RESUMO
BACKGROUND: Citrus is one of the most valuable fruits worldwide and an economic pillar industry in southern China. Nevertheless, it frequently suffers from undesirable environmental stresses during the growth cycle, which severely restricts the growth, development and yield of citrus. In plants, the growth-regulating factor (GRF) family of transcription factors (TF) is extensively distributed and plays an vital part in plant growth and development, hormone response, as well as stress adaptation. However, the systematic identification and functional analysis of GRF TFs in citrus have not been reported. RESULTS: Here, a genome-wide identification of GRF TFs was performed in Citrus sinensis, 9 members of CsGRFs were systematically identified and discovered to be scattered throughout 5 chromosomes. Subsequently, physical and chemical properties, phylogenetic relationships, structural characteristics, gene duplication events, collinearity and cis-elements of promoter were elaborately analyzed. In particular, the expression patterns of the CsGRF genes in response to multiple phytohormone and abiotic stress treatments were investigated. Predicated on this result, CsGRF04, which exhibited the most differential expression pattern under multiple phytohormone and abiotic stress treatments was screened out. Virus-induced gene silencing (VIGS) technology was utilized to obtain gene silenced plants for CsGRF04 successfully. After the three stress treatments of high salinity, low temperature and drought, the CsGRF04-VIGS lines showed significantly reduced resistance to high salinity and low temperature stresses, but extremely increased resistance to drought stress. CONCLUSIONS: Taken together, our findings systematically analyzed the genomic characterization of GRF family in Citrus sinensis, and excavated a CsGRF04 with potential functions under multiple abiotic stresses. Our study lay a foundation for further study on the function of CsGRFs in abiotic stress and hormone signaling response.
Assuntos
Citrus sinensis , Citrus , Citrus sinensis/genética , Filogenia , Reguladores de Crescimento de Plantas/farmacologia , Peptídeos e Proteínas de Sinalização Intercelular , HormôniosRESUMO
It is urgent to pursue appropriate gate photoactive materials for gate-to-channel signal modulation to achieve superior transconductance performances of organic photoelectrochemical transistor (OPECT) sensors. Notably, a hole transfer layer (HTL) participant CdZnS/sulfur-doped Ti3C2 MXene (S-MXene) gate was designed and developed in this work, which exhibited a remarkable signal modulation performance by up to 3 orders of magnitude. Because of the incorporation of S-MXene with an enhanced electrical conductivity as the effective HTL, the signal modulation capabilities of the CdZnS/S-MXene photoactive gate were superior to those of CdZnS and CdZnS/MXene. This incorporation inhibited the recombination of the interfacial charge and facilitated the transfer of photogenerated holes, thus enhancing the photoelectric conversion performance. This enhancement facilitated fast electron transfer with a larger effective photovoltage to augment the dedoping ability of channel ions. Based on these findings, an aptasensing platform that exhibited good performance was constructed using the proposed OPECT device, with ofloxacin as a model target and an aptamer for specific recognition. The developed OPECT aptasensor had various advantages, including a high sensitivity, good linear range (1.0 × 10-13 to 1.0 × 10-6 M), and low limit of detection (3.3 × 10-15 M). This study provided a proof-of-concept for the generalized development of HTL participant gates for OPECT sensors and other related applications.
RESUMO
Iron oxide nanoparticles (IONPs) have garnered significant attention as a promising platform for reactive oxygen species (ROS)-dependent disease treatment, owing to their remarkable biocompatibility and Fenton catalytic activity. However, the low catalytic activity of IONPs is a major hurdle in their clinical translation. To overcome this challenge, IONPs of different compositions are examined for their Fenton reaction under pharmacologically relevant conditions. The results show that wüstite (FeO) nanoparticles exhibit higher catalytic activity than magnetite (Fe3 O4 ) or maghemite (γ-Fe2 O3 ) of matched size and coating, despite having a similar surface oxidation state. Further analyses suggest that the high catalytic activity of wüstite nanoparticles can be attributed to the presence of internal low-valence iron (Fe0 and Fe2+ ), which accelerates the recycling of surface Fe3+ to Fe2+ through intraparticle electron transport. Additionally, ultrasmall wüstite nanoparticles are generated by tuning the thermodecomposition-based nanocrystal synthesis, resulting in a Fenton reaction rate 5.3 times higher than that of ferumoxytol, an FDA-approved IONP. Compared with ferumoxytol, wüstite nanoparticles substantially increase the level of intracellular ROS in mouse mammary carcinoma cells. This study presents a novel mechanism and pivotal improvement for the development of highly efficient ROS-inducing nanozymes, thereby expanding the horizons for their therapeutic applications.
Assuntos
Óxido Ferroso-Férrico , Nanopartículas , Camundongos , Animais , Transporte de Elétrons , Espécies Reativas de Oxigênio , Compostos Férricos/química , Compostos FerrososRESUMO
AIM: To identify the spectrum of autoimmune encephalitis antibody biomarkers (AE-Abs) in children with suspected autoimmune encephalitis and explore the clinical features indicating AE-Abs presence. METHOD: We included children with suspected autoimmune encephalitis who underwent AE-Abs tests at the Children's Hospital of Chongqing Medical University between June 2020 and June 2022. Clinical features suggestive of AE-Abs were analysed based on AE-Abs test results. RESULTS: A total of 392 children were tested for AE-Abs with suspected autoimmune encephalitis. Of these, 49.5% were male, with a median age of 7 years 11 months (6 months-17 years 11 months); 93.6% (367/392) of all patients had both serum and cerebrospinal fluid (CSF) tests performed. The antibody-positive rate in the cohort was 23.7% (93/392), the serum antibody-positive rate was 21.9% (84/384), and the CSF antibody-positive rate was 20.8% (78/375). Eleven different AE-Abs were detected. Serum analysis revealed that N-methyl-D-aspartate receptor immunoglobulin-G (NMDAR-IgG) (15.1%) was greater than myelin oligodendrocyte glycoprotein (MOG)-IgG (14.6%) and glial fibrillary acidic protein (GFAP)-IgG (3.3%). CSF analysis revealed that NMDAR-IgG (16.3%) was greater than MOG-IgG (13.8%) and GFAP-IgG (3.3%). Compared with antibody-negative patients, antibody-positive patients were more often female (odds ratio [OR] 1.86, p = 0.03), with memory impairment (OR 2.91, p = 0.01) and sleep disorders (OR 2.08, p = 0.02). INTERPRETATION: In children, the most frequent AE-Abs detected were NMDAR-IgG and MOG-IgG. Female sex, memory impairment, and sleep disorders predict a higher likelihood of AE-Abs.
Assuntos
Encefalite Antirreceptor de N-Metil-D-Aspartato , Encefalite , Doença de Hashimoto , Transtornos do Sono-Vigília , Criança , Humanos , Masculino , Feminino , Encefalite Antirreceptor de N-Metil-D-Aspartato/diagnóstico , Glicoproteína Mielina-Oligodendrócito , Autoanticorpos , Imunoglobulina G , Receptores de N-Metil-D-AspartatoRESUMO
Cyclobutrifluram (TYMIRIUM® technology), a new succinate dehydrogenase inhibitor (SDHI) fungicide, is currently being registered by SYNGENTA for controlling Fusarium crown rot (FCR) of wheat in China. The application of 15 or 30 g of active ingredient/100 kg seed of cyclobutrifluram significantly reduced pre-emergence damping-off, discoloration on the stem base and formation of whiteheads caused by FCR. The EC50 values of cyclobutrifluram for 60 isolates of F. pseudograminearum, 30 isolates of F. asiaticum and 30 isolates of F. graminearum ranged from 0.016 to 0.142 mg L-1, 0.010 to 0.041 mg L-1 and 0.012 to 0.059 mg L-1, respectively. One hundred and seven cyclobutrifluram-resistant (CR) mutants were obtained from three Fusarium species isolates, with ten types of mutations identified in Sdh genes. Three Fusarium species isolates exhibited similar resistance mechanisms, with the most prevalent mutations, SdhC1A83V and SdhC1R86K, accounting for 61.68% of mutants. The CR mutants possessed comparable or slightly impaired fitness compared to the corresponding parental isolates. The CR mutants carrying FpSdhBH248Y/Q/D exhibited increased sensitivity to fluopyram. An overall moderate risk of resistance development in three Fusarium species was recommended for cyclobutrifluram.
Assuntos
Fusarium , Fusarium/genética , Triticum , Doenças das Plantas/prevenção & controle , Mutação , Ácido SuccínicoRESUMO
Fusarium crown rot (FCR), caused by Fusarium pseudograminearum, significantly impacts wheat yield and quality in China's Huanghuai region. The rapid F. pseudograminearum epidemic and FCR outbreak within a decade remain unexplained. In this study, two high-quality, chromosome-level genomes of F. pseudograminearum strains producing 3-acetyl-deoxynivalenol (3AcDON) and 15-acetyl-deoxynivalenol (15AcDON) toxins were assembled. Additionally, 38 related strains were resequenced. Genomic differences such as single nucleotide polymorphisms (SNPs), insertions/deletions (indels), and structural variations (SVs) among F. pseudograminearum strains were analyzed. The whole-genome SNP locus-based population classification mirrored the toxin chemotype (3AcDON and 15AcDON)-based classification, indicating the presence of genes associated with the trichothecene toxin gene cluster. Further analysis of differential SNP, indel, and SV loci between the 3AcDON and 15AcDON populations revealed a predominant connection to secondary metabolite synthesis genes. Notably, the majority of the secondary metabolite biosynthesis gene cluster loci were located in SNP-dense genomic regions, suggesting high mutability and a possible contribution to F. pseudograminearum population structure and environmental adaptability. This study provides insightful perspectives on the distribution and evolution of F. pseudograminearum and for forecasting the spread of wheat FCR, thereby aiding in the development of preventive measures and control strategies.
Assuntos
Fusarium , Genoma Fúngico , Doenças das Plantas , Polimorfismo de Nucleotídeo Único , Metabolismo Secundário , Tricotecenos , Triticum , Fusarium/genética , Triticum/microbiologia , Doenças das Plantas/microbiologia , Tricotecenos/metabolismo , China , Metabolismo Secundário/genética , Micotoxinas/genéticaRESUMO
The efficient fault detection (FD) of traction control systems (TCSs) is crucial for ensuring the safe operation of high-speed trains. Transient faults (TFs) can arise due to prolonged operation and harsh environmental conditions, often being masked by background noise, particularly during dynamic operating conditions. Moreover, acquiring a sufficient number of samples across the entire scenario presents a challenging task, resulting in imbalanced data for FD. To address these limitations, an unsupervised transfer learning (TL) method via federated Cycle-Flow adversarial networks (CFANs) is proposed to effectively detect TFs under various operating conditions. Firstly, a CFAN is specifically designed for extracting latent features and reconstructing data in the source domain. Subsequently, a transfer learning framework employing federated CFANs collectively adjusts the modified knowledge resulting from domain alterations. Finally, the designed federated CFANs execute transient FD by constructing residuals in the target domain. The efficacy of the proposed methodology is demonstrated through comparative experiments.
RESUMO
Multiple organs and tissues coordinate to respond to dietary and environmental challenges. It is interorgan crosstalk that contributes to systemic metabolic homeostasis. The liver and brain, as key metabolic organs, have their unique dialogue to transmit metabolic messages. The interconnected pathogenesis of liver and brain is implicated in numerous metabolic and neurodegenerative disorders. Recent insights have positioned the liver not only as a central metabolic hub but also as an endocrine organ, capable of secreting hepatokines that transmit metabolic signals throughout the body via the bloodstream. Metabolites from the liver or gut microbiota also facilitate a complex dialogue between liver and brain. In parallel to humoral factors, the neural pathways, particularly the hypothalamic nuclei and autonomic nervous system, are pivotal in modulating the bilateral metabolic interplay between the cerebral and hepatic compartments. The term "liver-brain axis" vividly portrays this interaction. At the end of this review, we summarize cutting-edge technical advancements that have enabled the observation and manipulation of these signals, including genetic engineering, molecular tracing, and delivery technologies. These innovations are paving the way for a deeper understanding of the liver-brain axis and its role in metabolic homeostasis.
Assuntos
Encéfalo , Fígado , Humanos , Encéfalo/metabolismo , Fígado/metabolismo , Animais , Homeostase , Microbioma GastrointestinalRESUMO
BACKGROUND: Migraine is a common neurological disorder with a strong genetic component. Despite the identification of over 100 loci associated with migraine susceptibility through genome-wide association studies (GWAS), the underlying causative genes and biological mechanisms remain predominantly elusive. METHODS: The FinnGen R10 dataset, consisting of 333,711 subjects (20,908 cases and 312,803 controls), was utilized in conjunction with the Genotype-Tissue Expression Project (GTEx) v8 EQTls files to conduct cross-tissue transcriptome association studies (TWAS). Functional Summary-based Imputation (FUSION) was employed to validate these findings in single tissues. Additionally, candidate susceptibility genes were screened using Gene Analysis combined with Multi-marker Analysis of Genomic Annotation (MAGMA). Subsequent Mendelian randomization (MR) and colocalization analyses were conducted. Furthermore, GeneMANIA analysis was employed to enhance our understanding of the functional implications of these susceptibility genes. RESULTS: We identified a total of 19 susceptibility genes associated with migraine in the cross-tissue TWAS analysis. Two novel susceptibility genes, REV1 and SREBF2, were validated through both single tissue TWAS and MAGMA analysis. Mendelian randomization and colocalization analyses further confirmed these findings. REV1 may reduce the migraine risk by regulating DNA damage repair, while SREBF2 may increase the risk of migraine by regulating cholesterol metabolism. CONCLUSION: Our study identified two novel genes whose predicted expression was associated with the risk of migraine, providing new insights into the genetic framework of migraine.
Assuntos
Predisposição Genética para Doença , Estudo de Associação Genômica Ampla , Transtornos de Enxaqueca , Transcriptoma , Humanos , Transtornos de Enxaqueca/genética , Predisposição Genética para Doença/genética , Transcriptoma/genética , Análise da Randomização Mendeliana , Polimorfismo de Nucleotídeo Único/genéticaRESUMO
Developing fluorescent chemosensors with sensitivity and high specificity for recognizing fluorides is still challenging. Herein, four innovative compounds based on 13-8-13-membered tricyclic ladder-type siloxanes hybridized with BINOLs (abbreviated as TLS-BINOLs) were prepared through the B(C6F5)3-catalyzed Piers-Rubinsztajn reaction. The well-defined ladder-type structure of the TLS-BINOLs was determined by X-ray crystallographic analysis. Additionally, the fluorescent sensing ability of the TLS-BINOLs toward anions was studied. Our finding revealed that all four ladder-type compounds (TLS-BINOLs) exhibited high specificity in recognizing fluorides through fluoride-triggered structural decomposition. The detection limits for fluorides were determined to be 0.37, 0.35, 0.39, and 0.48 µM for the respective TLS-BINOLs. The nonemissive product induced by the fluorides was also determined using single-crystal X-ray diffraction analysis.
RESUMO
As the terminal oxidase of cell respiration in mitochondria and aerobic bacteria, the proton pumping mechanism of ba3-type cytochrome c oxidase (CcO) of Thermus thermophiles is still not fully understood. Especially, the functions of key residues which were considered as the possible proton loading sites (PLSs) above the catalytic center, as well as water located above and within the catalytic center, remain unclear. In this work, molecular dynamic simulations were performed on a set of designed mutants of key residues (Asp287, Asp372, His376, and Glu126II). The results showed that Asp287 may not be a PLS, but it could modulate the ability of the proton transfer pathway to transfer protons through its salt bridge with Arg225. Maintaining the closed state of the water pool above the catalytic center is necessary for the participation of inside water molecules in proton transfer. Water molecules inside the water pool can form hydrogen bond chains with PLS to facilitate proton transfer. Additional quantum cluster models of the Fe-Cu metal catalytic center are established, indicating that when the proton is transferred from Tyr237, it is more likely to reach the OCu atom directly through only one water molecule. This work provides a more profound understanding of the functions of important residues and specific water molecules in the proton pumping mechanism of CcO.
Assuntos
Complexo IV da Cadeia de Transporte de Elétrons , Bombas de Próton , Complexo IV da Cadeia de Transporte de Elétrons/química , Prótons , Água/química , Simulação de Dinâmica Molecular , OxirreduçãoRESUMO
PURPOSE: This study aimed to explore Chinese breast cancer patients' quality of sexual life (QSL) and factors associated with QSL. METHODS: The questionnaires in this cross-sectional study include the general information questionnaire, cognition and assessment of sexual health questionnaire, Self-acceptance Questionnaire (SAQ), Medical Coping Modes Questionnaire (MCMQ), and Quality of Sexual Life Questionnaire (QSLQ); 201 breast cancer patients were required to complete the questionnaires assessing characteristic information, cognition and assessment of sexual health, QSL, self-acceptance, and coping style. Finally, hierarchical regression was used to analyze the factors associated with QSL in Chinese breast cancer patients. RESULTS: The mean age (at the time of the survey) of the breast cancer patients was 48.31±9.15. The mean score of the QSLQ (range 28-140) was 75.14±16.57. Hierarchical regression analysis showed that the associated factors of breast cancer patients' QSL included age (at the time of the survey), education level, type of surgery, cognition and assessment of sexual health, self-acceptance, and avoidance and acceptance-resignation coping styles, that independent variables explained 60.4% of the variance. CONCLUSION: The QSL among Chinese breast cancer patients needs to be improved. Our findings indicated that breast cancer patients with older age, lower education level, or modified radical mastectomy have poor QSL. Breast cancer patients learn correct information about sexual health, enhance self-acceptance, and reduce acceptance-resignation, and avoidance coping could be intervention strategies to improve their QSL.
Assuntos
Neoplasias da Mama , Feminino , Humanos , Adaptação Psicológica , Estudos Transversais , População do Leste Asiático , Mastectomia , Qualidade de Vida , Inquéritos e Questionários , ChinaRESUMO
Air pollution has become a global public health risk factor as rapid urbanization advances. To observe the air pollution situation, air monitoring stations have been established in many cities, which record six air pollutants. Previous studies have identified cities exhibiting similar air pollution characteristics by combining principal component analysis (PCA) with cluster analysis (CA). However, spatial and temporal effects were neglected. In this paper, we focus on the combination of GTWPCA and STCA, which fully incorporates spatio-temporal effects. It is then applied to air pollution data from the top 10 urban agglomerations in China during 2016-2021. Key experimental findings include: 1. GTWPCA provides a more detailed interpretation of local variation than PCA. 2. Compared with CA, STCA highlights the coupling effect in the spatial and temporal dimensions. 3. The combination of GTWPCA and STCA captures similar air pollution characteristics from spatio-temporal perspectives, which has the potential to help environmental authorities take further action to control air pollution.
Assuntos
Poluentes Atmosféricos , Poluição do Ar , Poluição do Ar/análise , Poluentes Atmosféricos/análise , China , Cidades , Urbanização , Monitoramento Ambiental/métodos , Material Particulado/análiseRESUMO
PURPOSE: Retinol-binding protein 4 (RBP4) has been considered to be related to metabolic related diseases, such as hyperuricemia, obesity, and diabetes mellitus. However, whether nonalcoholic fatty liver disease (NAFLD) is related to RBP4 is unclear. Previous studies on the relationship between NAFLD and RBP4 levels have yielded inconsistent results. Hence, this meta-analysis was aimed to clarify whether circulating RBP4 levels are in relation to the risk of NAFLD. METHODS: A meta-analysis was performed by applying observational studies to evaluate circulating RBP4 levels and NAFLD. Eligible studies published up to September 23, 2022, were searched in Embase, PubMed, and Cochrane databases. RESULTS: In this study, 17 cross-sectional studies involving 8423 participants were included. Results from a random effects model showed that circulating RBP4 levels were higher in NAFLD patients than non-NAFLD (standardized mean difference (SMD) 0.28; 95% confidence intervals (CI): 0.11-0.46, I2: 89.8%). This association was confirmed in the Yellow race. However, no significant association was noted in the Caucasian race. After excluding the morbidly obese Population from the weight loss study (n = 2), the results of the comparison remained largely unchanged (SMD 0.28; 95% CI: 0.10-0.47, I2: 90.8%). Remarkable publication bias was not found. Although considerable heterogeneity was observed among the studies, no potential sources of heterogeneity were found in the subgroup analysis. Diagnostic methods for NAFLD were determined to be a potential source of statistical heterogeneity in meta-regression. CONCLUSION: The findings provide evidence that NAFLD patients exhibit higher levels of circulating RBP4 compared with controls, but high heterogeneity was observed. Thus, a high RBP4 level is probably a potential risk factor for NAFLD. To confirm the causal link between NAFLD and RBP4 level of causality, further prospective cohort studies are needed.
Assuntos
Hepatopatia Gordurosa não Alcoólica , Obesidade Mórbida , Humanos , Estudos Transversais , Hepatopatia Gordurosa não Alcoólica/metabolismo , Proteínas Plasmáticas de Ligação ao Retinol/genética , Fatores de Risco , População Branca , AsiáticoRESUMO
This study aimed to adopt the item-method directed forgetting (DF) paradigm to explore the effects of cognitive reappraisal on intentional forgetting of negative emotional pictures. Behavioral results showed that the recognition of to-be-forgotten but remembered (TBF-r) was significantly greater than that of to-be-remembered and remembered (TBR-r) in the recognition test, which was the opposite result to the DF effect. Event-related potential (ERP) results showed that in the 450-660 ms (ms) of cue presentation, the F-cue of the cognitive reappraisal condition (imagining the upcoming pictures to be "fake or performed by actors" to avoid or reduce the intensity of negative emotions caused by the pictures) elicited more positive late positive potential (LPP) than passive viewing (participants watched freely and paid attention to the characters, scenes, and other details in the picture). This indicated that cognitive reappraisal required stronger inhibition than passive viewing for the to-be- forgotten (TBF) items. In the test phase, both the TBR-r and TBF-r items in the cognitive reappraisal condition evoked more positive ERP than correctly rejected (CR) unseen items in the study phase, which induced the frontal old/new effect (P200, 160-240 ms). In addition, this study also found that the LPP amplitudes of 450-660 ms in the frontal area induced by F-cues in cognitive reappraisal were significantly negatively correlated with the LPP amplitudes of 300-3500 ms induced by cognitive reappraisal instructions, and positive waves in the frontal area were significantly positively correlated with the TBF-r behavioral results. However, these results were not observed in the passive viewing group. The above results show that cognitive reappraisal enhances the retrieval ability for TBR and TBF items, and TBF-r is associated with cognitive reappraisal in the study phase and inhibitory control of F-cues.
Assuntos
Eletroencefalografia , Potenciais Evocados , Humanos , Eletroencefalografia/métodos , Tempo de Reação/fisiologia , Potenciais Evocados/fisiologia , Sinais (Psicologia) , Emoções/fisiologia , CogniçãoRESUMO
Epidemiological studies have demonstrated that exposure to air particulate matter (PM) increases the incidence of cardiovascular and respiratory diseases and exerts a significant neurotoxic effect on the nervous system, especially on the immature nervous system. Here, we selected PND28 rats to simulate the immature nervous system of young children and used neurobehavioral methods to examine how exposure to PM affected spatial learning and memory, as well as electrophysiology, molecular biology, and bioinformatics to study the morphology of hippocampus and the function of hippocampal synapses. We discovered that spatial learning and memory were impaired in rats exposed to PM. The morphology and structure of the hippocampus were altered in the PM group. In addition, after exposure to PM, the relative expression of synaptophysin (SYP) and postsynaptic density 95 (PSD95) proteins decreased dramatically in rats. Furthermore, PM exposure impaired long-term potentiation (LTP) in the hippocampal Schaffer-CA1 pathway. Interestingly, RNA sequencing and bioinformatics analysis revealed that the differentially expressed genes (DEGs) were rich in terms associated with synaptic function. Five hub genes (Agt, Camk2a, Grin2a, Snca, and Syngap1) that may play a significant role in the dysfunctionality of hippocampal synapses were identified. Our findings implied that exposure to PM impaired spatial learning and memory via exerting impacts on the dysfunctionality of hippocampal synapses in juvenile rats and that Agt, Camk2a, Grin2a, Snca, and Syngap1 may drive PM-caused synaptic dysfunction.
Assuntos
Plasticidade Neuronal , Aprendizagem Espacial , Ratos , Animais , Plasticidade Neuronal/fisiologia , Material Particulado/metabolismo , Memória , Hipocampo/metabolismo , SinapsesRESUMO
OBJECTIVES: Extraction of impacted mandibular third molars (IMTMs) is the most common surgery performed in the Department of Oral and Maxillofacial Surgery. Inferior alveolar nerve (IAN) injury is a rare but severe complication, and the risk is significantly higher in cases of IMTM near the inferior alveolar canal (IAC). The existing surgical method to extract such IMTMs is either not safe enough or is time-consuming. A better surgical design is needed. MATERIALS AND METHODS: From August 2019 to June 2022, 23 patients underwent IMTM extraction by Dr. Zhao at Nanjing Stomatological Hospital, Affiliated Hospital of Medical School, Nanjing University, and were found to have IMTMs in close proximity to the IAC. Due to high IAN injury risk, these patients underwent coronectomy-miniscrew traction to extract their IMTMs. RESULTS: The time between coronectomy-miniscrew insertion and complete removal of the IMTM was 32.65 ± 2.110 days, which was significantly shorter than that of traditional orthodontic traction. Two-point discrimination testing revealed no IAN injury, and no injury was reported by patients during follow-up. Other complications, such as severe swelling, severe bleeding, dry socket, and limited mouth opening, were not observed. Postoperative pain levels were not significantly higher in the coronectomy-miniscrew traction group than in the traditional IMTM extraction group. CLINICAL RELEVANCE: For IMTMs that are in close proximity to the IAC and must be extracted, coronectomy-miniscrew traction is a novel approach to minimize the risk of IAN injury in a less time-consuming way with a lower possibility of complications.
Assuntos
Dente Impactado , Traumatismos do Nervo Trigêmeo , Humanos , Canal Mandibular , Dente Serotino/cirurgia , Traumatismos do Nervo Trigêmeo/prevenção & controle , Traumatismos do Nervo Trigêmeo/etiologia , Extração Dentária/efeitos adversos , Tração/efeitos adversos , Mandíbula/cirurgia , Dente Impactado/cirurgia , Nervo MandibularRESUMO
As one of the crucial targets of epigenetics, histone lysine-specific demethylase 1 (LSD1) is significant in the occurrence and development of various tumors. Although several irreversible covalent LSD1 inhibitors have entered clinical trials, the large size and polarity of the FAD-binding pocket and undesired toxicity have focused interest on developing reversible LSD1 inhibitors. In this study, targeting the substrate-binding pocket of LSD1, structure-based and ligand-based virtual screenings were adopted to expand the potential novel structures with molecular docking and pharmacophore model strategies, respectively. Through drug-likeness evaluation, ADMET screening, molecular dynamics simulations, and binding free energy screening, we screened out one and four hit compounds from the databases of 2,029,554 compounds, respectively. Generally, these hit compounds can be divided into two categories, amide (Lig2 and Comp2) and 1,2,4-triazolo-4,3-α-quinazoline (Comp3, Comp4, Comp7). Among them, Comp4 exhibits the strongest binding affinity. Finally, the binding mechanisms of the hit compounds were further calculated in detail by the residue free energy decomposition. It was found that van der Waals interactions contribute most to the binding, and FAD is also helpful in stabilizing the binding and avoiding off-target effects. We believe this work not only provides a solid theoretical foundation for the design of LSD1 substrate reversible inhibitors, but also expands the diversity of parent nucleus, offering new insights for synthetic chemists.
Assuntos
Inibidores Enzimáticos , Histonas , Simulação de Acoplamento Molecular , Relação Estrutura-Atividade , Inibidores Enzimáticos/farmacologia , Inibidores Enzimáticos/química , Histonas/metabolismo , Simulação de Dinâmica Molecular , Histona Desmetilases/metabolismoRESUMO
Pyxinol skeleton is a promising framework of anti-inflammatory agents formed in the human liver from 20S-protopanaxadiol, the main active aglycone of ginsenosides. In the present study, a new series of amino acid-containing derivatives were produced from 12-dehydropyxinol, a pyxinol oxidation metabolite, and its anti-inflammatory activity was assessed using an NO inhibition assay. Interestingly, the dehydrogenation at C-12 of pyxinol derivatives improved their potency greatly. Furthermore, half of the derivatives exhibited better NO inhibitory activity than hydrocortisone sodium succinate, a glucocorticoid drug. The structure-activity relationship analysis indicated that the kinds of amino acid residues and their hydrophilicity influenced the activity to a great extent, as did R/S stereochemistry at C-24. Of the various derivatives, 5c with an N-Boc-protected phenylalanine residue showed the highest NO inhibitory activity and relatively low cytotoxicity. Moreover, derivative 5c could dose-dependently suppress iNOS, IL-1ß, and TNF-α via the MAPK and NF-κB pathways, but not the GR pathway. Overall, pyxinol derivatives hold potential for application as anti-inflammatory agents.
Assuntos
Anti-Inflamatórios , Ginsenosídeos , Humanos , Anti-Inflamatórios/farmacologia , NF-kappa B/metabolismo , Extratos Vegetais/farmacologia , Relação Estrutura-Atividade , Ginsenosídeos/farmacologia , LipopolissacarídeosRESUMO
Temozolomide (TMZ) is a standard-of-care chemotherapeutic drug for the treatment of glioblastoma (GBM), but TMZ-acquired resistance limits its therapeutic effect. In this study, TMZ-loaded gold nanoparticles (TMZ@GNPs) with anti-EphA3 modification on the surface (anti-EphA3-TMZ@GNPs) were synthesized for chemical and auxiliary plasma photothermal treatment (GNPs-PPTT), aiming to overcome the problem of glioma resistance to TMZ and improve the therapeutic effects of GBM. The prepared anti-EphA3-TMZ@GNPs were spherical with a particle size of 45.88 ± 1.9 nm, and the drug loading was 7.31 ± 0.38%. In vitro, cell-culture-based experiments showed that anti-EphA3 increased the cellular uptake of GNPs in T98G cells. Upon laser irradiation, the cytotoxicity and apoptosis rate in the anti-EphA3-TMZ@GNPs-treated group were significantly higher than those in the GNPs and nonphotothermal groups (p < 0.001). The Western blot analysis showed that the GNPs-PPTT-mediated killing of tumor cells induced apoptosis by regulating the apoptotic signaling molecules and cell cycle inhibitors; the expression of MGMT significantly decreased upon p53 induction, thereby reversing drug resistance. After photothermal treatment, the survival time of the subcutaneous GBM model of nude mice in the anti-EphA3-TMZ@GNPs group was prolonged to 46 days, 1.64-fold longer as compared to that in the TMZ group. Based on H&E and TUNEL staining, GNPs-PPTT could elevate apoptosis in T98G cells. In vivo thermal imaging results showed that GNPs could enter the brain via intranasal administration and be eliminated in 2 days, indicating that GNPs are safe for brain. In conclusion, GNPs-PPTT could effectively induce apoptosis in glioma cells and reverse TMZ resistance, thereby, indicative of a promising treatment strategy for GBM.