DeepCBA: a deep learning framework for gene expression prediction in maize based on DNA sequence and chromatin interaction.

Chromatin interactions create spatial proximity between distal regulatory elements and target genes in the genome, which has an important impact on gene expression, transcriptional regulation, and phenotypic traits. To date, several methods have been developed for predicting gene expression. However, existing methods do not take into consideration the impact of chromatin interactions on target gene expression, thus potentially reduces the accuracy of gene expression prediction and mining of important regulatory elements. In this study, a highly accurate deep learning-based gene expression prediction model (DeepCBA) based on maize chromatin interaction data was developed. Compared with existing models, DeepCBA exhibits higher accuracy in expression classification and expression value prediction. The average Pearson correlation coefficients (PCC) for predicting gene expression using gene promoter proximal interactions, proximal-distal interactions, and proximal and distal interactions were 0.818, 0.625, and 0.929, respectively, representing an increase of 0.357, 0.16, and 0.469 over the PCC of traditional methods that only use gene proximal sequences. Some important motifs were identified through DeepCBA and were found to be enriched in open chromatin regions and expression quantitative trait loci (eQTL) and have the molecular characteristic of tissue specificity. Importantly, the experimental results of maize flowering-related gene ZmRap2.7 and tillering-related gene ZmTb1 demonstrate the feasibility of DeepCBA in exploring regulatory elements that affect gene expression. Moreover, the promoter editing and verification of two reported genes (ZmCLE7, ZmVTE4) demonstrated new insights of DeepCBA in precise designing of gene expression and even future intelligent breeding. DeepCBA is available at http://www.deepcba.com/ or http://124.220.197.196/.

Active Dual-Protein Coating Assisted by Stepwise Protein-Protein Interactions Assembly Reduces Thrombosis and Infection.

Universal protein coatings have recently gained wide interest in medical applications due to their biocompatibility and ease of fabrication. However, the challenge persists in protein activity preservation, significantly complicating the functional design of these coatings. Herein, an active dual-protein surface engineering strategy assisted by a facile stepwise protein-protein interactions assembly (SPPIA) method for catheters to reduce clot formation and infection is proposed. This strategy is realized first by the partial oxidation of bovine serum albumin (BSA) and lysozyme (LZM) for creating stable nucleation platforms via hydrophobic interaction, followed by the assembly of nonoxidized BSA (pI, the isoelectric point, ≈4.7) and LZM (pI ≈11) through electrostatic interaction owing to their opposite charge under neutral conditions. The SPPIA method effectively preserves the conformation and functionality of both BSA and LZM, thus endowing the resultant coating with potent antithrombotic and bactericidal properties. Furthermore, the stable nucleation platform ensures the adhesion and durability of the coating, resisting thrombosis and bacterial proliferation even after 15 days of PBS immersion. Overall, the SPPIA approach not only provides a new strategy for the fabrication of active protein coatings but also shows promise for the surface engineering technology of catheters.

Research on dynamic characteristics of cutter breaking frozen soil and optimal drum rotation speed of the new shaft tunneling machine.

To improve the efficiency of frozen soil excavation, the new shaft tunneling machine was developed. The new shaft tunneling machine exerts pressure on the frozen soil through the cutter under the joint action of its own gravity, the drum rotational force and the inertia force, and the frozen soil is damaged. By unique way of breaking frozen soil to improve the efficiency of frozen soil excavation, the drum rotation speed is one of the factors affecting the performance of frozen soil excavation. This article applies SolidWorks software to establish the model of cutter breaking frozen soil, takes advantage of Hyper Mesh finite element software coupled with LS-DYNA solver to acquire the regular pattern of change in the force change, frozen soil stress-strain and specific energy of cutter crushing frozen soil, etc., which analyzes the destruction of frozen soil when the drum of the new shaft tunneling machine is rotating at the speed of 25-40 rpm. Combine with field test to investigate the mechanism of cutter breaking frozen soil under the optimal drum rotation speed. The investigation results demonstrate that: when frozen soil's self-bearing capacity is lower than the force of cutter, it breaks up and detaches from the soil body, and frozen soil undergoes tensile, compressive and shear damages. For this research, it is instructive for practical engineering.

Enhancement of photodynamic bactericidal activity of curcumin against Pseudomonas Aeruginosa using polymyxin B.

BACKGROUND: Pseudomonas aeruginosa (P. aeruginosa) is an emerging opportunistic pathogen, which can cause bacterial skin diseases such as green nail syndrome, interdigital infections and folliculitis. Curcumin-mediated antimicrobial photodynamic therapy (aPDT) has been demonstrated as a promising therapeutic option for the treatment of skin infection though its inactivation of gram-negative bacteria such as P. aeruginosa. MATERIALS AND METHODS: In the present study, we examined the adjuvant effect of polymyxin B on the antibacterial activity of curcumin-mediated aPDT against P. aeruginosa. P. aeruginosa was treated with curcumin in the presence of 0.1-0.5 mg/L polymyxin B and irradiated by blue LED light (10 J/cm2). Bacterial cultures treated with curcumin alone served as controls. Colony forming units (CFU) were counted and the viability of P. aeruginosa was calculated after aPDT treatment. The possible underlying mechanisms for the enhanced killing effects were also explored. RESULTS: The killing effects of curcumin-mediated aPDT against P. aeruginosa was significantly enhanced by polymyxin B (over 2-log reductions). Moreover, it was also observed that addition of polymyxin B in the curcumin-mediated aPDT led to the apparent bacterial membrane damage with increased leakage of cytoplasmic contents and extensive DNA and protein degradation. DISCUSSION: The photodynamic action of curcumin against P. aeruginosa could be significantly enhanced by the FDA-approved drug polymyxin B. Our results highlight the potential of introducing polymyxin B to enhance the effects of aPDT treatment against gram-negative skin infections, in particular, P. aeruginosa.

Sludge-based activated carbon catalyzed H2O2 oxidation of reactive azo dyes.

Sludge-based activated carbon (ZAC) was successfully employed as both adsorbent and catalyst for the oxidation process of reactive yellow 86 (RY86) and reactive black 5 (RB5). Physicochemical properties of the prepared sewage sludge-derived activated carbon were evaluated by N2 adsorption/desorption, Fourier transform infrared spectroscopy (FT-IR) and scanning electron microscopy (SEM). The effects of parameters such as initial pH, H2O2 concentrations, ZAC dosages, dye concentrations and temperature on the removal of RY86 and RB5 were investigated. Kinetics results showed that the adsorption rates of RY86 and RB5 by ZAC can be approximated by the pseudo-first order model, and that the oxidation rates by Behnajady-Modirshahla-Ghanbery (BMG) model. Under the optimum conditions in the experiment, i.e. pH = 6.0, T = 303 K, [H2O2] = 49.5 mmol/L, [ZAC] = 4 g/L, [dyes] = 300 mg/L and t = 150 min, 99%, 88% and 84% of colour, COD and TOC were removed by Fenton -like oxidation for RY86, while for RB5, the three removal rates were 90%, 70% and 62%, respectively, indicating that sludge-based activated carbon can be used as an effective catalyst to oxidation of dyes by H2O2 from coloured wastewater.

Potent USP10/13 antagonist spautin-1 suppresses melanoma growth via ROS-mediated DNA damage and exhibits synergy with cisplatin.

Malignant melanoma is one of the most invasive tumours. However, effective therapeutic strategies are limited, and overall survival rates remain low. By utilizing transcriptomic profiling, tissue array and molecular biology, we revealed that two key ubiquitin-specific proteases (USPs), ubiquitin-specific peptidase10 (USP10) and ubiquitin-specific peptidase10 (USP13), were significantly elevated in melanoma at the mRNA and protein levels. Spautin-1 has been reported as a USP10 and USP13 antagonist, and we demonstrated that spautin-1 has potent anti-tumour effects as reflected by MTS and the colony formation assays in various melanoma cell lines without cytotoxic effects in HaCaT and JB6 cell lines. Mechanistically, we identified apoptosis and ROS-mediated DNA damage as critical mechanisms underlying the spautin-1-mediated anti-tumour effect by utilizing transcriptomics, qRT-PCR validation, flow cytometry, Western blotting and immunofluorescence staining. Importantly, by screening spautin-1 with targeted or chemotherapeutic drugs, we showed that spautin-1 exhibited synergy with cisplatin in the treatment of melanoma. Pre-clinically, we demonstrated that spautin-1 significantly attenuated tumour growth in a cell line-derived xenograft mouse model, and its anti-tumour effect was further enhanced by cotreatment with cisplatin. Taken together, our study revealed a novel molecular mechanism of spautin-1 effecting in melanoma and identified a potential therapeutic strategy in treatment of melanoma patients.

Benserazide is a novel inhibitor targeting PKM2 for melanoma treatment.

The M2 splice isoform of pyruvate kinase (PKM2) is a key enzyme for generating pyruvate and ATP in the glycolytic pathway, whereas the role of PKM2 in tumorigenesis remains a subject of debate. In our study, we found PKM2 is highly expressed in melanoma patients and the malignance is positively correlated with high PKM2 activity and glycolytic capability in melanoma cells. Suppression of PKM2 expression by knocking down markedly attenuated malignant phenotype both in vitro and in vivo, and restoration of PKM2 expression in PKM2 depleted cells could rescue melanoma cells proliferation, invasion and metastasis. With the data indicating PKM2 as a potential therapeutic target, we performed screening for PKM2 inhibitors and identified benserazide (Ben), a drug currently in clinical use. We demonstrated that Ben directly binds to and blocks PKM2 enzyme activity, leading to inhibition of aerobic glycolysis concurrent up-regulation of OXPHOS. Of note, despite PKM2 is very similar to PKM1, Ben does not affect PKM1 enzyme activity. We showed that Ben significantly inhibits cell proliferation, colony formation, invasion and migration in vitro and in vivo. The specificity of Ben was demonstrated by the findings that, suppression of PKM2 expression diminishes the efficacy of Ben in inhibition of melanoma cell growth; ectopic PKM2 expression in normal cells sensitizes cells to Ben treatment. Interestingly, PKM2 activity and aerobic glycolysis are upregulated in BRAFi-resistant melanoma cells. As a result, BRAFi-resistant cells exhibit heightened sensitivity to suppression of PKM2 expression or treatment with Ben both in vitro and in vivo.

CX-F9, a novel RSK2 inhibitor, suppresses cutaneous melanoma cells proliferation and metastasis through regulating autophagy.

Approximately 60% of melanoma have BRAF mutation which leads to the abnormal activation of MAPK signaling pathway. Therefore, targeting these signaling pathways is particularly important for melanoma therapy. Ribosomal S6 Kinase 2 (RSK2) is a downstream target of ERK1/2 in MAPK/ERK pathway and inhibition of RSK2 suppresses the tumorigenesis and metastasis of neoplasm. We investigated whether CX-F9, a novel RSK2 inhibitor predicted by computer, inhibits the malignant phenotype of melanoma cells. In this study, we found knockdown of RSK2 expression in melanoma cells induces autophagy and inhibits its proliferation, migration and invasion. CX-F9 directly binds to RSK2 and inhibits the kinase activity. CX-F9 significantly suppressed cell proliferation, induced autophagy, apoptosis and cycle arrest, as well as inhibited migration and invasion in SK-MEL-5 and SK-MEL-28 cells. Western blotting revealed that CX-F9 declined the activation of p-CREB. Moreover, CX-F9 inhibited tumor formation and metastasis in vivo. Furthermore, CX-F9 suppressed cell proliferation, migration, invasion in BRAF inhibitor resistant melanoma cells. These findings reveal a new RSK2 inhibitor CX-F9 could significantly suppressed malignant phenotype of melanoma in vitro and in vivo, which provide a novel strategy for melanoma treatment in clinic.

Recent Advances on Polymeric Beads or Hydrogels as Embolization Agents for Improved Transcatheter Arterial Chemoembolization (TACE).

Transcatheter arterial chemoembolization (TACE), aiming to block the hepatic artery for inhibiting tumor blood supply, became a popular therapy for hepatocellular carcinoma (HCC) patients. Traditional TACE formulation of anticancer drug emulsion in ethiodized oil (i.e., Lipiodol®) and gelatin sponge (i.e., Gelfoam®) had drawbacks on patient tolerance and resulted in undesired systemic toxicity, which were both significantly improved by polymeric beads, microparticles, or hydrogels by taking advantage of the elegant design of biocompatible or biodegradable polymers, especially amphiphilic polymers or polymers with both hydrophilic and hydrophobic chains, which could self-assemble into proposed microspheres or hydrogels. In this review, we aimed to summarize recent advances on polymeric embolization beads or hydrogels as TACE agents, with emphasis on their material basis of polymer architectures, which are important but have not yet been comprehensively summarized.

[Protective effect of "neiguan" (PC 6)-electroacupuncture preconditioning on the myocardium in myocardial ischemia/reperfusion rats].

OBJECTIVE: To investigate the effects of "Neiguan" (PC 6)-electroacupunture (EA) preconditioning on the myocardium and its mast cells in myocardial ischemia/reperfusion (MI/R) rats. METHODS: Eighteen male SD rats were randomly assigned to sham group, model (IR) group and EA group (n=6/ group). MI/R model was established by occlusion of the descending anterior branch of the coronary artery. Blood samples were taken from the femoral vein before MI (T0), EA for 30 min (T1), 30 min after MI (T2), 30 min after MI/R (T3) and 120 min after MI/R (T4) for assaying serum tumor necrosis factor (TNF)-alpha and histamine contents by using ELISA. Serum lactate dehydrogenase (LDH) and creatinkinase isoenzyme (CK-MB) levels were measured at T0, T3 and T4 by using an automatic biochemistry analyzer. The infarct size was detected by Evan's blue and tetrazolium chloride (TTC) staining. Myocardial TNF-alpha and histamine contents were detected by ELISA. The percentage of mast cell degranulation was determined by toluidine blue staining. RESULTS: Following MI/R, serum LDH and CK-MB levels at phase T3 and T4, serum TNF-alpha and histamine contents at phase T2 and T3, and myocardial mast cell degranulation rate increased significantly, and myocardial TNF-alpha and histamine contents decreased in model group in comparison with pre-MI/R (P < 0.05). Compared with IR model group, serum LDH and CK-MB levels at phase T3 and T4, myocardial TNF-alpha and histamine contents all decreased significantly (P < 0.05), but serum TNF-al infarct size was remarkably smaller in EA group than that in IR model group (P < 0.05). CONCLUSION: "Neiguan" (PC 6)-EA preconditioning has a cardioprotective effect on the ischemia-reperfusion myocardium by promoting mast cell degranulation.

Enhanced stabilization of reverse micelles by compressed CO2.

The effect of compressed CO2 on the solubilization capacity of water in reverse micelles of sodium bis(2-ethylhexyl) sulfosuccinate (AOT) in longer chain n-alkanes was studied at different temperatures and pressures. It was found that the amount of solubilized water is increased considerably by CO2 in a suitable pressure range. The suitable CO2 pressure range in which the solubilization capacity of water could be enhanced decreased with increasing W0 (water-to-AOT molar ratio). The microenvironments in the CO2-stabilized reverse micelles were investigated by UV/Vis adsorption spectroscopy with methyl orange (MO) as probe. The mechanism by which the reverse micelles are stabilized by CO2 is discussed in detail. The main reason is likely to be that CO2 has a much smaller molecular volume than the n-alkane solvents studied in this work. Therefore, it can penetrate the interfacial film of the reverse micelles and stabilize them by increasing the rigidity of the micellar interface and thus reducing the attractive interaction between the droplets. However, if the CO2 pressure is too high, the solvent strength of the solvents is reduced markedly, and this induces phase separation in the micellar solution.