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AIMS: This study aimed to assess the pharmacokinetic/pharmacodynamic (PK/PD) targets of danofloxacin to minimize the risk of selecting resistant Pasteurella multocida mutants and to identify the mechanisms underlying their resistance in an in vitro dynamic model, attaining the optimum dosing regimen of danofloxacin to improve its clinical efficacy based on the mutant selection window (MSW) hypothesis. METHODS AND RESULTS: Danofloxacin at seven dosing regimens and 5 days of treatment were simulated to quantify the bactericidal kinetics and enrichment of resistant mutants upon continuous antibiotic exposure. The magnitudes of PK/PD targets associated with different efficacies were determined in the model. The 24 h area under the concentration-time curve (AUC) to minimum inhibitory concentration (MIC) ratios (AUC24h/MIC) of danofloxacin associated with bacteriostatic, bactericidal and eradication effects against P. multocida were 34, 52, and 64 h. This translates to average danofloxacin concentrations (Cav) over 24 h being 1.42, 2.17, and 2.67 times the MIC, respectively. An AUC/MIC-dependent antibacterial efficacy and AUC/mutant prevention concentration (MPC)-dependent enrichment of P. multocida mutants in which maximum losses in danofloxacin susceptibility occurred at a simulated AUC24h/MIC ratio of 72 h (i.e. Cav of three times the MIC). The overexpression of efflux pumps (acrAB-tolC) and their regulatory genes (marA, soxS, and ramA) was associated with reduced susceptibility in danofloxacin-exposed P. multocida. The AUC24h/MPC ratio of 19 h (i.e. Cav of 0.8 times the MPC) was determined to be the minimum mutant prevention target value for the selection of resistant P. multocida mutants. CONCLUSIONS: The emergence of P. multocida resistance to danofloxacin exhibited a concentration-dependent pattern and was consistent with the MSW hypothesis. The current clinical dosing regimen of danofloxacin (2.5 mg kg-1) may have a risk of treatment failure due to inducible fluoroquinolone resistance.
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Antibacterianos , Farmacorresistência Bacteriana , Fluoroquinolonas , Testes de Sensibilidade Microbiana , Pasteurella multocida , Pasteurella multocida/efeitos dos fármacos , Pasteurella multocida/genética , Fluoroquinolonas/farmacologia , Antibacterianos/farmacologia , Farmacorresistência Bacteriana/genética , MutaçãoRESUMO
OBJECTIVE: The pathogenesis of diarrhea-predominant irritable bowel syndrome (IBS-D) is related to damage to the intestinal mucosal barrier function. Based on the Mast cell (MC)/Tryptase/Protease-activated receptor-2 (PAR-2)/Myosin light chain kinase (MLCK) pathway, this study explored the effect of electroacupuncture (EA) on IBS-D rats and its possible mechanism of protecting the intestinal mucosal barrier. METHODS: The IBS-D rat model was established by mother-offspring separation, acetic acid enema, and chronic restraint stress. The efficacy of EA on IBS-D rats was evaluated by observing the rate of loose stool (LSP) and the minimum volume threshold of abdominal withdrawal reflex (AWR) in rats. Mast cells and the ultrastructure of intestinal mucosa were observed by H&E staining, toluidine blue staining, and transmission electron microscopy. The expression levels of Tryptase, PAR-2, MLCK, zonula occludens-1 (ZO-1), and Occludin in rats were detected by ELISA, qRT-PCR, and western blot. RESULTS: After 7 days of intervention, compared to the IBS-D group, the loose stool rates of rats in IBS-D + EA group and IBS-D + ketotifen group were decreased (P < 0.01), the minimum volume thresholds of AWR were improved (P < 0.01), the inflammation of colon tissue decreased, the number of MCs were decreased (P < 0.01), the expression of Tryptase, PAR-2, and MLCK were lowered (P < 0.01, P < 0.05), and the expression of ZO-1 and Occludin were enhanced (P < 0.01, P < 0.05). Compared to the EA group, there was no significant difference in each index between the ketotifen groups (P > 0.05). CONCLUSION: EA has a good therapeutic effect on IBS-D rats. Regulating the MCs/Tryptase/PAR-2/MLCK pathway may be a mechanism to protect the intestinal mucosal barrier.
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As industrial and societal advancements progress, an increasing number of environmental pollutants linked to human existence have been substantiated to elicit neurotoxicity and developmental neural toxicity. For research in this field, human-derived neural cell lines have become excellent in vitro models. This study examines the utilization of immortalized cell lines, specifically the SH-SY5Y human neuroblastoma cell line, and neural cells derived from human pluripotent stem cells, in the investigation of neurotoxicity and developmental neural toxicity caused by environmental pollutants. The study also explores the culturing techniques employed for these cell lines and provides an overview of the standardized assays used to assess various biological endpoints. The environmental pollutants involved include a variety of organic compounds, heavy metals, and microplastics. The utilization of cell lines derived from human sources holds significant significance in elucidating the neurotoxic effects of environmental pollutants and the underlying mechanisms. Finally, we propose the possibility of improving the in vitro model of the human nervous system and the toxicity detection methods.
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Poluentes Ambientais , Neuroblastoma , Humanos , Poluentes Ambientais/toxicidade , Plásticos , Linhagem Celular , Neurônios/fisiologia , Linhagem Celular TumoralRESUMO
BACKGROUND: Child maltreatment can increase the risk of lifetime non-suicidal self-injury (NSSI) and suicidal self-injury (SSI), but there is limited knowledge regarding the differences of potentially psychological mechanisms between NSSI with and without SSI. METHODS: Participants, 3918 community-based Chinese young men aged 18-34 years in Chengdu, were included in this study. We investigated the association between depression, anxiety, psychosis, child maltreatment, adulthood traumatic events, impulsivity, alcohol dependence, drug abuse, and lifetime of NSSI among participants with and without SSI. Parallel mediation analysis was utilized to explore the mediators for the relation between child maltreatment and NSSI. RESULTS: The prevalence of lifetime NSSI was 6.1 % (95 % CI: 5.4 %-6.9 %) among young men. Anxiety and impulsivity partially mediated the effect of child maltreatment on NSSI either with (indirect effect: 51.2 %) or without SSI (indirect effect: 34.3 %). Depression was independently and significantly associated with only NSSI but not with NSSI+SSI. Alcohol dependence and psychosis were independently and significantly associated with NSSI+SSI and mediated the effect of child maltreatment on NSSI+SSI. LIMITATIONS: The cross-sectional survey data limits the robustness of the proof to the causal relationships. CONCLUSIONS: Anxiety and impulsivity are associated with NSSI either with or without SSI and partially mediate the effect of child maltreatment on NSSI. Depression is associated with only NSSI, while alcohol dependence and psychosis are only associated with NSSI+SSI. It could be crucial to improve treatment and recovery of alcohol dependence and psychosis for preventing young men engaged in NSSI from attempting SSI.
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Experiências Adversas da Infância , Alcoolismo , Comportamento Autodestrutivo , Adulto , Humanos , Masculino , Ansiedade/epidemiologia , Ansiedade/psicologia , Estudos Transversais , Comportamento Impulsivo , Fatores de Risco , Comportamento Autodestrutivo/epidemiologia , Comportamento Autodestrutivo/psicologia , Ideação Suicida , Adolescente , Adulto JovemRESUMO
Fish, as top predators in aquatic ecosystems, play an important role in maintaining the structure and functioning of these ecosystems, making their diversity a topic of great interest. This study focused on the Yangtze River Basin to investigate the fish community structure and diversity using environmental DNA (eDNA) technology. The results showed that a total of 71616 fish operational taxonomic units (OTUs) and 90 fish belonging to 23 families were detected, with the Cyprinidae family being the dominant group, followed by the Cobitidae, Amblycipitidae, etc. Compared to historical traditional morphological fish surveys, the quantity of fish detected using eDNA was relatively low, but the overall distribution pattern of fish communities was generally consistent. The highest fish Shannon-Wiener diversity index in the Yangtze River Basin sites reaches 2.60 with an average value of 1.25. The fish diversity index was higher in the downstream compared to the middle and upstream regions, and there were significant differences among different sampling sites. Significant environmental factors influencing α-diversity included chlorophyll-a, chemical oxygen demand, dissolved oxygen, total nitrogen, and elevation. Non-metric multidimensional scaling (NMDS) analysis revealed significant differences in fish community composition between the upstream and middle/lower reaches of the Yangtze River, while the composition of fish communities in the middle and lower reaches was more similar. Redundancy analysis (RDA) indicated that total organic carbon (TOC) was positively correlated with fish community distribution in the upstream, while water temperature and NO3-N were negatively correlated with fish distribution in the upstream. NH3-N and CODMn were negatively correlated with fish distribution in the middle and downstream regions, indicating a relatively severe water pollution in these areas. Additionally, fish communities in the Yangtze River displayed a typical distance decay pattern.
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Cyprinidae , DNA Ambiental , Humanos , Animais , Ecossistema , Cyprinidae/genética , Poluição da Água , Rios , Monitoramento Ambiental , ChinaRESUMO
Vehicles tend to produce more pollutants especially particles at an urban intersection than other segments. Meanwhile, pedestrians at an intersection are inevitably exposed to high particle level and suffered from the health problem. Especially, some particles can deposit in different thoracic areas of the respiratory system and cause serious health problems. Hence, in this paper, the particles from 0.3 to 10 µm in 16 channels were measured to compare the spatio-temporal characteristics of them on the crosswalk and the roadside. Based on the roadside of fixed measurements, submicron particles (< 1 µm) are discovered to have a high relation with traffic signal and exhibit a bimodal distribution pattern in the green phase. On the crosswalk of mobile measurements, submicron particles present decreasing trend along the crosswalk while crossing. Additionally, mobile measurements were conducted across six time intervals that correspond to different pedestrian's journey when passing the crosswalk. The results showed that all size particles in the first three journeys present high concentrations than that in other journeys. Furthermore, pedestrian exposure to all 16 channel particles was assessed. The total and regional deposition fractions of these particles in different sizes and age groups are determined. What ought to be paid attention to is that these real-world measurement results contribute to advancing the understanding of pedestrian exposure to size-fractionated particles on crosswalk and assisting the pedestrian to make better informed choice so as to limit particle exposure in these pollution hotspots.
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Poluentes Atmosféricos , Poluentes Ambientais , Pedestres , Humanos , Poluentes Atmosféricos/análise , Poluição Ambiental , Acidentes de TrânsitoRESUMO
OBJECTIVE: To observe the effects of electroacupuncture (EA) combined with acellular nerve allograft (ANA) on the morphological structure of spinal ganglion cells and the protein expressions of nerve growth factor (NGF) and phosphorylated protein kinase B (p-Akt) in rats with sciatic nerve injury (SNI), so as to explore the protective mechanism of EA combined with ANA on spinal ganglia. METHODS: SPF male SD rats were randomly divided into normal, model, single ANA bridging (bridging) and EA + ANA (combination) groupsï¼ with 10 rats in each group. The SNI rat model was established by right sciatic nerve transection. Rats in the bridging group were bridged with ANA to the two broken ends of injured sciatic nerves. Rats in the combination group were treated with EA at "Yanglingquan" (GB34) and "Huantiao" (GB30) 2 d after ANA bridging, with dilatational wave, frequency of 1 Hz/20 Hz, intensity of 1 mA, 15 min/d, 7 d as a course of treatment for 4 consecutive courses. Sciatic function index (SFI) was observed by footprint test. Wet weight ratio of tibialis anterior muscle was calculated after weighing. Morphology of rat spinal ganglion cells was observed after Nissl staining. The protein expressions of NGF and p-Akt were detected by immunofluorescence and Western blot. RESULTS: Compared with the normal group, the SFI and wet weight ratio of tibialis anterior muscle were significantly decreased (P<0.05), the number of Nissl bodies in spinal ganglion cells was significantly reduced (P<0.05) with dissolution and incomplete structureï¼ the protein expressions of NGF and p-Akt in ganglion cells were significantly decreased (P<0.05) in the model group. Following the interventions and in comparison with the model group, the SFI and the wet weight ratio of tibialis anterior muscle were significantly increased (P<0.05), the damage of Nissl bodies in ganglion cells was reduced and the number was obviously increased (P<0.05), and the protein expressions of NGF and p-Akt in ganglion cells were significantly increased (P<0.05) in the bridging and combination groups. Compared with the bridging group, the SFI and the wet weight ratio of tibialis anterior muscle were increased (P<0.05), the morphology of Nissl bodies in ganglion cells was more regular and the number was increased (P<0.05), the protein expressions of NGF and p-Akt in spinal ganglion cells were significantly increased (P<0.05) in the combination group. CONCLUSION: EA combined with ANA can improve the SFI and the wet weight ratio of tibialis anterior muscle in SNI rats, improve the morphology and structure of Nissl bodies in spinal ganglion cells, and increase the protein expressions of NGF and p-Akt in spinal ganglion, so as to play a protective role on spinal ganglia.
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Aloenxertos , Eletroacupuntura , Gânglios Espinais , Traumatismos dos Nervos Periféricos , Nervo Isquiático , Animais , Masculino , Ratos , Aloenxertos/metabolismo , Gânglios Espinais/citologia , Gânglios Espinais/metabolismo , Fator de Crescimento Neural/genética , Fator de Crescimento Neural/metabolismo , Traumatismos dos Nervos Periféricos/terapia , Proteínas Proto-Oncogênicas c-akt/genética , Proteínas Proto-Oncogênicas c-akt/metabolismo , Ratos Sprague-Dawley , Nervo Isquiático/lesõesRESUMO
Background: To avoid public health risks, all governments ensure monitoring and treatment of mentally ill persons if they offend and assess their level of criminal responsibility. The Criminal Procedure Law of the People's Republic of China (2013) instituted special procedures. However, there are few articles in English which explain the implementation of mandatory treatment procedures in China. Methods: We collected 5,262 qualified documents from 2013 to 2021 from the China Judgments Documents Online. We analyzed social demographic characteristics, trial-related information as well as the mandatory treatment-related content, to investigate the mandatory treatment of China's mentally ill offenders without criminal responsibility, from 2013 to 2021. Simple descriptive statistics and chi-square tests were used to compare differences among several types of documents. Results: There was an overall change trend of the number of documents: increasing year by year from 2013 to 2019 after the implementation of the new law, but with sharp decrease in 2020 and 2021 during covid-19 pandemic. From 2013 to 2021, a total of 3,854 people had applications made for mandatory treatment, of whom 3,747 (97.2%) were given mandatory treatment, 107 (2.8%) had applications rejected. "Schizophrenia and other psychotic disorders" was the most common diagnosis in both groups and all offenders receiving mandatory treatment (3,747, 100.0%) were considered to have no criminal responsibility. A total of 1,294 patients had applications made for relief of mandatory treatment, of whom 827 (63.9%) were subsequently approved for relief, 467 (36.1%) were rejected. A total of 118 patients had applications for relief two or more times, and 56 (47.5%) were finally relieved. Conclusion: Our study presents the Chinese model of a criminal mandatory treatment system to the international community which has been in operation since the implementation of the new law. Legislatory changes and covid-19 pandemic can have effect on the number of mandatory treatment cases. Patients, their close relatives and mandatory treatment institutions have the right to apply for relief from mandatory treatment, but the final decision in China is taken by the court.
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The mechanism behind textural changes in scallop adductor muscle during boiling was investigated through proteomic analysis, determination of water holding capacity (WHC) and oxidative indices, as well as observation with scanning electron microscopy and multiphoton nonlinear optical microscopy. The hardness and shear force showed the trend of first rising and then falling in 45 min-boiling time. The results suggested that short-time boiling caused the oxidation, denaturation and aggregation of proteins, resulting in the transverse contraction of myofibers and lateral cross-linked aggregation of muscle fibers and a rise in WHC, which led to the increase in hardness and shear force. While long-time boiling caused the progressive degradation of structural proteins such as fibrillin-1, collagen alpha-2(I) chain, myosin heavy chain, basement membrane-specific heparan sulfate proteoglycan core protein, and paramyosin, resulting in a loose myofibril network and the decrease in WHC, which led to the decrease in hardness and shear force.
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Pectinidae , Proteômica , Animais , Músculo Esquelético/fisiologia , Miofibrilas , Cadeias Pesadas de Miosina/metabolismo , Pectinidae/metabolismo , Temperatura AltaRESUMO
Among 26 sous-vide cooking conditions of scallop adductor muscle (SAM), 65 °C-5.5 h, 70 °C-1.5 h and 100 °C-5 min were selected by the differential scanning calorimetry analysis. After sous-vide cooking, the shear force, hardness, springiness, cohesiveness, chewiness and recoverability of SAM increased significantly compared to fresh sample. The cooking also changed the secondary structures of the proteins in SAM with the rising ß-sheet and descending α-helix, and the chemical interactions with the rising hydrophobic interactions and disulfide bonds but the descending ionic bonds and hydrogen bonds. These caused the longitudinal shrinkage and transverse aggregation of muscle fibers, and the aggregation and cross-linking between myofibrils which led to the squeeze of immobile water from myofibril network structure. This indicated that the denaturation, oxidation, aggregation and cross-linking of proteins caused by heat treatment changed the microstructure and water distribution, which contributed to the increased textural indicators of sous-vide cooked SAM.
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Culinária , Pectinidae , Animais , Músculo Esquelético/química , Miofibrilas/química , Água/análiseRESUMO
The nonlinearity of semiconductor quantum dots under the condition of low light levels has many important applications. In this study, linear absorption, self-Kerr nonlinearity, fifth-order nonlinearity and cross-Kerr nonlinearity of multiple quantum dots, which are coupled by multiple tunneling, are investigated by using the probability amplitude method. It is found that the linear and nonlinear properties of multiple quantum dots can be modified by the tunneling intensity and energy splitting of the system. Most importantly, it is possible to realize enhanced self-Kerr nonlinearity, fifth-order nonlinearity and cross-Kerr nonlinearity with low linear absorption by choosing suitable parameters for the multiple quantum dots. These results have many potential applications in nonlinear optics and quantum information devices using semiconductor quantum dots.
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Mitochondrial genomes are widely used for phylogenetic and phylogeographic analyses among arthropods, but there is a lack of sufficient mitochondrial genome sequence data for spiders. Herein, we sequenced and characterized the complete mitochondrial genome of a crab spider Ebrechtella tricuspidata (Araneae: Thomisidae). The circular mitochondrial genome is 14,352â¯bp long, including a standard set of 37 genes and an Aâ¯+â¯T-rich region. Nucleotide composition is highly biased toward Aâ¯+â¯T nucleotides (77.3%). A novel gene order rearrangement is detected by a tRNA (trnL1) translocation. Tandem repeats are not identified in the Aâ¯+â¯T-rich region. Most of the tRNAs are greatly reduced in size and cannot be folded into typical cloverleaf-shaped secondary structures. The phylogenetic analysis confirms that the mitochondrial genome sequences are useful in resolving higher-level relationship of Araneae. Overall, our data present in this study will elevate our knowledge on the architecture and evolution of spider mitochondrial genome.
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Genoma Mitocondrial , RNA de Transferência/genética , Aranhas/genética , Animais , Proteínas de Artrópodes/genética , Evolução Molecular , Filogenia , RNA Ribossômico/genética , Aranhas/classificaçãoRESUMO
Ladybird beetles (Coleoptera: Coccinellidae), with broad morphological diversity, wide geographic distribution and substantial agricultural significance, are a challenging group for taxonomists and phylogenetics. As a promising tool to identify and discover new species, DNA barcoding might offer significant potential for identification, taxonomy and phylogeny of ladybird beetles. In the present study, a total of 1364 COI (cytochrome C oxidase subunit I) sequences representing 128 species from 52 genera of ladybird beetles were screened for barcoding evaluation and phylogenetic analysis. Our results from the barcoding analysis revealed that COI displays a similar level of species identification efficiency (nearly 90%) either based on Kimura two-parameter (K2P) distances calculation or on simplified neighbour-joining (NJ) tree construction. The phylogenetic relationships within the family Coccinellidae was analyzed by Bayesian-inference (BI) method. The phylogenetic results confirmed the monophyly of the subfamilies Microweisinae and Coccinellinae sensu Slipinski (2007), and suggested that the subfamilies Coccidulinae, Chilocorinae and Scymninae are paraphyletic. However, the phylogenetic relationships among different subfamilies are not clearly defined and thus remain to be thoroughly studied. Overall, our study confirmed the usefulness of DNA barcoding for coccinellid species identification and phylogenetic inference.
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Besouros/genética , Filogenia , Animais , Besouros/classificação , Código de Barras de DNA Taxonômico/métodos , Código de Barras de DNA Taxonômico/normas , Complexo IV da Cadeia de Transporte de Elétrons/genética , Proteínas de Insetos/genéticaRESUMO
The complete mitochondrial genome of an orb-weaver spider Araneus angulatus is 14,205 bp in length and contains 13 protein-coding genes, 2 ribosomal RNAs, 22 transfer RNAs, and a control region. The A + T content of the major strand is 75.4%. Nine of the protein-coding genes are initiated by typical ATN codons, one gene (COI) starts with TTA and other three genes (ND6, COII, and COIII) begin with TTG. The truncated stop codon (T) occurs in ND3, ND4L, and ND6, whereas the rest ten genes end with the canonical stop codon (TAA and TAG). Fifteen tRNAs lack the potential to form the typically cloverleaf-shaped secondary structure. The control region is 649 bp in length and contains a long tandem repeat region. The result of phylogenetic analysis shows that the relationship of A. angulatus was close to the species in the same family Araneidae.