Enhancement Mechanism of Pt/Pd-Based Catalysts for Oxygen Reduction Reaction.

The oxygen reduction reaction (ORR) is one of the key catalytic reactions for hydrogen fuel cells, biofuel cells and metal-air cells. However, due to the complex four-electron catalytic process, the kinetics of the oxygen reduction reaction are sluggish. Platinum group metal (PGM) catalysts represented by platinum and palladium are considered to be the most active ORR catalysts. However, the price and reserves of Pt/Pd are major concerns and issues for their commercial application. Improving the catalytic performance of PGM catalysts can effectively reduce their loading and material cost in a catalytic system, and they will be more economical and practical. In this review, we introduce the kinetics and mechanisms of Pt/Pd-based catalysts for the ORR, summarize the main factors affecting the catalytic performance of PGMs, and discuss the recent progress of Pt/Pd-based catalysts. In addition, the remaining challenges and future prospects in the design and improvement of Pt/Pd-based catalysts of the ORR are also discussed.

Anticancer Activity of Diosgenin and Its Molecular Mechanism.

Diosgenin, a steroidal sapogenin, obtained from Trigonella foenum-graecum, Dioscorea, and Rhizoma polgonati, has shown high potential and interest in the treatment of various cancers such as oral squamous cell carcinoma, laryngeal cancer, esophageal cancer, liver cancer, gastric cancer, lung cancer, cervical cancer, prostate cancer, glioma, and leukemia. This article aims to provide an overview of the in vivo, in vitro, and clinical studies reporting the diosgenin's anticancer effects. Preclinical studies have shown promising effects of diosgenin on inhibiting tumor cell proliferation and growth, promoting apoptosis, inducing differentiation and autophagy, inhibiting tumor cell metastasis and invasion, blocking cell cycle, regulating immunity and improving gut microbiome. Clinical investigations have revealed clinical dosage and safety property of diosgenin. Furthermore, in order to improve the biological activity and bioavailability of diosgenin, this review focuses on the development of diosgenin nano drug carriers, combined drugs and the diosgenin derivatives. However, further designed trials are needed to unravel the diosgenin's deficiencies in clinical application.

Recent Progress of Energy-Storage-Device-Integrated Sensing Systems.

With the rapid prosperity of the Internet of things, intelligent human-machine interaction and health monitoring are becoming the focus of attention. Wireless sensing systems, especially self-powered sensing systems that can work continuously and sustainably for a long time without an external power supply have been successfully explored and developed. Yet, the system integrated by energy-harvester needs to be exposed to a specific energy source to drive the work, which provides limited application scenarios, low stability, and poor continuity. Integrating the energy storage unit and sensing unit into a single system may provide efficient ways to solve these above problems, promoting potential applications in portable and wearable electronics. In this review, we focus on recent advances in energy-storage-device-integrated sensing systems for wearable electronics, including tactile sensors, temperature sensors, chemical and biological sensors, and multifunctional sensing systems, because of their universal utilization in the next generation of smart personal electronics. Finally, the future perspectives of energy-storage-device-integrated sensing systems are discussed.

Fast constructing polarity-switchable zinc-bromine microbatteries with high areal energy density.

Microbatteries (MBs) are promising candidates to provide power for various miniaturized electronic devices, yet they generally suffer from complicated fabrication procedures and low areal energy density. Besides, all cathodes of current MBs are solid state, and the trade-off between areal capacity and reaction kinetics restricts their wide applications. Here, we propose a dual-plating strategy to facilely prepare zinc-bromine MBs (Zn-Br2 MBs) with a liquid cathode to achieve both high areal energy density and fast kinetics simultaneously. The Zn-Br2 MBs deliver a record high areal energy density of 3.6 mWh cm-2, almost an order of magnitude higher than available planar MBs. Meanwhile, they show a polarity-switchable feature to tolerate confusion of cathode and anode. This strategy could also be extended to other battery systems, such as Zn-I2 and Zn-MnO2 MBs. This work not only proposes an effective construction method for MBs but also enriches categories of microscale energy storage devices.

Fixture-free omnidirectional prestretching fabrication and integration of crumpled in-plane micro-supercapacitors.

Multidimensional folded structures with elasticity could provide spatial charge storage capability and shape adaptability for micro-supercapacitors (MSCs). Here, highly crumpled in-plane MSCs with superior conformality are fabricated in situ and integrated by a fixture-free omnidirectional elastic contraction strategy. Using carbon nanotube microelectrodes, a single crumpled MSC holds an ultrahigh volumetric capacitance of 9.3 F cm-3, and its total areal capacitance is 45 times greater than the initial state. Experimental and theoretical simulation methods indicate that strain-induced improvements of adsorption energy and conductance for crumpled microelectrodes are responsible for the prominent enhancement of electrochemical performance. With outstanding morphological randomicity, the integrated devices can serve as smart coatings in moving robots, withstanding extreme mechanical deformations. Notably, integration on a spherical surface is possible by using a spherical mask, in which a small area of the microdevice array (3.9 cm2) can produce a high output voltage of 100 V.

Enabling fast-charging selenium-based aqueous batteries via conversion reaction with copper ions.

Selenium (Se) is an appealing alternative cathode material for secondary battery systems that recently attracted research interests in the electrochemical energy storage field due to its high theoretical specific capacity and good electronic conductivity. However, despite the relevant capacity contents reported in the literature, Se-based cathodes generally show poor rate capability behavior. To circumvent this issue, we propose a series of selenium@carbon (Se@C) composite positive electrode active materials capable of delivering a four-electron redox reaction when placed in contact with an aqueous copper-ion electrolyte solution (i.e., 0.5 M CuSO4) and copper or zinc foils as negative electrodes. The lab-scale Zn | |Se@C cell delivers a discharge voltage of about 1.2 V at 0.5 A g-1 and an initial discharge capacity of 1263 mAh gSe-1. Interestingly, when a specific charging current of 6 A g-1 is applied, the Zn | |Se@C cell delivers a stable discharge capacity of around 900 mAh gSe-1 independently from the discharge rate. Via physicochemical characterizations and first-principle calculations, we demonstrate that battery performance is strongly associated with the reversible structural changes occurring at the Se-based cathode.

A Cascade Battery: Coupling Two Sequential Electrochemical Reactions in a Single Battery.

Currently, rechargeable electrochemical batteries generally operate on one reversible electrochemical reaction during discharging and charging cycles. Here, a cascade battery that couples two sequential electrochemical reactions in a single battery is proposed. Such a concept is demonstrated in an aqueous Zn-S hybrid battery, where solid sulfur serves as the cathode in the first discharge step and the generated Cu2 S catalyzes Cu2+ reduce to Cu/Cu2 O to provide the second discharge step. The cascade battery shows many merits compared to traditional batteries. First, it integrates two batteries internally, eliminating the use of additional inactive connecting materials required for external integration. Second, it can more fully utilize the inactive reaction chamber of the battery than traditional batteries. Third, cascade battery can bypass the challenges of thick solid electrode to access high areal capacity. An ultrahigh areal capacity of 48 mAh cm-2 is achieved even at a low solid cathode loading (9.6 mg cm-2 ). The cascade battery design breaks the stereotype of conventional battery configuration, providing a paradigm for constructing two-in-one batteries.

All-pH-Tolerant In-Plane Heterostructures for Efficient Hydrogen Evolution Reaction.

Generally, electrocatalytic hydrogen evolution reaction (HER) by water splitting is a pH-dependent reaction, which limits the widespread harvesting of hydrogen energy. Herein, we present a simple way for chemical bonding of MoS2 (002) planes and α-MoC {111} planes to form in-plane heterostructures capable of efficient pH-universal HER. Due to the lattice strain from mismatched lattice parameters between α-MoC and MoS2, this catalyst changes the electronic configuration of the MoS2 and thus acquires the favorable proton adsorption and desorption activity, suggested by the platinum (Pt)-like free Gibbs energy. Consequently, only a low 78 mV overpotential is needed to achieve the current density of 10 mA cm-2 in acidic solution along with a favorable Tafel kinetic process with a Tafel slope of 38.7 mV dec-1. Owing to the synergistic interaction between MoS2 (002) planes and α-MoC {111} planes with strong water dissociation activities, this catalyst also exhibits high HER performances beyond that of Pt in neutral and alkaline. This work proves the advances of in-plane heterostructures and illustrates the production of low-cost but highly efficient pH-universal HER catalytic materials, promising for future sustainable hydrogen energy.

Retarding Ostwald Ripening to Directly Cast 3D Porous Graphene Oxide Bulks at Open Ambient Conditions.

Graphene aerogels (GAs) with attractive properties have shown tremendous potentials in energy- and environment-related applications. Unfortunately, current assembly methods for GAs such as sol-gel and freeze-casting processes must be conducted in enclosed spaces with unconventional conditions, thus being literally inoperative for in situ and continuous productions. Herein, a direct slurry-casting method at open ambient conditions is established to arbitrarily prepare three-dimensional (3D) porous graphene oxide (GO) bulks without macroscopic dimension limits on a wide range of solid surfaces by retarding Ostwald ripening of 3D liquid GO foams when being dried in air. A subsequent fast thermal reduction (FTR) of GO foams leads to the formation of graphene aerogels (denoted as FTR-GAs) with hierarchical closed-cellular graphene structures. The FTR-GAs show outstanding high-temperature thermal insulation (70% decrease for 400 °C), as well as superelasticity (>1000 compression-recovery cycles at 50% strain), ultralow density (10-28 mg cm-3), large specific surface area (BET, 206.8 m2 g-1), and high conductivity (ca. 100 S m-1). This work provides a viable method to achieve in situ preparations of high-performance GAs as multifunctional structural materials in aircrafts, high-speed trains, or even buildings for the targets of energy efficiency, comfort, and safety.

Regulation of 2D Graphene Materials for Electrocatalysis.

Benefiting from unique excellent physical and chemical characteristics, graphene has attracted widespread attention in the application of electrocatalysis. As a promising candidate, graphene is usually regulated with surface defects, heteroatoms, metal atoms and other active materials through covalent or non-covalent bonds to substitute for noble metal catalysts, which has not been targeted in a report yet. In this review, we summarize the recent advances of approaches for engineering graphene-based electrocatalysts and emphasize the corresponding electrocatalytic active sites in various electrocatalysis circumstances, such as electrocatalytic hydrogen evolution reaction (HER), oxygen evolution reaction (OER), oxygen reduction reaction (ORR), etc. The opportunities and challenges in the future development of graphene-based catalysts are also discussed.

Hybrid Energy Storage Device: Combination of Zinc-Ion Supercapacitor and Zinc-Air Battery in Mild Electrolyte.

In this work, a new type of hybrid energy storage device is constructed by combining the zinc-ion supercapacitor and zinc-air battery in mild electrolyte. Reduced graphene oxide with rich defects, large surface area, and abundant oxygen-containing functional groups is used as active material, which exhibits two kinds of charge storage mechanisms of capacitor and battery simultaneously. Apart from the physical adsorption/desorption of anions on the surface of graphene, the zinc ions in electrolyte will be electrochemically adsorbed/desorbed onto the oxygen-containing groups of graphene during the charge/discharge process, contributing extra capacitance to the device. Moreover, the defects in graphene will further improve the electrochemical performance of the energy storage device via catalyzing the oxygen reduction reaction with exposure to air. Consequently, the synergistic effect leads to a record high capacitance of 370.8 F g-1 at a current density of 0.1 A g-1, which is higher than that of zinc-ion supercapacitors reported previously. Furthermore, the hybrid device exhibits a superior cycling stability with 94.5% capacitance retention even after 10000 charge/discharge cycles at a high current density of 5 A g-1. Interestingly, the developed hybrid device can be self-charging automatically after the power is exhausted in the ambient atmosphere. Other electrode materials, such as carbon nanotube paper, are also used to build a hybrid device to verify the feasibility of this strategy. This facile, green, and convenient strategy provides new insight for developing a high performance storage device, showing great application prospect in other hybrid energy storage devices in mild electrolyte.

A coiled-coil masking domain for selective activation of therapeutic antibodies.

The use of monoclonal antibodies in cancer therapy is limited by their cross-reactivity to healthy tissue. Tumor targeting has been improved by generating masked antibodies that are selectively activated in the tumor microenvironment, but each such antibody necessitates a custom design. Here, we present a generalizable approach for masking the binding domains of antibodies with a heterodimeric coiled-coil domain that sterically occludes the complementarity-determining regions. On exposure to tumor-associated proteases, such as matrix metalloproteinases 2 and 9, the coiled-coil peptides are cleaved and antigen binding is restored. We test multiple coiled-coil formats and show that the optimized masking domain is broadly applicable to antibodies of interest. Our approach prevents anti-CD3-associated cytokine release in mice and substantially improves circulation half-life by protecting the antibody from an antigen sink. When applied to antibody-drug conjugates, our masked antibodies are preferentially unmasked at the tumor site and have increased anti-tumor efficacy compared with unmasked antibodies in mouse models of cancer.

Tumor-Associated Macrophages Can Contribute to Antitumor Activity through FcγR-Mediated Processing of Antibody-Drug Conjugates.

The primary mechanism of antibody-drug conjugates (ADC) is targeted delivery of a cytotoxic payload to tumor cells via cancer-associated membrane receptors. However, the tumor microenvironment likely plays a role in ADC penetration, distribution, and processing and thus impacts the overall antitumor activity. Here, we report on the potential contribution of Fc-FcγR interactions between ADCs and tumor-associated macrophages (TAM) to the preclinical antitumor activities of ADCs. In the CD30+ L-428 Hodgkin lymphoma model, anti-CD30-vcMMAE and a non-binding control (hIgG-vcMMAE) demonstrated similar antitumor activity as well as similar payload release in the tumors. IHC analysis revealed L-428 tumors contained highly abundant TAMs, which were confirmed to bind ADCs by IHC and flow cytometry. The infiltration of TAMs was further found to correlate with the antitumor activity of the non-binding hIgG-vcMMAE in five additional xenograft models. hIgG1V1-vcMMAE, bearing a mutation in the Fc region which ablates Fc gamma receptor (FcγR) binding, lost antitumor activity in three TAM-high xenograft models, suggesting Fc-FcγR interactions modulate the TAM-ADC interaction. Our results suggest that TAMs can contribute to ADC processing through FcγR interaction in preclinical tumor models and may represent an important additional mechanism for drug release from ADCs. Correlative studies in clinical trials will further shed light on whether TAMs play a role in patients' response to ADC therapies. Mol Cancer Ther; 16(7); 1347-54. ©2017 AACR.

Orthogonal Cysteine Protection Enables Homogeneous Multi-Drug Antibody-Drug Conjugates.

A strategy for the preparation of homogeneous antibody-drug conjugates (ADCs) containing multiple payloads has been developed. This approach utilizes sequential unmasking of cysteine residues with orthogonal protection to enable site-specific conjugation of each drug. In addition, because the approach utilizes conjugation to native antibody cysteine residues, it is widely applicable and enables high drug loading for improved ADC potency. To highlight the benefits of ADC dual drug delivery, this strategy was applied to the preparation of ADCs containing two classes of auristatin drug-linkers that have differing physiochemical properties and exert complementary anti-cancer activities. Dual-auristatin ADCs imparted activity in cell line and xenograft models that are refractory to ADCs comprised of the individual auristatin components. This work presents a facile method for construction of potent dual-drug ADCs and demonstrates how delivery of multiple cytotoxic warheads can lead to improved ADC activities. Lastly, we anticipate that the conditions utilized herein for orthogonal cysteine unmasking are not restricted to ADCs and can be broadly utilized for site-specific protein modification.

One-Dimensional CoO@C Core­Shell Nanostructures for Improved Lithium Storage Properties.

Exploring conversion-type anode materials with large and stable lithium storage properties as well as good rate performance still remains a great challenge. This work presents one-dimensional core­shell CoO@C nanostructures as high-performance anode materials for lithium ion batteries. TEM measurements show that interior voids and carbon shell can be observed in the core­shell nanostructures. Electrochemical impedance spectroscopy reveals that the coated carbon layer can remarkably reduce the charge transfer resistance of the electrochemical conversion reaction. Endowed with the combined advantages mentioned above, the present sample exhibits good electrochemical properties when tested as anode materials, such as high and stable lithium storage properties (877.2 mAh g⁻¹ after 100 cycles at 100 mA g⁻¹ and 661.5 mAh g⁻¹ after 500 cycles at 1 A g⁻¹), superior rate performance, and long cycling life (over 500 cycles at high current density of 1 A g⁻¹). These good performances make it a promising candidate for high-performance anode materials.

Intracellular Released Payload Influences Potency and Bystander-Killing Effects of Antibody-Drug Conjugates in Preclinical Models.

Antibody-drug conjugates (ADC) comprise targeting antibodies armed with potent small-molecule payloads. ADCs demonstrate specific cell killing in clinic, but the basis of their antitumor activity is not fully understood. In this study, we investigated the degree to which payload release predicts ADC activity in vitro and in vivo ADCs were generated to target different receptors on the anaplastic large cell lymphoma line L-82, but delivered the same cytotoxic payload (monomethyl auristatin E, MMAE), and we found that the intracellular concentration of released MMAE correlated with in vitro ADC-mediated cytotoxicity independent of target expression or drug:antibody ratios. Intratumoral MMAE concentrations consistently correlated with the extent of tumor growth inhibition in tumor xenograft models. In addition, we developed a robust admixed tumor model consisting of CD30(+) and CD30(-) cancer cells to study how heterogeneity of target antigen expression, a phenomenon often observed in cancer specimens, affects the treatment response. CD30-targeting ADC delivering membrane permeable MMAE or pyrrolobenzodiazepine dimers demonstrated potent bystander killing of neighboring CD30(-) cells. In contrast, a less membrane permeable payload, MMAF, failed to mediate bystander killing in vivo, suggesting local diffusion and distribution of released payloads represents a potential mechanism of ADC-mediated bystander killing. Collectively, our findings establish that the biophysical properties and amount of released payloads are chief factors determining the overall ADC potency and bystander killing. Cancer Res; 76(9); 2710-9. ©2016 AACR.

Metabolic engineering of monoclonal antibody carbohydrates for antibody-drug conjugation.

The role that carbohydrates play in antibody function and pharmacokinetics has made them important targets for modification. The terminal fucose of the N-linked glycan structure, which has been shown to be involved in modulation of antibody-directed cellular cytotoxicity, is a particularly interesting location for potential modification through incorporation of alternative sugar structures. A library of fucose analogues was evaluated for their ability to incorporate into antibody carbohydrates in place of the native fucose. A number of efficiently incorporated molecules were identified, demonstrating the ability of fucosyltransferase VIII to utilize a variety of non-natural sugars as substrates. Among these structures was a thiolated analogue, 6-thiofucose, which was incorporated into the antibody carbohydrate with good efficiency. This unnatural thio-sugar could then be used for conjugation using maleimide chemistry to produce antibody-drug conjugates with pronounced cytotoxic activities and improved homogeneity compared to drug attachment through hinge disulfides.

Development of orally active inhibitors of protein and cellular fucosylation.

The key role played by fucose in glycoprotein and cellular function has prompted significant research toward identifying recombinant and biochemical strategies for blocking its incorporation into proteins and membrane structures. Technologies surrounding engineered cell lines have evolved for the inhibition of in vitro fucosylation, but they are not applicable for in vivo use and drug development. To address this, we screened a panel of fucose analogues and identified 2-fluorofucose and 5-alkynylfucose derivatives that depleted cells of GDP-fucose, the substrate used by fucosyltransferases to incorporate fucose into protein and cellular glycans. The inhibitors were used in vitro to generate fucose-deficient antibodies with enhanced antibody-dependent cellular cytotoxicity activities. When given orally to mice, 2-fluorofucose inhibited fucosylation of endogenously produced antibodies, tumor xenograft membranes, and neutrophil adhesion glycans. We show that oral 2-fluorofucose treatment afforded complete protection from tumor engraftment in a syngeneic tumor vaccine model, inhibited neutrophil extravasation, and delayed the outgrowth of tumor xenografts in immune-deficient mice. The results point to several potential therapeutic applications for molecules that selectively block the endogenous generation of fucosylated glycan structures.

Intracellular activation of SGN-35, a potent anti-CD30 antibody-drug conjugate.

PURPOSE: SGN-35 is an antibody-drug conjugate (ADC) containing the potent antimitotic drug, monomethylauristatin E (MMAE), linked to the anti-CD30 monoclonal antibody, cAC10. As previously shown, SGN-35 treatment regresses and cures established Hodgkin lymphoma and anaplastic large cell lymphoma xenografts. Recently, the ADC has been shown to possess pronounced activity in clinical trials. Here, we investigate the molecular basis for the activities of SGN-35 by determining the extent of targeted intracellular drug release and retention, and bystander activities. EXPERIMENTAL DESIGN: SGN-35 was prepared with (14)C-labeled MMAE. Intracellular ADC activation on CD30(+) and negative cell lines was determined using a combination of radiometric and liquid chromatograhpy/mass spectrometry-based assays. The bystander activity of SGN-35 was determined using mixed tumor cell cultures consisting of CD30(+) and CD30(-) lines. RESULTS: SGN-35 treatment of CD30(+) cells leads to efficient intracellular release of chemically unmodified MMAE, with intracellular concentrations of MMAE in the range of 500 nmol/L. This was due to specific ADC binding, uptake, MMAE retention, and receptor recycling or resynthesis. MMAE accounts for the total detectable released drug from CD30(+) cells, and has a half-life of retention of 15 to 20 h. Cytotoxicity studies with mixtures of CD30(+) and CD30(-) cell lines indicated that diffusible released MMAE from CD30(+) cells was able to kill cocultivated CD30(-) cells. CONCLUSIONS: MMAE is efficiently released from SGN-35 within CD30(+) cancer cells and, due to its membrane permeability, is able to exert cytotoxic activity on bystander cells. This provides mechanistic insight into the pronounced preclinical and clinical antitumor activities observed with SGN-35.

The pharmacologic basis for antibody-auristatin conjugate activity.

Antibody-drug conjugates (ADCs) made with auristatin antimitotic agents have shown significant preclinical and clinical oncology activity. SGN-75 is composed of the anti-CD70 antibody h1F6 conjugated to monomethylauristatin F through a noncleavable maleimidocaproyl linkage. To understand the pharmacologic basis of the activity of this ADC, its pharmacokinetics and biodistribution were evaluated in a mouse xenograft model with use of a dual-radiolabeled ADC. The concentrations of antibody, total auristatin (conjugated plus unconjugated), and unconjugated auristatin were measured simultaneously in serum, tumor, and 16 normal tissues. Serum pharmacokinetic parameters for antibody and total auristatin were similar with very little unconjugated auristatin observed, demonstrating a high degree of stability. The kinetic values in normal tissues generally tracked with serum: the first time point (1 h) had the highest antibody and total auristatin concentrations with low unconjugated auristatin concentrations, with the exception of organs expected to be involved in hepatobiliary clearance of the ADC, where total and unconjugated auristatin concentrations peaked at 4 h and then rapidly decreased. In tumors, antibody concentrations were maximal at 1 day, with total auristatin increasing until 2 days. Intratumoral unconjugated auristatin was a substantial fraction of the total auristatin and reached concentrations much higher than in normal tissues. The exposure of the tumor to total and unconjugated auristatin was tens to hundreds times higher than normal tissue exposure. The data establish the pharmacologic basis of activity of the ADC through specific tumor targeting, intratumoral auristatin retention, and ADC stability in the systemic circulation.