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.

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.

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.

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.

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.

Enhanced Chemodynamic Therapy and Chemotherapy via Delivery of a Dual Threat ArtePt and Iodo-Click Reaction Mediated Glutathione Consumption.

Cisplatin has been used as standard regimen for hepatocellular carcinoma (HCC), but its therapeutic efficacy is greatly limited by the drug resistance. Cisplatin alone cannot achieve an ideal therapeutic outcome. Herein, a dual threat hybrid artemisinin platinum (ArtePt) is synthesized to combine chemodynamic therapy (CDT) with chemotherapy. On the one hand, artesunate can react with intracellular ferrous ion to generate reactive oxygen species (ROS) via Fenton reaction for CDT. On the other hand, cisplatin can target DNA for chemotherapy. However, GSH in cancer cells can effectively consume free radicals and detoxify cisplatin simultaneously, which compromised the efficacy of CDT and chemotherapy. Hence, an amphiphilic polymer with an iodine atom in the side chain is designed and encapsulated ArtePt to form NP(ArtePt). This iodine containing polymer NP(ArtePt) can effectively deplete intracellular GSH via an Iodo-Click reaction, thereby enhancing the effect of CDT as well as chemotherapy. Thereafter, a patient-derived xenograft model of hepatic carcinoma (PDXHCC ) is established to evaluate the therapeutic effect of NP(ArtePt), and a significant antitumor effect is achieved with NP(ArtePt). Overall, this study provides an effective strategy to combine CDT with chemotherapy to enhance the efficacy of cisplatin via Iodo-Click reaction, opening a new avenue for the cancer treatment.

LncRNA FOXD3-AS1 Promotes the Malignant Progression of Nasopharyngeal Carcinoma Through Enhancing the Transcription of YBX1 by H3K27Ac Modification.

BACKGROUND: Long noncoding RNAs (lncRNAs) can affect the progression of various tumors, including nasopharyngeal carcinoma (NPC). Here, lncRNA FOXD3-AS1 is highly expressed in NPC tissues through bioinformatics analysis and related to the malignant progression of NPC. METHODS: Bioinformatics analysis and real-time reverse transcription quantitative PCR(RT-qPCR) assay were applied to identify the expression of FOXD3-AS1 in NPC tissues and cells. Specific short hairpin RNAs (shRNAs) or overexpression plasmids were used to knockdown or upregulate FOXD3-AS1 in NPC cells. The effect of FOXD3-AS1 on proliferation and metastasis of NPC was confirmed by CCK8, colony formation, transwell assays in vitro and mouse tumor growth and metastasis models in vivo, of which the mechanism was explored by RNA pull down, mass spectrometry (MS), RNA Immunoprecipitation (RIP), chromatin immunoprecipitation (CHIP) and luciferase assays. RESULTS: FOXD3-AS1 was highly expressed in NPC tissues and cells. Knockdown of FOXD3-AS1 significantly inhibited proliferation, migration, and invasion of NPC cells in vitro and vivo. FOXD3-AS1 could specifically bind to YBX1 and have a positive effect on the expression of YBX1. Bioinformatics analysis showed that the promoter of YBX1 had a high enrichment of H3K27ac, which promote mRNA transcription and protein translation of YBX1. Moreover, overexpression of YBX1 could reverse the proliferation, migration and invasion arrest caused by FOXD3-AS1 knockdown. CONCLUSION: LncRNA FOXD3-AS1 is highly expressed and promotes malignant phenotype in NPC, which may provide a new molecular mechanism for NPC.

Nabe: an energetic database of amino acid mutations in protein-nucleic acid binding interfaces.

Protein-nucleic acid complexes play essential roles in regulating transcription, translation, DNA replication, repair and recombination, RNA processing and translocation. Site-directed mutagenesis has been extremely useful in understanding the principles of protein-DNA and protein-RNA interactions, and experimentally determined mutagenesis data are prerequisites for designing effective algorithms for predicting the binding affinity change upon mutation. However, a vital challenge in this area is the lack of sufficient public experimentally recognized mutation data, which leads to difficulties in developing computational prediction methods. In this article, we present Nabe, an integrated database of amino acid mutations and their effects on the binding free energy in protein-DNA and protein-RNA interactions for which binding affinities have been experimentally determined. Compared with existing databases and data sets, Nabe is the largest protein-nucleic acid mutation database, containing 2506 mutations in 473 protein-DNA and protein-RNA complexes, and of that 1751 are alanine mutations in 405 protein-nucleic acid complexes. For researchers to conveniently utilize the data, Nabe assembles protein-DNA and protein-RNA benchmark databases by adopting the data-processing procedures in the majority of models. To further facilitate users to query data, Nabe provides a searchable and graphical web page. Database URL: http://nabe.denglab.org.

FOXO3a inhibits the EMT and metastasis of breast cancer by regulating TWIST-1 mediated miR-10b/CADM2 axis.

BACKGROUND: Breast cancer is the most common malignancy and has been considered as a leading cause of cancer death in women. Exploring the mechanism of breast cancer metastasis is extremely important for seeking novel therapeutic strategies and improving prognosis. METHODS: Clinical specimens and pathological characteristics were collected for evaluating the expression of forkhead box class O 3a (FOXO3a) and twist-related protein 1 (TWIST-1) in breast cancer tissues. CCK-8 assay was used to analyze cell proliferation. Cell invasion and migration were assessed by transwell assays. The expression of FOXO3a, TWIST-1, miR-10b, CADM2, FAK, phosphor-AKT and the epithelial-mesenchymal transition (EMT)-related protein (N-cadherin, E-cadherin and vimentin) were analyzed by RT-qPCR, immunohistochemical staining, immunofluorescence assay or western blot, respectively. Xenograft mouse models were used to analyze the role of the FOXO3a in breast cancer. RESULTS: FOXO3a was down-regulated and TWIST-1 was up-regulated in breast cancer tissues. Overexpression of FOXO3a or knockdown of TWIST-1 suppressed the proliferation, invasion, migration and EMT of breast cancer cells. Overexpression of TWIST-1 could reverse the effect of FOXO3a on the proliferation, invasion, migration and EMT of breast cancer. Moreover, FOXO3a suppressed the growth and metastasis of breast cancer by targeting TWIST1 in vivo. CONCLUSION: FOXO3a inhibited the EMT and metastasis of breast cancer via TWIST-1/miR-10b/CADM2 axis.

Prothymosin α promotes colorectal carcinoma chemoresistance through inducing lipid droplet accumulation.

Colorectal cancer (CRC) affects millions of people worldwide. Chemoresistance seriously impairs the therapeutic effects. Lipid droplets (LDs) abnormally accumulate in CRC supported chemoresistance. Exploring the mechanism of LD-induced chemoresistance is extremely important for improving prognosis of CRC patients. The expression of PTMA was increased in both CRC tissues and cells, which was positively correlated with LD production. PTMA facilitated chemoresistance to gemcitabine by inducing LD production in CRC cells. PTMA enhanced LD biogenesis and chemoresistance to gemcitabine by promoting SREBP-1-mediated lipogenesis and STAT3 activation in CRC.

lncRNA MIR22HG-Derived miR-22-5p Enhances the Radiosensitivity of Hepatocellular Carcinoma by Increasing Histone Acetylation Through the Inhibition of HDAC2 Activity.

BACKGROUND: With the development of radiotherapy technology, radiotherapy has been increasingly used to treat primary hepatocellular carcinoma (HCC). However, due to radioresistance and the intolerance of the adjacent organs to radiation, the effects of radiotherapy are often unsatisfactory. Therefore, it is necessary to study radiosensitization in HCC. METHOD: A microarray was used to analyze the genes that were significantly associated with radiosensitivity. HCC cells, HepG2 and MHCC97H, were subjected to radiation in vitro. Real-time PCR was performed to determine MIR22HG (microRNA22 host gene) and miR-22-5p expression levels. Western blotting was performed to determine histone expression levels. A histone deacetylase (HDAC) whole cell assay was used to determine the activity of HDAC2. MTT, colony formation, 5-ethynyl-2'-deoxyuridine, and wound healing assays were performed to examine the function of MIR22HG and miR-22-5p in cellular radiosensitivity. Chromatin immunoprecipitation-PCR was used to confirm that HDAC2 affects the acetylation level of the MIR22HG promoter region. Finally, animal experiments were performed to demonstrate the in vivo effect of MIR22HG on the radiosensitivity of hepatoma. RESULTS: Irradiation can up-regulate MIR22HG expression and down-regulate HDAC2 expression. Inhibition of HDAC2 expression promotes histone acetylation in the MIR22HG promoter region and up-regulates MIR22HG expression. MIR22HG can increase radiosensitivity via miR-22-5p in HCC. CONCLUSION: Inhibition of HDAC2 expression promotes histone acetylation in the MIR22HG promoter region, thereby up-regulating the expression of MIR22HG and promoting the production of miR-22-5p, and ultimately increasing the sensitivity of liver cancer radiotherapy.

LncRNA HOTAIR recruits SNAIL to inhibit the transcription of HNF4α and promote the viability, migration, invasion and EMT of colorectal cancer.

Colorectal cancer causes severe burdensome on the health by its high fatality and poor prognosis. Hox transcript antisense intergenic RNA (HOTAIR) was believed closely related with the genesis and development of colorectal cancer, but the regulatory mechanism is still to be investigated. The expression of HOTAIR was analyzed in colorectal cancer using both qRT-PCR and ISH assay. The cell viability, migration, invasion and apoptosis rate were evaluated using MTT, BrdU,Transwell and flow cytometryexperiments. The interaction between HOTAIR and SNAIL was detected using RIP and RNA pull-down. The binding of SNAIL to HNF4α promoter was assessed by ChIP. The cell lines that knock down HOTAIR, SNAIL or overexpress HNF4α were constructed using retroviral vector system. The tumorigenic and metastatic capacity of colorectal cancer cells after knocking down HOTAIR were evaluated based on xenograft assay and liver metastases model. HOTAIR was highly expressed in both tissue and cell lines of colorectal cancer, indicated a regulatory function in colorectal cancer. Knock-down of HOTAIR suppressed cell viability, migration, invasion and epithelial-mesenchymal transition (EMT) of colorectal cancer cells in vitro, and inhibited the growth and metastasis of colorectal tumor in nude mice. We further found that HOTAIR suppressed HNF4α via recruiting SNAIL, and the overexpression of HNF4α inhibited cell viability, migration, invasion and EMT of colorectal cancer cells. We demonstrated that HOTAIR regulates the level of HNF4α via recruiting SNAIL, knocking down HOTAIR repressed the cell viability and metestasis of colorectal cancer cell line in vitro, and suppressed the tomorgenesis and migration/invasion of colorectal cancer in vivo.

Microorganism structure variation in urban soil microenvironment upon ZnO nanoparticles contamination.

Nanoparticles (NPs) sink into the soil via agricultural spreading, surface water, atmospheric deposition, and industrial emission, which affects plant growth and soil microenvironment. To understand how NPs influence urban soil microenvironment, the effect of typical nano-pollutants zinc oxide nanoparticles (ZnONPs) was investigated in urban solid-waste land. Pokeweed (Phytolacca Americana L.) soil samples from solid-waste land were collected and exposed to 200, 500, and 1000 mg kg-1 ZnONPs. The physiological characteristics of pokeweed, soil bacterial community composition, and soil physiochemical properties and enzymatic activities were determined. Our results show that pokeweed growth was slightly inhibited, and soil acid-base homeostasis was affected in ZnONPs-contaminated samples. Meanwhile, enzymatic activities related to soil C cycle were enhanced, and bacterial community structure at the phylum and genus levels was altered. Specifically, the abundance of hydrocarbon-degrading taxa reduced substantially upon ZnONPs exposure. The phenoloxidase (PPO) activity and the refractory hydrocarbon-degrading bacteria Bacteroidetes was adversely affected by ZnONPs exposure. In addition, Subgroup_10 of Acidobacteria was identified as an indicator of soil ZnONPs contamination. Our study detected changes in plant growth, soil environmental factors, and soil microbe community composition in urban solid-waste land treated by ZnONPs. The results of this research provide evidence for ZnONPs toxicology on urban soil microenvironment.

Computationally identifying hot spots in protein-DNA binding interfaces using an ensemble approach.

BACKGROUND: Protein-DNA interaction governs a large number of cellular processes, and it can be altered by a small fraction of interface residues, i.e., the so-called hot spots, which account for most of the interface binding free energy. Accurate prediction of hot spots is critical to understand the principle of protein-DNA interactions. There are already some computational methods that can accurately and efficiently predict a large number of hot residues. However, the insufficiency of experimentally validated hot-spot residues in protein-DNA complexes and the low diversity of the employed features limit the performance of existing methods. RESULTS: Here, we report a new computational method for effectively predicting hot spots in protein-DNA binding interfaces. This method, called PreHots (the abbreviation of Predicting Hotspots), adopts an ensemble stacking classifier that integrates different machine learning classifiers to generate a robust model with 19 features selected by a sequential backward feature selection algorithm. To this end, we constructed two new and reliable datasets (one benchmark for model training and one independent dataset for validation), which totally consist of 123 hot spots and 137 non-hot spots from 89 protein-DNA complexes. The data were manually collected from the literature and existing databases with a strict process of redundancy removal. Our method achieves a sensitivity of 0.813 and an AUC score of 0.868 in 10-fold cross-validation on the benchmark dataset, and a sensitivity of 0.818 and an AUC score of 0.820 on the independent test dataset. The results show that our approach outperforms the existing ones. CONCLUSIONS: PreHots, which is based on stack ensemble of boosting algorithms, can reliably predict hot spots at the protein-DNA binding interface on a large scale. Compared with the existing methods, PreHots can achieve better prediction performance. Both the webserver of PreHots and the datasets are freely available at: http://dmb.tongji.edu.cn/tools/PreHots/ .

Bi(OAc)3/chiral phosphoric acid catalyzed enantioselective allylation of seven-membered cyclic imines, dibenzo[b,f][1,4]oxazepines.

An efficient asymmetric allylation reaction of allylboronates with seven-membered cyclic imines, dibenzo[b,f][1,4]oxazepines, is described. The reaction, which is catalyzed by a Bi(OAc)3/CPA system, gives a range of chiral nitrogen-containing heterocycle structures in high yields and with good enantioselectivities. The conversion of these products to nitrogen-containing heterocycles is also demonstrated.

Direct C-H difluoromethylation of heterocycles via organic photoredox catalysis.

The discovery of modern medicine relies on the sustainable development of synthetic methodologies to meet the needs associated with drug molecular design. Heterocycles containing difluoromethyl groups are an emerging but scarcely investigated class of organofluoro molecules with potential applications in pharmaceutical, agricultural and material science. Herein, we developed an organophotocatalytic direct difluoromethylation of heterocycles using O2 as a green oxidant. The C-H oxidative difluoromethylation obviates the need for pre-functionalization of the substrates, metals and additives. The operationally straightforward method enriches the efficient synthesis of many difluoromethylated heterocycles in moderate to excellent yields. The direct difluoromethylation of pharmaceutical moleculars demonstrates the practicability of this methodology to late-stage drug development. Moreover, 2'-deoxy-5-difluoromethyluridine (F2TDR) exhibits promising activity against some cancer cell lines, indicating that the difluoromethylation methodology might provide assistance for drug discovery.