Unraveling the Intrinsic Origin of the Superior Sodium-Ion Storage Performance of Metal Selenides Anode in Ether-Based Electrolytes.

Metal selenides show outstanding sodium-ion storage performance when matched with an ether-based electrolyte. However, the intrinsic origin of improvement and deterministic interface characteristics have not been systematically elucidated. Herein, employing FeSe2 anode as the model system, the electrochemical kinetics of metal selenides in ether and ester-based electrolytes and associated solid electrolyte interphase (SEI) are investigated in detail. Based on the galvanostatic intermittent titration technique and in situ electrochemical impedance spectroscopy, it is found that the ether-based electrolyte can ensure fast Na+ transfer and low interface impedance. Additionally, the ether-derived thin and smooth double-layer SEI, which is critical in facilitating ion transport, maintaining structural stability, and inhibiting electrolyte overdecomposition, is concretely visualized by transmission electron microscopy, atomic force microscopy, and depth-profiling X-ray photoelectron spectroscopy. This work provides a deep understanding of the optimization mechanism of electrolytes, which can guide available inspiration for the design of practical electrode materials.

Identification and bioinformatics analysis of lncRNAs in serum of patients with ankylosing spondylitis.

OBJECTIVES: The aim of this study was to explore the long non-coding RNA (lncRNA) expression profiles in serum of patients with ankylosing spondylitis (AS). The role of these lncRNAs in this complex autoimmune situation needs to be evaluated. METHODS: We used high-throughput whole-transcriptome sequencing to generate sequencing data from three patients with AS and three normal controls (NC). Then, we performed bioinformatics analyses to identify the functional and biological processes associated with differentially expressed lncRNAs (DElncRNAs). We confirmed the validity of our RNA-seq data by assessing the expression of eight lncRNAs via quantitative reverse transcription polymerase chain reaction (qRT-PCR) in 20 AS and 20 NC samples. We measured the correlation between the expression levels of lncRNAs and patient clinical index values using the Spearman correlation test. RESULTS: We identified 72 significantly upregulated and 73 significantly downregulated lncRNAs in AS patients compared to NC. qRT-PCR was performed to validate the expression of selected DElncRNAs; the results demonstrated that the expression levels of MALAT1:24, NBR2:9, lnc-DLK1-35:13, lnc-LARP1-1:1, lnc-AIPL1-1:7, and lnc-SLC12A7-1:16 were consistent with the sequencing analysis results. Enrichment analysis showed that DElncRNAs mainly participated in the immune and inflammatory responses pathways, such as regulation of protein ubiquitination, major histocompatibility complex class I-mediated antigen processing and presentation, MAPkinase activation, and interleukin-17 signaling pathways. In addition, a competing endogenous RNA network was constructed to determine the interaction among the lncRNAs, microRNAs, and mRNAs based on the confirmed lncRNAs (MALAT1:24 and NBR2:9). We further found the expression of MALAT1:24 and NBR2:9 to be positively correlated with disease severity. CONCLUSION: Taken together, our study presents a comprehensive overview of lncRNAs in the serum of AS patients, thereby contributing novel perspectives on the underlying pathogenic mechanisms of this condition. In addition, our study predicted MALAT1 has the potential to be deeply involved in the pathogenesis of AS.

Metal Selenides Anode Materials for Sodium Ion Batteries: Synthesis, Modification, and Application.

The powerful and rapid development of lithium-ion batteries (LIBs) in secondary batteries field makes lithium resources in short supply, leading to rising battery costs. Under the circumstances, sodium-ion batteries (SIBs) with low cost, inexhaustible sodium reserves, and analogous work principle to LIBs, have evolved as one of the most anticipated candidates for large-scale energy storage devices. Thereinto, the applicable electrode is a core element for the smooth development of SIBs. Among various anode materials, metal selenides (MSex ) with relatively high theoretical capacity and unique structures have aroused extensive interest. Regrettably, MSex suffers from large volume expansion and unwished side reactions, which result in poor electrochemistry performance. Thus, strategies such as carbon modification, structural design, voltage control as well as electrolyte and binder optimization are adopted to alleviate these issues. In this review, the synthesis methods and main reaction mechanisms of MSex are systematically summarized. Meanwhile, the major challenges of MSex and the corresponding available strategies are proposed. Furthermore, the recent research progress on layered and nonlayered MSex for application in SIBs is presented and discussed in detail. Finally, the future development focuses of MSex in the field of rechargeable ion batteries are highlighted.

Screening of Sintering Aids for Oxide Ceramics: A Case of NASICON Electrolyte.

In this work, an efficient screening method to select appropriate sintering aids for a wide range of oxide material systems is developed. Consequently, Na2 B4 O7 , NaF, and CuO are selected as sintering aids for sodium super ionic conductor (NASICON)-type Na3 Zr2 Si2 PO12 ceramic to verify the feasibility of the as-proposed method. As evidenced by the results, the sinterability and densification of ceramic matrix are apparently improved. Specifically, Na3 Zr2 Si2 PO12 -7%Na2 B4 O7 , Na3 Zr2 Si2 PO12 -3%NaF, and Na3 Zr2 Si2 PO12 -3%CuO endow much higher room temperature ionic conductivity of 1.03 × 10-3 , 1.61 × 10-3 , and 1.63 × 10-3  S cm-1 , respectively, in comparison with the pristine (7.23 × 10-4  S cm-1 ). The underlying mechanism for the enhanced performance is also discussed. The symmetric sodium cells assembled with sintering aids modified Na3 Zr2 Si2 PO12 ceramic electrolyte exhibit ultra-stable metallic Na plating/stripping at room temperature. Moreover, solid-state sodium batteries paired with Na3 V1.5 Cr0.5 (PO4 )3 cathode active material and modified Na3 Zr2 Si2 PO12 ceramic electrolyte demonstrate superior cycling stability and excellent rate capability. Furthermore, an as-developed strategy can be universally extended to synthesize high-performance oxide ceramics.

Ether-based electrolytes for sodium ion batteries.

Sodium-ion batteries (SIBs) are considered to be strong candidates for large-scale energy storage with the benefits of cost-effectiveness and sodium abundance. Reliable electrolytes, as ionic conductors that regulate the electrochemical reaction behavior and the nature of the interface and electrode, are indispensable in the development of advanced SIBs with high Coulombic efficiency, stable cycling performance and high rate capability. Conventional carbonate-based electrolytes encounter numerous obstacles for their wide application in SIBs due to the formation of a dissolvable, continuous-thickening solid electrolyte interface (SEI) layer and inferior stability with electrodes. Comparatively, ether-based electrolytes (EBEs) are emerging in the secondary battery field with fascinating properties to improve the performance of batteries, especially SIBs. Their stable solvation structure enables highly reversible solvent-co-intercalation reactions and the formation of a thin and stable SEI. However, although EBEs can provide more stable cycling and rapid sodiation kinetics in electrodes, benefitting from their favorable electrolyte/electrode interactions such as chemical compatibility and good wettability, their special chemistry is still being investigated and puzzling. In this review, we provide a thorough and comprehensive overview on the developmental history, fundamental characteristics, superiorities and mechanisms of EBEs, together with their advances in other battery systems. Notably, the relation among electrolyte science, interfacial chemistry and electrochemical performance is highlighted, which is of great significance for the in-depth understanding of battery chemistry. Finally, future perspectives and potential directions are proposed to navigate the design and optimization of electrolytes and electrolyte/electrode interfaces for advanced batteries.

Cefazolin and imipenem enhance AmpC expression and resistance in NagZ-dependent manner in Enterobacter cloacae complex.

BACKGROUND: Enterobacter cloacae complex (ECC) is a common opportunistic pathogen and is responsible for causing various infections in humans. Owing to its inducible chromosomal AmpC ß-lactamase (AmpC), ECC is inherently resistant to the 1st- and 2nd- generation cephalosporins. However, whether ß-lactams antibiotics enhance ECC resistance remains unclear. RESULTS: In this study, we found that subinhibitory concentrations (SICs) of cefazolin (CFZ) and imipenem (IMP) can advance the expression of AmpC and enhance its resistance towards ß-lactams through NagZ in Enterobacter cloacae (EC). Further, AmpC manifested a substantial upregulation in EC in response to SICs of CFZ and IMP. In nagZ knockout EC (ΔnagZ), the resistance to ß-lactam antibiotics was rather weakened and the effect of CFZ and IMP on AmpC induction was completely abrogated. NagZ ectopic expression can rescue the induction effects of CFZ and IMP on AmpC and increase ΔnagZ resistance. More importantly, CFZ and IMP have the potential to induce the expression of AmpR's target genes in a NagZ-dependent manner. CONCLUSIONS: Our findings suggest that NagZ is a critical determinant for CFZ and IMP to promote AmpC expression and resistance and that CFZ and IMP should be used with caution since they may aggravate ECC resistance. At the same time, this study further improves our understanding of resistance mechanisms in ECC.

Selective Enrichment of Phosphorylated Peptides by Monolithic Polymers Surface Imprinted with bis-Imidazolium Moieties by UV-Initiated Cryopolymerization.

Reversible protein phosphorylation on serine, threonine, and tyrosine residues is essential for fast, specific, and accurate signal transduction in cells. Up to now, the identification and quantification of phosphorylated amino acids, peptides, and proteins continue to be one of the significant challenges in contemporary bioanalytical research. In this paper, a series of surface grafted monoliths in the capillary format targeting phosphorylated serine has been prepared by first synthesizing a monolithic core substrate material based on trimethylolpropane trimethacrylate, onto which a thin surface-imprinted layer was established by oriented photografting of a variety of mono- and bis-imidazolium host monomers at subzero temperature, using six different continuous or pulsed UV light sources. The imprinted monolith capillaries were evaluated in a capillary liquid chromatographic system connected to a mass spectrometer in order to test the specific retention of phosphorylated peptides. Site-specific recognition selectivity and specificity for phosphorylated serine was demonstrated when separating amino acids and peptides, proving that the optimized materials could be used as novel trapping media in affinity-based phosphoproteomic analysis.

Enhanced Electrochemical Performance of Simple Electrospun Non-Woven Nickel/Carbon Nanofibers as a Functional Interlayer for Lithium-Sulfur Batteries.

Non-woven nickel/carbon nanofibers (NW(Ni/C)NFs) are developed using a facile one-pot electrospinning method as a functional interlayer for rechargeable lithium-sulfur (Li-S) batteries. The functional interlayer of NW(Ni/C)NFs is sandwiched between a sulfur cathode and the separator and acts as a shuttle inhibitor to sulfur and polysulfides. Because of the sandwiched structure and the nickel additive, the Li-S cell shows better performance in terms of capacity utilization and reversibility. When the NW(Ni/C)NFs were calcined at 900 °C with 1 g of nickel salt additive, the discharge capacity of the cells was the best, and the initial discharge capacity was 1062 mAh g-1. With 200 charge-discharge cycles at 1 C, the discharge capacity of the cells remained above 910 mAh g-1, which is about 85.7% of its initial capacity. The improvement to the cells' electrochemical performance is attributed to the 3D architecture of the NW(Ni/C)NFs as a functional interlayer and to the appropriate amount of nickel addition. This provides a good conductive network with structural stability and the migrating polysulfide reduces the "shuttling phenomenon" during the charge-discharge processes.

Molecularly Imprinted Porous Monolithic Materials from Melamine-Formaldehyde for Selective Trapping of Phosphopeptides.

Thirty-five melamine-formaldehyde (MF) monolithic materials with bimodal pore distributions were synthesized in fused silica capillaries by catalyst-free polycondensation, starting with an aqueous MF precondensate, using acetonitrile as the macroporogen and a variety of aliphatic polyethers and triblock copolymeric surfactants as porogens and mesoporogens, respectively. By varying the prepolymer composition and the type and molecular weight of the polymeric porogen components, a library of porous monolithic materials was produced, covering a range of meso- and macroporous properties. A multivariate evaluation revealed that the amount of surfactant was the strongest contributor to specific surface area and pore volume and to the inversely related mesopore size, whereas the macropore dimensions were controlled mainly by the amount of aliphatic polyether porogen. One of these capillary monoliths, chosen based on the combination of meso- and macropores providing optimal percolative flow and accessible surface area, was synthesized in the presence of N-Fmoc and O-Et protected phosphoserine and phosphotyrosine to prepare molecularly imprinted monoliths with surface layers selective for phosphopeptides. These imprinted monoliths were characterized alongside nonimprinted monoliths by a variety of techniques and finally evaluated by liquid chromatography-mass spectrometry in the capillary format to assess their abilities to trap and release phosphorylated amino acids and peptides from partly aqueous media. Selective enrichment of phosphorylated targets was demonstrated, suggesting that these materials could be useful as trapping media in affinity-based phosphoproteomics.

Dual-Functionalized Ca Enables High Sodiation Kinetics for Hard Carbon in Sodium-Ion Batteries.

Hard carbons (HCs), while a leading candidate for sodium-ion battery (SIB) anode materials, face challenges in their unfavorable sodiation kinetics since the intricate microstructure of HCs complicates the Na+ diffusion channel. Herein, a Hovenia dulcis-derived HC realizes a markedly enhanced high-rate performance in virtue of dual-functionalized Ca. The interlayer doped Ca2+ effectively enlarges the interlayer spacing, while the in situ-formed CaSe templates induce the formation of hierarchical pore structures and intrinsic defects, significantly providing fast Na+ diffusion channels and abundant active sites and thus enhancing the sodium storage kinetics. Achieved by the synergistic effect of regulation of intrinsic microcrystalline and pore structures, the optimized HC shows remarkable performance enhancements, including a high reversible capacity of 350.3 mA h g-1 after 50 cycles at 50 mA g-1, a high-capacity retention rate of 95.3% after 1000 cycles, and excellent rate performance (108.4 mA h g-1 at 2 A g-1). This work sheds light on valuable insight into the structural adjustment of high-rate HCs, facilitating the widespread utilization of SIBs.

Multilevel Gradient-Ordered Silicon Anode with Unprecedented Sodium Storage.

While cost-effective sodium-ion batteries (SIBs) with crystalline silicon anodes promise high theoretical capacities, they perform poorly because silicon stores sodium ineffectively (capacity <40 mAh g-1 ). To address this issue, herein an atomic-order structural-design tactic is adopted for obtaining unique multilevel gradient-ordered silicon (MGO-Si) by simple electrochemical reconstruction. In situ-formed short-range-, medium-range-, and long-range-ordered structures construct a stable MGO-Si, which contributes to favorable Na-Si interaction and fast ion diffusion channels. These characteristics afford a high reversible capacity (352.7 mAh g-1 at 50 mA g-1 ) and stable cycling performance (95.2% capacity retention after 4000 cycles), exhibiting record values among those reported for pure silicon electrodes. Sodium storage of MGO-Si involves an adsorption-intercalation mechanism, and a stepwise construction strategy of gradient-ordered structure further improves the specific capacity (339.5 mAh g-1 at 100 mA g-1 ). Reconstructed Si/C composites show a high reversible capacity of 449.5 mAh g-1 , significantly better than most carbonaceous anodes. The universality of this design principle is demonstrated for other inert or low-capacity materials (micro-Si, SiO2 , SiC, graphite, and TiO2 ), boosting their capacities by 1.5-6 times that of pristine materials, thereby providing new solutions to facilitate sodium storage capability for better-performing battery designs.

HydrogelFinder: A Foundation Model for Efficient Self-Assembling Peptide Discovery Guided by Non-Peptidal Small Molecules.

Self-assembling peptides have numerous applications in medicine, food chemistry, and nanotechnology. However, their discovery has traditionally been serendipitous rather than driven by rational design. Here, HydrogelFinder, a foundation model is developed for the rational design of self-assembling peptides from scratch. This model explores the self-assembly properties by molecular structure, leveraging 1,377 self-assembling non-peptidal small molecules to navigate chemical space and improve structural diversity. Utilizing HydrogelFinder, 111 peptide candidates are generated and synthesized 17 peptides, subsequently experimentally validating the self-assembly and biophysical characteristics of nine peptides ranging from 1-10 amino acids-all achieved within a 19-day workflow. Notably, the two de novo-designed self-assembling peptides demonstrated low cytotoxicity and biocompatibility, as confirmed by live/dead assays. This work highlights the capacity of HydrogelFinder to diversify the design of self-assembling peptides through non-peptidal small molecules, offering a powerful toolkit and paradigm for future peptide discovery endeavors.

ASS1 inhibits triple-negative breast cancer by regulating PHGDH stability and de novo serine synthesis.

Argininosuccinate synthase (ASS1), a critical enzyme in the urea cycle, acts as a tumor suppressor in many cancers. To date, the anticancer mechanism of ASS1 has not been fully elucidated. Here, we found that phosphoglycerate dehydrogenase (PHGDH), a key rate-limiting enzyme in serine synthesis, is a pivotal protein that interacts with ASS1. Our results showed that ASS1 directly binds to PHGDH and promotes its ubiquitination-mediated degradation to inhibit serine synthesis, consequently suppressing tumorigenesis. Importantly, the tumor suppressive effects of ASS1 were strongly abrogated by PHGDH knockout. In addition, ASS1 knockout and knockdown partially rescued cell proliferation when serine and glycine were depleted, while the inhibitory effect of ASS1 overexpression on cell proliferation was restored by the addition of serine and glycine. These findings unveil a novel role of ASS1 and suggest that the ASS1/PHGDH serine synthesis pathway is a promising target for cancer therapy.

Interfacial-Catalysis-Enabled Layered and Inorganic-Rich SEI on Hard Carbon Anodes in Ester Electrolytes for Sodium-Ion Batteries.

Constructing a homogenous and inorganic-rich solid electrolyte interface (SEI) can efficiently improve the overall sodium-storage performance of hard carbon (HC) anodes. However, the thick and heterogenous SEI derived from conventional ester electrolytes fails to meet the above requirements. Herein, an innovative interfacial catalysis mechanism is proposed to design a favorable SEI in ester electrolytes by reconstructing the surface functionality of HC, of which abundant CO (carbonyl) bonds are accurately and homogenously implanted. The CO (carbonyl) bonds act as active centers that controllably catalyze the preferential reduction of salts and directionally guide SEI growth to form a homogenous, layered, and inorganic-rich SEI. Therefore, excessive solvent decomposition is suppressed, and the interfacial Na+ transfer and structural stability of SEI on HC anodes are greatly promoted, contributing to a comprehensive enhancement in sodium-storage performance. The optimal anodes exhibit an outstanding reversible capacity (379.6 mAh g-1 ), an ultrahigh initial Coulombic efficiency (93.2%), a largely improved rate capability, and an extremely stable cycling performance with a capacity decay rate of 0.0018% for 10 000 cycles at 5 A g-1 . This work provides novel insights into smart regulation of interface chemistry to realize high-performance HC anodes for sodium storage.

CC-115 Mediates GSDME-Dependent Pyroptosis in Lung Adenocarcinoma Through the Akt/Bax Pathway.

Chemotherapeutic agents remain the first-line treatment for solid tumors, including lung cancer, but chemotherapy resistance is hampering global efforts to treat this disease. CC-115 is a novel antitumoral compound used in phase I clinical trials. However, it is unclear whether CC-115 is effective against lung adenocarcinoma (LUAD). In the present study, we found that CC-115 induced lytic cell death in A549 and H1650 tumor cells via swelling of cells and formation of large bubbles on the plasma membrane that closely resembled those typical of pyroptosis, a type of programmed cell death linked to chemotherapy. We demonstrated that CC-115 exerts antitumor effects in LUAD through gasdermin E (GSDME)-mediated pyroptosis by acting as a dual inhibitor of DNA-PK and mTOR. CC-115 can inhibit Akt phosphorylation, impairing its inhibitory effect on Bax, thereby inducing pyroptosis via the Bax-mitochondrial intrinsic pathway. CC-115-induced pyroptosis was abrogated by treatment with the Akt activator SC79 or by depletion of Bax. Importantly, CC-115 significantly upregulated the expression of Bax and GSDME-N in a xenograft mouse model, with a reduction in tumor size. Our results revealed that CC-115 suppresses tumor growth by inducing GSDME-mediated pyroptosis through the Akt/Bax-mitochondrial intrinsic pathway, indicating CC-115 as a promising therapeutic agent for LUAD.

Time to Positivity Facilitates an Early Differential Diagnosis of Candida tropicalis from Other Candida species.

Background: Candidemia caused by Candida tropicalis has more serious adverse consequences and an even higher mortality. Time to positivity (TTP) has been widely used to identify microbial species, resistant microorganisms and distinguish real pathogens and pollutants. However, few studies have demonstrated TTP as a presumptive diagnosis of C. tropicalis in patients with candidemia. Patients and Methods: A retrospective study of 136 episodes of candidemia and simulated blood cultures with 314 episodes of confirmed Candida strains were applied to explore the role of TTPs in diagnosing C. tropicalis. TTPs were recorded as the shorter one if both aerobic and anaerobic vials were positive. Lastly, relationships were tested between TTPs and resistance and initial inocula concentration. Results: For the retrospective study, the mean of TTPs for C. tropicalis from 136 patients with candidemia was significantly shorter than other Candida species. The area under the receiver operating characteristics (ROC) curve was 0.8896 ± 0.030 with a sensitivity of 92.86% and a specificity of 77.87%, respectively, indicating TTPs with a cut-off value of <25.50 h had a strong diagnostic power for C. tropicalis in patients with candidemia. Moreover, TTPs from 314 simulated blood cultures showed similar results as the retrospective study, demonstrating TTP is a powerful diagnostic tool in early diagnosing C. tropicalis in patients with candidemia. Additionally, our results showed no statistical significance between TTPs and initial inocula concentration and resistance of Candida species, suggesting initial inocula concentration does not impact TTPs, and TTPs may not be promising in predicting the resistance of all Candida species. Conclusion: TTP can be employed to early distinguish C. tropicalis from other Candida species in patients with candidemia, which is extremely helpful to initiate empiric antifungal treatments to improve clinical outcomes.

Sulfur/phosphorus doping-mediated morphology transformation of carbon nitride from rods to porous microtubes with superior photocatalytic activity.

Hetero-atoms doping or morphology controlling of carbon nitride (g-C3N4) can availably regulate its electronic band structure and optimize photocatalytic performance under visible light. Herein, sulful (S), phosphorus (P) co-doped porous carbon nitride microtubes (SPCN) was synthesized by using ammonium dihydrogen phosphate and melamine as precursors, in which ammonium dihydrogen phosphate can not only control the morphology of carbon nitride from nanorods to porous microtubes, but also provide a potential P source for P-doped CN. The prepared SPCN0.1 with the content of 0.1 g ammonium dihydrogen phosphate displayed the highest photocatalytic hydrogen generation rate of 4200.3 µmol g-1h-1, which was approximately 25 and 1.6 folds by bulk g-C3N4 (CN) and sulphur doped g-C3N4 microrods (SCN), respectively. Moreover, the apparent quantum efficiency of HER reached up to 10.3 % at 420 nm. The enhanced photocatalytic performance may be attributed to the synergistic effect of S, P doping and morphology structure of carbon nitride, which effectively accelerated the separation and transfer of photogenerated electron-hole pairs, proved by photoluminescence spectra, time-resolved PL spectra, electrochemical impedance spectrum and transient photocurrent responses. The novel synthetic method described in this paper is an effective approach to regulate the morphology of g-C3N4via non-metal doping with superior photocatalytic performance.

Sulfur Encapsulation and Sulfur Doping Synergistically Enhance Sodium Ion Storage in Microporous Carbon Anodes.

MOF-based materials are a class of efficient precursors for the preparation of heteroatom-doped porous carbon materials that have been widely applied as anode materials for Na-ion batteries. Thereinto, sulfur is often introduced to increase defects and act as an active species to directly react with sodium ions. Although the sulfur introduction and high surface area can synergistically improve capacity and rate capability, the initial Coulombic efficiency (ICE) and electrical conductivity of carbon material are inevitably reduced. Therefore, balancing sodium storage capacity and ICE is still the bottleneck faced by adsorbent carbon materials. Here, sulfur-encapsulated microporous carbon material with nitrogen, sulfur dual-doping (NSPC) is synthesized by postprocessing, achieving the reduced specific surface area by encapsulating sulfur in micropores, and the increased active sites by edge sulfur doping. The synergy between encapsulation and sulfur doping effectively balances specific capacity, rate capability, and ICE. The NSPC material exhibits capacities of 591.5 and 244.2 mAh g-1 at 0.5 and at 10 A g-1, respectively, and the ICE is as high as 72.3%. Moreover, the effect of nitrogen and sulfur on the improvement of electron/ion diffusion kinetics is resonantly demonstrated by density functional theory calculations. This synergistic preparation method may reveal a feasible thought for fabricating excellent-performance adsorption-type carbon materials for Na-ion batteries.

Novel recombinant protein flagellin A N/C attenuates experimental autoimmune encephalomyelitis by suppressing the ROS/NF-κB/NLRP3 signaling pathway.

Multiple sclerosis (MS) is a chronic inflammatory autoimmune disease characterized by demyelination and neurodegeneration, for which traditional treatment offers limited relief. Microglial/macrophage modulation plays a critical role in the pathogenesis of MS. Oxygen free radical accumulation can induce axonal and nerve cell damage, and further promote MS development. We created a new recombinant protein based on flagellin from Legionella pneumophila named flagellin A with linked C- and N-terminal ends (FLaAN/C), which is an independent intellectual property of our team. We previously showed that FLaAN/C might mitigate radiation-induced damage by inhibiting inflammatory responses and oxidative stress. However, whether FLaAN/C protects against MS remains unknown. Here, we investigated the anti-inflammatory effects of FLaAN/C on mice with experimental autoimmune encephalomyelitis (EAE) induced by oligodendrocyte glycoprotein peptide 35-55 (MOG35-55). The mice were injected intraperitoneally with FLaAN/C after the onset of clinical symptoms, then clinical behavior scores and changes in body weight were recorded daily. The spinal lumbar spine in model mice was enlarged and accompanied by inflammatory cell infiltration and demyelination that were reversed by FLaAN/C. FLaAN/C also induced microglia/macrophages to generate less pro-inflammatory (CD86, iNOS, and TNF-α), and more anti-inflammatory (CD206, IL-10, and Arginase-1) cytokines. These findings suggesting that FLaAN/C promoted microglial/macrophages polarization from the inflammatory M1 to the anti-inflammatory M2 phenotype. Moreover, FLaAN/C inhibited release of the inflammatory cytokines, TNF-α, IL-8, IL-6, IL-17, and IFN-γ. These results indicated that the anti-inflammatory effect of FLaAN/C was associated with the inhibited generation of reactive oxygen species. FLaAN/C downregulated the expression of phosphorylated NF-κB-p65 and prevented downstream NLRP3 inflammasome-mediated pyroptosis. Collectively, these results indicated that FLaAN/C prevents pyroptosis by inhibiting the ROS/NF-κB/NLRP3 signaling pathway, and promotes the microglial/macrophage M1/M2 polarization that significantly alleviated inflammation in mouse models of EAE. Our findings suggested that FLaAN/C could be a promising candidate for MS therapy.

A Multifunctional Gradient Solid Electrolyte Remarkably Improving Interface Compatibility and Ion Transport in Solid-State Lithium Battery.

Solid electrolytes with both interface compatibility and efficient ion transport have been an urgent technical requirement for the practical application of solid-state lithium batteries. Herein, a multifuctional poly(1,3-dioxolane) (PDOL) electrolyte combining the gradient structure from the solid state to the gel state with the Li6.4La3Zr1.4Ta0.6O12 (LLZTO) interfacial modification layer was designed, in which the "solid-to-gel" gradient structure greatly improved the electrode/electrolyte interface compatibility and ion transport, while the solid PDOL and LLZTO layers effectively improved the interface stability of the electrolyte/lithium anode and the inhibition of the lithium dendrites via their high mechanical strength and forming a stable interfacial SEI composite film. This gradient PDOL/LLZTO composite electrolyte possesses a high ionic conductivity of 2.9 × 10-4 S/cm with a wide electrochemical window up to 4.9 V vs Li/Li+. Compared with the pristine PDOL electrolyte and PDOL solid electrolyte membrane coated with a layer of LLZTO, the gradient PDOL/LLZTO composite electrolyte shows better electrode/electrolyte interfacial compatibility, lower interface impedance, and smaller polarization, resulting in enhanced rate and cycle performances. The NCM622/PDOL-LLZTO/Li battery can be stably cycled 200 times at 0.3C and 25 °C. This multifunctional gradient structure design will promote the development of high-performance solid electrolytes and is expected to be widely used in solid-state lithium batteries.