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Rev1 has two important functions in the translesion synthesis pathway, including dCMP transferase activity, and acts as a scaffolding protein for other polymerases involved in translesion synthesis. However, the role of Rev1 in mutagenesis and tumorigenesis in vivo remains unclear. We previously generated Rev1-overexpressing (Rev1-Tg) mice and reported that they exhibited a significantly increased incidence of intestinal adenoma and thymic lymphoma (TL) after N-methyl-N-nitrosourea (MNU) treatment. In this study, we investigated mutagenesis of MNU-induced TL tumorigenesis in wild-type (WT) and Rev1-Tg mice using diverse approaches, including whole-exome sequencing (WES). In Rev1-Tg TLs, the mutation frequency was higher than that in WT TL in most cases. However, no difference in the number of nonsynonymous mutations in the Catalogue of Somatic Mutations in Cancer (COSMIC) genes was observed, and mutations involved in Notch1 and MAPK signaling were similarly detected in both TLs. Mutational signature analysis of WT and Rev1-Tg TLs revealed cosine similarity with COSMIC mutational SBS5 (aging-related) and SBS11 (alkylation-related). Interestingly, the total number of mutations, but not the genotypes of WT and Rev1-Tg, was positively correlated with the relative contribution of SBS5 in individual TLs, suggesting that genetic instability could be accelerated in Rev1-Tg TLs. Finally, we demonstrated that preleukemic cells could be detected earlier in Rev1-Tg mice than in WT mice, following MNU treatment. In conclusion, Rev1 overexpression accelerates mutagenesis and increases the incidence of MNU-induced TL by shortening the latency period, which may be associated with more frequent DNA damage-induced genetic instability.
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DNA Polimerase Dirigida por DNA , Metilnitrosoureia , Mutagênese , Nucleotidiltransferases , Neoplasias do Timo , Animais , Camundongos , DNA Polimerase Dirigida por DNA/genética , DNA Polimerase Dirigida por DNA/metabolismo , Sequenciamento do Exoma , Linfoma/genética , Linfoma/induzido quimicamente , Linfoma/patologia , Metilnitrosoureia/toxicidade , Camundongos Transgênicos , Mutação , Nucleotidiltransferases/genética , Nucleotidiltransferases/metabolismo , Neoplasias do Timo/genética , Neoplasias do Timo/induzido quimicamente , Neoplasias do Timo/patologiaRESUMO
Interconnect materials play the critical role of routing energy and information in integrated circuits. However, established bulk conductors, such as copper, perform poorly when scaled down beyond 10 nm, limiting the scalability of logic devices. Here, a multi-objective search is developed, combined with first-principles calculations, to rapidly screen over 15,000 materials and discover new interconnect candidates. This approach simultaneously optimizes the bulk electronic conductivity, surface scattering time, and chemical stability using physically motivated surrogate properties accessible from materials databases. Promising local interconnects are identified that have the potential to outperform ruthenium, the current state-of-the-art post-Cu material, and also semi-global interconnects with potentially large skin depths at the GHz operation frequency. The approach is validated on one of the identified candidates, CoPt, using both ab initio and experimental transport studies, showcasing its potential to supplant Ru and Cu for future local interconnects.
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Three-dimensional (3D) hetero-integration technology is poised to revolutionize the field of electronics by stacking functional layers vertically, thereby creating novel 3D circuity architectures with high integration density and unparalleled multifunctionality. However, the conventional 3D integration technique involves complex wafer processing and intricate interlayer wiring. Here we demonstrate monolithic 3D integration of two-dimensional, material-based artificial intelligence (AI)-processing hardware with ultimate integrability and multifunctionality. A total of six layers of transistor and memristor arrays were vertically integrated into a 3D nanosystem to perform AI tasks, by peeling and stacking of AI processing layers made from bottom-up synthesized two-dimensional materials. This fully monolithic-3D-integrated AI system substantially reduces processing time, voltage drops, latency and footprint due to its densely packed AI processing layers with dense interlayer connectivity. The successful demonstration of this monolithic-3D-integrated AI system will not only provide a material-level solution for hetero-integration of electronics, but also pave the way for unprecedented multifunctional computing hardware with ultimate parallelism.
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BACKGROUND: The aging process in the tobacco production, as in other food industries, is an important process for improving the quality of raw materials. In the spontaneous aging, the complex components in flue-cured tobacco (FT) improve flavor or reduce harmful compounds through chemical reactions, microbial metabolism, and enzymatic catalysis. Some believed that tobacco-microbe played a significant part in this process. However, little information is available on how microbes mediate chemical composition to improve the quality of FT, which will lay the foundation for the time-consuming spontaneous aging to seek ways to shorten the aging cycle. RESULTS: Comparing aged and unaged FT, volatile and non-volatile differential compounds (DCs) were multi-dimensionally analyzed with the non-targeted metabolomes based on UPLC-QTOP-MS (the ultra-performance liquid chromatography quadrupole time-of-flight mass spectrometry), GC-MS (gas chromatography-mass spectrometer) assisted derivatization and HP-SPME-GC/MS (headspace solid-phase micro-extraction assisted GC-MS). Products associated with the degradation pathways of terpenoids or higher fatty acids were one of the most important factors in improving FT quality. With the microbiome, the diversity and functions of microbial flora were analyzed. The high relative abundance function categories were in coincidence with DCs-related metabolic pathways. According to the correlation analysis, Acinetobacter, Sphingomonas and Aspergillus were presumed to be the important contributor, in which Aspergillus was associated with the highest number of degradation products of terpenoids and higher fatty acids. At last, the screened Aspergillus nidulans strain F4 could promote the degradation of terpenoids and higher fatty acids to enhance tobacco flavor by secreting highly active lipoxygenase and peroxidase, which verified the effect of tobacco-microbes on FT quality. CONCLUSIONS: By integrating the microbiome and metabolome, tobacco-microbe can mediate flavor-related substances to improve the quality of FT after aging, which provided a basis for identifying functional microorganisms for reforming the traditional spontaneous aging.
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Nicotiana , Melhoria de Qualidade , Ácidos Graxos , Cromatografia Gasosa-Espectrometria de Massas/métodos , TerpenosRESUMO
Periodic visual stimulation can induce stable steady-state visual evoked potentials (SSVEPs) distributed in multiple brain regions and has potential applications in both neural engineering and cognitive neuroscience. However, the underlying dynamic mechanisms of SSVEPs at the whole-brain level are still not completely understood. Here, we addressed this issue by simulating the rich dynamics of SSVEPs with a large-scale brain model designed with constraints of neuroimaging data acquired from the human brain. By eliciting activity of the occipital areas using an external periodic stimulus, our model was capable of replicating both the spatial distributions and response features of SSVEPs that were observed in experiments. In particular, we confirmed that alpha-band (8-12 Hz) stimulation could evoke stronger SSVEP responses; this frequency sensitivity was due to nonlinear entrainment and resonance, and could be modulated by endogenous factors in the brain. Interestingly, the stimulus-evoked brain networks also exhibited significant superiority in topological properties near this frequency-sensitivity range, and stronger SSVEP responses were demonstrated to be supported by more efficient functional connectivity at the neural activity level. These findings not only provide insights into the mechanistic understanding of SSVEPs at the whole-brain level but also indicate a bright future for large-scale brain modeling in characterizing the complicated dynamics and functions of the brain.
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Córtex Cerebral/fisiologia , Conectoma , Potenciais Evocados Visuais/fisiologia , Modelos Teóricos , Rede Nervosa/anatomia & histologia , Rede Nervosa/fisiologia , Estimulação Luminosa , Eletroencefalografia , HumanosRESUMO
BACKGROUND AND AIMS: Up to 30% of adenomas might be missed during screening colonoscopy-these could be polyps that appear on-screen but are not recognized by endoscopists or polyps that are in locations that do not appear on the screen at all. Computer-aided detection (CADe) systems, based on deep learning, might reduce rates of missed adenomas by displaying visual alerts that identify precancerous polyps on the endoscopy monitor in real time. We compared adenoma miss rates of CADe colonoscopy vs routine white-light colonoscopy. METHODS: We performed a prospective study of patients, 18-75 years old, referred for diagnostic, screening, or surveillance colonoscopies at a single endoscopy center of Sichuan Provincial People's Hospital from June 3, 2019 through September 24, 2019. Same day, tandem colonoscopies were performed for each participant by the same endoscopist. Patients were randomly assigned to groups that received either CADe colonoscopy (n=184) or routine colonoscopy (n=185) first, followed immediately by the other procedure. Endoscopists were blinded to the group each patient was assigned to until immediately before the start of each colonoscopy. Polyps that were missed by the CADe system but detected by endoscopists were classified as missed polyps. False polyps were those continuously traced by the CADe system but then determined not to be polyps by the endoscopists. The primary endpoint was adenoma miss rate, which was defined as the number of adenomas detected in the second-pass colonoscopy divided by the total number of adenomas detected in both passes. RESULTS: The adenoma miss rate was significantly lower with CADe colonoscopy (13.89%; 95% CI, 8.24%-19.54%) than with routine colonoscopy (40.00%; 95% CI, 31.23%-48.77%, P<.0001). The polyp miss rate was significantly lower with CADe colonoscopy (12.98%; 95% CI, 9.08%-16.88%) than with routine colonoscopy (45.90%; 95% CI, 39.65%-52.15%) (P<.0001). Adenoma miss rates in ascending, transverse, and descending colon were significantly lower with CADe colonoscopy than with routine colonoscopy (ascending colon 6.67% vs 39.13%; P=.0095; transverse colon 16.33% vs 45.16%; P=.0065; and descending colon 12.50% vs 40.91%, P=.0364). CONCLUSIONS: CADe colonoscopy reduced the overall miss rate of adenomas by endoscopists using white-light endoscopy. Routine use of CADe might reduce the incidence of interval colon cancers. chictr.org.cn study no: ChiCTR1900023086.
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Pólipos Adenomatosos/patologia , Neoplasias do Colo/patologia , Pólipos do Colo/patologia , Colonoscopia , Aprendizado Profundo , Diagnóstico por Computador , Interpretação de Imagem Assistida por Computador , Adolescente , Adulto , Idoso , China , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Diagnóstico Ausente , Valor Preditivo dos Testes , Estudos Prospectivos , Reprodutibilidade dos Testes , Adulto JovemRESUMO
Microplastics pollution presents an increasing concern worldwide due to the large amount and potential risks. However, data on microplastics in the freshwater environment are still limited, especially in southwest China. This study investigated the microplastics distribution, characteristics and risks in urban water of different cities in the Tuojiang River basin in southwest China. Microplastics were found in all seven cities of the Tuojiang River basin and the concentrations varied from 911.57 ± 199.73 to 3395.27 ± 707.22 items/m3, among which Ziyang urban water had the highest microplastics concentration. Fiber (34.88-65.85%) was a typical and abundant microplastic type. The small size (0.5-1 mm) (27.27-66.67%) was predominant, and white (23.30-54.29%) was the dominant color among all samples. Polypropylene was identified as the main polymer type by Fourier transform infrared spectroscopy. The morphological analysis by scanning electron microscopy indicated that the surfaces of the microplastics had many cracks and a multitude of particles were adsorbed onto it. According to correlation analysis, there was a significant positive correlation between gross domestic product(P=0.015<0.05) and gross domestic product of the secondary industries(P=0.014<0.05) of cities in the Tuojiang River basin and microplastics concentrations, demonstrating impacts of the secondary industries on the microplastics pollution. In addition, water bodies with lower oxidation-reduction potential tended to have higher microplastics abundance. In the Tuojiang River basin, microplastics pollution was more serious in location where water quality was poor. The polymer risk index (H) was calculated to assess the environmental risk of microplastics in different cities, and the results showed that Fushun sites had the highest risk in regard to microplastics. This study provides a valuable reference for a better understanding of the microplastics level and source identification in southwest China.
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Rios , Poluentes Químicos da Água , China , Cidades , Monitoramento Ambiental , Microplásticos , Plásticos , Poluentes Químicos da Água/análiseRESUMO
In this study, the difference in oxidative capacity for removing antibiotics and the mechanism between the Cu(II)/peroxymonosulfate (PMS)/UV and Cu(II)/persulfate (PDS)/UV systems were compared under various conditions. The optimal Cu(II) concentration in the Cu(II)/PMS/UV system was 30 µM, and in the Cu(II)/PDS/UV system was 50 µM. With the PMS or PDS concentration increasing, higher tetracycline (TC) degradation in these two systems occurred. Investigation on the mechanism revealed that â¢OH was the primary radical in the Cu(II)/PMS/UV system, while SO4 -⢠was the primary radical in the Cu(II)/PDS/UV system where â¢OH also played an important role. In these two systems, it was observed that Cu(I) was generated by PMS or PDS activated via UV illumination; however, oxygen alone could not promote TC removal. The degradation of TC was increased with the increasing pH level. In addition, TC degradation in the Cu(II)/PMS/UV system followed the pseudo-first-order kinetics model during the entire reaction period. It was found that the TC degradation kinetics in the Cu(II)/PDS/UV system can be divided into two parts (0 to 7 min and 10 to 50 min) and these two parts had good agreement with the pseudo-first-order kinetics model, respectively.
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Peróxidos/química , Sulfatos/química , Tetraciclina/química , Poluentes Químicos da Água/química , Antibacterianos , Oxirredução , Processos Fotoquímicos , Raios UltravioletaAssuntos
Colite Isquêmica/induzido quimicamente , Colite Ulcerativa/induzido quimicamente , Medicamentos de Ervas Chinesas/efeitos adversos , Dor Abdominal/tratamento farmacológico , Colite Isquêmica/patologia , Colite Ulcerativa/patologia , Diarreia/tratamento farmacológico , Medicamentos de Ervas Chinesas/uso terapêutico , Feminino , Hemorragia Gastrointestinal/etiologia , Humanos , Linfócitos/patologia , Fagócitos/patologia , Plasmócitos/patologia , Adulto JovemRESUMO
Machine learning enabled auscultating diagnosis can provide promising solutions especially for prescreening purposes. The bottleneck for its potential success is that high-quality datasets for training are still scarce. An open auscultation dataset that consists of samples and annotations from patients and healthy individuals is established in this work for the respiratory diagnosis studies with machine learning, which is of both scientific importance and practical potential. A machine learning approach is examined to showcase the use of this new dataset for lung sound classifications with different diseases. The open dataset is available to the public online.
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Auscultação , Aprendizado de Máquina , Sons Respiratórios , Humanos , Auscultação/métodos , Sons Respiratórios/classificaçãoRESUMO
Ultrathin catalysts predominantly expose surface active atoms to deliver promising applications in oxygen reduction reactions (ORRs). However, they are commonly synthesized at high reaction temperatures, with tedious chemical routes involved. Herein, we report a low temperature (273 K) electric field driven route to synthesize zigzag-surface ultrathin copper nanowires. Interestingly, the ultrathin copper nanowires assemble into three-dimensional microspheres, which exhibit hydrophobic-aerophilic features, eventually resulting in good ORR activities. The aerophilicity and hydrophobicity of copper nanowires are related to their Cu2O active sites and hierarchical protuberances, respectively. Our findings open a new door to grow ultrathin catalysts for new energy storage systems.
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Introduction: The risk that a large polyp (≥10 mm) evolves into high-grade dysplasia (HGD) is relatively high compared with that of a small/diminutive polyp (<10 mm). Recently, the detection of small and diminutive polyps has been substantially improved with the advancement of endoscopy. However, further research is needed on the role of the incidence of HGD caused by the co-occurrence of small and diminutive polyps in the progression of HGD. In this study, we aim to investigate whether and how the small and diminutive polyps correlate with the incidence of HGD in the population. Methods: The pooled data were deeply analyzed from four published randomized controlled trials (RCTs) regarding colon polyp detection. All polyps detected were examined and confirmed by pathologists. The primary outcome was the composition ratio of the HGD polyps in each polyp size category. Results: Among a total of 3,179 patients with 2,730 polyps identified, there were 83 HGD polyps confirmed, and 68 patients had at least one polyp with HGD. The risk of development of HGD was lower for a single small and diminutive polyp than for one large polyp (2.18% vs. 22.22%, P < 0.0001). On the contrary, the composition ratio for HGD from small and diminutive polyps was significantly higher than that from the large ones (68.67% vs. 31.33%, P < 0.0001). The combined number of HGD presented a trend negatively correlated to size. Conclusions: Our data demonstrated that the absolute number of HGD significantly derives more from small and diminutive polyps than from the large ones, and the collective number of small and diminutive polyps per patient is indicative of his/her HGD exposure. These findings positively provide novel perspectives on the management of polyps and may further optimize the prevention of colorectal cancer. Systematic Review Registration: http://www.chictr.org.cn, identifier ChiCTR1900025235, ChiCTR1800017675, ChiCTR1800018058, and ChiCTR1900023086.
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BACKGROUND: Current treatment strategies for advanced non-small cell lung cancer (NSCLC) are highly individualized and subject to ongoing debates. In the era of immunotherapy, surgery assumes a critical role. The aim of this study was to investigate if subsequent surgical intervention, following a favorable response to immunotherapy and chemotherapy, could yield a more favorable prognosis for patients with advanced stage III NSCLC compared to the continuation of immunotherapy and chemotherapy. METHODS: We included patients whose tumors exhibited a favorable response (including partial response [PR] and complete response [CR]) to immunotherapy and chemotherapy. These patients were categorized into two groups based on their subsequent treatment plans: surgical and nonsurgical (continuation of maintenance immunotherapy and chemotherapy). The efficacy and long-term prognosis of these groups were compared after matching them in a 1:1 ratio using propensity scores. RESULTS: In total, 186 patients (93 in each group) were included in this study after matching via propensity scores. The 1- and 3-year overall survival (OS) and progression-free survival (PFS) rates were 96.0%, 88.5%, and 93.1%, 80.7% in the surgical group, and 93.2%, 83.1%, and 57.7%, 50.4% in the nonsurgical group, respectively. Patients in the surgical group exhibited significantly superior PFS and OS compared to those in the nonsurgical group (p = 0.025 and p = 0.00086). Univariate and multivariate analyses confirmed ΔBMI, Δtumor size reduction, tumor response, earlier clinical stage (IIIb vs. IIIa), and surgery as independent protective factor for patient prognosis. We further selected 101 patients with CR (39 in the surgical group and 62 in the nonsurgical group) and found that patients in the surgical group were significantly better in both PFS and OS. Our subgroup analysis in postoperative patients demonstrated that different surgical strategies did not significantly affect the long-term prognosis of patients (PFS and OS) but could impact their perioperative experience. CONCLUSION: Patients with advanced stage III NSCLC, whose tumors achieved PR and CR after 2-4 cycles of immunotherapy combined with chemotherapy, experience a more promising prognosis with subsequent surgical intervention compared with the continued immunotherapy. Despite encountering formidable obstacles, such as protracted surgical procedures and associated trauma, we must rise to the challenge and unleash the power of surgery after immunotherapy in advanced NSCLC.
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Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/cirurgia , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/cirurgia , Terapia Neoadjuvante , Estudos Retrospectivos , Estadiamento de Neoplasias , Imunoterapia/métodosRESUMO
In oxygen (O2)-controlled cell culture, an indispensable tool in biological research, it is presumed that the incubator setpoint equals the O2 tension experienced by cells (i.e., pericellular O2). However, it is discovered that physioxic (5% O2) and hypoxic (1% O2) setpoints regularly induce anoxic (0% O2) pericellular tensions in both adherent and suspension cell cultures. Electron transport chain inhibition ablates this effect, indicating that cellular O2 consumption is the driving factor. RNA-seq analysis revealed that primary human hepatocytes cultured in physioxia experience ischemia-reperfusion injury due to cellular O2 consumption. A reaction-diffusion model is developed to predict pericellular O2 tension a priori, demonstrating that the effect of cellular O2 consumption has the greatest impact in smaller volume culture vessels. By controlling pericellular O2 tension in cell culture, it is found that hypoxia vs. anoxia induce distinct breast cancer transcriptomic and translational responses, including modulation of the hypoxia-inducible factor (HIF) pathway and metabolic reprogramming. Collectively, these findings indicate that breast cancer cells respond non-monotonically to low O2, suggesting that anoxic cell culture is not suitable for modeling hypoxia. Furthermore, it is shown that controlling atmospheric O2 tension in cell culture incubators is insufficient to regulate O2 in cell culture, thus introducing the concept of pericellular O2-controlled cell culture.
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Neoplasias da Mama , Técnicas de Cultura de Células , Oxigênio , Humanos , Oxigênio/metabolismo , Neoplasias da Mama/metabolismo , Neoplasias da Mama/genética , Técnicas de Cultura de Células/métodos , Feminino , Hipóxia Celular/fisiologia , Consumo de OxigênioRESUMO
Non-small cell lung cancer (NSCLC) accounts for 80-85% of all lung cancers, which has the highest cancer-related mortality worldwide. Regardless of the therapeutic effects of chemotherapy or targeted therapy, drug resistance will occur after 1 year. Heat shock proteins (HSPs) are a class of molecular chaperones participated in protein stability and multiple intracellular signaling pathways. It has been widely reported that HSPs family is over expressed in non-small cell lung cancer, and these molecules are also associated with protein stability and multiple intracellular signaling pathways. The effect of chemotherapy drugs or targeted drugs on cancer cells is usually to induce apoptosis. It is necessary to explore the interaction between heat shock protein family and apoptosis pathway in NSCLC. Here we provide a brief review of how HSPs affect the apoptotic pathway in NSCLC.
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Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Humanos , Proteínas de Choque Térmico/metabolismo , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/genética , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , ApoptoseRESUMO
Glioma is the most aggressive malignant tumor of the central nervous system, and most patients suffer from a recurrence. Unfortunately, recurrent glioma often becomes resistant to established chemotherapy and radiotherapy treatments. Immunotherapy, a rapidly developing anti-tumor therapy, has shown a potential value in treating recurrent glioma. Multiple immune strategies have been explored. The most-used ones are immune checkpoint blockade (ICB) antibodies, which are barely effective in monotherapy. However, when combined with other immunotherapy, especially with anti-angiogenesis antibodies, ICB has shown encouraging efficacy and enhanced anti-tumor immune response. Oncolytic viruses and CAR-T therapies have shown promising results in recurrent glioma through multiple mechanisms. Vaccination strategies and immune-cell-based immunotherapies are promising in some subgroups of patients, and multiple new tumor antigenic targets have been discovered. In this review, we discuss current applicable immunotherapies and related mechanisms for recurrent glioma, focusing on multiple preclinical models and clinical trials in the last 5 years. Through reviewing the current combination of immune strategies, we would like to provide substantive thoughts for further novel therapeutic regimes treating recurrent glioma.
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To determine their involvement in the onset of the disease, we investigated the changing levels of liver fibrosis-related proteins, namely, type-I collagen, α-smooth muscle actin (α-SMA), and transforming growth factor ß1 and ß3 (TGF-ß1, ß3). The four groups of Sprague-Dawley (SD) rats were involved in the study, namely, (i) normal control group, (ii) high-fat diet group (HFD), (iii) carbon tetrachloride (CCl4) group, and (iv) NAFLD group (animal model) which were chosen at random. The NAFLD model received HFD combined with subcutaneous injection of small doses of CCl4. Histopathological examination confirmed extent of liver fibrosis, while other immunological and molecular methods were used to evaluate expression and distribution of α-SMA, type I collagen TGF-ß1 and TGF-ß3, at both m-RNA and protein levels. In contrast to the normal control group, the NAFLD group showed moderately elevated expressions of TGF-ß1, α-SMA, and type I collagen, which was proportional on temporal scale of NAFLD persistence in the model (P < 0.05). In the early phage of NAFLD, enhancement in the mRNA transcripts and, henceforth, protein expression of TGF-ß3 was observed. However, these were found to be downregulated in case of liver fibrosis (P < 0.05). This NAFLD rat model shows the histopathologic changes of human NAFLD and is suitable for the study of NAFLD pathogenesis. These findings suggest that type I collagen and the liver fibrosis-related factors TGF- ß1, TGF- ß3, and α-SMA may be significant contributors to NAFLD. Although NAFLD model is previously demonstrated by other researchers, our study is novel in terms of exploration of involvement of fibrosis-related factors and in particular aforementioned proteins at the early stage of NAFLD vis-à-vis dynamics of type-I collagen distribution.
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Despite the significant attention given to microplastics in urban areas, our understanding of microplastics in rural drinking water systems is still limited. To address this knowledge gap, we investigated the presence and pathways of microplastics in rural drinking water system, including reservoir, water treatment plant (WTP), and tap water of end-users. The results showed that the treatment processes in the WTP, including coagulation-sedimentation, sand-granular active carbon filtration, and ultrafiltration, completely removed microplastics from the influent. However, the microplastic abundance increased during pipe transport from WTP to residents' homes, resulting in the presence of 1.4 particles/L of microplastics in tap water. This microplastic increase was also observed during the transportation from the reservoir to the WTP, suggesting that the plastic pipe network is a key source of microplastics in the drinking water system. The main types of polymers were PET, PP, and PE, and plastic breakdown, atmospheric deposition, and surface runoff were considered as their potential sources. Furthermore, this study estimated that rural residents could ingest up to 1034 microplastics annually by drinking 2 L of tap water every day. Overall, these findings provide essential data and preliminary insights into the fate of microplastics in rural drinking water systems.
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Água Potável , Poluentes Químicos da Água , Microplásticos , Plásticos , Poluentes Químicos da Água/análise , Monitoramento Ambiental , ChinaRESUMO
The 70 kDa heat shock proteins (HSP70s) are a group of highly conserved and inducible heat shock proteins. One of the main functions of HSP70s is to act as molecular chaperones that are involved in a large variety of cellular protein folding and remodeling processes. HSP70s are found to be over-expressed and may serve as prognostic markers in many types of cancers. HSP70s are also involved in most of the molecular processes of cancer hallmarks as well as the growth and survival of cancer cells. In fact, many effects of HSP70s on cancer cells are not only related to their chaperone activities but rather to their roles in regulating cancer cell signaling. Therefore, a number of drugs directly or indirectly targeting HSP70s, and their co-chaperones have been developed aiming to treat cancer. In this review, we summarized HSP70-related cancer signaling pathways and corresponding key proteins regulated by the family of HSP70s. In addition, we also summarized various treatment approaches and progress of anti-tumor therapy based on targeting HSP70 family proteins.
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Proteínas de Choque Térmico HSP70 , Neoplasias , Humanos , Proteínas de Choque Térmico HSP70/metabolismo , Dobramento de Proteína , Proteínas de Choque Térmico/metabolismo , Chaperonas Moleculares/metabolismo , Neoplasias/tratamento farmacológico , Transdução de SinaisRESUMO
In this study, the adsorption capacity of activated carbon was enhanced after zinc chloride activation. The effects of pore filling, n-π and π-π interaction and electrostatic interaction on the adsorption of polystyrene nanoplastics (PSNPs) by activated carbon were determined by SEM, BET, Raman spectrum, FTIR and surface Zeta potential. Pore filling, electrostatic interaction and n-π interaction and π-π interaction all played a role in the adsorption process, but n-π interaction and π-π interaction was not the decisive role. The adsorption of PSNPs on activated carbon conformed to the pseudo-second-order kinetics and Langmuir isotherm, and there was spontaneous physical adsorption process driven by entropy in the adsorption process. Further, the effects of common anions SO42-, HCO3-, and Cl- in water on the adsorption of PSNPs by activated carbon were investigated, and the results showed that the presence of these ions could increase the adsorption capacity to some extent. ZCAC has a stable adsorption capacity under tap water, but its adsorption capacity is affected under lake water. In addition, the reuse of activated carbon was investugated, and the adsorption capacity of activated carbon was fully recovered after high temperature calcination. This study provided a direction for materials modification of adsorbed nanoplastics and a feasible method for removal of nanoplastics in drinking water treatment plants.