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Gemcitabine (GEM) is widely employed in the treatment of various cancers, including pancreatic cancer. Despite their clinical success, challenges related to GEM resistance and toxicity persist. Therefore, a deeper understanding of its intracellular mechanisms and potential targets is urgently needed. In this study, through mass spectrometry analysis in data-dependent acquisition mode, we carried out quantitative proteomics (three independent replications) and thermal proteome profiling (TPP, two independent replications) on MIA PaCa-2 cells to explore the effects of GEM. Our proteomic analysis revealed that GEM led to the upregulation of the cell cycle and DNA replication proteins. Notably, we observed the upregulation of S-phase kinase-associated protein 2 (SKP2), a cell cycle and chemoresistance regulator. Combining SKP2 inhibition with GEM showed synergistic effects, suggesting SKP2 as a potential target for enhancing the GEM sensitivity. Through TPP, we pinpointed four potential GEM binding targets implicated in tumor development, including in breast and liver cancers, underscoring GEM's broad-spectrum antitumor capabilities. These findings provide valuable insights into GEM's molecular mechanisms and offer potential targets for improving treatment efficacy.
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Desoxicitidina , Gencitabina , Proteômica , Proteínas Quinases Associadas a Fase S , Desoxicitidina/análogos & derivados , Desoxicitidina/farmacologia , Desoxicitidina/uso terapêutico , Humanos , Proteômica/métodos , Linhagem Celular Tumoral , Proteínas Quinases Associadas a Fase S/metabolismo , Proteínas Quinases Associadas a Fase S/genética , Antimetabólitos Antineoplásicos/farmacologia , Antimetabólitos Antineoplásicos/uso terapêutico , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Neoplasias Pancreáticas/tratamento farmacológico , Neoplasias Pancreáticas/metabolismo , Proteínas de Ciclo Celular/metabolismo , Proteínas de Ciclo Celular/genética , Regulação para Cima/efeitos dos fármacos , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacosRESUMO
Second-harmonic-generation (SHG) switching is an emerging phenomenon with potential applications in bistable storage and optical switches while also serving as a sensitive probe for inversion-symmetry. Temperature-induced disorder-order phase transition has been proven to be a rational design strategy for achieving SHG bi-state switching; however, pressure-sensitive SHG switching via a disorder-order structural transition mechanism is rarely reported and lacks sensitivity and cyclicity as practical switching materials. Herein, we demonstrate the pressure-induced "dynamical disorder-order" phase transition as an effective strategy for triggering SHG and SHG switching in NH4Cl. The "dynamical disorder-order" phase transition of NH4Cl occurring at as low as 1 GPa is confirmed by comprehensive in situ high-pressure XRD, molecular vibrational spectra, and Brillouin scattering spectra. The pressure-induced SHG is responsive to a wide excitation wavelength region (800-1500 nm), and the "off-on" switching is reversible for up to 50 cycles, setting a record for pressure-driven switching materials. It is worth noting that when pressure is further increased to 14 GPa, NH4Cl exhibits another SHG "on-off" switching, which makes it the first triplet SHG "off-on-off" switching material. Molecular dynamics simulations reveal the key role of N-H···Cl hydrogen bonding in the pressure-induced "dynamic disorder-order" mechanism. Finally, we verified that chemical pressure and physical pressure can jointly regulate the SHG switching behavior of NH4X (X = Cl, Br). The pressure-driven "dynamic disorder-order" transition mechanism sheds light on the rational design of multistable SHG switching materials for photoswitches and information storage.
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Spin-crossover (SCO) materials exhibit remarkable potential as bistable switches in molecular devices. However, the spin transition temperatures (Tc) of known compounds are unable to cover the entire ambient temperature spectrum, largely limiting their practical utility. This study reports an exemplary two-dimensional SCO solid solution system, [FeIII(H0.5LCl)2-2x(H0.5LF)2x]·H2O (H0.5LX = 5-X-2-hydroxybenzylidene-hydrazinecarbothioamide, X = F or Cl, x = 0 to 1), in which the adjacent layers are adhered via hydrogen bonding. Notably, the Tc of this system can be fine-tuned across 90 K (227-316 K) in a linear manner by modulating the fraction x of the LF ligand. Elevating x results in strengthened hydrogen bonding between adjacent layers, which leads to enhanced intermolecular interactions between adjacent SCO molecules. Single-crystal diffraction analysis and periodic density functional theory calculations revealed that such a special kind of alteration in interlayer interactions strengthens the FeIIIN2O2S2 ligand field and corresponding SCO energy barrier, consequently resulting in increased Tc. This work provides a new pathway for tuning the Tc of SCO materials through delicate manipulation of molecular interactions, which could expand the application of bistable molecular solids to a much wider temperature regime.
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A syringe-based, semi-automatic environmental monitoring device is developed for on-site detection of harmful heavy metal ions in water. This portable device consists of a spring-embedded syringe and a polydimethylsiloxane (PDMS) membrane-based flow regulator for semi-automatic fix-and-release fluidic valve actuation, and a paper-based analytical device (PAD) with two kinds of gold nanoclusters (AuNCs) for sensitive Hg2+ and Co2+ ion detection, respectively. The thickness of the elastic PDMS membrane can be adjusted to stabilize and modulate the flow rates generated by the pushing force provided by the spring attached to the plunger. Also, different spring constants can drastically alter the response time. People of all ages can extract the fix-volume sample solutions and then release them to automatically complete the detection process, ensuring high reliability and repeatability. The PAD comprises two layers of modified paper, and each layer is immobilized with bovine serum albumin-capped gold nanoclusters (R-AuNCs) and glutathione-capped gold clusters (G-AuNCs), respectively. The ligands functionalized on the surface of the AuNCs not only can fine-tune the optical properties of the nanoclusters but also enable specific and simultaneous detection of Hg2+ and Co2+ ions via metallophilic Au+ -Hg2+ interaction and the Co2+ -thiol complexation effect, respectively. The feasibility of the device for detecting heavy metal ions at low concentrations in various environmental water samples is demonstrated. The Hg2+ and Co2+ ions can be seen simultaneously within 20 min with detection limits as low as 1.76 nm and 0.27 µm, respectively, lower than those of the regulatory restrictions on water by the US Environmental Protection Agency and the European Union. we expect this sensitive, selective, portable, and easy-to-use device to be valid for on-site multiple heavy metal ion pollution screenings in resource-constrained settings.
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Bioactive triterpenes feature complex fused-ring structures, primarily shaped by the first-committed enzyme, 2,3-oxidosqualene cyclases (OSCs) in plant triterpene biosynthesis. Triterpenes with B,C-ring-opened skeletons are extremely rare with unknown formation mechanisms, harbouring unchartered chemistry and biology. Here, through mining the genome of Chenopodium quinoa followed by functional characterization, we identified a stress-responsive and neofunctionalized OSC capable of generating B,C-ring-opened triterpenes, including camelliol A and B and the novel (-)-quinoxide A as wax components of the specialized epidermal bladder cells, namely the quinoxide synthase (CqQS). Protein structure analysis followed by site-directed mutagenesis identified key variable amino acid sites underlying functional interconversion between pentacyclic ß-amyrin synthase (CqbAS1) and B,C-ring-opened triterpene synthase CqQS. Mutation of one key residue (N612K) in even evolutionarily distant Arabidopsis ß-amyrin synthase could generate quinoxides, indicating a conserved mechanism for B,C-ring-opened triterpene formation in plants. Quantum computation combined with docking experiments further suggests that conformations of conserved W613 and F413 of CqQS might be key to selectively stabilizing intermediate carbocations towards B,C-ring-opened triterpene formation. Our findings shed light on quinoa triterpene skeletal diversity and mechanisms underlying B,C-ring-opened triterpene biosynthesis, opening avenues towards accessing their chemistry and biology and paving the way for quinoa trait engineering and quality improvement.
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Chenopodium quinoa , Transferases Intramoleculares , Triterpenos , Chenopodium quinoa/metabolismo , Triterpenos/metabolismo , Transferases Intramoleculares/genética , Transferases Intramoleculares/metabolismoRESUMO
BACKGROUND: Stress hyperglycemia and glycemic variability (GV) can reflect dramatic increases and acute fluctuations in blood glucose, which are associated with adverse cardiovascular events. This study aimed to explore whether the combined assessment of the stress hyperglycemia ratio (SHR) and GV provides additional information for prognostic prediction in patients with coronary artery disease (CAD) hospitalized in the intensive care unit (ICU). METHODS: Patients diagnosed with CAD from the Medical Information Mart for Intensive Care-IV database (version 2.2) between 2008 and 2019 were retrospectively included in the analysis. The primary endpoint was 1-year mortality, and the secondary endpoint was in-hospital mortality. Levels of SHR and GV were stratified into tertiles, with the highest tertile classified as high and the lower two tertiles classified as low. The associations of SHR, GV, and their combination with mortality were determined by logistic and Cox regression analyses. RESULTS: A total of 2789 patients were included, with a mean age of 69.6 years, and 30.1% were female. Overall, 138 (4.9%) patients died in the hospital, and 404 (14.5%) patients died at 1 year. The combination of SHR and GV was superior to SHR (in-hospital mortality: 0.710 vs. 0.689, p = 0.012; 1-year mortality: 0.644 vs. 0.615, p = 0.007) and GV (in-hospital mortality: 0.710 vs. 0.632, p = 0.004; 1-year mortality: 0.644 vs. 0.603, p < 0.001) alone for predicting mortality in the receiver operating characteristic analysis. In addition, nondiabetic patients with high SHR levels and high GV were associated with the greatest risk of both in-hospital mortality (odds ratio [OR] = 10.831, 95% confidence interval [CI] 4.494-26.105) and 1-year mortality (hazard ratio [HR] = 5.830, 95% CI 3.175-10.702). However, in the diabetic population, the highest risk of in-hospital mortality (OR = 4.221, 95% CI 1.542-11.558) and 1-year mortality (HR = 2.013, 95% CI 1.224-3.311) was observed in patients with high SHR levels but low GV. CONCLUSIONS: The simultaneous evaluation of SHR and GV provides more information for risk stratification and prognostic prediction than SHR and GV alone, contributing to developing individualized strategies for glucose management in patients with CAD admitted to the ICU.
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Doença da Artéria Coronariana , Diabetes Mellitus , Hiperglicemia , Humanos , Feminino , Idoso , Masculino , Doença da Artéria Coronariana/diagnóstico , Estudos Retrospectivos , Glicemia/análise , Fatores de RiscoRESUMO
BACKGROUND: The triglyceride-glucose (TyG) index and estimated glucose disposal rate (eGDR), which are calculated using different parameters, are widely used as markers of insulin resistance and are associated with cardiovascular diseases and prognosis. However, whether they have an additive effect on the risk of mortality remains unclear. This study aimed to explore whether the combined assessment of the TyG index and eGDR improved the prediction of long-term mortality in individuals with and without diabetes. METHODS: In this cross-sectional and cohort study, data were derived from the National Health and Nutrition Examination Survey (NHANES) 2001-2018, and death record information was obtained from the National Death Index. The associations of the TyG index and eGDR with all-cause and cardiovascular mortality were determined by multivariate Cox regression analysis and restricted cubic splines. RESULTS: Among the 17,787 individuals included in the analysis, there were 1946 (10.9%) all-cause deaths and 649 (3.6%) cardiovascular deaths during a median follow-up of 8.92 years. In individuals with diabetes, the restricted cubic spline curves for the associations of the TyG index and eGDR with mortality followed a J-shape and an L-shape, respectively. The risk of mortality significantly increased after the TyG index was > 9.04 (all-cause mortality) or > 9.30 (cardiovascular mortality), and after eGDR was < 4 mg/kg/min (both all-cause and cardiovascular mortality). In individuals without diabetes, the association between eGDR and mortality followed a negative linear relationship. However, there was no association between the TyG index and mortality. Compared with individuals in the low TyG and high eGDR group, those in the high TyG and low eGDR group (TyG > 9.04 and eGDR < 4) showed the highest risk for all-cause mortality (hazard ratio [HR] = 1.592, 95% confidence interval [CI] 1.284-1.975) and cardiovascular mortality (HR = 1.683, 95% CI 1.179-2.400) in the overall population. Similar results were observed in individuals with and without diabetes. CONCLUSIONS: There was a potential additive effect of the TyG index and eGDR on the risk of long-term mortality in individuals with and without diabetes, which provided additional information for prognostic prediction and contributed to improving risk stratification.
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Biomarcadores , Glicemia , Doenças Cardiovasculares , Causas de Morte , Diabetes Mellitus , Resistência à Insulina , Inquéritos Nutricionais , Triglicerídeos , Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Glicemia/metabolismo , Medição de Risco , Triglicerídeos/sangue , Biomarcadores/sangue , Estudos Transversais , Doenças Cardiovasculares/mortalidade , Doenças Cardiovasculares/sangue , Doenças Cardiovasculares/diagnóstico , Diabetes Mellitus/mortalidade , Diabetes Mellitus/sangue , Diabetes Mellitus/diagnóstico , Fatores de Tempo , Prognóstico , Idoso , Adulto , Estados Unidos/epidemiologia , Valor Preditivo dos Testes , Fatores de RiscoRESUMO
KEY MESSAGE: The rust resistance genes Lr53 and Yr35 were introgressed into bread wheat from Aegilops longissima or Aegilops sharonensis or their S-genome containing species and mapped to the telomeric region of chromosome arm 6BS. Wheat leaf and stripe rusts are damaging fungal diseases of wheat worldwide. Breeding for resistance is a sustainable approach to control these two foliar diseases. In this study, we used SNP analysis, sequence comparisons, and cytogenetic assays to determine that the chromosomal segment carrying Lr53 and Yr35 was originated from Ae.longissima or Ae. sharonensis or their derived species. In seedling tests, Lr53 conferred strong resistance against all five Chinese Pt races tested, and Yr35 showed effectiveness against Pst race CYR34 but susceptibility to race CYR32. Using a large population (3892 recombinant gametes) derived from plants homozygous for the ph1b mutation obtained from the cross 98M71 × CSph1b, both Lr53 and Yr35 were successfully mapped to a 6.03-Mb telomeric region of chromosome arm 6BS in the Chinese Spring reference genome v1.1. Co-segregation between Lr53 and Yr35 was observed within this large mapping population. Within the candidate region, several nucleotide-binding leucine-rich repeat genes and protein kinases were identified as candidate genes. Marker pku6B3127 was completely linked to both genes and accurately predicted the absence or presence of alien segment harboring Lr53 and Yr35 in 87 tetraploid and 149 hexaploid wheat genotypes tested. We developed a line with a smaller alien segment (< 6.03 Mb) to reduce any potential linkage drag and demonstrated that it conferred resistance levels similar to those of the original donor parent 98M71. The newly developed introgression line and closely linked PCR markers will accelerate the deployment of Lr53 and Yr35 in wheat breeding programs.
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Aegilops , Mapeamento Cromossômico , Resistência à Doença , Genes de Plantas , Puccinia , Aegilops/genética , Aegilops/microbiologia , Cromossomos de Plantas/genética , Resistência à Doença/genética , Introgressão Genética , Ligação Genética , Marcadores Genéticos , Melhoramento Vegetal , Doenças das Plantas/genética , Doenças das Plantas/microbiologia , Polimorfismo de Nucleotídeo Único , Puccinia/fisiologia , Triticum/genética , Triticum/microbiologiaRESUMO
Nowadays, easy, convenient, and sensitive sensing strategies are still critical for organophosphorus pesticides in environmental water samples. Herein, a novel organophosphorus pesticide (OP) assay based on acetylcholinesterase (AChE) and a MnO2 nanosheet-mediated CRISPR/Cas12a reaction is reported. The single-strand DNA (ssDNA) activator of CRISPR/Cas12a was simply adsorbed on the MnO2 nanosheets as the nanoswitches of the assay. In the absence of target OPs, AChE hydrolyzed acetylcholine (ATCh) to thiocholine (TCh), which reduced the MnO2 nanosheets to Mn2+, resulting in the release of the activator followed by activation of the CRISPR/Cas12a system. The activated Cas12a thereafter nonspecifically cleaved the FAM/BHQ1-labeled ssDNA (FQ-reporter), producing a fluorescence signal. Upon the addition of target OPs, the hydrolysis of ATCh by AChE was inhibited owing to OPs combining with AChE, and thus effective quantification of OPs could be achieved by measuring the fluorescence changes of the system. As a proof of concept, dichlorvos (DDVP) was chosen as a model OP analyte to address the feasibility of the proposed method. Attributed to the excellent trans-cleavage activity of Cas12a, the fluorescent biosensor exhibits a satisfactory limit of detection (LOD) for DDVP at 0.135 ng mL-1. In addition, the excellent recoveries for the detection of DDVP in environmental water samples demonstrate the applicability of the proposed assay in real sample research.
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Técnicas Biossensoriais , Praguicidas , Praguicidas/análise , Compostos Organofosforados , Acetilcolinesterase/genética , Acetilcolinesterase/metabolismo , Sistemas CRISPR-Cas , Diclorvós , Água , Compostos de Manganês , Óxidos , Acetilcolina , Técnicas Biossensoriais/métodosRESUMO
To mine fascinating molecules from the rhizomes of Atractylodes chinensis, the known molecular formula of atrachinenin A was used as a bait to search LC-HRMS data in different subfractions. Sixteen new meroterpenoids, atrachinenins D-S (1-16) including three unprecedented carbon skeletons (1-5) and eleven new oxygen-bridged hybrids (6-16) were obtained by the targeted isolation. Their structures and absolute configurations were elucidated by the spectroscopic data and electronic circular dichroism (ECD) calculations. The isolated compounds were evaluated for their inhibitory activity of NO production and compounds 1, 4, 8, and 13 showed moderate anti-inflammatory activity. The proposed biosynthetic pathways of 1-5 were also discussed.
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Atractylodes , Atractylodes/química , Hidroquinonas , Anti-Inflamatórios , Dicroísmo Circular , Estrutura MolecularRESUMO
Three new strains of dissimilatory perchlorate-reducing bacteria (DPRB), QD19-16, QD1-5, and P3-1, were isolated from an active sludge. Phylogenetic trees based on 16S rRNA genes indicated that QD19-16, QD1-5, and P3-1 belonged to Brucella, Acidovorax, and Citrobacter, respectively, expanding the distribution of DPRB in the Proteobacteria. The three strains were gram-negative and facultative anaerobes with rod-shaped cells without flagella, which were 1.0-1.6 µm long and 0.5-0.6 µm wide. The three DPRB strains utilized similar broad spectrum of electron donors and acceptors and demonstrated a similar capability to reduce perchlorate within 6 days. The enzyme activity of perchlorate reductase in QD19-16 toward chlorate was higher than that toward perchlorate. The high sequence similarity of the perchlorate reductase operon and chlorite dismutase genes in the perchlorate reduction genomic islands (PRI) of the three strains implied that they were monophyletic origin from a common ancestral PRI. Two transposase genes (tnp1 and tnp2) were found in the PRIs of strain QD19-16 and QD1-5, but were absent in the strain P3-1 PRI. The presence of fragments of IR sequences in the P3-1 PRI suggested that P3-1 PRI had previously contained these two tnp genes. Therefore, it is plausible to suggest that a common ancestral PRI transferred across the strains Brucella sp. QD19-16, Acidovorax sp. QD1-5, and Citrobacter sp. P3-1 through horizontal gene transfer, facilitated by transposases. These results provided a direct evidence of horizontal gene transfer of PRI that could jump across phylogenetically unrelated bacteria through transposase. KEY POINTS: ⢠Three new DPRB strains can effectively remove high concentration of perchlorate. ⢠The PRIs of three DPRB strains are acquired from a single ancestral PRI. ⢠PRIs are incorporated into different bacteria genome through HGT by transposase.
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Ilhas Genômicas , Percloratos , Filogenia , Oxirredução , Transferência Genética Horizontal , RNA Ribossômico 16S/genética , Bactérias/genética , Oxirredutases/genética , Ecossistema , Transposases/genéticaRESUMO
The optical surface of extreme ultraviolet (EUV) lithography machines is highly vulnerable to contamination by hydrocarbons, resulting in the formation of carbon deposits that significantly degrade the quality and efficiency of lithography. The dynamic gas lock (DGL) has been proven as an effective approach to alleviate carbon deposition. However, the majority of existing studies on carbon deposition neglect the influence of the DGL. This paper is dedicated to investigating the phenomena of hydrocarbon adsorption, desorption, and cleavage with considering the effects of the DGL. A comprehensive mathematical model of the carbon deposition process is established, and the impact of radiation intensity, temperature, and hydrocarbon types on the depositing rate is considered. The results suggest that the primary cause of carbon deposition is the direct cracking of hydrocarbons induced by photons with a wavelength range between 12.5 and 14.5 nm. Additionally, it has been observed that the carbon deposition rate decreases exponentially as clean gas flow increases when EUV radiation intensity exceeds 50 mW/mm2. Conversely, at low EUV radiation intensity, clean gas flow has little effect on the carbon deposition rate. An effective approach to mitigate carbon deposition is to elevate the temperature of the optical surface and employ light hydrocarbon materials in the EUV process.
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DAVID is a popular bioinformatics resource system including a web server and web service for functional annotation and enrichment analyses of gene lists. It consists of a comprehensive knowledgebase and a set of functional analysis tools. Here, we report all updates made in 2021. The DAVID Gene system was rebuilt to gain coverage of more organisms, which increased the taxonomy coverage from 17 399 to 55 464. All existing annotation types have been updated, if available, based on the new DAVID Gene system. Compared with the last version, the number of gene-term records for most annotation types within the updated Knowledgebase have significantly increased. Moreover, we have incorporated new annotations in the Knowledgebase including small molecule-gene interactions from PubChem, drug-gene interactions from DrugBank, tissue expression information from the Human Protein Atlas, disease information from DisGeNET, and pathways from WikiPathways and PathBank. Eight of ten subgroups split from Uniprot Keyword annotation were assigned to specific types. Finally, we added a species parameter for uploading a list of gene symbols to minimize the ambiguity between species, which increases the efficiency of the list upload and eliminates confusion for users. These current updates have significantly expanded the Knowledgebase and enhanced the discovery power of DAVID.
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Bases de Dados Genéticas , Software , Humanos , Biologia Computacional , Computadores , Bases de Conhecimento , Anotação de Sequência Molecular , InternetRESUMO
The transition from childhood to adolescence is marked by pronounced shifts in brain structure and function that coincide with the development of physical, cognitive, and social abilities. Prior work in adult populations has characterized the topographical organization of the cortex, revealing macroscale functional gradients that extend from unimodal (somatosensory/motor and visual) regions through the cortical association areas that underpin complex cognition in humans. However, the presence of these core functional gradients across development as well as their maturational course have yet to be established. Here, leveraging 378 resting-state functional MRI scans from 190 healthy individuals aged 6 to 17 y old, we demonstrate that the transition from childhood to adolescence is reflected in the gradual maturation of gradient patterns across the cortical sheet. In children, the overarching organizational gradient is anchored within the unimodal cortex, between somatosensory/motor and visual territories. Conversely, in adolescence, the principal gradient of connectivity transitions into an adult-like spatial framework, with the default network at the opposite end of a spectrum from primary sensory and motor regions. The observed gradient transitions are gradually refined with age, reaching a sharp inflection point in 13 and 14 y olds. Functional maturation was nonuniformly distributed across cortical networks. Unimodal networks reached their mature positions early in development, while association regions, in particular the medial prefrontal cortex, reached a later peak during adolescence. These data reveal age-dependent changes in the macroscale organization of the cortex and suggest the scheduled maturation of functional gradient patterns may be critically important for understanding how cognitive and behavioral capabilities are refined across development.
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Córtex Cerebral/crescimento & desenvolvimento , Adolescente , Criança , Humanos , Rede Nervosa/fisiologiaRESUMO
AIM: To investigate the DNA damage response (DDR) in a cyclophosphamide (CTX)-induced mouse model of premature ovarian failure (POF). METHODS: The POF model was established by injecting mice with CTX. The body, ovarian weights, the estrus cycle, and pathological changes of the ovaries were recorded. The serum levels of 17 ß-estradiol (E2) and follicle-stimulating hormone (FSH) were measured. The expression of Ki67, ß-galactosidase (ß-gal), p21, p53, γH2AX, and pATM in ovarian tissues was detected by immunohistochemistry. The expression of ß-gal, γH2AX, and pATM was analyzed by immunofluorescence staining of primary cultured granulosa cells (GCs). RESULTS: The body and ovarian weights decreased, the estrus cycles were erratic, and the FSH level increased, whereas the E2 level decreased in POF mice compared to controls. The pathological consequences of POF revealed an increase in atretic follicles, corpus luteum, and primordial follicles and a decrease in the number of primary, secondary, and tertiary follicles. Ki67 expression was reduced, ß-gal, p21, p53, γH2AX, and pATM expression were elevated in the ovaries of POF mice. The expression of ß-gal, γH2AX, and pATM increased in GCs with the concentration in a time-dependent manner. CONCLUSION: In total, CTX induced POF in mice, which was mediated by the DDR pathway of ATM-P53-P21.
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OBJECTIVES/INTRODUCTION: The purpose of the current study was to investigate the association between Aspartate Transaminase (AST)/Alanine transaminase(ALT) and type 2 diabetes (T2DM) in nonalcoholic fatty liver disease (NAFLD) patients and to determine whether there were sex differences. METHODS: In the retrospective study, we collected data on NAFLD patients (1, 896 men and 465 women) at Murakami Memorial Hospital from 2004 to 2015. Data were stratified by sex to investigate the association between AST/ALT and T2DM incidence by sex. Multiple regression analysis, smooth curve fitting model and subgroup analysis were used to determine the correlation, non-linear relationship and threshold effect between AST/ALT and T2DM. RESULTS: In our study, 157 men and 40 women developed T2DM at follow-up. After adjusting for risk factors, AST/ALT was significantly associated with T2DM in men with NAFLD but not in women with NAFLD. The risk of T2DM increased as the AST/ALT ratio decreased. Besides, in male NAFLD patients, AST/ALT showed a non-linear relationship with T2DM, with an inflection point value of 0.964. When the AST to ALT ratio was below the threshold (AST/ALT <0.964), AST/ALT was significantly negatively associated with T2DM (HR = 0.177, 95% CI 0.055-0.568; P = 0.0036). In contrast, when AST/ALT >0.964, no significant association was found (HR = 3.174, 95% CI 0.345-29.167; P = 0.3074). Moreover, subgroup analysis showed that GGT could alter the relationship between AST/ALT and T2DM. In the group with GGT ≤ 40, AST/ALT was strongly associated with T2DM (HR = 0.24, 95% CI 0.09-0.66; P = 0.0059). CONCLUSIONS: These results suggested that there were sex differences in the association between AST/ALT and T2DM in NAFLD participants. A non-linear association between AST/ALT and T2DM was observed in males. AST/ALT in the normal GGT group (GGT ≤40) might better facilitate the early screening of T2DM.
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Diabetes Mellitus Tipo 2 , Hepatopatia Gordurosa não Alcoólica , Feminino , Humanos , Masculino , Aspartato Aminotransferases , Diabetes Mellitus Tipo 2/epidemiologia , Diabetes Mellitus Tipo 2/complicações , Incidência , Japão , Hepatopatia Gordurosa não Alcoólica/epidemiologia , Estudos Retrospectivos , Caracteres Sexuais , Alanina Transaminase/metabolismoRESUMO
Stripe rust, caused by Puccinia striiformis f. sp. tritici (Pst), is one of the most destructive fungal diseases of wheat. Cultivated einkorn (Triticum monococcum L. ssp. monococcum, 2n = 2x = 14, AmAm), one of the founder crops of agriculture, harbors unexploited genetic sources for wheat improvement. An advanced wheat line, Z15-1949, with 42 chromosomes, selected from the hybrids of Pst-susceptible common wheat cultivar Crocus and resistant T. monococcum accession 10-1, exhibits high resistance to a mixture of the prevalent Chinese Pst races. Genetic analysis on F1, F2, and F2:3 generations of the cross between Z15-1949 and Pst-susceptible common wheat SY95-71 indicated that the resistance of Z15-1949 was conferred by a recessive gene, tentatively designated as YrZ15-1949. This gene was mapped to the short arm of chromosome 7D using the Wheat 55K single nucleotide polymorphism array, flanked by markers KASP-1949-2 and KASP-1949-10 within a 3.3-cM genetic interval corresponding to a 1.12-Mb physical region in the Chinese Spring reference genome V2.0. The gene differs from previously reported Yr genes on 7D based on their physical positions and is probably a novel gene. YrZ15-1949 would be a valuable resource for developing Pst-resistant wheat cultivars, and the linked markers could be used for marker-assisted selection.
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Basidiomycota , Mapeamento Cromossômico , Resistência à Doença , Doenças das Plantas , Puccinia , Triticum , Triticum/microbiologia , Triticum/genética , Doenças das Plantas/microbiologia , Doenças das Plantas/imunologia , Resistência à Doença/genética , Basidiomycota/fisiologia , Basidiomycota/genética , Genes Recessivos , Cromossomos de Plantas/genética , Genes de Plantas/genética , Polimorfismo de Nucleotídeo Único/genética , Marcadores Genéticos/genéticaRESUMO
BACKGROUND: There is an increasing number of different brands of robotic total knee arthroplasty (TKA) systems. Most robotic TKA systems share the same coronal alignment, while the definitions of sagittal alignment vary. The purpose of this study was to investigate whether these discrepancies impact the sagittal alignment of the lower extremity. METHODS: A total of 72 lower extremity computed tomography scans were included in our study, and 3-dimensional models were obtained using software. A total of 7 brands of robotic TKA systems were included in the study. The lower extremity axes were defined based on the surgical guide for each implant. We also set the intramedullary axis as a reference to evaluate the discrepancies in sagittal alignment of each brand of robotic system. RESULTS: On the femoral side, the axis definition was the same for all 7 robotic TKA systems. The robotic TKA axes showed a 2.41° (1.58°, 3.38°) deviation from the intramedullary axis. On the tibial side, the 7 robots had different axis definitions. The tibial mechanical axis of 6 of the TKA systems was more flexed than that of the intramedullary axis, which means the posterior tibial slope was decreased while the tibial mechanical axis of the remaining system was more extended. CONCLUSIONS: The sagittal alignment of the lower extremity for 7 different brands of robotic TKA systems differed from each other and all deviated from the intramedullary axis. Surgeons should be aware of this discrepancy when using different brands of robotic TKA systems to avoid unexpected sagittal alignment and corresponding adverse clinical outcomes. LEVEL OF EVIDENCE: Level IV, Therapeutic Study.
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Artroplastia do Joelho , Procedimentos Cirúrgicos Robóticos , Humanos , Artroplastia do Joelho/métodos , Artroplastia do Joelho/instrumentação , Procedimentos Cirúrgicos Robóticos/métodos , Masculino , Feminino , Articulação do Joelho/cirurgia , Articulação do Joelho/diagnóstico por imagem , Tomografia Computadorizada por Raios X , Prótese do Joelho , Tíbia/cirurgia , Tíbia/diagnóstico por imagem , Idoso , Extremidade Inferior/cirurgia , Extremidade Inferior/diagnóstico por imagem , Fêmur/cirurgia , Fêmur/diagnóstico por imagem , Pessoa de Meia-Idade , Imageamento TridimensionalRESUMO
The ubiquity of solid-liquid interfaces in nature and the significant role of their atomic-scale structure in determining interfacial properties have led to intensive research. Particularly in electrocatalysis, however, a molecular-level picture that clearly describes the dynamic interfacial structures and organizations with their correlation to preferred reaction pathways in electrochemical reactions remains poorly understood. In this review, CO2 electroreduction reaction (CO2RR) is spatially and temporally understood as a result of intricate interactions at the interface, in which the interfacial features are highly relevant. We start with the discussion of current understandings and model development associated with the charged electrochemical interface as well as its dynamic landscape. We further highlight the interactive dynamics from the interfacial field, catalyst surface charges and various gradients in electrolyte and interfacial water structures at interfaces under CO2RR working conditions, with emphasis on the interfacial-structure dependence of catalytic reactivity/selectivity. Significantly, a probing energy-dependent "in situ characterization map" for dynamic interfaces based on various complementary in situ/operando techniques is proposed, aiming to present a comprehensive picture of interfacial electrocatalysis and to provide a more unified research framework. Moreover, recent milestones in both experimental and theoretical aspects to establish the correct profile of electrochemical interfaces are stressed. Finally, we present key scientific challenges with related perspectives toward future opportunities for this exciting frontier.
RESUMO
PURPOSE: Robot-assisted surgical systems for performing total knee arthroplasty (TKA) have gained significant attention. This study was designed to compare the surgical outcomes in primary TKA surgery between the recently developed "SkyWalker" robot system and the more commonly used MAKO robot. METHODS: A total of 75 patients undergoing primary TKA surgery by the same surgical team were included in this study, with 30 patients in the "SkyWalker" group and 45 patients in the "MAKO" group. We documented the osteotomy plan for both robotic systems. The lower limb alignment angles were evaluated by postoperative radiographic assessment. The operation time, estimated blood loss, postoperative hospital stays, and changes in laboratory indexes were collected during hospitalization. In addition, a comparative evaluation of knee functional assessments and complications was conducted during six month and one year follow-ups. RESULTS: There were no significant differences between the two groups in terms of the accuracy of restoring lower limb alignment, estimated blood loss, or operation time. The knee function assessments at six months and one year postoperatively were similar in both groups. Except for day three after surgery, the level of interleukin-6 (IL-6) and the change in IL-6 (∆IL-6) from preoperative baseline were higher in the "SkyWalker" group than in the MAKO group (median: 20.53 vs. 14.17, P=0.050 and median: 17.30 vs. 10.09, P=0.042, respectively). Additionally, one patient from the MAKO group underwent revision surgery at nine months postoperatively due to ongoing periprosthetic discomfort. CONCLUSIONS: The newly developed "SkyWalker" robot showed comparable efficacy to the MAKO robot in terms of lower limb alignment accuracy and postoperative six month and one year follow-up of clinically assessed resumption of knee function.