Design, synthesis, and biological evaluation of selective covalent inhibitors of FGFR4.

Aberrant signaling via fibroblast growth factor 19 (FGF19)/fibroblast growth factor receptor 4 (FGFR4) has been identified as a driver of tumorigenesis and the development of many solid tumors, making FGFR4 is a promising target for anticancer therapy. Herein, we designed and synthesized a series of bis-acrylamide covalent FGFR4 inhibitors and evaluated their inhibitory activity against FGFRs, FGFR4 mutants, and their antitumor activity. CXF-007, verified by mass spectrometry and crystal structures to form covalent bonds with Cys552 of FGFR4 and Cys488 of FGFR1, exhibited stronger selectivity and potent inhibitory activity for FGFR4 and FGFR4 cysteine mutants. Moreover, CXF-007 exhibited significant antitumor activity in hepatocellular carcinoma cell lines and breast cancer cell lines through sustained inhibition of the FGFR4 signaling pathway. In summary, our study highlights a novel covalent FGFR4 inhibitor, CXF-007, which has the potential to overcome drug-induced FGFR4 mutations and might provide a new strategy for future anticancer drug discovery.

Ultra-Sleek High Entropy Alloy Tights: Realizing Superior Cyclability for Anode-Free Battery.

The development of Li-free anodes to inhibit Li dendrite formation and provide high energy density Li batteries is highly applauded. However, the lithiophobic interphase and heterogeneous Li deposition hindered the practical application. In this work, a 20 nm ultra-sleek high entropy alloy (HEA, NiCdCuInZn) tights loaded with HEA nanoparticles are developed by a thermodynamically driven phase transition method on the carbon fiber (HEA/C). Multiple Li+ transport paths and abundant active sites are enabled by the cocktail effect of different constituent elements in HEA. These active sites with gradient absorption energies (-3.18 to -2.03 eV) facilitate selective binding, providing a low barrier for homogeneous Li nucleation. Simultaneously, multiple transport paths promote Li diffusion behavior with uniform Li deposition. Thus, the HEA/C achieves high reversibility of Li plating/stripping processes over 2000 cycles with a coulombic efficiency of 99.6% at 5 mA cm-2 /1 mAh cm-2 in asymmetric cells, as well as over 7200 h at 60 mA cm-2 /60 mAh cm-2 in symmetric cells. Moreover, the anode-free full cell with the HEA/C host has an average coulombic efficiency of 99.5% at 1 C after 160 cycles. This advanced HEA structure design shows a favorable potential application for anode-free Li metal batteries.

Insight into Dendrites Issue in All Solid-State Batteries with Inorganic Electrolyte: Mechanism, Detection and Suppression Strategies.

All solid-state batteries (ASSBs) are regarded as one of the promising next-generation energy storage devices due to their expected high energy density and capacity. However, failures due to unrestricted growth of lithium dendrites (LDs) have been a critical problem. Moreover, the understanding of dendrite growth inside solid-state electrolytes is limited. Since the dendrite process is a multi-physical field coupled process, including electrical, chemical, and mechanical factors, no definitive conclusion can summarize the root cause of LDs growth in ASSBs till now. Herein, the existing works on mechanism, identification, and solution strategies of LD in ASSBs with inorganic electrolyte are reviewed in detail. The primary triggers are thought to originate mainly at the interface and within the electrolyte, involving mechanical imperfections, inhomogeneous ion transport, inhomogeneous electronic structure, and poor interfacial contact. Finally, some of the representative works and present an outlook are comprehensively summarized, providing a basis and guidance for further research to realize efficient ASSBs for practical applications.

Presence of lymph nodes and metastasis within prostatic anterior fat pad in radical prostatectomy patients: A single Chinese institution experience and literature review.

INTRODUCTION: Limited data from China, aim to investigate the incidence and the risk fctors of lymph node metastases in the prostatic anterior fat pad (PAFP). MATERIAL AND METHODS: Patients underwent radical prostatectomy (RP) were enrolled between March 2020 to December 2022 at a single institution. Separate pathological analysis of PAFP was performed within this area. Univariate analysis and Multivariate analysis were performed to determine the risk factor of PAFP metastasis. RESULT: A total of 255 patients were included. The study revealed an average age of 67.72 ± 7.07 years, with a mean total tumor volume of 41.54 ± 23.79 mL, and an average Pre-op PSA of 16.85 ng/mL. Clinical T stage was divided into T2, T3, and T4 (226, 25, 4 cases, respectively), while the Clinical M stage was categorized as M0 and M1 (248 and 7 cases, respectively). Out of the patients with PAFP, 19 (7.45 %) had lymph node in PAFP, and 3 (1.18 %) patients had metastases. In the univariate and multivariate analysis, Clinical M stage and anterior primary tumor were found to be a significant high-risk factor. Among the other 15 studies, six examined the risk factors associated with it, including anterior tumors, higher tumour volume, intermediate or high risk prostate cancer. CONCLUSION: Due to the low proportion of lymph node involvement (7.45 %) and rare tumor metastasis (1.18 %), routine separate pathological analysis of PAFP is not recommended in all RP patients unless there are anterior tumors, higher tumor volume, or intermediate/high risk prostate cancer.

Insight into Accelerating Polysulfides Redox Kinetics by BN@MXene Heterostructure for Li-S Batteries.

Sluggish redox kinetics and shuttle effect of polysulfides hinder the extensive application of the lithium-sulfur batteries (LSBs). Herein a functional heterostructure of boron nitride (BN) and MXene with an alternately layered structure (BN@MXene) is designed as separator interlayer. High efficiency Li+ transmission, uniform lithium deposition, strong adsorption, and efficient catalytic conversion activities of lithium polysulfides (LiPSs) realized by this heterostructure are confirmed by experiments and theoretical calculations. The alternately layered structure provides unblocked ion transmission channels and abundant active sites to accelerate the polysulfides redox kinetics with reduced energy barriers of oxidation and reduction reactions. As a result, the LSBs deliver an initial discharge capacity of up to 1273.9 mAh g-1 at 0.2 °C and a low decay of 0.058% per cycle in long-term cycling up to 700 cycles at 1 °C. This work provides an effective designing strategy to accelerate the polysulfides redox kinetics for advanced Li-S electrochemical system.

Highly Deformable High-Strength SiO2 Aerogel Designed with an Alternating Structure of Hard Cores and Flexible Chains for Thermal Insulation.

Thermally insulating aerogels can now be prepared from ceramics, polymers, carbon, and metals and composites between them. However, it is still a great challenge to make aerogels with high strength and excellent deformability. We propose a design concept of hard cores and flexible chains that alternately construct the aerogel skeleton structure. The approach gives the designed SiO2 aerogel excellent compressive (fracture strain 83.32%), tensile. and shear deformabilities, corresponding to maximum strengths of 22.15, 1.18, and 1.45 MPa, respectively. Also, the SiO2 aerogel can stably perform 100 load-unload cycles at a 70% large compression strain, demonstrating an excellent resilient compressibility. In addition, the low density of 0.226 g/cm3, the high porosity of 88.7%, and the average pore size of 45.36 nm effectively inhibit heat conduction and heat convection, giving the SiO2 aerogel outstanding thermal insulation properties [0.02845 W/(m·K) at 25 °C and 0.04895 W/(m·K) at 300 °C], and the large number of hydrophobic groups itself also gives it excellent hydrophobicity and hydrophobic stability (hydrophobic angle of 158.4° and saturated mass moisture absorption rate of about 0.327%). The successful practice of this concept has provided different insights into the preparation of high-strength aerogels with high deformability.

Plasma and magnetron sputtering constructed dual-functional polysulfides barrier separator for high-performance lithium-sulfur batteries.

In order to fundamentally suppress the shuttle effect, N2 Plasma & Al2O3 magnetron sputtered separators (Al2O3@N-PP) are proposed for lithium-sulfur batteries (LSBs). Such a dual-functional polysulfides (LiPSs) barrier separator greatly inhibits the shuttle effect from the perspective of physical and chemical interaction. Physically, the inherently electronegative amorphous Al2O3 first achieves the repulsion of LiPSs to the sulfur cathode through the electrostatic repulsive effect, effectively preventing a large amount of soluble LiPSs from accumulating at the separator. At the same time, the Al2O3 film seals the shuttle channel of LiPSs to a certain extent. Chemically, N2 plasma-doped N heteroatoms form a lithium bond with Li+ in LiPSs to achieve the first step chemical adsorption and anchoring of LiPSs. When the LiPSs reaches the amorphous Al2O3 film, more stable chemical bonds are formed between Al3+ and S2-, Li+ and O2- to achieve more effective adsorption and anchoring of LiPSs. At 1C with a high sulfur loading up to 3-5 mg cm-2 the LSB contributes a specific charge capacity of 717.4 mAh g-1, with high retention rate up to 75.49 % after 450 cycles. The U-shaped electrolytic cell experiment and ultraviolet-visible spectrum experiment confirmed the LiPSs barrier function of the functional separator.

Lead zirconate titanate aerogel piezoelectric composite designed with a biomimetic shell structure for underwater acoustic transducers.

In this study, we used lead zirconate titanate (PZT) aerogels prepared by a solvothermal assisted sol-gel method as raw materials to synthesize PZT aerogel/PVDF composite coatings and PZT aerogel sintered sheets through natural annealing and PVDF composite and hot pressing, respectively, and then combined them with the design principle of a biomimetic shell structure to prepare an alternate coating/sheet structured PZT aerogel piezoelectric composite with natural distinguished mechanical properties. It had excellent piezoelectric properties with a piezoelectric coefficient d33 of 435.15 pC N-1 and d31 of -144.55 pC N-1, excellent electromechanical coupling properties with a planar electromechanical coupling coefficient of 60.14%, low dielectric loss of 0.76% at 40 Hz and low density of 3.04 g cm-3. When used as the piezoelectric material in underwater acoustic transducers (UATs), compared with all kinds of piezoelectric ceramics, it achieved higher piezoelectric and comprehensive mechanical properties, lower dielectric loss, lower density, and electromechanical coupling properties similar to that of Pb-containing piezoelectric ceramics, thus showing extremely promising application prospects in UATs.

Intelligent phase-transition MnO2 single-crystal shell enabling a high-capacity Li-rich layered cathode in Li-ion batteries.

Layered, Li-rich Mn-based oxides (LLMOs) are the most promising next-generation, high-energy batteries due to their relatively high specific capacities and high voltages. However, the practical application of LLMO cathodes is limited by low initial coulombic efficiencies (CEs) and poor cycling performance. Herein, we used the reaction of KMnO4 and MnSO4 under hydrothermal conditions to grow a nano-SCMO shell on the LLMO material surface (SCMO@LLMO). The unique particle/sheet compound structure of the SCMO shell is beneficial to the electrochemical reaction. SCMO has good Li storage characteristics and excellent surface structure stability in the single-crystal phase which further improves the reversible capacity, CE, and cyclic stability of the LLMO cathode. Therefore, the optimal coated sample (feedstock: 2 M KMnO4, SCMO@LLMO-2.0) exhibits a good initial discharge capacity (238.2 mA h g-1 at 1C and 173.8 mA h g-1 at 5C), initial CE (89.6% at 1C and 86.5% at 5C), and cycling performance (capacity retention of 84.67% at 1C and 62.72% at 5C after 200 cycles). This work adopts a hydrothermal method to synthesize a nano-single crystal composite material, laying a foundation for the preparation of the SCMO@LLMO cathodes for LLMO primary battery cathodes with high electrochemical performance.

Enhanced Electrochemical and Thermal Transport Properties of Graphene/MoS2 Heterostructures for Energy Storage: Insights from Multiscale Modeling.

Graphene has been combined with molybdenum disulfide (MoS2) to ameliorate the poor cycling stability and rate performance of MoS2 in lithium ion batteries, yet the underlying mechanisms remain less explored. Here, we develop multiscale modeling to investigate the enhanced electrochemical and thermal transport properties of graphene/MoS2 heterostructures (GM-Hs) with a complex morphology. The calculated electronic structures demonstrate the greatly improved electrical conductivity of GM-Hs compared to MoS2. Increasing the graphene layers in GM-Hs not only improves the electrical conductivity but also stabilizes the intercalated Li atoms in GM-Hs. It is also found that GM-Hs with three graphene layers could achieve and maintain a high thermal conductivity of 85.5 W/(m·K) at a large temperature range (100-500 K), nearly 6 times that of pure MoS2 [∼15 W/(m·K)], which may accelerate the heat conduction from electrodes to the ambient. Our quantitative findings may shed light on the enhanced battery performances of various graphene/transition-metal chalcogenide composites in energy storage devices.

A Facile Approach to Tune the Electrical and Thermal Properties of Graphene Aerogels by Including Bulk MoS2.

Graphene aerogels (GAs) have attracted extensive interest in diverse fields, owing to their ultrahigh surface area, low density and decent electrical conductivity. However, the undesirable thermal conductivity of GAs may limit their applications in energy storage devices. Here, we report a facile hydrothermal method to modulate both the electrical and thermal properties of GAs by including bulk molybdenum disulfide (MoS2). It was found that MoS2 can help to reduce the size of graphene sheets and improve their dispersion, leading to the uniform porous micro-structure of GAs. The electrical measurement showed that the electrical conductivity of GAs could be decreased by 87% by adding 0.132 vol % of MoS2. On the contrary, the thermal conductivity of GAs could be increased by ~51% by including 0.2 vol % of MoS2. The quantitative investigation demonstrated that the effective medium theories (EMTs) could be applied to predict the thermal conductivity of composite GAs. Our findings indicated that the electrical and thermal properties of GAs can be tuned for the applications in various fields.

[Early evaluation of brain injury by electroencephalogram in neonates with asphyxia].

OBJECTIVE: To explore the value of electroencephalogram (EEG) in early diagnosis of brain injury in neonates with asphyxia. METHODS: EEG examination was performed in 49 neonates with asphyxia (mild: n=9; severe: n=40) within 6 hrs of their births. Of the 49 asphyxiated neonates, 33 had concurrent HIE, including 20 cases of mild, 9 cases of moderate and 4 cases of severe HIE. RESULTS: Twenty-one (63.6%) out of the 33 patients with HIE showed abnormal EEG, but only one (6.3%) in the asphyxia group without HIE. All of 13 patients with moderate-severe HIE showed abnormal EEG. The degree of EEG abnormality in neonates with HIE was consistent with the clinical grading of HIE. The neonates whose EEG showed electrical silence and burst suppression and the abnormalities were kept unrecoverable for more than 2 weeks had very poor prognosis. CONCLUSIONS: EEG can reflect brain injury caused by neonatal asphyxia and the severity of brain injury. It may be useful for early diagnosis of brain injury following asphyxia in neonates.