Effect of Retrogression with Different Cooling Ways on the Microstructure and Properties of T'/η' Strengthened Al-Zn-Mg-Cu Alloys.

Retrogression and re-aging (RRA) treatment has been proven to effectively overcome the trade-off between strength and corrosion resistance. Current research focuses on the heating rate, temperature, and holding time of retrogression treatment while ignoring the retrogression cooling ways. In this paper, the effects of RRA treatment with different retrogression cooling ways on the microstructure and properties of newly developed T'/η' strengthened Al-Zn-Mg-Cu alloys were investigated by performing tests on mechanical properties, intergranular corrosion (IGC) resistance, and electrochemical corrosion behavior. The results show that the mechanical properties of samples subject to RRA treatment with water-quenching retrogression (ultimate tensile strength, yield strength, and elongation of 419.2 MPa, 370.2 MPa, and 15.9, respectively) are better than those of air-cooled and furnace-cooled samples. The corrosion resistance of water-quenching (IGC depth of 162.2 µm, corrosion current density of 0.833 × 10-5 A/cm2) and furnace-cooled samples (IGC depth of 123.7 µm, corrosion current density of 0.712 × 10-5 A/cm2) is better than that of air-cooled samples. Microstructure characterization reveals that the effect of the retrogression cooling rate on mechanical properties is related to the size of T'/η' precipitates with grains as well as the proportion of T' and η', while the difference in corrosion resistance depends on the continuity of grain boundary precipitates (GBPs). With mechanical properties, corrosion resistance, and time cost taken into consideration, it is appropriate to select water quenching for retrogression. These findings offer valuable insights for further design to achieve superior performance in various applications.

Edoxaban for stroke prevention in atrial fibrillation and factors associated with dosing: patient characteristics from the prospective observational ETNA-AF-China registry.

Real-world data on effectiveness and safety of a single non-vitamin K antagonist oral anticoagulant in the Chinese population with atrial fibrillation (AF) are limited. This study reports characteristics of patients treated with edoxaban and factors associated with dosing patterns from routine care in China. ETNA-AF-China (NCT04747496) is a multicentre, prospective, observational study enrolling edoxaban-treated patients from four economic regions with a targeted 2-year follow-up. Of the 4930 patients with AF (mean age: 70.2 ± 9.5 years; male, 57.1%), the mean creatinine clearance (CrCl), CHA2DS2-VASc, and HAS-BLED scores were 71.2 mL/min, 2.9, and 1.6. Overall, 6.4% of patients were perceived as frail by investigators. Available label dose reduction criteria (N = 4232) revealed that 3278 (77.5%) patients received recommended doses and 954 (22.5%) non-recommended doses. Northeast (53.0%) and West (43.1%) regions had the highest prescriptions of 60 mg and 30 mg recommended doses, respectively. Non-recommended 30 mg doses were more frequently prescribed in patients with antiplatelet use and history of heart failure than recommended 60 mg. Multivariate analysis identified advanced age as the strongest associated factor with non-recommended doses. Frailty had the strongest association with 30 mg except for age, and history of TIA was the most relevant factor associated with 60 mg. In conclusion, patients in the ETNA-AF-China study were predominantly aged 65 years and older, had mild-to-moderate renal impairment and good label adherence. Advanced age was associated with non-recommended doses, with frailty most common for non-recommended 30 mg and a history of TIA for the non-recommended 60 mg dose.

An Integrated Arterial Remodeling Hydrogel for Preventing Restenosis After Angioplasty.

The high incidence of restenosis after angioplasty has been the leading reason for the recurrence of coronary heart disease, substantially increasing the mortality risk for patients. However, current anti-stenosis drug-eluting stents face challenges due to their limited functions and long-term safety concerns, significantly compromising their therapeutic effect. Herein, a stent-free anti-stenosis drug coating (denoted as Cur-NO-Gel) based on a peptide hydrogel is proposed. This hydrogel is formed by assembling a nitric oxide (NO) donor-peptide conjugate as a hydrogelator and encapsulating curcumin (Cur) during the assembly process. Cur-NO-Gel has the capability to release NO upon ß-galactosidase stimulation and gradually release Cur through hydrogel hydrolysis. The in vitro experiments confirmed that Cur-NO-Gel protects vascular endothelial cells against oxidative stress injury, inhibits cellular activation of vascular smooth muscle cells, and suppresses adventitial fibroblasts. Moreover, periadventitial administration of Cur-NO-Gel in the angioplasty model demonstrate its ability to inhibit vascular stenosis by promoting reendothelialization, suppressing neointima hyperplasia, and preventing constrictive remodeling. Therefore, the study provides proof of concept for designing a new generation of clinical drugs in angioplasty.

Pericardial Delivery of SDF-1α Puerarin Hydrogel Promotes Heart Repair and Electrical Coupling.

The stromal-derived factor 1α/chemokine receptor 4 (SDF-1α/CXCR4) axis contributes to myocardial protection after myocardial infarction (MI) by recruiting endogenous stem cells into the ischemic tissue. However, excessive inflammatory macrophages are also recruited simultaneously, aggravating myocardial damage. More seriously, the increased inflammation contributes to abnormal cardiomyocyte electrical coupling, leading to inhomogeneities in ventricular conduction and retarded conduction velocity. It is highly desirable to selectively recruit the stem cells but block the inflammation. In this work, SDF-1α-encapsulated Puerarin (PUE) hydrogel (SDF-1α@PUE) is capable of enhancing endogenous stem cell homing and simultaneously polarizing the recruited monocyte/macrophages into a repairing phenotype. Flow cytometry analysis of the treated heart tissue shows that endogenous bone marrow mesenchymal stem cells, hemopoietic stem cells, and immune cells are recruited while SDF-1α@PUE efficiently polarizes the recruited monocytes/macrophages into the M2 type. These macrophages influence the preservation of connexin 43 (Cx43) expression which modulates intercellular coupling and improves electrical conduction. Furthermore, by taking advantage of the improved "soil", the recruited stem cells mediate an improved cardiac function by preventing deterioration, promoting neovascular architecture, and reducing infarct size. These findings demonstrate a promising therapeutic platform for MI that not only facilitates heart regeneration but also reduces the risk of cardiac arrhythmias.

Influence of Interface on Mechanical Behavior of Al-B4C/Al Laminated Composites under Quasi-Static and Impact Loading.

In this study, Al-B4C/Al laminated composites with high interlayer bonding strength were fabricated by integrated hot-pressed sintering accompanied with hot rolling. The mechanical properties and interface behavior of the Al-B4C/Al laminated composites were investigated under quasi-static and impact loading. The results show that the Al-B4C/Al laminated composites obtain a high interface bonding strength, because no interlayer delamination occurs even after fractures under quasi-static and impact loads. The Al-B4C/Al laminated composites exhibit a better comprehensive mechanical performance, and the fracture can be delayed due to the high bonding strength interface. Moreover, laminated composites can absorb more impact energy than the monolithic material under impact loading due to the stress transition and relaxation.

A Novel Multi-Scale Ceramic-Based Array (SiCb+B4Cp)/7075Al as Promising Materials for Armor Structure.

Ceramic panel collapse will easily lead to the failure of traditional targets. One strategy to solve this problem is to use separate ceramic units as armor panels. Based on this idea, we propose an aluminum matrix composite using pressure infiltration, containing an array of ceramic balls, the reinforcement of which consists of centimeter-scale SiC balls and micron-scale B4C particles. Three different array layouts were designed and fabricated: compact balls in the front panel (F-C), non-compact balls in the front panel (F-NC), and compact balls inside the target (I-C). The penetration resistance properties were tested using a 12.7 mm armor-piercing incendiary (API). The results show that there are no significant internal defects, and the ceramic balls are well-bonded with the matrix composite. The F-NC structure behaves the best penetration resistance with minimal overall damage; the I-C structure has a large area of spalling and the most serious damage. Finite element simulation reveals that the ceramic balls play a major role in projectile erosion; in the non-compact structure, the composite materials between the ceramic balls can effectively disperse the stress, thereby avoiding the damage caused by direct contact between ceramic balls and improving the efficiency of ceramic ball erosion projectiles. Furthermore, it is essential to have a certain thickness of supporting materials to prevent spalling failure caused by stress wave transmission during penetration. This multi-scale composite exhibits excellent ballistic performance, providing valuable insights for developing anti-penetration composite armor in future applications.

Effect of Lattice Constants and Precipitates on the Dimensional Stability of Rolled 2024Al during Isothermal Aging.

The change in material dimensional will lead to the decline of instrument accuracy and reliability. In this paper, the characterization and analysis of the lattice constant, precipitates, and dislocation density of the material by X-ray diffraction (XRD) and transmission electron microscopy (TEM) reveals the reason why the relative dimensional change in the rolled 2024Al is one order of magnitude lower than that of the as-cast 2024Al during isothermal aging. Compared with as-cast 2024Al, the dislocation density of rolled 2024Al is higher, the lattice constant decreases less before and after aging, and the precipitates have orientation and more content, resulting in the dimensional change in rolled 2024Al being smaller than that of as-cast 2024Al. In addition, two main reasons for decreasing the dimensional change in rolled 2024Al are discussed: the decrease in lattice constant, the formation and growth of the S phase before and after aging.

Effect of Interfacial Strength on Mechanical Behavior of Be/2024Al Composites by Pressure Infiltration.

In this paper, two kinds of Be/2024Al composites were prepared by the pressure infiltration method using two different beryllium powders as reinforcements and 2024Al as a matrix. The effect of interfacial strength on the mechanical behavior of Be/2024Al composites was studied. Firstly, the microstructure and mechanical properties of the two composites were characterized, and then the finite element analysis (FEA) simulation was used to further illustrate the influence of interfacial strength on the mechanical properties of the two Be/2024Al composites. The mechanical tensile test results show that the tensile strength and elongation of the beryllium/2024Al composite prepared by the blocky impact grinding beryllium powder (blocky-Be/2024Al composite) are 405 MPa and 1.58%, respectively, which is superior to that of the beryllium/2024Al composite prepared by the spherical atomization beryllium powder (spherical-Be/2024Al composite), as its strength and elongation are 331 MPa and 0.38%, respectively. Meanwhile, the fracture of the former shows brittle fracture of beryllium particles and ductile fracture of aluminum, while the latter shows interface debonding. Further FEA simulation illustrates that the interfacial strength of the blocky-Be/2024Al composite is 600 MPa, which is higher than that of the spherical-Be/2024Al composite (330 MPa). Therefore, it can be concluded that the better mechanical properties of the blocky-Be/2024Al composite contribute to its stronger beryllium/aluminum interfacial strength, and the better interfacial strength might be due to the rough surface and microcrack morphology of blocky beryllium particles. These research results provide effective experimental and simulation support for the selection of beryllium powder and the design and preparation of high-performance beryllium/aluminum composites.

A machine learning-based risk stratification tool for in-hospital mortality of intensive care unit patients with heart failure.

BACKGROUND: Predicting hospital mortality risk is essential for the care of heart failure patients, especially for those in intensive care units. METHODS: Using a novel machine learning algorithm, we constructed a risk stratification tool that correlated patients' clinical features and in-hospital mortality. We used the extreme gradient boosting algorithm to generate a model predicting the mortality risk of heart failure patients in the intensive care unit in the derivation dataset of 5676 patients from the Medical Information Mart for Intensive Care III database. The logistic regression model and a common risk score for mortality were used for comparison. The eICU Collaborative Research Database dataset was used for external validation. RESULTS: The performance of the machine learning model was superior to that of conventional risk predictive methods, with the area under curve 0.831 (95% CI 0.820-0.843) and acceptable calibration. In external validation, the model had an area under the curve of 0.809 (95% CI 0.805-0.814). Risk stratification through the model was specific when the hospital mortality was very low, low, moderate, high, and very high (2.0%, 10.2%, 11.5%, 21.2% and 56.2%, respectively). The decision curve analysis verified that the machine learning model is the best clinically valuable in predicting mortality risk. CONCLUSION: Using readily available clinical data in the intensive care unit, we built a machine learning-based mortality risk tool with prediction accuracy superior to that of linear regression model and common risk scores. The risk tool may support clinicians in assessing individual patients and making individualized treatment.

Correction: Furin-instructed molecular self-assembly actuates endoplasmic reticulum stress-mediated apoptosis for cancer therapy.

Correction for 'Furin-instructed molecular self-assembly actuates endoplasmic reticulum stress-mediated apoptosis for cancer therapy' by Chenxing Fu et al., Nanoscale, 2020, 12, 12126-12132, DOI: .

Trends in incidence and long-term prognosis of acute kidney injury following coronary angiography in Chinese cohort with 11,943 patients from 2013 to 2017: an observational study.

BACKGROUND: Contrast-associated acute kidney injury (CA-AKI) is a common complication with poor prognosis after coronary angiography (CAG). With the prevention methods widely being implemented, the temporal trends of incidence and mortality of CA-AKI are still unknown over the last five years. The study aims to determine the incidence and prognosis of CA-AKI in China. METHODS: This retrospective cohort study was based on the registry at Guangdong Provincial People's Hospital in China (ClinicalTrials.gov NCT04407936). We analyzed data from hospitalization patients who underwent CAG and with preoperative and postoperative serum creatinine (Scr) values from January 2013 to December 2017. RESULTS: 11,943 patients were included in the study, in which the mean age was 63.01 ± 10.79 years and 8,469 (71.1 %) were male. The overall incidence of CA-AKI was 11.2 %. Compared with 2013, the incidence of CA-AKI in 2017 was significantly increased from 9.7 to 13.0 % (adjusted odds ratios [aOR], 1.38; 95 %CI, 1.13-1.68; P-value < 0.01, P for trend < 0.01). The temporal trends of incidence among patients of different ages and genders yielded similar findings. During a standardized follow-up of 1 year, 178 (13.7 %) CA-AKI patients died in total, which showed no obvious decreased trend in this 5 five years from 21.1 to 16.5 (adjusted hazard ratio [aHR], 0.72; 95 %CI, 0.36-1.45; P-value = 0.35, P for trend = 0.24). CONCLUSIONS: Our Chinese cohort showed that the incidence of CA-AKI increased significantly, while CA-AKI associated mortality showed no obvious decreased trend in the last five years. Our findings support more active measures to prevent CA-AKI and improve the prognosis of CA-AKI patients.

Furin-instructed molecular self-assembly actuates endoplasmic reticulum stress-mediated apoptosis for cancer therapy.

Protein quality control and proteostasis are essential to maintain cell survival as once disordered, they will trigger endoplasmic reticulum (ER) stress and even initiate apoptosis. Severe ER stress-mediated apoptosis is the cause of neurodegenerative diseases and expected to be a new target for cancer therapy. In this study, we designed a small molecule of 1-Nap to execute furin-instructed molecular self-assembly for selectively inhibiting the growth of MDA-MB-468 cells in vitro and in vivo. According to the results of transmission electron microscopy (TEM) and HPLC tracing analysis, 1-Nap is capable of self-assembling upon furin-instructed cleavage that transforms 1-Nap nanoparticles to 1-Nap nanofibers. Fluorescence imaging and Western-blot analysis results indicate that the furin-instructed self-assembly of 1-Nap rather than its ER-targeting interaction is indispensable for the ER stress and activation of apoptosis. The furin-instructed self-assembly of 1-Nap is associated with both the ER (1-Nap's targeting location) and the trans-Golgi network (furin's location); this inspired us to reasonably believe that the blocking of ER-to-Golgi traffic in the secretory pathway by molecular self-assembly may be the intrinsic motivation for controlling cell fate. This work provides a new way for the targeted disturbance of the proteostasis of cells through molecular self-assembly for developing cancer therapeutics.

Rationale and design of the Web-basEd soCial media tecHnology to improvement in Adherence to dual anTiplatelet Therapy following Drug-Eluting Stent Implantation (WECHAT): protocol for a randomised controlled study.

BACKGROUND: Dual antiplatelet therapy (DAPT) is frequently discontinued after drug-eluting stent (DES) implantation, which could increase the risk of major adverse cardiovascular events (MACEs). Few studies have attempted to improve DAPT adherence through web-based social media. OBJECTIVE: To explore the effect of social media on DAPT adherence following DES implantation. METHODS/DESIGN: The WeChat trial is a multicentre, single-blind, randomised study (1:1). It will recruit 760 patients with DES who require 12 months of DAPT. The control group will only receive usual care and general educational messages on medical knowledge. The intervention group will receive a personalised intervention, including interactive responses and medication and follow-up reminders beyond the general educational messages. The primary endpoint will be the discontinuation rate which is defined as the cessation of any dual antiplatelet drug owing to the participants' discretion within 1 year of DES implantation. The secondary endpoints will include medication adherence and MACEs. Both groups will receive messages or reminders four times a week with follow-ups over 12 months. ETHICS AND DISSEMINATION: Ethical approval was granted by Ethics Committee of Guangdong Provincial People's Hospital (GDREC2018327H). Results will be disseminated via peer-reviewed publications and presentations at international conferences. TRIAL REGISTRATION NUMBER: NCT03732066.

Urolithin B suppresses tumor growth in hepatocellular carcinoma through inducing the inactivation of Wnt/ß-catenin signaling.

Consumption of dietary ellagitannins (ETs) has been proven to benefit multiple chronic health disorders including cancers and cardiovascular diseases. Urolithins, gut microbiota metabolites derived from ETs, are considered as the molecules responsible for these health effects. Previous studies have demonstrated that urolithins exhibit antiproliferative effects on prostate, breast, and colon cancers. However, as for hepatocellular carcinoma (HCC), it remains elusive. Herein, we aim to investigate the function of urolithin B (UB), a member of urolithins family, in HCC. The effects of UB on cell viability, cell cycle and apoptosis were evaluated in HCC cells, and we found UB could inhibit the proliferation of HCC cells, which resulted from cell cycle arrest and apoptosis. Furthermore, UB could increase phosphorylated ß-catenin expression and block its translocation from nuclear to cytoplasm, thus inducing the inactivation of Wnt/ß-catenin signaling. Using a xenograft mice model, UB was found to suppress tumor growth in vivo. In conclusion, our data demonstrated that UB could inhibit the proliferation of HCC cells in vitro and in vivo via inactivating Wnt/ß-catenin signaling, suggesting UB could be a promising candidate in the development of anticancer drugs targeting HCC.

Bifunctional Supramolecular Hydrogel Alleviates Myocardial Ischemia/Reperfusion Injury by Inhibiting Autophagy and Apoptosis.

Generally, nitric oxide (NO) is an important multi-functional cardioprotective soluble gas molecule. However, it may be detrimental when in excessive levels or combined with O2- a kind of reactive oxygen species (ROS)-to form ONOO-. The latter will rapidly decompose to highly reactive oxidant components. ROS will be abundantly produced during the ischemia/reperfusion (I/R) procedure. Therefore, an NO donor coupled with another antioxidant would be a more promising strategy for I/R treatment. In this study, we report on a novel self-assembly supramolecular hydrogel capable of constantly releasing both NO and curcumin (Cur) simultaneously, and we found that the combinational treatment of Cur and NO from the gel could efficiently reduce I/R injuries. The underlining mechanism revealed that the hydrogel could reduce the ROS level and thus inhibit the expression of the ROS-associated p38 MAPK/NF-κB signaling pathway. Moreover, the hydrogel also significantly suppressed over-stimulated autophagy and apoptosis during I/R treatment which was responsible for mediating severe post-ischemia myocardial cell death. The results indicated that our supramolecular hydrogel was a promising biomaterial for the treatment of myocardial I/R injuries.

Aerobic oxidative acylation of nitroarenes with arylacetic esters under mild conditions: facile access to diarylketones.

A facile and regioselective base-mediated aerobic oxidative acylation of nitroarenes to access diarylketones under mild conditions has been developed. It features the use of bench-stable and readily available arylacetates as acyl surrogates, and the absence of transition-metals and synthetic oxidants. This protocol involves a cascade CDC/oxidative decarboxylation process.

Treatment of Myocardial Infarction with Gene-modified Mesenchymal Stem Cells in a Small Molecular Hydrogel.

The effect of transplanted rat mesenchymal stem cells (MSCs) can be reduced by extracellular microenvironment in myocardial infarction (MI). We tested a novel small-molecular hydrogel (SMH) on whether it could provide a scaffold for hepatocyte growth factor (HGF)-modified MSCs and alleviate ventricular remodeling while preserving cardiac function after MI. Overexpression of HGF in MSCs increased Bcl-2 and reduced Bax and caspase-3 levels in response to hypoxia in vitro. Immunocytochemistry demonstrated that cardiac troponin (cTnT), desmin and connexin 43 expression were significantly enhanced in the 5-azacytidine (5-aza) with SMH group compared with the 5-aza only group in vitro and in vivo. Bioluminescent imaging indicated that retention and survival of transplanted cells was highest when MSCs transfected with adenovirus (ad-HGF) were injected with SMH. Heart function and structure improvement were confirmed by echocardiography and histology in the Ad-HGF-SMHs-MSCs group compared to other groups. Our study showed that: HGF alleviated cell apoptosis and promoted MSC growth. SMHs improved stem cell adhesion, survival and myocardial cell differentiation after MSC transplantation. SMHs combined with modified MSCs significantly decreased the scar area and improved cardiac function.

A Glycyrrhetinic Acid-Modified Curcumin Supramolecular Hydrogel for liver tumor targeting therapy.

Curcumin (Cur), a phenolic anti-oxidant compound obtained from Curcuma longa plant, possesses a variety of therapeutic properties. However, it is suffered from its low water solubility and low bioavailability property, which seriously restricts its clinical application. In this study, we developed a glycyrrhetinic acid (GA) modified curcumin supramolecular pro-gelator (GA-Cur) and a control compound Nap-Cur by replacing GA with the naphthylacetic acid (Nap). Both compounds showed good water solubility and could form supramolecular gels by disulfide bond reduction triggered by glutathione (GSH) in vitro. Both formed gels could sustainedly release Cur in buffer solutions. We also investigated the cytotoxicity of pro-gelators to HepG2 cells by a MTT assay and determined the cellular uptake behaviours of them by fluorescence microscopy and LC-MS. Due to the over expression of GA receptor in liver cancer cells, our pro-gelator of GA-Cur showed an enhanced cellular uptake and better inhibition capacity to liver tumor cells than Nap-Cur. Therefore, the GA-Cur could significantly inhibit HepG2 cell growth. Our study provides a novel nanomaterial for liver tumor chemotherapy.

Nanostructure formation-induced fluorescence turn-on for selectively detecting protein thiols in solutions, bacteria and live cells.

We report the design and synthesis of a light-up probe of DBT-2(EEGK-maleimide), which can serve as a unique probe for selectively detecting protein thiols in various environments, including aqueous solutions, bacteria and live cells.