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Rhodamine, a colorant prohibited in various consumer products due to its demonstrated carcinogenic, mutagenic, and toxic properties, necessitates the development of a straightforward, efficient, sensitive, environmentally friendly, and cost-effective analytical method. This review provides an overview of recent advancements in the pretreatment and determination techniques for rhodamine across diverse sample matrices since 2017. Sample preparation methods encompass both commonly used pretreatment techniques such as filtration, centrifugation, solvent extraction, and cloud point extraction, as well as innovative approaches including solid phase extraction, dispersive liquid-liquid microextraction, hollow fiber liquid phase microextraction, magnetic solid phase extraction, and matrix solid phase dispersion. The analytical techniques encompass high performance liquid chromatography, surface-enhanced Raman scattering, and sensor-based methods. Furthermore, a comprehensive examination is conducted to offer insights for future research on rhodamine regarding the advantages, disadvantages, and advancements in various pretreatment and determination methodologies.
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Contaminação de Alimentos , Rodaminas , Rodaminas/química , Rodaminas/análise , Contaminação de Alimentos/análise , Cromatografia Líquida de Alta Pressão , Microextração em Fase Líquida/métodos , Extração em Fase Sólida , Corantes de Alimentos/análise , Corantes de Alimentos/química , Análise de AlimentosRESUMO
As an important part of the unmanned driving system, the detection and recognition of traffic sign need to have the characteristics of excellent recognition accuracy, fast execution speed and easy deployment. Researchers have applied the techniques of machine learning, deep learning and image processing to traffic sign recognition successfully. Considering the hardware conditions of the terminal equipment in the unmanned driving system, in this research work, the goal was to achieve a convolutional neural network (CNN) architecture that is lightweight and easily implemented for an embedded application and with excellent recognition accuracy and execution speed. As a classical CNN architecture, LeNet-5 network model was chosen to be improved, including image preprocessing, improving spatial pool convolutional neural network, optimizing neurons, optimizing activation function, etc. The test experiment of the improved network architecture was carried out on German Traffic Sign Recognition Benchmark (GTSRB) database. The experimental results show that the improved network architecture can obtain higher recognition accuracy in a short interference time, and the algorithm loss is significantly reduced with the progress of training. At the same time, compared with other lightweight network models, this network architecture gives a good recognition result, with a recognition accuracy of 97.53%. The network structure is simple, the algorithm complexity is low, and it is suitable for all kinds of terminal equipment, which can have a wider application in unmanned driving system.
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Glutamate is one of the most important excitatory neurotransmitters within the mammalian central nervous system. The role of glutamate in regulating neural network signaling transmission through both synaptic and extra-synaptic paths highlights the importance of the real-time and continuous monitoring of its concentration and dynamics in living organisms. Progresses in multidisciplinary research have promoted the development of electrochemical glutamate sensors through the co-design of materials, interfaces, electronic devices, and integrated systems. This review summarizes recent works reporting various electrochemical sensor designs and their applicability as miniaturized neural probes to in vivo sensing within biological environments. We start with an overview of the role and physiological significance of glutamate, the metabolic routes, and its presence in various bodily fluids. Next, we discuss the design principles, commonly employed validation models/protocols, and successful demonstrations of multifunctional, compact, and bio-integrated devices in animal models. The final section provides an outlook on the development of the next generation glutamate sensors for neuroscience and neuroengineering, with the aim of offering practical guidance for future research.
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Sistema Nervoso Central , Técnicas Eletroquímicas , Ácido Glutâmico , Ácido Glutâmico/análise , Ácido Glutâmico/metabolismo , Técnicas Eletroquímicas/métodos , Técnicas Eletroquímicas/instrumentação , Animais , Sistema Nervoso Central/metabolismo , Humanos , Técnicas Biossensoriais/métodosRESUMO
BACKGROUND: Both of lung cancer incidence and mortality rank first among all cancers in China. Previous lung cancer screening trials were mostly selective screening for high-risk groups such as smokers. Non-smoking women accounted for a considerable proportion of lung cancer cases in Asia. This study aimed to evaluate the outcome of community-based mass screening in Guangzhou and identify the high-risk factors for lung cancer. METHODS: Residents aged 40-74 years in Guangzhou were screened with low-dose computed tomography (LDCT) for lung cancer and the pulmonary nodules were classified and managed according to China National Lung Cancer Screening Guideline with Low-dose Computed Tomography (2018 version). The detection rate of positive nodules was calculated. Before the LDCT examination, residents were required to complete a "lung cancer risk factors questionnaire". The risk factors of the questionnaire were analyzed by least absolute shrinkage and selection operator (LASSO) penalized Logistic regression analysis. RESULTS: A total of 6256 residents were included in this study. 1228 positive nodules (19.63%) and 117 lung cancers were confirmed, including 6 cases of Tis, 103 cases of stage I (accounting for 88.03% of lung cancer). The results of LASSO penalized Logistic regression analysis indicated that age ≥50 yr (OR=1.07, 95%CI: 1.06-1.07), history of cancer (OR=3.29, 95%CI: 3.22-3.37), textile industry (OR=1.10, 95%CI: 1.08-1.13), use coal for cooking in childhood (OR=1.14, 95%CI: 1.13-1.16) and food allergy (OR=1.10, 95%CI: 1.07-1.13) were risk factors of lung cancer for female in this district. CONCLUSIONS: This study highlighted that numerous early stages of lung cancer cases were detected by LDCT, which could be applied to screening of lung cancer in women. Besides, age ≥50 yr, personal history of cancer, textile industry and use coal for cooking in childhood are risk factors for women in this district, which suggested that it's high time to raise the awareness of early lung cancer screening in this group.
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Detecção Precoce de Câncer , Neoplasias Pulmonares , Tomografia Computadorizada por Raios X , Humanos , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/epidemiologia , Neoplasias Pulmonares/diagnóstico , Pessoa de Meia-Idade , Feminino , Masculino , Fatores de Risco , Idoso , Adulto , China/epidemiologia , Detecção Precoce de Câncer/métodos , Inquéritos e QuestionáriosRESUMO
Major depressive disorder demonstrated sex differences in prevalence and symptoms, which were more pronounced during adolescence. Yet, research on sex-specific brain network characteristics in adolescent-onset major depressive disorder remains limited. This study investigated sex-specific and nonspecific alterations in resting-state functional connectivity of three core networks (frontoparietal network, salience network, and default mode network) and subcortical networks in adolescent-onset major depressive disorder, using seed-based resting-state functional connectivity in 50 medication-free patients with adolescent-onset major depressive disorder and 56 healthy controls. Irrespective of sex, compared with healthy controls, adolescent-onset major depressive disorder patients showed hypoconnectivity between bilateral hippocampus and right superior temporal gyrus (default mode network). More importantly, we further found that females with adolescent-onset major depressive disorder exhibited hypoconnectivity within the default mode network (medial prefrontal cortex), and between the subcortical regions (i.e. amygdala, striatum, and thalamus) with the default mode network (angular gyrus and posterior cingulate cortex) and the frontoparietal network (dorsal prefrontal cortex), while the opposite patterns of resting-state functional connectivity alterations were observed in males with adolescent-onset major depressive disorder, relative to their sex-matched healthy controls. Moreover, several sex-specific resting-state functional connectivity changes were correlated with age of onset, sleep disturbance, and anxiety in adolescent-onset major depressive disorder with different sex. These findings suggested that these sex-specific resting-state functional connectivity alterations may reflect the differences in brain development or processes related to early illness onset, underscoring the necessity for sex-tailored diagnostic and therapeutic approaches in adolescent-onset major depressive disorder.
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Encéfalo , Transtorno Depressivo Maior , Imageamento por Ressonância Magnética , Rede Nervosa , Caracteres Sexuais , Humanos , Transtorno Depressivo Maior/fisiopatologia , Transtorno Depressivo Maior/diagnóstico por imagem , Feminino , Adolescente , Masculino , Encéfalo/fisiopatologia , Encéfalo/diagnóstico por imagem , Rede Nervosa/diagnóstico por imagem , Rede Nervosa/fisiopatologia , Vias Neurais/fisiopatologia , Vias Neurais/diagnóstico por imagem , Adulto Jovem , Idade de Início , Mapeamento Encefálico , Rede de Modo Padrão/fisiopatologia , Rede de Modo Padrão/diagnóstico por imagemRESUMO
Limited alliinase resources cause difficulties in the biosynthesis of thiosulfinates (e.g., allicin), restricting their applications in the agricultural and food industries. To effectively biosynthesize thiosulfinates, this study aimed to excavate bacterial alliinase resources and elucidate their catalytic properties. Two bacterial cystathionine ß-lyases (MetCs) possessing high alliinase activity (>60 U mg -1) toward L-(-)-alliin were identified from Allium sativum rhizosphere isolates. Metagenomic exploration revealed that cystathionine ß-lyase from Bacillus cereus (BcPatB) possessed high activity toward both L-(±)-alliin and L-(+)-alliin (208.6 and 225.1 U mg -1), respectively. Although these enzymes all preferred l-cysteine S-conjugate sulfoxides as substrates, BcPatB had a closer phylogenetic relationship with Allium alliinases and shared several similar features with A. sativum alliinase. Interestingly, the Trp30Ile31Ala32Asp33 Met34 motif in a cuspate loop of BcPatB, especially sites 31 and 32 at the top of the motif, was modeled to locate near the sulfoxide of L-(+)-alliin and is important for substrate stereospecificity. Moreover, the stereoselectivity and activity of mutants I31V and A32G were higher toward L-(+)-alliin than those of mutant I31L/D33E toward L-(-)-alliin. Using bacterial alliinases and chemically synthesized substrates, we obtained thiosulfinates with high antimicrobial and antinematode activities that could provide insights into the protection of crops and food.
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Proteínas de Bactérias , Alho , Especificidade por Substrato , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo , Proteínas de Bactérias/química , Alho/química , Alho/enzimologia , Alho/genética , Ácidos Sulfínicos/química , Ácidos Sulfínicos/metabolismo , Bacillus cereus/enzimologia , Bacillus cereus/genética , Bacillus cereus/metabolismo , Dissulfetos/química , Dissulfetos/metabolismo , Filogenia , Estereoisomerismo , Sequência de Aminoácidos , Bactérias/enzimologia , Bactérias/genética , Bactérias/classificação , Bactérias/metabolismo , Cinética , Liases de Carbono-Enxofre/metabolismo , Liases de Carbono-Enxofre/genética , Liases de Carbono-Enxofre/química , Cisteína/análogos & derivadosRESUMO
The powerful capability of multi-stimulus-responsive luminescent hydrogen-bonded organic frameworks (HOFs) to respond to external chemical or physical stimuli in various manners makes them appealing in the luminescence anti-counterfeiting field. Herein, a novel Eu3+-functionalized HOF (Eu@GC-2) that combines the emission of HOFs with the characteristic emission of Eu3+ ions has been successfully synthesized, which can generate various fluorescence at different excitation wavelengths. Eu@GC-2 has enormous potential as a raw material for a paper-based sensor that is designed for detecting the pesticides thiram and caffeic acid in crops with favorable selectivity, anti-interference, and high efficiency. Based on the above excellent properties, Ln3+-functionalized HOFs (Ln@GC-2) were then employed to produce four luminescent anti-counterfeiting inks. With the incorporation of back-propagation neural network and Gray code conversion functions, a multi-stimulus-responsive luminescent anti-counterfeiting platform, coregulated by the excitation light and the chemical reagent, has been constructed. This approach can not only achieve multiple encryptions and fast information identification but also enhance the code-breaking complexity, making it an efficient strategy for information encryption and decryption.
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BACKGROUND: Splicing factors are vital for the regulation of RNA splicing, but some have also been implicated in regulating transcription. The underlying molecular mechanisms of their involvement in transcriptional processes remain poorly understood. RESULTS: Here, we describe a direct role of splicing factor RBM22 in coordinating multiple steps of RNA Polymerase II (RNAPII) transcription in human cells. The RBM22 protein widely occupies the RNAPII-transcribed gene locus in the nucleus. Loss of RBM22 promotes RNAPII pause release, reduces elongation velocity, and provokes transcriptional readthrough genome-wide, coupled with production of transcripts containing sequences from downstream of the gene. RBM22 preferentially binds to the hyperphosphorylated, transcriptionally engaged RNAPII and coordinates its dynamics by regulating the homeostasis of the 7SK-P-TEFb complex and the association between RNAPII and SPT5 at the chromatin level. CONCLUSIONS: Our results uncover the multifaceted role of RBM22 in orchestrating the transcriptional program of RNAPII and provide evidence implicating a splicing factor in both RNAPII elongation kinetics and termination control.
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Fator B de Elongação Transcricional Positiva , RNA Polimerase II , Humanos , Cromatina , Fator B de Elongação Transcricional Positiva/genética , Fator B de Elongação Transcricional Positiva/metabolismo , RNA Polimerase II/metabolismo , Splicing de RNA , Fatores de Processamento de RNA/genética , Transcrição Gênica , Fatores de Elongação da Transcrição/genética , Fatores de Elongação da Transcrição/metabolismoRESUMO
Potato common scab, an economically important disease worldwide, is caused by pathogenic Streptomyces strains mainly through the effects of thaxtomin. The cello-oligosaccharides binding protein CebE is proposed as a gateway to the pathogenic development of Streptomyces scabiei. In this study, two functional CebE encoding genes, GEO5601 and GEO7671, were identified in pathogenic Streptomyces sp. AMCC400023. With a higher binding affinity towards signal molecules, the deletion of GEO5601 severely impaired thaxtomin-producing capacity and reduced the strain's pathogenicity. Transcriptional analysis confirmed that CebE5601 is also responsible for the import and provision of carbon sources for cell growth. With lower binding affinity, the pathogenicity island (PAI)-localized CebE7671 may assume a new function of mediating the biological process of sporulation, given the significantly impaired formation of ΔGEO7671 spores. The mechanisms of action of CebE proteins unraveled in Streptomyces sp. AMCC400023 will help pave the way for more effective prevention of the potato common scab disease.
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Perfluoroalkyl ether carboxylic acids (PFECA) have emerged as novel alternatives to legacy per- and polyfluoroalkyl substances (PFAS). Existing research has revealed hepatoxicity induced by various PFAS, including PFECA. However, these studies have primarily focused on overall changes in whole liver tissue, particularly in hepatocytes, with the impact of PFAS on diverse liver non-parenchymal cells (NPCs) still inadequately understood. In the present study, we examined the heterogeneous responses of hepatic NPCs following exposure to perfluoro-3,5,7,9,11-pentaoxadodecanoic acid (PFO5DoDA), a type of PFECA, by administering PFO5DoDA (5 µg/L)-contaminated water to male mice for one year. Single-cell RNA sequencing (scRNA-seq) of 15 008 cells from the liver identified 10 distinct NPC populations. Notably, although relative liver weight remained largely unchanged following exposure to 5 µg/L PFO5DoDA, there was an observed increase in proliferating cells, indicating that proliferating NPCs may contribute to the hepatomegaly frequently noted in PFAS-exposed livers. There was also a considerable alteration in the composition of hepatic NPCs. Specifically, the total number of B cells decreased substantially, while many other cells, such as monocytes and macrophages, increased after PFO5DoDA exposure. In addition, interactions among the hepatic NPC populations changed variously after PFO5DoDA exposure. The findings emphasize the heterogeneity in the responses of hepatic NPCs to PFO5DoDA exposure. Taken together, the changes in immune cell populations and their intercellular interactions suggest that PFO5DoDA disrupts immune homeostasis in the liver. These findings offer new insights into the cellular mechanisms of PFAS-induced liver damage.
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Ácidos Alcanossulfônicos , Fluorocarbonos , Camundongos , Masculino , Animais , Hepatócitos , Fígado , Fluorocarbonos/toxicidade , Éteres , Ácidos Carboxílicos , Etil-Éteres , Análise de Sequência de RNARESUMO
Objectives: This study aimed to evaluate the effectiveness of radiomics analysis with R2* maps in predicting early recurrence (ER) in single hepatocellular carcinoma (HCC) following partial hepatectomy. Methods: We conducted a retrospective analysis involving 202 patients with surgically confirmed single HCC having undergone preoperative magnetic resonance imaging between 2018 and 2021 at two different institutions. 126 patients from Institution 1 were assigned to the training set, and 76 patients from Institution 2 were assigned to the validation set. A least absolute shrinkage and selection operator (LASSO) regularization was conducted to operate a logistic regression, then features were identified to construct a radiomic score (Rad-score). Uni- and multi-variable tests were used to assess the correlations of clinicopathological features and Rad-score with ER. We then established a combined model encompassing the optimal Rad-score and clinical-pathological risk factors. Additionally, we formulated and validated a predictive nomogram for predicting ER in HCC. The nomogram's discrimination, calibration, and clinical utility were thoroughly evaluated. Results: Multivariable logistic regression revealed the Rad-score, microvascular invasion (MVI), and α fetoprotein (AFP) level > 400 ng/mL as significant independent predictors of ER in HCC. We constructed a nomogram based on these significant factors. The areas under the receiver operator characteristic curve of the nomogram and precision-recall curve were 0.901 and 0.753, respectively, with an F1 score of 0.831 in the training set. These values in the validation set were 0.827, 0.659, and 0.808. Conclusion: The nomogram that integrates the radiomic score, MVI, and AFP demonstrates high predictive efficacy for estimating the risk of ER in HCC. It facilitates personalized risk classification and therapeutic decision-making for HCC patients.
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Horizontal gene transfer has been demonstrated to be an important driver for the emergency of multidrug-resistant pathogens. Recently, a transferable gene cluster tmexCD1-toprJ1 of the resistance-nodulation-division (RND) superfamily was identified in the plasmids of animal-derived Klebsiella pneumoniae strains, with a higher efflux capacity for various drugs than the Escherichia coli AcrAB-TolC homolog system. In this study, we focused on the differences in the inner membrane pump of these two systems and identified some key residues that contribute to the robust efflux activity of the TMexCD1 system. With the aid of homologous modeling and molecular docking, eight residues from the proximal binding pocket (PBP) and nine from the distal binding pocket (DBP) were selected and subjected to site-directed mutagenesis. Several of them, such as S134, I139, D181, and A290, were shown to be important for substrate binding in the DBP region, and all residues in PBP and DBP showed certain substrate preferences. Apart from the conservative switch loop (L613-623TMexD1) previously identified in the E. coli AcrB (EcAcrB), a relatively unconservative loop (L665-675TMexD1) at the bottom of PBP was proposed as a critical element for the robust activity of TMexD1, due to variations at sites E669, G670, N673, and S674 compared to EcAcrAB, and the significantly altered efflux activity due to their mutations. The conservation and flexibility of these key factors can contribute to the evolution of the RND efflux pumps and thus serve as potential targets for developing inhibitors to block the widespread of the TMexCD1 system.
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Proteínas de Escherichia coli , Escherichia coli , Animais , Escherichia coli/genética , Escherichia coli/metabolismo , Proteínas de Escherichia coli/metabolismo , Antibacterianos/química , Simulação de Acoplamento Molecular , Farmacorresistência Bacteriana Múltipla/genética , Proteínas Associadas à Resistência a Múltiplos Medicamentos/genética , Testes de Sensibilidade MicrobianaRESUMO
In our study, ammoniated hollow mesoporous silica nanoparticles (NH2-HMSN) with uniform diameter and stable structure were successively prepared via SiO2 core hard template method. Fourier transformed infrared spectroscopy revealed that amino group was effectively modified. Adsorption experiments showed that adsorption capacity of NH2-HMSN towards free fatty acids (FFAs) was superior to aminated mesopores or silica microspheres. Following through optimization of extraction conditions, FFAs from edible oil samples were successfully gathered by NH2-HMSN and showed favorable linearities (0.2-90 µg g-1), remarkably low limit of detections (0.03-0.15 nmol g-1), acceptable recoveries (85.08-96.82 %) and relatively accurate precisions (1.64-4.99 %). In comparison to existing adsorbent, NH2-HMSN could be successfully prepared via the chemical reaction of common raw materials under normal pressure and temperature. Furthermore, NH2-HMSN with hollow and mesoporous structure was more effective than the current adsorbents aimed at FFAs analysis in aspect of surface area and adsorption capacity.
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Neuropatia Hereditária Motora e Sensorial , Nanopartículas , Humanos , Ácidos Graxos não Esterificados , Dióxido de Silício/química , Nanopartículas/química , Espectroscopia de Infravermelho com Transformada de Fourier , AdsorçãoRESUMO
In order to avoid the time-consuming and laborious identification of tumor-specific antigens (TSAs) during the traditional vaccine fabrication process, a versatile photodynamic therapy (PDT)-based method is developed to construct a whole-tumor antigen tumor vaccine (TV) from surgically resected tumor tissues for personalized immunotherapy. Mucoadhesive nanoparticles containing small-molecular photosensitizer are fabricated and directly co-incubated with suspended tumor cells obtained after cytoreduction surgery. After irradiation with a 405 nm laser, potent immunogenic cell death of cancer cells could be induced. Along with the release of TSAs, the as-prepared TV could activate safe and robust tumor-specific immune responses, leading to efficient suppression of postsurgery tumor recurrence and metastasis. The as-prepared TV cannot only be applied alone through various administration routes but also synergize with immunoadjuvant, chemotherapeutics, and immune checkpoint blockers to exert more potent immune responses. This work provides an alternative way to promote the clinical translation of PDT, which is generally restricted by the limited penetration of light. Moreover, the versatile strategy of vaccine fabrication also facilitates the clinical application of personalized whole-cell tumor vaccines.
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Vacinas Anticâncer , Metástase Neoplásica , Fotoquimioterapia , Fotoquimioterapia/métodos , Vacinas Anticâncer/uso terapêutico , Animais , Humanos , Medicina de Precisão/métodos , Linhagem Celular Tumoral , Recidiva Local de Neoplasia/prevenção & controle , Fármacos Fotossensibilizantes/uso terapêutico , Fármacos Fotossensibilizantes/farmacologia , Fármacos Fotossensibilizantes/química , Camundongos , Nanopartículas/química , Antígenos de Neoplasias/imunologia , Imunoterapia/métodos , FemininoRESUMO
Gastric cancer (GC) is a rising global health issue, with increasing incidence and mortality rates. The pathogenesis of GC is highly complex and involves a combination of genetic and environmental factors. Therefore, identifying new genes and pathways that contribute to the development and progression of GC is essential for improving diagnosis and treatment outcomes. Long noncoding RNAs (lncRNAs) have recently emerged as a promising area of research in understanding the molecular mechanisms underlying various cancers, including GC. These RNA molecules are longer than 200 nucleotides and do not code proteins. Although initially considered "junk DNA", lncRNAs have been demonstrated to play significant roles in various biological processes, including cell proliferation, differentiation, and apoptosis, as well as in the pathogenesis of various cancers. In this study, we screened clinical specimens for a novel lncRNA, LINC00853, which showed high expression in GC tissues and promoted the proliferation, migration, and invasion of GC cells. Furthermore, in vivo experiments confirmed its ability to facilitate the growth and metastasis of GC. These results suggest that LINC00853 plays a crucial role in the development and progression of GC.
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RNA Longo não Codificante , Neoplasias Gástricas , Humanos , Neoplasias Gástricas/patologia , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , Transformação Celular Neoplásica/genética , Proliferação de Células/genética , Linhagem Celular Tumoral , Regulação Neoplásica da Expressão Gênica/genética , Movimento Celular/genéticaRESUMO
BACKGROUND: Colorectal cancer (CRC) is a major cause of cancer-related deaths worldwide, and chemoresistance is a major obstacle in its treatment. Despite advances in therapy, the molecular mechanism underlying chemoresistance in CRC is not fully understood. Recent studies have implicated the key roles of long noncoding RNAs (lncRNAs) in the regulation of CRC chemoresistance. METHODS: In this study, we investigated the role of the lncRNA LINC01852 in CRC chemoresistance. LINC01852 expression was evaluated in multiple CRC cohorts using quantitative reverse transcription PCR. We conducted in vitro and in vivo functional experiments using cell culture and mouse models. RNA pull-down, RNA immunoprecipitation, chromatin immunoprecipitation, and dual luciferase assays were used to investigate the molecular mechanism of LINC01852 in CRC. RESULTS: Our findings revealed that a lncRNA with tumor-inhibiting properties, LINC01852, was downregulated in CRC and inhibited cell proliferation and chemoresistance both in vitro and in vivo. Further mechanistic investigations revealed that LINC01852 increases TRIM72-mediated ubiquitination and degradation of SRSF5, inhibiting SRSF5-mediated alternative splicing of PKM and thereby decreasing the production of PKM2. Overexpression of LINC01852 induces a metabolic switch from aerobic glycolysis to oxidative phosphorylation, which attenuates the chemoresistance of CRC cells by inhibiting PKM2-mediated glycolysis. CONCLUSIONS: Our results demonstrate that LINC01852 plays an important role in repressing CRC malignancy and chemoresistance by regulating SRSF5-mediated alternative splicing of PKM, and that targeting the LINC01852/TRIM72/SRSF5/PKM2 signaling axis may represent a potential therapeutic strategy for CRC.
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Neoplasias Colorretais , RNA Longo não Codificante , Animais , Camundongos , Humanos , Processamento Alternativo , Resistencia a Medicamentos Antineoplásicos , Carcinogênese , Transformação Celular Neoplásica , Imunoprecipitação da CromatinaRESUMO
Phototherapy and sonodynamic therapy (SDT) are widely used for the synergistic treatment of tumors and have received considerable attention. However, an inappropriate tumor microenvironment, including pH, H2O2, oxygen, and glutathione levels, can reduce the therapeutic effects of synergistic phototherapy and SDT. Here, a novel Bi-based soluble microneedle (MN) is designed for the CT imaging of breast tumors and starvation therapy/gas therapy-enhanced phototherapy/SDT. The optimized Bi/BiVO4 Schottky heterojunction serves as the tip of the MN, which not only has excellent photothermal conversion ability and CT contrast properties, but its heterojunction can also avoid the rapid combination of electrons and hole pairs, thereby enhancing the photodynamic/sonodynamic effects. A degradable MN with excellent mechanical properties is fabricated by optimizing the ratios of poly(vinyl alcohol), poly(vinyl pyrrolidone), and sodium hyaluronate. Glucose oxidase (GOx) and diallyl trisulfide are loaded into the MN to achieve tumor starvation and gas therapy, respectively; And the controlled release of GOx and H2S can be achieved under ultrasound or near-infrared laser irradiation. The in vitro and in vivo results demonstrate that this multifunctional MN can achieve high therapeutic efficacy through starvation therapy/gas therapy-enhanced phototherapy/SDT. The designed multifunctional MN provides a prospective approach for synergistic phototherapy and SDT.
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Nanopartículas , Neoplasias , Humanos , Peróxido de Hidrogênio , Linhagem Celular Tumoral , Neoplasias/patologia , Fototerapia/métodos , Raios Infravermelhos , Tomografia Computadorizada por Raios X , Nanopartículas/química , Microambiente TumoralRESUMO
BACKGROUND: Periodontitis is one of the most common chronic oral inflammatory diseases. Over the past decade, herpes viruses, particularly Epstein-Barr virus (EBV), have been considered promising pathogenic candidates for periodontitis. However, the specific mechanism by which EBV contributes to the development of periodontitis is still unknown. This study aimed to explore the mechanism of EBV underlying the inflammatory response in human gingival fibroblasts (HGFs). MATERIALS AND METHODS: HGFs were stimulated with different concentrations of EBV (104, 105, 106, 107, and 108 DNA copies/mL) for 0, 8, 24, or 48 hours. The mRNA levels of interleukin (IL)-1ß, tumour necrosis factor-α (TNF-α), IL-8, monocyte chemoattractant protein-1 (MCP-1), and Toll-like receptor 9 (TLR9) were measured using quantitative real-time polymerase chain reaction (PCR). Enzyme-linked immunosorbent assays (ELISAs) were performed for determining the mRNA and protein levels of IL-1ß, TNF-α, IL-8, and MCP-1. Real-time PCR and ELISA were performed to determine the protein levels of IL-1ß, TNF-α, IL-8, and MCP-1. Activation of the TLR9/myeloid differentiation factor 88 (MyD88)/nuclear factor kappa B (NF-κB) pathway was evaluated using western blotting. RESULTS: The expressions of IL-1ß, TNF-α, IL-8, and MCP-1 were significantly upregulated in HGFs under EBV stimulation in a concentration- and time-dependent manner. EBV promoted TLR9 and MyD88 expression and induced NF-κB transcription. On the contrary, the upregulation of these factors and the activation of NF-κB pathway were drastically inhibited by TLR9 antagonists. CONCLUSIONS: Our findings demonstrate that EBV promotes the production of inflammatory cytokines IL-1ß and TNF-α and chemokines IL-8 and MCP-1 in HGFs through the TLR9/MyD88/NF-κB pathway.
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Quimiocina CCL2 , Citocinas , Fibroblastos , Gengiva , Herpesvirus Humano 4 , Interleucina-1beta , Receptor Toll-Like 9 , Humanos , Fibroblastos/virologia , Fibroblastos/metabolismo , Gengiva/virologia , Gengiva/citologia , Citocinas/metabolismo , Receptor Toll-Like 9/metabolismo , Quimiocina CCL2/metabolismo , Interleucina-1beta/metabolismo , Fator 88 de Diferenciação Mieloide/metabolismo , Fator de Necrose Tumoral alfa/metabolismo , NF-kappa B/metabolismo , Reação em Cadeia da Polimerase em Tempo Real , Células Cultivadas , Ensaio de Imunoadsorção Enzimática , RNA Mensageiro/metabolismo , Interleucina-8/metabolismo , Periodontite/virologia , Periodontite/metabolismoRESUMO
Nervonic acid benefits the treatment of neurological diseases and the health of brain. In this study, we employed the oleaginous yeast Yarrowia lipolytica to overproduce nervonic acid oil by systematic metabolic engineering. First, the production of nervonic acid was dramatically improved by iterative expression of the genes ecoding ß-ketoacyl-CoA synthase CgKCS, fatty acid elongase gELOVL6 and desaturase MaOLE2. Second, the biosynthesis of both nervonic acid and lipids were further enhanced by expression of glycerol-3-phosphate acyltransferases and diacylglycerol acyltransferases from Malania oleifera in endoplasmic reticulum (ER). Third, overexpression of a newly identified ER structure regulator gene YlINO2 led to a 39.3% increase in lipid production. Fourth, disruption of the AMP-activated S/T protein kinase gene SNF1 increased the ratio of nervonic acid to lignoceric acid by 61.6%. Next, pilot-scale fermentation using the strain YLNA9 exhibited a lipid titer of 96.7 g/L and a nervonic acid titer of 17.3 g/L (17.9% of total fatty acids), the highest reported titer to date. Finally, a proof-of-concept purification and separation of nervonic acid were performed and the purity of it reached 98.7%. This study suggested that oleaginous yeasts are attractive hosts for the cost-efficient production of nervonic acid and possibly other very long-chain fatty acids (VLCFAs).
Assuntos
Yarrowia , Yarrowia/genética , Engenharia Metabólica , Ácidos Graxos/metabolismo , Aciltransferases/metabolismoRESUMO
Nicotine and its major metabolite cotinine are widely used as markers of tobacco smoke abstinence as well as indicators of active smoking levels and the assessment of passive inhalation of tobacco smoke in nonsmokers. Therefore, using an easy-to-prepare sensing platform that can provide a rapid, highly sensitive response for the simultaneous detection of salivary nicotine levels and urinary cotinine levels is especially crucial for helping heavy cigarette smokers quit smoking and protecting public health. Hydrogen-bonded organic frameworks, as a novel class of porous crystalline materials, show immense potential for functional modification and optical sensing. Herein, a new HOF was prepared by a simple solvent evaporation method, and a dual-emitting material Eu(bpy)@HOF-215(1) was obtained by the postsynthetic modification of HOF by lanthanide luminescent complexes, which maintains favorable structural stability and introduces the characteristic emitting of Eu, allowing use as a ratiometric fluorescent sensor for salivary nicotine and urinary cotinine, with a limit of detection of nicotine of 0.045 µM in saliva and a limit of detection of cotinine of 0.591 µM in urine. Furthermore, luminescent inks based on HOF-215 have been fabricated based on the photoresponse variations of 1 to NIC and COT, which enables the multilevel encryption and decryption of information, in a dynamic and recyclable process. This work not only synthesizes a novel blue HOF but also provides a representative successful case of a dual-function platform for simultaneous application to ratiometric sensing and dynamic anticounterfeiting.