Advanced Insights on MXenes: Categories, Properties, Synthesis, and Applications in Alkali Metal Ion Batteries.

The development and optimization of promising anode material for next-generation alkali metal ion batteries are significant for clean energy evolution. 2D MXenes have drawn extensive attention in electrochemical energy storage applications, due to their multiple advantages including excellent conductivity, robust mechanical properties, hydrophilicity of its functional terminations, and outstanding electrochemical storage capability. In this review, the categories, properties, and synthesis methods of MXenes are first outlined. Furthermore, the latest research and progress of MXenes and their composites in alkali metal ion storage are also summarized comprehensively. A special emphasis is placed on MXenes and their hybrids, ranging from material design and fabrication to fundamental understanding of the alkali ion storage mechanisms to battery performance optimization strategies. Lastly, the challenges and personal perspectives of the future research of MXenes and their composites for energy storage are presented.

TGFß and Hippo Signaling Pathways Coordinate to Promote Acinar to Ductal Metaplasia in Human Pancreas.

BACKGROUND & AIMS: Acinar-to-ductal metaplasia (ADM) serves as a precursor event in the development of pancreatic ductal adenocarcinoma (PDAC) upon constitutive environmental and genetical stress. While the role of ADM in PDAC progression has been established, the molecular mechanisms underlying human ADM remain elusive. We previously demonstrated the induction of ADM in human acinar cells through the transforming growth factor beta (TGFß) signaling pathway. We aim to investigate the interaction between TGFß and Hippo pathways in mediating ADM. METHODS: RNA-sequencing was conducted on sorted normal primary human acinar, ductal, and AD (acinar cells that have undergone ADM) cells. ATAC-seq analysis was utilized to reveal the chromatin accessibility in these three cell types. ChIP-Seq of YAP1, SMAD4, and H3K27ac was performed to identify the gene targets of YAP1 and SMAD4. The role of YAP1/TAZ in ADM-driven cell proliferation, as well as in oncogenic KRAS driven proliferation, was assessed using sphere formation assay. RESULTS: AD cells have a unique transcription profile, with upregulated genes in open chromatin states in acinar cells. YAP1 and SMAD4 co-occupy the loci of ADM-related genes, including PROM1, HES1, and MMP7, co-regulating biological functions such as cell adhesion, cell migration, and inflammation. Overexpression of YAP1/TAZ promoted acinar cell proliferation but still required the TGFß pathway. YAP1/TAZ were also crucial for TGFß-induced sphere formation and were necessary for KRAS-induced proliferation. CONCLUSIONS: Our study reveals the intricate transition between acinar and AD states in human pancreatic tissues. It unveils the complex interaction between the Hippo and TGF-ß pathways during ADM, highlighting the pivotal role of YAP1/TAZ and SMAD4 in PDAC initiation.

Enabling Global Analysis of Protein Citrullination via Biotin Thiol Tag-Assisted Mass Spectrometry.

Citrullination is a key post-translational modification (PTM) that affects protein structures and functions. Although it has been linked to various biological processes and disease pathogenesis, the underlying mechanism remains poorly understood due to a lack of effective tools to enrich, detect, and localize this PTM. Herein, we report the design and development of a biotin thiol tag that enables derivatization, enrichment, and confident identification of citrullination via mass spectrometry. We perform global mapping of the citrullination proteome of mouse tissues. In total, we identify 691 citrullination sites from 432 proteins which represents the largest data set to date. We discover novel distribution and functions of this PTM. This study depicts a landscape of protein citrullination and lays the foundation for further deciphering their physiological and pathological roles.

Synergetic Anion Vacancies and Dense Heterointerfaces into Bimetal Chalcogenide Nanosheet Arrays for Boosting Electrocatalysis Sulfur Conversion.

Vacancy and interface engineering are regarded as effective strategies to modulate the electronic structure and enhance the activity of metal chalcogenides. However, the practical application of metal chalcogenides in lithium-sulfur (Li-S) batteries is limited by their low conductivity, rapid decline in catalytic activity, and large volume variation during the discharging/charging process. Herein, bimetal sulfide (CoZn-S) nanosheet arrays with sulfur vacancies and dense heterointerfaces are proposed to accelerate sulfur conversion and improve the performance of Li-S batteries. Systematic investigations reveal that sulfur-vacancy and build-in interfacial field in CoZn-S facilitate the electron transfer and regulate the electronic structure. The well-designed 3D nanosheet array structures shorten the ion-transport pathway and inhibit the volume fluctuation of CoZn-S during the electrocatalysis process. Density functional theory studies confirm that the built-in interfacial field and sulfur vacancy can promote the thermodynamic formation and decomposition of Li2 S, thus improving their intrinsic activity.

Engineering Catalytic CoSe-ZnSe Heterojunctions Anchored on Graphene Aerogels for Bidirectional Sulfur Conversion Reactions.

Sluggish sulfur reduction and lithium sulfide (Li2 S) oxidation prevent the widespread use of lithium-sulfur (Li-S) batteries, which are attractive alternatives to Li-ion batteries. The authors propose that a transition metal selenide heterojunction (CoSe-ZnSe) catalytically accelerates bidirectional sulfur conversion reactions. A combination of synchrotron X-ray absorption spectroscopy and density functional theory calculations show that a highly active heterointerface with charge redistribution and structure distortion effectively immobilizes sulfur species, facilitates Li ion diffusion, and decreases the sulfur reduction and Li2 S oxidation energy barriers. The CoSe-ZnSe catalytic cathode exhibits high areal capacities, good rate capability, and superior cycling stability with capacity fading rate of 0.027% per cycle over 1700 cycles. Furthermore, CoSe-ZnSe heterojunctions anchored on graphene aerogels (CoSe-ZnSe@G) enhance ionic transport and catalytic activity under high sulfur loading and lean electrolyte conditions. A high areal capacity of 8.0 mAh cm-2 is achieved at an electrolyte/sulfur ratio of 3 µL mg-1 . This study demonstrates the importance of bidirectional catalytic heterojunctions and structure engineering in boosting Li-S battery performances.

Oligo(Lactic Acid)8-Docetaxel Prodrug-Loaded PEG-b-PLA Micelles for Prostate Cancer.

Docetaxel (DTX) is among the most frequently prescribed chemotherapy drugs and has recently been shown to extend survival in advanced prostate cancer patients. However, the poor water solubility of DTX prevents full exploitation of this potent anticancer drug. The current marketed formulation, Taxotere®, contains a toxic co-solvent that induces adverse reactions following intravenous injection. Nano-sized polymeric micelles have been proposed to create safer, water-soluble carriers for DTX, but many have failed to reach the clinic due to poor carrier stability in vivo. In this study, we aimed to improve micelle stability by synthesizing an ester prodrug of DTX, oligo(lactic acid)8-docetaxel (o(LA)8-DTX), for augmented compatibility with the core of poly(ethylene glycol)-b-poly(lactic acid) (PEG-b-PLA) micelles. Due to the enhancement of drug-carrier compatibility, we were able to load 50% (w/w) prodrug within the micelle, solubilize 20 mg/mL o(LA)8-DTX (~12 mg/mL DTX-equivalent) in aqueous media, and delay payload release. While the micelle core prohibited premature degradation, o(LA)8-DTX was rapidly converted to parent drug DTX through intramolecular backbiting (t1/2 = 6.3 h) or esterase-mediated degradation (t1/2 = 2.5 h) following release. Most importantly, o(LA)8-DTX micelles proved to be as efficacious but less toxic than Taxotere® in a preclinical mouse model of prostate cancer.

Rational Design of MOF-Based Materials for Next-Generation Rechargeable Batteries.

Metal-organic framework (MOF)-based materials with high porosity, tunable compositions, diverse structures, and versatile functionalities provide great scope for next-generation rechargeable battery applications. Herein, this review summarizes recent advances in pristine MOFs, MOF composites, MOF derivatives, and MOF composite derivatives for high-performance sodium-ion batteries, potassium-ion batteries, Zn-ion batteries, lithium-sulfur batteries, lithium-oxygen batteries, and Zn-air batteries in which the unique roles of MOFs as electrodes, separators, and even electrolyte are highlighted. Furthermore, through the discussion of MOF-based materials in each battery system, the key principles for controllable synthesis of diverse MOF-based materials and electrochemical performance improvement mechanisms are discussed in detail. Finally, the major challenges and perspectives of MOFs are also proposed for next-generation battery applications.

Cobalt Selenide Hollow Polyhedron Encapsulated in Graphene for High-Performance Lithium/Sodium Storage.

Owing to the high specific capacities, high electrochemical activity, and various electronic properties, transition metal selenides are considered as promising anodes for lithium- and sodium-ion storage. However, poor electronic conductivity and huge volume expansion during cycling are still responsible for their restricted electrochemical performance. Herein, CoSe hollow polyhedron anchoring onto graphene (CoSe/G) is synthesized by self-assembly and subsequent selenization. In CoSe/G composites, the CoSe nanoparticles, obtained by in situ selenization of metal-organic frameworks (MOFs) in high temperature, are distributed among graphene sheets, realizing N element doping, developing robust heterostructures with a chemical bond. The unique architecture ensures the cohesion of the structure and endorses the reaction kinetics for metal ions, identified by in situ and ex situ testing techniques, and kinetics analysis. Thus, the CoSe/G anodes achieve excellent cycling performance (1259 mAh g-1 at 0.1 A g-1 after 300 cycles for lithium storage; 214 mAh g-1 at 2 A g-1 after 600 cycles for sodium storage) and rate capability (732 mAh g-1 at 5 A g-1 for lithium storage; 290 mAh g-1 at 5 A g-1 for sodium storage). The improved electrochemical performance for alkali-ion storage provides new insights for the construction of MOFs derivatives toward high-performance storage devices.

Self-Assembly of 0D-2D Heterostructure Electrocatalyst from MOF and MXene for Boosted Lithium Polysulfide Conversion Reaction.

The design of nanostructured electrocatalysts with high activity and long-term durability for the sluggish lithium polysulfide (LiPS) conversion reaction is essential for the development of high-performance lithium-sulfur (Li-S) batteries. Here, the self-assembly of bimetallic selenides on nitrogen-doped MXene (CoZn-Se@N-MX) based on the self-assembly of metal-organic framework and MXene is reported. A combination of 0D CoZn-Se nanoparticles and 2D N-MX nanosheet co-catalysts forms double lithiophilic-sulfifilic binding sites that effectively immobilize and catalytically convert LiPS intermediates. This 0D-2D heterostructure catalyst has a hierarchical porous architecture with a large active area and enables rapid Li ion diffusion, reduces the activation energy of Li2 S deposition, and lowers the energy barrier of Li2 S dissolution. In addition, an assembled CoZn-Se@N-MX hybrid synergistically prevents the aggregation of the CoZn-Se nanoparticles and restacking of the active areas of N-MX nanosheets during assembly and the LiPS conversion process. The Li-S battery with this 0D-2D catalyst delivers excellent rate capability, ultralong cycling life (over 2000 cycles), and a high areal capacity of 6.6 mAh cm-2 with a low electrolyte/sulfur ratio of 5 µL mg-1 .

Bimetallic Antimony-Vanadium Oxide Nanoparticles Embedded in Graphene for Stable Lithium and Sodium Storage.

Bimetallic oxides have received considerable attention as anodes for lithium/sodium-ion batteries (LIBs/SIBs) due to their high electrochemical activity and theoretical specific capacity. However, their cycling performance is limited by large volume variation, severe aggregation, and pulverization of bimetallic oxide nanoparticles during repeated metal ion insertion/extraction processes. Herein, bimetallic antimony-vanadium oxide nanoparticles embedded in graphene (SbVO4/G) composites are prepared by a one-step hydrothermal method. Bimetallic SbVO4 with abundant redox reaction sites can provide high specific capacity by a multi-electron reaction. A robust graphene substrate can not only alleviate volume expansion but also prevent aggregation and collapse of highly active bimetallic SbVO4. Due to the excellent synergy between the two building components, SbVO4/G hybrids exhibit excellent electrochemical activity, structural stability, and electrochemical performance. When employed as anodes for LIBs and SIBs, SbVO4/G composites display excellent cycling performance (1079.5 mAh g-1 at 0.1 A g-1 after 150 cycles for LIBs and 401.6 mAh g-1 at 0.1 A g-1 after 450 cycles for SIBs) and impressive rate capability. This work demonstrates that SbVO4/G composites are promising anodes for both LIBs and SIBs.

Engineering Selectivity for Reduced Toxicity of Bacterial Kinase Inhibitors Using Structure-Guided Medicinal Chemistry.

Tuberculosis is a major global public health concern, and new drugs are needed to combat both the typical form and the increasingly common drug-resistant form of this disease. The essential tuberculosis kinase PknB is an attractive drug development target because of its central importance in several critical signaling cascades. A major hurdle in kinase inhibitor development is the reduction of toxicity due to nonspecific kinase activity in host cells. Here a novel class of PknB inhibitors was developed from hit aminopyrimidine 1 (GW779439X), which was originally designed for human CDK4 but failed to progress clinically because of high toxicity and low specificity. Replacing the pyrazolopyridazine headgroup of the original hit with substituted pyridine or phenyl headgroups resulted in a reduction of Cdk activity and a 3-fold improvement in specificity over the human kinome while maintaining PknB activity. This also resulted in improved microbiological activity and reduced toxicity in THP-1 cells and zebrafish.

A High-Efficiency CoSe Electrocatalyst with Hierarchical Porous Polyhedron Nanoarchitecture for Accelerating Polysulfides Conversion in Li-S Batteries.

Lithium-sulfur (Li-S) batteries are recognized as promising candidates for next-generation electrochemical energy storage systems owing to their high energy density and cost-effective raw materials. However, the sluggish multielectron sulfur redox reactions are the root cause of most of the issues for Li-S batteries. Herein, a high-efficiency CoSe electrocatalyst with hierarchical porous nanopolyhedron architecture (CS@HPP) derived from a metal-organic framework is presented as the sulfur host for Li-S batteries. The CS@HPP with high crystal quality and abundant reaction active sites can catalytically accelerate capture/diffusion of polysulfides and precipitation/decomposition of Li2 S. Thus, the CS@HPP sulfur cathode exhibits an excellent capacity of 1634.9 mAh g-1 , high rate performance, and a long cycle life with a low capacity decay of 0.04% per cycle over 1200 cycles. CoSe nanopolyhedrons are further fabricated on a carbon cloth framework (CC@CS@HPP) to unfold the electrocatalytic activity by its high electrical conductivity and large surface area. A freestanding CC@CS@HPP sulfur cathode with sulfur loading of 8.1 mg cm-2 delivers a high areal capacity of 8.1 mAh cm-2 under a lean electrolyte. This work will enlighten the rational design of structure-catalysis engineering of transition-metal-based nanomaterials for diverse applications.

A general strategy for diversifying complex natural products to polycyclic scaffolds with medium-sized rings.

The interrogation of complex biological pathways demands diverse small molecule tool compounds, which can often lead to important therapeutics for the treatment of human diseases. Since natural products are the most valuable source for the discovery of therapeutics, the derivatization of natural products has been extensively investigated to generate molecules for biological screenings. However, most previous approaches only modified a limited number of functional groups, which resulted in a limited number of skeleta. Here we show a general strategy for the preparation of a library of complex small molecules by combining state-of-the-art chemistry - the site-selective oxidation of C-H bonds - with reactions that expand rigid, small rings in polycyclic steroids to medium-sized rings. This library occupies a unique chemical space compared to selected diverse reference compounds. The diversification strategy developed herein for steroids can also be expanded to other types of natural products.

Identification of a novel class of RIP1/RIP3 dual inhibitors that impede cell death and inflammation in mouse abdominal aortic aneurysm models.

Receptor interacting protein kinase-1 and -3 (RIP1 and RIP3) are essential mediators of cell death processes and participate in inflammatory responses. Our group recently demonstrated that gene deletion of Rip3 or pharmacological inhibition of RIP1 attenuated pathogenesis of abdominal aortic aneurysm (AAA), a life-threatening degenerative vascular disease characterized by depletion of smooth muscle cells (SMCs), inflammation, negative extracellular matrix remodeling, and progressive expansion of aorta. The goal of this study was to develop drug candidates for AAA and other disease conditions involving cell death and inflammation. We screened 1141 kinase inhibitors for their ability to block necroptosis using the RIP1 inhibitor Necrostatin-1s (Nec-1s) as a selection baseline. Positive compounds were further screened for cytotoxicity and virtual binding to RIP3. A cluster of top hits, represented by GSK2593074A (GSK'074), displayed structural similarity to the established RIP3 inhibitor GSK'843. In multiple cell types including mouse SMCs, fibroblasts (L929), bone marrow derived macrophages (BMDM), and human colon epithelial cells (HT29), GSK'074 inhibited necroptosis with an IC50 of ~3 nM. Furthermore, GSK'074, but not Nec-1s, blocked cytokine production by SMCs. Biochemical analyses identified both RIP1 and RIP3 as the biological targets of GSK'074. Unlike GSK'843 which causes profound apoptosis at high doses (>3 µM), GSK'074 showed no detectable cytotoxicity even at 20 µM. Daily intraperitoneal injection of GSK'074 at 0.93 mg/kg significantly attenuated aortic expansion in two mouse models of AAA (calcium phosphate: DMSO 66.06 ± 9.17% vs GSK'074 27.36 ± 8.25%, P < 0.05; Angiotensin II: DMSO 85.39 ± 15.76% vs GSK'074 36.28 ± 5.76%, P < 0.05). Histologically, GSK'074 treatment diminished cell death and macrophage infiltration in aneurysm-prone aortae. Together, our data suggest that GSK'074 represents a new class of necroptosis inhibitors with dual targeting ability to both RIP1 and RIP3. The high potency and minimum cytotoxicity make GSK'074 a desirable drug candidate of pharmacological therapies to attenuate AAA progression and other necroptosis related diseases.

Thiourea-phosphonium salts from amino acids: cooperative phase-transfer catalysts in the enantioselective aza-Henry reaction.

New chiral bifunctional thiourea-phosphonium salts have been developed based on natural amino acids as highly efficient phase-transfer catalysts in the enantioselective aza-Henry reaction.

Asymmetric synthesis of fluorine-containing compounds using organocatalysts.

Asymmetric synthesis of fluorine-containing compounds using organocatalysts has been extensively investigated and several important strategies have been developed in the last decade. This review focuses on the recent advances in the introduction of the fluorine atom into organic molecules by: i) electrophilic fluorination reactions; ii) the use of easily available fluorine-containing building blocks, both of interest in our research laboratory.

Hierarchical mesoporous TS-1 zeolite: a highly active and extraordinarily stable catalyst for the selective oxidation of 2,3,6-trimethylphenol.

We report the synthesis of a new hierarchical mesoporous TS-1 type zeolite by a simple steam-assisted crystallization method. This novel product exhibits high catalytic activity and a strongly prolonged lifetime in the selective oxidation of 2,3,6-trimethylphenol to trimethyl-p-benzoquinone.