GSDMD knockout alleviates sepsis-associated skeletal muscle atrophy by inhibiting IL18/AMPK signaling.

BACKGROUND: Sepsis commonly leads to skeletal muscle atrophy, characterized by substantial muscle weakness and degeneration, ultimately contributing to an adverse prognosis. Studies have shown that programmed cell death is an important factor in the progression of muscle loss in sepsis. However, the precise role and mechanism of pyroptosis in skeletal muscle atrophy are not yet fully comprehended. Therefore, we aimed to examine the role and mechanism of action of the pyroptosis effector protein GSDMD in recognized cellular and mouse models of sepsis. METHODS: The levels of GSDMD and N-GSDMD in skeletal muscle were evaluated 2, 4, and 8 days after CLP. Sepsis was produced in mice that lacked the Gsdmd gene (Gsdmd knockout) and in mice with the normal Gsdmd gene (wild-type) using a procedure called cecal ligation and puncture (CLP). The degree of muscular atrophy in the gastrocnemius and tibialis anterior muscles was assessed 72 hours after surgery in the septic mouse model. In addition, the architecture of skeletal muscles, protein expression, and markers associated with pathways leading to muscle atrophy were examined in mice from various groups 72 hours after surgery. The in vitro investigations entailed the use of siRNA to suppress Gsdmd expression in C2C12 cells, followed by stimulation of these cells with lipopolysaccharide (LPS) to evaluate the impact of Gsdmd downregulation on muscle atrophy and the related signaling cascades. RESULTS: This study has demonstrated that the GSDMD protein, known as the "executive" protein of pyroptosis, plays a crucial role in the advancement of skeletal muscle atrophy in septic mice. The expression of N-GSDMD in the skeletal muscle of septic mice was markedly higher compared to the control group. The Gsdmd knockout mice exhibited notable enhancements in survival, muscle strength, and body weight compared to the septic mice. Deletion of the Gsdmd gene reduced muscular wasting in the gastrocnemius and tibialis anterior muscles caused by sepsis. Studies conducted in living organisms (in vivo) and in laboratory conditions (in vitro) have shown that the absence of the Gsdmd gene decreases indicators of muscle loss associated with sepsis by blocking the IL18/AMPK signaling pathway. CONCLUSION: The results of this study demonstrate that the lack of Gsdmd has a beneficial effect on septic skeletal muscle atrophy by reducing the activation of IL18/AMPK and inhibiting the UPS and autophagy pathways. Therefore, our research provides vital insights into the role of pyroptosis in sepsis-related skeletal muscle wasting, which could potentially lead to the development of therapeutic and interventional approaches for preventing septic skeletal muscle atrophy.

Role of mesenchymal stem cells in sepsis and their therapeutic potential in sepsis­associated myopathy (Review).

Sepsis­induced myopathy (SIM) is one of the leading causes of death in critically ill patients. SIM mainly involves the respiratory and skeletal muscles of patients, resulting in an increased risk of lung infection, aggravated respiratory failure, and prolonged mechanical ventilation and hospital stay. SIM is also an independent risk factor associated with increased mortality in critically ill patients. At present, no effective treatment for SIM has yet been established. However, mesenchymal stem cells (MSCs) have emerged as a promising therapeutic approach and have been utilized in the treatment of various clinical conditions. A significant body of basic and clinical research supports the efficacy of MSCs in managing sepsis and muscle­related diseases. This literature review aims to explore the relationship between MSCs and sepsis, as well as their impact on skeletal muscle­associated diseases. Additionally, the present review discusses the potential mechanisms and therapeutic benefits of MSCs in the context of SIM.

Correlating local structure and migration dynamics in Na/Li dual ion conductor Na5YSi4O12.

Na5YSi4O12 (NYSO) is demonstrated as a promising electrolyte with high ionic conductivity and low activation energy for practical use in solid Na-ion batteries. Solid-state NMR was employed to identify the six types of coordination of Na+ ions and migration pathway, which is vital to master working mechanism and enhance performance. The assignment of each sodium site is clearly determined from high-quality 23Na NMR spectra by the aid of Density Functional Theory calculation. Well-resolved 23Na exchangespectroscopy and electrochemical tracer exchange spectra provide the first experimental evidence to show the existence of ionic exchange between sodium at Na5 and Na6 sites, revealing that Na transport route is possibly along three-dimensional chain of open channel-Na4-open channel. Variable-temperature NMR relaxometry is developed to evaluate Na jump rates and self-diffusion coefficient to probe the sodium-ion dynamics in NYSO. Furthermore, NYSO works well as a dual ion conductor in Na and Li metal batteries with Na3V2(PO4)3 and LiFePO4 as cathodes, respectively.

Efficient Room-Temperature Phosphorescence in 2D Perovskite via Mixed Organic Cation Incorporation.

The achievement of RTP in hybrid organic-inorganic perovskites (HIOPs) via molecular engineering remains relatively uncommon. Here, a series of novel 2D HIOPs composed of mixed organic cations such as naphthalene methylamine (NMA) and 2-(4-methylphenyl) ethanamine (4MPEA) are reported. Efficient RTP and tunable emissions ranging from green to yellow to orange, depending on the doping ratio, are activated in the organic cation-mixed 2D HIOPs system. It has been certified that the triplet excitons of NMA primarily stem from the Wannier excitons of the inorganic layer through an energy transfer process. By gradually altering the halide composition from Br to Cl, the NMA substituted chlorine-based 2D HIOPs show an outstandingly long lifetime of 176 ms. Moreover, potential applications in multiple information encryption and displays have been demonstrated. Our study confirms the effectiveness of strategically hybridizing organic cations with inorganic matrices at the molecular level to achieve high performance RTP.

The spatial variations and driving factors of C, N, P stoichiometric characteristics of plant and soil in the terrestrial ecosystem.

Carbon(C), nitrogen(N), and phosphorus(P) are crucial elements in the element cycling in the terrestrial ecosystems. In the past decades, the spatial patterns and driving mechanisms of plant and soil ecological stoichiometry have been hot topics in ecological geography. So far, many studies at different spatial and ecological scales have been conducted, but systematic review has not been reported to summarize the research status. In this paper, we tried to fill this gap by reviewing both the spatial variations and driving factors of C, N, P stoichiometric characteristics of plant and soil at regional to large scale. Additionally, we synthesized researches on the relationships between plant and soil C, N and P stoichiometric characteristics. At the global scale, plant C, N, P stoichiometric characteristics exhibited some trends along latitude and temperature gradient. Plant taxonomic classification was the main factor controlling the spatial variations of plant C, N and P stoichiometric characteristics. Climate factor and soil properties showed varying impacts on the spatial variations of plant C, N, P stoichiometric characteristics across different spatial scales. Soil C, N, P stoichiometric characteristics also varied along climate gradient at large scale. Their spatial variations resulted from the combined effects of climate, topography, soil properties, and vegetation characteristics at regional scale. The spatial pattern of soil C, N, P stoichiometric characteristics and the driving effects from environmental factors could be notably different among different ecosystems and vegetation types. Plant C:N:P was obviously higher than that of soil, and there existed a positive correlation between plant and soil C:N:P. Their trends along longitude and latitude were similar, but this correlation varied significantly among different vegetation types. Finally, based on the issues identified in this paper, we highlighted eight potential research themes for the future studies.

Enhanced Efficiency and Stability of Inverted Perovskite Solar Cells via Primary Amine Molecular Reaction.

The inverted perovskite solar cells have drawn considerable attention owing to their low cost, good compatibility, and easy production processes. However, the device performance is still limited by some important factors, such as surface imperfections and interfacial nonradiative recombination losses. Here, N-acetylethylenediamine (N-AE) is introduced to bind to the surface of the perovskite film via an ammonia condensation reaction. This process creates a stable interfacial layer with n-type doping to enhance the open-circuit voltage (VOC). Moreover, during post-treatment, N-AE dissolves a portion of the perovskite on the surface, leading to perovskite recrystallization. This process enhances the surface quality of the perovskite film and reduces nonradiative recombination. As a result, the inverted perovskite solar cell exhibits a power conversion efficiency approaching 20%, with a rise in VOC from 0.96 to 1.05 V. More impressively, the unencapsulated devices display excellent stability at 85 °C annealing and retained 88% of the initial PCE for 816 h.

Evaluation and impact factors of international competitiveness of China's cobalt industry from the perspective of trade networks.

In recent years, with the development of the new energy industry, the demand for cobalt as a raw material for power batteries has been increasing. However, China itself has a shortage of cobalt resources. Therefore, overcoming poor resource conditions and enhancing the international competitiveness of the cobalt industry have become urgent issues. This paper is based on global trade data on cobalt resources from 2007 to 2020. A panel regression model is constructed from the perspective of trade networks, and Entropy-Topsis is used to construct a comprehensive evaluation index system for the international competitiveness of critical nonferrous metals. This study empirically examines the impact of the trade network characteristics of cobalt resources on international competitiveness, assigns practical significance to trade network characteristic indicators, and analyses the overall competitiveness changes in the global cobalt industry chain and its upstream, midstream, and downstream sectors. The research findings reveal the following key points: (1) In recent years, the competitive focus of the cobalt industry chain in various countries has shifted from upstream and midstream to midstream and downstream, with increasingly fierce trade competition downstream, gradually tilting toward countries such as South Korea, Japan, and China. (2) Cobalt trade competition, which was initially characterized by competition among multiple countries, has gradually become more centralized and stable, with differences in the competitiveness of various countries occurring at different stages of the cobalt industry chain. (3) Network centrality and network heterogeneity both have a significant promoting effect on the international competitiveness of the industry, while network connectivity has a significant inhibitory effect on the improvement of international competitiveness.On this basis, the study also suggests some policy implications. The purpose of the study is to enhance the international competitiveness of China's cobalt industry from a trade perspective and to investigate the developments of cobalt trade between China and the rest of the world.

Mn(II)-Based Metal Halide with Near-Unity Quantum Yield for White LEDs and High-Resolution X-ray Imaging.

Metal halides have drawn great interest as luminescent materials and scintillators due to their outstanding optical properties. Exploring new types of phosphors with easy production processes, excellent photophysical properties, high light yields, and environmentally friendly compositions is crucial and quite challenging. Herein, a novel Mn(II)-based metal halide (4-BTP)2MnBr4 was produced using a facile solvent evaporation method, which exhibited a strong green emission peaking at 524 nm from the d-d transition of tetrahedral-coordinated Mn2+ ion and a near-unity quantum yield. The prepared white light-emitting diode device has a wide color gamut of 100.7% NTSC with CIE chromaticity coordinates of (0.32, 0.32). In addition, (4-BTP)2MnBr4 demonstrates excellent characteristics in X-ray scintillation, including a high light yield of 98 000 photons/MeV, a sensitive detection limit of 37.4 nGy/s, excellent resistance to radiation damage, and successful demonstration of X-ray imaging with high resolution at 21.3 lp/mm, revealing the potential for application in diagnostic X-ray medical imaging and industry radiation detection.

Spontaneous Compositional-Interfacial Co-Modification Engineering via Ion Exchange Reaction Between Perovskite and Electron-Transporting Layer for Exceptionally Long-Term Stability of Photovoltaics.

The long-term stability of perovskite solar cells (PSCs) is still challenging for commercialization and mainly linked to the life span of perovskite films. Herein, a spontaneous compositional-interfacial co-modification strategy is developed based on the ion exchange reaction by introducing ammonium hexafluorophosphate (NH4PF6) into antisolvent to form gradient structures through a simple one-step solvent engineering. With the assistance of the ion exchange reaction, NH4PF6 forms a multifunctional structure to protect perovskite films from both internal and external factors for the exceptionally long-term stability of photovoltaics. The reason for this is linked to the high hydrophobicity of NH4PF6 for preventing H2O invasion, suppressing ion migration by forming hydrogen bonding, and reducing perovskite defects. The resulting unencapsulated devices show exceptionally long-term stability under standardized the International Summit on Organic Photovoltaic Stability (ISOS) protocols, with over 94%, 81%, and 83% retained power conversion efficiencies after aging tests under N2 (ISOS-D-1I), ambient air (ISOS-D-1), and 85 °C (ISOS-D-2I) for 14016, 2500, and 1248 h, respectively. These performances compare well with the state-of-the-art stability of inverted PSCs. Further investigations are conducted to study the evolution of macroscopic morphology and microscopic crystal structure in aged perovskite films, aiming to provide evidence supporting the aforementioned improvements in stability.

Identification of ferroptosis-associated genes and potential pharmacological targets in sepsis-induced myopathy.

Background: The role of Ferroptosis in the course of sepsis-induced myopathy is yet unclear. The objective of our work is to identify key genes connected with Ferroptosis in sepsis-induced myopathy and investigate possible pharmaceutical targets related to this process. This research aims to provide new insights into the management of sepsis-induced myopathy. Methods: We got the GSE13205 dataset from the Gene Expression Omnibus (GEO) and extracted Ferroptosis-associated genes from the FerrDb database. After conducting a functional annotation analysis of these genes, we created a protein-protein interaction network using Cytoscape software to identify important genes. Subsequently, we employed CMap to investigate prospective pharmaceuticals that could target these crucial genes. Results: A total of 61 genes that are expressed differently (DEGs) have been found concerning Ferroptosis. These genes are involved in a wide range of biological functions, including reacting to signals from outside the cell and the availability of nutrients, programmed cell death, controlling apoptosis, and responding to peptides, chemical stressors, and hormones. The KEGG pathway study revealed that these pathways are involved in Ferroptosis, autophagy, P53 signaling, PI3K-Akt signaling, mTOR signaling, HIF-1 signaling, endocrine resistance, and different tumorigenic processes. In addition, we created a network that shows the simultaneous expression of important genes and determined the top 10 medications that have the potential to treat sepsis-induced myopathy. Conclusion: The bioinformatics research undertaken sheds insight into the probable role of Ferroptosis-associated genes in sepsis-induced myopathy. The identified critical genes show potential as therapeutic targets for treating sepsis-induced myopathy, offering opportunities for the development of tailored medicines.

The glass phase in the grain boundary of Na3Zr2Si2PO12, created by gallium modulation.

Na3Zr2Si2PO12 has been proven to be a promising electrolyte for solid-state sodium batteries. However, its poor conductivity prevents application, caused by the large ionic resistance created by the grain boundary. Herein, we propose an additional glass phase (Na-Ga-Si-P-O phase) to connect the grain boundary via Ga ion introduction, resulting in enhanced sodium-ion conduction and electrochemical performance. The optimized Na3Zr2Si2PO12-0.15Ga electrolyte exhibits Na+ conductivity of 1.65 mS cm-1 at room temperature and a low activation energy of 0.16 eV, with 20% newly formed glass phase enclosing the grain boundary. Temperature-dependent NMR line shapes and spin-lattice relaxation were used to estimate the Na self-diffusion and Na ion hopping. The dense glass-ceramic electrolyte design strategy and the structure-dynamics-property correlation from NMR, can be extended to the optimization of other materials.

Spatio-temporal patterns and drivers of CH4 and CO2 fluxes from rivers and lakes in highly urbanized areas.

Gaseous carbon exchange at the water-air interface of rivers and lakes is an essential process for regional and global carbon cycle assessments. Many studies have shown that rivers surrounding urban landscapes can be hotspots for greenhouse gas (GHG) emissions. Here we investigated the variability of diffusive GHG (methane [CH4] and carbon dioxide [CO2]) emissions from rivers in different landscapes (i.e., urban, agricultural and mixed) and from lakes in Suzhou, a highly urbanized region in eastern China. GHG emissions in the Suzhou metropolitan water network followed a typical seasonal pattern, with the highest fluxes in summer, and were primarily influenced by temperature and dissolved oxygen concentration. Surprisingly, lakes were emission hotspots, with mean CH4 and CO2 fluxes of 2.80 and 128.89 mg m-2 h-1, respectively, translating to a total CO2-equivalent flux of 0.21 g CO2-eq m-2 d-1. The global warming potential of urban and mixed rivers (0.19 g CO2-eq m-2 d-1) was comparable to that for lakes, but about twice the value for agricultural rivers (0.10 g CO2-eq m-2 d-1). Factors related to the high GHG emissions in lakes included hypoxic water conditions and an adequate nutrient supply. Riverine CH4 emissions were primarily associated with the concentrations of total dissolved solids (TDS), ammonia­nitrogen and chlorophyll a. CO2 emissions in rivers were mainly closely related to TDS, with suitable conditions allowing rapid organic matter decomposition. Compared with other types of rivers, urban rivers had more available organic matter and therefore higher CO2 emissions. Overall, this study emphasizes the need for a deeper understanding of the impact of GHG emissions from different water types on global warming in rapidly urbanizing regions. Flexible management measures are urgently needed to mitigate CO2 and CH4 emissions more effectively in the context of the shrinking gap between urban and rural areas with growing socio-economic development.

Early warning system enables accurate mortality risk prediction for acute gastrointestinal bleeding admitted to intensive care unit.

Acute gastrointestinal (GI) bleeding are potentially life-threatening conditions. Early risk stratification is important for triaging patients to the appropriate level of medical care and intervention. Patients admitted to intensive care unit (ICU) has a high mortality, but risk tool is scarce for these patients. This study aimed to develop and validate a risk score to improve the prognostication of death at the time of patient admission to ICU. We developed and internally validated a nomogram for mortality in patients with acute GI bleeding from the eICU Collaborative Research Database (eICU-CRD), and externally validated it in patients from the Medical Information Mart for Intensive Care III database (MIMIC-III) and Wuhan Tongji Hospital. The performance of the model was assessed by examining discrimination (C-index), calibration (calibration curves) and usefulness (decision curves). 4750 patients were included in the development cohort, with 1184 patients in the internal validation cohort, 1406 patients in the MIMIC-III validation cohort, and 342 patients in the Tongji validation cohort. The nomogram, which incorporated ten variables, showed good calibration and discrimination in the training and validation cohorts, yielded C-index ranged from 0.832 (95%CI 0.811-0.853) to 0.926 (95CI% 0.905-0.947). The nomogram-defined high-risk group had a higher mortality than the low-risk group (44.8% vs. 3.5%, P < 0.001; 41.4% vs 3.1%, P < 0.001;53.6% vs 7.5%, P < 0.001; 38.2% vs 4.2%, P < 0.001). The model performed better than the conventional Glasgow-Blatchford score, AIMS65 and the newer Oakland and Sengupta scores for mortality prediction in both the derivation and validation cohorts concerning discrimination and usefulness. Our nomogram is a reliable prognostic tool that might be useful to identify high-risk acute GI bleeding patients admitted to ICU.

Suppression of deep-level traps via semicarbazide hydrochloride additives for high-performance tin-based perovskite solar cells.

Tin perovskites with exemplary optoelectronic properties offer potential application in lead-free perovskite solar cells. However, Sn vacancies and undercoordinated Sn ions on the tin perovskite surfaces can create deep-level traps, leading to non-radiative recombination and absorption of nucleophilic O2 molecules, impeding further device efficiency and stability. Here, in this study, a new additive of semicarbazide hydrochloride (SEM-HCl) with a N-C=O functional group was introduced into the perovskite precursor to fabricate high-quality films with a low concentration of deep-level trap densities. This, in turn, serves to prevent undesirable interaction between photogenerated carriers and adsorbed oxygen molecules in the device's operational environment, ultimately reducing the proliferation of superoxide entities. As the result, the SEM-HCl-derived devices show a peak efficiency of 10.9% with improved device stability. These unencapsulated devices maintain almost 100% of their initial efficiencies after working for 100 h under continuous AM1.5 illumination conditions.

Enhanced Resonance for Facilitated Modulation of Large-Area Perovskite Films with Stable Photovoltaics.

Upscaling efficient and stable perovskite films is a challenging task in the industrialization of perovskite solar cells partly due to the lack of high-performance hole transport materials (HTMs), which can simultaneously promote hole transport and regulate the quality of perovskite films especially in inverted solar cells. Here, a novel HTM based on N-C = O resonance structure is designed for facilitating the modulation of the crystallization and bottom-surface defects of perovskite films. Benefiting from the resonance interconversion (N-C = O and N+ = C-O- ) in donor-resonance-donor (D-r-D) architecture and interactions with uncoordinated Pb2+ in perovskite, the resulting D-r-D HTM with two donor units exhibits not only excellent hole extraction and transport capacities, but also efficient crystallization modulation of perovskite for high-quality photovoltaic films in large area. The D-r-D HTM-based large-area (1.02 cm2 ) devices exhibit high power conversion efficiencies (PCEs) up to 21.0%. Moreover, the large-area devices have excellent photo-thermal stability, showing only a 2.6% reduction in PCE under continuous AM 1.5G light illumination at elevated temperature (≈65 °C) for over 1320 h without encapsulation.

Achieving Ultralong Room-Temperature Phosphorescence in Two-Dimensional Metal Halide Perovskites by Alkyl Chain Engineering.

Two-dimensional (2D) metal halide perovskites with highly efficient ultralong room-temperature phosphorescence (URTP) are rare due to their uncertain structures and complicated intermolecular interactions. Herein, by varying the alkyl length of organic units, we synthesized two single-component 2D metal hybrid perovskites, i.e., B-MACC and B-EACC, with obvious URTP emission. In particular, B-EACC exhibits a green-yellow URTP emission with an ultralong lifetime (579 ms) and a high efficiency (14.86%). It is found that the molecular packing of B-EA+ cations because of the presence one more carbon in the alkyl chain affords strong hydrogen bonding and π-π stacking interactions, which immobilizes and reduces the triplet exciton quenching. Moreover, B-MACC and B-EACC with space-time dual-resolved characteristics can be utilized for dynamic information encryption and optical logic gate applications. This study is the first to disclose the relation between the characteristics of molecular packing and the resultant URTP of 2D metal hybrid perovskites, significantly advancing the development of next-generation URTP materials for versatile applications.

Development and validation of a nomogram for predicting persistent inflammation, immunosuppression, and catabolism syndrome in trauma patients.

Background: Persistent Inflammation, Immunosuppression, and Catabolism Syndrome (PIICS) is a significant contributor to adverse long-term outcomes in severe trauma patients. Objective: The objective of this study was to establish and validate a PIICS predictive model in severe trauma patients, providing a practical tool for early clinical prediction. Patients and methods: Adult severe trauma patients with an Injury Severity Score (ISS) of ≥16, admitted between October 2020 and December 2022, were randomly divided into a training set and a validation set in a 7:3 ratio. Patients were classified into PIICS and non-PIICS groups based on diagnostic criteria. LASSO regression was used to select appropriate variables for constructing the prognostic model. A logistic regression model was developed and presented in the form of a nomogram. The performance of the model was evaluated using calibration and ROC curves. Results: A total of 215 patients were included, consisting of 155 males (72.1%) and 60 females (27.9%), with a median age of 51 years (range: 38-59). NRS2002, ISS, APACHE II, and SOFA scores were selected using LASSO regression to construct the prognostic model. The AUC of the ROC analysis for the predictive model in the validation set was 0.84 (95% CI 0.72-0.95). The Hosmer-Lemeshow test in the validation set yielded a χ2 value of 14.74, with a value of p of 0.098. Conclusion: An accurate and easily implementable PIICS risk prediction model was established. It can enhance risk stratification during hospitalization for severe trauma patients, providing a novel approach for prognostic prediction.

Ultralong Red Room-Temperature Phosphorescence of 2D Organic-Inorganic Metal Halide Perovskites for Afterglow Red LEDs and X-ray Scintillation Applications.

Organic-inorganic metal hybrid perovskites (OIHPs) have emerged as a promising class of materials for next-generation optoelectronic applications. However, the realization of red and near-infrared (NIR) room-temperature phosphorescence (RTP) in these materials remains limited. In this study, a very strong red RTP emission centered at 610 nm is achieved by doping Mn2+ ions into Cd-based 2D OIHPs. Notably, the optimized B-EACC:Mn2+ exhibited a high quantum yield of 44.11%, an ultralong lifetime of up to 378 ms, and excellent stability against high temperatures and various solvents, surpassing most reported counterparts of 2D OIHPs. Moreover, the B-EACC:Mn2+ can be used as a red emitter for coating an ultraviolet light-emitting diode chip, exhibiting an observable afterglow to the naked eye for approximately 4 s. In addition, the B-EACC:Mn2+ demonstrates interesting characteristics under X-ray excitation, exhibiting X-ray response at radiation doses in the range of 34.75-278 µGy s-1. This work suggests the infinite possibility of doping guest ions to realize red RTP in 2D OIHPs, promoting the development of long-persistent phosphorescent emitters for multifunctional light-emitting applications.

Targeting NAT10 protects against sepsis-induced skeletal muscle atrophy by inhibiting ROS/NLRP3.

AIMS: To identify N-acetyltransferase 10 (NAT10) and its downstream signaling pathways in myocytes and skeletal muscle, and to investigate its role in inflammation-induced muscle atrophy. MATERIALS AND METHODS: Cecal ligation and puncture models were used to induce sepsis in C57BL/6 mice, which were treated with either a NAT10 inhibitor or a control agent. The therapeutic effect of NAT10 inhibitor was investigated by evaluating the mass, morphology, and molecular characteristics of mouse skeletal muscle. C2C12 cells were stimulated with LPS, and the expression of the NAT10 gene, downstream protein content, and atrophy phenotype were analyzed using a NAT10 inhibitor, to further explore the atrophic effect of NAT10 on C2C12 differentiated myotubes. RESULTS: Gene set enrichment analysis revealed that NAT10 expression was elevated in the Lateral femoris muscle of patients with ICUAW. In vitro and in vivo experiments showed that sepsis or LPS induced the upregulation of NAT10 expression in skeletal muscles and C2C12 myotubes. Skeletal muscle mass, tissue morphology, gene expression, and protein content were associated with atrophic response in sepsis models. Remodelin ameliorated the LPS-induced skeletal muscle weight loss, as well as muscular atrophy, and improved survival. Remodelin reversed the atrophy program that was induced by inflammation through the downregulation of the ROS/NLRP3 pathway, along with the inhibition of the expression of MuRF1 and Atrogin-1. CONCLUSION: NAT10 is closely related to skeletal muscle atrophy during sepsis. Remodelin improves the survival rate of mice by improving the systemic inflammatory response and skeletal muscle atrophy by downregulating the ROS/NLRP3 signaling pathway.

Gut-muscle axis and sepsis-induced myopathy: The potential role of gut microbiota.

Sepsis is described as an immune response disorder of the host to infection in which microorganisms play a non-negligible role. Most survivors of sepsis experience ICU-acquired weakness, also known as septic myopathy, characterized by skeletal muscle atrophy, weakness, and irreparable damage/regenerated or dysfunctional. The mechanism of sepsis-induced myopathy is currently unclear. It has been believed that this state is triggered by circulating pathogens and their related harmful factors, leading to impaired muscle metabolism. Sepsis and its resulting alterations in the intestinal microbiota are associated with sepsis-related organ dysfunction, including skeletal muscle wasting. There are also some studies on interventions targeting the flora, including fecal microbiota transplants, the addition of dietary fiber and probiotics in enteral feeding products, etc., aiming to improve sepsis-related myopathy. In this review, we critically assess the potential mechanisms and therapeutic prospects of intestinal flora in the development of septic myopathy.