Introduction. Sex hormones play an important role in the development and maintenance of bone and muscle mass. However, studies regarding serum testosterone levels, osteoporosis, and sarcopenia in men ...are relatively sparse and have led to contradictory conclusions. Therefore, this study aimed to investigate the association between serum testosterone levels and body composition, including bone mineral density (BMD), appendicular lean mass index (ALMI), and appendicular fat mass index (AFMI), among men 20–59 years of age through a cross-sectional analysis of the National Health and Nutrition Examination Survey. Materials and Methods. Our analysis was based on the data for 3,875 men, 20–59 years of age. Weighted multiple regression analyses were used to estimate the independent association between serum testosterone levels and body composition. Weighted generalized additive models and smooth curve fittings were used to characterize the nonlinear associations between them. Results. The association between the serum testosterone level and lumbar BMD was positive in each multivariable linear regression model. In the model adjusted for age and race, the serum testosterone level was negatively associated with ALMI. However, in the models adjusted for body mass index, this association became positive. In addition, the association between the serum testosterone level and AFMI was negative in each multivariable linear regression model. Conclusion. Our study demonstrated a positive association of serum testosterone level with lumbar BMD and ALMI, and a negative association with AFMI, among men 20–59 years of age, suggesting that increasing testosterone levels may be beneficial to skeletal health in young and middle-aged men with low testosterone levels.
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FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, UL, UM, UPUK
New strategies to rapidly develop broad-spectrum antiviral therapies are urgently required for emerging and re-emerging viruses. Host-targeting antivirals (HTAs) that target the universal host ...factors necessary for viral replication are the most promising approach, with broad-spectrum, foresighted function, and low resistance. We and others recently identified that host dihydroorotate dehydrogenase (DHODH) is one of the universal host factors essential for the replication of many acute-infectious viruses. DHODH is a rate-limiting enzyme catalyzing the fourth step in
pyrimidine synthesis. Therefore, it has also been developed as a therapeutic target for many diseases relying on cellular pyrimidine resources, such as cancers, autoimmune diseases, and viral or bacterial infections. Significantly, the successful use of DHODH inhibitors (DHODHi) against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection further supports the application prospects. This review focuses on the advantages of HTAs and the antiviral effects of DHODHi with clinical applications. The multiple functions of DHODHi in inhibiting viral replication, stimulating ISGs expression, and suppressing cytokine storms make DHODHi a potent strategy against viral infection.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Taking the fractured gas constant volume body as the research unit, considering the boundary conditions such as the height of the constant volume body, the cross-sectional area of the constant volume ...body, the initial formation pressure, the initial bottom hole pressure and the initial overflow, a mathematical model of the average pressure of the fractured formation of the constant volume body varying with the overflow time is proposed; With the help of programming language, the model is solved. Taking well ST1 as an example, the results show that with the increase of fracture dip angle, the fracture width increases and the fracture permeability also increases; The permeability of fractured gas reservoir is most affected by matrix stress, followed by dip angle and fracture spacing. With the constant volume overflow, the overflow flow decreases rapidly in the initial stage, and then remains stable for a long time until it decreases again in the end; With the increase of throttle back pressure and gas influx, the annular gas holdup increases. The mathematical model of average pressure of fractured formation with constant volume can calculate the change value of average pressure with time, and can guide the design of kill fluid density and the loading of backpressure target value in the process of circulating exhaust.
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DOBA, EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, IZUM, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UILJ, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
(SRBSDV) is a devastating newly emerged rice reovirus in Eastern and Southeastern Asia transmitted by a long-distance migratory pest, the white-backed planthopper (WBPH). We previously showed that ...SRBSDV infection decreased the cold tolerance but improved the heat tolerance of its vector, WBPH. Comparative metabolomic analysis was used to explore the potential mechanisms underlying these changes in temperature stress response. Fourth-generation WBPH nymphs were treated with SRBSDV and/or extreme temperature stress and were analyzed using gas chromatography-time of flight-mass spectrometry. A total of 605 distinguishable peaks were identified and 165, 207, and 202 differentially accumulated metabolites were identified in WBPH after virus infection, cold, or heat stress, respectively. The nucleic acids and fatty acids were the major categories of metabolites regulated by SRBSDV infection, whereas temperature stress regulated tricarboxylic acid cycle compounds, sugars, and polyols. For the WBPH samples infected with SRBSDV and subjected to temperature stress, amino acids, sugars, and polyols were the most significant regulated metabolites. The metabolomics study suggests that SRBSDV may influence the extreme temperature tolerance of WBPH by regulating the accumulation of amino acids, sugars, and polyols in the insect body.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Emerging evidence suggests bright prospects of some natural antioxidants in the treatment of osteoporosis. 6'-O-Galloylpaeoniflorin (GPF), an antioxidant isolated from peony roots (one of very widely ...used Oriental medicines, with various anti-inflammatory, antitumor, and antioxidant activities), shows a series of potential clinical applications. However, its effects on osteoporosis remain poorly investigated. The current study aimed to explore whether GPF can attenuate osteoclastogenesis and relieve ovariectomy-induced osteoporosis via attenuating reactive oxygen species (ROS), and investigate the possible mechanism. After the culture of primary murine bone marrow-derived macrophages/monocytes were induced by the use of macrophage colony-stimulating factor (M-CSF) and the receptor activator of NF-κB ligand (RANKL) and then treated with GPF. Cell proliferation and viability were assessed by Cell Counting Kit-8 (CCK-8) assay. Thereafter, the role of GPF in the production of osteoclasts and the osteogenic resorption of mature osteoclasts were evaluated by tartrate-resistant acid phosphatase (TRAP) staining, podosome belt formation, and resorption pit assay. Western blotting and qRT-PCR examination were performed to evaluate proteins' generation and osteoclast-specific gene levels, respectively. The ROS generation in cells was measured
by 2',7'-Dichlorodi-hydrofluorescein diacetate (DCFH-DA). Ovariectomy-induced osteoporosis mouse administered with GPF or vehicle was performed to explore the
potential of GPF, then a micro-CT scan was performed in combination with histological examination for further analysis. GPF suppressed the formation of osteoclasts and podosome belts, as well as bone resorption when induced by RANKL through affecting intracellular ROS activity, MAPKs signaling pathway, and subsequent NFATc1 translocation and expression, as well as osteoclast-specific gene expression
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study suggested that exposure to GPF prevented osteoporosis-related bone loss in the ovariectomized mice. These findings indicate that GPF attenuates osteoclastogenesis and relieves ovariectomy-induced osteoporosis by inhibiting ROS and MAPKs/c-Fos/NFATc1 signaling pathway. This suggested that GPF may be potentially used to treat bone diseases like periodontitis, rheumatoid arthritis, and osteoporosis associated with osteoclasts.
Osteoporosis is a debilitating condition characterized by reduced bone density and microstructure, leading to increased susceptibility to fractures and increased mortality, particularly among older ...individuals. Despite the availability of drugs for osteoporosis treatment, the need for targeted and innovative agents with fewer adverse effects persists. Trifolirhizin, a natural pterostalin derived from the root of Sophora flavescens, has been previously studied for its effects on certain anticancer and antiinflammatory. The impact of trifolirhizin on the formation and function of osteoclasts remain unclear.
Herein, the possible roles of trifolirhizin the formation and function of osteoclasts and the underlying mechanism were explored. Methods: Bone marrow-derived macrophages (BMMs) were employed to evaluate the roles of trifolirhizin on steoclastogenesis, bone absorption and the underlying mechanism in vitro. Bone loss model was established by ovariectomy(OVX) in mice in vivo.
Trifolirhizin repressed osteoclastogenesis, bone resorption induced by receptor activator of nuclear factor kappa B ligand (RANKL) in vitro. Mechanistically, trifolirhizin inhibits RANKL-induced MAPK signal transduction and NFATc1 expression. Moreover, trifolirhizin inhibited osteoclast marker gene expression, including NFATc1, CTSK, MMP9, DC-STAMP, ACP5, and V-ATPase-D2. Additionally, trifolirhizin was found to protect against ovariectomy(OVX)-induced bone loss in mice.
Trifolirhizin can effectively inhibit osteoclast production and bone resorption activity. The results of our study provide evidence for trifolirhizin as a potential drug for the prevention and treatment of osteoporosis and other osteolytic diseases.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Osteoporosis (OP) is a debilitating illness distinguished by a reduction in bone density and microstructure, which leads to fragility, fracture risk, and increased mortality, particularly in the ...elderly and postmenopausal women. Growing evidence suggests that various plant derivatives could be a potential therapy for osteoporosis. Ellagic acid is a phenolic found naturally in extracts from plants such as pomegranate, blackberry and berry. In earlier research, ellagic acid (EA) was reported to have certain benefits on osteoporosis, however, EA was limited by its weak bioactivity. Urolithin A (UA), an ellagic acid metabolite present in the intestinal bacteria, which had a greater bioavailability. However, its therapeutic effects and mechanisms in osteoporosis remain to be explored.
In this work, we explored about how UA affected the molecular processes of osteoclasts differentiation in vitro. We also performed the ovariectomy-induced osteoporotic mice model in order to evaluate how UA impacted the bone loss of osteoporosis.
1. TRAP staining analysis to examine the impact of UA on osteoclast differentiation. 2. RT-PCR for evaluating UA's impact on the expression of genes relevant to osteoclasts. Bone resorption experiment and scan by electron microscope in order to determine the impact of UA on osteoclast function. 3.Using western blotting, investigate the impact of UA on the osteoclast differentiation-related signaling pathway. 4. Developed an osteoporosis mouse model for evaluating the preventative impact of UA on bone loss after an ovariectomy.
1. UA reduced osteoclast development in a dosage manner without cytotoxicity. 2. UA suppresses osteoclast-related gene expression as well as the function of osteoclast bone resorption. 3. UA regulates osteoclast development by decreasing PI3K/AKT/mTOR signaling pathway phosphorylation as well as Nfatc1 transcription and translation. 4. Animal study demonstrated that UA reduced bone loss in ovariectomy-induced osteoporotic mice.
UA reduced the development and bone resorption function of osteoclast, was shown as inhibiting expression of osteoclast-associated specific genes as well as the PI3K/AKT/mTOR signaling pathway and decreasing Nfatc1 expression. In vivo, UA prevented bone loss in ovariectomy-induced osteoporotic mice. Finally, UA shown tremendous promise in the prevention and treatment of osteoporosis.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
The tedious preparation procedures and difficulty in free structure formation and recycling have restricted the widespread application of existing enzyme immobilization strategies. Here, we report a ...novel type of enzyme immobilization strategy utilizing additive manufacturing (also known as 3D printing). The shape and structures of carbon fiber reinforced polylactic acid (C-PLA) scaffolds could be flexibly designed and printed (cube, sphere, and pyramid shapes and microfluidic reactors). After chemical modification with piranha solution, peracetic acid, and a silane coupling agent, the resultant scaffolds achieved a high specific surface area (2.2 m2/g, a 3.63-fold increase) with an abundance of surface-active groups. As a proof of concept, four kinds of enzymes (penicillin G acylase (PGA), protease, glycosidase, and lipase) were successfully immobilized on the chemically modified 3D scaffolds. The final yield was 185.6 mM for the reaction catalyzed by PGA, and the final yield of lactosucrose reached 142 g/L for the glycosidase-catalyzed reaction. After 10 cycles, the retention rate of enzymatic activity was 88% for PGA and 92.8% for glycosidase. Thus, tunable 3D-printed enzyme immobilization carriers offer a promising solution to building a simple platform that is low cost and flexible enough to accommodate various enzymes and reactors for industrial applications.
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IJS, KILJ, NUK, PNG, UL, UM
The upcoming flu season in the Northern Hemisphere merging with the current COVID-19 pandemic raises a potentially severe threat to public health. Through experimental coinfection with influenza A ...virus (IAV) and either pseudotyped or live SARS-CoV-2 virus, we found that IAV preinfection significantly promoted the infectivity of SARS-CoV-2 in a broad range of cell types. Remarkably, in vivo, increased SARS-CoV-2 viral load and more severe lung damage were observed in mice coinfected with IAV. Moreover, such enhancement of SARS-CoV-2 infectivity was not observed with several other respiratory viruses, likely due to a unique feature of IAV to elevate ACE2 expression. This study illustrates that IAV has a unique ability to aggravate SARS-CoV-2 infection, and thus, prevention of IAV infection is of great significance during the COVID-19 pandemic.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Industrial-scale production of acetaldehyde relies heavily on homogeneous catalysts. Here, we used ethane as the feedstock and developed ZSM-5-supported PdO nanoparticles for the direct oxidation of ...ethane to acetaldehyde by utilizing O
2
and CO. PdO nanoparticles clearly demonstrate effective activity and prevent the further deep oxidation of acetaldehyde.
Industrial-scale production of acetaldehyde relies heavily on homogeneous catalysts.