RESUMO

Fluoride ions (F-) are one of the essential trace elements for the human body and are widely existed in nature. In this study, we present a novel fluorescent probe (YF-SZ-F) designed and synthesized for the specific detection of F-. The probe exhibits high sensitivity, excellent selectivity, and low cytotoxicity, making it a promising tool for biomedical applications. Imaging experiments conducted on zebrafish and Arabidopsis roots demonstrate the probe's remarkable cellular permeability and biocompatibility, laying a solid foundation for its potential biomedical utility. Furthermore, the probe holds potential for practical applications in environmental monitoring and public health through its capability to detect fluoride ions in water samples and via mobile phone software. This multifaceted functionality underscores the broad applicability and significance of the fluorescent probe, not only in scientific research but also in real-world scenarios, contributing to the development of more convenient and precise methods for fluoride detection.

Assuntos

Benzotiazóis , Corantes Fluorescentes , Fluoretos , Peixe-Zebra , Corantes Fluorescentes/química , Corantes Fluorescentes/síntese química , Fluoretos/análise , Animais , Benzotiazóis/química , Humanos , Arabidopsis/química , Espectrometria de Fluorescência/métodos , Imagem Óptica

RESUMO

Yeast two-hybrid (YTH) technology is a powerful tool for studying protein interactions and has been widely used in various fields of molecular biology, including the study of antiviral innate immunity. This chapter presents detailed information and experimental procedures for identifying virus-host protein interactions involved in immune regulation using yeast two-hybrid technology.

Assuntos

Interações Hospedeiro-Patógeno , Imunidade Inata , Técnicas do Sistema de Duplo-Híbrido , Humanos , Interações Hospedeiro-Patógeno/imunologia , Proteínas Virais/imunologia , Proteínas Virais/metabolismo , Saccharomyces cerevisiae/imunologia , Saccharomyces cerevisiae/genética , Ligação Proteica , Mapeamento de Interação de Proteínas/métodos

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While rivers as primary conduits for land-based plastic particles transferring to their "ultimate" destination, the ocean, have garnered increasing attention, research on microplastic pollution at the scale of whole large river basins remains limited. Here we conducted a large-scale investigation of microplastic contamination in water and sediment of the world's third-largest river, the Yangtze River. We found concentrations of microplastics in water and sediment to be 5.13 items/L and 113.9 items/kg (dry weight), respectively. Moreover, microplastic pollution levels exhibited a clear decreasing trend from upstream to downstream. The detected microplastics were predominantly transparent in color, with fibrous shapes predominating, sizes mainly concentrated below 1 mm and composed primarily of PP and PE polymers. Our analysis results indicated that compared to geographical and water quality parameters, anthropogenic factors primarily determined the spatial distribution pattern of microplastics. Moreover, the microplastic abundance in sediment upstream of the dam was significantly higher than that in the downstream sediment, while the trend of microplastic concentrations in water was opposite. Therefore, more effort is needed to monitor microplastic contamination and their ecological environmental effects of sediment before dams in future research.

RESUMO

BACKGROUND AND OBJECTIVE: This study focuses on investigating the role of CDKN1A in cisplatin-induced AKI ( acute kidney injury, AKI) and its potential as a biomarker for early diagnosis and therapeutic intervention by integrating bioinformatics analysis, machine learning, and experimental validation. METHODS: We analyzed the GSE85957 dataset to find genes that changed between control and cisplatin-treated rats. Using bioinformatics and machine learning, we found 13 important genes related to ferroptosis and the P53 pathway. The key gene, CDKN1A, was identified using various algorithms. We then tested how reducing CDKN1A in human kidney cells affected cell health, ROS, and iron levels. We also checked how CDKN1A changes the levels of proteins linked to ferroptosis using Q-PCR and Western Blot. RESULTS: CDKN1A was found to negatively regulate the G1/S phase transition and was associated with ferroptosis in p53 signaling. Experiments in human renal tubular epithelial cells (HK-2) and rat NRK-52E cells showed that CDKN1A knockdown mitigated cisplatin-induced cell injury by reducing oxidative stress and ferroptosis. CONCLUSION: Our integrated approach identified CDKN1A as a biomarker for cisplatin-induced AKI. Its regulation could be key in AKI pathogenesis, offering new therapeutic insights and aiding in early diagnosis and intervention.

RESUMO

The severe mismatch between solid bioelectronics and dynamic biological tissues has posed enduring challenges in the biomonitoring community. Here, we developed a reconfigurable liquid cardiac sensor capable of adapting to dynamic biological tissues, facilitating ambulatory cardiac monitoring unhindered by motion artifacts or interference from other biological activities. We employed an ultrahigh-resolution 3D scanning technique to capture tomographic images of the skin on the wrist. Then, we established a theoretical model to gain a deep understanding of the intricate interaction between our reconfigurable sensor and dynamic biological tissues. To properly elucidate the advantages of this sensor, we conducted cardiac monitoring alongside benchmarks such as the electrocardiogram. The liquid cardiac sensor was demonstrated to produce stable signals of high quality (23.1 dB) in ambulatory settings.

Assuntos

Monitorização Ambulatorial , Humanos , Monitorização Ambulatorial/instrumentação , Monitorização Ambulatorial/métodos , Eletrocardiografia/instrumentação , Eletrocardiografia/métodos , Desenho de Equipamento , Punho , Técnicas Biossensoriais/instrumentação , Técnicas Biossensoriais/métodos , Pele , Dispositivos Eletrônicos Vestíveis , Imageamento Tridimensional/instrumentação , Coração/fisiologia , Coração/diagnóstico por imagem

RESUMO

Wearable thermoelectric generators provide a reliable power generation method for self-powered wearable electronic devices. However, there has been a lack of research regarding the comfort of wearable thermoelectric generators. Here we propose a design for a comfortable wearable thermoelectric generators system with high output power based on sandwiched thermoelectric model. This model paves the way for simultaneously optimizing comfort (skin temperature and pressure perception) and output power by systematically considering a variety of thermal resistive environments and bending states, the properties of the thermoelectric and encapsulation materials, and the device structure. To verify this strategy, we fabricate wearable thermoelectric generators using Mg-based thermoelectric materials. These materials have great potential for replacing traditional Bi2Te3-based materials and enable our wearable thermoelectric generators with a power density of 18.4 µWcm-2 under a wearing pressure of 0.8 kPa and with a skin temperature of 33 °C, ensuring the wearer's comfort.

RESUMO

Yoga is effective in binge eating disorder (BED) treatment, but it does not seem effective enough to improve low physical fitness. In contrast, high-intensity interval training (HIIT) is effective in improving physical fitness but has never been studied in the context of BED. In the study, 47 young inactive females with mild to moderate BED were recruited and randomly assigned to a HIIT group (HIIT), a Yoga group (YG), or a control group (CG; age, 19.47 ± 0.74, 19.69 ± 0.874, and 19.44 ± 0.63 years; BMI, 21.07 ± 1.66, 21.95 ± 2.67, and 20.68 ± 2.61 kg/m2, respectively). The intervention groups participated in 8-week specific exercises, while the CG maintained their usual daily activity. Before and after the training, participants were evaluated for BED using the binge eating scale (BES) and for physical fitness. The obtained data were compared within groups and between groups, and a correlation analysis between BES and physical fitness parameters was performed. After the training, the YG presented significant improvements in BES (- 20.25%, p = 0.006, ηp2 = 0.408), fat mass (FM, - 3.13%, p = 0.033, ηp2 = 0.269), and maximal oxygen consumption (VO2max, 11.51%, p = 0.000, ηp2 = 0.601), whereas the HIIT showed significant improvements in body weight (BW, - 1.78%, p = 0.006, ηp2 = 0.433), FM (- 3.94%, p = 0.033, ηp2 = 0.285), and BMI (- 1.80%, p = 0.006, ηp2 = 0.428), but not in BES. Comparisons between groups revealed that both HIIT and YG had significantly higher VO2max levels than CG (HIIT 12.82%, p = 0.006, ηp2 = 0.088; YG: 11.90%, p = 0.009, ηp2 = 0.088) with no difference between HIIT and YG. Additionally, YG presented significantly lower BES than both HIIT (15.45%, p = 0.02, ηp2 = 0.03) and CG (11.91%, p = 0.022, ηp2 = 0.03). In conclusion, Yoga is an effective treatment for BED, but HIIT is not, despite its high efficacy in improving physical fitness.

Assuntos

Treinamento Intervalado de Alta Intensidade , Aptidão Física , Yoga , Humanos , Feminino , Aptidão Física/fisiologia , Treinamento Intervalado de Alta Intensidade/métodos , Adulto Jovem , Transtorno da Compulsão Alimentar/terapia , Adulto , Adolescente , Comportamento Sedentário , Índice de Massa Corporal , Bulimia/terapia , Bulimia/fisiopatologia

RESUMO

Background: Calvatia gigantea (CG) is widely used as a traditional Chinese medicine for wound treatment. In this study, we aimed to determine the effects of CG extract (CGE) on diabetic wound healing and the commensal wound microbiome. Method: A wound model was established using leptin receptor-deficient db/db mice, with untreated mice as the control group and CGE-treated mice as the treatment group. The wound healing rate, inflammation and histology were analyzed. Additionally, wound microbiome was evaluated via 16S ribosomal RNA (rRNA) gene sequencing. Results: CGE significantly accelerated the healing of diabetic ulcer wounds, facilitated re-epithelialization, and downregulated the transcription levels of the inflammatory cytokines, interleukin-1ß and tumor necrosis factor-α. Furthermore, CGE treatment positively affected the wound microbiome, promoting diversity of the microbial community and enrichment of Escherichia-Shigella bacteria in the CGE-treated group. Conclusions: Overall, CGE enhanced diabetic wound healing by modulating the wound microbiome and facilitating macrophage polarization during inflammation. These findings suggest modulation of the commensal wound microbiome using medicinal plants as a potential therapeutic strategy for diabetic wounds.

RESUMO

Maturity and drying treatment are important factors affecting the processing characteristics of lotus seeds and its starch. This study aimed to investigate the effect of maturity (from low to high-M-1, M-2, M-3, M-4) on far-infrared drying kinetics of lotus seeds, and on the variation of structure, gelation and digestive properties of lotus seed starch (LSS) before and after drying. As the maturity increased, the drying time reduced from 5.8 to 1.0 h. The reduction of drying time was correlated with the decrease of initial moisture content, the increase of water freedom and the destruction of tissue structure during ripening. The increased maturity and drying process altered the multiscale structure of LSS, including an increase in amylose content, disruption of the short-range structure, and a decrease in relative crystallinity and molecular weight. The viscosity, pasting temperature and enthalpy of LSS decreased during ripening, and drying treatment caused the further decrease. The digestibility of LSS increased during ripening and drying. Lotus seeds at M-4 would be optimal for obtaining shorter drying time, lower pasting temperature and enthalpy, and higher digestibility. This study provided theoretical guidance for achieving effective drying process and screening LSS with suitable processing properties through maturity sorting.

Assuntos

Lotus , Sementes , Amido , Sementes/química , Lotus/química , Amido/química , Dessecação/métodos , Viscosidade , Amilose/química , Peso Molecular , Digestão , Géis/química , Água/química , Temperatura , Estrutura Molecular

RESUMO

BACKGROUND: Research studies on gastric cancer have not investigated the combined impact of body composition, age, and tumor staging on gastric cancer prognosis. To address this gap, we used machine learning methods to develop reliable prediction models for gastric cancer. METHODS: This study included 1,132 gastric cancer patients, with preoperative body composition and clinical parameters recorded, analyzed using Cox regression and machine learning models. RESULTS: The multivariate analysis revealed that several factors were associated with recurrence-free survival (RFS) and overall survival (OS) in gastric cancer. These factors included age (≥65 years), tumor-node-metastasis (TNM) staging, low muscle attenuation (MA), low skeletal muscle index (SMI), and low visceral to subcutaneous adipose tissue area ratios (VSR). The decision tree analysis for RFS identified six subgroups, with the TNM staging I, II combined with high MA subgroup showing the most favorable prognosis and the TNM staging III combined with low MA subgroup exhibiting the poorest prognosis. For OS, the decision tree analysis identified seven subgroups, with the subgroup featuring high MA combined with TNM staging I, II showing the best prognosis and the subgroup with low MA, TNM staging II, III, low SMI, and age ≥65 years associated with the worst prognosis. CONCLUSION: Cox regression identified key factors associated with gastric cancer prognosis, and decision tree analysis determined prognoses across different risk factor subgroups. Our study highlights that the combined use of these methods can enhance intervention planning and clinical decision-making in gastric cancer.

RESUMO

Antibiotics are widely used in the breeding production of Bamei pigs, affecting the quality and safety of pork and causing enormous harm to human health, the environment, and public health. The use of probiotic fermented feed to replace antibiotic feed is one of the solutions, which has the potential to improve the intestinal microbiota, promote animal growth, and enhance immunity. The purpose of this study was to evaluate the effect of fermented feed with Lactiplantibacillus (L.) plantarum QP28-1a or Bacillus (B.) subtilis QB8a on feed, growth performance, gut microbiota, and immunity of weaned piglets. A total of 60 freshly weaned piglets from the Tibetan Plateau were randomly divided into five groups and fed basal feed, L. plantarum fermented feed, B. subtilis fermented feed, mixed fermented feed, and antibiotic fermented feed for 60 days, respectively. The results showed fermented feed supplemented with L. plantarum QP28-1a or B. subtilis QB8a significantly lowered the pH of the feed (P < 0.05), produced lactic acid and acetic acid, inhibited the growth of harmful bacteria in the feed, and reduced the feed conversion rate in the group fed mixed fermented feed (P < 0.05). The fermented feed increased the α-diversity and prominently altered the ß-diversity of the intestinal microbiota, increasing the relative abundance of beneficial bacteria such as Lactobacillus and Turicibacter and decreasing the relative abundance of conditional pathogens such as Streptococcus and Clostridium, improving the intestinal microbiota of the Bamei piglets. Notably, the mixed fermented feed improved the immunity of Bamei piglets by modulating the production of pro-inflammatory cytokines, anti-inflammatory cytokines, and inflammatory-related signaling pathways. Spearman's correlation analysis revealed that the increased expression of immune-related cytokines may be associated with a significant enrichment of Lactobacillus, Prevotellaceae, Erysipelotrichaceae, and Ruminococcaceae in the gut. In conclusion, the probiotic fermented feed maintained an acidic environment conducive to suppressing pathogens, reduced the feed conversion ratio, optimized the intestinal microbiota, improved immunity, and alleviated intestinal inflammation that may be caused by weaning, demonstrating the excellent application prospects of L. plantarum QP28-1a and B. subtilis QB8a fermented feed in the feeding of Bamei piglets.

RESUMO

Extremity soft tissue sarcoma (ESTS) is a rare malignant nonepithelial disease, calling for combined modality treatments with surgery to further improve local control rates and long-term survival, especially in patients with multiple local recurrences with or without risk of amputation. In this double-arm, open-label, Phase II clinical trial, we will enroll 30 patients with pathologically confirmed ESTS without nodal involvement or distant metastases. Patients are randomly assigned to the combination treatment group or the radiation monotherapy group. Additionally, tumor and biological samples will be obtained directly before and after neoadjuvant therapy, allowing for studies of immune response and primary drug resistance mechanisms.Clinical Trial Registration: ChiCTR2200060659 (http://www.chictr.org.cn) (ClinicalTrials.gov).

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[Box: see text].

RESUMO

Upon the pressure of conventional land agriculture and marine environment facing the future of human beings, the emerging of alternative proteins represented by cultured meat is expected with a breakthrough of efficient, safe and sustainable production. However, the cell proliferation efficiency and final myofiber density in current animal-derived scaffolds are still limited. Here, we incorporated five plant-derived edible polymeric glucosyl nanoparticles (GNPs) into gelatin/alginate hydrogels to spontaneously form nanoaggregates where nanotopographies were observed inside. The nanoscale topological morphology significantly enhances the adhesion and proliferation efficiencies of piscine satellite cells (PSCs) in the tailored extracellular matrix of as-prepared scaffold. Physically, the presence of GNP-induced nanoaggregate increases the interaction between ITG-A1 (membrane protein of PSCs) and hydrogel microenvironment, which activates the focal adhesion-integrin-cytoskeleton mechanotransduction signaling to promote cell proliferation. With a controlled diameter of hydrogel filament, these inner topological GNP nanoaggregates can also improve the density, alignment and differentiation efficiency of PSCs. When cultured in vitro for 15 days, the cell density, size and orientation of muscle fibers in the GNP-stimulated cultured fish fillet are very similar to the total cell mass in native fish muscle tissue.

RESUMO

BACKGROUND: The objectives of this study were twofold: (1) to compare gait characteristics between cerebral small vessel disease (CSVD) patients with low-risk oral frailty (OF) and high-risk OF, particularly during dual-task walking (DTW); (2) to investigate the association of OF, the gait characteristics of DTW, and falls among older adults patients with CSVD. METHODS: A total of 126 hospitalized patients diagnosed with CSVD were recruited and classified into a low-risk group (n = 90) and a high-risk group (n = 36) based on OF status in our study. Comprehensive data pertaining to basic parameters (cadence, as well as stride time, velocity and length), variability, asymmetry, and coordination were gathered during both single-task walking (STW) and DTW. Additionally, the number of falls was calculated. Subsequently, t-test or chi-squared test was used for comparison between the two groups. Furthermore, linear regression analysis was employed to elucidate the association of the OF index-8 score and gait parameters during cognitive DTW. Also, logistic regression models were utilized to assess the independent association of OF risk and falls. RESULTS: During cognitive DTW, the high-risk group demonstrated inferior performance in terms of basic parameters (p < 0.01), coefficient of variation (CV) of velocity and stride length (p < 0.05), as well as phase coordination index (PCI) when compared with the low-risk group (p < 0.05). Notably, differences in basic gait parameters were observed in cognitive DTW and STW conditions between the two groups (p < 0.01). However, only the high-risk group evinced significant variations in CV and PCI during cognitive DTW, as opposed to those during STW (p < 0.05). Furthermore, our findings also revealed the association of OF, the gait characteristics of cognitive DTW, (p < 0.01) and falls (p < 0.05). CONCLUSION: CSVD patients with a high risk of OF need to pay more attention to their gait variability or coordination. Also, they are recommended to undergo training involving dual-task activities while walking in daily life, thereby reducing the deterioration and mitigating the risk of falls. Besides, this study has confirmed an association of OF and DTW gait as well as falls in patients with CSVD.

Assuntos

Doenças de Pequenos Vasos Cerebrais , Fragilidade , Marcha , Humanos , Masculino , Doenças de Pequenos Vasos Cerebrais/complicações , Doenças de Pequenos Vasos Cerebrais/epidemiologia , Doenças de Pequenos Vasos Cerebrais/fisiopatologia , Feminino , Idoso , Fragilidade/epidemiologia , Fragilidade/fisiopatologia , Marcha/fisiologia , Acidentes por Quedas/estatística & dados numéricos , Pessoa de Meia-Idade , Idoso de 80 Anos ou mais , Transtornos Neurológicos da Marcha/fisiopatologia , Transtornos Neurológicos da Marcha/epidemiologia , Transtornos Neurológicos da Marcha/etiologia , Caminhada/fisiologia

RESUMO

BACKGROUND: Sialylation in uterine corpus endometrial carcinoma (UCEC) differs significantly from apoptotic and ferroptosis pathways. It plays a crucial role in cancer progression and immune response modulation. Exploring how sialylation affects tumor behavior and its link with long non-coding RNAs (lncRNAs) may provide new insights into UCEC prognosis and treatment. METHODS: We obtained RNA transcriptome, clinical, and mutation data of UCEC samples from the TCGA database. Our approach involved developing a risk model based on the co-expression patterns of sialylation genes and lncRNAs. Prognostic lncRNAs were identified through Cox regression and further refined using LASSO analysis. To understand the biological functions and pathways of model-associated differentially expressed genes (MADEGs), we conducted enrichment analyses. We also assessed the immune infiltration status of MADEGs using eight different algorithms, which helped in evaluating the potential for immunotherapy. Additionally, we validated the expression of these lncRNAs in UCEC using cell lines and clinical samples. RESULTS: We developed a UCEC risk model using five sialylation-related lncRNAs (AC004884.2, AC026202.2, LINC01579, LINC00942, SLC16A1-AS1). This model, confirmed through Cox analysis and clinical evaluation, effectively predicted patient outcomes. Survival data analysis across entire cohort, as well as within training and test groups, indicated better survival in low-risk UCEC patients. Enrichment analyses linked MADEGs to sialylation functions and cancer pathways. High-risk patients showed increased responsiveness to immune checkpoint inhibitors (ICIs), as indicated by immunological assessments. Subgroup C2 patients showed superior outcomes and a robust response to immunotherapy and chemotherapy. Notably, LINC01579, LINC00942, and SLC16A1-AS1 were significantly overexpressed in UCEC clinical tumor samples as well as in Ishikawa and HEC-1-B cell lines, compared to the normal groups. CONCLUSIONS: This lncRNA signature associated with sialylation could guide prognosis, enhance the understanding of molecular mechanisms, and inform treatment strategies in UCEC. It highlights the potential for the use of ICIs and chemotherapy.

RESUMO

Background: Ventricular septal defect (VSD) is one of the most common congenital heart diseases. This study aims to evaluate the clinical value and benefit of transesophageal echocardiography (TEE) in transthoracic minimally invasive closure of VSDs using a completely biodegradable occluders, summarize the main points of surgical procedures, and analyze the follow-up results of short-term and medium-term treatment. Methods: We conducted a retrospective analysis of 24 pediatric cases of VSD, successfully treated with TEE-guided minimally invasive closure using fully biodegradable occluders between June 2019 and June 2022. The preoperative TEE meticulously examined the defect's location, size, and surrounding anatomical relationships, aiding in the selection of appropriate occluders and guiding the entire closure process. All patients were followed up for 1 year. Results: In our cohort, 13 cases were perimembranous inlet VSDs, and 11 involved VSDs with membranous aneurysm formation. The effective shunt size of VSD measured by TEE preoperatively ranged from 2.8 to 4.9 mm, with the defect located 2-6 mm from the aortic valve. Occluders used were 6-8 mm in diameter. All 24 procedures were successful. TEE confirmed that the occluders were tightly fitted at the edges of the VSDs. Twenty-three cases had no residual shunt post-surgery, while one case exhibited a small left-to-right shunt (<1.5 mm) at the occluder's edge. Follow-up was conducted on postoperative day 3, and in months 1, 3, 6, and 12, showing that the occluder's position remained normal in all patients. Except for one child who had a 1.2 mm left-to-right shunt at the edge of the occluder, no residual shunts were observed in the others. The occluder started to degrade from month 6, and the sizes of the left and right occluder discs were significantly smaller compared to those on postoperative day 3 (P=0.003). Conclusions: TEE-guided minimally invasive VSD occlusion using fully biodegradable occluders has the advantages of minimal trauma, high safety, and few complications, with satisfactory recent efficacy, and good prospects for clinical safety applications.

RESUMO

Engineering the glycerol-3-phosphate pathway could enhance erythritol production by accelerating glycerol uptake. However, little work has been conducted on the alternative dihydroxyacetone (DHA) pathway in Yarrowia lipolytica. Herein, this route was identified and characterized in Y. lipolytica by metabolomic and transcriptomic analysis. Moreover, the reaction catalyzed by dihydroxyacetone kinase encoded by dak2 was identified as the rate-limiting step. By combining NHEJ-mediated insertion mutagenesis with a push-and-pull strategy, Y. lipolytica strains with high-yield erythritol synthesis from glycerol were obtained. Screening of a library of insertion mutants allows the identification of a mutant with fourfold increased erythritol production. Overexpression of DAK2 and glycerol dehydrogenase GCY3 together with gene encoding transketolase and transaldolase from the nonoxidative part of the pentose phosphate pathway led to a strain with further increased productivity with a titer of 53.1 g/L and a yield 0.56 g/g glycerol, which were 8.1- and 4.2-fold of starting strain.

RESUMO

Osimertinib is a third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (EGFR-TKI) approved for patients with EGFR T790M resistance mutations as first- or second-line treatment of EGFR-positive patients. Resistance to Osimertinib will inevitably develop, and the underlying mechanisms are largely unknown. In this study, we discovered that acquired resistance to Osimertinib is associated with abnormal DNA damage response (DDR) in lung adenocarcinoma cells. We discovered that the polycomb protein Lethal(3) Malignant Brain Tumor-Like Protein 1 (L3MBTL1) regulates chromatin structure, thereby contributing to DDR and Osimertinib resistance. EGFR oncogene inhibition reduced L3MBTL1 ubiquitination while stabilizing its expression in Osimertinib-resistant cells. L3MBTL1 reduction and treatment with Osimertinib significantly inhibited DDR and proliferation of Osimertinib-resistant lung cancer cells in vitro and in vivo. L3MBTL1 binds throughout the genome and plays an important role in EGFR-TKI resistance. It also competes with 53BP1 for H4K20Me2 and inhibits the development of drug resistance in Osimertinib-resistant lung cancer cells in vitro and in vivo. Our findings suggest that L3MBTL1 inhibition is a novel approach to overcoming EGFR-TKI-acquired resistance.

Assuntos

Acrilamidas , Adenocarcinoma de Pulmão , Compostos de Anilina , Dano ao DNA , Resistencia a Medicamentos Antineoplásicos , Epigênese Genética , Receptores ErbB , Neoplasias Pulmonares , Humanos , Acrilamidas/farmacologia , Resistencia a Medicamentos Antineoplásicos/genética , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Compostos de Anilina/farmacologia , Compostos de Anilina/uso terapêutico , Adenocarcinoma de Pulmão/genética , Adenocarcinoma de Pulmão/tratamento farmacológico , Adenocarcinoma de Pulmão/patologia , Adenocarcinoma de Pulmão/metabolismo , Dano ao DNA/efeitos dos fármacos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/metabolismo , Epigênese Genética/efeitos dos fármacos , Animais , Linhagem Celular Tumoral , Receptores ErbB/metabolismo , Receptores ErbB/genética , Camundongos , Proteínas do Grupo Polycomb/metabolismo , Proteínas do Grupo Polycomb/genética , Camundongos Nus , Proteína 1 de Ligação à Proteína Supressora de Tumor p53/metabolismo , Proteína 1 de Ligação à Proteína Supressora de Tumor p53/genética , Inibidores de Proteínas Quinases/farmacologia , Proliferação de Células/efeitos dos fármacos , Ubiquitinação/efeitos dos fármacos , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Indóis , Pirimidinas

RESUMO

When a naïve observer meets with a familiar conspecific in pain, mice may have a myriad of social (sniffing, allolicking, allogrooming, huddling) and non-social (self-grooming) behaviors under dyadic social interaction (DSI) paradigm. Unlike male, female observers express more allolicking behavior toward injury site of a familiar female in pain, but with less body allogrooming. In current study, we investigated roles of natural estrus cycle phases and ovarian estrogen in these behaviors and results showed that: (1) there was no changes in above behaviors in terms of latency, time and bouts across different natural estrus cycle phases in intact female. (2) however, ovariectomy (OVX) changed estrus cycle phases, lowered circulating level of ovarian estrogen, reduced time and bouts of allolicking behavior and increased time of self-grooming without affecting other behaviors. Moreover, OVX in observers decreased social buffering effect of DSI on spontaneous pain-related behavior in demonstrator relative to naïve and sham controls. (3) treatment of OVX-female with ß-estradiol (E2) or progesterone (PROG) as replacement therapies, only E2 reversed impairment of allolicking behavior. (4) Additionally, socially transferred pain could be identified in intact female across all estrus cycle phases post-DSI, but disappeared in OVX-female, which could be reversed completely by E2 but not by PROG. (5) Finally, serum levels of estrogen, PROG, oxytocin, arginine vasopressin (AVP), prolactin, norepinephrine and 5-HT were examined by ELISA after E2, results showed only AVP level was significantly increased. These results suggest both injury site-targeted caring behavior and socially transferred pain are selectively dependent on ovarian estrogen.

RESUMO

Heritable endosymbionts widely occur in arthropod and nematode hosts. Among these endosymbionts, Wolbachia has been extensively detected in many arthropods, such as insects and crustaceans. Maternal inheritance is the most basic and dominant mode of transmission of Wolbachia, and it might regulate the reproductive system of the host in four ways: feminization, parthenogenesis, male killing, and cytoplasmic incompatibility. There is a relatively high percentage (10%) of thelytokous species in Oribatida, a suborder under the subclass Acari of arthropods, but the study of the endosymbionts in oribatid mites is almost negligible. In this paper, we detected endosymbiotic bacteria in two parthenogenetic oribatid species, Nothrus anauniensis Canestrini and Fanzago, 1877, which has never been tested for endosymbionts, and Oppiella nova, in which Wolbachia and Cardinium have been reported before. The results showed that Wolbachia was first found in N. anauniensis with an infection rate of 100% across three populations. Phylogenetic analysis showed that Wolbachia in N. anauniensis belonged to the supergroup K, marking the second supergroup of Wolbachia found in oribatid mites. Unlike previous studies, our study did not detect Wolbachia in O. nova, leading to the exclusion of Wolbachia's role in mediating thelytoky in this species.