Phosphorylation-mediated interaction between human E26 transcription factor 1 and specific protein 1 is required for tumor cell migration.

Transcription factors, human E26 transcription factor 1 (Ets1) and specific protein 1 (Sp1), are known to induce gene expression in tumorigenicity. High Ets1 expression is often associated with colorectal tumorigenesis. In this study, we discover that metastasis and clone formation in SW480 cells mainly depend on the direct interaction between Ets1 and Sp1 instead of high Ets1 expression. The interaction domains are further addressed to be the segment at Sp1(626-708) and the segment at Ets1(244-331). In addition, the phosphorylation inhibition of Ets1 at Tyr283 by either downregulation of Src kinase or Src family inhibitor treatment decreases the interaction between Sp1 and Ets1 and suppresses SW480 migration. Either administration or overexpression of the peptides harboring the interaction segment strongly inhibits the colony formation and migration of SW480 cells. Our findings suggest that the interaction between Ets1 and Sp1 rather than Ets1 alone promotes transformation in SW480 cells and provide new insight into the Ets1 and Sp1 interaction as an antitumour target in SW480 cells.

Identification of sitagliptin binding proteins by affinity purification mass spectrometry.

Type 2 diabetes mellitus (T2DM) is recognized as a serious public health concern with increasing incidence. The dipeptidyl peptidase-4 (DPP-4) inhibitor sitagliptin has been used for the treatment of T2DM worldwide. Although sitagliptin has excellent therapeutic outcome, adverse effects are observed. In addition, previous studies have suggested that sitagliptin may have pleiotropic effects other than treating T2DM. These pieces of evidence point to the importance of further investigation of the molecular mechanisms of sitagliptin, starting from the identification of sitagliptin-binding proteins. In this study, by combining affinity purification mass spectrometry (AP-MS) and stable isotope labeling by amino acids in cell culture (SILAC), we discover seven high-confidence targets that can interact with sitagliptin. Surface plasmon resonance (SPR) assay confirms the binding of sitagliptin to three proteins, i. e., LYPLAL1, TCP1, and CCAR2, with binding affinities (K D) ranging from 50.1 µM to 1490 µM. Molecular docking followed by molecular dynamic (MD) simulation reveals hydrogen binding between sitagliptin and the catalytic triad of LYPLAL1, and also between sitagliptin and the P-loop of ATP-binding pocket of TCP1. Molecular mechanics Poisson-Boltzmann Surface Area (MMPBSA) analysis indicates that sitagliptin can stably bind to LYPLAL1 and TCP1 in active sites, which may have an impact on the functions of these proteins. SPR analysis validates the binding affinity of sitagliptin to TCP1 mutant D88A is ~10 times lower than that to the wild-type TCP1. Our findings provide insights into the sitagliptin-targets interplay and demonstrate the potential of sitagliptin in regulating gluconeogenesis and in anti-tumor drug development.

Tunable Lifshitz Transitions and Multiband Transport in Tetralayer Graphene.

As the Fermi level and band structure of two-dimensional materials are readily tunable, they constitute an ideal platform for exploring the Lifshitz transition, a change in the topology of a material's Fermi surface. Using tetralayer graphene that host two intersecting massive Dirac bands, we demonstrate multiple Lifshitz transitions and multiband transport, which manifest as a nonmonotonic dependence of conductivity on the charge density n and out-of-plane electric field D, anomalous quantum Hall sequences and Landau level crossings that evolve with n, D, and B.

Interlayer resistance of misoriented MoS2.

Interlayer misorientation in transition metal dichalcogenides alters their interlayer distance, total energy, electronic band structure, and vibrational modes, but its effect on the interlayer resistance is not known. This study analyzes the interlayer resistance of misoriented bilayer MoS2 as a function of the misorientation angle, and it shows that interlayer misorientation exponentially increases the electron resistivity while leaving the hole resistivity almost unchanged. The physics, determined by the wave functions at the high symmetry points, are generic among the popular semiconducting transition metal dichalcogenides (TMDs). The asymmetrical effect of misorientation on the electron and hole transport may be exploited in the design and optimization of vertical transport devices such as a bipolar transistor. Density functional theory provides the interlayer coupling elements used for the resistivity calculations.

Constructing a Highly Robust Interface Film for Enhancing Rate Performance of Graphite Anode via a Novel Electrolyte Additive.

Solid electrolyte interphase (SEI) is regarded as a key factor to enable high power outputs of Lithium-ion batteries (LIBs). Herein, we demonstrate a modified electrolyte consisting of a novel electrolyte additive, 1H,1H,2H,2H-perfluorooctyltrimethoxysilane (FTMS) to construct a highly robust and stable SEI on a graphite anode for LIBs to enhance its rate performance. With 2% FTMS, the anode presents an improved capacity retention from 77.6 to 91.2% at 0.5 C after 100 cycles and an improved capacity from 86 to 229 mAh g-1 at 2 C. Experimental characterizations and theoretical calculations reveal that FTMS is preferentially absorbed and reduced on graphite to construct an interface chemistry with uniform fluoride-containing organic lithium salt and silicon-containing polymer, which exhibits high flexibility and conductivity and endows the SEI with high robustness and stability. This work provides an effective way to address the issue of slow lithium insertion/desertion kinetics of graphite anodes.

Specific pupylation as IDEntity reporter (SPIDER) for the identification of protein-biomolecule interactions.

Protein-biomolecule interactions play pivotal roles in almost all biological processes. For a biomolecule of interest, the identification of the interacting protein(s) is essential. For this need, although many assays are available, highly robust and reliable methods are always desired. By combining a substrate-based proximity labeling activity from the pupylation pathway of Mycobacterium tuberculosis and the streptavidin (SA)-biotin system, we developed the Specific Pupylation as IDEntity Reporter (SPIDER) method for identifying protein-biomolecule interactions. Using SPIDER, we validated the interactions between the known binding proteins of protein, DNA, RNA, and small molecule. We successfully applied SPIDER to construct the global protein interactome for m6A and mRNA, identified a variety of uncharacterized m6A binding proteins, and validated SRSF7 as a potential m6A reader. We globally identified the binding proteins for lenalidomide and CobB. Moreover, we identified SARS-CoV-2-specific receptors on the cell membrane. Overall, SPIDER is powerful and highly accessible for the study of protein-biomolecule interactions.

Banana stem and leaf biochar as an effective adsorbent for cadmium and lead in aqueous solution.

Lead (Pb) and cadmium (Cd) are toxic heavy metals commonly found in aqueous environments. Biochar as a green adsorbent generated from biomass feedstock may be used for effective removal of these heavy metals. This study investigated the adsorption kinetics and isotherms of Pb2+ and Cd2+ in aqueous solutions at different pH by biochar prepared from banana stem and leaf (BSL-BC) at 400 °C. Characterizations using scanning electron microscope, X-ray diffraction, and Fourier-transform infrared spectroscopy showed that the synthesized BSL-BC had rough surface, porous structure, and oxygen-containing functional groups. The adsorption of Pb2+ and Cd2+ onto BSL-BC reached equilibrium in 8 h and 200 min, respectively, with faster adsorption attained at higher pH and the optimum pH occurred at 5 (Pb2+) and 8 (Cd2+). All adsorption kinetic data followed the pseudo-second-order rate model. The adsorption isotherm data of Pb2+ and Cd2+ could be well-described by the Langmuir and Freundlich models, respectively, whereas neither the Temkin or Dubinin-Radushkevich models provided satisfactory fitting results. The maximum adsorption capacities for Pb2+ and Cd2+ were 302.20 and 32.03 mg/g, respectively. The calculated mechanism contributions showed that complexation with oxygen-containing functional groups, ion exchange, mineral precipitation, and Pb2+/Cd2+-π coordination accounted for 0.1%, 8.4%, 88.8%, and 2.6% to Pb2+ adsorption, and 0.4%, 6.3%, 83.0%, and 10.4% to Cd2+ adsorption, respectively. Therefore, mineral precipitation was likely the major mechanism responsible for adsorption of both Pb2+ and Cd2+ by BSL-BC. The results suggest that the synthesized BSL-BC has great potential for adsorption of Pb2+ and Cd2+ from aqueous solutions.

[Advances and Prospect of Sampling Techniques and Analytical Methods for Trace Elements in the Ocean: Progress of Trace Element Platform Construction in Xiamen University].

Trace elements, which are important chemical components in the ocean, generally refer to those chemical elements with concentrations below 10 µmol·kg-1in seawater. Some trace elements, such as Fe and Zn, serve as essential micronutrients for marine organisms, which regulate marine primary productivity and are closely related to the biogeochemical cycle of carbon and nitrogen and therefore affect the global environment and climate change. In contrast, some elements, such as Pb, are anthropogenic pollutants largely released by human activities. In addition, some trace elements and their isotopes can be used as tracers for oceanographic processes and proxies for paleoceanography. However, the high saline matrix and extremely low trace element concentrations in seawater, as well as the contamination from research vessels, sampling equipment, and the surrounding environment during the process of sample collection, pretreatment, and analysis, have restricted researchers from obtaining reliable trace element data in the ocean for a long period of time. Nevertheless, high quality samples and accurate data are prerequisites for investigating the biogeochemical and environmental behavior of marine trace elements. This paper reviews the development of sampling techniques and analytical methods for trace elements in seawater, introduces the research history and platform construction activities in Xiamen University in this field, summarizes the advantages and disadvantages of various sampling and analytical techniques and methods, and presents the perspectives on future developments in the research on trace elements in the ocean.

Folic Acid and Poly(ethylene glycol) Decorated Paclitaxel Nanocrystals Exhibit Enhanced Stability and Breast Cancer-Targeting Capability.

In part because of their high drug loading, nanocrystals (NCs) have seen extensive use in drug delivery, particularly for insoluble or poorly soluble drugs. It remains a challenge, however, to prepare stable nanocrystals with tumor-targeting capability. Here, we designed a novel preparation of stable paclitaxel (PTX) nanocrystals with efficient active tumor-targeting properties. PTX NC was prepared using a bottom-up method and modified with both poly(ethylene glycol) (PEG) and folic acid (FA) derivatives using film hydration. The resulting PTX NC@lipid-PEG-FA had a rodlike shape, with hydrodynamic diameters and drug loading values of 201.90 ± 2.92 nm and 31.07 ± 3.41%, respectively. The size of the PTX NC@lipid-PEG-FA was unchanged after 168 h in the presence of plasma, whereas nonmodified paclitaxel nanocrystals (PTX NC) exceeded 600 nm within 12 h under the same conditions. Cellular uptake and cellular growth inhibition experiments in 4T1 breast cancer cells showed the superiority of PTX NC@lipid-PEG-FA over PTX NC or PEGylated paclitaxel nanocrystals without FA modification (PTX NC@lipid-PEG). A pharmacokinetic evaluation in rats revealed that PTX NC@lipid-PEG-FA significantly prolonged the circulation of PTX in the bloodstream, in comparison with PTX NC or Taxol. Tissue distribution and in vivo antitumor studies in 4T1 orthotopic breast cancer-bearing nude mice showed that PTX NC@lipid-PEG-FA significantly increased the intratumor accumulation of PTX and efficiently inhibited tumor growth, in comparison with PTX NC@lipid-PEG, PTX NC, or Taxol. In summary, PTX NC@lipid-PEG-FA showed good potential for breast cancer-targeted delivery for insoluble therapeutics.

A picoampere A/D converter for biosensor applications.

Detection and analysis of biological and biochemical signals via compact sensor systems require low-power and compact analog-to-digital converter (ADC) systems. Here we present a highly sensitive flash current-mode ADC (IADC) design with resolution down to 15pA. The IADC's small-size and low-power capabilities allow integration for stand-alone biological or chemical microsensor applications.

Desorption process and morphological analysis of real polycyclic aromatic hydrocarbons contaminated soil by the heterogemini surfactant and its mixed systems.

Surfactant-enhanced remediation (SER) is an efficient and low-cost technology for polycyclic aromatic hydrocarbons (PAHs) contaminated sites. This study assessed the desorption processes and effects of Heterogemini surfactant (Dodecyldimethylammonium bromide/tetradecyldimethylammonium bromide, DBTB), two traditional surfactants (Hexadecyl trimethyl ammonium bromide, CTAB; Sorbitan monolaurate, Span 20) and their mixed systems on the real PAHs-contaminated soil from an abandoned coking plant, as well they were analyzed micro morphologically. DBTB had greater desorption capability for PAHs and favorable interaction with the traditional surfactants confirmed by reaction parameters ßm and Gibbs. Whether for total PAHs (TPAHs) or different molecular weight PAHs, the mixed system Span 20/DBTB had larger molar solubilization ratio (MSR) and partition coefficient (Km) than CTAB/DBTB, the highest desorption rate for TPAHs reaching 68.83%. Additionally, microscopic morphology showed micelles of Span 20/DBTB were more dispersed and formed strings easily, explaining its good desorption capability. What resulted demonstrated the feasibility of DBTB, a novel Heterogemini surfactant, and its mixed systems remediating PAHs-contaminated soil of abandoned industrial site.

[Enhanced Phytoextraction of Cadmium Contaminated Soil by Trifolium Repens with Biodegradable Chelate GLDA].

Chelating agents can increase the bioavailability of heavy metals and enhance their enrichment in plants. The effects of different concentrations of biodegradable chelating agent L-glutamic acid N, N-diacetic acid (GLDA) on the remediation of heavy metal-contaminated soil by super-enriched plant Trifolium repens were investigated by pot experiments with Cd-contaminated soil. Results show that low-dose GLDA could significantly promote the growth of Trifolium repens, and the biomass of Trifolium repens was the highest at 2.5 mmol·kg-1-GLDA, which was 1.30 times that of the control group. Different concentrations of GLDA can increase Cd content of various parts of Trifolium repens. In general, the treatment effect of 5 mmol·kg-1 GLDA was ideal. In this scenario, the root, aerial parts, and whole Cd content were 3.57, 4.69, and 4.67 times of the control group, respectively. GLDA can significantly increase the available Cd content in soil, promote direct absorption at the Trifolium repens roots, and provide better transport to the aerial parts. The prediction model obtained by fitting the linear relationship between physical and chemical properties of soil indicates that GLDA and Trifolium repens Cd content can provide references for the future research of soil-Trifolium repens enrichment. Studies have shown that the biodegradable chelating agent GLDA has potential applications for enhancing phytoremediation of heavy metal Cd contaminated soil.

Enhancing LiAlOX synaptic performance by reducing the Schottky barrier height for deep neural network applications.

Although good performance has been reported in shallow neural networks, the application of memristor synapses towards realistic deep neural networks has met more stringent requirements on the synapse properties, particularly the high precision and linearity of the synaptic analog weight tuning. In this study, a LiAlOX memristor synapse was fabricated and optimized to address these demands. By delicately tuning the initial conductance states, 120-level continuously adjustable conductance states were obtained and the nonlinearity factor was substantially reduced from 8.96 to 0.83. The significant enhancements were attributed to the reduced Schottky barrier height (SBH) between the filament tip and the electrode, which was estimated from the measured I-V curves. Furthermore, a deep neural network for realistic action recognition task was constructed, and the recognition accuracy was found to be increased from 15.1% to 91.4% on the Weizmann video dataset by adopting the above-described device optimization method.

Stabilizing resistive random access memory by constructing an oxygen reservoir with analyzed state distribution.

In this paper, the instability mechanism of resistive random access memory (RRAM) was investigated, and a technique was developed to stabilize the distribution of high resistance states (HRS) and better concentrate the set voltage. Due to the accumulation of oxygen, an interface-type switching characteristic was observed on the I-V curves beneath the filament-type switching behavior. In this work, the interface-type switching characteristic is used to fit the natural distribution of HRS as an analysis of the instability mechanism. According to the results, the HRS distribution is attributed to the accumulation of excess oxygen ions left from the lower oxygen content and oxygen vacancy recombination during the reset process. The proposed solution with simple plasma treatment, can create an excess oxygen reservoir by changing the surface topography of the electrode to store the surplus oxygen ions from the reset process, eliminating the oxygen accumulation effect and further improving the device stability.

Exosomes as Carriers for Antitumor Therapy.

Exosomes are bilayer vesicles with particle sizes between 50 and 150 nm. Owing to their bilayer membrane structure, cell-to-cell communication, and good absorbability, exosomes are increasingly used as carriers for drug delivery through phospholipid membrane structures to lesion sites with enhanced targeting. Exosome sources and drug-loading methods are important factors affecting their use as drug carriers. There are various ways to pack species in exosomes, and researchers are constantly seeking new and improved approaches. In both in vivo and in vitro evaluations, exosomal vectors have achieved good antitumor efficacies. Despite the importance of exosomes as drug delivery systems with accurate targeting ability and biocompatibility, improvements are needed to facilitate their widespread clinical use. This review focuses on the preparation of exosomes as carriers and their utilization in antitumor research.

Construction and in vitro and in vivo evaluation of folic acid-modified nanostructured lipid carriers loaded with paclitaxel and chlorin e6.

Breast cancer remains a major threat to women's health, and the incidence of breast cancer continues to increase each year. Paclitaxel (PTX) is commonly used to treat breast cancer, but shows limited solubility and is associated with major side effects, limiting its clinical applications. Photodynamic therapy (PDT) is a promising treatment for breast cancer but is limited by the poor solubility of photosensitizers and difficulties in targeting and enriching the tumor tissue with photosensitizers. Here, we prepared a new nanocarrier system using nanostructured lipid carriers (PTX@FA-NLC-PEG-Ce6) harboring PTX, chlorin e6 (Ce6), and folic acid-targeted head to overcome the limitations of PTX and Ce6 in hydrophobicity and increase the target efficiency of chemotherapy drugs and photosensitizers at the tumor. The results showed that the drug-loading system met the requirements for intravenous injection, had tumor targeting ability, and could be easily taken up by MDA-MB-231 cells. Moreover, Ce6 could be dissociated from the surface of the drug-loading system and evenly distributed in cells after a period of time when the nanostructured lipid carriers had entered lysosomes through endocytosis. Additionally, reactive oxygen species were then produced to induce PDT at a specific wavelength of illumination. In vitro pharmacodynamic experiments showed that combined PDT and chemotherapy had synergistic effects (combination index: 0.647). Furthermore, pharmacodynamic experiments in nude mice showed that the drug-loading system had ideal antitumor effects without obvious side effects. Thus, PTX@FA-NLC-PEG-Ce6 may have applications as a promising drug-loading system for PDT combined with chemotherapy in patients with breast cancer.

Percutaneous absorption and brain distribution facilitation of borneol on tetramethylpyrazine in a microemulsion-based transdermal therapeutic system.

In this study, we show that the percutaneous absorption and brain distribution of tetramethylpyrazine (TMP) is enhanced when combined with borneol (BN) in a microemulsion-based transdermal therapeutic system (ME-TTS). The formulation of the TMP and BN microemulsion (TEM-BN-ME) was optimized in skin permeation studies in vitro following a uniform experimental design. Male Sprague-Dawley rats were used for the in vivo pharmacokinetic and tissue distribution studies of TMP-BN-ME-TTS. In the pharmacokinetic study, the TMP-BN-ME-TTS treated rats had significantly higher (P < 0.05) C max and AUC of TMP than the TMP-ME-TTS treated rats, indicating that BN improves the rate and extent of TMP percutaneous absorption. In the tissue distribution study, the AUC of TMP in brain was significantly higher in the TMP-BN-ME-TTS group (P < 0.05), indicating that BN facilitates the distribution of TMP in brain. In summary, BN enhanced the percutaneous absorption and brain distribution of TMP in a microemulsion-based transdermal therapeutic system.

Investigation of the Capacitance-Voltage Electrical Characteristics of Thin-Film Transistors Caused by Hydrogen Diffusion under Negative Bias Stress in a Moist Environment.

In this study, the impact of moisture on the electrical characteristics of an amorphous In-Ga-Zn-O thin-film transistor (a-IGZO TFT) was investigated. In commercial applications of such TFTs, high stability and quality performance in humid environments are essential. During TFT operation under ambient moisture, the electrolysis of water molecules occurs via the tip electric field effect. Hydrogen diffuses from the etch-stop layer or back-channel into the main channel under a negative electric field. The hydrogen atoms act as shallow donors (which causes the carrier concentration in the channel to rise), causing the threshold voltage (VTH) to shift in the negative direction. Hydrogen diffusion from the overlap of the source/drain and gate electrodes to the channel center caused by the tip electric field induces a significant barrier lowering and VTH shifts in a short-channel device. However, under negative bias stress (NBS) in ambient moisture, the negative VTH shift is more obvious in short- than in long-channel devices, indicating suppressed hydrogen diffusion in long-channel devices. This is attributed to the electrolysis of water by the tip electric field at the source, drain, and gate electrodes, which causes hydrogen to diffuse to the center of the channel. Here, a novel physical model of the capacitance-voltage (C-V) electrical property changes under ambient moisture is proposed, based on the early appearance of abnormalities in the C-V measurements. The electrolysis of water caused by the tip electric field and electrical abnormalities caused by hydrogen diffusion into the a-IGZO active layer are explained by this model. A secondary-ion mass spectrometry analysis shows that hydrogen content in the channel generally increases under NBS in ambient moisture. The degradation behavior due to moisture in a-IGZO is clarified. Thus, inhibiting the tip electric field may benefit future flexible-display and gas-sensing applications.

Bimolecular-induced hierarchical nanoporous LiTi2(PO4)3/C with superior high-rate and cycling performance.

We employed a facile bimolecular (glucose and DMEA) assisted hydrothermal reaction and a solid-state reaction to obtain carbon-coated hierarchical LiTi2(PO4)3 on a large scale. The nanoporous material exhibits excellent high-rate and cycling performance owing to enhanced electronic conductivity from the ultrathin carbon layer, Ti3+ and the shortened path for Li+ diffusion by nanoporous frameworks.

Enhanced immunization via dissolving microneedle array-based delivery system incorporating subunit vaccine and saponin adjuvant.

PURPOSE: To enhance the immunogenicity of the model subunit vaccine, ovalbumin (OVA) was combined with platycodin (PD), a saponin adjuvant. To reduce the toxicity of PD, OVA, and adjuvant were loaded together into liposomes before being incorporated into a dissolving microneedle array. METHODS: OVA- and PD-loaded liposomes (OVA-PD-Lipos) were prepared using the film dispersion method. Their uptake behavior, toxicity to mouse bone marrow dendritic cells (BMDCs), and hemolytic activity to rabbit red blood cells (RBCs) were evaluated. The OVA-PD-Lipos were incorporated into a dissolving microneedle array. The chemical stability of OVA and the physical stability of OVA-PD-Lipos in microneedle arrays were investigated. The immune response of Institute of Cancer Research mice and potential skin irritation reaction of rabbits to OVA-PD-Lipos-MNs were evaluated. RESULTS: The uptake of OVA by mouse BMDCs was greatly enhanced when OVA was prepared as OVA-PD-Lipos, and in this form, the toxicity of PD was dramatically reduced. OVA was chemically stable as OVA-PD-Lipos, when OVA-PD-Lipos was incorporated into a dissolving microneedle array. Institute of Cancer Research mice treated with OVA-PD-Lipos-MNs showed a significantly enhanced immune response. PD combined with OVA elicited a balanced Th1 and Th2 humoral immune response in mice, with minimal irritation in rabbit skin. CONCLUSION: The dissolving microneedle array-based system is a promising delivery vehicle for subunit vaccine and its adjuvant.