Sepsis-associated encephalopathy (SAE) is commonly complicated by septic conditions, and is responsible for increased mortality and poor outcomes in septic patients. Uncontrolled neuroinflammation ...and ischemic injury are major contributors to brain dysfunction, which arises from intractable immune malfunction and the collapse of neuroendocrine immune networks, such as the cholinergic anti-inflammatory pathway, hypothalamic-pituitary-adrenal axis, and sympathetic nervous system. Dysfunction in these neuromodulatory mechanisms compromised by SAE jeopardizes systemic immune responses, including those of neutrophils, macrophages/monocytes, dendritic cells, and T lymphocytes, which ultimately results in a vicious cycle between brain injury and a progressively aberrant immune response. Deep insight into the crosstalk between SAE and peripheral immunity is of great importance in extending the knowledge of the pathogenesis and development of sepsis-induced immunosuppression, as well as in exploring its effective remedies.
Ferroptosis is a nonapoptotic form of programmed cell death triggered by the accumulation of reactive oxygen species (ROS) depended on iron overload. Although most investigations focus on the ...relationship between ferroptosis and cancer, neurodegenerative diseases, and ischemia/reperfusion injury, research on ferroptosis induced by immune-related inflammatory diseases, especially sepsis, is scarce. Sestrin2 (Sesn2), a highly evolutionary and stress-responsive protein, is critically involved in defense against oxidative stress challenges. Upregulated expression of Sesn2 has been observed in preliminary experiments to have an antioxidative function in the context of an inflammatory response. Nevertheless, the underlying function of Sesn2 in inflammation-mediated ferroptosis in the immune system remains uncertain. The current study aimed to demonstrate the protective effect of Sesn2 on ferroptosis and even correlations with ferroptosis and the functions of ferroptotic-dendritic cells (DCs) stimulated with lipopolysaccharide (LPS). The mechanism underlying DCs protection from LPS-induced ferroptosis by Sesn2 was further explored in this study. We found that the immune response of DCs assessed by co-stimulatory phenotypes was gradually enhanced at the peak time of 12 h upon 1 μg/ml LPS stimulation while ferroptosis in DCs treated with LPS at 24 h was significantly detected. LPS-induced ferroptosis showed a suppressive impact on DCs in phenotypic maturation, which was conversely relieved by the ferroptotic inhibitor. Compared with wild-type (WT) mice, DCs in genetic defective mice of Sesn2 (Sesn2
) exhibited exacerbated ferroptosis. Furthermore, the protective effect of Sesn2 on ferroptosis was noticed to be associated with the ATF4-CHOP-CHAC1 pathway, eventually exacerbating ferroptosis by degrading of glutathione. These results indicate that Sesn2 can suppress the ferroptosis of DCs in sepsis by downregulating the ATF4-CHOP-CHAC1 signaling pathway, and it might play an antioxidative role.
Lithium (Li) metal anodes hold great promise for next‐generation high‐energy‐density batteries, while the insufficient fundamental understanding of the complex solid electrolyte interphase (SEI) is ...the major obstacle for the full demonstration of their potential in working batteries. The characteristics of SEI highly depend on the inner solvation structure of lithium ions (Li+). Herein, we clarify the critical significance of cosolvent properties on both Li+ solvation structure and the SEI formation on working Li metal anodes. Non‐solvating and low‐dielectricity (NL) cosolvents intrinsically enhance the interaction between anion and Li+ by affording a low dielectric environment. The abundant positively charged anion–cation aggregates generated as the introduction of NL cosolvents are preferentially brought to the negatively charged Li anode surface, inducing an anion‐derived inorganic‐rich SEI. A solvent diagram is further built to illustrate that a solvent with both proper relative binding energy toward Li+ and dielectric constant is suitable as NL cosolvent.
The introduction of cosolvents with non‐solvating and low‐dielectricity (NL) properties can intrinsically enhance the interaction between anion and Li+ and regulate the solvation structures in electrolytes, which favors an upgraded anion‐derived solid electrolyte interphase (SEI) on lithium metal anodes.
The structural integrity and functional stability of organelles are prerequisites for the viability and responsiveness of cells. Dysfunction of multiple organelles is critically involved in the ...pathogenesis and progression of various diseases, such as chronic obstructive pulmonary disease, cardiovascular diseases, infection, and neurodegenerative diseases. In fact, those organelles synchronously present with evident structural derangement and aberrant function under exposure to different stimuli, which might accelerate the corruption of cells. Therefore, the quality control of multiple organelles is of great importance in maintaining the survival and function of cells and could be a potential therapeutic target for human diseases. Organelle-specific autophagy is one of the major subtypes of autophagy, selectively targeting different organelles for quality control. This type of autophagy includes mitophagy, pexophagy, reticulophagy (endoplasmic reticulum), ribophagy, lysophagy, and nucleophagy. These kinds of organelle-specific autophagy are reported to be beneficial for inflammatory disorders by eliminating damaged organelles and maintaining homeostasis. In this review, we summarized the recent findings and mechanisms covering different kinds of organelle-specific autophagy, as well as their involvement in various diseases, aiming to arouse concern about the significance of the quality control of multiple organelles in the treatment of inflammatory diseases.
Abbreviations: ABCD3: ATP binding cassette subfamily D member 3; AD: Alzheimer disease; ALS: amyotrophic lateral sclerosis; AMBRA1: autophagy and beclin 1 regulator 1; AMPK: AMP-activated protein kinase; ARIH1: ariadne RBR E3 ubiquitin protein ligase 1; ATF: activating transcription factor; ATG: autophagy related; ATM: ATM serine/threonine kinase; BCL2: BCL2 apoptosis regulator; BCL2L11/BIM: BCL2 like 11; BCL2L13: BCL2 like 13; BECN1: beclin 1; BNIP3: BCL2 interacting protein 3; BNIP3L/NIX: BCL2 interacting protein 3 like; CALCOCO2/NDP52: calcium binding and coiled-coil domain 2; CANX: calnexin; CAT: catalase; CCPG1: cell cycle progression 1; CHDH: choline dehydrogenase; COPD: chronic obstructive pulmonary disease; CSE: cigarette smoke exposure; CTSD: cathepsin D; DDIT3/CHOP: DNA-damage inducible transcript 3; DISC1: DISC1 scaffold protein; DNM1L/DRP1: dynamin 1 like; EIF2AK3/PERK: eukaryotic translation initiation factor 2 alpha kinase 3; EIF2S1/eIF2α: eukaryotic translation initiation factor 2 alpha kinase 3; EMD: emerin; EPAS1/HIF-2α: endothelial PAS domain protein 1; ER: endoplasmic reticulum; ERAD: ER-associated degradation; ERN1/IRE1α: endoplasmic reticulum to nucleus signaling 1; FBXO27: F-box protein 27; FKBP8: FKBP prolyl isomerase 8; FTD: frontotemporal dementia; FUNDC1: FUN14 domain containing 1; G3BP1: G3BP stress granule assembly factor 1; GBA: glucocerebrosidase beta; HIF1A/HIF1: hypoxia inducible factor 1 subunit alpha; IMM: inner mitochondrial membrane; LCLAT1/ALCAT1: lysocardiolipin acyltransferase 1; LGALS3/Gal3: galectin 3; LIR: LC3-interacting region; LMNA: lamin A/C; LMNB1: lamin B1; LPS: lipopolysaccharide; MAPK8/JNK: mitogen-activated protein kinase 8; MAMs: mitochondria-associated membranes; MAP1LC3B/LC3B: microtubule-associated protein 1 light chain 3 beta; MFN1: mitofusin 1; MOD: multiple organelles dysfunction; MTPAP: mitochondrial poly(A) polymerase; MUL1: mitochondrial E3 ubiquitin protein ligase 1; NBR1: NBR1 autophagy cargo receptor; NLRP3: NLR family pyrin domain containing 3; NUFIP1: nuclear FMR1 interacting protein 1; OMM: outer mitochondrial membrane; OPTN: optineurin; PD: Parkinson disease; PARL: presenilin associated rhomboid like; PEX3: peroxisomal biogenesis factor 3; PGAM5: PGAM family member 5; PHB2: prohibitin 2; PINK1: PTEN induced putative kinase 1; PRKN: parkin RBR E3 ubiquitin protein ligase; RB1CC1/FIP200: RB1 inducible coiled-coil 1; RETREG1/FAM134B: reticulophagy regulator 1; RHOT1/MIRO1: ras homolog family member T1; RIPK3/RIP3: receptor interacting serine/threonine kinase 3; ROS: reactive oxygen species; RTN3: reticulon 3; SEC62: SEC62 homolog, preprotein translocation factor; SESN2: sestrin2; SIAH1: siah E3 ubiquitin protein ligase 1; SNCA: synuclein alpha; SNCAIP: synuclein alpha interacting protein; SQSTM1/p62: sequestosome 1; STING1: stimulator of interferon response cGAMP interactor 1; TAX1BP1: Tax1 binding protein 1; TBK1: TANK binding kinase 1; TFEB: transcription factor EB; TICAM1/TRIF: toll-like receptor adaptor molecule 1; TIMM23: translocase of inner mitochondrial membrane 23; TNKS: tankyrase; TOMM: translocase of the outer mitochondrial membrane; TRIM: tripartite motif containing; UCP2: uncoupling protein 2; ULK1: unc-51 like autophagy activating kinase; UPR: unfolded protein response; USP10: ubiquitin specific peptidase 10; VCP/p97: valosin containing protein; VDAC: voltage dependent anion channels; XIAP: X-linked inhibitor of apoptosis; ZNHIT3: zinc finger HIT-type containing 3.
Tumor necrosis factor (TNF)-α-induced protein 8-like 2 (TIPE2) is a newly discovered negative immunoregulatory protein that is involved in various cellular immune responses to infections. However, ...the underlying mechanism by which TIPE2 affects the immune function of dendritic cells (DCs) is not yet understood. This study aimed to determine the correlations among DCs TIPE2 expression, autophagic activity and immune function in the context of sepsis. In addition, the signaling pathway by which TIPE2 regulates autophagy in DCs was investigated. We reported for the first time that TIPE2 overexpression (knock-in, KI) exerted an inhibitory effect on autophagy in DCs and markedly suppressed the immune function of DCs upon septic challenge both in vitro and in vivo. In addition, TIPE2 knockout (KO) in DCs significantly enhanced autophagy and improved the immune response of DCs in sepsis. Of note, we found that the transforming growth factor-β (TGF-β)-activated kinase-1 (TAK1)/c-Jun N-terminal kinase (JNK) pathway was inhibited by TIPE2 in DCs, resulting in downregulated autophagic activity. Collectively, these results suggest that TIPE2 can suppress the autophagic activity of DCs by inhibiting the TAK1/JNK signaling pathway and further negatively regulate the immune function of DCs in the development of septic complications.
Lithium–sulfur (Li–S) batteries are considered as promising next‐generation energy storage devices due to their ultrahigh theoretical energy density, where soluble lithium polysulfides are crucial in ...the Li–S electrochemistry as intrinsic redox mediators. However, the poor mediation capability of the intrinsic polysulfide mediators leads to sluggish redox kinetics, further rendering limited rate performances, low discharge capacity, and rapid capacity decay. Here, an organodiselenide, diphenyl diselenide (DPDSe), is proposed to accelerate the sulfur redox kinetics as a redox comediator. DPDSe spontaneously reacts with lithium polysulfides to generate lithium phenylseleno polysulfides (LiPhSePSs) with improved redox mediation capability. The as‐generated LiPhSePSs afford faster sulfur redox kinetics and increase the deposition dimension of lithium sulfide. Consequently, the DPDSe comediator endows Li–S batteries with superb rate performance of 817 mAh g−1 at 2 C and remarkable cycling stability with limited anode excess. Moreover, Li–S pouch cells with the DPDSe comediator achieve an actual initial energy density of 301 Wh kg−1 and 30 stable cycles. This work demonstrates a novel redox comediation strategy with an effective organodiselenide comediator to facilitate the sulfur redox kinetics under pouch cell conditions and inspires further exploration in mediating Li–S kinetics for practical high‐energy‐density batteries.
An organodiselenide, diphenyl diselenide (DPDSe), is proposed to accelerate the sulfur redox kinetics as a redox comediator, which endows Li–S batteries with superb rate performance, remarkable cycling stability, and high actual energy density of 301 Wh kg−1. This work demonstrates a novel redox comediation strategy to facilitate the sulfur redox kinetics under practical pouch cell conditions.
Aims
The aim of this study was to investigate the tumor microenvironment immune types (TMIT) based on tumor cell programmed cell death ligand 1 (PD‐L1) expression and tumor‐infiltrating lymphocytes ...(TILs) distribution and whether distinct TMIT subtypes (TMIT I, PD‐L1high/TILhigh; TMIT II, PD‐L1low/TILlow; TMIT III, PD‐L1high/TILlow; and TMIT IV, PD‐L1low/TILhigh) differentially affect clinical outcomes of patients with lung adenocarcinoma (LAC) and squamous cell carcinoma (SCC).
Methods and results
Immunohistochemistry (IHC) was applied to evaluate the expression of PD‐L1 and the spatial distribution of programmed cell death 1 (PD‐1) and CD8 TILs on the surgically resected specimens from 205 cases of LAC and 149 cases of SCC. PD‐1 and CD8 TILs were more frequently distributed in SCC than those in LAC, regardless of their infiltrating in the tumor islets or stroma. The density of TILs was a poor prognostic factor in LAC but a favorable one in SCC. PD‐L1 levels and its clinical prognostic significance differed in LAC vs SCC. LAC patients with TMIT III and SCC patients with TMIT I had the longest survival, respectively (P = .0197 and .0049). Moreover, TMIT stratification based on tumor cell PD‐L1 expression and stromal CD8+ TILs could be considered as an independent prognostic factor of SCC patients' survival as determined by both univariate and multivariate analysis.
Conclusion
Our study indicates that different type of TMIT provides its specific microenvironment with diverse impact on survival of LAC and SCC patients and highlights the importance of the integrative assessment of PD‐L1 status and TILs' spatial distribution to predict patients' prognosis.
Our study indicates that different type of TMIT provides its specific microenvironment with diverse impact on survival of lung adenocarcinoma and squamous cell carcinoma patients and highlights the importance of the integrative assessment of programmed cell death ligand 1 status and tumor‐infiltrating lymphocytes' spatial distribution to predict patients' prognosis.
Poly(cyclopentene carbonate) (PCPC) produced by copolymerization of CO2 and cyclopentene oxide (CPO) is a promising but challenging chemical recyclable polymer that has high potential in minimizing ...plastic pollution and maximizing CO2 utilization. Currently, problems remain to be solved, include low reactivity of toxic metal catalysts, inevitable byproducts, and especially the ambiguous mechanism understanding. Herein, we present the first metal‐free access to PCPC by using a series of modular dinuclear organoboron catalysts. PCPC was afforded in an unprecedented catalytic efficiency of 1.0 kg of PCPC/g of catalyst; while the depolymerization of PCPC abides by a combination pathway of random chain scission and chain unzipping, returning CPO in near‐quantitative yield (>99 %). The preparation and depolymerization of PCPC along with in depth understanding of related mechanisms would be helpful for further development of advanced catalysts and recyclable plastics.
The first metal‐free access to poly(cyclopentene carbonate) and its chemical recycling to monomer were achieved by using a dinuclear bifunctional organoboron catalyst, enriching the portfolio of the circular plastic economy.
High‐energy‐density lithium (Li) metal batteries are severely hindered by the dendritic Li deposition dictated by non‐uniform solid electrolyte interphase (SEI). Despite its unique advantages in ...improving the uniformity of Li deposition, the current anion‐derived SEI is unsatisfactory under practical conditions. Herein regulating the electrolyte structure of anions by anion receptors was proposed to construct stable anion‐derived SEI. Tris(pentafluorophenyl)borane (TPFPB) anion acceptors with electron‐deficient boron atoms interact with bis(fluorosulfonyl)imide anions (FSI−) and decrease the reduction stability of FSI−. Furthermore, the type of aggregate cluster of FSI− in electrolyte changes, FSI− interacting with more Li ions in the presence of TPFPB. Therefore, the decomposition of FSI− to form Li2S is promoted, improving the stability of anion‐derived SEI. In working Li | LiNi0.5Co0.2Mn0.3O2 batteries under practical conditions, the anion‐derived SEI with TPFPB undergoes 194 cycles compared with 98 cycles of routine anion‐derived SEI. This work inspires a fresh ground to construct stable anion‐derived SEI by manipulating the electrolyte structure of anions.
Directly regulating the electrolyte structure of anions by an anion receptor was proposed for the construction of a stable anion‐derived solid electrolyte interphase (SEI). The introduction of an anion receptor decreases the reduction stability of FSI− and increases the amount of FSI− in the form of AGG‐II. The decomposition of FSI− to form Li2S is promoted, improving the stability of the anion‐derived SEI under practical conditions.
The performance of Li‐ion batteries (LIBs) is highly dependent on their interfacial chemistry, which is regulated by electrolytes. Conventional electrolyte typically contains polar solvents to ...dissociate Li salts. Herein we report a weakly solvating electrolyte (WSE) that consists of a pure non‐polar solvent, which leads to a peculiar solvation structure where ion pairs and aggregates prevail under a low salt concentration of 1.0 M. Importantly, WSE forms unique anion‐derived interphases on graphite electrodes that exhibit fast‐charging and long‐term cycling characteristics. First‐principles calculations unravel a general principle that the competitive coordination between anions and solvents to Li ions is the origin of different interfacial chemistries. By bridging the gap between solution thermodynamics and interfacial chemistry in batteries, this work opens a brand‐new way towards precise electrolyte engineering for energy storage devices with desired properties.
A weakly solvating electrolyte affords a new path towards anion‐derived interfacial chemistry in lithium‐ion batteries. By formulating electrolyte with a non‐polar solvent, ion pairs and aggregates prevail under normal concentrations and give rise to anion‐derived interphases on graphite electrodes with superior electrochemical performances.
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