Paraquat (PQ) promotes cell senescence in brain tissue, which contributes to Parkinson's disease. Furthermore, PQ induces heart failure and oxidative damage, but it remains unknown whether and how PQ ...induces cardiac aging. Here, we demonstrate that PQ induces phenotypes associated with senescence of cardiomyocyte cell lines and results in cardiac aging‐associated phenotypes including cardiac remodeling and dysfunction in vivo. Moreover, PQ inhibits the activation of Forkhead box O3 (FoxO3), an important longevity factor, both in vitro and in vivo. We found that PQ‐induced senescence phenotypes, including proliferation inhibition, apoptosis, senescence‐associated β‐galactosidase activity, and p16INK4a expression, were significantly enhanced by FoxO3 deficiency in cardiomyocytes. Notably, PQ‐induced cardiac remolding, apoptosis, oxidative damage, and p16INK4a expression in hearts were exacerbated by FoxO3 deficiency. In addition, both in vitro deficiency and in vivo deficiency of FoxO3 greatly suppressed the activation of antioxidant enzymes including catalase (CAT) and superoxide dismutase 2 (SOD2) in the presence of PQ, which was accompanied by attenuation in cardiac function. The direct in vivo binding of FoxO3 to the promoters of the Cat and Sod2 genes in the heart was verified by chromatin immunoprecipitation (ChIP). Functionally, overexpression of Cat or Sod2 alleviated the PQ‐induced senescence phenotypes in FoxO3‐deficient cardiomyocyte cell lines. Overexpression of FoxO3 and CAT in hearts greatly suppressed the PQ‐induced heart injury and phenotypes associated with aging. Collectively, these results suggest that FoxO3 protects the heart against an aging‐associated decline in cardiac function in mice exposed to PQ, at least in part by upregulating the expression of antioxidant enzymes and suppressing oxidative stress.
Paraquat (PQ) exposure results in aging‐like phenotypes such as oxidative injury, apoptosis, senescence, and hypertrophy in heart; these cardiac aging‐associated phenotypes are further exacerbated by Forkhead box O3 (FoxO3) deficiency. FoxO3 protects PQ‐induced cardiac dysfunction through upregulating the expression of antioxidants including catalase (Cat) and superoxide dismutase 2 (Sod2).
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DOBA, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, UILJ, UKNU, UL, UM, UPUK
The management and treatment of disease are achieved via the use of pharmacologically active substances or drugs. Drugs do not, however, have an intrinsic ability to be effective; rather, how well ...they work depends on how they are administered or supplied. Treatment of a variety of biological illnesses, such as autoimmune disorders, cancer, and bacterial infections, requires effective drug delivery. Drug absorption, distribution, metabolism, duration of therapeutic impact, pharmacokinetics, excretion, and toxicity can all be impacted by drug administration. Improved chemistry and materials are required for the delivery of therapeutic concentration of novel treatments to the specified targets within the body, as well as for the necessary duration of time. This requirement is accompanied by the development of new therapeutics. Formulating a medication as a DDS is a promising strategy for directly addressing numerous typical barriers to adherence, such as frequent dosage, such as frequent dosage, side effects, and a delayed beginning of the action. In the current review, we give a compendium of drug delivery and controlled release and subsequently highlight some of the newest developments in the realm, with a particular emphasis on cutting-edge methods for targeted therapy. In each instance, we outline the obstacles to efficient drug administration as well as the chemical and material developments that are allowing the sector to overcome these obstacles and have a positive clinical impact.
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•Drug delivery systems (DDSs) can improve therapeutic efficacy of drugs with reduced side effects.•Drug stability, release, and tissue/cell-specific targeting are challenging to anticipate.•Injectable materials localize the drug to the site of action, reducing off-target toxicity and improving clinical impact.•Intratumoral implantation reduced off-target effects and maximize therapeutic benefit.•Systemic RNA treats genetic disease by finding abnormal body regions and restoring their essential functions.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Ether derivatives are widespread as essential building blocks in various drugs, natural products, agrochemicals, and materials. Modern economy requires developing green strategies with improved ...efficiency and reduction of waste. Due to its atom and step-economy, the cross-dehydrogenative coupling (CDC) reaction has become a major strategy for ether functionalization. This review covers C–H/C–H cross-coupling reactions of ether derivatives with various C–H bond substrates via non-noble metal catalysts (Fe, Cu, Co, Mn, Ni, Zn, Y, Sc, In, Ag). We discuss advances achieved in these CDC reactions and hope to attract interest in developing novel methodologies in this field of organic chemistry.
This work studies the underwater detection and tracking of diver targets under a low signal-to-reverberation ratio (SRR) in active sonar systems. In particular, a particle filter track-before-detect ...based on a knowledge-aided (KA-PF-TBD) algorithm is proposed. Specifically, the original echo data is directly used as the input of the algorithm, which avoids the information loss caused by threshold detection. Considering the prior motion knowledge of the underwater diver target, we established a multi-directional motion model as the state transition model. An efficient method for calculating the statistical characteristics of echo data about the extended target is proposed based on the non-parametric kernel density estimation theory. The multi-directional movement model set and the statistical characteristics of the echo data are used as the knowledge-aided information of the particle filter process: this is used to calculate the particle weight with the sub-area instead of the whole area, and then the particles with the highest weight are used to estimate the target state. Finally, the effectiveness of the proposed algorithm is proved by simulation and sea-level experimental data analysis through joint evaluation of detection and tracking performance.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
An efficient synthesis of a variety of 2,5-diaryloxazole derivatives
via
a rhodium-catalyzed annulation of triazoles and aldehydes is achieved. Various oxazole derivatives could be obtained in good ...to excellent yields. A concise synthesis of antimycobaterial natural products balsoxin and texamine has been achieved using this method.
An efficient synthesis of a variety of 2,5-diaryloxazole derivatives
via
a rhodium-catalyzed annulation of triazoles and aldehydes is achieved.
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IJS, KILJ, NUK, UL, UM, UPUK
Aim
Exercise training exerts protective effects against sepsis‐associated multiple organ dysfunction. This study aimed to investigate whether aerobic exercise protected against sepsis‐associated ...acute kidney injury (AKI) via modulating R‐spondin 3 (RSPO3) expression.
Methods
To investigate the effects of aerobic exercise on lipopolysaccharide (LPS)‐induced AKI, LPS (20 mg/kg) was intraperitoneally injected after six weeks of treadmill training. To investigate the role of RSPO3 in LPS‐induced AKI, wild‐type (WT) or inducible endothelial cell‐specific RSPO3 knockout (RSPO3EC−/−) mice were intraperitoneally injected with 12 mg/kg LPS. RSPO3 was intraperitoneally injected 30 min before LPS treatment.
Results
Aerobic exercise‐trained mice were more resistant to LPS‐induced body weight loss and hypothermia and had a significant higher survival rate than sedentary mice exposed to LPS. Exercise training restored the LPS‐induced decreases in serum and renal RSPO3 levels. Exercise or RSPO3 attenuated, whereas inducible endothelial cell‐specific RSPO3 knockout exacerbated LPS‐induced renal glycocalyx loss, endothelial hyperpermeability, inflammation, and AKI. Bioinformatics analysis results revealed significant increases in the expression of matrix metalloproteinases (MMPs) in kidney tissues of mice exposed to sepsis or endotoxaemia, which was validated in renal tissue from LPS‐exposed mice and LPS‐treated human microvascular endothelial cells (HMVECs). Both RSPO3 and MMPs inhibitor restored LPS‐induced downregulation of tight junction protein, adherens junction protein, and glycocalyx components, thus ameliorating LPS‐induced endothelial leakage. Exercise or RSPO3 reversed LPS‐induced upregulation of MMPs in renal tissues.
Conclusion
Increased renal expression of RSPO3 contributes to aerobic exercise‐induced protection against LPS‐induced renal endothelial hyperpermeability and AKI by suppressing MMPs‐mediated disruption of glycocalyx and tight and adherens junctions.
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Background
The impact of tumor necrosis relative to prognosis among patients undergoing curative-intent resection for hepatocellular carcinoma (HCC) remains ill-defined.
Methods
Patients who ...underwent curative-intent resection for HCC without any prior treatment between 2000 and 2017 were identified from an international multi-institutional database. Tumor necrosis was graded as absent, moderate (< 50% area), or extensive (≥ 50% area) on histological examination. The relationship between tumor necrosis, clinicopathologic characteristics, and long-term survival were analyzed.
Results
Among 919 patients who underwent curative-intent resection for HCC, the median tumor size was 5.0 cm (IQR, 3.0–8.5). Tumor necrosis was present in 367 (39.9%) patients (no necrosis:
n
= 552, 60.1% vs < 50% necrosis:
n
= 256, 27.9% vs ≥ 50% necrosis:
n
= 111, 12.1%). Extent of tumor necrosis was also associated with more advanced tumor characteristics. HCC necrosis was associated with OS (median OS: no necrosis, 84.0 months vs < 50% necrosis, 73.6 months vs ≥ 50% necrosis: 59.3 months;
p
< 0.001) and RFS (median RFS: no necrosis, 49.6 months vs < 50% necrosis, 38.3 months vs ≥ 50% necrosis: 26.5 months;
p
< 0.05). Patients with T1 tumors with extensive ≥ 50% necrosis had an OS comparable to patients with T2 tumors (median OS, 62.9 vs 61.8 months;
p
= 0.645). In addition, patients with T2 disease with necrosis had long-term outcomes comparable to patients with T3 disease (median OS, 61.8 vs 62.4 months;
p
= 0.713).
Conclusion
Tumor necrosis was associated with worse OS and RFS, as well as T-category upstaging of patients. A modified AJCC T classification that incorporates tumor necrosis should be considered in prognostic stratification of HCC patients.
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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
499.
Quantum dimensions and quantum Galois theory DONG, CHONGYING; JIAO, XIANGYU; XU, FENG
Transactions of the American Mathematical Society,
12/2013, Volume:
365, Issue:
12
Journal Article
Peer reviewed
Open access
The quantum dimensions of modules for vertex operator algebras are defined and their properties are discussed. The possible values of the quantum dimensions are obtained for rational vertex operator ...algebras. A criterion for simple currents of a rational vertex operator algebra is given and a full Galois theory for rational vertex operator algebras is established using the quantum dimensions.
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BFBNIB, INZLJ, NMLJ, NUK, PNG, SAZU, UL, UM, UPUK, ZRSKP
•High-intensity ultrasound caused oxidation and aggregation of N. taihuensis MP.•High-intensity ultrasound improved functional properties of N. taihuensis MP.•High-intensity ultrasound enhanced ...viscoelasticity of N. taihuensis MP emulsion.•High-intensity ultrasound improved oxidative stability of N. taihuensis MP emulsion.
This study aimed to investigate the effects of high-intensity ultrasound treatment on the functional properties and emulsion stability of Neosalanx taihuensis myofibrillar protein (MP). The results showed that the carbonyl groups, emulsification properties, intrinsic fluorescence intensity, and surface hydrophobicity of the ultrasound treated MP solution were increased compared to the MP without ultrasound treatment. The results of secondary structure showed that the ultrasound treatment could cause a huge increase of β-sheet and a decline of α-helix of MP, indicating that ultrasound induced molecular unfolding and stretching. Moreover, ultrasound reduced the content of total sulfhydryl and led to a certain degree of MP cross-linking. The microscopic morphology of MP emulsion indicated that the emulsion droplet decreased with the increase of ultrasound power. In addition, ultrasound could also increase the storage modulus of the MP emulsion. The results for the lipid oxidation products indicated that ultrasound significantly improved the oxidative stability of N. taihuensis MP emulsions. This study offers an important reference theoretically for the ultrasound modification of aquatic proteins and the future development of N. taihuensis deep-processed products represented by surimi.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
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