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This study aimed to investigate the efficacy of Everolimus (EVE) in combination with immune checkpoint inhibitors (ICIs) in bladder cancer treatment and the underlying mechanisms. In vitro, MB49 cells were exposed to gradient concentrations (0 nM-100 nM) of EVE for 48 h, to investigate the cell viability and cell proliferative potential. In vivo, we applied a subcutaneous tumor mouse model of bladder cancer and the mice were treated with EVE monotherapy (different doses) or in combination with anti-programmed cell death protein 1 (PD-1) agents to study the impacts on tumor growth and explore the immune mechanism. The influences of treatments on peripheral immune profiles and tumor immune microenvironment were also discussed. EVE could inhibit the growth of MB49 cells in vitro. Though high-dose EVE monotherapy could induce tumor regression in vivo, it also contributed to immunosuppression. High-dose EVE inhibited the expression of PD-L1 by inhibiting Th1 cytokine secretion, while combined therapy with PD-1 inhibitors showed no extra profit. Low-dose EVE in combination with PD-1 inhibitors could effectively suppress tumor growth by increasing periphery CD8+ T cell frequency and GZMB+ CD8+ T cell frequency in the tumor microenvironment. High-dose EVE monotherapy induced tumor regression, but with immunosuppression to some content. Combination therapy with low-dose EVE and PD-1 inhibitor could effectively inhibit the growth of bladder tumors by enhancing the antitumor immunity of CD8+ T cells in both periphery and tumor microenvironment.Urban waste (UW) has caused a series of problems regarding its management. UW comprises domestic, hospital and industrial residues, which makes the destination of this waste a matter of concern, as it may contain a variety of highly toxic environmental polluters. Deactivated dumps can represent sources of contamination of the environment that surround these deposits, harming rivers and inhabiting organisms. Knowledge of the microbial profile of water bodies that can be affected by these toxic residues is essential for the development of alternatives and improvements in treatments applied in rivers and streams. In this sense, this work aimed to analyze the microbial community present in sediments of the Arroio Dourado stream in the municipality of Foz do Iguaçu, a stream located near a deactivated open-air dump. 16S rDNA metabarcoding suggested the dominance of acidogenic bacteria belonging to Acidobacteriota phylum, followed by less abundant phyla Actinobacteriota, Myxococcota, Chloroflexi and a small community of sulfate reducers (Desulfobacteriota). However, more than 50% of amplicon sequence variants (ASVs) were not taxonomically classified. In addition, an expressive abundance was attributed to the genus Anaeromyxobacter, a metabolically versatile group, which can thrive in the presence of polluting compounds present in the deactivated landfill. Thus, a possible stream treatment process can be developed. In addition, culture media can be developed for the recovery of taxonomic groups identified involved in the biodegradation of organic compounds. The results presented expand the knowledge of bacterial diversity in sediment samples recovered from the Arroio Dourado stream.

To determine if responses given to each question of the Scoliosis Research Society-22 (SRS22), Oswestry disability index (ODI) and Short Form-36 (SF-36) questionnaires are influenced by the radiological parameters.

Patients enrolled in a multi-centre prospectively collected adult spinal deformity database who had complete SRS22, ODI and SF-36 data at baseline and at one-year follow-up were analysed. The presence of a differential item function of each question within each score in relation to radiological parameters was analysed using a mixed Rasch model with the radiological threshold value(s) determined.

Of those patients analysed (n = 1745; 1406 female, average age 51.0 ± 19.8years), 944 were surgically and 801 were non-surgically treated. For the SRS22, questions (Q) 3, 5 and 18 were sensitive to almost all radiological parameters and the overall score was found sensitive to the Cobb angle. For the ODI, Q3, 6, 9 and 10 were not sensitive to any radiologic parameters whereas Q4 and 5 were sensitive to most. In contrast, only 3 of the SF-36 items were sensitive to radiological parameters.

78% of the SRS-22, 60% of the ODI and 8% of the questions in the SF-36 are sensitive to radiological parameters. Sagittal imbalance is independently associated with a poor overall outcome, but affects mental status and function more than pain and self-image. The assembly of questions responsive to radiological parameters may be useful in establishing a connection between changes in radiologic parameters and HRQL.

78% of the SRS-22, 60% of the ODI and 8% of the questions in the SF-36 are sensitive to radiological parameters. Sagittal imbalance is independently associated with a poor overall outcome, but affects mental status and function more than pain and self-image. The assembly of questions responsive to radiological parameters may be useful in establishing a connection between changes in radiologic parameters and HRQL.

To evaluate the measurement properties of the Brazilian version of the Copenhagen Neck Functional Disability Scale (CNFDS) in patients with chronic neck pain.

One hundred and five patients were included in the study. The structural validity of the CNFDS was assessed by exploratory and confirmatory factor analysis with the following fit indices chi-square divided by degrees of freedom (chi-square/df), root mean square error of approximation (RMSEA), comparative fit index (CFI), and Tucker-Lewis index (TLI). To test the construct validity, the CNFDS score was correlated with the Numerical Pain Rating Scale, the Tampa Scale of Kinesiophobia, the Pain-Related Catastrophizing Thoughts Scale, and Neck Disability Index (NDI). A subsample of 43 patients filled the CNFDS at two different times, and test-retest reliability was measured using the intraclass correlation coefficient (ICC), standard error of measurement (SEM), and minimum detectable change (MDC). The internal consistency of the CNFDS was analyzed by Cronbach’s alpha.

CNFDS presented a unidimensional structure, with goodness of fit indices chi-square/df = 1.37, CFI = 0.94, TLI = 0.93, RMSEA = 0.059. The CNFDS showed satisfactory results of reliability (ICC = 0.93) and internal consistency (Cronbach’s alpha = 0.84). The SEM was 1.72 and the MDC was 4.76. The CNFDS showed a high correlation with the NDI (rho = 0.718) and a low correlation with the other instruments. There were no floor and ceiling effects.

The Brazilian version of the CNFDS with a one-dimensional structure and 15 items has adequate measurement properties.

The Brazilian version of the CNFDS with a one-dimensional structure and 15 items has adequate measurement properties.LncRNAs are associated with malignancies with their tumor suppressor/oncogenic properties. Although many studies are conducted related to the mechanism of action for dasatinib and ponatinib in chronic myeloid leukemia (CML), their comparative effects on lncRNA expressions are largely unknown. Hence, we aimed to define the lncRNAs involved in the treatment of CML with dasatinib and ponatinib. We measured the cytotoxicities of dasatinib/ponatinib with CCK-8 assay and identified differentially expressed lncRNAs (DEL) by qRT-PCR. We determined the principal functions of DELs by Ingenuity Pathway Analysis (IPA) and performed gene ontology (GO) analysis for apoptosis and anti-proliferation-related lncRNAs. Apoptotic and anti-proliferative activities of dasatinib/ponatinib were confirmed by flow-cytometry. In K562 cells, dasatinib/ponatinib re-regulated lncRNAs which were dysregulated in leukemia. DELs after treatment (forty with dasatinib, thirty-seven with ponatinib) were related to increased cell death; decreased cell viability, proliferation, tumor growth, invasion, migration. Dasatinib-mediated network was related to cancer, hematological disease while ponatinib-mediated network was associated with cancer, cell death/survival, cell-to-cell signaling/interaction. Both treatments predicted activation of IFNγ, IL1β, TNF as upstream regulators, specially this effect was higher in dasatinib. Comparison analysis showed that ponatinib was predicted more effective in cell death of tumor cell line than dasatinib. We confirmed that ponatinib was more potent than dasatinib to induce apoptosis and inhibit proliferation of CML cells, in consensus with IPA and GO analysis results. see more LncRNAs are specifically involved in anti-leukemic activities of dasatinib and ponatinib. Our findings will contribute to understanding signalization occurring in CML cells after standard treatments.Ni-containing carbon monoxide dehydrogenase (Ni-CODH) plays an important role in the CO/CO2-based carbon and energy metabolism of microbiomes. Ni-CODH is classified into distinct phylogenetic clades, A-G, with possibly distinct cellular roles. However, the types of Ni-CODH clade used by organisms in different microbiomes are unknown. Here, we conducted a metagenomic survey of a protein database to determine the relationship between the phylogeny and biome distribution of Ni-CODHs. Clustering and phylogenetic analyses showed that the metagenome assembly-derived Ni-CODH sequences were distributed in ~ 60% Ni-CODH clusters and in all Ni-CODH clades. We also identified a novel Ni-CODH clade, clade H. Biome mapping on the Ni-CODH phylogenetic tree revealed that Ni-CODHs of almost all the clades were found in natural aquatic environmental and engineered samples, whereas those of specific subclades were found only in host-associated samples. These results are comparable with our finding that the diversity in the phylum-level taxonomy of host-associated Ni-CODH owners is statistically different from those of the other biomes. Our findings suggest that while Ni-CODH is a ubiquitous enzyme produced across diverse microbiomes, its distribution in each clade is biased and mainly affected by the distinct composition of microbiomes.Most Pseudoxanthomonas species described have been derived from water, plants, or contaminated soils. Here, a strain Pseudoxanthomonas sp. X-1 isolated from bromoxynil octanoate (BO)-contaminated soil is presented. Strain X-1 could degrade BO and produce bromoxynil. The optimal conditions for degradation of BO by strain X-1 were an initial BO concentration of 0.1 mM, 30 °C, pH 7, and Mn2+ concentration of 1.0 mM. The bacterial morphological, physiological, and biochemical characteristics of strain X-1 were described, which showed differences comparing with other related type strains. The genome of strain X-1 was sequenced, and a comparative genomic analysis of X-1 and other Pseudoxanthomonas species was conducted to explore the mechanisms underlying the differences among these strains. The genome of strain X-1 encodes 4160 genes, 4078 of which are protein-coding genes and 68 are RNA coding genes. Specifically, strain X-1 encodes enzymes belonging to 778 Enzyme Commission (EC) numbers, much more than those of other related strains, and 62 of them are unique. Eight genes coding esterase are detected in strain X-1 which leads to the ability of BO degradation. This study provides strain, enzyme, and genome resources for the microbial remediation of environments polluted by herbicide BO.