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This study conducted risk ranking for risk substances present in meat products, exploring the temporal and spatial distribution patterns of these risk items. The entropy weight method was used to calculate the risk values of different risk substances in circulation, production and catering links, and the risk substances were ranked by the 80-20 principle. The descriptive statistical method was used to explore the temporal and spatial distribution patterns of meat product production links. Through global and local correlation analysis, the characteristics of the spatial distribution of high-risk and relatively high-risk substances nationwide were studied. The high-risk substances in the production and circulation links were N-dimethylnitrosamine, benzo[a]pyrene, cadmium, peroxide value, new red, nitrite, arsenic, mercury, coliforms, and total bacteria number, while the relatively high-risk substances in the catering link was the total bacteria number. The highest meat product unqualified rate was 0.21% in 2017, followed by 0.19% in 2020. In various regions, the highest unqualified rate was in Ningxia, at 0.30%. For meat products from all provinces nationwide, the qualified rates for high and relatively high-risk substances only exhibited global spatial correlation for arsenic, allura red, and total bacterial count (P

Fluorine (F) and Cadmium (Cd) have given rise to public concern regarding their adverse impacts on the environment and human beings. Yet, the toxic interplay between F and Cd on the intestine is still vague. Aiming to investigate the role of F on Cd-damaged intestine, a total of five groups of 30 SD rats were picked at random to be gavaged for 90 days: Control group (Ultra-pure water), Cd (Cd 1 mg/kg), Cd+LF (Cd 1 mg/kg+F 15 mg/kg), Cd+MF (Cd 1 mg/kg+F 45 mg/kg), and Cd+HF (Cd 1 mg/kg+F 75 mg/kg). It demonstrated that Cd enriched in the intestine and disordered intestinal barrier of rats. Interestingly, two side effects of F were observed resisting to the Cd toxicity. The Cd levels in colon contents were attenuated by 45.45 %, 28.11 %, and 19.54 % by F supplement, respectively. In the Cd+LF group, SOD, GSH-Px, and CAT activities elevated by 0.93, 1.76, and 1.78 times, respectively, and the MDA content reduced 0.67 times; the expressions of NQO1, SOD2, and GSH-Px mRNA markedly enhanced, as well as the Keap1 mRNA significantly decreased. Nevertheless, all indexes above in the Cd+HF group showed the opposite trends. Furthermore, LPS levels decreased by 45.93 % for the Cd+LF group and increased by 12.70 % in that the Cd+HF group. The ZO-1 expression in the Cd+LF group increased, whereas the Cd+HF group's expressions of Claudin-1, Occludin, and ZO-1 were all diminished by 35.46 %, 27.23 %, and 16.32 %, respectively. Moreover, the levels of TNF-α, IL-1β and TLR-4 decreased and IL-10 level promoted, while all showed opposite trends in the Cd+HF group. Collectively, it indicated there is a twofold interplay between F and Cd on intestinal damage and mainly depends on F dosages.

Hexaconazole is a widely used and frequently detected fungicide which is also reported to be persistent in environment. The toxicity of Hex to non-organisms such as reproductive toxicity, endocrine disrupting toxicity, and carcinogenic toxicity had been reported. However, study on the Hex-induced neurotoxicity is rare and the mechanism is still unclear. Therefore, in this study, environmental related concentrations of Hex were chosen to investigate the effects of Hex on nervous system from the aspect of biological rhythm under 90 d sub-chronic exposure. The results showed that Hex significantly affected the cognitive function of rats resulting in the deterioration of learning and memory ability and induced oxidative stress in rat brain. Moreover, the notable changes of neurotransmitters in rat brain suggested the disorder of nerve signaling conduction induced by Hex. The influence of Hex on biological rhythm was further detected which showed that levels of rhythm regulatory genes and proteins significantly disturbed at four monitored time periods. Based on these results, it was supposed that the underlying mechanism of Hex-induced cognitive dysfunction might through oxidative stress pathway. Our findings could systematically and comprehensively clarify the effects of Hex on nervous system and were helpful for prevention neurological diseases induced by triazole pesticides.

Abstract Biochar (BC) and biodegradable mulch film (BMF) are both commonly used means of production in agriculture. In recent years, most studies have focused on the effects of BC or BMF on soil heavy metal pollution, while they have neglected the combined effects. In this study, a pot experiment was conducted to examine the impacts of BMF, BC, and combined BMF and BC (CMB) on the mobility of chromium (Cr) and the agronomic characteristics of flue-cured tobacco. Compared with the control, BMF, BC, and CMB significantly reduced the concentrations of diethylenetriamine pentaacetic acid (DTPA) extractable Cr in soils by 29.07–29.75%, 45.35–48.54%, and 34.21–37.92%, respectively. In comparison to the application of BMF and BC alone, co-application reduced the availability of Cr in soil via increasing the adsorption of soil Cr and soil enzyme activity, which resulted in the decrease of Cr content and bioconcentration factor and in plants. Moreover, the combined application increased the plant height, stem diameter, leaf area, total root area, root tip number, and root activity of tobacco, which leaded to increase in leaf and root biomass by 11.40–67.01% and 23.91–50.74%, respectively. Therefore, the application of CMB can reduce the heavy metal residues in tobacco leaves and improve tobacco yield and quality.

P-glycoprotein (Pgp) is a prototypical ATP-binding cassette (ABC) transporter of great biological and clinical significance.Pgp confers cancer multidrug resistance and mediates the bioavailability and pharmacokinetics of many drugs (Juliano and Ling, 1976; Ueda et al., 1986; Sharom, 2011). Decades of structural and biochemical studies have provided insights into how Pgp binds diverse compounds (Loo and Clarke, 2000; Loo et al., 2009; Aller et al., 2009; Alam et al., 2019; Nosol et al., 2020; Chufan et al., 2015), but how they are translocated through the membrane has remained elusive. Here, we covalently attached a cyclic substrate to discrete sites of Pgp and determined multiple complex structures in inward- and outward-facing states by cryoEM. In conjunction with molecular dynamics simulations, our structures trace the substrate passage across the membrane and identify conformational changes in transmembrane helix 1 (TM1) as regulators of substrate transport. In mid-transport conformations, TM1 breaks at glycine 72. Mutation of this residue significantly impairs drug transport of Pgp in vivo, corroborating the importance of its regulatory role. Importantly, our data suggest that the cyclic substrate can exit Pgp without the requirement of a wide-open outward-facing conformation, diverting from the common efflux model for Pgp and other ABC exporters. The substrate transport mechanism of Pgp revealed here pinpoints critical targets for future drug discovery studies of this medically relevant system.

The adverse effects of heavy metals have arousing concern in the high geological background area, especially in southwestern Guizhou, China. However, the pollution status of heavy metals are still unclear when exposed to rice and corn in Guizhou province. Therefore, the concentration, pollution level, spatial distribution, and probabilistic health risks of Ni, Cr, Pb, Cu, and Zn are estimated in rice and corn. A total of 241 samples (117 for rice and 124 for corn) were collected from Guizhou province and measured by a method of inductively coupled plasma-mass spectrometry (ICP-MS). The results showed that rice and corn were contaminated with Ni and Cr. High concentrations of Ni were presented in the southeast of rice. It indicated that 22.0 % of rice samples were contaminated with Ni. HI values for children and adults exceeded 1.0 in rice and corn, suggesting that humans might be subject to probabilistic non-carcinogenic risks. FTCR demonstrated that rice and corn might cause probabilistic carcinogenic risks to children and adults, which were both greatly higher than 1.0 × 10−4. Moreover, the contributions of Ni to the HI and FTCR were the highest for adults and children. Therefore, more attention should be paid to the exposure of heavy metals in rice and corn, especially in Ni. The results would provide a novel prospective for pollution control and be helpful for environmental regulation.

Nitrogen application delays rice quality deterioration due to changes in its pasting characteristics; however, the underlying mechanisms remain unclear. Using a label-free quantitative proteomics approach, we identified differentially expressed proteins (DEPs) during storage in paddy rice treated with different nitrogen levels. On combining the changes in physiological indicators, high-nitrogen treatment was found to downregulate β-1,3-glucanase, reduce the decomposition of cell wall components, downregulate three proteins involved in starch metabolism, decrease the range of the amylose content and increase the range of the amylopectin, upregulate three proteins related to the lysosomal pathway, and enhance glutelin degradation. In addition, it upregulated three proteins related to flavonoid synthesis, which enhanced the stress response ability of rice, thereby contributing to the stability of biological macromolecules. The discovery of these key DEPs provides potential targets for further control over the deterioration of crop seed storage quality.

In light of the documented elevated concentrations of total mercury (Hg) and methylmercury (MeHg) in poultry originating from Hg-contaminated sites, a knowledge gap persists regarding the levels of Hg found in home-produced eggs (HPEs) and the associated dietary exposure risks in regions affected by Hg mining. To address this knowledge gap, a comprehensive investigation was undertaken with the primary objectives of ascertaining the concentrations of THg and MeHg in HPEs and evaluating the potential hazards associated with the consumption of eggs from the Wanshan Hg mining area in Southwest China. The results showed that THg concentrations in HPEs varied within a range of 10.5–809 ng/g (with a geometric mean (GM) of 64.1 ± 2.7 ng/g), whereas MeHg levels spanned from 1.3 to 291 ng/g (GM, 23.1 ± 3.4 ng/g). Remarkably, in half of all eggs, as well as those collected from regions significantly impacted by mining activities, THg concentrations exceeded the permissible maximum allowable value for fresh eggs (50 ng/g). Consumption of these eggs resulted in increased exposure risks associated with THg and MeHg, with GM values ranging from 0.024 to 0.17 µg/kg BW/day and 0.0089–0.066 µg/kg BW/day, respectively. Notably, the most substantial daily dosage was observed among children aged 2–3 years. The study found that consuming HPEs could result in a significant IQ reduction of 34.0 points for the whole mining area in a year. These findings highlight the potential exposure risk, particularly concerning MeHg, stemming from the consumption of local HPEs by residents in mining areas, thereby warranting serious consideration within the framework of Hg exposure risk assessment in mining locales.

Abstract We present two robust and well‐dated paleomagnetic poles from upper Eocene and Oligocene volcanics in the Urumieh‐Dokhtar magmatic arc, Central Iran. These two poles place Iran ∼3.7°–3° of latitude south of its present position between ca. 40 and 23 Ma. Our new paleomagnetic declination data indicate that the Central Iran block may have experienced a ∼11.6° clockwise rotation since the Late Eocene. We integrated our new data with the retrodeformed margins of the Zagros collision zone and contemporaneous Arabia positions to better constrain the age and configuration of the Arabia and Eurasia assembly process. In our model, the Arabia‐Eurasia collision occurred first in the western Main Zagros suture between ca. 35 and 30 Ma and then diachronously spread eastwards. Our paleogeographic reconstruction and initial continental collision timing supports the Arabia‐Eurasia collision as a first‐order driver of global cooling, Red Sea rifting, and Mediterranean extension.

Pseudostellaria heterophylla (or Taizishen in Chinese), a medicinal, edible, and ornamental Chinese herb, is seriously affected by leaf spot disease (LSD). Oligochitosan is a natural agricultural antibiotic that is produced via the degradation of chitosan, which is deacetylated from chitin; pyraclostrobin is a broad-spectrum and efficient strobilurin fungicide. In this work, the ability of pyraclostrobin, oligochitosan, and their formula to manage P. heterophylla leaf spot disease and their role in its resistance, leaf photosynthesis, agronomic plant traits, root growth, and root quality were studied. The results show that the joint application of oligochitosan and low-dosage pyraclostrobin could control LSD more efficiently, with control effects of 85.75–87.49% compared to high-dosage pyraclostrobin or oligochitosan alone. Concurrently, the application of this formula could more effectively improve the resistance, leaf photosynthesis, agronomic plant traits, root yield, and medicinal quality of P. heterophylla, as well as reduce the application of pyraclostrobin. This finding suggests that 30% pyraclostrobin suspension concentrate (SC) 1500-time + 5% oligosaccharin aqueous solutions (AS) 500-time diluent can be recommended for use as a feasible formula to manage LSD and reduce the application of chemical pesticides.

P-glycoprotein (Pgp) is a multidrug transporter that uses the energy from ATP binding and hydrolysis to export from cells a wide variety of hydrophobic compounds including anticancer drugs, and mediates the bioavailability and pharmacokinetics of many drugs. Lipids and cholesterol have been shown to modulate the substrate-stimulated ATPase activity of purified Pgp in detergent solution and the substrate transport activity after reconstitution into proteoliposomes. While lipid extracts from E. coli, liver or brain tissues generally support well Pgp’s functionality, their ill-defined composition and high UV absorbance make them less suitable for optical biophysical assays. On the other hand, studies with defined synthetic lipids, usually the bilayer-forming phosphatidylcholine with or without cholesterol, are often plagued by low ATPase activity and low binding affinity of Pgp for drugs. Drawing from the lipid composition of mammalian plasma membranes, we here investigate how different head groups modulate the verapamil-stimulated ATPase activity of purified Pgp in detergent-lipid micelles and compare them with components of E. coli lipids. Our general approach was to assay modulation of verapamil-stimulation of ATPase activity by artificial lipid mixtures starting with the bilayer-forming palmitoyloyl-phosphatidylcholine (POPC) and -phosphatidylethanolamine (POPE). We show that POPC/POPE supplemented with sphingomyelin (SM), cardiolipin, or phosphatidic acid enhanced the verapamil-stimulated activity (Vmax) and decreased the concentration required for half-maximal activity (EC50). Cholesterol (Chol) and more so its soluble hemisuccinate derivative cholesteryl hemisuccinate substantially decreased EC50, perhaps by supporting the functional integrity of the drug binding sites. High concentrations of CHS (>15%) resulted in a significantly increased basal activity which could be due to binding of CHS to the drug binding site as transport substrate or as activator, maybe acting cooperatively with verapamil. Lastly, Pgp reconstituted into liposomes or nanodiscs displayed higher basal activity and sustained high levels of verapamil stimulated activity. The findings establish a stable source of artificial lipid mixtures containing either SM and cholesterol or CHS that restore Pgp functionality with activities and affinities similar to those in the natural plasma membrane environment and will pave the way for future functional and biophysical studies.

Abstract Background Dapagliflozin, a selective inhibitor of sodium-glucose cotransporter 2 (SGLT2), can reduce cardiovascular events and mortality in patients with heart failure. A number of mechanisms have been proposed to explain the beneficial effects of SGLT2 inhibitors. The purpose of this study was to determine whether dapagliflozin can improve pulmonary vascular remodelling and the efficacy of dapagliflozin as an add-on therapy to sildenafil in rats with pulmonary arterial hypertension (PAH). Methods A monocrotaline (MCT)-induced PAH rat model was used in our study. MCT-injected rats were randomly divided into four groups and treated for 3 weeks with daily per os treatment with vehicle, dapagliflozin (1 mg/kg/day), sildenafil (25 mg/kg/day), or a combination of dapagliflozin (1 mg/kg/day) and sildenafil (25 mg/kg/day). Haemodynamic measurements, histological analysis, enzyme-linked immunosorbent assay and western blotting analysis were employed to detect the changes in PAH rats after treatments. Results Dapagliflozin significantly attenuated MCT-induced increases in right ventricular systolic pressure (RVSP) and right ventricular hypertrophy (RVH) in PAH rats. Dapagliflozin effectively decreased the thickening of pulmonary artery media and decreased the muscularization of pulmonary arterioles in PAH rats. Moreover, dapagliflozin attenuated nucleotide-binding domain-like receptor protein 3 (NLRP3) inflammasome activation in lung tissues and the levels of interleukin-1β (IL-1β) and interleukin-18 (IL-18) in plasma. However, dapagliflozin as an add-on therapy to sildenafil in rats with PAH did not show a more pronounced beneficial effect on right ventricular systolic pressure and pulmonary vascular remodelling in MCT rats than sildenafil alone. Conclusions Dapagliflozin reduces right ventricular systolic pressure and pulmonary vascular remodelling in a rat model of PAH. However, combination therapy with dapagliflozin and sildenafil was not more effective than monotherapy with sildenafil in PAH rats.

In the over seventy years of Kenya's national park practice, Nairobi National Park, the oldest one among 24 national parks in Kenya, has plentiful experience as a representative in conservation, nature education, and management mechanisms on Kenya national parks. Therefore, it is the epitome of exploring the Kenyan National Park System. This paper takes Nairobi National Park as a case to analyze the Kenyan National Park System. It pragmatically explains the park's role in biodiversity conservation, its socio-cultural and economic value, and the threats it faces, and then highlights the management strategies set to address these challenges. It reviews the relationship between the three elements (roles, threats and management of national park system) and how this relationship influences the state of national park system. It proposes that the ideal state of the national park system is where roles are fulfilled, threats are managed and the governing policies are effective, efficient and economic.

Pseudostellaria heterophylla (Miq.) Pax is a popular clinical herb and nutritious health food. However, leaf spot disease caused by fungal pathogens frequently occurs and seriously influences the growth, quality, and yield of P. heterophylla. In this work, the field control roles of difenoconazole, chitosan, and their combination in the leaf spot disease in P. heterophylla and their effects on the disease resistance, photosynthetic capacity, medicinal quality, and root yield of P. heterophylla are investigated. The results manifest that 37% difenoconazole water-dispersible granule (WDG) with 5000-time + chitosan 500-time dilution liquid had a superior control capacity on leaf spot disease with the control effects of 91.17%~88.19% at 15~30 days after the last spraying, which significantly (p < 0.05) exceeded that of 37% difenoconazole WDG 3000-time dilution liquid and was significantly (p < 0.01) higher than that of 37% difenoconazole WDG 5000-time dilution liquid, chitosan 500-time dilution liquid, or chitosan 1000-time dilution liquid. Simultaneously, this combination could more effectively enhance the disease resistance, photosynthetic capacity, medicinal quality, and tuberous root yield of P. heterophylla compared to when these elements were applied alone, as well as effectively reduce difenoconazole application. This study emphasizes that chitosan combined with a low dosage of difenoconazole can be proposed as a green, efficient, and alternative formula for controlling leaf spot disease in P. heterophylla and enhancing its resistance, photosynthesis, quality, and yield.

The terrain of China is relatively complex, which leads to the complex and changeable working conditions of high-speed trains during braking. Studying the influence under different braking conditions on the performance of train brake pads is a problem worthy of in-depth discussion. In order to explore the performance changes of powder metallurgy brake pads during train braking, this paper summarizes the friction and wear properties and wear mechanism of powder metallurgy brake pads under different braking conditions; combined with the research status of powder metallurgy brake pad materials, it provides directions for the research of new powder metallurgy materials. Provide reference for the improvement of brake pads of high-speed train in the future.

The pollution status of crops planted in Guizhou province of Southwestern China with high background values of Fluorine (F) and Cadmium (Cd) has attracted people’s concern. The present study aimed to investigate the spatial distributions of F and Cd in rice, corn and wheat grains, and further evaluate their health risks to residents in Guizhou province. The contents of F and Cd were measured by fluoride ion-selective electrode and inductively coupled plasma mass spectrometry (ICP-MS) methods, respectively. Additionally, the inverse distance weighted (IDW) technique was conducted to analyze spatial distribution, and the health risk was estimated by target hazard quotient (THQ) and hazardous index (HI). The results indicate that Cd contents in samples varied from 0.000 to 0.463 for rice, 0.000 to 0.307 for corn, and 0.012 to 0.537 (mg/kg) for wheat, while F contents ranged from 0.825 to 5.193 (rice), 0.946 to 8.485 (corn), and 0.271 to 9.143 (wheat) mg/kg. The Cd exceeding ratios were 11.600% for rice, 13.500% for corn, and 45.100% for wheat grains, respectively. In terms of spatial distribution, high levels of F and Cd in rice were found in the northern and central in Guizhou, while Cd in corn was distributed in the eastern and F in corn were distributed in the west area of Guizhou. Moreover, the high levels of F and Cd in wheat were distributed in the western and eastern areas. The mean carcinogenic risks (R) of Cd in rice, corn, and wheat in children were 4.150 × 10–4, 1.670 × 10–4 and 3.470 × 10–4, respectively, and that in adults were 3.430 × 10–4, 0.471 × 10–4, and 2.190 × 10–4, respectively. The HI for adults in rice, corn and wheat grains were 0.756, 0.154, and 0.514, respectively, and that for children were 0.913, 0.549, and 0.814, respectively. Collectively, the potential risks produced by F and Cd to the local residents should not be ignored.

Bijie is located at a typical karst landform of Southwestern Guizhou, which presented high geological background values of potentially toxic elements (PTEs). Recently, whether PTE of wheat in Bijie is harmful to human health has aroused people’s concern. To this end, the objectives of this study are to determine the concentrations of PTE [chromium (Cr), nickel (Ni), arsenic (As), lead (Pb), cadmium (Cd), and fluorine (F)] in wheat grains, identify contaminant sources, and evaluate the probabilistic risks to human beings. A total of 149 wheat grain samples collected from Bijie in Guizhou were determined using the inductively coupled plasma mass spectrometer (ICP-MS) and fluoride-ion electrode methods. The mean concentrations of Cr, Ni, As, Cd, Pb, and F were 3.250, 0.684, 0.055, 0.149, 0.039, and 4.539 mg/kg, respectively. All investigated PTEs met the standard limits established by the Food and Agriculture Organization except for Cr. For the source identification, Cr and Pb should be originated from industry activities, while Ni, As, and Cd might come from mixed sources, and F was possibly put down to the high geological background value. The non-carcinogenic and carcinogenic health risks were evaluated by the probabilistic approach (Monte Carlo simulation). The mean hazard quotient (HQ) values in the three populations were lower than the safety limit (1.0) with the exception of As (children: 1.03E+00). However, the mean hazard index (HI) values were all higher than 1.0 and followed the order: children (2.57E+00) > adult females (1.29E+00) > adult males (1.12E+00). In addition, the mean carcinogenic risk (CR) values for Cr, As, Pb, and Cd in three populations were all higher than 1E-06, which cannot be negligible. The mean threshold CR (TCR) values were decreased in the order of children (1.32E-02) > adult females (6.61E-03) > adult males (5.81E-03), respectively, all at unacceptable risk levels. Moreover, sensitivity analysis identified concentration factor (CW) as the most crucial parameter that affects human health. These findings highlight that co-exposure of PTE in wheat grains revealed a probabilistic human health risk. Corresponding measures should be undertaken for controlling pollution sources and reducing the risks for the local populace.

Hexaconazole (Hex) has been widely used in agricultural products, and its residues may pose a potential risk to human health. However, the metabolic behavior of Hex enantiomers in mammal organisms is still unknown, which is important for evaluating the differences in their toxicity. In this study, the distribution of S-(+)- and R-(−)-Hex in mice was detected by an ultra-high performance liquid chromatography coupled with tandem mass spectrometry (UPLC–MS/MS), and the mechanism differences in the toxicokinetic behavior were analyzed by molecular docking. Good linearities, accuracies, and precisions were achieved for S-(+)- and R-(−)-Hex, with recoveries of 88.7~104.2% and RSDs less than 9.45% in nine tissues of mice. This established method was then used to detect the toxicokinetic of Hex enantiomers in mice after oral administration within 96 h. The results showed that the half-lives of S-(+)- and R-(−)-Hex were 3.07 and 3.71 h in plasma. Hex was mainly accumulated in the liver, followed by the kidneys, brain, lungs, spleen, and heart. The enantiomeric fraction (EF) values of Hex enantiomers in most of the samples were below 1, indicating that S-(+)-Hex decreased faster than its antipode. The molecular docking showed that the binding of S-(+)-Hex with P450arom was much more stable than R-(−)-Hex, which verified the fact that S-(+)-Hex was prefer to decrease in most of the tissues. The results of this study could be helpful for further evaluating the potential toxic risk of Hex enantiomers and for the development and usage of its pure monomer.

Abstract Background MicroRNAs (miRNAs) regulate adipose tissue development, which are closely related to subcutaneous and intramuscular fat deposition and adipocyte differentiation. As an important economic and agricultural animal, rabbits have low adipose tissue deposition and are an ideal model to study adipose regulation. However, the miRNAs related to fat deposition during the growth and development of rabbits are poorly defined. Methods In this study, miRNA-sequencing and bioinformatics analyses were used to profile the miRNAs in rabbit perirenal adipose tissue at 35, 85 and 120 days post-birth. Differentially expressed (DE) miRNAs between different stages were identified by DEseq in R. Target genes of DE miRNAs were predicted by TargetScan and miRanda. To explore the functions of identified miRNAs, Gene Ontology (GO) enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were performed. Results Approximately 1.6 GB of data was obtained by miRNA-seq. A total of 987 miRNAs (780 known and 207 newly predicted) and 174 DE miRNAs were identified. The miRNAs ranged from 18 nt to 26 nt. GO enrichment and KEGG pathway analyses revealed that the target genes of the DE miRNAs were mainly involved in zinc ion binding, regulation of cell growth, MAPK signaling pathway, and other adipose hypertrophy-related pathways. Six DE miRNAs were randomly selected, and their expression profiles were validated by q-PCR. Conclusions This is the first report of the miRNA profiles of adipose tissue during different growth stages of rabbits. Our data provide a theoretical reference for subsequent studies on rabbit genetics, breeding and the regulatory mechanisms of adipose development.

Nowadays, the efficient identification of the lung nodule greatly leads to the chance of lung cancer risk assessment. Hence, the exact locations of lung nodules are a critical and complicated task. Researchers in this area have been working widely for almost two years. However, previous computer-aided detection (CAD) modules, such as transforming CT, segmenting the lung nodule and extracting the features are mostly complex and time-consuming, because more modules will require the creation of a complete image processing system. In addition, certain state-of-the-art deep learning systems are specified in the database standard. For this purpose, this paper suggests an efficient identification system for lung nodules based on Multi-Scene Deep Learning Framework (MSDLF) by the vesselness filter. A four-channel CNN model is designed to enhance the radiologist's knowledge in the detection of four-stage nodules by integrating two image Scenes. This model can be applied in two different classes. The results show that the Multi-Scene Deep Learning Framework (MSDLF) is efficient for increasing the accuracy and significantly reducing false positives in an enormous amount of image data in the detection of lung nodules.

Community gardens offer broad research opportunities and analytical resources encompassing urban planning to environmental sustainability, food systems, and social capital. However, little is known about the knowledge structure and research development related to community gardens. This study presents an in-depth bibliometric performance analysis and visual scientific mapping analysis of the literature on community gardens by examining 487 published papers selected from the Web of Science database. The results indicated a considerable rise in research papers in this subject area from 2012 onwards, with most contributions from the United States. Studies from high-income countries accounted for 93.22%, and 38 countries have cooperated 167 times in this field. “Health” is the most frequent keyword, and the terms “ecosystem services” has been gaining popularity over the last five years. A combination of co-citation clustering and keyword co-occurrence clustering analysis identified three major research themes in the field of community gardens: “ecosystem services and disservices”, “multidimensional association”, and “sustainable garden systems”. The development of ecosystem value assessment frameworks, the establishment of region-wide soil monitoring databases, accounting for the cost-effectiveness of nature-based solutions, the integration of garden systems into smart cities, and the integration of water management into regulation will be important future research directions regarding community gardens. Overall, this study provides scholars with a systematic and quantitative understanding of community gardens.

The high detected frequencies of hexaconazole (Hex) and arsenic (As) increased the probabilities of their co-existence in agricultural products. However, the combined toxicity effect and mechanism of action for these two pollutants were still unclear. In this study, an untargeted metabolomics method with ultra high performance liquid chromatography and tandem mass spectrometry (UPLC-MS/MS) was developed to monitor the changes of endogenous metabolites and metabolism pathways in mice liver. Our study revealed that significant differences in metabolomics profiles were observed after Hex, As, and Hex+As exposure for 90 d. Hex exposure altered 54 metabolites and 11 pathways significantly which were mainly lipid-related. For As exposure, 63 metabolites and 9 pathways were affected most of which were amino acid-related. Hex+As induced 93 metabolites changes with 34% was lipids and lipid-like molecules and 22% was organic acids and derivatives. Hex+As exposure shared the pathways that altered by Hex and As indicated that the interaction of Hex and As might be independent action. The results of this study could provide an important insight for understanding the mechanism of combined toxicity for Hex and As and be helpful for evaluating their health risk to human.

The soft gripper has received extensive attention, due to its good adaptability and flexibility. The dielectric elastomer (DE) actuator as a flexible electroactive polymer that provides a new approach for soft grippers. However, they have the disadvantage of having a poor rigidity. Therefore, the optimization design method of a rigid-flexible soft finger is presented to improve the rigidity of the soft finger. We analyzed the interaction of the rigid and soft materials, using the finite element method (FEM), and researched the influence of the parameters (compression of the spring and pre-stretching ratio of the DE) on the bending angle. The optimal parameters were obtained using the FEM. We experimentally verified the accuracy of the proposed method. The maximum bending angle is 19.66°. Compared with the theoretical result, the maximum error is 3.84%. Simultaneously, the soft gripper with three fingers can grasp various objects and the maximum grasping quality is 11.21 g.

Evidence shows that physical activity has multiple health benefits for the body and mind of oneself, but little is known about the impacts of the setting and the intensity on exercise experience, especially for obese people. This study investigated the physiological and psychological effects of four walking conditions with different settings (park vs. gym) and intensity (slow vs. fast) on young obese adults. Subjects were 18–21 years old Chinese university students (N = 77), who were diagnosed as obese. They were randomly assigned to participate in one of the four activities in the field: slow walk in the park (2.8 km/h), fast walk in the park (5.5 km/h), slow walk in the gym, and fast walk in the gym. Physiological indices, including blood pressure and heart rate, were measured before and after the walk. Psychological responses were measured by the Symbol Digit Modalities Test, the mood states scale, and the semantic differential scale. This study of obese people aged 18–21 years confirmed the previous findings that exercising in natural environments better relieved stress and restored attentional level than indoor activities. The results suggested that the mood states of the participants and their environmental perceptions may be influenced by the walking conditions with different setting and speed. The findings can be used in planning and designing urban green spaces for promoting physical activity and making exercise plans for obese people.

Augmented reality (AR) technology has been applied to the industrial field; however, at present, most industrial AR applications are developed for specific application scenarios, which are difficult to develop and have a long development cycle, and lack universality. To this end, this paper proposed a quick development toolkit for augmented reality visualization (QDARV) of a factory by using the script configuration and parsing approach. With QDARV, designers can quickly develop industrial AR applications, achieve AR registration based on quick response (QR) code and simultaneous localization and mapping (SLAM), and superpose information such as disassembly animations, industrial instruments, pictures, and texts on real scenes. In QDARV, an AR registration method based on SLAM map reloading is proposed. Through saving and reloading the map and the configuration and analysis of the SLAM-AR display content script, the AR scene configured by the designer is displayed. Meanwhile, the objects detected using YOLOv5 are used as a landmark to assist the SLAM system in positioning. The QDARV can be applied to realize AR visualization of factories with a large area.

Soft rot disease caused by Botryosphaeria dothidea and Phomopsis sp. is the most serious fungal disease of the kiwifruit production area in southwest China. In this work, the role of the co-application of tetramycin and matrine in the resistance of kiwifruit fruits against soft rot disease and its effects on development, quality and amino acids of kiwifruit fruits were investigated. The results indicate that matrine exhibited an outstanding toxicity against B. dothidea RF-1 and Phomopsis sp. RF-2 with EC50 values of 0.442 and 0.332 mg kg−1. The foliar co-application of 0.3% tetramycin aqueous solutions (AS) 5000-fold liquid + 0.5% matrine AS 1000-fold liquid could effectively control soft rot disease with a control efficacy of 82.68%, which was significantly (p < 0.05) higher than 75.19% of 0.3% tetramycin AS 5000-fold liquid and significantly (p < 0.01) higher than 68.50% of 0.5% matrine AS 500-fold liquid. Moreover, the co-application of tetramycin and matrine was more effective than tetramycin or matrine alone in improving disease resistance, quality and amino acids of kiwifruit fruits. This study highlights that the co-application of tetramycin and matrine can be used as a practicable, cost-effective and environmentally friendly candidate or alternative approach for controlling soft rot disease of kiwifruit.

Abstract Background Sirtuin 3 (Sirt3) is a key regulator of energy metabolism and oxidative stress. To investigate the role of Sirt3 in contrast-induced acute kidney injury (CIAKI), we established the model both in vivo and in vitro to explore the potential mechanisms. Methods In vivo, we established CIAKI models in wild-type (WT) and Sirt3-knockout (Sirt3-KO) mice. Blood urea nitrogen (BUN) and serum creatinine (Scr) were detected by enzyme-linked immunosorbent assay, Glomerular Filtration Rate (GFR) and creatinine clearance were also investigated. We detected the production of reactive oxygen species (ROS) via 2′7′-dichlorodihydro-fluorescein diacetate. The expressions of Sirt3, oxidative stress and apoptosis related markers (MnSOD, Catalase, Acetyl-MnSOD K68, Nox4, Bax, Bcl-2 and Caspase3) were measured and analyzed. In addition, we observed the effect of nicotinamide riboside (NR) on CIAKI in WT and Sirt3-KO mice. In vitro, Sirt3 was knocked out by siRNA transfection method in HK-2 cells. Sirt3, ROS, oxidative stress and apoptosis markers in HK-2 cells were also measured. Results Our data demonstrated that the levels of Scr and BUN in Sirt3-KO mice were increased while the levels of the GFR and creatinine clearance were decreased in CIAKI mice. In Sirt3-KO or siRNA groups, the activities of MnSOD and Catalase were markedly down-regulated. Also, the expression of Caspase3 were markedly increased and the ratio of Bcl-2/Bax was decreased, while the ROS level was increased in Sirt3 deficiency groups. NR ameliorated CIAKI in WT mice but not in Sirt3-KO mice. Conclusion Our results suggest that Sirt3 deficiency aggravates contrast-induced acute kidney injury. Sirt3 is critical in NR-mediated renoprotection in CIAKI.

Purpose: To explore the risk factors that may predict the lymph node metastasis potential of these lesions and new prevention strategies in papillary thyroid carcinoma patients.Materials and Methods: In total, 9,369 papillary thyroid carcinoma patients with 37.17% lymph node metastasis were analyzed (Revman 5.3 software) in this study. The PubMed and Embase databases were used for searching works systematically that were published through to January 22, 2020.Results: Several factors were related to the increased risk of lymph node metastasis in patients with papillary thyroid carcinoma: age 1 cm), tumor location (1/3 upper), capsular invasion, and extra thyroidal extension. Bilateral tumors and Hashimoto's thyroiditis were unrelated to lymph node metastasis in patients with papillary thyroid cancer.

Cytochromes P450 (CYP) are one of the major xenobiotic metabolizing enzymes with increasing importance in pharmacogenetics. The CYP2C9 enzyme is responsible for the metabolism of a wide range of clinical drugs. More than sixty genetic variations have been identified in CYP2C9 with many demonstrating reduced activity compared to the wild-type (WT) enzyme. The CYP2C9*8 allele is predominantly found in persons of African ancestry and results in altered clearance of several drug substrates of CYP2C9. The X-ray crystal structure of CYP2C9*8, which represents an amino acid variation from arginine to histidine at position 150 (R150H), was solved in complex with losartan. The overall conformation of the CYP2C9*8-losartan complex was similar to the previously solved complex with wild type (WT) protein, but it differs in the occupancy of losartan. One molecule of losartan was bound in the active site and another on the surface in an identical orientation to that observed in the WT complex. However, unlike the WT structure, the losartan in the access channel was not observed in the *8 complex. Furthermore, isothermal titration calorimetry studies illustrated weaker binding of losartan to *8 compared to WT. Interestingly, the CYP2C9*8 interaction with losartan was not as weak as the CYP2C9*3 variant, which showed up to three-fold weaker average dissociation constant compared to the WT. Taken together, the structural and solution characterization yields insights into the similarities and differences of losartan binding to CYP2C9 variants and provides a useful framework for probing the role of amino acid substitution and substrate dependent activity.

Growth differentiation factor 11 (GDF11), is a member of the transforming growth factor-beta (TGF-β) superfamily and bone morphogenetic protein (BMP) subfamily. In this study, we aimed to assess the expression profile of GDF11, its prognostic value in terms of OS, as well as the potential mechanisms leading to its dysregulation in uveal melanoma. A retrospective study was conducted using our primary data and genetic, clinicopathological and overall survival (OS) data from the Cancer Genome Atlas-Uveal Melanoma (TCGA-UVM). Results showed that GDF11 expression was significantly higher in tumor tissues compared with that in adjacent normal tissues. High GDF11 expression was associated with uveal melanoma in advanced stages (IV), epithelioid cell dominant subtype, as well as extrascleral extension. Univariate analysis showed that older age, epithelioid cell dominant, with extrascleral extension and increased GDF11 expression were associated with unfavorable OS. Multivariate analysis confirmed that GDF11 expression was an independent prognostic indicator of unfavorable OS (HR: 1.704, 95%CI: 1.143-2.540, p = 0.009), after adjustment of age, histological subtypes and extrascleral extension. Among the 80 cases of uveal melanoma, only 3 cases had low-level copy gain (+1) and 2 cases had heterozygous loss (-1). No somatic mutations, including SNPs and small INDELs were observed in GDF11 DNA. The methylation of these four CpG sites had weakly (cg22950598 and cg23689080), moderately (cg09890930), or strongly (cg05511733) negative correlation with GDF11 expression. In addition, the patients with high methylation of these four sites had significantly better OS compared to the group with low methylation. Based on these findings, we infer that methylation modulated GDF11 expression might be a valuable prognostic biomarker regarding OS in uveal melanoma.

Intercellular signalling can be mediated by gap junction channels, and calcium blocks this signally during tissue injury. Here, the authors use X-ray crystallography and molecular dynamics to show that the calcium forms an electrostatic barrier to prevent transport of cations.

Nicotinamide nucleotide transhydrogenase (TH) is an enzyme complex in animal mitochondria and bacteria that utilizes the electrochemical proton gradient across membranes to drive the production of NADPH. The enzyme plays an important role in maintaining the redox balance of cells with implications in aging and a number of human diseases. TH exists as a homodimer with each protomer containing a proton-translocating transmembrane domain and two soluble nucleotide binding domains that mediate hydride transfer between NAD(H) and NADP(H). The three-domain architecture of TH is conserved across species but polypeptide composition differs substantially. The complex domain coupling mechanism of TH is not fully understood despite extensive biochemical and structural characterizations. Herein the progress is reviewed, focusing mainly on structural findings from 3D crystallization of isolated soluble domains and more recently of the transmembrane domain and the holo-enzyme from Thermus thermophilus. A structural perspective and impeding challenges in further elucidating the mechanism of TH are discussed.

Cardiovascular calcification is one of the most severe outcomes associated with cardiovascular disease and often results in significant morbidity and mortality. Previous reports indicated that epigenomic regulation of microRNAs (miRNAs) might play important roles in vascular smooth muscle cell (VSMC) calcification. Here, we identified potential key miRNAs involved in vascular calcification in vivo and investigated the role of miR-32-5p (miR-32). According to microarray analysis, we observed increased expression of miR-125b, miR-30a, and miR-32 and decreased expression of miR-29a, miR-210, and miR-320 during the progression of vascularcalcification. Additionally, gain- and loss-of-function studies of miR-32 confirmed promotion of VSMC calcification in mice through the enhanced expression of bonemorphogenetic protein-2, runt-related transcription factor-2(RUNX2), osteopontin, and the bone-specific phosphoprotein matrix GLA protein in vitro. Moreover, miR-32 modulated vascularcalcification progression by activating phosphoinositide 3-kinase (PI3K)signaling and increasing RUNX2 expression and phosphorylation by targeting the 3'-untranslated region of phosphatase and tensin homolog Mrna (PTEN) in mouse VSMCs. Furthermore, we detected higher miR-32 levels in plasmafrom patients with coronary artery disease with coronary artery calcification (CAC) as compared with levels observed in non-CAC patients (P = 0.016), further confirming miR-32 as a critical modulator and potential diagnostic marker for CAC.

Two high-speed countercurrent chromatography (HSCCC) modes were compared by separation of major alkaloids from crude extract of Picrasma quassioides. The conventional HSCCC separation was performed with a two-phase solvent system composed of petroleum ether–ethyl acetate–methanol–water (5:5:4.5:5.5, v/v/v/v) with 200 mg loading. pH-Zone-refining CCC was performed with two-phase solvent system composed of petroleum ether–ethyl acetate–n-butanol–water (3:2:7:9, v/v/v/v) where triethylamine (10 mM) was added to the upper organic stationary phase and hydrochloric acid (5 mM) was added to the lower aqueous phase with 2 g loading. From 2 g of crude extract, 87 mg of 5-methoxycanthin-6-one (a), 38 mg of 1-methoxy-β-carboline (b), 134 mg of 1-ethyl-4,8-dimethoxy-β-carboline (c), 74 mg of 1-ethoxycarbonyl-β-carboline (d), 56 mg of 1-vinyl-4,8-dimethoxy-β-carboline (e) and 26 mg of 1-vinyl-4-dimethoxy-β-carboline (f) were obtained with purities of over 97.0%. The results indicated that pH-zone-refining CCC is an excellent separations tool at the multigram level.

pH-Zone refining counter-current chromatography was successfully applied to the preparative isolation and purification of six alkaloids from the ethanol extracts of Uncaria macrophylla Wall. Because of the low content of alkaloids (about 0.2%, w/w) in U. macrophylla Wall, the target compounds were enriched by pH-zone refining counter-current chromatography using a two-phase solvent system composed of petroleum ether–ethyl acetate–isopropanol–water (2:6:3:9, v/v), adding 10 mM triethylamine in organic stationary phase and 5 mM hydrochloric acid in aqueous mobile phase. Then pH-zone refining counter-current chromatography using the other two-phase solvent system was used for final purification. Six target compounds were finally isolated and purified by following two-phase solvent system composed of methyl tert-butyl ether (MTBE)–acetonitrile–water (4:0.5:5, v/v), adding triethylamine (TEA) (10 mM) to the organic phase and HCl (5 mM) to aqueous mobile phase. The separation of 2.8 g enriched total alkaloids yielded 36 mg hirsutine, 48 mg hirsuteine, 82 mg uncarine C, 73 mg uncarine E, 163 mg rhynchophylline, and 149 mg corynoxeine, all with purities above 96% as verified by HPLC Their structures were identified by electrospray ionization-mass spectrometry (ESI-MS) and 1H-NMR spectroscopy.

Chemical genetic studies on acetyl-CoA carboxylases (ACCs), rate-limiting enzymes in long chain fatty acid biosynthesis, have greatly advanced the understanding of their biochemistry and molecular biology and promoted the use of ACCs as targets for herbicides in agriculture and for development of drugs for diabetes, obesity and cancers. In mammals, ACCs have both biotin carboxylase (BC) and carboxyltransferase (CT) activity, catalyzing carboxylation of acetyl-CoA to malonyl-CoA. Several classes of small chemicals modulate ACC activity, including cellular metabolites, natural compounds, and chemically synthesized products. This article reviews chemical genetic studies of ACCs and the use of ACCs for targeted therapy of cancers.

The over two dozen CYP2B structures of human, rabbit, and woodrat enzymes solved in the last decade have significantly enhanced our understanding of the structure-function relationships of drug metabolizing enzymes. More recently, an important role has emerged for halogen-π interactions in the CYP2B6 active site in substrate selectivity, explaining in part the preference for halogenated ligands as substrates. The mechanism by which such ligands interact with CYP2B enzymes involves conserved phenylalanine side chains, in particular F108, F115, or F297, in the active site, which form π bonds with halogens. To illustrate such halogen-π interactions using drugs that are major substrates of CYP2B6, we present here a crystal structure of CYP2B6 in complex with an analog of the widely used anti-HIV drug efavirenz, which contains a methyl group in place of the carbonyl oxygen. The chlorine of the efavirenz analog forms a π bond with the aromatic ring of F108, whereas the putative metabolism site on the distal end of the molecule is oriented towards the heme iron. The crystal structure showcases how CYP2B6 accommodates this important drug analog of considerable size in the active site by movement of various side chains without substantially increasing the active site volume. Furthermore, the CYP2B6-efavirenz analog complex provides a useful platform to investigate computationally as well as biophysically the effect of genetic polymorphisms on binding of the widely studied efavirenz.