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To compare the diagnostic performance of contrast enhanced CT (CE-CT), CE-CT combined with non-enhanced MRI (NE-MRI) or contrast enhanced MRI (CE-MRI) for colorectal liver metastasis (CRLM). Sixty-six colorectal cancer patients with 198 focal liver lesions who underwent preoperative abdominal CE-CT and MRI examinations were included respectively. The images were assessed independently by two readers in three protocols (1: CE-CT, 2: CE-CT+NE-MRI, 3: CE-CT+CE-MRI). The diagnostic performance of each protocol was analyzed by receiver operating characteristic (ROC) curve and the areas under ROC (AUCs) were calculated and compared. The detection rates of protocol 2 were 90.9%-92.9% for liver lesions and 86.4%-89.6% for CRLM, and both significantly higher than protocol 1 of 82.8%-85.4% and 76.8%-80.8% (p <0.001-0.001), whereas similar to protocol 3 of 91.9%-94.4% and 87.2%-91.2% (p 0.250-1.000). The AUCs of protocol 2 were greater than protocol 1 for all lesions (0.914-0.934 vs. 0.779-0.799, p <0.001) and lesions < 10mm (0.726-0.776 vs. 0.528-0.561, p <0.001), and were not inferior to that of protocol 3 (0.929-0.949 in all lesions and 0.754-0.821 in lesion < 10mm, p 0.053-0.162). CE-CT combined with NE-MRI offered superior diagnostic performance for CRLM compared to CE-CT alone and showed comparable performance to CE-CT combined with CE-MRI. [ABSTRACT FROM AUTHOR]

In this study, the influence of the slenderness and diameter-thickness ratio on the interfacial bonding performance of hollow steel tube and Ultra-high toughness cementitious composite (UHTCC) was analysed by conducting push-out test. The study examined the specimens' failure modes, strain distribution curves along the longitudinal direction of the steel tube, load-slip behaviour, and interfacial bonding mechanisms. A finite element model was developed and validated against experimental findings. The results indicated that neither the hollow steel tube nor the UHTCC reached their respective yield strengths during testing. The strain on the inner surface of the steel tube increased with increasing load. The interface load-slip curve revealed distinct cementation, slip, and friction phases. The stress distribution and load-slip characteristics of the steel tube simulated via finite element analysis closely match the experimental outcomes. Subsequently, considering the influence of the steel tube length and diameter, a statistical regression analysis was performed to determine the bond strength and bond failure load of the hollow steel tube and UHTCC, yielding calculation formulas correlating these parameters with the slenderness and thickness ratios. An error analysis validated the derived formulas against experimental and simulation results. Furthermore, two variables, namely the shear modulus of the bonding layer and the wall thickness of steel tubes, were introduced for the finite-element simulation under linear elastic conditions, and the changes in the related properties of the hollow steel tube and UHTCC members in response to the variation of some factors were discussed and analysed. • The circular hollow steel tube and UHTCC composite structure was subjected to a push-out test. • The interfacial bonding mechanisms of the circular hollow steel tube and UHTCC composite structure were proposed. • The design method for the circular hollow steel tube and UHTCC composite structure under push-out test was developed. [ABSTRACT FROM AUTHOR]

The association between dietary diversity (DD) changes and mortality remains unclear. We aimed to investigate the association between DD changes and all-cause mortality among older people. A total of 17,959 participants with a mean age of 84.8 years old were enrolled at baseline. Food groups were collected at baseline and follow-up using simplified food frequency questionnaire (FFQ), and then overall, plant-based and animal-based dietary diversity score (DDS) were calculated. DDS changes were calculated using DDS at baseline and the first follow-up. The association between three DDS changes (overall, plant-based and animal-based DDS) and subsequent all-cause mortality were evaluated. Nonparametrically restricted cubic splines and a multivariable-adjusted Cox proportional hazards model were used to estimate HRs and 95% CIs. We documented 12,974 deaths over a 129,590 person-years of follow up. Compared with high-to-high DDS pattern, participants with lower overall DDS patterns had increased mortality risk with HRs (95%CI) of 1.39 (1.29–1.49), 1.53 (1.37–1.70), 1.38 (1.18–1.60) and 1.55 (1.31–1.83) for medium-to-medium, low-to-low, low-to-high and high-to-low patterns, respectively. And compared with high-to-high DDS pattern, the estimates were 1.34 (1.23–1.46), 1.49 (1.35–1.65), 1.43 (1.23–1.67) and 1.62 (1.40–1.88) for plant-based DDS, and 1.23 (1.15–1.31), 1.29 (1.20–1.40), 1.24 (1.12–1.37) and 1.28 (1.15–1.44) for animal-based DDS for medium-to-medium, low-to-low, low-to-high and high-to-low patterns, respectively. There was a U-shaped association between DDS change scores and mortality, and compared with participants with whose DDS remained stable, those with extreme declines and extreme improvements had higher risks of mortality with HRs (95% CI) of 1.15 (1.09–1.22) and 1.11 (1.04–1.17). Maintaining a lower DDS, extreme declines and extreme improvements in DDS were all associated with an increased risk of all-cause mortality. [ABSTRACT FROM AUTHOR]

The adsorption and utilization of Fe(Ⅲ) can be impeded by precipitation in anaerobic reactors. In this study, we investigated whether the bioavailability of Fe(Ⅲ) can be enhanced by EDTA-Fe(Ⅲ), thereby improving the stability of anammox system. Fe(Ⅲ) and EDTA-Fe(Ⅲ) were added to two parallel up-flow anaerobic sludge blanket (UASB) reactors, respectively. After 186 days of operation, when the nitrogen loading rate (NLR) was 0.8 g-N/L/d, the nitrogen removal rate (NRR) of R2 was stable at 0.675 g-N/L/d, which was higher than that of R1 at 0.557 g-N/L/d. The anammox activity of R2 reached its peak in phase Ⅲ (158.55 ± 4.53 mg-N/g-VSS/d), while the anammox activity of R1 was only 28.37 ± 5.96 mg-N/g-VSS/d. Moreover, in phase Ⅱ-Ⅴ, the bioavailability of Fe(Ⅲ) in R2 was increased by 15.63%, 38.37%, 65.90%, and 39.63%, respectively, compared with R1. The results showed that EDTA-Fe(Ⅲ) can prevent precipitation encasing anammox granular sludge, which can enhance substrate transport and Fe(Ⅲ) adsorption utilization. High throughput sequencing suggested that EDTA-Fe(Ⅲ) could better increase the abundance of anammox bacteria (AnAOB). In conclusion, this research proved that EDTA could increase the bioavailability of Fe(Ⅲ) and thereby ensuring the stability of the reactors. [Display omitted] • EDTA-Fe(Ⅲ) could enhance the bioavailability of Fe(Ⅲ) by 15.63%-65.90%. • EDTA-Fe(Ⅲ) could stabilize the Anammox granule sludge system. • EDTA-Fe(Ⅲ) could facilitate the granulation of Anammox sludge. • EDTA-Fe(Ⅲ) better increase the abundance of Anammox Bacteria. [ABSTRACT FROM AUTHOR]

Relaxin family peptide receptor 3 (RXFP3) is an A-class G protein-coupled receptor. It is implicated in the regulation of food intake and stress response upon activation by the neuropeptide relaxin-3. So far, preparation of enough functional RXFP3 for structural analysis is still challenging due to its integral membrane protein nature. In the present study, we overexpressed an N-terminally secretory maltose-binding protein (sMBP)-fused shortened human RXFP3 in prokaryotic host Escherichia coli . A small fraction of the sMBP-RXFP3 fusion protein could be integrated into the E. coli cell membrane and this fraction retained ligand binding function although the measured binding parameters were different from those of sMBP-RXFP3 overexpressed in mammalian cells due to different cell membrane lipids of the different host cells. Our present work paved the way for production of functional RXFP3 using the low-cost E. coli expression system. [ABSTRACT FROM AUTHOR]

A series of novel 6-(4-(4-methylpiperazin-1-yl)phenyl)- 1H -benzo[ d ]imidazole-based p21-activited kinase 4 (PAK4) inhibitors were designed and synthesized based on the structure of lead compound GNE-2861 and that of anticancer inhibitors reported in our previous studies. All target compounds so designed were preliminarily screened in vitro for anti-tumor potency through kinase inhibitory assays and MTT assays, which revealed that most compounds exhibited significant inhibitory effects on PAK4 enzyme as well as prominent antiproliferative activities against four cancer cell models (A549, NCI–H1975, MDA-MB-231 and SK-BR-3) and low damage to healthy cells. In particular, the hit compound 12i was identified as the most effective and rather selective compound both at the enzyme and cellular level. Meanwhile, molecular docking and dynamic studies disclosed that compound 12i could bind to PAK4 stably via multiple interactions applied between the compound and the enzyme. Further mechanism studies indicated that compound 12i could inhibit the proliferation and suppress the migratory potential of MDA-MB-231 cells by inhibiting the phosphorylation of PAK4 and LIMK1, arresting cell cycle in the G0/G1 phase, inducing apoptosis and promoting ROS production. Notably, compound 12i could effectively inhibit triple-negative breast cancer (TNBC) growth with little toxicity in the MDA-MB-231 cell xenograft model. Taken together, in vitro and in vivo results demonstrated that compound 12i possessed high drug potential as an inhibitor of PAK4 to inhibit the growth and metastasis of TNBC. [Display omitted] • Novel benzimidazole-derived PAK4 inhibitors were designed and synthesized. • Compound 12i (IC 50 = 7.68 nM) was more effective than the lead compound GNE-2861. • Compound 12i could inhibit the proliferation and migration of MDA-MB-231 cells. • Compound 12i could bind to PAK4 stably via multiple interactions. • Compound 12i significantly inhibited the growth of MDA-MB-231 xenograft tumors. [ABSTRACT FROM AUTHOR]

[Display omitted] • We performed the first bibliometric analysis aiming at the glucose oxidase-like activity of Au NPs. • New trends in regional distribution, institution and journal performance, collaborative patterns, and knowledge structures of this field were provided. • Au NPs could potentially be utilized to treat autoimmune diseases, inflammation, pathogens, etc. • The basic and clinical problems and new perspectives were presented. With the advancement of scientific research, an increasing number of studies on metal nanozymes, particularly Au NPs, have been conducted. They possess glucose oxidase (GOD)-like activity and peroxidase (POD)-like activity, with GOD-like activity receiving the most attention. However, there is a lack of research and summary on future trends in Au NPs in biomedical field. Therefore, we conducted a study on the GOD-like activity of Au NPs based on 158 relevant publications downloaded from the Web of Science Core Collection between 2007 and 2023, using citation metrics, authors, nations, institutions, cited references, and keywords. We found that Au NPs were initially utilized for glucose biosensors, glucose detection in human serum, and the detection of other carbohydrates and proteins. Researchers have recently focused on its application in oncotherapy and diabetic wound treatment. In addition to being utilized to treat autoimmune illnesses, inflammation, and other diseases, Au NPs may eventually replace insulin and antibiotics. We anticipate that the use of Au NPs will increase in the future. We hope this study will serve as a guide for future researchers so that Au NPs can be applied more broadly and competently. [ABSTRACT FROM AUTHOR]

P-glycoprotein (P-gp) is an important factor leading to multidrug resistance (MDR) in cancer treatment. The co-administration of anticancer drugs and P-gp inhibitors has been a treatment strategy to overcome MDR. In recent years, tyrosine kinase inhibitor Lapatinib has been reported to reverse MDR through directly interacting with ABC transporters. In this work, a series of P-gp inhibitors (1–26) was designed and synthesized by integrating the quinazoline core of Lapatinib into the molecule framework of the third-generation P-gp inhibitor Tariquidar. Among them, compound 14 exhibited better MDR reversal activity than Tariquidar. The docking results showed compound 14 displayed the L-shaped molecular conformation. Importantly, compound 14 increased the accumulation of Adriamycin (ADM) and rhodamine 123 (Rh123) in MCF7/ADM cells. Besides, compound 14 significantly increased ADM-induced apoptosis and inhibited the proliferation, migration and invasion of MCF7/ADM cells. It was also demonstrated that compound 14 significantly inhibited the growth of MCF7/ADM xenograft tumors by increasing the sensitivity of ADM. In summary, compound 14 has the potential to overcome MDR caused by P-gp. [Display omitted] • Novel P-gp inhibitors were designed, synthesized and bioevaluated. • Compound 14 exhibits better MDR reversal activity than third-generation P-gp inhibitor Tariquidar. • Compound 14 inhibited the efflux function of P-gp. • Compound 14 significantly inhibited the growth of MCF7/ADM xenograft tumors. [ABSTRACT FROM AUTHOR]

To identify and analyze the compounds that delay aging and extend the lifespan is an important aspect of the gerontology research. A number of compounds, including the ones with the antioxidant properties, have been shown to extend the lifespan of Caenorhabditis elegans . Here, we report that methyl 3,4-dihydroxybenzoate (MDHB), a small antioxidant molecule, prolongs the C. elegans ' lifespan under normal as well as stress conditions, delays the age-associated decline in the pharyngeal pumping rate, and obviously enhances the abilities of scavenging intracellular reactive oxygen species (ROS). To further investigate the mechanism underlying the anti-aging action of MDHB, microarray analyses were performed, which demonstrated that 13 genes were differentially expressed in worms treated with MDHB for 48 and 144 h in common. RNA interference of W06A7.4 (NM_001269697.1), the most significantly up-regulated gene, shortened the lifespan of worms by 14%, compared with the L4440 control. Our findings demonstrate that W06A7.4 is a potentially positive determinant of the MDHB induced C. elegans ' lifespan extension effect. [ABSTRACT FROM AUTHOR]