Abstract DNA methylation plays vital roles in both prokaryotes and eukaryotes. There are three forms of DNA methylation in prokaryotes: N 6 -methyladenine (6mA), N 4 -methylcytosine (4mC), and 5-methylcytosine (5mC). Although many sequencing methods have been developed to sequence specific types of methylation, few technologies can be used for efficiently mapping multiple types of methylation. Here, we present NT-seq for mapping all three types of methylation simultaneously. NT-seq reliably detects all known methylation motifs in two bacterial genomes and can be used for identifying de novo methylation motifs. NT-seq provides a simple and efficient solution for detecting multiple types of DNA methylation.
Abstract Although the flexibility of the quasi−solid polymer electrolyte favors its surface conformal to the electrode, interfacial damage originating from side reactions between the electrolyte and the electrode remains dominant for battery failure. The design of quasi−solid electrolytes compatible with both aggressive nickel−rich cathode and lithium metal anode persists critical to the application of quasi−solid high−voltage lithium metal batteries (LMBs). Herein, a chemical/electrochemical response strategy is proposed to construct simultaneously stable cathodic and anodic interfaces relying on the synergistic effect of 1,4,7,10,13,16−hexaoxacyclooctadecane (18C6) and LiNO 3 . The distinctive [18C6Li] + NO 3 − cluster modifies electric double layer structure by specific adsorption on the electrode, thereby regulating the interfacial layer composition and construction. The NO 3 − on electrode preferentially decomposes to improve the interfacial performances, leaving the [18C6Li] + to cut off the side reaction. Furthermore, the 18C6 coordinates with detrimental transition metal ions from NMC811 cathode and converts into useful clusters alleviating the knock−on effect. Thus, the quasi−solid electrolyte with 18C6 and LiNO 3 enables Li||NMC811 coin cell to cycle stably over wide operation temperature (0−55 °C), especially, achieving high capacity retention of 79.2% after 300 cycles at 30 °C. This chemical/electrochemical response strategy projects new insights into the design of smart reactive electrolytes for high−voltage LMBs.
Constructing composite solid electrolytes (CSEs) integrating the merits of inorganic and organic components is a promising approach to developing high-performance all-solid-state lithium metal batteries (ASSLMBs). CSEs are now capable of achieving homogeneous and fast Li-ion flux, but how to escape the trade-off between mechanical modulus and adhesion is still a challenge. Herein, a strategy to address this issue is proposed, that is, intercalating highly conductive, homogeneous, and viscous-fluid ionic conductors into robust coordination laminar framework to construct laminar solid electrolyte with homogeneous and fast Li-ion conduction (LSE-HFC). A 9 µm-thick LSH-HFC, in which poly(ethylene oxide)/succinonitrile is adsorbed by coordination laminar framework with metal-organic framework nanosheets as building blocks, is used here as an example to determine the validity. The Li-ion transfer mechanism is verified and works across the entire LSE-HFC, which facilitates homogeneous Li-ion flux and low migration energy barriers, endowing LSE-HFC with high ionic conductivity of 5.62 × 10
This study aimed to identify biomarkers for chronic kidney disease (CKD) by studying serum metabolomics. Serum samples were collected from 194 non-dialysis CKD patients and 317 healthy controls (HC). Using ultra-high-performance liquid chromatography-tandem mass spectrometry (UPLC-MS), untargeted metabolomics analysis was conducted. A random forest model was developed and validated in separate sets of HC and CKD patients. The serum metabolomic profiles of patients with chronic kidney disease (CKD) exhibited significant differences compared to healthy controls (HC). A total of 314 metabolites were identified as significantly different, with 179 being upregulated and 135 being downregulated in CKD patients. KEGG enrichment analysis revealed several key pathways, including arginine biosynthesis, phenylalanine metabolism, linoleic acid metabolism, and purine metabolism. The diagnostic efficacy of the classifier was high, with an area under the curve of 1 in the training and validation sets and 0.9435 in the cross-validation set. This study provides comprehensive insights into serum metabolism in non-dialysis CKD patients, highlighting the potential involvement of abnormal biological metabolism in CKD pathogenesis. Exploring metabolites may offer new possibilities for the management of CKD.
Abstract Inorganic superionic conductor holds great promise for high‐performance all‐solid‐state lithium batteries. However, the ionic conductivity of traditional inorganic solid electrolytes (ISEs) is always unsatisfactory owing to the grain boundary resistance and large thickness. Here, a 13 μm‐thick laminar framework with ≈1.3 nm interlayer channels is fabricated by self‐assembling rigid, hydrophilic vermiculite (Vr) nanosheets. Then, Li 0.33 La 0.557 TiO 3 (LLTO) precursors are impregnated in interlayer channels and afterwards in situ sintered to large‐size, oriented, and defect‐free LLTO crystal. We demonstrate that the confinement effect permits ordered arrangement of LLTO crystal along the c ‐axis (the fastest Li + transfer direction), permitting the resultant 15 μm‐thick Vr‐LLTO electrolyte an ionic conductivity of 8.22×10 −5 S cm −1 and conductance of 87.2 mS at 30 °C. These values are several times’ higher than that of traditional LLTO‐based electrolytes. Moreover, Vr‐LLTO electrolyte has a compressive modulus of 1.24 GPa. Excellent cycling performance is demonstrated with all‐solid‐state Li/LiFePO 4 battery.
The occurrence of markedly accelerated tumor growth during immunotherapy is considered a new mode of progression called hyperprogressive disease (HPD) and its impact on pancreatic cancer (PC) patients receiving immunotherapy is unknown. In this study, we described and explored the incidence, prognosis and predictors of HPD in patients with advanced PC treated with programmed cell death-1 (PD-1) inhibitors. We retrospectively analyzed clinicopathological data from 104 patients with advanced pancreatic cancer who were treated with PD-1 inhibitors at our institution during 2015–2020 and identified 10 (9.6%) patients with HPD. Overall survival (OS) was significantly poorer in patients with HPD compared to patients with progressive disease (PD) (median OS: 5.6 vs. 3.6 months, p < .01). Clinicopathological factors associated with the occurrence of HPD included smoking, metastatic sites >2, liver metastasis, antibiotic therapy within 21 days before immunotherapy (Abx B21), hemoglobin (Hb) level <110 g/L, and PD-1 inhibitor treatment line >2. Subgroup analysis showed that high levels of CA19-9 at baseline were associated with the development of subsequent HPD (p = .024) and a worse prognosis (mOS:16.2 months vs. 6.1 months, p < .01). Our study demonstrated that HPD may occur in PC patients treated with PD-1 inhibitors and is associated with several clinicopathological characteristics and poor prognosis. The baseline tumor marker CA19-9 may be one of the early predictors of HPD development in PC patients receiving immunotherapy.
Smart Electrolytes In article number 2304532, Yun Lu, Yuefeng Su, Lai Chen, and co-workers report on a quasi−solid polymer electrolyte that enables the operation of high−voltage lithium metal batteries under critical conditions by addressing the nasty interface issues. The proposed chemical/electrochemical response triggered by 18-crown-6 and LiNO3 is critical for battery performance improvement and could potentially contribute to more knowledge−driven engineering of smart electrolytes.
Developing laminar composite solid electrolyte with ultrathin thickness and continuous conduction channels in vertical direction holds great promise for all‐solid‐state lithium batteries. Herein, a thin, laminar solid electrolyte is synthesized by filtrating –NH 2 functionalized metal‐organic framework nanosheets and then being threaded with poly(ethylene oxide) chains induced by the hydrogen‐bonding interaction from –NH 2 groups. It is demonstrated that the threaded poly(ethylene oxide) chains lock the adjacent metal‐organic framework nanosheets, giving highly enhanced structural stability (Young’s modulus, 1.3 GPa) to 7.5‐μm‐thick laminar composite solid electrolyte. Importantly, these poly(ethylene oxide) chains with stretching structure serve as continuous conduction pathways along the chains in pores. It makes the non‐conduction laminar metal‐organic framework electrolyte highly conductive: 3.97 × 10 −5 S cm −1 at 25 °C, which is even over 25 times higher than that of pure poly(ethylene oxide) electrolyte. The assembled lithium cell, thus, acquires superior cycling stability, initial discharge capacity (148 mAh g −1 at 0.5 C and 60 °C), and retention (94% after 150 cycles). Besides, the pore size of nanosheet is tailored (24.5–40.9 Å) to evaluate the mechanisms of chain conformation and ion transport in confined space. It shows that the confined pore only with proper size could facilitate the stretching of poly(ethylene oxide) chains, and meanwhile inhibit their disorder degree. Specifically, the pore size of 33.8 Å shows optimized confinement effect with trans ‐poly(ethylene oxide) and cis ‐poly(ethylene oxide) conformation, which offers great significance in ion conduction. Our design of poly(ethylene oxide)‐threaded architecture provides a platform and paves a way to the rational design of next‐generation high‐performance porous electrolytes.
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