Search

Urban neighborhoods with locations of environmental contamination, known as brownfields, impact entire neighborhoods, but corrective environmental remedial action on brownfields is often tracked on an individual property basis, neglecting the larger neighborhood-level impact. This study addresses this impact by examining spatial differences between brownfields with unmitigated environmental concerns (open site) and sites that are considered fully mitigated or closed in urban neighborhoods (closed site) on the US census tract scale in Wayne County, MI. Michigan’s Department of Environment, Great Lakes, and Energy’s leaking underground storage tank (LUST) database provided brownfield information for Wayne County. Local indicators of spatial association (LISA) produced maps of spatial clustering and outliers. A McNemar’s test demonstrated significant discordances in LISA categories between LUST open and closed sites (p p

In the present study, liquid chromatography tandem mass equipped method was developed for the separation and quantification of bioactive flavonoids and phenolic acid from fermented mulberry. This novel method was also validated for accuracy, precision and limit of quantification. A good recovery ranging from 80.1 to 92.1% and precision was achieved with seven compounds with the relative standard deviation of intraday ranging from 1.5-3.2 %. Consequently, the validated method for concurrent quantification of seven bioactive compounds in the fermented mulberry using LC-ESI-MS/MS analysis.

As one of the important structures of composite materials, polymethacrylimide (PMI) foam sandwich structure is prone to debonding and delamination defects during manufacturing and service, which seriously affects the mechanical properties of materials. Therefore, it is necessary to detect the defects of foam sandwich structure. A linear frequency modulation infrared thermal wave nondestructive testing system was built to study the correlation between the geometric characteristics (diameter and depth) of the defect and the surface temperature signal and its influence on the detection effect. The image sequence is processed by principal component analysis, discrete Fourier transform, thermal wave signal reconstruction, and other algorithms. Studies have shown that the larger the defect diameter, the shallower the depth, easy to detect defects, detection effect is good. The detection system can effectively detect and identify debonding and de-lamination defects. The thermal wave signal reconstruction method is superior to the principal component analysis method and the discrete Fourier transform method in the signal-to-noise ratio index, which improves the quality of the image and is conducive to the effective identification of the image surface defect information.

Regioselective hydroesterification of alkenes and alkenylphenols was achieved utilizing CO2 as a CO source with the assistance of PMHS.

Synthesis of drug metabolites, which often have complex structures, is an integral step in the evaluation of drug candidate metabolism, pharmacokinetic (PK) properties, and safety profiles. Frequently, such synthetic endeavors entail arduous, multiple-step de novo synthetic routes. Herein, we present the one-step Shono-type electrochemical synthesis of milligrams of chiral α-hydroxyl amide metabolites of two orexin receptor antagonists, MK-8133 and MK-6096, as revealed by a small-scale (pico- to nano-mole level) reaction screening using a lab-built online electrochemistry (EC)/mass spectrometry (MS) (EC/MS) platform. The electrochemical oxidation of MK-8133 and MK-6096 was conducted in aqueous media and found to produce the corresponding α-piperidinols with exclusive regio- and stereoselectivity, as confirmed by high-resolution nuclear magnetic resonance (NMR) characterization of products. Based on density functional theory (DFT) calculations, the exceptional regio- and stereoselectivity for this electrochemical oxidation are governed by more favorable energetics of the transition state, leading to the preferred secondary carbon radical α to the amide group and subsequent steric hindrance associated with the U-shaped conformation of the cation derived from the secondary α-carbon radical, respectively.

Anthocyanins play a critical role in flower colour pattern formation, and their biosynthesis is typically regulated by transcription factors (TFs). Curcuma alismatifolia is a well-known ornamental plant with colourful flowers. However, little is known about the genes that regulate anthocyanin accumulation in C. alismatifolia. In the present study, high-quality RNA was extracted from three flowering stages of ‘Dutch Red’ and the blossoming stage of ‘Chocolate’. In all, 576.45 Mb clean data and 159,687 de-redundant sequences were captured. The Kyoto Encyclopedia of Genes and Genomes analysis showed that the pathways of phenylpropanoid biosynthesis, flavonoid biosynthesis, flavone and flavonol biosynthesis, and terpenoid backbone biosynthesis were the most enriched. Thirty unique isoforms were annotated as encoding enzymes or TFs involved in anthocyanin biosynthesis. Further analysis showed that the up-regulation of anthocyanin biosynthesis genes was associated with the red colour formation of ‘Dutch Red’, and their expression was induced at the initial flowering stage. The gene flavonoid 3′, 5′-hydroxylase, a key enzyme in the formation of delphinidin-based anthocyanins, reduced expression in ‘Chocolate’. In addition, we identified totally 14 TFs including 11 MYB proteins and 3 WD proteins, which might play important roles in the regulation of anthocyanin biosynthesis. The quantitative Real-Time Polymerase Chain Reaction (qRT-PCR) results were generally consistent with the high-throughput sequencing results. Together, the results of our study provide a valuable resource for the regulatory mechanism of anthocyanin biosynthesis in C. alismatifolia and for the breeding of Curcuma cultivars with novel and charming flower colours.

Xanthine dehydrogenase, a member of the molybdenum enzyme family, participates in purine metabolism and catalyzes the generation of ureides from xanthine and hypoxanthine. However, the mechanisms by which xanthine dehydrogenase affects rice growth and development are poorly understood. In the present study, we identified a mutant with early leaf senescence and reduced tillering that we named early senescence and less-tillering 1 (esl1). Map-based cloning revealed that ESL1 encodes a xanthine dehydrogenase, and it was expressed in all tissues. Chlorophyll content was reduced and chloroplast maldevelopment was severe in the esl1 mutant. Mutation of ESL1 led to decreases in allantoin, allantoate, and ABA contents. Further analysis revealed that the accumulation of reactive oxygen species in esl1 resulted in decreased photosynthesis and impaired chloroplast development, along with increased sensitivity to abscisic acid and abiotic stresses. Ttranscriptome analysis showed that the ESL1 mutation altered the expression of genes involved in the photosynthesis process and reactive oxygen species metabolism. Our results suggest that ESL1 is involved in purine metabolism and the induction of leaf senescence. These findings reveal novel molecular mechanisms of ESL1 gene-mediated plant growth and leaf senescence.

Dryopteris sect. Diclisodon is a small section of ferns with about 12 species mainly distributed in East Asia. Here, we carried out morphological and phylogenetic analyses of this section. A new species from southwest China, D. gaoligongensis, is described and illustrated. Dryopteris gaoligongensis resembles D. indonesiana and D. sparsa, but differs by having a creeping rhizome and large 4-pinnate fronds. We also show that D. glabrior Ching & Z.Y. Liu is a distinct species; however, because it is a later homonym of D. glabrior Copeland, it should be renamed D. renchangiana. We conclude that a species previously known as D. nitidula, also an illegitimate homonym, should be recognized with a new name, D. sinonepalensis. We resolve the phylogenetic position of D. yoroii as sister to other sampled species of D. sect. Diclisodon. Our phylogenetic analyses confirm the distinctiveness of D. gaoligongensis, D. renchangiana, and D. sinonepalensis. A key to species of D. sect. Diclisodon in China is provided.

BackgroundVascular Dementia (VaD) refers to dementia caused by cerebrovascular disease and/or reduced blood flow to the brain and is the second most common form of dementia after Alzheimer’s disease. We previously found that in middle-aged rats subjected to a multiple microinfarction (MMI) model of VaD, treatment with AV-001, a Tie2 receptor agonist, significantly improves short-term memory, long-term memory, as well as improves preference for social novelty compared to control MMI rats. In this study, we tested the early therapeutic effects of AV-001 on inflammation and glymphatic function in rats subjected to VaD.MethodsMale, middle-aged Wistar rats (10–12 m), subjected to MMI, were randomly assigned to MMI and MMI + AV-001 treatment groups. A sham group was included as reference group. MMI was induced by injecting 800 ± 200, 70–100 μm sized, cholesterol crystals into the internal carotid artery. Animals were treated with AV-001 (1 μg/Kg, i.p.) once daily starting at 24 h after MMI. At 14 days after MMI, inflammatory factor expression was evaluated in cerebrospinal fluid (CSF) and brain. Immunostaining was used to evaluate white matter integrity, perivascular space (PVS) and perivascular Aquaporin-4 (AQP4) expression in the brain. An additional set of rats were prepared to test glymphatic function. At 14 days after MMI, 50 μL of 1% Tetramethylrhodamine (3 kD) and FITC conjugated dextran (500 kD) at 1:1 ratio were injected into the CSF. Rats (4–6/group/time point) were sacrificed at 30 min, 3 h, and 6 h from the start of tracer infusion, and brain coronal sections were imaged using a Laser scanning confocal microscope to evaluate tracer intensities in the brain.ResultTreatment of MMI with AV-001 significantly improves white matter integrity in the corpus callosum at 14 days after MMI. MMI induces significant dilation of the PVS, reduces AQP4 expression and impairs glymphatic function compared to Sham rats. AV-001 treatment significantly reduces PVS, increases perivascular AQP4 expression and improves glymphatic function compared to MMI rats. MMI significantly increases, while AV-001 significantly decreases the expression of inflammatory factors (tumor necrosis factor-α (TNF-α), chemokine ligand 9) and anti-angiogenic factors (endostatin, plasminogen activator inhibitor-1, P-selectin) in CSF. MMI significantly increases, while AV-001 significantly reduces brain tissue expression of endostatin, thrombin, TNF-α, PAI-1, CXCL9, and interleukin-6 (IL-6).ConclusionAV-001 treatment of MMI significantly reduces PVS dilation and increases perivascular AQP4 expression which may contribute to improved glymphatic function compared to MMI rats. AV-001 treatment significantly reduces inflammatory factor expression in the CSF and brain which may contribute to AV-001 treatment induced improvement in white matter integrity and cognitive function.

The newly identified Neoproterozoic Yuanmou high-Nb mafic and adakitic rocks at the western margin of the Yangtze Block in South China are investigated for petrogenesis and geodynamic implications. Zircon U-Pb ages show the adakitic granodiorite host and mafic microgranular enclaves (MMEs) were synchronously emplaced at 811−806 Ma, and were cut by an 802 ± 11.5 Ma mafic dike. The medium-grained granodiorites consist mainly of plagioclase, quartz, K-felspar, biotite, and amphibole. High SiO2 (62.8−67.5 wt%), Al2O3 (13.1−16.8 wt%) contents, high Sr/Y (17.4−49.0), and (La/Yb)N (16.3−52.6) but low Y (6.83−16.1 ppm) and Yb (0.74−1.82 ppm) concentrations of the granodiorites point toward their calc-alkaline and adakitic nature. Further, their high Dy/Yb (1.52−2.31) and Gd/Y (2.35−4.43) and low K2O/Na2O (0.22−0.48) and Th/La (0.14−0.20) ratios, constant bulk rock εNd(t) (−0.5 to −1.5) and zircon εHf(t) (0.0 to +2.3) values, suggest that the granodiorites were derived from partial melting of a mafic lower crustal source. The MMEs in the granodiorites and mafic dike intrusions are composed of amphibole, plagioclase, clinopyroxene, and olivine, and have similar chemical compositions, such as high Nb (15.7−41.9 ppm) and TiO2 (2.13−3.39 wt%) contents and high Nb/U (18.7−30.9) values, akin to alkaline high-Nb basalts (HNB). Their variable Ba/Nb (7.68−79.2), Nb/Zr (0.09−0.16), high Nb/Th (5.47−6.68), and low Th/Zr (0.01−0.03) and La/Nb (1.03−1.37) ratios indicate a mantle source modified by melts derived from subducted oceanic crust and sediments. The Yuanmou HNB with high εNd(t) (+4.8 to +6.9) were probably generated during back-arc extension by decompression melting of a mantle source metasomatized by adakitic slab melts formed during earlier stages of the subduction. This implies that the location of the back-arc was far from the subducted oceanic slab, possibly due to a slab rollback process. In this scenario, HNB intrusions provided the heat for partial melting and adakitic melt formation in the mafic lower crust. The model suggests that the Yuanmou and other similar associations of HNBs and adakitic rocks emplaced along the western margin of the Yangtze Block are products of a widespread Neoproterozoic back-arc extension.

Two-dimensional covalent organic frameworks (2D COFs) are promising for gas sensing owing to the large surface area, abundant active sites, and their semiconducting nature. However, 2D COFs are usually produced in the form of insoluble micro-crystallites. Their poor contacts between grain boundaries severely suppress the conductivity, which are too low for chemresistive gas sensing. Here, we demonstrate that halide perovskites can be employed as electric glues to bond 2D COF crystallites to improve their conductivity by two orders of magnitude, activating them to detect NO2 with high selectivity and sensitivity. Resonant microcantilever, grand canonical Monte Carlo, density functional theory and sum-frequency generation analyses prove that 2D COFs can enrich and transfer electrons to NO2 molecules, leading to increased device conductivity. This work provides a facile approach for improving the conductivity of polycrystalline 2D COF films and may expand their applications in semiconductor devices, such as sensors, resistors, memristors and field-emission transistors.

BackgroundThe advancement of digital technology implies the importance of polychronic learning. Since polychronicity is not equivalent to multitasking behavior, they need to be considered separately. However, less research has been explored on how polychronicity is related to multitasking behavior in the educational field.ObjectiveTo explore the relationships among polychronicity, multitasking behavior and learning performance (including knowledge acquisition and learning satisfaction) in an online learning environment.MethodsThe relationship among variables was analyzed from 865 responses obtained from a questionnaire survey, and independent sample t tests and SEM analysis were used to examine the research hypotheses.ResultsCollege students showed a higher frequency of multitasking behavior, time tangibility and scheduling preference, and learning satisfaction in multitasking online learning environments than high school students. Additionally, college students were different from high school students on the paths of involvement with people to multitasking behavior (Δ χ2= 5.42, p = 0.02) and scheduling preference to learning satisfaction (Δχ2 = 9.54, p = 0.002).ConclusionThe relationship among polychronicity, multitasking behavior and perceived learning performance in an online learning environment varies by student educational stage.

Changes of cell types based on (a) MCP-Counter and (b) Danaher module with post- vs pre-treatment samples. All tests were performed by non-parametric Wilcoxon test.

CONSORT diagram

Volcano plots of differentially expressed genes of different clinical scenarios (a) partial responders vs non-partial responders (b) progression-free survival longer vs shorter than 6 months (c) post- and pre-treatment samples.

Cell type predictive of treatment efficacy. Cell type differences of (a) partial response vs non-partial responders (b) progression-free survival longer vs shorter than 6 months by MCP-Counter. All p-values were derived from non-parametric Wilcoxon test.

Supplementary Table 1a. Differentially expressed genes between Post-treatment vs Pre-treatment; Supplementary Table 1b. Differentially expressed genes between Responders vs Nonresponders; Supplementary Table 1c. Differentially expressed genes between PFS longer than 6 months vs PFS shorter than 6 months.

Decision on Final Phase II dose; Guidelines combination dose level adjustments in the phase Ib phase; Schema for dose adjustments if more than 2 patients have DLT; Definitions of DLT

Purpose:Satisfactory treatment options for advanced leiomyosarcoma and liposarcoma are limited. The LEADER study (NCT03526679) investigated the safety and efficacy of lenvatinib plus eribulin.Patients andMethods:LEADER is a multicenter phase Ib/II study for advanced leiomyosarcoma or liposarcoma. The phase Ib part enrolled 6 patients to determine the dose-limiting toxicity (DLT) and recommended phase II dose (RP2D) with the starting dose of lenvatinib 18 mg/day and eribulin 1.1 mg/m2 D1, D8 every 21 days. The primary endpoint of the phase II part was objective response rate (ORR) based on Response Evaluation Criteria in Solid Tumors 1.1, with phase Ib patients preplanned to be included in the efficacy analysis. Translational analyses were based on the transcriptomic data obtained from the NanoString nCounter platform.Results:Thirty patients were enrolled (leiomyosarcoma 21, liposarcoma 9); the median age was 59. One patient had to temporarily stop lenvatinib due to grade 2 arthritis in the first cycle, meeting DLT criteria. Four of 6 patients had to decrease the dose of lenvatinib to 14 mg between cycles two and three. RP2D was determined at lenvatinib 14 mg/day and eribulin 1.1 mg/m2. The confirmed ORR was 20%, and the ORR was not significantly different between phase Ib/II cohorts (P = 0.23). The median progression-free survival was 8.56 months (95% confidence interval, 4.40–not reached). Translational studies suggested increased dendritic cells in the tumor microenvironment (TME) after treatment.Conclusions:Lenvatinib plus eribulin has a manageable safety profile and exhibits promising efficacy for treating advanced leiomyosarcoma and liposarcoma.

A method for purifying compounds bearing pyridine structure from Mitsunobu reaction mixtures using zinc chloride and releasing bipyridines from Ullmann coupling reaction mixtures by using sulfide anion for competitively coordinating the copper ion were developed for the facile synthesis of the chiral 2,2′-bipyridine ligand (Ra ,S,S)-C3-ACBP. With these improvements, an improved synthesis of the chiral ligand at a 7 gram scale has been fulfilled in 48% overall yield without column chromatography within 3–4 days.

Background and purposeNon-alcoholic fatty liver disease (NAFLD) is known to adversely affect stroke recovery. However, few studies investigate how stroke elicits liver dysfunction, particularly, how stroke in type 2 diabetes mellitus (T2DM) exacerbates progression of NAFLD. In this study, we test whether exosomes harvested from human umbilical cord blood (HUCBC) derived CD133 + cells (CD133 + Exo) improves neuro-cognitive outcome as well as reduces liver dysfunction in T2DM female mice.MethodsFemale, adult non-DM and T2DM mice subjected to stroke presence or absence were considered. T2DM-stroke mice were randomly assigned to receive PBS or Exosome treatment group. CD133 + Exo (20 μg/200 μl PBS, i.v.) was administered once at 3 days after stroke. Evaluation of neurological (mNSS, adhesive removal test) and cognitive function [novel object recognition (NOR) test, odor test] was performed. Mice were sacrificed at 28 days after stroke and brain, liver, and serum were harvested.ResultsStroke induces severe and significant short-term and long-term neurological and cognitive deficits which were worse in T2DM mice compared to non-DM mice. CD133 + Exo treatment of T2DM-stroke mice significantly improved neurological function and cognitive outcome indicated by improved discrimination index in the NOR and odor tests compared to control T2DM-stroke mice. CD133 + Exo treatment of T2DM stroke significantly increased vascular and white matter/axon remodeling in the ischemic brain compared to T2DM-stroke mice. However, there were no differences in the lesion volume between non-DM stroke, T2DM-stroke and CD133 + Exo treated T2DM-stroke mice. In T2DM mice, stroke induced earlier and higher TLR4, NLRP3, and cytokine expression (SAA, IL1β, IL6, TNFα) in the liver compared to heart and kidney, as measured by Western blot. T2DM-stroke mice exhibited worse NAFLD progression with increased liver steatosis, hepatocellular ballooning, fibrosis, serum ALT activity, and higher NAFLD Activity Score compared to T2DM mice and non-DM-stroke mice, while CD133 + Exo treatment significantly attenuated the progression of NAFLD in T2DM stroke mice.ConclusionTreatment of female T2DM-stroke mice with CD133 + Exo significantly reduces the progression of NAFLD/NASH and improves neurological and cognitive function compared to control T2DM-stroke mice.

Entecavir (ETV) and tenofovir disoproxil fumarate (TDF) are the first-line treatment agents for chronic hepatitis B virus (HBV). Recently, whether the degree to which the risk of hepatocellular carcinoma (HCC) may be reduced by ETV vs TDF has been debated. We compared the incidence of HCC among treatment-naïve patients receiving TDF vs ETV in the United States.From a large administrative medical claims database of commercially insured patients, we identified 166,933 adults with a diagnosis of chronic hepatitis B and a minimum of 12 months of prior enrolment, of whom 3934 and 6127 initiated ETV and TDF respectively. Fine-Gray hazard regression models incorporating treatment propensity scores (PS) were used to estimate the risk of HCC incidence associated with TDF vs ETV; variables considered for adjustment included demographic characteristics, concomitant medication use and baseline comorbidities, as well as competing events including liver transplantation and medication changes.After PS weighting, the TDF and ETV groups were well-matched. During the follow-up, 90 patients developed HCC, including 50 receiving ETV and 40 receiving TDF, giving rise to crude incidence rates of 0.62 per 100 person-years (PY) and 0.30 per 100 PY respectively. In PS-weighted, multivariable analysis, TDF was associated with a subdistribution hazard ratio for HCC of 0.58 (95% confidence interval [CI]: 0.38-0.89) compared to ETV. Results were similar when patients ≥40 years and men and women were analysed separately.Among commercially insured, treatment-naïve patients with chronic hepatitis B in the United States, treatment with TDF was associated with significantly lower risk of HCC than ETV.

Hepatitis B virus (HBV) infection causes hepatocellular carcinoma but its association with other cancers is not well established. We compared age-adjusted incidence of primary cancers among 5773 HBV-infected persons with US cancer registries during 2006–2018. Compared with the US population, substantially higher incidence among HBV-infected persons was observed for hepatocellular carcinoma (standardized rate ratio [SRR], 30.79), gastric (SRR, 7.95), neuroendocrine (SRR, 5.88), cholangiocarcinoma (SRR, 4.62), and ovarian (SRR, 3.72) cancers, and non-Hodgkin lymphoma (SRR, 2.52). Clinicians should be aware of a heightened potential for certain nonhepatic malignancies among hepatitis B patients, as earlier diagnosis favors improved survival.