To discover trace phosphorylated proteins or peptides with great biological significance for in-depth phosphoproteome analysis, it is urgent to develop a novel technique for highly selective and effective enrichment of phosphopeptides. In this work, an IMAC (immobilized metal ion affinity chromatography) material with polydopamine coated on the surface of graphene and functionalized with titanium ions (denoted as Ti(4+)-G@PD) was initially designed and synthesized. The newly prepared Ti(4+)-G@PD with enhanced hydrophilicity and biological compatibility was characterized using scanning electron microscopy (SEM), transmission electron microscopy (TEM), and infrared (IR), and its performance for selective and effective enrichment of phosphopeptide was evaluated with both standard peptide mixtures and human serum.

In this work, for the first time, Ti(4+)-Fe3O4@polydopamine microspheres were designed and synthesized for efficient and selective enrichment of phosphopeptides in biological samples.

The physical interactions of growing bacterial cells with each other and with their surroundings significantly affect the structure and dynamics of biofilms. Here a 3D agent-based model is formulated to describe the establishment of simple bacterial colonies expanding by the physical force of their growth. With a single set of parameters, the model captures key dynamical features of colony growth by non-motile, non EPS-producing E. coli cells on hard agar. The model, supported by experiment on colony growth in different types and concentrations of nutrients, suggests that radial colony expansion is not limited by nutrients as commonly believed, but by mechanical forces. Nutrient penetration instead governs vertical colony growth, through thin layers of vertically oriented cells lifting up their ancestors from the bottom. Overall, the model provides a versatile platform to investigate the influences of metabolic and environmental factors on the growth and morphology of bacterial colonies.

It holds great promise to develop thrombolytic agent delivery systems with prolonged circulation time, minimized adverse effect, and preferential thrombolytic activity at the thrombus site. In this work, a pH-triggered delivery system for the thrombolytic agent was synthesized. Fluorescein isothiocyanate-labeled urokinase-type plasminogen activator (uPA) was conjugated to oxidized dextran (Oxd) via the pH-sensitive imine linkage, and then the conjugation was modified with RGD peptide. The uPA-Oxd conjugates displayed enhanced stability to resist enzymatic hydrolysis in comparison with the native uPA. Meanwhile, the bioactivity of uPA in the uPA-Oxd conjugates was masked at physiological pH and regenerated under weak acidic condition due to the release of uPA via the hydrolysis of imine bond in the conjugates. RGD modification endowed the conjugates with targeting ability to the thrombus site due to the specific peptide-GP IIb/IIIa binding and enhanced the thrombolysis efficacy via an endogenous low-pH triggered uPA release at the thrombus site, reducing the risk of acute hemorrhage complication. Thus, the RGD modified pH-sensitive uPA-Oxd conjugates provide a promising potential of the system in local thrombolysis therapy.

The gearbox is one of the most fragile parts of a wind turbine (WT). Fault diagnosis of the WT gearbox is of great importance to reduce operation and maintenance (O&M) costs and improve cost-effectiveness. At present, intelligent fault diagnosis methods based on long short-term memory (LSTM) networks have been widely adopted. As the traditional softmax loss of an LSTM network usually lacks the power of discrimination, this paper proposes a fault diagnosis method for wind turbine gearboxes based on optimized LSTM neural networks with cosine loss (Cos-LSTM). The loss can be converted from Euclid space to angular space by cosine loss, thus eliminating the effect of signal strength and improve the diagnosis accuracy. The energy sequence features and the wavelet energy entropy of the vibration signals are used to evaluate the Cos-LSTM networks. The effectiveness of the proposed method is verified with the fault vibration data collected on a gearbox fault diagnosis experimental platform. In addition, the Cos-LSTM method is also compared with other classic fault diagnosis techniques. The results demonstrate that the Cos-LSTM has better performance for gearbox fault diagnosis.

The development of covalent organic framework (COF)-derived materials with additional functions and applications is highly desired. In this work, a unique COF-functionalized hydrophilic magnetic nanosphere (FeO@PDA@TbBd) with FeO as a magnetic core, polydopamine (PDA) as a hydrophilic middle layer, and TbBd as an outer COF shell was facilely prepared as a novel hydrophilic platform for efficient detection of phthalic acid esters (PAEs). The resultant FeO@PDA@TbBd nanosphere displayed strong magnetic response, high surface area, and good hydrophilicity. Accordingly, the newly synthesized COF exhibited great potential in phthalate analysis with a wide linearity (50-8000 ng/mL), good recovery (92.3-98.9%), a low limit of detection (0.0025-0.01 ng/mL), and a small relative standard deviation (for intraday less than 4.6% and for interday less than 6.8%). More excitingly, the new COF was applied to analyze nine PAEs in the human plasma sample. This work opens up new avenues for the development and application of functionalized COF-derived materials.

In this work, a facile route was initially developed for preparation of a novel metal oxide affinity chromatography (MOAC) material by grafting titania nanoparticles on polydopamine (PD)-coated graphene (denoted as G@PD@TiO2). In the first step, self-assemble polymerization of dopamine on graphene was performed in basic solution at room temperature, which not only offered the coupling linker between titania and graphene but also improved the hydrophilicity and biological compatibility of the nanohybrids. Thereafter, the titania nanoparticles were grafted on the surface of the PD-coated graphene via a simple hydrothermal treatment. The as-prepared G@PD@TiO2 nanohybrids exhibited high sensitivity (detection limit of 5 fmol) and high selectivity for phosphopeptides at a low molar ratio of phosphopeptides/nonphosphopeptides (1:1000). Moreover, the as-prepared nanohybrids were also investigated for enrichment of phosphopeptides from real biological samples (human serum and mouse brain). A total number of 556 phosphorylation sites were identified from the digest of mouse brain proteins, showing great potential in the practical application.

Metal oxide affinity chromatography (MOAC) is a powerful technique in phosphoproteome research. However, the achievement of highly specific enrichment and sensitive detection of phosphopeptide by MOAC remains a big challenge since the lack of high specificity and large binding capacity of conventional MOAC materials. In this work, a new MOAC material, TiO2-coated hierarchically ordered macro/mesoporous silica (denoted as HOMMS@TiO2) composites, was prepared via a facile process. The HOMMS@TiO2 composites were demonstrated to have low limit of detection (8 fmol) and great specificity with a very rapid enrichment speed (within 1 min). These experimental results have demonstrated that the HOMMS@TiO2 exhibit great potential in phosphoproteome research.