Deletion of histamine H2 receptor in VTA dopaminergic neurons of mice induces behavior reminiscent of mania.

Hyperfunction of the dopamine system has been implicated in manic episodes in bipolar disorders. How dopaminergic neuronal function is regulated in the pathogenesis of mania remains unclear. Histaminergic neurons project dense efferents into the midbrain dopaminergic nuclei. Here, we present mice lacking dopaminergic histamine H2 receptor (H2R) in the ventral tegmental area (VTA) that exhibit a behavioral phenotype mirroring some of the symptoms of mania, including increased locomotor activity and reduced anxiety- and depression-like behavior. These behavioral deficits can be reversed by the mood stabilizers lithium and valproate. H2R deletion in dopaminergic neurons significantly enhances neuronal activity, concurrent with a decrease in the γ-aminobutyric acid (GABA) type A receptor (GABAAR) membrane presence and inhibitory transmission. Conversely, either overexpression of H2R in VTA dopaminergic neurons or treatment of H2R agonist amthamine within the VTA counteracts amphetamine-induced hyperactivity. Together, our results demonstrate the engagement of H2R in reducing VTA dopaminergic activity, shedding light on the role of H2R as a potential target for mania therapy.

Design Unsaturated Selenium Coordinated NbSe2-x as Multifunctional Sulfur Electrocatalyst toward Fast and Durable Sulfur Reduction Reaction.

Lithium-sulfur (Li-S) battery are considered as the next generation energy storage system owing to their ultra-high theoretical specific capacity and energy density. However, the commercialization of Li-S battery is still hindered by the intrinsically low conductivity of sulfur, sluggish catalytic conversion and notorious shuttle effect of polysulfides. The implantation of defects in sulfur electrocatalyst can effectively increase its conductivity and catalytic efficiency of lithium polysulfides, but the current mainstream defective materials are limited and lack of in-depth research. Herein, a defective niobium selenide (NbSe2-x) nanosheet sulfur electrocatalyst is constructed with enriched selenium defects, which demonstrates strong interaction with sulfur species, endowing NbSe2-x with rapid and reliable sulfur reduction reaction. As a result, the Li-S cell with NbSe2-x exhibits excellent multiplicative performance in both coin cell and pouch cell, which maintains stable cycling for over 2000 cycles under 5 C, corresponding to a low-capacity fading rate of 0.024% per cycle. Ah level pouch cell is also fabricated, showing a decent energy density of 378 Wh kg-1. This creative strategy not only emphasizes the importance of selenium defect engineering in Li-S batterie toward practical application, but also enlightens the material engineering to realize superior performance in related energy storage and conversion area.

Designing Cooperative Ion Transport Pathway in Ultra-Thin Solid-State Electrolytes toward Practical Lithium Metal Batteries.

Solid polymer electrolytes (SPEs) are promising for high-energy-density solid-state Li metal batteries due to their decent flexibility, safety, and interfacial stability. However, their development was seriously hindered by the interfacial instability and limited conductivity, leading to inferior electrochemical performance.  Herein, we proposed to design ultra-thin solid-state electrolyte with long-range cooperative ion transport pathway to effectively increase the ionic conductivity and stability. The impregnation of PVDF-HFP inside pores of  fluorinated covalent organic framework (CF3-COF) can disrupt its symmetry, rendering rapid ion transportation and inhibited anion imigration. The functional groups of CF3-COF can interact with PVDF-HFP to form fast Li+ transport channels, which enables the uniform and confined Li+ conduction within the electrolyte. The introduction of CF3-COF also enhances the mechanical strength and flexibility of SPEs, as well as ensures homogeneous Li deposition and inhibited dendrite growth.  Hence, a remarkably high conductivity of 1.21×10-3 S cm-1 can be achieved. Finally, the ultra-thin SPEs with an extremely long cycle life exceed 9000 h can be obtained (the longest cycle life reported until now) while the NCM523/Li pouch cell demonstrates a high capacity of 760 mAh and 96% capacity retention after cycling, holding great promises to be utilized for practical solid-state Li metal batteries.

Molybdenum-Doped Cobalt-Free Cathode Realizing the Electrochemical Stability by Enhanced Covalent Bonding.

The doping strategy effectively enhances the capacity and cycling stability of cobalt-free nickel-rich cathodes. Understanding the intrinsic contributions of dopants is of great importance to optimize the performances of cathodes. This study investigates the correlation between the structure modification and their performances of Mo-doped LiNi0.8Mn0.2O2 (NM82) cathode. The role of doped Mo's valence state has been proved functional in both lattice structural modification and electronic state adjustment. Although the high-valence of Mo at the cathode surface inevitably reduces Ni valence for electronic neutrality and thus causes ion mixing, the original Mo valence will influence its diffusion depth. Structural analyses reveal Mo doping leads to a mixed layer on the surface, where high-valence Mo forms a slender cation mixing layer, enhancing structural stability and Li-ion transport. In addition, it is found that the high-valence dopant of Mo6+ ions partially occupies the unfilled 4d orbitals, which may strengthen the Mo─O bond through increased covalency and therefore reduce the oxygen mobility. This results in an impressive capacity retention (90.0% after 200 cycles) for Mo-NM82 cathodes with a high Mo valence state. These findings underscore the valence effect of doping on layered oxide cathode performance, offering guidance for next-generation cathode development.

Generation of attosecond gigawatt soft x-ray pulses through coherent Thomson backscattering.

Collision between relativistic electron sheets and counterpropagating laser pulses is recognized as a promising way to produce intense attosecond x rays through coherent Thomson backscattering (TBS). In a double-layer scheme, the electrons in an ultrathin solid foil are first pushed out by an intense laser driver and then interact with the laser reflected off a second foil to form a high-density relativistic electron sheet with vanishing transverse momentum. However, the repulsion between these concentrated electrons can increase the thickness of the layer, reducing both its density and subsequently the coherent TBS. Here, we present a systematic study on the evolution of the flying electron layer and find that its resulting thickness is determined by the interplay between the intrinsic space-charge expansion and the velocity compression induced by the drive laser. How the laser driver, the target areal density, the reflector, and the collision laser intensity affect the properties of the produced x rays is explored. Multidimensional particle-in-cell simulations indicate that employing this scheme in the nonlinear regime has the potential to stably produce soft x rays with several gigawatt peak power in hundreds of terawatt ultrafast laser facilities. The pulse duration can be tuned to tens of attoseconds. This compact and intense attosecond x-ray source may have broad applications in attosecond science.

Conductive Zeolite Supported Indium-Tin Alloy Nanoclusters for Selective and Scalable Formic Acid Electrosynthesis.

Upgrading excess CO2 toward the electrosynthesis of formic acid is of significant research and commercial interest. However, simultaneously achieving high selectivity and industrially relevant current densities of CO2-to-formate conversion remains a grand challenge for practical implementations. Here, an electrically conductive zeolite support is strategically designed by implanting Sn ions into the skeleton structure of a zeolite Y, which impregnates ultrasmall In0.2Sn0.8 alloy nanoclusters into the supercages of the tailored 12-ring framework. The prominent electronic and geometric interactions between In0.2Sn0.8 nanoalloy and zeolite support lead to the delocalization of electron density that enhances orbital hybridizations between In active site and *OCHO intermediate. Thus, the energy barrier for the rate-limiting *OCHO formation step is reduced, facilitating the electrocatalytic hydrogenation of CO2 to formic acid. Accordingly, the developed zeolite electrocatalyst achieves an industrial-level partial current density of 322 mA cm-2 and remarkable Faradaic efficiency of 98.2% for formate production and stably maintains Faradaic efficiency above 93% at an industrially relevant current density for over 102 h. This work opens up new opportunities of conductive zeolite-based electrocatalysts for industrial-level formic acid electrosynthesis from CO2 electrolysis and toward practically accessible electrocatalysis and energy conversion.

Conformal Engineering of Both Electrodes Toward High-Performance Flexible Quasi-Solid-State Zn-Ion Micro-Supercapacitors.

The severe Zn-dendrite growth and insufficient carbon-based cathode performance are two critical issues that hinder the practical applications of flexible Zn-ion micro-ssupercapacitors (FZCs). Herein, a self-adaptive electrode design concept of the synchronous improvement on both the cathode and anode is proposed to enhance the overall performance of FZCs. Polypyrrole doped with anti-expansion graphene oxide and acrylamide (PPy/GO-AM) on the cathode side can exhibit remarkable electrochemical performance, including decent capacitance and cycling stability, as well as exceptional mechanical properties. Meanwhile, a robust protective polymeric layer containing reduced graphene oxide and polyacrylamide is self-assembled onto the Zn surface (rGO/PAM@Zn) at the anode side, by which the "tip effect" of Zn small protuberance can be effectively alleviated, the Zn-ion distribution homogenized, and dendrite growth restricted. Benefiting from these advantages, the FZCs deliver an excellent specific capacitance of 125 mF cm-2 (125 F cm-3) at 1 mA cm-2, along with a maximum energy density of 44.4 µWh cm-2, and outstanding long-term durability with 90.3% capacitance remained after 5000 cycles. This conformal electrode design strategy is believed to enlighten the practical design of high-performance in-plane flexible Zn-based electrochemical energy storage devices (EESDs) by simultaneously tackling the challenges faced by Zn anodes and capacitance-type cathodes.

Cellular heterogeneity and dynamics of the human uterus in healthy premenopausal women.

The human uterus is a complex and dynamic organ whose lining grows, remodels, and regenerates in every menstrual cycle or upon tissue damage. Here we applied single-cell RNA sequencing to profile more the 50,000 uterine cells from both the endometrium and myometrium of 5 healthy premenopausal individuals, and jointly analyzed the data with a previously published dataset from 15 subjects. The resulting normal uterus cell atlas contains more than 167K cells representing the lymphatic endothelium, blood endothelium, stromal, ciliated epithelium, unciliated epithelium, and immune cell populations. Focused analyses within each major cell type and comparisons with subtype labels from prior studies allowed us to document supporting evidence, resolve naming conflicts, and to propose a consensus annotation system of 39 subtypes. We release their gene expression centroids, differentially expressed genes, and mRNA patterns of literature-based markers as a shared community resource. We find many subtypes show dynamic changes over different phases of the cycle and identify multiple potential progenitor cells: compartment-wide progenitors for each major cell type, transitional cells that are upstream of other subtypes, and potential cross-lineage multipotent stromal progenitors that may be capable of replenishing the epithelial, stromal, and endothelial compartments. When compared to the healthy premenopausal samples, a postpartum and a postmenopausal uterus sample revealed substantially altered tissue composition, involving the rise or fall of stromal, endothelial, and immune cells. The cell taxonomy and molecular markers we report here are expected to inform studies of both basic biology of uterine function and its disorders. SIGNIFICANCE: We present single-cell RNA sequencing data from seven individuals (five healthy pre-menopausal women, one post-menopausal woman, and one postpartum) and perform an integrated analysis of this data alongside 15 previously published scRNA-seq datasets. We identified 39 distinct cell subtypes across four major cell types in the uterus. By using RNA velocity analysis and centroid-centroid comparisons we identify multiple computationally predicted progenitor populations for each of the major cell compartments, as well as potential cross-compartment, multi-potent progenitors. While the function and interactions of these cell populations remain to be validated through future experiments, the markers and their "dual characteristics" that we describe will serve as a rich resource to the scientific community. Importantly, we address a significant challenge in the field: reconciling multiple uterine cell taxonomies being proposed. To achieve this, we focused on integrating historical and contemporary knowledge across multiple studies. By providing detailed evidence used for cell classification we lay the groundwork for establishing a stable, consensus cell atlas of the human uterus.

Cellular atlas of the human ovary using morphologically guided spatial transcriptomics and single-cell sequencing.

The reproductive and endocrine functions of the ovary involve spatially defined interactions among specialized cell populations. Despite the ovary's importance in fertility and endocrine health, functional attributes of ovarian cells are largely uncharacterized. Here, we profiled >18,000 genes in 257 regions from the ovaries of two premenopausal donors to examine the functional units in the ovary. We also generated single-cell RNA sequencing data for 21,198 cells from three additional donors and identified four major cell types and four immune cell subtypes. Custom selection of sampling areas revealed distinct gene activities for oocytes, theca, and granulosa cells. These data contributed panels of oocyte-, theca-, and granulosa-specific genes, thus expanding the knowledge of molecular programs driving follicle development. Serial samples around oocytes and across the cortex and medulla uncovered previously unappreciated variation of hormone and extracellular matrix remodeling activities. This combined spatial and single-cell atlas serves as a resource for future studies of rare cells and pathological states in the ovary.

Steric-hindrance Effect Tuned Ion Solvation Enabling High Performance Aqueous Zinc Ion Batteries.

Despite many additives have been reported for aqueous zinc ion batteries, steric-hindrance effect of additives and its correlation with Zn2+ solvation structure have been rarely reported. Herein, large-sized sucrose biomolecule is selected as a paradigm additive, and steric-hindrance electrolytes (STEs) are developed to investigate the steric-hindrance effect for solvation structure regulation. Sucrose molecules do not participate in Zn2+ solvation shell, but significantly homogenize the distribution of solvated Zn2+ and enlarge Zn2+ solvation shell with weakened Zn2+-H2O interaction due to the steric-hindrance effect. More importantly, STEs afford the water-shielding electric double layer and in situ construct the organic and inorganic hybrid solid electrolyte interface, which effectively boost Zn anode reversibility. Remarkably, Zn//NVO battery presents high capacity of 3.9 mAh ⋅ cm-2 with long cycling stability for over 650 cycles at lean electrolyte of 4.5 µL ⋅ mg-1 and low N/P ratio of 1.5, and the stable operation at wide temperature (-20 °C~+40 °C).

Selective and Scalable CO2 Electrolysis Enabled by Conductive Zinc Ion-Implanted Zeolite-Supported Cadmium Oxide Nanoclusters.

Catalyst supports play an essential role in catalytic reactions, hinting at pronounced metal-support effects. Zeolites are a propitious support in heterogeneous catalysts, while their use in the electrocatalytic CO2 reduction reaction has been limited as yet because of their electrically insulating nature and serious competing hydrogen evolution reaction (HER). Enlightened by theoretical prediction, herein, we implant zinc ions into the structural skeleton of a zeolite Y to strategically tailor a favorable electrocatalytic platform with remarkably enhanced electronic conduction and strong HER inhibition capability, which incorporates ultrafine cadmium oxide nanoclusters as guest species into the supercages of the tailored 12-ring window framework. The metal d-bandwidth tuning of cadmium by skeletal zinc steers the extent of substrate-molecule orbital mixing, enhancing the stabilization of the key intermediate *COOH while weakening the CO poisoning effect. Furthermore, the strong cadmium-zinc interplay causes a considerable thermodynamic barrier for water dissociation in the conversion of H+ to *H, potently suppressing the competing HER. Therefore, we achieve an industrial-level partial current density of 335 mA cm-2 and remarkable Faradaic efficiency of 97.1% for CO production and stably maintain Faradaic efficiency above 90% at the industrially relevant current density for over 120 h. This work provides a proof of concept of tailored conductive zeolite as a favorable electrocatalytic support for industrial-level CO2 electrolysis and will significantly enhance the adaptability of conductive zeolite-based electrocatalysts in a variety of electrocatalysis and energy conversion applications.

Longevous Cycling of Rechargeable Zn-Air Battery Enabled by "Raisin-Bread" Cobalt Oxynitride/Porous Carbon Hybrid Electrocatalysts.

Developing commercially viable electrocatalyst lies at the research hotspot of rechargeable Zn-air batteries, but it is still challenging to meet the requirements of energy efficiency and durability in realistic applications. Strategic material design is critical to addressing its drawbacks in terms of sluggish kinetics of oxygen reactions and limited battery lifespan. Herein, a "raisin-bread" architecture is designed for a hybrid catalyst constituting cobalt nitride as the core nanoparticle with thin oxidized coverings, which is further deposited within porous carbon aerogel. Based on synchrotron-based characterizations, this hybrid provides oxygen vacancies and Co-Nx -C sites as the active sites, resulting from a strong coupling between CoOx Ny nanoparticles and 3D conductive carbon scaffolds. Compared to the oxide reference, it performs enhanced stability in harsh electrocatalytic environments, highlighting the benefits of the oxynitride. Furthermore, the 3D conductive scaffolds improve charge/mass transportation and boost durability of these active sites. Density functional theory calculations reveal that the introduced N species into hybrid can synergistically tune the d-band center of cobalt and improve its bifunctional activity. As a result, the obtained air cathode exhibits bifunctional overpotential of 0.65 V and a battery lifetime exceeding 1350 h, which sets a new record for rechargeable Zn-air battery reported so far.

Deriving early single-rosette brain organoids from human pluripotent stem cells.

Brain organoid methods are complicated by multiple rosette structures and morphological variability. We have developed a human brain organoid technique that generates self-organizing, single-rosette cortical organoids (SOSR-COs) with reproducible size and structure at early timepoints. Rather than patterning a 3-dimensional embryoid body, we initiate brain organoid formation from a 2-dimensional monolayer of human pluripotent stem cells patterned with small molecules into neuroepithelium and differentiated to cells of the developing dorsal cerebral cortex. This approach recapitulates the 2D to 3D developmental transition from neural plate to neural tube. Most monolayer fragments form spheres with a single central lumen. Over time, the SOSR-COs develop appropriate progenitor and cortical laminar cell types as shown by immunocytochemistry and single-cell RNA sequencing. At early time points, this method demonstrates robust structural phenotypes after chemical teratogen exposure or when modeling a genetic neurodevelopmental disorder, and should prove useful for studies of human brain development and disease modeling.

Homozygous CDH2 variant may be associated with hypopituitarism without neurological disorders.

Context: Congenital hypopituitarism is a genetically heterogeneous condition. Whole exome sequencing (WES) is a promising approach for molecular diagnosis of patients with this condition. Objectives: The aim of this study is to conduct WES in a patient with congenital hypopituitarism born to consanguineous parents, CDH2 screening in a cohort of patients with congenital hypopituitarism, and functional testing of a novel CDH2 variant. Design: Genomic DNA from a proband and her consanguineous parents was analyzed by WES. Copy number variants were evaluated. The genetic variants were filtered for population frequency (ExAC, 1000 genomes, gnomAD, and ABraOM), in silico prediction of pathogenicity, and gene expression in the pituitary and/or hypothalamus. Genomic DNA from 145 patients was screened for CDH2 by Sanger sequencing. Results: One female patient with deficiencies in growth hormone, thyroid-stimulating hormone, adrenocorticotropic hormone, luteinizing hormone, and follicle-stimulating hormone and ectopic posterior pituitary gland contained a rare homozygous c.865G>A (p.Val289Ile) variant in CDH2. To determine whether the p.Val289Ile variant in CDH2 affects cell adhesion properties, we stably transfected L1 fibroblast lines, labeled the cells with lipophilic dyes, and quantified aggregation. Large aggregates formed in cells expressing wildtype CDH2, but aggregation was impaired in cells transfected with variant CDH2 or non-transfected. Conclusion: A homozygous CDH2 allelic variant was found in one hypopituitarism patient, and the variant impaired cell aggregation function in vitro. No disease-causing variants were found in 145 other patients screened for CDH2 variants. Thus, CDH2 is a candidate gene for hypopituitarism that needs to be tested in different populations. Significance statement: A female patient with hypopituitarism was born from consanguineous parents and had a homozygous, likely pathogenic, CDH2 variant that impairs cell aggregation in vitro. No other likely pathogenic variants in CDH2 were identified in 145 hypopituitarism patients.

Histamine H2 receptor deficit in glutamatergic neurons contributes to the pathogenesis of schizophrenia.

Schizophrenia is a serious mental disorder, and existing antipsychotic drugs show limited efficacy and cause unwanted side effects. The development of glutamatergic drugs for schizophrenia is currently challenging. Most functions of histamine in the brain are mediated by the histamine H1 receptor; however, the role of the H2 receptor (H2R) is not quite clear, especially in schizophrenia. Here, we found that expression of H2R in glutamatergic neurons of the frontal cortex was decreased in schizophrenia patients. Selective knockout of the H2R gene (Hrh2) in glutamatergic neurons (CaMKIIα-Cre; Hrh2 fl/fl) induced schizophrenia-like phenotypes including sensorimotor gating deficits, increased susceptibility to hyperactivity, social withdrawal, anhedonia, and impaired working memory, as well as decreased firing of glutamatergic neurons in the medial prefrontal cortex (mPFC) in in vivo electrophysiological tests. Selective knockdown of H2R in glutamatergic neurons in the mPFC but not those in the hippocampus also mimicked these schizophrenia-like phenotypes. Furthermore, electrophysiology experiments established that H2R deficiency decreased the firing of glutamatergic neurons by enhancing the current through hyperpolarization-activated cyclic nucleotide-gated channels. In addition, either H2R overexpression in glutamatergic neurons or H2R agonism in the mPFC counteracted schizophrenia-like phenotypes in an MK-801-induced mouse model of schizophrenia. Taken together, our results suggest that deficit of H2R in mPFC glutamatergic neurons may be pivotal to the pathogenesis of schizophrenia and that H2R agonists can be regarded as potentially efficacious medications for schizophrenia therapy. The findings also provide evidence for enriching the conventional glutamate hypothesis for the pathogenesis of schizophrenia and improve the understanding of the functional role of H2R in the brain, especially in glutamatergic neurons.

Myh6 promoter-driven Cre recombinase excises floxed DNA fragments in a subset of male germline cells.

Myh6-Cre transgenic mouse line was known to express Cre recombinase only in the heart. Nevertheless, during breeding Myh6-Cre to Rosa26fstdTom reporter (tdTom) mouse line, we observed that a significant part of their F2 tdTom/+ offspring had tdTom reporter gene universally activated. Our results show that Myh6-Cre transgenic mice have Cre recombinase activity in a subpopulation of the male germline cells, and that Myh6 gene transcripts are enriched in the interstitial Leydig cells and the undifferentiated spermatogonia stem cells. In summary, the current study confirms that the previously known "heart-specific" Myh6 promoter drives Cre expression in the testis.

Advanced Material Engineering to Tailor Nucleation and Growth towards Uniform Deposition for Anode-Less Lithium Metal Batteries.

Anode-less lithium metal batteries (ALMBs), whether employing liquid or solid electrolytes, have significant advantages such as lowered costs and increased energy density over lithium metal batteries (LMBs). Among many issues, dendrite growth and non-uniform plating which results in poor coulombic efficiency are the key issues that viciously decrease the longevity of the ALMBs. As a result, lowering the nucleation barrier and facilitating lithium growth towards uniform plating is even more critical in ALMBs. While extensive reviews have focused to describe strategies to achieve high performance in LMBs and ALMBs, this review focuses on strategies designed to directly facilitate nucleation and growth of dendrite-free ALMBs. The review begins with a discussion of the primary components of ALMBs, followed by a brief theoretical analysis of the nucleation and growth mechanism for ALMBs. The review then emphasizes key examples for each strategy in order to highlight the mechanisms and rationale that facilitate lithium plating. By comparing the structure and mechanisms of key materials, the review discusses their benefits and drawbacks. Finally, major trends and key findings are summarized, as well as an outlook on the scientific and economic gaps in ALMBs.

Regulation of Outer Solvation Shell Toward Superior Low-Temperature Aqueous Zinc-Ion Batteries.

Aqueous Zn-ion batteries are well regarded among a next-generation energy-storage technology due to their low cost and high safety. However, the unstable stripping/plating process leading to severe dendrite growth under high current density and low temperature impede their practical application. Herein, it is demonstrated that the addition of 2-propanol can regulate the outer solvation shell structure of Zn2+ by replacing water molecules to establish a "eutectic solvation shell", which provides strong affinity with the Zn (101) crystalline plane and fast desolvation kinetics during the plating process, rendering homogeneous Zn deposition without dendrite formation. As a result, the Zn anode exhibits promising cycle stability over 500 h under an elevated current density of 15 mA cm-2 and high depth of discharge of 51.2%. Furthermore, remarkable electrochemical performance is achieved in a 150 mAh Zn|V2 O5 pouch cell over 1000 cycles at low temperature of -20 °C. This work not only offers a new strategy to achieve excellent performance of aqueous Zn-ion batteries under harsh conditions, but also reveals electrolyte structure designs that can be applied in related energy storage and conversion fields.

"Tree-Trunk" Design for Flexible Quasi-Solid-State Electrolytes with Hierarchical Ion-Channels Enabling Ultralong-Life Lithium-Metal Batteries.

The construction of robust (quasi)-solid-state electrolyte (SSE) for flexible lithium-metal batteries is desirable but extremely challenging. Herein, a novel, flexible, and robust quasi-solid-state electrolyte (QSSE) with a "tree-trunk" design is reported for ultralong-life lithium-metal batteries (LMBs). An in-situ-grown metal-organic framework (MOF) layer covers the cellulose-based framework to form hierarchical ion-channels, enabling rapid ionic transfer kinetics and excellent durability. A conductivity of 1.36 × 10-3  S cm-1 , a transference number of 0.72, an electrochemical window of 5.26 V, and a good rate performance are achieved. The flexible LMBs fabricated with as-designed QSSEs deliver areal capacity of up to 3.1 mAh cm-2 at the initial cycle with high mass loading of 14.8 mg cm-2 in Li-NCM811 cells and can retain ≈80% capacity retention after 300 cycles. An ultralong-life of 3000 cycles (6000 h) is also achieved in Li-LiFePO4 cells. This work presents a promising route in constructing a flexible QSSE toward ultralong-life LMBs, and also provides a design rationale for material and structure development in the area of energy storage and conversion.