In situ atomic observations of aggregation growth and evolution of penta-twinned gold nanocrystals.

The twin boundaries and inherent lattice strain of five-fold twin (5-FT) structures offer a promising and innovative approach to tune nanocrystal configurations and properties, enriching nanomaterial performance. However, a comprehensive understanding of the nonclassical growth models governing 5-FT nanocrystals remains elusive, largely due to the constraints of their small thermodynamically stable size and complex twin configurations. Here, we conducted in situ investigations to elucidate the atomic-scale mechanisms driving size-dependent and twin configuration-related aggregation phenomena between 5-FT and other nanoparticles at the atomic scale. Our results reveal that surface diffusion significantly shapes the morphology of aggregated nanoparticles, promoting the symmetrical formation of 5-FT, especially in smaller nanoparticles. Moreover, the inherent structural characteristics of 5-FT mitigate the dominance of surface diffusion in its morphological evolution, retarding the aggregation evolution process and fostering intricate twin structures. These findings contribute to advancing our capacity to manipulate the configuration of twinned particles, enabling more predictable synthesis of functional nanomaterials for advanced engineering applications.

The Association between Non-Alcohol Liver Fatty Disease and Coronary Artery Calcification: A Two-Sample Mendelian Randomization Study.

BACKGROUND: Although prior observational studies have suggested that patients with non-alcohol fatty liver disease (NAFLD) may have a higher risk of coronary artery calcification (CAC), these findings remain controversial. This study aimed to explore the causal association between NAFLD and CAC at genetic level by two-sample Mendelian randomization (MR) analysis. METHOD: Utilizing summary-level data from multiple large-scale genome-wide association studies (GWAS) in European populations, a two-sample MR analysis was initially conducted to explore the potential causal association between NAFLD and CAC. The results of the MR analysis were pooled through random-effect meta-analysis. The inverse variance weighting (IVW) method served as the primary approach for MR analysis. Additionally, the weighted median, MR-Egger and MR-pleiotropy residual sum and outlier (MR-PRESSO) methods was applied for sensitivity analysis. Summary-level data on liver fatty content was utilized for validation analysis, while summary-level data on cirrhosis served as positive control, further ensuring the validity and robustness of our findings. Reverse MR analysis was performed to assess the association between CAC and NAFLD, employing instrument variables derived from CAC. RESULTS: The MR analysis indicated that genetically predicted NAFLD had no effects on the risk of CAC (Beta: 0.01, 95% CI: -0.02 to 0.03, P = 0.74). Likewise, the reverse MR analysis found no significant genetic association between CAC and NAFLD (OR: 1.00, 95% CI: 0.96 to 1.06, P = 0.88). Validation analysis yielded consistent results, showing no significant association between fatty liver content and CAC. CONCLUSION: Our two-sample MR analysis did not support that there is a causal association between NAFLD and CAC at genetic level. The association between NAFLD and CAC reported in some previous observational studies may rely on NAFLD complicated with metabolic disorders, rather than being directly linked to the hepatic steatosis.

This study used a genetic approach to investigate whether non-alcoholic fatty liver disease (NAFLD) directly causes coronary artery calcification (CAC), finding no evidence of a causal relationship at genetic level. The Mendelian randomization (MR) analysis revealed no genetic association between NAFLD and the risk of developing CAC, as well as no reverse association from CAC to NAFLD. The findings suggest that previous reports association between NAFLD and CAC may be influenced by metabolic disorders rather than a direct connection between the two conditions.

Suppression of RCAN1 alleviated lipid accumulation and mitochondrial fission in diabetic cardiomyopathy.

BACKGROUND: Although metabolic disturbance is a characteristic of diabetic cardiomyopathy (DbCM), the detailed pathogenesis of DbCM remains unknown. METHODS: We used a heart transplantation (HTx) cohort to explore the effect of diabetes mellitus on heart failure (HF) progression dependent of myocardium. Microscopic and ultramicroscopic pathology were used to depict the pathological features of human myocardium of DbCM. We performed targeted metabolomics to characterize the metabolic phenotype of human DbCM. Transcriptomics data were analyzed and weighted gene co-expression network analysis was performed to explore the potential upstream regulator for metabolic remodeling of DbCM. In vivo and in vitro experiments were further conducted to demonstrate the therapeutic effects and molecular mechanisms. RESULTS: DbCM promoted the progression of HF and increased death or HF-rehospitalization after HTx. Lipid accumulation and mitochondrial fission were the obvious pathological features of DbCM myocardium. The concentrations of C14:0-CoA and C16:1-CoA were significantly increased in the myocardium, and they were positively correlated with the accelerated HF progression and RCAN1 expression in DbCM patients. Knockdown of RCAN1 improved cardiac dysfunction, lipid accumulation, and mitochondrial fission in db/db mice. In vitro studies showed that RCAN1 knockdown improved mitochondrial dysfunction in DbCM cardiomyocytes via the RCAN1-p-Drp1 Ser616 axis. CONCLUSIONS: Diabetes is associated with faster progression of HF and causes poor prognosis after HTx, accompanied by metabolic remodeling in the myocardium. Accumulation of long chain acyl-CoA in the myocardium is the metabolic hallmark of human DbCM and is associated with more rapid disease progression for DbCM patients. Upregulation of RCAN1 in the myocardium is associated with the metabolic signatures of DbCM and RCAN1 is a potential therapeutic target for DbCM.

Partial CArdiac Denervation to Prevent Postoperative Atrial Fibrillation After Coronary Artery Bypass Grafting (pCAD-POAF): Study Protocol for a Randomized Controlled Trial.

Postoperative atrial fibrillation (POAF) is commonly seen in patients who underwent coronary artery bypass grafting (CABG), increasing the risk of morbidity, mortality, and hospital expenses. This study aimed to evaluate the effect of partial cardiac denervation, which is achieved by cutting off the ligament of Marshall and resecting the fat pad along the Waterston groove, on the prevention of POAF after CABG. Patients planned for CABG at our center were screened for eligibility in this study. A total of 430 patients were randomized into the intervention (partial cardiac denervation) group and control group. Intraoperative high-frequency electrical stimulation and further histologic analysis were performed in a certain number of patients to confirm the existence of ganglia. All patients were continuously monitored for the incidence of POAF through an electrophysiologic device until the sixth day postoperatively, and required to complete a 30-day follow-up (12-lead electrocardiogram and echocardiogram assessment) after discharge. The primary end point is the incidence of POAF, whereas the secondary end points are the cost-effectiveness and safety outcomes. In conclusion, this trial will evaluate whether partial cardiac denervation through cutting off the ligament of Marshall and resecting the fat pad along the Waterston groove can reduce the incidence of POAF after CABG. If this procedure is revealed to be effective and safe, it may provide a potential therapeutic approach to prevent POAF in this group of patients.

Clinical outcomes of on-pump versus off-pump coronary-artery bypass surgery: a meta-analysis.

BACKGROUND: The ongoing debate regarding off-pump coronary artery bypass grafting (CABG) and on-pump CABG has endured for over three decades. Although numerous randomized controlled trials (RCTs) and meta-analyses have been reported, new evidence has emerged. Therefore, an updated and comprehensive meta-analysis to guide clinical practice is essential. MATERIALS AND METHODS: A comprehensive search for eligible articles published after 2000, reporting RCTs involving at least 100 patients and comparing off-pump CABG with on-pump CABG, was performed throughout the databases including Embase, Ovid Medline, and Web of Science. The primary interested outcomes included the short-term incidence of stroke and long-term mortality. The primary analysis utilized fixed-effect model with the inverse variance method. The Grade of Recommendations Assessment, Development, and Evaluation (GRADE) was used to evaluate the certainty of evidence. RESULTS: After thorough screening, 39 articles were included, consisting of 28 RCTs and involving a total of 16 090 patients. Off-pump CABG significantly reduced the incidence of short-term stroke (1.27 vs. 1.78%, OR: 0.74, P =0.03, high certainty). However, it was observed to be associated with increased mid-term coronary reintervention (2.77 vs. 1.85%, RR: 1.49, P <0.01, high certainty) and long-term mortality (21.8 vs. 21.0%, RR: 1.09, P =0.02, moderate certainty). CONCLUSIONS: Off-pump CABG significantly reduces the short-term incidence of stroke, but it also increases the incidence of mid-term coronary reintervention. Moreover, it may increase long-term mortality.

Coronary endarterectomy combined with coronary artery bypass grafting might decrease graft patency: A cohort study.

BACKGROUND: Little is known about the graft patency after coronary endarterectomy (CE) combined with coronary artery bypass grafting (CABG). This study aimed to investigate the graft patency after CABG + CE. METHODS: Eligible patients hospitalized at our center during September 2008 and July 2022 with complete follow-up coronary angiographic data available were retrospectively enrolled. The primary end point was the follow-up graft patency of CE targets. Logistic regression was performed to explore the potential predictors of the CE-targeted graft failure. RESULTS: A total of 160 patients (age: 59.4 ± 9.3 years, male: 75.6%) were enrolled, and 560 grafts were anastomosed. CE was performed on 166 sites, including LAD (36.1%), right coronary artery (RCA, 48.2%), left circumflex artery (9.6%), and diagonal branches (6.0%). Postoperative myocardial infarction was observed in 7 (4.4%) of the patients. During a median follow-up of 12.1 months, the CE-targeted graft patency was 69.9%. The CE-targeted graft patency rate was much higher among the LAD-CE patients than the non-LAD-CE patients (80.0% vs. 64.2%, P = 0.032) but lower than non-endarterectomized LAD (80.0% vs. 92.9%, P = 0.013). No difference was observed regarding the graft patency between off-pump and on-pump surgery (P = 0.585). In the logistic regression, RCA-CE was associated with an increased risk of graft failure even after multiple adjustments (odds ratio: 2.35, 95% confidence interval: 1.05-5.28, P = 0.028). CONCLUSIONS: CABG + CE might be associated with decreased graft patency, especially in those who received RCA-CE, irrespective of surgical technique or antiplatelet/anticoagulation regimen. A multi-center prospective, possibly randomized study with a larger sample size is warranted.

Killing two birds with one stone: A therapeutic copper-loaded bio-patch promoted abdominal wall repair via VEGF pathway.

Hernia and life-threatening intestinal obstruction often result from abdominal wall injuries, and the regeneration of abdominal wall defects is limited due to the lack of biocompatible, antibacterial and angiogenic scaffolding materials for treating injured tissues. Taking inspiration from the facile preparation of dopamine polymerization and its surface modification technology, in this study, multi-therapeutic copper element was introduced into porcine small intestinal submucosa (SIS) bio-patches through polydopamine (PDA) deposition, in order to regenerate abdominal wall injury. In both in vitro antibacterial assays, cytocompatibility assays and in vivo abdominal wall repair experiments, the SIS/PDA/Cu bio-patches exhibited robust antibacterial efficiency (＞99%), excellent biocompatibility to cells (＞90%), and enhanced neovascularization and improved collagen maturity compared to other commercially available patches (3.0-fold higher than the PP mesh), due to their activation of VEGF pathway. These findings indicated the bio-patch was a promising application for preventing visceral adhesion, bacterial infection, and promoting soft tissue regeneration.

Risk Prediction After Coronary Artery Bypass Grafting Combined With Coronary Endarterectomy.

Coronary endarterectomy (CE) combined with coronary artery bypass grafting (CABG) is used for complete revascularization of diffusely diseased coronary arteries. Nevertheless, studies reported an increased risk after this procedure. Therefore, risk prediction in these patients is essential. Patients who underwent CABG + CE during September 2008 and July 2022 at our center were retrospectively recruited. A total of 32 characteristics were analyzed. The least absolute shrinkage and selection operator regression were used for the feature selection, and multivariable Cox regression was applied to develop a nomogram for risk prediction. The primary outcome was the major adverse cardiovascular and cerebrovascular events (MACCE), a composite of all-cause death, nonfatal myocardial infarction, repeat revascularization, and stroke. A total of 570 patients with 601 CE targets, including left anterior descending (41.4%), right coronary artery (43.9%), left circumflex artery (6.8%), and diagonal branches/intermedius ramidus (8.0%), were enrolled. The mean age was 61.0 ± 8.9 years, and 77.7% were men. A total of 4 features were identified as the predictors of MACCE, including age ≥65 years (hazard ratio [HR] 2.12, 95% confidence interval [CI] 1.38 to 3.25, p <0.001), left main disease (HR 2.56, 95% CI 1.46 to 4.49, p = 0.001), mitral regurgitation (≥mild, HR 1.91, 95% CI 1.01 to 3.65, p = 0.049), and left anterior descending endarterectomy (HR 1.69, 95% CI 1.09 to 2.62, p = 0.018), and a nomogram for the 1- and 3-year MACCE prediction was developed. The model showed relatively good discrimination (C-index 0.68), calibration, and clinical usefulness. In conclusion, the nomogram provides estimation of the 1- and 3-year MACCE risk after CABG + CE.

Impact of concomitant mitral valve surgery on the clinical outcomes of patients with moderate functional mitral regurgitation and HFpEF undergoing aortic valve replacement: a cohort study.

BACKGROUND: Functional mitral regurgitation (FMR) worsens the prognosis of patients with heart failure with preserved ejection fraction (HFpEF). While concomitant mitral valve surgery (MVS) is recommended for severe FMR during aortic valve replacement (AVR), the optimal treatment of moderate FMR, especially in those with HFpEF, remains unclear. This study aimed to evaluate the effect of MVS in patients with moderate FMR and HFpEF undergoing AVR. METHODS: A total of 212 consecutive patients (AVR: 34.0%, AVR-MVS: 66.0%) during 2010 and 2019 were enrolled. Survival outcomes were compared. Inverse probability treatment weighting (IPTW) was used to balance the baseline characteristics. Kaplan-Meier curve and log-rank test were applied to compare the survival outcomes. The primary endpoint was the overall mortality. RESULTS: The mean age was 58.9 [Formula: see text] 11.9 years, and 27.8% of them were female. During a median follow-up of 16.4 months, AVR-MVS did not reduce the risk of mid-term MACCE (hazard ratio [HR]: 1.53, 95% confidence interval [CI]: 0.57-4.17, Plog-rank = 0.396), while it showed a tendency toward higher MACCE risk in the IPTW analysis (HR: 2.62, 95% CI: 0.84-8.16, Plog-rank = 0.096). In addition, AVR-MVS increased the risk of mortality as compared to isolated AVR (0 vs. 10%, Plog-rank = 0.016), which was sustained in the IPTW analysis  (0 vs. 9.9%, Plog-rank<0.001). CONCLUSION: In patients with moderate FMR and HFpEF, isolated AVR might be more reasonable than AVR-MVS.

Treatment of Moderate Functional Mitral Regurgitation during Aortic Valve Replacement: A Cohort Study.

Background: Treatment of moderate functional mitral regurgitation (FMR) during aortic valve replacement (AVR) is controversial. This study aimed to evaluate the effect of different surgical strategies in patients with moderate FMR undergoing AVR. Methods: A total of 468 patients with moderate FMR undergoing AVR from January 2010 to December 2019 were retrospectively studied comparing 3 different surgical strategies, namely isolated AVR, AVR + mitral valve repair (MVr) and AVR + mitral valve replacement (MVR). Survival was estimated using the Kaplan-Meier method and compared with the log-rank test, followed by inverse probability treatment weighting (IPTW) analysis to adjust the between-group imbalances. The primary outcome was overall mortality. Results: Patients underwent isolated AVR (35.3%), AVR + MVr (30.3%), or AVR + MVR (34.4%). The median follow-up was 27.1 months. AVR + MVR was associated with better improvement of FMR during the early and follow-up period compared to isolated AVR and AVR + MVr (p < 0.001). Compared to isolated AVR, AVR + MVR increased the risk of mid-term mortality (hazard ratio [HR]: 2.13, 95% confidence interval [CI]: 1.01-4.48, p = 0.046), which was sustained in the IPTW analysis (HR: 4.15, 95% CI: 1.69-10.15, p = 0.002). In contrast, AVR + MVr showed only a tendency to increase the risk of follow-up mortality (HR: 1.63, 95% CI: 0.72-3.67, p = 0.239), which was more apparent in the IPTW analysis (HR: 2.54, 95% CI: 0.98-6.56, p = 0.054). Conclusions: In patients with severe aortic valve disease and moderate FMR, isolated AVR might be more reasonable than AVR + MVr or AVR + MVR.

Iron Deficiency Might Impair the Recovery of Left Ventricular Function after Surgical Revascularization in Diabetic Patients: A Retrospective Study.

Background: Iron deficiency (ID) is one of the most common micronutrient deficiencies affecting public health. Studies show that ID affects the prognosis of patients with heart disease, including heart failure, coronary artery disease and myocardial infarction. However, there is limited information regarding the impact of ID on patients undergoing cardiac surgery. This study aimed to evaluate the influence of preoperative ID on the prognosis of type 2 diabetes mellitus (T2DM) patients undergoing coronary artery bypass grafting (CABG). Methods: In the Glycemic control using mobile-based intervention in patients with diabetes undergoing coronary artery bypass to promote self-management (GUIDEME) study, patients with T2DM undergoing CABG were prospectively recruited. In this study, only those patients with preoperative iron metabolism results were enrolled. Patients were grouped based on the presence of preoperative ID. The primary endpoint was defined as the significant improvement of follow-up ejection fraction (EF) compared to postoperative levels (classified according to the 75th percentile of the change, and defined as an improvement of greater than or equal to 5%). Univariable logistic regression was performed to explore the potential confounders, followed by multiple adjustment. Results: A total of 302 patients were enrolled. No deaths were observed during the study period. A higher incidence of the primary endpoint was observed in the ID group (25.4% vs 12.9%, p = 0.015). The postoperative and follow-up EF were similar beween the two groups. In the regression analysis, ID was noticed to be a strong predictor against the significant improvement of EF in both univariable (odds ratio [OR]: 0.44, 95% confidence interval [CI]: 0.22-0.86, p = 0.017) and multivariable (OR: 0.43, 95% CI: 0.24-0.98, p = 0.043) logistic regression. In the subgroup analysis, ID was a predictor of significant improvement of EF in age ≤ 60 years, male, EF ≤ 60%, and on-pump CABG patients. Conclusions: In T2DM patients undergoing CABG, ID might negatively affect the early recovery of left ventricular systolic function in terms of recovery of EF 3-6 months after surgery, especially in patients age ≤ 60 years, males, EF ≤ 60% and in those undergoing on-pump CABG.

Evaluating the impact of experience value promotes user voice toward social media: Value co-creation perspective.

Experience value is positively associated with user voice toward social media, but existing research lacks an examination of its mechanisms of action. Based on value co-creation theory, this paper explores the relationship between experience value (i.e., social value, entertainment value, information value) and customer voice, and explains the specific influence mechanism through the mediating role of user loyalty. The results of the empirical tests show that social value, entertainment value and information value have significant effects on user loyalty; user loyalty has a significant effect on promotive voice but not on prohibitive voice; user loyalty mediates the relationship between body social value, entertainment value, information value and promotive voice. The findings of this research reveal the important role of experience value on customer voice, which is an important guide for social media to achieve sustainable development.

Surgical treatment of patients with aortic valve disease complicated with moderate functional mitral regurgitation and heart failure with midrange ejection fraction: a cohort study.

Background: Controversies exist on the treatment of moderate functional mitral regurgitation (FMR) in patients with severe aortic valve disease undergoing the aortic valve replacement (AVR). While a substantial proportion of these patients can be complicated with heart failure with midrange ejection fraction (HFmrEF), established studies show that the latter might compromise the patient outcome. This study was aimed to evaluate the prognostic value of concomitant mitral valve surgery during AVR in patients with severe aortic valve disease followed by moderate FMR and HFmrEF. Methods: A total of 78 consecutive patients were retrospectively recruited. Patients were divided into control (isolated AVR) and treatment (AVR + mitral valve surgery) groups. Follow-up outcomes were compared by Kaplan-Meier method, followed by multiple adjustment with inverse probability treatment weighting (IPTW) analysis. The primary outcome was the occurrence of major adverse cardiovascular and cerebrovascular events (MACCE). Results: Thirty-six patients received isolated AVR, while 42 received AVR with mitral valve repair or replacement. The median follow-up time was 28.7 months. Unadjusted analysis showed that there was no significant difference in the rate of MACCE between the two groups [hazard ratio (HR): 1.14, 95% confidence interval (CI): 0.48-2.69, Plogrank=0.770], which was sustained in IPTW analysis (HR: 1.64, 95% CI: 0.59-4.55, Plogrank=0.342). In addition, while concomitant mitral valve surgery improved follow-up FMR more completely (P=0.026) in the IPTW analysis, the ejection fraction was comparable between the two groups (P=0.276). Furthermore, IPTW analysis also showed that mitral valve surgery was associated with the increased risk of postoperative acute kidney injury (P=0.007). Conclusions: In patients with aortic valve disease followed by moderate FMR and HFmrEF, mitral valve surgery concomitant to AVR may not bring extra benefit in the MACCE-free survival and the improvement of HFmrEF. However, while concomitant mitral valve surgery has priority on the complete improvement of FMR, it might increase the risk of postoperative acute kidney injury.

Exosomal microRNA-551b-3p from bone marrow-derived mesenchymal stromal cells inhibits breast cancer progression via regulating TRIM31/Akt signaling.

Mesenchymal stromal cells (MSCs) play an important role in the development of human cancer. Meanwhile, exosomes released by MSCs can mediate cell-cell communication by delivering microRNAs (miRNAs/miRs). Hence, this study aimed to explore the role of bone marrow mesenchymal stromal cell (BMSC)-derived exosomal miR-551b-3p in breast cancer. In this study, we found that upregulation of miR-551b-5p suppressed the proliferation and migration and induced the apoptosis of breast cancer cells via downregulating tripartite motif-containing protein 31 (TRIM31). In addition, miR-551b-5p could be transferred from BMSCs to breast cancer cells via exosomes; BMSC-derived exosomal miR-551b-3p suppressed the proliferation and migration and promoted the apoptosis and oxidative stress of MDA-MB-231 cells via inhibiting TRIM31. Furthermore, a xenograft mouse model was used to explore the role of BMSC-derived exosomal miR-551b-3p in vivo. We found that BMSC-derived exosomal miR-551b-3p inhibited tumor growth in a mouse xenograft model of breast cancer in vivo. Collectively, these findings indicated that BMSC-derived exosomal miR-551b-3p could suppress the development of breast cancer via downregulating TRIM31. Thus, miR-551b-3p could serve as a potential target for the treatment of breast cancer.

Effect of ß-blocker on patients with moderate functional mitral regurgitation undergoing surgical aortic valve replacement.

AIMS: The optimal treatment for severe aortic valve disease complicated with moderate function mitral regurgitation (FMR) remains controversial. Although isolated surgical aortic valve replacement (SAVR) is reasonable, previous studies also show that moderate FMR might deteriorate after surgical treatment and result in poorer prognosis. Because the left ventricular remodelling plays a critical role in the development of FMR, these patients might potentially benefit from the administration of ß-blocker (BB). Unfortunately, relevant clinical evidence is lacking. This study aimed to investigate the impact of post-operative administration of BB on the outcomes of moderate FMR patients undergoing isolated SAVR. METHODS: In this single-centre cohort study, patients who underwent isolated SAVR and complicated with pre-operative moderate FMR during 2010 and 2019 at our centre were retrospectively recruited. Patients were divided into two groups according to postoperative administration of BB (BB group vs. control group). The cumulative survival rates were calculated using the Kaplan-Meier method and tested by the log-rank test, followed by inverse probability treatment weighting (IPTW) analysis to further control the between-group imbalances. The primary outcome was the major adverse cardiovascular and cerebrovascular events (MACCE), a composite endpoint of all-cause death, repeat heart valve surgery, non-fatal myocardial infarction, stroke, and hospitalization for heart failure. RESULTS: A total of 165 patients were enrolled, 57 (34.6%) of whom were female, and the mean age was 59.2 ± 12.2 years. Eighty (48.5%) patients received post-operative BB therapy. The median follow-up time was 18.4 months. The administration of BB was not associated with lower risk of MACCE [hazard ratio (HR): 0.68, 95% confidence interval (CI): 0.29-1.62, P = 0.388] or all-cause death (HR: 1.03, 95% CI: 0.30-0.56, P = 0.967). In the IPTW dataset, the total number of patients were 326.89, and the outcomes regarding the risk of MACCE (HR: 0.79, 95% CI: 0.31-1.97, P = 0.607) and all-cause death (HR: 1.33, 95% CI:0.35-5.05, P = 0.674) were in line with the unmatched analysis. The follow-up echocardiographic results were available for 72.2% of the overall cohort, and the use of BB was observed to be associated with higher improvement rate of follow-up FMR according to the IPTW analysis (92.2% vs. 98.3%, P = 0.033). CONCLUSIONS: The administration of BB after SAVR was not associated with lower risk of MACCE for patients of severe aortic valve disease complicated with moderate FMR, but was potentially beneficial for improving FMR.

AZD3463, an IGF-1R inhibitor, suppresses breast cancer metastasis to bone via modulation of the PI3K-Akt pathway.

BACKGROUND: The bone-derived insulin-like growth factor I (IGF-1) and its receptor IGF-1R play a crucial role in promoting the survival and proliferation of cancer cells, and have thus been considered as prime targets for the development of novel antitumor therapeutics. METHODS: By using the MDA-MB-231BO cell line, which is the osteotropic metastatic variant of the human breast adenocarcinoma cell line MDA-MB-231, and an in vivo model of breast cancer metastasis to bone, the current study evaluated the effect of AZD3463, an IGF-1R inhibitor, used alone or in combination with zoledronic acid (ZA), on the regulation of IGF-1R associated signal pathway and treatment of bone metastases (BM). Cell proliferation and invasion were measured by methyl thiazolyl tetrazolium (MTT) and Transwell assay respectively. Apoptotic cell number was detected by terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling (TUNEL). RESULTS: AZD3463 was shown to alleviate IGF-1R phosphorylation promoted by IGF-1 treatment in MDA-MB-231BO cells in a dose-dependent manner. In both the cells and the mouse model, 5 nM of AZD3463 stimulated cell apoptosis and suppressed proliferation on a level similar to that of 100 µM of ZA. Remarkably, the combined use of AZD3463 and ZA exhibited a synergistic effect and greater antitumor activity compared to when they were employed individually. Mechanistic investigations indicated that the apoptosis-inducing activity of AZD3463 could be associated to its role in the activation of the phosphoinositide 3-kinase (PI3K)-Akt signaling pathway. CONCLUSIONS: These findings suggested that AZD3463 could serve as a promising therapeutic molecule for treating BM in breast cancer patients, particularly when applied in conjunction with ZA or other antitumor agents.

Nanostructure Characteristics of Al3Sc1-xZrx Nanoparticles and Their Effects on Mechanical Property and SCC Behavior of Al-Zn-Mg Alloys.

The Nanostructure characteristics of Al3Sc1-xZrx nanoparticles and their effects on the mechanical properties and stress corrosion cracking (SCC) behavior of Al-Zn-Mg alloys were investigated by 3D atom probe analyses, high-angle annular-dark-field scanning transmission electron microscopy methods, electron back scattered diffraction techniques, electrochemical measurements, slow strain rate tests and quantitative calculations. The results show that adding small amounts of scandium (0.10 percent by weight) and zirconium into Al-Zn-Mg extrusion bars can precipitate Al3Sc1-xZrx nanoparticles with a number density of (7.80 ± 3.83) × 1021 per cubic meter. Those particles, with a low lattice misfit with matrix (1.14 ± 0.03 percent) and stable core-shell L12-nanostructure in aged Al-Zn-Mg alloys, can increase the yield strength by 161 ± 7 MPa via strong Orowan strengthening (the theoretical calculated value is 159 MPa) and weak Hall-Petch strengthening (the theoretical calculated value is 6 MPa). Moreover, Al3Sc1-xZrx nanoparticles can change the fracture mechanism of alloys in 3.5% NaCl solution from intergranular cracks to transgranular failure, and decrease the proportion of high-angle grain boundaries from 87% to 31%, thus reducing the microchemistry differences around the grain boundaries and anodic dissolution kinetics, and improving intergranular SCC resistance and ductility. This study offers a new approach to the simultaneous improvement in mechanical property and corrosion performance of high strength alloys.

MORC4 is a novel breast cancer oncogene regulated by miR-193b-3p.

A better understanding of breast cancer pathogenesis would contribute to improved diagnosis and therapy and potentially decreased mortality rates. Here, we found that the MORC family CW-type zinc finger 4 (MORC4) overexpression in breast cancer tissues is associated with poor survival, and the short-interfering RNA knockdown of MORC4 suppresses the growth of breast cancer cells by promoting apoptosis. To investigate the mechanisms associated with MORC4 upregulation, microRNAs potentially targeting MORC4 were analyzed, with miR-193b-3p identified as the regulator and a negative correlation between miR-193b-3p and MORC4 expression determined in both breast cancer cell lines and tissues. Further analysis verified that MORC4 silencing did not affect miR-193b-3p expression, although altered miR-193b-3p expression attenuated MORC4 protein levels. Moreover, dual-luciferase reporter assays verified miR-193b-3p binding to the 3' untranslated region of MORC4. Furthermore, restoration of miR-193b-3p expression in breast cancer cells led to decreased growth and activation of apoptosis, which was consistent with results associated with MORC4 silencing in breast cancer cells. These results identified MORC4 as differentially expressed in breast cancer cells and tissues and its downregulation by miR-193b-3p, as well as its roles in regulating the growth of breast cancer cells via regulation of apoptosis. Our findings offer novel insights into potential mechanisms associated with breast cancer pathogenesis.

Incidence, risk factors and prognostic characteristics of bone metastases and skeletal-related events (SREs) in breast cancer patients: A systematic review of the real world data.

PURPOSE: The aim was to systematically extrapolate the occurrence, risk factors, prognostic characteristics, management and outcome of bone metastases (BM) and skeletal related events (SREs) of breast cancer survivors in the real world clinical setting. METHODS: A systematic literature search of PubMed, Web of Science, EMBASE OvidSP and EBSCO Academic Search Complete was conducted. Published prospective and retrospective papers investigating BM and SREs in breast cancer patients in non-trial settings were identified and systematically reviewed. RESULTS: Twenty-four studies met the inclusion criteria. Incidences of BM based on new diagnosis, length of BM-free interval (BMFI) and number and sites of BM were detected by 17 of 24 studies. Seven studies included in the review were subjected to analyses of risk factors for BM. Developments of SREs regarding the occurrence ratio of total and specific SREs, SERs-free interval (SREFI) and the first-line therapy for SREs were observed in 16 of 24 studies. Out of 5 studies, we extracted uni- and multivariate analysis of risk factor for SREs and out of 16 studies - predictors for survival in breast cancer patients with BM. CONCLUSIONS: BM and SREs are common problems in non-trial breast cancer populations. Patient demographics, clinical stage, tumor pathological type, molecular receptors status are significantly risk factors for incidence of BM, SREs and the survival. The unique characteristics of BM and SREs in breast cancer patients should be taken into account in future randomized controlled trials, as to optimize individual treatment options and assure a maximally long good quality of life.

Preparation of the MoS2/TiO2/HMFs ternary composite hollow microfibres with enhanced photocatalytic performance under visible light.

A novel route for synthesis of MoS2/TiO2/hollow microfibers (HMFs) ternary composite photocatalyst using sol-gel method combined with high temperature calcination under a nitrogen circumstances was reported for the first time. The morphology, structure and optical properties of the novel MoS2/TiO2/HMFs photocatalysts were fully characterized by Fourier transform infrared spectroscopy (FT-IR), scanning electron microscopy (SEM), high-resolution transmission electron microscopy (TEM), energy dispersive X-ray spectroscopy (EDX), X-ray diffraction (XRD), X-ray photoelectron spectroscopy (XPS), specific surface area (BET) and thermogravimetric analysis (TG). The photocatalytic activities were evaluated by photodegradating Methylene blue (MB) and Rhodamine B (RB) under visible light irradiation. The results showed the MoS2/TiO2/HMFs ternary composite hollow microfibre photocatalysts had a purification of more than 98.7% for MB and RB of simulating wastewater, and acquired the superior synergistic effect of adsorption and catalysis for organic pollutants. That's because the sensitization of MoS2 enlarged the wavelength response range to the visible region of the solar spectrum, the HMFs could beneficially increase adsorption capability for organic pollutants, and the mixed crystalline phase of TiO2 accelerated the decomposition of organic pollutant. A detailed study of involved active species unraveled the mechanism regarding photocatalysis. So, the synergistic photocatalytic effect of HMFs, TiO2 and MoS2 was very important and significant for wastewater treatment or prevention of air pollution.