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A Gram-stain-negative, aerobic, motile with flagella and rod- or ovoid-shaped bacterium, designated GG15T, was isolated from tidal flat sediment sampled in Zhoushan, Zhejiang Province. Strain GG15T grew at 20-40â°C (optimum, 30â°C), at pH 5.5-9.5 (optimum, pH 7.0-8.0) and with 1.0-10.0â% (w/v) NaCl (optimum, 1.5â%). Colony diameters ranged from 1 to 3 mm within the first week, reaching a maximum of 6-7 mm after 15 days of cultivation. Strain GG15T exhibited highest 16S rRNA gene sequence similarity to Microbulbifer taiwanensis CCM 7856T (98.1 %), with similarity to other species within the genus Microbulbifer ranging from 97.8 to 93.8â%. Similarity values to other genera were below 93.8â%. Strain GG15T exhibited positive activity for ß-glucosidase, trypsin and chymotrypsin, whereas the reference strain showed negative activity. Chemotaxonomic analyses indicated that strain GG15T contained Q-8 as the sole respiratory quinone, C16â:â0 (9.1â%), iso-C15â:â0 (30.9â%) and iso-C11â:â0 3-OH (7.2â%) as the predominant fatty acids, and phosphatidylethanolamine, phosphatidylglycerol, three unidentified lipids, four unidentified glycolipids, one unidentified phospholipid, two unidentified aminolipids and two unidentified aminophospholipids as the main polar lipids. The genome of strain GG15T was 4â307â641 bp long, comprising 3861 protein-coding genes. The G+C content of strain GG15T was 61.5âmol% based on its genomic sequence. Strain GG15T showed low digital DNA-DNA hybridization (<70â%) and average nucleotide identity values (<95â%) with other Microbulbifer species. As a result, a novel species within the genus Microbulbifer, named Microbulbifer magnicolonia sp. nov., is proposed. The type strain is GG15T (MCCC 1K08802T=KCTC 8210T).
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Alteromonadaceae , Ácidos Graxos , Composição de Bases , Ácidos Graxos/química , RNA Ribossômico 16S/genética , Filogenia , Análise de Sequência de DNA , DNA Bacteriano/genética , Técnicas de Tipagem Bacteriana , ChinaRESUMO
This study explored the role of circular RNA circ_0006168 in the progression of hepatocellular carcinoma (HCC) and its interaction with microRNA-125b. The expression of circ_0006168 was examined in 42 pairs of HCC tumor and adjacent tissue specimens using quantitative polymerase chain reaction (qPCR). Elevated circ_0006168 expression in HCC tissues was significantly associated with advanced pathological staging and lower overall survival rates. Lentivirus-mediated circ_0006168 knockdown in HCC cell lines (Hep3B and Huh7) demonstrated a notable reduction in cell proliferation and an increase in apoptosis. MicroRNA-125b expression exhibited a marked reduction in HCC tissues, negatively correlating with circ_0006168 levels. Luciferase reporting assays indicated that circ_0006168 was a direct target of microRNA-125b. Additionally, cell recovery experiments suggested a reciprocal regulation between circ_0006168 and microRNA-125b, contributing to the accelerated malignant progression of HCC. The study underscored the significantly increased expression of circ_0006168 in both HCC tissues and cell lines, highlighting its association with advanced pathological stages and poor prognosis in HCC patients. Furthermore, circ_0006168 appeared to play a pivotal role in elevating the proliferation rate of HCC cells through its modulation of microRNA-125b. These findings contribute to a deeper understanding of the molecular mechanisms underlying HCC development and may offer potential therapeutic targets for intervention.
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Apoptose , Carcinoma Hepatocelular , Proliferação de Células , Regulação Neoplásica da Expressão Gênica , Neoplasias Hepáticas , MicroRNAs , RNA Circular , Humanos , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/patologia , Carcinoma Hepatocelular/metabolismo , MicroRNAs/genética , MicroRNAs/metabolismo , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/patologia , RNA Circular/genética , RNA Circular/metabolismo , Proliferação de Células/genética , Linhagem Celular Tumoral , Masculino , Feminino , Pessoa de Meia-Idade , Apoptose/genética , Prognóstico , Sequência de Bases , Progressão da DoençaRESUMO
A Gram-stain-negative bacterium with a rod-to-ovoid shape, named strain M216T, was isolated from sand sediment from the coastal intertidal zone of Huludao, Liaoning Province, China. Growth was observed at 8-40 °C (optimal, 30 °C), pH 5.5-9.5 (optimal, pH 6.5) and 0.5-14.0% (w/v) NaCl (optimal, 6%). Strain M216T possessed ubiquinone-9 as its sole respiratory quinone and phosphatidylethanolamine, diphosphatidylglycerol, phosphatidylglycerol, one unidentified aminophosphoglycolipid, one unidentified aminophospholipid, two unidentified phosphoglycolipids, three unidentified phospholipids and three unidentified glycolipids as the main polar lipids. C12:0, C16:0, C12:0 3-OH, C16:1 ω9c, C18:1 ω9c and summed features 3 (C16:1 ω7c and/or C16:1 ω6c) were the major fatty acids (> 5%). The 16S rRNA gene sequence of strain M216T exhibited high similarity to those of 'Marinobacter arenosus' CAU 1620T and Marinobacter adhaerens HP15T (99.3% and 98.5%, respectively) and less than 98.5% similarity to those of the other type strains. The ANI and dDDH values between the strain M216T and 'Marinobacter arenosus' CAU 1620T were 87.4% and 33.3%, respectively; these values were the highest among the other type strains but lower than the species threshold. The G+C content of strain M216T was 58.3%. Genomic analysis revealed that strain M216T harbors the major CAZymes of GH13, GH23, GH73, and PL5, which are responsible for polysaccharide degradation and the potential ability to reduce nitrate to ammonia. Through phenotypic, genotypic, and chemotaxonomic analyses, we proposed the name Marinobacter albus sp. nov., a novel species in the genus Marinobacter, with its type strain M216T (= MCCC 1K08600T = KCTC 82894T).
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Marinobacter , Marinobacter/genética , RNA Ribossômico 16S/genética , Areia , Amônia , ChinaRESUMO
Accurate identification of tumor margins during cancer surgeries relies on a rapid detection technique that can perform high-throughput detection of multiple suspected tumor lesions at the same time. Unfortunately, the conventional histopathological analysis of frozen tissue sections, which is considered the gold standard, often demonstrates considerable variability, especially in many regions without adequate access to trained pathologists. Therefore, there is a clinical need for a multitumor-suitable complementary tool that can accurately and high-throughput assess tumor margins in every direction within the surgically resected tissue. We herein describe a high-throughput three-dimensional (3D) histological electrophoresis device that uses tumor-specific proteins to identify and contour tumor margins intraoperatively. Testing on seven cell-line xenograft models and human cervical cancer models (representing five types of tissues) demonstrated the high-throughput detection utility of this approach. We anticipate that the 3D histological electrophoresis device will improve the accuracy and efficiency of diagnosing a wide range of cancers.
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Eletroforese , Margens de Excisão , Neoplasias , Humanos , Neoplasias/diagnóstico , AnimaisRESUMO
A magnetic field (MF) sensor with a stable structure and high sensitivity has been proposed and experimentally verified. We used the water bath method to produce a layer of Fe2O3 nanorods on a tapered few mode fiber (FMF) surface to form a Mach-Zehnder interferometer (MZI). The experiment found that the nanostructure produced on the surface of FMF were particularly stable and firm. Under the action of an external MF, the magnetic permeability of a Fe2O3 nanorod will change, leading to a change in its refractive index, resulting in a linear shift in the resonance wavelength of MZI. The experimental results showed that the MF sensitivity of MZI reached -0.5348â nm/mT in 10â mTâ¼80â mT. In addition, MZI has a certain sensitivity to environmental humidity and temperature. A long-period fiber grating and a fiber Bragg grating are cascaded with MZI to achieve a simultaneous measurement of three quantities and eliminate their cross-sensitivity.
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A Gram-stain negative, strictly aerobic, and rod-shaped bacterium, designated as strain L182T, was isolated from coastal sediment in Beihai, Guangxi Province, PR China. Colonies of strain L182T were yellow, 2 mm in diameter, round, opaque, smooth and convex after incubation on marine ager at 30 °C for 3 days. Cells were catalase-positive but oxidase-negative. Growth of strain L182T was observed at 4-40 °C (optimum, 25 °C), pH 5.5-10.0 (optimum, pH 5.5-8.0) and with 0-6% (w/v) NaCl (optimum, 0.5-4.0%). The G + C content based on the genome sequence was 36.0%. The only respiratory quinone was MK-6. The main polar lipids included phosphatidylethanolamine, phosphatidylglycerol, one unidentified aminophospholipid, one unidentified glycolipids, four unidentified aminolipids and six unidentified lipids. The major fatty acids (> 10%) were iso-C15:0, iso-C15:1 G and iso-C17:0 3-OH. The 16S rRNA gene sequence similarity between strain L182T and Aestuariibaculum suncheonense SC17T was 98.2%, and the similarities with other type strains of the genus Aestuariibaculum were 96.1-97.2%. The average nucleotide identity and in silicon DNA-DNA hybridization values between the strain L182T and its closely related Aestuariibaculum species were 80.8-85.2% and 22.0-29.5%. According to the above results, Aestuariibaculum lutulentum sp. nov. was proposed as a novel species. The type strain is L182T (= MCCC 1K08065T = KCTC 92530T).
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Ácidos Graxos , Água do Mar , Água do Mar/microbiologia , RNA Ribossômico 16S/genética , Filogenia , China , DNA Bacteriano/genética , Ácidos Graxos/análise , Técnicas de Tipagem Bacteriana , Análise de Sequência de DNA , Vitamina K 2/químicaRESUMO
A Gram-stain-negative, strictly aerobic and rod- to coccoid-shaped bacterium, designated as strain M366T, was isolated from coastal sediment of Jiaoshanjiao, Zhejiang Province, PR China (121°54' E 29â°38' N). The draft genome of strain M366T was 3â225â479 bp long (with 55.6âmol% G+C content) and assembled into four contigs. The N50 value was 563â270 bp and the genomic completeness and contamination were estimated to be 99.34 and 0.05â%, respectively. Colonies of strain M366T were yellow-orange, 1 mm in diameter, round, opaque, smooth and convex after incubation on marine agar at 30 °C for 3 days. Cells were catalase-positive but oxidase-negative. Strain M366T was observed to grow at 20-40â°C (optimum, 30â°C), pH 5.5-9.0 (optimum, pH 6.5-7.0) and with 0.5-8.0â% (w/v) NaCl (optimum, 2.5â%). Strain M366T shown highest 16S rRNA gene sequence similarity of 98.1â% to Robiginitalea sediminis O458T, 95.6-95.9â% to other type strains of the genus Robiginitalea and below 93â% to other genera. The average nucleotide identity and digital DNA-DNA hybridization values between strain M366T and its closely related Robiginitalea species were 71.1-75.9â% and 17.5-19.0â%. Menaquinone-6 was the only respiratory quinone. The major fatty acids (>10â%) were iso-C15â:â0, iso-C17â:â0 3-OH and summed feature 1 (iso-C15â:â1 h and/or C13â:â0 3-OH). The main polar lipids included phosphatidylethanolamine, two unidentified phospholipid, two unidentified aminophospholipid, one unidentified glycolipid and five unidentified lipids. According to the above results, Robiginitalea aestuariiviva sp. nov. is proposed and the type strain is M366T (=KCTC 92866T=MCCC 1K04524T=CGMCC 1.61708T).
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Ácidos Graxos , Composição de Bases , Ácidos Graxos/química , RNA Ribossômico 16S/genética , Filogenia , Análise de Sequência de DNA , DNA Bacteriano/genética , Técnicas de Tipagem Bacteriana , ChinaRESUMO
BACKGROUND: A20 is an anti-inflammatory molecule in nucleus pulposus (NP) cells. The anti-inflammatory properties of A20 are mainly attributed to its ability to suppress the NF-κB pathway. However, A20 can protect cells from death independently of NF-κB regulation. This study aimed to investigate the effects of A20 on pyroptosis and apoptosis of NP cells induced by lipopolysaccharide (LPS). METHODS: NP cells induced by LPS were used as an in vitro model of the inflammatory environment of the intervertebral disc. Pyroptosis, apoptosis, and mitophagy marker proteins were detected. Then, NP cells were transfected with A20 overexpressed lentivirus or A20-siRNA. Annexin V FITC/PI, Western blotting, and immunofluorescence assays were used to detect the apoptosis, pyroptosis, and mitophagy of NP cells. Furthermore, the expressions of A20, related proteins, and related inflammatory cytokines were detected by western blotting, and ELISA. RESULTS: Apoptosis and pyroptosis of NP cells increased gradually treated with LPS for 12 h, 24 h, and 48 h. Differently, the level of mitophagy increased first and then decreased, and was the highest at LPS treatment for 12 h. Overexpression or knockdown of A20 in NP cells revealed that A20 attenuated the pyroptosis, apoptosis, and production of inflammatory cytokines of NP cells induced by LPS, while A20 sponsored mitophagy, reduced ROS production and collapse of mitochondrial membrane potential (ΔΨm). Moreover, A20 also promoted mitochondrial dynamic homeostasis and attenuated LPS-induced excessive mitochondrial fission. Excitingly, inhibition of mitophagy attenuated the effect of A20 on the negative regulation of pyroptosis of NP cells induced by LPS. Pyroptosis was accompanied by a large release of inflammatory cytokines. Inhibition of pyroptosis also significantly reduced apoptosis of NP cells. Finally, The mitochondria-targeted active peptide SS-31 inhibited LPS-induced pyroptosis and ROS production in NP cells. CONCLUSIONS: To sum up, A20 attenuates pyroptosis and apoptosis of NP cells via promoting mitophagy and stabilizing mitochondrial dynamics. Besides, A20 reduces LPS-induced NP cell apoptosis by inhibiting NLRP3 inflammasome-mediated pyroptosis. It provides theoretical support for the reduction of functional NP cell loss in the intervertebral disc through the gene-targeted intervention of A20.
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Núcleo Pulposo , Anti-Inflamatórios/farmacologia , Apoptose , Citocinas/metabolismo , Lipopolissacarídeos/farmacologia , Dinâmica Mitocondrial , Mitofagia , NF-kappa B/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Piroptose , Espécies Reativas de Oxigênio/metabolismoRESUMO
Current pharmacological intervention for the treatment of osteolytic bone diseases such as osteoporosis focuses on the prevention of excessive osteoclastic bone resorption but does not enhance osteoblast-mediated bone formation. In our study, we have shown that 4-iodo-6-phenylpyrimidine (4-IPP), an irreversible inhibitor of macrophage migration inhibitory factor (MIF), can inhibit receptor activator of NF-κB ligand (RANKL)-induced osteoclastogenesis and potentiate osteoblast-mediated mineralization and bone nodule formation in vitro. Mechanistically, 4-IPP inhibited RANKL-induced p65 phosphorylation and nuclear translocation by preventing the interaction of MIF with thioredoxin-interacting protein-p65 complexes. This led to the suppression of late osteoclast marker genes such as nuclear factor of activated T cells cytoplasmic 1, resulting in impaired osteoclast formation. In contrast, 4-IPP potentiated osteoblast differentiation and mineralization also through the inhibition of the p65/NF-κB signaling cascade. In the murine model of pathologic osteolysis induced by titanium particles, 4-IPP protected against calvarial bone destruction. Similarly, in the murine model of ovariectomy-induced osteoporosis, 4-IPP treatment ameliorated the bone loss associated with estrogen deficiency by reducing osteoclastic activities and enhancing osteoblastic bone formation. Collectively, these findings provide evidence for the pharmacological targeting of MIF for the treatment of osteolytic bone disorders.-Zheng, L., Gao, J., Jin, K., Chen, Z., Yu, W., Zhu, K., Huang, W., Liu, F., Mei, L., Lou, C., He, D. Macrophage migration inhibitory factor (MIF) inhibitor 4-IPP suppresses osteoclast formation and promotes osteoblast differentiation through the inhibition of the NF-κB signaling pathway.
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Diferenciação Celular/efeitos dos fármacos , Oxirredutases Intramoleculares/antagonistas & inibidores , Fatores Inibidores da Migração de Macrófagos/antagonistas & inibidores , NF-kappa B/metabolismo , Osteoblastos/efeitos dos fármacos , Pirimidinas/farmacologia , Transdução de Sinais/efeitos dos fármacos , Animais , Reabsorção Óssea , Subunidade alfa 1 de Fator de Ligação ao Core/metabolismo , Feminino , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Osteoblastos/citologia , Osteoblastos/metabolismo , Osteogênese/efeitos dos fármacos , Osteoporose/etiologia , Osteoporose/prevenção & controle , Ovariectomia , Ligante RANK/metabolismoRESUMO
In recent years, new energy vehicles (NEVs) have taken the world by storm. A large number of NEV batteries have been scrapped, and research on NEV battery recycling is important for promoting the sustainable development of NEVs. Battery recycling is an important aspect of the sustainable development of NEVs. In this study, we conducted an in-depth analysis of the current status of research on NEV battery recycling from a new perspective using bibliometric methods and visualization software. This study shows that research targeting the recycling of NEV batteries is growing rapidly, and collaborative networks exist among researchers from different countries, institutions, and fields. The focus of research has shifted from lead-acid batteries to lithium batteries, and the supply chain and circular economy related to NEV battery recycling is an emerging research hotspot. Based on our analysis, we propose that the government should establish policies to improve the recycling networks at the collection stage and provide subsidies to attract consumers. Enterprises should develop low-cobalt and cobalt-free technologies, utilize green solvents, and develop new battery swap modes. The establishment of an information platform is conducive to the further development of collaborative networks.
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BACKGROUND: Hepatocellular carcinoma (HCC) is the most common primary liver cancer worldwide. Cancer cells' local infiltration, proliferation, and spread are mainly influenced by the protein hydrolyzing function of different matrix metalloproteinases (MMPs). However, no study has determined the relationship between MMPs and prognostic prediction in HCC. METHODS: Expression profiles of mRNA and MMPs-related genes were obtained from publicly available databases. Cox regression and LASSO Cox regression analysis were used to identify and predict MMPs-related prognostic signature and construct predictive models for overall survival (OS). A nomogram was used to validate the accuracy of the prediction model. Drug prediction was performed using the Genomics of Drug Sensitivity in Cancer (GDSC) dataset, and single-cell clustering analysis was performed to further understand the significance of the MMPs-related signature. RESULTS: A MMPs-related prognostic signature (including RNPEPL1, ADAM15, ADAM18, ADAMTS5, CAD, YME1L1, AMZ2, PSMD14, and COPS6) was identified. Using the median value, HCC patients in the high-risk group showed worse OS than those in the low-risk group. Immune microenvironment analysis showed that patients in the high-risk group had higher levels of M0 and M2 macrophages. Drug sensitivity analysis revealed that the IC50 values of sorafenib, cisplatin, and cytarabine were higher in the high-risk group. Finally, the single-cell cluster analysis results showed that YME1L1 and COPS6 were the major genes expressed in the monocyte cluster. CONCLUSIONS: A novel MMPs-related signature can be used to predict the prognosis of HCC. The findings of this research could potentially impact the predictability of the prognosis and treatment of HCC.
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Carcinoma Hepatocelular , Neoplasias Hepáticas , Metaloproteinases da Matriz , Microambiente Tumoral , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/mortalidade , Carcinoma Hepatocelular/tratamento farmacológico , Carcinoma Hepatocelular/patologia , Humanos , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/mortalidade , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/patologia , Prognóstico , Metaloproteinases da Matriz/metabolismo , Metaloproteinases da Matriz/genética , Microambiente Tumoral/genética , Regulação Neoplásica da Expressão Gênica , Biomarcadores Tumorais/metabolismo , Biomarcadores Tumorais/genética , Nomogramas , Masculino , Perfilação da Expressão Gênica , Feminino , TranscriptomaRESUMO
BACKGROUND: Cellular senescence features irreversible growth arrest and secretion of multiple proinflammatory cytokines. Cyclic GMP-AMP synthase (cGAS) detects DNA damage and activates the DNA-sensing pathway, resulting in the upregulation of inflammatory genes and induction of cellular senescence. This study aimed to investigate the effect of cGAS in regulating senescence of nucleus pulposus (NP) cells under inflammatory microenvironment. METHODS: The expression of cGAS was evaluated by immunohistochemical staining in rat intervertebral disc (IVD) degeneration model induced by annulus stabbing. NP cells were harvested from rat lumbar IVD and cultured with 10ng/ml IL-1ß for 48 h to induce premature senescence. cGAS was silenced by cGAS specific siRNA in NP cells and cultured with IL-1ß. Cellular senescence was evaluated by senescence-associated beta-galactosidase (SA-ß-gal) staining and flow cytometry. The expression of senescence-associated secretory phenotype including IL-6, IL-8, and TNF-a was evaluated by ELISA and western blotting. RESULTS: cGAS was detected in rat NP cells in cytoplasm and the expression was significantly increased in degenerated IVD. Culturing in 10ng/ml IL-1ß for 48 h induced cellular senescence in NP cells with attenuation of G1-S phase transition. In senescent NP cells the expression of cGAS, p53, p16, NF-kB, IL-6, IL-8, TNF-α was significantly increased while aggrecan and collagen type II was reduced than in normal NP cells. In NP cells with silenced cGAS, the expression of p53, p16, NF-kB, IL-6, IL-8, and TNF-α was reduced in inflammatory culturing with IL-1ß. CONCLUSION: cGAS was increased by NP cells in degenerated IVD promoting cellular senescence and senescent inflammatory phenotypes. Targeting cGAS may alleviate IVD degeneration by reducing NP cell senescence.
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Senescência Celular , Degeneração do Disco Intervertebral , Nucleotidiltransferases , Núcleo Pulposo , Ratos Sprague-Dawley , Senescência Celular/fisiologia , Animais , Núcleo Pulposo/metabolismo , Núcleo Pulposo/patologia , Degeneração do Disco Intervertebral/patologia , Degeneração do Disco Intervertebral/metabolismo , Nucleotidiltransferases/metabolismo , Nucleotidiltransferases/genética , Células Cultivadas , Ratos , Masculino , Inflamação/metabolismo , Inflamação/patologia , Interleucina-1beta/metabolismoRESUMO
Background: YinChen WuLing Powder (YCWLP) has been recommended by consensus for the treatment of non-alcoholic steatohepatitis (NASH); nevertheless, its specific pharmacological mechanisms remain to be elucidated. This study aims to dissect the mechanisms underlying the therapeutic effects of YCWLP on NASH using a hybrid approach that encompasses network pharmacology, molecular docking, and in vitro experimental validation. Methods: We compiled the chemical constituents of YCWLP from the Traditional Chinese Medicine System Pharmacological Database and Analysis Platform (TCMSP), while potential targets were predicted using the SwissTargetPrediction database. To identify NASH-related candidate targets, comprehensive retrieval was carried out using five authoritative databases. Protein-Protein Interaction (PPI) networks of direct targets of YCWLP in NASH treatment were then constructed using the String database, and functional enrichment analyses, including Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway, were conducted through the Database for Annotation, Visualization, and Integrated Discovery (DAVID) database. Core targets were discerned using the Molecular Complex Detection (MCODE) and cytoHubba algorithms. Subsequently, molecular docking of key compounds to core targets was conducted using AutoDock software. Moreover, we established a free fatty acid-induced HepG2 cell model to simulate NASH in vitro, with YCWLP medicated serum intervention employed to corroborate the network pharmacology-derived hypotheses. Furthermore, a combination of enzyme-linked immunosorbent assay (ELISA), and Western blotting analyses was employed to investigate the lipid, hepatic enzyme, SHP2/PI3K/NLRP3 signaling pathway and associated cytokine levels. Results: The network pharmacology analysis furnished a list of 54 compounds from YCWLP and 167 intersecting targets associated with NASH. Through analytic integration with multiple algorithms, PTPN11 (also known as SHP2) emerged as a core target of YCWLP in mitigating NASH. The in vitro experiments validated that 10% YCWLP medicated serum could remarkably attenuate levels of total cholesterol (TC, 1.25 vs. 3.32) and triglyceride (TG, 0.23 vs. 0.57) while ameliorating alanine aminotransferase (ALT, 7.79 vs. 14.78) and aspartate aminotransferase (AST, 4.64 vs. 8.68) leakage in NASH-afflicted cells. In addition, YCWLP significantly enhanced the phosphorylation of SHP2 (0.55 vs. 0.20) and downregulated the expression of molecules within the SHP2/PI3K/NLRP3 signaling axis, including p-PI3K (0.42 vs. 1.02), NLRP3 (0.47 vs. 0.93), along with downstream effectors-cleaved Caspase-1 (0.21 vs. 0.49), GSDMD-NT (0.24 vs. 0.71), mature interleukin-1ß (IL-1ß, 0.17 vs. 0.48), pro-IL-1ß (0.49 vs. 0.89), mature interleukin-18 (IL-18, 0.15 vs. 0.36), and pro-IL-18 (0.48 vs. 0.95). Conclusion: Our research reveals that YCWLP exerts therapeutic effects against NASH by inhibiting lipid accumulation and inflammation, which involves the attenuation of pyroptosis via the SHP2/PI3K/NLRP3 pathway.
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Background: Non-alcoholic fatty liver disease (NAFLD) is a highly prevalent liver disease worldwide and lack of research on the diagnostic utility of mitochondrial regulators in NAFLD. Mitochondrial dysfunction plays a pivotal role in the development and progression of NAFLD, especially oxidative stress and acidity ß-oxidative overload. Thus, we aimed to identify and validate a panel of mitochondrial gene expression biomarkers for detection of NAFLD. Methods: We selected the GSE89632 dataset and identified key mitochondrial regulators by intersecting DEGs, WGCNA modules, and MRGs. Classification of NAFLD subtypes based on these key mitochondrial regulatory factors was performed, and the pattern of immune system infiltration in different NAFLD subtypes were also investigated. RF, LASSO, and SVM-RFE were employed to identify possible diagnostic biomarkers from key mitochondrial regulatory factors and the predictive power was demonstrated through ROC curves. Finally, we validated these potential diagnostic biomarkers in human peripheral blood samples and a high-fat diet-induced NAFLD mouse model. Results: We identified 25 key regulators of mitochondria and two NAFLD subtypes with different immune infiltration patterns. Four potential diagnostic biomarkers (BCL2L11, NAGS, HDHD3, and RMND1) were screened by three machine learning methods thereby establishing the diagnostic model, which showed favorable predictive power and achieved significant clinical benefit at certain threshold probabilities. Then, through internal and external validation, we identified and confirmed that BCL2L11 was significantly downregulated in NAFLD, while the other three were significantly upregulated. Conclusion: The four MRGs, namely BCL2L11, NAGS, HDHD3, and RMND1, are novel potential biomarkers for diagnosing NAFLD. A diagnostic model constructed using the four MRGs may aid early diagnosis of NAFLD in clinics.
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Medical waste incineration ash (MWIA) has significant concentrations of heavy metals, dioxins, and chlorine that, if handled incorrectly, might cause permanent damage to the environment and humans. The low content of calcium (Ca), silicon (Si), and aluminum (Al) is a brand-new challenge for the melting technique of MWIA. This work added coal fly ash (CFA) to explore the effect of melting on the detoxication treatment of MWIA. It was found that the produced vitrification product has a high vitreous content (98.61%) and a low potential ecological risk, with an initial ash solidification rate of 67.38%. By quantitatively assessing the morphological distribution features of heavy metals in ashes before melting and molten products, the stabilization and solidification rules of heavy metals during the melting process were investigated. This work ascertained the feasibility of co-vitrification of MWIA and CFA. In addition, the high-temperature melting and vitrification accelerated the detoxification of MWIA and the solidification of heavy metals.
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Cinza de Carvão , Incineração , Metais Pesados , Vitrificação , Cinza de Carvão/química , Incineração/métodos , Metais Pesados/análise , Resíduos de Serviços de Saúde/análise , Eliminação de Resíduos de Serviços de Saúde/métodosRESUMO
Melting is an efficient method to turn municipal solid waste incineration (MSWI) fly ash (FA) into non-hazardous material. Coal fly ash (CFA) was selected as the silica-alumina source to carry out co-melting research with MSWI FA in this work. The effects of the temperature and the CFA content on mineral transformation and the migration characteristics of heavy metals were analyzed. The results showed that the mixtures of MSWI FA and CFA reacted at high temperatures to mainly generate Ca2Al2SiO7, Ca2SiO4, and CaAl2Si2O8 primarily and then melted and formed the amorphous-phase vitreous body when the CFA content was more than 40% and the temperature was higher than 1300 °C. During the melting process, Cd and Pb were almost volatilized, while Cr, Mn, and Ni were almost retained. Besides, the volatilization rates of Cu and Zn fluctuated with the temperature and the CFA content. Suitable treatment temperature and CFA content were conducive to the transformation of the heavy metals in the FA into stable forms, and the melting products were no longer hazardous wastes because the vitreous body could effectively encapsulate heavy metals. This study aims to help reuse the FA and CFA collaboratively and be more environmentally friendly.
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Cinza de Carvão , Incineração , Metais Pesados , Minerais , Resíduos Sólidos , Cinza de Carvão/química , Minerais/químicaRESUMO
OBJECTIVE: To evaluate the anti-tumor effector of Liuwei Dihuang Decoction (LWDHD) in prostate cancer (PCa) and explore the potential mechanism using experimental validation, network pharmacology, bioinformatics analysis, and molecular docking. METHODS: CCK test, Clone formation assay and wound-healing assays were used to determine the effect of LWDHD on prostate cancer growth and metastasis. The active ingredients and targets of LWDHD were obtained from the TCMSP database, and the relevant targets were selected by GeneCards, OMIM and DisGeNET databases for PCa. The cross-targets of drugs and disease were imported into the STRING database to construct protein interactions. The network was also visualized using Cytoscape software and core targets are screened using the Network Analyzer plug-in. The Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment were analyzed using R software. TCGA database was used to analyze the correlation of bioinformatics genes. AutoDock vina was used to predict the molecular docking and binding ability of active ingredients to key targets. Through WB and q-PCR experiments, the above gene targets were detected to verify the effect of LWDHD on PCa. RESULTS: CCK and scratch tests confirmed that LWDHD could inhibit the proliferation, invasion and migration of prostate cancer cells. Clone formation experiments showed that LWDHD inhibited the long-term proliferative capacity of PC3 cells. LWDHD and PCa had a total of 99 common targets, establishing a "drug-ingredient-common target" network. Through GO and KEGG enrichment analysis, PI3K/AKT, MAPK, TP53 pathway, MYC, TNF pathway and other signaling pathways were found. Bioinformatics analysis showed that MYC gene was highly expressed and CCND1 and MAPK1 were low expressed in prostate cancer tissues. In addition, TP53, AKT1, MYC, TNF and CCND1 were positively correlated with MAPK1, among which AKT1 and CCND1 were most closely correlated with MAPK1. Molecular docking results showed that quercetin, kaempferol, ß-sitosterol and other main active ingredients of LWDHD treatment for PCa were combined with core proteins MAPK1 and AKT1 well. WB and q-PCR results showed that LWDHD inhibited the expression of PI3K and AKT in PC3 cells. CONCLUSION: The mechanism of LWDHD therapy for PCa is a multi-target and multi-pathway complex process, which may be related to the biological processes mediated by MAPK1 and AKT1 pathways, such as cell proliferation and inhibition of metastasis, and the regulation of signaling pathways. The PI3K/AKT signaling pathway may be a central pathway of LWDHD to inhibit prostate cancer proliferation.
Assuntos
Medicamentos de Ervas Chinesas , Simulação de Acoplamento Molecular , Farmacologia em Rede , Neoplasias da Próstata , Masculino , Medicamentos de Ervas Chinesas/farmacologia , Medicamentos de Ervas Chinesas/química , Neoplasias da Próstata/tratamento farmacológico , Humanos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Mapas de Interação de ProteínasRESUMO
Targeting cellular senescence and Senescence Associated Secretory Phenotype (SASP) through autophagy has emerged as a promising intervertebral disc (IVD) degeneration (IDD) treatment strategy in recent years. This study aimed to clarify the role and mechanism of autophagy in preventing IVD SASP. Methods involved in vitro experiments with nucleus pulposus (NP) tissues from normal and IDD patients, as well as an in vivo IDD animal model. GATA4's regulatory role in SASP was validated both in vitro and in vivo, while autophagy modulators were employed to assess their impact on GATA4 and SASP. Transcriptomic sequencing identified Oxidized low-density lipoprotein receptor 1 (OLR1) as a key regulator of autophagy and GATA4. A series of experiments manipulated OLR1 expression to investigate associated effects. Results demonstrated significantly increased senescent NP cells (NPCs) and compromised autophagy in IDD patients and animal models, with SASP closely linked to IDD progression. The aged disc milieu impeded autophagic GATA4 degradation, leading to elevated SASP expression in senescent NPCs. Restoring autophagy reversed senescence by degrading GATA4, hence disrupting the SASP cascade. Moreover, OLR1 was identified for its regulation of autophagy and GATA4 in senescent NPCs. Silencing OLR1 enhanced autophagic activity, suppressing GATA4-induced senescence and SASP expression in senescent NPCs. In conclusion, OLR1 was found to control autophagy-GATA4 and SASP, with targeted OLR1 inhibition holding promise in alleviating GATA4-induced senescence and SASP expression while delaying extracellular matrix degradation, offering a novel therapeutic approach for IDD management.
RESUMO
As a chronic respiratory disease, asthma is related to airway inflammation and remodeling. Macrophages are regarded as main innate immune cells in the airway that exert various functions like antigen recognition and presentation, phagocytosis, and pathogen clearance, playing a crucial role in the pathogeneses of asthma. Non-coding RNAs (ncRNAs), mainly include microRNA, long non-coding RNA and circular RNA, have been extensively investigated on the regulation of pathological process in asthma. Recent studies have indicated that ncRNA-regulated macrophages affect macrophage polarization, airway inflammation, immune regulation and airway remodeling, which suggests that modulating macrophages by ncRNAs may be a promising strategy for the treatment of asthma. This review summarizes the effect of macrophages in asthma and the regulatory mechanisms of ncRNAs, as well as focuses on the role of ncRNAs-regulated macrophages in asthma, for the development of novel therapeutic strategies in this disease.
Assuntos
Asma , MicroRNAs , RNA Longo não Codificante , Humanos , RNA não Traduzido/genética , Asma/genética , Asma/patologia , MicroRNAs/genética , RNA Longo não Codificante/genética , Macrófagos/patologia , Inflamação/patologiaRESUMO
Cyanobacteria are the only prokaryotes capable of oxygenic photosynthesis, which have potential to serve as "autotrophic cell factories". However, the synthesis of biofuels and chemicals using cyanobacteria as chassis are suffered from poor stress tolerance and low yield, resulting in low economic feasibility for industrial production. Thus, it's urgent to construct new cyanobacterial chassis by means of synthetic biology. In recent years, adaptive laboratory evolution (ALE) has made great achievements in chassis engineering, including optimizing growth rate, increasing tolerance, enhancing substrate utilization and increasing product yield. ALE has also made some progress in improving the tolerance of cyanobacteria to high light intensity, heavy metal ions, high concentrations of salt and organic solvents. However, the engineering efficiency of ALE strategy in cyanobacteria is generally low, and the molecular mechanisms underpinning the tolerance to various stresses have not been fully elucidated. To this end, this review summarizes the ALE-associated technical strategies and their applications in cyanobacteria chassis engineering, following by discussing how to construct larger ALE mutation library, increase mutation frequency of strains and shorten evolution time. Moreover, exploration of the construction principles and strategies for constructing multi-stress tolerant cyanobacteria, and efficient analysis the mutant libraries of evolved strains as well as construction of strains with high yield and strong robustness are discussed, with the aim to facilitate the engineering of cyanobacteria chassis and the application of engineered cyanobacteria in the future.