Metagenomic and metabolomic remodeling in nonagenarians and centenarians and its association with genetic and socioeconomic factors.

A better understanding of the biological and environmental variables that contribute to exceptional longevity has the potential to inform the treatment of geriatric diseases and help achieve healthy aging. Here, we compared the gut microbiome and blood metabolome of extremely long-lived individuals (94-105 years old) to that of their children (50-79 years old) in 116 Han Chinese families. We found extensive metagenomic and metabolomic remodeling in advanced age and observed a generational divergence in the correlations with socioeconomic factors. An analysis of quantitative trait loci revealed that genetic associations with metagenomic and metabolomic features were largely generation-specific, but we also found 131 plasma metabolic quantitative trait loci associations that were cross-generational with the genetic variants concentrated in six loci. These included associations between FADS1/2 and arachidonate, PTPA and succinylcarnitine and FLVCR1 and choline. Our characterization of the extensive metagenomic and metabolomic remodeling that occurs in people reaching extreme ages may offer new targets for aging-related interventions.

Implications of driver genes associated with a high tumor mutation burden identified using next-generation sequencing on immunotherapy in hepatocellular carcinoma.

Immune checkpoint blockade (ICB) therapy is a treatment strategy for hepatocellular carcinoma (HCC); however, its clinical efficacy is limited to a select subset of patients. Next-generation sequencing has identified the value of tumor mutation burden (TMB) as a predictor for ICB efficacy in multiple types of tumor, including HCC. Specific driver gene mutations may be indicative of a high TMB (TMB-H) and analysis of such mutations may provide novel insights into the underlying mechanisms of TMB-H and potential therapeutic strategies. In the present study, a hybridization-capture method was used to target 1.45 Mb of the genomic sequence (coding sequence, 1 Mb), analyzing the somatic mutation landscape of 81 HCC tumor samples. Mutations in five genes were significantly associated with TMB-H, including mutations in tumor protein 53 (TP53), Catenin®1 (CTNNB1), AT-rich interactive domain-containing protein 1A (ARID1A), myeloid/lymphoid or mixed-lineage leukemia (MLL) and nuclear receptor co-repressor 1 (NCOR1). Further analysis using The Cancer Genome Atlas Liver Hepatocellular Carcinoma database showed that TP53, CTNNB1 and MLL mutations were positively correlated with TMB-H. Meanwhile, mutations in ARID1A, TP53 and MLL were associated with poor overall survival of patients with HCC. Overall, TMB-H and associated driver gene mutations may have potential as predictive biomarkers of ICB therapy efficacy for treatment of patients with HCC.

Effect of cephalexin after heterogeneous Fenton-like pretreatment on the performance of anaerobic granular sludge and activated sludge.

Effects of Fe3O4 NPs heterogeneous Fenton-like pretreatment on the physicochemical properties and microbial community structure of anaerobic granular sludge (AGS) and activated sludge (AS) with cephalexin were investigated. Results showed that the average removal rate of chemical oxygen demand (COD) by the AGS was 80.9%, 85.9%, 90.3% and 91.6%, respectively, at cephalexin without pretreatment, pretreatment with 20% (H2O2), 40% (H2O2) and 60% (H2O2). Compared to the reactor without pretreatment, the COD removal rate increased by 24.14% with 60% (H2O2) pretreatment for the AS. Dehydrogenase levels in the AS were 313.05, 351.12, 434.81 and 480.77 mg TF (g·h)-1, which increased with higher concentrations of the pretreatment. Three-dimensional fluorescence (EEM) spectra analysis showed that the absorption peak intensities of humic acid in soluble microbial products (SMP) decreased in the AGS with increasing pretreatment. In the AGS, the dominant bacterial populations were Levilinea, Litorilinea and Clostridium sensu stricto. Clostridium sensu stricto accounting for 4.35% without pretreatment, while it was as high as 17% when it was pretreated with 60% (H2O2). The increase in the proportion of Clostridium sensu stricto was beneficial to the removal of organic pollutants. The pretreatment was also beneficial to the growth of acetic acid producing Methanothrix. For the AS, Gemmobacter were the dominant species, which increased from 6.56% to 32.61% after increasing the pretreatment to 40% (H2O2). Furthermore, the microbial capacities of amino acid metabolism and carbohydrate metabolism were enhanced by addition of pretreatment.

Characterization of thermal desorption with the Deans-switch technique in gas chromatographic analysis of volatile organic compounds.

This study presents a novel application based on the Deans-switch cutting technique to characterize the thermal-desorption (TD) properties for gas chromatographic (GC) analysis of ambient volatile organic compounds (VOCs). Flash-heating of the sorbent bed at high temperatures to desorb trapped VOCs to GC may easily produce severe asymmetric or tailing GC peaks affecting resolution and sensitivity if care is not taken to optimize the TD conditions. The TD peak without GC separation was first examined for the quality of the TD peak by analyzing a standard gas mixture from C2 to C12 at ppb level. The Deans switch was later applied in two different stages. First, it was used to cut the trailing tail of the TD peak, which, although significantly improved the GC peak symmetry, led to more loss of the higher boiling compounds than the low boiling ones, thus suggesting compound discrimination. Subsequently, the Deans switch was used to dissect the TD peak into six 30s slices in series, and an uneven distribution in composition between the slices were found. A progressive decrease in low boiling compounds and increase in higher boiling ones across the slices indicated severe inhomogeneity in the TD profile. This finding provided a clear evidence to answer the discrimination problem found with the tail cutting approach to improve peak symmetry. Through the use of the innovated slicing method based on the Deans-switch cutting technique, optimization of TD injection for highly resolved, symmetric and non-discriminated GC peaks can now be more quantitatively assessed and guided.

Functionalized Graphene Oxide with Hepatocyte Targeting as Anti-Tumor Drug and Gene Intracellular Transporters.

In order to realize the hepatocyte-specific targeted delivery of anti-tumor drug and gene, lactosylated chitosan oligosaccharide (LCO) functionalized graphene oxides (GO-LCO) containing quaternary ammonium groups (GO-LCO+) were prepared. The formation and composition of GO-LCO+ were confirmed by FTIR, AFM, TGA and zeta-potential. The in vitro cells uptakes of this functionalized GO were investigated and the results showed that GO-LCO+ can deliver fluorescein FAM-labeled DNA sequence (FAM-DNA) into human hepatic carcinoma cells (QGY-7703) with higher efficiency than positively charged chitosan oligosaccharide (CO) functionalized graphene oxides (GO-CO+) without Lactose acid modification. The loading efficiency of doxorubicin chloride (Dox) on GO-LCO+ with 477 µg/mg was obtained at the initial Dox concentration of 0.45 mg/ml and release of Dox on GO-LCO+ showed strong pH dependence. The toxicity of GO-LCO+ before and after loading with Dox toward QGY-7703 cells was further investigated. Our results suggest the functionalized GO to be used as a nanocarrier for hepatocyte targeted co-delivery of anti-tumor drugs and genes with low cytotoxicity, promising for future applications in anticancer drug and gene combined therapy.