MicroRNA-7 inhibits epithelial-to-mesenchymal transition and metastasis of breast cancer cells via targeting FAK expression

10.1371/journal.pone.0041523PLoS ONE78

Enhanced B7-H4 expression in gliomas with low PD-L1 expression identifies super-cold tumors.

BACKGROUND: Characterizing expression profiles of different immune checkpoint molecules are promising for personalized checkpoint inhibitory immunotherapy. Gliomas have been shown as potential targets for immune checkpoint inhibitors recently. Our study was performed to determine coexpression levels of two major B7 immune regulatory molecules programmed death ligand 1 (PD-L1) and B7-H4, both of which have been demonstrated to inhibit antitumor host immunity in gliomas. METHODS: We assessed tumor tissues from stage II-IV primary gliomas (n=505) by immunohistochemistry (IHC) for protein levels of both PD-L1 and B7-H4. Gene coexpression analysis assessing clusters based on extent of PD-L1/B7-H4 classifier genes expression were investigated in two transcriptome datasets (The Cancer Genome Atlas and Chinese Glioma Genome Atlas). In addition, levels of immune cell infiltrates were estimated with IHC and RNA-seq data for assessing the tumor immune microenvironment of PD-L1/B7-H4 subgroups. RESULTS: High expression of PD-L1 and B7-H4 in gliomas was 23% and 20%, respectively, whereas coexpression of two proteins at high levels was limited to 2% of the cases. Comparable results were seen in RNA-seq datasets where PD-L1 mRNA expression levels negatively correlated with that of B7-H4. Gene coexpression modules clustered within each grade of gliomas demonstrated lack of double-high modules (cluster with high expression of both PD-L1 and B7-H4 classifier genes). B7-H4 mRNA expression levels showed negative correlation with extent of immune cell infiltration and High-B7-H4 module gliomas (high B7-H4 but low PD-L1 classifier genes expression) had less tumor-infiltrating lymphocytes (TILs) and tumor-associated macrophages (TAMs). IHC assessment also showed few TILs and TAMs in High-B7-H4 subgroup gliomas. CONCLUSIONS: The majority of gliomas express PD-L1 or B7-H4, however, coexpression of both at high levels is minimal. The high-B7-H4 patients could be considered as \u27super-cold\u27 gliomas with significantly deficient in TILs, suggesting that B7-H4 might inhibit T-cell trafficking into the central nervous system. This study demonstrated that PD-L1 and B7-H4 may serve as mutually compensatory immune checkpoint molecules in gliomas for immune targeted or active-specific immunotherapy. The distinct B7-H4 pathways modulating T-cell function and immune evasion in glioma patients deserved to be further explored in the future during immunotherapy

Genome-wide association study on salt tolerance of core germplasm resources in watermelon

[Objective] The watermelon root system is relatively weak and sensitive to salt stress during the seedling stage, which results in a significant decline in both yield and quality. Breeding new salt-tolerant watermelon varieties presents an effective solution to this issue. This study aims to identify key candidate genes associated with salt tolerance in watermelon, thereby providing a crucial foundation for understanding the mechanisms underlying watermelon responses to salt stress and for the cultivation of new salt-tolerant varieties. [Methods] The related indexes of salt tolerance of 121 watermelon core germplasm materials were measured, which included 15 C. mucosospermus accessions,3 C. amarus accessions, 1 C. ecirrhosus accession,4 C. colocynthis accessions, 10 C. megalospermus accessions and 88 C. lanatus accessions. The phenotypic indicators assessed included above-ground fresh weight, above-ground dry weight, root length, root surface area, chlorophyll content, root proline, root potassium ion (K+) content, root sodium ion (Na+) content, and root soluble sugar content. We employed the FaST-LMM (factored spectrally transformed linear mixed models) method to conduct a genome-wide association study (GWAS) on the phenotypic data, locating and displaying the single nucleotide polymorphisms (SNPs) associated with these phenotypic traits using a Manhattan plot. Additionally, we utilized the watermelon genome for gene expression analysis and gene function annotation, ultimately leveraging transcriptome data from both salt-tolerant and saltsensitive materials to identify key candidate genes related to salt tolerance. [Results] The variation of the nine phenotypic data ranged from 9.05% to 91.41%, among which the coefficient of variation of root soluble sugar was the largest 91.41%, the variation range was from 0.03 mg·g-1 to 7.06 mg·g-1 and the average value was 1.08 mg·g-1. The coefficient of variation of chlorophyll content was the smallest 9.05%, the variation range was from 31.35 to 59.87, and the average value was 44.51. There were no significantly related SNP sites in the five indicators of above-ground fresh weight, above-ground dry weight, root length, chlorophyll content and root proline. However, there were SNP sites that were significantly associated with four traits: root surface area, root K+ content, root Na+ content and root soluble sugar content. One significant SNP site located on chromosome 2 was identified under the root surface area index, and twenty-three genes were obtained within the candidate interval, but only twenty genes were found to reach expression levels in salt- tolerant and salt- sensitive materials, and Cla97C02G043360, Cla97C02G043200, Cla97C02G043190, Cla97C02G043250, Cla97C02G043350, Cla97C02G043290 and Cla97C02G043320 were induced by salt stress. Twenty-five significant SNP sites were identified under the root K+ content index, including four SNPs on chromosome 8 and twenty-one SNPs on chromosome 10. There were twenty-five genes were obtained in the candidate interval, and only twelve genes achieved expression levels, among them Cla97C08G145130, Cla97C10G191810, Cla97C08G145090, Cla97C08G145150 and Cla97C08G145120 were induced by salt stress. Two significant SNP sites located on chromosome 1 were identified under the root Na+ content index, and ten genes were obtained in the candidate interval and only seven genes had expression levels, among them Cla97C01G009540, Cla97C01G009490 and Cla97C01G009510 were induced by salt stress. One significant SNP site located on chromosome 4 was identified under the root soluble sugar content index, eighteen genes were obtained in the candidate interval, and seventeen genes had expression levels, among them Cla97C04G073310, Cla97C04G073300, Cla97C04G073240, Cla97C04G073230, Cla97C04G073290, Cla97C04G073280, Cla97C04G073190, Cla97C04G073210 and Cla97C04G073270 were induced by salt stress. In salt-tolerant and salt-sensitive materials before and after 150 mmol·L-1 NaCl treatment, the expression changes of fifty-six candidate genes were analyzed, and nine of them were differentially expressed genes (DEGs). Among them, Cla97C08G145130, Cla97C04G073300, Cla97C01G009540, Cla97C10G191810, Cla97C02G043360, Cla97C02G043190 and Cla97C04G073310 were significantly up-regulated by salt stress, whereas Cla97C04G073170 and Cla97C02G043310 were significantly down-regulated by salt stress. These nine genes can be divided into two classes. It is worth noting that in category I, Cla97C08G145130 (mannan endo-1, 4-beta-mannosidase 1-like, ManA1) showed the most significant changes, and increased by 255.82 and 7.80 times in salt-sensitive and salt-tolerant materials, respectively. It was followed by Cla97C04G073300 (dehydration-responsive element-binding protein 2A, DREB2A) and Cla97C01G009540 (phloem protein 2-like A9, PP2A9), which increased by 31.63 and 9.18 times, 13.10 and 3.56 times in salt-sensitive and salt-tolerant materials, respectively. [Conclusion] It was speculated that these three genes may be key candidate genes related to watermelon salt tolerance, which provides a basis for analyzing the molecular mechanism of improving watermelon salt tolerance and developing molecular markers for assisted selection breeding

Embellished hollow spherical catalyst boosting activity and durability for oxygen reduction reaction

The final publication is available at Elsevier via https://doi.org/10.1016/j.nanoen.2018.07.031. © 2018. This manuscript version is made available under the CC-BY-NC-ND 4.0 license http://creativecommons.org/licenses/by-nc-nd/4.0/Transition metals hybridized to heteroatom doped carbon material can be regarded as the most promising non-noble candidate for boosting the sluggish kinetics of oxygen reduction reaction (ORR). However, it has always been a challenge to vastly boost the activity, and simultaneously retain a favorable structure from the supporting material. Herein, we prepared a high surface area hollow spherical carbon as a supporting material, and employed aminothiophenol (ATI) and poly-aminothiophenol (PATI) as heteroatom precursors to synthesize nitrogen and sulfur co-doped catalysts, i.e. HCS-A and HCS-PA, respectively. The two catalysts possessed chemically similar surface composition, and nearly identical chemical states for each element. However, only HCS-A was able to vastly inherit both morphological advantage and high surface area from the carbon support. In further half-cell electrochemical testing, HCS-A performed better ORR activities and higher selectivity toward 4 electron pathway than HCS-PA in both acidic and alkaline media. Moreover, HCS-A was proven to have excellent durability in half-cell testing, methanol tolerance as well as outstanding peak power density in both fuel cells and zinc-air batteries. This work not only indicates the promising performances of HCS-A, but more importantly offers a new viewpoint on the selection of heteroatom precursor to retain a favorable structure.University of WaterlooWaterloo Institute for NanotechnologyBallard Power SystemsCatalysis Research for Polymer Electrolyte Fuel Cells (CaRPE-FC), Simon Fraser UniversityNatural Sciences and Engineering Research Council || Automotive Partnership Canada Grant no. APCPJ 417858-1

Environmental Analysis Of Quasi-Static Electric Field Changes Of Tropical Lightning Flashes

The environmental conditions leading to the bouncing-wave discharge and the subsequent electron beam remain to be investigated in more detailed future studies. The analysis of quasi-static initial electric field changes (IECs) were found at the beginning of all 24 lightning flashes detected within reversal distance (22 Negative Cloud-to-Ground (–CG) and 2 normal Intra-Cloud (IC) flashes) in a tropical storm on June 15th, 2017 close to our station in Malacca, Malaysia (2.314077° N, 102.318282° E). The IECs durations averaged 4.28 ms for –CG flashes (range 1.48 to 9.45 ms) and averaged 11.30 ms for normal ICs flashes (range 7.24 to 15.35 ms). In comparison to Florida storms, the duration of IECs for –CG and IC flashes were 0.18 ms (range 0.08 to 0.33 ms) and 1.53 ms (range 0.18 to 5.70 ms), respectively. Moreover, the magnitudes of E-change for tropical thunderstorm were 0.13 V/m (range 0.03 to 0.44 V/m) for –CG flashes and-0.20 V/m (range-0.13 to-0.27 V/m) for IC flashes. The E-change magnitudes of tropical flashes are significantly larger than Florida flashes

Environmental Analysis Of Quasi-Static Electric Field Changes Of Tropical Lightning Flashes

The environmental conditions leading to the bouncing-wave discharge and the subsequent electron beam remain to be investigated in more detailed future studies. The analysis of quasi-static initial electric field changes (IECs) were found at the beginning of all 24 lightning flashes detected within reversal distance (22 Negative Cloud-to-Ground (–CG) and 2 normal Intra-Cloud (IC) flashes) in a tropical storm on June 15th, 2017 close to our station in Malacca, Malaysia (2.314077° N, 102.318282° E). The IECs durations averaged 4.28 ms for –CG flashes (range 1.48 to 9.45 ms) and averaged 11.30 ms for normal ICs flashes (range 7.24 to 15.35 ms). In comparison to Florida storms, the duration of IECs for –CG and IC flashes were 0.18 ms (range 0.08 to 0.33 ms) and 1.53 ms (range 0.18 to 5.70 ms), respectively. Moreover, the magnitudes of E-change for tropical thunderstorm were 0.13 V/m (range 0.03 to 0.44 V/m) for –CG flashes and-0.20 V/m (range-0.13 to-0.27 V/m) for IC flashes. The E-change magnitudes of tropical flashes are significantly larger than Florida flashes

High-Energy Radiation from Thunderstorms with ADELE: TGFs, Steps, and Glows

The biggest challenge in the study of high-energy processes in thunderstorms is getting a detector to the vicinity of the electrically active regions of a storm. The Airborne Detector for Energetic Lightning Emissions (ADELE) has been used to detect gamma rays from aircraft above storms and from a storm-chasing van on the ground. In August 2009, ADELE flew above Florida storms in a Gulfstream V jet, detecting the first terrestrial gamma-ray flash (TGF) seen from a plane and continuous glows of high-energy emission above thunderclouds. The presence of these glows suggests that a gradual process of relativistic runaway and feedback may help limit the total amount of charging in thunderstorms, in contrast to the traditional view that only lightning discharges compete with the charging process. The upper limits on TGF emission from intracloud and cloud-to-ground lightning from the ADELE flights demonstrated conclusively that a TGF of the sort seen from space is not associated with most lightning and not necessary to trigger it. In August 2010, observations from a van detected stepped-leader x-ray emission from at least four lightning strikes in ten days of operations. This mode of operation is therefore promising for future observations of the stepping process, although a more varied suite of instrumentation, in particular a flash-distance detector, would be useful. We will report on these results and on future possibilities for ADELE campaigns

Cholesterol 25-hydroxylase suppresses SARS-CoV-2 replication by blocking membrane fusion

Cholesterol 25-hydroxylase (CH25H) is an interferon (IFN)-stimulated gene that shows broad antiviral activities against a wide range of enveloped viruses. Here, using an IFN-stimulated gene screen against vesicular stomatitis virus (VSV)-SARS-CoV and VSV-SARS-CoV-2 chimeric viruses, we identified CH25H and its enzymatic product 25-hydroxycholesterol (25HC) as potent inhibitors of SARS-CoV-2 replication. Internalized 25HC accumulates in the late endosomes and potentially restricts SARS-CoV-2 spike protein catalyzed membrane fusion via blockade of cholesterol export. Our results highlight one of the possible antiviral mechanisms of 25HC and provide the molecular basis for its therapeutic development