Preparation of PLCL/ECM nerve conduits by electrostatic spinning technique and evaluationin vitroandin vivo.

Objective. Artificial nerve scaffolds composed of polymers have attracted great attention as an alternative for autologous nerve grafts recently. Due to their poor bioactivity, satisfactory nerve repair could not be achieved. To solve this problem, we introduced extracellular matrix (ECM) to optimize the materials.Approach.In this study, the ECM extracted from porcine nerves was mixed with Poly(L-Lactide-co-ϵ-caprolactone) (PLCL), and the innovative PLCL/ECM nerve repair conduits were prepared by electrostatic spinning technology. The novel conduits were characterized by scanning electron microscopy (SEM), tensile properties, and suture retention strength test for micromorphology and mechanical strength. The biosafety and biocompatibility of PLCL/ECM nerve conduits were evaluated by cytotoxicity assay with Mouse fibroblast cells and cell adhesion assay with RSC 96 cells, and the effects of PLCL/ECM nerve conduits on the gene expression in Schwann cells was analyzed by real-time polymerase chain reaction (RT-PCR). Moreover, a 10 mm rat (Male Wistar rat) sciatic defect was bridged with a PLCL/ECM nerve conduit, and nerve regeneration was evaluated by walking track, mid-shank circumference, electrophysiology, and histomorphology analyses.Main results.The results showed that PLCL/ECM conduits have similar microstructure and mechanical strength compared with PLCL conduits. The cytotoxicity assay demonstrates better biosafety and biocompatibility of PLCL/ECM nerve conduits. And the cell adhesion assay further verifies that the addition of ECM is more beneficial to cell adhesion and proliferation. RT-PCR showed that the PLCL/ECM nerve conduit was more favorable to the gene expression of functional proteins of Schwann cells. Thein vivoresults indicated that PLCL/ECM nerve conduits possess excellent biocompatibility and exhibit a superior capacity to promote peripheral nerve repair.Significance.The addition of ECM significantly improved the biocompatibility and bioactivity of PLCL, while the PLCL/ECM nerve conduit gained the appropriate mechanical strength from PLCL, which has great potential for clinical repair of peripheral nerve injuries.

Enhancing neuroinduction activity of PLCL-based nerve conduits through native epineurium integration.

Autologous nerve grafts have been considered the gold standard for peripheral nerve grafts. However, due to drawbacks such as functional loss in the donor area and a shortage of donor sources, nerve conduits are increasingly being considered as an alternative approach. Polymer materials have been widely studied as nerve repair materials due to their excellent processing performance. However, their limited biocompatibility has restricted further clinical applications. The epineurium is a natural extra-neural wrapping structure. After undergoing decellularization, the epineurium not only reduces immune rejection but also retains certain bioactive components. In this study, decellularized epineurium (DEP) derived from the sciatic nerve of mammals was prepared, and a bilayer nerve conduit was created by electrospinning a poly (l-lactide-co-ε-caprolactone) (PLCL) membrane layer onto the outer surface of the DEP. Components of the DEP were examined; the physical properties and biosafety of the bilayer nerve conduit were evaluated; and the functionality of the nerve conduit was evaluated in rats. The results demonstrate that the developed bilayer nerve conduit exhibits excellent biocompatibility and mechanical properties. Furthermore, this bilayer nerve conduit shows significantly superior therapeutic effects for sciatic nerve defects in rats compared to the pure PLCL nerve conduit. In conclusion, this research provides a novel strategy for the design of nerve regeneration materials and holds promising potential for further clinical translation.

Rapid Self-Healing Hydrogel with Ultralow Electrical Hysteresis for Wearable Sensing.

Self-healing hydrogels are in high demand for wearable sensing applications due to their remarkable deformability, high ionic and electrical conductivity, self-adhesiveness to human skin, as well as resilience to both mechanical and electrical damage. However, these hydrogels face challenges such as delayed healing times and unavoidable electrical hysteresis, which limit their practical effectiveness. Here, we introduce a self-healing hydrogel that exhibits exceptionally rapid healing with a recovery time of less than 0.12 s and an ultralow electrical hysteresis of less than 0.64% under cyclic strains of up to 500%. This hydrogel strikes an ideal balance, without notable trade-offs, between properties such as softness, deformability, ionic and electrical conductivity, self-adhesiveness, response and recovery times, durability, overshoot behavior, and resistance to nonaxial deformations such as twisting, bending, and pressing. Owing to this unique combination of features, the hydrogel is highly suitable for long-term, durable use in wearable sensing applications, including monitoring body movements and electrophysiological activities on the skin.

Machine embroidery of light-emitting textiles with multicolor electroluminescent threads.

Advances in electroluminescent threads, suitable for weaving or knitting, have opened doors for the development of light-emitting textiles, driving growth in the market for flexible and wearable displays. Although direct embroidery of these textiles with custom designs and patterns could offer substantial benefits, the rigorous demands of machine embroidery challenge the integrity of these threads. Here, we present embroiderable multicolor electroluminescent threads-in blue, green, and yellow-that are compatible with standard embroidery machines. These threads can be used to stitch decorative designs onto various consumer fabrics without compromising their wear resistance or light-emitting capabilities. Demonstrations include illuminating specific messages or designs on consumer products and delivering emergency alerts on helmet liners for physical hazards. Our research delivers a comprehensive toolkit for integrating light-emitting textiles into trendy, customized crafts tailored to the unique requirements of diverse flexible and wearable displays.

In Situ Spray Polymerization of Conductive Polymers for Personalized E-textiles.

E-textiles, also known as electronic textiles, seamlessly merge wearable technology with fabrics, offering comfort and unobtrusiveness and establishing a crucial role in health monitoring systems. In this field, the integration of custom sensor designs with conductive polymers into various fabric types, especially in large areas, has presented significant challenges. Here, we present an innovative additive patterning method that utilizes a dual-regime spray system, eliminating the need for masks and allowing for the programmable inscription of sensor arrays onto consumer textiles. Unlike traditional spray techniques, this approach enables in situ, on-the-fly polymerization of conductive polymers, enabling intricate designs with submillimeter resolution across fabric areas spanning several meters. Moreover, it addresses the nozzle clogging issues commonly encountered in such applications. The resulting e-textiles preserve essential fabric characteristics such as breathability, wearability, and washability while delivering exceptional sensing performance. A comprehensive investigation, combining experimental, computational, and theoretical approaches, was conducted to examine the critical factors influencing the operation of the dual-regime spraying system and its role in e-textile fabrication. These findings provide a flexible solution for producing e-textiles on consumer fabric items and hold significant implications for a diverse range of wearable sensing applications.

Preparation and assessment of an optimized multichannel acellular nerve allograft for peripheral nerve regeneration.

Peripheral nerve regeneration after injury is still a clinical problem. The application of autologous nerve grafting, the gold standard treatment, is greatly restricted. Acellular nerve allografts (ANAs) are considered promising alternatives, but they are difficult to achieve satisfactory therapeutic outcomes, which may be attributed to their compact inherent ultrastructure and substantial loss of extracellular matrix (ECM) components. Regarding these deficiencies, this study developed an optimized multichannel ANA by a modified decellularization method. These innovative ANAs were demonstrated to retain more ECM bioactive molecules and regenerative factors, with effective elimination of cellular antigens. The presence of microchannels with larger pore size allowed ANAs to gain higher porosity and better swelling performance, which improves their internal ultrastructure. Their mechanical properties were more similar to those of native nerves. Moreover, the optimized ANAs exhibited good biocompatibility and possessed significant advantages in supporting the proliferation and migration of Schwann cells in vitro. The in vivo results further confirmed their superior capacity to promote axon regrowth and myelination as well as restore innervation of target muscles, leading to better functional recovery than the conventional ANAs. Overall, this study demonstrates that the optimized multichannel ANAs have great potential for clinical application and offer new insight into the further improvement of ANAs.

In vitro continuous protein evolution empowered by machine learning and automation.

Directed evolution has become one of the most successful and powerful tools for protein engineering. However, the efforts required for designing, constructing, and screening a large library of variants can be laborious, time-consuming, and costly. With the recent advent of machine learning (ML) in the directed evolution of proteins, researchers can now evaluate variants in silico and guide a more efficient directed evolution campaign. Furthermore, recent advancements in laboratory automation have enabled the rapid execution of long, complex experiments for high-throughput data acquisition in both industrial and academic settings, thus providing the means to collect a large quantity of data required to develop ML models for protein engineering. In this perspective, we propose a closed-loop in vitro continuous protein evolution framework that leverages the best of both worlds, ML and automation, and provide a brief overview of the recent developments in the field.

Enzyme function prediction using contrastive learning.

Enzyme function annotation is a fundamental challenge, and numerous computational tools have been developed. However, most of these tools cannot accurately predict functional annotations, such as enzyme commission (EC) number, for less-studied proteins or those with previously uncharacterized functions or multiple activities. We present a machine learning algorithm named CLEAN (contrastive learning-enabled enzyme annotation) to assign EC numbers to enzymes with better accuracy, reliability, and sensitivity compared with the state-of-the-art tool BLASTp. The contrastive learning framework empowers CLEAN to confidently (i) annotate understudied enzymes, (ii) correct mislabeled enzymes, and (iii) identify promiscuous enzymes with two or more EC numbers-functions that we demonstrate by systematic in silico and in vitro experiments. We anticipate that this tool will be widely used for predicting the functions of uncharacterized enzymes, thereby advancing many fields, such as genomics, synthetic biology, and biocatalysis.

Nerve ECM and PLA-PCL based electrospun bilayer nerve conduit for nerve regeneration.

Introduction: The porcine nerve-derived extracellular matrix (ECM) fabricated as films has good performance in peripheral nerve regeneration. However, when constructed as conduits to bridge nerve defects, ECM lacks sufficient mechanical strength. Methods: In this study, a novel electrospun bilayer-structured nerve conduit (BNC) with outer poly (L-lactic acid-co-ε-caprolactone) (PLA-PCL) and inner ECM was fabricated for nerve regeneration. The composition, structure, and mechanical strength of BNC were characterized. Then BNC biosafety was evaluated by cytotoxicity, subcutaneous implantation, and cell affinity tests. Furthermore, BNC was used to bridge 10-mm rat sciatic nerve defect, and nerve functional recovery was assessed by walking track, electrophysiology, and histomorphology analyses. Results: Our results demonstrate that BNC has a network of nanofibers and retains some bioactive molecules, including collagen I, collagen IV, laminin, fibronectin, glycosaminoglycans, nerve growth factor, and brain-derived neurotrophic factor. Biomechanical analysis proves that PLA-PCL improves the BNC mechanical properties, compared with single ECM conduit (ENC). The functional evaluation of in vivo results indicated that BNC is more effective in nerve regeneration than PLA-PCL conduit or ENC. Discussion: In conclusion, BNC not only retains the good biocompatibility and bioactivity of ECM, but also obtains the appropriate mechanical strength from PLA-PCL, which has great potential for clinical repair of nerve defects.

The risk of all-cause death with dapagliflozin versus placebo: a systematic review and meta-analysis of phase III randomized controlled trials.

BACKGROUND: Dapagliflozin has proven cardioprotective and nephroprotective effects. However, the risk of all-cause death with dapagliflozin remains unclear. RESEARCH DESIGN AND METHODS: We performed a meta-analysis of phase III randomized controlled trials (RCTs) for the risk of all-cause death and safety events with dapagliflozin compared to placebo. PubMed and EMBASE were searched from inception to 20 September 2022. RESULTS: Five trials were included in the final analysis. Compared with the placebo, dapagliflozin demonstrated an 11.2% reduction in the risk of all-cause death (OR 0.88, 95% CI 0.81-0.94). No statistically significant difference in urinary tract infection (OR: 0.95, 95% CI: 0.78 to 1.17), bone fracture (OR: 1.06, 95% CI: 0.94 to 1.20), and amputation (OR: 1.01, 95% CI: 0.82 to 1.23) was observed between patients treated with dapagliflozin and placebo. Compared with placebo, dapagliflozin was associated with a significant reduction in acute kidney injury (OR: 0.71, 95% CI: 0.60 to 0.83), and increased the risk of genital infection (OR: 8.21, 95% CI: 4.19 to 16.12). CONCLUSIONS: Dapagliflozin was associated with significantly reduced all-cause death and increased genital infection. Dapagliflozin was safe concerning urinary tract infection, bone fracture, amputation, and acute kidney injury, compared with the placebo.

Sequential expression of miR-221-3p and miR-338-3p in Schwann cells as a therapeutic strategy to promote nerve regeneration and functional recovery.

The functional properties of endogenous Schwann cells (SCs) during nerve repair are dynamic. Optimizing the functional properties of SCs at different stages of nerve repair may have therapeutic benefit in improving the repair of damaged nerves. Previous studies showed that miR-221-3p promotes the proliferation and migration of SCs, and miR-338-3p promotes the myelination of SCs. In this study, we established rat models of sciatic nerve injury by bridging the transected sciatic nerve with a silicone tube. We injected a miR-221 lentiviral vector system together with a doxycycline-inducible Tet-On miR-338 lentiviral vector system into the cavity of nerve conduits of nerve stumps to sequentially regulate the biological function of endogenous SCs at different stages of nerve regeneration. We found that the biological function of SCs was sequentially regulated, the diameter and density of myelinated axons were increased, the expression levels of NF200 and myelin basic protein were increased, and the function of injured peripheral nerve was improved using this system. miRNA Target Prediction Database prediction, Nanopore whole transcriptome sequencing, quantitative PCR, and dual luciferase reporter gene assay results predicted and verified Cdkn1b and Nrp1 as target genes of miR-221-3p and miR-338-3p, respectively, and their regulatory effects on SCs were confirmed in vitro. In conclusion, here we established a new method to enhance nerve regeneration through sequential regulation of biological functions of endogenous SCs, which establishes a new concept and model for the treatment of peripheral nerve injury. The findings from this study will provide direct guiding significance for clinical treatment of sciatic nerve injury.

The role of exosomes and exosomal microRNA in diabetic cardiomyopathy.

Diabetic cardiomyopathy, a formidable cardiovascular complication linked to diabetes, is witnessing a relentless surge in its incidence. Despite extensive research efforts, the primary pathogenic mechanisms underlying this condition remain elusive. Consequently, a critical research imperative lies in identifying a sensitive and dependable marker for early diagnosis and treatment, thereby mitigating the onset and progression of diabetic cardiomyopathy (DCM). Exosomes (EXOs), minute vesicles enclosed within bilayer lipid membranes, have emerged as a fascinating frontier in this quest, capable of transporting a diverse cargo that mirrors the physiological and pathological states of their parent cells. These exosomes play an active role in the intercellular communication network of the cardiovascular system. Within the realm of exosomes, MicroRNA (miRNA) stands as a pivotal molecular player, revealing its profound influence on the progression of DCM. This comprehensive review aims to offer an introductory exploration of exosome structure and function, followed by a detailed examination of the intricate role played by exosome-associated miRNA in diabetic cardiomyopathy. Our ultimate objective is to bolster our comprehension of DCM diagnosis and treatment strategies, thereby facilitating timely intervention and improved outcomes.

Efficacy and Prediction Model Construction of Drug-Coated Balloon Combined with Cutting Balloon Angioplasty in the Treatment of Drug-Eluting Stent In-Stent Restenosis.

Objective: To investigate the efficacy of drug-coated balloon (DCB) combined with cutting balloon angioplasty (CBA) in the treatment of drug-eluting stent in-stent restenosis (DES-ISR) and to construct a predictive model for the occurrence of DES-ISR. Methods: According to the criteria of diagnosis, inclusion, and exclusion, DES-ISR patients who were treated in the outpatient and inpatient departments of cardiovascular medicine of Second People's Hospital of Guangdong Province from July 2021 to December 2021 were included. A total of 72 cases were planned to be enrolled, including 36 cases in the control group and 36 cases in the experimental group. The control group was treated with DCB, and the experimental group was combined with CBA. The treatment success rate, coronary angiography results before and after surgery, and the incidence of major adverse cardiovascular events during the follow-up period were compared between the two groups. Seventy-two DES-ISR patients were divided into ISR group and 59 non-ISR patients were divided into non-ISR group. The clinical data of the two groups were compared to analyze the risk factors affecting the occurrence of DES-ISR, and the prediction model was established. Results: The surgical success rate of the experimental group was 94.44% (34/36), which was higher than the 77.78% (28/36) of the control group (P < 0.05). The minimum lumen diameter (MLD) of the experimental group 6 months after operation was greater than that of the control group, the late lumen loss (LL) and lumen stenosis rate were higher than those in the control group, and the incidence of major adverse cardiovascular events was lower than that in the control group (P < 0.05). In the ISR group, the proportion of patients with abnormal BMI, smoking, hypertension, diabetes, and family history of coronary heart disease and multivessel coronary artery disease was higher than that in the non-ISR group, the degree of stenosis target lesion was higher than that in the non-ISR group, the diameter of target lesion and stent diameter were smaller than those in the non-ISR group, and the length of target lesion and stent length were longer than those in the non-ISR group; the number of stents was more than that in the non-ISR group (P < 0.05). Combined hypertension, multiple coronary artery lesions, stenosis target lesion degree ≥85.05%, and target lesion length ≥36.88 mm were risk factors for DES-ISR, and target lesion diameter ≥3.15 mm and stent diameter ≥3.15 mm were protective factors (P < 0.05). The prediction model of DES-ISR was obtained by multiple logistic regression analysis, P = 1[1 + e (2.281 + 3.321Xhypertension + 3.427Xumber of arterial lesions + 3.359Xstenosis target lesion degree - 3.143Xtarget lesion diameter + 0.650Xtarget lesion length - 10.159Xstent diameter)]. The Hosmer-Lemeshow test showed that Hosmer-Lemeshow χ 2 = 0.925, P =0.413; the ROC curve analysis showed that the AUC of the prediction model for the occurrence of DES-ISR was 0.924, the SE value was 0.022, and the 95% CI was 0.880-0.967. Conclusion: DCB combined with CBA has good clinical efficacy in the treatment of DES-ISR, which can reduce the rate of lumen stenosis and the incidence of adverse cardiovascular events. The prediction model established according to risk factors has high predictive value for the occurrence of DES-ISR.

SGLT2 inhibitors for the composite of cardiorenal outcome in patients with chronic kidney disease: A systematic review and meta-analysis of randomized controlled trials.

To conduct a systematic review and meta-analysis of specific chronic kidney disease (CKD) trials focusing on the composite of cardiorenal outcome, and assess indirectly the clinical outcome of treatments with three inhibitors of sodium-glucose cotransporter-2 (SGLT2) by Bayesian network meta-analysis, we used PubMed and Embase for randomized controlled trials comparing the efficacy of SGLT2 inhibitors in patients with established CKD. We estimated the composite of cardiorenal outcome of SGLT2 inhibitors versus control by pairwise meta-analysis. We included three trials including four treatment strategies (canagliflozin, dapagliflozin, sotagliflozin, and placebo) that met our inclusion criteria. SGLT2 inhibitors reduced the composite of cardiorenal outcome by 27.5% (OR 0.70, 95% CI 0.57-0.86, I2 = 72%). Results were corroborated in subgroup analysis. SGLT2 inhibitors reduced the composite of cardiorenal outcome in patients with and without diabetes (OR 0.72, 95% CI 0.60-0.86, and OR 0.51, 95% CI 0.35-0.75, respectively). The composite of cardiorenal outcome showed no significant difference in the comparison among three drugs: canagliflozin and dapagliflozin (OR 1.14, 95% CI 0.46-3.16), canagliflozin and sotagliflozin (OR 0.79, 95% CI 0.30-2.06), dapagliflozin and sotagliflozin (OR 0.69, 95% CI 0.26-1.73). Dapagliflozin was identified as having the lowest risk of the composite of cardiorenal outcome. In conclusion, SGLT2 inhibitors have robust benefits on the composite of cardiorenal outcome in patients with CKD. There was no significant difference in the composite of cardiorenal outcome among treatments with three SGLT2 inhibitors; however, dapagliflozin may be associated with the lowest risk of the composite of cardiorenal outcome.

Smart Electronic Textiles for Wearable Sensing and Display.

Increasing demand of using everyday clothing in wearable sensing and display has synergistically advanced the field of electronic textiles, or e-textiles. A variety of types of e-textiles have been formed into stretchy fabrics in a manner that can maintain their intrinsic properties of stretchability, breathability, and wearability to fit comfortably across different sizes and shapes of the human body. These unique features have been leveraged to ensure accuracy in capturing physical, chemical, and electrophysiological signals from the skin under ambulatory conditions, while also displaying the sensing data or other immediate information in daily life. Here, we review the emerging trends and recent advances in e-textiles in wearable sensing and display, with a focus on their materials, constructions, and implementations. We also describe perspectives on the remaining challenges of e-textiles to guide future research directions toward wider adoption in practice.

Navigating Calcium and Reactive Oxygen Species by Natural Flavones for the Treatment of Heart Failure.

Heart failure (HF), the leading cause of death among men and women world-wide, causes great health and economic burdens. HF can be triggered by many factors, such as coronary artery disease, heart attack, cardiomyopathy, hypertension, obesity, etc., all of which have close relations with calcium signal and the level of reactive oxygen species (ROS). Calcium is an essential second messenger in signaling pathways, playing a pivotal role in regulating the life and death of cardiomyocytes via the calcium-apoptosis link mediated by the cellular level of calcium. Meanwhile, calcium can also control the rate of energy production in mitochondria that are the major resources of ROS whose overproduction can lead to cell death. More importantly, there are bidirectional interactions between calcium and ROS, and such interactions may have therapeutic implications in treating HF through finely tuning the balance between these two by certain drugs. Many naturally derived products, e.g., flavones and isoflavones, have been shown to possess activities in regulating calcium and ROS simultaneously, thereby leading to a balanced microenvironment in heart tissues to exert therapeutic efficacies in HF. In this mini review, we aimed to provide an updated knowledge of the interplay between calcium and ROS in the development of HF. In addition, we summarized the recent studies (in vitro, in vivo and in clinical trials) using natural isolated flavones and isoflavones in treating HF. Critical challenges are also discussed. The information collected may help to evoke multidisciplinary efforts in developing novel agents for the potential prevention and treatment of HF.

A Lamellibranchia-inspired epidermal electrode for electrophysiology.

The capability to accurately monitor electrophysiological signals and instantly provide feedback to users is crucial for wearable healthcare. However, commercial gel electrodes suffer from drying out and irritation on skin with time, severely affecting signal quality for practical use. Toward a gel-free electrophysiology, epidermal electrodes that can accurately detect biosignals and simultaneously achieve the multifunctional properties of on-skin electronics needs are highly desirable. In this work, inspired by Lamellibranchia, which can adhere tightly to various surfaces using their extensible, adhesive and self-healing byssal threads, we developed a gel-free epidermal electrode to acquire high-quality electrophysiological signals based on a novel polymer substrate design. This polymer (STAR) features extreme stretchability (>2300% strain), high transparency (>90% transmittance at λ = 550 nm), gentle adhesion (adhesion strengths: tens of kPa), and rapid self-healing ability (95% healing efficiency in 10 min). Combined with silver nanowires as conductors, STAR was employed as a self-healing, stretchable and adhesive epidermal electrode for electrophysiological signal recording, showing a signal-to-noise ratio (SNR) even higher than that of commercial electrodes, and being able to control an artificial limb as an intermediate for human-machine interface. We believe our Lamellibranchia inspired STAR will pave a new way to design multifunctional polymers for epidermal electronics, accelerating the development of emerging wearable healthcare.

ECNet is an evolutionary context-integrated deep learning framework for protein engineering.

Machine learning has been increasingly used for protein engineering. However, because the general sequence contexts they capture are not specific to the protein being engineered, the accuracy of existing machine learning algorithms is rather limited. Here, we report ECNet (evolutionary context-integrated neural network), a deep-learning algorithm that exploits evolutionary contexts to predict functional fitness for protein engineering. This algorithm integrates local evolutionary context from homologous sequences that explicitly model residue-residue epistasis for the protein of interest with the global evolutionary context that encodes rich semantic and structural features from the enormous protein sequence universe. As such, it enables accurate mapping from sequence to function and provides generalization from low-order mutants to higher-order mutants. We show that ECNet predicts the sequence-function relationship more accurately as compared to existing machine learning algorithms by using ~50 deep mutational scanning and random mutagenesis datasets. Moreover, we used ECNet to guide the engineering of TEM-1 ß-lactamase and identified variants with improved ampicillin resistance with high success rates.

High-Voltage and Wide-Temperature Lithium Metal Batteries Enabled by Ultrathin MOF-Derived Solid Polymer Electrolytes with Modulated Ion Transport.

Solid polymer electrolytes (SPEs) of superior ionic conductivity, long-term cycling stability, and good interface compatibility are regarded as promising candidates to enable the practical applications of solid lithium metal batteries (SLMBs). Here, a mixed-matrix SPE (MMSE) with incorporated metal-organic frameworks (MOFs) and ionic liquid is prepared. The dissociation of Li salt in MMSE can be promoted effectively due to the introduction of MOF via the Fourier-transform infrared spectroscopy (FT-IR) analysis, density functional theory calculation, and molecular dynamics simulation. The as-formed MMSE exhibits an ultralow thickness of 20 µm with a satisfactory ionic conductivity and lithium-ion transference number (1.1 mS cm-1 at 30 °C, 0.72). The optimized SLMBs with high-voltage LiMn0.75Fe0.25PO4 (LMFP) exhibit an excellent cyclability at 4.2 V under room temperature. Moreover, Li/MMSE/LiFePO4 cells have desirable cycle performance from -20 to 100 °C, and their capacity remains 143.3 mA h g-1 after being cycled 300 times at 10 C at 100 °C. The Li/LiFePO4 pouch cells also show excellent safety under extreme conditions. The Li symmetric cells can work steadily even at a supreme current density of 4 mA cm-2 at 100 °C. From the above analysis, these MMSEs present new opportunities for the development of SLMBs with good electrochemical properties.