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In November 2017, a group of farmed rainbow trout (Oncorhynchus mykiss) died in Yunnan Province, China, likely due to infection. These rainbow trout exhibited slow movement, no feeding, dark body color, exophthalmia, and occasional ulcers on the body surface. Pathogens were isolated from diseased rainbow trout livers, head kidneys, spleens, and eyes, and the strain was preliminarily identified as Acinetobacter johnsonii based on morphology, biochemical tests, and 16S rRNA and rpoB sequences. The isolated strains were highly sensitive to florfenicol, ciprofloxacin, oxolinic acid, and norfloxacin but resistant to ampicillin, doxycycline, sulfadiazine, thiamphenicol, and sulfamethazine. The selected isolate was performed for the experimental infection of rainbow trout to confirm its pathogenicity. Experimentally infected fish showed disease symptoms similar to those observed in fish naturally infected with these bacteria. Vacuolar degeneration was prevalent in the liver and spleen of diseased fish. Cytoplasm volume was very high in the lymphocytes of the head kidney. The protein structure and topology of monomeric outer membrane protein A (OmpA), outer membrane protein 34 (Omp34), and a nucleoside-specific outer membrane transporter protein Tsx (OmpTsx) of A. johnsonii were predicted by AlphaFold 2. The predicted local distance difference test (pLDDT) score was used for the assessment of structure prediction. Comprehensive analysis of antigenic determinants of the OMP family member, OmpA, contains three antigenic determinants, which are 90% similar with epitopes of A. baumannii. OmpA is a recombinant protein with 35 kDa expressed in the Escherichia coli system. Based on these findings, A. johnsonii is regarded as an emerging opportunistic pathogen in farmed rainbow trout. OmpA protein can be used as a subunit vaccine candidate molecule of A. johnsonii.

Proof of concept enantioselective transformation via photoelectrocatalysis was reported on Cu-catalyzed enantioselective decarboxylative cyanation, which features mild conditions, high enantioselectivity and a reasonable range of functionalities.

Pharmacological targeting cancer stem cells are emerging as a novel therapeutic modality for cancer treatment and prevention. Human cytochrome P450 enzyme CYP4Z1 represents a promising target for its potential role in attenuating the stemness of breast cancer cells. In order to develop potent and selective CYP4Z1 inhibitors, a series of novel

Background Frailty is an age-related geriatric syndrome that leads to a series of clinically negative events. A better understanding of the factors associated with frailty assists in preventing its progression. The triglyceride-glucose (TyG) index, a simple alternative index of insulin resistance, has not yet been proven to be associated with frailty. The present study aimed to investigate the association between the TyG index and its trajectory with frailty from a cross-sectional, retrospective and prospective level based on an ongoing cohort. Methods This longitudinal study included 1,866 older residents from the “Fujian prospective aging cohort” (ChiCTR 2000032949). The TyG index was calculated as ln [fasting triglyceride (mg/dL) ╳ fasting plasma glucose (mg/dL)/2] and group-based trajectory model (GBTM) was applied to identify the trajectory of TyG index. The association between different trajectory groups of TyG index with frailty risk were estimated using multinomial logistic regression analysis. Results In the cross-sectional analysis, the highest quartile of the TyG index was associated with an increased risk of frailty (TyG index Q4 vs. Q1, OR = 1.50, 95% CI 1.00–2.25, P = 0.048). Restricted cubic splines demonstrated an increasing trend for TyG index and frailty risk. During a follow-up of ten years, three distinct trajectories of the TyG index were identified: low-stable (n=697, 38.3%), moderate-stable (n=910, 50.0%) and high-stable (n=214, 11.7%). Compared with those in the stable-low group of TyG index trajectory, the ORs (95% CI) of prefrailty and frailty risk were 1.79 (95% CI 1.11–2.88) and 2.17 (95% CI 1.01–3.88) for the high-stable group, respectively (P=0.017 and P=0.038). In the subgroup analysis, the association of the high-stable trajectory of TyG and frailty status were only observed in subjects with BMI ≥24kg/m2. Prospectively, the highest quartile of the TyG index was associated with a 2.09-fold significantly increased risk of one-year ADL/IADL decline (P = 0.045). Conclusions The present study suggests a potential role for a high and sustainable level of TyG index in the risk of frailty. The trajectories of the TyG index can help to identify older individuals at a higher risk of frailty who deserve primitive preventive and therapeutic approaches.

Objective This study aimed to investigate the longitudinal circulating eosinophil (EOS) data impacted by the COVID-19 vaccine, the predictive role of circulating EOS in the disease severity, and its association with T cell immunity in patients with SARS-CoV-2 Omicron BA.2 variant infection in Shanghai, China. Methods We collected a cohort of 1,157 patients infected with SARS-CoV-2 Omicron/BA.2 variant in Shanghai, China. These patients were diagnosed or admitted between Feb 20, 2022, and May 10, 2022, and were classified as asymptomatic (n = 705), mild (n = 286) and severe (n = 166) groups. We compiled and analyzed data of patients’ clinical demographic characteristics, laboratory findings, and clinical outcomes. Results COVID-19 vaccine reduced the incidence of severe cases. Severe patients were shown to have declined peripheral blood EOS. Both the 2 doses and 3 doses of inactivated COVID-19 vaccines promoted the circulating EOS levels. In particular, the 3rd booster shot of inactivated COVID-19 vaccine was shown to have a sustained promoting effect on circulating EOS. Univariate analysis showed that there was a significant difference in age, underlying comorbidities, EOS, lymphocytes, CRP, CD4, and CD8 T cell counts between the mild and the severe patients. Multivariate logistic regression analysis and ROC curve analysis indicate that circulating EOS (AUC = 0.828, p = 0.025), the combination of EOS and CD4 T cell (AUC = 0.920, p = 0.017) can predict the risk of disease severity in patients with SARS-CoV-2 Omicron BA.2 variant infection. Conclusions COVID-19 vaccine promotes circulating EOS and reduces the risk of severe illness, and particularly the 3rd booster dose of COVID-19 vaccine sustainedly promotes EOS. Circulating EOS, along with T cell immunity, may have a predictive value for the disease severity in SARS-CoV-2 Omicron infected patients.

Magnetic elastic abrasive particles are a new type of particle that combine the characteristics of magnetic abrasive particles and elastic abrasive particles by embedding magnetic media and abrasive particles in a particular proportion into a flexible polymer to form particles with a specific shape. First, a method for preparing magnetic elastic abrasive particles is proposed. A representative micro-unit model of magnetic elastic abrasive particles is established using 3DMAX software. The finite element software ABAQUS is used to analyze the micromechanical properties of magnetic elastic abrasive particles with silicon carbide (SiC) and alumina (Al2O3) particles as the abrasive phase, respectively. Secondly, based on the characteristics of double disk magnetic force passivation of magnetic elastic abrasive particles, a method is proposed to predict the life of magnetic elastic abrasive particles by predicting the surface roughness of the tool edge. The effects of particle size and abrasive phase on the wear and life of magnetic elastic abrasive particles are studied experimentally. Finally, the magnetic field force is analyzed, and a mathematical model of material removal for magnetic elastic abrasive particles is established based on the characteristics of the mixing phase. The effects of particle size and abrasive degree on material removal volume are studied, and the influence of magnetic elastic abrasive particle size on tool passivation is experimentally analyzed. A comparison is made with the vertical rotary passivation method. The superiority of the magnetic elastic abrasive particle passivation method is verified by examining the passivated tool's edge profile, surface roughness, and service life.

Background Hemodynamic parameters derived from pulse wave analysis have been shown to predict long-term outcomes in patients with heart failure (HF). Here we aimed to develop a deep-learning based algorithm that incorporates pressure waveforms for the identification and risk stratification of patients with HF. Methods The first study, with a case-control study design to address data imbalance issue, included 431 subjects with HF exhibiting typical symptoms and a left ventricular ejection fraction (LVEF) less than 45% and 1545 control participants with no history of HF (non-HF). Carotid pressure waveforms were obtained from all the participants using applanation tonometry. The HF score, representing the probability of HF, was derived from a one-dimensional deep neural network (DNN) model trained with characteristics of the normalized carotid pressure waveform. In the second study of HF patients, we constructed a Cox regression model with 83 candidate clinical variables along with the HF score to predict the risk of all-cause mortality with rehospitalization. Results To identify subjects using the HF score, the sensitivity, specificity, accuracy, F1 score, and area under receiver operating characteristic curve were 0.867, 0.851, 0.874, 0.878, and 0.93, respectively, from the 10-fold cross-validation of the DNN, which was better than other machine learning models, including logistic regression, support vector machine, and random forest. With a median follow-up of 5.8 years, the multivariable Cox model using the HF score and other clinical variables outperformed the other HF risk prediction models with concordance index of 0.71, in which only the HF score and five clinical variables were independent significant predictors (p N-terminal pro-brain natriuretic peptide, and hemoglobin. Conclusions Our study demonstrated the diagnostic and prognostic utility of arterial waveforms in subjects with HF using a DNN model. Pulse wave contains valuable information that can benefit the clinical care of patients with HF.

This study investigates the mechanism of digital linguistic landscapes in enabling engineering education for smart construction according to the educational dimensions of A (ability), S (skill), and K (knowledge). A questionnaire survey was conducted based on the core concepts of the informative dimension and symbolic dimension in digital language landscape as well as the ability dimension, knowledge dimension, and skill dimension in engineering education. Structural equation modeling (SEM) was used as the test method. The results of the research demonstrate that the informative dimension and symbolic dimension are two main aspects of DLL in education of engineering students for smart construction. Additionally, DLL has a significant positive impact on the ability, knowledge, and skill education of engineering students for smart construction. The research has theoretical and practical significance, as it not only enriches research on the relationship between DLL and engineering education for smart construction but also expands the theoretical understanding of engineering education from the perspective of linguistics. Furthermore, the study explores the path of the practical application of digital language landscape to engineering education for smart construction.

Gastrointestinal (GI) tract involvement is a major determinant for subsequent morbidity and mortality arising during graft-versus-host disease (GVHD). CD4+ T cells that produce granulocyte-macrophage colony stimulating factor (GM-CSF) have emerged as central mediators of inflammation in this tissue site as GM-CSF serves as a critical cytokine link between the adaptive and innate arms of the immune system. However, cellular heterogeneity within the CD4+ GM-CSF+ T-cell population due to the concurrent production of other inflammatory cytokines has raised questions as to whether these cells have a common ontology or if a unique CD4+ GM-CSF+ subset exists that differs from other defined T helper subtypes. Using single-cell RNA sequencing analysis (scRNAseq), we identified two CD4+ GM-CSF+ T-cell populations that arose during GVHD and were distinguishable according to the presence or absence of interferon-γ (IFN-γ) coexpression. CD4+ GM-CSF+ IFN-γ− T cells, which emerged preferentially in the colon, had a distinct transcriptional profile, used unique gene regulatory networks, and possessed a nonoverlapping T-cell receptor repertoire compared with CD4+ GM-CSF+ IFN-γ+ T cells as well as all other transcriptionally defined CD4+ T-cell populations in the colon. Functionally, this CD4+ GM-CSF+ T-cell population contributed to pathologic damage in the GI tract that was critically dependent on signaling through the interleukin-17 (IL-7) receptor but was independent of type 1 interferon signaling. Thus, these studies help to unravel heterogeneity within CD4+ GM-CSF+ T cells that arise during GVHD and define a developmentally distinct colitogenic T helper subtype GM-CSF+ subset that mediates immunopathology.

Background Sorafenib is a first-line drug targeting the RTK-MAPK signalling pathway used to treat advanced hepatocellular carcinoma (HCC). However, tumour cells readily develop sorafenib resistance, limiting long-term therapy with this drug. In our previous study, we found that human menstrual blood-derived stem cells (MenSCs) altered the expression of some sorafenib resistance-associated genes in HCC cells. Therefore, we wanted to further explore the feasibility of MenSC-based combination therapy in treating sorafenib-resistant HCC (HCC-SR) cells. Methods The therapeutic efficiency of sorafenib was determined using CCK-8 (Cell Counting Kit-8), Annexin V/PI and clone formation assays in vitro and a xenograft mouse model in vivo. DNA methylation was determined using RT‒PCR and methylated DNA immunoprecipitation (MeDIP). Autophagy was detected by measuring LC3-II degradation and autophagosome maturation. Transmission electron microscopy identified autophagosomes and mitochondria. Physiological functions of mitochondria were assessed by measuring the ATP content, reactive oxygen species (ROS) generation, and mitochondrial membrane potential (MMP). Results The tumour suppressor genes BCL2 interacting protein 3 (BNIP3) and BCL2 interacting protein 3 like (BNIP3L) were silenced by promoter methylation and that BNIP3 and BNIP3L levels correlated negatively with sorafenib resistance in HCC-SR cells. Strikingly, MenSCs reversed sorafenib resistance. MenSCs upregulated BNIP3 and BNIP3L expression in HCC-SR cells via tet methylcytosine dioxygenase 2 (TET2)-mediated active demethylation. In HCC-SR cells receiving sorafenib and MenSC combination therapy, pressure from sorafenib and elevated BNIP3 and BNIP3L levels disrupted balanced autophagy. Hyperactivation of mitophagy significantly caused severe mitochondrial dysfunction and eventually led to the autophagic death of HCC-SR cells. Conclusions Our research suggests that combining sorafenib and MenSCs may be a potentially new strategy to reverse sorafenib resistance in HCC-SR cells.

Purpose: Extensive research over the past decade has revealed that the proinflammatory microenvironment plays a critical role in the development of colorectal cancer. Whether nimbolide, a limonoid triterpene, can inhibit the growth of colorectal cancer was investigated in the present study.Experimental Design: The effect of nimbolide on proliferation of colorectal cancer cell lines was examined by MTT assay, apoptosis by caspase activation and poly-ADP ribose polymerase cleavage, NF-κB activation by DNA-binding assay, and protein expression by Western blotting. The effect of nimbolide on the tumor growth in vivo was examined in colorectal cancer xenografts in a nude mouse model.Results: Nimbolide inhibited proliferation, induced apoptosis, and suppressed NF-κB activation and NF-κB–regulated tumorigenic proteins in colorectal cancer cells. The suppression of NF-κB activation by nimbolide was caused by sequential inhibition of IκB kinase (IKK) activation, IκBα phosphorylation, and p65 nuclear translocation. Furthermore, the effect of nimbolide on IKK activity was found to be direct. In vivo, nimbolide (at 5 and 20 mg/kg body weight), injected intraperitoneally after tumor inoculation, significantly decreased the volume of colorectal cancer xenografts. The limonoid-treated xenografts exhibited significant downregulation in the expression of proteins involved in tumor cell survival (Bcl-2, Bcl-xL, c-IAP-1, survivin, and Mcl-1), proliferation (c-Myc and cyclin D1), invasion (MMP-9, ICAM-1), metastasis (CXCR4), and angiogenesis (VEGF). The limonoid was found to be bioavailable in the blood plasma and tumor tissues of treated mice.Conclusions: Our studies provide evidence that nimbolide can suppress the growth of human colorectal cancer through modulation of the proinflammatory microenvironment. Clin Cancer Res; 19(16); 4465–76. ©2013 AACR.

PDF file - 130K, Nimbolide is bioavailable in the plasma and colorectal tumor tissues of nude mice. A, HPLC chromatogram of pure nimbolide. B, HPLC chromatogram of nimbolide in plasma. C, HPLC chromatogram of nimbolide in tumor tissues.

The supplementary infomation containing Figure legends, seven supplemental figures and one supplemental table. Figure S1 XIST expression is preferentially correlated with brain metastasis in breast cancer. Figure S2 Knockout of XIST preferentially promotes brain metastases. Figure S3 Knockout of XIST enhances tumor growth and distant metastases. Figure S4 Knockdown of XIST promotes EMT and stemness. Figure S5 c-Met is regulated by X-chromosome gene, MSN. Figure S6 miR-503 promotes the conversion of M1 to M2 phenotype of microglia. Figure S7 Fludarabine selectively suppresses the growth of XISTlow cells. Table S1 reagent and resource.

supplementary figure legend

Ethnicity is considered to be one of the major risk factors in certain subtypes of breast cancer. However, the mechanism of this racial disparity remains poorly understood. Here, we demonstrate that SOS1, a key regulator of Ras pathway, is highly expressed in African-American (AA) patients with breast cancer compared with Caucasian-American patients. Because of the higher obesity rate in AA women, increased levels of SOS1 facilitated signal transduction of the c-Met pathway, which was highly activated in AA patients with breast cancer via hepatocyte growth factor secreted from adipocytes. Elevated expression of SOS1 also enhanced cancer stemness through upregulation of PTTG1 and promoted M2 polarization of macrophages by CCL2 in metastatic sites. SOS1 was epigenetically regulated by a super-enhancer identified by H3K27ac in AA patients. Knockout of the super-enhancer by CRISPR in AA cell lines significantly reduced SOS1 expression. Furthermore, SOS1 was posttranscriptionally regulated by miR-483 whose expression is reduced in AA patients through histone trimethylation (H3K27me3) on its promoter. The natural compound, taxifolin, suppressed signaling transduction of SOS1 by blocking the interaction between SOS1 and Grb2, suggesting a potential utility of this compound as a therapeutic agent for AA patients with breast cancer.Significance:These findings elucidate the signaling network of SOS1-mediated metastasis in African-American patients, from the epigenetic upregulation of SOS1 to the identification of taxifolin as a potential therapeutic strategy against SOS1-driven tumor progression.

Up to 30% of patients with metastatic breast cancer eventually develop brain metastasis, yet the pathologic mechanism behind this development remains poorly understood. Here, we profiled long noncoding RNAs in brain metastatic tumors from patients with breast cancer and found that the X-inactive–specific transcript (XIST) was significantly downregulated in these tissues. XIST expression levels inversely correlated with brain metastasis, but not with bone metastasis in patients. Silencing of XIST preferentially promoted brain metastatic growth of XISThigh cells in our xenograft models. Moreover, knockout of XIST in mice mammary glands accelerated primary tumor growth as well as metastases in the brain. Decreased expression of XIST stimulated epithelial–mesenchymal transition and activated c-Met via MSN-mediated protein stabilization, which resulted in the promotion of stemness in the tumor cells. Loss of XIST also augmented secretion of exosomal miRNA-503, which triggered M1–M2 polarization of microglia. This M1–M2 conversion upregulated immune suppressive cytokines in microglia that suppressed T-cell proliferation. Furthermore, we screened an FDA-approved drug library and identified fludarabine as a synthetic lethal drug for XISTlow breast tumor cells and found that fludarabine blocked brain metastasis in our animal model. Our results indicate that XIST plays a critical role in brain metastasis in breast cancer by affecting both tumor cells and the tumor microenvironment and that the XIST-mediated pathway may serve as an effective target for treating brain metastasis.Significance: These findings describe mechanisms of how loss of the lncRNA XIST promotes brain metastasis in breast cancer and identify fludarabine as a potential therapeutic agent that specifically eliminates XISTlow tumor cells in the brain. Cancer Res; 78(15); 4316–30. ©2018 AACR.

Supplementary Legends 1-6 from MicroRNA-145 Suppresses Cell Invasion and Metastasis by Directly Targeting Mucin 1

Supplementary Figures 1-6, Table 1 from MicroRNA-145 Suppresses Cell Invasion and Metastasis by Directly Targeting Mucin 1

Resina Draconis (RD) is known as the "holy medicine for promoting blood circulation" and possesses antitumor properties against various types of cancer, including breast cancer (BC); however, the underlying mechanism is not well understood. To explore the potential mechanism of RD against BC using network pharmacology and experimental validation, data on bioactive compounds, potential targets of RD, and related genes of BC were obtained from multiple public databases. Gene Ontology (GO) and KEGG pathway analyses were performed via the DAVID database. Protein interactions were downloaded from the STRING database. The mRNA and protein expression levels and survival analysis of the hub targets were analyzed using the UALCAN, HPA, Kaplan‒Meier mapper, and cBioPortal databases. Subsequently, molecular docking was used to verify the selected key ingredients and hub targets. Finally, the predicted results of network pharmacology methods were verified by cell experiments. In total, 160 active ingredients were obtained, and 148 RD target genes for the treatment of BC were identified. KEGG pathway analysis indicated that RD exerted its therapeutic effects on BC by regulating multiple pathways. Of these, the PI3K-AKT pathway was indicated to play an important role. In addition, RD treatment of BC seemed to involve the regulation of hub targets that were identified based on PPI interaction network analysis. Validation in different databases showed that AKT1, ESR1, HSP90AA1, CASP3, SRC and MDM2 may be involved in the carcinogenesis and progression of BC and that ESR1, IGF1 and HSP90AA1 were correlated with worse overall survival (OS) in BC patients. Molecular docking results showed that 103 active compounds have good binding activity with the hub targets, among which flavonoid compounds were the most important active components. Therefore, the sanguis draconis flavones (SDF) were selected for subsequent cell experiments. The experimental results showed that SDF significantly inhibited the cell cycle and cell proliferation of MCF-7 cells through the PI3K/AKT pathway and induced MCF-7 cell apoptosis. This study has preliminarily reported on the active ingredients, potential targets, and molecular mechanism of RD against BC, and RD was shown to exert its therapeutic effects on BC by regulating the PI3K/AKT pathway and related gene targets. Importantly, our work could provide a theoretical basis for further study of the complex anti-BC mechanism of RD.

Background. The cholinergic anti-inflammatory pathway connects the immune response system and the nervous system via the vagus nerve. The key regulatory receptor is the α7-subtype of the nicotinic acetylcholine receptor (α7nAChR). Cholinergic anti-inflammatory pathway has been proved to be effective in suppressing the inflammation responses in acute lung injury (ALI). Dendritic cells (DCs), the important antigen-presenting cells, also express the α7nAChR. Past studies have indicated that reducing the quantity of mature conventional DCs and inhibiting the maturation of pulmonary DCs may prove effective for the treatment of ALI. However, the effects of cholinergic anti-inflammatory pathway on maturation, function, and quantity of DCs and conventional DCs in ALI remain unclear. Objective. It was hypothesized that cholinergic anti-inflammatory pathway may inhibit the inflammatory response of ALI by regulating maturation, phenotype, and quantity of DCs and conventional DCs. Methods. GTS-21 (GTS-21 dihydrochloride), an α7nAchR agonist, was prophylactically administered in sepsis-induced ALI mouse model and LPS-primed bone marrow-derived dendritic cells. The effects of GTS-21 were observed with respect to maturation, phenotype, and quantity of DCs, conventional DCs, and conventional DCs2 (type 2 conventional DCs) and the release of DC-related proinflammatory cytokines in vivo and in vitro. Results. The results of the present study revealed that GTS-21 treatment decreased the maturation of DCs and the production of DC-related proinflammatory cytokines in vitro and in sepsis-induced ALI mouse model; it reduced the quantity of CD11c+MHCII+ conventional DCs and CD11c+CD11b+ conventional DCs2 in vivo experiment. Conclusions. Cholinergic anti-inflammatory pathway contributes to the reduction in the inflammatory response in ALI by regulating maturation, phenotype, and quantity of DCs, conventional DCs, and conventional DCs2.

Background: G-protein-coupled receptor 43 (GPR43) is a posttranscriptional regulator involved in cholesterol metabolism. This study aimed to investigate the possible roles of GPR43 activation in podocyte lipotoxicity in diabetic nephropathy (DN) and explore the potential mechanisms. Methods: The experiments were conducted by using diabetic GPR43-knockout mice and a podocyte cell culture model. Lipid deposition and free cholesterol levels in kidney tissues were measured by BODIPY staining and quantitative cholesterol assays, respectively. The protein expression of GPR43, LC3II, p62, beclin1, low-density lipoprotein receptor (LDLR) and early growth response protein 1 (EGR1) in kidney tissues and podocytes was measured by real-time PCR, immunofluorescent staining and Western blotting. Results: There were increased LDL cholesterol levels in plasma and cholesterol accumulation in the kidneys of diabetic mice. However, GPR43 gene knockout inhibited these changes. An in vitro study further demonstrated that acetate treatment induced cholesterol accumulation in high glucose-stimulated podocytes, which was correlated with increased cholesterol uptake mediated by LDLR and reduced cholesterol autophagic degradation, as characterized by the inhibition of LC3 maturation, p62 degradation and autophagosome formation. Gene knockdown or pharmacological inhibition of GPR43 prevented these effects on podocytes. Furthermore, GPR43 activation increased extracellular regulated protein kinases 1/2 (ERK1/2) activity and EGR1 expression in podocytes, which resulted in an increase in cholesterol influx and autophagy inhibition. In contrast, after GPR43 deletion, these changes in podocytes were improved, as shown by the in vivo and in vitro results. Conclusion: GPR43 activation-mediated lipotoxicity contributes to podocyte injury in DN by modulating the ERK/EGR1 pathway.

Supplemental Material for The impact response and failure mechanism of sandwich plates with M-type foldcore under low-velocity impact by Yunfei Deng, Yuan Yin, Huapeng Wu, Chunping Zhou and Xianzhi Zeng in Journal of Sandwich Structures & Materials

Additional file 1: Fig. S1 to S18.

Magneto-elastic abrasive grains have magnetism, low elastic modulus and excellent abrasive performance, and have the characteristics of bonded abrasive grains and loose abrasive grains. The dual-disk magnetic preparation greatly improves the preparation quality and efficiency. Firstly, the magneto-elastic abrasive particles are introduced into the edge preparation of the dual-disk magnetic tool, and the preparation method of 4035 silica gel magneto-elastic abrasive particles is proposed. According to the microscopic characteristics of the magneto-elastic abrasive particles, the finite element software ABAQUS is used to establish the magneto-elastic abrasive particles. The meso-level representative volume element (RVE) model is built to analyze the stress and strain law of magneto-elastic abrasive particles under tension and compression. Secondly, an experimental platform for magnetic preparation of magneto-elastic abrasive particles with dual disks was built to analyze the force of magneto-elastic abrasive particles. Finally, Through the magnetic preparation experiment of the magneto-elastic abrasive dual-disk magnetic force, the influence of the disk rotation speed, abrasive particle size and relative magnetic permeability on the cutting edge wear is studied. And compared to the magnetic abrasive particles double-disk magnetic and drag finishing method, the magneto-elastic abrasive particle double-disk magnetic preparation method can obtain the maximum edge wear amount and the maximum surface roughness decreasing amplitude. The research results are of great significance to promote the progress of our country's magnetic high-efficiency processing and magneto-finishing processing technology.

Breast cancer displays disparities in mortality between African Americans and Caucasian Americans. However, the exact molecular mechanisms remain elusive. Here, we identify miR-1304-3p as the most upregulated microRNA in African American patients. Importantly, its expression significantly correlates with poor progression-free survival in African American patients. Ectopic expression of miR-1304 promotes tumor progression in vivo. Exosomal miR-1304-3p activates cancer-associated adipocytes that release lipids and enhance cancer cell growth. Moreover, we identify the anti-adipogenic gene GATA2 as the target of miR-1304-3p. Notably, a single nucleotide polymorphism (SNP) located in the miR-1304 stem-loop region shows a significant difference in frequencies of the G allele between African and Caucasian American groups, which promotes the maturation of miR-1304-3p. Therefore, our results reveal a mechanism of the disparity in breast cancer progression and suggest a potential utility of miR-1304-3p and the associated SNP as biomarkers for predicting the outcome of African American patients.

Resina draconis(RD), is known as the "holy medicine for promoting blood circulation", which is shown to possess anti-tumor properties in various types of cancer include Breast cancer(BC), however, the underlying mechanism is not well understood. To explore the potential mechanism of RD against BC using network pharmacology and experimental validation. Data on bioactive compounds, potential targets of RD, related genes of BC, were obtained from multiple public databases. Gene ontology (GO) and KEGG pathway analysis were performed via the DAVID database. The protein interaction was download from STRING database. The mRNA, protein expression levels and survival analysis of the hub targets were analyzed using UALCAN, HPA, Kaplan-Meier Mapper, and cBioPortal databases. Subsequently, molecular docking was used to verify the selected key ingredients and hub targets. Finally, the predicted results of network pharmacology methods were verified by cells experiments. In total, 160 active ingredients were obtained, 148 RD target genes for the treatment of BC were identified. KEGG pathway analysis indicated that RD could exert its therapeutic effects on BC by regulating multiple pathways. Of these, the PI3K-AKT pathway could play an important role. In addition, RD could treat BC by regulating hub targets that were determined with the PPI interaction network. The validation in different databases showed that may AKT1, ESR1, HSP90AA1, CASP3, SRC and MDM2 be involved in the carcinogenesis and progression of BC, as well as ESR1, IGF1 and HSP90AA1 were correlated to worse overall survival (OS) in BC. Molecular docking results showed that flavonoids compounds have good binding activity with the hub targets. Therefore, the sanguis draconis flavones (SDF) were selected for subsequent cell experiments. The experimental results showed that SDF significantly inhibits the cell cycle and cell proliferation through the PI3K-AKT pathway and that it can induce apoptosis of MCF-7 cells. The study has preliminarily discussed the active ingredients, potential targets, and molecular mechanism of RD against BC; and RD could exert its therapeutic effects on BC by regulating PI3K/AKT pathway and related gene targets. Importantly, our work could provide a theoretical basis for further study on its complex anti-BC mechanism.

Background We have witnessed frailty, which characterized by a decline in physiological reserves, become a major public health issue in older adults. Understanding the influential factors associated with frailty may help prevent or if possible reverse frailty. The present study aimed to investigate factors associated with frailty status and frailty transition in a community-dwelling older population. Methods A prospective cohort study on community-dwelling subjects aged ≥ 60 years was conducted, which was registered beforehand (ChiCTR 2,000,032,949). Participants who had completed two visits during 2020–2021 were included. Frailty status was evaluated using the Fried frailty phenotype. The least absolute shrinkage and selection operator (LASSO) regression was applied for variable selection. Bayesian network analysis with the max-min hill-climbing (MMHC) algorithm was used to identify factors related to frailty status and frailty transition. Results Of 1,981 subjects at baseline, 1,040 (52.5%) and 165 (8.33%) were classified as prefrailty and frailty. After one year, improved, stable, and worsening frailty status was observed in 460 (35.6%), 526 (40.7%), and 306 (23.7%) subjects, respectively. Based on the variables screened by LASSO regression, the Bayesian network structure suggested that age, nutritional status, instrumental activities of daily living (IADL), balance capacity, and social support were directly related to frailty status. The probability of developing frailty is 14.4% in an individual aged ≥ 71 years, which increases to 20.2% and 53.2% if the individual has balance impairment alone, or combined with IADL disability and malnutrition. At a longitudinal level, ADL/IADL decline was a direct predictor of worsening in frailty state, which further increased the risk of hospitalization. Low high-density lipoprotein cholesterol (HDL-C) and diastolic blood pressure (DBP) levels were related to malnutrition, and further had impacts on ADL/IADL decline, and ultimately led to the worsening of the frailty state. Knowing the status of any one or more of these factors can be used to infer the risk of frailty based on conditional probabilities. Conclusion Older age, malnutrition, IADL disability, and balance impairment are important factors for identifying frailty. Malnutrition and ADL/IADL decline further predict worsening of the frailty state.

Paneth cell metaplasia (PCM) typically arises in the setting of pre-existing gastrointestinal (GI) diseases; however, the mechanistic pathway that induces metaplasia and whether PCM is initiated exclusively by disorders intrinsic to the GI tract has not been delineated. Herein, we describe the development of PCM in a murine model of inducible bcr/abl oncogene-driven chronic myelogenous leukemia (CML) in which metaplasia is causally and temporally linked to the development of leukemia. Mechanistically, CML induced a proinflammatory state within the GI tract that resulted in the production of epithelial-derived IL-33. Binding of IL-33 to ST2 led to the production of IL-9 by type 2 innate lymphoid cells (ILC2s) which was directly responsible for the induction of PCM in the colon and Paneth cell hyperplasia in the ileum. In addition, IL-9 directed remodeling of the small intestines characterized by goblet and tuft cell hyperplasia along with the expansion of mucosal mast cells. Thus, we identify that an extra intestinal disease can trigger an ILC2/IL-9 immune circuit which induces PCM and regulates epithelial cell fate decisions in the GI tract.

This paper investigates the application of nonorthogonal multiple access (NOMA) in millimeter-Wave (mmWave) communications to address resource allocation issues for multiuser downlink transmission. Inspired by the K-means clustering algorithm, a NOMA user grouping policy is first employed in accordance with the channel correlation between users. The first-stage decoding order for each NOMA group is then determined by merely utilizing the users’ channel gain to formulate a joint power allocation and hybrid beamforming optimization problem. Specifically, we use signal-to-leakage-plus-noise ratio (SLNR) as the performance index of the optimization problem to reduce the computational complexity, because it can decouple the design of the beamforming and power allocation issues so they can be executed iteratively. Under given beamforming matrix, the power allocation issue is expressed as a quadratic programming (QP) problem, and then transformed into a convex problem by introducing an auxiliary-positive real variable to solve through the Lagrange multiplier method. On the contrary, the beamforming optimization problem is non-convex and very difficult to solve due to the constant modulus constraints in the hybrid architecture. However, the optimum solution of the ideal full-digital beamforming can be acquired primarily by generalized eigenvalue decomposition (GED). In this condition, two hybrid beamforming algorithms are proposed, in which normalized phase matching and equal gain transmission are performed respectively in the analog domain. On this basis, a second-stage decoding order can be employed according to the effective channel gain of users to perform successive interference cancellation (SIC) successfully. Numerical results show that the proposed joint power allocation and hybrid beamforming algorithms are superior to the classical mmWave-NOMA and orthogonal multiple access (OMA) schemes not only in lower implementation complexity, but also in better spectrum efficiency and energy efficiency performance.

Background Poststroke social isolation could worsen poststroke depression and dampen neurogenesis. (R,S)-ketamine has antidepressant and neuroprotective effects; however, its roles and mechanisms in social isolation–mediated depressive-like behaviors and sensorimotor recovery remain unclear. Methods Mice were subjected to transient middle cerebral artery occlusion, and then were pair-housed with ovariectomized female mice or were housed isolated (ISO) starting at 3 days postischemia. ISO mice received 2 weeks of (R,S)-ketamine treatment starting at 14 days postischemia. Primary ependymal epithelial cells and choroid plexus epithelial cells were cultured and treated with recombinant human atrial natriuretic peptide (ANP) protein. Results The poststroke social isolation model was successfully established using middle cerebral artery occlusion combined with poststroke isolation, as demonstrated by a more prominent depression-like phenotype in ISO mice compared with pair-housed mice. (R,S)-ketamine reversed ISO-mediated depressive-like behaviors and increased ANP levels in the atrium. The depression-like phenotype was negatively correlated with ANP levels in both the atrium and plasma. Atrial GLP-1 and GLP-1 receptor signaling was essential to the promoting effects of (R,S)-ketamine on the synthesis and secretion of ANP from the atrium in ISO mice. (R,S)-ketamine also increased ANP and TGF-β1 levels in the choroid plexus of ISO mice. Recombinant human ANP increased TGF-β1 levels in both the primarily cultured ependymal epithelial cells and choroid plexus epithelial cells. Furthermore, (R,S)-ketamine increased TGF-β1 levels in the ischemic hemisphere and promoted striatal neurogenesis and sensorimotor recovery via ANP in ISO mice. Conclusions (R,S)-ketamine alleviated poststroke ISO-mediated depressive-like behaviors and thus promoted striatal neurogenesis and sensorimotor recovery via ANP.

Cellular activities such as DNA synthesis, adenosine triphosphate production, and mitochondrial respiration are affected by iron metabolism. Disturbance of iron homeostasis usually leads to damage in cells and organs in the context of iron overload or deficiency. Thus, iron, a key regulator in nutritional immunity, was shown to be critical in innate and adaptive immunity. Unlike apoptosis, ferroptosis, a feature of iron-dependent lipid peroxidation, is thought to be associated with immune regulation because of its immunogenic nature. In this review, we summarize the role of iron and ferroptosis in immune regulation and discuss their therapeutic potential in the treatment of arthropathies like osteoarthritis and rheumatoid arthritis.

Background It is simple, convenient, inexpensive, proven, extensive, and safe for acupuncture in the treatment of postherpetic neuralgia (PHN). However, there are no comparisons between various acupuncture therapies that can directly and effectively provide specific guidance to clinicians. The development of a guideline for the optimization of acupuncture for PHN is of great importance for the development of clinical acupuncture. Therefore, we attempted to design a study protocol for a network meta-analysis of randomized controlled trials of acupuncture for PHN to provide evidence to support the treatment of acupuncture for PHN. Methods A search of 8 databases, Chinese Scientific Journal Database, China National Knowledge Infrastructure Database, Wanfang, China Biomedical Literature Database, PubMed, Cochrane Library, Embase, and Web of Science, was conducted to collect randomized controlled trials about acupuncture for PHN. RevMan 5.3 and Stata 14.0 software were used for data analysis. Results This meta-analysis will provide additional and more robust evidence for acupuncture treatment of PHN. Our findings will assist clinicians in making treatment decisions. Conclusion This study will provide comprehensive and reliable evidence-based evidence for the treatment of PHN with acupuncture.

The aim of the study was to analyze acoustic emission (AE) signals generated in different magnetic fluid sealing processes to estimate the status of the seal. Based on a magnetic fluid rotary sealing experimental setup, the AE sensor is respectively attached to the shell at the corresponding position of the seal, and the external pressure is applied to the magnetic fluid seal by a gas supply system. As the pressure gradually increases, the magnetic fluid sealing rings under different pole teeth are gradually broken, and processes such as pressure transfer between the seal stages occur. These processes generate different AE signals, which are collected by the sensors. The results show that the root-mean-square values of AE signals generated at the moment of sealing failure are different from those generated before and after. At the same time, by analyzing the characteristic values of AE signals generated in the whole process, we can infer the time when the rupture begins under different pole pieces and further estimate the status of the magnetic fluid seal. For the first time, this research demonstrates the experimental and data analysis procedures of AE technology for magnetic fluid seals.