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Sulfamethazine (SAT) is widely present in sediment, soil, rivers, and groundwater. Unfortunately, traditional water treatment technologies are inefficient at eliminating SAT from contaminated water. Therefore, developing an effective and ecologically friendly treatment procedure to effectively remove SAT is critical. This has raised concerns about its potential impact on the environment and human health. In this study, metal-organic-inorganic composites consisting of graphene-encapsulated Fe-Mn metal catalyst (Mn3Fe1-NC) were synthesized by calcining MnFe Prussian blue analogs (PBA) under a nitrogen atmosphere. The composites were applied to activate peroxymonosulfate (PMS) and facilitate the degradation of SAT in aquatic environments. The Mn3Fe1-NC, dosed with 5 mg, in combination with PMS, dosed with 1.5 mmol L-1, achieved a 91.8% degradation efficiency of SAT. The transformation of the CN skeleton led to the formation of a carbon shell structure, which consequently reduced metal ion leaching from the material. At various pH levels, the iron and manganese ions were observed to leach out at levels lower than 0.1392 and 0.0580 mg L-1, respectively. In contrast, the Mn3Fe1-NC was found to be minimally impacted by pH levels and coexisting ions present in the aqueous environment. Radical burst experiments and electrochemical analysis tests verified that degradation primarily occurs through the nonradical pathway of electron transfer. The active sites responsible for this process were identified as the Mn (IV) and graphitic-N atoms on the material, which facilitate direct electron transfer. Additionally, the presence of Fe atoms promotes the valence cycling of Mn atoms. This study introduces new insights into the reaction mechanism and the constitutive relationship of catalytic centers in nonradical oxidation reactions.
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INTRODUCTION: Focal segmental glomerulosclerosis (FSGS) is a common glomerulopathy with an unclear mechanism. The demand for FSGS clinical diagnostic biomarkers has not yet been met. Circular RNA (circRNA) is a novel non-coding RNA with multiple functions, but its diagnostic value for FSGS remains unexplored. This study aimed to identify circRNAs that could aid in early clinical diagnosis and to investigate their mechanisms in podocyte injury. METHODS: The signature of plasma circRNAs for FSGS was identified by circRNA microarray. The existence of circRNAs was confirmed by quantitative real-time polymerase chain reaction (qRT-PCR), RNase R assay, and DNA sequencing. Plasma levels of circRNAs were evaluated by qRT-PCR. The diagnostic value was appraised by the receiver operating characteristic curve. The circRNA-miRNA-mRNA network was built with Cytoscape 7.3.2. Statistically significant differences were calculated by the Mann-Whitney U test. RESULTS: A total of 493 circRNAs (165 upregulated, 328 downregulated) were differentially expressed in the plasma of FSGS patients (n = 3) and normal controls (n = 3). Eight candidate circRNAs were demonstrated to be circular and stable transcripts. Among them, hsa_circ_0001230 and hsa_circ_0023879 were significantly upregulated in FSGS patients (n = 29) compared to normal controls (n = 51). The areas under the curve value of hsa_circ_0001230 and hsa_circ_0023879 were 0.668 and 0.753, respectively, while that of the two-circRNA panel was 0.763. The RNA pull-down analysis revealed that hsa_circ_0001230 and hsa_circ_0023879 could sponge hsa-miR-106a. Additionally, hsa_circ_0001230 and hsa_circ_0023879 positively regulated hsa-miR-106a target genes phosphatase and tensin homolog (PTEN) and Bcl-2-like protein 11 (BCL2L11) in podocytes. CONCLUSION: hsa_circ_0001230 and hsa_circ_0023879 are novel blood biomarkers for FSGS. They may regulate podocyte apoptosis by competitively binding to hsa-miR-106a.
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Biomarcadores , Glomerulosclerose Segmentar e Focal , MicroRNAs , RNA Circular , RNA Mensageiro , Humanos , Glomerulosclerose Segmentar e Focal/sangue , Glomerulosclerose Segmentar e Focal/genética , Glomerulosclerose Segmentar e Focal/diagnóstico , RNA Circular/sangue , RNA Circular/genética , Biomarcadores/sangue , MicroRNAs/sangue , MicroRNAs/genética , RNA Mensageiro/sangue , RNA Mensageiro/genética , Podócitos/metabolismo , Podócitos/patologia , Masculino , Feminino , Adulto , Redes Reguladoras de GenesRESUMO
Rapid corneal re-epithelialization is important for corneal wound healing. Corneal epithelial cell motility and oxidative stress are important targets for therapeutic intervention. In this study, we covalently conjugated the antioxidant caffeic acid (CA) with a bioactive peptide sequence (PHSRN) to generate a CA-PHSRN amphiphile, which was formulated into nanoparticular eye drops with an average size of 43.21 ± 16 nm. CA-PHSRN caused minimal cytotoxicity against human corneal epithelial cells (HCECs) and RAW264.7 cells, exhibited an excellent free radical scavenging ability, and remarkably attenuated reactive oxygen species (ROS) levels in H2O2-stimulated HCECs. The antioxidant and anti-inflammatory activities of CA-PHSRN were assessed in lipopolysaccharide (LPS)-stimulated RAW264.7 cells. The results show that CA-PHSRN treatment effectively prevented LPS-induced DNA damage and significantly reduced the levels of LPS-induced pro-inflammatory cytochemokines (i.e., iNOS, NO, TNF-α, IL-6, and COX-2) in a dose-dependent manner. Moreover, using a rabbit corneal epithelial ex vivo migration assay, we demonstrated that the proposed CA-PHSRN accelerated corneal epithelial cell migration and exhibited high ocular tolerance and ocular bioavailability after topical instillation. Taken together, the proposed CA-PHSRN nanoparticular eye drops are a promising therapeutic formulation for the treatment of corneal epithelial injury.
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Lesões da Córnea , Epitélio Corneano , Animais , Humanos , Coelhos , Antioxidantes/farmacologia , Fibronectinas , Peróxido de Hidrogênio/farmacologia , Lipopolissacarídeos/farmacologia , Fragmentos de Peptídeos , Lesões da Córnea/tratamento farmacológico , Peptídeos/farmacologia , Soluções Oftálmicas/farmacologiaRESUMO
ns2-Metal halide perovskites have attracted wide attention due to their fascinating photophysical properties. However, achieving high photoluminescence (PL) properties is still an enormous challenge, and the relationship between the lattice environment and ns2-electron expression is still elusive. Herein, an organic-inorganic Bi3+-based halide (C5H14N2)2BiCl6·Cl·2H2O (C5H14N22+ = doubly protonated 1-methylpiperazine) with a six-coordinated structure has been successfully prepared, which, however, exhibits inferior PL properties due to the chemically inert expression of Bi3+-6s2 lone-pair electrons. After reasonably embedding Sb3+ with 5s2 electrons into the lattice of (C5H14N2)2BiCl6·Cl·2H2O, the host lattice environment induces the Sb-Cl moiety to change from the original five-coordinated to six-coordinated structure, thereby resulting in a broad-band yellow emission with a PL efficiency up to 50.75%. By utilizing the host lattice of (C5H14N2)2BiCl6·Cl·2H2O, the expression of Sb3+-5s2 lone-pair electrons is improved and thus promotes the radiative recombination from the Sb3+-3P1 state, resulting in the enhanced PL efficiency. This work will provide an in-depth insight into the effect of the local structure on the expression of Sb3+-5s2 lone-pair electrons.
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BACKGROUND: Prolonged length of stay in post-anesthesia care unit (PLOS in PACU) is a combination of risk factors and complications that can compromise quality of care and operating room efficiency. Our study aimed to develop a nomogram to predict PLOS in PACU of patients undergoing elective surgery. METHODS: Data from 24017 patients were collected. Least absolute shrinkage and selection operator (LASSO) was used to screen variables. A logistic regression model was built on variables determined by a combined method of forward selection and backward elimination. Nomogram was designed with the model. The nomogram performance was evaluated with the area under the receiver operating characteristic curve (AUC) for discrimination, calibration plot for consistency between predictions and actuality, and decision curve analysis (DCA) for clinical application value. RESULTS: A nomogram was established based on the selected ten variables, including age, BMI < 21 kg/m2, American society of Anesthesiologists Physical Status (ASA), surgery type, chill, delirium, pain, naloxone, operation duration and blood transfusion. The C-index value was 0.773 [95% confidence interval (CI) = 0.765 - 0.781] in the development set and 0.757 (95% CI = 0.744-0.770) in the validation set. The AUC was > 0.75 for the prediction of PLOS in PACU. The calibration curves revealed high consistencies between the predicted and actual probability. The DCA showed that if the threshold probability is over 10% , using the models to predict PLOS in PACU and implement intervention adds more benefit. CONCLUSIONS: This study presented a nomogram to facilitate individualized prediction of PLOS in PACU for patients undergoing elective surgery.
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Anestesia , Nomogramas , Humanos , Tempo de Internação , Procedimentos Cirúrgicos Eletivos , Modelos LogísticosRESUMO
The emergence of methicillin-resistant Staphylococcus aureus (MRSA) has become a critical global concern. Identifying new anti-S. aureus agents or therapeutic strategies are urgently needed to treat S. aureus infection. The present study investigated the antibacterial activity of 16 phenolic compounds against MRSA, four of which exhibited antibacterial activity. Their antibacterial activities increased in a dose-dependent manner but showed different responses with the extension of treatment time. Trialdehyde phloroglucinol (TPG) and 2-nitrophloroglucinol (NPG) maintained stable antibacterial activity; however, that of dichlorophenol and myricetin decreased rapidly over 24 hr of treatment. Checkerboard and time-kill assays indicated that TPG and NPG exhibited strong synergistic antibacterial activities with penicillin or bacitracin. Microscopic observation and membrane integrity analysis showed that the combination of TPG and penicillin destroyed the MRSA cell membrane, resulting in the leakage of intracellular biomacromolecules, marked changes in surface zeta potential, and the collapse of membrane potential. Moreover, the combination significantly decreased penicillinase activity and penicillin-binding protein 2a mRNA expression, inhibiting MRSA growth. Taken together, these results demonstrated that the combination of the phloroglucinol derivative TPG and penicillin has significant synergistic anti-MRSA activity and can serve as a potential therapeutic strategy to treat MRSA infections.
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Antibacterianos , Staphylococcus aureus Resistente à Meticilina , Antibacterianos/farmacologia , Sinergismo Farmacológico , Testes de Sensibilidade Microbiana , Penicilinas/farmacologia , Staphylococcus aureus , Floroglucinol/farmacologiaRESUMO
A series of thioether pleuromutilin derivatives containing 1,2,4-triazole on the side chain of C14 were designed and synthesized. The in vitro antibacterial activities experiments of the synthesized derivatives showed that compounds 72 and 73 displayed superior in vitro antibacterial effect against MRSA minimal inhibitory concentration (MIC = 0.0625 µg/mL) than tiamulin (MIC = 0.5 µg/mL). The results of time-kill study and postantibiotic effect study indicated that compound 72 could inhibit the growth of MRSA quickly (-2.16 log10 CFU/mL) and showed certain postantibiotic effect (PAE) time (exposure to 2 × MIC and 4 × MIC for 2 h, the PAE was 1.30 and 1.35 h) against MRSA. Furthermore, the binding mode between compound 72 and 50S ribosome of MRSA was explored by molecular docking and five hydrogen bonds were formed between compound 72 and 50S ribosome.
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Antibacterianos , Compostos Policíclicos , Simulação de Acoplamento Molecular , Antibacterianos/química , Compostos Policíclicos/farmacologia , Compostos Policíclicos/química , Testes de Sensibilidade Microbiana , Relação Estrutura-Atividade , PleuromutilinasRESUMO
Two series of pleuromutilin derivatives were designed and synthesized as inhibitors against Staphylococcus aureus (S. aureus). 6-chloro-4-amino-1-R-1H-pyrazolo[3,4-d]pyrimidine or 4-(6-chloro-1-R-1H-pyrazolo[3,4-d]pyrimidine-4-yl)amino-phenylthiol were connected to pleuromutilin. A diverse array of substituents was introduced at the N-1 position of the pyrazole ring. The in vitro antibacterial activities of these semisynthetic derivatives were evaluated against two standard strains, Methicillin-resistant Staphylococcus aureus (MRSA) ATCC 43300, Staphylococcus aureus (S. aureus), ATCC 29213 and two clinical S. aureus strains (144, AD3) using the broth dilution method. Compounds 12c, 19c and 22c (MIC = 0.25 µg/mL) manifested good in vitro antibacterial ability against MRSA which was similar to that of tiamulin (MIC = 0.5 µg/mL). Among them, compound 22c killed MRSA in a time-dependent manner and performed faster bactericidal kinetics than tiamulin in time-kill curves. In addition, compound 22c exhibited longer PAE than tiamulin, and showed no significant inhibition on the cell viability of RAW 264.7, Caco-2 and 16-HBE cells at high doses (≤8 µg/mL). The neutropenic murine thigh infection model study revealed that compound 22c displayed more effective in vivo bactericidal activity than tiamulin in reducing MRSA load. The molecular docking studies indicated that compound 22c was successfully localized inside the binding pocket of 50S ribosomal, and four hydrogen bonds played important roles in the binding of them.
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Diterpenos , Staphylococcus aureus Resistente à Meticilina , Compostos Policíclicos , Infecções Estafilocócicas , Animais , Camundongos , Humanos , Staphylococcus aureus , Simulação de Acoplamento Molecular , Células CACO-2 , Testes de Sensibilidade Microbiana , Antibacterianos/química , Diterpenos/química , Compostos Policíclicos/farmacologia , Pirimidinas/farmacologia , Pirimidinas/química , Infecções Estafilocócicas/tratamento farmacológico , PleuromutilinasRESUMO
OBJECTIVES: To derive the paternity index (PI) calculation formula of the alleged father (AF) when the AF is a relative (parent/child, siblings, grandparent/grandchild, uncle/nephew, first cousins) of the child's biological mother. METHODS: For the case when the AF is related to the child's biological mother, the existence of the relationship in the numerator and denominator hypothesis of PI was considered. The genotype frequency of the AF was calculated by using the frequency formula in which the mother's genotype was considered, while the random male in the denominator was substituted as another relative of the mother's same rank. The PI calculation formula was derived to eliminate the effect of the relationship between AF and the child's biological mother. RESULTS: When the AF and the biological mother have first, second and tertiary kinship, a more conservative PI was obtained from the PI calculation formula derived in this study compared with the PI calculation method which did not consider kinship. CONCLUSIONS: The calculation method provided in this study can eliminate the effect of the relation of the AF and mother on the PI in incest cases, to obtain more accurate and conservative identification conclusions.
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Mães , Paternidade , Feminino , Humanos , Masculino , Criança , Genótipo , PaiRESUMO
Because of its excellent monodispersity, high throughput, and low volume, microfluidics-based droplet PCR has become the core technology of digital PCR, next-generation sequencing, and other technology platforms. This study constructed a microfluidic water-in-oil droplet PCR system and amplified a commercially available forensic 22-plex short tandem repeat detection system. We analyzed the sensitivity, concordance, amplification efficiency of the droplet PCR, and influence factors of the above aspects. The droplet PCR showed high concordance with conventional bulk PCR and had high sensitivity as 0.125 ng. Furthermore, we observed the performance of droplet PCR in high-order mixed DNA. As the mixture ratios from 10:1 to 30:1, droplet PCR presented more mixture proportion (Mx) increased loci from 11 (57.89%) to 17 (89.47%). In the mixture ratios 20:1, 25:1, and 30:1, significant Mx differences between droplet PCR and bulk PCR were observed (p < 0.05). The results showed that the droplet PCR could improve the identification of the minor contributor's DNA in a two-person mixture and alleviate the imbalanced amplification problem. This study provides a reference and basis for the wide application of droplet PCR in forensic science.
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Microfluídica , Repetições de Microssatélites , DNA/análise , DNA/genética , Impressões Digitais de DNA/métodos , Ciências Forenses , Humanos , Repetições de Microssatélites/genética , Reação em Cadeia da Polimerase/métodosRESUMO
Inflammatory markers play an important role in the pathophysiology of patients with oral problems such as oral lichen planus. This study aimed to investigate the relationship between vitamin D levels and inflammatory markers and total antioxidants in people with oral lichen planus. In this case-control study, 131 patients with oral lichen planus (67 in the lichen planus group and 54 in the control group) were examined. 8 cc of blood was taken from all participants to assess blood factors, inflammatory markers and antioxidant levels. Data were analyzed using SPSS statistical software. The mean age of subjects was 42 years. Vitamin D3 levels in the lichen planus group were lower than in the control group, but this decrease was not statistically significant (P> 0.05). According to statistical findings in the lichen planus group, there was a significant relationship between vitamin D3 levels, inflammatory markers and cellular stress factors (P≤0.05). It is concluded that vitamin D3 in people with oral lichen planus can play an important role in the pathogenesis of oral disease and increase inflammation. Because patients with oral lichen planus are affected by various inflammatory factors, paying attention to vitamin D levels in these patients can be effective in reducing inflammation caused by lichen planus.
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Líquen Plano Bucal , Líquen Plano , Adulto , Antioxidantes , Biomarcadores , Estudos de Casos e Controles , Colecalciferol , Humanos , Inflamação , Vitamina DRESUMO
The novel pleuromutilin derivative, which showed excellent in vitro antibacterial activity against MRSA, 22-(2-(2-(4-((4-(4-nitrophenyl)piperazin-1-yl)methyl)-1H-1,2,3-triazol-1-yl)acetamido)phenyl)thioacety-l-yl-22-deoxypleuromutilin (Z33), was synthesized and characterized in our previous work. In this study, the preliminary pharmacodynamics and safety of Z33 were further evaluated. In in vitro antibacterial activity assays, Z33 was found to be a potent bactericidal antibiotic against MRSA that induced dose-dependent growth inhibition and long-term post-antibiotic effect (PAE). The drug-resistance test demonstrated that Z33 possessed a narrow mutant selection window and lower propensities to select resistance than that of tiamulin. Cytochrome P450 (CYP450) inhibition assay determined that the inhibitory effect of Z33 was similar to that of tiamulin against the activity of CYP3A4, and was lower than that of tiamulin on the activity of CYP2E1. Toxicity determination showed that both Z33 and tiamulin displayed low cytotoxicity of RAW264.7 cells. Furthermore, Z33 was found to be a high-security compound with a 50% lethal dose (LD50) above 5000 mg/kg in the acute oral toxicity test in mice. In an in vivo antibacterial activity test, Z33 displayed better therapeutic effectiveness than tiamulin in the neutropenic mouse thigh infection model. In summary, Z33 was worthy of further development as a highly effective and safe antibiotic agent against MRSA infection.
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Diterpenos , Staphylococcus aureus Resistente à Meticilina , Compostos Policíclicos , Animais , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Diterpenos/farmacologia , Diterpenos/uso terapêutico , Camundongos , Testes de Sensibilidade Microbiana , Compostos Policíclicos/farmacologia , PleuromutilinasRESUMO
Infectious diseases have a devastating impact on individual health and social development. Different external environmental factors will affect the scale and the speed of disease outbreaks, such as sanitary conditions and policy interventions. In this paper, we attempt to establish a dual-system susceptible-infectious-quarantine-recovered model with different environmental impacts to explore it. For the deterministic model, we calculate the basic reproduction number, simultaneously, and investigate the local asymptotic stability of the disease-free equilibrium and the endemic equilibrium. Numerical simulations and theoretical analyses verify the conclusion of this paper. It is a surprise that there is a great probability of finding a quarantine inflection point, which can effectively control the scale of infection outbreak when two different systems of infection rate and recovery rate are determined.
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Skeletal muscle dysfunction is one of the important comorbidities of chronic obstructive pulmonary disease (COPD); however, the underlying mechanisms remain largely unknown. RANKL (receptor activator of nuclear factor κB ligand), a key mediator in osteoclast differentiation, was also found to play a role in skeletal muscle pathogenesis. Whether RANKL is involved in COPD-related skeletal muscle dysfunction is as-of-yet unknown. We examined the expression of RANKL/RANK in skeletal muscles from mice exposed to cigarette smoke (CS) for 24 weeks. Grip strength and exercise capacity as well as muscular morphology were evaluated in CS-exposed mice with or without anti-RANKL treatment. The expressions of protein synthesis- or muscle growth-related molecules (IGF-1, myogenin, and myostatin), muscle-specific ubiquitin E3 ligases (MuRF1 and atrogin-1), and the NF-κb inflammatory pathway were also evaluated in skeletal muscles. The effect of CS extract on RANKL/RANK expression and that of exogenous RANKL on the ubiquitin-proteasome pathway in C2C12 myotubes were investigated in vitro. Long-term CS exposure induced skeletal muscle dysfunction and atrophy together with upregulation of RANKL/RANK expression in a well-established mouse model of COPD. RANKL neutralization prevented skeletal muscle dysfunction and atrophy. RANKL inhibition decreased expressions of myostatin and MuRF1/Atrogin1 and suppressed the NF-κb pathway in skeletal muscles from CS-exposed mice. In in vitro experiments with C2C12 myotubes, CS extract induced expression of RANKL/RANK, and exogenous RANKL induced activation of the ubiquitin-proteasome pathway and NF-κb pathway via RANK. Our results revealed an important role of the RANKL/RANK pathway in muscle atrophy induced by CS exposure, suggesting that RANKL may be a potential therapeutic target in COPD-related skeletal muscle dysfunction.
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Atrofia Muscular/genética , NF-kappa B/genética , Doença Pulmonar Obstrutiva Crônica/genética , Ligante RANK/genética , Receptor Ativador de Fator Nuclear kappa-B/genética , Animais , Anticorpos Neutralizantes/farmacologia , Linhagem Celular , Fumar Cigarros/efeitos adversos , Misturas Complexas/antagonistas & inibidores , Misturas Complexas/farmacologia , Modelos Animais de Doenças , Feminino , Regulação da Expressão Gênica , Força da Mão/fisiologia , Fator de Crescimento Insulin-Like I/genética , Fator de Crescimento Insulin-Like I/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Fibras Musculares Esqueléticas/efeitos dos fármacos , Fibras Musculares Esqueléticas/metabolismo , Fibras Musculares Esqueléticas/patologia , Proteínas Musculares/genética , Proteínas Musculares/metabolismo , Força Muscular/efeitos dos fármacos , Força Muscular/genética , Músculo Esquelético/efeitos dos fármacos , Músculo Esquelético/metabolismo , Músculo Esquelético/patologia , Atrofia Muscular/metabolismo , Atrofia Muscular/patologia , Atrofia Muscular/prevenção & controle , Miogenina/genética , Miogenina/metabolismo , Miostatina/genética , Miostatina/metabolismo , NF-kappa B/metabolismo , Doença Pulmonar Obstrutiva Crônica/induzido quimicamente , Doença Pulmonar Obstrutiva Crônica/metabolismo , Doença Pulmonar Obstrutiva Crônica/prevenção & controle , Ligante RANK/antagonistas & inibidores , Ligante RANK/metabolismo , Receptor Ativador de Fator Nuclear kappa-B/metabolismo , Proteínas Ligases SKP Culina F-Box/genética , Proteínas Ligases SKP Culina F-Box/metabolismo , Transdução de Sinais , Proteínas com Motivo Tripartido/genética , Proteínas com Motivo Tripartido/metabolismo , Ubiquitina-Proteína Ligases/genética , Ubiquitina-Proteína Ligases/metabolismoRESUMO
It has long been established that neuronal growth cone navigation depends on changes in microtubule (MT) and F-actin architecture downstream of guidance cues. However, the mechanisms by which MTs and F-actin are dually coordinated remain a fundamentally unresolved question. Here, we report that the well-characterized MT polymerase, XMAP215 (also known as CKAP5), plays an important role in mediating MT-F-actin interaction within the growth cone. We demonstrate that XMAP215 regulates MT-F-actin alignment through its N-terminal TOG 1-5 domains. Additionally, we show that XMAP215 directly binds to F-actin in vitro and co-localizes with F-actin in the growth cone periphery. We also find that XMAP215 is required for regulation of growth cone morphology and response to the guidance cue, Ephrin A5. Our findings provide the first strong evidence that XMAP215 coordinates MT and F-actin interaction in vivo We suggest a model in which XMAP215 regulates MT extension along F-actin bundles into the growth cone periphery and that these interactions may be important to control cytoskeletal dynamics downstream of guidance cues. This article has an associated First Person interview with the first author of the paper.
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Actinas/metabolismo , Axônios/metabolismo , Cones de Crescimento/metabolismo , Proteínas Associadas aos Microtúbulos/metabolismo , Microtúbulos/metabolismo , Proteínas de Xenopus/metabolismo , Citoesqueleto de Actina/metabolismo , Animais , Orientação de Axônios/efeitos dos fármacos , Efrina-A5/farmacologia , Xenopus laevis/embriologia , Xenopus laevis/metabolismoRESUMO
CE is the primary methodology used in forensic DNA typing. Alleles of commonly used types of genetic markers could be separated and detected via CE based on dye color and migration time. Insertion/deletion (InDel) is an ideal genetic marker for forensic DNA analysis due to their abundance in the human genome, low mutation rate, availability of their allele types via CE, and elimination of stutter peaks. Moreover, InDels could be used as ancestry informative markers since allele frequencies of InDels is different among geographically separated populations. Several ancestry informative insertion/deletion panels have been established based on CE platform to achieve the intercontinental populations distinction. However, improvements to differentiate intracontinental populations is few. In this study, 21 InDels with fixation index (FST ) > 0.15 were selected and assembled into one ancestry informative insertion/deletion panel. Using well-designed primers, those 21 InDels could be amplified successfully and genotyped on the CE platform accurately and completely. The panel showed a large FST distance distinction among the ten Asian populations. Using clustering analysis, ten Asian populations were classified into three subgroups: East Asian, Southeast Asian, and South Asian subgroups. To evaluate the panel's capability in ancestry inference, a validation experiment was undertaken with 319 individuals from four geographically separated populations in China. Four Chinese populations were classified into different ancestry subgroups and 81.8% test individuals' ancestry could be inferred correctly. Our result showed that development of high ancestry informative InDels panel based on CE platform is a potential for individual ancestry inference among intracontinental populations.
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Eletroforese Capilar , Povo Asiático/genética , Genética Forense , Frequência do Gene/genética , Marcadores Genéticos/genética , Genética Populacional , Genótipo , Humanos , Mutação INDEL , Polimorfismo de Nucleotídeo ÚnicoRESUMO
Most studies examining the effect of extended exposure to general anesthetic agents (GAAs) have demonstrated that extended exposure induces both structural and functional changes in the central nervous system. These changes are frequently accompanied by neurobehavioral changes that include impulse control disorders that are generally characterized by deficits in behavioral inhibition and executive function. In this review, we will.
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Anestésicos Gerais/efeitos adversos , Encéfalo/efeitos dos fármacos , Transtornos Disruptivos, de Controle do Impulso e da Conduta/induzido quimicamente , Rede Nervosa/efeitos dos fármacos , Anestésicos Gerais/administração & dosagem , Animais , Encéfalo/metabolismo , Transtornos Disruptivos, de Controle do Impulso e da Conduta/diagnóstico , Transtornos Disruptivos, de Controle do Impulso e da Conduta/metabolismo , Humanos , Rede Nervosa/metabolismo , Fatores de RiscoRESUMO
The production of natural antimicrobial peptides has emerged as an important mechanism of innate immunity in animals. Defensins, members of a large family of antimicrobial peptides, have been suggested as effector molecules in host defence against bacteria, fungi, protozoa and enveloped viruses. However, the molecular mechanism underlying defensin upregulation in bacterial infection remains poorly understood. The modification of mRNA by N6-adenosine methylation (m6A) on internal bases influences gene expression in eukaryotes. Here, we show that ß-defensin production triggered by Enterotoxigenic Escherichia coli K88 (E. coli K88) infection is controlled by the cellular m6A methyltransferase METTL3. Adding back with METTL3 robustly stimulated the re-expression of defensin, which further supports the conclusion. Furthermore, using a MeRIP-seq approach, we identified a functional connection between m6A dependent GPR161 signalling and the expression of defensins. Mechanistically, we found that the transcription factor FOXO6 interacted with METTL3 to trigger the transcription of GPR161 and the subsequent regulation of ß-defensin expression. The study has shed light on the mechanisms by which enterotoxigenic Escherichia coli infection promotes enteric defensin expression.
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Defensinas/genética , Escherichia coli Enterotoxigênica/fisiologia , Mucosa Intestinal/metabolismo , Animais , Células Cultivadas , Defensinas/metabolismo , Infecções por Escherichia coli/genética , Infecções por Escherichia coli/metabolismo , Fatores de Transcrição Forkhead/genética , Fatores de Transcrição Forkhead/metabolismo , Células HEK293 , Humanos , Mucosa Intestinal/microbiologia , Intestinos/microbiologia , Metilação , Metiltransferases/genética , Metiltransferases/metabolismo , Receptores Acoplados a Proteínas G/genética , Receptores Acoplados a Proteínas G/metabolismo , Transdução de Sinais/genética , SuínosRESUMO
Camera calibration is essential for various vision-based 3D metrological techniques. In this paper, a novel camera calibration method, to the best of our knowledge, combining synthetic speckle pattern and an improved gray wolf optimizer algorithm is presented. The synthetic speckle pattern serves as the calibration target. The particle swarm algorithm-based digital image correlation is employed to achieve matches among 3D control points and 2D image points; then the improved gray wolf optimizer algorithm is used to calculate the camera parameters. For verification, simulated and real tests are conducted. Through the analysis of calibration results, the proposed method performs better and is more stable than other calibration targets. Research on the influence of camera pose and optimization algorithm is conducted, showing that the improved gray wolf optimizer algorithm performs better than other benchmark algorithms. The camera parameters can be obtained through one captured image when the speckle patterns are added in the portion of the camera sensor.
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The genetic structure differences in population is one of the key elements in medical research involving multi-population samples. A set of ancestry-informative single nucleotide polymorphisms (AI-SNPs) can be utilized to analyze genetic component of a population, infer ancestral origin of individuals and pre-filter samples to reduce the impact of population genetic structure differences on medical research. However, most of the published studies were focused on revealing the differences between populations of continents or regions of a continent. In this paper, AI-SNPs were screened by calculating FST value in each pair of five East Asian populations: Japanese in Tokyo (JPT), Han Chinese in Beijing (CHB), Southern Han Chinese (CHS), Chinese Dai in Xishuangbanna (CDX) and Kinh in Ho Chi Minh City (KHV) in the 1000 Genomes Project phase 3 (GRCh37.p13) to analyze differences in subcontinent populations. The results demonstrate that the five East Asian populations in our study were assigned to three clusters: JPT, CHB and CHS, CDX and KHV. A set of AI-SNPs can be used for analysis of individual genetic composition and selection of representative individuals. Individuals with over 80% population representative genetic components have good representativeness of a population. This paper demonstrated the practical value of the method, which was performed to verify the ancestral composition and select representative samples with a panel of screened AI-SNPs by FST value, thereby reducing the influence of genetic structure differences in subcontinent populations on population-related medical research.