Corrigendum: LncRNA FOXD3-AS1 promotes the malignant progression of nasopharyngeal carcinoma through enhancing the transcription of YBX1 by H3K27Ac modification.

[This corrects the article DOI: 10.3389/fonc.2021.715635.].

Exosomal-miR-522-3p derived from cancer-associated fibroblasts accelerates tumor metastasis and angiogenesis via repression bone morphogenetic protein 5 in colorectal cancer.

BACKGROUND: Colorectal cancer (CRC) is a gastrointestinal tract malignancy. Exosomes secreted by cancer-associated fibroblasts (CAFs) are reported to participate in tumor progression by delivering noncoding RNA or small proteins. However, the function of exosomal miR-522-3p in CRC remains unclear. METHODS: CAFs were derived from tumor tissues, and exosomes were identified by western blot or TEM/NTA and originated from CAFs/NFs. The viability, invasion, and migration of HUVECs and CRC cells was examined using MTT, Transwell, and wound healing assays, respectively. The molecular interactions were validated using dual luciferase reporter assay and RIP. Xenograft and lung metastasis mouse models were generated to assess tumor growth and metastasis. RESULTS: Exosomes extracted from CAFs/NFs showed high expression of CD63, CD81, and TSG101. CAF-derived exosomes significantly increased the viability, angiogenesis, invasion, and migration of HUVECs and CRC cells, thereby aggravating tumor growth, invasion, and angiogenesis in vivo. miR-522-3p was upregulated in CAF-derived exosomes and CRC tissues. Depletion of miR-522-3p reversed the effect of exosomes derived from CAFs in migration, angiogenesis, and invasion of HUVECs and CRC cells. Furthermore, bone morphogenetic protein 5 (BMP5) was identified as a target gene of miR-522-3p, and upregulation of BMP5 reversed the promoting effect of miR-522-3p mimics or CAF-derived exosomes on cell invasion, migration, and angiogenesis of HUVECs and CRC cells. CONCLUSION: Exosomal miR-522-3p from CAFs promoted the growth and metastasis of CRC through downregulating BMP5, which might provide new strategies for the treatment of CRC.

HPC-Atlas: Computationally Constructing A Comprehensive Atlas of Human Protein Complexes.

A fundamental principle of biology is that proteins tend to form complexes to play important roles in the core functions of cells. For a complete understanding of human cellular functions, it is crucial to have a comprehensive atlas of human protein complexes. Unfortunately, we still lack such a comprehensive atlas of experimentally validated protein complexes, which prevents us from gaining a complete understanding of the compositions and functions of human protein complexes, as well as the underlying biological mechanisms. To fill this gap, we built Human Protein Complexes Atlas (HPC-Atlas), as far as we know, the most accurate and comprehensive atlas of human protein complexes available to date. We integrated two latest protein interaction networks, and developed a novel computational method to identify nearly 9000 protein complexes, including many previously uncharacterized complexes. Compared with the existing methods, our method achieved outstanding performance on both testing and independent datasets. Furthermore, with HPC-Atlas we identified 751 severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-affected human protein complexes, and 456 multifunctional proteins that contain many potential moonlighting proteins. These results suggest that HPC-Atlas can serve as not only a computing framework to effectively identify biologically meaningful protein complexes by integrating multiple protein data sources, but also a valuable resource for exploring new biological findings. The HPC-Atlas webserver is freely available at http://www.yulpan.top/HPC-Atlas.

Particle Size Determines the Phytotoxicity of ZnO Nanoparticles in Rice (Oryza sativa L.) Revealed by Spatial Imaging Techniques.

To understand the nanotoxicity effects on plants, it is necessary to systematically study the distribution of NPs in vivo. Herein, elemental and particle-imaging techniques were used to unravel the size effects of ZnO NPs on phytotoxicity. Small-sized ZnO NPs (5, 20, and 50 nm) showed an inhibitory effect on the length and biomass of rice (Oryza sativa L.) used as a model plant. ZnO NP nanotoxicity caused rice root cell membrane damage, increased the malondialdehyde content, and activated antioxidant enzymes. As a control, the same dose of Zn2+ salt did not affect the physiological and biochemical indices of rice, suggesting that the toxicity is caused by the entry of the ZnO NPs and not the dissolved Zn2+. Laser ablation inductively coupled plasma optical emission spectroscopy analysis revealed that ZnO NPs accumulated in the rice root vascular tissues of the rhizodermis and procambium. Furthermore, transmission electron microscopy confirmed that the NPs were internalized to the root tissues. These results suggest that ZnO NPs may exist in the rice root system and that their particle size could be a crucial factor in determining toxicity. This study provides evidence of the size-dependent phytotoxicity of ZnO NPs.

Characterization and application of Fe-modified biochar alleviating Cr(VI) stress in pak choi seedling cultivated in Cr-polluted hydroponics.

Chromium (Cr) is one of the common environmental pollutants, which causes severe health hazards on human health and environmental security. In this study, we characterized two biochars, a raw biochar (RBC) and a Fe-modified biochar (MBC) made from poplar wood chips and determined the effect of the two biochars on remediation of hexavalent chromium (Cr(VI)) in hydroponic system by monitoring Pak choi growth. Results showed the surface area, pore number and pore volume were significantly higher in MBC than in PBC, but the pore size was larger in PBC than in MBC. When compared to the control, low concentrations of Cr(VI) (≤2 mg L-1) promoted the growth and biomass production of Pak choi by 10-78%. In contrast, the high concentrations of Cr(VI) (≥4 mg L-1) showed a significantly reduction of the growth and biomass production of Pak choi by 10-28%. Fe-modified biochar (MBC) had a more significant impact than RBC on the remediation of Cr in the Cr(VI) pollution and improved growth and biomass production of Pak choi to a greater extent. Our study indicated that MBC has a better effect on degrading Cr(VI) pollution. The findings provide scientific basis and reference for the remediation of heavy metals in aquatic ecosystems by using biochar.

PCGAN: a generative approach for protein complex identification from protein interaction networks.

MOTIVATION: Protein complexes are groups of polypeptide chains linked by non-covalent protein-protein interactions, which play important roles in biological systems and perform numerous functions, including DNA transcription, mRNA translation, and signal transduction. In the past decade, a number of computational methods have been developed to identify protein complexes from protein interaction networks by mining dense subnetworks or subgraphs. RESULTS: In this article, different from the existing works, we propose a novel approach for this task based on generative adversarial networks, which is called PCGAN, meaning identifying Protein Complexes by GAN. With the help of some real complexes as training samples, our method can learn a model to generate new complexes from a protein interaction network. To effectively support model training and testing, we construct two more comprehensive and reliable protein interaction networks and a larger gold standard complex set by merging existing ones of the same organism (including human and yeast). Extensive comparison studies indicate that our method is superior to existing protein complex identification methods in terms of various performance metrics. Furthermore, functional enrichment analysis shows that the identified complexes are of high biological significance, which indicates that these generated protein complexes are very possibly real complexes. AVAILABILITY AND IMPLEMENTATION: https://github.com/yul-pan/PCGAN.

Effects of perfluorinated compounds homologues on chemical property, microbial composition, richness and diversity of urban forest soil.

Perfluorinated compounds (PFCs), as an important class of new persistent organic pollutants, are widely distributed in the environment. Yet the effects of different types and concentrations of PFCs on soil microbial community in urban forest ecosystems are remain uncertain. Here, two typical PFCs, perfluorooctanoic acid (PFOA) and perfluorooctane sulfonic acid (PFOS), were selected to carry out a pot experiment in greenhouse with singly and joint treatment at different concentrations, to examine their effects on composition and diversity of soil microorganisms and availability of soil macronutrients by using high-throughput Illumina sequencing approach. The results showed both PFOA and PFOS application significantly increased soil NO3--N and NH4+-N content, but did not alter total phosphorus content, compared to the control check (CK) treatments. Total potassium content was reduced in PFOA treatments but increased in PFOS and PFOA×PFOS treatments. The most dominant bacterial phylum was Chloroflexi in low and medium PFCs concentrations and the CK treatments, but it was switched to Acidobacteria in high concentrations. No obvious change was detected for the composition of the dominant fungi community in PFCs treatments compared to the CK treatments. With the increase of PFCs concentrations, soil bacterial richness decreased but its diversity increased, whereas the richness and diversity of fungal community usually decreased. Redundancy analyses revealed that soil fungal community was more sensitive to PFCs pollutants than soil bacterial communities. Further data analysis revealed by structural equation model (SEM) that the PFCs exposed for 60 days indirectly affects the diversity and richness of soil bacteria and fungi by directly affecting NO3--N and NH4+-N content. The results suggested the concentration of PFCs pollutants played a primary role in determining the composition, richness and diversity of forest soil microbial communities.

Retrospective study of hypofractionated stereotactic radiotherapy combined with whole brain radiotherapy for patients with brain metastases.

BACKGROUND AND PURPOSE: To evaluate the clinical outcomes of hypofractionated stereotactic radiotherapy (HFSRT) combined with whole brain radiotherapy (WBRT) in patients with brain metastases (BMs). MATERIALS AND METHODS: From May 2018 to July 2020, 50 patients (111 lesions) received HFSRT (18 Gy/3F) + WBRT (40 Gy/20F). The RECIST 1.1 and RANO-BM criteria were used to evaluate treatment efficacy. Five prognostic indexes (RPA, GPA, SIR, BS-BM, and GGS) were applied. The primary endpoint was intracranial local control (iLC). Secondary endpoints were overall survival (OS) and the safety of treatment. RESULTS: Intracranial objective response rates (iORR) using the RECIST 1.1 and RANO-BM criteria were 62.1% and 58.6%, respectively. The iLC rate was 93.1%, the 6- and 12-month iLC rates were 90.8% and 57.4%, respectively. The median intracranial progression-free survival (iPFS) was not reached (range 0-23 months). The 6-, 12-, and 24-month OS rates were 74.2%, 58.2%, and 22.9%, respectively. The KPS score showed statistical significance in univariate analysis of survival. The 6, 12, and 24 month OS rates for patients with KPS ≥ 70 were 83.8%, 70.5%, and 29.7%, respectively. The median survival time (MST) for all patients and for patients with KPS ≥ 70 were 13.6 and 16.5 months, respectively. Sex, KPS score, and gross tumor volume were significant factors in the multivariate analysis of survival. OS was significantly associated with RPA, SIR, BS-BM, and GGS classes. No acute toxicities of grade 3 or higher were noted. CONCLUSION: HFSRT combined with WBRT is a safe and effective local treatment modality for BM patients.

A feedback loop between GATA2-AS1 and GATA2 promotes colorectal cancer cell proliferation, invasion, epithelial-mesenchymal transition and stemness via recruiting DDX3X.

BACKGROUND: Colorectal cancer (CRC) is a common malignant tumor with a high risk of metastasis. Long non-coding RNAs (lncRNAs) have been reported to be implicated in cancer progression via regulating its nearby gene. Herein, we investigated the function of GATA binding protein 2 (GATA2) and lncRNA GATA2 antisense RNA 1 (GATA2-AS1) in CRC and the mechanism underlying their interaction. METHODS: Colony formation assay, flow cytometry analysis and transwell assay were implemented to detect cell proliferation, apoptosis and invasion. Western blot analysis and sphere formation assay were conducted to assess epithelial-mesenchymal transition (EMT) and cancer stemness of CRC cells. RNA pull down, RNA-binding protein immunoprecipitation (RIP), chromatin immunoprecipitation (ChIP) and luciferase reporter assays were implemented to investigate the regulatory mechanism between GATA2-AS1 and GATA2. RESULTS: GATA2-AS1 and GATA2 were highly expressed in CRC cells. Knockdown of GATA2-AS1 and GATA2 impeded CRC cell proliferation, invasion, EMT and cancer stemness, and induced cell apoptosis. GATA2-AS1 expression was positively correlated with GATA2. GATA2-AS1 recruited DEAD-box helicase 3 X-linked (DDX3X) to stabilize GATA2 mRNA. GATA2 combined with GATA2-AS1 promoter to enhance GATA2-AS1 expression. CONCLUSION: Our study confirmed that a feedback loop between GATA2-AS1 and GATA2 promotes CRC progression, which might offer novel targets for CRC treatment.

Combined toxicity of zinc oxide nanoparticles and cadmium inducing root damage in Phytolacca americana L.

In recent years, nano-contamination in the soil environment has aroused concern. But it is still uncertain whether the interactions of nano- and metal-pollutants would have a combined toxic effect on plants. In this study, we investigated the effects of joint exposure to zinc oxide nanoparticles (ZnO NPs) and Cd on the root tissue of Phytolacca americana L. Spin-polarized density functional theory simulations assumed that the plant may undergo metal toxicity or acidosis upon joint exposure to ZnO NPs/Cd. Subsequently, experimental exposure of P. americana verified the combined toxic effects. The plant grew normally with a single treatment of ZnO NPs (500 mg/kg) or low doses of Cd (10 mg/kg). However, root growth was significantly inhibited with the combined treatments (up to 43% reduction); additionally, Cd ions were transported to the shoot, leading to shoot growth inhibition (translocation factor > 1). The antioxidant enzymes in the root (superoxide dismutase, peroxidase, and catalase) were highly activated to resist stress, accompanied by a greater than two-fold increase in thiobarbituric acid reactive substances. Corresponding to physiological indicators, biological transmission electron microscopy revealed severe damage to the root cells. Moreover, ZnO NPs/Cd accumulation was observed in the root cytoderm, which confirmed the toxicity of the combined effects. Our study provides insight into the potential combined toxicity of ZnO NPs and heavy metals in polluted environments, such as mining areas and electronic waste sites, and agricultural soils.