Cellular specificity of lactate metabolism and a novel lactate-related gene pair index for frontline treatment in clear cell renal cell carcinoma

BackgroundAlthough lactate metabolism-related genes (LMRGs) have attracted attention for their effects on cancer immunity, little is known about their function in clear cell renal cell carcinoma (ccRCC). The aim of this study was to examine the cellular specificity of lactate metabolism and how it affected the first-line treatment outcomes in ccRCC.MethodsGSE159115 was used to examine the features of lactate metabolism at the single-cell level. Utilizing the transcriptome, methylation profile, and genomic data from TCGA-KIRC, a multi-omics study of LMRG expression characteristics was performed. A prognostic index based on a gene-pair algorithm was created to assess how LMRGs affected patients’ clinical outcomes. To simulate the relationship between the prognostic index and the frontline treatment, pRRophetic and Subclass Mapping were used. E-MTAB-1980, E-MTAB-3267, Checkmate, and Javelin-101 were used for external validation.ResultsThe variable expression of some LMRGs in ccRCC can be linked to variations in DNA copy number or promoter methylation levels. Lactate metabolism was active in tumor cells and vSMCs, and LDHA, MCT1, and MCT4 were substantially expressed in tumor cells, according to single-cell analysis. The high-risk patients would benefit from immune checkpoint blockade monotherapy (ICB) and ICB plus tyrosine kinase inhibitors (TKI) therapy, whereas the low-risk individuals responded to mTOR-targeted therapy.ConclusionsAt the single-cell level, our investigation demonstrated the cellular specificity of lactate metabolism in ccRCC. We proposed that the lactate-related gene pair index might be utilized to identify frontline therapy responders in ccRCC patients as well as predict prognosis

Development of PLGA nanoparticle loaded dissolving microneedles and comparison with hollow microneedles in intradermal vaccine delivery

Skin is an attractive but also very challenging immunisation site for particulate subunit vaccines. The aim of this study was to develop hyaluronan (HA)-based dissolving microneedles (MNs) loaded with PLGA nanoparticles (NPs) co-encapsulating ovalbumin (OVA) and poly(I:C) for intradermal immunisation. The NP:HA ratio used for the preparation of dissolving MNs appeared to be critical for the quality of MNs and their dissolution in ex vivo human skin. Asymmetrical flow field-flow fractionation and dynamic light scattering were used to analyse the NPs released from the MNs in vitro. Successful release of the NPs depended on the drying conditions during MN preparation. The delivered antigen dose from dissolving MNs in mice was determined to be 1 µg OVA, in NPs or as free antigen, by using near-infrared fluorescence imaging. Finally, the immunogenicity of the NPs after administration of dissolving MNs (NP:HA weight ratio 1:4) was compared with that of hollow MN-delivered NPs in mice. Immunization with free antigen in dissolving MNs resulted in equally strong immune responses compared to delivery by hollow MNs. However, humoral and cellular immune responses evoked by NP-loaded dissolving MNs were inferior to those elicited by NPs delivered through a hollow MN. In conclusion, we identified several critical formulation parameters for the further development of NP-loaded dissolving MNs

Study on the Tensile Strength and Crack Development of Granite Crystal Models with Different Fabrics

According to the relationship between the development of hydraulic fracture and the distribution of different rock and mineral fabrics, digital image technology was used in this study based on the discrete element particle flow method. An SCGM numerical model, which can control fabric and refine mesoscopic crystal defects, was constructed. The tensile strength test of granite specimens with different component contents and polymerization conditions was conducted, with the monitorization of damaged cracks. The test results showed that (1) the SCGM model could construct a model of a crystal structure containing variable components and polymerization, to achieve numerical experiments of different parameters; (2) compared with previous models, the SCGM model can reflect internal stress change of a specimen with the variation of the structure. At the same time, the contained crystal structure can characterize different failure modes such as intergranular cracks of different components, grain boundary cracks of the same component, and transgranular cracks, which were in good agreement with the actual failure state of granite; (3) the mica content of the specimen and its strength presented a linear relationship of y=−14.723x+12.642. The degree of polymerization of the components and the strength of the specimens were both affected by the accumulation of microcracks and stress concentration, which appeared to increase first and then decrease. When the specimen was broken, the number of microcracks and the degree of polymerization of the components also increased first and then decreased. The SCGM model can construct a numerical model of granite with arbitrary fabric and crystal structure and provide a hydraulic fracturing analysis method

Analyzing sleep status in children with acute leukemia

Abstract Background Quality sleep is essential for physical and mental health. We aimed to analyze sleep disorders in children with acute leukemia and explore associated factors. Methods General data and sleep disorders in children with acute leukemia during chemotherapy were collected by general questionnaires, Children's Sleep Disorders Scale and the Parenting Stress Index-short form. Results In total, 173 valid questionnaires were collected. The total Sleep Disorder Scale score > 39 is considered a sleep disorder, while sleep disorders accounted for 45.66% (79/173). In the cohort, 167 children had acute lymphoblastic leukemia, with 40.12% (67/167) having sleep disorders, while six children had acute non-lymphoblastic leukemia, with 50.00% (3/6) having sleep disorders. Single- and multi-factor regression analyses of age, gender, number of children in the family, and time spent using electronic devices showed that factors influencing sleep disorders in these children were mainly parental scolding and adenoid hypertrophy. Children with sleep disorders had more parental stress than those without sleep disorders (P < 0.05). Conclusions The high incidence of sleep disorders in children with acute leukemia is related to airway conditions and parental behaviors. Sleep disorders in children can increase parenting stress. Factors potentially affecting sleep quality should be addressed as early as possible, while parental education should be strengthened to better facilitate the physical and psychological recovery of their children

Using "Umbrella Deconstruction & Energy Dispersive Spectrometer (UD-EDS)" technique to quantify the anisotropic elements distribution of "Chang 7" shale and its significance

This study utilizes the experimental technique named "Umbrella Deconstruction & Energy Dispersive Spectrometer (UD-EDS)" method to quantify the anisotropic element distribution of shale which has been proved significant in the stimulation of shale. Direct quantification of anisotropic distribution of element in shale from the Triassic Yanchang formation in the HJS" district was carried out to ensure both observational resolution and sample representativeness. Results show that many types of elements distribution vary in eight directions. The element contents are similar in three directions - 90 degrees (270 degrees), 112.5 degrees (292.5 degrees) and 135 degrees (315 degrees), they are quite different from which in other five directions, which has obvious significance in shale stimulation. Results also prove that the evidence of dominant fracture direction in fracturing can be found in brittle minerals. As to "Chang 7" shale, the dominant fracture direction of shale reservoir is distributed in a specific area instead of overall extending along a single direction. In this specific area the best dominant fracture direction can be found. The subsequent results would offer the microscopic evidences for the shale fracturing and point to an innovative direction for research on exploration and development of the unconventional oil and gas. (C) 2019 Elsevier Ltd. All rights reserved

Organocatalyzed Beckmann Rearrangement of Cyclohexanone Oxime in a Microchemical System

A microchemical system, constructed with two micromixers and a delay loop, is designed to carry out the organocatalyzed Beckmann rearrangement of cyclohexanone oxime to ε-caprolactam with trifluoroacetic acid as the catalyst. In the microsystem, cyclohexanone oxime which is dissolved in acetonitrile mixes with trifluoroacetic acid in the first micromixer to realize uniform reaction condition, and then the mixture passes through the delay loop to continue the reaction. Finally, a large amount of acetonitrile is pumped into the second micromixer to stop the reaction by cooling and diluting the reaction system. The viscosity and reaction enthalpy of the organic reaction system are determined. The results show that both two are favorable for avoiding the clogging, increasing the heat transfer and improving the process safety. Two different catalytic systems are adopted and elevated in this microsystem. The influences of temperature, residence time, and oxime concentration on the reaction performance are investigated. Under optimized conditions, the reaction can be accomplished with a residence time less than 48 s and the selectivity of 99+%. The results show that Beckmann rearrangement can be realized in the microsystem with much more efficiency and safety