HNF4A guides the MLL4 complex to establish and maintain H3K4me1 at gene regulatory elements.

Hepatocyte nuclear factor 4A (HNF4A/NR2a1), a transcriptional regulator of hepatocyte identity, controls genes that are crucial for liver functions, primarily through binding to enhancers. In mammalian cells, active and primed enhancers are marked by monomethylation of histone 3 (H3) at lysine 4 (K4) (H3K4me1) in a cell type-specific manner. How this modification is established and maintained at enhancers in connection with transcription factors (TFs) remains unknown. Using analysis of genome-wide histone modifications, TF binding, chromatin accessibility and gene expression, we show that HNF4A is essential for an active chromatin state. Using HNF4A loss and gain of function experiments in vivo and in cell lines in vitro, we show that HNF4A affects H3K4me1, H3K27ac and chromatin accessibility, highlighting its contribution to the establishment and maintenance of a transcriptionally permissive epigenetic state. Mechanistically, HNF4A interacts with the mixed-lineage leukaemia 4 (MLL4) complex facilitating recruitment to HNF4A-bound regions. Our findings indicate that HNF4A enriches H3K4me1, H3K27ac and establishes chromatin opening at transcriptional regulatory regions.

Synergistic Effect of Calcination and Sintering on the Reduction of Grain Boundary Resistance of LATP Solid Electrolyte.

The NASICON-type Li1.4Al0.4Ti1.6(PO4)3 (LATP) solid electrolyte is a promising candidate for next-generation lithium-ion batteries due to its high stability in air and moisture, as well as high bulk ion conductivity. However, the grain boundary resistance of LATP limits its overall ionic conductivity, which remains a major obstacle to the commercialization of all-solid-state batteries. In this study, we made efforts to solve the problem by promoting the minimization of voids and the formation of well-defined grain boundaries by controlling the temperature of two heat treatments during the synthesis process. The crystallization temperature was confirmed through thermogravimetric analysis/DTA analysis, and the degree of crystallization was confirmed using XRD analysis. The formation of grain boundaries and the presence of voids were evaluated by cross-sectional SEM images after sintering. After sintering, the LA_900 °C sample, characterized by a high degree of crystallization and well-formed grain boundaries without voids, demonstrated a low bulk and grain boundary resistance, which was confirmed by electrochemical impedance spectroscopy analysis. The result was an ionic conductivity of 1.72 × 10-4 S/cm. These results provide valuable insights into the facile synthesis of LATP.

Composition, organization and mechanisms of the transition zone, a gate for the cilium.

The cilium evolved to provide the ancestral eukaryote with the ability to move and sense its environment. Acquiring these functions required the compartmentalization of a dynein-based motility apparatus and signaling proteins within a discrete subcellular organelle contiguous with the cytosol. Here, we explore the potential molecular mechanisms for how the proximal-most region of the cilium, termed transition zone (TZ), acts as a diffusion barrier for both membrane and soluble proteins and helps to ensure ciliary autonomy and homeostasis. These include a unique complement and spatial organization of proteins that span from the microtubule-based axoneme to the ciliary membrane; a protein picket fence; a specialized lipid microdomain; differential membrane curvature and thickness; and lastly, a size-selective molecular sieve. In addition, the TZ must be permissive for, and functionally integrates with, ciliary trafficking systems (including intraflagellar transport) that cross the barrier and make the ciliary compartment dynamic. The quest to understand the TZ continues and promises to not only illuminate essential aspects of human cell signaling, physiology, and development, but also to unravel how TZ dysfunction contributes to ciliopathies that affect multiple organ systems, including eyes, kidney, and brain.

A strategy of enhancing the ionic conductivity of Li7La3Zr2O12 under accurate sintering conditions.

Garnet-type Li7La3Zr2O12 (LLZO) oxide solid electrolytes are spotlighted as solid electrolytes for lithium-ion secondary batteries due to their high thermal and electrochemical stability. However, LLZO has a low ionic conductivity compared to liquid electrolytes, which is one of the biggest problems hindering the commercialization of all-solid-state batteries (ASSBs). Essential conditions for improving the ionic conductivity can be classified into two factors: (1) formation of a cubic LLZO phase related to bulk ionic conductivity and (2) formation of grain boundaries for low interfacial resistance. In this work, cubic LLZO phase formation conditions were first confirmed by TGA-DTA analysis. The LLZO phase was pre-formed via a holding range of furnace temperature profile (HRFTP) found by TGA-DTA analysis. The pre-formed LLZO phase could stabilize the cubic LLZO phase after a sintering process. This was confirmed by XRD analysis. Stabilized cubic LLZO under HRFTP conditions could enhance the bulk ionic conductivity, the main factor affecting the total ionic conductivity. In addition, to confirm the characteristics of sintering temperature changes, the grain boundaries of LLZO surfaces and the color of LZO pellets were investigated by SEM in detail. By setting the holding time process at 600 °C, the pre-formed LLZO phase stabilized the cubic LLZO phase formation after the sintering process. By optimizing the sintering temperature, both bulk and grain boundary ionic conductivities were improved. As a result, an ionic conductivity of 1.87 × 10-4 S cm-1 of the cubic LLZO phase was confirmed by EIS analysis. These results provide an insight into the reproducibility of the facile synthesis of LLZO. This strategy can be successfully applied to next-generation ASSBs.

A Synergistic Effect of Na+ and Al3+ Dual Doping on Electrochemical Performance and Structural Stability of LiNi0.88Co0.08Mn0.04O2 Cathodes for Li-Ion Batteries.

The synergistic effect of Na+/Al3+ dual doping is investigated to improve the structural stability and electrochemical performance of LiNi0.88Co0.08Mn0.04O2 cathodes for Li-ion batteries. Rietveld refinement and density functional theory calculations confirm that Na+/Al3+ dual doping changes the lattice parameters of LiNi0.88Co0.08Mn0.04O2. The changes in the lattice parameters and degree of cation mixing can be alleviated by maintaining the thickness of the LiO6 slab because the energy of Al-O bonds is higher than that of transition metal (TM)-O bonds. Moreover, Na is an abundant and inexpensive metal, and unlike Al3+, Na+ can be doped into the Li slab. The ionic radius of Na+ (1.02 Å) is larger than that of Li+ (0.76 Å); therefore, when Na+ is inserted into Li sites, the Li slab expands, indicating that Na+ serves as a pillar ion for the Li diffusion pathway. Upon dual doping of the Li and TM sites of Ni-rich Ni0.88Co0.08Mn0.04O2 (NCM) with Na+ and Al3+, respectively, the lattice structure of the obtained NNCMA is more ideal than those of bare NCM and Li+- and Na+-doped NCM (NNCM and NCMA, respectively). This suggests that NNCMA with an ideal lattice structure presents several advantages, namely, excellent structural stability, a low degree of cation mixing, and favorable Li-ion diffusion. Consequently, the rate capability of NNCMA (83.67%, 3 C/0.2 C), which presents favorable Li-ion diffusion because of the expanded Li sites, is higher than those of bare NCM (78.68%), NNCM (81.15%), and NCMA (83.18%). The Rietveld refinement, differential capacity analysis, and galvanostatic intermittent titration technique results indicate that NNCMA exhibits low polarization, favorable Li-ion diffusion, and a low degree of cation mixing; moreover, its phase transition is hindered. Consequently, NNCMA demonstrates a higher capacity retention (84%) than bare NCM (79%), NNCM (82%), and NCMA (82%) after 50 cycles at 1 C. This study provides insight into the fabrication of Ni-rich NCMs with excellent electrochemical performance.

IFT trains overcome an NPHP module barrier at the transition zone.

Cilia harbor diffusion barriers for soluble and membrane proteins within their proximal-most transition zone (TZ) region and employ an intraflagellar transport (IFT) system to form dynamic motile and signaling compartments. In this issue, De-Castro and colleagues (2021. J. Cell Biol.https://doi.org/10.1083/jcb.202010178) uncover a long-suspected role for the TZ in gating IFT particles.

An Efficient Indoor Positioning Method Based on Wi-Fi RSS Fingerprint and Classification Algorithm.

Wi-Fi received signal strength (RSS) fingerprint-based indoor positioning has been widely used because of its low cost and universality advantages. However, the Wi-Fi RSS is greatly affected by multipath interference in indoor environments, which can cause significant errors in RSS observations. Many methods have been proposed to overcome this issue, including the average method and the error handling method, but these existing methods do not consider the ever-changing dynamics of RSS in indoor environments. In addition, traditional RSS-based clustering algorithms have been proposed in the literature, but they make clusters without considering the nonlinear similarity between reference points (RPs) and the signal distribution in ever-changing indoor environments. Therefore, to improve the positioning accuracy, this paper presents an improved RSS measurement technique (IRSSMT) to minimize the error of RSS observation by using the number of selected RSS and its median values, and the strongest access point (SAP) information-based clustering technique, which groups the RPs using their SAP similarity. The performance of this proposed method is tested by experiments conducted in two different experimental environments. The results reveal that our proposed method can greatly outperform the existing algorithms and improve the positioning accuracy by 89.06% and 67.48%, respectively.

CDKL kinase regulates the length of the ciliary proximal segment.

Cilia are organelles found throughout most unicellular eukaryotes and different metazoan cell types. To accomplish their essential roles in cell motility, fluid flow, and signaling, cilia are divided into subcompartments with variable structures, compositions, and functions. How these specific subcompartments are built remains almost completely unexplored. Here, we show that C. elegans CDKL-1, related to the human CDKL kinase family (CDKL1/CDKL2/CDKL3/CDKL4/CDKL5), specifically controls the length of the proximal segment, a ciliary subdomain conserved in evolution from Tetrahymena motile cilia to C. elegans chemosensory, mammalian olfactory, and photoreceptor non-motile cilia. CDKL-1 associates with intraflagellar transport (IFT), influences the distribution of the IFT anterograde motors heterotrimeric kinesin-II and homodimeric OSM-3-kinesin/KIF17 in the proximal segment, and shifts the boundary between the proximal and distal segments (PS/DS boundary). CDKL-1 appears to function independently from several factors that influence cilium length, namely the kinases DYF-5 (mammalian CILK1/MAK) and NEKL-1 (NEK9), as well as the depolymerizing kinesins KLP-13 (KIF19) and KLP-7 (KIF2). However, a different kinase, DYF-18 (CCRK), is needed for the correct localization and function of CDKL-1 and similarly influences the length of the proximal segment. Loss of CDKL-1, which affects proximal segment length without impairing overall ciliary microtubule structural integrity, also impairs cilium-dependent processes, namely cGMP-signaling-dependent body length control and CO2 avoidance. Collectively, our findings suggest that cilium length is regulated by various pathways and that the IFT-associated kinase CDKL-1 is essential for the construction of a specific ciliary compartment and contributes to development and sensory physiology.

l-Tryptophan: Antioxidant as a Film-Forming Additive for a High-Voltage Cathode.

l-tryptophan (TrP) was investigated as a functional film-forming additive on a lithium-rich layered oxide cathode because it has a much lower oxidation potential than other common carbonate-based electrolytes. Owing to its prior oxidation to a base electrolyte, an artificial cathode-electrolyte interphase (CEI) was formed on the cathode surface, which could be confirmed via X-ray photoelectron spectroscopy and scanning electron microscopy and verified through density functional theory calculations. The functional film formed on the cathode surface suppressed the side reactions between the cathode and electrolyte during cell cycling. As a result, the film prevented CEI thickening and performance deterioration. The optimum weight of TrP was determined to be 0.4 wt % for obtaining the best performance.

High-Ni cathode material improved with Zr for stable cycling of Li-ion rechargeable batteries.

The Zr solvent solution method, which allows primary and secondary particles of LiNi0.90Co0.05Mn0.05O2 (NCM) to be uniformly doped with Zr and simultaneously to be coated with an Li2ZrO3 layer, is introduced in this paper. For Zr doped NCM, which is formed using the Zr solvent solution method (L-NCM), most of the pinholes inside the precursor disappear owing to the diffusion of the Zr dopant solution compared with Zr-doped NCM, which is formed using the dry solid mixing method from the (Ni0.90Co0.05Mn0.05)(OH)2 precursor and the Zr source (S-NCM), and Li2ZrO3 is formed at the pinhole sites. The mechanical strength of the powder is enhanced by the removal of the pinholes by the formation of Li2ZrO3 resulting from diffusion of the solvent during the mixing process, which provides protection from cracking. The coating layer functions as a protective layer during the washing process for removing the residual Li. The electrochemical performance is improved by the synergetic effects of suitable coatings and the enhanced structural stability. The capacity-retentions for 2032 coin cells are 86.08%, 92.12%, and 96.85% at the 50th cycle for pristine NCM, S-NCM, and L-NCM, respectively. The superiority of the liquid mixing method is demonstrated for 18 650 full cells. In the 300th cycle in the voltage range of 2.8-4.35 V, the capacity-retentions for S-NCM and L-NCM are 77.72% and 81.95%, respectively.

EFHC1, implicated in juvenile myoclonic epilepsy, functions at the cilium and synapse to modulate dopamine signaling.

Neurons throughout the mammalian brain possess non-motile cilia, organelles with varied functions in sensory physiology and cellular signaling. Yet, the roles of cilia in these neurons are poorly understood. To shed light into their functions, we studied EFHC1, an evolutionarily conserved protein required for motile cilia function and linked to a common form of inherited epilepsy in humans, juvenile myoclonic epilepsy (JME). We demonstrate that C. elegans EFHC-1 functions within specialized non-motile mechanosensory cilia, where it regulates neuronal activation and dopamine signaling. EFHC-1 also localizes at the synapse, where it further modulates dopamine signaling in cooperation with the orthologue of an R-type voltage-gated calcium channel. Our findings unveil a previously undescribed dual-regulation of neuronal excitability at sites of neuronal sensory input (cilium) and neuronal output (synapse). Such a distributed regulatory mechanism may be essential for establishing neuronal activation thresholds under physiological conditions, and when impaired, may represent a novel pathomechanism for epilepsy.

Machine learning assisted optimization of electrochemical properties for Ni-rich cathode materials.

Optimizing synthesis parameters is the key to successfully design ideal Ni-rich cathode materials that satisfy principal electrochemical specifications. We herein implement machine learning algorithms using 330 experimental datasets, obtained from a controlled environment for reliability, to construct a predictive model. First, correlation values showed that the calcination temperature and the size of the particles are determining factors for achieving a long cycle life. Then, we compared the accuracy of seven different machine learning algorithms for predicting the initial capacity, capacity retention rate, and amount of residual Li. Remarkable predictive capability was obtained with the average value of coefficient of determinant, R2 = 0.833, from the extremely randomized tree with adaptive boosting algorithm. Furthermore, we propose a reverse engineering framework to search for experimental parameters that satisfy the target electrochemical specification. The proposed results were validated by experiments. The current results demonstrate that machine learning has great potential to accelerate the optimization process for the commercialization of cathode materials.

High-Performance and Industrially Feasible Ni-Rich Layered Cathode Materials by Integrating Coherent Interphase.

For developing the industrially feasible Ni-rich layered oxide cathode with extended cycle life, it is necessary to mitigate both the mechanical degradation due to intergranular cracking between primary particles and gas generation from the reaction between the electrolyte and residual Li in the cathode. To simultaneously resolve these two issues, we herein propose a simple but novel method to reinforce the primary particles in LiNi0.91Co0.06Mn0.03O2 by providing a Li-reactive material, whose spinel interphase is coherent with the surface of the cathode. The modified structure significantly outperforms analogous bare samples: they conserve more than 90% of the initial capacity after 50 cycles and also exhibit a greater rate capability. By tracking the same particle location during cycling, we confirmed that the current method significantly reduces crack generation because the provided coating material can penetrate inside the grain boundary of the secondary particle and help maintain the volume of the primary particle. Finally, first-principles calculations were implemented to determine the role of this spinel material, i.e., having intrinsically isotropic lattice parameters, superior mechanical properties, and only a small volume change during delithiation. We believe that the proposed method is straightforward and cost-effective; hence, it is directly applicable for the mass production of Ni-rich cathode material to enable its commercialization.

The Effects of Curcuma longa L., Purple Sweet Potato, and Mixtures of the Two on Immunomodulation in C57BL/6J Mice Infected with LP-BM5 Murine Leukemia Retrovirus.

The immune response is stimulated to protect the body from external antigens and is controlled by several types of immune cells. In the present study, the immunomodulatory effects of Curcuma longa L., purple sweet potato, and mixtures of the two (CPM) were investigated in C57BL/6 mice infected with LP-BM5 murine leukemia virus (MuLV). Mice were divided into seven groups as follows: normal control, infected control (LP-BM5 MuLV infection), positive control (LP-BM5 MuLV infection+dietary supplement of red ginseng 300 mg/kg body weight), the original powder of C. longa L. (C; LP-BM5 MuLV infection+dietary supplement of C 189 mg/kg body weight), the original powder of purple sweet potato (P; LP-BM5 MuLV infection+dietary supplement of P 1811 mg/kg body weight), CPM Low (CPL; LP-BM5 MuLV infection+CPM 2 g/kg body weight), and CPM High (CPH; LP-BM5 MuLV infection+CPM 5 g/kg body weight). Dietary supplementation lasted for 12 weeks. Dietary supplementation of CPM inhibited LP-BM5 MuLV-induced lymphadenopathy and splenomegaly and inhibited reduction of messenger RNA (mRNA) expression of major histocompatibility complex (MHC) I and II. Moreover, CPM reduced the decrease in T- and B cell proliferation, reduced the population of CD4(+)/CD8(+) T cells, and remedied the unbalanced production of T helper-1 (Th1)/T helper-2 (Th2) cytokines in LP-BM5 MuLV-infected mice. In addition, CPM inhibited reduction of phagocytosis in peritoneal macrophages and decreased serum levels of immunoglobulin A (IgA), immunoglobulin E (IgE), and immunoglobulin G (IgG). These results suggest that CPM had a positive effect on immunomodulation in C57BL/6 mice induced by LP-BM5 leukemia retrovirus infection.

CDKL Family Kinases Have Evolved Distinct Structural Features and Ciliary Function.

Various kinases, including a cyclin-dependent kinase (CDK) family member, regulate the growth and functions of primary cilia, which perform essential roles in signaling and development. Neurological disorders linked to CDK-Like (CDKL) proteins suggest that these underexplored kinases may have similar functions. Here, we present the crystal structures of human CDKL1, CDKL2, CDKL3, and CDKL5, revealing their evolutionary divergence from CDK and mitogen-activated protein kinases (MAPKs), including an unusual ?J helix important for CDKL2 and CDKL3 activity. C. elegans CDKL-1, most closely related to CDKL1-4 and localized to neuronal cilia transition zones, modulates cilium length; this depends on its kinase activity and ?J helix-containing C terminus. Human CDKL5, linked to Rett syndrome, also localizes to cilia, and it impairs ciliogenesis when overexpressed. CDKL5 patient mutations modeled in CDKL-1 cause localization and/or cilium length defects. Together, our studies establish a disease model system suggesting cilium length defects as a pathomechanism for neurological disorders, including epilepsy.

Graphene balls for lithium rechargeable batteries with fast charging and high volumetric energy densities.

Improving one property without sacrificing others is challenging for lithium-ion batteries due to the trade-off nature among key parameters. Here we report a chemical vapor deposition process to grow a graphene-silica assembly, called a graphene ball. Its hierarchical three-dimensional structure with the silicon oxide nanoparticle center allows even 1 wt% graphene ball to be uniformly coated onto a nickel-rich layered cathode via scalable Nobilta milling. The graphene-ball coating improves cycle life and fast charging capability by suppressing detrimental side reactions and providing efficient conductive pathways. The graphene ball itself also serves as an anode material with a high specific capacity of 716.2 mAh g-1. A full-cell incorporating graphene balls increases the volumetric energy density by 27.6% compared to a control cell without graphene balls, showing the possibility of achieving 800 Wh L-1 in a commercial cell setting, along with a high cyclability of 78.6% capacity retention after 500 cycles at 5C and 60 °C.

Improved electrochemical properties of LiNi0.91Co0.06Mn0.03O2 cathode material via Li-reactive coating with metal phosphates.

Ni-rich layered oxides are promising cathode materials due to their high capacities. However, their synthesis process retains a large amount of Li residue on the surface, which is a main source of gas generation during operation of the battery. In this study, combined with simulation and experiment, we propose the optimal metal phosphate coating materials for removing residual Li from the surface of the Ni-rich layered oxide cathode material LiNi0.91Co0.06Mn0.03O2. First-principles-based screening process for 16 metal phosphates is performed to identify an ideal coating material that is highly reactive to Li2O. By constructing the phase diagram, we obtain the equilibrium phases from the reaction of coating materials and Li2O, based on a database using a DFT hybrid functional. Experimental verification for this approach is accomplished with Mn3(PO4)2, Co3(PO4)2, Fe3(PO4)2, and TiPO4. The Li-removing capabilities of these materials are comparable to the calculated results. In addition, electrochemical performances up to 50 charge/discharge cycles show that Mn-, Co-, Fe-phosphate materials are superior to an uncoated sample in terms of preventing capacity fading behavior, while TiPO4 shows poor initial capacity and rapid reduction of capacity during cycling. Finally, Li-containing equilibrium phases examined from XRD analysis are in agreement with the simulation results.

Computational Screening for Design of Optimal Coating Materials to Suppress Gas Evolution in Li-Ion Battery Cathodes.

Ni-rich layered oxides are attractive materials owing to their potentially high capacity for cathode applications. However, when used as cathodes in Li-ion batteries, they contain a large amount of Li residues, which degrade the electrochemical properties because they are the source of gas generation inside the battery. Here, we propose a computational approach to designing optimal coating materials that prevent gas evolution by removing residual Li from the surface of the battery cathode. To discover promising coating materials, the reactions of 16 metal phosphates (MPs) and 45 metal oxides (MOs) with the Li residues, LiOH, and Li2CO3 are examined within a thermodynamic framework. A materials database is constructed according to density functional theory using a hybrid functional, and the reaction products are obtained according to the phases in thermodynamic equilibrium in the phase diagram. In addition, the gravimetric efficiency is calculated to identify coating materials that can eliminate Li residues with a minimal weight of the coating material. Overall, more MP and MO materials react with LiOH than with Li2CO3. Specifically, MPs exhibit better reactivity to both Li residues, whereas MOs react more with LiOH. The reaction products, such as Li-containing phosphates or oxides, are also obtained to identify the phases on the surface of a cathode after coating. On the basis of the Pareto-front analysis, P2O5 could be an optimal material for the reaction with both Li residuals. Finally, the reactivity of the coating materials containing 3d/4d transition metal elements is better than that of materials containing other types of elements.

Re-construction layer effect of LiNi0.8Co0.15Mn0.05O2 with solvent evaporation process.

The solvent evaporation method on the structural changes and surface chemistry of the cathode and the effect of electrochemical performance of Li1.0Ni0.8Co0.15Mn0.05O2 (NCM) has been investigated. After dissolving of Li residuals using minimum content of solvent in order to minimize the damage of pristine material and the evaporation time, the solvent was evaporated without filtering and remaining powder was re-heated at 700 °C in oxygen environment. Two kinds of solvent, de-ionized water and diluted nitric acid, were used as a solvent. The almost 40% of Li residuals were removed using solvent evaporation method. The NCM sample after solvent evaporation process exhibited an increase in the initial capacity (214.3 mAh/g) compared to the pristine sample (207.4 mAh/g) at 0.1C because of enhancement of electric conductivity caused by decline of Li residuals. The capacity retention of NCM sample after solvent evaporation process (96.0% at the 50th cycle) was also improved compared to that of the pristine NCM sample (90.6% at the 50th cycle). The uniform Li residual layer after solvent treated and heat treatment acted like a coating layer, leading to enhance the cycle performance. The NCM sample using diluted nitric acid showed better performance than that using de-ionized water.

Tetrathiafulvalene as a Conductive Film-Making Additive on High-Voltage Cathode.

Tetrathiafulvalene (TTF) is investigated as a conductive film-making additive on an overlithiated layered oxide (OLO) cathode. When the OLO/graphite cell is cycled at high voltage, carbonate-based electrolyte without the additive decomposes continuously to form a thick and highly resistant surface film on the cathode. In contrast, TTF added into the electrolyte becomes oxidized before the electrolyte solvents, creating a thinner film on the cathode surface. This film inhibits further electrolyte decomposition through cycling and stabilizes the interface between the cathode and the electrolyte. The cells containing the OLO cathode with TTF-added electrolyte afforded enhanced capacity retention and rate capability, making TTF a prospective electrolyte additive for higher energy density lithium-ion cells.