Physical and social environmental enrichment alleviate ferroptosis and inflammation with inhibition of TLR4/MyD88/p38MAPK pathway in chronic cerebral hypoperfusion rats

A typical enriched environment (EE), which combines physical activity and social interaction, has been proven to mitigate cognitive impairment caused by chronic cerebral hypoperfusion (CCH). However, it remains unclear how the different components of EE promote cognitive recovery after CCH. This study stripped out the different components of EE into physical environmental enrichment (PE) and social environmental enrichment (SE), and compared the neuroprotective effects of PE, SE and typical EE (PSE) in CCH. The results of novel object recognition and Morris water maze tests showed that PE, SE, and PSE improved cognitive function in CCH rats. Additionally, Nissl and TUNEL staining revealed that three EEs reduced neuronal loss in the hippocampus. PSE exhibited superior neuroprotective and functional improvement effects compared to PE and SE, while there was no significant difference between PE and SE. Furthermore, three EEs reduced lipid peroxidation in the hippocampus with decreasing the levels of MDA and increasing the activities of SOD and GSH. The expression of SLC7A11 and GPX4 was increased, while the level of p53 was reduced in three EEs. This suggested that three EEs inhibited ferroptosis by maintaining the redox homeostasis in the hippocampus. Three EEs reduced the levels of IL-β, TNF-α, and IL-6, thereby inhibiting neuroinflammation. Additionally, Western blotting and immunofluorescence results indicated that three EEs also inhibited the TLR4/MyD88/p38MAPK signaling pathway. These findings collectively demonstrated that the three EEs alleviated hippocampal ferroptosis and neuroinflammation in CCH rats, thereby reducing neuronal loss, which might be associated with the inhibition of the TLR4/MyD88/p38MAPK signaling pathway. Moreover, the study results supported that it is only through the combination of physical exercise and social interaction that the optimal neuroprotective effects can be achieved. These findings provided valuable insights for the prevention and treatment of vascular cognitive impairment

Experimental Research on Characteristics of Impulse Coupling and Plasma Plume Generated by Laser Irradiating Copper Target with Nanosecond Pulsed Laser Propulsion

The ejection of the plasma plume produced by laser ablation is an important process for inducing mechanical effects. Therefore, in this paper, the characteristics of the plasma plume are investigated in order to analyze the impulse coupling mechanism with two laser spot diameters, 300 μm and 1100 μm, respectively. The impulse generated by laser irradiating the copper target was measured by the torsion pendulum, and the plasma plume was investigated using fast photography and optical emission spectroscopy. The experimental results show that the optimal laser intensity is independent of the beam spot size. However, when the laser intensity is greater than 2.8 × 109 W/cm2, the impulse coupling coefficient with the small beam spot starts to gradually decrease, while that with the large beam spot tends to saturate. Additionally, the stream-like structure and the semi-ellipsoid structure of the plasma plume were observed, respectively. Furthermore, the electron number density was estimated using the Stark broadening method, and the effect of the plasma plume on the impulse coupling coefficient was discussed. The results provide a technical reference for several applications including orbital debris removal with lasers, laser thrusters, and laser despinning

Simulation of the Residual Stress of the Y2O3/Al2O3 Composite Deuterium Permeation Barrier under Thermal Shock

A deuterium permeation barrier is an essential part in the core component of nuclear reactors. It can protect the structure made of steel from being penetrated by deuterium in a fusion reactor. However, residual stress induced in the operation would dramatically influence the mechanical endurance of the coating, threatening the safety of the facilities. In this paper, finite element analysis was conducted to investigate the residual stress in nanoscale Al2O3 and Y2O3 coatings and their composites under thermal shock, from 700°C to 25°C. The max principal stress is assumed as the cause of crack initiation in the coating, because ceramics are brittle and fragile under tensile stress. Max shear stress and max Mises stress in the systems are also analyzed, and the effect of thickness in the range 100 nm to 1000 nm was investigated. The max principal stress in Al2O3 coating reaches its maximum value, 1.33 GPa, when the thickness of coating reaches 450 nm. And the max principal stress decreases at a very low rate as the thickness increases exceeding 450 nm. The max principal stress in Y2O3 coating increases rapidly as the thickness increases when the thickness of the coating is below 250 nm, and the max principal stress is at about 0.9 GPa when the thickness exceeds 500 nm. The max principal stress in the Y2O3/Al2O3 (150 nm) composite coating occurs in the Al2O3 layer and shows no difference from the single layer of 150 nm thick Al2O3 coating. The max principal stress site of all three kinds of coating is located at the edge of the coating 25 nm away from the interface. The result shows that residual thermal stress in the coating increases as the thickness increases when the thickness of the coating is below 200 nm due to the stress singularity of the interface. And as the thickness exceeds 500 nm, the increase in thickness has little impact on the residual thermal stress in the coating. Coating an Y2O3 top layer will not introduce any more residual thermal stress under the thermal shock condition. The Y2O3 coating causes much less residual stress under thermal shock compared with Al2O3 owing to its much lower Young’s modulus. The max principal stress in the 300 nm thick Y2O3 coating is 0.85 GPa while that of the Al2O3 coating is 1.16 GPa. The max residual stress of the composite Y2O3/Al2O3 (150 nm) coating is determined by the Al2O3 layer

Study on the Influence of Introducing Al Transition Layer on Deuterium Resistance of Al2O3 Coating

The Al/Al2O3 composite deuterium barrier was deposited on the polished side of 316 L stainless steel by the method of radio-frequency magnetron sputtering. The influence of the introduction of Al transition layer on the deuterium resistance performance of Al2O3 ceramic coating was studied. The field emission scanning electron microscope (SEM), the grazing incident X-ray diffraction technique (GIXRD), and the auger electron spectroscopy (AES) were used to analyze the microscopic morphology, phase, and element distribution in the depth direction of the Al/Al2O3 coating, and the gas-driver permeation method was used to measure the deuterium permeation behavior of the coating sample. The results show that Al2O3 is amorphous after annealing at 873 K. Due to the oxidation of the Al transition layer, the connection between the coating and the substrate is tightly connected. Under the combined action of permeation temperature and pressure of 873 K and 80 kPa, the deuterium permeability of Al/Al2O3 coating is 6.35×10−14 mol·m-1·s-1·Pa-0.5, which shows that the Al/Al2O3 coating has excellent deuterium permeation resistance. Furthermore, deuterium permeability of the Al/Al2O3 coating was diminished by about 2 orders of magnitude compared with 316 L stainless steel, and it is reduced 2~3 times compared with the single Al2O3 coating sample. The study indicates that the introduction of the Al transition layer can significantly enhance the barrier effect of the Al/Al2O3 coating sample

Long Noncoding RNA PVT1 as a Novel Diagnostic Biomarker and Therapeutic Target for Melanoma

Accumulating evidences indicated that plasmacytoma variant translocation 1 (PVT1) plays vital roles in several cancers. However, the expression, functions, and clinical values of PVT1 in melanoma are still unknown. In this study we measured the expression of PVT1 in clinical tissues and serum samples and explored the diagnostic value of PVT1 for melanoma and the effects of PVT1 on melanoma cell proliferation, cell cycle, and migration. Our results, combined with publicly available PVT1 expression data, revealed that PVT1 is upregulated in melanoma tissues compared with nonneoplastic nevi tissues. Serum PVT1 level is significantly increased in melanoma patients compared with age and gender-matched nonmelanoma controls with melanocytic nevus. Receiver operating characteristic curve analyses revealed that serum PVT1 level could sensitively discriminate melanoma patients from controls. Furthermore, serum PVT1 level indicted melanoma dynamics. Functional experiments showed that overexpression of PVT1 promotes melanoma cells proliferation, cell cycle progression, and migration, while depletion of PVT1 significantly inhibits melanoma cells proliferation, cell cycle progression, and migration. Collectively, our results indicate that PVT1 functions as an oncogene in melanoma and could be a potential diagnostic biomarker and therapeutic target for melanoma

Effect of Tetramethylpyrazine on Neuroplasticity after Transient Focal Cerebral Ischemia Reperfusion in Rats

Tetramethylpyrazine (TMP) has been widely used in ischemic stroke in China. The regulation of neuroplasticity may underlie the recovery of some neurological functions in ischemic stroke. Middle cerebral artery occlusion (MCAO) model was established in this study. Rats were divided into three groups: sham group, model group, and TMP group. The neurological function was evaluated using modified neurological severity score (mNSS). Following the neurological function test, expression of synaptophysin (SYP) and growth-associated protein 43 (GAP-43) were analyzed through immunohistochemistry at 3 d, 7 d, 14 d, and 28 d after MCAO. Finally, the synaptic structural plasticity was investigated using transmission electron microscopy (TEM). The TMP group showed better neurological function comparing to the model group. SYP levels increased gradually in ischemic penumbra (IP) in the model group and could be enhanced by TMP treatment at 7 d, 14 d, and 28 d, whereas GAP-43 levels increased from 3 d to 7 d and thereafter decreased gradually from 14 d to 28 d in the model group, which showed no significant improvement in the TMP group. The results of TEM showed a flatter synaptic interface, a thinner postsynaptic density (PSD), and a wider synaptic cleft in the model group, and the first two alterations could be ameliorated by TMP. Then, a Pearson’s correlation test revealed mNSS markedly correlated with SYP and synaptic ultrastructures. Taken together, TMP is capable of promoting functional outcome after ischemic stroke, and the mechanisms may be partially associated with regulation of neuroplasticity

DoSurvive: A webtool for investigating the prognostic power of a single or combined cancer biomarker

Summary: We present DoSurvive, a user-friendly survival analysis web tool and a cancer prognostic biomarker centered database. DoSurvive is the first database that allows users to perform multivariant survival analysis for cancers with customized gene/patient list. DoSurvive offers three survival analysis methods, Log rank test, Cox regression and accelerated failure time model (AFT), for users to analyze five types of quantitative features (mRNA, miRNA, lncRNA, protein and methylation of CpG islands) with four survival types, i.e. overall survival, disease-specific survival, disease-free interval, and progression-free interval, in 33 cancer types. Notably, the implemented AFT model provides an alternative method for genes/features which failed the proportional hazard assumption in Cox regression. With the unprecedented number of survival models implemented and high flexibility in analysis, DoSurvive is a unique platform for the identification of clinically relevant targets for cancer researcher and practitioners. DoSurvive is freely available at http://dosurvive.lab.nycu.edu.tw/

Value of lymph node ratio as a prognostic factor of recurrence in medullary thyroid cancer

Background and Objectives The purpose of this study is to evaluate the relationship between lymph node status (the number of resected lymph nodes; the number of metastatic lymph nodes, LNM, and lymph node ratio, LNR) and biochemical recurrence, disease-free survival (DFS), as well as overall survival (OS) in medullary thyroid carcinoma (MTC). Methods This study enrolled MTC patients at Tianjin Medical University Cancer Institute and Hospital between 2011 and 2019. We used Logistic regression analysis, Cox regression models and Kaplan-Meier test to identify risk factors influencing biochemical recurrence, DFS, and OS. Results We identified 160 patients who satisfied the inclusion criteria from 2011 to 2019. We used ROC analysis to define the cut-off value of LNR with 0.24. Multifocality, preoperative calcitonin levels, pathologic N stage, resected lymph nodes, LNM, LNR, and the American Joint Committee on Cancer (AJCC) clinical stage were significant (P < 0.05) prognostic factors influencing biochemical cure. In univariable analyses, gross extrathyroidal extension, preoperative calcitonin levels, pathologic T classification, pathologic N stage, resected lymph nodes, LNM, LNR, AJCC clinical stage, and biochemical cure were significant (P < 0.05) factors of DFS. When the multivariable analysis was performed, LNR was identified as predictor of DFS (HR = 4.818, 95% CI [1.270–18.276]). Univariable Cox regression models reflected that tumor size, pathologic N stage, and LNR were predictor of OS. Furthermore, multivariable analysis manifested that LNR was predictor of OS (HR = 10.061, 95% CI [1.222–82.841]). Conclusions This study illustrated that LNR was independent prognostic factor of DFS and OS in MTC. In addition, LNR influenced biochemical cure. Further investigations are needed to determine the optimal cut-off value for predicting prognosis

Tantalum Nanoparticles Reinforced Polyetheretherketone Shows Enhanced Bone Formation

Polyetheretherketone (PEEK) has been used in orthopedic surgery for several decades. Numerous methods were invented to alter the properties of PEEK. By adding nanoparticles, fibers, etc., elastic modulus and strength of PEEK can be changed to meet certain demand. In this study, tantalum (Ta), a promising metal, was introduced to modify the properties of PEEK, in which PEEK was reinforced with different contents of tantalum nanoparticles (from 1 wt% to 9 wt%). Mechanical properties and biological functions (both in vitro and in vivo) were then investigated. The highest elastic modulus and compressive strength were observed in 3%Ta-PEEK. Cell experiments as cell adhesion, collagen secretion, biomineralization and osteogenesis related gene expression showed preferable results in 3%Ta-PEEK and 5%Ta-PEEK. Improved bone integration was shown in 3%Ta-PEEK and 5%Ta-PEEK in vivo. Above all, enhanced mechanical properties and promoted bone formation were proved for 3%Ta-PEEK and 5%Ta-PEEK compared to others groups both in vitro and in vivo, suggesting that the addition of tantalum nanoparticles modified the osseointegration ability of PEEK. This composite of tantalum and PEEK could have a clinical potential for orthopedic implants