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.

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).

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.

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.

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.

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.

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%.

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.

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.

A role for whey acidic protein four-disulfide-core 12 (WFDC12) in the pathogenesis and development of psoriasis disease.

Whey acidic protein four-disulfide core domain protein 12 (WFDC12) has been implicated in the pathogenesis of psoriasis but the specific molecular mechanism is not clearly defined. In this study, we found the expression of WFDC12 protein closely correlated with psoriasis. WFDC12 in keratinocyte might increase infiltration of Langerhans cells (LCs) and monocyte-derived dendritic cells (moDDCs), up-regulating the co-stimulation molecular CD40/CD86. Th1 cells in lymph nodes were higher in K14-WFDC12 transgenic psoiasis-like mice. Meanwhile, the mRNA of IL-12 and IFN-γ in the lesion skin was significantly increased in transgenic mice. Moreover, we found that the expression of the proteins that participated in the retinoic acid-related pathway and immune signaling pathway was more changed in the lesion skin of K14-WFDC12 transgenic psoriasis-like mice. Collectively, the results implied that WFDC12 might affect the activation of the retinoic acid signaling pathway and regulate the infiltration of DC cells in the skin lesions and lymph nodes, thereby inducing Th1 cells differentiation and increasing the secretion of IFN-γ to exacerbate psoriasis in mice.

Microbiome in cancer: An exploration of carcinogenesis, immune responses and immunotherapy.

Cancer is a major disease endangering human health. More and more studies have shown that microorganisms play an extremely important role in the occurrence, development and treatment of tumors. As a very promising tumor treatment strategy, immunotherapy has also been proved to have a great relationship with microorganisms. Here, the authors review the contribution of the microbiota to cancer and the research on its impact on cancer immunotherapy. We also highlight the possible mechanism of their interaction and outlined the potential application of microbiota in tumor immunotherapy.

SerpinB7 deficiency contributes to development of psoriasis via calcium-mediated keratinocyte differentiation dysfunction.

Defective execution of proteases and protease inhibitors that mediate abnormal signaling cascades is emerging as a key contributor to skin diseases, such as psoriasis. SerpinB7 is identified as a skin-specific endogenous protease inhibitor, but the role and underlying mechanism in psoriasis are poorly understood. Here we found that SerpinB7 is highly expressed in psoriatic keratinocytes of patients and imiquimod-induced psoriatic lesions in mice. SerpinB7-/- mice showed abnormal epidermal barrier integrity and skin architecture in homeostasis, and aggravated psoriatic lesion with inhibiting terminal differentiation and increasing inflammatory cells infiltration compared to SerpinB7+/+ mice after Imiquimod treatment. Mechanistically, SerpinB7 deficiency results in excessive proliferation and impaired differentiation, as well as increased chemokines and antimicrobial peptide expression in normal human epidermal keratinocyte and mouse primary keratinocyte. Transcriptomics and proteomics results showed that the SeprinB7 deficiency affected keratinocyte differentiation and proinflammatory cytokines, possibly by affecting the calcium ion channel-related proteins. Notably, we demonstrated that SerpinB7 deficiency prevented the increase in intracellular Ca2+ influx, which was partly eliminated by the intracellular Ca2+ chelator BAPTA-AM. Our findings first described the critical role of SerpinB7 in the regulation of keratinocyte differentiation and psoriatic microenvironment mediated via keratinocytes' intracellular calcium flux, proposing a new candidate for therapeutic targets in psoriasis.