FROM AUTHOR]

In this study, hydrogenotrophic methanogenesis with respect to methanogenic activity and microbial structures under extreme-thermophilic conditions were examined, and compared with the conventional thermophilic condition. The hydrogenotrophic methanogens were successfully acclimated to the temperatures of 55, 65 and 70 °C. Although acclimation was slower at 65 and 70 °C, hydrogenotrophic methanogenesis remained fairly stable. High-throughput sequencing using 16S rRNA analysis showed that the higher temperatures resulted in single archaea community dominated by hydrogenotrophic Methanothermobacter . Moreover, the syntrophic bacteria changed from Coprothermobacter and Thermodesulfovibrio at 55 °C to Thermodesulfovibrio at 70 °C. Specific hydrogenotrophic methanogenic rate at 70 °C was 98.6 ± 4.2 Nml CH 4 /g VS/hr, which was over 4-folds higher than that 8at 55 °C. The lag phase under extreme-thermophilic conditions was longer than thermophilic condition, which was probably due to the archaeal structure with low diversity. Extreme-thermophilic condition resulted in a shift in methanogenesis pathway from acetoclastic methanogenesis to hydrogenotrophic methanogenesis with the enrichment of Methanothermobacter thermautotrophicus. [ABSTRACT FROM AUTHOR]

Objectives Sarcoma family kinase activity is associated with multiple diseases including ischemia and cancer; however, its role in the mechanism of migraine aura has been less well characterised. This study aims to investigate whether sarcoma family kinase is required for cortical spreading depression. Methods Cortical spreading depression was induced by topical application of K+ to the cerebral cortex and was monitored using electrophysiology in rats, and intrinsic optical signal in mouse brain slices. Drugs were perfused into the contralateral cerebral ventricle for pharmacological manipulations in rats. Western blot analysis was used for detecting the level of phosphorylated, and total, sarcoma family kinase in the ipsilateral cortex of rats. Key results The data demonstrate that a single cortical spreading depression in rats induced ipsilateral cortical sarcoma family kinase phosphorylation at the Y416 site. Deactivation of sarcoma family kinase by its inhibitor (3-(4-chlorophenyl) 1-(1,1-dimethylethyl)-1 H-pyrazolo[3,4- dpyrimidin-4-amine) suppressed the elevated enzyme activity and cortical susceptibility to cortical spreading depression. Interestingly, the inhibitory effect of the N-methyl-D-aspartate receptor antagonist NVP-AAM077 on cortical spreading depression was reversed by the sarcoma family kinase activator pYEEI (EPQY(PO3H2)EEEIPIYL), suggesting a link between this enzyme and N-methyl-D-aspartate receptors. Similarly, after deactivation of sarcoma family kinase, a reduction of sarcoma family kinase phosphorylation and cortical susceptibility to cortical spreading depression was observed with NVP-AAM077. Conclusions We conclude that activation of sarcoma family kinase is required for cortical spreading depression, and this process is regulated by recruiting N-methyl-D-aspartate receptors. This study provides novel insight for sarcoma family kinase function in the mechanism of migraine aura. [ABSTRACT FROM AUTHOR]

In this study, a novel polysaccharide (PCPs) was obtained from bamboo shoots ( Chimonobambusa quadrangularis ) processing by-products through the ultrasonic-assisted extraction (UAE) and Sephadex G-100 size-exclusion chromatography purification. By using a Box–Behnken design (BBD) to optimize the parameters for extracting the crude PCPs with UAE, the maximum yield of crude PCPs (8.76%) was obtained under the optimal extraction conditions as follows: ratio of water to raw material 20.2 mL/g, extraction temperature 49 °C, ultrasonic power 240 W, and extraction time 40 min. Structurally, PCPs was identified as hetero-polysaccharides, which was composed of Man, Rha, GlcA, GalA, Glc, Gal, Xyl, and Ara in a molecular ratio of 1.00:2.05:2.28:2.36:15.76:49.06:16.70:39.86. The molecular weight distribution analysis showed that PCPs had three components with molecular weights of 136.1, 29.7 and 8.3 kD, respectively. The glycosidic linkage analysis showed that PCPs contained 1 → or 1 → 6 glycosidic linkages (35.1%), 1 → 2 or 1 → 4 glycosidic linkages (14.8%), and 1 → 3 glycosidic linkages (50.1%). conformations. The obtained results revealed that PCPs with a semi-crystalline structure exhibited important functional properties including the repose angle, swelling index (SC), water retention capacity (WRC), and oil retention capacity (ORC). The viscoelastic property of PCPs system exhibited a gel-like behavior with storage modulus G′ always being higher than loss modulus G″. PCPs displayed excellent thermal stability as assessed by rheology and TGA/DSC. Furthermore, PCPs exhibited good chemical antioxidant activities in DPPH, ABTS and hydroxyl radical scavenging abilities, and metal chelating activity. [ABSTRACT FROM AUTHOR]

A novel and potentially active dihydroorotate dehydrogenase (DHODH) inhibitor, namely 3-({( E)-[( E)-1-(biphenyl-4-yl)ethylidene]hydrazinylidene}methyl)-1 H-indole (BEHI) acetonitrile disolvate, C23H19N3·2CH3CN, has been designed and synthesized. The structure of BEHI was characterized by elemental analysis, Q-TOF (quadrupole time-of-flight) MS, NMR, UV-Vis and single-crystal X-ray diffraction. The antitumour activity of the target molecule was evaluated by the MTT method. Results indicated that BEHI exhibited rather potent cytotoxic activity against human A549 (IC50 = 20.5 µ M) and mouse breast 4T1 (IC50 = 18.5 µ M) cancer cell lines. Meanwhile, to rationalize its potencies in the target, BEHI was docked into DHODH and the interactions with the active site residues were analyzed. Single-crystal structure analysis indicated that hydrogen bonds are present only between BEHI and acetonitrile solvent molecules in the asymmetric unit. The interplay of weak π-π stacking and weak C(N)-H...π interactions between neighbouring BEHI molecules play crucial roles in the formation of the final supramolecular frameworks. [ABSTRACT FROM AUTHOR]

• The first cocrystal of 5-flucytosine with hydroxycinnamic acid was reported. • The reduced trend in dissolving capacity was predicted via theoretical calculations. • The descent of solubility and dissolution rate was verified by experimental test. • The cocrystallization exemplified the potential for overcoming toxicity side effects. The present investigation aims to fully exploit the structural dominance and liver protective efficacy of phenolic acid nutraceutical ferulic acid (FUA) towards decreasing antifungal drug 5-fluorocytosine (FTS) in solubility and dissolution rate through a cocrystallization stratagem, thereby achieving some fire-new understandings for addressing the side effects generated by the fast and inappropriate absorption from FTS. Toward this end, the cocrystalline complex of FTS with FUA, viz. FTS-FUA, as the first cocrystal of FTS with phenolic acid nutrient of hydroxycinnamic acid subgroup is directionally assembled and fully characterized. The crystal structure determined by the single-crystal X-ray diffraction method demonstrates that FUA molecules in the lattice seize the polar sites in situ of FTS founded on the compact hydrogen-bond interaction, therefore leading to the formation of a rigid S-shaped module (RSM) with hydrophobic potentials, which induces a simultaneous down-regulation of the cocrystal in solubility and intrinsic dissolution rate versus raw drug FTS itself. The experimental outcomes are strongly verified by relevant theoretical investigations. The molecular electrostatic potential and the mutual penetration distance authenticate that the RSM's polarity in the cocrystal is lower than that of FTS per se, which complies with the abatement in polarity attributable to the reinforced hydrogen-bonds energy as per topology analysis with atoms in molecules theory, thus giving a remarkable improvement in hydrophobicity for the cocrystal. As a result, the current contribution not only provides a new crystallization form for FTS, but also exemplifies the feasibility of cocrystallization clue from integrated experimental with a systematic theoretical approach to overcome intractable adverse effects of the antifungal agent. Cocrystallization of 5-fluorocytosine (FTS) and ferulic acid (FUA) was firstly reported. The systematic studies combining theory with experiment revealed that both solubility and dissolution rate of FTS can be down-regulated due to the establishment of rigid S-shaped modules in the cocrystal, showing the potentials to reduce FTS's adverse reaction. [Display omitted] [ABSTRACT FROM AUTHOR]

The impact of three cold atmospheric plasma (CAP) sources, atmospheric pressure plasma jet (APPJ), two- dimension dielectric barrier discharge (2D-DBD), and nanosecond pulsed discharge (ns-pulsed) on the structure, functionality, and amino acid composition of pea protein was evaluated. Different plasma sources and associated reactive species resulted in protein denaturation, increased surface hydrophobicity, formation of soluble aggregates mostly by disulfide linkages, and changes in secondary structures. Enhancement in surface properties, presence of soluble aggregates, and increase in β-sheet contributed to significant improvement in gelation and emulsification. Enhanced emulsion stability was attributed to relatively small droplet sizes and high surface-charge. Differences among CAP-treated samples were attributed to differences in fluence and composition of plasma-produced reactive species. While all three plasma treatments could be appreciable functionalization approaches, 2D-DBD (Ar + O 2) treatment for 30 min had insignificant effect on the amino acid composition. [Display omitted] • The impact of three cold atmospheric plasma sources on pea protein was elucidated. • The fluence and composition of reactive species caused protein structural changes. • Surface properties, aggregates, and β-sheet changes caused functional enhancement. • All three CAP treatments proved to be appreciable functionalization approaches. • 2D-DBD treatment had the least impact on amino acid composition. [ABSTRACT FROM AUTHOR]

Introduction: Vaccine safety surveillance commonly includes a serial testing approach with a sensitive method for 'signal generation' and specific method for 'signal validation.' The extent to which serial testing in real-world studies improves or hinders overall performance in terms of sensitivity and specificity remains unknown. Methods: We assessed the overall performance of serial testing using three administrative claims and one electronic health record database. We compared type I and II errors before and after empirical calibration for historical comparator, self-controlled case series (SCCS), and the serial combination of those designs against six vaccine exposure groups with 93 negative control and 279 imputed positive control outcomes. Results: The historical comparator design mostly had fewer type II errors than SCCS. SCCS had fewer type I errors than the historical comparator. Before empirical calibration, the serial combination increased specificity and decreased sensitivity. Type II errors mostly exceeded 50%. After empirical calibration, type I errors returned to nominal; sensitivity was lowest when the methods were combined. Conclusion: While serial combination produced fewer false-positive signals compared with the most specific method, it generated more false-negative signals compared with the most sensitive method. Using a historical comparator design followed by an SCCS analysis yielded decreased sensitivity in evaluating safety signals relative to a one-stage SCCS approach. While the current use of serial testing in vaccine surveillance may provide a practical paradigm for signal identification and triage, single epidemiological designs should be explored as valuable approaches to detecting signals. [ABSTRACT FROM AUTHOR]

BCB is emerging as an attractive bonding adhesive for wafer bonding in 3-D integration. Although the bonding strength of BCB is satisfactory with the assist of adhesion promoter, it is found that BCB suffers from interface delamination in harsh chemical or thermal conditions. This paper proposes, at chemical bond level, that the mechanism of interface delamination in KOH solution is attributed to the decomposition of Si O Si bonds at the interface between substrates and AP3000 adhesion promoter as a result of hydrolysis. Silicon dioxide and silicon nitride films with various densities of Si H and Si N bonds are prepared, and the bond densities are measured using infrared spectroscopy. The corresponding interface delamination rates of these films and BCB in KOH solution are measured, and the relations between the bond densities and the delamination rates are obtained for silicon dioxide and silicon nitride. It shows that the delamination rates decrease with the increase in the densities of Si O Si. These results demonstrate that the decomposition of Si O Si in KOH is the main reason for BCB delamination, and increase in the density of Si O Si improves the bonding strength. [ABSTRACT FROM AUTHOR]

Two kinds of aluminum-based coagulants and epichlorohydrin-dimethylamine (DAM-ECH) were used in the treatment of humic acid-kaolin simulated water by coagulation-ultrafiltration (C-UF) hybrid process. Coagulation performance, floc characteristics, including floc size, compact degree, and strength were investigated in this study. Ultrafiltration experiments were conducted by a dead-end batch unit to implement the resistance analyses to explore the membrane fouling mechanisms. Results showed that DAM-ECH aid significantly increased the UV 254 and DOC removal efficiencies and contributed to the formation of larger and stronger flocs with a looser structure. Aluminum chloride (Al) gave rise to better coagulation performance with DAM-ECH compared with poly aluminum chloride (PACl). The consequences of ultrafiltration experiments showed that DAM-ECH aid could reduce the membrane fouling mainly by decreasing the cake layer resistance. The flux reductions for PACl, Al/DAM-ECH (dosing both Al and DAM-ECH) and PACl/DAM-ECH (dosing both PACl and DAM-ECH) were 62%, 56% and 44%, respectively. Results of this study would be beneficial for the application of PACl/DAM–ECH and Al/DAM–ECH composite coagulants in water treatment processes. [ABSTRACT FROM AUTHOR]

[Display omitted] • A cocrystal-entrapped micelle self-assembly strategy is proposed by integrating nanomicellar preparation and cocrystallization technologies together. • Zwitterionic cocrystal of 5-fluorouracil with l -phenylalanine previously reported by our group was encapsulated into nanocarriers, assembling into cocrystal nano-micelles. • The morphology of the cocrystal nano-micelle was characterized by dynamic light scattering and transmission electron microscope. • The in vitro / vivo traits of cocrystal nano-micelles are systematically investigated by combining simulation study of interaction energy with experimental tests. • The long-acting and high-efficiency antitumor activities of the cocrystal nano-micelles were observed. In order to simultaneously perfect the release behavior and antiproliferation effect of anticarcinogen 5-fluorouracil (Fu), and achieve the dual optimization with both long-term efficacy and high-performance, thus gaining bran-new insights into the development of functional nano-formulation for anticancer pharmaceutical cocrystals, a cocrystal-entrapped micelle self-assembly strategy is proposed by integrating nanomicellar preparation and cocrystallization technologies together. Therein, the physico-chemical properties of Fu are regulated by cocrystallization technique, improving its antitumor activity; while the long-term efficacy can be maintained by giving full play to superiority of nanomicellar preparation technology. Along this line, the zwitterionic cocrystal of Fu with l -phenylalanine (Phe), viz. Fu-Phe, previously reported by our group with superior antitumor activities has been encapsulated into nanocarriers PEG-PCL, successfully assembling into cocrystal micelles, which feature the spherical particles of 182.8 nm with good uniformity and dispersion. The in vitro / vivo traits of the cocrystal micelles are systematically investigated by combining theoretical calculations with experimental tests. The outcomes suggest that the entrapment efficiency and drug loading for the obtained cocrystal micelles are far beyond Fu itself micelles, which has also been revealed by the simulation study of the interaction energy between PEG-PCL and the loaded drugs based on the theoretical calculations of electrostatic potential together with geometric optimization. The excellent encapsulation effects of the cocrystal micelles have not only given rise to ameliorated antitumor ability with low IC 50 values, but eventually brought about the better in vivo pharmacokinetics with enhanced bioavailability and extended half-life. Noticeably, the present cocrystal micelles also display significant sustained-release ability relative to Fu micelles, which lays a cornerstone for further realizing the long lasting-efficacy and reducing frequent administration and even toxicity. These findings provide an innovative dosage form for Fu cocrystal with long-acting and high efficiency, thus breaking fresh pathway for the formulation development of antitumor pharmaceutical cocrystals. [ABSTRACT FROM AUTHOR]

[Display omitted] In order to highlight the advantages of cocrystallization technique in perfecting in vitro / vivo natures of marine drug cytarabine (ARC), and fill the gap of the research of marine pharmaceutical cocrystals with synergistic antitumor effects, the first dual-drug cocrystal simultaneously containing ARC and antitumor drug 5-fluorouracil (FU), viz. ARC-FU, is successfully designed and assembled. The accurate structure is perfectly resolved by single-crystal X-ray diffraction and other approaches. The analytical outcomes demonstrate that the codrug cocrystal consists of ARC and FU with a molar ratio of 1:1, in which FU molecule plays an important role by participating in the formation of both "pyrimidine-pyrimidine" and "pyrimidine-sugar" cyclic hydrogen-bonding systems with ARC molecules. In the cocrystal, there are twofold hydrogen-bonding helixes of ARC molecules and a whole three-dimensional hydrogen-bonding network which also contains the aromatic stacking interaction between pyrimidine rings of both components. Such structural feature and aggregation model have crucial influences on the improvements of in vitro/vivo properties, which is methodically verified by the combination of theoretical analyses and experimental measurements. The in vitro studies exhibit the suitably reduced solubility and obviously increased permeability for the cocrystal that is in accord with the theoretical prediction. Importantly, the ameliorated in vitro peculiarities realize in vivo pharmacokinetic optimization including the extended residence time and enhanced relative bioavailability. Of greater significance, ARC exerts synergistic antitumor effects in association with FU that brings about potentiation of cell growth inhibition with lower IC 50. Thus, this research not only provides a novel crystalline form for ARC with forward-looking development value, but also breaks new ground for the development of synergistic antitumor pharmaceutical cocrystals with marine characteristics. [ABSTRACT FROM AUTHOR]

[Display omitted] In order to highlight the advantages of cocrystallization technique in perfecting in vitro / vivo natures of marine drug cytarabine (ARC), and fill the gap of the research of marine pharmaceutical cocrystals with synergistic antitumor effects, the first dual-drug cocrystal simultaneously containing ARC and antitumor drug 5-fluorouracil (FU), viz. ARC-FU, is successfully designed and assembled. The accurate structure is perfectly resolved by single-crystal X-ray diffraction and other approaches. The analytical outcomes demonstrate that the codrug cocrystal consists of ARC and FU with a molar ratio of 1:1, in which FU molecule plays an important role by participating in the formation of both "pyrimidine-pyrimidine" and "pyrimidine-sugar" cyclic hydrogen-bonding systems with ARC molecules. In the cocrystal, there are twofold hydrogen-bonding helixes of ARC molecules and a whole three-dimensional hydrogen-bonding network which also contains the aromatic stacking interaction between pyrimidine rings of both components. Such structural feature and aggregation model have crucial influences on the improvements of in vitro/vivo properties, which is methodically verified by the combination of theoretical analyses and experimental measurements. The in vitro studies exhibit the suitably reduced solubility and obviously increased permeability for the cocrystal that is in accord with the theoretical prediction. Importantly, the ameliorated in vitro peculiarities realize in vivo pharmacokinetic optimization including the extended residence time and enhanced relative bioavailability. Of greater significance, ARC exerts synergistic antitumor effects in association with FU that brings about potentiation of cell growth inhibition with lower IC 50. Thus, this research not only provides a novel crystalline form for ARC with forward-looking development value, but also breaks new ground for the development of synergistic antitumor pharmaceutical cocrystals with marine characteristics. [ABSTRACT FROM AUTHOR]