A new type of metabolizable and efficient radiosensitizers for cancer radiotherapy is presented by combining ultrasmall Au nanoclusters (NCs, <2 nm) with biocompatible coating ligands (glutathione, ...GSH). The new nanoconstruct (GSH-coated Au25 NCs) inherits attractive features of both the Au core (strong radiosensitizing effect) and GSH shell (good biocompatibility). It can preferentially accumulate in tumor via the improved EPR effect, which leads to strong enhancement for cancer radiotherapy. After the treatment, the small-sized GSH-Au25 NCs can be efficiently cleared by the kidney, minimizing any potential side effects due to the accumulation of Au25 NCs in the body.
Background:
Cerebral small vessel disease (CSVD) is a group of clinical syndromes covering all pathological processes of small vessels in the brain, which can cause stroke and serious dementia. ...However, as the pathogenesis of CSVD is not clear, so the treatment is limited. Endothelial cell dysfunction is earlier than clinical symptoms, such as hypertension and leukosis. Therefore, the treatment of endothelial cells is expected to be a new breakthrough. Quercetin, a flavonoid present in a variety of plants, has the function of anti-inflammation and anti-oxidation. This study aimed to investigate the protective effect of quercetin on endothelial cell injury and provide a basic theory for subsequent application in the clinic.
Methods:
Human brain microvascular endothelial cells (HBMECs) were cultured
in vitro
, and the injury model of endothelial cells was established by hypoxia and reoxygenation (H/R). The protective effects of quercetin on HBMECs were studied from the perspectives of cell viability, cell migration, angiogenesis and apoptosis. In order to further study the mechanism of quercetin, oxidative stress and endoplasmic reticulum stress were analyzed. What’s more, blood-brain barrier (BBB) integrity was also studied.
Results:
Quercetin can promote the viability, migration and angiogenesis of HBMECs, and inhibit the apoptosis. In addition, quercetin can also activate Keap1/Nrf2 signaling pathway, reduce ATF6/GRP78 protein expression. Further study showed that quercetin could increase the expression of Claudin-5 and Zonula occludens-1.
Conclusions:
Our experiments show that quercetin can protect HBMECs from H/R, which contains promoting cell proliferation, cell migration and angiogenesis, reducing mitochondrial membrane potential damage and inhibiting cell apoptosis. This may be related to its antioxidation and inhibition of endoplasmic reticulum stress. At the same time, quercetin can increase the level of BBB connexin, suggesting that quercetin can maintain BBB integrity.
The effect of equal channel angular pressing (ECAP) and further cold upsetting (CU) process on the kinetics of precipitation during aging of solid solution treated 7050 Al alloy were studied using ...differential scanning calorimetry and transmission electron microscopy. Results indicate that the activation energy of η′ phase was reduced from 120.371 kJ/mol to 73.387 kJ/mol after ECAP process and to 59.740 kJ/mol after CU process, because of the accumulation of dislocations. Thus, the peak aging time was shortened from 333 h to 7 h and 3 h after ECAP and ECAP−CU composite process respectively. Additionally, the precipitation of the η phase was suppressed after ECAP, but accelerated after ECAP−CU process, with the change of activation energy from 185.323 kJ/mol to 208.266 kJ/mol and 156.060 kJ/mol respectively. The annihilation of dislocations and precipitation of phases during aging treatment led to the competition of softening and strengthening of mechanical strength, indicating that the increasement of elongation is coupled with slight reduction of strength. After peak aging treatment, the tensile strength remained approximately unchanged of 546 ± 14 MPa, while the uniform elongation increased by about 35.3% from 5.1 ± 0.6 to 6.9 ± 1.5.
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•A strengthening method innovatively proposes for obtaining Al alloy fasteners with excellent performance.•Ultrafine-grained Al alloy fasteners with high strength and elongation were produced by composite deformation.•The peak aging time of composite deformed alloys were shortened because of the reduction of activation energy of η′ phase.•The annihilation of dislocations and precipitation of phases occurred at the same time during aging treatment.
Herein, isothermal compression experiments are conducted on EA4T steel at 970–1170 °C, with strain rates of 0.01–1.0 s−1 and a strain of 0.2–0.8 s−1. Based on the experimental data, a ...high‐temperature constitutive model is developed for EA4T steel. The activation energy of dynamic recrystallization (DRX) is calculated to be 383 666 J mol−1, and the correlation coefficient and root mean square error between the results of the constitutive model and experimental results are 0.9943 and 4.6823, respectively. The average grain size for each deformation condition is determined using the linear‐intercept method. The grain growth model widely used in cellular automaton (CA) simulations is found unsuitable for EA4T steel. Therefore, a modified CA model of DRX behavior suitable for EA4T steel is developed. The nucleation rates and solute drag effect coefficients under different deformation conditions are determined. Furthermore, simulations are performed under other deformation conditions using the CA model. The simulated results for the average grain size, microstructure morphology, and DRX fraction agree well with the experimental results. The reason for the deviation between the observed and simulated DRX fractions is also explored.
A high‐temperature constitutive model of EA4T steel has been established based on the results of isothermal compression experiments. A modified cellular automaton model of dynamic recrystallization (DRX) behavior suitable for EA4T steel is established. The average grain size, grain morphology, and DRX fraction obtained from the simulation are in good agreement with the experimental results.
Microstructural evolution and flow behavior greatly affect the hot forming process of IN718. In this research, hot deformation behaviors of IN718 were investigated by performing hot compression tests ...at temperature range of 1000–1100 °C with strain rates of 0.1–20.0 s
−1
. By incorporating physically based internal state variables such as dislocation density, volume fraction of dynamic recrystallization, and grain size, a set of unified viscoplastic constitutive equations were developed to predict the microstructural evolution and flow behavior of IN718. The material constants were determined using a genetic algorithm (GA)-based optimization method. Comparisons of the computed and experimental results indicate that the constitutive equations established in this study can accurately describe the hot deformation behavior and microstructural evolution of IN718.
The innovative combination of equal channel angular pressing (ECAP) and cold upsetting (CU) is significant for producing high-strength Al alloy fasteners with ultrafine grains. However, the ...relationship between microstructure evolution and mechanical strength during composite deformation remains unclear. In this study, using transmission electron microscopy, electron backscatter diffraction, and mechanical property tests, it is found that the mechanical strength increases with each step of composite forming operations due to the accumulation of dislocations. Forest dislocations also contribute to the generation of ultrafine grains within deformed grains, particularly in ECAP-CU processed grains. Moreover, we observe the formation of lamellar structures within the shear bands in the head of the ultrafine grain fastener after final composite deformation, which is full of dense dislocation walls and dislocation cells. The rearrangement of these fine grains and lamellar structures yield a strong (011) (brass) texture during composite deformation under the effect of shear force and accumulation of plastic strain. This study provides a theoretical reference for the manufacture of high-strength aluminum alloy fasteners through composite deformation and helps improve processing technology.
Objective
Cerebral small vessel disease (CSVD) is a clinical syndrome caused by pathological changes in small vessels. Anxiety is a common symptom of CSVD. Previous studies have reported the ...association between inflammatory factors and anxiety in other diseases, but this association in patients with CSVD remains uncovered. Our study aimed to investigate whether serum inflammatory factors correlated with anxiety in patients with CSVD.
Methods
A total of 245 CSVD patients confirmed using brain magnetic resonance imaging (MRI) were recruited from December 2019 to December 2021. Hamilton Anxiety Rating Scale (HAMA) was used to assess the anxiety symptoms of CSVD patients. Patients with HAMA scores ≥7 were considered to have anxiety symptoms. The serum levels of interleukin-1β (IL-1β), IL-2R, IL-6, IL-8, IL-10, tumor necrosis factor-α (TNF-α), serum amyloid A (SAA), C-reactive protein (CRP), high-sensitivity C-reactive protein (hs-CRP) and erythrocyte sedimentation rate (ESR) were detected. We compared levels of inflammatory factors between the anxiety and non-anxiety groups. Logistic regression analyses examined the correlation between inflammatory factors and anxiety symptoms. We further performed a gender subgroup analysis to investigate whether this association differed by gender.
Results
In the fully adjusted multivariate logistic regression analysis model, we found that lower levels of IL-8 were linked to a higher risk of anxiety symptoms. Moreover, higher levels of SAA were linked to a lower risk of anxiety symptoms. Our study identified sex-specific effects, and the correlation between IL-8 and anxiety symptoms remained significant among males, while the correlation between SAA and anxiety symptoms remained significant among females.
Conclusions
In this study, we found a suggestive association between IL-8, SAA, and anxiety symptoms in CSVD participants. Furthermore, IL-8 and SAA may have a sex-specific relationship with anxiety symptoms.
Objective:
Immune checkpoint inhibitors (ICIs) are effective anti-cancer drugs that can improve survival in cancer patients, but their use may be associated with adverse cardiovascular side effects. ...Therefore, there is a clinical unmet need to identify non-invasive biomarker to detect subclinical cardiac toxicity after ICI treatment. The aim of this study is to examine the plasma levels of biomarkers in cancer survivors who were treated with ICIs.
Patients and Methods:
In a cohort of 19 cancer patients, biomarkers were evaluated at baseline, 1 month, 3 and 6 months after ICI administration. These biomarkers, hypothesized to be mechanistically relevant to cardiotoxicity, included cardiac troponin I (cTnI), high-sensitivity C-reactive protein (Hs-CRP), N-terminal pro–B-type natriuretic peptide (NT-pro BNP), CK (creatine kinase), CK-MB (creatine kinase-MB), Pentraxin-related protein 3 (PTX3), growth differentiation factor 15 (GDF-15), heart type-fatty acid binding protein (H-FABP) and galectin 3 (Gal-3).
Results:
H-FABP, but not other biomarkers, were increased at 3 months, which persisted at 6 months (529.28 ± 312.83 vs. 752.33 ± 283.65 vs. 808.00 ± 289.69 pg/ml,
p
= 0.031 and
p
= 0.013). Left ventricular ejection fraction (63.00 ± 4.15% vs. 63.74 ± 4.07%,
p
> 0.05) was not significantly reduced at this time point.
Conclusions:
H-FABP, but not other biomarkers, were increased in patients who were treated using ICIs. H-FABP might be a more sensitive biomarker to detect ICI-related subclinical myocardial damage than traditional cardiac biomarkers.
In this letter, we design an external invisibility cloak that has the cloaking performance for various scattering objects positioned in the outer canceled air layer. The external cloak has an ...arbitrary geometry, and the "anti-objects" that embedded in the negative index shell can keep the same shape without being geometrically transformed. Compared to the traditional cloak, the external cloak has a finite canceled air layer but does not cover the objects surfaces. The external cloak has a smaller size than the traditional cloak. Simultaneously, the object in the core layer can also be cloaked and see outside situations. This system can produce an illusion image for an object embedded in the core layer.
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