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The pentose phosphate pathway (PPP) plays a critical role in macromolecule biosynthesis and maintaining cellular redox homoeostasis in rapidly proliferating cells. Upregulation of the PPP has been shown in several types of cancer. However, how the PPP is regulated to confer a selective growth advantage on cancer cells is not well understood. Here we show that glucose-6-phosphate dehydrogenase (G6PD), the rate-limiting enzyme of the PPP, is dynamically modified with an O-linked β-N-acetylglucosamine sugar in response to hypoxia. Glycosylation activates G6PD activity and increases glucose flux through the PPP, thereby providing precursors for nucleotide and lipid biosynthesis, and reducing equivalents for antioxidant defense. Blocking glycosylation of G6PD reduces cancer cell proliferation in vitro and impairs tumor growth in vivo . Importantly, G6PD glycosylation is increased in human lung cancers. Our findings reveal a mechanistic understanding of how O-glycosylation directly regulates the PPP to confer a selective growth advantage to tumours. The pentose phosphate pathway is aberrantly activated in cancer cells but the mechanism is unclear. Here, the authors show that G6PD, the rate-limiting enzyme in the pathway, is post-translationally modified with a sugar moiety under hypoxic conditions leading to increased production of precursors for macromolecular synthesis and antioxidants.

Background The apple snail, Pomacea canaliculata , is one of the world’s 100 worst invasive alien species and vector of some pathogens relevant to human health. Methods On account of the importance of gut microbiota to the host animals, we compared the communities of the intestinal microbiota from P. canaliculata collected at different developmental stages (juvenile and adult) and different sexes by using high-throughput sequencing. Results The core bacteria phyla of P. canaliculata gut microbiota included Tenericutes (at an average relative abundance of 45.7 %), Firmicutes (27.85 %), Proteobacteria (11.86 %), Actinobacteria (4.45 %), and Cyanobacteria (3.61 %). The female group possessed the highest richness values, whereas the male group possessed the lowest bacterial richness and diversity compared with the female and juvenile group. Both the developmental stages and sexes had important effects on the composition of the intestinal microbiota of P. canaliculata. By LEfSe analysis, microbes from the phyla Proteobacteria and Actinobacteria were enriched in the female group, phylum Bacteroidetes was enriched in the male group, family Mycoplasmataceae and genus Leuconostoc were enriched in the juvenile group. PICRUSt analysis predicted twenty-four metabolic functions in all samples, including general function prediction, amino acid transport and metabolism, transcription, replication, recombination and repair, carbohydrate transport and metabolism, etc. Conclusions This study provided a general understanding of the diversity characteristics of intestinal microbial communities of P. canaliculata , and indicated that developmental stage and gender could both influence the intestinal microbes of P. canaliculata. Further study may focus on the interaction between the gut microbiota and their host.

Burkholderia pseudomallei is a Gram-negative intracellular bacterium that causes melioidosis, a life-threatening disease. The interaction of B. pseudomallei with its host is complicated, and cellular response to B. pseudomallei infection is still largely unknown. In this study, we aimed to determine host-cell responses to B. pseudomallei at the proteomics level. We performed proteomic profiling of B. pseudomallei HNBP001-infected mouse macrophage RAW264.7 cells to characterize the cellular response dynamics during infection. Western blot analysis was utilized for the validation of changes in protein expression. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were conducted using the clusterProfiler R package. Compared with the negative control (NC) group, 811 common proteins varied over time, with a cut-off level of two fold change and an adjusted P -value less than 0.05. The bioinformatics analysis revealed that the proteins significantly changed in the B. pseudomallei HNBP001 infection group ( Bp group) were enriched in glycometabolism pathways, including glycolysis, fructose and mannose metabolism, pentose phosphate pathway, galactose metabolism, and carbon metabolism. Western blot analysis verified three selected proteins involved in glycometabolism pathways, namely PGM1, PKM, and PGK1 were increase over time post the infection. Furthermore, in vitro functional analysis revealed an increased glucose uptake and decreased ATP production and O-GlcNAcylation in the Bp group compared with control group, suggesting that B. pseudomallei HNBP001 infection induces changes in glycometabolism in RAW264.7 cells. These results indicate that glycometabolism pathways change in RAW264.7 cells post B. pseudomallei HNBP001 infection, providing important insights into the intimate interaction between B. pseudomallei and macrophages.

Cytokine-induced killer cells induced with tumor antigen-pulsed dendritic cells (DC-CIK) immunotherapy is a promising strategy for the treatment of malignant tumors. However, itsefficacy isrestricted by the immunosuppression, which is mediated by the cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) pathway. In order to overcome the negative co-stimulation from these T cells,we screened a nanobody targeted for CTLA-4 (Nb36) and blocked the CTLA-4 signaling with Nb36. Peripheral blood mononuclear cells (PBMCs) were collected from healthy donors to beused to induce CIK cells in vitro, after which they were co-cultured with DC cells that had received tumor antigens. In addition, wetested whether blocking CTLA-4 signaling with Nb36 could promote in vitro DC-CIK cells proliferation, pro-inflammatory cytokine production and cytotoxicity,or not. For the in vivo experiments, we constructed a subcutaneously transplanted tumor model and placed it in NOD/SCID mice to verify the anti-tumor effect of this therapy. After stimulation with Nb36, the DC-CIK cells presented enhanced proliferation and production of IFN-[gamma] in vitro, which strengthened the killing effect on the tumor cells. For the in vivo experiments, it was found that Nb36-treated DC-CIK cells significantly inhibited the growth of subcutaneously transplanted livercancer tumors, as well as reduced the tumor weight and prolonged the survival of tumor-bearing NOD/SCID mice. Ourfindings demonstrated that in response to CTLA-4 specific nanobody stimulation, DC-CIK cells exhibited a better anti-tumor effect. In fact, this Nb-based CTLA-4 blocking strategy achieved an anti-tumor efficacy close to that of monoclonal antibodies. Our findings suggest that DC-CIK cells + Nb36 have the potential totreatmalignant tumors through in vivo adoptive therapy.

This observational investigation aimed to explore potential risk factors for anemia in pregnancy. Firstly, a cross-sectional study was conducted, encompassing a review of clinical data of 43,201 pregnant women admitted to the Hainan Women and Children’s Medical Center between January 2017 and December 2020. Comparison between women with and without anemia in pregnancy revealed significant differences between the two groups concerning age, gestational diabetes, hypothyroidism, hyperthyroidism, chronic hepatitis B virus infection, syphilis infection, and human immunodeficiency virus infection. Multivariable logistic regression analysis showed that chronic hepatitis B virus infection was significantly associated with anemia during pregnancy (AOR   2.97, 95% CI 2.57–3.44, p  < 0.0001). Subsequently, a retrospective cohort comprising 86 cases with chronic hepatitis B virus infection and 129 control subjects recruited from the Hainan Women and Children’s Medical Center from November 2021 and January 2023 was examined. Results of the examination revealed a corroborative association between chronic hepatitis B virus infection and anemia in pregnancy (OR  2.13, 95% CI 1.20–3.79, p  = 0.0092), particularly manifesting in the third trimester of gestation. Further analysis unveiled distinctive hematological alterations among cases with chronic hepatitis B virus infection, characterized by diminished erythrocyte size and reduced levels of corpuscular hemoglobin. Collectively, these findings underscore a positive association of chronic hepatitis B virus infection with anemia during pregnancy.

(1) Background: With unknown causes and no effective treatment available, Alzheimer’s disease (AD) places enormous pressure on families and society. Our previous study had shown that Ebselen at a high concentration (10.94 μM) improved the cognition of triple-transgenic AD (3×Tg-AD) mice and alleviated the related pathological indicators but showed toxicity to the mice. Here, we dedicated to study the therapeutic effect and molecular mechanism of Ebselen at a much lower concentration on 3×Tg-AD mice. (2) Methods: Various behavioral experiments were applied to detect the behavioral ability of mice. Western blot, thioflavin T staining and a transmission electron microscope were used to evaluate the pathology of AD mice. The mitochondrial membrane potential and respiration were assessed with the corresponding assay kit. (3) Results: Ebselen remarkably increased cognitive ability of AD mice, eliminated β-Amyloid (Aβ) oligomers and recovered the synaptic damage in AD mice brain. In addition, the destroyed mitochondrial morphologies and function were repaired by Ebselen through ameliorating mitochondrial energy metabolism, mitochondrial biogenesis and mitochondrial fusion/fission balance in N2a-SW cells and brain tissues of AD mice. (4) Conclusions: This research indicated that Ebselen might exert its therapeutic effect via protecting mitochondria in AD.

The Wuyi Mountains in China are one of the largest and most complete subtropical forest ecosystems at the same latitude in the world. However, our limited understanding of the function of this distinctive ecosystem means that the interrelationship between species diversity and ecosystem functioning needs to be investigated if evergreen broadleaf forests (EBLFs) are to be protected. Here, we calculated species richness, the Shannon–Wiener index, and the Pielou index in large-, medium-, and small-scale (20 m × 20 m, 10 m × 10 m, and 5 m × 5 m) forest dynamics plots (FDPs). We also investigated the interrelationships between species diversity and aboveground biomass (AGB)/productivity in FDPs at the different scales using the generalized linear regression model. The results showed that species diversity and AGB positively interrelated with each other, whereas there was no species diversity-productivity interrelationship in the subtropical BLF on the Wuyi Mountains. The structural equation model (SEM) showed that elevation was a key factor directly affecting AGB. These findings lead to the conclusion that productivity is not solely correlated with species diversity and that abiotic factors probably mediate the positive interrelationship between species diversity and ecosystem functioning. This study provides theoretical basis that can be used to protect EBLFs in subtropical areas and the results can be used to improve the construction of artificial forest communities and vegetation restoration at the same latitude.

Dendrobium officinale is a critically endangered perennial herb endemic to China. Determining the levels of genetic diversity and patterns of population genetic structure of this species would assist in its conservation and management. Data of 12 populations were used to assess its genetic diversity and population structure, employing the method of amplified fragment length polymorphism (AFLP). A high level of genetic diversity was detected (H E = 0.269) with POPGENE. As revealed by AMOVA analysis, there was moderate variation between pairs of populations with ΦST values ranging from 0.047 to 0.578 and on average 26.97% of the genetic variation occurred among populations. Three main clusters were shown in UPGMA dendrogram using TFPGA, which is consistent with the result of principal coordinate ananlysis (PCO) using NTSYS. Keeping a stable environment is critical for the in situ conservation and management of this rare and endangered plant, and for ex situ conservation it is important to design an integrated germplasm bank.

Considering the spatial and temporal effects of atmospheric pollutants, using the geographically and temporally weighted regression and geo-intelligent random forest (GTWR-GeoiRF) model and Sentinel-5P satellite remote sensing data, combined with meteorological, emission inventory, site observation, population, elevation, and other data, the high-precision ozone concentration and its spatiotemporal distribution near the ground in China from March 2020 to February 2021 were estimated. On this basis, the pollution status, near-surface ozone concentration, and population exposure risk were analyzed. The findings demonstrate that the estimation outcomes of the GTWR-GeoiRF model have high precision, and the precision of the estimation results is higher compared with that of the non-hybrid model. The downscaling method enhances estimation results to some extent while addressing the issue of limited spatial resolution in some data. China’s near-surface ozone concentration distribution in space shows obvious regional and seasonal characteristics. The eastern region has the highest ozone concentrations and the lowest in the northeastern region, and the wintertime low is higher than the summertime high. There are significant differences in ozone population exposure risks, with the highest exposure risks being found in China’s eastern region, with population exposure risks mostly ranging from 0.8 to 5.