Acute exposure to polystyrene nanoparticles promotes liver injury by inducing mitochondrial ROS-dependent necroptosis and augmenting macrophage-hepatocyte crosstalk.

BACKGROUND: The global use of plastic materials has undergone rapid expansion, resulting in the substantial generation of degraded and synthetic microplastics and nanoplastics (MNPs), which have the potential to impose significant environmental burdens and cause harmful effects on living organisms. Despite this, the detrimental impacts of MNPs exposure towards host cells and tissues have not been thoroughly characterized. RESULTS: In the present study, we have elucidated a previously unidentified hepatotoxic effect of 20 nm synthetic polystyrene nanoparticles (PSNPs), rather than larger PS beads, by selectively inducing necroptosis in macrophages. Mechanistically, 20 nm PSNPs were rapidly internalized by macrophages and accumulated in the mitochondria, where they disrupted mitochondrial integrity, leading to heightened production of mitochondrial reactive oxygen species (mtROS). This elevated mtROS generation essentially triggered necroptosis in macrophages, resulting in enhanced crosstalk with hepatocytes, ultimately leading to hepatocyte damage. Additionally, it was demonstrated that PSNPs induced necroptosis and promoted acute liver injury in mice. This harmful effect was significantly mitigated by the administration of a necroptosis inhibitor or systemic depletion of macrophages prior to PSNPs injection. CONCLUSION: Collectively, our study suggests a profound toxicity of environmental PSNP exposure by triggering macrophage necroptosis, which in turn induces hepatotoxicity via intercellular crosstalk between macrophages and hepatocytes in the hepatic microenvironment.

Transformer Monitoring with Electromagnetic Energy Transmission and Wireless Sensing.

To ensure stable and normal transformer operation, light gas protection of the transformer Buchholz relay is essential. However, false alarms related to light gas protection are common, and troubleshooting them often requires on-site gas sampling by personnel. During this time, the transformer's operating state may rapidly deteriorate, posing a safety threat to field staff. To tackle these challenges, this work presents the near-field, thin-sliced transformer monitoring system that uses Electromagnetic Energy Transmission and Wireless Sensing Device (ETWSD). The system leverages external wireless energy input to power gas monitoring sensors. Simultaneously, it employs Near-Field Communication to obtain real-time concentrations of light gases, along with the electrified state and temperature. In field testing conducted on transformer relays' gas collection chambers, the ETWSD effortlessly monitors parameters within warning ranges, encompassing methane gas concentrations around 1000 ppm, leakage voltage ranging from 0-100 V, and relay working temperatures up to 90 °C. Additionally, to facilitate real-time diagnosis for electrical workers, we have developed an Android-based APP software that displays current light gas concentrations, leakage voltage collection values, and temperature, while also enabling threshold judgment, alarms, and data storage. The developed ETWSD is expected to aid on-site personnel in promptly and accurately evaluating transformer light gas protection error alarm faults. It provides a method for simultaneous, contactless, and rapid monitoring of multiple indicators.

Glutamine sustains energy metabolism and alleviates liver injury in burn sepsis by promoting the assembly of mitochondrial HSP60-HSP10 complex via SIRT4 dependent protein deacetylation.

Burns and burn sepsis, characterized by persistent and profound hypercatabolism, cause energy metabolism dysfunction that worsens organ injury and systemic disorders. Glutamine (Gln) is a key nutrient that remarkably replenishes energy metabolism in burn and sepsis patients, but its exact roles beyond substrate supply is unclear. In this study, we demonstrated that Gln alleviated liver injury by sustaining energy supply and restoring redox balance. Meanwhile, Gln also rescued the dysfunctional mitochondrial electron transport chain (ETC) complexes, improved ATP production, reduced oxidative stress, and protected hepatocytes from burn sepsis injury. Mechanistically, we revealed that Gln could activate SIRT4 by upregulating its protein synthesis and increasing the level of Nicotinamide adenine dinucleotide (NAD+), a co-enzyme that sustains the activity of SIRT4. This, in turn, reduced the acetylation of shock protein (HSP) 60 to facilitate the assembly of the HSP60-HSP10 complex, which maintains the activity of ETC complex II and III and thus sustain ATP generation and reduce reactive oxygen species release. Overall, our study uncovers a previously unknown pharmacological mechanism involving the regulation of HSP60-HSP10 assembly by which Gln recovers mitochondrial complex activity, sustains cellular energy metabolism and exerts a hepato-protective role in burn sepsis.

Elimination of Acrolein by Disodium 5'-Guanylate or Disodium 5'-Inosinate at High Temperature and Its Application in Roasted Pork Patty.

Acrolein (ACR) is a highly active, simple unsaturated aldehyde found in various high-temperature processed foods. Its long-term accumulation in the human body increases the risk of chronic diseases. Animal and plant foodstuffs are rich in disodium 5'-guanylate (GMP) and disodium 5'-inosinate (IMP), which are authorized flavor enhancers. Herein, we used liquid chromatography with tandem mass spectrometry to explore the reaction-active kinetics and pathway of the interaction between GMP/IMP and ACR and validated it in roasted pork patties. Our results suggested that GMP and IMP could efficiently eliminate ACR by forming ACR adducts (GMP-ACR, IMP-ACR). In addition, IMP exhibited a higher reaction rate, whereas GMP had a good trapping capacity at a later stage. As carriers of GMP and IMP, dried mushrooms and shrimp exhibited an effective ACR-trapping ability in the ACR model and roasted pork patty individually and in combination. Adding 10% of dried mushroom or shrimp alone or 5% of dried mushroom and shrimp in combination eliminated up to 53.9%, 55.8%, and 55.2% ACR in a roasted pork patty, respectively. This study proposed a novel strategy to eliminate the generation of ACR in roasted pork patties by adding foodstuffs rich in GMP and IMP.

Theanine in Tea: An Effective Scavenger of Single or Multiple Reactive Carbonyl Species at the Same Time.

Reactive carbonyl species (RCS) are generated during thermal food processing, and their accumulation in the body increases the risk of various chronic diseases. Herein, the RCS-scavenging ability of theanine, a unique nonproteinogenic amino acid, was evaluated in terms of the scavenging rate, reaction kinetics, and reaction pathway using LC-MS/MS. Three major products of theanine conjugated with acrolein (ACR) and glyoxal (GO) were prepared and identified using nuclear magnetic resonance. Thereafter, the simultaneous reactions of four types of RCS (namely, ACR, crotonaldehyde, methylglyoxal, and GO) with theanine were discussed in RCS-theanine and RCS-tea models. Under different reaction ratios, theanine could nonspecifically scavenge the four coexisting RCS by forming adducts with them. The amount of theanine-RCS adducts in green and black tea was more than that of catechin (epigallocatechin gallate, epigallocatechin, epicatechin gallate, and epicatechin)-RCS adducts despite the lower content of theanine than catechins. Thus, theanine, as a food additive and dietary supplement, could demonstrate new bioactivity as a promising RCS scavenger in food processing.

Microfluidic synthesis of pH-responsive molecularly imprinted silica nanospheres for fluorescence sensing target glycoprotein.

Here, fluorescent artificial antibodies for sensing ovalbumin in food were synthesized by molecular imprinting technique in a microfluidic reactor. A phenylboronic acid-functionalized silane was employed as the functional monomer to enable the polymer has pH-responsive property. Fluorescent molecularly imprinted polymers (FMIPs) could be produced continuously in a short time. Both fluorescein isothiocyanate (FITC) and rhodamine B isothiocyanate (RB)-based FMIPs can specifically recognize the target ovalbumin, particularly FITC-based FMIP, giving an imprinting factor of 2.5 and cross-reactivity factors of 2.7 (ovotransferrin), 2.8 (ß-lactoglobulin) and 3.4 (bovine serum albumin), and was applied for the detection of ovalbumin in milk powder with recovery rates of 93-110%; moreover, the FMIP can be reused at least four times. Such FMIPs have promising future in replacing the fluorophore-labelled antibodies to fabricate fluorescent sensing devices or establish immunoassay methods, which have extra merits of low-cost, high stability and recyclability, easy to carry and store at ambient environments.

Synergistic Inhibitory Effect of Multiple Polyphenols from Spice on Acrolein during High-Temperature Processing.

Acrolein (ACR) is a toxic unsaturated aldehyde that is produced during food thermal processing. Here, we investigated the synergistic effect of polyphenols in binary, ternary, and quaternary combinations on ACR by the Chou-Talalay method, and then explored the synergistic effect of cardamonin (CAR), alpinetin (ALP), and pinocembrin (PIN) in fixed proportion from Alpinia katsumadai Hayata (AKH) combined with curcumin (CUR) in the model, and roasted pork using LC-MS/MS. Our results showed that their synergistic effect depended on the intensification of their individual trapping ACR activities, which resulted in the formation of more ACR adducts. In addition, by adding 1% AKH (as the carrier of CAR, ALP, and PIN) and 0.01% CUR (vs. 6% AKH single) as spices, more than 71.5% (vs. 54.0%) of ACR was eliminated in roast pork. Our results suggested that selective complex polyphenols can synergistically remove the toxic ACR that is produced in food processing.

Effects of hesperidin combined with synephrine on the capture of acrolein in a mouse model, or in humans by citrus consumption.

Acrolein (ACR) is a highly reactive α,ß-unsaturated aldehyde that plays a key role in the pathogenesis of human diseases, such as atherosclerosis and pulmonary, cardiovascular, and neurodegenerative disorders. We investigated the capture capacity of hesperidin (HES) and synephrine (SYN) on ACR by individual and combined means in vitro, in vivo (utilizing a mouse model), and via a human study. After proving that HES and SYN could efficiently capture ACR by generating ACR adducts in vitro, we further detected the adducts of SYN-2ACR, HES-ACR-1, and hesperetin (HESP)-ACR in mouse urine by ultraperformance liquid chromatography-tandem mass spectrometry. Quantitative assays revealed that adduct formation occurred in a dose-dependent manner, and that there was a synergistic effect of HES and SYN on capturing ACR in vivo. Moreover, quantitative analysis suggested that SYN-2ACR, HES-ACR-1, and HESP-ACR were formed and excreted through the urine of healthy volunteers consuming citrus. The maximum excretions of SYN-2ACR, HES-ACR-1, and HESP-ACR were at 2-4, 8-10, and 10-12 h, respectively, after dosing. Our findings propose a novel strategy for eliminating ACR from the human body via the simultaneous consumption of a flavonoid and an alkaloid.

Acetylated α-tubulin alleviates injury to the dendritic spines after ischemic stroke in mice.

BACKGROUND AND AIM: Functional recovery is associated with the preservation of dendritic spines in the penumbra area after stroke. Previous studies found that polymerized microtubules (MTs) serve a crucial role in regulating dendritic spine formation and plasticity. However, the mechanisms that are involved are poorly understood. This study is designed to understand whether the upregulation of acetylated α-tubulin (α-Ac-Tub, a marker for stable, and polymerized MTs) could alleviate injury to the dendritic spines in the penumbra area and motor dysfunction after ischemic stroke. METHODS: Ischemic stroke was mimicked both in an in vivo and in vitro setup using middle cerebral artery occlusion and oxygen-glucose deprivation models. Thy1-YFP mice were utilized to observe the morphology of the dendritic spines in the penumbra area. MEC17 is the specific acetyltransferase of α-tubulin. Thy1 CreERT2-eYFP and MEC17fl/fl mice were mated to produce mice with decreased expression of α-Ac-Tub in dendritic spines of pyramidal neurons in the cerebral cortex. Moreover, AAV-PHP.B-DIO-MEC17 virus and tubastatin A (TBA) were injected into Thy1 CreERT2-eYFP and Thy1-YFP mice to increase α-Ac-Tub expression. Single-pellet retrieval, irregular ladder walking, rotarod, and cylinder tests were performed to test the motor function after the ischemic stroke. RESULTS: α-Ac-Tub was colocalized with postsynaptic density 95. Although knockout of MEC17 in the pyramidal neurons did not affect the density of the dendritic spines, it significantly aggravated the injury to them in the penumbra area and motor dysfunction after stroke. However, MEC17 upregulation in the pyramidal neurons and TBA treatment could maintain mature dendritic spine density and alleviate motor dysfunction after stroke. CONCLUSION: Our study demonstrated that α-Ac-Tub plays a crucial role in the maintenance of the structure and functions of mature dendritic spines. Moreover, α-Ac-Tub protected the dendritic spines in the penumbra area and alleviated motor dysfunction after stroke.

Glutamine alleviates intestinal injury in a murine burn sepsis model by maintaining intestinal intraepithelial lymphocyte homeostasis.

Intestinal intraepithelial lymphocytes (IELs) play a sentinel role in the mucosal immune system because of their unique anatomical location in the epithelial layer. The disruption of IEL homeostasis is implicated in driving the intestinal injury of many typical inflammatory disorders, such as inflammatory bowel disease (IBD) and sepsis. Therefore, it is meaningful to alleviate intestinal injury by restoring IEL homeostasis in disease conditions. This study explores the effects of glutamine on intestinal IEL homeostasis in a murine model of burn sepsis. We report that glutamine inhibits inflammatory response and reduces injury in the small intestine of burn septic mice. This effect is attributed to the maintaining of IEL homeostasis by suppressing apoptosis and restoring the disrupted subpopulation balance induced by burn sepsis. Mechanistically, we show that glutamine does not affect the IL-15 dependent mechanisms that drive the maintenance and differentiation of IELs. Instead, glutamine sustains IEL homeostasis by upregulate aryl hydrocarbon receptor (AHR) and interleukin (IL)-22 transcription and expression. Consistently, the protective roles of glutamine in burn septic mice were repressed by further supplement with an AHR antagonist CH-223191. Collectively, our study reveals a new role of glutamine to maintain IEL homeostasis by activating the AHR signaling pathway, which in turn ameliorates intestinal injury in burn sepsis.

Of mice and men: Laboratory murine models for recapitulating the immunosuppression of human sepsis.

Prolonged immunosuppression is increasingly recognized as the major cause of late phase and long-term mortality in sepsis. Numerous murine models with different paradigms, such as lipopolysaccharide injection, bacterial inoculation, and barrier disruption, have been used to explore the pathogenesis of immunosuppression in sepsis or to test the efficacy of potential therapeutic agents. Nonetheless, the reproducibility and translational value of such models are often questioned, owing to a highly heterogeneric, complex, and dynamic nature of immunopathology in human sepsis, which cannot be consistently and stably recapitulated in mice. Despite of the inherent discrepancies that exist between mice and humans, we can increase the feasibility of murine models by minimizing inconsistency and increasing their clinical relevance. In this mini review, we summarize the current knowledge of murine models that are most commonly used to investigate sepsis-induced immunopathology, highlighting their strengths and limitations in mimicking the dysregulated immune response encountered in human sepsis. We also propose potential directions for refining murine sepsis models, such as reducing experimental inconsistencies, increasing the clinical relevance, and enhancing immunological similarities between mice and humans; such modifications may optimize the value of murine models in meeting research and translational demands when applied in studies of sepsis-induced immunosuppression.

Food additive octyl gallate eliminates acrolein and inhibits bacterial growth in oil-rich food.

Acrolein (ACR) is predominantly generated from oil-rich food during thermos- processing. Accumulation of ACR in vivo through food consumption has been associated with an increased risk of developing chronic diseases. Here, we investigated the inhibitory effect of octyl gallate (OG), a new food additive tolerant to high-temperature, alkaline and fat-soluble saturations, on the generation of ACR in OG-ACR, oil-Rancimat models, and real-world frying. Our results demonstrate that approximately 80% and 60% of ACR was eliminated by OG in the two models, respectively, and OG-ACR was detected in the deep-frying process using LC-MS/MS. The reaction pathways were clarified by synthesis and OG-ACR and OG-2ACR adduct structural elucidation. Our work reveals that the antibacterial activity of OG-ACR against Escherichia coli (gram-negative) was four times higher than that of OG. Thus, OG can be developed as a promising novel ACR scavenger for high-temperature food processing and an antibacterial agent in food storage.

A Liquid Metal-Enhanced Wearable Thermoelectric Generator.

It is a key challenge to continuously power personal wearable health monitoring systems. This paper reports a novel liquid metal-enhanced wearable thermoelectric generator (LM-WTEG that directly converts body heat into electricity for powering the wearable sensor system. The gallium-based liquid metal alloys with room-temperature melting point (24~30 °C) and high latent heat density (about 500 MJ/m3) are used to design a new flexible finned heat sink, which not only absorbs the heat through the solid-liquid phase change of the LM and enhances the heat release to the ambient air due to its high thermal conduction. The LM finned is integrated with WTEG to present high biaxial flexibility, which could be tightly in contact with the skin. The LM-WTEG could achieve a super high output power density of 275 µW/cm2 for the simulated heat source (37 °C) with the natural convective heat transfer condition. The energy management unit, the multi-parameter sensors (including temperature, humidity, and accelerometer), and Bluetooth module with a total energy consumption of about 65 µW are designed, which are fully powered from LM-WTEG through harvesting body heat.

Vibration Energy Harvesting from the Subwavelength Interface State of a Topological Metamaterial Beam.

Topological metamaterial has been a research hotpot in both physics and engineering due to its unique ability of wave manipulation. The topological interface state, which can efficiently and robustly centralize the elastic wave energy, is promising to attain high-performance energy harvesting. Since most of environmental vibration energy is in low frequency range, the interface state is required to be designed at subwavelength range. To this end, this paper developed a topological metamaterial beam with local resonators and studied its energy-harvesting performance. First, the unit cell of this topological metamaterial beam consists of a host beam with two pairs of parasitic beams with tip mass. Then, the band structure and topological features are determined. It is revealed that by tuning the distance between these two pairs of parasitic beams, band inversion where topological features inverse can be obtained. Then, two sub-chains, their design based on two topologically distinct unit cells, are assembled together with a piezoelectric transducer placed at the conjunction, yielding the locally resonant, topological, metamaterial, beam-based piezoelectric energy harvester. After that, its transmittance property and output power were obtained by using the frequency domain analysis of COMSOL Multiphysics. It is clear that the subwavelength interface state is obtained at the band-folding bandgap. Meanwhile, in the interface state, elastic wave energy is successfully centralized at the conjunction. From the response distribution, it is found that the maximum response takes place on the parasitic beam rather than the host beam. Therefore, the piezoelectric transducer is recommended to be placed on the parasitic beam rather than host beam. Finally, the robustness of the topological interface state and its potential advantages on energy harvesting were studied by introducing a local defect. It is clear that in the interface state, the maximum response is always located at the conjunction regardless of the defect degree and location. In other words, the piezoelectric transducer placed at the conjunction can maintain a stable and high-efficiency output power in the interface state, which makes the whole system very reliable in practical implementation.

Dual effects of cardamonin/alpinetin and their acrolein adducts on scavenging acrolein and the anti-bacterial activity from Alpinia katsumadai Hayata as a spice in roasted meat.

Acrolein (ACR) is frequently produced by the thermal degradation of carbohydrates and amino acids and lipid peroxidation in the thermal processing of food. Long-term exposure to ACR can cause various chronic diseases. Here, we screened two high-temperature-resistant ACR inhibitors, cardamonin (CAR) and alpinetin (ALP), which can interconvert without any loss at 100 °C, and were obtained from Alpinia katsumadai Hayata (AKH). They demonstrated the best activity among the six spices investigated and could scavenge ACR generated in roasted pork by forming adducts. After three ACR adducts were prepared, namely CAR-ACR-1, CAR-ACR-2 and ALP-ACR, quantitative analysis showed that the amount of CAR-ACR-1 generated in lean roasted pork with 2% AKH addition reached the minimal inhibitory concentration against Escherichia coli and Staphylococcus aureus, which was 20 times lower than that of CAR, and the higher the generation of ACR, the stronger its antibacterial activity. These results provided well-defined evidence to promote the application of AKH to ACR inhibitors in food processing.

Three Frequency Up-Converting Piezoelectric Energy Harvesters Caused by Internal Resonance Mechanism: A Narrative Review.

Low frequency mechanical vibrations are ubiquitous in practical environments, and how to efficiently harvest them with piezoelectric materials remains a challenge. Frequency up-conversion strategies-up-converting low frequency vibrations to high frequency self-oscillations-can improve the power density of piezoelectric materials. This paper mainly introduces a kind of frequency which up-converts piezoelectric energy harvesters based on an internal resonance mechanism, compared with the other mechanisms caused by mechanical impact, mechanical plucking, etc.; the internal resonance-based harvesters can up-convert the frequency under a condition of lower excitation level, less energy loss, and less wideband operation bandwidth. Benefits to practical vibrations also exist in these multi-degree-of-freedom nonlinear dynamic systems. Moreover, the value of the frequency up-conversion factor based on the 1:2:6 internal resonance mechanism can reach as much as six so far, which is also a quite a high frequency up-conversion value.

Acute exposure to gold nanoparticles aggravates lipopolysaccharide-induced liver injury by amplifying apoptosis via ROS-mediated macrophage-hepatocyte crosstalk.

BACKGROUND: Gold nanoparticles (AuNPs) are increasingly utilized in industrial and biomedical fields, thereby demanding a more comprehensive knowledge about their safety. Current toxicological studies mainly focus on the unfavorable biological impact governed by the physicochemical properties of AuNPs, yet the consequences of their interplay with other bioactive compounds in biological systems are poorly understood. RESULTS: In this study, AuNPs with a size of 10 nm, the most favorable size for interaction with host cells, were given alone or in combination with bacterial lipopolysaccharide (LPS) in mice or cultured hepatic cells. The results demonstrated that co exposure to AuNPs and LPS exacerbated fatal acute liver injury (ALI) in mice, although AuNPs are apparently non-toxic when administered alone. AuNPs do not enhance systemic or hepatic inflammation but synergize with LPS to upregulate hepatic apoptosis by augmenting macrophage-hepatocyte crosstalk. Mechanistically, AuNPs and LPS coordinate to upregulate NADPH oxidase 2 (NOX2)-dependent reactive oxygen species (ROS) generation and activate the intrinsic apoptotic pathway in hepatic macrophages. Extracellular ROS generation from macrophages is then augmented, thereby inducing calcium-dependent ROS generation and promoting apoptosis in hepatocytes. Furthermore, AuNPs and LPS upregulate scavenger receptor A expression in macrophages and thus increase AuNP uptake to mediate further apoptosis induction. CONCLUSIONS: This study reveals a profound impact of AuNPs in aggravating the hepatotoxic effect of LPS by amplifying ROS-dependent crosstalk in hepatic macrophages and hepatocytes.

Glutamine mitigates murine burn sepsis by supporting macrophage M2 polarization through repressing the SIRT5-mediated desuccinylation of pyruvate dehydrogenase.

Background: Alternative (M2)-activated macrophages drive the anti-inflammatory response against sepsis, a leading cause of death in patients suffering from burn injury. Macrophage M2 polarization is intrinsically linked with dominant oxidative phosphorylation (OXPHOS). Glutamine serves as a major anaplerotic source to fuel OXPHOS, but it remains unknown whether glutamine can modulate metabolic checkpoints in OXPHOS that favour M2 polarization. The study aims to explore whether glutamine essentially supports M2 polarization in IL-4-stimulated murine macrophages by sustaining the activity of PDH and whether glutamine augments macrophage M2 polarization and thus alleviates inflammation and organ injury in a murine burn sepsis model. Methods: To understand how glutamine promotes M2 activation in interleukin (IL-4)-treated murine macrophages, we detected glutamine-dependent M2 polarization and its relationship with the pyruvate dehydrogenase (PDH) complex by RT-PCR, flow cytometry and western blot. To explore how glutamine modulates PDH activity and thus supports M2 polarization, we compared the expression, phosphorylation and succinylation status of PDHA1 and then examined sirtuin SIRT5-dependent desuccinylation of PDHA1 and the effects of SIRT5 overexpression on M2 polarization by RT-PCR, flow cytometry and western blot. To determine whether glutamine or its metabolites affect M2 polarization, macrophages were cocultured with metabolic inhibitors, and then SIRT5 expression and M2 phenotype markers were examined by RT-PCR, flow cytometry and western blot. Finally, to confirm the in vivo effect of glutamine, we established a burn sepsis model by injecting Pseudomonas aeruginosa into burn wounds and observing whether glutamine alleviated proinflammatory injuries by RT-PCR, flow cytometry, western blot, immunofluorescent staining, hematoxylin-eosin staining and enzyme-linked immuno sorbent assay. Results: We showed that consumption of glutamine supported M2 activation in IL-4-treated murine macrophages by upregulating the activity of PDH. Mechanistically, glutamine did not affect the expression or alter the phosphorylation status of PDHA1 but instead downregulated the expression of SIRT5 and repressed SIRT5-dependent desuccinylation on PDHA1, which in turn recovered PDH activity and supported M2 polarization. This effect was implemented by its secondary metabolite α-ketoglutarate (αKG) rather than glutamine itself. Finally, we demonstrated that glutamine promoted macrophage M2 polarization in a murine burn sepsis model, thereby repressing excessive inflammation and alleviating organ injury in model mice. Conclusions: Glutamine mitigates murine burn sepsis by essentially supporting macrophage M2 polarization, with a mechanism involving the repression of the SIRT5-mediated desuccinylation of pyruvate dehydrogenase that replenishes OXPHOS and sustains M2 macrophages.

TFEB Dependent Autophagy-Lysosomal Pathway: An Emerging Pharmacological Target in Sepsis.

Sepsis is a life-threatening syndrome induced by aberrant host response towards infection. The autophagy-lysosomal pathway (ALP) plays a fundamental role in maintaining cellular homeostasis and conferring organ protection. However, this pathway is often impaired in sepsis, resulting in dysregulated host response and organ dysfunction. Transcription factor EB (TFEB) is a master modulator of the ALP. TFEB promotes both autophagy and lysosomal biogenesis via transcriptional regulation of target genes bearing the coordinated lysosomal expression and regulation (CLEAR) motif. Recently, increasing evidences have linked TFEB and the TFEB dependent ALP with pathogenetic mechanisms and therapeutic implications in sepsis. Therefore, this review describes the existed knowledge about the mechanisms of TFEB activation in regulating the ALP and the evidences of their protection against sepsis, such as immune modulation and organ protection. In addition, TFEB activators with diversified pharmacological targets are summarized, along with recent advances of their potential therapeutic applications in treating sepsis.