Beta-amyloid (Aβ), the hallmark protein in Alzheimer’s disease (AD), induces neurotoxicity that involves oxidative stress and mitochondrial dysfunction, leading to cell death. Carnosic acid (CA), a ...polyphenolic diterpene isolated from the herb rosemary (
Rosemarinus officinalis
), was investigated in our study to assess its neuroprotective effect and underlying mechanism against Aβ-induced injury in human neuroblastoma SH-SY5Y cells. We found that CA pretreatment alleviated the Aβ
25–35
-induced loss of cell viability, inhibited both Aβ
1–42
accumulation and tau hyperphosphorylation, reduced reactive oxygen species generation, and maintained the mitochondrial membrane potential. Moreover, CA increased the microtubule-associated protein light chain 3 (LC3)-II/I ratio and decreased SQSTM1(p62), indicating that CA could induce autophagy. Autophagy inhibitor 3-methyladenine (3-MA) attenuated the neuroprotective effect of CA, suggesting that autophagy was involved in the neuroprotection of CA. It was also observed that CA activated AMP-activated protein kinase (AMPK) but inhibited mammalian target of rapamycin (mTOR). Furthermore, blocking AMPK with si-AMPKα successfully inhibited the upregulation of LC3-II/I, prevented the downregulation of phosphorylation of mTOR and SQSTM1(p62), indicating that CA induced autophagy in SH-SY5Y cells via the activation of AMPK. These results suggested that CA might be a potential agent for preventing AD.
Introduction
The gain/amplification (amp) of 1q21 is one of the most common high‐risk chromosome abnormality (HRCA) in multiple myeloma (MM). The prognostic value of 1q21+ remains to be controversial ...on the status of gain or amp and the combination of other HRCAs.
Methods
In this retrospective study, we included 318 newly diagnosed MM (NDMM) patients who had fluorescence in situ hybridization (FISH) data and treated with novel agents in our department.
Results
Our study noted MM patients with amp 1q21 were more likely accompanied with t(4;14), t(14;16), and t(14;20). Patients with amp 1q21 presented with elder age, advanced Revised International Staging System (R‐ISS) stages, anemia, and more plasma cells in bone marrow compared to patients with gain 1q21 alone and no 1q21+. Moreover, amp 1q21 alone correlated with shorter progression‐free survival (PFS) (22.8m vs. 40.5m vs. 39.6m) and overall survival (OS) (45.2m vs. NA vs. 83.5m) compared with gain 1q21 alone and no FISH abnormalities. Although the high ratio of proteasome inhibitor and immunomodulatory drugs used in patients with amp 1q21, the overall response (ORR) was the lowest compared with no 1q21+ and gain 1q21. Multivariate analysis defined amp 1q21 as an independent prognostic marker for NDMM patients, rather than gain 1q21.
Conclusion
The amp 1q21 predict inferior treatment response and survival, especially coexisted with high‐risk IgH translocation.
The prognostic value of 1q21+ detected by FISH remains to be controversial on the status of gain or amp for multiple myeloma (MM). The real‐world data demonstrated MM patients with amp 1q21 more likely combined with other high‐risk chromosome abnormality. Meanwhile, the individualism of amp 1q21 correlated with poor treatment response and survival.
Aims
Patients with heart failure (HF) and with diabetes experienced significantly worse outcomes than those without diabetes. However, data on the prognostic impact of prediabetes in HF are ...inconclusive. This meta‐analysis aimed to explore the association between prediabetes and the risk of all‐cause mortality and adverse cardiac outcomes in patients with HF.
Materials and methods
We searched multiple electronic databases (PubMed, Embase and Google Scholar) for relevant studies up to 31 March 2021. Studies were included for analysis if multivariable adjusted relative risks of adverse outcomes were reported in patients with prediabetes and with HF compared with those with normoglycaemia. Random‐effects models were used to calculate the pooled hazard ratios (HRs) and 95% confidence intervals (CIs).
Results
Twelve studies comprising 28 643 patients with HF reported the risk of all‐cause mortality and cardiac outcomes associated with prediabetes. The prevalence of prediabetes ranged from 9.6% to 37.2%. After a median follow‐up duration of 2.3 years, patients with HF and with prediabetes were associated with an increased risk of all‐cause mortality (HR 1.29, 95% CI 1.06‐1.58), cardiovascular mortality (HR 1.59, 95% CI 1.09‐2.32), HF hospitalization (HR 1.33, 95% CI 1.09‐1.61), all‐cause mortality and/or HF hospitalization (HR 1.22, 95% CI 1.01‐1.47), as well as cardiovascular mortality and/or HF hospitalization (HR 1.21, 95% CI 1.07‐1.37).
Conclusions
Prediabetes is associated with a worse prognosis in patients with HF. Further risk stratification and effective treatment strategies are needed in patients with prediabetes and with HF to improve the prognosis.
Cardiovascular diseases (CVDs) present a major social problem worldwide due to their high incidence and mortality rate. Many pathophysiological mechanisms are involved in CVDs, and oxidative stress ...plays a vital mediating role in most of these mechanisms. The ubiquitin–proteasome system (UPS) is the main machinery responsible for degrading cytosolic proteins in the repair system, which interacts with the mechanisms regulating endoplasmic reticulum homeostasis. Recent evidence also points to the role of UPS dysfunction in the development of CVDs. The UPS has been associated with oxidative stress and regulates reduction–oxidation homeostasis. However, the mechanisms underlying UPS-mediated oxidative stress’s contribution to CVDs are unclear, especially the role of these interactions at different disease stages. This review highlights the recent research progress on the roles of the UPS and oxidative stress, individually and in combination, in CVDs, focusing on the pathophysiology of key CVDs, including atherosclerosis, ischemia–reperfusion injury, cardiomyopathy, and heart failure. This synthesis provides new insight for continued research on the UPS–oxidative stress interaction, in turn suggesting novel targets for the treatment and prevention of CVDs.
Various relations existing in Electroencephalogram (EEG) data are significant for EEG feature representation. Thus, studies on the graph-based method focus on extracting relevancy between EEG ...channels. The shortcoming of existing graph studies is that they only consider a single relationship of EEG electrodes, which results an incomprehensive representation of EEG data and relatively low accuracy of emotion recognition. In this paper, we propose a fusion graph convolutional network (FGCN) to extract various relations existing in EEG data and fuse these extracted relations to represent EEG data more comprehensively for emotion recognition. First, the FGCN mines brain connection features on topology, causality, and function. Then, we propose a local fusion strategy to fuse these three graphs to fully utilize the valuable channels with strong topological, causal, and functional relations. Finally, the graph convolutional neural network is adopted to represent EEG data for emotion recognition better. Experiments on SEED and SEED-IV demonstrate that fusing different relation graphs are effective for improving the ability in emotion recognition. Furthermore, the emotion recognition accuracy of 3-class and 4-class is higher than that of other state-of-the-art methods.
Cyclooxygenase-2 in Endometriosis Lai, Zhen-Zhen; Yang, Hui-Li; Ha, Si-Yao ...
International journal of biological sciences,
01/2019, Letnik:
15, Številka:
13
Journal Article
Recenzirano
Odprti dostop
Endometriosis (EMS) is the most common gynecological disease in women of reproductive age, and it is associated with chronic pelvic pain, dyspareunia and infertility. As a consequence of genetic, ...immune and environmental factors, endometriotic lesions have high cyclooxygenase (COX)-2 and COX-2-derived prostaglandin E
(PGE
) biosynthesis compared with the normal endometrium. The transcription of the PTGS2 gene for COX-2 is associated with multiple intracellular signals, which converge to cause the activation of mitogen-activated protein kinases (MAPKs). COX-2 expression can be regulated by several factors, such as estrogen, hypoxia, proinflammatory cytokines, environmental pollutants, metabolites and metabolic enzymes, and platelets. High concentrations of COX-2 lead to high cell proliferation, a low level of apoptosis, high invasion, angiogenesis, EMS-related pain and infertility. COX-2-derived PGE
performs a crucial function in EMS development by binding to EP2 and EP4 receptors. These basic findings have contributed to COX-2-targeted treatment in EMS, including COX-2 inhibitors, hormone drugs and glycyrrhizin. In this review, we summarize the most recent basic research in detail and provide a short summary of COX-2-targeted treatment.
Strong near‐infrared absorption in ultrathin semiconductor layers is essential for increasing the speed and efficiency of photocarrier extraction in optoelectronic devices. However, the absorption of ...a free‐standing ultrathin film can never exceed 50% in principle. In this article, an all‐dielectric germanium metasurface absorber in the near‐infrared region (800–1600 nm) is proposed theoretically and experimentally. Near‐unity absorption can be achieved in such a subwavelength‐thin (≈0.13 λ0) layer of nanostructures based on the destructive interference between simultaneously excited electric and magnetic dipoles inside each element in the backward direction in combination with the destructive interference between the scattered field and the incident field in the forward direction. Its response is both polarization‐independent and angle‐insensitive, with over 80% absorption at an incident angle up to 28°. This ultrathin and flexible design paves the way for realizing next generation optoelectronic devices aimed for high‐speed photon detection and energy harvesting.
To break the 50% absorption limit of an ultrathin free‐standing film, an ultrathin (≈0.13 λ0) germanium nanoantenna‐based all‐dielectric metasurface with near‐unity absorption in the near‐infrared region is proposed theoretically and experimentally. This design paves the way for realizing next generation optoelectronic devices aimed for high‐speed photon detection and energy harvesting.
Abstract
Advanced multispectral detection technologies have emerged as a significant threat to objects, necessitating the use of multiband camouflage. However, achieving effective camouflage and ...thermal management across the entire infrared spectrum, especially the short-wave infrared (SWIR) band, remains challenging. This paper proposes a multilayer wavelength-selective emitter that achieves effective camouflage across the entire infrared spectrum, including the near-infrared (NIR), SWIR, mid-wave infrared (MWIR), and long-wave infrared (LWIR) bands, as well as the visible (VIS) band. Furthermore, the emitter enables radiative heat dissipation in two non-atmospheric windows (2.5–3 μm and 5–8 μm). The emitter’s properties are characterized by low emittance of 0.270/0.042/0.218 in the SWIR/MWIR/LWIR bands, and low reflectance of 0.129/0.281 in the VIS/NIR bands. Moreover, the high emittance of 0.742/0.473 in the two non-atmospheric windows ensures efficient radiative heat dissipation, which results in a temperature decrement of 14.4 °C compared to the Cr reference at 2000 W m
−2
input power density. This work highlights the role of solar radiance in camouflage, and provides a comprehensive guideline for developing multiband camouflage compatible with radiative heat dissipation, from the visible to LWIR.
The hot carrier injection (HCI) reliability of n-type FinFETs in ring oscillators (ROs) is investigated with consideration of the circuit-level time-varying electrothermal effects in the ROs. The ...oscillating voltages and electrical power in a nine-stage RO are captured by circuit simulation in Cadence with its layout that is designed and verified based on FreePDK15. Spatial temperature response is obtained by heat conduction simulation with finite element analysis in the 3-D integrated structure that is accordingly constructed from the layout of the RO, where the heat generation is extracted from the Cadence simulation. With the obtained ac stress voltages and transient temperature, the HCI-induced threshold voltage shift (TVS) of n-type FinFETs under the circuit-level time-varying electrothermal effects is successfully predicted. The impacts of electrical and thermal parameters of the RO, including the supply voltage and thermal surrounding, on the electrothermal response and HCI reliability of FinFETs are also revealed.
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