Dry and wet experiments reveal diagnostic clustering and immune landscapes of cuproptosis patterns in patients with ankylosing spondylitis.

Cuproptosis is a new manner of mitochondrial cell death induced by copper. There is evidence that serum copper has a crucial impact on ankylosing spondylitis (AS) by copper-induced inflammatory response. However, the molecular mechanisms of cuproptosis modulators in AS remain unknown. We aimed to use a bioinformatics-based method to comprehensively investigate cuproptosis-related subtype identification and immune microenvironment infiltration of AS. Additionally, we further verified the results by in vitro experiments, in which peripheral blood and fibroblast cells from AS patients were used to evaluate the functions of significant cuproptosis modulators on AS. Finally, eight significant cuproptosis modulators were identified by analysis of differences between controls and AS cases from GSE73754 dataset. Eight prognostic cuproptosis modulators (LIPT1, DLD, PDHA1, PDHB, SLC31A1, ATP7A, MTF1, CDKN2A) were identified using a random forest model for prediction of AS risk. A nomogram model of the 8 prognostic cuproptosis modulators was then constructed; the model could be beneficial in clinical settings, as indicated by decision curve analysis. Consensus clustering analysis was used to divide AS patients into two cuproptosis subtypes (clusterA & B) according to significant cuproptosis modulators. The cuproptosis score of each sample was calculated by principal component analysis to quantify cuproptosis subtypes. The cuproptosis scores were higher in clusterB than in clusterA. Additionally, cases in clusterA were closely associated with the immunity of activated B cells, Activated CD4 T cell, Type17 T helper cell and Type2 T helper cell, while cases in clusterB were linked to Mast cell, Neutrophil, Plasmacytoid dendritic cell immunity, indicating that clusterB may be more correlated with AS. Notably, key cuproptosis genes including ATP7A, MTF1, SLC31A1 detected by RT-qPCR with peripheral blood exhibited significantly higher expression levels in AS cases than controls; LIPT1 showed the opposite results; High MTF1 expression is correlated with increased osteogenic capacity. In general, this study of cuproptosis patterns may provide promising biomarkers and immunotherapeutic strategies for future AS treatment.

Nontrivial Topological Properties and Synthesis of Sn2CoS with L21 Structure.

We synthesize Sn2CoS in experiment and study its topological properties in theory. By first-principles calculations, we study the band structure and surface state of Sn2CoS with L21 structure. It is found that the material has type-II nodal line in the Brillouin zone and clear drumhead-like surface state when the spin-orbit coupling is not considered. In the case of spin-orbit coupling, the nodal line will open gap, leaving the Dirac points. To check the stability of the material in nature, we synthesize Sn2CoS nanowires with L21 structure in an anodic aluminum oxide (AAO) template directly by the electrochemical deposition (ECD) method with direct current (DC). Additionally, the diameter of the typical Sn2CoS nanowires is about 70 nm, with a length of about 70 µm. The Sn2CoS nanowires are single crystals with an axis direction of [100], and the lattice constant determined by XRD and TEM is 6.0 Å. Overall, our work provides realistic material to study the nodal line and Dirac fermions.

Bioinformatics identification and experimental validation of m6A-related diagnostic biomarkers in the subtype classification of blood monocytes from postmenopausal osteoporosis patients.

Background: Postmenopausal osteoporosis (PMOP) is a common bone disorder. Existing study has confirmed the role of exosome in regulating RNA N6-methyladenosine (m6A) methylation as therapies in osteoporosis. However, it still stays unclear on the roles of m6A modulators derived from serum exosome in PMOP. A comprehensive evaluation on the roles of m6A modulators in the diagnostic biomarkers and subtype identification of PMOP on the basis of GSE56815 and GSE2208 datasets was carried out to investigate the molecular mechanisms of m6A modulators in PMOP. Methods: We carried out a series of bioinformatics analyses including difference analysis to identify significant m6A modulators, m6A model construction of random forest, support vector machine and nomogram, m6A subtype consensus clustering, GO and KEGG enrichment analysis of differentially expressed genes (DEGs) between different m6A patterns, principal component analysis, and single sample gene set enrichment analysis (ssGSEA) for evaluation of immune cell infiltration, experimental validation of significant m6A modulators by real-time quantitative polymerase chain reaction (RT-qPCR), etc. Results: In the current study, we authenticated 7 significant m6A modulators via difference analysis between normal and PMOP patients from GSE56815 and GSE2208 datasets. In order to predict the risk of PMOP, we adopted random forest model to identify 7 diagnostic m6A modulators, including FTO, FMR1, YTHDC2, HNRNPC, RBM15, RBM15B and WTAP. Then we selected the 7 diagnostic m6A modulators to construct a nomogram model, which could provide benefit with patients according to our subsequent decision curve analysis. We classified PMOP patients into 2 m6A subtypes (clusterA and clusterB) on the basis of the significant m6A modulators via a consensus clustering approach. In addition, principal component analysis was utilized to evaluate the m6A score of each sample for quantification of the m6A subgroups. The m6A scores of patients in clusterB were higher than those of patients in clusterA. Moreover, we observed that the patients in clusterA had close correlation with immature B cell and gamma delta T cell immunity while clusterB was linked to monocyte, neutrophil, CD56dim natural killer cell, and regulatory T cell immunity, which has close connection with osteoclast differentiation. Notably, m6A modulators detected by RT-qPCR showed generally consistent expression levels with the bioinformatics results. Conclusion: In general, m6A modulators exert integral function in the pathological process of PMOP. Our study of m6A patterns may provide diagnostic biomarkers and immunotherapeutic strategies for future PMOP treatment.

Investigation of the deactivation and regeneration of an Fe2O3/Al2O3•SiO2 catalyst used in catalytic ozonation of coal chemical industry wastewater.

Catalyst deactivation is an ongoing concern for industrial application of catalytic ozonation processes. In this study, we systematically investigated the performance of a catalytic ozonation process employing Fe2O3/Al2O3•SiO2 catalyst for the treatment of coal chemical industry (CCI) wastewater using pilot-scale and laboratory-scale systems. Our results show that the activity of the Fe2O3/Al2O3•SiO2 catalyst for organic contaminant removal deteriorated over time due to formation of a dense and thin carbonaceous layer on the Fe2O3 catalyst surface. EPR and fluorescence imaging analysis confirm that the passivation layer essentially inhibited the O3-catalyst interaction thereby minimizing formation of surficial •OH and associated oxidation of organic contaminants on the catalyst surface. Calcination was demonstrated to be effective in restoring the activity of the catalyst since the carbonaceous layer could be efficiently combusted during calcination to re-establish the surficial •OH-mediated oxidation process. The combustion of the carbonaceous layer and restoration of the Fe layer on the surface on calcination was confirmed based on SEM-EDX, FTIR and thermogravimetric analysis. Cost analysis indicates that regeneration using calcination is economically viable compared to catalyst replacement. The results of this study are expected to pave the way for developing appropriate regeneration techniques for deactivated catalysts and optimising the catalyst synthesis procedure.

Impact of Defects for AlN Single Crystal Thin Film by Metal Nitride Vapor Phase Epitaxy.

Herein, the defect-related properties of an AlN sample prepared based on the optimal process parameters by metal nitride vapor phase epitaxy (MNVPE) were investigated. The FWHM values of the (0002)/(101̅2) planes of the sample by MNVPE are 397/422 arcsec; the advantages of similar FWHM values of (0002) and (101̅2) planes will have a huge advantage over other preparation methods such as MOCVD. From the cross-sectional TEM images of the AlN sample, it is found that the fusion of a large number of a + c type dislocations occur at the interface of the low temperature buffer layer and the epitaxial layer, which affects the growth mode of the epitaxial layer. The lower FHWM value of the E 2(high) peak of the Raman spectrum, the lower the point defect concentration, which made the sample gain higher energy defect emission bands in the PL spectra and higher transmittance in the UV-vis transmission spectrum.

Myristic acid alleviates hippocampal aging correlated with GABAergic signaling.

Previous studies have shown that myristic acid (MA), a saturated fatty acid, could promote the proliferation and differentiation of neural stem cells in vitro. However, the effect of MA on hippocampal neurons aging has not been reported in vivo. Here we employed 22-month-old naturally aged C57BL/6 mice to evaluate the effect and mechanism of MA on hippocampal aging. First, we examined a decreased exploration and spatial memory ability in aging mice using the open field test and Morris water maze. Consistently, aging mice showed degenerative hippocampal histomorphology by H&E and Nissl staining. In terms of mechanism, imbalance of GABRB2 and GABRA2 expression in aging mice might be involved in hippocampus aging by mRNA high throughput sequencing (mRNA-seq) and immunohistochemistry (IHC) validation. Then, we revealed that MA alleviated the damage of exploration and spatial memory ability and ameliorated degeneration and aging of hippocampal neurons. Meanwhile, MA downregulated GABRB2 and upregulated GABRA2 expression, indicating MA might alleviate hippocampal aging correlated with GABAergic signaling. In conclusion, our findings revealed MA alleviated hippocampal aging correlated with GABAergic signaling, which might provide insight into the treatment of aging-associated diseases.

Structure and Optical Properties of AlN Crystals Grown by Metal Nitride Vapor Phase Epitaxy with Different V/III Ratios.

The epitaxial aluminum nitride (AlN) crystals were grown on c-plane sapphire using high-temperature metal nitride vapor phase epitaxy at the source materials' different molar flow ratios (V/III ratios). The effects of various V/III ratios on the surface morphology, crystalline quality, material straining, and optical properties of heteroepitaxial AlN thin films were studied using X-ray diffraction, scanning electron microscopy, Raman spectroscopy, and photoluminescence (PL). With the increase in the V/III ratio from 1473 to 7367, the substrate surface underwent changes that vary from whiskers to three-dimensional island structures, two-dimensional layered stack structures, and stacked sheet structures. Additionally, due to the presence of nanoscale pits on the substrate surface, almost all samples were tensile stressers. The PL spectra demonstrated the defect luminescence of the epitaxial films, indicating that nitrogen vacancies and oxygen impurities were the samples' main defects.

iTRAQ-based quantitative proteomic analysis in liver of Pomacea canaliculata induced by oleanolic acid stress.

BACKGROUND: Triterpene acid is one of the typical active constituents of Eucalyptus bark, which is the main by-product of the Eucalyptus wood industry. Our studies have demonstrated that triterpene acid stress could inhibit climbing and increase mortality in Pomacea canaliculata (Lamarck). However, limited attention has been paid to the proteomic responses of this snail under triterpene acid stress. RESULT: Using iTRAQ-based quantitative proteomics, we elucidated the regulatory mechanism in the livers of P. canaliculata held in chlorine-free water and exposed to 100 mg L-1 oleanolic acid (OA) for 24 h. A total of 4308 proteins were identified, of which 274 were differentially expressed proteins (DEPs) including 168 (61.31%) differentially upregulated proteins and 106 (38.69%) differentially downregulated proteins. Bioinformatics analysis revealed that P. canaliculata responses to OA stress are mainly involved in glucose metabolism, energy synthesis, immune response, stress response, protein synthesis, and apoptosis. According to KEGG analysis, the 274 DEPs were mapped to 168 KEGG pathways and 10 KEGG pathways were significantly enriched (P < 0.05). Furthermore, qRT-PCR was performed for histone H4, catalase, isocitrate dehydrogenase, superoxide dismutase, ferritin, lipase, and tropomyosin to validate the iTRAQ results. CONCLUSION: Proteomic analysis suggested that OA stress led to the disruption of glucose metabolism, energy synthesis, and protein synthesis, and triggered a series of molecular pathways containing many key proteins involved in the immune process, thereby helping P. canaliculata resist OA stress. © 2022 Society of Chemical Industry.

Zuo-Gui-Wan Aqueous Extract Ameliorates Glucocorticoid-Induced Spinal Osteoporosis of Rats by Regulating let-7f and Autophagy.

Objective: This study proposes to explore the protective effect of Zuo-Gui-Wan (ZGW) aqueous extract on spinal glucocorticoid-induced osteoporosis (GIOP) in vivo and in vitro, and the underlying mechanisms of ZGW in GIOP and osteogenic differentiation of bone marrow-derived mesenchymal stem cells (BMSCs) were conducted. Methods: In vivo, SD rats were randomly divided into three groups: control group (CON), dexamethasone (DEXM) group, and ZGW group, which were given vehicle, DEXM injection, and ZGW intragastric administration at the same time. Vertebral bone microarchitecture, biomechanics, histomorphology, serum AKP activity, and the autophagosome of osteoblasts were examined. The mRNA expressions of let-7f, autophagy-associated genes (mTORC1, Beclin-1, ATG12, ATG5, and LC3), Runx2, and CTSK were examined. In vitro, the let-7f overexpression/silencing vector was constructed and transfected to evaluate the osteogenic differentiation of BMSCs. Western blot was employed to detect the expression of autophagy-associated proteins (ULK2, ATG5, ATG12, Beclin-1, LC3). Results: In vivo, ZGW promoted the bone quantity, quality, and strength; alleviated histological damage; increased the serum AKP activity; and reduced the autophagosome number in osteoblasts. Moreover, ZGW increased the let-7f, mTORC1, and Runx2 mRNA expressions and reduced the Beclin-1, ATG12, ATG5, LC3, and CTSK mRNA expressions. In vitro, bioinformatics prediction and dual luciferase reporter gene assay verified that let-7f targeted the binding to ULK2 and negatively regulated the ULK2 expression. Furthermore, by let-7f overexpression/silencing, ZGW may promote osteoblast differentiation of BMSCs by regulating let-7f and autophagy as evidenced by Western blot (ULK2, ATG5, ATG12, Beclin-1, LC3). Conclusions: ZGW may ameliorate GC-induced spinal osteoporosis by promoting osteoblast differentiation of BMSCs by activation of let-7f and suppression of autophagy.

Anisotropic porous designed polymer coatings for high-performance passive all-day radiative cooling.

Porous polymer radiative cooling coatings (PPCs) have attracted attention due to their ability of drawing and radiating heat from a hot object into the outer space, without any energy consumption. However, high performance of PPCs has yet to be achieved and the large-scale production of radiative cooling technology is still facing high cost and complex manufacturing constraints. Here, we propose a simple, inexpensive, scalable approach to fabricate anisotropic (P(VdF-HFP))ap PPCs (TPCs) by dissolution and diffusion between solvent and non-solvent-induced phase separation. By adjusting the porosity, pore size, and geometry, a sub-ambient temperature drop of ∼6.3°C in daytime and 10.1°C in night-time was achieved under a solar reflectance of 0.92 and an atmospheric window emittance of 0.96. A thermoelectric generator with an output voltage of almost zero reached 7 V/m2 after coating with TPCs. This could provide a convenient, economical, and environment-friendly way for PPCs materials toward efficient cooling and power generations.

Binary pentagonal auxetic materials for photocatalysis and energy storage with outstanding performances.

Since the discovery of penta-graphene, two-dimensional (2-D) pentagonal-structured materials have been highly expected to have desirable performance because of their unique structures and accompanied physical properties. Hence, based on the first-principles calculations, we performed a systematical study on the structure, stability, mechanical and electronic properties, and potential applications on carbon-based pentagonal materials with binary compositions, namely, Penta-CnX6-n (n = 1, 2, 4, 5; X = B, N, Al, Si, P, Ga, Ge, As). We found that eleven out of thirty-two Penta-CnX6-n have good stability and can be further studied. Among them, two materials, namely, Penta-C4P2 and Penta-C5P are metallic, and others are indirect band gap semiconductors, whose band gaps calculated by the HSE06 functional are in the range of 1.37-6.43 eV, covering the infrared-visible-ultraviolet regions. Furthermore, we found that metallic Penta-CnX6-n can become promising anode materials for Na-ion batteries (NIBs) with high storage capacity, while some semiconducting Penta-CnX6-n can become excellent water splitting photocatalysts. In addition, Penta-C4P2 and Penta-C2Al4 were found to have obvious in-plane negative Poisson's ratio (NPR) of -0.083 and -0.077, respectively. More interestingly, we found that Penta-C2Al4 exhibits a peculiar in-plane half negative Poisson's ratio (H-NPR) with the fundamental mechanism clarified. These outstanding performances endow binary pentagonal materials with excellent application prospects.

Influence of salinity on the heterogeneous catalytic ozonation process: Implications to treatment of high salinity wastewater.

The heterogeneous catalytic ozonation process is a promising treatment option for high salinity reverse osmosis concentrate (ROC) however the influence of salts on the catalyst performance is not well understood. In this work, we investigate the effect of salts on the performance of the catalytic ozonation process for treatment of synthetic ROC using a commercially available Fe-loaded Al2O3 catalyst. Our results show that the presence of salts influences the rate and extent of degradation of organic compounds present in the synthetic ROC when subjected to the heterogeneous catalytic ozonation process. Scavenging of aqueous O3 by chloride ions and/or transformation of organics (particularly humics) to more hydrophobic form as a result of charge shielding between adjacent functional groups and/or intramolecular binding by cations inhibits the bulk oxidation of organics to a measurable extent. While the scavenging of aqueous hydroxyl radicals at the salt concentrations investigated here was minimal, the accumulation of chloride ions in the electric double layer near the catalyst surface, particularly when pH< pHpzc, results in more significant scavenging of surface associated hydroxyl radicals. Overall, the presence of salts (particularly chloride ions) has a significant influence on the performance of both conventional and catalytic ozonation processes with some scope to mitigate this effect through appropriate choice of catalyst.

Two-dimensional metallic carbon allotrope with multiple rings for ion batteries.

Two-dimensional (2-D) materials, especially carbon allotropes, have larger storage capacity and faster diffusion rate due to their unique structures and are usually used in ion batteries. Recently, a new stable two-dimensional carbon allotrope, namely PAI-graphene, was reported by first-principles calculations. Due to its lightweight and multiple-ring structure, great stability and excellent properties, here, we theoretically reveal the excellent performance of PAI-graphene as an anode material for Li-/Na-ion batteries. Our results show that PAI-graphene has intrinsic metallicity before and after adsorption of Li/Na, which ensures that it has good conductivity when working as an electrode material. In addition, PAI-graphene exhibits quite low open circuit voltage (0.342-0.190 V for Li, 0.339-0.233 V for Na) and diffusion barrier (0.34 eV for Li, 0.17 eV for Na), which indicates its superiority as an anode material. Most noteworthily, the Na storage capacity of PAI-graphene is up to 1674 mA h g-1, which is much higher than that of most 2-D anode materials. Thus, we believe that PAI-graphene can be an outstanding anode material with outstanding performance.

Improved photocatalytic activity and stability of InGaN quantum dots/C3N4heterojunction photoelectrode for CO2reduction and hydrogen production.

Photocatalytic conversion of CO2to produce fuel is considered a promising approach to reduce CO2emissions and tackle energy crisis. GaN-based materials have been studied for CO2reduction because of their excellent optical properties and band structure. However, low photocatalytic activity and severe photocorrosion of GaN-based photoelectrode greatly limit their applications. In this work, photocatalytic activity was improved by adopting InGaN quantum dots (QDs) combined with C3N4nano-sheets as photoanode, and thus the efficiency of CO2reduction and the selectivity of hydrogen production were increased significantly. In addition, the photoelectron-chemical corrosion of photoelectrodes has been apparently controlled. InGaN QDs/C3N4has the highest CO and H2productions rates of 14.69µmol mol-1h-1and 140µmol mol-1h-1which were 2.2 times and 14.5 times than that of InGaN film photoelectrode, respectively. The enhancement of photocatalytic activity is attributed to C3N4modification and a large electric dipole forming on the surface of InGaN QDs, which facilitate the separation and transfer of photo-generated carriers and thus promote CO2reduction reaction. This work provides a promising strategy for the development of GaN-based photoanodes with superior stability and efficiency.

Network pharmacology integrated with experimental validation reveals the regulatory mechanism of plastrum testudinis in treating senile osteoporosis.

ETHNOPHARMACOLOGICAL RELEVANCE: Plastrum testudinis (PT) has been used in traditional Chinese medicine to treat bone diseases such as senile osteoporosis (SOP) for thousands of years. However, the underlying mechanisms remain largely unknown. AIM OF THE STUDY: This study aims to investigate the possible molecular mechanism of PT in the treatment of SOP using an integrated strategy of network pharmacology and experimental validation. MATERIALS AND METHODS: The compounds of PT and its targets were identified through the BATMAN-TCM database. The SOP-related targets were retrieved from the GeneCards database. Protein-protein interaction information was obtained by inputting the intersection targets into the STRING database. Cytoscape software was used to construct a protein-protein interaction network and a PT-compound-target-SOP network. Using Cytoscape and R software, we conducted GO function and KEGG pathway enrichment analyses. We also conducted in vivo and in vitro experiments to verify the network pharmacology findings. RESULTS: In total, 6 active compounds and 342 targets of PT were screened, of which 57 common targets were related to SOP. The GO biological process enrichment analysis identified 880 entries, mainly relating to the regulation of hormone response, the cell apoptotic process, the apoptotic signaling pathway, NF-kappaB transcription factor activity, fatty acid transportation, osteoclast differentiation, macrophage activation, and inflammatory response. The KEGG pathway enrichment analysis identified 52 entries, including 14 related signaling pathways, which mainly involved the TNF, MAPK, IL-17, AGE-RAGE, estrogen, relaxin, and other signaling pathways. Our in vivo experiments confirmed that PT alleviates SOP, while the in vitro experiments demonstrated that PT exerts a suppressive effect on osteoclast differentiation and bone resorption in a concentration-dependent manner. Furthermore, we observed that PT downregulates the expression of osteoclast-specific genes, including C-FOS, TNF, and BDNF, in the MAPK signaling pathway. CONCLUSION: Through network pharmacology and experimental validation, this study is the first to report that PT downregulates the expression of osteoclast-specific genes, including C-FOS, TNF, and BDNF, in the MAPK signaling pathway, thus exerting a suppressive effect on osteoclast differentiation and bone resorption, which may be the molecular mechanism for PT treatment of SOP.

Pentagonal B2C monolayer with extremely high theoretical capacity for Li-/Na-ion batteries.

Recently, two-dimensional (2-D) materials with a Penta-atomic-configuration such as Penta-graphene have received considerable attention because of their potential applications in electronics, spintronics and ion batteries. Previously, Penta-graphene has been proposed as an excellent anode material for Li-/Na-ion batteries with a high theoretical capacity (1489 mA h g-1). Here, based on the first-principles calculations, we report that a new 2-D material namely Penta-B2C can become another excellent anode material with even higher theoretical capacity for Li-/Na-ion batteries than Penta-graphene. Our results demonstrate that Li/Na atoms can be stably adsorbed on Penta-B2C. Meanwhile, Penta-B2C shows metallic conductivity during the adsorption. Most strikingly, the theoretical capacities of Penta-B2C are as high as 1594 for Li and 2391 mA h g-1 for Na, which are superior to those of the most known 2-D anode materials. Especially, the Na theoretical capacity of Penta-B2C sets a new record among known 2-D anode materials. In addition, Penta-B2C possesses relatively low open-circuit voltage and a low diffusion barrier for ions, which are vital for anode materials. These results highly promise that Penta-B2C can be an excellent anode material with a fast charge/discharge rate and extremely high theoretical capacity for Li-/Na-ion batteries.

The emerging role of miR-128 in musculoskeletal diseases.

MicroRNA-128 (miR-128) is associated with cell proliferation, differentiation, migration, apoptosis, and survival. Genetic analysis studies have demonstrated that miR-128 participates in bone metabolism, which involves bone marrow-derived mesenchymal stem cells, osteoblasts, osteoclasts, and adipocytes. miR-128 also participates in regeneration of skeletal muscles by targeting myoblast-associated proteins. The deregulation of miR-128 could lead to a series of musculoskeletal diseases. In this review, we discuss recent findings of miR-128 in relation to bone metabolism and muscle regeneration to determine its potential therapeutic effects in musculoskeletal diseases, and to propose directions for future research in this significant field.