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The ubiquitin-proteasome system (UPS), which involves E3 ligases and deubiquitinases (DUBs), is critical for protein homeostasis. The epigenetic reader ZMYND8 (zinc finger MYND-type containing 8) has emerged as an oncoprotein, and its protein levels are elevated in various types of cancer, including breast cancer. However, the mechanism by which ZMYND8 protein levels are increased in cancer remains elusive. Although ZMYND8 has been reported to be regulated by the E3 ligase FBXW7, it is still unknown whether ZMYND8 could be modulated by DUBs. Here, we identified USP7 (ubiquitin carboxyl-terminal hydrolase 7) as a bona fide DUB for ZMYND8. Mechanically, USP7 directly binds to the PBP (PHD-BRD-PWWP) domain of ZMYND8 via its TRAF (tumor necrosis factor receptor-associated factor) domain and UBL (ubiquitin-like) domain and removes F-box and WD repeat domain containing 7 (FBXW7)-catalyzed poly-ubiquitin chains on lysine residue 1034 (K1034) within ZMYND8, thereby stabilizing ZMYND8 and stimulating the transcription of ZMYND8 target genes ZEB1 (zinc finger E-box binding homeobox 1) and VEGFA (Vascular Endothelial Growth Factor A). Consequently, USP7 enhances the capacity of breast cancer cells for migration and invasion through antagonizing FBXW7-mediated ZMYND8 degradation. Importantly, the protein levels of USP7 positively correlates with those of ZMYND8 in breast cancer tissues. These findings delineate an important layer of migration and invasion regulation by the USP7-ZMYND8 axis in breast cancer cells.
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GINS1 regulates DNA replication in the initiation and elongation phases and plays an important role in the progression of various malignant tumors. However, the role of GINS1 in hepatocellular carcinoma (HCC) remains largely unclear. In this study, we investigated the role and underlying mechanisms of GINS1 in contributing to HCC metastasis. We found that GINS1 was significantly upregulated in HCC tissues and cell lines, especially in HCC tissues with vascular invasion and HCC cell lines with highly metastatic properties. Additionally, high expression of GINS1 was positively correlated with the progressive clinical features of HCC patients, including tumor number (multiple), tumor size (>5 cm), advanced tumor stage, vascular invasion and early recurrence, suggesting that GINS1 upregulation was greatly involved in HCC metastasis. Moreover, Kaplan-Meier survival analysis revealed that high GINS1 expression predicted a poor prognosis. Both in vitro and in vivo, silencing of GINS1 inhibited proliferation, migration, invasion and metastasis, while overexpression of GINS1 induced opposite effects. Mechanistically, we found that ZEB1 was a crucial regulator of GINS1-induced epithelial-mesenchymal transition (EMT), and GINS1 promoted EMT and tumor metastasis through ß-catenin signaling. Overall, the present study demonstrated that GINS1 promoted ZEB1-mediated EMT and tumor metastasis via ß-catenin signaling in HCC.
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Carcinoma Hepatocelular , Movimento Celular , Proteínas Cromossômicas não Histona , Proteínas de Ligação a DNA , Transição Epitelial-Mesenquimal , Regulação Neoplásica da Expressão Gênica , Neoplasias Hepáticas , Homeobox 1 de Ligação a E-box em Dedo de Zinco , beta Catenina , Animais , Feminino , Humanos , Masculino , Camundongos , Pessoa de Meia-Idade , beta Catenina/metabolismo , beta Catenina/genética , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/patologia , Carcinoma Hepatocelular/metabolismo , Linhagem Celular Tumoral , Movimento Celular/genética , Proliferação de Células/genética , Proteínas Cromossômicas não Histona/metabolismo , Proteínas Cromossômicas não Histona/genética , Transição Epitelial-Mesenquimal/genética , Regulação Neoplásica da Expressão Gênica/genética , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/metabolismo , Camundongos Endogâmicos BALB C , Camundongos Nus , Invasividade Neoplásica , Metástase Neoplásica , Transdução de Sinais , Homeobox 1 de Ligação a E-box em Dedo de Zinco/genética , Homeobox 1 de Ligação a E-box em Dedo de Zinco/metabolismoRESUMO
The design of smart stimuli-responsive photoluminescent materials capable of multi-level encryption and complex information storage is highly sought after in the current information era. Here, a novel adamantyl-capped CsPbBr3 (AD-CsPbBr3) perovskite NCs, along with its supramolecular host-guest assembly partner a modified ß-CD (mCD), mCD@AD-CsPbBr3, are designed and prepared. By dispersing these two materials in different solvents, namely, AD-CsPbBr3 in toluene, mCD@AD-CsPbBr3 in toluene, and mCD@AD-CsPbBr3 in methanol, the three solutions exhibit diverse photoluminescence (PL) turn-on/off or PL discoloration response upon supramolecular stimulus. Based on these responses, a proof-of-principle programmable Multi-Level Photoluminescence Encoding System (MPLES) is established. Three types of four-level and three types of three-level information encoding are achieved by the system. A layer-by-layer four-level information encryption and decryption as well as a two-level encrypted 3D code are successfully achieved.
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The lone pair electrons in the electronic structure of molecules have been a prominent research focus in chemistry for more than a century. Stable s2lone pair electrons significantly influence material properties, including thermoelectric properties, nonlinear optical properties, ferroelectricity, and electro(photo)catalysis.While major advances have been achieved in understanding the influence of lone pair electrons on material characteristics, research on this effect in organic-inorganic hybrid materials is in its initial stage. In this work, we successfully obtained a novel organic-inorganic hybrid material incorporating Ge with 4s2 lone pair electrons, (MeHDabco)2[GeBr3]4-H2O (MeHDabco = N-methyl-1,4-diazabicyclo[2.2.2]octane) (1). Driven by the stereochemically active lone pair electrons on the Ge2+, 1 crystallizes in the noncentrosymmetric space group P21 at room temperature and exhibits good second harmonic generation (SHG) responses. Interestingly, 1 also shows electrocatalytic activity for the hydrogen evolution reaction due to the existence of lone pair electrons on Ge2+ cations. The electrochemical experiment combined with the DFT calculations revealed the lone pair electrons act as both an active site for proton adsorption and facilitate the ionization of water. This work not only emphasizes the important role of lone pair electrons in material properties and functions but also provides new insight for designing novel Ge-based hybrid materials.
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Escherichia coli O157:H7 (E. coli O157:H7) is a foodborne pathogenic microorganism that is commonly found in the environment and poses a significant threat to human health, public safety, and economic stability worldwide. Thus, early detection is essential for E. coli O157:H7 control. In recent years, a series of E. coli O157:H7 detection methods have been developed, but the sensitivity and portability of the methods still need improvement. Therefore, in this study, a rapid and efficient testing platform based on the CRISPR/Cas12a cleavage reaction was constructed. Through the integration of recombinant polymerase amplification and lateral flow chromatography, we established a dual-interpretation-mode detection platform based on CRISPR/Cas12a-derived fluorescence and lateral flow chromatography for the detection of E. coli O157:H7. For the fluorescence detection method, the limits of detection (LODs) of genomic DNA and E. coli O157:H7 were 1.8 fg/µL and 2.4 CFU/mL, respectively, within 40 min. Conversely, for the lateral flow detection method, LODs of 1.8 fg/µL and 2.4 × 102 CFU/mL were achieved for genomic DNA and E. coli O157:H7, respectively, within 45 min. This detection strategy offered higher sensitivity and lower equipment requirements than industry standards. In conclusion, the established platform showed excellent specificity and strong universality. Modifying the target gene and its primers can broaden the platform's applicability to detect various other foodborne pathogens.
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Sistemas CRISPR-Cas , Escherichia coli O157 , Limite de Detecção , Escherichia coli O157/genética , Escherichia coli O157/isolamento & purificação , DNA Bacteriano/análise , DNA Bacteriano/genética , Microbiologia de Alimentos/métodos , Proteínas Associadas a CRISPR/genética , Humanos , Endodesoxirribonucleases/genéticaRESUMO
Colorectal cancer (CRC) is a prevalent form of gastrointestinal malignancy with challenges in chemotherapy resistance and side effects. Effective and low toxic drugs for CRC treatment are urgently needed. Ferroptosis is a novel mode of cell death, which has garnered attention for its therapeutic potential against cancer. Baicalein (5, 6, 7-trihydroxyflavone) is the primary flavone extracted from the dried roots of Scutellaria baicalensis that exhibits anticancer effects against several malignancies including CRC. In this study, we investigated whether baicalein induced ferroptosis in CRC cells. We showed that baicalein (1-64 µM) dose-dependently inhibited the viability of human CRC lines HCT116 and DLD1. Co-treatment with the ferroptosis inhibitor liproxstatin-1 (1 µM) significantly mitigated baicalein-induced CRC cell death, whereas autophagy inhibitor chloroquine (25 µM), necroptosis inhibitor necrostatin-1 (10 µM), or pan-caspase inhibitor Z-VAD-FMK (10 µM) did not rescue baicalein-induced CRC cell death. RNA-seq analysis confirmed that the inhibitory effect of baicalein on CRC cells is associated with ferroptosis induction. We revealed that baicalein (7.5-30 µM) dose-dependently decreased the expression levels of GPX4, key regulator of ferroptosis, in HCT116 and DLD1 cells by blocking janus kinase 2 (JAK2)/STAT3 signaling pathway via direct interaction with JAK2, ultimately leading to ferroptosis in CRC cells. In a CRC xenograft mouse model, administration of baicalein (10, 20 mg/kg, i.g., every two days for two weeks) dose-dependently inhibited the tumor growth with significant ferroptosis induced by inhibiting the JAK2/STAT3/GPX4 axis in tumor tissue. This study demonstrates that ferroptosis contributes to baicalein-induced anti-CRC activity through blockade of the JAK2/STAT3/GPX4 signaling pathway, which provides evidence for the therapeutic application of baicalein against CRC.
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Neoplasias Colorretais , Ferroptose , Flavanonas , Janus Quinase 2 , Fosfolipídeo Hidroperóxido Glutationa Peroxidase , Fator de Transcrição STAT3 , Flavanonas/farmacologia , Flavanonas/uso terapêutico , Humanos , Ferroptose/efeitos dos fármacos , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/metabolismo , Neoplasias Colorretais/patologia , Fator de Transcrição STAT3/metabolismo , Fator de Transcrição STAT3/antagonistas & inibidores , Animais , Janus Quinase 2/metabolismo , Janus Quinase 2/antagonistas & inibidores , Camundongos , Fosfolipídeo Hidroperóxido Glutationa Peroxidase/metabolismo , Fosfolipídeo Hidroperóxido Glutationa Peroxidase/antagonistas & inibidores , Camundongos Nus , Camundongos Endogâmicos BALB C , Transdução de Sinais/efeitos dos fármacos , Linhagem Celular Tumoral , Células HCT116 , Ensaios Antitumorais Modelo de Xenoenxerto , Sobrevivência Celular/efeitos dos fármacos , Relação Dose-Resposta a DrogaRESUMO
The study is devoted to the effect of lowered resuscitation temperature (26 °C) on cryopreserved porcine adrenal glands functional activity in vitro and in vivo under xenotransplantation. The adrenals were collected from newborn pigs, cryopreserved with 5 % DMSO at a rate of 1 °C/min, resuscitated at 26 or 37 °C for 48 h (5 % CO2, DMEM), embedded into small intestinal submucosa, and transplanted to bilaterally adrenalectomized rats. It has been shown that the glands resuscitated at 26 °C have suppressed free-radical processes and can produce cortisol and aldosterone in vitro, and may lead to elevated blood levels of these hormones. Moreover, the adrenal grafts maintain blood glucose levels and promote the formation of glycogen stores. Thus, the resuscitation at 26 °C can improve the quality of grafts and favor the introduction and application of the cryopreserved organs and tissues for transplantation in clinical and experimental practice.
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Glândulas Suprarrenais , Criopreservação , Hidrocortisona , Transplante Heterólogo , Animais , Glândulas Suprarrenais/metabolismo , Transplante Heterólogo/métodos , Criopreservação/métodos , Suínos , Hidrocortisona/sangue , Ratos , Glicemia/metabolismo , Glicemia/análise , Aldosterona/sangue , Aldosterona/metabolismo , Masculino , Glicogênio/metabolismo , Ressuscitação/métodos , Preservação de Órgãos/métodos , Crioprotetores/farmacologia , Dimetil Sulfóxido/farmacologiaRESUMO
BACKGROUND: Severe neonatal hyperbilirubinemia could lead to kernicterus and neonatal death. This study aimed to analyze the association between single nucleotide polymorphisms in genes involved in bilirubin metabolism and the incidence of severe hyperbilirubinemia. METHODS: A total of 144 neonates with severe hyperbilirubinemia and 50 neonates without or mild hyperbilirubinemia were enrolled in 3 institutions between 2019 and 2020. Twelve polymorphisms of 5 genes (UGT1A1, SLCO1B1, SLCO1B3, BLVRA, and HMOX1) were analyzed by PCR amplification of genomic DNA. Genotyping was performed using an improved multiplex ligation detection reaction technique based on ligase detection reaction. RESULTS: The frequencies of the A allele in UGT1A1-rs4148323 and the C allele in SLCO1B3-rs2417940 in the severe hyperbilirubinemia group (30.2% and 90.6%, respectively) were significantly higher than those in the controls (30.2% vs.13.0%, 90.6% vs. 78.0%, respectively, both p < 0.05). Haplotype analysis showed the ACG haplotype of UGT1A1 were associated with an increased hyperbilirubinemia risk (OR 3.122, p = 0.001), whereas the GCG haplotype was related to a reduced risk (OR 0.523, p = 0.018). CONCLUSION: The frequencies of the A allele in rs4148323 and the C allele in rs2417940 are highly associated with the incidence of severe hyperbilirubinemia in Chinese Han neonates. TRIAL REGISTRATION: Trial registration number:ChiCTR1800020424; Date of registration:2018-12-29.
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Hiperbilirrubinemia Neonatal , Polimorfismo de Nucleotídeo Único , Recém-Nascido , Humanos , Transportador 1 de Ânion Orgânico Específico do Fígado/genética , Alelos , Hiperbilirrubinemia Neonatal/genética , Glucuronosiltransferase/genética , China/epidemiologia , Membro 1B3 da Família de Transportadores de Ânion Orgânico Carreador de Soluto/genética , Heme Oxigenase-1/genética , Heme Oxigenase-1/metabolismoRESUMO
Objective: With the improvement of living standards, consumers are paying more and more attention to the quality of rice. Traditional rice quality detection relies on human sensory judgment, which is inaccurate and inefficient. With the continuous development of molecular imaging technology, more and more scholars at home and abroad have begun to pay attention to its application in the nondestructive testing of agricultural products. Molecular imaging technology combines the advantages of spectral technology and image technology, which can achieve rapid, nondestructive and accurate detection of rice quality. In this paper, taking rice as the research object, we carried out nondestructive detection research on rice varieties, moisture and starch content using molecular imaging technology. We proposed a rapid detection method based on molecular imaging technology for rice variety identification, moisture content and starch content. Molecular images of the rice samples from four origins were obtained using a molecular imaging system, the regions of interest of the rice were identified and, spectral data, textural features and morphological features of the rice were extracted. Spectral, textural and morphological features were selected by principal component analysis (PCA), and nine feature wavelengths were obtained and an optimal model was established with an accuracy of 91.67%, which demonstrated the feasibility of molecular imaging. By comparing the models, the BCC-LS-SVR model based on the RB function had the highest accuracy with R2 of 0.989, RMSEP of 0.767%, R2 of 0.985, and RMSEC of 0.591%. Moreover, starchy rice was detected using molecular imaging. The PCA-SVR model based on the RBF kernel function had the highest accuracy with R2 of 0.989, RMSEC of 0.445%, R2 of 0.991, and RMSEP of 0.669%. Our models demonstrated high accuracy in identifying rice varieties, as well as quantifying moisture and starch content, showcasing the feasibility of molecular imaging technology in rice quality assessment. This research offers a rapid, nondestructive, and accurate method for rice quality assessment, promising significant benefits for agricultural producers and consumers.
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Roguing and elimination of vectors are the most commonly seen biological control strategies regarding the spread of plant viruses. It is practically significant to establish the mathematical models of plant virus transmission and regard the effect of removing infected plants as well as eliminating vector strategies on plant virus eradication. We proposed the mathematical models of plant virus transmission with nonlinear continuous and pulse removal of infected plants and vectors. In terms of the nonlinear continuous control strategy, the threshold values of the existence and stability of multiple equilibria have been provided. Moreover, the conditions for the occurrence of backward bifurcation were also provided. Regarding the nonlinear impulsive control strategy, the stability of the disease-free periodic solution and the threshold of the persistence of the disease were given. With the application of the fixed point theory, the conditions for the existence of forward and backward bifurcations of the model were presented. Our results demonstrated that there was a backward bifurcation phenomenon in continuous systems, and there was also a backward bifurcation phenomenon in impulsive control systems. Moreover, we found that removing healthy plants increased the threshold $ R_{1}. $ Finally, numerical simulation was employed to verify our conclusions.
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Modelos Biológicos , Vírus de Plantas , Modelos Teóricos , Simulação por Computador , Plantas , Dinâmica não LinearRESUMO
The worldwide incidence of cognitive impairment is escalating, yet no effective solutions for these afflictions have been discovered. Consequently, the importance of early identification and immediate intervention is heightened. Advanced eye movements-a form of voluntary eye movements that includes anti-saccades, memory-guided saccades, predictive saccades, pro-saccades and gap/overlap saccades, mediated by the cerebral cortex and subcortical pathways reflect cognitive levels and functions across different domains. In view of their objectivity, reproducibility, and non-invasive characteristics, advanced eye movement examination possesses significant prospective utility across a wide range of cognitive impairment. This paper extensively reviews various models associated with advanced eye movement examinations and their current applications in cognitive impairment such as Alzheimer's disease, Lewy body dementia and frontotemporal dementia. Advanced eye movement examination can serve as a biomarker for early screening diagnosis and research on cognitive impairment. In the future, combining advanced eye movement examination with neuropsychological scale assessment and other diagnostic methods may contribute to further early identification of these types of diseases.
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Polyhydroxyalkanoate (PHA) is a family of naturally-occurring biopolymers synthesized by more than 300 microorganisms in the environment. These biopolymers have been investigated as a source material to substitute fossil fuel-based polymers; hence the synthesis of biopolymers and their characterization is a critical step in optimizing the process. Because of this, the biological production of PHA using PHA-producing microorganisms is currently the dominating process; however, the use of microbial mixed culture (MMC), such as wastewater sludge, is gaining attention. Different than pure cultures, MMC has higher culturing condition tolerance since the complex species composition and is easily obtained from wastewater treatment plants, which shortens the culturing time, lowers the cost, and promotes the application. The main constraint in MMC-based PHA is the extraction and quantification of PHA from the more complex matrix. In this paper, Fourier-transform infrared (FTIR) spectroscopy is evaluated to be used as a quantification method of PHA in MMC systems. Firstly, commercially available analytical standards, which consist of PHA/PHB, and two different solvents (chloroform and dichloromethane), were used and tested by this method, with KBr card and liquid cell methods, and the results are validated by gas chromatography mass spectrometry (GC/MS). The method was then tested using 12 samples from wastewater treatment plants. The PHA content in biomass varied from 3.42 w/w% to 1.22 w/w% following extraction with chloroform as solvent as determined by this method. In the four different combination standards, the best one is consisted of PHB and chloroform, and FTIR-liquid cell showed higher promise for PHA quantification in complex matrices.
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Poli-Hidroxialcanoatos , Águas Residuárias , Esgotos/química , Poli-Hidroxialcanoatos/análise , Espectroscopia de Infravermelho com Transformada de Fourier/métodos , Clorofórmio , Reatores Biológicos , BiopolímerosRESUMO
3D bioprinting has unlocked new possibilities for generating complex and functional tissues and organs. However, one of the greatest challenges lies in selecting the appropriate seed cells for constructing fully functional 3D artificial organs. Currently, there are no cell sources available that can fulfill all requirements of 3D bioprinting technologies, and each cell source possesses unique characteristics suitable for specific applications. In this review, we explore the impact of different 3D bioprinting technologies and bioink materials on seed cells, providing a comprehensive overview of the current landscape of cell sources that have been used or hold potential in 3D bioprinting. We also summarized key points to guide the selection of seed cells for 3D bioprinting. Moreover, we offer insights into the prospects of seed cell sources in 3D bioprinted organs, highlighting their potential to revolutionize the fields of tissue engineering and regenerative medicine.
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With the rapid development of artificial intelligence, automated endoscopy-assisted diagnostic systems have become an effective tool for reducing the diagnostic costs and shortening the treatment cycle of patients. Typically, the performance of these systems depends on deep learning models which are pre-trained with large-scale labeled data, for example, early gastric cancer based on endoscopic images. However, the expensive annotation and the subjectivity of the annotators lead to an insufficient and class-imbalanced endoscopic image dataset, and these datasets are detrimental to the training of deep learning models. Therefore, we proposed a Swin Transformer encoder-based StyleGAN (STE-StyleGAN) for unbalanced endoscopic image enhancement, which is composed of an adversarial learning encoder and generator. Firstly, a pre-trained Swin Transformer is introduced into the encoder to extract multi-scale features layer by layer from endoscopic images. The features are subsequently fed into a mapping block for aggregation and recombination. Secondly, a self-attention mechanism is applied to the generator, which adds detailed information of the image layer by layer through recoded features, enabling the generator to autonomously learn the coupling between different image regions. Finally, we conducted extensive experiments on a private intestinal metaplasia grading dataset from a Grade-A tertiary hospital. The experimental results show that the images generated by STE-StyleGAN are closer to the initial image distribution, achieving a Fréchet Inception Distance (FID) value of 100.4. Then, these generated images are used to enhance the initial dataset to improve the robustness of the classification model, and achieved a top accuracy of 86 %.
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Aprendizado Profundo , Humanos , Neoplasias Gástricas/diagnóstico por imagem , Neoplasias Gástricas/patologia , Aumento da Imagem/métodos , Endoscopia/métodos , Interpretação de Imagem Assistida por Computador/métodos , Processamento de Imagem Assistida por Computador/métodosRESUMO
PURPOSE: To develop and validate a nomogram for the preoperative diagnosis of T2 and T3 stage rectal cancer using MRI radiomics features of mesorectal fat. METHODS: The data of 288 patients with T2 and T3 stage rectal cancer were retrospectively collected. Radiomics features were extracted from the lesion region of interest (ROI) in the MRI high-resolution T2WI, apparent diffusion coefficient (ADC), and diffusion-weighted imaging (DWI) sequences. After using ICC inter-group consistency analysis and Pearson correlation analysis to reduce dimensions, LASSO regression analysis was performed to select features and calculate Rad-score for each sequence. Then, Combined_Radscore and nomogram were constructed based on the LASSO-selected features and clinical data for each sequence. Receiver operating characteristic curve (ROC) area under the curve (AUC) was used to evaluate the performance of the Rad-score model and nomogram. Decision curve analysis (DCA) was performed to evaluate the clinical usability of the radiomics nomogram, which were combined with calibration curves to evaluate the prediction accuracy. RESULTS: The nomogram based on MRI-report T status and Combined_Radscore achieved AUCs of 0.921 and 0.889 in the training and validation cohorts, respectively. CONCLUSION: The nomogram can be stated that the radiomics nomogram based on multi-sequence MRI imaging of the mesorectal fat has excellent diagnosing performance for preoperative differentiation of T2 and T3 stage rectal cancer.
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Imageamento por Ressonância Magnética , Estadiamento de Neoplasias , Nomogramas , Neoplasias Retais , Humanos , Neoplasias Retais/diagnóstico por imagem , Neoplasias Retais/patologia , Masculino , Feminino , Pessoa de Meia-Idade , Estudos Retrospectivos , Imageamento por Ressonância Magnética/métodos , Idoso , Adulto , Tecido Adiposo/diagnóstico por imagem , RadiômicaRESUMO
B-cell acute lymphoblastic leukemia (B-ALL) is a malignant blood disorder, particularly detrimental to children and adolescents, with recurrent or unresponsive cases contributing significantly to cancer-associated fatalities. IKBKE, associated with innate immunity, tumor promotion, and drug resistance, remains poorly understood in the context of B-ALL. Thus, this research aimed to explore the impact of the IKBKE inhibitor MCCK1 on B-ALL cells. The study encompassed diverse experiments, including clinical samples, in vitro and in vivo investigations. Quantitative real-time fluorescence PCR and protein blotting revealed heightened IKBKE mRNA and protein expression in B-ALL patients. Subsequent in vitro experiments with B-ALL cell lines demonstrated that MCCK1 treatment resulted in reduced cell viability and survival rates, with flow cytometry indicating cell cycle arrest. In vivo experiments using B-ALL mouse tumor models substantiated MCCK1's efficacy in impeding tumor proliferation. These findings collectively suggest that IKBKE, found to be elevated in B-ALL patients, may serve as a promising drug target, with MCCK1 demonstrating potential for inducing apoptosis in B-ALL cells both in vitro and in vivo.
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Apoptose , Proliferação de Células , Quinase I-kappa B , Animais , Humanos , Camundongos , Quinase I-kappa B/antagonistas & inibidores , Quinase I-kappa B/metabolismo , Linhagem Celular Tumoral , Apoptose/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Feminino , Sobrevivência Celular/efeitos dos fármacos , Masculino , Leucemia-Linfoma Linfoblástico de Células Precursoras B/tratamento farmacológico , Leucemia-Linfoma Linfoblástico de Células Precursoras B/patologia , Criança , Adolescente , Ensaios Antitumorais Modelo de Xenoenxerto , Inibidores de Proteínas Quinases/farmacologiaRESUMO
PURPOSE: The aim of this study was to evaluate the effectiveness and safety of repeated low-level red light (RLRL) therapy in controlling myopia progression in children through a meta-analysis. METHODS: We searched several databases including PubMed, Embase, The Cochrane Library, Web of Science, CNKI, WANFANG, CBM, and VIP with languages restricted to both Chinese and English. The search was conducted from the establishment of the databases to March 23, 2023. We collected randomized controlled trials and controlled experiments to evaluate changes in axial length (AL) and spherical equivalent (SE) before and after RLRL intervention. Two researchers performed literature screening and data extraction, and RevMan software (Ver 5.3) and StataMP 17.0 were used for meta-analysis. RESULTS: A total of 141 articles were retrieved, and finally, six randomized controlled trials met the inclusion and exclusion criteria, including 820 eyes (RLRL group: 411 eyes, control group: 409 eyes). The meta-analysis results showed that the RLRL group was significantly better than the control group in controlling AL, and the difference between the two groups was statistically significant (mean difference [MD] = -0.22, 95% confidence interval [CI] [ - 0.28, -0.16]; P < 0.001). The RLRL group was also better than the control group in terms of SE, and the difference between the two groups was statistically significant (MD = 0.46, 95% CI [0.32, 0.6]; P < 0.001). Five studies reported adverse reactions in the RLRL group, and two cases stopped treatment due to the feeling of too bright light, while the others had no significant side effects in the short term. CONCLUSION: RLRL therapy is a safe and effective method for controlling myopia, which can inhibit the growth of AL and slow down the progression of myopia. However, further research and validation are needed to determine its treatment efficacy and course.
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Miopia , Luz Vermelha , Criança , Humanos , Adolescente , Ensaios Clínicos Controlados Aleatórios como Assunto , Miopia/diagnóstico , Miopia/terapia , Refração OcularRESUMO
To investigate the role of miR-223-3p in the modulatory effect of paeonol (Pae) on high glucose (HG)-induced endothelial cell apoptosis. HG (25 mmol/L) was used to induce cellular damage and apoptosis in the mouse cardiac microvascular endothelial cells (MCMECs). Various concentration of Pae was tested and 60 µmol/L Pae was selected for the subsequent studies. MCMECs were transfected with exogenous miR-223-3p mimics or anti-miR-223-3p inhibitors. Cell viability was assessed by MTT assay and apoptosis was quantified by flow cytometry. The expression of miR-223-3p and NLRP3 mRNA was measured using real-time quantitative RT-PCR, and protein level of NLRP3 and apoptosis-related proteins was detected by immunoblotting. Pae significantly attenuated HG-induced apoptosis of MCMECs in a concentration-dependent manner. In addition, Pae (60 µmol/L) significantly reversed HG-induced down-regulation of miR-223-3p and up-regulation of NLRP3. Pae (60 µmol/L) also significantly blocked HG-induced up-regulation of Bax and Caspase-3 as well as down-regulation of Bcl-2. Moreover, exogenous miR-223-3p mimics not only significantly attenuated HG-induced apoptosis, but also significantly suppressed NRLP-3 and pro-apoptotic proteins in the MCMECs. In contrast, transfection of exogenous miR-223-3p inhibitors into the MCMECs resulted in not only significantly increased apoptosis of the cells, but also significant suppression of NLRP3 and pro-apoptotic proteins in the cells. Pae attenuated HG-induced apoptosis of MCMECs in a concentration-dependent manner. MiR-223-3p may mediate the modulatory effects of Pae on MCMEC survival or apoptosis through targeting NLRP3 and regulating apoptosis-associated proteins.
Assuntos
Acetofenonas , Apoptose , Células Endoteliais , Glucose , MicroRNAs , Animais , MicroRNAs/genética , MicroRNAs/metabolismo , Apoptose/efeitos dos fármacos , Camundongos , Células Endoteliais/efeitos dos fármacos , Células Endoteliais/metabolismo , Glucose/farmacologia , Acetofenonas/farmacologia , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/genética , Regulação para Cima/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Células Cultivadas , Microvasos/citologia , Microvasos/metabolismo , Microvasos/efeitos dos fármacosRESUMO
The accumulation and transformation of lead (Pb) and arsenic (As) during the digestion of sewage sludge (SS) by black soldier fly larvae (BSFL) remain unclear. In this study, we used 16 s rRNA and metagenomic sequencing techniques to investigate the correlation between the microbial community, metalloregulatory proteins (MRPs), and Pb and As migration and transformation. During the 15-day test period, BSFL were able to absorb 34-48 % of Pb and 32-45 % of As into their body. Changes in bacterial community abundance, upregulation of MRPs, and redundancy analysis (RDA) results confirmed that ZntA, EfeO, CadC, ArsR, ArsB, ArsD, and ArsA play major roles in the adsorption and stabilization of Pb and As, which is mainly due to the high contribution rates of Lactobacillus (48-59 %) and Enterococcus (21-23 %). Owing to the redox reaction, the regulation of the MRPs, and the change in pH, the Pb and As in the BSFL residue were mainly the residual fraction (F4). The RDA results showed that Lactobacillus and L.koreensis could significantly (P < 0.01) reduce the reducible fraction (F2) and F4 of Pb, whereas Firmicutes and L.fermentum can significantly (P < 0.05) promote the transformation of As to F4, thus realizing the passivation Pb and As. This study contributes to the understanding of Pb and As in SS adsorbed by BSFL and provides important insights into the factors that arise during the BSFL-mediated migration of Pb and As.
Assuntos
Arsênio , Dípteros , Eliminação de Resíduos , Animais , Larva/metabolismo , Esgotos , Perda e Desperdício de Alimentos , Chumbo/metabolismo , Alimentos , Biotransformação , Bactérias , LactobacillusRESUMO
This study aimed to evaluate the usefulness of optical coherence tomography angiography (OCTA) in assessing retinal microvascular structural changes in preterm-born children and compare them with those in term-born children. The Web of Science Library, Cochrane Library, PubMed, Embase, CNKI, Wanfang, VIP, and Sino Med databases were searched systematically to extract studies published till April 25, 2023. Two independent reviewers searched all the literature and completed the data extraction and quality assessment. Mean differences (MDs) with 95% confidence intervals (CIs) were used to assess the continuous estimates. STATA software (v15.1; StataCorp, College Station, TX) was used to analyze the data. Twelve published studies were eligible for inclusion in this study. The meta-analysis revealed that the foveal avascular zone (FAZ) area of preterm-born children was remarkably smaller than that of term-born children, with the laser photocoagulation (LP)-ROP group showing the most pronounced reduction. The foveal superficial capillary plexus vessel density (SCP-VD) and deep capillary plexus vessel density (DCP-VD) were remarkably higher in the preterm-born group than in the control group, with variations in subgroups (LP-ROP, anti-VEGF-ROP, SR-ROP, and Pre-T-ROP). The parafoveal SCP-VD was remarkably lower in preterm-born children compared to that of the controls, while no significant difference was identified in the parafoveal DCP-VD. Preterm-born children had a smaller FAZ area, higher foveal SCP-VD and DCP-VD, and lower parafoveal SCP-VD compared to their term-born counterparts. The parafoveal DCP-VD did not differ substantially between preterm- and term-born children. OCTA is an effective modality for assessing alterations in the retinal microvasculature in preterm children.