Search Results (25)

Background/Objectives: The location and distribution of excess fat, rather than overall adiposity, are stronger predictors of cardiometabolic risk and are commonly assessed using the waist-to-hip ratio (WHR). Fat distribution in women has a heritable component, yet the genetic factors that influence it remain poorly understood. We aim to assess the association between obesity-related polymorphisms with WHR and cardiometabolic risk in overweight and obese women. Methods: A cohort study was conducted in 512 women (56.1 ± 6.4 years; body mass index (BMI) ≥ 25 kg/m²). WHR was calculated, and participants were classified into android (WHR > 0.85) or gynoid (WHR ≤ 0.85) obesity groups. We genotyped 15 SNPs previously associated with obesity using TaqMan real-time PCR. Different genetic models (dominant, recessive, and allelic) were analysed, and bivariate and multivariate analyses were performed to compare the fat distribution groups. Results: Of the 15 SNPs studied, only 3 presented a significant association with WHR > 0.85. PSRC1 rs599839 in a dominant model (AA + GA vs. GG) with OR = 3.18 (p = 0.041), SLC30A8 rs1326634 in a recessive model (CC vs. TC + TT) (OR = 2.38; p = 0.004), both showing increased susceptibility to central obesity. KIF6 rs20455 offers protection in a recessive model (CC vs. TC + TT) with an OR of 0.47 (p = 0.043). After adjusted multivariate analysis, only SLC30A8 and diabetes remained independently associated with an increased risk of android obesity (OR = 2.50; p = 0.003 and OR = 3.63; p = 0.004, respectively). Conclusions: The SLC30A8 variant was significantly associated with android fat distribution and high cardiometabolic risk in overweight/obese women. Identifying genetic factors that influence fat distribution may help specify targeted lifestyle changes or pharmacological interventions to reduce risk. Full article

The eccentrically braced frame (EBF) is a typical structural system used in high-rise buildings. Current related design methods focus on the concrete and steel structures rather than on the complex composite structure. In addition, they tend to overlook the contribution of the energy-dissipation unit and its corresponding additional influence on the structure. In this study, a precast composite EBF structure is selected as a case study, including the partially steel-reinforced concrete (PSRC) beam and the concrete-filled steel tubular (CFST) column. A modified energy-based design method is proposed to leverage the excellent seismic performance of the precast composite EBF structure. The multi-stage energy-dissipation mechanism and the additional influence of the eccentric braces are systematically considered through the energy distribution coefficient and the layout of dampers. A case study of a 12-floor, three-bay precast composite EBF structure is conducted using a series of nonlinear time-history analyses. Critical seismic responses, including the maximum inter-story drift ratio, residual inter-story drift ratio, and peak acceleration, are systematically analyzed to evaluate the effectiveness of the proposed design theory. The distribution coefficient is recommended to range from 0.70 to 0.80 to balance the energy-dissipation contribution between the frame and the eccentric braces. In terms of the damper layout, the energy-dissipation contribution of the eccentric brace should differ among the lower, middle, and upper floors. Full article

Integrating Non-Orthogonal Multiple Access (NOMA) backscatter with Cognitive Radio (CR) can effectively alleviate the pressure of large-scale Internet of Things (IoT) device connections while reducing power consumption. In the downlink of NOMA backscatter-based CR networks (NB-CR), most researchers only consider the case of a single backscatter device (BD), ignoring the fact that multiple BDs can prolong device usage and enhance system robustness. The resource allocation (RA) problem is crucial in the downlink of NB-CR networks. Most existing RA algorithms focus on system throughput but rarely consider energy efficiency (EE). In this paper, we propose the RA problem for downlink communication (NBCR-RA) in NB-CR networks with multiple BDs. We jointly optimize power allocation coefficients and reflection coefficients (RCs) to maximize EE. We model the NBCR-RA problem as a non-convex problem and divide it into two subproblems: power allocation optimization and RC optimization. Firstly, we propose a Lagrange-based power allocation optimization (L-PA) algorithm to obtain the optimal power allocation coefficients. Secondly, we design an RC optimization algorithm, PS-RC, based on a particle swarm algorithm to determine the optimal RCs. Finally, we validate the superiority of L-PA and PS-RC algorithms in terms of EE. Through multiple experiments, we obtained a $95\%$ confidence interval of [10.5552, 10.6465]. Full article

In this paper, the plastic properties of prestressed high-strength steel reinforced concrete (PHSSRC) beams are studied, by performing static load tests on eight built-in Q460 and Q690 prestressed high-strength steel reinforced concrete continuous beams and one built-in Q355 prestressed steel reinforced concrete (PSRC) continuous beam. The design parameters of the specimens were the steel strength grade, the steel ratio, the comprehensive reinforcement ratio, and the stirrup ratio. The failure mode, load–deflection curve, internal force redistribution ability, curvature ductility, plastic hinge performance, and moment modification coefficient of continuous beams under the influence of various parameters were analyzed to measure the plastic performance of the continuous beams. These results show that after the plastic hinge is formed in the middle support and mid-span of the prestressed high-strength steel reinforced concrete continuous beam, the test beam eventually becomes a rotating mechanism and is destroyed with increasing load. The built-in high-strength steel can significantly improve the bearing capacity of the specimen, and the maximum increase in the bearing capacity is 37.3%. The specimen still has a high bearing capacity after reaching the ultimate bearing capacity. With a decrease in the steel ratio, the degree of internal force redistribution is deepened, the curvature ductility is improved, and the plastic performance is enhanced. Increasing the comprehensive reinforcement ratio and the stirrup ratio can improve the plastic performance of the specimen. The calculation formula of the equivalent plastic hinge zone length is proposed. The calculation formula of the moment modification coefficient, with the relative plastic rotation angle and relative compression zone height as independent variables, is established. When the relative plastic rotation angle is not greater than 0.829 × 10⁻⁵, the moment modification coefficient increases with increasing plastic rotation angle and is not greater than 0.37. In the range of 0.3~0.4, the moment modification coefficient decreases with increasing height of the relative compression zone. Full article

A horizontal magnetic disturbance accompanying the co-seismic earthquake light (EQL) of the M7.3 Fukushima earthquake of 16 March 2022 was detected by a fluxgate magnetometer installed at the KAK station, which is 270 km south of the EQL and 210 km west of the epicenter. The instantaneous change of the declination component of the geomagnetic field reached about 1.7″, much exceeding the threshold of three-fold error (0.72″). Considering the direction information of the geomagnetic data, the horizontal magnetic disturbance vector was further analyzed, which manifested the normal of the horizontal magnetic disturbance vector passing through the position of the EQL. Combined with the experimental results of pressure-simulated rock current (PSRC), the mechanism of the EQL and the geomagnetic anomaly was proposed to interpret the spatiotemporal correlation between the EQL and the horizontal magnetic disturbance vector, which should be a manifest of the induced magnetic horizontal vector (IMHV), attributed to the upward seismic PSRC. Different from previous precursor studies on geomagnetic disturbance on the power spectrum, vertical component, or polarization, this paper focuses on the direction information of the horizontal magnetic disturbance vector, which could be further applied to locate potential seismogenic zones based on the IMHVs observed by multiple geomagnetic stations. Full article

Cancer is a serious health problem due to the complexity of establishing an effective treatment. The purpose of this work was to evaluate the activity of a triazaspirane as a migration and invasion inhibitor in PC3 prostatic tumor cells through a possible negative regulation of the FAK/Src signal transduction pathway and decreased secretion of metalloproteinases 2 and 9. Molecular docking analysis was performed using Moe 2008.10 software. Migration (wound-healing assay) and invasion (Boyden chamber assay) assays were performed. In addition, the Western blot technique was used to quantify protein expression, and the zymography technique was used to observe the secretion of metalloproteinases. Molecular docking showed interactions in regions of interest of the FAK and Src proteins. Moreover, the biological activity assays demonstrated an inhibitory effect on cell migration and invasion, an important suppression of metalloproteinase secretion, and a decrease in the expression of p-FAK and p-Src proteins in treated PC3 cells. Triazaspirane-type molecules have important inhibitory effects on the mechanisms associated with metastasis in PC3 tumor cells. Full article

Bioceramics are calcium-phosphate-based materials used in medical and dental implants for replacing or repairing damaged bone tissues; however, the effect of bioceramic sintering on the intracellular signaling pathways remains unknown. In order to address this, we analyzed the impact of sintering on the cell signaling pathways of osteoblast cells using sintered and non-sintered hydroxyapatite (HA) and beta-tricalcium phosphate (β-TCP). X-ray diffraction indicated that only the morphology of HA was affected by sintering; however, the sintered bioceramics were found to have elevated the calcium concentrations in relation to the non-sintered variants. Both bioceramics inhibited the JNK signaling pathway; the sintered HA exhibited half the value of the non-sintered variant, while the sintered β-TCP rarely expressed a p-JNK value. The total Src and Raptor protein concentrations were unaffected by the sintering, while the p-Src concentrations were decreased. The p-EGFR signaling pathway was regulated by the non-sintered bioceramics, while the p-p38 concentrations were reduced by both the sintered β-TCP and HA. All of the bioceramics attenuated the total AKT concentrations, particularly the non-sintered HA, and the AKT phosphorylation concentration, except for the non-sintered β-TCP. Thus, the sintering of bioceramics affects several intracellular signaling pathways. These findings may elucidate the bioceramic function and expand their application scope as novel substrates in clinical applications. Full article

A cluster of three genes CELSR2, PSRC1, and SORT1 has been associated with cardiovascular diseases. Thus, the aim of this study was (i) to perform a systematic review and updated meta-analysis of the association of three polymorphisms (rs646776, rs599839, and rs464218) of this cluster with cardiovascular diseases, and (ii) to explore by PheWAS signals of the three SNPs in cardiovascular diseases and to evaluate the effect of rs599839 with tissue expression by in silico tools. Three electronic databases were searched to identify eligible studies. The meta-analysis showed that the rs599839 (allelic OR 1.19, 95% CI 1.13–1.26, dominant OR 1.22, 95% CI 1.06–1.39, recessive OR 1.23, 95% CI 1.15–1.32), rs646776 (allelic OR 1.46, 95% CI 1.17–1.82) polymorphisms showed an increased risk for cardiovascular diseases. PheWas analysis showed associations with coronary artery disease and total cholesterol. Our results suggest a possible involvement of the CELSR2-PSRC1-SORT1 cluster variants in the risk association of cardiovascular diseases, particularly coronary artery disease. Full article

Doxorubicin (Dox) is one of the most frequently prescribed anti-cancer drugs. However, treatment with Dox is limited due to cumulative cardiotoxicity. 3-O-β-d-Sophorosylkaempferol-7-O-{3-O-[2(E)-2,6-dimethyl-6-hydroxyocta-2,7-dienoyl]}-α-L-rhamnoside (F-A), kaempferol 3-sophoroside 7-rhamnoside (F-B), and hippophanone (F-C) were successfully obtained by purification and separation of seabuckthorn seed residue in our previous research. This study was undertaken to investigate the protective effect of three flavonoids against Dox-induced H9c2 cell apoptosis. Cell proliferation was detected by MTT assay. 2′,7′-Dichlorofluorescein diacetate (DCFH-DA) was used to determine the production of intracellular reactive oxygen species (ROS). ATP content was measured using an assay kit. Transmission electron microscopy (TEM) was used to observe changes in mitochondrial ultrastructure. The expression levels of proteins (p-JNK, JNK, p-Akt, Akt, p-P38, P38, p-ERK, ERK, p-Src, Src, Sab, IRE1α, Mfn1, Mfn2, and cleaved caspase-3) were evaluated by Western blot. Molecular docking was performed using AutoDock Vina. The three flavonoids could significantly relieve Dox-induced cardiac injury and inhibit cardiomyocyte apoptosis. The mechanisms were mainly related to the stability of mitochondrial structure and function maintained by suppressing the production of intracellular ROS, p-JNK and cleaved caspase-3, and increasing ATP contents and protein expression of mitochondrial mitofusin (Mfn1, Mfn2), Sab and p-Src. Pretreatment with flavonoids from Hippophae rhamnoides Linn. can reduce Dox-induced H9c2 cell apoptosis based on the ‘JNK-Sab-Ros’ signal pathway. Full article

Many species in the genus Guettarda are known to exert anti-inflammatory effects and are used as traditional medicinal plants to treat various inflammatory symptoms. However, no studies on the inflammatory activities of Guettarda crispiflora Vahl have been reported. The aim of the study was to investigate in vitro and in vivo the anti-inflammatory effects of a methanol extract of Guettarda crispiflora Vahl (Gc-ME). To determine the anti-inflammatory activity of Gc-ME, lipopolysaccharide (LPS)-, poly(I:C)-, or Pam3CSK4-treated RAW264.7 cells, HCl/EtOH- and LPS-treated mice were employed for in vitro and in vivo tests. LPS-induced nitric oxide production in RAW264.7 cells was determined by Griess assays and cytokine gene expression in LPS-activated RAW264.7 cells, confirmed by RT- and real-time PCR. Transcriptional activation was evaluated by luciferase reporter gene assay. Target protein validation was assessed by Western blot analysis and cellular thermal shift assays (CETSA) with LPS-treated RAW264.7 and gene-transfected HEK293 cells. Using both a HCl/EtOH-induced gastritis model and an LPS-induced lung injury model, inflammatory states were checked by scoring or evaluating gastric lesions, lung edema, and lung histology. Phytochemical fingerprinting of Gc-ME was observed by using liquid chromatography–mass spectrometry. Nitric oxide production induced by LPS and Pam3CSK4 in RAW264.7 cells was revealed to be reduced by Gc-ME. The LPS-induced upregulation of iNOS, COX-2, IL-6, and IL-1β was also suppressed by Gc-ME treatment. Gc-ME downregulated the promotor activities of AP-1 and NF-κB triggered by MyD88- and TRIF induction. Upstream signaling proteins for NF-κB activation, namely, p-p50, p-p65, p-IκBα, and p-Src were all downregulated by Ch-EE. Moreover, Src was revealed to be directly targeted by Gc-ME. This extract, orally treated strongly, attenuated the inflammatory symptoms in HCl/EtOH-treated stomachs and LPS-treated lungs. Therefore, these results strongly imply that Guettarda crispiflora can be developed as a promising anti-inflammatory remedy with Src-suppressive properties. Full article

Hydrocephalus induced by intraventricular hemorrhage (IVH) is associated with unfavorable prognosis. The increased permeability of choroid plexus and breakdown of the blood–brain barrier (BBB) was reported as a prominent mechanism of IVH-induced hydrocephalus, and vascular endothelial–cadherin (VE–cadherin) was demonstrated to be relevant. Metformin was reported to protect endothelial junction and preserve permeability widely; however, its role in hydrocephalus remains unclear. In this study, the decreased expression of VE–cadherin in the choroid plexus, accompanied with ventricle dilation, was investigated in an IVH rat model induced by intraventricular injection of autologous blood. Metformin treatment ameliorated hydrocephalus and upregulated VE–cadherin expression in choroid plexus meanwhile. We then observed that the internalization of VE–cadherin caused by the activation of vascular endothelial growth factor (VEGF) signaling after IVH was related to the occurrence of hydrocephalus, whereas it can be reversed by metformin treatment. Restraining VEGF signaling by antagonizing VEGFR2 or inhibiting Src phosphorylation increased the expression of VE–cadherin and decreased the severity of hydrocephalus after IVH. Our study demonstrated that the internalization of VE–cadherin via the activation of VEGF signaling may contribute to IVH-induced hydrocephalus, and metformin may be a potential protector via suppressing this pathway. Full article

Recently, many manufacturers have been developing or producing imitation crab sticks (ICSs) that are highly similar to real snow crab leg meat (RC). This study evaluated the similarities between commercial ICSs and RC based on the analysis of physicochemical and sensory properties. Normal ICS (NS) and premium ICSs either with real crab leg meat (PS-RC) or without it (PS) were compared with RC. The sensory evaluation results showed that PS and NS had the highest and lowest levels of similarity to RC, respectively. The carbohydrate contents of ICSs (10–23%) were higher than that of RC (0.5%). Among ICSs, PS showed more similarity with RC than NS and PS-RC in terms of gel strength and texture profiles. PS-RC and PS showed a microstructural pattern that slightly imitated the muscle fiber arrangement of RC. The electric tongue analysis of taste compounds, such as sugars, free amino acids, and nucleotides, showed that the taste profile of ICSs is distinctly different from that of RC. The electronic nose analysis identified 32 volatile compounds, while the principal component analysis using electronic nose data successfully distinguished three clusters: PS-RC and PS, RC, and NS. Our results could provide useful information for the development of ICSs with higher similarity to RC. Full article

Malus baccata (L.) Borkh. is a widely used medical plant in Asia. Since the anti-inflammatory mechanism of this plant is not fully understood, the aim of this study was to explore the anti-inflammatory function and mechanism of Malus baccata (L.) Borkh. methanol extract (Mb-ME). For in vitro experiments, nitric oxide production assay, PCR, overexpression strategy, immunoblotting, luciferase reporter assay, and immunoprecipitation were employed to explore the molecular mechanism and the target proteins of Mb-ME. For in vivo experiments, an HCl/EtOH-induced gastritis mouse model was used to confirm the anti-inflammatory function. Mb-ME showed a strong ability to inhibit the production of nitric oxide and the expression of inflammatory genes. Mb-ME decreased NF-κB luciferase activity mediated by MyD88 and TRIF. Moreover, Mb-ME blocked the activation of Src, Syk, p85, Akt, p50, p60, IKKα/β, and IκBα in LPS-induced RAW264.7 cells. Overexpression and immunoprecipitation analyses suggested Syk and Src as the target enzymes of Mb-ME. In vitro results showed that Mb-ME could alleviate gastritis and relieve the protein expression of p-Src, p-Syk, and COX-2, as well as the gene expression of COX-2 and TNF-α. In summary, this study implied that Mb-ME performs an anti-inflammatory role by suppressing Syk and Src in the NF-κB signaling pathway, both in vivo and in vitro. Full article

Background and Aims: Dyslipidemia and cardiovascular diseases (CVD) are comorbidities of nonalcoholic fatty liver disease (NAFLD), which ranges from steatosis to hepatocellular carcinoma (HCC). The rs599839 A>G variant, in the CELSR2-PSRC1-SORT1 gene cluster, has been associated CVD, but its impact on metabolic traits and on the severity liver damage in NAFLD has not been investigated yet. Methods: We evaluated the effect of the rs599839 variant in 1426 NAFLD patients (Overall cohort) of whom 131 had HCC (NAFLD-HCC), in 500,000 individuals from the UK Biobank Cohort (UKBBC), and in 366 HCC samples from The Cancer Genome Atlas (TCGA). Hepatic PSRC1, SORT1 and CELSR2 expressions were evaluated by RNAseq (n = 125). Results: The rs599839 variant was associated with reduced circulating LDL, carotid intima-media thickness, carotid plaques and hypertension (p < 0.05) in NAFLD patients and with protection against dyslipidemia in UKBBC. The minor G allele was associated with higher risk of HCC, independently of fibrosis severity (odds ratio (OR): 5.62; 95% c.i. 1.77–17.84, p = 0.003), poor prognosis and advanced tumor stage (p < 0.05) in the overall cohort. Hepatic PSRC1, SORT1 and CELSR2 expressions were increased in NAFLD patients carrying the rs599839 variant (p < 0.0001). SORT1 mRNA levels negatively correlated with circulating lipids and with those of genes involved in lipoprotein turnover (p < 0.0001). Conversely, PSRC1 expression was positively related to that of genes implicated in cell proliferation (p < 0.0001). In TCGA, PSRC1 over-expression promoted more aggressive HCC development (p < 0.05). Conclusions: In sum, the rs599839 A>G variant is associated with protection against dyslipidemia and CVD in NAFLD patients, but as one it might promote HCC development by modulating SORT1 and PSRC1 expressions which impact on lipid metabolism and cell proliferation, respectively. Full article

Anoikis is a type of apoptosis induced by cell detachment from the extracellular matrix (ECM), which removes mislocalized cells. Acquisition of anoikis resistance is critical for cancer cells to survive during circulation and, thus, metastasize at a secondary site. Although the sensitization of cancer cells to anoikis is a potential strategy to prevent metastasis, the mechanism underlying anoikis resistance is not well defined. Although family with sequence similarity 188 member B (FAM188B) is predicted as a new deubiquitinase (DUB) member, its biological function has not been fully studied. In this study, we demonstrated that FAM188B knockdown sensitized anoikis of lung cancer cell lines expressing WT-EGFR (A549 and H1299) or TKI-resistant EGFR mutant T790M/L858R (H1975). FAM188B knockdown using si-FAM188B inhibited the growth of all three human lung cancer cell lines cultured in both attachment and suspension conditions. FAM188B knockdown resulted in EGFR downregulation and thus decreased its activity. FAM188B knockdown decreased the activities of several oncogenic proteins downstream of EGFR that are involved in anoikis resistance, including pAkt, pSrc, and pSTAT3, with little changes to their protein levels. Intriguingly, si-FAM188B treatment increased EGFR mRNA levels but decreased its protein levels, which was reversed by treatment with the proteasomal inhibitor MG132, indicating that FAM188B regulates EGFR levels via the proteasomal pathway. In addition, cells transfected with si-FAM188B had decreased expression of FOXM1, an oncogenic transcription factor involved in cell growth and survival. Moreover, FAM188B downregulation reduced metastatic characteristics, such as cell adhesion, invasion, and migration, as well as growth in 3D culture conditions. Finally, tail vein injection of si-FAM188B-treated A549 cells resulted in a decrease in lung metastasis and an increase in mice survival in vivo. Taken together, these findings indicate that FAM188B plays an important role in anoikis resistance and metastatic characteristics by maintaining the levels of various oncogenic proteins and/or their activity, leading to tumor malignancy. Our study suggests FAM188B as a potential target for controlling tumor malignancy. Full article