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We study a quasi-one-dimensional non-reciprocal Hermitian hourglass photonic lattice that can accomplish multiple functions. Under the effect of non-reciprocal coupling, this lattice can produce an energy isolation effect, two kinds of flatbands, and energy band inversion. The excitation and propagation of a single energy band and multiple energy bands can be realized; in the flatband condition, the system has compact localized states, and the flatbands can be excited by a straightforward method. Our findings advance the theory of energy band regulation in artificial photonic lattices.
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The prevalence and clinical correlates of antibiotic resistance genes (ARGs) in bronchiectasis are not entirely clear. We aimed to profile the ARGs in sputum from adults with bronchiectasis, and explore the association with airway microbiome and disease severity and subtypes. In this longitudinal study, we prospectively collected 118 sputum samples from stable and exacerbation visits of 82 bronchiectasis patients and 19 healthy subjects. We profiled ARGs with shotgun metagenomic sequencing, and linked these to sputum microbiome and clinical characteristics, followed by validation in an international cohort. We compared ARG profiles in bronchiectasis according to disease severity, blood and sputum inflammatory subtypes. Unsupervised clustering revealed a Pseudomonas predominant subgroup (n = 16), Haemophilus predominant subgroup (n = 48), and balanced microbiome subgroup (N = 54). ARGs of multi-drug resistance were over-dominant in the Pseudomonas-predominant subgroup, while ARGs of beta-lactam resistance were most abundant in the Haemophilus-predominant subgroup. Pseudomonas-predominant subgroup yielded the highest ARG diversity and total abundance, while Haemophilus-predominant subgroup and balanced microbiota subgroup were lowest in ARG diversity and total abundance. PBP-1A, ksgA and emrB (multidrug) were most significantly enriched in Haemophilus-predominant subtype. ARGs generally correlated positively with Bronchiectasis Severity Index, fluoroquinolone use, and modified Reiff score. 68.6% of the ARG-clinical correlations could be validated in an independent international cohort. In conclusion, ARGs are differentially associated with the dominant microbiome and clinical characteristics in bronchiectasis.
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Bronquiectasia , Haemophilus , Adulto , Humanos , Pseudomonas , Estudos Longitudinais , Bronquiectasia/diagnóstico , Bronquiectasia/genética , Sistema Respiratório , Antibacterianos/uso terapêuticoRESUMO
We propose a mechanism to achieve the group velocity control of bifurcation light via an imaginary coupling effect in the non-reciprocal lattice. The physical model is composed of two-layer photonic lattices with non-reciprocal coupling in each unit cell, which can support a real energy spectrum with a pair of Dirac points due to the hermicity. Furthermore, we show that the systems experience topological phase transition at the Dirac points, allowing the existence of topological edge states on the left or right boundaries of respective lattice layers. By adjusting the imaginary coupling and the wave number, the group velocity of the light wave can be manipulated, and bifurcation light transmission can be achieved both at the Dirac points and the condition without the group velocity dispersion. Our work might guide the design of photonic directional couplers with group velocity control functions.
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RNA-binding motif protein 10 (RBM10) primarily regulates alternative splicing of certain genes. Loss-of-function mutations in RBM10 have been frequently reported in patients with various cancers. However, how RBM10 levels affect cell proliferation and tumorigenesis remains unknown. To elucidate the role of RBM10 in cell proliferation, we established HepG2-RBM10 knockout cell lines and derivative doxycycline-inducible RBM10-expressing cells. RBM10 over-expression caused growth arrest in the M phase with a monopolar spindle because of impaired centriole duplication. Two RBM10 splicing mutants, one with F345A/F347A and the other with only the C-terminal half (401-930), were sufficient to cause growth arrest, whereas an RBM10 mutant with cytoplasmic localization forced by an NES did not show growth arrest. RBM10 over-expression induced the formation of many large nuclear domains containing RBM10, PLK4, STIL and SAS6, which are the regulatory proteins involved in centriole duplication. Consistently, the centrioles in the RBM10-over-expressing HepG2 cells lost PLK4 and STIL, accounting for the unsuccessful centriole duplication. In contrast, RBM10 depletion resulted in elevated levels of cytoplasmic PLK4 with a concomitant increase in the number of centrioles in HepG2 cells but not in A549 cells. Thus, nuclear RBM10 regulates normal chromosomal division in a cell-type-specific manner, independent of alternative RNA splicing.
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Núcleo Celular/metabolismo , Centríolos/metabolismo , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Proteínas Serina-Treonina Quinases/metabolismo , Proteínas de Ligação a RNA/genética , Proteínas de Ligação a RNA/metabolismo , Carcinogênese/genética , Ciclo Celular/genética , Ciclo Celular/fisiologia , Proteínas de Ciclo Celular/metabolismo , Proliferação de Células , Regulação da Expressão Gênica , Técnicas de Inativação de Genes , Células Hep G2 , Humanos , TranscriptomaRESUMO
Signal transducer and activator of transcription 3 (STAT3) is involved in many biological processes, including immunity and cancer. STAT3 becomes phosphorylated at Tyr705 and Ser727 on IL-6 stimulation. Phospho-Tyr705 (pY705) stabilizes the STAT3 dimer with reciprocal interactions between pY705 and the SH2 of the other molecule and phospho-Ser727 (pS727) accelerates pY705 dephosphorylation. We study how pS727 regulates STAT3 in both structural and biological perspectives. Using STAT3 reconstituted in HepG2-stat3-knockout cells, we show that pS727, together with a handshake N-terminal domain (NTD) interaction, causes rapid inactivation of STAT3 for pY705 dephosphorylation and a chromosome region maintenance 1 (CRM1)-independent nuclear export, which is critical for faithful STAT3 response to the cellular signals. The various N-terminal tags, GFP-related Ruby and FLAG, rendered the export CRM1-dependent and especially FLAG-tag caused nuclear accumulation of STAT3, indicating the presence of conformational changes in inactivation. Impaired reactivation of STAT3 by S727A or FLAG-tag delayed or inhibited the IL-6-induced saa1 mRNA expression, respectively. The detailed analysis of the pY705-SH2 structure identified the C-terminal tail (CTT) from L706 to P715 as a key regulator of the CTT-CTT intermolecular and the CTT-SH2 intramolecular interactions that support pY705-SH2 association. The functional studies using multiple STAT3 mutants indicated that the degree of the two interactions determines the stability of pY705-SH2 interaction. Importantly, Pro715 was critical for the pS727's destabilizing activity and the known phosphorylation and acetylation at the CTT structurally inhibited the pY705-SH2 interaction. Thus, pS727 triggers pY705-SH2 dissociation by weakening the supportive interactions likely through CTT modulation, inducing rapid cycles of STAT3 activation-inactivation for proper function of STAT3.
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Fator de Transcrição STAT3/imunologia , Serina/imunologia , Tirosina/imunologia , Células Cultivadas , Células HEK293 , Células Hep G2 , Humanos , Fosforilação , Fator de Transcrição STAT3/deficiência , Fator de Transcrição STAT3/genética , Domínios de Homologia de src/imunologiaRESUMO
With the global rise in cancer incidence and mortality rates, research on the topic has become increasingly urgent. Among the significant players in this field are heat shock proteins (HSPs), particularly HSPA4 from the HSP70 subfamily, which has recently garnered considerable interest for its role in cancer progression. However, despite numerous studies on HSPA4 in specific cancer types, a comprehensive analysis across all cancer types is lacking. This study employs various bioinformatics techniques to delve into the role of HSPA4 in pan-cancer. Our objective is to assess its potential in clinical diagnosis, prognosis, and as a future molecular target for therapy. The research findings reveal significant differences in HSPA4 expression across different cancer types, suggesting its diagnostic value and close association with cancer staging and patient survival rates. Furthermore, genetic variations and methylation status of HSPA4 play critical roles in tumorigenesis. Lastly, the interaction of HSPA4 with immune cells is linked to the tumor microenvironment (TME) and immunotherapy. In summary, HSPA4 emerges as a promising cancer biomarker and a vital member of the HSPs family, holding potential applications in diagnosis, prognosis, and immunotherapy.
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Proteínas de Choque Térmico HSP110 , Neoplasias , Humanos , Proteínas de Choque Térmico HSP110/genética , Proteínas de Choque Térmico HSP110/metabolismo , Prognóstico , Neoplasias/diagnóstico , Neoplasias/genética , Neoplasias/terapia , Proteínas de Choque Térmico HSP70/genética , Proteínas de Choque Térmico/genética , Imunoterapia , Microambiente Tumoral/genéticaRESUMO
Systemic lupus erythematosus (SLE) is a complex autoimmune disorder with a pathogenesis that remains incompletely understood, resulting in limited treatment options. MCC950, a highly specific NLRP3 inflammasome inhibitor, effectively suppresses the activation of NLRP3, thus reducing the production of caspase-1, the pro-inflammatory cytokines IL-1ß and IL-18. This review highlights the pivotal role of NLRP3 inflammasome activation pathways in the pathogenesis of SLE and discusses the potential therapeutic application of MCC950 in SLE. Notably, it comprehensively elucidates the mechanism of MCC950 targeting the NLRP3 pathway in SLE treatment, outlining its potential role in regulating autophagy and necroptosis. The insights gained contribute to a deeper understanding of the value of MCC950 in SLE therapy, serving as a robust foundation for further research and potential clinical applications.
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Doenças Autoimunes , Indenos , Lúpus Eritematoso Sistêmico , Humanos , Inflamassomos , Proteína 3 que Contém Domínio de Pirina da Família NLR , Lúpus Eritematoso Sistêmico/tratamento farmacológico , Furanos/uso terapêutico , Indenos/uso terapêutico , SulfonamidasRESUMO
Objective: The objective of this study is to elucidate the influence of MCU on the clinical pathological features of GC patients, to investigate the function and mechanism of the mitochondrial calcium uptake transporter MCU in the initiation and progression of GC, and to explore its impact on the metabolic pathways and biosynthesis of mitochondria. The ultimate goal is to identify novel targets and strategies for the clinical management of GC patients. Methods: Tumor and adjacent tissue specimens were obtained from 205 patients with gastric cancer, and immunohistochemical tests were performed to assess the expression of MCU and its correlation with clinical pathological characteristics and prognosis. Data from TCGA, GTEx and GEO databases were retrieved for gastric cancer patients, and bioinformatics analysis was utilized to investigate the association between MCU expression and clinical pathological features. Furthermore, we conducted an in-depth analysis of the role of MCU in GC patients. We investigated the correlation between MCU expression in GC and its impact on mitochondrial function, metabolism, biosynthesis, and immune cells. Additionally, we studied the proteins or molecules that interact with MCU. Results: Our research revealed high expression of MCU in the GC tissues. This high expression was associated with poorer T and N staging, and indicated a worse disease-free survival period. MCU expression was positively correlated with mitochondrial function, mitochondrial metabolism, nucleotide, amino acid, and fatty acid synthesis metabolism, and negatively correlated with nicotinate and nicotinamide metabolism. Furthermore, the MCU also regulates the function of the mitochondrial oxidative respiratory chain. The MCU influences the immune cells of GC patients and regulates ROS generation, cell proliferation, apoptosis, and resistance to platinum-based drugs in gastric cancer cells. Conclusion: High expression of MCU in GC indicates poorer clinical outcomes. The expression of the MCU are affected through impacts the function of mitochondria, energy metabolism, and cellular biosynthesis in gastric cancer cells, thereby influencing the growth and metastasis of gastric cancer cells. Therefore, the mitochondrial changes regulated by MCU could be a new focus for research and treatment of GC.
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For some food applications, it is desirable to control the flavor release profiles of volatile flavor compounds. In this study, the effects of crosslinking method and protein composition on the flavor release properties of emulsion-filled protein hydrogels were explored, using peppermint essential oil as a model volatile compound. Emulsion-filled protein gels with different properties were prepared using different crosslinking methods and gelatin concentrations. Flavor release from the emulsion gels was then monitored using an electronic nose, gas chromatography-mass spectrometry (GC-MS), and sensory evaluation. Enzyme-crosslinked gels had greater hardness and storage modulus than heat-crosslinked ones. The hardness and storage modulus of the gels increased with increasing gelatin concentration. For similar gel compositions, flavor release and sensory perception were faster from the heat-crosslinked gels than the enzyme-crosslinked ones. For the same crosslinking method, flavor release and perception decreased with increasing gelatin concentration, which was attributed to retardation of flavor diffusion through the hydrogel matrix. Overall, this study shows that the release of hydrophobic aromatic substances can be modulated by controlling the composition and crosslinking of protein hydrogels, which may be useful for certain food applications.
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Emulsões , Aromatizantes , Cromatografia Gasosa-Espectrometria de Massas , Mentha piperita , Óleos de Plantas , Mentha piperita/química , Emulsões/química , Humanos , Óleos de Plantas/química , Aromatizantes/química , Gelatina/química , Reagentes de Ligações Cruzadas/química , Paladar , Hidrogéis/química , Nariz Eletrônico , Masculino , Feminino , AdultoRESUMO
Interleukin 12 (IL-12) is a potent immunostimulatory cytokine mainly produced by antigen-presenting cells (e.g., dendritic cells, macrophages) and plays an important role in innate and adaptive immunity against cancers. Therapies that can synergistically modulate innate immunity and stimulate adaptive anti-tumor responses are of great interest for cancer immunotherapy. Here we investigated the lipid nanoparticle-encapsulated self-replicating RNA (srRNA) encoding IL-12 (referred to as JCXH-211) for the treatment of cancers. Both local (intratumoral) and systemic (intravenous) administration of JCXH-211 in tumor-bearing mice induced a high-level expression of IL-12 in tumor tissues, leading to modulation of tumor microenvironment and systemic activation of antitumor immunity. Particularly, JCXH-211 can inhibit the tumor-infiltration of polymorphonuclear myeloid-derived suppressor cells (PMN-MDSCs). When combined with anti-PD1 antibody, it was able to enhance the recruitment of T cells and NK cells into tumors. In multiple mouse solid tumor models, intravenous injection of JCXH-211 not only eradicated large preestablished tumors, but also induced protective immune memory that prevented the growth of rechallenged tumors. Finally, intravenous injection of JCXH-211 did not cause noticeable systemic toxicity in tumor-bearing mice and non-human primates. Thus, our study demonstrated the feasibility of intravenous administration of JCXH-211 for the treatment of advanced cancers.
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Lipossomos , Nanopartículas , Neoplasias , Camundongos , Animais , Interleucina-12/genética , Imunidade Adaptativa , Imunoterapia , Administração Intravenosa , Microambiente Tumoral , Linhagem Celular TumoralRESUMO
In pyloric metaplasia, mature gastric chief cells reprogram via an evolutionarily conserved process termed paligenosis to re-enter the cell cycle and become spasmolytic polypeptide-expressing metaplasia (SPEM) cells. Here, we use single-cell RNA sequencing (scRNA-seq) following injury to the murine stomach to analyze mechanisms governing paligenosis at high resolution. Injury causes induced reactive oxygen species (ROS) with coordinated changes in mitochondrial activity and cellular metabolism, requiring the transcriptional mitochondrial regulator Ppargc1a (Pgc1α) and ROS regulator Nf2el2 (Nrf2). Loss of the ROS and mitochondrial control in Ppargc1a-/- mice causes the death of paligenotic cells through ferroptosis. Blocking the cystine transporter SLC7A11(xCT), which is critical in lipid radical detoxification through glutathione peroxidase 4 (GPX4), also increases ferroptosis. Finally, we show that PGC1α-mediated ROS and mitochondrial changes also underlie the paligenosis of pancreatic acinar cells. Altogether, the results detail how metabolic and mitochondrial changes are necessary for injury response, regeneration, and metaplasia in the stomach.
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Sistema y+ de Transporte de Aminoácidos , Ferroptose , Metaplasia , Coativador 1-alfa do Receptor gama Ativado por Proliferador de Peroxissomo , Espécies Reativas de Oxigênio , Regeneração , Estômago , Animais , Espécies Reativas de Oxigênio/metabolismo , Camundongos , Ferroptose/fisiologia , Estômago/patologia , Regeneração/fisiologia , Sistema y+ de Transporte de Aminoácidos/metabolismo , Sistema y+ de Transporte de Aminoácidos/genética , Metaplasia/metabolismo , Coativador 1-alfa do Receptor gama Ativado por Proliferador de Peroxissomo/metabolismo , Coativador 1-alfa do Receptor gama Ativado por Proliferador de Peroxissomo/genética , Mitocôndrias/metabolismo , Fator 2 Relacionado a NF-E2/metabolismo , Fator 2 Relacionado a NF-E2/genética , Mucosa Gástrica/metabolismo , Camundongos Endogâmicos C57BL , Celulas Principais Gástricas/metabolismo , Células Acinares/metabolismo , Camundongos Knockout , Fosfolipídeo Hidroperóxido Glutationa Peroxidase , Peptídeos e Proteínas de Sinalização IntercelularRESUMO
Exploring efficient and low-cost bifunctional catalysts for hydrogen evolution reaction (HER) and hydrogen oxidation reaction (HOR) is highly desirable for the achievement of unitized regenerative fuel cells. Herein, a facile method to prepare hetero-interfacial Ni-Ni0.2 Mo0.8 N nanosheets with tailored d-band for efficient alkaline hydrogen electrocatalysis is presented. Mechanism studies indicate that interface engineering can downshift the d-band center of Ni-Ni0.2 Mo0.8 N nanosheets due to the electron transfer from Ni to Ni0.2 Mo0.8 N, which weakens the binding strength of reaction intermediates, thereby boosting the catalytic performance. Relative to pure Ni, Ni-Ni0.2 Mo0.8 N nanosheets show a lower overpotential of 83â mV at -10â mA cm-2 and good stability during 2,000 cycles for HER. Meanwhile, Ni-Ni0.2 Mo0.8 N nanosheets exhibit an improved exchange current density for HOR with a 10.2-fold enhancement in comparison with that of pure Ni. This work provides valuable insight into the reasonable design of efficient energy-related electrocatalysts based on the tailoring of d-band center by interface engineering.
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Introduction: Increasing evidence suggests that seasonal changes can trigger the alternation of airway microbiome. However, the dynamics of the upper airway bacterial ecology of chronic obstructive pulmonary disease (COPD) patients across different seasons remains unclear. Methods: In this study, we present a 16S ribosomal RNA survey of the airway microbiome on 72 swab samples collected in different months (March, May, July, September, and November) in 2019 from 18 COPD patients and from six resampled patients in November in 2020. Results: Our study uncovered a dynamic airway microbiota where changes appeared to be associated with seasonal alternation in COPD patients. Twelve clusters of temporal patterns were displayed by differential and clustering analysis along the time course, systematically revealing distinct microbial taxa that prefer to grow in cool and warm seasons, respectively. Moreover, the upper airway microbiome composition was relatively stable in the same season in different years. Discussion: Given the tight association between airway microbiome and COPD disease progression, this study can provide useful information for clinically understanding the seasonal trend of disease phenotypes in COPD patients.
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Microbiota , Doença Pulmonar Obstrutiva Crônica , Humanos , Doença Pulmonar Obstrutiva Crônica/diagnóstico , Doença Pulmonar Obstrutiva Crônica/microbiologia , Estações do Ano , Escarro/microbiologia , Microbiota/genética , TraqueiaRESUMO
Exposure to environmental pollution influences respiratory health. The role of the airway microbial ecosystem underlying the interaction of exposure and respiratory health remains unclear. Here, through a province-wide chronic obstructive pulmonary disease surveillance program, we conducted a population-based survey of bacterial (n = 1,651) and fungal (n = 719) taxa and metagenomes (n = 1,128) from induced sputum of 1,651 household members in Guangdong, China. We found that cigarette smoking and higher PM2.5 concentration were associated with lung function impairment through the mediation of bacterial and fungal communities, respectively, and that exposure was associated with an enhanced inter-kingdom microbial interaction resembling the pattern seen in chronic obstructive pulmonary disease. Enrichment of Neisseria was associated with a 2.25-fold increased risk of high respiratory symptom burden, coupled with an elevation in Aspergillus, in association with occupational pollution. We developed an individualized microbiome-based health index, which covaried with exposure, respiratory symptoms and diseases, with potential generalizability to global datasets. Our results may inform environmental risk prevention and guide interventions that harness airway microbiome.
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Microbiota , Doença Pulmonar Obstrutiva Crônica , Humanos , Sistema Respiratório , Doença Pulmonar Obstrutiva Crônica/etiologia , Doença Pulmonar Obstrutiva Crônica/microbiologia , Exposição Ambiental/efeitos adversos , Escarro/microbiologiaRESUMO
Acetaminophen (APAP) overdose is a leading cause of drug-induced liver injury (DILI). The impact of the gut microbiota and associated metabolites on APAP and liver function remains unclear. We show that APAP disturbance is associated with a distinct gut microbial community, with notable decreases in Lactobacillus vaginalis. Mice receiving L. vaginalis showed resistance to APAP hepatotoxicity due to the liberation of the isoflavone daidzein from the diet by bacterial ß-galactosidase. The hepatoprotective effects of L. vaginalis in APAP-exposed germ-free mice were abolished with a ß-galactosidase inhibitor. Similarly, ß-galactosidase-deficient L. vaginalis produced poorer outcomes in APAP-treated mice than the wild-type strain, but these differences were overcome with daidzein administration. Mechanistically, daidzein prevented ferroptotic death, which was linked to decreased expression of farnesyl diphosphate synthase (Fdps) that activated a key ferroptosis pathway involving AKT-GSK3ß-Nrf2. Thus, liberation of daidzein by L. vaginalis ß-galactosidase inhibits Fdps-mediated hepatocyte ferroptosis, providing promising therapeutic approaches for DILI.
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Doença Hepática Induzida por Substâncias e Drogas , Microbioma Gastrointestinal , Isoflavonas , Animais , Camundongos , Acetaminofen/farmacologia , beta-Galactosidase/metabolismo , Doença Hepática Induzida por Substâncias e Drogas/prevenção & controle , Doença Hepática Induzida por Substâncias e Drogas/metabolismo , Isoflavonas/farmacologia , Fígado/metabolismo , Camundongos Endogâmicos C57BL , Fator 2 Relacionado a NF-E2RESUMO
In this study, the removals of sodium p-toluenesulfonate (NaTSA) by catalytic ozonation with two different cobalt-iron compounds, CoxFe oxides prepared by co-precipitation/calcination (CPO) and CoxFe oxides prepared by direct calcination (DCO), as the catalysts, had a difference of about 12%. It was found that the CPO surface contained active type c water, which was generally adsorbed on the oxygen vacancy. The test of oxygen temperature-programmed desorption (O2-TPD) showed that the surface of CPO was rich in oxygen vacancy. Through the electrochemical oxygen evolution reaction (OER) detection, a pair of Co valence redox peaks were detected from the CV curves, and the results of XPS test showed the replacement of octahedral Co3+ with Fe3 + in the Co3O4 during preparation of CPO. The enriched oxygen vacancy could be used as active sites for ozone adsorption and improve the charge transfer capacity. The number of hydroxyl radicals was detected by electron spin resonance (EPR) and it indicated that CPO contained more hydroxyl radicals, so it had higher effect in catalytic ozonation for organic pollutant degradation. In this paper, the relationship between oxygen vacancy and reactive center in the microstructure of the catalysts was established to discuss their working mechanism. The influence of the initial pH value, catalyst dosage, and ozone concentration on the removal of NaTSA was investigated by response surface design, and the optimal experimental conditions were predicted and verified.
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A major hurdle for single particle cryo-EM in structural determination lies in the specimen preparation impaired by the air-water interface (AWI) and preferential particle-orientation problems. In this work, we develop functionalized graphene grids with various charges via a dediazoniation reaction for cryo-EM specimen preparation. The graphene grids are paraffin-assistant fabricated, which appear with less contaminations compared with those produced by polymer transfer method. By applying onto three different types of macromolecules, we demonstrate that the high-yield charged graphene grids bring macromolecules away from the AWI and enable adjustable particle-orientation distribution for more robust single particle cryo-EM structural determination.
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Grafite , Grafite/química , Microscopia Crioeletrônica/métodos , Substâncias Macromoleculares/química , Manejo de Espécimes/métodos , ÁguaRESUMO
Chromium based metal-organic framework (MIL-53(Cr)) has enormous potential in the removal of organic contaminants from aqueous solutions due to its outstanding water stability, whereas its poor adsorption capacity limits the application. In this study, La/LaF3-MIL-53(Cr) was successfully synthesized by taking the advantages of La doping and LaF3 encapsulation with one-step hydrothermal method. Diverse analysis tools were utilized to verify that La not only existed in the framework, but also was loaded in the pores in the form of LaF3. The adsorption experiment results demonstrated that 0.3-La/LaF3-MIL-53(Cr) exhibited significantly improved adsorption capacity by four times compared with the pristine MIL-53(Cr) material. XPS and FTIR revealed that the affinity of La to tetracycline was significantly stronger than that of Cr and the excellent dispersion of LaF3 in the material may also be the cause of the increase in adsorption capacity. This study described a simple method to combine two different forms of modification and the modified material was potential for tetracycline adsorption.
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Cromo , Estruturas Metalorgânicas , Adsorção , TetraciclinaRESUMO
Background and Aims: Drug-induced liver injury (DILI) is a common cause of acute liver failure and represents a significant global public health problem. When discussing the gut-liver axis, although a great deal of research has focused on the role of gut microbiota in regulating the progression of DILI, the gut commensal fungal component has not yet been functionally identified. Methods: Mice were pretreated with fluconazole (FC) to deplete the gut commensal fungi and were then subject to acetaminophen (APAP) gavage. In addition, transcriptome sequencing was performed to identify differentially expressed genes (DEGs) between control and fluconazole-pretreated groups of the mice challenged with APAP. Results: Gut commensal fungi ablation through fluconazole pretreatment predisposed mice to APAP-induced hepatotoxicity, characterized by elevated serum liver enzyme levels and more severe centrilobular necrosis, which appears to be caused by robust inflammation and oxidative stress. The 16S rDNA sequencing results indicated that Akkermansia muciniphila abundance had significantly decreased in gut fungi-depleted mice, whereas increased abundance of Helicobacter rodentium was observed. The gene interaction network between DEGs identified by the transcriptome sequencing highlighted a significant enrichment of Cyp2a5 in the liver of APAP-treated mice that were preadministrated with fluconazole. Pharmacological inhibition of Cyp2a5 by 8-methoxypsoralen (8-MOP) could significantly attenuate hepatic inflammation and oxidative stress in mice, thereby conferring resistance to acute liver injury caused by APAP administration. Conclusion: Our data highlighted the significance of gut commensal fungi in hepatic inflammation and oxidative stress of APAP mice, shedding light on promising therapeutic strategies targeting Cyp2a5 for DILI treatment.
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The gut microbiome is associated with hepatitis B virus (HBV)-induced liver disease, which progresses from chronic hepatitis B, to liver cirrhosis, and eventually to hepatocellular carcinoma. Studies have analyzed the gut microbiome at each stage of HBV-induced liver diseases, but a consensus has not been reached on the microbial signatures across these stages. Here, we conducted by a systematic meta-analysis of 486 fecal samples from publicly available 16S rRNA gene datasets across all disease stages, and validated the results by a gut microbiome characterization on an independent cohort of 15 controls, 23 chronic hepatitis B, 20 liver cirrhosis, and 22 hepatocellular carcinoma patients. The integrative analyses revealed 13 genera consistently altered at each of the disease stages both in public and validation datasets, suggesting highly robust microbiome signatures. Specifically, Colidextribacter and Monoglobus were enriched in healthy controls. An unclassified Lachnospiraceae genus was specifically elevated in chronic hepatitis B, whereas Bilophia was depleted. Prevotella and Oscillibacter were depleted in liver cirrhosis. And Coprococcus and Faecalibacterium were depleted in hepatocellular carcinoma. Classifiers established using these 13 genera showed diagnostic power across all disease stages in a cross-validation between public and validation datasets (AUC = 0.65-0.832). The identified microbial taxonomy serves as non-invasive biomarkers for monitoring the progression of HBV-induced liver disease, and may contribute to microbiome-based therapies.