In Situ Formed Heterostructure Interface and Well-Tuned Electronic Structure Ensuring Long Cycle Stability for 4.9 V High-Voltage Li-Rich Layered Oxide Cathodes.

High-voltage lithium-rich manganese-based layered oxides (LMLOs) are considered as the most competitive cathode materials for next-generation high-energy-density lithium-ion batteries (LIBs). However, LMLOs still suffer from irreversible lattice oxygen release, uncontrollable interface side reactions, and surface structural degradation. Herein, we propose an integration strategy combining La/Al codoping and LixCoPO4 nanocoating to improve the electrochemical performance of LMLOs comprehensively. La/Al codoping regulates the electronic structure to enhance the redox activity of anions and cations and inhibit structural degradation. The LixCoPO4 nanocoating formed by in situ reaction with the surface residual lithium can not only promote Li-ion migration but also reduce interfacial side reactions. The induced Layered@Rocksalt@LixCoPO4 heterostructure suppresses lattice volume variation and structural degradation during cycling. Under the synergistic effect of the heterostructure interface and well-tuned electronic structure, the capacity retention rate of comodified LMLO materials reaches 80.06% after 500 cycles (2.0-4.65 V) and 75.1% after 340 cycles at 1C under a high cut-off voltage of 4.9 V.

Recent Advances in BTK Inhibitors for the Treatment of Inflammatory and Autoimmune Diseases.

Bruton's tyrosine kinase (BTK) plays a crucial role in B-cell receptor and Fc receptor signaling pathways. BTK is also involved in the regulation of Toll-like receptors and chemokine receptors. Given the central role of BTK in immunity, BTK inhibition represents a promising therapeutic approach for the treatment of inflammatory and autoimmune diseases. Great efforts have been made in developing BTK inhibitors for potential clinical applications in inflammatory and autoimmune diseases. This review covers the recent development of BTK inhibitors at preclinical and clinical stages in treating these diseases. Individual examples of three types of inhibitors, namely covalent irreversible inhibitors, covalent reversible inhibitors, and non-covalent reversible inhibitors, are discussed with a focus on their structure, bioactivity and selectivity. Contrary to expectations, reversible BTK inhibitors have not yielded a significant breakthrough so far. The development of covalent, irreversible BTK inhibitors has progressed more rapidly. Many candidates entered different stages of clinical trials; tolebrutinib and evobrutinib are undergoing phase 3 clinical evaluation. Rilzabrutinib, a covalent reversible BTK inhibitor, is now in phase 3 clinical trials and also offers a promising future. An analysis of the protein-inhibitor interactions based on published co-crystal structures provides useful clues for the rational design of safe and effective small-molecule BTK inhibitors.

Stretch Formability of an AZ61 Alloy Plate Prepared by Multi-Pass Friction Stir Processing.

The stretch formability behavior of an AZ61 magnesium alloy plate produced by multi-pass friction stir processing (M-FSP) was investigated, with the applied load vs. displacement curves recorded during Erichsen cupping tests at different punching speeds at room temperature. The stretch formability of M-FSP AZ61 magnesium alloy was significantly enhanced, compared with that of its cast counterpart. The highest Erichsen index of 3.7 mm was obtained at a punching speed of 0.1 mm/min. The improved stretch formability was mainly attributed to the grain refinement stemming from the M-FSP and the presence of extension twinning to accommodate deformation during Erichsen cupping testing.

Stabilization of Chemical-Vapor-Deposition-Grown WS2 Monolayers at Elevated Temperature with Hexagonal Boron Nitride Encapsulation.

Chemical vapor deposition (CVD)-grown flakes of high-quality monolayers of WS2 can be stabilized at elevated temperatures by encapsulation with several layer hexagonal boron nitride (h-BN), but to different degrees in the presence of ambient air, flowing N2, and flowing forming gas (95% N2, 5% H2). The best passivation of WS2 at elevated temperature occurs for h-BN-covered samples with flowing N2 (after heating to 873 K), as judged by optical microscopy and photoluminescence (PL) intensity after a heating/cooling cycle. Stability is worse for uncovered samples, but best with flowing forming gas. PL from trions, in addition to that from excitons, is seen for covered WS2 only for forming gas, during cooling below ∼323 K; the trion has an estimated binding energy of ∼28 meV. It might occur because of doping level changes caused by charge defect generation by H2 molecules diffusing between the h-BN and the SiO2/Si substrate. The decomposition of uncovered WS2 flakes in air suggests a dissociation and chemisorption energy barrier of O2 on the WS2 surface of ∼1.6 eV. Fitting the high-temperature PL intensities in air gives a binding energy of a free exciton of ∼229 meV.

Rate-Determining Process at Electrode/Electrolyte Interfaces for All-Solid-State Fluoride-Ion Batteries.

Developing high-performance solid electrolytes that are operable at room temperature is one of the toughest challenges related to all-solid-state fluoride-ion batteries (FIBs). In this study, tetragonal ß-Pb0.78Sn1.22F4, a promising solid electrolyte material for mild-temperature applications, was modified through annealing under various atmospheres using thin-film models. The annealed samples exhibited preferential growth and enhanced ionic conductivities. The rate-determining factor for electrode/electrolyte interface reactions in all-solid-state FIBs was also investigated by comparing ß-Pb0.78Sn1.22F4 with representative fluoride-ion- and lithium-ion-conductive materials, namely, LaF3, CeF3, and Li7La3Zr2O12. The overall rate constant of the interfacial reaction, k0, which included both mass and charge transfers, was determined using chronoamperometric measurements and Allen-Hickling simulations. Arrhenius-type correlations between k0 and temperature indicated that activation energies calculated from k0 and ionic conductivities (σion) were highly consistent. The results indicated that the mass transfer (electrolyte-side fluoride-ion conduction) should be the rate-determining process at the electrode/electrolyte interface. ß-Pb0.78Sn1.22F4, with a large σion value, had a larger k0 value than Li7La3Zr2O12. Therefore, it is hoped that the development of high-conductivity solid electrolytes can lead to all-solid-state FIBs with superior rate capabilities similar to those of all-solid-state Li-ion batteries.

A Comprehensive Overview of Structure-Activity Relationships of Small-Molecule Splicing Modulators Targeting SF3B1 as Anticancer Agents.

The pre-mRNA splicing factor SF3B1 shows recurrent mutations among hematologic malignancies and some solid tumors. In 2007, the identification of two cytotoxic natural products, which showed splicing inhibition by binding to SF3b, prompted the development of small-molecule splicing modulators of SF3B1 as therapeutics for cancer. Recent studies suggested that spliceosome-mutant cells are preferentially sensitive to pharmacologic splicing modulation; therefore, exploring the clinical utility of splicing modulator therapies in patients with spliceosome-mutant hematologic malignancies who have failed current therapies is greatly needed, as these patients have few treatment options. H3B-8800 had unique pharmacological activity and exhibited favorable data in phase I clinical trials to treat patients with advanced myeloid malignancies, indicating that further clinical trials are promising. The most established small-molecule modulators of SF3B1 can be categorized into three classes: the bicycles, the monopyranes, and the 12-membered macrolides. This review provides a comprehensive overview of the structure-activity relationships of small-molecule SF3B1 modulators, with a detailed analysis of interactions between modulators and protein binding pocket. The future strategy for splicing modulators development is also discussed.

Microstructure and Properties of Nano-Hydroxyapatite Reinforced WE43 Alloy Fabricated by Friction Stir Processing.

This research mainly focuses on the successful fabrication of nano-hydroxyapatite (nHA) reinforced WE43 alloy by two-pass friction stir processing (FSP). Microstructure evolution, mechanical properties, and in vitro corrosion behavior of FSPed WE43/nHA composite and FSPed WE43 alloy were studied. The results show that nHA particles are effectively dispersed in the processing zone, and the well-dispersed nHA particles can enhance the grain refine effect of FSP. The average grain sizes of FSPed WE43 alloy and WE43/nHA composite are 5.7 and 3.3 µm, respectively. However, a slight deterioration in tensile strength and yield strength is observed on the WE43/nHA composite, compared to the FSPed WE43 alloy, which is attributed to the locally agglomerated nHA particles and the poor quality of interfacial bonding between nHA particles and matrix. The electrochemical test and in vitro immersion test results reveal that the corrosion resistance of the WE43 alloy is greatly improved after FSP. With the addition of nHA particles, the corrosion resistance of the WE43/nHA composite shows an even greater improvement.

A 7-Hydroxybenzoxazinone-Containing Fluorescence Turn-On Probe for Biothiols and Its Bioimaging Applications.

In this work, a novel 7-hydroxybenzoxazinone-based fluorescent probe (PBD) for the selective sensing of biothiols is reported. Upon treatment with biothiols, PBD shows a strong fluorescence enhancement (up to 70-fold) and a large Stokes shift (155 nm). Meanwhile, this probe exhibits high resistance to interference from other amino acids and competing species. PBD features good linearity ranges with a low detection limit of 14.5 nM for glutathione (GSH), 17.5 nM for cysteine (Cys), and 80.0 nM for homocysteine (Hcy), respectively. Finally, the potential utility of this probe for biothiol sensing in living HeLa cells is demonstrated.

Multi-purpose barbituric acid derivatives with aggregation induced emission.

Three D-π-A barbituric acid derivatives with simple structure and intramolecular charge transfer (ICT) mechanisms were synthesized. Molecular dynamics simulations have successfully explained that CB-1 exhibits the best aggregate induced emission (AIE) activity due to the electron-deficient barbituric acid and the electron-rich carbazole exhibit a conformation which similar to π-π stacking, resulting in a strong electrostatic attraction between the molecules, meanwhile the N-atom substituent of the carbazole is n-propane plays a hydrophobic role. At the same time, barbituric acid derivatives also have mechanochromic fluorescent properties. In addition, CB-1 and CB-3 exhibited outstanding fluorescence stability than CB-2 in aggregation state which can be used to detect nitroaromatic explosives in aqueous media. The Stern-Volmer quenching constant (Ksv) of CB-1 and CB-3 is 6.6 × 104 and 1 × 105 M-1, respectively.

Electrochemical Property-Structure Correlation for Ni-Based Layered Na-Ion Cathodes.

A class of Ni-based layered Na xNi0.5Mn0.3Co0.2O2 oxide composites is prepared via a solid-state process. Mixed P-, O-, and P-/O-type phases can be obtained by tuning the Na content and annealing temperature, as demonstrated by structural and chemical characterization. Among these materials, the triphase P2/P'3/O'3-type composite exhibits the best overall electrochemical performance. Specifically, this triphase composite delivers a high specific capacity of 126 mA h g-1 in the potential range of 1.5-4.2 V, high rate capability (∼72% of its initial capacity at a rate of 5 C), and good capacity retention after 100 cycles at 0.5 C. The structural transition mechanism for each phase upon electrochemical cycling is investigated, providing insights into the correlation between electrochemical properties and the crystal structure of Ni-rich layered Na xNi0.5Mn0.3Co0.2O2 oxide composites.

Deformylation reaction-based probe for in vivo imaging of HOCl.

The detection of hypochlorous acid (HOCl) in vivo is vitally important because the local concentration of HOCl is highly correlated with some diseases such as atherosclerosis and rheumatoid arthritis. However, in vivo detection of HOCl remains a challenge due to the lack of a suitable probe. We report here a near-infrared (NIR) emissive "turn-on" probe (FDOCl-1) based on a methylene blue derivative, which can quickly detect HOCl via a newly found deformylation mechanism. FDOCl-1 displays remarkable selectivity and sensitivity towards HOCl. The dramatic changes in colour and NIR emission were used to detect HOCl in vitro and in vivo in a mouse arthritis model.

Understanding the Improved Kinetics and Cyclability of a Li2MnSiO4 Cathode with Calcium Substitution.

Limited practical capacity and poor cyclability caused by sluggish kinetics and structural instability are essential aspects that constrain the potential application of Li2MnSiO4 cathode materials. Herein, Li2Mn1- xCa xSiO4/C nanoplates are synthesized using a diethylene-glycol-assisted solvothermal method, targeting to circumvent its drawbacks. Compared with the pristine material, the Ca-substituted material exhibits enhanced electrochemical kinetics and improved cycle life performance. In combination with experimental studies and first-principles calculations, we reveal that Ca incorporation enhances electronic conductivity and the Li-ion diffusion coefficient of the Ca-substituted material, and it improves the structural stability by reducing the lattice distortion. It also shrinks the crystal size and alleviates structure collapse to enhance cycling performance. It is demonstrated that Ca can alleviate the two detrimental factors and shed lights on the further searching for suitable dopants.

Microstructure Evolution during Dissimilar Friction Stir Welding of AA7003-T4 and AA6060-T4.

In this work, the dissimilar joint of AA7003-T4 and 6060-T4 alloy has been produced by friction stir welding (FSW). The microstructure was examined by optical microscope (OM), electron back scattered diffraction (EBSD), transmission electron microscopy (TEM), and the mechanical properties of the joint were investigated. It is demonstrated that sound dissimilar joint can be produced through FSW. In the nugget; precipitations dissolve into the matrix and η' reprecipitate subsequently; and the elongated aluminum grains are replaced by fine and equiaxed grains due to dynamic recrystallization (DRX). In the heat affected zone (HAZ), coarse ß' and η precipitates are formed and the aluminum grains are coarser as compared to the base materials. In the thermo-mechanical affected zone (TMAZ), equiaxed and elongated grains coexist due to incomplete DRX. The ultimate tensile strength of the dissimilar joint is 159.2 MPa and its elongation is 10.4%. The weak area exists in the HAZ of 6060 alloy, which is placed in the retreating side during FSW. The correlations between the microstucture and mechanical properties of the dissimilar joint are discussed.

Crystallographic Habit Tuning of Li2MnSiO4 Nanoplates for High-Capacity Lithium Battery Cathodes.

Li2MnSiO4 has attracted significant attention as a cathode material for lithium ion batteries because of its high theoretical capacity (330 mA h g-1 with two Li+ ions per formula unit), low cost, and environmentally friendly nature. However, its intrinsically poor Li diffusion, low electronic conductivity, and structural instability preclude its use in practical applications. Herein, elongated hexagonal prism-shaped Li2MnSiO4 nanoplates with preferentially exposed {001} and {210} facets have been successfully synthesized via a solvothermal method. Density functional theory calculations and experimental characterization reveal that the formation mechanism involves the decomposition of solid precursors to nanosheets, self-assembly into nanoplates, and Ostwald ripening. Hydroxyl-containing solvents such as ethylene glycol and diethylene glycol play a crucial role as capping agents in tuning the preferential growth. Li2MnSiO4@C nanoplates demonstrate a near theoretical discharge capacity of 326.7 mA h g-1 at 0.05 C (1 C = 160 mA h g-1), superior rate capability, and good cycling stability. The enhanced electrochemical performance is ascribed to the electrochemically active {001} and {210} exposed facets, which provide short and fast Li+ diffusion pathways along the [001] and [100] axes, a conformal carbon nanocoating, and a nanoscaled platelike structure, which offers a large electrode/electrolyte contact interface for Li+ extraction/insertion processes.

Constitutive Equation and Hot Compression Deformation Behavior of Homogenized Al-7.5Zn-1.5Mg-0.2Cu-0.2Zr Alloy.

The deformation behavior of homogenized Al-7.5Zn-1.5Mg-0.2Cu-0.2Zr alloy has been studied by a set of isothermal hot compression tests, which were carried out over the temperature ranging from 350 °C to 450 °C and the strain rate ranging from 0.001 s-1 to 10 s-1 on Gleeble-3500 thermal simulation machine. The associated microstructure was studied using electron back scattered diffraction (EBSD) and transmission electron microscopy (TEM). The results showed that the flow stress is sensitive to strain rate and deformation temperature. The shape of true stress-strain curves obtained at a low strain rate (≤0.1 s-1) conditions shows the characteristic of dynamic recrystallization (DRX). Two Arrhenius-typed constitutive equation without and with strain compensation were established based on the true stress-strain curves. Constitutive equation with strain compensation has more precise predictability. The main softening mechanism of the studied alloy is dynamic recovery (DRV) accompanied with DRX, particularly at deformation conditions, with low Zener-Holloman parameters.

Improving the Mechanical Properties of Cu-15Ni-8Sn Alloys by Addition of Titanium.

The effect of Ti addition on the microstructure and mechanical properties of Cu-15Ni-8Sn alloys was investigated. Optical microscopy (OM), scanning electronic microscopy (SEM), and transmission electron microscopy (TEM) were used to determine grain size and distribution of the second phases in the alloys. The results indicate that the tensile properties of Cu-15Ni-8Sn alloys are improved significantly with Ti addition. Tensile elongation increased from 2.7% for the alloy without Ti to 17.9% for the alloy with 0.3% Ti, while tensile strength was maintained and even increased from 935 MPa to 1024 MPa. The improvement of the mechanical properties of Cu-15Ni-8Sn alloys by the addition of Ti is attributed to the grain refinement and suppression of discontinuous precipitation during heat treatment.

Ductility Improvement of an AZ61 Magnesium Alloy through Two-Pass Submerged Friction Stir Processing.

Friction stir processing (FSP) has been considered as a novel technique to refine the grain size and homogenize the microstructure of metallic materials. In this study, two-pass FSP was conducted under water to enhance the cooling rate during processing, and an AZ61 magnesium alloy with fine-grained and homogeneous microstructure was prepared through this method. Compared to the as-cast material, one-pass FSP resulted in grain refinement and the ß-Mg17Al12 phase was broken into small particles. Using a smaller stirring tool and an overlapping ratio of 100%, a finer and more uniform microstructure with an average grain size of 4.6 µm was obtained through two-pass FSP. The two-pass FSP resulted in a significant improvement in elongation of 37.2% ± 4.3%, but a slight decrease in strength compared with one-pass FSP alloy. Besides the microstructure refinement, the texture evolution in the stir zone is also considered responsible for the ductility improvement.

Forming Nanoparticle Monolayers at Liquid-Air Interfaces by Using Miscible Liquids.

One standard way of forming monolayers (MLs) of nanoparticles (NPs) is to drop-cast a NP dispersion made using one solvent onto a second, immiscible solvent; after this upper solvent evaporates, the NP ML can be transferred to a solid substrate by liftoff. We show that this previously universal use of only immiscible solvent pairs can be relaxed and close-packed, hexagonally ordered NP monolayers can self-assemble at liquid-air interfaces when some miscible solvent pairs are used instead. We demonstrate this by drop-casting an iron oxide NP dispersion in toluene on a dimethyl sulfoxide (DMSO) liquid substrate. The NPs are energetically stable at the DMSO surface and remain there even with solvent mixing. Excess NPs coagulate and precipitate in the DMSO, and this limits NPs at the surface to approximately 1 ML. The ML domains at the surface nucleate independently, which is in contrast to ML growth at the receding edge of the drying drop, as is common in immiscible solvent pair systems and seen here for the toluene/diethylene glycol immiscible solvent pair system. This new use of miscible solvent pairs can enable the formation of MLs for a wider range of NPs.

In Vitro Corrosion Study of Friction Stir Processed WE43 Magnesium Alloy in a Simulated Body Fluid.

Corrosion behavior of friction stir processing (FSP) WE43 alloy in a simulated body fluid (SBF) was investigated. Micro-galvanic corrosion was the dominated corrosion behavior, and the corrosion resistance of FSP WE43 alloy was improved compared to the cast counterpart. Furthermore, due to the fine-grained and homogeneous microstructure, uniform corrosion morphology was observed on FSP WE43 alloy. According to the tensile properties of specimens with different immersion time intervals, FSP WE43 alloy shows better performance to maintain the mechanical integrity in SBF as compared to the as-cast alloy.

mTOR signaling in T cell immunity and autoimmunity.

The mammalian target of rapamycin (mTOR), a phosphoinositide-3-kinase-related protein kinase, acts as a rheostat capable of integrating a variety of environmental cues in the form of nutrients, energy, and growth factors to modulate organismal processes and homeostasis. Recently, there is a growing appreciation of mTOR in adaptive immunity for its crucial roles in keeping a proper balance between T cell quiescence and activation. Under steady-state circumstances, mTOR is subtly inhibited by multiple mechanisms to maintain normal T cell homeostasis. Antigen recognition by naïve T cells leads to mTOR activation, which subsequently promotes the differentiation of these cells into distinct effector T cell subsets. This review focuses primarily on the recent literature with respect to the regulatory effects and mechanisms of mTOR signaling in dictating T cell fate, and discusses the therapeutic implications of mTOR modulation in T-cell-mediated autoimmunity.