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The development of Zn-ion batteries (ZIBs) is always hindered by the ruleless interface reactions between the solid electrode and liquid electrolyte, and seeking appropriate electrolyte additives is considered as a valid approach to stabilize the electrode/electrolyte interphases for high-performance ZIBs. Benefiting from the unique solubility of TiOSO4 in acidic solution, the composite electrolyte of 2 m ZnSO4+30 mm TiOSO4 (ZSO/TSO) is configured and its positive contribution to Zn//Zn cells, Zn//Cu cells, and Zn//NH4V4O10 batteries are comprehensively investigated by electrochemical tests and theoretical calculations. Based on the theoretical calculations, the introduction of TiOSO4 contributes to facilitating the desolvation kinetics of Zn2+ ions and guarantees the stable interface reactions of both zinc anode and NH4V4O10 cathode. As expected, Zn//Zn cells keep long-term cycling behavior for 3750 h under the test condition of 1 mA cm-2-1 mAh cm-2, Zn//Cu cells deliver high Coulombic efficiency of 99.9% for 1000 cycles under the test condition of 5 mA cm-2-1 mAh cm-2, and Zn//NH4V4O10 batteries maintain reversible specific capacity of 193.8 mAh g-1 after 1700 cycles at 5 A g-1 in ZSO/TSO electrolyte. These satisfactory results manifest that TiOSO4 additive holds great potential to improve the performances of ZIBs.
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BACKGROUND: Nitrile Hydratase (NHase) is one of the most important industrial enzyme widely used in the petroleum exploitation field. The enzyme, composed of two unrelated α- and ß-subunits, catalyzes the conversion of acrylonitrile to acrylamide, releasing a significant amount of heat and generating the organic solvent product, acrylamide. Both the heat and acrylamide solvent have an impact on the structural stability of NHase and its catalytic activity. Therefore, enhancing the stress resistance of NHase to toxic substances is meaningful for the petroleum industry. METHODS AND RESULTS: To improve the thermo-stability and acrylamide tolerance of NHase, the two subunits were fused in vivo using SpyTag and SpyCatcher, which were attached to the termini of each subunit in various combinations. Analysis of the engineered strains showed that the C-terminus of ß-NHase is a better fusion site than the N-terminus, while the C-terminus of α-NHase is the most suitable site for fusion with a larger protein. Fusion of SpyTag and SpyCatcher to the C-terminus of ß-NHase and α-NHase, respectively, led to improved acrylamide tolerance and a slight enhancement in the thermo-stability of one of the engineered strains, NBSt. CONCLUSION: These results indicate that in vivo ligation of different subunits using SpyTag/SpyCatcher is a valuable strategy for enhancing subunit interaction and improving stress tolerance.
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Hidroliases , Rhodococcus , Rhodococcus/enzimologia , Rhodococcus/genética , Hidroliases/metabolismo , Hidroliases/genética , Hidroliases/química , Estabilidade Enzimática , Estresse Fisiológico , Acrilamida/metabolismo , Proteínas de Bactérias/metabolismo , Proteínas de Bactérias/genética , Proteínas de Bactérias/química , Subunidades Proteicas/metabolismo , Subunidades Proteicas/genéticaRESUMO
Protein expression is a critical process in diverse biological systems. For Escherichia coli, a widely employed microbial host in industrial catalysis and healthcare, researchers often face significant challenges in constructing recombinant expression systems. To maximize the potential of E. coli expression systems, it is essential to address problems regarding the low or absent production of certain target proteins. This article presents viable solutions to the main factors posing challenges to heterologous protein expression in E. coli, which includes protein toxicity, the intrinsic influence of gene sequences, and mRNA structure. These strategies include specialized approaches for managing toxic protein expression, addressing issues related to mRNA structure and codon bias, advanced codon optimization methodologies that consider multiple factors, and emerging optimization techniques facilitated by big data and machine learning.
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Escherichia coli , Proteínas Recombinantes , Escherichia coli/genética , Escherichia coli/metabolismo , Proteínas Recombinantes/genética , Proteínas Recombinantes/biossíntese , Proteínas Recombinantes/metabolismo , Códon/genética , RNA Mensageiro/genética , RNA Mensageiro/metabolismoRESUMO
Zinc dendrite, active iodine dissolution, and polyiodide shuttle caused by the strong interaction between liquid electrolyte and solid electrode are the chief culprits for the capacity attenuation of aqueous zinc-iodine batteries (ZIBs). Herein, mullite is adopted as raw material to prepare Zn-based solid-state electrolyte (Zn-ML) for ZIBs through zinc ion exchange strategy. Owing to the merits of low electronic conductivity, low zinc diffusion energy barrier, and strong polyiodide adsorption capability, Zn-ML electrolyte can effectively isolate the redox reactions of zinc anode and AC@I2 cathode, guide the reversible zinc deposition behavior, and inhibit the active iodine dissolution as well as polyiodide shuttle during cycling process. As expected, wide operating voltage window of 2.7 V (vs Zn2+/Zn), high Zn2+ transference number of 0.51, and low activation energy barrier of 29.7 kJ mol-1 can be achieved for the solid-state Zn//Zn cells. Meanwhile, high reversible capacity of 127.4 and 107.6 mAh g-1 can be maintained at 0.5 and 1 A g-1 after 3 000 and 2 100 cycles for the solid-state Zn//AC@I2 batteries, corresponding to high-capacity retention ratio of 85.2% and 80.7%, respectively. This study will inspire the development of mineral-derived solid electrolyte, and facilitate its application in Zn-based secondary batteries.
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TonB-dependent siderophore receptors play a critical transport role for Flavobacterium columnare virulence formation and growth, and have become valuable targets for the development of novel antimicrobial agents. Traditional Chinese medicine has demonstrated notable efficacy in the treatment of fish diseases and includes potential antibacterial agents. Herein, we performed molecular docking-based virtual screening to discover novel TonB-dependent siderophore receptor inhibitors from traditional Chinese medicine and provide information for developing novel antibacterial agents. Firstly, we efficiently obtained 11 potential inhibitors with desirable drug-like characteristics from thousands of compounds in the TCM library based on virtual screening and property prediction. The antibacterial activity of Enoxolone, along with its interaction characteristics, were determined via an MIC assay and molecular dynamic simulation. Transcriptional profiling, along with validation experiments, subsequently revealed that an insufficient uptake of iron ions by bacteria upon binding to the TonB-dependent siderophore receptors is the antibacterial mechanism of Enoxolone. Finally, Enoxolone's acceptable toxicity was illustrated through immersion experiments. In summary, we have used virtual screening techniques for the first time in the development of antimicrobial agents in aquaculture. Through this process, we have identified Enoxolone as a promising compound targeting the TonB-dependent siderophore receptor of F. columnare. In addition, our findings will provide new ideas for the advancement of innovative antimicrobial medications in aquaculture.
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To develop a cost-effective, high-viscosity asphalt for porous asphalt pavement, we utilized SBS, tackifier, and solubilizer as the main raw materials, identified the optimal composition through an orthogonal experiment of three factors and three levels, and prepared a low-cost high-viscosity asphalt. We compared its conventional and rheological properties against those of rubber asphalt, SBS modified asphalt, and matrix asphalt, employing fluorescence microscopy and Fourier transform infrared spectroscopy for microstructural analysis. The results indicate that the optimal formula composition for high-viscosity asphalt was 4-5% styrene-butadiene-styrene (SBS) + 1-2% tackifier +0-3% solubilizer +0.15% stabilizer. The components evenly dispersed and the performances were enhanced with chemical and physical modification. Compared with SBS modified asphalt, rubber asphalt, and matrix asphalt, the softening point, 5 °C ductility, and 60 °C dynamic viscosity of high-viscosity asphalt were significantly improved, while the 175 °C Brookfield viscosity was equivalent to SBS modified asphalt. In particular, the 60 °C dynamic viscosity reaches 383,180 Pa·s. Rheological tests indicate that the high- and low-temperature grade of high-viscosity asphalt reaches 88-18 °C, and that high-viscosity asphalt has the best high-temperature resistance to permanent deformation and low-temperature resistance to cracking. It can save about 30% cost compared to commercially available high-viscosity asphalt, which is conducive to the promotion and application of porous asphalt pavement.
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The recycling bio-waste shells problem has grown more and more serious in recent years and many efforts have been made to solve this problem. One possible solution is to put these bio-shells into concrete and recycle them as building materials using the aggregate matrix concrete approach. To verify the engineering feasibility, the mechanical properties of bio-shells aggregated concrete were invested via gradient substitution rates at 10%, 30%, and 50% with a total of 78 groups of specimens in this paper. Our results show that the mechanical properties of the concrete were enhanced in maximum flexural strength and maximum compressive. Economic performance was also analyzed and found that the costs of frame-shear structure, frame structure, and tube-in-tube structure were reduced by 10.2%, 10%, and 10.3%. The carbon environmental assessment also shows superiority in the carbon reduction of a single specimen with various rates of the shell. In summary, compared with ordinary concrete materials, it is very possible to use waste bio-shells as a substitute for aggregates to develop the sustainable recycling development of concrete materials.
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AIM: Blood-brain barrier (BBB) disorder is one of the early findings in cognitive impairments. We have recently found that Porphyromonas gingivalis bacteraemia can cause cognitive impairment and increased BBB permeability. This study aimed to find out the possible key virulence factors of P. gingivalis contributing to the pathological process. MATERIALS AND METHODS: C57/BL6 mice were infected with P. gingivalis or gingipains or P. gingivalis lipopolysaccharide (P. gingivalis LPS group) by tail vein injection for 8 weeks. The cognitive behaviour changes in mice, the histopathological changes in the hippocampus and cerebral cortex, the alternations of BBB permeability, and the changes in Mfsd2a and Cav-1 levels were measured. The mechanisms of Ddx3x-induced regulation on Mfsd2a by arginine-specific gingipain A (RgpA) in BMECs were explored. RESULTS: P. gingivalis and gingipains significantly promoted mice cognitive impairment, pathological changes in the hippocampus and cerebral cortex, increased BBB permeability, inhibited Mfsd2a expression and up-regulated Cav-1 expression. After RgpA stimulation, the permeability of the BBB model in vitro increased, and the Ddx3x/Mfsd2a/Cav-1 regulatory axis was activated. CONCLUSIONS: Gingipains may be one of the key virulence factors of P. gingivalis to impair cognition and enhance BBB permeability by the Ddx3x/Mfsd2a/Cav-1 axis.
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Barreira Hematoencefálica , Cisteína Endopeptidases Gingipaínas , Camundongos Endogâmicos C57BL , Porphyromonas gingivalis , Fatores de Virulência , Animais , Porphyromonas gingivalis/patogenicidade , Barreira Hematoencefálica/microbiologia , Camundongos , Fatores de Virulência/metabolismo , Adesinas Bacterianas/metabolismo , Masculino , Modelos Animais de Doenças , Permeabilidade , Disfunção Cognitiva/microbiologia , Disfunção Cognitiva/metabolismo , Hipocampo/metabolismo , Infecções por Bacteroidaceae/microbiologia , Infecções por Bacteroidaceae/complicaçõesRESUMO
Glioblastoma is the most lethal primary brain tumor with glioblastoma stem cells (GSCs) atop a cellular hierarchy. GSCs often reside in a perivascular niche, where they receive maintenance cues from endothelial cells, but the role of heterogeneous endothelial cell populations remains unresolved. Here, we show that lymphatic endothelial-like cells (LECs), while previously unrecognized in brain parenchyma, are present in glioblastomas and promote growth of CCR7-positive GSCs through CCL21 secretion. Disruption of CCL21-CCR7 paracrine communication between LECs and GSCs inhibited GSC proliferation and growth. LEC-derived CCL21 induced KAT5-mediated acetylation of HMGCS1 on K273 in GSCs to enhance HMGCS1 protein stability. HMGCS1 promoted cholesterol synthesis in GSCs, favorable for tumor growth. Expression of the CCL21-CCR7 axis correlated with KAT5 expression and HMGCS1K273 acetylation in glioblastoma specimens, informing patient outcome. Collectively, glioblastomas contain previously unrecognized LECs that promote the molecular crosstalk between endothelial and tumor cells, offering potentially alternative therapeutic strategies.
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Neoplasias Encefálicas , Glioblastoma , Humanos , Glioblastoma/terapia , Citocinas/metabolismo , Células Endoteliais/metabolismo , Receptores CCR7/metabolismo , Células-Tronco Neoplásicas/metabolismo , Células-Tronco Neoplásicas/patologia , Proliferação de Células , Colesterol/metabolismoRESUMO
Objective MiRNA-766-3p has been shown to be associated with a variety of cancers. However, few studies have been done in gastric cancer (GC). This study explores the mechanism of miR-766-3p in GC. Methods The potential targets of microRNA (miRNA) were predicted using Tarbase and Targetscan databases. The results are intersected with differential genes (DEGs) (fold change > 1.5, P < 0.05) in gastric cancer to obtain potential core targets. The hub targets screened by constructing PPI networks (degree > 5, expression > 0.5). Validating the differential expression and expression in immunohistochemistry of these targets through the database. And the binding sites between miRNAs and mRNAs were verified using dual-luciferase Assay. Finally, qRT-PCR and Western Blot experiments were conducted to validate the hub targets and signal pathways. Results The potential hub targets from the PPI network were THBS2, COL1A1, FGG, FGB, and PLAU. Combining database, luciferase Assay and experimental validation, miR-766-3p can sponge COL1A1 and it plays the most important role in gastric cancer progression. In GC, COL1A1 was upregulated and the enrichment analysis revealed that COL1A1 regulates PI3K/AKT signal pathway, and AKT is also highly expressed in gastric cancer. Conclusion The miR-766-3p can inhibit the progression of gastric cancer by targeting COL1A1 and regulating the PI3K/AKT signal pathway. It could be a potential therapy option for the GC.
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The intestinal microbiota interacts with the host and plays an important role in the immune response, digestive physiology, and regulation of body functions. In addition, it is also well documented that the intestinal microbiota of aquatic animals are closely related to their growth rate. However, whether it resulted in different sizes of crayfish in the rice-crayfish coculture model remained vague. Here, we analyzed the intestinal microbiota characteristics of crayfish of three sizes in the same typical rice-crayfish coculture field by high-throughput sequencing technology combined with quantitative real-time polymerase chain reaction (qRT-PCR) and enzyme activity, investigating the relationship between intestinal microbiota in crayfish and water and sediments. The results showed that the dominant intestinal microbiota of crayfish was significantly different between the large size group (BS), normal size group (NS), and small size group (SS), where Bacteroides and Candidatus_Bacilloplasma contributed to the growth of crayfish by facilitating food digestion through cellulolysis, which might be one of the potential factors affecting the difference in sizes. Follow-up experiments confirmed that the activity of lipase (LPS) and protease was higher in BS, and the relative expression of development-related genes, including alpha-amylase (α-AMY), myocyte-specific enhancer factor 2a (MEF2a), glutathione reductase (GR), chitinase (CHI), and ecdysone receptor (EcR), in BS was significantly higher than that in SS. These findings revealed the intestinal microbiota characteristics of crayfish of different sizes and their potential impact on growth, which is valuable for managing and manipulating the intestinal microbiota in crayfish to achieve high productivity in practice. KEY POINTS: ⢠Significant differences in the dominant microflora of BS, NS, and SS in crayfish. ⢠Cellulolysis might be a potential factor affecting different sizes in crayfish. ⢠Adding Bacteroides and Candidatus_Bacilloplasma helped the growth of crayfish.
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Microbioma Gastrointestinal , Microbiota , Oryza , Animais , Astacoidea , Alimentos Marinhos , BacteroidesRESUMO
Because of the low host specificity, Ichthyophthirius multifiliis (Ich) can widely cause white spot disease in aquatic animals, which is extremely difficult to treat. Prior research has demonstrated a considerable impact of concentrated mannan-oligosaccharide (cMOS) on the prevention of white spot disease in goldfish, but the specific mechanism is still unknown. In this study, transcriptome sequencing, histological analysis, immunofluorescence analysis, phagocytosis activity assay and qRT-PCR assay were used to systematically reveal the potential mechanism of cMOS in supporting the resistance of goldfish (Carrasius auratus) to Ich invasion. According to the transcriptome analysis, the gill tissue of goldfish receiving the cMOS diet showed greater expression of mannose-receptor (MRC) related genes, higher phagocytosis activity, up-regulated expression of phagocytosis-related genes and inflammatory-related genes compared with the control, indicating that cMOS can have an effect on phagocytosis and non-specific immunity of goldfish. After the Ich challenge, transcriptome analysis revealed that cMOS fed goldfish displayed a higher level of phagocytic response, whereas non-cMOS fed goldfish displayed a greater inflammatory reaction. Besides, after Ich infection, cMOS-fed goldfish displayed greater phagocytosis activity, a stronger MRC positive signal, higher expression of genes associated with phagocytosis (ABCB2, C3, MRC), and lower expression of genes associated with inflammation (IL-1ß, IL-17, IL-8, TNF-α, NFKB). In conclusion, our experimental results suggest that cMOS may support phagocytosis by binding to MRC on the macrophage cell membrane and change the non-specific immunity of goldfish by stimulating cytokine expression. The results of this study provide new insights for the mechanism of cMOS on parasitic infection, and also suggest phagocytosis-related pathways may be potential targets for prevention of Ich infection.
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Doenças dos Peixes , Carpa Dourada , Animais , Mananas/farmacologia , Citocinas/genética , Macrófagos/metabolismo , FagocitoseRESUMO
Gastric cancer (GC) is one of the most common malignancies worldwide and the leading cause of cancer-related deaths. Exosomes are nanoscale extracellular vesicles secreted by a variety of cells and play an important role in cellular communication and epigenetics by transporting bioactive substances in the tumor microenvironment (TME). Circular RNA (circRNA) is a type of non-coding RNA (ncRNA) with a specific structure, which is widely enriched in exosomes and is involved in various pathophysiological processes mediated by exosomes. Exosomal circRNAs play a critical role in the development of GC by regulating epithelial-mesenchymal transition (EMT), angiogenesis, proliferation, invasion, migration, and metastasis of GC. Given the biological characteristics of exosomal circRNAs, they have more significant diagnostic sensitivity and specificity in the clinic and may become biomarkers for GC diagnosis and prognosis. In this review, we briefly describe the biogenesis of exosomes and circRNAs and their biological functions, comprehensively summarize the mechanisms of exosomal circRNAs in the development of GC and chemotherapy resistance, and finally, we discuss the potential clinical application value and challenges of exosomal circRNAs in GC.
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Eucommia ulmoides Oliver (EuO) is a natural medicine that can improve the composition of intestinal flora in fish, but more experiments and data are needed to support whether it can effectively improve the changes of intestinal flora and intestinal damage caused by high starch. This study examined the changes in intestinal structure as well as intestinal flora before and after the addition of EuO to high-starch diets and analyzed the effects of such changes on immune and digestive functions. The results showed that EuO reduces mortality during Nocardia seriolae attack and can reduce starch-induced intestinal inflammation. Eucommia ulmoides Oliver supplementation was able to alter the changes of intestinal flora in fatty acid degradation, bacterial chemotaxis, porphyrin metabolism and flagella assembly caused by high starch. By analyzing the abundance and correlation of bacterial communities, three bacterial communities that were significantly related to the intervention effect of EuO were screened. Further analysis revealed that EuO supplementation reduced the increase in abundance of Limnochordaceae, Nitrolancea, Lysinibacillus, and Hydrogenispora induced by high starch, which were negatively correlated with levels of the immunoreactive substance LZM in fish. This study reveals the regulatory effects of EuO on the intestinal flora of Micropterus salmoides fed on high starch diets, and provides a theoretical basis for reducing starch damage to fish in production.
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Elizabethkingia miricola is an emerging opportunistic pathogen that is highly pathogenic in both immunocompromised humans and animals. Once the disease occurs, treatment can be very difficult. Therefore, a deep understanding of the pathological mechanism of Elizabethkingia miricola is the key to the prevention and control of the disease. In this study, we isolated the pathogenic bacteria from bullfrogs with dark skin color, weak limbs, wryneck, and cataracts. Via subsequent morphological observations and a 16S rRNA gene sequence analysis, the pathogen was identified as Elizabethkingia miricola. The histopathological and transmission electron microscopy analysis revealed that the brain was the main target organ. Therefore, brain samples from diseased and healthy bullfrogs were used for the RNA-Seq analysis. The comparative transcriptome analysis revealed that the diseased bullfrog brain was characterized by the immune activation and inflammatory response, which were mediated by the "NOD-like receptor signaling pathway" and the "Toll-like receptor signaling pathway". We also performed qRT-PCR to examine the expression profile of inflammation-related genes, which further verified the reliability of our transcriptome data. Based on the above results, it was concluded that the NOD/Toll-like receptor-related networks that dominate the immune activation and inflammatory response were activated in the brain of Elizabethkingia miricola-infected bullfrogs. This study contributes to the search for therapeutic targets for bullfrog meningitis and provides basic information for establishing effective measures to prevent and control bullfrog meningitis.
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Infecções por Flavobacteriaceae , Flavobacteriaceae , Meningite , Animais , Humanos , Rana catesbeiana , RNA Ribossômico 16S/genética , Reprodutibilidade dos Testes , Infecções por Flavobacteriaceae/microbiologia , Infecções por Flavobacteriaceae/patologia , Ranidae , Transdução de SinaisRESUMO
The development of polymer-modified asphalt (asphalt = asphalt binder) is significant because the polymer modifier can improve the performance of asphalt mixture and meet the requirements of the modern asphalt pavement. Herein, we present a novel polysiloxane-modified asphalt with enhanced performance, formed by simply mixing hydroxy-terminated polysiloxane (HO-PDMS) into base asphalt at 140 °C. The interaction mechanism of HO-PDMS in base asphalt was characterized by FT-IR, GPC, and DSC. It reveals that HO-PDMS polymers have been chemically bonded into the asphalt, and, thus, the resultant asphalt exhibits optimal compatibility and storage stability. The results based on fluorescence microscopy and a segregation test prove that HO-PDMS has good compatibility with base asphalt. Moreover, by virtue of the intriguing properties of polysiloxane, the present asphalt possesses improved low- and high-temperature properties, higher thermal stability, and enhanced hydrophobicity compared to conventional asphalt when using an appropriate dosage of HO-PDMS. DSC indicated that the Tg of modified asphalt (-12.8 °C) was obviously lower than that of base asphalt (-7.1 °C). DSR shows that the rutting parameter of modified asphalt was obviously higher than that of base asphalt. BBR shows that modified asphalt exhibited the lowest stiffness modulus and the highest creep rate with an HO-PDMS dosage of 6% and 4%, respectively. These results demonstrate that polysiloxane-modified asphalt can be promisingly utilized in realistic asphalt pavement with specific requirements, particularly high-/low-temperature resistance.
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Small cell lung cancer (SCLC) is highly lethal due to its prevalent metastasis. Most SCLCs have inactivating mutations in TP53 and RB1. We find that loss of YAP expression is key for SCLC cells to acquire rapid ameboid migration and high metastatic potential. YAP functions through its target genes CCN1/CCN2 to inhibit SCLC ameboid migration. RB1 mutation contributes to YAP transcriptional silencing via E2F7, which recruits the RCOR co-repressor complex to YAP promoter. We discover that benzamide family HDAC inhibitors stimulate YAP expression by inhibiting the RCOR-HDAC complex, thereby suppressing SCLC metastasis and improving survival in a mouse model. Our study unveils the molecular and cellular basis underlying SCLC's high metastatic potential, the previously unrecognized role of YAP in suppressing ameboid migration and tumor metastasis, and the mechanism of YAP transcription regulation involving E2F7, RCOR, and Sin3 HDAC. This study reveals a therapeutic potential of benzamides for SCLC treatment.
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Antipsicóticos , Neoplasias Pulmonares , Carcinoma de Pequenas Células do Pulmão , Animais , Humanos , Camundongos , Mutação com Perda de Função , Neoplasias Pulmonares/genética , Mutação , Carcinoma de Pequenas Células do Pulmão/genéticaRESUMO
ETHNOPHARMACOLOGICAL RELEVANCE: The efficacy of the herbal formula Huosu-Yangwei (HSYW) in the treatment of advanced gastric cancer and chronic atrophic gastritis with precancerous lesions has been reported in clinical trials. However, the molecular mechanisms underlying its inhibition of gastric tumor are not well-understood. AIM OF THE STUDY: Combined with transcriptomics and systems network-based molecular mechanism to explore the potential circRNA-miRNA-mRNA network of HSYW in the treatment of gastric cancer. MATERIALS AND METHODS: Animal experiments were conducted to investigate the effect of HSYW on tumor growth in vivo. RNA sequencing (RNA-seq) was implemented to identify the differentially expressed (DE) genes. Predictive miRNA targets and mRNA were used to construct circRNA-miRNA-mRNA networks and protein-protein interaction (PPI) networks. Quantitative real-time PCR (qRT-PCR) was utilized to verify the accuracy of the proposed circRNA-miRNA-mRNA networks. Additionally, the differentially expressed target proteins between gastric cancer (GC) and normal patients were assessed using data from the TCGA (The Cancer Genome Atlas) and HPA (The Human Protein Atlas) databases. RESULTS: We demonstrate HSYW significantly inhibits tumor growth of N87 cell-bearing Balb/c mice. Transcriptomic analysis revealed the existence of 119 differentially expressed (DE) circRNAs and 200 DE mRNAs between HSYW-treated and model mice. By associating predicted circRNA-miRNA pairs and miRNA-mRNA pairs, we constructed a circRNA-miRNA-mRNA (CMM) network. Furthermore, a protein-protein interaction (PPI) network was developed using the differential expressed mRNAs. Consequently, the reconstructed core CMM network and qRT-PCR validation indicated that 4 circRNAs, 5 miRNAs and 6 mRNAs could potentially serve as biomarkers to assess the therapeutic effects of HSYW-treated N87-bearing Balb/c mice. The TCGA and HPA databases also demonstrated that mRNA KLF15 and PREX1 had substantial differences between gastric cancer (GC) and healthy controls. CONCLUSIONS: By combining the experimental and bioinformatics analysis, this study confirms that the circRNA_00240/hsa-miR-642a-5p/KLF15 and circRNA_07980/hsa-miR-766-3p/PREX1 pathways play critical roles in HSYW-treated gastric cancer.
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MicroRNAs , Neoplasias Gástricas , Humanos , Camundongos , Animais , RNA Circular/genética , Neoplasias Gástricas/tratamento farmacológico , Neoplasias Gástricas/genética , Transcriptoma , MicroRNAs/genética , MicroRNAs/metabolismo , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Redes Reguladoras de GenesRESUMO
The Arf family proteins are best known for their roles in the vesicle biogenesis. However, they also play fundamental roles in a wide range of cellular regulation besides vesicular trafficking, such as modulation of lipid metabolic enzymes, cytoskeleton remodeling, ciliogenesis, lysosomal, and mitochondrial morphology and functions. Growing studies continue to expand the downstream effector landscape of Arf proteins, especially for the less-studied members, revealing new biological functions, such as amino acid sensing. Experiments with cutting-edge technologies and in vivo functional studies in the last decade help to provide a more comprehensive view of Arf family functions. In this review, we summarize the cellular functions that are regulated by at least two different Arf members with an emphasis on those beyond vesicle biogenesis.
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Fatores de Ribosilação do ADP , Fatores de Ribosilação do ADP/metabolismoRESUMO
Soundscape is an important part and one of the main factors of the underground space environment. Field surveys were conducted to evaluate the soundscape of underground commercial spaces and to compare it with the soundscape of the above-ground commercial spaces between two cities (Lu'an City and Hefei City) in China, consequently presenting the construction strategy of the soundscape of underground commercial spaces in urban areas. The results showed that the sound in the shopping center, which people found comfortable, was at the lower to intermediate level. The main sounds that people perceived as "general" sounds were environmental sounds such as music, the humming of the air conditioning, people talking, walking, and the hawking of the stores. Nevertheless, "very comfortable" sounds were background music and the sound of live performances, which were indicated in the majority of people's opinions on evaluating a comfortable feeling, thus reflecting the impact of the sound of mall music on people's cognitive psychology. Therefore, it is necessary to control the volume of environmental noise at a certain level so that people's health is not adversely affected. It also helps shoppers to feel more comfortable psychologically and physiologically.