Pb exposure causes non-linear accumulation of Pb in D. melanogaster controlled by metallothionein B and exerts ecological effects.

Pb pollution can harm human health and the ecosystem. Therefore, it is worthwhile to study the metabolic processes of heavy metals in individual bodies and their influence on ecological systems. In this work, we analyzed the genetic responses and physiological changes of D. melanogaster which took diets exposed to different doses of Pb using transcriptomic analysis, ICP-MS, and various other physiological methods. We found that the Pb accumulated in D. melanogaster in a nonlinear pattern with the increase of Pb content in food. Metallothioneins (Mtns), especially the MtnB directly affects the accumulation and excretion of metal Pb in D. melanogaster, and causes the nonlinear accumulation. Metal regulatory transcription factor-1 (MTF-1) is involved in the regulation of Pb-induced high expressions of Mtns. Furthermore, an interaction between the metal metabolism pathway and xenobiotic response pathway leads to the cross-tolerances of Pb-exposed D. melanogaster to insecticides and other toxins. The oxidative stress induced by Pb toxicity may be the bridge between them. Our findings provide a physiological and molecular genetic basis for further study of the accumulation and metabolism of Pb in D. melanogaster.

Maternal Outcomes Among Pregnant Women With Congenital Heart Disease-Associated Pulmonary Hypertension.

BACKGROUND: Studies focused on pregnant women with congenital heart disease (CHD)-associated pulmonary hypertension (PH) are scarce and limited by small sample sizes and single-center design. This study sought to describe the pregnancy outcomes in women with CHD with and without PH. METHODS: Outcomes for pregnant women with CHD were evaluated retrospectively from 1993 to 2016 and prospectively from 2017 to 2019 from 7 tertiary hospitals. PH was diagnosed on the basis of echocardiogram or catheterization. The incidence of maternal death, cardiac complications, and obstetric and offspring complications was compared for women with CHD and no PH, mild, and moderate-to-severe PH. RESULTS: A total of 2220 pregnant women with CHD had completed pregnancies. PH associated with CHD was identified in 729 women, including 398 with mild PH (right ventricle to right atrium gradient 30-50 mm Hg) and 331 with moderate-to-severe PH (right ventricle to right atrium gradient >50 mm Hg). Maternal mortality occurred in 1 (0.1%), 0, and 19 (5.7%) women with CHD and no, mild, or moderate-to-severe PH, respectively. Of the 729 patients with PH, 619 (85%) had CHD-associated pulmonary arterial hypertension, and 110 (15%) had other forms of PH. Overall, patients with mild PH had better maternal outcomes than those with moderate-to-severe PH, including the incidence of maternal mortality or heart failure (7.8% versus 39.6%; P<0.001), other cardiac complications (9.0% versus 32.3%; P<0.001), and obstetric complications (5.3% versus 15.7%; P<0.001). Brain natriuretic peptide >100 ng/L (odds ratio, 1.9 [95% CI, 1.0-3.4], P=0.04) and New York Heart Association class III to IV (odds ratio, 2.9 [95% CI, 1.6-5.3], P<0.001) were independently associated with adverse maternal cardiac events in pregnancy with PH, whereas follow-up with a multidisciplinary team (odds ratio, 0.4 [95% CI, 0.2-0.6], P<0.001) and strict antenatal supervision (odds ratio, 0.5 [95% CI, 0.3-0.7], P=0.001) were protective. CONCLUSIONS: Women with CHD-associated mild PH appear to have better outcomes compared with women with CHD-associated moderate-to-severe PH, and with event rates similar for most outcomes with women with CHD and no PH. Multimodality risk assessment, including PH severity, brain natriuretic peptide level, and New York Heart Association class, may be useful in risk stratification in pregnancy with PH. Follow-up with a multidisciplinary team and strict antenatal supervision during pregnancy may also help to mitigate the risk of adverse maternal cardiac events.

Quantitative analysis of degree of substitution/molar substitution of etherified polysaccharide derivatives.

Due to the unique properties such as nontoxicity, biodegradability, availability from renewable resources, and cost-effectiveness, polysaccharides play a very important part in the science and technology field. The various chemically modified derivatives of these offer a wide range of high value-added in both food and non-food industries. Among the chemical modification, etherified polysaccharide is one of the most widespread derivatives by introducing an ether group which is commonly stable in both acidic and alkaline conditions. Hydroxyalkylation, alkylation, carboxymethylation, cationization, and cyanoethylation are some of the modifications commonly employed to prepare polysaccharides ethers derivatives. There also has been a growing tendency for creating new types of modification by combining the different means of chemical techniques. The correct determination of degree of substitution (DS)/molar substitution (MS) is crucially important. The objective of this article is to summarize developments in synthetic etherified polysaccharides, involving analytical methods for determination of MS/DS, measurement processes, and the associated mechanisms.

Investigation on Fatigue Performance of Diatomite/Basalt Fiber Composite Modified Asphalt Mixture.

The fatigue resistance of asphalt mixture is an important indicator to evaluate the durability of asphalt pavement. In order to improve the fatigue properties of asphalt mixture, diatomite and environmental basalt fiber were added. Four types of asphalt mixtures, ordinary asphalt mixture (AM), diatomite modified asphalt mixture (DAM), basalt fiber modified asphalt mixture (BFAM) and diatomite/basalt fiber composite modified asphalt mixture (DBFAM), were chosen, whose optimum asphalt-aggregate ratio, optimum content of diatomite and optimum content of basalt fiber could be determined by Marshall test and response surface methodology (RSM). The multi-functional pneumatic servo Cooper test machine was carried out by a four-point bending fatigue test. Through the comparative analysis of flexural-tensile stiffness modulus (S), initial stiffness modulus(S0), residual stiffness modulus ratio, lag angle (ϕ) and cumulative dissipation energy (ECD), the fatigue resistance of asphalt mixture can be effectively improved by adding diatomite and basalt fiber. Grey correlation analysis was also used to analyze the degree of correlation between the fatigue life and the influencing factors such as VV, VMA, VFA, OAC, S, and ECD. The analysis results indicate that ECD has the greatest impact on the fatigue life of the asphalt mixture.

Piezo-photocatalytic effect mediating reactive oxygen species burst for cancer catalytic therapy.

A piezo-photocatalytic therapy based on thermally treated natural sphalerite nanosheet (NSH700 NS) heterojunction was applied to efficiently induce intracellular ROS burst and apoptosis of cancer cells. Upon ultrasound and laser irradiation, the formation of a polarized electric field and band bending of NSH700 NSs allow the directional separation of charges both in the bulk and their interface, thereby minimizing the probability of charge recombination. The piezo-photocatalytic effect leads to an efficient catalytic performance, exhibiting high-performance superoxide radical (˙O2-) and hydroxyl radical (˙OH) generation and glutathione (GSH) depletion, which results in a intracellular ROS burst-triggered apoptosis of cancer cells both in vitro and in vivo.

Metal-metal interaction and metal toxicity: a comparison between mammalian and D. melanogaster.

1. Non-essential heavy metals such as mercury (Hg), arsenic (As), cadmium (Cd), and aluminium (Al) are useless to organisms and have shown extensive toxic effects. Previous studies show that two main molecular mechanisms of metal toxicity are oxidative stress and metal-metal interaction which can disrupt metal homeostasis.2. In this paper, we mainly illustrate metal toxicity and metal-metal interaction through examples in mammalians and D. melanogaster (fruit fly).3. We describe the interference of metal homeostasis by metal-metal interactions in three aspects including replacement, cellular transporter competition, and disruption of the regulation mechanism, and elaborate the mechanisms of metal toxicity to better deal with the challenges of heavy metal pollution and related health problems.

Structural design of cobalt phosphate on nickel foam for electrocatalytic oxygen evolution.

The elaborate design and synthesis of low-cost, efficient and stable electrocatalysts for the oxygen evolution reaction (OER), which may alleviate the current energy shortage and environment pollution, is still a great challenge. Herein, metal phosphonate precursors with controllable morphologies were synthesizedin situon the surface of nickel foam with different solvents, and could be easily converted into carbon- and nitrogen-doped cobalt phosphate through a calcination method. The OER catalytic performance of the final products was studied in detail. The results showed that the nanowire shaped samples of CoPiNF-800 synthesized with deionized water under hydrothermal conditions had the strongest electrochemical performance. They exhibited extraordinary catalytic activity with a very low overpotential of 222 mV at 100 mA cm-2, the smallest impedance and excellent electrochemical stability. These results not only demonstrate the possibility of preparing low-cost OER catalysts based on transition metal phosphate, but also aid our understanding of the controllable synthesis process of different morphologies.

Chitopentaose inhibits hepatocellular carcinoma by inducing mitochondrial mediated apoptosis and suppressing protective autophagy.

Hepatocellular carcinoma (HCC) is one of the most prevalent and deadliest cancers. In this study, the anti-tumor effect of singular degree of polymerization (DP) chitooligosaccharides (COS) (DP 2-5) and the underlay molecular mechanisms were investigated on HCC cell line HepG2. MTT assay showed that (GlcN)5 have the best anti-proliferation effect among the different DP of COS (DP2-5). Furthermore, the administration of (GlcN)5 could decrease mitochondrial membrane potential, release cytochrome c into cytoplasm, activate the cleavage of Caspases9/3, thus inducing mitochondrial-mediated apoptosis in HepG2 cells (accounting for 24.57 ± 2.25%). In addition, (GlcN)5 treatment could increase the accumulation of autophagosomes. Further investigation showed that (GlcN)5 suppressed protective autophagy at the fusion of autophagosomes and lysosomes. Moreover, the inhibition of protective autophagy flux by (GlcN)5 could further decrease cell viability and increase the apoptosis rate. Our findings suggested that (GlcN)5 suppressed HepG2 proliferation through inducing apoptosis via the intrinsic pathway and impairing cell-protective autophagy. COS might have the potential to be an agent for lowering the risk of HCC.

Defective modulation of LINE-1 retrotransposition by cancer-associated SAMHD1 mutants.

Long interspersed nuclear elements (LINE-1) is now considered as the only active autonomous mobile DNA in humans, LINE-1 retrotransposition activities are associated with and fluctuate during cancer initiation and progression; however, the mechanism underlying the increased LINE-1 activity in cancer is poorly understood. SAMHD1 has been reported to be a potent inhibitor of LINE-1 retrotransposition, and SAMHD1 mutations are frequently associated with cancer development. To gain insights on whether cancer-related SAMHD1 mutants affect LINE-1 activity, we explored the biochemical and cellular properties of some human mutants known correlate with the development of cancer. Most of the tested SAMHD1 cancer-related mutations were defective in LINE-1 inhibition. Interestingly we also found that SAMHD1 mutant K288T was defective for dNTPase activity but showed potent activity against LINE-1 retrotransposition. These findings suggest that LINE-1 inhibition does not depend solely on the dNTPase activity of SAMHD1. In contrast, SAMHD1's ability to inhibit ORF2p-mediated LINE-1 RNP reverse transcription was correlated with SAMHD1-mediated LINE-1 inhibition. Together, our data could also facilitate the deeper understanding for the inhibition of endogenous LINE-1 elements by SAMHD1.

Low-Temperature Performance and Damage Constitutive Model of Eco-Friendly Basalt Fiber⁻Diatomite-Modified Asphalt Mixture under Freeze⁻Thaw Cycles.

Asphalt pavement located in seasonal frozen regions usually suffers low-temperature cracking and freeze⁻thaw damage. For this reason, diatomite and basalt fiber were used to modify asphalt mixtures. An indirect tensile test was used to determine the low-temperature performance of the asphalt mixture. The influences of freeze⁻thaw (F⁻T) cycles on strength, tensile failure strain, stiffness modulus, and strain energy density were analyzed. The variation of the stress⁻strain curve under F⁻T cycles was analyzed. The stress⁻strain curve was divided into a linear zone and nonlinear zone. The linear zone stress ratio and linear zone strain ratio were proposed as indexes to evaluate the nonlinear characteristics of the stress⁻strain curve. The results show that the basalt fiber⁻diatomite-modified asphalt mixture had better low temperature crack resistance and antifreeze⁻thaw cycles capacity compared to the control asphalt mixture. The F⁻T cycles made the nonlinear characteristics of the stress⁻strain relationship of the asphalt mixture remarkable, and also decreased the linear zone stress ratio and linear zone strain ratio. The damage constitutive model established in this paper can describe the stress⁻strain relationship after F⁻T damage well.

Laboratory Evaluation on Performance of Eco-Friendly Basalt Fiber and Diatomite Compound Modified Asphalt Mixture.

This study proposed an asphalt mixture modified by basalt fiber and diatomite. Performance of diatomite modified asphalt mixture (DAM), basalt fiber modified asphalt mixture (BFAM), diatomite and basalt fiber compound modified asphalt mixture (DBFAM), and control asphalt mixture (AM) were investigated by experimental methods. The wheel tracking test, low-temperature indirect tensile test, moisture susceptibility test, fatigue test and freeze⁻thaw cycles test of four kinds of asphalt mixtures were carried out. The results show that the addition of basalt fiber and diatomite can improve the pavement performance. Diatomite has a significant effect on the high temperature stability, moisture susceptibility and resistance to moisture and frost damage under freeze⁻thaw cycles of asphalt mixture. Basalt fiber has a significant effect on low-temperature cracking resistance of asphalt mixture. Composed modified asphalt mixture has obvious advantages on performance compared to the control asphalt mixture. It will provide a reference for the design of asphalt mixture in seasonal frozen regions.

Design, synthesis and biological evaluation of 5-aminolaevulinic acid/3-hydroxypyridinone conjugates as potential photodynamic therapeutical agents.

5-Aminolaevulinic acid (ALA) prodrugs have been widely used in photodynamic therapy (PDT) as precursors to the natural photosensitizer, protoporphyrin IX (PpIX). The main disadvantage of this therapy is that ALA is poorly absorbed by cells due to its high hydrophilicity. In order to improve the therapeutical effect and induce higher yields of PpIX, a range of prodrugs of ALA conjugated to 3-hydroxypyridin-4-ones (HPO) were synthesized. Pharmacokinetic studies indicated that some of the ALA-HPO conjugates are more efficient than ALA for PpIX production in the human breast adenocarcinoma cell line (MDA-MB-468). The intracellular porphyrin fluorescence levels showed good correlation with cellular phototoxicity following light exposure, suggesting the potential application of the ALA-HPO conjugates in photodynamic therapy.

Breeding and preliminarily phenotyping of a congenic mouse model with alopecia areata.

In the current study, the alopecia areata gene was introduced into the C57BL/6 (B6) mouse through repeated backcrossing/intercrossing, and the allelic homozygosity of congenic AA(tj)mice (named B6.KM-AA) was verified using microsatellites. The gross appearance, growth characteristics, pathological changes in skin, and major organs of B6.KM-AA mice were observed. Counts and proportions of CD4⁺ and CD8⁺ T lymphocytes in peripheral blood were determined by flow cytometry. Results show that congenic B6.KM-AA mice were obtained after 10 generations of backcrossing/intercrossing. B6.KM-AA mice grew slower than B6 control mice and AA skin lesions were developed by four weeks of age. The number of hair follicles was reduced, but hair structures were normal. Loss of hair during disease progression was associated with CD4⁺ and CD8⁺ T lymphocytes infiltration peri-and intra-hair follicles. No pathological changes were found in other organs except for the skin. In the peripheral blood of B6.KM-AA mice, the percentage of CD4⁺ T cells was lower and percentage of CD8⁺ T cells higher than in control mice. These findings indicate that B6.KM-AA mice are characterized by a dysfunctional immune system, retarded development and T-cell infiltration mediated hair loss, making them a promising new animal model for human alopecia areata.

Design, synthesis, and antimicrobial evaluation of hexadentate hydroxypyridinones with high iron(III) affinity.

A range of hexadentate 3-hydroxypyridin-4-ones (HPOs) with high affinity for iron(III) has been synthesized. The log stability constants of two HPO-iron complexes (logK1 ) were determined to be over 34, and pFe values of the two HPOs were determined to be over 31. Antimicrobial assay indicated that they are able to markedly inhibit the growth of both Gram-positive and Gram-negative bacteria. Compounds 14a and 14e were found to exhibit the strongest inhibitory activity against Staphyloccocus aureus, Bacillus subtilis, Pseudomonas aeruginosa, and Escherichia coli, with MIC values of 8, 8, 16, and 8 µg/mL, respectively. These results indicate that hexadentate 3-hydroxypyridin-4-ones have potential application as antimicrobial agents, especially in the treatment of wound infection.

Structural insight into dGTP-dependent activation of tetrameric SAMHD1 deoxynucleoside triphosphate triphosphohydrolase.

SAMHD1 is a dGTP-activated deoxynucleoside triphosphate triphosphohydrolase (dNTPase) whose dNTPase activity has been linked to HIV/SIV restriction. The mechanism of its dGTP-activated dNTPase function remains unclear. Recent data also indicate that SAMHD1 regulates retrotransposition of LINE-1 elements. Here we report the 1.8-Å crystal structure of homotetrameric SAMHD1 in complex with the allosteric activator and substrate dGTP/dATP. The structure indicates the mechanism of dGTP-dependent tetramer formation, which requires the cooperation of three subunits and two dGTP/dATP molecules at each allosteric site. Allosteric dGTP binding induces conformational changes at the active site, allowing a more stable interaction with the substrate and explaining the dGTP-induced SAMHD1 dNTPase activity. Mutations of dGTP binding residues in the allosteric site affect tetramer formation, dNTPase activity and HIV-1 restriction. dGTP-triggered tetramer formation is also important for SAMHD1-mediated LINE-1 regulation. The structural and functional information provided here should facilitate future investigation of SAMHD1 function, including dNTPase activity, LINE-1 modulation and HIV-1 restriction.

Synthesis and in-vitro antimicrobial evaluation of a high-affinity iron chelator in combination with chloramphenicol.

OBJECTIVES: The objectives of this study were first to design and synthesize a hexadentate chelator with high iron(III) affinity and, second, to evaluate its antimicrobial activity in the presence and absence of chloramphenicol. METHODS: A hexadentate ligand was synthesized by conjugating a protected bidentate compound onto a tripodal structure. The pKa values and iron affinity of the chelator were determined by spectophotometric titration. Minimum inhibitory concentrations were determined by visual inspection of broth turbidity. The bactericidal rates were calculated by counting the colony numbers on a light board after incubation with and without an antimicrobial agent. KEY FINDINGS: A hexadentate 3-hydroxypyridin-4-one was found to possess a high affinity for iron(III), with a pFe value of 31.2 (negative logarithm of concentration of the free iron(III) in solution (when [Fe³âº](Total) = 10⁻6) M; [Ligand](Total) = 105 M; pH = 7.4). We found that this chelator had an appreciable inhibitory effect in vitro against the two bacterial strains Providencia stuartii and Staphylococcus aureus, particularly in the presence of chloramphenicol. CONCLUSIONS: A 3-hydroxypyridin-4-one hexadentate ligand has potential as an antimicrobial agent. Combination therapy with this iron chelator plus chloramphenicol has potential for the treatment of extracellular infections.

Characterization of full-length enterovirus 71 strains from severe and mild disease patients in northeastern China.

Human enterovirus 71 (EV71)-associated hand, foot, and mouth disease (HFMD) has been a leading cause of childhood infection in China since 2008. Epidemic and molecular characteristics of HFMD have been examined in many areas of China, including the central and southern regions. However, clinical and genetic characterization of EV71 in the northeastern region of China is scarce. In this study, a series of analyses were performed on seven full-length EV71 sequences from HFMD patients who had either severe or mild disease. We have determined that these seven circulating EV71 viruses from Changchun, China are actually complex recombinant viruses involving multiple type A human enterovirus (HEV). Classified as EV71 subtype C4 (EV71 C4), these Changchun EV71 viruses contain genetic recombination events between the CA4, CA5, EV71B4 and EV71C1 strains. Most of the structural protein region (P1) of these viruses resembled that of the prototype EV71 C1 strains. The non-structural protein domains (P2 and P3) showed a high degree of similarity with CA4, CA5 and EV71 B4 in different regions. The 5'UTR had unclassified recombination,while partial 3D region of these viruses showed a high degree of similarity to CA16. Phylogenetic analysis of full-length or partial sequences of isolates from severe or mild disease patients in Changchun always formed a single cluster in various phylogenetic analyses of different genomic regions, suggesting that all seven strains originated from one single common ancestor. There was no correlation between viral genomic sequence and virulence. Thus, we found that circulating recombinant forms of EV71 are prevalent among HFMD patients in Northeastern China. The existence of a unique cluster of EV71 related viruses in Northeast China has important implications for vaccine development that would address the increasing prevalence of HFMD.

Extraction of naringin from pomelo peels as dihydrochalcone's precursor.

A new method for the separation of naringin from pomelo peels was investigated by using ultrasonic-assisted extraction and macroporous resin purification technology. The ultrasonic extraction efficiency was dependent on agent's concentration, ratio of sample and solvent and ultrasonic time. Several parameters of macroporous resin-purified process, including resin selection, initial concentration, concentration of eluted agent and pH, were optimized. The experimental results showed that the naringin content in the mature pomelo peels was 2.20% and purification rate of naringin was 77.26% under optimum conditions of purification. The structure of synthetic naringin dihydrochalcone was determined by a series of spectroscopic methods, such as UV, NMR and MS.

Charge dynamic characteristics in corona-charged polytetrafluoroethylene film electrets.

In this work, the charge dynamics characteristics of injection, transport and decay in porous and non-porous polytetrafluoroethylene (PTFE) film electrets were investigated by means of corona charging, isothermal and thermal stimulating surface-potential decay measurements. The results showed that the initial surface potential, whether positively or negatively charging, is much higher in non-porous PTFE than in porous PTFE. For porous film the value of initial surface potentials increases with increase of film thickness. Higher charging temperature can remarkably improve charge stability. The charge dynamics are correlated to materials microstructure according to their scanning electron micrographs. For non-porous PTFE films, polarizability change of C-F bonds is the main origin of electret charges; but for porous PTFE film a large number of bulk and interface type traps are expected because of the greater area of interface and higher crystallinity.