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To promote the construction industry and establish a green environment, the integration of sustainable building materials is urgently required. This study presents the influences of three materials (silica fume, fly ash, and recycled ceramic powder (RCP)) and different RCP dosages (0%, 10%, 20%, and 30%) on the mechanical properties and microstructure of concrete at different temperatures. The study presents the results of comprehensive flow tests, printability assessments, mechanical evaluations under different loading directions, high-temperature analyses, digital image correlation, X-ray powder diffraction and scanning electron microscopy. The experimental findings indicate the successful printing of all samples, with wall structure failure occurring only at a height of 730 mm. Furthermore, compared to those of other materials, the RCP displays a superior heat resistance, with a significant increase in compressive strength (28.9%) to 53.9 MPa at 300 °C. Additionally, the introduction of the RCP into 3D-printed concrete results in an anisotropic behaviour, with an initial enhancement in the mechanical strength, followed by attenuation as the RCP content increases. Microstructural analysis reveals enhanced interfacial adhesion with RCP addition, albeit accompanied by the emergence of numerous pores. The optimal mixture, which is designated as RCP-2-0-1 with 20% of the cement replaced by RCP, exhibits a significant anisotropic compressive strength (55.9 MPa) and an adequate anisotropic flexural strength (12.49 MPa) and impressive heat resistance (11.7% increase in compressive strength at 300 °C). This renders it a suitable sustainable impact-resistant thermal material for use in structural applications.

Abstract In this comprehensive genome-wide study, we identified and classified 83 Xylanase Inhibitor Protein (XIP) genes in wheat, grouped into five distinct categories, to enhance understanding of wheat's resistance to Fusarium head blight (FHB), a significant fungal threat to global wheat production. Our analysis reveals the unique distribution of XIP genes across wheat chromosomes, particularly at terminal regions, suggesting their role in the evolutionary expansion of the gene family. Several XIP genes lack signal peptides, indicating potential alternative secretion pathways that could be pivotal in plant defense against FHB. The study also uncovers the sequence homology between XIPs and chitinases, hinting at a functional diversification within the XIP gene family. Additionally, the research explores the association of XIP genes with plant immune mechanisms, particularly their linkage with plant hormone signaling pathways like abscisic acid and jasmonic acid. XIP-7A3, in particular, demonstrates a significant increase in expression upon FHB infection, highlighting its potential as a key candidate gene for enhancing wheat's resistance to this disease. This research not only enriches our understanding of the XIP gene family in wheat but also provides a foundation for future investigations into their role in developing FHB-resistant wheat cultivars. The findings offer significant implications for wheat genomics and breeding, contributing to the development of more resilient crops against fungal diseases.

Abstract Porcine reproductive and respiratory syndrome (PRRS), a highly contagious disease caused by Porcine reproductive and respiratory syndrome virus (PRRSV), results in huge economic losses to the world pig industry. MiRNAs have been reported to be involved in regulation of viral infection. In our study, miR-320 was one of 21 common differentially expressed miRNAs of Meishan, Pietrain, and Landrace pig breeds at 9-h post-infection (hpi). Bioinformatics and experiments found that PRRSV replication was inhibited by miR-320 through directly targeting PRRSV ORF6. In addition, the expression of CCAAT enhancer binding protein beta (CEBPB) was also inhibited by miR-320 by targeting the 3ʹ UTR of CEBPB, which significantly promotes PRRSV replication. Intramuscular injection of pEGFP-N1-miR-320 verified that miR-320 significantly inhibited the replication of PRRSV and alleviated the symptoms caused by PRRSV in piglets. Taken together, miR-320 have significant roles in the infection and may be promising therapeutic target for PRRS.

With the continuous development of experimental biology, the limitations of commonly utilized model organisms are becoming increasingly apparent. Discrepancies between research conducted on laboratory animals and humans significantly impede the translational application of findings derived from animal experiments. This review introduces ascidian Ciona intestinalis as a novel model organism, an invertebrate that is evolutionarily closest to vertebrates and is a sister group to vertebrates. The review summarizes recent research progress on Ciona intestinalis in various fields to illustrate the significant advantages and promising application prospects of it as a model organism. The research progress outlined in the review mainly encompasses: (1) The whole-genome sequencing of Ciona intestinalis has been determined and numerous related databases have been established. Various embryonic gene editing technologies have been successfully applied, making it an animal model easy to manipulate genetically and study the functions and interactions of target genes visually. (2) In the field of neurobiology, Ciona intestinalis boasts a central nervous system structure similar to that of vertebrates and possesses numerous homologous neuropeptides and hormone molecules. These features grant it an edge in exploring the mechanisms and functional evolution of endocrine and neuroendocrine-related molecules. Additionally, the sensitivity and habituation of its larvae to light stimulation provide an avenue for exploring mechanisms related to behavioral plasticity. (3) In the field of immunology, Ciona intestinalis possesses a mature innate immune system and has evolved precursor genes to the adaptive immune system, with a relatively simple coding of immune-related genes. These features make it an exemplary model organism for immunological studies. (4) In the field of developmental biology, many studies have focused on the notochord development process in Ciona intestinalis and the regulatory mechanisms of gene expression within it, indicating common evolutionary developmental strategies among chordates. Additionally, insights into its heart development also significantly enhance our comprehension on the genetic network of human heart development. (5) In medical research, the ability of Ciona intestinalis to regenerate its neural complex and siphon, as well as the resilience of its heart to recover contractile function from substantial damage, renders it a valuable animal model for the study of regeneration and heart injury. It also has unique advantages as a research model for Alzheimer's disease and new drug development. Furthermore, its brief five-month lifespan facilitates the observation and recording of the entire aging process and the exploration of the effects of various factors on aging. In summary, this review aims to demonstrate that Ciona intestinalis stands out as a model organism with unique attributes and is expected to play a significant role in a wider range of scientific research areas.

This paper systematically investigated the combined effects of sustained compressive loading and the salt frost resistance for recycled aggregate concrete (RAC) incorporating air-entraining agents (AEA) and nano silica (NS). The effects of different RCA replacement ratios, freeze-thaw cycles, AEA dosage and compressive stress level on the freeze-thaw damage properties including the apparent morphology, mass loss rate and relative dynamic elastic modulus (RDEM) were discussed. The microstructure evolution of RAC samples before and after freeze-thaw cycles were characterized and analyzed through the SEM observation, microhardness measurement and X-CT tests. The synergistic modification mechanism of NS and AEA on RAC under salt frost action were investigated, and the link between the macroscopic and microscopic properties of air-entrained NS-modified RAC was further explored. The results showed that the RAC mixed with a certain amount of AEA and NS dosages exhibited the stronger salt frost resistance compared to that of control group. The effect of AEA dosage and compressive stress level exhibited similar changing trends on the salt frost resistance of RAC. When adding a moderate amount of AEA and applying a certain sustained compressive loading, the RDEM loss of RAC was reduced so that the salt frost resistance was partly improved. Similarly, the moderate AEA dosages can reduce the deterioration at ITZs of RAC. The compound use of NS and AEA proved to be as an efficient method to strengthen the microstructure of RAC, further improving the frost resistance under the coupled actions of sustained compressive loading and chloride salt attack. This study provides a feasible approach to improve the salt frost resistance of RAC under the coupled actions of sustained compressive loading, which is expected to promote the application and extension of RAC in complex environmental regions.

The comprehensive detection and identification of active ingredients in complex matrices is a crucial challenge. Liquid chromatography coupled with high-resolution mass spectrometry (LC-HRMS) is the most prominent analytical platform for the exploration of novel active compounds from complex matrices. However, the LC-HRMS-based analysis workflow suffers from several bottleneck issues, such as trace content of target compounds, limited acquisition for fragment information, and uncertainty in interpreting relevant MS2 spectra. Lycibarbarspermidines are vital antioxidant active ingredients in Lycii Fructus, while the reported structures are merely focused on dicaffeoylspermidines due to their low content. To comprehensively detect the new structures of lycibarbarspermidine derivatives, a “depict” strategy was developed in this study. First, potential new lycibarbarspermidine derivatives were designed according to the biosynthetic pathway, and a comprehensive database was established, which enlarged the coverage of lycibarbarspermidine derivatives. Second, the polarity-oriented sample preparation of potential new compounds increased the concentration of the target compounds. Third, the construction of the molecular network based on the fragmentation pathway of lycibarbarspermidine derivatives broadened the comprehensiveness of identification. Finally, the weak response signals were captured by data-dependent scanning (DDA) followed by parallel reaction monitoring (PRM), and the efficiency of acquiring MS2 fragment ions of target compounds was significantly improved. Based on the integrated strategy above, 210 lycibarbarspermidine derivatives were detected and identified from Lycii Fructus, and in particular, 170 potential new compounds were structurally characterized. The integrated strategy improved the sensitivity of detection and the coverage of low-response components, and it is expected to be a promising pipeline for discovering new compounds.

Abstract Class B1 G protein-coupled receptors (GPCRs) are important regulators of many physiological functions such as glucose homeostasis, which is mainly mediated by three peptide hormones, i.e., glucagon-like peptide-1 (GLP-1), glucagon (GCG), and glucose-dependent insulinotropic polypeptide (GIP). They trigger a cascade of signaling events leading to the formation of an active agonist–receptor–G protein complex. However, intracellular signal transducers can also activate the receptor independent of extracellular stimuli, suggesting an intrinsic role of G proteins in this process. Here, we report cryo-electron microscopy structures of the human GLP-1 receptor (GLP-1R), GCG receptor (GCGR), and GIP receptor (GIPR) in complex with Gs proteins without the presence of cognate ligands. These ligand-free complexes share a similar intracellular architecture to those bound by endogenous peptides, in which, the Gs protein alone directly opens the intracellular binding cavity and rewires the extracellular orthosteric pocket to stabilize the receptor in a state unseen before. While the peptide-binding site is partially occupied by the inward folded transmembrane helix 6 (TM6)–extracellular loop 3 (ECL3) juncture of GIPR or a segment of GCGR ECL2, the extracellular portion of GLP-1R adopts a conformation close to the active state. Our findings offer valuable insights into the distinct activation mechanisms of these three important receptors. It is possible that in the absence of a ligand, the intracellular half of transmembrane domain is mobilized with the help of Gs protein, which in turn rearranges the extracellular half to form a transitional conformation, facilitating the entry of the peptide N-terminus.

Folic acid is a fully oxidized synthetic folate with high bioavailability and stability which has been extensively prescribed to prevent congenital disabilities. Here we revealed the immunosuppressive effect of folic acid by targeting splenic marginal zone B (MZB) cells. Folic acid demonstrates avid binding with the Fc domain of immunoglobulin M (IgM), targeting IgM positive MZB cells in vivo to destabilize IgM-B cell receptor (BCR) complex and block immune responses. The induced anergy of MZB cells by folic acid provides an immunological escaping window for antigens. Covalent conjugation of folic acid with therapeutic proteins and antibodies induces immunological evasion to mitigate the production of anti-drug antibodies, which is a major obstacle to the long-term treatment of biologics by reducing curative effects and/or causing adverse reactions. Folic acid acts as a safe and effective immunosuppressant via IgM-mediated MZB cells targeting to boost the clinical outcomes of biologics by inhibiting the production of anti-drug antibodies, and also holds the potential to treat other indications that adverse immune responses need to be transiently shut off.

AbstractContext Morroniside (MOR) possesses antiosteoporosis (OP) effects, but its molecular target and relevant mechanisms remain unknown.Objective We investigated the effects of MOR on glucocorticoid-induced OP and osteoblastogenesis and its underlying mechanisms.Materials and methods The effects of MOR (10–100 μM) on the proliferation and differentiation of MC3T3-E1 cells were studied in vitro. The glucocorticoid-induced zebrafish OP model was treated with 10, 20 and 40 μM MOR for five days to evaluate its effects on vertebral bone density and related osteogenic markers. In addition, molecular targets prediction and molecular docking analysis were carried out to explore the binding interactions of MOR with the target proteins.Results In cultured MC3T3-E1 cells, 20 μM MOR significantly increased cell viability (1.64 ± 0.12 vs. 0.95 ± 0.16; p

Abstract With the large-scale vaccination of lipid nanoparticles (LNP)-based COVID-19 mRNA vaccines, elucidating the potential polyethylene glycol (PEG)-associated immune responses triggered by clinically relevant LNP has become imminent. However, inconsistent findings were observed across very limited population-based studies. Herein we initiated a study using LNP carrier of Comirnaty® as a representative, and simulated real-world clinical practice covering a series of time points and various doses correlated with approved LNP-delivered drugs in a rat model. We demonstrated the time- and dose-dependency of LNP-induced anti-PEG antibodies in rats. As a thymus-independent antigen, LNP unexpectedly induced isotype switch and immune memory, leading to rapid enhancement and longer lasting time of anti-PEG IgM and IgG upon re-injection in rats. Importantly, initial LNP injection accelerated the blood clearance of subsequent dosing in rats. These findings refine our understandings on LNP and possibly other PEG derivatives, and may promote optimization of related premarket guidelines and clinical protocols.

The objective of this study was to elucidate the mechanism of action of the active components of Coptidis rhizoma against porcine epidemic diarrhea and to provide a theoretical foundation for further development of novel anti-PED therapeutic agents based on Coptidis rhizoma. The potential targets of Coptidis rhizoma against PEDV were identified through a comprehensive literature review and analysis using the TCMSP pharmacological database, SwissDrugDesign database, GeneCards database, and UniProt database. Subsequently, the STRING database and Cytoscape 3.7.1 software were employed to construct a protein–protein interaction (PPI) network and screen key targets. Gene Ontology (GO) function and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were conducted on the identified targets. Molecular docking studies were performed using AutoDock 1.5.7 software to analyze the binding energy and modes of interaction between the active components of Coptidis rhizoma and the target proteins. The PyMOL 2.5.0a0 software was employed to visualize the docking results. Through comprehensive analysis, 74 specific targets of active components of Coptidis rhizoma against PEDV were identified. The core gene targets were screened, and an interaction network diagram was subsequently generated. Ultimately, 14 core targets were identified, with STAT3, ESR1, CASP3, and SRC exhibiting the most significant interactions. GO enrichment analysis revealed a total of 215 molecular items, including 48 biological function items, 139 biological process items, and 28 cellular component items. KEGG enrichment analysis identified 140 signaling pathways. Molecular docking analysis demonstrated that epiberberine and palmatine exhibited high binding affinity with STAT3 protein, worenine showed high binding affinity with ESR1 protein, obacunone exhibited high binding affinity with CASP3 protein, and epiberberine, obacunone, berberine, and berberruine exhibited high binding affinity with SRC protein. A network pharmacology and molecular docking technology approach was employed to screen six important active components of Coptidis rhizoma and four important potential targets against PEDV infection. The findings indicated that the active components of Coptidis rhizoma could serve as promising pharmaceutical agents for the prevention and control of PEDV, with significant potential for clinical application.

Grain processed by lactic acid (LA) is known to improve ruminant growth and health. However, the exact mechanism regarding rumen hydrolysis of LA-treated grain is still ambiguous. This experiment was designed to compare the effects of 5% LA treatment on the trophic and morphological variations in corn and to discover the alternations in ruminal hydrolysis between LA-treated and untreated corn macroscopically and microscopically using in vitro fermentation method. The results showed that, compared with untreated corn (CN), corn treated with 5% LA for 48 h (CNLA) experienced a decrease in the dry matter, albumin fraction, aNDFom, and water-soluble carbohydrate content but an increase in the resistant starch content. The in vitro fermentation showed that the pH of CNLA was higher, but dry matter disappearance was lower than that of CN. Most of the fermentation indices were unaffected, except for decreased iso-butyrate and iso-valerate. The abundances of total bacteria, Prevotella spp., Streptococcus bovis, and Selenomonas ruminantium were higher, but those of Ruminococcus flavefaciens and Ruminococcus albus were lower in CNLA than in CN. There were differences in the scanning electron micrographs between CNLA and CN after 3 h of fermentation. This study suggests that treating corn with LA for 48 h can induce changes in its nutrient composition and alter the bacterial flora during subsequent in vitro fermentation. These changes appeared to be crucial contributors to the beneficial effects observed in rumen fermentation.

Purposes The excellent thickening and suspension properties of Xanthan Gum meet the R&D needs of high-end gel ink, but its rigid structure will lead to the flocculation of carbon black particles in the gel ink, which is not conducive to dispersion. Methods The effect of homogenization modification on the system dispersion and stabilization of carbon black particles in Xanthan Gum gel ink was studied, and the mechanism was discussed. Findings The results indicate that the gel ink with 0.15% Xanthan Gum and 7 times homogenization under 50 MPa pressure got a particle size of 82 nm, its thixotropic value was 5.04, the rheological property was the best, the thermal storage property was greatly improved, the slip value was 0.178 N, and the writing performance was good, which met the requirements of high-quality ink. SEM images showed that the gel ink had higher centrifugal stability after homogenization. According to FTIR comparation of the samples before and after homogenization, a 41 cm-1 red shift occurred at 952 cm-1, indicating that the modification enhanced the intermolecular and intramolecular hydrogen bond force of Xanthan Gum. From the combined test results and characterization analyses, it is inferred that the hydrogen bonding force is formed by the adsorption of the active groups such as pyruvic acid and acetyl in Xanthan gum with the abundant functional groups on the surface of carbon black. Conclusions This study provides a theoretical and experimental basis for the development of high-quality gel ink, and a new idea for the application of homogenizer in gel ink.

Microorganisms are important sources of various natural products that have been commercialized for human medicine and animal healthcare. Bacitracin is an important antibacterial natural product predominantly produced by Bacillus licheniformis and Bacillus subtilis, and it is characterized by a broad antimicrobial spectrum, strong activity and low resistance, thus bacitracin is extensively applied in animal feed and veterinary medicine industries. In recent years, various strategies have been proposed to improve bacitracin production. Herein, we systematically describe the regulation of bacitracin biosynthesis in genus Bacillus and its associated mechanism, to provide a theoretical basis for bacitracin overproduction. The metabolic engineering strategies applied for bacitracin production are explored, including improving substrate utilization, using an enlarged precursor amino acid pool, increasing ATP supply and NADPH generation, and engineering transcription regulators. We also present several approaches of fermentation process optimization to facilitate the industrial large-scale production of bacitracin. Finally, the challenges and prospects associated with microbial bacitracin synthesis are discussed to facilitate the establishment of high-yield and low-cost biological factories.

Background: Xuelian injection (XI), a classic preparation extracted from Saussureae Involucratae Herba, has been clinically used to manage rheumatoid arthritis (RA) for nearly twenty years in China. However, the underlying anti-RA mechanism of XI remains unclear. In this study, complete Freund's adjuvant (CFA)-induced acute arthritic model was used to examine the anti-RA effects of XI in vivo. The molecular mechanisms of this action were further investigated using lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophages. Methods: XI and XI freeze dried powder were characterized by UPLC analysis. CD68 and TLR4 expression in the ankle joints was measured by immunohistochemistry. The secretion of inflammatory mediators was detected by ELISA. The expression levels of TLR4 involved components were measured by Western blotting. The localization of transcription factors was measured by immunofluorescence assay. Results: XI treatment ameliorated arthritic symptoms induced by CFA in the ankle joints of rats. The serum levels of inflammatory mediators, including TNF-α, MCP-1, and Rantes were decreased by XI treatment. The elevation of CD68 and TLR4 levels in ankle joints caused by CFA was suppressed by XI treatment. Moreover, XI treatment inhibited the secretion of nitric oxide and prostaglandin E2 in LPS-treated RAW264.7 macrophages. The expression of their enzymes iNOS and COX-2 was also decreased after XI treatment. The production of inflammatory mediators, including TNF-α, IL-6, IL-1β, MCP-1, MIP-1α, and Rantes was reduced by XI treatment in LPS-stimulated RAW264.7 cells. The phosphorylation of p38, JNK, ERK, TBK1, IKKα/β, IκB, p65, c-Jun, and IRF3 was reduced after XI treatment. Additionally, the expression levels of nuclear proteins of p65, c-Jun, and IRF3 were inhibited by XI treatment. Conclusions: Taken together, XI possesses potential anti-RA effect and the underlying mechanism may be closely associated with the inhibition of TLR4 signaling. Our findings provide further pharmacological justifications for the clinical use of XI in RA treatment.

Plant-derived diterpene synthases (PdiTPSs) play a critical role in the formation of structurally and functionally diverse diterpenoids. However, the specificity or functional-related features of PdiTPSs are not well understood. For a more profound insight, we collected, constructed, and curated 199 functionally characterized PdiTPSs and their corresponding 3D structures. The complex correlations among their sequences, domains, structures, and corresponding products were comprehensively analyzed. Ultimately, our focus narrowed to the geometric arrangement of local structures. We found that local structural alignment can rapidly localize product-specific residues that have been validated by mutagenesis experiments. Based on the 3D motifs derived from the residues around the substrate, we successfully searched diterpene synthases (diTPSs) from the predicted terpene synthases and newly characterized PdiTPSs, suggesting that the identified 3D motifs can serve as distinctive signatures in diTPSs (I and II class). Local structural analysis revealed the PdiTPSs with more conserved amino acid residues show features unique to class I and class II, whereas those with fewer conserved amino acid residues typically exhibit product diversity and specificity. These results provide an attractive method for discovering novel or functionally equivalent enzymes and probing the product specificity in cases where enzyme characterization is limited.

Abstract The impacts of cloud mixing and uptake on wet scavenging are not adequately resolved in global models which can lead to an overestimation of the removal of water‐soluble gases and aerosols from the atmosphere. To address this issue, we develop and implement novel parameterizations to consider the impacts of these processes. Our analysis of vertical profiles of nitric acid, inorganic nitrate, ammonium, and sulfate concentrations during the Atmospheric Tomography Mission periods indicates that air refreshing limitation has a significant impact above 800 hPa, while cloud ice uptake limitation plays an important role above 500 hPa. Incorporating these two processes resulted in a reduction of wet depositions of these species across source regions and a slight increase in their downwind regions. Wet depositions of nitrate, ammonium, and sulfate were reduced in source regions by 22.7%, 8.4%, and 8.3%, respectively and increased in downwind regions by 10.1%, 7.0%, and 4.3%, respectively.

Quality marker (Q-marker) serves as an important driver for the standardization of quality control in traditional Chinese medicine (TCM) formulas. However, it is still challenging to discover comprehensive and representative Q-markers. This study aimed to identify Q-markers of Hugan tablet (HGT), a famous TCM formula with ideal clinical effects in liver diseases. Here, we proposed a funnel-type stepwise filtering strategy that integrated secondary metabolites characterization, characteristic chromatogram, quantitative analysis, literature mining, biotransformation rules and network analysis. Firstly, the strategy of “secondary metabolites-botanical drugs-TCM formula” was applied to comprehensively identify the secondary metabolites of HGT. Then, the secondary metabolites with specificity and measurability in each botanical drug were identified by HPLC characteristic chromatogram, biosynthesis pathway and quantitative analysis. Based on literature mining, the effectiveness of botanical metabolites that met the above conditions was evaluated. Furthermore, the metabolism of the above metabolites in vivo was studied to reveal their biotransformation forms, which were used for network analysis. At last, according to biotransformation rules of the prototype drugs in vivo, the secondary metabolites were traced and preliminarily chosen as Q-markers. As a result, 128 plant secondary metabolites were identified in HGT, and 11 specific plant secondary metabolites were screened out. Then, the content of specific plant secondary metabolites in 15 batches of HGT was determined, which confirmed their measurability. And the results of literature mining showed that eight secondary metabolites had therapeutic effects in treating liver disease at the in vivo level, and three secondary metabolites inhibited liver disease-related indicators at the in vitro level. After that, 26 compounds absorbed into the blood (11 specific plant metabolites and their 15 metabolites in vivo) were detected in rats. Moreover, 14 compounds, including prototype components and their metabolites, were selected as Q-marker candidates by the “TCM formula-botanical drugs-compounds-targets-pathways” network. Finally, 9 plant secondary metabolites were defined as comprehensive and representative Q-markers. Our study not only provides a scientific basis for the improvement and secondary development of the quality standard of HGT, but also proposes a reference method for discovering and identifying Q-markers of TCM preparations.

Abstract The effective use of wind energy is an essential part of the sustainable development of human society, in particular, at the recent unprecedented pressure in shaping a low carbon energy environment. Accurate wind resource and power forecasting play a key role in improving the wind penetration. However, it has not been well adopted in the real‐world applications due to the strong stochastic characteristics of wind energy. In recent years, the application boost of deep learning methods provides new effective tools in wind forecasting. This paper provides a comprehensive overview of the forecasting models based on deep learning in the field of wind energy. Featured approaches include time‐series‐based recurrent neural networks, restricted Boltzmann machines, convolutional neural networks as well as auto‐encoder‐based approaches. In addition, future development directions of deep‐learning‐based wind energy forecasting have also been discussed.

ObjectiveThis study aims to evaluate the clinical efficacy and safety between Discover cervical disc arthroplasty (DCDA) and anterior cervical discectomy and fusion (ACDF) in Cervical degenerative disc diseases.MethodsTwo researchers independently conducted a search of PubMed, EMBASE, and Cochrane Central Register of Controlled Trails (CENTRAL) for randomized controlled trials (RCTs) following the Cochrane methodology guidelines. A fixed-effects or random-effects model was applied based on different heterogeneity. Review Manager (Version 5.4.1) software was used to perform data analysis.ResultsA total of 8 RCT studies were included in this meta-analysis. The results indicate that the DCDA group had a higher incidence of reoperation (P = 0.03) and a lower incidence of ASD (P = 0.04) than the CDA group. There was no significant difference between two groups regarding NDI score (P = 0.36), VAS ARM score (P = 0.73), VAS NECK score (P = 0.63), EQ-5D score (P = 0.61) and dysphagia incidence (0.18).ConclusionDCDA and ACDF have similar results in terms of NDI scores, VAS scores, EQ-5D scores, and dysphagia. In addition, DCDA can reduce the risk of ASD but increases the risk of reoperation.

Introduction: Hyperlipidemia is a common metabolic disorder with presence of excess fat or lipids in the blood, may induce liver injury, oxidative stress and inflammatory. Xuezhiping capsule (XZP) is a famous Chinese patent medicine clinically used for anti-hyperlipidemia. However, the regulation mechanism of XZP on hyperlipidemia has not been elucidated so far.Methods: This study aimed to explore the effects of XZP on hypolipidemic, antioxidant and anti-inflammatory effects, and the potential mechanism by a combination of untargeted metabolomics and 16S rRNA sequencing.Results: The results indicated that XZP reduced the level of total cholesterol (TC), triglyceride (TG), low density lipoprotein cholesterol (LDL-C), increased the level of high density liptein cholesterol (HDL-C), alleviated excessive accumulation of lipid droplets in liver. Biochemical indexes of liver function including gamma glutamyl transferase (GGT) and glutamic oxaloacetic transaminase (GOT) in liver were remarkably decreased. Meanwhile, XZP increased the level of oxidative stress biochemical indexes including superoxide dismutase (SOD) and glutathione (GSH). In addition, XZP increased the level of peroxisome proliferators-activated receptors α (PPARα), acetyl CoA carboxylase 1 (ACOX1) and cholesterol 7-alpha hydroxylase (CYP7A1) in liver, and improved lipid metabolism in serum, liver and fecal lipid metabolism. XZP increased diversity index and the ratio of Firmicutes and Bacteroidetes, regulated seventeen genera, and illustrated strong correlations with liver lipid metabolism and phenotypic indicators.Discussion: These findings suggest that XZP reduced blood lipid and liver lipid, protected liver function, anti inflammation and anti-oxidation, ameliorate lipid metabolic disorders by modulating alpha linolenic acid and linoleic acid metabolism, bile acid metabolism, arachidonic acid metabolism, and regulated gut microbiota composition of high-fat diet (HFD) hamsters.

PurposeThis study aimed to compare the surgical efficacy of enlarged laminectomy with lateral mass screw fixation (EL-LMSF) and anterior cervical decompression and fusion (ACDF) for multilevel cervical myelopathy and radiculopathy (CMR) related to kyphosis.Methods75 patients were retrospectively reviewed and divided into ACDF and EL-LMSF group. Clinical results including operative time, blood loss, and postoperative complications were compared. The JOA scoring system was used to evaluate spinal cord function and the VAS score evaluate nerve root pain severity. Cervical alignment a C2–C7 was measured with Cobb method and compared to confirm the reconstruction effect.ResultsData on 75 patients (M/F: 41:34; EL-LMSF/ACDF:42/33) with the mean age of 57.5 years (range 43–72 year old) were reviewed retrospectively. Discectomy and/or sub-toal corpectomy in ACDF group was performed with a mean of 3.24 levels (range, 3–4). Enlarged laminectomy in EL-LMSF group was performed with a mean of 3.89 enlarged levels (range, 3–5). The procedure of ACDF group showed a shorter operation time (103 ± 22 min vs. 125 ± 37 min, P = 0.000) and less blood loss (78 ± 15 ml vs. 226 ± 31 ml, P = 0.000) compared than that of the EL-LMSF group. Patients treated with EL-LMSF indicated lower VAS for upper extremity (1.3 ± 1.7 vs. 3.3 ± 1.3, P = 0.003) and better curvature corrected (10.7 ± 4.2° vs. 8.5 ± 3.5°, P = 0.013). The difference were of statistical significance. No statistical difference was found after surgery in the JOA score (14.1 ± 1.7 vs. 13.5 ± 2.1, P = 0.222). During the follow-up period, 15.2% of patients in the ACDF group had complications including 2 cases with transient dysphagia, 1 case with C5 palsy, 1 case with axial pain, and 1 case with screw pullout 3 month after surgery. However, only 9.5% of cases in the EL-LMSF group experienced complications, including 3 cases of axial pain and 1 case of epidural hematoma.ConclusionThe EL-LMSF procedure requires a longer operation time and more blood loss because of the incision of the stenosed foramen. However, the procedure has obvious advantages in relieving nerve root symptoms and correcting cervical curvature with fewer postoperative complications.

ObjectivePatients with osteoporotic vertebral fractures (OVFs) often suffer from residual low back pain (LBP) after percutaneous kyphoplasty (PKP). The purpose of this study was to identify risk factors for postoperative residual LBP and to develop a nomogram to predict the occurrence of residual LBP.MethodsWe retrospectively reviewed 236 patients who underwent PKP for OVFs and had a minimum follow-up of 12 months. The mean age was 72.1 ± 6.3, 74.3% were female and 25.7% were male. Patients with LBP VAS scores ≥ 3.5 at the 12th month postoperatively were considered to have residual LBP. Risk factors for residual LBP were identified by univariate and multifactorial logistic regression analysis. Then, a predictive nomogram was constructed and validated using the bootstrap method. The discrimination, calibration, and clinical utility of the nomogram were assessed using a receiver operating characteristic curve (ROC), a calibration curve, and a decision curve analysis (DCA).Resultsunivariate and multifactorial logistic regression analysis identified depression (P = 0.02), intravertebral vacuum cleft (P = 0.01), no anti-osteoporosis treatment (P

ProposeThis meta-analysis aimed to determine whether 3D-printed artificial vertebral body have superior clinical and radiographic outcome than Titanium Mesh Cage(TMC) in single-level anterior cervical corpectomy and fusion.MethodsA comprehensive search of the PubMed, Embase, Cochrane Library, Web of Science, and CNKI (China National Knowledge Infrastructure) databases was conducted to find randomized control trials (RCTs) or cohort studies that compared 3D-printed artificial vertebral body with conventional Titanium Mesh Cage (TMC) in single-level anterior cervical corpectomy and fusion (SL-ACCF). Operation time; intraoperative blood loss; subsidence of vertebral body; preoperative, and final follow-up C2–C7 Cobb angle, Japanese Orthopedic Association (JOA) scores, and Visual Analog Scale(VAS) scores were collected from eligible studies for meta-analysis.ResultsWe included 6 cohort studies with 341 patients. The results of the meta-analysis showed that the 3D group has a shorter operation time than the traditional TMC group(p = 0.04) and the TMC group had more severe subsidence(≥3 mm) of vertebral body than the 3D group(p

Rare earth elements are commonly used to improve the properties of magnesium alloys. In this paper, the effects of various La contents on the microstructure and thermal properties of Mg–2Sn alloys were investigated. Cooling curve thermal analysis technique was adopted to reveal the microstructure evolution of Mg-2Sn-xLa alloys. La addition contributed a new eutectic reaction to occur at 639 °C and the eutectic structure was determined to be LaMgSn phase. Mg12La, Mg2Sn and matrix precipitated phases may be generated in the microstructure with further increase of La content. The thermal conductivity of Mg–2Sn alloy can be effectively improved by La addition and the maximum value 149 W/(m·K) was achieved at the Sn/La atomic ratio of 1. The thermal conductivity of Mg-2Sn-2.3La alloy could further increase to 152 W/(m·K) after solution heat treatment. The addition of La reduced the amount of solute atoms and eliminated the Sn enriched region, resulted in a rapid increase in the thermal conductivity of the Mg–2Sn alloy. The spheroidization of Mg12La phase contributed to the further improvement of the thermal conductivity after solution treatment.

Objective: To investigate hypertriglyceridemia and hepatomegaly caused by Schisandrae Sphenantherae Fructus (FSS) and Schisandra chinensis Fructus (FSC) oils in mice. Methods: Mice were orally administered a single dose of Schisandrae Fructus oils. Serum and hepatic triglyceride (TG), triglyceride transfer protein (TTP), apolipoprotein B48 (Apo B48), very-low-density lipoprotein (VLDL), hepatocyte growth factor (HGF), alanine aminotransfease (ALT) and liver index were measured at 6-120 h post-dosing. Results: FSS and FSC oil caused time and dose-dependent increases in serum and hepatic TG levels, with maximum increases in the liver (by 297% and 340%) at 12 h post-dosing and serum (244% and 439%) at 24-h post-dosing, respectively. Schisandrae Fructus oil treatments also elevated the levels of serum TTP by 51% and 63%, Apo B48 by 152% and 425%, and VLDL by 67% and 38% in mice, respectively. FSS and FSC oil treatments also increased liver mass by 53% and 55% and HGF by 106% and 174%, but lowered serum ALT activity by 38% and 22%, respectively. Fenofibrate pre/ co-treatment attenuated the FSS and FSC oil-induced elevation in serum TG levels by 41% and 49% at 48 h post-dosing, respectively, but increased hepatic TG contents (by 38% and 33%, respectively) at 12 h post-dosing. Conclusions: Our findings provide evidence to support the establishment of a novel mouse model of hypertriglyceridemia by oral administration of FSS oil (mainly increasing endogenous TG) and FSC oil (mainly elevating exogenous TG).

Abstract Objectives To investigate the effects of β-ecdysterone on fracture healing and the underlying mechanism. Methods MTT assay was used to detect the cell viability. AO/PI and flow cytometry assays were used to determine the apoptotic rate. The expression level of RunX2, ATG7 and LC3 was evaluated by qRT-PCR and Western blot assays. X-ray and HE staining were conducted on the fractured femur. Immunohistochemical assay was used to detect the expression level of Beclin-1 and immunofluorescence assay was used to measure the expression level of LC3 in the fractured femurs. Western blot was utilized to determine the expression level of PI3K, p-AKT1, AKT1, p-mTOR, mTOR, p-p70S6K, and p70S6K. Results The ALP activity and the expression of RunX2 in fractured osteoblasts were significantly elevated, the apoptotic rate was suppressed by rapamycin, 60, and 80 μM β-ecdysterone. The state of autophagy both in fractured osteoblasts and femurs was facilitated by rapamycin and β-ecdysterone. Compared to control, Garrett score was significantly promoted in rapamycin and β-ecdysterone groups, accompanied by ameliorated pathological state. Lastly, the PI3K/AKT/mTOR pathway both in fractured osteoblasts and femurs was inhibited by rapamycin and β-ecdysterone. Conclusion β-ecdysterone might facilitate fracture healing by activating autophagy through suppressing PI3K/AKT/mTOR signal pathway.

Summary: Acute respiratory distress syndrome (ARDS) is a common lung disorder that involves severe inflammatory damage in the pulmonary barrier, but the underlying mechanisms remain elusive. Here, we demonstrated that pulmonary macrophages originating from ARDS patients and mice caused by bacteria were characterized by increased expression of ferroportin (FPN). Specifically deleting FPN in myeloid cells conferred significant resistance to bacterial infection with improved survival by decreasing extracellular bacterial growth and preserving pulmonary barrier integrity in mice. Mechanistically, macrophage FPN deficiency not only limited the availability of iron to bacteria, but also promoted tissue restoration via growth factor amphiregulin, which is regulated by cellular iron-activated Yes-associated protein signaling. Furthermore, pharmacological treatment with C-Hep, the self-assembled N-terminally cholesterylated minihepcidin that functions in the degradation of macrophage FPN, protected against bacteria-induced lung injury. Therefore, therapeutic strategies targeting the hepcidin-FPN axis in macrophages may be promising for the clinical treatment of acute lung injury.

Background: Currently, it is unclear whether there is a causal association between genetically predicted plasma homocysteine (Hcy) levels and the risk of sarcopenia. We performed a Mendelian randomization (MR) study to assess the association between circulating Hcy levels and the components [grip strength, walking pace, and appendicular lean mass (ALM)] of sarcopenia.Methods: Independent single nucleotide polymorphisms (SNPs) significantly associated with plasma Hcy levels served as instrumental variables. Summary-level data regarding the components of sarcopenia. Were obtained from the UK Biobank. Inverse variance weighted (IVW) as the primary method was used for Mendelian randomization (MR) analysis. We also use four models, weighted median, MR-Egger regression, Maximum likelihood, and Penalised weighted median, as supplementary methods to IVW. The MR-Egger intercept test, Cochran’s Q test, and “leave-one-out” sensitivity analysis were performed to evaluate the horizontal pleiotropy, heterogeneities, and stability of the causal association between Hcy levels and the components of sarcopenia.Results: The IVW-MR analysis suggested significant negative associations of increased plasma Hcy levels with grip strength (right: effect = −0.036, SE = 0.032, p = 5.53E-4; left: effect = −0.045, SE = 0.010, p = 1.45E-5), walking pace (effect = −0.038, SE = 0.011, p = 3.18E-4), and ALM (effect = −0.058, 0.013, p = 1.03E-5). However, there were no significant associations of decreased plasma Hcy levels with grip strength (right: effect = 0.005, SE = 0.021, p = 0.82; left: effect = −0.006, SE = 0.014, p = 0.64), walking pace (effect = 0.01, 0.020, p = 0.61), or ALM (effect = -0.034, SE = 0.018, p = 0.06).The accuracy and robustness of these findings were confirmed by sensitivity tests.Conclusion: Increased circulating Hcy levels were associated with lower grip strength, slower walking pace, and decreased ALM.

Porcine reproductive and respiratory syndrome (PRRS) is one of the most economically devastating diseases affecting the swine industry worldwide. To investigate the role of miRNAs in the infection and susceptibility of PRRS virus (PRRSV), twenty-four miRNA libraries were constructed and sequenced from PRRSV-infected and mock-infected Porcine alveolar macrophages (PAMs) of Meishan, Landrace, Pietrain and Qingping pigs at 9 hours post infection (hpi), 36 hpi, and 60 hpi. The let-7 family miRNAs were significantly differentially expressed between PRRSV-infected and mock-infected PAMs from 4 pig breeds. The let-7 family miRNAs could significantly inhibit PRRSV-2 replication by directly targeting the 3'UTR of the PRRSV-2 genome and porcine IL6, which plays an important role in PRRSV replication and lung injury. NEAT1 acts as a competing endogenous lncRNA (ceRNA) to upregulate IL6 by attaching let-7 in PAMs. EMSA and ChIP results confirmed that ARID3A could bind to the promoter region of pri-let-7a/let-7f/let-7d gene cluster and inhibit the expression of the let-7 family. Moreover, the NF-κB signaling pathway inhibits the expression of the let-7 family by affecting the nuclear import of ARID3A. The pEGFP-N1-let-7 significantly reduced viral infections and pathological changes in PRRSV-infected piglets. Taken together, NEAT1/ARID3A/let-7/IL6 play significant roles in PRRSV-2 infection and may be promising therapeutic targets for PRRS.

The present study aims to evaluate the effects of prepartum maternal supplementation of Capsicum oleoresin (CAP) on colostrum quality and growth performance in newborn buffalo calves. Twelve multiparous buffaloes were randomly assigned to two groups starting from 4 weeks prepartum: the control group with a basal diet (CON) and the treatment group with a basal diet supplemented with 20 mg CAP/kg dry matter (CAP20). After birth, all calves were weighed and received colostrum from their respective dam directly within 2 h. After that, calves received pasteurized milk and starter feed till 56 days of age. The results showed that CAP increased lactose (P < 0.05) in colostrum, and it tended to increase monounsaturated fatty acids; however, it decreased colostrum urea nitrogen (P < 0.10). CAP did not affect colostrum yield and immunoglobulin G and M concentrations. The weekly starter intake was not affected by maternal CAP supplementation during the first 6 weeks of life. There was an increasing tendency in weekly starter intake from weeks 7 and 8 (P < 0.10) in CAP20 compared with CON. At 7 days of age, calves in CAP20 had higher immunoglobulin G (P < 0.05) and a decreased tendency in calves' serum glucose compared with CON. Additionally, maternal CAP supplementation increased calves' serum β-hydroxybutyric acid (P < 0.05) and tended to increase total protein (P < 0.10), while decreased non-esterified fatty acids (P < 0.05) at 56 days of age. Calves in CAP20 had higher final withers height, final heart girth, average withers height, and average heart girth than the CON (P < 0.05). These results suggest that maternal CAP supplementation could improve colostrum quality and positively affect the performance of buffalo calves.

Abstract High shear wet granulation (HSWG) has been wildly used in manufacturing of oral solid dosage (OSD) forms, and process modeling is vital to understanding and controlling this complex process. In this paper, data fusion and multivariate modeling technique were applied to develop a formulation-process-quality model for HSWG process. The HSWG experimental data from both literature and the authors’ laboratory were fused into a single and formatted representation. A material database and material matching method were used to compensate the incomplete physical characterization of literature formulation materials, and dimensionless parameters were utilized to reconstruct process variables at different granulator scales. The exploratory study on input materials properties by principal component analysis (PCA) revealed that the formulation data collected from different articles generated a formulation library which was full of diversity. In prediction of the median granule size, the partial least squares (PLS) regression models derived from literature data only and a combination of literature data and laboratory data were compared. The results demonstrated that incorporating a small number of laboratory data into the multivariate calibration model could help significantly reduce the prediction error, especially at low level of liquid to solid ratio. The proposed data fusion methodology was beneficial to scientific development of HSWG formulation and process, with potential advantages of saving both experimental time and cost.

This study aimed to determine the effect of capsicum oleoresin (CAP) on rumen fermentation and microbial abundance under different temperature and dietary conditions in vitro. The experimental design was arranged in a 2 × 2 × 3 factorial format together with two temperatures (normal: 39°C; hyperthermal: 42°C), two forage/concentrate ratios (30:70; 70:30), and two CAP concentrations in the incubation fluid at 20 and 200 mg/L with a control group. Regarding the fermentation characteristics, high temperature reduced short-chain fatty acids (SCFA) production except for molar percentages of butyrate while increasing acetate-to-propionate ratio and ammonia concentration. The diets increased total SCFA, propionate, and ammonia concentrations while decreasing acetate percentage and acetate-to-propionate ratio. CAP reduced acetate percentage and acetate-to-propionate ratio. Under hyperthermal condition, CAP could reduce acetate percentage and increase acetate-to-propionate ratio, lessening the negative effect of high heat on SCFA. Hyperthermal condition and diet altered the relative abundance of microbial abundance in cellulose-degrading bacteria. CAP showed little effect on the microbial abundance which only increased Butyrivibrio fibrisolvens. Thus, CAP could improve rumen fermentation under different conditions, with plasticity in response to the ramp of different temperature and dietary conditions, although hardly affecting rumen microbial abundance.

Background: Mental disorders (MDs) are behavioral or mental patterns that cause significant distress or impairment of personal functioning. Previously, temperature has been linked to MDs, but most studies suffered from exposure misclassification due to limited monitoring sites. We aimed to assess whether multiple meteorological factors could jointly trigger MD-related emergency department (ED) visits in warm season, using a highly dense weather monitoring system. Methods: We conducted a time-stratified, case-crossover study. MDs-related ED visits (primary diagnosis) from May-October 2017–2018 were obtained from New York State (NYS) discharge database. We obtained solar radiation (SR), relative humidity (RH), temperature, heat index (HI), and rainfall from Mesonet, a real-time monitoring system spaced about 17 miles (126 stations) across NYS. We used conditional logistic regression to assess the weather-MD associations. Results: For each interquartile range (IQR) increase, both SR (excess risk (ER): 4.9%, 95% CI: 3.2–6.7%) and RH (ER: 4.0%, 95% CI: 2.6–5.4%) showed the largest risk for MD-related ED visits at lag 0–9 days. While temperature presented a short-term risk (highest ER at lag 0–2 days: 3.7%, 95% CI: 2.5–4.9%), HI increased risk over a two-week period (ER range: 3.7–4.5%), and rainfall hours showed an inverse association with MDs (ER: −0.5%, 95% CI: 0.9-(-0.1)%). Additionally, we observed stronger association of SR, RH, temperature, and HI in September and October. Combination of high SR, RH, and temperature displayed the largest increase in MDs (ER: 7.49%, 95% CI: 3.95–11.15%). The weather-MD association was stronger for psychoactive substance usage, mood disorders, adult behavior disorders, males, Hispanics, African Americans, individuals aged 46–65, or Medicare patients. Conclusions: Hot and humid weather, especially the joint effect of high sun radiation, temperature and relative humidity showed the highest risk of MD diseases. We found stronger weather-MD associations in summer transitional months, males, and minority groups. These findings also need further confirmation.

PurposeThis meta-analysis aimed to determine whether patients treated with robot-assisted kyphoplasty for vertebral compression fractures have superior clinical and radiographic improvement than those treated with fluoroscopy.MethodsA comprehensive search of the PubMed, Embase, Cochrane Library, Science Direct, and CNKI (China National Knowledge Infrastructure) databases was conducted to find randomized control trials (RCTs) or observational cohort studies that compared robotic-assisted kyphoplasty (RA-kyphoplasty) with fluoroscopy-assisted kyphoplasty (FA-kyphoplasty) in treating vertebral compression fractures. Preoperative, postoperative, and final follow-up data on vertebral height (VH), vertebral kyphosis angle (VKA), visual analog scale (VAS) for back pain, and cement leakage rate were collected from eligible studies for meta-analysis. Patients were divided into RA and FA groups depending on whether the operation was robotically or fluoroscopically guided.ResultsWe included 6 cohort studies with 491 patients and 633 vertebrae. The results of the meta-analysis showed that the RA group had a higher VH than the FA group at both postoperation (p

In order to study the bearing capacity of high-performance concrete-filled high-strength steel tube (HCHST) composite stub columns subjected to eccentrical load, 22 HCHST composite stub columns, 4 concrete-filled steel tube (CFST) composite stub columns and 8 high-performance concrete-filled steel tube (HCST) composite stub columns were designed with the cubic compressive strength of concrete (fcu), the yield strength of steel tube (fy), the thickness of tube wall (t), the eccentricity (e) and slenderness ratio (λ) as the main parameters. Considering the nonlinear constitutive model of concrete and simplified constitutive model of steel, the finite element (FE) model of HCHST composite stub columns was established by ABAQUS software. By comparison with the existing test results, the rationality of the constitutive model and boundary conditions was verified. The variation of ultimate bearing capacity and the typical failure modes of HCHST composite stub columns under different parameters was analyzed. The results show that the specimens exhibit obvious bulge outward at the end of the steel tube and shear failure at the end of concrete. High-performance concrete (HPC) can significantly improve the ultimate eccentrical compression bearing capacity of composite columns, and high-strength steel tubes have better restraint effect on HPC. With the increasing of t, the ultimate eccentrical compression bearing capacity and the load-holding capacity of HCHST columns increases gradually, while the ultimate eccentrical compression bearing capacity decreases gradually with the increasing of λ and e. By introducing the reduction coefficient of eccentricity (φ1) and the reduction coefficient of slenderness ratio (φ2), the calculation formula of the eccentric bearing capacity of HCHST columns is proposed by statistical regression, which can lay a foundation for the application of HCHST columns in practical engineering.

Ambient fine particulate matter (PM2.5) is one of the most important environmental health risk factors in many regions. Here, the authors present an assessment of PM2.5 emission sources and the related health impacts across global to sub-national scales and find that over 1 million deaths were avoidable in 2017 by eliminating PM2.5 mass associated with fossil fuel combustion emissions.

Abstract Sepsis, a highly life-threatening organ dysfunction caused by uncontrollable immune responses to infection, is a leading contributor to mortality in intensive care units. Sepsis-related deaths have been reported to account for 19.7% of all global deaths. However, no effective and specific therapeutic for clinical sepsis management is available due to the complex pathogenesis. Concurrently eliminating infections and restoring immune homeostasis are regarded as the core strategies to manage sepsis. Sophisticated nanoplatforms guided by supramolecular and medicinal chemistry, targeting infection and/or imbalanced immune responses, have emerged as potent tools to combat sepsis by supporting more accurate diagnosis and precision treatment. Nanoplatforms can overcome the barriers faced by clinical strategies, including delayed diagnosis, drug resistance and incapacity to manage immune disorders. Here, we present a comprehensive review highlighting the pathogenetic characteristics of sepsis and future therapeutic concepts, summarizing the progress of these well-designed nanoplatforms in sepsis management and discussing the ongoing challenges and perspectives regarding future potential therapies. Based on these state-of-the-art studies, this review will advance multidisciplinary collaboration and drive clinical translation to remedy sepsis.

Electrochemical CO2 reduction to the valuable n-propanol is challenging due to the complicated C3 forming mechanism. Here, authors demonstrate double sulfur vacancies formed on hexagonal copper sulfide can serve as efficient electrocatalytic centers.

Objective: To investigate the anti-inflammatory effects of the total flavonoids from Saussurea involucrata on lipopolysaccharides (LPS)-stimulated murine RAW264.7 macrophages and explore its underlying mechanism of action. Methods: Total flavonoids from Saussurea involucrata were extracted using chromatographic column method. Cell viability was determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide assay. The production of nitric oxide was detected by Griess assay and the release of cytokines (IL-10 and TNF-α) and chemokines (MCP-1, MIP-1a, and CCL5/RANTES) was determined by ELISA to evaluate the anti-inflammatory activity of total flavonoids from Saussurea involucrata. Moreover, nuclear translocation of p65, c-Jun, and IRF3 was detected by immunofluorescence microscopy and Western blotting analysis was performed to determine the expression of related proteins. Results: Total flavonoids extracted from Saussurea involucrata were 751.5 mg/g and the content of rutin was 506.5 mg/g. The production of inflammatory mediators including nitric oxide, cytokines, and chemokines was effectively inhibited by total flavonoids from Saussurea involucrata. Meanwhile, total flavonoids also suppressed the nuclear translocation of p65, c-Jun, and IRF3 in LPS-stimulated RAW264.7 cells. The LPS-induced expression of iNOS and COX-2 was remarkably reduced by treatment with total flavonoids from Saussurea involucrata. Moreover, total flavonoids decreased the expression levels of p-IKKa/β, p-TBK1, p-p38, p-ERK, p-JNK, p-p65, p-c-Jun, and p-IRF3 in LPS-exposed RAW264.7 macrophages. Conclusions: Total flavonoids from Saussurea involucrata potentially inhibit the secretion of pro-inflammatory mediators, which may be related to inhibition of p65, c-Jun, and IRF3 signaling pathways in LPS-stimulated RAW264.7 cells.

Colostrum is a vital performance for buffaloes and potentially functional foods in the future. Therefore, this study aimed to evaluate the difference between the parity of buffalo colostrum and mature milk. Twenty pregnant buffaloes (primiparous = 10; multiparous = 10) were assigned to the same diet prepartum and milking routine postpartum. Calves were separated from the dams immediately after birth and colostrum was harvested within 2 h, whilst mature milk was harvested at 7 days postpartum. The colostrum was analyzed for immunoglobulin G and milk composition as the mature milk. The results showed that there was a higher level of protein, solid not fat, and milk urea nitrogen (p < 0.05), with a tendency for higher total solids (p = 0.08) in primiparous buffaloes’ colostrum compared with multiparous. No parity effect was observed in colostrum immunoglobulin G, fat, lactose, and yields of colostrum and composition (p > 0.05). There was no difference in mature milk composition and yield by parity affected (p > 0.05). Compared with mature milk composition, colostrum had a higher content protein, total solids, solid not fat, and milk urea nitrogen (p < 0.05); however, fat and lactose were lower than that of mature milk (p < 0.05). For minerals, multiparous buffaloes’ colostrum had a higher concentration of Fe (p = 0.05), while the mature milk had higher concentrations of K and P compared with primiparous. Buffalo colostrum had higher concentrations of Na, Mg, Co, Fe, and K with a lower concentration of Ca relative to mature milk (p < 0.05). It was observed that parity affected colostrum characteristics rather than mature milk and caused subtle variations in minerals in colostrum and mature milk of buffaloes. As lactation proceeded, both milk composition and minerals in the milk changed drastically.

Among more than 800 known fast radio bursts (FRBs), only two, namely FRB 20121102A and FRB 20190520B, are confirmed to be associated with persistent radio sources (PRSs). Here, we report evidence of apparent temporal variability in the PRS associated with the bursting FRB 20190520B based on Karl G. Jansky Very Large Array observations taken in 2020 and 2021. Based on the analysis of the epoch-to-epoch variability of the PRS at the L , S , C , and X bands (1–12 GHz), we detected not only overall marginal variability, but also a likely radio flux decrease ( σ ∼ 3.2) between the observations taken in 2020 and 2021 at 3 GHz. Assuming no spectral variation in the PRS during these observations, we found evidence for an overall broadband radio flux decrease by about 20% between the 2020 and the 2021 observations, suggesting that the PRS probably evolves on a yearly timescale. If we attribute the marginal variability at 3 GHz as intrinsic or due to scintillation, the size of the potential variable component of the PRS is constrained to be subparsec. On the other hand, the size of the PRS can be also constrained to ≳0.22 pc from the time-averaged radio spectrum and the integrated radio luminosity in the 1–12 GHz band, based on equipartition and self-absorption arguments. We discuss the potential origins of the PRS and suggest that an accreting compact object origin might be able to explain the PRS’s temporal and spectral properties. Confirmation of the variability or flux decline of the PRS will be critical for our understanding of the PRS and its relation to the bursting source.

Ions (e.g., ${{\rm{H}}}_{3}^{+}$ , H _2 O ^+ ) have been used extensively to quantify the cosmic-ray ionization rate (CRIR) in diffuse sightlines. However, measurements of the CRIR in low-to-intermediate density gas environments are rare, especially when background stars are absent. In this work, we combine molecular line observations of CO, OH, CH, and HCO ^+ in the star-forming cloud IC 348, and chemical models to constrain the value of the CRIR and study the response of the distribution of chemical abundances. The cloud boundary is found to have an A _V of approximately 4 mag. From the interior to the exterior of the cloud, the observed ^13 CO line intensities drop by an order of magnitude. The calculated average abundance of ^12 CO (assuming ^12 C/ ^13 C=65) is (1.2 ± 0.9) × 10 ^−4 , which decreases by a factor of 6 from the interior to the outside regions. The average abundance of CH (3.3 ± 0.7 × 10 ^−8 ) is in good agreement with previous findings in diffuse and translucent clouds ( A _V < 5 mag). However, we did not find a decline in CH abundance in regions of high extinction ( A _V ≃ 8 mag) as previously reported in Taurus. By comparing the observed molecular abundances and chemical models, we find a decreasing trend of the CRIR as A _V increases. The inferred CRIR of ζ _cr = (4.7 ± 1.5) × 10 ^−16 s ^−1 at low A _V is consistent with ${{\rm{H}}}_{3}^{+}$ measurements toward two nearby massive stars.

The cosmic-ray ionization rate (CRIR, ζ _2 ) is one of the key parameters controlling the formation and destruction of various molecules in molecular clouds. However, the current most commonly used CRIR tracers, such as ${{\rm{H}}}_{3}^{+}$ , OH ^+ , and H _2 O ^+ , are hard to detect and require the presence of background massive stars for absorption measurements. In this work, we propose an alternative method to infer the CRIR in diffuse clouds using the abundance ratios of OH/CO and HCO ^+ /CO. We have analyzed the response of chemical abundances of CO, OH, and HCO ^+ on various environmental parameters of the interstellar medium in diffuse clouds and found that their abundances are proportional to ζ _2 . Our analytic expressions give an excellent calculation of the abundance of OH for ζ _2 ≤ 10 ^−15 s ^−1 , which are potentially useful for modeling chemistry in hydrodynamical simulations. The abundances of OH and HCO ^+ were found to monotonically decrease with increasing density, while the CO abundance shows the opposite trend. With high-sensitivity absorption transitions of both CO (1–0) and (2–1) lines from Atacama Large Millimeter/submillimeter Array, we have derived the H _2 number densities ( ${n}_{{{\rm{H}}}_{2}}$ ) toward 4 lines of sight; assuming a kinetic temperature of T _k = 50 K, we find a range of (0.14 ± 0.03–1.2 ± 0.1) × 10 ^2 cm ^−3 . By comparing the observed and modeled HCO ^+ /CO ratios, we find that ζ _2 in our diffuse gas sample is in the range of ${1.0}_{-1.0}^{+14.8}$ × 10 ${}^{-16}\mbox{--}{2.5}_{-2.4}^{+1.4}$ × 10 ^−15 s ^−1 . This is ∼2 times higher than the average value measured at higher extinction, supporting an attenuation of CRs as suggested by theoretical models.

Mg-3%Al alloy was refined by carbon inoculation combining with 0.2%Ca addition. High grain refining efficiency was obtained and the synergistic refining mechanism was deeply discussed in the present study. Al–C–O particles, actually Al4C3 particles, were formed in the carbon-inoculated Mg-3%Al alloy acting as nuclei for α-Mg grains. Ca addition had no obvious effect on size distribution of the nucleating particles. Ca segregation was proved on Al4C3 particles, which should reduce the interfacial energy of nuclei/Mg. The constitutional undercooling in front of nucleus/liquid was increased from 0.12 °C to 0.15 °C induced by 0.2%Ca addition. The synergistic grain refining efficiency can be attributed to the higher constitutional undercooling and lower the interface energy of nucleus/Mg induced by Ca addition. More nucleating particles with small size could be activated acting as potent nuclei of α-Mg grains. Consequently, Mg-3%Al alloy could be effectively refined due to the synergistic effect induced by carbon inoculation combining with Ca.

Abstract An amorphous Ni nanoparticles‐loaded ZnO nanowire array is controllably constructed on stainless steel mesh through combined electrodeposition and hydrothermal reaction. Its nano‐arrayed structure not only provides a platform to achieve stable and good dispersion of Ni nanoparticles, but also helps improve their ability to adsorb 4‐nitrophenolate ions and to capture hydrogen radicals, thereby accelerating the hydrogen transfer from metal hydride complex to 4‐nitrophenol. Benefiting from the abovementioned unique features, it outperforms most Ni‐based catalysts. While a 30‐s re‐electrodeposition of Ni can provide it extra 150 min of high catalytic activity towards the reduction of waste 4‐nitrophenol to valuable 4‐aminophenol, further demonstrating its outstanding reusability. The highly general methodology reported here paves the way to economically and effectively synthesize various other metal nanoparticles‐loaded ZnO nanowire arrays on different conductive substrates, which not only enrich the nanowire‐arrayed catalysts, but also significantly promote their practical utilizations in a wide range of environment‐related fields.

Objective: To determine the mechanism of the laxative effect of rhubarb (Rheum tanguticum Maxim. ex Balf.) in rats using a combined bioinformatic and in vivo approach. Methods: Substances derived from rhubarb that are present in the colorectum were identified using high-performance liquid chromatography, coupled with linear ion-trap quadrupole Orbitrap high-resolution mass spectrometry. The targets with a potential laxative effect were identified from databases and the literature, then used with rhubarb-derived substances in molecular docking modeling. The expression of candidate endogenous target molecules that bound specific components of rhubarb was then measured in constipated rats that had or had not been administered rhubarb by western blotting. Finally, potentially bioactive compounds were traced back to their prototype components. Results: We identified 17 anthraquinones and 21 anthrones derived from rhubarb in the colorectum of rats. G-scoring identified three potential mediators of the laxative effect: c-kit, 5-hydroxytryptamine receptor 4 (5-HT4), and aquaporin-3 (AQP3). In addition, 10 rhubarb-derived components (aloe-emodin, emodin, rhein, chrysophanol, physcion, sennoside A, sennoside C, physcionanthrone, aloe-emodinanthrone, and rheinanthrone), which have strong binding affinities for more than one of the three potential targets, were selected as likely active compounds. Rhubarb extract increased the expression of c-kit and 5-HT4, and reduced the expression of AQP3 in the colon of constipated rats, which might mediate its laxative effect. We also found that a single prototype component may be metabolized into several active metabolites, and a single active ingredient can also be generated from various prototype compounds. Conclusion: The present study demonstrates that various anthraquinones and anthrones present in rhubarb may be metabolized to form bioactive compounds that have additive or synergistic effects to promote defecation via c-kit, 5-HT4 and/or AQP3.

The paper proposes a new HCI mechanism for device-free gesture recognition on the table using acoustic signal, which can extend the gesture input and interactions beyond the tiny screen of mobile device and allow users to provide input without blocking screen view. Previous researches have either relied on additional devices (e.g., special wearable device and mouse) or required active acoustic signals which demand additional cost and be less prone to popularize, while we explore the device-free gesture recognition using passive acoustic signals. This technology is more challenging due to the lack of an effective approach to eliminate the inherent ambient noise disturbances and extract stable gesture features. We fuse both short time energy (STE) and zero-crossing rate (ZCR) to identify the effective signals from the original input, and leverage the Mel frequency cepstral coefficients (MFCC), cochlear filter cepstral coefficients (CFCC) to extract the stable features from different gestures. The unique features in support vector machine (SVM) classifier achieve a high gesture recognition accuracy from the noisy scenarios and mismatched conditions. Implementation on the Android system has realized real-time processing of the feature extraction and gesture recognition. Extensive evaluations show our algorithm has a better noise tolerant performance and the system could recognize seven common gestures (click, flip left/right, scroll up/down, zoom in/out) on smart devices with an accuracy of 93.2%.

Drugs targeting intestinal bacteria have shown great efficacy for alleviating symptoms of Alzheimer’s disease (AD), and microbial metabolites are important messengers. Our previous work indicated that Rheum tanguticum effectively improved cognitive function and reshaped the gut microbial homeostasis in AD rats. However, its therapeutic mechanisms remain unclear. Herein, this study aimed to elaborate the mechanisms of rhubarb for the treatment of AD by identifying effective metabolites associated with rhubarb-responsive bacteria. The results found that rhubarb reduced hippocampal inflammation and neuronal damage in APP/PS1 transgenic (Tg) mice. 16S rRNA sequencing and metabolomic analysis revealed that gut microbiota and their metabolism in Tg mice were disturbed in an age-dependent manner. Rhubarb-responsive bacteria were further identified by real-time polymerase chain reaction (RT-PCR) sequencing. Four different metabolites reversed by rhubarb were found in the position of the important nodes on rhubarb-responsive bacteria and their corresponding metabolites combined with pathological indicators co-network. Furthermore, in vitro experiments demonstrated o-tyrosine not only inhibited the viabilities of primary neurons as well as BV-2 cells, but also increased the levels of intracellular reactive oxygen species and nitric oxide. In the end, the results suggest that rhubarb ameliorates cognitive impairment in Tg mice through decreasing the abundance of o-tyrosine in the gut owing to the regulation of rhubarb-responsive bacteria. Our study provides a promising strategy for elaborating therapeutic mechanisms of bacteria-targeted drugs for AD.