HOXC10 promotes nasopharyngeal carcinoma cell proliferation and migration by regulating PI3K/AKT pathway

Purpose: To evaluate the role of homeobox C10 (HOXC10) in nasopharyngeal carcinoma (NPC). Methods: Cell Counting Kit-8 (CCK-8) and colony formation assays were conducted to determine NPC cell proliferation. Cell migration and invasion were assessed using a Transwell assay, while western blot was used to investigate the mechanism of action involved in HOXC10- mediated NPC. Results: HOXC10 levels were significantly elevated in NPC cells (p < 0.001). Over-expression of HOXC10 significantly increased NPC cell viability (p < 0.05) and proliferation. However, silencing HOXC10 reduced NPC cell proliferation. HOXC10 knockdown suppressed NPC cell migration and invasion. NPC expression of phosphorylated phosphoinositide-3-kinase (PI3K) and protein kinase B (AKT) proteins were up-regulated after HOXC10 over-expression but were down-regulated upon silencing HOXC10 (p < 0.05). Conclusion: HOXC10 knockdown reduces NPC cell proliferation and metastasis by inactivating PI3K/AKT pathway, and therefore, can potentially be developed for the treatment of nasopharyngeal carcinoma

Biotransformation of rare earth oxide nanoparticles eliciting microbiota imbalance

Background Disruption of microbiota balance may result in severe diseases in animals and phytotoxicity in plants. While substantial concerns have been raised on engineered nanomaterial (ENM) induced hazard effects (e.g., lung inflammation), exploration of the impacts of ENMs on microbiota balance holds great implications. Results This study found that rare earth oxide nanoparticles (REOs) among 19 ENMs showed severe toxicity in Gram-negative (G−) bacteria, but negligible effects in Gram-positive (G+) bacteria. This distinct cytotoxicity was disclosed to associate with the different molecular initiating events of REOs in G− and G+ strains. La2O3 as a representative REOs was demonstrated to transform into LaPO4 on G− cell membranes and induce 8.3% dephosphorylation of phospholipids. Molecular dynamics simulations revealed the dephosphorylation induced more than 2-fold increments of phospholipid diffusion constant and an unordered configuration in membranes, eliciting the increments of membrane fluidity and permeability. Notably, the ratios of G−/G+ reduced from 1.56 to 1.10 in bronchoalveolar lavage fluid from the mice with La2O3 exposure. Finally, we demonstrated that both IL-6 and neutrophil cells showed strong correlations with G−/G+ ratios, evidenced by their correlation coefficients with 0.83 and 0.92, respectively. Conclusions This study deciphered the distinct toxic mechanisms of La2O3 as a representative REO in G− and G+ bacteria and disclosed that La2O3-induced membrane damages of G− cells cumulated into pulmonary microbiota imbalance exhibiting synergistic pulmonary toxicity. Overall, these findings offered new insights to understand the hazard effects induced by REOs

Genomic fossils reveal adaptation of non-autonomous pararetroviruses driven by concerted evolution of noncoding regulatory sequences

The interplay of different virus species in a host cell after infection can affect the adaptation of each virus. Endogenous viral elements, such as endogenous pararetroviruses (PRVs), have arisen from vertical inheritance of viral sequences integrated into host germline genomes. As viral genomic fossils, these sequences can thus serve as valuable paleogenomic data to study the long-term evolutionary dynamics of virus-virus interactions, but they have rarely been applied for this purpose. All extant PRVs have been considered autonomous species in their parasitic life cycle in host cells. Here, we provide evidence for multiple non-autonomous PRV species with structural defects in viral activity that have frequently infected ancient grass hosts and adapted through interplay between viruses. Our paleogenomic analyses using endogenous PRVs in grass genomes revealed that these non-autonomous PRV species have participated in interplay with autonomous PRVs in a possible commensal partnership, or, alternatively, with one another in a possible mutualistic partnership. These partnerships, which have been established by the sharing of noncoding regulatory sequences (NRSs) in intergenic regions between two partner viruses, have been further maintained and altered by the sequence homogenization of NRSs between partners. Strikingly, we found that frequent region-specific recombination, rather than mutation selection, is the main causative mechanism of NRS homogenization. Our results, obtained from ancient DNA records of viruses, suggest that adaptation of PRVs has occurred by concerted evolution of NRSs between different virus species in the same host. Our findings further imply that evaluation of within-host NRS interactions within and between populations of viral pathogens may be important.Supporting information : http://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1006413#sec01

Replication Data for: Engineered Nanocomposites Prevent the Evolution of Antimicrobial Resistance

The data is LC-MS analysis for phospholipids (PC and PG) and DNA sequencing analysis for evolved E.coli strains, including norfloxacin, silver and La@GO nanoparticle treatment

Risk of nasopharyngeal carcinoma associated with single nucleotide polymorphisms in the MicroRNA binding site of SGK3

Objective: Serum/glucocorticoid regulated kinase is a serine/threonine kinase that is involved in regulating cell proliferation, apoptosis, the cell cycle, and ion channel function. The aim of this study was to analyze the relationship between single nucleotide polymorphisms (SNPs) in the microRNA (miRNA) binding site of the SGK3 gene and the risk of nasopharyngeal carcinoma (NPC). Methods: Three SGK3 loci, rs77572541, rs11994200, and rs78158330, were genotyped in 226 NPC patients and 226 healthy controls via Sanger sequencing. Quantitative real-time polymerase chain reaction was used to analyze levels of SGK3 messenger RNA (mRNA), hsa-miR-3529-5p, hsa-miR-379-5p, hsa-miR-498, hsa-miR-4320, and hsa-miR-590-3p. Western blot analysis was used to assess serum and glucocorticoid regulated kinase 3 (SGK3) protein expression. Results: SGK3 rs77572541 locus G allele carriers were 3.47 times more likely to develop NPC than carriers of the A allele (95% confidence interval [CI] = 1.98-6.09, p \u3c 0.01). The SGK3 rs11994200 locus C allele was a major risk factor for NPC (odds ratio = 2.68, 95% CI = 1.63-4.39, p \u3c 0.01). Similarly, carriers of the C allele of the SGK3 rs78158330 locus were 3.36 times more likely to develop NPC than those with the T allele (95% CI = 1.96-5.73, p \u3c 0.01). The SGK3 protein was highly expressed in NPC. The SGK3 rs77572541 locus G allele is the target of hsa-miR-379-5p and hsa-miR-3529-5p, but the A allele is not. The SGK3 rs11994200 locus C allele was the target of hsa-miR-4320, and the G allele was the target of hsa-miR-498. The SGK3 rs78158330 locus T allele was the target of hsa-miR-590-3p. Hsa-miR-3529-5p, hsa-miR-379-5p, and hsa-miR-4320 were down-regulated in NPC tissues (p \u3c 0.01), whereas hsa-miR-498 and hsa-miR-590-3p were highly expressed (p \u3c 0.01). Conclusions: SNPs at the SGK3 loci rs77572541, rs11994200, and rs78158330 are significantly associated with the risk for NPC. These effects may be related to the influence of miRNAs on different alleles, but this needs to be verified both in vitro and in vivo

The cause and influence of sequentially assembling higher and lower deacetylated chitosans on the membrane formation of microcapsule

Alginate-chitosan (AC) microcapsules with desired strength and biocompatibility are preferred in cell-based therapy. Sequential assembly of higher and lower deacetylated chitosans (C-1 and C-2) on alginate has produced AC(1)C(2) microcapsule with improved membrane strength and biocompatibility. In this article, the assembly and complexation processes of two cationic chitosans on anionic alginate were concerned, and the cause and influence of sequentially assembling chitosans on AC(1)C(2) microcapsules membrane formation were evaluated. It was found that C-1 complexation was the key factor for deciding the membrane thickness of AC(1)C(2) microcapsule. Specifically, the binding amount of C-2 positively related to the binding amount of C-1, which suggested the first layer by C-1 complexation on alginate had no obvious resistance on the sequential cationic C-2 complexation. Further analyses demonstrated that outward migration of alginate molecules and inward diffusion of both chitosans under electrostatic interaction contributed to the sequential coating of C-2 on first C-1 layer. Moreover, C-2 complexation through the surface to inner layer of membrane helped smoothen the first layer by C-1 complexation that displayed a synergy role on the formation of AC(1)C(2) microcapsule membrane. Therefore, the two chitosans played different roles and synergistically contributed to membrane properties that can be easily regulated with membrane complexation time. (c) 2015 Wiley Periodicals, Inc

Evolution of land use functions and their trade-offs/synergies relationship in resource-based cities

The industrialization of resource-based cities exerts a profound influence on their land system. The land use functions (LUFS), are concealed representation of this land system, can highlight issues in human-land relations. To address these challenges, we have developed a bottom-up approach for constructing an LFUS evaluation system tailored to resource-based cities. This system assesses the evolution of the LUFS, its trade-offs, and synergies on a grid scale, with applications in the resource-depleted city of Xintai. The research findings indicate the following:(1) From 1985 to 2021, the LFUS, including production function (PF) and living functions (LF), showed a generally increasing trend. Ecological function (EF), however, fluctuated, initially decreasing, then increasing, and subsequently decreasing again. (2) During this period, the trade-off relationship between PF and LF strengthened from 1985 to 1996, weakened in 2011, and PF-EF showed a weak trade-off in 1985, transitioned to a synergy from 1996 to 2011, and reverted to a trade-off in 2021. (3) The relationships among LUFS elements showed mechanisms for the formation of trade-off and synergy relationships among LUFS. Conflicts between cultivated land and construction land primarily contributed to the trade-off between PF and LF. Meanwhile, conflicts between cultivated land and ecological land led to the trade-off between PF and EF, and conflicts between construction land and ecological land contributed to the trade-off between LF and EF. This study presents a bottom-up approach for constructing a LUFS evaluation indicator system for resource-based cities. This research provides valuable insights for land use decision-making, addressing the sustainability needs of transitioning resource-based cities

Viral genome comparison and phylogenetic analysis of IGR sequences between the viruses of ePVCVL and ePVCVL2 <i>Oryza</i> groups.

<p>(<b>A</b>) Ancestral virus circular genomes of ePVCVL and ePVCV2 <i>Oryza</i> groups. ORFs are represented with arrows. Predicted domains are outlined in different colors, with white used for functionally unknown regions. Viruses of ePVCVL2 are defined as non-autonomous PRVs by the absence of a necessary CP domain. IGRs are represented as black curved lines. Black dots and diamonds indicate primer binding sites and polypurine tracts, respectively. Details on virus genome construction are provided in <a href="http://www.plospathogens.org/article/info:doi/10.1371/journal.ppat.1006413#ppat.1006413.s003" target="_blank">S3 Fig</a>. (<b>B</b>) Dot plots of pairwise sequence comparisons of ePVCVL vs. ePVCVL2 <i>Oryza</i> groups using consensus sequences of the respective alignments of ePVCVL and ePVCVL2 sequences in the <i>O</i>. <i>sativa</i> genome. Axes correspond to sequence alignment lengths. Linear virus genomic structures are shown. Rectangles with arrows indicate ORFs, and thick black lines represent IGRs. Black stars represent the zinc finger motif in the CP domain. (<b>C</b>) Phylogenetic relationships of IGR sequences (alignment length = 538 nt) of ePVCVL and ePVCVL2 in the <i>O</i>. <i>sativa</i> genome. The ML tree was rooted using the oldest identified ePVCVL segment (<a href="http://www.plospathogens.org/article/info:doi/10.1371/journal.ppat.1006413#ppat.1006413.g002" target="_blank">Fig 2C</a>, <a href="http://www.plospathogens.org/article/info:doi/10.1371/journal.ppat.1006413#ppat.1006413.s015" target="_blank">S4</a> and <a href="http://www.plospathogens.org/article/info:doi/10.1371/journal.ppat.1006413#ppat.1006413.s016" target="_blank">S5</a> Tables). ePVCVL and ePVCVL2 sequences in the tree are indicated by green and blue, respectively. Bootstrap support values greater than 60% based on 1,000 replicates are shown as percentages at branches. The scale bar represents evolutionary distance in terms of nucleotide substitutions per site. The tree of IGR sequences of ePVCVL and ePVCVL2 in other <i>Oryza</i> genomes is shown in <a href="http://www.plospathogens.org/article/info:doi/10.1371/journal.ppat.1006413#ppat.1006413.s010" target="_blank">S10 Fig</a>. (<b>D</b>) Single nucleotide polymorphisms shared by ePVCVL and ePVCVL2 sequences in the orange-highlighted clade of the tree. Relative positions in the alignment are shown, and gaps in the alignment are indicated by hyphens.</p