EDIL3 alleviates Mannan-induced psoriatic arthritis by slowing the intracellular glycolysis process in mononuclear-derived dendritic cells.

Psoriatic arthritis (PsA) is an immune-mediated, chronic inflammatory joint disease that commonly occurs as a complication of psoriasis. EGF-like repeats and discoidal I-like domain 3 (EDIL3) is a secreted protein with multiple structural domains and associated with various physiological functions. In this study, we employed a mannan-induced psoriatic arthritis model to investigate the impact of EDIL3 on PsA pathogenesis. Notably, a downregulation of EDIL3 expression was observed in the PsA model, which correlated with increased disease severity. EDIL3 knockout mice exhibited a more severe phenotype of PsA, which was ameliorated upon re-infusion of recombinant EDIL3 protein. The mitigation effect of EDIL3 on PsA depends on its regulation of the activation of monocyte-derived DCs (MoDCs) and T-help 17 cells (Th17). After inhibiting the function of MoDCs and Th17 cells with neutralizing antibodies, the beneficial effects of EDIL3 on PsA were lost. By inducing adenosine monophosphate (AMP)-activated protein kinase (AMPK) phosphorylation and suppressing protein kinase B (AKT) phosphorylation, EDIL3 attenuates intracellular glycolysis in MoDCs stimulated by glucose, thereby impeding their maturation and differentiation. Moreover, it diminishes the differentiation of Th17 cells and decelerates the progression of PsA. In conclusion, our findings elucidate the role and mechanism of EDIL3 in the development of PsA, providing a new target for clinical diagnosis and treatment.

Endoplasmic reticulum stress-related features predict the prognosis of osteosarcoma and reveal STC2 as a novel risk indicator for disease progression.

Endoplasmic reticulum (ER) stress exerts significant effects on cell growth, proliferation, migration, invasion, chemoresistance, and angiogenesis in various cancers. However, the impact of ER stress on the outcomes of osteosarcoma patients remains unclear. In this study, we established an ER stress risk model based on The Cancer Genome Atlas (TARGET) osteosarcoma dataset to reflect immune features and predict the prognosis of osteosarcoma patients. Survival analysis revealed significant differences in overall survival among osteosarcoma patients with different ER stress-related risk scores. Furthermore, ER stress-related risk features were significantly associated with the clinical pathological characteristics of osteosarcoma patients and could serve as independent prognostic indicators. Functional enrichment analysis indicated associations of the risk model with cell chemotaxis, leukocyte migration, and regulation of leukocyte migration. Additionally, the ER stress-related risk model suggested the presence of an immunosuppressive microenvironment and immune checkpoint responses. We validated the significance of 7 ER stress-related genes obtained from LASSO regression analysis through RT-qPCR testing on osteosarcoma samples from a local hospital, and inferred the importance of STC2 based on the literature. Subsequently, IHC experiments using samples from 70 osteosarcoma cases and 21 adjacent tissue samples confirmed differential expression of STC2 between cancer and normal tissues, and explored the gene's expression in pan-cancer and its association with clinical pathological parameters of osteosarcoma. In conclusion, we have proposed an ER stress risk model as an independent prognostic factor and identified STC2 as a novel risk indicator for disease progression, providing a promising direction for further research and treatment of osteosarcoma.

IL-38 Aggravates Atopic Dermatitis via Facilitating Migration of Langerhans cells.

Atopic dermatitis (AD) is a common inflammation skin disease that involves dysregulated interplay between immune cells and keratinocytes. Interleukin-38 (IL-38), a poorly characterized IL-1 family cytokine, its role and mechanism in the pathogenesis of AD is elusive. Here, we show that IL-38 is mainly secreted by epidermal keratinocytes and highly expressed in the skin and downregulated in AD lesions. We generated IL-38 keratinocyte-specific knockout mice (K14Cre/+-IL-38f/f ) and induced AD models by 2,4-dinitrofluorobenzene (DNFB). Unexpectedly, after treatment with DNFB, K14Cre/+-IL-38f/f mice were less susceptible to cutaneous inflammation of AD. Moreover, keratinocyte-specific deletion of IL-38 suppressed the migration of Langerhans cells (LCs) into lymph nodes which results in disturbed differentiation of CD4+T cells and decreased the infiltration of immune cells into AD lesions. LCs are a type of dendritic cell that reside specifically in the epidermis and regulate immune responses. We developed LC-like cells in vitro from mouse bone marrow (BM) and treated with recombined IL-38. The results show that IL-38 depended on IL-36R, activated the phosphorylated expression of IRAK4 and NF-κB P65 and upregulated the expression of CCR7 to promoting the migration of LCs, nevertheless, the upregulation disappeared with the addition of IL-36 receptor antagonist (IL-36RA), IRAK4 or NF-κB P65 inhibitor. Furthermore, after treatment with IRAK4 inhibitors, the experimental AD phenotypes were alleviated and so IRAK4 is considered a promising target for the treatment of inflammatory diseases. Overall, our findings indicated a potential pathway that IL-38 depends on IL-36R, leading to LCs migration to promote AD by upregulating CCR7 via IRAK4/NF-κB and implied the prevention and treatment of AD, supporting potential clinical utilization of IRAK4 inhibitors in AD treatment.

Optical freeform reflective imaging system design method with manufacturing constraints.

With the development of space optics, optical freeform surfaces have gradually been utilized in reflective optical imaging systems in recent years. Freeform surfaces not only bring many benefits to the optical imaging system, but also present many challenges to their manufacture. Regardless of the machining method used, machining errors during the fabrication of freeform surfaces will exist, which limits the accuracy of freeform surface machining. In this paper, the deviation root mean square (RMS) of a freeform surface from the reference aspheric surface is proposed to evaluate the manufacturability of the freeform surface by using single-point diamond turning. Then the deviation RMS of freeform surfaces is added to the design process of the optical system as a manufacturing constraint. Subsequently, an off-axis three-mirror system and an off-axis two-mirror system with and without manufacturing constraints are designed, respectively. Then the imaging quality of these optical systems and the linear interpolation error RMS of freeform mirror are analyzed. It can be concluded that, on the basis of reaching the imaging quality requirements, the machining difficulty of a freeform mirror can be reduced when adding manufacturing constraints to the design process.

Evaluation of activated pyrochar for boosting anaerobic digestion: Performances and microbial community.

In this study, the effects of CO2-activated/non-activated pyrochars (PCs) from cornstalk, cotton straw, and rice straw on anaerobic digestion (AD) performances and microbial characteristics were investigated. The maximum biogas production rate (2.2 L/L/d) with a methane content of 73% was obtained from the AD with CO2-activated cotton straw PC. The activated PC mainly played a strengthening role in the early and middle stages of AD. Specifically, the cornstalk PC could greatly relieve acid inhibition, and cotton straw PC had a significantly positive effect on the regulation of ammonia nitrogen concentration. The rare genera like Verrucomicrobia had obvious differences among groups of AD with PCs. Regarding differential metabolites, cornstalk PC-N2 displayed a positive correlation with isoleucyl-alanine, while exhibiting a negative correlation with deoxyinosine, and the corresponding relative expression levels were + 3.0 and -2.4, respectively. Overall, gas-activated PCs could promote methane production and affect the composition of microbial community.

Early depletion of M1 macrophages retards the progression of glucocorticoid-associated osteonecrosis of the femoral head.

Inflammation stands as a pivotal factor in the pathogenesis of glucocorticoid-associated osteonecrosis of the femoral head (GA-ONFH). However, the vital role played by M1 macrophages, the principal constituents of the inflammatory process, remains largely underexplored. In this study, we employed reverse transcription-quantitative polymerase chain Reaction (RT-PCR), western blot, and flow cytometry to assess the impact of M1-conditioned medium on cultures of mouse bone marrow-derived mesenchymal stem cells (BMSCs) and Murine Long bone Osteocyte-Y4 (MLO-Y4) in vitro. Moreover, we quantified the levels of inflammatory cytokines in the M1-conditioned medium through the employment of an enzyme-linked immunosorbent assay (ELISA). For in vivo analysis, we examined M1 macrophages and investigated the NF-kB signaling pathway in specimens obtained from the femoral heads of animals and humans. We found that the number of M1 macrophages in the femoral head of GA-ONFH patients grew significantly, and in the mice remarkably increase, maintaining high levels in the intramedullary. In vitro, the M1 macrophage-conditioned medium elicited apoptosis in BMSCs and MLO-Y4 cells, shedding light on the intricate interplay between macrophages and these cell types. The presence of TNF-α within the M1-conditioned medium activated the NF-κB pathway, providing mechanistic insight into the apoptotic induction. Moreover, employing a robust rat macrophage clearance model and GA-ONFH model, we demonstrated a remarkable attenuation in TNF-α expression and NF-kB signaling subsequent to macrophage clearance. This pronounced reduction engenders diminished cellular apoptosis and engenders a decelerated trajectory of GA-ONFH progression. In conclusion, our study reveals the crucial involvement of M1 macrophages in the pathogenesis of GA-ONFH, highlighting their indispensable role in disease progression. Furthermore, early clearance emerges as a promising strategy for impeding the development of GA-ONFH.

New Antibacterial Diterpenoids from the South China Sea Soft Coral Klyxum molle.

Fifteen new diterpenoids, namely xishaklyanes A-O (1-15), along with three known related ones (16-18), were isolated from the soft coral Klyxum molle collected from Xisha Islands, South China Sea. The stereochemistry of the new compounds was elucidated by a combination of detailed spectroscopic analyses, chemical derivatization, quantum chemical calculations, and comparison with the reported data. The absolute configuration of compound 18 was established by the modified Mosher's method for the first time. In bioassay, some of these compounds exhibited considerable antibacterial activities on fish pathogenic bacteria, and compound 4 showed the most effective activity with MIC of 0.225 µg/mL against Lactococcus garvieae.

Multiparametric MRI radiomics fusion for predicting the response and shrinkage pattern to neoadjuvant chemotherapy in breast cancer.

Purpose: During neoadjuvant chemotherapy (NACT), breast tumor morphological and vascular characteristics are usually changed. This study aimed to evaluate the tumor shrinkage pattern and response to NACT by preoperative multiparametric magnetic resonance imaging (MRI), including dynamic contrast-enhanced MRI (DCE-MRI), diffuse weighted imaging (DWI) and T2 weighted imaging (T2WI). Method: In this retrospective analysis, female patients with unilateral unifocal primary breast cancer were included for predicting tumor pathologic/clinical response to NACT (n=216, development set, n=151 and validation set, n=65) and for discriminating the tumor concentric shrinkage (CS) pattern from the others (n=193; development set, n=135 and validation set, n=58). Radiomic features (n=102) of first-order statistical, morphological and textural features were calculated on tumors from the multiparametric MRI. Single- and multiparametric image-based features were assessed separately and were further combined to feed into a random forest-based predictive model. The predictive model was trained in the testing set and assessed on the testing dataset with an area under the curve (AUC). Molecular subtype information and radiomic features were fused to enhance the predictive performance. Results: The DCE-MRI-based model showed higher performance (AUCs of 0.919, 0.830 and 0.825 for tumor pathologic response, clinical response and tumor shrinkage patterns, respectively) than either the T2WI or the ADC image-based model. An increased prediction performance was achieved by a model with multiparametric MRI radiomic feature fusion. Conclusions: All these results demonstrated that multiparametric MRI features and their information fusion could be of important clinical value for the preoperative prediction of treatment response and shrinkage pattern.

Two New Cembranoids from the Chinese Soft Coral Sarcophyton boettgeri.

Two new cembranoids, namely sarcoboettgerols D and E, together with four known related ones, have been isolated from the soft coral Sarcophyton boettgeri collected from Weizhou Island in the South China Sea. Their structures including absolute configurations were elucidated by extensive spectroscopic analysis, quantum mechanical nuclear magnetic resonance methods, time-dependent density functional theory-electronic circular dichroism calculations, as well as comparison with the reported data in the literature. A plausible biogenetic relationship of four cembranoids was proposed. In bioassays, sarcomililatin B exhibited cytotoxic activity against H1299 cell (IC50 =35.0 µM), whereas sarcomililatin B and sarcomililatin A displayed moderate antibacterial activities (MIC 17.4-34.8 µg/mL).

Deeper insights into the synergy of material transformation, microbial network, and energy balance during pilot thermophilic and mesophilic dry anaerobic digestion systems.

The present study investigated the synergistic characteristics between abiotic and biotic transformation with a view to improving the methane production efficiency of thermophilic and mesophilic sequencing batch dry anaerobic digestion (SBD-AD). The pilot scale experiment consisted of a lignocellulosic material based on a mixture of corn straw and cow dung. A leachate bed reactor was used for an AD cycle of 40 days. Several distinct differences are reflected in biogas (methane) production and VFA concentration and composition. A combination of first-order hydrolysis and a modified Gompertz model determined that the holocellulose (cellulose + hemicellulose) and maximum methanogenic efficiency at thermophilic temperatures were increased by 112.03 % and 90.09 %, respectively. Additionally, the methane production peak was extended by 3-5 days in comparison with that at mesophilic temperatures. The microbial community exhibited vastly different functional network relationships under the two temperature conditions (P < 0.05). The data indicate that Clostridales and Methanobacteria had preferable synergistic effects and that the metabolism of hydrophilic methanogens is necessary for the conversion of VFA to methane during thermophilic SBD-AD. The effect of mesophilic conditions on Clostridales was relative weakened, and acetophilic methanogens were mainly present. Moreover, simulation of the full-chain and operational strategy of SBD-AD engineering resulted in a decrease in heat energy consumption of 21.4-64.3 % at thermophilic temperatures and 30.0-90.0 % at mesophilic temperatures from winter to summer. Furthermore, the total net energy production of thermophilic SBD-AD was increased by 105.2 % in comparison with that at mesophilic temperatures, demonstrating strengthened energy recovery. Overall, raising the SBD-AD temperature to thermophilic levels has considerable application value for improving the treatment capacity of agricultural lignocellulosic waste.

WFDC12-overexpressing contributes to the development of atopic dermatitis via accelerating ALOX12/15 metabolism and PAF accumulation.

Atopic dermatitis (AD) is a chronic inflammatory skin disease characterized by eczema-like skin lesions, dry skin, severe itching, and recurrent recurrence. The whey acidic protein four-disulfide core domain gene WFDC12 is highly expressed in skin tissue and up-regulated in the skin lesions of AD patients, but its role and relevant mechanism in AD pathogenesis have not been studied yet. In this study, we found that the expression of WFDC12 was closely related to clinical symptoms of AD and the severity of AD-like lesions induced by DNFB in transgenic mice. WFDC12-overexpressing in the epidermis might promote the migration of skin-presenting cells to lymph nodes and increase Th cell infiltration. Meanwhile, the number and ratio of immune cells and mRNA levels of cytokines were significantly upregulated in transgenic mice. In addition, we found that ALOX12/15 gene expression was upregulated in the arachidonic acid metabolism pathway, and the corresponding metabolite accumulation was increased. The activity of epidermal serine hydrolase decreased and the accumulation of platelet-activating factor (PAF) increased in the epidermis of transgenic mice. Collectively, our data demonstrate that WFDC12 may contribute to the exacerbation of AD-like symptoms in DNFB-induced mouse model by enhancing arachidonic acid metabolism and PAF accumulation and that WFDC12 may be a potential therapeutic target for human atopic dermatitis.

Interleukin-37 promotes DMBA/TPA skin cancer through SIGIRR-mediated inhibition of glycolysis in CD103+DC cells.

Interleukin 37 (IL-37), a member of the IL-1 family, is considered a suppressor of innate and adaptive immunity and, hence is a regulator of tumor immunity. However, the specific molecular mechanism and role of IL-37 in skin cancer remain unclear. Here, we report that IL-37b-transgenic mice (IL-37tg) treated with the carcinogenic 7,12-dimethylbenzoanthracene (DMBA)/12-o-tetradecylphorbol-13-acetate (TPA) exhibited enhanced skin cancer and increased tumor burden in the skin by inhibiting the function of CD103+ dendritic cells (DCs). Notably, IL-37 induced rapid phosphorylation of adenosine 5'-monophosphate (AMP)-activated protein kinase (AMPK), and via single immunoglobulin IL-1-related receptor (SIGIRR), inhibited the long-term Akt activation. Specifically, by affecting the SIGIRR-AMPK-Akt signaling axis, which is related to the regulation of glycolysis in CD103+DCs, IL-37 inhibited their anti-tumor function. Our results show that a marked correlation between the CD103+DC signature (IRF8, FMS-like tyrosine kinase 3 ligand, CLEC9A, CLNK, XCR1, BATF3, and ZBTB46) and chemokines C-X-C motif chemokine ligand 9, CXCL10, and CD8A in a mouse model with DMBA/TPA-induced skin cancer. In a word, our results highlight that IL-37 as an inhibitor of tumor immune surveillance through modulating CD103+DCs and establishing an important link between metabolism and immunity as a therapeutic target for skin cancer.

Challenges in Recycling Spent Lithium-Ion Batteries: Spotlight on Polyvinylidene Fluoride Removal.

In the recycling of retired lithium-ion batteries (LIBs), the cathode materials containing valuable metals should be first separated from the current collector aluminum foil to decrease the difficulty and complexity in the subsequent metal extraction. However, strong the binding force of organic binder polyvinylidene fluoride (PVDF) prevents effective separation of cathode materials and Al foil, thus affecting metal recycling. This paper reviews the composition, property, function, and binding mechanism of PVDF, and elaborates on the separation technologies of cathode material and Al foil (e.g., physical separation, solid-phase thermochemistry, solution chemistry, and solvent chemistry) as well as the corresponding reaction behavior and transformation mechanisms of PVDF. Due to the characteristic variation of the reaction systems, the dissolution, swelling, melting, and degradation processes and mechanisms of PVDF exhibit considerable differences, posing new challenges to efficient recycling of spent LIBs worldwide. It is critical to separate cathode materials and Al foil and recycle PVDF to reduce environmental risks from the recovery of retired LIBs resources. Developing fluorine-free alternative materials and solid-state electrolytes is a potential way to mitigate PVDF pollution in the recycling of spent LIBs in the EV era.

Biogas Residues Improved Microbial Diversity and Disease Suppression Function under Extent Indigenous Soil Microbial Biomass.

Indigenous soil microbial biomass (ISMB) plays a key role in maintaining essential functions and biodiversity of soil health. One of the critical unknowns is how the indigenous microorganisms respond to different fertilizers which is directly related to agricultural production. Therefore, we used Mi-Seq sequencing and network analyses to compare the response of ISMB to biogas residue and chemical fertilizers. The results showed that crop production was profoundly influenced by levels of ISMB present and is further dependent on the strategy of fertilizer application. Higher ISMB primarily manifests through retention of richer microbial abundance, a balanced community structure, and tightened co-occurrence within a certain proportion of Nitrospirae, Rhizophlyctidaceae, and Gemmatimonadetes. Compared to chemical fertilizer, biogas residue resulted in higher production with more strongly linked nodes such as Actinobacteria, Chloroflexi and Gemmatimonadetes. Under the same level of ISMB, the microbial diversity was richer and co-occurrence was tighter when biogas residues were applied compared with chemical fertilizer. In addition, the higher level of ISMB with biogas residue applied had a lower abundance of potential fungal pathogens in both bulk and rhizosphere soil compared with chemical fertilizer. This study provides critical data to understand the influence of ISMB and biogas residue on soil ecological system.

Mechanochemical upcycling of spent LiCoO2 to new LiNi0.80Co0.15Al0.05O2 battery: An atom economy strategy.

The use of strong acids and low atom efficiency in conventional hydrometallurgical recycling of spent lithium-ion batteries (LIBs) results in significant secondary wastes and CO2 emissions. Herein, we utilize the waste metal current collectors in spent LIBs to promote atom economy and reduce chemicals consumption in a conversion process of spent Li1-xCoO2 (LCO) → new LiNi0.80Co0.15Al0.05O2 (NCA) cathode. Mechanochemical activation is employed to achieve moderate valence reduction of transition metal oxides (Co3+→Co2+,3+) and efficient oxidation of current collector fragments (Al0→Al3+, Cu0→Cu1+,2+), and then due to stored internal energy from ball-milling, the leaching rates of Li, Co, Al, and Cu in the ≤4 mm crushed products uniformly approach 100% with just weak acetic acid. Instead of corrosive precipitation reagents, larger Al fragments (≥4 mm) are used to control the oxidation/reduction potential (ORP) in the aqueous leachate and induce the targeted removal of impurity ions (Cu, Fe). After the upcycling of NCA precursor solution to NCA cathode powders, we demonstrate excellent electrochemical performance of the regenerated NCA cathode and improved environmental impact. Through life cycle assessments, the profit margin of this green upcycling path reaches about 18%, while reducing greenhouse gas emissions by 45%.

Intestinal dysbiosis exacerbates the pathogenesis of psoriasis-like phenotype through changes in fatty acid metabolism.

The intestinal microbiota has been associated with host immunity as well as psoriasis; however, the mechanism of intestinal microbiota regulating psoriasis needs to be demonstrated systematically. Here, we sought to examine its role and mechanism of action in the pathogenesis of psoriasis. We found that the severity of psoriasis-like skin phenotype was accompanied by changes in the composition of the intestinal microbiota. We performed co-housing and fecal microbial transplantation (FMT) experiments using the K14-VEGF transgenic mouse model of psoriasis and demonstrated that the transfer of intestinal microbiota from mice with severe psoriasis-like skin phenotype exacerbated psoriasiform skin inflammation in mice with mild symptoms, including increasing the infiltration and differentiation of Th17, and increased the abundance of Prevotella, while decreasing that of Parabacteroides distasonis, in the colon. These alterations affected fatty acid metabolism, increasing the abundance of oleic and stearic acids. Meanwhile, gentamicin treatment significantly reduced the abundance of Prevotella and alleviated the psoriasis-like symptoms in both K14-VEGF mice and imiquimod (IMQ)-induced psoriasis-like mice. Indeed, administration of oleic and stearic acids exacerbated psoriasis-like symptoms and increased Th17 and monocyte-derived dendritic cell infiltration in the skin lesion areas in vivo, as well as increased the secretion of IL-23 by stimulating DCs in vitro. At last, we found that, treatment of PDE-4 inhibitor alleviated psoriasis-like phenotype of K14-VEGF mice accompanied by the recovery of intestinal microbiota, including the decrease of Prevotella and increase of Parabacteroides distasonis. Overall, our findings reveal that the intestinal microbiota modulates host metabolism and psoriasis-like skin inflammation in mice, suggesting a new target for the clinical diagnosis and treatment of psoriasis.

Akkermansia muciniphila plays critical roles in host health.

Akkermansia muciniphila, an intestinal microorganism, belongs to Verrucomicrobia, one of the most abundant microorganisms in the mammalian gut. It is a mucin-degrading bacterium that can colonise intestines of mammals such as humans and mice by utilising mucin as the only nitrogen and carbon source. When A. muciniphila colonises the intestine, its metabolites interact with the intestinal barrier, affecting host health by consolidating the intestinal barrier, regulating metabolic functions of the intestinal and circulatory systems, and regulating immune functions. This review summarised the mechanisms of A. muciniphila-host interactions that are relevant to host health. We focussed on characteristics of A. muciniphila in relation to its metabolites to provide a comprehensive understanding of A. muciniphila and its effects on host health and disease processes.

Pathogenesis, multi-omics research, and clinical treatment of psoriasis.

Psoriasis is a common inflammatory skin disease involving interactions between keratinocytes and immune cells that significantly affects the quality of life. It is characterized by hyperproliferation and abnormal differentiation of keratinocytes and excessive infiltration of immune cells in the dermis and epidermis. The immune mechanism underlying this disease has been elucidated in the past few years. Research shows that psoriasis is regulated by the complex interactions among immune cells, such as keratinocytes, dendritic cells, T lymphocytes, neutrophils, macrophages, natural killer cells, mast cells, and other immune cells. An increasing number of signaling pathways have been found to be involved in the pathogenesis of psoriasis, which has prompted the search for new treatment targets. In the past decades, studies on the pathogenesis of psoriasis have focused on the development of targeted and highly effective therapies. In this review, we have discussed the relationship between various types of immune cells and psoriasis and summarized the major signaling pathways involved in the pathogenesis of psoriasis, including the PI3K/AKT/mTOR, JAK-STAT, JNK, and WNT pathways. In addition, we have discussed the results of the latest omics research on psoriasis and the epigenetics of the disease, which provide insights regarding its pathogenesis and therapeutic prospects; we have also summarized its treatment strategies and observations of clinical trials. In this paper, the various aspects of psoriasis are described in detail, and the limitations of the current treatment methods are emphasized. It is necessary to improve and innovate treatment methods from the molecular level of pathogenesis, and further provide new ideas for the treatment and research of psoriasis.