Osteoporosis is a serious health issue among aging postmenopausal women. The majority of postmenopausal women with osteoporosis have bone loss related to estrogen deficiency. The rapid bone loss ...results from an increase in bone turnover with an imbalance between bone resorption and bone formation. Osteoporosis can also result from excessive glucocorticoid usage, which induces bone demineralization with significant changes of spatial heterogeneities of bone at microscale, indicating potential risk of fracture. This review is a summary of current literature about the molecular mechanisms of actions, the risk factors, and treatment of estrogen deficiency related osteoporosis (EDOP) and glucocorticoid induced osteoporosis (GIOP). Estrogen binds with estrogen receptor to promote the expression of osteoprotegerin (OPG), and to suppress the action of nuclear factor-κβ ligand (RANKL), thus inhibiting osteoclast formation and bone resorptive activity. It can also activate Wnt/β-catenin signaling to increase osteogenesis, and upregulate BMP signaling to promote mesenchymal stem cell differentiation from pre-osteoblasts to osteoblasts, rather than adipocytes. The lack of estrogen will alter the expression of estrogen target genes, increasing the secretion of IL-1, IL-6, and tumor necrosis factor (TNF). On the other hand, excessive glucocorticoids interfere the canonical BMP pathway and inhibit Wnt protein production, causing mesenchymal progenitor cells to differentiate toward adipocytes rather than osteoblasts. It can also increase RANKL/OPG ratio to promote bone resorption by enhancing the maturation and activation of osteoclast. Moreover, excess glucocorticoids are associated with osteoblast and osteocyte apoptosis, resulting in declined bone formation. The main focuses of treatment for EDOP and GIOP are somewhat different. Avoiding excessive glucocorticoid use is mandatory in patients with GIOP. In contrast, appropriate estrogen supplement is deemed the primary treatment for females with EDOP of various causes. Other pharmacological treatments include bisphosphonate, teriparatide, and RANKL inhibitors. Nevertheless, more detailed actions of EDOP and GIOP along with the safety and effectiveness of medications for treating osteoporosis warrant further investigation.
It is demonstrated that carbon quantum dots derived from curcumin (Cur‐CQDs) through one‐step dry heating are effective antiviral agents against enterovirus 71 (EV71). The surface properties of ...Cur‐CQDs, as well as their antiviral activity, are highly dependent on the heating temperature during synthesis. The one‐step heating of curcumin at 180 °C preserves many of the moieties of polymeric curcumin on the surfaces of the as‐synthesized Cur‐CQDs, resulting in superior antiviral characteristics. It is proposed that curcumin undergoes a series of structural changes through dehydration, polymerization, and carbonization to form core–shell CQDs whose surfaces remain a pyrolytic curcumin‐like polymer, boosting the antiviral activity. The results reveal that curcumin possesses insignificant inhibitory activity against EV71 infection in RD cells half‐maximal effective concentration (EC50) >200 µg mL−1 but exhibits high cytotoxicity toward RD cells (half‐maximal cytotoxic concentration (CC50) <13 µg mL−1). The EC50 (0.2 µg mL−1) and CC50 (452.2 µg mL−1) of Cur‐CQDs are >1000‐fold lower and >34‐fold higher, respectively, than those of curcumin, demonstrating their far superior antiviral capabilities and high biocompatibility. In vivo, intraperitoneal administration of Cur‐CQDs significantly decreases mortality and provides protection against virus‐induced hind‐limb paralysis in new‐born mice challenged with a lethal dose of EV71.
Biocarbon quantum dots: a simple one‐step dry heating allows the synthesis of carbon quantum dots derived from curcumin. The obtained carbon quantum dots possess strong antiviral activity against enterovirus 71 through different mechanisms.
•A data-driven framework is proposed to optimize the sizing of a hybrid energy system.•A modified NSGA-II based on reinforcement learning is utilized to obtain Pareto set.•CRITIC-TOPSIS is used to ...decide the weight of objectives and select the best solution.•A optimal system with LCOE of 0.226 $/kWh, LPSP of 4.01% and PAR of 2.15% is obtained.
This paper proposes a data-driven two-stage multi-criteria decision-making (MCDM) framework to investigate the optimal configuration of a stand-alone wind/PV/hydrogen system. In the first stage, a modified non-dominated sorting genetic algorithm (NSGA)-II based on reinforcement learning is utilized to determine a set of Pareto solutions. The objectives considered are to minimize the levelized cost of energy (LCOE), the loss of power supply possibility (LPSP) and the power abandonment rate (PAR), simultaneously. In the second stage, the Criteria Importance Though Intercrieria Correlation (CRITIC) method is utilized to determine the weight of the three objectives, while the Technique for Order Preference by Similarity to Ideal Solution (TOPSIS) approach is employed to select the unique best solution from Pareto solutions. To verify the effectiveness, the framework is applied to the wind/PV/hydrogen system located in Aksay Kazak Autonomous County, Gansu Province, China to meet an off-grid industrial park’s load demand of 1603 kWh/day and peak load of 117.17 kW. The result states that the optimal system, which consists of 83.2 kW PV panels, 160 kW wind turbines, 20 kW fuel cells, 54 kW electrolyzers and 450 m3 hydrogen storage tanks, owns the LCOE of 0.226 $/kWh, the LPSP of 4.01% and the PAR of 2.15%.
Severe liver abscess infections caused by hypervirulent clonal-group CG23 Klebsiella pneumoniae have been increasingly reported since the mid-1980s. Strains typically possess several virulence ...factors including an integrative, conjugative element ICEKp encoding the siderophore yersiniabactin and genotoxin colibactin. Here we investigate CG23's evolutionary history, showing several deep-branching sublineages associated with distinct ICEKp acquisitions. Over 80% of liver abscess isolates belong to sublineage CG23-I, which emerged in ~1928 following acquisition of ICEKp10 (encoding yersiniabactin and colibactin), and then disseminated globally within the human population. CG23-I's distinguishing feature is the colibactin synthesis locus, which reportedly promotes gut colonisation and metastatic infection in murine models. These data show circulation of CG23 K. pneumoniae decades before the liver abscess epidemic was first recognised, and provide a framework for future epidemiological and experimental studies of hypervirulent K. pneumoniae. To support such studies we present an open access, completely sequenced CG23-I human liver abscess isolate, SGH10.
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•Metal nanozyme-based detection of heavy metal ions is reviewed.•Detection strategies for improving selectivity and reliability are reviewed.•The challenges in nanozyme-based assays ...for heavy metal ions are highlighted.•Future perspective of nanozyme-based assays for heavy metal ions is discussed.
Large scale mining, manufacturing industries, exploitation of underground water, depletion of groundwater level, and uncontrolled discharge of industrial wastes have caused severe heavy metal ion pollution to the environment throughout the world. Therefore, the rapid detection of such toxic metal ions is inevitable. However, conventional methods require sophisticated instruments and skilled manpower and are difficult to operate in on-field conditions. Recently, metal nanozyme-based assays have been found to have the potential as an alternative to conventional methods due to their portability, simplicity, and high sensitivity to detect metal ion concentration to as low as parts per trillion (ppt). Metal nanozyme-based systems for heavy metal ions enable rapid and cheap screening on the spot with a very simple instrument such as a UV–vis absorption spectrophotometer and therefore, are convenient for use in field operations, especially in remote parts of the world. The sensing mechanism of a nanozyme-based sensor is highly dependent on its surface properties and specific interactions with particular metal ion species. Such method often encounters selectivity issues, unlike natural enzyme-based assays. Therefore, in this review, we mainly focus our discussion on different types of target recognition and inhibition/enhancement mechanisms, and their responses toward the catalytic activity in the sensing of target metal ions, design strategies, challenges, and future perspectives.
In this paper, we propose a new multiattribute decision making method based on interval-valued intuitionistic fuzzy sets, particle swarm optimization (PSO) techniques, and the evidential reasoning ...methodology. The proposed method uses the evidential reasoning methodology to construct objective functions of the programming models and uses PSO techniques to get optimal weights of the attributes to get the aggregated interval-valued intuitionistic fuzzy value of each alternative. Then, it calculates the transformed value of the obtained interval-valued intuitionistic fuzzy value of each alternative. The larger the transformed value, the better the preference order of the alternative. The proposed method can overcome the drawbacks of the existing methods for multiattribute decision making based on interval-valued intuitionistic fuzzy sets. It provides us with a useful way for multiattribute decision making based on interval-valued intuitionistic fuzzy sets, PSO techniques, and the evidential reasoning methodology.
We conducted a search for an exotic spin- and velocity-dependent interaction for polarized electrons with an experimental approach based on a high-sensitivity spin-exchange relaxation-free (SERF) ...magnetometer, which serves as both a source of polarized electrons and a magnetic-field sensor. The experiment aims to sensitively detect magnetic-fieldlike effects from the exotic interaction between the polarized electrons in a SERF vapor cell and unpolarized nucleons of a closely located solid-state mass. We report experimental results on the interaction with 82 h of data averaging, which sets an experimental limit on the coupling strength around 10^{-19} for the axion mass m_{a}≲10^{-3} eV, within the important axion window.
Exotic spin-dependent interactions between fermions have recently attracted attention in relation to theories beyond the Standard Model. The exotic interactions can be mediated by hypothetical ...fundamental bosons which may explain several unsolved mysteries in physics. Here we expand this area of research by probing an exotic parity-odd spin- and velocity-dependent interaction between the axial-vector electron coupling and the vector nucleon coupling for polarized electrons. This experiment utilizes a high-sensitivity atomic magnetometer, based on an optically polarized vapor that is a source of polarized electrons, and a solid-state mass containing unpolarized nucleons. The atomic magnetometer can detect an effective magnetic field induced by the exotic interaction between unpolarized nucleons and polarized electrons. We set an experimental limit on the electron-nucleon coupling Formula: see text at the mediator boson mass below 10
eV, significantly improving the current limit by up to 17 orders of magnitude.
Ferroptosis is a novel regulated cell death pattern discovered when studying the mechanism of erastin-killing RAS mutant tumor cells in 2012. It is an iron-dependent programmed cell death pathway ...mainly caused by an increased redox imbalance but with distinct biological and morphology characteristics when compared to other known cell death patterns. Ferroptosis is associated with various diseases including acute kidney injury, cancer, and cardiovascular, neurodegenerative, and hepatic diseases. Moreover, activation or inhibition of ferroptosis using a variety of ferroptosis initiators and inhibitors can modulate disease progression in animal models. In this review, we provide a comprehensive analysis of the characteristics of ferroptosis, its initiators and inhibitors, and the potential role of its main metabolic pathways in the treatment and prevention of various diseased states. We end the review with the current knowledge gaps in this area to provide direction for future research on ferroptosis.
Abstract
Great earthquakes are one of the major threats to modern society due to their great destructive power and unpredictability. The maximum credible earthquake (MCE) for a specific fault, i.e., ...the largest magnitude earthquake that may occur there, has numerous potential scenarios with different source processes, making the future seismic hazard highly uncertain. We propose a full-scenario analysis method to evaluate the MCE hazards with deterministic broadband simulations of numerous scenarios. The full-scenario analysis is achieved by considering all uncertainties of potential future earthquakes with sufficient scenarios. Here we show an application of this method in the seismic hazard analysis for the Xiluodu dam in China by simulating 22,000,000 MCE scenarios in 0–10 Hz. The proposed method can provide arbitrary intensity measures, ground-motion time series, and spatial ground-motion fields for all hazard levels, which enables more realistic and accurate MCE hazard evaluations, and thus has great application potential in earthquake engineering.
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