Sja-let-7 suppresses the development of liver fibrosis via Schistosoma japonicum extracellular vesicles.

Schistosomiasis is a fatal zoonotic parasitic disease that also threatens human health. The main pathological features of schistosomiasis are granulomatous inflammation and subsequent liver fibrosis, which is a complex, chronic, and progressive disease. Extracellular vesicles (EVs) derived from schistosome eggs are broadly involved in host-parasite communication and act as important contributors to schistosome-induced liver fibrosis. However, it remains unclear whether substances secreted by the EVs of Schistosoma japonicum, a long-term parasitic "partner" in the hepatic portal vein of the host, also participate in liver fibrosis. Here, we report that EVs derived from S. japonicum worms attenuated liver fibrosis by delivering sja-let-7 into hepatic stellate cells (HSCs). Mechanistically, activation of HSCs was reduced by targeting collagen type I alpha 2 chain (Col1α2) and downregulation of the TGF-ß/Smad signaling pathway both in vivo and in vitro. Overall, these results contribute to further understanding of the molecular mechanisms underlying host-parasite interactions and identified the sja-let-7/Col1α2/TGF-ß/Smad axis as a potential target for treatment of schistosomiasis-related liver fibrosis.

R3 strain and Fe-Mn modified biochar reduce Cd absorption capacity of roots and available Cd content of soil by affecting rice rhizosphere and endosphere key flora.

Microorganisms have a significant role in regulating the absorption and transportation of Cd in the soil-plant system. However, the mechanism by which key microbial taxa play a part in response to the absorption and transportation of Cd in rice under Cd stress requires further exploration. In this study, the cadmium-tolerant endophytic bacterium Herbaspirillum sp. R3 (R3) and Fe-Mn-modified biochar (Fe-Mn) were, respectively, applied to cadmium-contaminated rice paddies to investigate the effects of key bacterial taxa in the soil-rice system on the absorption and transportation of Cd in rice under different treatments. The results showed that both R3 and Fe-Mn treatments considerably decreased the content of cadmium in roots, stems and leaves of rice at the peak tillering stage by 17.24-49.28% in comparison to the control (CK). The cadmium content reduction effect of R3 treatment is better than that of Fe-Mn treatment. Further analysis revealed that the key bacterial taxa in rice roots under R3 treatment were Sideroxydans and Actinobacteria, and that their abundance showed a substantial positive correlation and a significant negative correlation with the capacity of rice roots to assimilate Cd from the surroundings, respectively. The significant increase in soil pH under Fe-Mn treatment, significant reduction in the relative abundances of Acidobacteria, Verrucomicrobia, Subdivision3 genera incertae sedis, Sideroxydans, Geobacter, Gp1, and Gp3, and the significant increase in the relative abundance of Thiobacillus among the soil bacterial taxa may be the main reasons for the decrease in available Cd content of the soil. In addition, both the R3 and Fe-Mn treatments showed some growth-promoting effects on rice, which may be related to their promotion of transformations of soil available nutrients. This paper describes the possible microbial mechanisms by which strain R3 and Fe-Mn biochar reduce Cd uptake in rice, providing a theoretical basis for the remediation of Cd contamination in rice and soil by utilizing key microbial taxa.

Design of Solid Polycationic Electrolyte to Enable Durable Chloride-Ion Batteries.

The high energy density and cost-effectiveness of chloride-ion batteries (CIBs) make them promising alternatives to lithium-ion batteries. However, the development of CIBs is greatly restricted by the lack of compatible electrolytes to support cost-effective anodes. Herein, we present a rationally designed solid polycationic electrolyte (SPE) to enable room-temperature chloride-ion batteries utilizing aluminum (Al) metal as an anode. This SPE endows the CIB configuration with improved air stability and safety (i.e. free of flammability and liquid leakage). A high ionic conductivity (1.3×10-2 S cm-1 at 25 °C) has been achieved by the well-tailored coordination structure of the SPE. Meanwhile, the solid polycationic electrolyte ensures stable electrodes|electrolyte interfaces, which effectively inhibit the growth of dendrites on the Al anodes and degradation of the FeOCl cathodes. The Al|SPE|FeOCl chloride-ion batteries showcased a high discharge capacity around 250 mAh g-1 (based on the cathodes) and extended lifespan. Our electrolyte design opens a new avenue for developing low-cost chloride-ion batteries.

Molecular and functional characterization of Schistosoma japonicum annexin A13.

Schistosomiasis is a neglected tropical disease that affects humans and animals in tropical and subtropical regions worldwide. Schistosome eggs are responsible for the pathogenesis and transmission of schistosomiasis, thus reducing egg production is vital for prevention and control of schistosomiasis. However, the mechanisms underlying schistosome reproduction remain unclear. Annexin proteins (ANXs) are involved in the physiological and pathological functions of schistosomes, but the specific regulatory mechanisms and roles of ANX A13 in the development of Schistosoma japonicum and host-parasite interactions remain poorly understood. Therefore, in this study, the expression profiles of SjANX A13 at different life cycle stages of S. japonicum were assessed using quantitative PCR. In addition, the expression profiles of the homolog in S. mansoni were analyzed in reference to public datasets. The results of RNA interference showed that knockdown of SjANX A13 significantly affected the development and egg production of female worms in vivo. The results of an immune protection assay showed that recombinant SjANX A13 increased production of immunoglobulin G-specific antibodies. Finally, co-culture of S. japonicum exosomes with LX-2 cells using a transwell system demonstrated that SjANX A13 is involved in host-parasite interactions via exosomes. Collectively, these results will help to clarify the roles of SjANX A13 in the development of S. japonicum and host-parasite interactions as a potential vaccine candidate.

Mapping Isoform Abundance and Interactome of the Endogenous TMPRSS2-ERG Fusion Protein by Orthogonal Immunoprecipitation-Mass Spectrometry Assays.

TMPRSS2-ERG gene fusion, a molecular alteration found in nearly half of primary prostate cancer cases, has been intensively characterized at the transcript level. However limited studies have explored the molecular identity and function of the endogenous fusion at the protein level. Here, we developed immunoprecipitation-mass spectrometry assays for the measurement of a low-abundance T1E4 TMPRSS2-ERG fusion protein, its isoforms, and its interactome in VCaP prostate cancer cells. Our assays quantified total ERG (∼27,000 copies/cell) and its four unique isoforms and revealed that the T1E4-ERG isoform accounted for 52 ± 3% of the total ERG protein in VCaP cells, and 50 ± 11% in formalin-fixed paraffin-embedded prostate cancer tissues. For the first time, the N-terminal peptide (methionine-truncated and N-acetylated TASSSSDYGQTSK) unique for the T1/E4 fusion was identified. ERG interactome profiling with the C-terminal, but not the N-terminal, antibodies identified 29 proteins, including mutually exclusive BRG1- and BRM-associated canonical SWI/SNF chromatin remodeling complexes. Our sensitive and selective IP-SRM assays present alternative tools to quantify ERG and its isoforms in clinical samples, thus paving the way for development of more accurate diagnostics of prostate cancer.

Rational Design and Development of SARS-CoV-2 Serological Diagnostics by Immunoprecipitation-Targeted Proteomics.

Current design of serological tests utilizes conservative immunoassay approaches and is focused on fast and convenient assay development, throughput, straightforward measurements, and affordability. Limitations of common serological assays include semiquantitative measurements, cross-reactivity, lack of reference standards, and no differentiation between human immunoglobulin subclasses. In this study, we suggested that a combination of immunoaffinity enrichments with targeted proteomics would enable rational design and development of serological assays of infectious diseases, such as COVID-19. Immunoprecipitation-targeted proteomic assays allowed for sensitive and specific measurements of NCAP_SARS2 protein with a limit of detection of 313 pg/mL in serum and enabled differential quantification of anti-SARS-CoV-2 antibody isotypes (IgG, IgA, IgM, IgD, and IgE) and individual subclasses (IgG1-4 and IgA1-2) in plasma and saliva. Simultaneous evaluation of the numerous antigen-antibody subclass combinations revealed a receptor-binding domain (RBD)-IgG1 as a combination with the highest diagnostic performance. Further validation revealed that anti-RBD IgG1, IgG3, IgM, and IgA1 levels were significantly elevated in convalescent plasma, while IgG2, IgG4, and IgA2 were not informative. Anti-RBD IgG1 levels in convalescent (2138 ng/mL) vs negative (95 ng/mL) plasma revealed 385 ng/mL as a cutoff to detect COVID-19 convalescent plasma. Immunoprecipitation-targeted proteomic assays will facilitate improvement and standardization of the existing serological tests, enable rational design of novel tests, and offer tools for the comprehensive investigation of immunoglobulin subclass cooperation in immune response.

Single-shot optical sectioning microscopy based on structured illumination.

In this Letter, we present a single-shot 3D-resolved structured illumination microscopy (SIM) based on a digital micromirror device (DMD), a galvanometric mirror, and the HiLo algorithm. During imaging, the DMD rapidly generates sinusoidal and plane illuminations in the focal region. By synchronizing the DMD with a galvanometric scanner and exploiting the unique data readout process of the camera, the emissions from the specimen under two different illuminations, i.e., structured and uniform illumination, are projected to different regions on a camera, achieving high-resolution single-exposure optical sectioning at the camera's limiting speed, i.e., 200 Hz, without sacrificing the resolution. A model has been developed to guide the design and optimization of the optical system. Imaging experiments on pollen and mouse kidney samples have been performed to verify the predicted performance. The results show that the single-shot SIM with the HiLo algorithm achieves comparable resolution to the standard two-shot HiLo method with a twofold speed enhancement, which may find important applications in biophotonics, e.g., visualizing high-speed biological events in vivo.

Atmospheric Autoxidation of Organophosphate Esters.

Organophosphate esters (OPEs), widely used as flame retardants and plasticizers, have frequently been identified in the atmosphere. However, their atmospheric fate and toxicity associated with atmospheric transformations are unclear. Here, we performed quantum chemical calculations and computational toxicology to investigate the reaction mechanism of peroxy radicals of OPEs (OPEs-RO2•), key intermediates in determining the atmospheric chemistry of OPEs, and the toxicity of the reaction products. TMP-RO2• (R1) and TCPP-RO2• (R2) derived from trimethyl phosphate and tris(2-chloroisopropyl) phosphate, respectively, are selected as model systems. The results indicate that R1 and R2 can follow an H-shift-driven autoxidation mechanism under low NO concentration ([NO]) conditions, clarifying that RO2• from esters can follow an autoxidation mechanism. The unexpected autoxidation mechanism can be attributed to the distinct role of the ─(O)3P(═O) phosphate-ester group in facilitating the H-shift of OPEs-RO2• from commonly encountered ─OC(═O)─ and ─ONO2 ester groups in the atmosphere. Under high [NO] conditions, NO can mediate the autoxidation mechanism to form organonitrates and alkoxy radical-related products. The products from the autoxidation mechanism have low volatility and aquatic toxicity compared to their corresponding parent compounds. The proposed autoxidation mechanism advances our current understanding of the atmospheric RO2• chemistry and the environmental risk of OPEs.

Potential Application of Machine-Learning-Based Quantum Chemical Methods in Environmental Chemistry.

It is an important topic in environmental sciences to understand the behavior and toxicology of chemical pollutants. Quantum chemical methodologies have served as useful tools for probing behavior and toxicology of chemical pollutants in recent decades. In recent years, machine learning (ML) techniques have brought revolutionary developments to the field of quantum chemistry, which may be beneficial for investigating environmental behavior and toxicology of chemical pollutants. However, the ML-based quantum chemical methods (ML-QCMs) have only scarcely been used in environmental chemical studies so far. To promote applications of the promising methods, this Perspective summarizes recent progress in the ML-QCMs and focuses on their potential applications in environmental chemical studies that could hardly be achieved by the conventional quantum chemical methods. Potential applications and challenges of the ML-QCMs in predicting degradation networks of chemical pollutants, searching global minima for atmospheric nanoclusters, discovering heterogeneous or photochemical transformation pathways of pollutants, as well as predicting environmentally relevant end points with wave functions as descriptors are introduced and discussed.

Mass spectrometry-based proteomics in basic and translational research of SARS-CoV-2 coronavirus and its emerging mutants.

Molecular diagnostics of the coronavirus disease of 2019 (COVID-19) now mainly relies on the measurements of viral RNA by RT-PCR, or detection of anti-viral antibodies by immunoassays. In this review, we discussed the perspectives of mass spectrometry-based proteomics as an analytical technique to identify and quantify proteins of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and to enable basic research and clinical studies on COVID-19. While RT-PCR and RNA sequencing are indisputably powerful techniques for the detection of SARS-CoV-2 and identification of the emerging mutations, proteomics may provide confirmatory diagnostic information and complimentary biological knowledge on protein abundance, post-translational modifications, protein-protein interactions, and the functional impact of the emerging mutations. Pending advances in sensitivity and throughput of mass spectrometry and liquid chromatography, shotgun and targeted proteomic assays may find their niche for the differential quantification of viral proteins in clinical and environmental samples. Targeted proteomic assays in combination with immunoaffinity enrichments also provide orthogonal tools to evaluate cross-reactivity of serology tests and facilitate development of tests with the nearly perfect diagnostic specificity, this enabling reliable testing of broader populations for the acquired immunity. The coronavirus pandemic of 2019-2021 is another reminder that the future global pandemics may be inevitable, but their impact could be mitigated with the novel tools and assays, such as mass spectrometry-based proteomics, to enable continuous monitoring of emerging viruses, and to facilitate rapid response to novel infectious diseases.

Holography-based structured light illumination for temporal focusing microscopy.

In this Letter, we present a holography-based structured light illumination (SLI) method to enhance the resolution of widefield temporal focusing microscopy (TFM). In the system, a digital micromirror device is employed to simultaneously disperse the incoming femtosecond laser to induce temporal focusing at the focal plane and generate designed structured patterns via a Lee hologram. As the generated structured patterns do not contain the zeroth order beam, it improves the contrast and modulation frequency. Mathematical models have been derived to calculate the electric fields at the focal plane and to explain the effects of improved optical cross-sectioning capability. Imaging experiments have been devised and performed on fluorescent beads and mouse kidney sections; the results demonstrate enhanced axial confinement and improved suppression of out-of-focus fluorescence. The new SLI method realizes high-resolution TFM and can be readily applied to other microscopy platforms for biophotonics applications.

Light field microscopy based on structured light illumination.

In this Letter, we present the modeling, design, and characterization of a light sheet-based structured light illumination (SLI) light field microscopy (LFM) system for fast 3D imaging, where a digital micromirror device is employed to rapidly generate designed sinusoidal patterns in the imaging field. Specifically, we sequentially obtain uniformly illuminated and structured light field images, followed by post-processing with a new, to the best of our knowledge, algorithm that combines the deconvolution and HiLo algorithms. This enables fast volumetric imaging with improved optical cross-sectioning capability at a speed of 50 volumes per second over an imaging field of 250×250×80µm3 in the x, y, and z axis, respectively. Mathematical models have been derived to explain the performance enhancement due to suppressed background noises. To verify the results, imaging experiments on fluorescence beads, fern spore, and Drosophila brain samples, have been performed. The results indicate that the light sheet-based SLI-LFM presents a fast 3D imaging solution with substantially improved optical cross-sectioning capability in comparison with a standard light sheet-based LFM. The new light field imaging method may find important applications in the field of biophotonics.

Characterisation and preliminary functional analysis of N-acetyltransferase 13 from Schistosoma japonicum.

BACKGROUND: N-acetyltransferase 13 (NAT13) is a probable catalytic component of the ARD1A-NARG1 complex possessing alpha (N-terminal) acetyltransferase activity. RESULTS: In this study, a full-length complementary DNA (cDNA) encoding Schistosoma japonicum NAT13 (SjNAT13) was isolated from schistosome cDNAs. The 621 bp open reading frame of SjNAT13 encodes a polypeptide of 206 amino acids. Real-time PCR analysis revealed SjNAT13 expression in all tested developmental stages. Transcript levels were highest in cercariae and 21-day-old worms, and higher in male adult worms than female adult worms. The rSjNAT13 protein induced high levels of anti-rSjNAT13 IgG antibodies. In two independent immunoprotection trials, rSjNAT13 induced 24.23% and 24.47% reductions in the numbers of eggs in liver. RNA interference (RNAi) results showed that small interfering RNA (siRNA) Sj-514 significantly reduced SjNAT13 transcript levels in worms and decreased egg production in vitro. CONCLUSIONS: Thus, rSjNAT13 might play an important role in the development and reproduction of schistosomes.

An Optimized Trajectory Planner and Motion Controller Framework for Autonomous Driving in Unstructured Environments.

This paper proposes an optimized trajectory planner and motion planner framework, which aim to deal with obstacle avoidance along a reference road for autonomous driving in unstructured environments. The trajectory planning problem is decomposed into lateral and longitudinal planning sub-tasks along the reference road. First, a vehicle kinematic model with road coordinates is established to describe the lateral movement of the vehicle. Then, nonlinear optimization based on a vehicle kinematic model in the space domain is employed to smooth the reference road. Second, a multilayered search algorithm is applied in the lateral-space domain to deal with obstacles and find a suitable path boundary. Then, the optimized path planner calculates the optimal path by considering the distance to the reference road and the curvature constraints. Furthermore, the optimized speed planner takes into account the speed boundary in the space domain and the constraints on vehicle acceleration. The optimal speed profile is obtained by using a numerical optimization method. Furthermore, a motion controller based on a kinematic error model is proposed to follow the desired trajectory. Finally, the experimental results show the effectiveness of the proposed trajectory planner and motion controller framework in handling typical scenarios and avoiding obstacles safely and smoothly on the reference road and in unstructured environments.

lncRNA-PLACT1 sustains activation of NF-κB pathway through a positive feedback loop with IκBα/E2F1 axis in pancreatic cancer.

BACKGROUND: The activation of NF-κB signaling pathway is regarded as the dominant process that correlates with tumorigenesis. Recently, increasing evidence shows that long noncoding RNAs (lncRNAs) play crucial roles in sustaining the NF-κB signaling pathway. However, the underlying mechanisms have not yet been elucidated. METHODS: The expression and clinical features of PLACT1 were analyzed in a 166-case cohort of PDAC by qRT-PCR and in situ hybridization. The functional role of PLACT1 was evaluated by both in vitro and in vivo experiments. Chromatin isolation by RNA purification assays were utilized to examine the interaction of PLACT1 with IκBα promoter. RESULTS: We identified a novel lncRNA-PLACT1, which was significantly upregulated in tumor tissues and correlated with progression and poor survival in PDAC patients. Moreover, PLACT1 promoted the proliferation and invasion of PDAC cells in vitro. Consistently, PLACT1 overexpression fostered the progression of PDAC both in orthotopic and lung metastasis mice models. Mechanistically, PLACT1 suppressed IκBα expression by recruiting hnRNPA1 to IκBα promoter, which led to increased H3K27me3 that decreased the transcriptional level of IκBα. Furthermore, E2F1-mediated overexpression of PLACT1 modulated the progression of PDAC by sustained activation of NF-κB signaling pathway through forming a positive feedback loop with IκBα. Importantly, administration of the NF-κB signaling pathway inhibitor significantly suppressed PLACT1-induced sustained activation of NF-κB signaling pathway, leading to reduced tumorigenesis in vivo. CONCLUSIONS: Our findings suggest that PLACT1 provides a novel epigenetic mechanism involved in constitutive activation of NF-κB signaling pathway and may represent a new therapeutic target of PDAC.

Circular RNA circBFAR promotes the progression of pancreatic ductal adenocarcinoma via the miR-34b-5p/MET/Akt axis.

BACKGROUND: Accumulating evidence suggests that circular RNAs (circRNAs) are important participants in cancer progression. However, the biological processes and underlying mechanisms of circRNAs in pancreatic ductal adenocarcinoma (PDAC) are unclear. METHOD: CircRNAs were verified by Sanger sequencing. Colony formation, 5-Ethynyl-2'-deoxyuridine (EdU), and Transwell assays were performed to investigate the effect of circBFAR on the proliferation, invasion, and migration of PDAC cells in vitro. RNA pull-down assays were conducted to verify the binding of circBFAR with microRNA miR-34b-5p. RESULTS: In the present study, we identified a novel circRNA (termed as circBFAR, hsa_circ_0009065) that was upregulated in a 208-case cohort of patients with PDAC. The ectopic expression of circBFAR correlated positively with the tumor-node-metastasis (TNM) stage and was related to poorer prognosis of patients with PDAC. Moreover, circBFAR knockdown dramatically inhibited the proliferation and motility of PDAC cells in vitro and their tumor-promoting and metastasis properties in in vivo models. Mechanistically, circBFAR upregulated mesenchymal-epithelial transition factor (MET) expression via sponging miR-34b-5p. Additionally, circBFAR overexpression increased the expression of MET and activated downstream phosphorylation of Akt (Ser 473) and further activated the MET/PI3K/Akt signaling pathway, which ultimately promoted the progression of PDAC cells. Importantly, application of MET inhibitors could significantly attenuate circBFAR-mediated tumorigenesis in vivo. CONCLUSIONS: Our findings showed that circBFAR plays an important role in the proliferation and metastasis of PDAC, which might be explored as a potential prognostic marker and therapeutic target for PDAC.

Formation of Low-Volatile Products and Unexpected High Formaldehyde Yield from the Atmospheric Oxidation of Methylsiloxanes.

With stricter regulation of atmospheric volatile organic compounds (VOCs) originating from fossil fuel-based vehicles and industries, the use of volatile chemical products (VCPs) and the transformation mechanism of VCPs have become increasingly important to quantify air quality. Volatile methylsiloxanes (VMS) are an important class of VCPs and high-production chemicals. Using quantum chemical calculations and kinetics modeling, we investigated the reaction mechanism of peroxy radicals of VMS, which are key intermediates in determining the atmospheric chemistry of VMS. L2-RSiCH2O2• and D3-RSiCH2O2• derived from hexamethyldisiloxane and hexamethylcyclotrisiloxane, respectively, were selected as representative model systems. The results indicated that L2-RSiCH2O2• and D3-RSiCH2O2• follow a novel Si-C-O rearrangement-driven autoxidation mechanism, leading to the formation of low volatile silanols and high yield of formaldehyde at low NO/HO2• conditions. At high NO/HO2• conditions, L2-RSiCH2O2• and D3-RSiCH2O2• react with NO/HO2• to form organic nitrate, hydroperoxide, and active alkoxy radicals. The alkoxy radicals further follow a Si-C-O rearrangement step to finally form formate esters. The novel Si-C-O rearrangement mechanism of both peroxy and alkoxy radicals are supported by available experimental studies on the oxidation of VMS. Notably, the high yield of formaldehyde is estimated to significantly contribute to formaldehyde pollution in the indoor environment, especially during indoor cleaning.

HFO-LADRC Lateral Motion Controller for Autonomous Road Sweeper.

How to make a controller robust and stable to reject the disturbance of uncertainty is an inevitable challenge. Aiming at addressing the lateral control problem for an autonomous road sweeper, a heading-error-based first order linear active disturbance rejective controller (HFO-LADRC) is proposed in this paper. To eliminate the lateral error and the heading error at the same time, a new model, called the heading-error-based model, is proposed for lateral motion, and the Lyapunov function was employed to explore the convergence ability of the heading error and lateral error. Since the heading-error-based model is first order, the ADRC is designed as first order and linear, and each module of the HFO-LADRC has been devised in detail. To ensure solution accuracy, the fourth order Runge-Kutta method was adopted as the differential system solver, and a typical ring scenario and a double lane-changing scenario were designed referencing the standard. Considering the obvious influence, wheelbase uncertainty, steering ratio uncertainty and Gaussian white noise disturbance were taken into account for the tests. The results illustrate that, in the case of both wheelbase uncertainty and steer ratio uncertainty, the HFO-LADRC has strong robustness and stability compared with a typical pure pursuit controller and classical SO-LADRC.

Development of Prediction Models on Base-Catalyzed Hydrolysis Kinetics of Phthalate Esters with Density Functional Theory Calculation.

Many phthalate esters (PAEs) are chemicals of high production volume and of toxicological concern. The second-order rate constant for base-catalyzed hydrolysis ( kB) is a key parameter for assessing environmental persistence of PAEs. However, the kB values for most PAEs are lacking, and the experimental determination of kB encounters various difficulties. Herein, density functional theory (DFT) methods were selected by comparing empirical kB values of five PAEs and five carboxylic acid esters with the DFT-calculated ones. Results indicate that PAEs with cyclic side chains are more vulnerable to base-catalyzed hydrolysis than PAEs with linear alkyl side chains, followed by PAEs with branched alkyl side chains. By combining experimental and DFT-calculated second-order rate constants for base-catalyzed hydrolysis of one side chain in PAEs ( kB_side chain), quantitative structure-activity relationship models were developed. The models can differentiate PAEs with the departure of the leaving group (or the nucleophilic attack of OH-) as the rate-determining step in the hydrolysis and estimate kB values, which provides a promising way to predict hydrolysis kinetics of PAEs. The half-lives of the investigated PAEs were calculated and vary from 0.001 h to 558 years (pH = 7∼9), further illustrating the necessity of prediction models for hydrolysis kinetics in assessing the environmental persistence of chemicals.

Linc00511 acts as a competing endogenous RNA to regulate VEGFA expression through sponging hsa-miR-29b-3p in pancreatic ductal adenocarcinoma.

Pancreatic ductal adenocarcinoma (PDAC) is a lethal malignancy. Long non-coding RNAs (lncRNAs) are important regulators in pathological processes, yet their potential roles in PDAC are poorly understood. Here, we identify a fundamental role for a novel lincRNA, linc00511, in the progression of PDAC. Linc00511 levels in PDAC tissue specimens and cell lines were examined by quantitative real-time PCR. Corresponding adjacent non-neoplastic tissues were used as controls. The function of linc00511 in PDAC cell lines was determined by RNA interference approach in vitro and in vivo. Fluorescence in situ hybridization (FISH) was used to characterize linc00511 expression in PDAC cells. Insights of the mechanism of competitive endogenous RNAs (ceRNAs) were obtained from bioinformatic analysis, luciferase assays and RIP assays. The association between the linc00511/hsa-miR29b-3p axis and VEGFA was verified by Western blotting assay. Immunohistochemistry was performed to evaluate the expression of VEGFA in PDAC samples. The aberrant up-regulation of linc00511 was detected in PDAC cell lines and patient specimens compared with controls. An increase in linc00511 expression indicates the adverse clinical pathological characteristics and poor prognosis. Functionally, linc00511 depletion in PDAC cells decreased proliferation, migration, invasion and endothelial tube formation. Mechanistically, linc00511 could up-regulate VEGFA via its competing endogenous RNA (ceRNA) activity on hsa-miR-29b-3p. In summary, our results define an important axis controlling proliferation, invasion and tumour angiogenesis in PDAC. Linc00511 is a novel lncRNA that plays a significant regulatory role in the pathogenesis and progression of PDAC. Thus, Linc00511 represents a new prognostic biomarker to predict clinical outcome of PDAC patients after surgery and may serve as a potential therapeutic target for PDAC treatment.