PLEKHA4 Is a Prognostic Biomarker and Correlated with Immune Infiltrates in Glioma.

Objective: Gliomas are the most common and life-threatening intracranial tumors. Immune infiltration of the tumor microenvironment significantly affects tumor prognosis in glioma. Recently, PLEKHA4 was reported to be upregulated in melanoma and closely associated with tumor genesis and development, but its role in glioma is poorly understood. Our aim was to investigate the expression, functional role, and prognostic value of PLEKHA4 in glioma. Methods: The expression levels of PLEKHA4 in 33 types of cancer in the TCGA (The Cancer Genome Atlas) database were collected via the UCSC Xena browser. The clinical samples of glioma patients were downloaded from the TCGA database. Immunohistochemistry was used to verify PLEKHA4 expression in tumor tissues. We assessed the influence of PLEKHA4 on survival of glioma patients by survival module and GEPIA. Then, we downloaded datasets of glioma from TCGA and investigated the correlations between the clinical characteristics and PLEKHA4 expression using logistic regression. Moreover, we used TIMER to explore the collection of PLEKHA4 expression and immune infiltration level in glioma and to analyze cumulative survival in glioma. Gene Set Enrichment Analysis (GSEA) was performed using the TCGA dataset. Results: PLEKHA4 transcript levels were significantly upregulated in multiple cancer types, including gliomas. Moreover, immunohistochemical analysis verified that PLEKHA4 was overexpressed in gliomas compare to the corresponding normal tissues. Univariable survival and multivariate cox analysis show that increased PLEKHA4 expression significantly correlated with age, tumor grade, IDH mutation status, and 1p/19q codel status, and higher PLEKHA4 had shorter OS, DSS, and PFI. Specifically, PLEKHA4 expression level had significant positive correlations with infiltrating levels of B cell, CD4+ T cells, CD8+ T cells, macrophages, neutrophils, and DCs in glioma, and upregulation of PLEKHA4 expression was significantly related to immune cell biomarkers and immune checkpoint expression in glioma. In addition, several GO and Kyoto Encyclopedia of Genes and Genomes (KEGG) items associated with immune response, JAK STAT signal pathway, and cell cycle were significantly enriched in the high PLEKHA4 expression phenotype pathway. Conclusions: Our findings proposed that PLEKHA4 was an independent prognostic biomarker and correlated with immune infiltrates in glioma, and targeting PLEKHA4 might improve immunotherapy in glioma. Of course, these findings also need basic experiments and further clinical trials to confirm in the future.

Effect of phenol formaldehyde-associated microplastics on soil microbial community, assembly, and functioning.

Increasing investigations explore the effects of plastic pollutants on bacterial communities, diversity, and functioning in various ecosystems. However, the impact of microplastics (MPs) on the eukaryotic community, microbial assemblages, and interactions is still limited. Here, we investigated bacterial and micro-eukaryotic communities and functioning in soils with different concentrations of phenol formaldehyde-associated MPs (PF-MPs), and revealed the factors, such as soil properties, microbial community assembly, and interactions between microbes, influencing them. Our results showed that a high concentration (1%) of PF-MPs decreased the microbial interactions and the contribution of deterministic processes to the community assembly of microbes, and consequently changed the communities of bacteria, but not eukaryotes. A significant and negative relationship was determined between N2O emission rate and functional genes related to nitrification, indicating that the competitive interactions between functional microbes would affect the nitrogen cycling of soil ecosystem. We further found that vegetable biomass weakly decreased in treatments with a higher concentration of PF-MPs and positively related to the diversity of micro-eukaryotic communities and functional diversity of bacterial communities. These results suggest that a high concentration of the PF-MPs would influence crop growth by changing microbial communities, interactions, and eukaryotic and functional diversity. Our findings provide important evidence for agriculture management of phenol formaldehyde and suggest that we must consider their threats to microbial community compositions, diversity, and assemblage in soils due to the accumulation of PF-MPs widely used in the field.

Spatiotemporal variations of microbial assembly, interaction, and potential risk in urban dust.

Community and composition of dust-borne microbes would affect human health and are regulated by microbial community assembly. The dust in kindergarten is always collected to evaluate the microbial exposure of children, yet the microbial assembly, their interactions, and potential pathogens in kindergarten dust remain unclear. Here, we aim to investigate the microbial community assembly and structures, and potential bacterial pathogens in outdoor dust of kindergartens, and reveal the factors influencing the assembly and composition of microbial community. A total of 118 urban dust samples were collected on the outdoor impervious surfaces of 59 kindergartens from different districts of Xiamen in January and June 2020. We extracted microbial genomic DNA in these dusts and characterized the microbial (i.e., bacteria and fungi) community compositions and diversities using target gene-based (16S rRNA genes for bacterial community and ITS 2 regions for fungal community) high-throughput sequencing. Potential bacterial pathogens were identified and the interactions between microbes were determined through a co-occurrence network analysis. Our results showed the predominance of Actinobacteria and α-Proteobacteria in bacterial communities and Capnodiales in fungal communities. Season altered microbial assembly, composition, and interactions, with both bacterial and fungal communities exhibiting a higher heterogeneity in summer than those in winter. Although stochastic processes predominated in bacterial and fungal community assembly, the season-depended environmental factors (e.g., temperature) and interactions between microbes play important roles in dust microbial community assembly. Potential bacterial pathogens were detected in all urban dust, with significantly higher relative abundance in summer than that in winter. These results indicated that season exerted more profound effects on microbial community composition, assembly, and interactions, and suggested the seasonal changes of potential risk of microbes in urban dust. Our findings provide new insights into microbial community, community assembly, and interactions between microbes in the urban dust, and indicate that taxa containing opportunistic pathogens occur commonly in urban dust.

Response of soil viral communities to land use changes.

Soil viruses remain understudied when compared to virus found in aquatic ecosystems. Here, we investigate the ecological patterns of soil viral communities across various land use types encompassing forest, agricultural, and urban soil in Xiamen, China. We recovered 59,626 viral operational taxonomic units (vOTUs) via size-fractioned viromic approach with additional mitomycin C treatment to induce virus release from bacterial fraction. Our results show that viral communities are significantly different amongst the land use types considered. A microdiversity analysis indicates that selection act on soil vOTUs, resulting in disparities between land use associated viral communities. Soil pH is one of the major determinants of viral community structure, associated with changes of in-silico predicted host compositions of soil vOTUs. Habitat disturbance and variation of soil moisture potentially contribute to the dynamics of putative lysogenic vOTUs. These findings provide mechanistic understandings of the ecology and evolution of soil viral communities in changing environments.

YTHDF2 is a novel diagnostic marker of endometrial adenocarcinoma and endometrial atypical hyperplasia/ intraepithelial neoplasia.

Numerous studies show that some biomarkers are aberrantly expressed in endometrial endometrioid adenocarcinoma (EMAC) and endometrial atypical hyperplasia/endometrioid intraepithelial neoplasia (EAH/EIN) compared to endometrial benign lesions. Because of low sensitivity and/or specificity, the utility of these markers to distinguish EMAC and EAH/EIN from benign endometrial lesions is limited. YTH domain family 2 (YTHDF2) is a functional N6-methyladenosine (m6A)-specific reader protein that mainly regulates mRNA stability. Aberrant YTHDF2 expression has been reported in many cancers and plays important functions in tumorigenesis and cancer progression. However, its expression in endometrial benign and malignant lesions has not been investigated. We evaluated YTHDF2 mRNA and protein expression in EMAC and normal endometrium using the UALCAN database and validated the bioinformatic results in EMAC cells using qRT-PCR, Western blot, and immunohistochemical (IHC) staining. We found that YTHDF2 was weakly expressed in normal endometrium, benign endometrial lesions, endometrial hyperplasia without atypia, and adenomyosis. In contrast, YTHDF2 was upregulated in EAH/EIN and EMAC. These results indicate that YTHDF2 immunostaining may be a useful tool to distinguish EAH/EIN from EHWA. Finally, YTHDF2 expression can accurately assess the depth of myometrial invasion (DMI) in EMAC when EMAC coexists with adenomyosis.

Earthworms reduce the dissemination potential of antibiotic resistance genes by changing bacterial co-occurrence patterns in soil.

Globally distributed earthworms affect compositions of soil compounds, microbial community structures, as well as antibiotic resistance genes (ARGs). Compared to their surroundings, earthworm gut is a simpler environment which could filter out microbes when soil passes through it. However, little is known about how earthworms affect the dissemination of ARGs in soil, and the understanding of the relationship between microbe-microbe interactions and ARGs is still lacking. Here, we designed a microcosm experiment with earthworm addition, and determined bacterial and fungal community compositions based on amplicon sequencing. We also examined mobile genetic elements (MGEs) and ARGs in earthworm gut and soils using high-throughput qPCR. The results showed significant differences of bacterial, fungal and ARG patterns between gut and soil. Earthworms indirectly impacted the patterns of ARGs in soils by affecting bacterial communities and soil properties, which play key roles in the distribution of ARGs and MGEs. The absolute abundances of MGEs in earthworm gut were significantly lower than those in soils, and earthworms reduce the absolute abundance of MGEs in soils. Earthworms changed the microbial co-occurrence patterns, and reduced bacterial connectivity, which were significantly and positively correlated with MGE abundance. These results highlight the importance of earthworm on the distribution and dissemination of ARGs in soils.

An unusual case of anaplastic lymphoma kinase-positive large B-cell lymphoma in an elderly patient: A case report and discussion.

We present an unusual case of anaplastic lymphoma kinase (ALK)-positive large B-cell lymphoma, with rapid clinical progression, which occurred in a 90-year-old male patient. The patient presented with numerous enlarged lymph nodes in the neck and mediastinum. Histopathological analysis of a single lymph node detected diffuse large immunoblastic- or plasmablastic-like tumor cells, which were strongly immunoreactive for ALK in a granular cytoplasmic distribution, but negative for the expression of CD20 and CD79a. In addition, polymerase chain reaction assays were unable to detect clonal rearrangements of the T cell receptor-γ and immunoglobulin heavy chain genes in the tumor lesion, and in situ hybridization tested negative for infection with Epstein-Barr virus. The patient underwent a single cycle of chemotherapy using the cyclophosphamide, doxorubicin, vincristine, prednisone, and etoposide (E-CHOP) regimen; however, the patient developed pleural effusions with respiratory distress, associated with clinical deterioration. The patient succumbed to the disease within 4 months of initial presentation. To the best of our knowledge, this is the eldest patient with this type of lymphoma to be reported in the literature.

Activated carbon derived from melaleuca barks for outstanding high-rate supercapacitors.

Activated carbon (AC) was prepared via carbonizing melaleuca bark in an argon atmosphere at 600 °C followed with KOH activation for high-rate supercapacitors. This AC electrode has a high capacitance of 233 F g(-1) at a scan rate of 2 mV s(-1) and an excellent rate capability of ∼80% when increasing the sweep rate from 2 to 500 mV s(-1). The symmetric supercapacitor assembled by the above electrode can deliver a high energy density of 4.2 Wh kg(-1) with a power density of 1500 W kg(-1) when operated in the voltage range of 0-1 V in 1 M H2SO4 aqueous electrolyte while maintaining great cycling stability (less than 5% capacitance loss after 10 000 cycles at sweep rate of 100 mV s(-1)). All the outstanding electrochemical performances make this AC electrode a promising candidate for potential energy storage application.

Hierarchical TiO2 flowers built from TiO2 nanotubes for efficient Pt-free based flexible dye-sensitized solar cells.

A novel hierarchical TiO(2) flower consisting of anatase TiO(2) nanotubes on a Ti foil substrate has been prepared via a mild hydrothermal reaction of TiO(2) nanoparticles/Ti foil. The photovoltaic performance of DSSC based on hierarchical TiO(2) flowers/Ti (7.2%) is much higher than that of TiO(2) nanoparticle/Ti (6.63%) because of its superior light scattering ability and fast electron transport. Moreover, full flexible DSSC based on the novel hierarchical TiO(2) flowers/Ti foil photoelectrode and electrodeposited poly(3,4-ethylenedioxythiophene) (PEDOT) on indium tin oxide-coated poly(ethylene terephthalate) (ITO-PET) counter electrode shows a significant power conversion efficiency of 6.26%, accompanying a short-circuit current density of 11.96 mA cm(-2), an open-circuit voltage of 761 mV and a fill factor of 0.69.

CdS/CdSe quantum dot shell decorated vertical ZnO nanowire arrays by spin-coating-based SILAR for photoelectrochemical cells and quantum-dot-sensitized solar cells.

A CdS/CdSe composite shell is assembled onto the surface of ZnO nanowire arrays with a simple spin-coating-based successive ionic layer adsorption and reaction method. The as-prepared photoelectrode exhibit a high photocurrent density in photoelectrochemical cells and also generates good power conversion efficiency in quantum-dot-sensitized solar cells.

[The effects of nicotine on human airway epithelial cells].

OBJECTIVE: To investigate the genome changes of primary human airway epithelial cells exposed to nicotine in vitro, and therefore to understand the effect of nicotine on the cellular physiological process and phenotypes. METHODS: The primary human airway epithelial cells were divided into 4 groups: 4 h experimental group and control group, 48 h experimental group and control group, with 1×10(8)/L cells in each culture. Total RNA was extracted from cells after incubated with nicotine (1×10(-5) mol/L) for 4 h or 48 h respectively. The genes expressed differentially were detected by a gene chip, and those related to epithelial mesenchymal transition were selected to undergo real-time PCR for verification. RESULTS: Sixty-three up-regulated genes and 44 down-regulated genes were detected in the experimental group incubated with nicotine for 4 h, which were mainly involved in the stress response. There were 860 up-regulated genes and 582 down-regulated genes found in the cells treated with 1×10(-5) mol/L nicotine for 48 h, compared with the control. These genes were mainly involved in some important physiological processes and pathways with transdifferentiation, including embryonic development, cell polarity maintaining, cell adhesion, etc. Further analysis revealed that some epithelial markers such as epithelial keratin and epithelial mucin protein were down-regulated, while mesenchymal cell markers including fiber connecting protein 1 and N-cadherin were up-regulated. The results by real-time PCR showed consistency with those by gene chip examination. CONCLUSION: Nicotine could promote a series of changes in genes related to epithelial mesenchymal transdifferentiation process in human airway epithelial cells.

[Construction of a recombinant adenovirus Ad5F35-SD-EGFP and its effect on K562 cell proliferation].

OBJECTIVE: To construct a recombinant adenovirus vector for SH2-DED fusion gene and assess its inhibitory effect on the proliferation of K562 cells. METHODS: SH2-DED fusion gene and its mutant SH2mt-DED were amplified by splicing PCR and cloned into pAdTrack-CMV plasmid separately to construct the shuttle plasmids pAdT-SD-EGFP and pAdT-SmD-EGFP, respectively. After Pme I digestion, the shuttle plasmids were transformed into ultra-competent pAd5F35-BJ5183 cells to generate defective adenovirus vectors pAd5F35-SD-EGFP and pAd5F35- SmD-EGFP by homologous recombination. The vectors, linearized by Pac I digestion, were further transfected into AD293 cells for packaging and amplified by infecting AD293 cells repeatedly. K562 cells were then infected by the recombinant adenoviruses and the expression of SD was detected by Western blotting. MTT assay and flow cytometry were used to investigate the effect of Ad5F35-SD-EGFP and Ad5F35-SmD-EGFP on the proliferation of K562 cells. RESULTS: The recombinant adenovirus vectors pAd5F35-SD-EGFP and pAd5F35-SmD-EGFP were constructed correctly, with a titer reaching 1.5×10(12) pfu/ml after amplification. Western blotting demonstrated that the target proteins were effectively expressed in transfected K562 cells. MTT assay and flow cytometry showed that transfection with pAd5F35-SD-EGFP resulted in growth inhibition rate of 55.21% in K562 cells, significantly higher than the inhibition rate of 17.95% following transfection with pAd5F35- SmD-EGFP and 7.33% following PBS treatment (P<0.05). CONCLUSION: The recombinant adenovirus vector Ad5F35-SD-EGFP we constructed can significantly inhibit the proliferation of K562 cells in vitro.

The intracellular stability of DLC1 is regulated by the 26S proteasome in human hepatocellular carcinoma cell line Hep3B.

Deleted in liver cancer 1 (DLC1), a tumor suppressor gene identified in a primary human hepatocellular carcinoma, encodes a Rho GTPase-activating protein (RhoGAP). Although DLC1 expression has been studied at the transcriptional level, little is known about its regulation at the protein level. Here we show that DLC1 is an unstable protein that is degraded by the 26S proteasome in human hepatocellular carcinoma Hep3B cells. In addition, five putative PEST motifs were identified in the N-terminus of DLC1. Unexpectedly, the N-terminus of DLC1 appeared to be stable. Furthermore, deletion of any one of the five PEST motifs except PEST2 decreased the stability of the N-terminus of DLC1, which suggests that the PEST motifs may play an unrevealed role in maintaining the stability of DLC1. These data indicated that the intracellular stability of DLC1 is regulated by the 26S proteasome via its PEST motifs.