New information about the cyclable capacity fading process of a pouch cell with Li-rich layered oxide cathodes.

Most studies investigate the cyclable capacity fading mechanism of Li-rich layered oxides (LLOs) from the microscopic structure level, lacking discussions about how the structure degradation influences the performance of the pouch cell precisely and quantitatively. Based on the analysis of the evolution of key parameters during the whole cycling period, a new transition-type fading mechanism is proposed. From the early-to-middle stage of the cycling period, polarization increases, most of which is interface-related, causing about 67% of the whole capacity loss. From the middle-to-late stage of the cycling period, active material losses turn out to be the dominating factor, inducing about 61% of the total capacity loss. Diffusion-related polarization, replacing the interface type, is responsible for most of the increased overpotential. Relative analysis confirms that during the early stage, the increase of the charge transfer resistance, induced by CEI (cathode electrolyte interface) growth and initial surface layered-structure degradation, is the main source of interface polarization. As the cycling evolves to the late stage, severe bulky structure degradation, including lattice-oxygen release, Li/Ni mixture and generation of a new spinel phase, turns out to be the major factor, causing further capacity fading.

NCF4 attenuates colorectal cancer progression by modulating inflammasome activation and immune surveillance.

The spatiotemporal regulation of inflammasome activation remains unclear. To examine the mechanism underlying the assembly and regulation of the inflammasome response, here we perform an immunoprecipitation-mass spectrometry analysis of apoptosis-associated speck-like protein containing a CARD (ASC) and identify NCF4/1/2 as ASC-binding proteins. Reduced NCF4 expression is associated with colorectal cancer development and decreased five-year survival rate in patients with colorectal cancer. NCF4 cooperates with NCF1 and NCF2 to promote NLRP3 and AIM2 inflammasome activation. Mechanistically, NCF4 phosphorylation and puncta distribution switches from the NADPH complex to the perinuclear region, mediating ASC oligomerization, speck formation and inflammasome activation. NCF4 functions as a sensor of ROS levels, to establish a balance between ROS production and inflammasome activation. NCF4 deficiency causes severe colorectal cancer in mice, increases transit-amplifying and precancerous cells, reduces the frequency and activation of CD8+ T and NK cells, and impairs the inflammasome-IL-18-IFN-γ axis during the early phase of colorectal tumorigenesis. Our study implicates NCF4 in determining the spatial positioning of inflammasome assembly and contributing to inflammasome-mediated anti-tumor responses.

OTUD5 promotes the inflammatory immune response by enhancing MyD88 oligomerization and Myddosome formation.

Myddosome is an oligomeric complex required for the transmission of inflammatory signals from TLR/IL1Rs and consists of MyD88 and IRAK family kinases. However, the molecular basis for the self-assemble of Myddosome proteins and regulation of intracellular signaling remains poorly understood. Here, we identify OTUD5 acts as an essential regulator for MyD88 oligomerization and Myddosome formation. OTUD5 directly interacts with MyD88 and cleaves its K11-linked polyubiquitin chains at Lys95, Lys231 and Lys250. This polyubiquitin cleavage enhances MyD88 oligomerization after LPS stimulation, which subsequently promotes the recruitment of downstream IRAK4 and IRAK2 to form Myddosome and the activation of NF-κB and MAPK signaling and production of inflammatory cytokines. Consistently, Otud5-deficient mice are less susceptible to LPS- and CLP-induced sepsis. Taken together, our findings reveal a positive regulatory role of OTUD5 in MyD88 oligomerization and Myddosome formation, which provides new sights into the treatment of inflammatory diseases.

Design and Mechanism Study of High-Safety and Long-Life Electrolyte for High-Energy-Density Lithium-Ion Batteries.

Although nonflammable electrolytes are beneficial for battery safety, they often adversely affect the electrochemical performance of lithium-ion batteries due to their poor compatibility with electrodes. Herein, we design a nonflammable electrolyte consisting of cyclic carbonate and 2,2-difluoroethyl acetate (DFEA) solvents paired with several surface-film-forming additives, significantly improving the safety and cycling performance of NMC811||SiOx/graphite pouch cells. The DFEA solvent exhibits not only good flame retardancy but also lower lowest unoccupied molecular orbital (LUMO) energy, promoting the formation of a robust inorganic-rich and gradient-architecture hybrid interface between the SiOx/graphite anode and electrolyte. The double insurance of good flame retardancy of the DFEA solvent and decreased exothermic effects of both bulk electrolyte and DFEA-derived solid electrolyte interphase (SEI) can ensure the high safety of the pouch cell. Moreover, the highly robust SEI can prevent the excessive reduction decomposition of the electrolyte and alleviate the structural decay of the anode, which can restrain the formation of lithium deposition on the anode surface and further suppress the structural decay of NMC materials. This contributes to the unprecedented cycling performance of the NMC811||SiOx/graphite pouch cells with a capacity retention of 80% after 1000 cycles at a 0.33C rate.

TRIM26 alleviates fatal immunopathology by regulating inflammatory neutrophil infiltration during Candida infection.

Fungal infections have emerged as a major concern among immunocompromised patients, causing approximately 2 million deaths each year worldwide. However, the regulatory mechanisms underlying antifungal immunity remain elusive and require further investigation. The E3 ligase Trim26 belongs to the tripartite motif (Trim) protein family, which is involved in various biological processes, including cell proliferation, antiviral innate immunity, and inflammatory responses. Herein, we report that Trim26 exerts protective antifungal immune functions after fungal infection. Trim26-deficient mice are more susceptible to fungemia than their wild-type counterparts. Mechanistically, Trim26 restricts inflammatory neutrophils infiltration and limits proinflammatory cytokine production, which can attenuate kidney fungal load and renal damage during Candida infection. Trim26-deficient neutrophils showed higher proinflammatory cytokine expression and impaired fungicidal activity. We further demonstrated that excessive neutrophils infiltration in the kidney was because of the increased production of chemokines CXCL1 and CXCL2, which are mainly synthesized in the macrophages or dendritic cells of Trim26-deficient mice after Candida albicans infections. Together, our study findings unraveled the vital role of Trim26 in regulating antifungal immunity through the regulation of inflammatory neutrophils infiltration and proinflammatory cytokine and chemokine expression during candidiasis.

Mcam inhibits macrophage-mediated development of mammary gland through non-canonical Wnt signaling.

While canonical Wnt signaling is well recognized for its crucial regulatory functions in cell fate decisions, the role of non-canonical Wnt signaling in adult stem cells remains elusive and contradictory. Here, we identified Mcam, a potential member of the non-canonical Wnt signaling, as an important negative regulator of mammary gland epithelial cells (MECs) by genome-scale CRISPR-Cas9 knockout (GeCKO) library screening. Loss of Mcam increases the clonogenicity and regenerative capacity of MECs, and promotes the proliferation, differentiation, and ductal morphogenesis of mammary epithelial in knockout mice. Mechanically, Mcam knockout recruits and polarizes macrophages through the Il4-Stat6 axis, thereby promoting secretion of the non-canonical Wnt ligand Wnt5a and its binding to the non-canonical Wnt signaling receptor Ryk to induce the above phenotypes. These findings reveal Mcam roles in mammary gland development by orchestrating communications between MECs and macrophages via a Wnt5a/Ryk axis, providing evidences for non-canonical Wnt signaling in mammary development.

Listerin promotes cGAS protein degradation through the ESCRT pathway to negatively regulate cGAS-mediated immune response.

The enzyme cyclic GMP-AMP synthase (cGAS) is a key sensor for detecting misplaced double-stranded DNA (dsDNA) of genomic, mitochondrial, and microbial origin. It synthesizes 2'3'-cGAMP, which in turn activates the stimulator of interferon genes pathway, leading to the initiation of innate immune responses. Here, we identified Listerin as a negative regulator of cGAS-mediated innate immune response. We found that Listerin interacts with cGAS on endosomes and promotes its K63-linked ubiquitination through recruitment of the E3 ligase TRIM27. The polyubiquitinated cGAS is then recognized by the endosomal sorting complexes required for transport machinery and sorted into endosomes for degradation. Listerin deficiency enhances the innate antiviral response to herpes simplex virus 1 infection. Genetic deletion of Listerin also deteriorates the neuroinflammation and the ALS disease progress in an ALS mice model; overexpression of Listerin can robustly ameliorate disease progression in ALS mice. Thus, our work uncovers a mechanism for cGAS regulation and suggests that Listerin may be a promising therapeutic target for ALS disease.

Surface modification of rare earth Sm-doped WO3 films through polydopamine for enhanced electrochromic energy storage performance.

Electrochromic materials (ECMs) could exhibit reversible color changes upon application of the external electric field, which exhibits huge application prospects in smart windows, energy storage devices, and displays. For the practical application of ECMs, the fast response speed and long cyclic stability are urgent. In this work, the nanoporous Sm-doped WO3 (WSm) films were constructed using hydrothermal technology, then polydopamine (PDA) was modified on the surface of WSm film to obtain the WSm/Px (x = 0.25, 0.5, 1.0, and 2.0) hybrid films. WSm/Px hybrid films displayed high optical contrast and large areal capacitance. In addition, in comparison with WSm film, the WSm/Px hybrid films exhibited faster response speed and better cyclic stability because PDA film enhanced the interface ion transport ability and electrochemical structural stability of the nanoporous WSm film. Notably, the WSm/P1.0 hybrid film displayed the colored/bleached times of 7.4/2.9 s, retained 90.2% of the primitive optical contrast (68.5%) after 5000 electrochromic cycles. Furthermore, the areal capacitance of WSm film could be increased by 224% through the modification of the PDA. Therefore, WSm/Px hybrid films are great prospects for electrochromic energy-saving and storage windows.

Review on Hydrophobic Thin Films Prepared Using Magnetron Sputtering Deposition.

Hydrophobic thin films have gained significant attention due to their broad applications in self-cleaning, anti-corrosion, anti-icing, medicine, oil-water separation, and other fields. The target hydrophobic materials can be deposited onto various surfaces thanks to the scalable and highly reproducible nature of magnetron sputtering, which is comprehensively overviewed in this review. While alternative preparation methods have been extensively analyzed, a systematic understanding of hydrophobic thin films fabricated using magnetron sputtering deposition is still absent. After outlining the fundamental mechanism of hydrophobicity, this review briefly summarizes three types of sputtering-deposited thin films that originate from oxides, polytetrafluoroethylene (PTFE), and diamond-like carbon (DLC), respectively, primarily focusing on the recent advances in their preparation, characteristics, and applications. Finally, the future applications, current challenges, and development of hydrophobic thin films are discussed, and a brief perspective on future research directions is provided.

Ginsenoside Rk1-Loaded Manganese-Doped Hollow Titania for Enhancing Tumor Sonodynamic Therapy via Upregulation of Intracellular Reactive Oxygen Species.

Amplifying the intracellular reactive oxygen species (ROS) level remains an urgent challenge for efficient sonodynamic therapy (SDT) of tumors. Herein, by loading ginsenoside Rk1 with manganese-doped hollow titania (MHT), a Rk1@MHT sonosensitizer was conceived to strengthen the outcome of tumor SDT. The results verify that manganese-doping remarkably elevates the UV-visible absorption and decreases the bandgap energy of titania from 3.2 to 3.0 eV, which improves ROS production under ultrasonic irradiation. Immunofluorescence and Western blot analysis demonstrate that ginsenoside Rk1 can block the critical protein of the glutathione synthesis pathway, glutaminase, thus enhancing intracellular ROS by eliminating the endogenous glutathione-depleted pathway of ROS. Manganese-doping confers the nanoprobe T1-weighted MRI function (r2/r1 = 1.41). Moreover, the in vivo tests confirm that Rk1@MHT-based SDT eradicates liver cancer in tumor-bearing mice via dual upregulation of intracellular ROS production. In summary, our study provides a new strategy for designing high-performance sonosensitizer to achieve noninvasive cancer treatment.

Microbiota-derived acetate enhances host antiviral response via NLRP3.

Pathogenic viral infections represent a major challenge to human health. Host immune responses to respiratory viruses are closely associated with microbiome and metabolism via the gut-lung axis. It has been known that host defense against influenza A virus (IAV) involves activation of the NLRP3 inflammasome, however, mechanisms behind the protective function of NLRP3 are not fully known. Here we show that an isolated bacterial strain, Bifidobacterium pseudolongum NjM1, enriched in the gut microbiota of Nlrp3-/- mice, protects wild-type but not Nlrp3 deficient mice against IAV infection. This effect depends on the enhanced production of type I interferon (IFN-I) mediated by NjM1-derived acetate. Application of exogenous acetate reproduces the protective effect of NjM1. Mechanistically, NLRP3 bridges GPR43 and MAVS, and promotes the oligomerization and signalling of MAVS; while acetate enhances MAVS aggregation upon GPR43 engagement, leading to elevated IFN-I production. Thus, our data support a model of NLRP3 mediating enhanced induction of IFN-I via acetate-producing bacterium and suggest that the acetate-GPR43-NLRP3-MAVS-IFN-I signalling axis is a potential therapeutic target against respiratory viral infections.

Big data technology in infectious diseases modeling, simulation, and prediction after the COVID-19 outbreak.

After the outbreak of COVID-19, the interaction of infectious disease systems and social systems has challenged traditional infectious disease modeling methods. Starting from the research purpose and data, researchers improved the structure and data of the compartment model or used agents and artificial intelligence based models to solve epidemiological problems. In terms of modeling methods, the researchers use compartment subdivision, dynamic parameters, agent-based model methods, and artificial intelligence related methods. In terms of factors studied, the researchers studied 6 categories: human mobility, nonpharmaceutical interventions (NPIs), ages, medical resources, human response, and vaccine. The researchers completed the study of factors through modeling methods to quantitatively analyze the impact of social systems and put forward their suggestions for the future transmission status of infectious diseases and prevention and control strategies. This review started with a research structure of research purpose, factor, data, model, and conclusion. Focusing on the post-COVID-19 infectious disease prediction simulation research, this study summarized various improvement methods and analyzes matching improvements for various specific research purposes.

Application of big data and artificial intelligence in epidemic surveillance and containment.

Faced with the current time-sensitive COVID-19 pandemic, the overburdened healthcare systems have resulted in a strong demand to develop newer methods to control the spread of the pandemic. Big data and artificial intelligence (AI) have been leveraged amid the COVID-19 pandemic; however, little is known about their use for supporting public health efforts. In epidemic surveillance and containment, efforts are needed to treat critical patients, track and manage the health status of residents, isolate suspected cases, and develop vaccines and antiviral drugs. The applications of emerging practices of artificial intelligence and big data have become powerful "weapons" to fight against the pandemic and provide strong support in pandemic prevention and control, such as early warning, analysis and judgment, interruption and intervention of epidemic, to achieve goals of early detection, early report, early diagnosis, early isolation and early treatment. These are the decisive factors to control the spread of the epidemic and reduce the mortality. This paper systematically summarized the application of big data and AI in epidemic, and describes practical cases and challenges with emphasis on epidemic prevention and control. The included studies showed that big data and AI have the potential strength to fight against COVID-19. However, many of the proposed methods are not yet widely accepted. Thus, the most rewarding research would be on methods that promise value beyond COVID-19. More efforts are needed for developing standardized reporting protocols or guidelines for practice.

NLRP3 Attenuates Intraocular Inflammation by Inhibiting AIM2-Mediated Pyroptosis Through the Phosphorylated Salt-Inducible Kinase 1/Sterol Regulatory Element Binding Transcription Factor 1 Pathway.

OBJECTIVE: The NLRP3 inflammasome has been shown to be involved in the development of uveitis, but the exact mechanism remains elusive. This study was undertaken to explore the role of NLRP3 in the development of uveitis. METHODS: First, Nlrp3-deficient mice were used to study the role of NLRP3 in experimental autoimmune diseases, such as experimental autoimmune uveitis (EAU) and experimental autoimmune encephalomyelitis (EAE). Next, the gathering of ASC, activation of caspase 1 and gasdermin D, and secretion of lactate dehydrogenase and interleukin-1ß were detected to confirm macrophage pyroptosis and AIM2 activation in the Nlrp3-/- mice. Additionally, RNA sequencing and chromatin immunoprecipitation-polymerase chain reaction were used to investigate the phosphorylated salt-inducible kinase 1 (p-SIK1)/sterol regulatory element binding transcription factor 1 (SREBF1) pathway, which regulates the transcription of Aim2. Finally, overexpression of Nlrp3 was applied to treat EAU. RESULTS: Surprisingly, our findings show that NLRP3 plays an antiinflammatory role in 2 models of EAU and EAE. Additionally, macrophages show an increased M1 activation and pyroptosis in Nlrp3-/- mice. Further experiments indicate that this pyroptosis of macrophages was mediated by the up-regulated transcription of Aim2 as a result of Nlrp3 deficiency. In mechanistic studies, Nlrp3 deficiency was implicated in the down-regulation of p-SIK1 and subsequently the up-regulation of SREBF1, which binds to Aim2 and then promotes the latter's transcription. Finally, Aim2 deficiency, RNA silencing of Aim2 or Srebf1, and overexpression of Nlrp3 resulted in attenuated inflammation of EAU. CONCLUSION: Our data demonstrate that NLRP3 inhibits AIM2 inflammasome-mediated EAU by regulating the p-SIK1/SREBF1 pathway, highlighting the therapeutic potential of targeting Nlrp3.

Interference with LTßR signaling by tick saliva facilitates transmission of Lyme disease spirochetes.

Lyme spirochetes have coevolved with ticks to optimize transmission to hosts using tick salivary molecules (TSMs) to counteract host defenses. TSMs modulate various molecular events at the tick-host interface. Lymphotoxin-beta receptor (LTßR) is a vital immune receptor and plays protective roles in host immunity against microbial infections. We found that Ltbr knockout mice were more susceptible to Lyme disease spirochetes, suggesting the involvement of LTßR signaling in tick-borne Borrelia infection. Further investigation showed that a 15-kDa TSM protein from Ixodes persulcatus (I. persulcatus salivary protein; IpSAP) functioned as an immunosuppressant to facilitate the transmission and infection of Lyme disease spirochetes. IpSAP directly interacts with LTßR to block its activation, thus inhibiting the downstream signaling and consequently suppressing immunity. IpSAP immunization provided mice with significant protection against I. persulcatus-mediated Borrelia garinii infection. Notably, the immunization showed considerable cross-protection against other Borrelia infections mediated by other ixodid ticks. One of the IpSAP homologs from other ixodid ticks showed similar effects on Lyme spirochete transmission. Together, our findings suggest that LTßR signaling plays an important role in blocking the transmission and pathogenesis of tick-borne Lyme disease spirochetes, and that IpSAP and its homologs are promising candidates for broad-spectrum vaccine development.

The giant E3 ligase HUWE1 is linked to tumorigenesis, spermatogenesis, intellectual disability, and inflammatory diseases.

E3 ubiquitin ligases determine the substrate specificity and catalyze the ubiquitination of lysine residues. HUWE1 is a catalytic HECT domain-containing giant E3 ligase that contains a substrate-binding ring structure, and mediates the ubiquitination of more than 40 diverse substrates. HUWE1 serves as a central node in cellular stress responses, cell growth and death, signal transduction, etc. The expanding atlas of HUWE1 substrates presents a major challenge for the potential therapeutic application of HUWE1 in a particular disease. In addition, HUWE1 has been demonstrated to play contradictory roles in certain aspects of tumor progression in either an oncogenic or a tumor-suppressive manner. We recently defined novel roles of HUWE1 in promoting the activation of multiple inflammasomes. Inflammasome activation-mediated immune responses might lead to multifunctional effects on tumor therapy, inflammation, and autoimmune diseases. In this review, we summarize the known substrates and pleiotropic functions of HUWE1 in different types of cells and models, including its involvement in development, cancer, neuronal disorder and infectious disease. We also discuss the advances in cryo-EM-structural analysis for a functional-mechanistic understanding of HUWE1 in modulating the multitudinous diverse substrates, and introduce the possibility of revisiting the comprehensive roles of HUWE1 in multiple aspects within one microenvironment, which will shed light on the potential therapeutic application of targeting giant E3 ligases like HUWE1.

IL-3 Expands Pre-Basophil and Mast Cell Progenitors by Upregulating the IL-3 Receptor Expression.

Basophils and mast cells play a critical role in allergic inflammation and provide protective immunity against certain types of parasitic infections. Expansion of basophils and mast cells to the critical numbers is believed to be an essential step in enabling basophils and mast cells to carry out their protective functions. However, factors that drive basophil and mast cell expansion are still incompletely understood. We tested the roles of cytokines and growth factors IL-3, TSLP, GM-CSF, IL-5, SCF, IL-7, IL-25, and IL-33 in promoting the differentiation of pre-basophil and mast cell progenitors (pre-BMPs)in vitro.We found that while GM-CSF only expanded basophils, IL-3 promoted the differentiation of pre-BMPs into both basophils and mast cells. We found that IL-3 expanded the number of pre-BMPsin vivo. We showed that IL-3 upregulatedIl3ramRNA and protein expression on pre-BMPs, supporting that IL-3 expands pre-BMPs in part by upregulating the IL-3 receptor expression. Although Gata2 mRNA expression was upregulated by IL-3 treatment in pre-BMPs, it is dispensable for IL-3-mediated upregulation of IL-3 receptor expression. Our study reveals a novel mechanism through which IL-3 expands basophil and mast cells.

Improving the performance of silicon monoxide anodes via tuning a multiple pre-doping system: a first-principles study.

Silicon monoxide is a potentially viable anode material for high-performance lithium-ion batteries (LIBs). However, a low initial coulombic efficiency and large volume expansion limit its commercial application. Pre-lithiation is an efficient solution, but is expensive because of limited "pre-lithiation" sources. In this work, we theoretically investigated a novel multiple pre-doping SiO system (Li-NaMg-SiO). By comparing its lithiation behavior to that of the traditional Li-doping system (Li-SiO), we revealed the different doping effects during lithiation. Similar to the traditional Li-doping system, the insertion of Na and Mg disintegrates the Si-O host matrix to form Na-O and Mg-O bonds and active Si clusters. At the end of lithiation, the O-Li coordination number (CN) tends to saturate at CNO-Li ≈ 5 in Li-Na-SiO, Li-Mg-SiO, and Li-NaMg-SiO systems, while the value of CNO-Li in the Li-SiO system is more than 6, which suggests that there are reorganizations between Li, Na, and Mg in the silicate matrix. Doping sources of both Na and Mg can prevent the active Li ions from being trapped by O-Li bonds and increase the initial coulombic efficiency. From the density of states (DOS), we notice that all the different pre-doping systems have similar electronic structures, and they can be expected to undergo the same lithiation process. Furthermore, the higher ion-conductivity and smaller volume expansion during the lithiation process characterized by root mean square deviation (RMSD) and volume analysis prove the advantages of the binary doping system (Li-NaMg-SiO) for the improvement of cycle stability for Si-based materials. These advantages benefit from the loose and amorphous structures of doping systems during lithiation. Our work highlights the doping effects of multiple sources and the promotion of "inert compounds" on the entire lithiation process, which provide valuable insight for high-performance anode design.