Exploring the causal relationship between periodontitis and gut microbiome: Unveiling the oral-gut and gut-oral axes through bidirectional Mendelian randomization.

AIM: This Mendelian randomization (MR) study was performed to explore the potential bidirectional causal relationship between the gut microbiome (GM) and periodontitis. MATERIALS AND METHODS: We used genetic instruments from the genome-wide association study of European descent for periodontitis from the GeneLifestyle Interactions in Dental Endpoints (GLIDE) consortium (17,353 cases and 28,210 controls) and the FinnGen consortium (4434 cases and 259,234 controls) to investigate the causal relationship with GM (the MiBioGen consortium, 18,340 samples), and vice versa. Several MR techniques, which include inverse variance weighting (IVW), MR-Egger, weighted median, simple mode and weighted mode approaches, were employed to investigate the causal relationship between the exposures and the outcomes. Cochran's Q-test was performed to detect heterogeneity. The MR-Egger regression intercept and MR pleiotropy residual sum and outlier test (MR-PRESSO) were conducted to test potential horizontal pleiotropy. Leave-one-out sensitivity analyses were used to assess the stabilities of single nucleotide polymorphisms (SNPs). Finally, the IVW results from the two databases were analysed using meta-analysis. RESULTS: We confirmed three potential causal relationships between GM taxa and periodontitis at the genus level. Among them, the genera Alistipes and Holdemanella were genetically associated with an increased risk of periodontitis. In reverse, periodontitis may lead to a decreased abundance of the genus Ruminococcaceae UCG014. CONCLUSIONS: The demonstration of a causal link between GM and periodontitis provides compelling evidence, highlighting the interconnectivity and interdependence of the gut-oral and oral-gut axes.

Structural Evolution Governs Reversible Heat Generation in Electrical Double Layers.

Electrical double layer (EDL) formation determines the reversible heat generation of supercapacitors. While classical theories suggest an exothermic nature, experiments revealed that it can be endothermic, depending on the polarization and electrolyte. Here, we perform constant-potential molecular dynamics simulations and develop a lattice gas model to explore the reversible heat of EDL formation in aqueous and ionic liquid (IL) electrolytes. Our Letter reveals that EDL formation in aqueous electrolytes exhibits endothermicity under negative polarization; it shows new complexity of endothermicity followed by exothermicity in ILs, regardless of electrode polarity. These thermal behaviors are determined by the structural evolution during EDL formation, dominated by adsorbed solvent molecules rather than ions in aqueous electrolytes but governed by "demixing" and "vacancy occupation" phenomena in ILs. This Letter provides new insights into the reversible heat of supercapacitors and presents a theoretical approach to investigating thermal behaviors involving the dynamics of EDLs.

DNER and GNL2 are differentially m6A methylated in periodontitis in comparison with periodontal health revealed by m6A microarray of human gingival tissue and transcriptomic analysis.

OBJECTIVE: This study aims to investigate the differences in the epigenomic patterns of N6-methyladenosine (m6A) methylation in gingival tissues between patients with periodontitis (PD) and healthy controls, identifying potential biomarkers. BACKGROUND: As a multifactorial disease, PD involves multiple genetic and environmental effects. The m6A modification is the most prevalent internal mRNA modification and linked to various inflammatory diseases. However, the m6A modification pattern and m6A-related signatures in PD remain unclear. MATERIALS AND METHODS: An m6A microarray of human gingival tissues was conducted in eight subjects: four diagnosed with PD and four healthy controls. Microarray analysis was performed to identify the differentially m6A methylated mRNAs (DMGs) and the differentially expressed mRNAs (DEGs). The differentially methylated and expressed mRNAs (DMEGs) were subjected to functional enrichment analysis by Metascape. The weighted gene co-expression network analysis (WGCNA) algorithm, the least absolute shrinkage and selection operator (LASSO) regression, and univariate logistic regression were performed to identify potential biomarkers. The cell type localization of the target genes was determined using single-cell RNA-seq (scRNA-seq) analysis. The m6A methylation level and gene expression of hub genes were subsequently verified by m6A methylated RNA immunoprecipitation (MeRIP) and quantitative real-time PCR (qRT-PCR). RESULTS: In total, 458 DMGs, 750 DEGs, and 279 DMEGs were identified based on our microarray. Pathway analyses conducted for the DMEGs revealed that biological functions were mainly involved in the regulation of stem cell differentiation, ossification, circadian rhythm, and insulin secretion pathways. Besides, the genes involved in crucial biological processes were mainly expressed in fibroblast and epithelial cells. Furthermore, the m6A methylation and expression levels of two hub biomarkers (DNER and GNL2) were validated. CONCLUSION: The current study exhibited a distinct m6A epitranscriptome, identified and verified two PD-related biomarkers (DNER and GNL2), which may provide novel insights into revealing the new molecular mechanisms and latent targets of PD.

Revealing a potential necroptosis-related axis (RP11-138A9.1/hsa-miR-98-5p/ZBP1) in periodontitis by construction of the ceRNA network.

BACKGROUND AND OBJECTIVES: Periodontitis, a prevalent chronic inflammatory condition, poses a significant risk of tooth loosening and subsequent tooth loss. Within the realm of programmed cell death, a recently recognized process known as necroptosis has garnered attention for its involvement in numerous inflammatory diseases. Nevertheless, its correlation with periodontitis is indistinct. Our study aimed to identify necroptosis-related lncRNAs and crucial lncRNA-miRNA-mRNA regulatory axes in periodontitis to further understand the pathogenesis of periodontitis. MATERIALS AND METHODS: Gene expression profiles in gingival tissues were acquired from the Gene Expression Omnibus (GEO) database. Selecting hub necroptosis-related lncRNA and extracting the key lncRNA-miRNA-mRNA axes based on the ceRNA network by adding novel machine-learning models based on conventional analysis and combining qRT-PCR validation. Then, an artificial neural network (ANN) model was constructed for lncRNA in regulatory axes, and the accuracy of the model was validated by receiver operating characteristic (ROC) curve analysis. The clinical effect of the model was evaluated by decision curve analysis (DCA). Weighted correlation network analysis (WGCNA) and single-sample gene set enrichment analysis (ssGSEA) was performed to explore how these lncRNAs work in periodontitis. RESULTS: Seven hub necroptosis-related lncRNAs and three lncRNA-miRNA-mRNA regulatory axes (RP11-138A9.1/hsa-miR-98-5p/ZBP1 axis, RP11-96D1.11/hsa-miR-185-5p/EZH2 axis, and RP4-773 N10.4/hsa-miR-21-5p/TLR3 axis) were predicted. WGCNA revealed that RP11-138A9.1 was significantly correlated with the "purple module". Functional enrichment analysis and ssGSEA demonstrated that the RP11-138A9.1/hsa-miR-98-5p/ZBP1 axis is closely related to the inflammation and immune processes in periodontitis. CONCLUSION: Our study predicted a crucial necroptosis-related regulatory axis (RP11-138A9.1/hsa-miR-98-5p/ZBP1) based on the ceRNA network, which may aid in elucidating the role and mechanism of necroptosis in periodontitis.

Influence of METTL3 knockdown on PDLSC osteogenesis in E. coli LPS-induced inflammation.

OBJECTIVE: This study aimed to investigate the effect of METTL3 knockdown on osteogenic differentiation of human periodontal ligament stem cells (PDLSCs) in the weak inflammation microenvironments, as well as the underlying mechanisms. MATERIALS AND METHODS: PDLSCs were stimulated by lipopolysaccharide from Escherichia coli (E. coli LPS), followed by quantification of METTL3. METTL3 expression was assessed using RT-qPCR and Western blot analysis in periodontitis. METTL3 knockdown PDLSCs were stimulated with or without E. coli LPS. The evaluation included proinflammatory cytokines, osteogenic markers, ALP activity, and mineralized nodules. Bioinformatics analysis and Western blot determined the association between METTL3 and the PI3K/Akt pathway. RESULTS: METTL3 was overexpressed in periodontitis. METTL3 knockdown in PDLSCs reduced proinflammatory cytokines, osteogenic markers, ALP activity, and mineralized nodules in both environments. Bioinformatics analysis suggested a link between METTL3 and the PI3K/Akt pathway. METTL3 knockdown inhibited PI3K/Akt signaling pathway activation. CONCLUSION: METTL3 knockdown might inhibit osteogenesis in PDLSCs through the inactivation of PI3K/Akt signaling pathway. Concomitant findings might shed novel light on the roles and potential mechanisms of METTL3 in the LPS-stimulated inflammatory microenvironments of PDLSCs.

Exploration of cross-talk and pyroptosis-related gene signatures and molecular mechanisms between periodontitis and diabetes mellitus via peripheral blood mononuclear cell microarray data analysis.

OBJECTIVES: This bioinformatics study is aimed at identifying cross-talk genes, pyroptosis-related genes, and related pathways between periodontitis (PD) and diabetes mellitus (DM), which includes type 1 diabetes (T1DM) and type 2 diabetes (T2DM). METHODS: GEO datasets containing peripheral blood mononuclear cell (PBMC) data of PD and DM were acquired. After batch correction and normalization, differential expression analysis was performed to identify the differentially expressed genes (DEGs). And cross-talk genes in the PD-T1DM pair and the PD-T2DM pair were identified by overlapping DEGs with the same trend in each pair. The weighted gene coexpression network analysis (WGCNA) algorithm helped locate the pyroptosis-related genes that are related to cross-talk genes. Receiver-operating characteristic (ROC) curve analysis confirmed the predictive accuracy of these hub genes in diagnosing PD and DM. The correlation between hub genes and the immune microenvironment of PBMC in these diseases was investigated by Spearman correlation analysis. The experimentally validated protein-protein interaction (PPI) and gene-pathway network were constructed. Subnetwork analysis helped identify the key pathway connecting DM and PD. RESULTS: Hub genes in the PD-T1DM pair (HBD, NLRC4, AIM2, NLRP2) and in the PD-T2DM pair (HBD, IL-1Β, AIM2, NLRP2) were identified. The similarity and difference in the immunocytes infiltration levels and immune pathway scores of PD and DM were observed. ROC analysis showed that AIM2 and HBD exhibited pleasant discrimination ability in all diseases, and the subnetwork of these genes indicated that the NOD-like receptor signaling pathway is the most potentially relevant pathway linking PD and DM. CONCLUSION: HBD and AIM2 could be the most relevant potential cross-talk and pyroptosis-related genes, and the NOD-like receptor signaling pathway could be the top candidate molecular mechanism linking PD and DM, supporting a potential pathophysiological relationship between PD and DM.

Pyroptosis may play a crucial role in modifications of the immune microenvironment in periodontitis.

BACKGROUND AND OBJECTIVE: Published studies proved that both pyroptosis and periodontitis owned a substantial relationship with immunity, and recent research revealed a solid correlation between periodontitis and pyroptosis. While abundant findings have confirmed pyroptosis has a strong impact on the tumor microenvironment, the function of pyroptosis in influencing the periodontitis immune microenvironment remains poorly understood. Thus, we aimed to identify pyroptosis-related genes whose expression signature can well discriminate periodontitis from healthy controls and to comprehend the role of pyroptosis in the periodontitis immune microenvironment. MATERIALS AND METHODS: The periodontitis-related datasets were acquired from the Gene Expression Omnibus (GEO) database. A series of bioinformatics analyses were conducted to investigate the underlying mechanism of pyroptosis in the periodontitis immune microenvironment. Infiltrating immunocytes, immunological reaction gene sets, and the human leukocyte antigen (HLA) gene were all investigated as potential linkages between periodontitis immune microenvironment and pyroptosis. RESULTS: Twenty-one pyroptosis-related genes were dysregulated. A four-mRNA combined classification model was constructed, and the receiver operating characteristic (ROC) curve analysis demonstrated its prominent classification capabilities. Subsequently, the mRNA levels of the four hub markers (CYCS, CASP3, NOD2, CHMP4B) were validated by quantitative real-time PCR (qRT-PCR). The correlation coefficients between each hub gene and immune characteristics were calculated, and CASP3 exhibited the most significant correlations with the immune characteristics. Furthermore, distinct pyroptosis-related expression patterns were revealed, along with immunological features of each pattern. Afterward, we discovered 1868 pyroptosis phenotype-related genes, 134 of which were related to immunity. According to the functional enrichment analysis, these 134 genes were closely related to cytokine signaling in immune system, and defense response. Finally, a co-expression network was constructed via the 1868 gene expression profiles. CONCLUSION: Four hub mRNAs (CYCS, CASP3, NOD2, and CHMP4B) formed a classification model and concomitant results revealed the crucial role of pyroptosis in the periodontitis immune microenvironment, providing fresh insights into the etiopathogenesis of periodontitis and potential immunotherapy.

Retracted: Polyacrylamide Hydrogel Injection for Breast Augmentation: Another Injectable Failure.

This publication has been retracted by the Editor as it erroneously describes the effects of an injectable polyacrylamide gel.Reference:Zhenxiang Wang, Shirong Li, Lingli Wang, Shu Zhang, Yan Jiang, Jinping Chen, Donglin Luo. Polyacrylamide Hydrogel Injection for Breast Augmentation: Another Injectable Failure. Med Sci Monit, 2012; 18(6): CR399-408. DOI: 10.12659/MSM.882910.

Anchoring LiCl in the Nanopores of Metal-Organic Frameworks for Ultra-High Uptake and Selective Separation of Ammonia.

Ammonia (NH3 ) is an important chemical raw material and a unique carbon-free fuel with high hydrogen energy density. Thus, NH3 capture, storage, and desorption are of significant importance. However, high capacity capture, low energy desorption, and selective separation of NH3 are still challengs so far. Here, we report high-performance hybrid sorbents by anchoring LiCl in the nanopores of MIL-53-(OH)2 metal-organic frameworks (MOFs). It is found that the optimal composite shows a capture capacity of 33.9 mmol g-1 NH3 at 1.0 bar and 25 °C, which far exceeds the current record among the reported porous materials. Notably, the excellent capture capacity at low pressure and high temperature makes it possible to selectively capture NH3 from NH3 /N2 , NH3 /CO2 , and NH3 /H2 O. It is revealed that synergistic action of NH3 coordination to the highly dispersed Li+ in the MOF nanopores and hydrogen bonding of NH3 with Cl- account for such an excellent capture and selectivity performance.

Comprehensive evaluation of the learning curve to achieve satisfactory adenoma detection rate.

BACKGROUND AND AIM: The number of colonoscopies required to reach satisfactory adenoma detection rate (ADR) is not well established. The aim of this study was to identify the appropriate number of procedures required to attain satisfactory ADR for those well-trained endoscopists who have a cecal intubation rate (CIR) ≥ 90% and start to perform colonoscopy independently. METHODS: All endoscopists with compelete independent colonoscopy data during career in our database were enrolled. The number of procedures required to achieve ADR ≥ 20% was identified by cumulative summation (Cusum), learning curve Cusum (LC-Cusum), and moving average method. Mixed effect logistic regression model was developed to determine the relationship between endoscopist as well as patient-related factors and adenoma detection. RESULTS: A total of 24 943 procedures and 14 endoscopists were enrolled. By Cusum analysis, the interest point was at 207 procedures. By LC-Cusum analysis, 71% (10/14) and 86% (12/14) of endoscopists had attained satisfactory ADR after 200 and 300 procedures, respectively. By moving average method, endoscopists reached a mean ADR of 20% at 216 and 261 procedures over blocks of 50 and 100 procedures, respectively. The total number of procedures, number of daily procedures, patient age and gender, bowel preparation, sedation, and diverticulosis were significantly associated with adenoma detection. CONCLUSIONS: This is the first study to investigate the learning curve of ADR for those well-trained endoscopists who have a CIR ≥ 90% and start to perform colonoscopy independently. Two hundred procedures might be an optimal number required to reach an ADR ≥ 20%.

[Preparation of Rubber Accelerator Tetramethyl Thiuram Monosulfide and Its Spectral Analysis].

In the study, rubber accelerator tetramethyl thiuram monosulfide (TMTM) was synthesized firstly. Single crystal TMTM was cultivated by solvent evaporation method. TMTM was detected and characterized by XRD single crystal diffraction, FTIR, TG-DSC. The micro-structure and intrinsic regularity were revealed. The TMTM microstructure was revealed by XRD single crystal diffraction from the diffraction data, part of bond length and bond angle. Its highly efficient performance of rubber vulcanization promotion was decided due to its orientation structure and high order. Properties of TMTM was disclosed by TG-DSC analysis from the heat effect. The results of TG-DSC and FTIR showed that single crystal TMTM possessed with little CS2. The chemical bond types in TMTM were revealed by FTIR the same as single crystal diffraction testing by different way. The decomposition temperature of TMTM was very high. It could provided reference with research on rubber vulcanizing properties by TMTM on rubber vulcanizing machine. This study can help the enterprises to designate the working standard tracing detection of TMTM industrialized production. Performance index of TMTM was judged. The project of TMTM industry standard can be declared by the enterprises, written a draft standard. It can provide the basis experimental data on completing the revision of the national ministry of industry and information technology standard system project plan.

Effect of osteopontin in regulating bone marrow mesenchymal stem cell treatment of skin wounds in diabetic mice.

BACKGROUND: We aimed to investigate the role of osteopontin in regulating mesenchymal stem cells transplanted to promote wound healing in diabetic mice. METHODS: The mesenchymal stem cells of osteopontin knock-out (KO) and wild-type (WT) mice were isolated separately for in vitro culture and characterization. A skin wound on the back of mice was established by skin punching. In 27 osteopontin KO male mice, induced diabetes mellitus was via intraperitoneal injection of streptozotocin. 9 normal mice were used as controls. The mice were divided into four groups and injected with Dulbecco's modified Eagle's medium (DMEM) or mesenchymal stem cells via the tail vein: A (diabetic mice injected with DMEM), B (diabetic mice injected with osteopontin KO mesenchymal stem cells), C (diabetic mice injected with WT mesenchymal stem cells), D (normal mice injected with DMEM). The healing times and closure rates of skin wounds were recorded. The microvessel density of healing wounds was measured, and the localized expression of osteopontin was identified by western blotting and immunohistochemistry. The migration of mesenchymal stem cells was observed on normal mice with skin wound injected with mesenchymal stem cells of C57BL6~GFP transgenic mice, which show green fluorescent under UV light. RESULTS: Compared with normal mice, the healing time of wounds in the mice with diabetes and osteopontin KO was significantly prolonged (p < 0.01). After transplanting osteopontin KO mesenchymal stem cells, the healing time was slightly shorter. Meanwhile, the healing time was significantly shorter after transplanted with WT mesenchymal stem cells and more significant neovascularization at healing wounds (p < 0.05). The expression of osteopontin in local healing wounds after transplantation of WT mesenchymal stem cells was demonstrated with western blotting and immunohistochemistry. After 4 days, the green fluoresces were noted on the wounds of mice injected with mesenchymal stem cells of fluorescent mice. CONCLUSIONS: Mesenchymal stem cells can migrate to wound sites, and osteopontin plays a regulatory role in mesenchymal stem cells promoting the healing of diabetic skin wounds.

Comparison of Artecoll, Restylane and silicone for augmentation rhinoplasty in 378 Chinese patients.

PURPOSE: Dermal fillers have been proven to be safe in soft tissue augmentation; however, their efficacy in modeling the noses of Asian patients has not been demonstrated. METHODS: In this study, 378 patients were included and underwent augmentation rhinoplasty (Artecoll, n=126; Restylane, n=126 and silicone implants, n=126). The subjective and objective outcomes were evaluated on day 1, and months 1, 3, 6, and 12 after injection rhinoplasty. RESULTS: All patients achieved significant improvement in nasal shape and contour immediately after surgery. Patients treated with Restylane failed to maintain the nasal shape and contour 1 year after surgery, whereas patients undergoing Artecoll rhinoplasty completely maintained the post-treatment nasal shape and contour. More patients with silicone implants experienced adverse events and the severity of these events was greater in the silicone group compared to those in the Restylane and Acetoll groups. CONCLUSION: Artecoll rhinoplasty has a low incidence of adverse effects and the shape and contour of the nose are maintained for a prolonged period.

Organic Solvent Boosts Charge Storage and Charging Dynamics of Conductive MOF Supercapacitors.

Conductive metal-organic frameworks (c-MOFs) and ionic liquids (ILs) have emerged as auspicious combinations for high-performance supercapacitors. However, the nanoconfinement from c-MOFs and high viscosity of ILs slow down the charging process. This hindrance can, however, be resolved by adding solvent. Here, constant-potential molecular simulations are performed to scrutinize the solvent impact on charge storage and charging dynamics of MOF-IL-based supercapacitors. Conditions for >100% enhancement in capacity and ≈6 times increase in charging speed are found. These improvements are confirmed by synthesizing near-ideal c-MOFs and developing multiscale models linking molecular simulations to electrochemical measurements. Fundamentally, the findings elucidate that the solvent acts as an "ionophobic agent" to induce a substantial enhancement in charge storage, and as an "ion traffic police" to eliminate convoluted counterion and co-ion motion paths and create two distinct ion transport highways to accelerate charging dynamics. This work paves the way for the optimal design of MOF supercapacitors.

Overexpression of EphB2 in the basolateral amygdala is crucial for inducing visceral pain sensitization in rats subjected to water avoidance stress.

AIMS: Basolateral amygdala (BLA), as a center for stress responses and emotional regulation, is involved in visceral hypersensitivity of irritable bowel syndrome (IBS) induced by stress. In the present study, we aimed to investigate the role of EphB2 receptor (EphB2) in BLA and explore the underlying mechanisms in this process. METHODS: Visceral hypersensitivity was induced by water avoidance stress (WAS). Elevated plus maze test, forced swimming test, and sucrose preference test were applied to assess anxiety- and depression-like behaviors. Ibotenic acid or lentivirus was used to inactivate BLA in either the induction or maintenance stage of visceral hypersensitivity. The expression of protein was determined by quantitative PCR, immunofluorescence, and western blot. RESULTS: EphB2 expression was increased in BLA in WAS rats. Inactivation of BLA or downregulation of EphB2 in BLA failed to induce visceral hypersensitivity as well as anxiety-like behaviors. However, during the maintenance stage of visceral pain, visceral hypersensitivity was only partially relieved but anxiety-like behaviors were abolished by inactivation of BLA or downregulation of EphB2 in BLA. Chronic WAS increased the expression of EphB2, N-methyl-D-aspartate receptors (NMDARs), and postsynaptic density protein (PSD95) in BLA. Downregulation of EphB2 in BLA reduced NMDARs and PSD95 expression in WAS rats. However, activation of NMDARs after the knockdown of EphB2 expression still triggered visceral hypersensitivity and anxiety-like behaviors. CONCLUSIONS: Taken together, the results suggest that EphB2 in BLA plays an essential role in inducing visceral hypersensitivity. In the maintenance stage, the involvement of EphB2 is crucial but not sufficient. The increase in EphB2 induced by WAS may enhance synaptic plasticity in BLA through upregulating NMDARs, which results in IBS-like symptoms. These findings may give insight into the treatment of IBS and related psychological distress.

Integrated Machine Learning and Bioinformatic Analyses Constructed a Network Between Mitochondrial Dysfunction and Immune Microenvironment of Periodontitis.

Periodontitis is a prevalent and persistent inflammatory condition that impacts the supporting tissues of the teeth, including the gums and bone. Recent research indicates that mitochondrial dysfunction may be involved in the onset and advancement of periodontitis. The current work sought to reveal the interaction between mitochondrial dysfunction and the immune microenvironment in periodontitis. Public data were acquired from MitoCarta 3.0, Mitomap, and GEO databases. Hub markers were screened out by five integrated machine learning algorithms and verified by laboratory experiments. Single-cell sequencing data were utilized to unravel cell-type specific expression levels of hub genes. An artificial neural network model was constructed to discriminate periodontitis from healthy controls. An unsupervised consensus clustering algorithm revealed mitochondrial dysfunction-related periodontitis subtypes. The immune and mitochondrial characteristics were calculated using CIBERSORTx and ssGSEA algorithms. Two hub mitochondria-related markers (CYP24A1 and HINT3) were identified. Single-cell sequencing data revealed that HINT3 was primarily expressed in dendritic cells, while CYP24A1 was mainly expressed in monocytes. The hub genes based artificial neural network model showed robust diagnostic performance. The unsupervised consensus clustering algorithm revealed two distinct mitochondrial phenotypes. The hub genes exhibited a strong correlation with the immune cell infiltration and mitochondrial respiratory chain complexes. The study identified two hub markers that may serve as potential targets for immunotherapy and provided a novel reference for future investigations into the function of mitochondria in periodontitis.

Energy Storage Mechanism in Supercapacitors with Porous Graphdiynes: Effects of Pore Topology and Electrode Metallicity.

Porous graphdiynes are a new class of porous 2D materials with tunable electronic structures and various pore structures. They have potential applications as well-defined nanostructured electrodes and can provide platforms for understanding energy storage mechanisms underlying supercapacitors. Herein, the effect of stacking structure and metallicity on energy storage with such electrodes is investigated. Simulations reveal that supercapacitors based on porous graphdiynes of AB stacking structure can achieve both higher double-layer capacitance and ionic conductivity than AA stacking. This phenomenon is ascribed to more intense image forces in AB stacking, leading to a breakdown of ionic ordering and the formation of effective "free ions". Macroscale analysis shows that doped porous graphdiynes can deliver outstanding gravimetric and volumetric energy and power densities due to their enhanced quantum capacitance. These findings pave the way for designing high-performance supercapacitors by regulating pore topology and metallicity of electrode materials.

FBXO38 mediates FGL1 ubiquitination and degradation to enhance cancer immunity and suppress inflammation.

Upregulation of FGL1 helps tumors escape from immune surveillance, and therapeutic antibodies targeting FGL1 have potential as another immune checkpoint inhibitor. However, the underlying mechanism of high FGL1 protein level in cancers is not well defined. Here, we report that FBXO38 interacts with and ubiquitylates FGL1 to negatively regulate its stability and to mediate cancer immune response. Depletion of FBXO38 markedly augments FGL1 abundance, not only suppressing CD8+ T cell infiltration and enhancing immune evasion of tumor but also increasing inflammation in mice. Importantly, we observe a negative correlation of FBXO38 with FGL1 and IL-6 in non-small cell lung cancer specimens. FGL1 and IL-6 levels positively correlate with TNM (tumor, lymph node, metastasis) stages, while FBXO38 and the infiltrating CD8+ T cells negatively correlate with TNM stages. Our study identifies a mechanism regulating FGL1 stability and a target to enhance the immunotherapy and suggests that the combination of anti-FGL1 and anti-IL-6 is a potential therapeutic strategy for cancer immunotherapy.