Acetaminophen Improves Protein Translational Signaling in Aged Skeletal Muscle

Background: Age-related muscle atrophy is characterized by increased oxidative stress, diminished Akt enzymatic function, and reduced phosphorylation of the mammalian target of rapamycin (mTOR), which can be attenuated by chronic acetaminophen ingestion. Here we hypothesize that age-related impairments in Akt/ mTOR function are associated with reduced protein translational signaling, and that these changes, if present, can be attenuated by acetaminophen treatment. Results: Compared to 6- and 27-month old animals, the expression of the mTOR-complex proteins raptor and GbL and the phosphorylation of tuberin/TSC2 (Thr1462) were reduced in the soleus muscles of very aged rats (33 months old). These changes in Akt/mTOR pathway signaling proteins were in turn associated with decreased phosphorylation of S6 kinase p85S6K (Thr412) and eukaryotic translation initiation factor-4E (eIF4E) binding protein-1 (4EBP1, Thr37/46), reduced phosphorylation of S6 ribosomal protein (Ser235/236), and increased inhibition of eIF4E by binding to 4EBP1. Age-associated alterations in the Akt/mTOR pathway signaling and in the phosphorylation of the stress-responsive eIF2a protein were attenuated by chronic acetaminophen treatment (30 mg/kg body weight per day). Ex vivo incubation of adult muscles with hydrogen peroxide mimicked the age-related decreases seen in eIF4E and 4EBP1 phosphorylation, whereas the inclusion of acetaminophen in the muscle bath attenuated this effect. Conclusion: Aging is associated with impairments in the regulation of proteins thought to be important in controlling mRNA translation, and acetaminophen may be useful for the treatment of age-related muscle atrophy by reducing oxidative stress

Aging-Associated Dysfunction of Akt/Protein Kinase B: S-Nitrosylation and Acetaminophen Intervention

Background: Aged skeletal muscle is characterized by an increased incidence of metabolic and functional disorders, which if allowed to proceed unchecked can lead to increased morbidity and mortality. The mechanism(s) underlying the development of these disorders in aging skeletal muscle are not well understood. Protein kinase B (Akt/PKB) is an important regulator of cellular metabolism and survival, but it is unclear if aged muscle exhibits alterations in Akt function. Here we report a novel dysfunction of Akt in aging muscle, which may relate to S-nitrosylation and can be prevented by acetaminophen intervention. Principal Findings: Compared to 6- and 27-month rats, the phosphorylation of Akt (Ser473 and Thr308) was higher in soleus muscles of very aged rats (33-months). Paradoxically, these increases in Akt phosphorylation were associated with diminished mammalian target of rapamycin (mTOR) phosphorylation, along with decreased levels of insulin receptor beta (IR-b), phosphoinositide 3-kinase (PI3K), phosphatase and tensin homolog deleted on chromosome 10 (PTEN) and phosphorylation of phosphoinositide-dependent kinase-1 (PDK1) (Ser241). In vitro Akt kinase measurements and ex vivo muscle incubation experiments demonstrated age-related impairments of Akt kinase activity, which were associated with increases in Akt S-nitrosylation and inducible nitric oxide synthase (iNOS). Impairments in Akt function occurred parallel to increases in myocyte apoptosis and decreases in myocyte size and the expression of myosin and actin. These age-related disorders were attenuated by treating aged (27-month) animals with acetaminophen (30 mg/kg body weight/day) for 6- months. Conclusions: These data demonstrate that Akt dysfunction and increased S-nitrosylation of Akt may contribute to ageassociated disorders in skeletal muscle and that acetaminophen may be efficacious for the treatment of age-related muscle dysfunction

Risk factors for diabetic foot ulcers mortality and novel negative pressure combined with platelet-rich plasma therapy in the treatment of diabetic foot ulcers

The purpose of this study was to assess the risk factors for morbidity and mortality of diabetic foot ulcers (DFUs). For the treatment of diabetic foot ulcers, negative pressure wound therapy (NPWT) combined with platelet-rich plasma-fibrin glue (PRP) was also investigated. There were 653 patients in the diabetic foot ulcer group and 510 patients in the diabetic patients without foot ulceration (NFU) group, for a total of 1163 patients in the study samples after individuals without follow-up were excluded. The patients were randomized into two groups: the negative pressure wound therapy group and the negative pressure wound therapy combined with the PRP group. The findings of the univariate analysis revealed the blood indicators for predicting diabetic foot ulcer morbidity risk factors, such as C-reactive protein, albumin, creatinine, alkaline phosphatase, procalcitonin, platelets, 25-hydroxyvitamin D, β-2-microglobulin, monocyte ratio, low-density protein cholesterol (LDL), triglyceride, alanine aminotransferase (ALT), aminotransferase (AST), creatine kinase (CK) and total cholesterol. Using logistic regression analysis revealed only albumin and age to be independent predictors of diabetic foot ulcer mortality. Our study also revealed that, compared to negative pressure wound therapy alone, negative pressure wound therapy combined with PRP accelerated wound healing and reduced the mortality rate. According to the findings of this pilot study, new risk factors for diabetic foot ulcer morbidity and mortality have been found, and negative pressure wound therapy combined with PRP therapy may provide the first information that it is an effective adjunct treatment for diabetic foot ulcers

Neutrino Physics with JUNO

The Jiangmen Underground Neutrino Observatory (JUNO), a 20 kton multi-purposeunderground liquid scintillator detector, was proposed with the determinationof the neutrino mass hierarchy as a primary physics goal. It is also capable ofobserving neutrinos from terrestrial and extra-terrestrial sources, includingsupernova burst neutrinos, diffuse supernova neutrino background, geoneutrinos,atmospheric neutrinos, solar neutrinos, as well as exotic searches such asnucleon decays, dark matter, sterile neutrinos, etc. We present the physicsmotivations and the anticipated performance of the JUNO detector for variousproposed measurements. By detecting reactor antineutrinos from two power plantsat 53-km distance, JUNO will determine the neutrino mass hierarchy at a 3-4sigma significance with six years of running. The measurement of antineutrinospectrum will also lead to the precise determination of three out of the sixoscillation parameters to an accuracy of better than 1\%. Neutrino burst from atypical core-collapse supernova at 10 kpc would lead to ~5000inverse-beta-decay events and ~2000 all-flavor neutrino-proton elasticscattering events in JUNO. Detection of DSNB would provide valuable informationon the cosmic star-formation rate and the average core-collapsed neutrinoenergy spectrum. Geo-neutrinos can be detected in JUNO with a rate of ~400events per year, significantly improving the statistics of existing geoneutrinosamples. The JUNO detector is sensitive to several exotic searches, e.g. protondecay via the $p\to K^++\bar\nu$ decay channel. The JUNO detector will providea unique facility to address many outstanding crucial questions in particle andastrophysics. It holds the great potential for further advancing our quest tounderstanding the fundamental properties of neutrinos, one of the buildingblocks of our Universe

An Electrospun Porous CuBi2O4 Nanofiber Photocathode for Efficient Solar Water Splitting

While the CuBi2O4-based photocathode has emerged as an ideal candidate for photoelectrochemical water splitting, it is still far from its theoretical values due to poor charge carrier transport, poor electron–hole separation, and instability caused by self-photoelectric-corrosion with electrolytes. Establishing synthesis methods to produce a CuBi2O4 photocathode with sufficient cocatalyst sites would be highly beneficial for water splitting. Here, the platinum-enriched porous CuBi2O4 nanofiber (CuBi2O4/Pt) with uniform coverage and high surface area was prepared as a photocathode through an electrospinning and electrodeposition process for water splitting. The prepared photocathode material was composed of a CuBi2O4 nanofiber array, which has a freestanding porous structure, and the Pt nanoparticle is firmly embedded on the rough surface. The highly porous nanofiber structures allow the cocatalyst (Pt) better alignment on the surface of CuBi2O4, which can effectively suppress the electron–hole recombination at the electrolyte interface. The as-fabricated CuBi2O4 nanofiber has a tetragonal crystal structure, and its band gap was determined to be 1.8 eV. The self-supporting porous structure and electrocatalytic activity of Pt can effectively promote the separation of electron–hole pairs, thus obtaining high photocurrent density (0.21 mA/cm2 at 0.6 V vs. RHE) and incident photon-to-current conversion efficiency (IPCE, 4% at 380 nm). This work shows a new view for integrating an amount of Pt nanoparticles with CuBi2O4 nanofibers and demonstrates the synergistic effect of cocatalysts for future solar water splitting

NRF2 deficiency increases obesity susceptibility in a mouse menopausal model.

The risk of metabolic abnormalities in menopausal women increases significantly due to the decline in estrogen level. Nuclear factor E2-related factor 2 (NRF2) is an important oxidative stress sensor that plays regulatory role in energy metabolism. Therefore, an ovariectomized menopausal model in Nrf2-knockout (KO) mice was applied to evaluate the effect of Nrf2 deficiency on metabolism in menopausal females. The mice were divided into four groups according to their genotypes and treatments. Blood samples and bodyweights were obtained preoperatively and in the first to ninth postoperative weeks after overnight fasting. Serum levels of triglycerides (TG), total cholesterol (T-CHO), low-density lipoprotein (LDL), high-density lipoprotein (HDL), and glucose (GLU) were measured at postoperative weeks 0, 1, 3, 5, 7, and 9. Neurotransmitter dopamine (DA) and serotonin (5-HT) was analyzed in brain tissues after sacrifice at postoperative week 9. The results demonstrated that, compared with the corresponding wild-type (WT) mice, KO ovariectomized mice had a greater bodyweight gain (P<0.01). Serum analysis showed that the serum GLU, T-CHO, and TG were significantly lower (P<0.05) but LDL was significantly higher (P<0.05) in the KO control mice than that in WT control mice. However, different from the WT counterparts, an increase in blood GLU level (P<0.05), unchanged T-CHO, TG, and HDL levels, and a significant reduction in LDL (P<0.01) was found in the KO ovariectomized mice. In addition, the level of 5-HT was significantly reduced (P<0.05) in the KO mice after ovariectomy. In conclusion, the combination of Nrf2 deletion and a decline in estrogen level induced a significant increase in bodyweight, which may be associated with their altered glucose and LDL metabolism and decreased 5-HT levels. From a clinical perspective, women with antioxidant defense deficiency may have an increased risk of metabolic abnormalities after menopause

Effects of sorbitol-mediated curing on the physicochemical properties and bacterial community composition of loin ham during fermentation and ripening stages

In this study, the impacts of loin ham with sorbitol-mediated curing on its physicochemical properties and bacterial community composition during fermentation and ripening were investigated. The salt content, pH, and water activity (aw) were lower in the sorbitol group than in the control group throughout the fermentation and ripening stages (P < 0.05). In addition, the L* values were higher in the sorbitol group (P < 0.05). Additionally, microbial diversity diminished in all groups as the fermentation and ripening process proceeded, with Lactobacillus turning into the dominant genus in the control group and Staphylococcus and Lactobacillus becoming dominant in the sorbitol group. Pearson’s correlation analysis confirmed that the physicochemical properties have been significantly correlated with the bacterial community. In conclusion, sorbitol-mediated curing not only facilitates salt reduction while prolonging the storage period of loin ham, but also improves the distribution of bacterial community in loin ham and enhances its quality

Biodiesel-Assisted Ambient Aqueous Bitumen Extraction (BA³BE) from Athabasca Oil Sands

The water-based extraction process has been almost exclusively used in the current industry for Athabasca oil sands extraction to produce bitumen and heavy oil. However, the current method is facing various challenges, primarily including high energy intensity, poor processability with poor-quality ores, large consumption of fresh water, and concerns on considerable volume of tailings. Although the technology of using nonaqueous solvent as extraction medium has numerous advantages, problems such as solvent loss to tailings and high capital/operating costs are difficult to address. A biodiesel-assisted ambient aqueous bitumen extraction (BA³BE) process has been herein proposed as an alternative to water-based and solvent-based extraction processes. The results showed a significant improvement in both froth quality and bitumen recovery (increased from ∼10% to ∼80% with biodiesel addition) for processing poor-quality ores at ambient temperature (25 °C), which is much lower than the temperatures used in the current industrial practice (40–55 °C). The aqueous tailings generated in the BA³BE process were found to feature faster settling and enhanced densification, which is favorable for recovering processing water and improving land reclamation. Furthermore, the innovative BA³BE extraction process requires similar facilities and procedures as the current industrial processes, which can be considered as an advantage for commercialization

Glucan phosphate attenuates myocardial HMGB1 translocation in severe sepsis through inhibiting NF-κB activation

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Potential pathological mechanisms and pharmacological interventions for cadmium-induced miscarriage

The prevalence of cadmium (Cd) contamination has emerged as a significant global concern. Exposure to Cd during pregnancy is associated with adverse pregnancy outcomes, including miscarriage. However, there is currently a lack of comprehensive summaries on Cd-induced miscarriage. Therefore, it is imperative to further strengthen research into in vivo studies, clinical status, pathological mechanisms, and pharmacological interventions for Cd-induced miscarriage. This study systematically presents the current knowledge on animal models and clinical trials investigating Cd exposure-induced miscarriage. The underlying mechanisms involving oxidative stress, inflammation, endocrine disruption, and placental dysfunction caused by Cd-induced miscarriage are also extensively discussed. Additionally, potential drug interventions such as melatonin, vitamin C, and vitamin E are highlighted for their pharmacological role in mitigating adverse pregnancy outcomes induced by Cd