Temporal regulation of MDA5 inactivation by Caspase-3 dependent cleavage of 14-3-3η.

The kinetics of type I interferon (IFN) induction versus the virus replication compete, and the result of the competition determines the outcome of the infection. Chaperone proteins that involved in promoting the activation kinetics of PRRs rapidly trigger antiviral innate immunity. We have previously shown that prior to the interaction with MAVS to induce type I IFN, 14-3-3η facilitates the oligomerization and intracellular redistribution of activated MDA5. Here we report that the cleavage of 14-3-3η upon MDA5 activation, and we identified Caspase-3 activated by MDA5-dependent signaling was essential to produce sub-14-3-3η lacking the C-terminal helix (αI) and tail. The cleaved form of 14-3-3η (sub-14-3-3η) could strongly interact with MDA5 but could not support MDA5-dependent type I IFN induction, indicating the opposite functions between the full-length 14-3-3η and sub-14-3-3η. During human coronavirus or enterovirus infections, the accumulation of sub-14-3-3η was observed along with the activation of Caspase-3, suggesting that RNA viruses may antagonize 14-3-3η by promoting the formation of sub-14-3-3η to impair antiviral innate immunity. In conclusion, sub-14-3-3η, which could not promote MDA5 activation, may serve as a negative feedback to return to homeostasis to prevent excessive type I IFN production and unnecessary inflammation.

Exploring the Localization of Siderophore-Mediated Cargo Delivery in Gram-Negative Bacteria Using 3-Hydroxypyridin-4(1H)-one-Fluorescein Probes.

The design of siderophore-antibiotic conjugates is a promising strategy to overcome drug resistance in negative bacteria. However, accumulating studies have shown that only those antibiotics acting on the cell wall or cell membrane multiply their antibacterial effects when coupled with siderophores, while antibiotics acting on targets in the cytoplasm of bacteria do not show an obvious enhancement of their antibacterial effects when coupled with siderophores. To explore the causes of this phenomenon, we synthesized several conjugate probes using 3-hydroxypyridin-4(1H)-ones as siderophores and replacing the antibiotic cargo with 5-carboxyfluorescein (5-FAM) or malachite green (MG) cargo. By monitoring changes in the fluorescence intensity of FAM conjugate 20 in bacteria, the translocation of the conjugate across the outer membranes of Gram-negative pathogens was confirmed. Further, the use of the fluorogen activating protein(FAP)/MG system revealed that 3-hydroxypyridin-4(1H)-one-MG conjugate 26 was ultimately distributed mainly in the periplasm rather than being translocated into the cytosol of Escherichia coli and Pseudomonas aeruginosa PAO1. Additional mechanistic studies suggested that the uptake of the conjugate involved the siderophore-dependent iron transport pathway and the 3-hydroxypyridin-4(1H)-ones siderophore receptor-dependent mechanism. Meanwhile, we demonstrated that the conjugation of 3-hydroxypyridin-4(1H)-ones to the fluorescein 5-FAM can reduce the possibility of the conjugates crossing the membrane layers of mammalian Vero cells by passive diffusion, and the advantages of the mono-3-hydroxypyridin-4(1H)-ones as a delivery vehicle in the design of conjugates compared to the tri-3-hydroxypyridin-4(1H)-ones. Overall, this work reveals the localization rules of 3-hydroxypyridin-4(1H)-ones as siderophores to deliver the cargo into Gram-negative bacteria. It provides a theoretical basis for the subsequent design of siderophore-antibiotic conjugates, especially based on 3-hydroxypyridin-4(1H)-ones as siderophores.

Carboxylesterase Activatable Molecular Probe for Personalized Treatment Guidance by Analyte-Induced Molecular Transformation.

Accurate visualization of tumor microenvironment is of great significance for personalized medicine. Here, we develop a near-infrared (NIR) fluorescence/photoacoustic (FL/PA) dual-mode molecular probe (denoted as NIR-CE) for distinguishing tumors based on carboxylesterase (CE) level by an analyte-induced molecular transformation (AIMT) strategy. The recognition moiety for CE activity is the acetyl unit of NIR-CE, generating the pre-product, NIR-CE-OH, which undergoes spontaneous hydrogen atom exchange between the nitrogen atoms in the indole group and the phenol hydroxyl group, eventually transforming into NIR-CE-H. In cellular experiments and in vivo blind studies, the human hepatoma cells and tumors with high level of CE were successfully distinguished by both NIR FL and PA imaging. Our findings provide a new molecular imaging strategy for personalized treatment guidance.

Lamb wave-based damage assessment for composite laminates using a deep learning approach.

With the increasing utilization of composite materials due to their superior properties, the need for efficient structural health monitoring techniques rises rapidly to ensure the integrity and reliability of composite structures. Deep learning approaches have great potential applications for Lamb wave-based damage detection. However, it remains challenging to quantitatively detect and characterize damage such as delamination in multi-layered structures. These deep learning architectures still lack a certain degree of physical interpretability. In this study, a convolutional sparse coding-based UNet (CSCUNet) is proposed for ultrasonic Lamb wave-based damage assessment in composite laminates. A low-resolution image is generated using delay-and-sum algorithm based on Lamb waves acquired by transducer array. The encoder-decoder framework in the proposed CSCUNet enables the transformation of low-resolution input image to high-resolution damage image. In addition, the multi-layer convolutional sparse coding block is introduced into encoder of the CSCUNet to improve both performance and interpretability of the model. The proposed method is tested on both numerical and experimental data acquired on the surface of composite specimen. The results demonstrate its effectiveness in identifying the delamination location, size, and shape. The network has powerful feature extraction capability and enhanced interpretability, enabling high-resolution imaging and contour evaluation of composite material damage.

Combinatorial metabolic engineering of Streptomyces sp. CB03234-S for the enhanced production of anthraquinone-fused enediyne tiancimycins.

BACKGROUND: Anthraquinone-fused enediynes (AFEs) are excellent payloads for antibody-drug conjugates (ADCs). The yields of AFEs in the original bacterial hosts are extremely low. Multiple traditional methods had been adopted to enhance the production of the AFEs. Despite these efforts, the production titers of these compounds are still low, presenting a practical challenge for their development. Tiancimycins (TNMs) are a class of AFEs produced by Streptomyces sp. CB03234. One of their salient features is that they exhibit rapid and complete cell killing ability against various cancer cell lines. RESULTS: In this study, a combinatorial metabolic engineering strategy guided by the CB03234-S genome and transcriptome was employed to improve the titers of TNMs. First, re-sequencing of CB03234-S (Ribosome engineered mutant strains) genome revealed the deletion of a 583-kb DNA fragment, accounting for about 7.5% of its genome. Second, by individual or combined inactivation of seven potential precursor competitive biosynthetic gene clusters (BGCs) in CB03234-S, a double-BGC inactivation mutant, S1009, was identified with an improved TNMs titer of 28.2 ± 0.8 mg/L. Third, overexpression of five essential biosynthetic genes, including two post-modification genes, and three self-resistance auxiliary genes, was also conducted, through which we discovered that mutants carrying the core genes, tnmE or tnmE10, exhibited enhanced TNMs production. The average TNMs yield reached 43.5 ± 2.4 mg/L in a 30-L fermenter, representing an approximately 360% increase over CB03234-S and the highest titer among all AFEs to date. Moreover, the resulting mutant produced TNM-W, a unique TNM derivative with a double bond instead of a common ethylene oxide moiety. Preliminary studies suggested that TNM-W was probably converted from TNM-A by both TnmE and TnmE10. CONCLUSIONS: Based on the genome and transcriptome analyses, we adopted a combined metabolic engineering strategy for precursor enrichment and biosynthetic pathway reorganization to construct a high-yield strain of TNMs based on CB03234-S. Our study establishes a solid basis for the clinical development of AFE-based ADCs.

Effectiveness and safety of telitacicept for refractory generalized myasthenia gravis: a retrospective study.

Background: Refractory generalized myasthenia gravis (GMG) remains a substantial therapeutic challenge. Telitacicept, a recombinant human B-lymphocyte stimulator receptor-antibody fusion protein, holds promise for interrupting the immunopathology of this condition. Objectives: This study retrospectively assessed the effectiveness and safety of telitacicept in patients with refractory GMG. Design: A single-center retrospective study. Methods: Patients with refractory GMG receiving telitacicept (160 mg/week or biweekly) from January to September in 2023 were included. We assessed effectiveness using Myasthenia Gravis Foundation of America post-intervention status (MGFA-PIS), myasthenia gravis treatment status and intensity (MGSTI), quantitative myasthenia gravis (QMG), and MG-activity of daily living (ADL) scores, alongside reductions in prednisone dosage at 3- and 6-month intervals. Safety profiles were also evaluated. Results: Sixteen patients with MGFA class II-V refractory GMG were included, with eight females and eight males. All patients were followed up for at least 3 months, and 11 patients reached 6 months follow-up. At the 3-month evaluation, 75% (12/16) demonstrated clinical improvement with MGFA-PIS. One patient achieved pharmacological remission, two attained minimal manifestation status, and nine showed functional improvement; three remained unchanged, and one deteriorated. By the 6-month visit, 90.1% (10/11) sustained significant symptomatic improvement. MGSTI scores and prednisone dosages significantly reduced at both follow-ups (p < 0.05). MG-ADL and QMG scores showed marked improvement at 6 months (p < 0.05). The treatment was well tolerated, with no severe adverse events such as allergy or infection reported. Conclusion: Our exploratory investigation suggests that telitacicept is a feasible and well-tolerated add-on therapy for refractory GMG, offering valuable clinical evidence for this novel treatment option.

RNA-dependent RNA polymerases regulate ascospore discharge through the exonic-sRNA-mediated RNAi pathway.

Ascospores, forcibly released into the air from perithecia, are the primary inoculum for Fusarium head blight. In Fusarium graminearum, the biological functions of four RNA-dependent RNA polymerases (RdRPs) (Fgrdrp1-4) have been reported, but their regulatory mechanisms are poorly understood and the function of Fgrdrp5 is still unknown. In this study, we found that in addition to Fgrdrp1 and Fgrdrp2, Fgrdrp5 also plays an important role in ascospore discharge, and they all participate in the generation of turgor pressure in a polyol-dependent manner. Moreover, these three genes all affect the maturation of ascospores. Deep sequencing and co-analysis of small RNA and mRNA certified that Fgrdrp1, Fgrdrp2, and Fgrdrp5 partly share their functions in the biogenesis and accumulation of exonic small interference RNA (ex-siRNA), and these three RdRPs negatively regulate the expression levels of ex-siRNA corresponding genes, including certain genes associated with ascospore development or discharge. Furthermore, the differentially expressed genes of deletion mutants, those involved in lipid and sugar metabolism or transport as well as sexual development-related transcription factors, may also contribute to the defects in ascospore maturation or ascospore discharge. In conclusion, our study suggested that the components of the dicer-dependent ex-siRNA-mediated RNA interference pathway include at least Fgrdrp1, Fgrdrp2, and Fgrdrp5. IMPORTANCE: We found that in addition to Fgrdrp1 and Fgrdrp2, Fgrdrp5 also plays important roles in ascospore maturation and ascospore discharge of Fusarium graminearum. These three RNA-dependent RNA polymerases participate in the biogenesis and accumulation of exonic small interference RNA and then regulate ascospore discharge.

Efficient Photocatalytic CO2 Reduction in Ellagic Acid-Based Covalent Organic Frameworks.

Employing covalent organic frameworks (COFs) for the photocatalytic CO2 reduction reaction (CDRR) to generate high-value chemical fuels and mitigate greenhouse gas emissions represents a sustainable catalytic conversion approach. However, achieving superior photocatalytic CDRR performance is hindered by the challenges of low charge separation efficiency, poor stability, and high preparation costs associated with COFs. Herein, in this work, we utilized perfluorinated metallophthalocyanine (MPcF16) and the organic biomolecule compound ellagic acid (EA) as building blocks to actualize functional covalent organic frameworks (COFs) named EPM-COF (M = Co, Ni, Cu). The designed EPCo-COF, featuring cobalt metal active sites, demonstrated an impressive CO production rate and selectivity in the photocatalytic CO2 reduction reaction (CDRR). Moreover, following alkaline treatment (EPCo-COF-AT), the COF exposed carboxylic acid anion (COO-) and hydroxyl group (OH), thereby enhancing the electron-donating capability of EA. This modification achieved a heightened CO production rate of 17.7 mmol g-1 h-1 with an outstanding CO selectivity of 97.8% in efficient photocatalytic CDRR. Theoretical calculations further illustrated that EPCo-COF-AT functionalized with COO- and OH can effectively alleviate the energy barriers involved in the CDRR process, which facilitates the proton-coupled electron transfer processes and enhances the photocatalytic performance on the cobalt active sites within EPCo-COF-AT.

[Research progress on induced hepatic stellate cell ferroptosis in prevention and treatment of liver fibrosis].

Liver fibrosis is a key pathological stage in the progression of chronic liver disease. If the disease is mistreated, it can further deteriorate into liver failure, which seriously affects the quality of life of patients and brings heavy medical costs. Hepatic stellate cell(HSC) activation triggers extracellular matrix(ECM) deposition, which plays an important driving role in liver fibrosis, and ferroptosis is an effective strategy to clear or reverse the activation of HSCs into a deactivated phenotype. Therefore, inhibiting the activation and proliferation of HSCs by regulating ferroptosis is the key to the treatment of this disease, so as to derive the prospect of inducing ferroptosis of HSCs(including RNA-binding proteins, non-coding RNA, chemicals, and active components of traditional Chinese medicine) to intervene in liver fibrosis. On this basis, this paper started from the activation of HSCs to induce ECM deposition and focused on summarizing the mechanism of inducing HSC ferroptosis in delaying the progression of liver fibrosis, so as to continuously enrich the clinical practice of liver fibrosis and provide a reference for subsequent basic research.

Analysis of 15 bile acids in human plasma based on C18 functionalized magnetic organic polymer nanocomposite coupled with liquid chromatography-tandem mass spectrometry.

Because of the "enterohepatic circulation" of bile acid, liver damage can be reflected by monitoring the content of bile acid in the serum of the organism. To monitor the concentration of 15 bile acids in plasma samples, a new technique of PRiME (process, ruggedness, improvement, matrix effect, ease of use) pass-through cleanup procedure combined with high performance liquid chromatography-tandem quadrupole mass spectrometry (HPLC-MS/MS) was developed. The sorbent used in the PRiME pass-through cleanup procedure is a new type of magnetic organic resin composite nano-material modified by C18 (C18-PS-DVB-GMA-Fe3O4), which has high cleanup efficiency of plasma samples. It also shows good performance in the separation and analysis of 15 kinds of bile acids. Under the optimal conditions, the results show higher cleanup efficiency of C18-PS-DVB-GMA-Fe3O4 with recoveries in the range of 82.1-115 %. The limit of quantitative (LOQs) of 15 bile acids were in the range of 0.033 µg/L-0.19 µg/L, and the RSD values of 15 bile acids were in the range of 3.00-11.9 %. Validation results on linearity, specificity, accuracy and precision, as well as on the application to analysis of 15 bile acids in 100 human plasma samples demonstrate the applicability to clinical studies.

Based on Immune Microenvironment and Genomic Status, Exploring Immunotherapy in Advanced Hidradenocarcinoma: A Retrospective Analysis.

There are no standard treatment guidelines for hidradenocarcinoma, and the immune microenvironment and genomic data are very limited. Thus, in this study the immune microenvironment and genomic indicators in hidradenocarcinoma was investigated, and immunotherapy for hidradenocarcinoma was initially explored. Forty-seven hidradenocarcinoma patients were retrospectively collected. Immunohistochemical staining was performed to identify CD3/CD8+ T cells and programmed death ligand-1 expression. In total, 89.4% and 10.6% of samples had Immunoscores of 0-25% and 25-70%. Tumour proportion score distribution was as follows: tumour proportion score < 1% in 72.4%, 1-5% in 17.0%, and > 5% in 10.6%. Combined positive score distribution was as follows: combined positive score < 1 in 63.8%, 1-5 in 14.9%, and > 5 in 21.3%. Next-generation sequencing revealed that TP53 (33%), PI3KCA (22%), and ERBB3 (22%) were the most frequently mutated genes. The PI3K-Akt signalling pathway, growth, and MAPK signalling pathways were significantly enriched. Five patients had a low TMB (< 10 muts/Mb), and 9 patients had MSS. Three patients treated with immune combined with chemotherapy achieved significant tumour regression, and the progression-free survival was 28.8 months. In conclusion, the hidradenocarcinoma immune microenvironment tends to be noninflammatory. Evidence-based targets for targeted therapy are lacking. Immunotherapy combined with chemotherapy may be better for most advanced hidradenocarcinoma patients with a noninflammatory microenvironment.

Advances of ultrasound in tumor immunotherapy.

Immunotherapy has become a revolutionary method for treating tumors, offering new hope to cancer patients worldwide. Immunotherapy strategies such as checkpoint inhibitors, chimeric antigen receptor T-cell (CAR-T) therapy, and cancer vaccines have shown significant potential in clinical trials. Despite the promising results, there are still limitations that impede the overall effectiveness of immunotherapy; the response to immunotherapy is uneven, the response rate of patients is still low, and systemic immune toxicity accompanied with tumor cell immune evasion is common. Ultrasound technology has evolved rapidly in recent years and has become a significant player in tumor immunotherapy. The introductions of high intensity focused ultrasound and ultrasound-stimulated microbubbles have opened doors for new therapeutic strategies in the fight against tumor. This paper explores the revolutionary advancements of ultrasound combined with immunotherapy in this particular field.

Multifunctional laser-induced graphene circuits and laser-printed nanomaterials toward non-invasive human kidney function monitoring.

Faced with the increasing prevalence of chronic kidney disease (CKD), portable monitoring of CKD-related biomarkers such as potassium ion (K+), creatinine (Cre), and lactic acid (Lac) levels in sweat has shown tremendous potential for early diagnosis. However, a rapidly manufacturable portable device integrating multiple CKD-related biomarker sensors for ease of sweat testing use has yet to be reported. Here, a portable electrochemical sensor integrated with multifunctional laser-induced graphene (LIG) circuits and laser-printed nanomaterials based working electrodes fabricated by fully automatic laser manufacturing is proposed for non-invasive human kidney function monitoring. The sensor comprises a two-electrode LIG circuit for K+ sensing, a three-electrode LIG circuit with a Kelvin compensating connection for Cre and Lac sensing, and a printed circuit board based portable electrochemical workstation. The working electrodes containing Cu and Cu2O nanoparticles fabricated by two-step laser printing show good sensitivity and selectivity toward Cre and Lac sensing. The sensor circuits are fabricated by generating a hydrophilic-hydrophobic interface on a patterned LIG through laser. This sensor recruited rapid laser manufacturing and integrated with multifunctional LIG circuits and laser-printed nanomaterials based working electrodes, which is a potential kidney function monitoring solution for healthy people and kidney disease patients.

Rosmarinic acid alleviates fungal keratitis caused by Aspergillus fumigatus by inducing macrophage autophagy.

Fungal keratitis (FK) is an infectious keratopathy can cause serious damage to vision. Its severity is related to the virulence of fungus and response of inflammatory. Rosmarinic acid (RA) extracted from Rosmarinus officinalis exhibits antioxidant, anti-inflammatory and anti-viral properties. The aim of this study was to investigate the effect of RA on macrophage autophagy and its therapeutic effect on FK. In this study, we demonstrated that RA reduced expression of proinflammatory cytokine, lessened the recruitment of inflammatory cells in FK. The relative contents of autophagy markers, such as LC3 and Beclin-1, were significantly up-regulated in RAW 264.7 cells and FK. In addition, RA restored mitochondrial membrane potential (MMP) of macrophage to normal level. RA not only reduced the production of intracellular reactive oxygen species (ROS) but also mitochondria ROS (mtROS) in macrophage. At the same time, RA induced macrophage to M2 phenotype and down-regulated the mRNA expression of IL-6, IL-1ß, TNF-α. All the above effects could be offset by the autophagy inhibitor 3-Methyladenine (3-MA). Besides, RA promote phagocytosis of RAW 264.7 cells and inhibits spore germination, biofilm formation and conidial adherence, suggesting a potential therapeutic role for RA in FK.

MXene/ZnS/chitosan-cellulose composite with Schottky heterostructure for efficient removal of anionic dyes by synergistic effect of adsorption and photocatalytic degradation.

Nowadays, dye water pollution is becoming increasingly severe. Composite of MXene, ZnS, and chitosan-cellulose material (MX/ZnS/CC) was developed to remove anionic dyes through the synergistic effect of adsorption and photocatalytic degradation. MXene was introduced as the cocatalyst to form Schottky heterostructure with ZnS for improving the separation efficiency of photocarriers and photocatalytic performance. Chitosan-cellulose material mainly served as the dye adsorbent, while also could improve material stability and assist in generation of free radicals for dye degradation. The physics and chemistry properties of MX/ZnS/CC composite were systematically inspected through various characterizations. MX/ZnS/CC composite exhibited good adsorption ability to anionic dyes with adsorption capacity up to 1.29 g/g, and excellent synergistic effects of adsorption and photodegradation with synergistic removal capacity up to 5.63 g/g. MX/ZnS/CC composite performed higher synergistic removal ability and better optical and electrical properties than pure MXene, ZnS, chitosan-cellulose material, and MXene/ZnS. After compounding, the synergistic removal percentage of dyes increased by a maximum of 309 %. MX/ZnS/CC composite mainly adsorbs anionic dyes through electrostatic interactions and catalyzes the generation of •O2-, h+, and •OH to degrade dyes, which has been successfully used to remove anionic dyes from environmental water, achieving a 100 % removal of 50 mg/L dye.

A Versatile Cryomicroneedle Patch for Traceable Photodynamic Therapy.

Photodynamic therapy (PDT) continues to encounter multifarious hurdles, stemming from the ineffectual preservation and delivery system of photosensitizers, the dearth of imaging navigation, and the antioxidant/hypoxic tumor microenvironment. Herein, a versatile cryomicroneedle patch (denoted as CMN-CCPH) was developed for traceable PDT. The therapeutic efficacy was further amplified by catalase (CAT)-induced oxygen (O2) generation and Cu2+-mediated glutathione (GSH) depletion. The CMN-CCPH is composed of cryomicroneedle (CMN) as the vehicle and CAT-biomineralized copper phosphate nanoflowers (CCP NFs) loaded with hematoporphyrin monomethyl ether (HMME) as the payload. Importantly, the bioactive function of HMME and CAT could be optimally maintained under the protection of CCPH and CMN for a duration surpassing 60 days, leading to a bolstered bioavailability and notable enhancements in PDT efficacy. The in vivo visualization of HMME and oxyhemoglobin saturation (sO2) monitored by fluorescence (FL)/photoacoustic (PA) duplex real-time imaging unveiled the noteworthy implications of CMN-delivered CCPH for intratumoral enrichment of HMME and O2 with reduced systemic toxicity. This versatile CMN patch demonstrated distinct effectiveness in neoplasm elimination, underscoring its promising clinical prospects. This article is protected by copyright. All rights reserved.

The neuroprotective effects of caffeic acid phenethyl ester against methamphetamine-induced neurotoxicity.

Methamphetamine (METH) is a highly abused substance on a global scale and has the capacity to elicit toxicity within the central nervous system. The neurotoxicity induced by METH encompasses neuronal degeneration and cellular demise within the substantia nigra-striatum and hippocampus. Caffeic acid phenethyl ester (CAPE), a constituent of propolis, is a diminutive compound that demonstrates antioxidative and anti-inflammatory characteristics. Numerous investigations have demonstrated the safeguarding effects of CAPE in various neurodegenerative ailments. Our hypothesis posits that CAPE may exert a neuroprotective influence on METH-induced neurotoxicity via specific mechanisms. In order to validate the hypothesis, a series of experimental techniques including behavioral tests, immunofluorescence labeling, RNA sequencing, and western blotting were employed to investigate the neurotoxic effects of METH and the potential protective effects of CAPE. The results of our study demonstrate that CAPE effectively ameliorates cognitive memory deficits and anxiety symptoms induced by METH in mice. Furthermore, CAPE has been observed to attenuate the upregulation of neurotoxicity-associated proteins that are induced by METH exposure and also reduced the loss of hippocampal neurons in mice. Moreover, transcriptomics analysis was conducted to determine alterations in gene expression within the hippocampus of mice. Subsequently, bioinformatics analysis was employed to investigate the divergent outcomes and identify potential key genes. Interferon-stimulated gene 15 (ISG15) was successfully identified and confirmed through RT-qPCR, western blotting, and immunofluorescence techniques. Our research findings unequivocally demonstrated the neuroprotective effect of CAPE against METH-induced neurotoxicity, with ISG15 may have an important role in the underlying protective mechanism. These results offer novel perspectives on the treatment of METH-induced neurotoxicity.

Tuning Ion Mobility in Lithium Argyrodite Solid Electrolytes via Entropy Engineering.

The development of improved solid electrolytes (SEs) plays a crucial role in the advancement of bulk-type solid-state battery (SSB) technologies. Recently, multicomponent or high-entropy SEs are gaining increased attention for their advantageous charge transport and (electro)chemical properties. However, a comprehensive understanding of how configurational entropy affects ionic conductivity is largely lacking. Herein we have investigated a series of multication-substituted lithium argyrodites with the general formula Li6+x[M1aM2bM3cM4d]S5I, with M being P, Si, Ge, and Sb. Structure-property relationships related to ion mobility were probed using a combination of diffraction techniques, solid-state nuclear magnetic resonance spectroscopy, and charge-transport measurements. We present, to the best of our knowledge, the first experimental evidence of a direct correlation between occupational disorder in the cationic host lattice and lithium transport. By controlling the configurational entropy through the composition, high bulk ionic conductivities up to 18 mS cm-1 at room temperature were achieved for optimized lithium argyrodite compositions. Our results indicate the possibility of improving ionic conductivity in ceramic ion conductors via entropy engineering, unlocking the compositional limitations for the design of advanced electrolytes and opening up new avenues in the field.