Optimized In Situ Doping Strategy Stabling Single-Crystal Ultrahigh-Nickel Layered Cathode Materials.

Single-crystal Ni-rich cathodes offer promising prospects in mitigating intergranular microcracks and side reaction issues commonly encountered in conventional polycrystalline cathodes. However, the utilization of micrometer-sized single-crystal particles has raised concerns about sluggish Li+ diffusion kinetics and unfavorable structural degradation, particularly in high Ni content cathodes. Herein, we present an innovative in situ doping strategy to regulate the dominant growth of characteristic planes in the single-crystal precursor, leading to enhanced mechanical properties and effectively tackling the challenges posed by ultrahigh-nickel layered cathodes. Compared with the traditional dry-doping method, our in situ doping approach possesses a more homogeneous and consistent modifying effect from the inside out, ensuring the uniform distribution of doping ions with large radius (Nb, Zr, W, etc). This mitigates the generally unsatisfactory substitution effect, thereby minimizing undesirable coating layers induced by different solubilities during the calcination process. Additionally, the uniformly dispersed ions from this in situ doping are beneficial for alleviating the two-phase coexistence of H2/H3 and optimizing the Li+ concentration gradient during cycling, thus inhibiting the formation of intragranular cracks and interfacial deterioration. Consequently, the in situ doped cathodes demonstrate exceptional cycle retention and rate performance under various harsh testing conditions. Our optimized in situ doping strategy not only expands the application prospects of elemental doping but also offers a promising research direction for developing high-energy-density single-crystal cathodes with extended lifetime.

Correlating concerted cations with oxygen redox in rechargeable batteries.

Rechargeable batteries currently power much of our world, but with the increased demand for electric vehicles (EVs) capable of traveling hundreds of miles on a single charge, new paradigms are necessary for overcoming the limits of energy density, particularly in rechargeable batteries. The emergence of reversible anionic redox reactions presents a promising direction toward achieving this goal; however this process has both positive and negative effects on battery performance. While it often leads to higher capacity, anionic redox also causes several unfavorable effects such as voltage fade, voltage hysteresis, sluggish kinetics, and oxygen loss. However, the introduction of cations with topological chemistry tendencies has created an efficient pathway for achieving long-term oxygen redox with improved kinetics. The cations serve as pillars in the crystal structure and meanwhile can interact with oxygen in ways that affect the oxygen redox process through their impact on the electronic structure. This review delves into a detailed examination of the fundamental physical and chemical characteristics of oxygen redox and elucidates the crucial role that cations play in this process at the atomic and electronic scales. Furthermore, we present a systematic summary of polycationic systems, with an emphasis on their electrochemical performance, in order to provide perspectives on the development of next-generation cathode materials.

A Fluoride-Rich Solid-Like Electrolyte Stabilizing Lithium Metal Batteries.

To address the problems associated with Li metal anodes, a fluoride-rich solid-like electrolyte (SLE) that combines the benefits of solid-state and liquid electrolytes is presented. Its unique triflate-group-enhanced frame channels facilitate the formation of a functional inorganic-rich solid electrolyte interphase (SEI), which not only improves the reversibility and interfacial charge transfer of Li anodes but also ensures uniform and compact Li deposition. Furthermore, these triflate groups contribute to the decoupling of Li+ and provide hopping sites for rapid Li+ transport, enabling a high room-temperature ionic conductivity of 1.1 mS cm-1 and a low activation energy of 0.17 eV, making it comparable to conventional liquid electrolytes. Consequently, Li symmetric cells using such SLE achieve extremely stable plating/stripping cycling over 3500 h at 0.5 mA cm-2 and support a high critical current up to 2 mA cm-2 . The assembled Li||LiFePO4 solid-like batteries exhibit exceptional cyclability for over 1 year and a half, even outperforming liquid cells. Additionally, high-voltage cylindrical cells and high-capacity pouch cells are demonstrated, corroborating much simpler processibility in battery assembly compared to all-solid-state batteries.

Structure-based discovery of a new series of nucleoside-derived ring-opening PRMT5 inhibitors.

The ubiquitous methyltransferases employing SAM as the methyl donor have emerged as potential targets in many disease treatments, especially in anticancer. Therefore, developing SAM-competitive inhibitors of methyltransferases is of great interest to the drug research. To explore this direction, herein, we rationally designed a series of nucleoside derivatives as potent PRMT5 inhibitors with novel scaffold. The representative compounds A2 and A8 exhibited highly potent PRMT5 inhibition activity as well as good selectivity over other PRMTs and PKMTs. Further cellular experiments revealed that compounds A2 and A8 potently reduced the level of sDMA and inhibited the proliferation of Z-138 and MOLM-13 cell lines by inducing apoptosis. Moreover, compounds A8 which had favorable pharmacokinetic properties exhibited potent antitumor efficacy without the loss of body weight in a subcutaneous MOLM-13 xenograft model. In summary, our efforts provided a series of novel nucleoside analogs as potent PRMT5 inhibitors and may also offer a new strategy to develop SAM analogs as other methyltransferases' inhibitors.

Revealing the aging process of solid electrolyte interphase on SiOx anode.

As one of the most promising alternatives to graphite negative electrodes, silicon oxide (SiOx) has been hindered by its fast capacity fading. Solid electrolyte interphase (SEI) aging on silicon SiOx has been recognized as the most critical yet least understood facet. Herein, leveraging 3D focused ion beam-scanning electron microscopy (FIB-SEM) tomographic imaging, we reveal an exceptionally characteristic SEI microstructure with an incompact inner region and a dense outer region, which overturns the prevailing belief that SEIs are homogeneous structure and reveals the SEI evolution process. Through combining nanoprobe and electron energy loss spectroscopy (EELS), it is also discovered that the electronic conductivity of thick SEI relies on the percolation network within composed of conductive agents (e.g., carbon black particles), which are embedded into the SEI upon its growth. Therefore, the free growth of SEI will gradually attenuate this electron percolation network, thereby causing capacity decay of SiOx. Based on these findings, a proof-of-concept strategy is adopted to mechanically restrict the SEI growth via applying a confining layer on top of the electrode. Through shedding light on the fundamental understanding of SEI aging for SiOx anodes, this work could potentially inspire viable improving strategies in the future.

Design and synthesis of 1H-pyrazolo[3,4-d]pyrimidine derivatives as hematopoietic progenitor kinase 1 (HPK1) inhibitors.

Despite immune checkpoint inhibitors' tremendous success in the treatment of tumors, the moderate response rate limits their widespread use. Hematopoietic progenitor kinase 1 (HPK1) is served as an essential negative regulator of T-cell receptor, which has been identified as a promising target for enhancing antitumor immunity. However, the development of a selective HPK1 inhibitor is still challenging. Herein, we reported a novel series of 1H-pyrazolo[3,4-d]pyrimidine derivatives as HPK1 inhibitors by structure-based rational design. The optimal compound 10n significantly inhibited HPK1 with an IC50 value of 29.0 nM and the phosphorylation of SLP76 at a concentration as low as 0.1 µM. Furthermore, compound 10n exhibited good selectivity over a panel of 25 kinases, including GLK from the same MAP4K family. Together, the current study provided a novel, potent, and selective HPK1 inhibitor, acting as a lead compound for the future development of cancer immunotherapy.

Species-Selective Detection of Volatile Organic Compounds by Ionic Liquid-Based Electrolyte Using Electrochemical Methods.

The detection of volatile organic compounds (VOCs) is an important topic for environmental safety and public health. However, the current commercial VOC detectors suffer from cross-sensitivity and low reproducibility. In this work, we present species-selective detection for VOCs using an electrochemical cell based on ionic liquid (IL) electrolytes with features of high selectivity and reliability. The voltammograms measured with the IL-based electrolyte absorbing different VOCs exhibited species-selective features that were extracted and classified by linear discriminant analysis (LDA). The detection system could identify as many as four types of VOCs, including methanol, ethanol, acetone, formaldehyde, and additional water. A mixture of methanol and formaldehyde was detected as well. The sample required for the VOCs classification system was 50 µL, or 1.164 mmol, on average. The response time for each VOC measurement is as fast as 24 s. The volume of VOCs such as formaldehyde in solution could also be quantified by LDA and electrochemical impedance spectroscopy techniques, respectively. The system showed a tunable detection range for 1.6 and 16% (w/v) CH2O solution by adjusting the composition of the electrolyte. The limit of detection was as low as 1 µL. For the 1.6% CH2O solution, the linearity calibration range was determined to be from 5.30 to 53.00 µmol with a limit of detection at 0.53 µmol. The mechanisms for VOCs determination and quantification are also thoroughly discussed. It is expected that this work could provide a new insight into the concept of electrochemical detection of VOCs with machine learning analysis and be applied to both VOCs gas monitoring and fluid detection.

Engineering Functionalized 2D Metal-Organic Frameworks Nanosheets with Fast Li+ Conduction for Advanced Solid Li Batteries.

Solid-state batteries can ensure high energy density and safety in lithium metal batteries, while polymer electrolytes are plagued by slow ion kinetics and low selective transport of Li+ . Metal-organic frameworks (MOFs) are proposed as emerging fillers for solid-state poly(ethylene oxide)(PEO) electrolytes, however, developing functionalized MOFs and understanding their roles on ion transfer has proven challenging. Herein, combining computational and experimental results, the functional group regulation in MOFs can effectively change surficial charge distribution and limit anion movement is revealed, providing a potential solution to these issues. Specifically, functionalized 2D MOF sheets are designed through molecular engineering to construct high-performance composite electrolytes, where the electron-donating effect of substituents in 2D-MOFs effectively limits the movement of ClO4 - and promotes mechanical properties and ion migration numbers (0.36 up to 0.64) of PEO. As a result, Li/Li cells with composite electrolyte exhibit superior cyclability for 1000 h at a current density of 0.2 mA cm-2 . Meanwhile, the solid LiFePO4 /Li battery delivers highly reversible capacities of 148.8 mAh g-1 after 200 cycles. These findings highlight a new approach for anion confinement through the use of functional group electronic effects, leading to enhanced ionic conductivity, and a feasible direction for high-performance solid-state batteries.

Imitating Architectural Mortise-Tenon Structure for Stable Ni-Rich Layered Cathodes.

Ni-rich layered oxides are the most promising cathodes for Li-ion batteries, but chemo-mechanical failures during cycling and large first-cycle capacity loss hinder their applications in high-energy batteries. Herein, by introducing spinel-like mortise-tenon structures into the layered phase of LiNi0.8 Co0.1 Mn0.1 O2 (NCM811), the adverse volume variations in cathode materials can be significantly suppressed. Meanwhile, these mortise-tenon structures play the role of the expressway for fast lithium-ion transport, which is substantiated by experiments and calculations. Moreover, the particles with mortise-tenon structures usually terminate with the most stable (003) facet. The new cathode exhibits a discharge capacity of 215 mAh g-1 at 0.1 C with an initial Coulombic efficiency of 97.5%, and capacity retention of 82.2% after 1200 cycles at 1 C. This work offers a viable lattice engineering to address the stability and low initial Coulombic efficiency of the Ni-rich layered oxides, and facilitates the implementation of Li-ion batteries with high-energy density and long durability.

Structure-based discovery of potent USP28 inhibitors derived from Vismodegib.

Ubiquitin-specific proteases (USPs) 28 is overexpressed in multiple types of cancers. The development of potent USP28 inhibitors is still in primitive stage. We previously reported our discovery of Vismodegib as a USP28 inhibitor by screening a commercially available drug library. Herein, we report our efforts to solve the cocrystal structure of Vismodegib bound to USP28 for the first time and subsequent structure-based optimization leading to a series of Vismodegib derivatives as potent USP28 inhibitors. Based on the cocrystal structure, elaborative SARs exploration was carried out to afford much more potent USP28 inhibitors than Vismodegib. The representative compounds 9l, 9o and 9p bearing high potency on USP28 showed high selectivity over USP2, USP7, USP8, USP9x, UCHL3 and UCHL5. The detailed cellular assay suggested that compounds 9l, 9o and 9p could cause cytotoxicity in both human colorectal cancer and lung squamous carcinoma cells and significantly enhance the sensitivity of colorectal cancer cells to Regorafenib. Further immunoblotting analysis indicated that compounds 9l, 9o and 9p could dose-dependently down-regulate the cellular level of c-Myc through ubiquitin-proteasome system and anti-cancer effects could mainly be attributed to their inhibition on USP28 but not involving the Hedgehog-Smoothened pathway. Thus, our work provided a series of novel and potent USP28 inhibitors derived from Vismodegib and may contribute to the development of USP28 inhibitors.

A room temperature rechargeable Li2O-based lithium-air battery enabled by a solid electrolyte.

A lithium-air battery based on lithium oxide (Li2O) formation can theoretically deliver an energy density that is comparable to that of gasoline. Lithium oxide formation involves a four-electron reaction that is more difficult to achieve than the one- and two-electron reaction processes that result in lithium superoxide (LiO2) and lithium peroxide (Li2O2), respectively. By using a composite polymer electrolyte based on Li10GeP2S12 nanoparticles embedded in a modified polyethylene oxide polymer matrix, we found that Li2O is the main product in a room temperature solid-state lithium-air battery. The battery is rechargeable for 1000 cycles with a low polarization gap and can operate at high rates. The four-electron reaction is enabled by a mixed ion-electron-conducting discharge product and its interface with air.

Development of a series of quinazoline-2,5-diamine derivatives as potent hematopoietic progenitor kinase 1 (HPK1) inhibitors.

Hematopoietic progenitor kinase 1 (HPK1) is a serine/threonine kinase that serves as the negative regulator of multiple immune signaling pathways. Genetic studies using HPK1 knockout and kinase-dead mice suggested that inhibiting HPK1 either alone or in combination with immune checkpoint blockade could be a promising strategy in cancer immunotherapy. Herein, we report the design, synthesis and structure-activity relationship (SAR) study of a series of potent HPK1 inhibitors bearing quinazoline-2,5-diamine scaffold. Three rounds of SAR exploration led to the identification of 9h, the most potent compound in this series which harbors a 2-methyl-1,2,3,4-tetrahydroisoquinolin-7-yl substituent. Further biological assessments using human immune cells demonstrated that 9h could strongly inhibit downstream phosphorylation, augment interleukin-2 (IL-2) production and reverse prostaglandin E2 (PGE2)-induced immune suppression. Overall, our study on these quinazoline-2,5-diamine derivatives provided not only a tool compound for the community to help with elucidating the HPK1 pharmacology, but also a reliable reference for subsequent development of HPK1 inhibitors.

Probing Distinctive Redox Mechanism in Ni-Rich Cathode Via Real-Time Quick X-Ray Absorption Spectroscopy.

X-ray radiation damage on the measuring system has been a critical issue regularly for a long-time exposure to X-ray beam during the in operando characterizations, which is particularly severe when the applied X-ray energy is near the absorption edges (M, L, K, etc.) of the interest element. To minimize the negative effects raised by beam radiation, we employ quick X-ray absorption spectroscopy (QXAS) to study the electrochemical reaction mechanism of a Ni-rich layered structure cathode for lithium-ion batteries. With the advanced QXAS technique, the electronic structure and local coordination environment of the transition metals (TMs) are monitored in-operando with limited radiation damage. Compared to the conventional step-mode X-ray absorption spectroscopy, the QXAS can provide more reliable oxidation state change and more detailed local structure evolutions surrounding TMs (Ni and Co) in Ni-rich layered oxides. By leveraging these advantages of QXAS, we demonstrated that the Ni dominates the electrochemical process with the Co being almost electrochemically inactive. Reversible Ni ions movement between TMs sites and Li sites is also revealed by the time-resolved QXAS technique.

Quenching-Induced Defects Liberate the Latent Reversible Capacity of Lithium Titanate Anode.

Interest in defect engineering for lithium-ion battery (LIB) materials is sparked by its ability to tailor electrical conductivity and introduce extra active sites for electrochemical reactions. However, harvesting excessive intrinsic defects in the bulk of the electrodes rather than near their surface remains a long-standing challenge. Here, a versatile strategy of quenching is demonstrated, which is exercised in lithium titanate (Li4 Ti5 O12 , LTO), a renowned anode for LIBs, to achieve off-stoichiometry in the interior region. In situ synchrotron analysis and atomic-resolution microscopy reveal the enriched oxygen vacancies and cation redistribution after ice-water quenching, which can facilitate the native unextractable Li ions to participate in reversible cycling. The fabricated LTO anode delivers a sustained capacity of 202 mAh g-1 in the 1.0-2.5 V range with excellent rate capability and overcomes the poor cycling stability seen in conventional defective electrodes. The feasibility of tuning the degree of structural defectiveness via quenching agents is also proven, which can open up an intriguing avenue of research to harness the intrinsic defects for improving the energy density of rechargeable batteries.

Structure-activity relationship study of a series of nucleoside derivatives bearing sulfonamide scaffold as potent and selective PRMT5 inhibitors.

Protein arginine methyltransferase 5 (PRMT5) is a promising target for the treatment of malignant tumors. The discovery of nucleoside-derived inhibitors against PRMT5 with novel scaffold has been challenging. Herein, we report our effort on the design and synthesis of nucleoside derivatives bearing sulfonamide scaffold as potent PRMT5 inhibitors. The representative compound 23n was identified as a potent and selective PRMT5 inhibitor with an IC50 value of 8 nM. Molecular docking study demonstrated the binding mode of compound 23n and illustrated its inhibitory activity to PRMT5. The Trimethyl Lock prodrug strategy was used to afford prodrug 36 with lower polarity which could rapidly release the active compound 23n after entering the tumor cells. Cell-based assays revealed that the prodrug 36 restrained the proliferation of Z-138 and MOLM-13 cells and suppressed methylation of PRMT5 substrate more potently than 23n. Additionally, both compound 23n and 36 exerted antiproliferative effects against Z-138 cells mainly by inducing apoptosis effectively rather than arresting cell cycle. Thus, compounds 23n and 36 represent a series of potent PRMT5 inhibitor with novel scaffold.

Strain-retardant coherent perovskite phase stabilized Ni-rich cathode.

The use of state-of-the-art Ni-rich layered oxides (LiNixCoyMn1-x-yO2, x > 0.5) as the cathode material for lithium-ion batteries can push the energy and power density to a higher level than is currently available1,2. However, volume variation associated with anisotropic lattice strain and stress that is being developed during lithium (de)intercalation induces severe structural instability and electrochemical decay of the cathode materials, which is amplified further when the battery is operating at a high voltage (above 4.5 V), which is essential for unlocking its high energy3-6. Even after much effort by the research community, an intrinsic strain-retardant method for directly alleviating the continuous accumulation of lattice strain remains elusive. Here, by introducing a coherent perovskite phase into the layered structure functioning as a 'rivet', we significantly mitigate the pernicious structural evolutions by a pinning effect. The lattice strain evolution in every single cycle is markedly reduced by nearly 70% when compared with conventional materials, which significantly enhances morphological integrity leading to a notable improvement in battery cyclability. This strain-retardant approach broadens the perspective for lattice engineering to release the strain raised from lithium (de)intercalation and paves the way for the development of high-energy-density cathodes with long durability.

Discovery of Novel N-(5-(Pyridin-3-yl)-1H-indazol-3-yl)benzamide Derivatives as Potent Cyclin-Dependent Kinase 7 Inhibitors for the Treatment of Autosomal Dominant Polycystic Kidney Disease.

Recent evidence suggests that CDK7 is a novel potential drug target for autosomal dominant polycystic kidney disease (ADPKD) treatment. Herein, on the basis of structural analysis, a hit compound 3 with a novel scaffold was designed and subsequent medicinal chemistry efforts by a rational design strategy were conducted to improve CDK7 inhibitors' potency and selectivity. The representative compound B2 potently inhibited CDK7 with an IC50 value of 4 nM and showed high selectivity over CDKs. Compound B2 showed high potency to inhibit cyst growth and exhibited lower cytotoxicity than THZ1 in an in vitro Madin-Darby canine kidney cyst model. In addition, compound B2 was also highly efficacious in suppressing renal cyst development in an ex vivo embryonic kidney cyst model and in vivo ADPKD mouse model. These results indicate that compound B2 represents a promising lead compound that deserves further investigation to discover novel therapeutic agents for ADPKD.

Structure/Interface Coupling Effect for High-Voltage LiCoO2 Cathodes.

LiCoO2 (LCO) is widely applied in today's rechargeable battery markets for consumer electronic devices. However, LCO operations at high voltage are hindered by accelerated structure degradation and electrode/electrolyte interface decomposition. To overcome these challenges, co-modified LCO (defined as CB-Mg-LCO) that couples pillar structures with interface shielding are successfully synthesized for achieving high-energy-density and structurally stable cathode material. Benefitting from the "Mg-pillar" effect, irreversible phase transitions are significantly suppressed and highly reversible Li+ shuttling is enabled. Interestingly, bonding effects between the interfacial lattice oxygen of CB-Mg-LCO and amorphous Cox By coating layer are found to elevate the formation energy of oxygen vacancies, thereby considerably mitigating lattice oxygen loss and inhibiting irreversible phase transformation. Meanwhile, interface shielding effects are also beneficial for mitigating parasitic electrode/electrolyte reactions, subsequent Co dissolution, and ultimately enable a robust electrode/electrolyte interface. As a result, the as-designed CB-Mg-LCO cathode achieves a high capacity and excellent cycle stability with 94.6% capacity retention at an extremely high cut-off voltage of 4.6 V. These findings provide new insights for cathode material modification methods, which serves to guide future cathode material design.

Elastic Lattice Enabling Reversible Tetrahedral Li Storage Sites in a High-Capacity Manganese Oxide Cathode.

The key to breaking through the capacity limitation imposed by intercalation chemistry lies in the ability to harness more active sites that can reversibly accommodate more ions (e.g., Li+ ) and electrons within a finite space. However, excessive Li-ion insertion into the Li layer of layered cathodes results in fast performance decay due to the huge lattice change and irreversible phase transformation. In this study, an ultrahigh reversible capacity is demonstrated by a layered oxide cathode purely based on manganese. Through a wealth of characterizations, it is clarified that the presence of low-content Li2 MnO3 domains not only reduces the amount of irreversible O loss; but also regulates Mn migration in LiMnO2 domains, enabling elastic lattice with high reversibility for tetrahedral sites Li-ion storage in Li layers. This work utilizes bulk cation disorder to create stable Li-ion-storage tetrahedral sites and an elastic lattice for layered materials, with a reversible capacity of 600 mA h g-1 , demonstrated in th range 0.6-4.9 V versus Li/Li+ at 10 mA g-1 . Admittedly, discharging to 0.6 V might be too low for practical use, but this exploration is still of great importance as it conceptually demonstrates the limit of Li-ions insertion into layered oxide materials.