The mechanism of action and biodistribution of a novel EGFR/VEGF bispecific fusion protein that exhibited superior antitumor activities.

Despite the promising clinical benefits of therapies targeting epidermal growth factor receptor (EGFR) or vascular endothelial growth factor (VEGF) with antibodies in various cancers, resistance to these therapies will inevitably develop following treatment. Recent studies suggest that crosstalk between the EGFR and VEGF signaling pathways might be involved in the development of resistance. Therefore, simultaneous blockade of EGFR and VEGF signaling may be able to counteract this resistance and improve clinical outcomes.

A strategy for the efficient construction of anti-PD1-based bispecific antibodies with desired IgG-like properties.

Targeting PD1/PDL1 with blocking antibodies for cancer therapy has shown promising benefits in the clinic, but only approximately 20-30% of patients develop durable clinical responses to the treatment. Bispecific antibodies (BsAbs) that combine PD1/PDL1 blockade with the modulation of another immune checkpoint target may have greater potential to enhance immune checkpoint blockade therapy. In this study, we identified an anti-PD1 monoclonal antibody, 609A, whose heavy chain can pair with a variety of light chains from different antibodies while maintaining its PD1 binding/blocking activity.

Bispecific antibody simultaneously targeting PD1 and HER2 inhibits tumor growth via direct tumor cell killing in combination with PD1/PDL1 blockade and HER2 inhibition.

Immune checkpoint blockade has shown significant clinical benefit in multiple cancer indications, but many patients are either refractory or become resistant to the treatment over time. HER2/neu oncogene overexpressed in invasive breast cancer patients associates with more aggressive diseases and poor prognosis. Anti-HER2 mAbs, such as trastuzumab, are currently the standard of care for HER2-overexpressing cancers, but the response rates are below 30% and patients generally suffer relapse within a year.

Tumor-targeting anti-EGFR x anti-PD1 bispecific antibody inhibits EGFR-overexpressing tumor growth by combining EGFR blockade and immune activation with direct tumor cell killing.

We developed a strategy to combine conventional targeted therapy with immune checkpoint blockade using a tumor-targeting bispecific antibody (BsAb) to treat solid tumors. The BsAb was designed to simultaneously engage a tumor-associated antigen, epidermal growth factor receptor (EGFR), and programed cell death protein 1 (PD1). In addition to its direct anti-tumor activity via EGFR inhibition, the BsAb mediated efficient antibody-dependent cellular cytotoxicity (ADCC) and activated T cell antitumor im munity through blockade of PD1 from interacting with its counterpart, programed cell death ligand 1 (PDL1).

A new anti-HER2 antibody that enhances the anti-tumor efficacy of trastuzumab and pertuzumab with a distinct mechanism of action.

The majority of patients with metastatic breast cancer who are treated with the anti-HER2 monoclonal antibody, trastuzumab, generally develop resistance to the drug within a year after initiation of the treatment. Here we describe a new anti-HER2 humanized monoclonal antibody, 19H6-Hu, which binds to HER2 extracellular domain (ECD) with high affinity and inhibits proliferation of multiple HER2-overexpressing cancer cell lines as a single agent or in combination with trastuzumab. 19H6-Hu binds to the domain III in proximity to the domain IV of HER2 ECD, which differs from trastuzumab and pertuzumab.

Important roles of CD32 in promoting suppression of IL-4 induced immune responses by a novel anti-IL-4Rα therapeutic antibody.

Asthma is characterized by airway hyperresponsiveness and inflammation, as well as underlying structural changes to the airways. Interleukin-4 (IL-4) is a key T-helper type 2 (Th2) cytokine that plays important roles in the pathogenesis of atopic and eosinophilic asthma. We developed a novel humanized anti-IL-4Rα antibody that can potently inhibit IL-4/IL-13-mediated TF-1 cell proliferation.

Visible-Light Direct Conversion of Ethanol to 1,1-Diethoxyethane and Hydrogen over a Non-Precious Metal Photocatalyst.

Converting renewable biomass and their derivatives into chemicals and fuels has received much attention to reduce the dependence on fossil resources. Photocatalytic ethanol dehydrogenation-acetalization to prepare value-added 1,1-diethoxyethane and H was achieved over non-precious metal CdS/Ni-MoS catalyst under visible light. The system displays an excellent production rate and high selectivity of 1,1-diethoxyethane, 52.

Impairment of Akt activity by CYP2E1 mediated oxidative stress is involved in chronic ethanol-induced fatty liver.

Protein kinase B (PKB/Akt) plays important roles in the regulation of lipid homeostasis, and impairment of Akt activity has been demonstrated to be involved in the development of non-alcoholic fatty liver disease (NAFLD). Previous studies suggest that cytochrome P4502E1 (CYP2E1) plays causal roles in the pathogenesis of alcoholic fatty liver (AFL). We hypothesized that Akt activity might be impaired due to CYP2E1-induced oxidative stress in chronic ethanol-induced hepatic steatosis.

Electrochemical oxygen reduction mechanism on FeN-graphene.

Metal-coordinated nitrogen-doped carbons are highly active in promoting electrochemical oxygen reduction reactions (ORR). The detailed kinetic and thermodynamic ORR behavior on three different FeN-graphene [FeN-G (A), (B) and (C)] structures was investigated in this work. The results show that formation of these FeN-G configurations is energetically favorable; however, not all of them are effective for ORR.

A site-holding effect of TiO surface hydroxyl in the photocatalytic direct synthesis of 1,1-diethoxyethane from ethanol.

To understand the mechanism of the photocatalytic direct synthesis of 1,1-diethoxyethane (DEE) from ethanol is vital for enhancing the reaction efficiency. Based on photocatalytic data of different phase TiO and F-TiO catalysts, radical trapping data, and GC-MS data, we proposed a photocatalytic mechanism for the preparation of both DEE in neat ethanol and 2,3-butanediol (2,3-BD) in ethanol-HO using photocatalytic methods. In neat ethanol, hydroxyl isn't involved in the catalytic cyclic process but hydroxyl has an indirect site-holding effect, thus leading to more hydroxyl groups with higher activity.

Chlorine-Induced In Situ Regulation to Synthesize Graphene Frameworks with Large Specific Area for Excellent Supercapacitor Performance.

Three-dimensional (3D) graphene frameworks are usually limited by a complicated preparation process and a low specific surface area. This paper presents a facile suitable approach to effectively synthesize 3D graphene frameworks (GFs) with large specific surface area (up to 1018 m(2) g(-1)) through quick thermal decomposition from sodium chloroacetate, which are considerably larger than those of sodium acetate reported in our recent study. The chlorine element in sodium chloroacetate may possess a strong capability to induce in situ activation and regulate graphene formation during pyrolysis in one step.

Tunneling Interlayer for Efficient Transport of Charges in Metal Oxide Electrodes.

Due to the limited electronic conductivity, the application of many metal oxides that may have attractive (photo)-electrochemical properties has been limited. Regarding these issues, incorporating low-dimensional conducting scaffolds into the electrodes or supporting the metal oxides onto the conducting networks are common approaches. However, some key electronic processes like interfacial charge transfer are far from being consciously concerned.

Ammonia-induced robust photocatalytic hydrogen evolution of graphitic carbon nitride.

We report a new and effective method to prepare high activity graphitic carbon nitride (g-C3N4) by a simple ammonia etching treatment. The obtained g-C3N4 displays a high BET surface area and enhanced electron/hole separation efficiency. The hydrogen evolution rates improved from 52 μmol h(-1) to 316.

Multifunctional Nitrogen-Doped Carbon Nanodots for Photoluminescence, Sensor, and Visible-Light-Induced H2 Production.

Herein, multifunctional N-doped carbon nanodots (NCNDs) were prepared through the one-step hydrothermal treatment of yeast. Results show that the NCNDs can be used as a new photocatalyst to drive the water-splitting reaction under UV light. Moreover, the NCNDs can efficiently catalyze the hydrogen evolution reaction.

A bi-functional antibody-receptor domain fusion protein simultaneously targeting IGF-IR and VEGF for degradation.

Bi-specific antibodies (BsAbs), which can simultaneously block 2 tumor targets, have emerged as promising therapeutic alternatives to combinations of individual monoclonal antibodies. Here, we describe the engineering and development of a novel, human bi-functional antibody-receptor domain fusion molecule with ligand capture (bi-AbCap) through the fusion of the domain 2 of human vascular endothelial growth factor receptor 1 (VEGFR1) to an antibody directed against insulin-like growth factor - type I receptor (IGF-IR). The bi-AbCap possesses excellent stability and developability, and is the result of minimal engineering.

Understanding the formation mechanism of graphene frameworks synthesized by solvothermal and rapid pyrolytic processes based on an alcohol-sodium hydroxide system.

The determination of ways to facilitate the 2D-oriented assembly of carbons into graphene instead of other carbon structures while restraining the π-π stacking interaction is a challenge for the controllable bulk synthesis of graphene, which is vital both scientifically and technically. In this study, graphene frameworks (GFs) are synthesized by solvothermal and rapid pyrolytic processes based on an alcohol-sodium hydroxide system. The evolution mechanism of GFs is investigated systematically.

Intramolecular hydrogen bonds quench photoluminescence and enhance photocatalytic activity of carbon nanodots.

Understanding the photoluminescence (PL) and photocatalytic properties of carbon nanodots (CNDs) induced by environmental factors such as pH through surface groups is significantly important to rationally tune the emission and photodriven catalysis of CNDs. Through adjusting the pH of an aqueous solution of CNDs, it was found that the PL of CNDs prepared by ultrasonic treatment of glucose is strongly quenched at pH 1 because of the formation of intramolecular hydrogen bonds among the oxygen-containing surface groups. The position of the strongest PL peak and its corresponding excitation wavelength strongly depend on the surface groups.

Photocatalytic direct conversion of ethanol to 1,1- diethoxyethane over noble-metal-loaded TiO2 nanotubes and nanorods.

As one of the most important biomass platform molecules, ethanol needs to have its product chain chemically extended to meet future demands in renewable fuels and chemicals. Additionally, chemical conversion of ethanol under mild and green conditions is still a major challenge. In this work, ethanol is directly converted into 1,1-diethoxyethane (DEE) and H2 under mild photocatalytic conditions over platinum-loaded TiO2 nanotubes and nanorods.

Self-assembly of gridlike zinc oxide lamellae for chemical-sensing applications.

Hexagonal gridlike ZnO lamellae (GZL) with uniform thickness are synthesized by the o-phthalic acid-assisted hydrothermal method. Here, a systematic study of the assembly behaviors of gridlike ZnO lamellae obtained by the synergistic effect of urea and o-phthalic acid is presented. The morphology evolution and formation mechanism of GZL are also discussed in detail.

Graphene frameworks promoted electron transport in quantum dot-sensitized solar cells.

Graphene frameworks (GFs) were incorporated into TiO2 photoanode as electron transport medium to improve the photovoltaic performance of quantum dot-sensitized solar cells (QDSSCs) for their excellent conductivity and isotropic framework structure that could permit rapid charge transport. Intensity modulated photocurrent/photovoltage spectroscopy and electrochemical impedance spectroscopy results show that the electron transport time (τ(d)) of 1.5 wt % GFs/TiO2 electrode is one-fifth of that of the TiO2 electrode, and electron lifetime (τ(n)) and diffusion path length (Ln) are thrice those of the TiO2 electrode.

Construction of two-dimensional MoS₂/CdS p-n nanohybrids for highly efficient photocatalytic hydrogen evolution.

2D MoS2 nanosheets have been utilized to fabricate 2D MoS2/CdS p-n nanohybrids through a one-pot solvothermal process. Due to the unique p-n junction heterostructure, large specific surface area, and decreased band gap, MoS2/CdS nanohybrids manifested a superior H2 -production rate of ~137 μmol h(-1) under visible-light irradiation and an apparent quantum yield of 10.5% at 450 nm.

Strategy to improve photovoltaic performance of DSSC sensitized by zinc prophyrin using salicylic acid as a tridentate anchoring group.

Three new zinc porphyrin dyes attached to ethynyl benzoic acid as an electron transmission and anchoring group have been designed, synthesized, and well-characterized. The performances of their sensitized solar cells have been investigated by optical, photovoltaic, and electrochemical methods. The photoelectric conversion efficiency of the solar cells sensitized by the dye with salicylic acid as an anchoring group demonstrated obvious enhancement when compared with that sensitized by the dye with carboxylic acid as an anchoring group.

Titania nanosheet-mediated construction of a two-dimensional titania/cadmium sulfide heterostructure for high hydrogen evolution activity.

Two-dimensional titania nanosheets have been utilized to fabricate 2D titania-based mesoporous silica through a controlled sol-gel method, which can further serve as a robust and versatile template to construct various 2D heterostructures via a nanocasting technology. 2D titania-based CdS has been fabricated. This heterostructure manifests an excellent H2 -production rate of 285 μmol·h(-1) under visible-light irradiation and an apparent quantum yield of 6.

A density functional theory study on oxygen reduction reaction on nitrogen-doped graphene.

Nitrogen (N)-doped carbons reportedly exhibit good electrocatalytic activity for the oxygen reduction reaction (ORR) of fuel cells. This work provides theoretical insights into the ORR mechanism of N-doped graphene by using density functional theory calculations. All possible reaction pathways were investigated, and the transition state of each elementary step was identified.