SATCAS: A CRISPR/Cas13a-based simultaneous amplification and testing platform for one-pot RNA detection and SNPs distinguish in clinical diagnosis.

The clinical diagnosis of pathogen infectious diseases increasingly requires sensitive and rapid RNA detection technologies. The RNA-guided clustered regularly interspaced short palindromic repeats (CRISPR)/Cas13a system has shown immense potential in molecular diagnostics due to its trans-cleavage activity. However, most Cas13a-based detection methods require an amplicon transcription step, and the multi-step open-tube operations are prone to contamination, limiting their widespread application. Here, we propose an ultrasensitive (single-copy range, ∼aM) and rapid (within 40 min) isothermal one-pot RNA detection platform, termed SATCAS (Simultaneous Amplification and Testing platform based on Cas13a). This method effectively distinguishes viable bacteria (0%-100%) under constant total bacterial conditions, demonstrating its robustness and universality. SATCAS excels in identifying single nucleotide polymorphisms (SNPs), particularly detecting 0.5% drug-resistant mutations. We validated SATCAS by detecting infections in biological samples from 68 HBV, 23 EBV, and 48 SARS-CoV-2 patients, achieving 100% sensitivity, 92.86% specificity, and 97.06% accuracy in HBV infection testing. We anticipate that SATCAS has broad application potential in the early diagnosis, subtyping, drug resistance detection, and point-of-care monitoring of pathogen infectious diseases.

Acute nitrite exposure causes gut microbiota dysbacteriosis and proliferation of pathogenic Photobacterium in shrimp.

Nitrite exposure has become a significant concern in the aquaculture industry, posing a severe threat to aquatic animals such as shrimp. While studies have reported the adverse effects of nitrite on shrimp growth, the part played by the gut microbiota in shrimp mortality resulting from nitrite exposure is poorly understood. Here, the effects of nitrite on shrimp gut bacterial community were investigated using 16S rRNA amplicon sequencing, bacterial isolation, genomic analysis, and infection experiments. Compared to the control_healthy group, changes in the bacterial composition of the nitrite_dead group were associated with reduced abundance of specific beneficial bacteria and increased abundance of certain pathogenic bacteria. Notably, members of the Photobacterium genus were found to be significantly enriched in the nitrite_dead group. Genomic analysis of a representative Photobacterium strain (LvS-8n3) revealed a variety of genes encoding bacterial toxins, including hemolysin, adhesin, and phospholipase. Furthermore, it was also found that LvS-8n3 exhibits strong pathogenicity, probably due to its high production of pathogenic factors and the ability to utilize nitrite for proliferation. Therefore, the proliferation of pathogenic Photobacterium species appears pivotal for driving shrimp mortality caused by nitrite exposure. These findings provide novel insights into the disease mechanism in shrimp under conditions of environmental change.

Lethal and sublethal effects of spinosad on dengue vector mosquito, Aedes albopictus and bancroftian filariasis vector mosquito, Culex pipiens pallens.

BACKGROUND OBJECTIVES: Aedes albopictu and Culex pipiens pallens are important vectors of many viruses and have had resistance to chemical pesticide. Spinosad is a selective biological insecticide to control urban mosquito. The aim of this study was to reveal the sublethal effects of spinosad on mosquito and provide reference basis for integrated mosquito management. METHODS: The toxicity of spinosad against Ae. albopictus and Cx. pipiens pallens were determined under laboratory conditions by exposing early third-instar larvae to different concentrations. RESULTS: The LC50 values of spinosad to Ae. albopictus and Cx. Pipiens pallens larvaes were 4.44×10-3 mg∙L-1 and 1.93×10-3 mg∙L-1 respectively after 72 h exposure. Spinosad at sublethal concentrations has many negative effects on Ae. albopictus and Cx. Pipiens pallens larval, pupae, adult and offspring eggs, including significantly reduced their larvae pupation rate by 51.37% and 58.47%, significantly prolonged pupae length by 21.43% and 16.18%, reduced female wing-spans by 20.19% and 14.89%, reduced male wing-spans by 3.84% and 7.54%, reduced female weight by 29.04% and 31.52%, reduced male weight by 7.47% and 9.07%, reduced female and male ratio by 51.98% and 45.21%, reduced individual egg-laying amount by 15.73% and 35.51%, in addition, offspring egg hatchability were dramatically decreased by 25.71% and 34.04%, egg periods were significantly prolonged by 14.42% and 62.82% respectively. No significant effect on larval period, pupae emergence rate, female bite rates were observed. INTERPRETATION CONCLUSION: These results suggest that spinosad might affect pest population dynamics significantly and is fairly expected to be a candidate biological pesticide for mosquito control.

Efficient and markerless gene integration with SlugCas9-HF in Kluyveromyces marxianus.

The nonconventional yeast Kluyveromyces marxianus has potential for industrial production, but the lack of advanced synthetic biology tools for precise engineering hinders its rapid development. Here, we introduce a CRISPR-Cas9-mediated multilocus integration method for assembling multiple exogenous genes. Using SlugCas9-HF, a high-fidelity Cas9 nuclease, we enhance gene editing precision. Specific genomic loci predisposed to efficient integration and expression of heterologous genes are identified and combined with a set of paired CRISPR-Cas9 expression plasmids and donor plasmids to establish a CRISPR-based biosynthesis toolkit. This toolkit enables genome integration of large gene modules over 12 kb and achieves simultaneous quadruple-locus integration in a single step with 20% efficiency. As a proof-of-concept, we apply the toolkit to screen for gene combinations that promote heme production, revealing the importance of HEM4Km and HEM12Sc. This CRISPR-based toolkit simplifies the reconstruction of complex pathways in K. marxianus, broadening its application in synthetic biology.

Prevalence and associated factors of myopia among adolescents aged 12-15 in Shandong Province, China: a cross-sectional study.

Myopia is a growing concern worldwide, especially among adolescents. This study aimed to investigate the prevalence and associated factors of myopia in adolescents aged 12-15 in Shandong Province, China. This cross-sectional study adhered to the Strengthening the Reporting of Observational Studies in Epidemiology guidelines and involved stratified random cluster sampling of 128,678 students from 186 middle schools across 17 cities in Shandong Province. Data collection was conducted from March to April 2024. We excluded students with organic eye diseases, abnormal binocular vision functions, or a history of eye injuries or surgeries. Myopia was assessed using the standard logarithmic visual acuity chart and autorefractor without inducing ciliary muscle paralysis. A comprehensive questionnaire survey was conducted to gather demographic characteristics and daily life behaviors. With the chi-squared test for univariable analysis and multivariable logistic regression for identifying significant factors. This study included 126,375 participants, with a gender distribution of 51.02% male and 48.98% female. The overall prevalence of myopia was 71.34%. Higher prevalence was observed in girls (72.26%) compared to boys (70.45%), and the prevalence increased with age, peaking at 73.12% in 15-year-olds. Urban residents had a higher prevalence (71.86%) than rural (70.39%). Factors such as increased frequency of eye usage while lying down or leaning forward, frequent use of eyes while walking or riding in a car, prolonged screen time, and extended homework duration were associated with higher odds of developing myopia. Conversely, higher frequency of outdoor exercise, maintaining proper posture during reading and writing, greater distance from eyes to screen, and longer sleep duration were associated with lower odds. Additionally, female gender, older age, urban residence, and parental history of myopia increased the risk. The high prevalence of myopia among adolescents in Shandong Province was influenced by a combination of demographic, behavioral, and environmental factors. The study highlighted the importance of lifestyle modifications, such as increasing outdoor activities and maintaining proper visual habits, limiting the duration of screen exposure and homework sessions, and extending sleep duration, to mitigate the risk of developing myopia. These findings underscored the need for targeted public health interventions and educational campaigns to address this significant public health issue.

Characterization of NiCas12b for In Vivo Genome Editing.

The RNA-guided clustered regularly interspaced short palindromic repeats (CRISPR)/Cas12b system represents the third family of CRISPR-Cas systems that are harnessed for genome editing. However, only a few nucleases have demonstrated activity in human cells, and their in vivo therapeutic potential remains uncertain. In this study, a green fluorescent protein (GFP)-activation assay is conducted to screen a panel of 15 Cas12b orthologs, and four of them exhibited editing activity in mammalian cells. Particularly noteworthy is the NiCas12b derived from Nitrospira sp., which recognizes a "TTN" protospacer adjacent motif (PAM) and facilitates efficient genome editing in various cell lines. Importantly, NiCas12b also exhibits a high degree of specificity, rendering it suitable for therapeutic applications. As proof of concept, the adeno-associated virus (AAV) is employed to introduce NiCas12b to target the cholesterol regulatory gene proprotein convertase subtilisin/ kexin type 9 (Pcsk9) in the mouse liver. After 4 weeks of injections, an impressive is observed over 16.0% insertion/deletion (indel) efficiency, resulting in a significant reduction in serum cholesterol levels. NiCas12b provides a novel option for both basic research and clinical applications.

Mechanically Interlocked [an]Daisy Chain Adhesives with Simultaneously Enhanced Interfacial Adhesion and Cohesion.

Adhesives have been widely used to splice and repair materials to meet practical needs of humanity for thousands of years. However, developing robust adhesives with balanced adhesive and cohesive properties still remains a challenging task. Herein, we report the design and preparation of a robust mechanically interlocked [an]daisy chain network (DCMIN) adhesive by orthogonal integration of mechanical bond and 2-ureido-4[1H]-pyrimidone (UPy) H-bonding in a single system. Specifically, the UPy moiety plays dual roles: cross-linking for network formation and multivalent interactions with substrate for strong interfacial bonding. Mechanically interlocked [an]daisy chain, serving as the polymeric backbone of the adhesive, is able to effectively alleviate applied stress and uphold network integrity through synergistic intramolecular motions and thus significantly improve the cohesive performance. Therefore, comparative analyses with the control made of the same quadruple H-bonding network but with non-interlocked [an]daisy chain backbones demonstrate that our DCMIN possesses superior adhesion properties over a wide temperature range. These findings not only contribute to a deep understanding of the structure-property relationships between microscopic mechanical bond motions and macroscopic adhesive properties but also provide a valuable guidance for optimizing design principles of robust adhesives.

Discovery and engineering of ChCas12b for precise genome editing.

Many clustered regularly interspaced short palindromic repeat and CRISPR-associated protein 12b (CRISPR-Cas12b) nucleases have been computationally identified, yet their potential for genome editing remains largely unexplored. In this study, we conducted a GFP-activation assay screening 13 Cas12b nucleases for mammalian genome editing, identifying five active candidates. Candidatus hydrogenedentes Cas12b (ChCas12b) was found to recognize a straightforward WTN (W = T or A) proto-spacer adjacent motif (PAM), thereby dramatically expanding the targeting scope. Upon optimization of the single guide RNA (sgRNA) scaffold, ChCas12b exhibited activity comparable to SpCas9 across a panel of nine endogenous loci. Additionally, we identified nine mutations enhancing ChCas12b specificity. More importantly, we demonstrated that both ChCas12b and its high-fidelity variant, ChCas12b-D496A, enabled allele-specific disruption of genes harboring single nucleotide polymorphisms (SNPs). These data position ChCas12b and its high-fidelity counterparts as promising tools for both fundamental research and therapeutic applications.

Engineering of a high-fidelity Cas12a nuclease variant capable of allele-specific editing.

CRISPR-Cas12a, often regarded as a precise genome editor, still requires improvements in specificity. In this study, we used a GFP-activation assay to screen 14 new Cas12a nucleases for mammalian genome editing, successfully identifying 9 active ones. Notably, these Cas12a nucleases prefer pyrimidine-rich PAMs. Among these nucleases, we extensively characterized Mb4Cas12a obtained from Moraxella bovis CCUG 2133, which recognizes a YYN PAM (Y = C or T). Our biochemical analysis demonstrates that Mb4Cas12a can cleave double-strand DNA across a wide temperature range. To improve specificity, we constructed a SWISS-MODEL of Mb4Cas12a based on the FnCas12a crystal structure and identified 8 amino acids potentially forming hydrogen bonds at the target DNA-crRNA interface. By replacing these amino acids with alanine to disrupt the hydrogen bond, we tested the influence of each mutation on Mb4Cas12a specificity. Interestingly, the F370A mutation improved specificity with minimal influence on activity. Further study showed that Mb4Cas12a-F370A is capable of discriminating single-nucleotide polymorphisms. These new Cas12a orthologs and high-fidelity variants hold substantial promise for therapeutic applications.

Stretchable poly[2]rotaxane elastomers.

Mechanically interlocked polymers (MIPs) are promising candidates for the construction of elastomeric materials with desirable mechanical performance on account of their abilities to undergo inherent rotational and translational mechanical movements at the molecular level. However, the investigations on their mechanical properties are lagging far behind their structural fabrication, especially for linear polyrotaxanes in bulk. Herein, we report stretchable poly[2]rotaxane elastomers (PREs) which integrate numerous mechanical bonds in the polymeric backbone to boost macroscopic mechanical properties. Specifically, we have synthesized a hydroxy-functionalized [2]rotaxane that subsequently participates in the condensation polymerization with diisocyanate to form PREs. Benefitting from the peculiar structural and dynamic characteristics of the poly[2]rotaxane, the representative PRE exhibits favorable mechanical performance in terms of stretchability (∼1200%), Young's modulus (24.6 MPa), and toughness (49.5 MJ/m3). Moreover, we present our poly[2]rotaxanes as model systems to understand the relationship between mechanical bonds and macroscopic mechanical properties. It is concluded that the mechanical properties of our PREs are mainly determined by the unique topological architectures which possess a consecutive energy dissipation pathway including the dissociation of host-guest interaction and consequential sliding motion of the wheel along the axle in the [2]rotaxane motif.

Task-related brain activation associated with violence in patients with schizophrenia: A meta-analysis.

This study investigates specific changes in brain function during cognitive and emotional tasks in patients with schizophrenia and a history of violence (VSCZ) compared with non-violent patients with schizophrenia and healthy controls. A comprehensive literature search was conducted at the Web of Science, Medline, and PubMed. Ten studies met the inclusion criteria. In which, eight studies compared brain activation between patients with VSCZ and non-violent patients with schizophrenia, and the former exhibited increased activation at the middle occipital gyrus and rectus compared with the latter. Seven studies compared brain activation between patients with VSCZ and controls, and the former exhibited increased activation at the anterior cingulate cortex, cerebellum VI region, lingual gyrus and fusiform. Subgroup analysis in five studies performing emotional tasks revealed that patients with VSCZ showed increased activation at the middle occipital gyrus compared with non-violent patients with schizophrenia. Our findings suggest that abnormal emotion perception and regulation significantly contribute to the increased risk of violence in patients with schizophrenia. Notably, the middle occipital gyrus and rectus emerge as key neurophysiological correlates associated with this phenomenon.

Clinical prognostic significance of xeroderma pigmentosum group C and IFN­Î³ in non­small cell lung cancer.

Lung cancer is the most common cancer in the world due to its high incidence and recurrence. Genetic instability is one of the main factors leading to its occurrence, development and poor prognosis. Decreased xeroderma pigmentosum group C (XPC) expression notably enhances the stem cell properties of lung cancer cells and increases their proliferation and migration. Additionally, patients with lung cancer and low XPC expression had a poor prognosis. The purpose of the present study was to analyze the effect of XPC and IFN-γ on the clinical prognosis of patients with non-small cell lung cancer (NSCLC). Lung adenocarcinoma specimens were collected from a total of 140 patients with NSCLC. Additionally, from these 140 patients, 48 paracarcinoma tissue specimens were also collected, which were later used to construct tissue microarrays. The expression of XPC and IFN-γ in cancer tissues and in paraneoplastic tissues was detected using immunohistochemistry. The prognosis and overall survival of patients were determined through telephone follow-up. The results showed a positive correlation between expression of XPC and IFN-γ in NSCLC. Additionally, high expression of both markers was associated with a favorable prognosis in patients with NSCLC. The aforementioned findings suggest that the expression of XPC and IFN-γ has prognostic value in clinical practice and is expected to become a marker for clinical application.

Anion-Coordination Foldamer-Based Polymer Network: from Molecular Spring to Elastomer.

Foldamer is a scaled-down version of coil spring, which can absorb and release energy by conformational change. Here, polymer networks with high density of molecular springs were developed by employing anion-coordination-based foldamers as the monomer. The coiling of the foldamer is controlled by oligo(urea) ligands coordinating to chloride ions; subsequently, the folding and unfolding of foldamer conformations endow the polymer network with excellent energy dissipation and toughness. The mechanical performance of the corresponding polymer networks shows a dramatic increase from P-L2UCl (non-folding), to P-L4UCl (a full turn), and then to P-L6UCl (1.5 turns), in terms of strength (2.62 MPa; 14.26 MPa; 22.93 MPa), elongation at break (70 %; 325 %; 352 %), Young's modulus (2.69 MPa; 63.61 MPa; 141.50 MPa), and toughness (1.12 MJ/m3; 21.39 MJ/m3; 49.62 MJ/m3), respectively, which is also better than those without anion centers and the non-foldamer based counterparts. Moreover, P-L6UCl shows enhanced strength and toughness than most of the molecular-spring based polymer networks. Thus, an effective strategy for designing high-performance anion-coordination-based materials is presented.

Aquaporins enriched in endothelial vacuole membrane regulate the diameters of microvasculature in hyperglycaemia.

AIMS: In patients with diabetic microvascular complications, decreased perfusion or vascular occlusion, caused by reduced vascular diameter, is a common characteristic that will lead to insufficient blood supply. Yet, the regulatory mechanism and effective treatment approach remain elusive. METHODS AND RESULTS: Our initial findings revealed a notable decrease in the expression of human AQP1 in both diabetic human retina samples (49 healthy vs. 54 diabetic samples) and high-glucose-treated human retinal microvascular endothelial cells. Subsequently, our investigations unveiled a reduction in vascular diameter and compromised perfusion within zebrafish embryos subjected to high glucose treatment. Further analysis indicated a significant down-regulation of two aquaporins, aqp1a.1 and aqp8a.1, which are highly enriched in ECs and are notably responsive to hyperglycaemic conditions. Intriguingly, the loss of function of aqp1a.1 and/or aqp8a.1 resulted in a reduction of intersegmental vessel diameters, effectively mirroring the phenotype observed in the hyperglycaemic zebrafish model. The overexpression of aqp1a.1/aqp8a.1 in zebrafish ECs led to notable enlargement of microvascular diameters. Moreover, the reduced vessel diameters resulting from high-glucose treatment were effectively rescued by the overexpression of these aquaporins. Additionally, both aqp1a.1 and apq8a.1 were localized in the intracellular vacuoles in cultured ECs as well as the ECs of sprouting ISVs, and the loss of Aqps caused the reduction of those vacuoles, which was required for lumenization. Notably, while the loss of AQP1 did not impact EC differentiation from human stem cells, it significantly inhibited vascular formation in differentiated ECs. CONCLUSION: EC-enriched aquaporins regulate the diameter of blood vessels through an intracellular vacuole-mediated process under hyperglycaemic conditions. These findings collectively suggest that aquaporins expressed in ECs hold significant promise as potential targets for gene therapy aimed at addressing vascular perfusion defects associated with diabetes.

Colon-targeted hydroxyethyl starch-curcumin microspheres with high loading capacity ameliorate ulcerative colitis via alleviating oxidative stress, regulating inflammation, and modulating gut microbiota.

Curcumin (CUR) is a natural polyphenol that holds promise for treating ulcerative colitis (UC), yet oral administration of CUR exhibits limited bioavailability and existing formulations for oral delivery of CUR often suffer from unsatisfactory loading capacity. This study presents hydroxyethyl starch-curcumin microspheres (HC-MSs) with excellent CUR loading capacity (54.52 %), and the HC-MSs can further encapsulate anti-inflammatory drugs dexamethasone (DEX) to obtain a combination formulation (DHC-MSs) with high DEX loading capacity (19.91 %), for combination therapy of UC. The microspheres were successfully engineered, retaining the anti-oxidative and anti-inflammatory activities of parental CUR and demonstrating excellent biocompatibility and controlled release properties, notably triggered by α-amylase, facilitating targeted drug delivery to inflamed sites. In a mouse UC model induced by dextran sulfate sodium, the microspheres effectively accumulated in inflamed colons and both HC-MSs and DHC-MSs exhibited superior therapeutic efficacy in alleviating UC symptoms compared to free DEX. Moreover, mechanistic exploration uncovered the multifaceted therapeutic mechanisms of these formulations, encompassing anti-inflammatory actions, mitigation of spleen enlargement, and modulation of gut microbiota composition. These findings underscore the potential of HC-MSs and DHC-MSs as promising formulations for UC, with implications for advancing treatment modalities for various inflammatory bowel disorders.

Neuropathological characteristics of abnormal white matter functional signaling in adolescents with major depression.

BACKGROUND: Major depression disorder (MDD) constitutes a significant mental health concern. Epidemiological surveys indicate that the lifetime prevalence of depression in adolescents is much higher than that in adults, with a corresponding increased risk of suicide. In studying brain dysfunction associated with MDD in adole-scents, research on brain white matter (WM) is sparse. Some researchers even mistakenly regard the signals generated by the WM as noise points. In fact, studies have shown that WM exhibits similar blood oxygen level-dependent signal fluctuations. The alterations in WM signals and their relationship with disease severity in adolescents with MDD remain unclear. AIM: To explore potential abnormalities in WM functional signals in adolescents with MDD. METHODS: This study involved 48 adolescent patients with MDD and 31 healthy controls (HC). All participants were assessed using the Patient Health Questionnaire-9 Scale and the mini international neuropsychiatric interview (MINI) suicide inventory. In addition, a Siemens Skyra 3.0T magnetic resonance scanner was used to obtain the subjects' image data. The DPABI software was utilized to calculate the WM signal of the fractional amplitude of low frequency fluctuations (fALFF) and regional homogeneity, followed by a two-sample t-test between the MDD and HC groups. Independent component analysis (ICA) was also used to evaluate the WM functional signal. Pearson's correlation was performed to assess the relationship between statistical test results and clinical scales. RESULTS: Compared to HC, individuals with MDD demonstrated a decrease in the fALFF of WM in the corpus callosum body, left posterior limb of the internal capsule, right superior corona radiata, and bilateral posterior corona radiata [P < 0.001, family-wise error (FWE) voxel correction]. The regional homogeneity of WM increased in the right posterior limb of internal capsule and left superior corona radiata, and decreased in the left superior longitudinal fasciculus (P < 0.001, FWE voxel correction). The ICA results of WM overlapped with those of regional homo-geneity. The fALFF of WM signal in the left posterior limb of the internal capsule was negatively correlated with the MINI suicide scale (P = 0.026, r = -0.32), and the right posterior corona radiata was also negatively correlated with the MINI suicide scale (P = 0.047, r = -0.288). CONCLUSION: Adolescents with MDD involves changes in WM functional signals, and these differences in brain regions may increase the risk of suicide.

Acute Ammonia Causes Pathogenic Dysbiosis of Shrimp Gut Biofilms.

Acute ammonia exposure has detrimental effects on shrimp, but the underlying mechanisms remain to be fully explored. In the present study, we investigated the impact of acute ammonia exposure on the gut microbiota of the white shrimp Litopenaeus vannamei and its association with shrimp mortality. Exposure to a lethal concentration of ammonia for 48 h resulted in increased mortality in L. vannamei, with severe damage to the hepatopancreas. Ammonia exposure led to a significant decrease in gut microbial diversity, along with the loss of beneficial bacterial taxa and the proliferation of pathogenic Vibrio strains. A phenotypic analysis revealed a transition from the dominance of aerobic to facultative anaerobic strains due to ammonia exposure. A functional analysis revealed that ammonia exposure led to an enrichment of genes related to biofilm formation, host colonization, and virulence pathogenicity. A species-level analysis and experiments suggest the key role of a Vibrio harveyi strain in causing shrimp disease and specificity under distinct environments. These findings provide new information on the mechanism of shrimp disease under environmental changes.

Mechanically Interlocked Interphase with Energy Dissipation and Fast Li-Ion Transport for High-Capacity Lithium Metal Batteries.

Constructing an artificial solid electrolyte interphase (ASEI) on Li metal anodes (LMAs) is a potential strategy for addressing the dendrite issues. However, the mechanical fatigue of the ASEI caused by stress accumulation under the repeated deformation from the Li plating/stripping is not taken seriously. Herein, this work introduces a mechanically interlocked [an]daisy chain network (DCMIN) into the ASEI to stabilize the Li metal/ASEI interface by combining the functions of energy dissipation and fast Li-ion transport. The DCMIN featured by large-range molecular motions is cross-linked via efficient thiol-ene click chemistry; thus, the DCMIN has flexibility and excellent mechanical properties. As an ASEI, the crown ether units in DCMIN not only interact with the dialkylammonium of a flexible chain, forming the energy dissipation behavior but also coordinate with Li ion to support the fast Li-ion transport in DCMIN. Therefore, a stable 2800 h-symmetrical cycling (1 mA cm-2) and an excellent 5 C-rate (full cell with LiFePO4) performance are achieved by DCMIN-based ASEI. Furthermore, the 1-Ah pouch cell (LiNi0.88Co0.09Mn0.03O2 cathode) with DCMIN-coated LMA exhibits improved capacity retention (88%) relative to the Control. The molecular design of DCMIN provides new insights into the optimization of an ASEI for high-energy LMAs.