In vitro and in vivo anti-tumor effect of Trichobakin fused with urokinase-type plasminogen activator ATF-TBK.

BACKGROUND: Trichobakin (TBK), a member of type I ribosome-inactivating proteins (RIPs), was first successfully cloned from Trichosanthes sp Bac Kan 8-98 in Vietnam. Previous study has shown that TBK acts as a potential protein synthesis inhibitor; however, the inhibition efficiency and specificity of TBK on cancer cells remain to be fully elucidated. METHODS AND RESULTS: In this work, we employed TBK and TBK conjugated with a part of the amino-terminal fragment (ATF) of the urokinase-type plasminogen activator (uPA), which contains the Ω-loop that primarily interacts with urokinase-type plasminogen activator receptor, and can be a powerful carrier in the drug delivery to cancer cells. Four different human tumor cell lines and BALB/c mice bearing Lewis lung carcinoma cells (LLC) were used to evaluate the role of TBK and ATF-TBK in the inhibition of tumor growth. Here we showed that the obtained ligand fused RIP (ATF-TBK) reduced the growth of four human cancer cell lines in vitro in the uPA receptor level-dependent manner, including the breast adenocarcinoma MDA-MB 231 cells and MCF7 cells, the prostate carcinoma LNCaP cells and the hepatocellular carcinoma HepG2 cells. Furthermore, the conjugate showed anti-tumor activity and prolonged the survival time of tumor-bearing mice. The ATF-TBK also did not cause the death of mice with doses up to 48 mg/kg, and they were not significantly distinct on parameters of hematology and serum biochemistry between the control and experiment groups. CONCLUSIONS: In conclusion, ATF-TBK reduced the growth of four different human tumor cell lines and inhibited lung tumor growth in a mouse model with little side effects. Hence, the ATF-TBK may be a target to consider as an anti-cancer agent for clinical trials.

Nanodiamond Solid-Phase Extraction and Triton X-114 Cloud Point Separation for Robust Fractionation and Shotgun Proteomics Analysis of the Human Serum Proteome.

Human serum is one of the most attractive specimens in biomarker research. However, its overcomplicated properties have hindered the analysis of low-abundance proteins by conventional mass spectrometry techniques. This work proposes an innovative strategy for utilizing nanodiamonds (NDs) in combination with Triton X-114 protein extraction to fractionate the crude serum to six pH-tuned fractions, simplifying the overall proteome and facilitating protein profiling with high efficiency. A total of 663 proteins are identified and evenly distributed among the fractions along with 39 FDA-approved biomarkers─a remarkable increase from the 230 proteins found in unfractionated crude serum. In the low-abundance protein section, 88 proteins with 7 FDA-approved biomarkers are detected─a marked increase from the 15 proteins (2 biomarkers) observed in the untreated sample. Notably, fractions at pH 11, derived from the aqueous phase of detergent separation, suggest potential applications in rapid and robust serum proteome analysis. Notably, by outlining the excellent properties of NDs for proteomic research, this work suggests a promising extraction protocol utilizing the great compatibility of NDs with streamlined serum proteomics and identifies potential avenues for future developments. Finally, we believe that this work not just improves shotgun proteomics but also opens up studies on the interaction between NDs and the human proteome. Data are available via ProteomeXchange with the identifier PXD029710.

Enhanced out-of-plane electromechanical response of Janus ZrSeO.

Two-dimensional piezoelectric materials have attracted great attention as they could play a vital role in nano-electromagnetic systems. Herein, we investigate the compelling piezoelectric properties of Janus ZrSeO in monolayer and bulk structures using density functional theory calculations with a van der Waals correction. One of the two independent out-of-plane piezoelectric coefficients (e31) of the bulk ZrSeO is as high as 287.60 pC m-1, which is over five times larger than that of monolayer ZrSeO due to charge changes in the internal structure within each Zr, Se, and O layer. Interestingly, another large negative out-of-plane piezoelectric stress coefficient (e33) of bulk ZrSeO (-467.40 pC m-1) results from the displacement difference between the electronic and ionic center positions, which is at least three times larger than those previously reported for Janus Mo/W/Hf-based transition metal dichalcogenides. The charge transformation between atoms under strain induces negative piezoelectric stress, a process that is clarified using maximally localized Wannier functions (MLWF) and Bader charge analysis. This research also reveals the dependence of piezoelectricity in Janus MXY on the metal (M = Zr, Hf, W, Mo) and chalcogenide (X,Y = S, Se, O) components, which are directly proportional to the electronegativity and the atomic size difference.

Enhanced Hydrogen Evolution Performance at the Lateral Interface between Two Layered Materials Predicted with Machine Learning.

While economical and effective catalysts are required for sustainable hydrogen production, low-dimensional interfacial engineering techniques have been developed to improve the catalytic activity in the hydrogen evolution reaction (HER). In this study, we used density functional theory (DFT) calculations to measure the Gibbs free energy change (ΔGH) in hydrogen adsorption in two-dimensional lateral heterostructures (LHSs) MX2/M'X'2 (MoS2/WS2, MoS2/WSe2, MoSe2/WS2, MoSe2/WSe2, MoTe2/WSe2, MoTe2/WTe2, and WS2/WSe2) and MX2/M'X' (NbS2/ZnO, NbSe2/ZnO, NbS2/GaN, MoS2/ZnO, MoSe2/ZnO, MoS2/AlN, MoS2/GaN, and MoSe2/GaN) at several different positions near the interface. Compared to the interfaces of LHS MX2/M'X'2 and the surfaces of the monolayer MX2 and MX, the interfaces of LHS MX2/M'X' display greater hydrogen evolution reactivity due to their metallic behavior. The hydrogen absorption is stronger at the interfaces of LHS MX2/M'X', and that facilitates proton accessibility and increases the usage of catalytically active sites. Here, we develop three types of descriptors that can be used universally in 2D materials and can explain changes in ΔGH for different adsorption sites in a single LHS using only the basic information of the LHSs (type and number of neighboring atoms to the adsorption points). Using the DFT results of the LHSs and the various experimental data of atomic information, we trained machine learning (ML) models with the chosen descriptors to predict promising combinations and adsorption sites for HER catalysts among the LHSs. Our ML model achieved an R2 score of 0.951 (regression) and an F1 score of 0.749 (classification). Furthermore, the developed surrogate model was implemented to predict the structures in the test set and was based on confirmation from the DFT calculations via ΔGH values. The LHS MoS2/ZnO is the best candidate for HER among 49 candidates considered using both DFT and ML models because it has a ΔGH of -0.02 eV on top of O at the interface position and requires only -171 mV of overpotential to obtain the standard current density (10 A/cm2).

Highly Efficient Van Der Waals Heterojunction on Graphdiyne toward the High-Performance Photodetector.

Graphdiyne (GDY), a new 2D material, has recently proven excellent performance in photodetector applications due to its direct bandgap and high mobility. Different from the zero-gap of graphene, these preeminent properties made GDY emerge as a rising star for solving the bottleneck of graphene-based inefficient heterojunction. Herein, a highly effective graphdiyne/molybdenum (GDY/MoS2 ) type-II heterojunction in a charge separation is reported toward a high-performance photodetector. Characterized by robust electron repulsion of alkyne-rich skeleton, the GDY based junction facilitates the effective electron-hole pairs separation and transfer. This results in significant suppression of Auger recombination up to six times at the GDY/MoS2 interface compared with the pristine materials owing to an ultrafast hot hole transfer from MoS2 to GDY. GDY/MoS2 device demonstrates notable photovoltaic behavior with a short-circuit current of -1.3 × 10-5 A and a large open-circuit voltage of 0.23 V under visible irradiation. As a positive-charge-attracting magnet, under illumination, alkyne-rich framework induces positive photogating effect on the neighboring MoS2 , further enhancing photocurrent. Consequently, the device exhibits broadband detection (453-1064 nm) with a maximum responsivity of 78.5 A W-1 and a high speed of 50 µs. Results open up a new promising strategy using GDY toward effective junction for future optoelectronic applications.