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Six polycyclic aromatic hydrocarbons (PAHs) including naphthalene (Nap), fluorene (Flu), phenanthrene (Phe), fluoranthene (Fla), pyrene (Pyr), and chrysene (Chr) were detected in runoff from five athletic fields during three rainfall events. The event mean concentration (EMC) of ∑6PAHs ranged from 3.96 to 23.23 μg/L, which was much higher than the EMC in urban traffic area runoff. Except for Nap, the PAH concentrations followed in the order of artificial turf > badminton court > basketball court > plastic runway > optennis court. The surface characteristics of the athletic fields, such as the composition of materials and roughness, played an essential role in the release of PAHs. ∑6PAHs concentration during the 2nd rainfall event (July 22nd) was the highest among the three rainfall events, indicating that high rainfall intensity facilitated the PAHs release. PAHs during three rainfall events showed little first flush effect except for the artificial turf during the 2nd (22nd July) and 3rd (29th July) rainfall events. The first flush effect could be affected by rainfall characters, PAH properties, and surface characteristics of athletic fields. Ecological risk assessment showed that PAHs in runoff corresponded to moderate-to-high risk, while health risk assessment showed that PAHs could pose a potential carcinogenic danger to human health via dermal contact.

The regulatory mechanism of the MBW (MYB-bHLH-WD40) complex in safflower (Carthamus tinctorius) remains unclear. In the present study, we show that the separate overexpression of the genes CtbHLH41, CtMYB63, and CtWD40-6 in Arabidopsis thaliana increased anthocyanin and procyanidin contents in the transgenic plants and partially rescued the trichome reduction phenotype of the corresponding bhlh41, myb63, and wd40-6 single mutants. Overexpression of CtbHLH41, CtMYB63, or CtWD40-6 in safflower significantly increased the content of the natural pigment hydroxysafflor yellow A (HYSA) and negatively regulated safflower petal size. Yeast two-hybrid, functional, and genetic assays demonstrated that the safflower E3 ligase CtBB1 (BIG BROTHER 1) can ubiquitinate CtbHLH41, marking it for degradation through the 26S proteasome and negatively regulating flavonoid accumulation. CtMYB63/CtWD40-6 enhanced the transcriptional activity of CtbHLH41 on the CtDFR (Dihydroflavonol 4-reductase) promoter. We propose that the MBW-CtBB1 regulatory module may play an important role in coordinating HYSA accumulation with other response mechanisms. This article is protected by copyright. All rights reserved.

Colorectal cancer (CRC) raises concerns to people because of its high recurrence and metastasis rate, diagnosis challenges, and poor prognosis. Various studies have shown the association of altered autophagy with tumorigenesis, tumor-stroma interactions, and resistance to cancer therapy in CRC. Autophagy is a highly conserved cytosolic catabolic process in eukaryotes that plays distinct roles in CRC occurrence and progression. In early tumorigenesis, autophagy may inhibit tumor growth through diverse mechanisms, whereas it exhibits a tumor promoting function in CRC progression. This different functions of autophagy in CRC occurrence and progression make developing therapies targeting autophagy complicated. In this review, we discuss the classification and process of autophagy as well as its dual roles in CRC, functions in the tumor microenvironment, cross-talk with apoptosis, and potential usefulness as a CRC therapeutic target.

Age structure and delay play a significant role in determining the dynamics of the diseases. In this paper, an SEIRS epidemic model with age structure and time delay is investigated, where the loss of the acquired immunity and delay are incorporated. Through some rigorous analyses, an explicit formula for the basic reproduction number of the model is calculated, and some results about stability and instability of equilibria for the model are established. The findings show that the age structure and delay can produce Hopf bifurcation for an SEIRS model. The numerical examples are executed to illustrate the theoretical results.

The mechanism of antibiotic photodegradation on SA-BiOCl.

The prevalence of nonalcoholic fatty liver disease (NAFLD) is increasing worldwide with ill-defined etiology and pathogenesis, and no approved effective therapy is presently available. Exosome-dependent intercellular communication has been identified as a potential signaling involved in tissue repair. Unfortunately, the exact influence and underlying mechanism of mesenchymal stem cells (MSCs)-derived exosome (Exo) in modulating fatty liver have not been well determined. Here in our study, in vitro results initially showed that human umbilical cord-derived mesenchymal stem cells (hUC-MSCs)-derived Exo treatment significantly suppressed lipid accumulation, reactive oxygen species (ROS) generation and inflammatory response in palmitate (PA)-stimulated mouse hepatocytes. Consistently, MSCs-derived Exo administration strongly ameliorated metabolic disorders, hepatic dysfunction and steatosis in high fat diet (HFD)-induced mouse model with NAFLD. Furthermore, Exo derived from MSCs significantly alleviated hepatic lipid metabolism disturbance, inflammation and oxidative stress induced by HFD. Exo treatment resulted in a stronger increase in miR-24-3p expression in hepatocytes. Reducing miR-24-3p in MSCs markedly abrogated the protective effects of Exo in hepatocytes under PA stimulation. Mechanistically, miR-24-3p directly targeted Kelch-like ECH-associated protein 1 (Keap-1), and suppressed its expression. In addition, the effects of MSCs-derived exosomal miR-24-3p to restrain lipid accumulation, ROS generation and inflammation in vitro were largely Keap-1 dependent via Keap-1 depression. Collectively, our study demonstrated that MSCs-derived exosomal miR-24-3p had hepaprotective effects through targeting Keap-1 signaling, providing a potential therapeutic value for NAFLD treatment.

Bougainvillea Comm. ex Juss. (Nyctaginaceae; Bougainvillea) is a popular ornamental plant with vigorous growth, luxuriant blooming, colorful bracts, and a high tolerance to the stresses of temperature, drought, and soil pollution, and thus is widely cultivated in tropical and subtropical regions. However, the paucity of information on ploidy and the genomic constitution is a significant challenge to genome research and cultivar improvement. We present a flow cytometry method for ploidy detection in bougainvillea based on evaluating different lysates and tissues, identify the ploidy level of a batch of bougainvillea accessions, and infer the genome size of horticultural species Bougainvillea glabra, Bougainvillea spectobilis, and Bougainvillea peruviana. The results show that tender leaves and woody plant buffer (WPB) were optimal for flow cytometry analysis. The 2C nuclear DNA amounts in 176 bougainvillea accessions ranged from 4.66 ± 0.04 to 12.26 ± 0.1 pg, which represents 161 diploids, 13 triploids, 1 tetraploid, and 1 di-tetraploid mixoploid. For B. glabra, B. spectobilis, and B. peruviana, the mean 1C values were 3.201, 3.066, and 2.915 pg, respectively. The genome size of B. glabra was significantly larger than that of B. peruviana (P = 0.0004), but had no significant variation with that of B. spectobilis (P = 0.1061). These results reveal fundamental cytogenetic information for bougainvillea that are beneficial to whole-genome sequencing and hybrid breeding programs.

JNJ-73763989, composed of the 2 short-interfering RNA triggers JNJ-73763976 and JNJ-73763924, targets all hepatitis B virus messenger RNAs, thereby reducing all viral proteins. In this phase 1, single-site, open-label, parallel-group, randomized study, participants were given 1 subcutaneous injection of JNJ-73763989 (100 or 200 mg) to investigate the pharmacokinetics, safety, and tolerability of JNJ-73763989 in healthy Chinese adult participants. Plasma and urine pharmacokinetic parameters were determined for each trigger up to 48 hours after dosing. Eighteen participants, 9 per dose group, were enrolled. The median age and weight were 33.0 years and 73.65 kg; 83.3% were male. Exposure of both triggers increased dose proportionally. Median time to maximum concentration ranged from 6.0 to 10.0 hours, and mean elimination half-life ranged from 4.5 to 4.8 hours across both triggers and doses. Mean urinary excretion for JNJ-73763976 and JNJ-73763924 ranged from 17.7% to 19.4% and 13.1% to 13.2% for the 100- and 200-mg dose groups, respectively. All treatment-emergent adverse events (AEs) were mild and resolved by study end, and no AEs or serious AEs resulted in premature study discontinuation or death. Overall, the pharmacokinetics of JNJ-73763989 in healthy Chinese participants were consistent with previous studies, and JNJ-73763989 was generally safe and well tolerated after a single dose.

Methyl methacrylate (MMA) has emerged as an essential industrial monomer. However, the toxic by-production and shortage supply of MMA in the global market has gained great attention. Herein, a one-step synthesis to produce MMA from isobutene via a direct oxidative esterification process has been demonstrated to curb the aforementioned downsides. Thermodynamic analysis via Gibbs free energy minimization method proved the feasibility of this route via the equilibrium constant. Despite tert-butanol and isobutane showed higher equilibrium constant than isobutene, they should be avoided. Isobutane is highly flammable while the precursor of tert-butanol is exorbitant. Thus, isobutene was selected for the equilibrium compositions screening. Isobutene conversion was 90% and 15% MMA yield at 700 °C and IBN: O2: MeOH ratio with 1:7:1. This route is mainly limited by the generation of side reactions from the reaction of CH3OH and O2. By varying the feedstock ratio at 1:2:1, the MMA yield increased to ~25%. Copyright © 2022 by Authors, Published by BCREC Group. This is an open access article under the CC BY-SA License (https://creativecommons.org/licenses/by-sa/4.0).

Although many dopant-free hole transport materials (HTMs) for perovskite solar cells (PSCs) have been investigated in the literature, novel and useful molecular designs for high-performance HTMs are still needed. In this work, a hydrogen-bonding association system (NH⋯CO) between amide and carbonyl is introduced into the pure HTM layer. Our study demonstrates that the hydrogen-bonding association can not only significantly increase the HTM’s hole transport mobility and functionalize the surface passivation to the perovskite layer, but also form Pb–N coordination bonds at the interface to promote the hole extraction while hindering the interfacial charge recombination. As a result, the PSCs based on dopant-free hydrogen-bonded HTMs can achieve a champion power conversion efficiency (PCE) of 21.62%, which is around 32% higher than the pristine PSC without the hydrogen-bonding association. Furthermore, the dopant-free hydrogen-bonded HTMs based device shows remarkable long-term light stability, retaining 87% of its original value after 500 h continuous illumination, measured at the maximum power point. This work not only provides a potential HTM with hydrogen-bonding association in PSCs, but also demonstrates that introducing hydrogen bonding into the materials is a useful and simple strategy for developing high-performance dopant-free HTMs. publishedVersion

Transforming growth factor-beta 2 (TGFβ2) is a major contributor to the pathologic changes occurring in human trabecular meshwork (HTM) cells in primary open-angle glaucoma (POAG). TGFβ2 activates extracellular-signal-regulated kinase (ERK) and Rho-associated kinase (ROCK) signaling pathways, both affecting HTM cell behavior. However, exactly how these signaling pathways converge to regulate HTM cell contractility is unclear. Here, we investigated the molecular mechanism underlying TGFβ2-induced pathologic HTM cell contractility, and the crosstalk between ERK and ROCK signaling pathways with different culture substrates.Hydrogels were engineered by mixing collagen type I, elastin-like polypeptide, and hyaluronic acid, each containing photoactive functional groups, followed by UV crosslinking. Primary HTM cells were seeded atop pre-formed hydrogels for comparisons with glass, or encapsulated within the hydrogels. Changes in actin cytoskeleton, extracellular matrix (ECM) production, phospho-myosin light chain (p-MLC) levels, and hydrogel contraction were assessed.HTM cell morphology and filamentous (F)-actin organization were affected by the underlying culture substrates. TGFβ2 increased HTM cell contractilityOur data suggest that ERK signaling negatively regulates ROCK-mediated HTM cell contractility. These findings emphasize the critical importance of using tissue-mimetic ECM substrates for investigating HTM cell physiology and glaucomatous pathophysiology

The incidence of lung cancer is extremely high. For treatment, the chemotherapy of lung cancer is low, and drug resistance and recurrence are frequently observed, in which hypoxic tumor microenvironments play a key role. We investigated the upregulation of long non-coding ribonucleic acid (lncRNA) H19 expression and the induction of drug resistance in non-small cell lung cancer (NSCLC) cells under hypoxic conditions.We used cobaltous chloride (CoCl2) to create hypoxic culture environments for the A549 and H1650 cells, and they were divided into normoxia and hypoxia groups. We used real-time quantitative PCR detecting system (qPCR) to detect the messenger RNA (mRNA) expressions of lncRNA H19, hypoxia-inducible factor 1-α (HIF1-α), multi-drug resistant associated protein 1 (MRP1), and heme oxygenase-1 (HO-1), and western blot to detect the protein expressions of HIF1-α, MRP1, HO-1, and P-glycoprotein (P-gp). We performed cell migration and invasion assays. Annexin V-Allophycocyanin (APC) and flow cytometry were used to detect the apoptotic rates.We found that the expression levels of lncRNA H19, HIF1-α, HO-1, multi-drug resistant associated protein 1 (MRP1), and P-glycoprotein increased significantly in the NSCLC cell lines (A549 and H1650) under hypoxic conditions, as determined by the qPCR and western blot analyses. In NSCLC cells cultured under hypoxic conditions, the invasion and migration ability of tumor cells increased significantly, resistance to cisplatin increased, and cisplatin-induced apoptosis decreased considerably. In addition, chemoresistance was also induced in tumor cells under hypoxic conditions.These results indicate that hypoxia increased the expression levels of lncRNA H19 and induced chemoresistance in tumor cells.

The Earth’s geologic record of Milankovitch cycles closely tracks Solar System solutions for the past 50 million years. Prior to 50 million years ago (Ma), however, the solutions lose accuracy rapidly due to chaotic behavior of the Solar System. Here we reconstruct a 10.173 million year-long record from 82.358 Ma to 92.531 Ma of Earth’s orbital parameters from a continental lacustrine sequence in the Songliao Basin, China, constrained by four in situ high-resolution radioisotopic U-Pb ages and magnetic reversal stratigraphy. Analysis of thorium and ostracode shell abundance records from the Songliao Basin reveal evidence for two chaotic secular resonance transitions in the orbital motions of Earth and Mars from 85.2 Ma to 91.55 Ma. The evidence validates similar observations in western North American marine stratigraphy. A unique phasing between the observed orbital eccentricity and obliquity modulations may explain the anoxic events that occurred in both marine and continental environments during this time. Taken together, the continental and marine stratigraphic evidence demonstrates a strong global reach of Late Cretaceous Milankovitch cycles, and provides an important constraint on Solar System chaoticity and the calculation of accurate orbital solutions prior to 50 Ma.

Myocardial ischemia/reperfusion injury (MI/RI) is the main cause of deaths in the worldwide, leading to severe cardiac dysfunction. Resveratrol (RSV) is a polyphenol plant-derived compound. Our study aimed to elucidate the underlying molecular mechanism of preconditioning RSV in protecting against MI/RI. Mice were ligated and re-perfused by the left anterior descending branch with or without RSV (30 mg/kg·ip) for 7 days. Firstly, we found that RSV pretreatment significantly alleviated myocardial infarct size, improved cardiac function and decreased oxidative stress. Furthermore, RSV activated p-AMPK and SIRT1, ameliorated inflammation including the level of TNF-α and IL-1β, and promoting autophagy level. Moreover, neonatal rat ventricular myocytes (NRVMs) and H9c2 cells with knockdown the expression of AMPK, SIRT1 or FOXO1 were used to uncover the underlying molecular mechanism for the cardio-protection of RSV. In NRVMs, RSV increased cellular viability, decreased LDH release and reduced oxidative stress. Importantly, Compound C(CpC) and EX527 reversed the effect of RSV against MI/RI in vivo and in vitro and counteracted the autophagy level induced by RSV. Together, our study indicated that RSV could alleviate oxidative stress in cardiomyocytes through activating AMPK/SIRT1-FOXO1 signallingpathway and enhanced autophagy level, thus presenting high potential protection on MI/RI.

The small GTPase ADP-ribosylation factor 6 (ARF6) mediates chemokine (C-C motif) ligand 18 (CCL18)-induced activation of breast cancer (BC) metastasis through its downstream effector AMAP1. However, the molecular mechanisms underlying CCL18 up-regulating ARF6 remain largely unclear. Here, microRNAs (miRNAs) that target ARF6 were predicted and selected in high metastatic BC cells treated with CCL18. Next, we assessed the role of exosomal miR-760

Abstract: Paraffin emulsion is a highly dispersed, thermodynamically unstable system. Emulsifiers play a key role in promoting emulsion formation and improving emulsion stability. However, a single emulsifier has limitations in maintaining emulsion stability, usually, it is necessary to compound more than two emulsifiers or add other additives to make the paraffin emulsion have better stability. Therefore, how to keep paraffin emulsion high dispersibility and stability for a long time are the problems that the majority of researchers have been concerned about. This paper expounded the instability mechanism of paraffin wax emulsion. The process of paraffin emulsion destabilization is the process of gradually reducing the free energy of the system and the interaction force between emulsion droplets determines the speed of emulsion destabilization. Sedimentation and stratification, flocculation, coalescence, and Ostwald Ripening were the main factors leading to paraffin instability; the prevention and improvement methods are proposed for the above four mechanisms. From the instability mechanism, the factors affecting the stability of paraffin emulsion mainly include the mechanical strength and film elasticity of the interface film, the interfacial charge or obstruction between the emulsion droplets, the appropriate system viscosity, and the uniform droplet size distribution will affect the stability of the paraffin emulsion. Through literature research, several methods to improve the stability of paraffin emulsion were summarized. Polar paraffin has good emulsifying properties, compounding with paraffin can not only reduce the amount of emulsifier but also enhance the stability of paraffin emulsion, adding thickeners can reduce the Brownian motion of droplets and improve the chemical and mechanical stability of wax emulsions, the addition of ionic surfactants can reduce the diffusion rate of the dispersed phase, the addition of inorganic salts can make the emulsion droplets generate strong repulsion when they are close to each other, and improve the stability of the emulsion, the addition of small molecular alcohols can improve the flexibility of the oil-water interface film properties, reduce the surface tension coefficient of the emulsion, and increase the stability of the paraffin emulsion. This paper can provide a theoretical reference for the research on the stability of paraffin emulsion.

This paper studies a Balakrishnan–Taylor viscoelastic wave equation with strong time-dependent delay. Under suitable assumptions on the coefficients of the delay term, we establish a generalized stability result, which improve some earlier results in the literature.

A new paleomagnetic study is carried out on the ca. 1150 Ma mafic dykes from the North China Craton (NCC). After stepwise thermal demagnetization, most samples yielded two components. The low-temperature component directs north and down with intermediate inclination, which is interpreted as a viscous remanent magnetization of the present magnetic field. The high-temperature component (HC) directs east and down with steep inclination. Positive baked-contact tests and a reversal test suggest the HC is primary. Combined with the relevant paleomagnetic data previously published (Hou et al., 2009; Wang et al., 2020), a new pole is calculated from more than thirty high-quality virtual geomagnetic poles. The pole has averaged out the paleo-secular variation and is different from any younger paleomagnetic poles of the NCC. The pole places the NCC in a mid-latitude region. Combined with the reported 1230-780 Ma paleomagnetic poles from NCC and Laurentia, the new results suggest the two continents assembled during ca. 1150–1110 Ma at high-latitude region. They then together moved to low-latitude region and merged with Amazonia, Baltica, Kalahari to become a part of Rodinia.

We present new rock magnetic and paleomagnetic results from late Mesoproterozoic carbonate successions of the Jingeryu Formation (Fm) in the northern North China craton (NCC). Rock magnetic experiments, including thermomagnetic susceptibility curves, isothermal remanent magnetization (IRM) and thermal demagnetization of three-axis IRM, carried out for representative samples from the Jingeryu Fm indicate that both hematite and magnetite are abundant in the purplish-red limestone in the lower part of strata and the magnetic carriers of the pale blue limestone in the upper part are magnetite grains. For most samples subjected to stepwise thermal demagnetization, a high-temperature component (HTC) was isolated after removing a low-temperature component of viscous magnetic remanence acquired in recent geomagnetic fields. The HTC is characterized by steep inclinations, whose primary nature is supported by the presence of geomagnetic reversals. The similarities in paleomagnetic results and the correlatable lithologic sequence support that the Jingeryu Fm, the Nanfen Fm in the eastern Liaoning region in northeastern NCC and the Xinxing Fm in the Xuzhou region in southeastern NCC are correlative strata deposited in the polar region. Recently published radiogenic isotopic results constrain the depositional age of the Nanfen and Xinxing formations around ca. 1.1 Ga. Those high-latitude carbonate rocks widely distributed in the NCC predict an extraordinary climate condition around ca. 1.1 Ga.

Cancer-associated fibroblasts (CAFs) are a kind of stromal cells in the cholangiocarcinoma (CCA) microenvironment, playing crucial roles in cancer development. However, the potential mechanisms of the interaction between CCA cells and CAFs remain obscure. This work investigated the role of circ_0020256 in CAFs activation. We proved circ_0020256 was up-regulated in CCA. High circ_0020256 expression facilitated TGF-β1 secretion from CCA cells, which activated CAFs via the phosphorylation of Smad2/3. Mechanistically, circ_0020256 recruited EIF4A3 protein to stabilize KLF4 mRNA and upregulate its expression, then KLF4 bound to TGF-β1 promoter and induced its transcription in CCA cells. KLF4 overexpression abrogated the inhibition of circ_0020256 silencing in TGF-β1/Smad2/3-induced CAFs activation. Furthermore, CCA cell growth, migration, and epithelial-mesenchymal transition were favored by CAFs-secreted IL-6 via autophagy inhibition. We also found circ_0020256 accelerated CCA tumor growth in vivo. In conclusion, circ_0020256 promoted fibroblast activation to facilitate CCA progression via EIF4A3/KLF4 pathway, providing a potential intervention for CCA progression.

Abstract: Drug-related adverse events are higher in older patients than in non-older patients, increasing the risk of medication and reducing compliance. Aging is accompanied by a decline in physiological functions and metabolic weakening. Most tissues and organs undergo anatomical and physiological changes that may affect the pharmacokinetic (PK) and pharmacodynamic (PD) characteristics of drugs. Clinical trials are the gold standard for selecting appropriate dosing regimens. However, older patients are generally underrepresented in clinical trials, resulting in a lack of evidence for establishing an optimal dosing regimen for older adults. The physiologically based pharmacokinetic (PBPK) model is an effective approach to quantitatively describe the absorption, distribution, metabolism, and excretion of drugs in older adults by integrating physiological parameters, drug physicochemical properties, and preclinical or clinical PK data. The PBPK model can simulate the PK/PD characteristics of clinical drugs in different scenarios, ultimately compensating for inadequate clinical trial data in older adults, and is recommended by the Food and Drug Administration for clinical pharmacology studies in older adults. This review describes the effects of physiological changes on the PK/PD process in older adults and summarises the research progress of PBPK models. Future developments of PBPK models are also discussed, together with the application of PBPK models in older adults, aiming to assist the development of clinical study strategies in older adults.

This paper proposes a three-dimensional laser beam-riding guidance (LBRG) scheme with finite distance convergence for the interception guidance problem of laser beam-riding guided missiles (LBRGMs). First, the motion relationship between the guidance station, missile, and target is constructed, and a three-dimensional LBRG model based on position deviation is designed. Considering the finite range of the laser beam and convergence performance of the guidance system, a finite-distance convergence performance function is proposed, and its guidance law is designed by combining the prescribed performance and sliding mode control methods. Then, considering the unknown maneuvering information of the target, the acquired maneuvering information is converted into an estimation of the line-of-sight angle and its rate, estimated by designing the command filter. In addition, Lyapunov theory is employed to prove the stability of the guidance scheme. The position deviation converged to the steady-state value within the prescribed flight distance, thereby satisfying the prescribed transient and steady-state performance requirements and realizing the interception of the maneuvering target. Finally, the effectiveness of the guidance scheme is verified through simulations.