We report the results of searches for solar axions and galactic dark matter axions or axionlike particles with the CDEX-1 experiment at the China Jinping Underground Laboratory, using 335.6 kg days ...of data from a p-type point-contact germanium detector. The data are compatible with the background model, and no excess signals are observed. Limits of solar axions on the model-independent coupling gAe<2.5×10−11 from Compton, bremsstrahlung, atomic-recombination, and deexcitation channels and gANeff×gAe<6.4×10−17 from a Fe57 M1 transition at 90% confidence level are derived. Within the framework of the Dine-Fischler-Srednicki-Zhitnitskiy and Kim-Shifman-Vainshtein-Zakharov models, our results exclude the axion mass heavier than 0.9 and 177 eV/c2, respectively. The derived constraints for dark matter axions below 1 keV improve over the previous results.
Allograft vasculopathy (AV) is characterized by diffuse stenoses in the vasculature of solid organ transplants. Previously, we developed two humanized models showing that alloantibody and ischemia ...reperfusion injury (IRI) exacerbated T cell–mediated AV in human arterial xenografts in vivo. Herein we examined a causal role for terminal complement activation in both settings. IRI, in contrast to alloantibody, elicited widespread membrane attack complex (MAC) assembly throughout the vessel wall. Both alloantibody and IRI caused early (24 h) and robust endothelial cell (EC) activation localized to regions of intimal MAC deposition, indicated by increases in nuclear factor kappa B (NF‐κB)–inducing kinase, an MAC‐dependent activator of noncanonical NF‐kB, VCAM‐1 expression and Gr‐1+ neutrophil infiltration. Endothelial cell activation by alloantibody was inhibited by antimouse C5 mAb, but not by anti‐C5a mAb or by control mAb, implicating MAC as the primary target of anti‐C5 mAb. Antimouse C5 mAb significantly reduced alloantibody‐ and IRI‐enhanced T cell infiltration and AV‐like changes, including neointimal hyperplasia as well as intraluminal thrombosis in a subset of IRI‐treated arterial grafts. These results indicate that increased AV lesion formation in response to either alloantibody or IRI is dependent on complement C5 activation and, accordingly, inhibition of this pathway may attenuate AV.
Inhibition of terminal complement activation with anti‐C5 antibody prevents membrane attack complex assembly, blocks endothelial cell activation, and significantly reduces the severity of disease in two humanized mouse models of allograft vasculopathy.
We report findings of strong anomalies in both mutual inductance and inelastic Raman spectroscopy measurements of single-unit-cell FeSe film grown on Nb-doped SrTiO3, which occur near the temperature ...where the superconductinglike energy gap opens. Analysis suggests that the anomaly is associated with a broadened ferroelectric transition in a thin layer near the FeSe/SrTiO3 interface. The coincidence of the ferroelectric transition and gap-opening temperatures adds credence to the central role played by the film-substrate interaction on the strong Cooper pairing in this system. We discuss scenarios that could explain such a coincidence.
To investigate the pharmacist's knowledge about rational use of antimicrobials in Shanxi of China, so as to find out the problems and provide support for the management of antimicrobials.
A ...questionnaire survey was conducted, which included the basic information of the respondents, the basic knowledge about antimicrobial management and the related knowledge about antimicrobial drugs. SPSS 25.0 was used for statistical analysis.
A total of 462 pharmacists were investigated. The average score of the knowledge related to rational use of antimicrobials was 10.49 ± 4.05. It showed that the hospital type, grade, pharmacist's education, professional title and years of experience had effect on the pharmacist's knowledge level about antimicrobial drugs (P < 0.05). Multivariable logistic regression analysis showed that hospital grade and pharmacist's education were the main influencing factors (P < 0.05).
Pharmacists have insufficient knowledge about the rational use of antibacterial drugs. It is essential to strengthen the training in management regulations and application of antibacterial drugs.
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Summary
Symptoms of depression are common among patients before surgery. Depression may be associated with worse postoperative pain and other pain‐related outcomes. This review aimed to characterise ...the impact of pre‐operative depression on postoperative pain outcomes. We conducted a systematic review of observational studies that reported an association between pre‐operative depression and pain outcomes after major surgery. Multilevel random effects meta‐analyses were conducted to pool standardised mean differences and 95%CI for postoperative pain scores in patients with depression compared with those without depression, at different time intervals. A meta‐analysis was performed for studies reporting change in pain scores from the pre‐operative period to any time‐point after surgery. Sixty studies (n = 501,962) were included in the overall review, of which 18 were eligible for meta‐analysis. Pre‐operative depression was associated with greater pain scores at < 72 h (standardised mean difference 0.97 (95%CI 0.37–1.56), p = 0.009, I2 = 41%; moderate certainty) and > 6 months (standardised mean difference 0.45 (95%CI 0.23–0.68), p < 0.001, I2 = 78%; low certainty) after surgery, but not at 3–6 months after surgery (standardised mean difference 0.54 (95%CI ‐0.06–1.15), p = 0.07, I2 = 83%; very low certainty). The change in pain scores from pre‐operative baseline to 1–2 years after surgery was similar between patients with and without pre‐operative depression (standardised mean difference 0.13 (95%CI ‐0.06–0.32), p = 0.15, I2 = 54%; very low certainty). Overall, pre‐existing depression before surgery was associated with worse pain severity postoperatively. Our findings highlight the importance of incorporating psychological care into current postoperative pain management approaches in patients with depression.
Biochar has been exploited as a substitution of carbon black in the rubber industry and various biochars exhibit diverse reinforcing abilities due to the different compositions. This work aims at ...studying the effect of silica on the modification process and reinforcing performance through the comparison of three biochars with different contents of silica, pyrolytic rice husks (PRH, 34 wt%), pyrolytic bamboos (PB, 7 wt%) and pyrolytic corn cobs (PC, 0.4 wt%). The results reveal that PRH requires higher rotational speed (300 min
) than PB (200 min
) and PC (200 min
) to achieve similar particle sizes during the ball milling process because of the aggregations of higher silica content. Meanwhile, silica-rich pyrolytic biomass exhibits enhanced reinforcement on mechanical properties and thermal stability of rubber, and the elongation at break of vulcanizates continues to improve with increasing silica contents. Combined with the energy consumption and reinforcement, biochar containing a little amount of silica is more suitable to be widely used as bio-filler in rubber industry. This work should serve as a valuable reference to select appropriate biochar for the production of bio-fillers with high reinforcement.
Cynomorium songaricum Rupr., a holoparasitic plant that grows in the desert and has important dietetic and medical value. However, the medicinal efficacy of C. songaricum collected in different ...seasons varies greatly, and the difference in the transformation and accumulation of its major metabolites is still unclear. In this paper, UPLC-QTOF/MS and NMR were used to study the metabolomics of C. songaricum in different growth stages, so as to explore the metabolic differences and regularity of C. songaricum in different phenological periods during one cycle. The results showed that there were thirty and sixteen compounds with significant differences based on UPLC-QTOF/MS and NMR, respectively, which were distributed in flavonoids, organic acids, sugars and amino acids. Among them, the content of secondary metabolites such as catechins and procyanidins accumulated more in the Unearthing (U), and Maturing (M) stages, while other differential compounds accumulated more in the Tubercle (T), Sprouting (S) and Atrophy (A) stages. The differential metabolic pathways of C. songaricum in different stages involved in flavonoids, sugar, amino acid and other pathways. This provides scientific basis for understand of metabolites accumulation, quality evaluation and use as medicinal materials for C. songaricum.
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Patients with high tumor mutational burden (TMB) levels do not consistently respond to immune checkpoint inhibitors (ICIs), possibly because a high TMB level does not necessarily ...result in adequate infiltration of CD8+ T cells. Using bulk ribonucleic acid sequencing (RNA-seq) data from 9311 tumor samples across 30 cancer types, we developed a novel tool called the modulator of TMB-associated immune infiltration (MOTIF), which comprises genes that can determine the extent of CD8+ T cell infiltration prompted by a certain TMB level. We confirmed that MOTIF can accurately reflect the integrity and defects of the cancer-immunity cycle. By analyzing 84 human single-cell RNA-seq datasets from 32 types of solid tumors, we revealed that MOTIF can provide insights into the diverse roles of various cell types in the modulation of CD8+ T cell infiltration. Using pretreatment RNA-seq data from 13 ICI-treated cohorts, we validated the use of MOTIF in predicting CD8+ T cell infiltration and ICI efficacy. Among the components of MOTIF, we identified EMC3 as a negative regulator of CD8+ T cell infiltration, which was validated via in vivo studies. Additionally, MOTIF provided guidance for the potential combinations of programmed death 1 blockade with certain immunostimulatory drugs to facilitate CD8+ T cell infiltration and improve ICI efficacy.
Ovarian cancer is a leading killer of women, and no cure for advanced ovarian cancer is available. Alisertib (ALS), a selective Aurora kinase A (AURKA) inhibitor, has shown potent anticancer effects, ...and is under clinical investigation for the treatment of advanced solid tumor and hematologic malignancies. However, the role of ALS in the treatment of ovarian cancer remains unclear. This study investigated the effects of ALS on cell growth, apoptosis, autophagy, and epithelial to mesenchymal transition (EMT), and the underlying mechanisms in human epithelial ovarian cancer SKOV3 and OVCAR4 cells. Our docking study showed that ALS, MLN8054, and VX-680 preferentially bound to AURKA over AURKB via hydrogen bond formation, charge interaction, and π-π stacking. ALS had potent growth-inhibitory, proapoptotic, proautophagic, and EMT-inhibitory effects on SKOV3 and OVCAR4 cells. ALS arrested SKOV3 and OVCAR4 cells in G2/M phase and induced mitochondria-mediated apoptosis and autophagy in both SKOV3 and OVCAR4 cell lines in a concentration-dependent manner. ALS suppressed phosphatidylinositol 3-kinase/protein kinase B (Akt)/mammalian target of rapamycin (mTOR) and p38 mitogen-activated protein kinase pathways but activated 5'-AMP-dependent kinase, as indicated by their altered phosphorylation, contributing to the proautophagic activity of ALS. Modulation of autophagy altered basal and ALS-induced apoptosis in SKOV3 and OVCAR4 cells. Further, ALS suppressed the EMT-like phenotype in both cell lines by restoring the balance between E-cadherin and N-cadherin. ALS downregulated sirtuin 1 and pre-B cell colony enhancing factor (PBEF/visfatin) expression levels and inhibited phosphorylation of AURKA in both cell lines. These findings indicate that ALS blocks the cell cycle by G2/M phase arrest and promotes cellular apoptosis and autophagy, but inhibits EMT via phosphatidylinositol 3-kinase/Akt/mTOR-mediated and sirtuin 1-mediated pathways in human epithelial ovarian cancer cells. Further studies are warranted to validate the efficacy and safety of ALS in the treatment of ovarian cancer.
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