Search Results (49)

Nucleotide excision repair (NER) is the most universal repair pathway, which removes a wide range of DNA helix-distorting lesions caused by chemical or physical agents. The final steps of this repair process are gap-filling repair synthesis and subsequent ligation. XPA is the central NER scaffolding protein factor and can be involved in post-incision NER stages. Replication machinery is loaded after the first incision of the damaged strand that is performed by the XPF–ERCC1 nuclease forming a damaged 5′-flap processed by the XPG endonuclease. Flap endonuclease I (FEN1) is a critical component of replication machinery and is absolutely indispensable for the maturation of newly synthesized strands. FEN1 also contributes to the long-patch pathway of base excision repair. Here, we use a set of DNA substrates containing a fluorescently labeled 5′-flap and different size gap to analyze possible repair factor–replication factor interactions. Ternary XPA–FEN1–DNA complexes with each tested DNA are detected. Furthermore, we demonstrate XPA–FEN1 complex formation in the absence of DNA due to protein–protein interaction. Functional assays reveal that XPA moderately inhibits FEN1 catalytic activity. Using fluorescently labeled XPA, formation of ternary RPA–XPA–FEN1 complex, where XPA accommodates FEN1 and RPA contacts simultaneously, can be proposed. We discuss possible functional roles of the XPA–FEN1 interaction in NER related DNA resynthesis and/or other DNA metabolic processes where XPA can be involved in the complex with FEN1. Full article

It is a common belief amongst strength and power athletes that nutritional supplementation strategies aid recovery by shifting the anabolic/catabolic profile toward anabolism. Factors such as nutrient quantity, nutrient quality, and nutrient timing significantly impact upon the effectiveness of nutritional strategies in optimizing the acute responses to resistance exercise and the adaptive response to resistance training (i.e., muscle growth and strength expression). Specifically, the aim of this review is to address carbohydrates (CHOs), protein (PRO), and/or amino acids (AAs) supplementation strategies, as there is growing evidence suggesting a link between nutrient signaling and the initiation of protein synthesis, muscle glycogen resynthesis, and the attenuation of myofibrillar protein degradation following resistance exercise. Collectively, the current scientific literature indicates that nutritional supplementation strategies utilizing CHO, PRO, and/or AA represents an important approach aimed at enhancing muscular responses for strength and power athletes, primarily increased muscular hypertrophy and enhanced strength expression. There appears to be a critical interaction between resistance exercise and nutrient–cell signaling associated with the principle of nutrient timing (i.e., pre-exercise, during, and post-exercise). Recommendations for nutritional supplementation strategies to promote muscular responses for strength and athletes are provided. Full article

Citrulline malate (CM) has been touted as a nutritional ergogenic aid for sports performance, with purported mechanisms of increased muscle blood flow, ammonia clearance, and adenosine triphosphate resynthesis. Combined, these physiological benefits may be best applied to whole-body endurance exercises, such as swimming, though this postulate has not yet been explored. In a double-blind, randomised, and crossover design, 11 national-level swimmers (age: 17 ± 3 years, height: 1.71 ± 0.05 m, body mass: 60.6 ± 8.3 kg) from a high-performance swimming club ingested either 15 g CM or a placebo (PLA) 60 min before six × 300 m freestyle bouts (at 4.5 min intervals). Blood lactate, blood pressure, and ratings of perceived exertion were measured at baseline, 60 min post-ingestion, and immediately post-exercise. Neither mean 300 m swimming time (CM: 212.0 ± 9.6 vs. PLA: 212.8 ± 7.7 s, p = 0.683, g = 0.09) nor any individual swimming bouts (p = 0.679, Pŋ² = 0.02) were improved with CM ingestion. Moreover, no differences in any physiological or subjective measures were identified between conditions (all p > 0.05). Whether the proposed CM mechanisms were active was unclear as more direct physiological measures (i.e., plasma NO, ammonia) may have been required. Resultantly, these observations do not support an ergogenic effect of acute CM ingestion in highly trained swimmers. Full article

Relative to carbohydrate (CHO) alone, exogenous ketones followed by CHO supplementation during recovery from glycogen-lowering exercise have been shown to increase muscle glycogen resynthesis. However, whether this strategy improves subsequent exercise performance is unknown. The objective of this study was to assess the efficacy of ketone monoester (KME) followed by CHO ingestion after glycogen-lowering exercise on subsequent 20 km (TT_20km) and 5 km (TT_5km) best-effort time trials. Nine recreationally active men (175.6 ± 5.3 cm, 72.9 ± 7.7 kg, 28 ± 5 y, 12.2 ± 3.2% body fat, VO₂max = 56.2 ± 5.8 mL· kg BM⁻¹·min⁻¹; mean ± SD) completed a glycogen-lowering exercise session, followed by 4 h of recovery and subsequent TT_20km and TT_5km. During the first 2 h of recovery, participants ingested either KME (25 g) followed by CHO at a rate of 1.2 g·kg⁻¹·h⁻¹ (KME + CHO) or an iso-energetic placebo (dextrose) followed by CHO (PLAC + CHO). Blood metabolites during recovery and performance during the subsequent two-time trials were measured. In comparison to PLAC + CHO, KME + CHO displayed greater (p < 0.05) blood beta-hydroxybutyrate concentration during the first 2 h, lower (p < 0.05) blood glucose concentrations at 30 and 60 min, as well as greater (p < 0.05) blood insulin concentration 2 h following ingestion. However, no treatment differences (p > 0.05) in power output nor time to complete either time trial were observed vs. PLAC + CHO. These data indicate that the metabolic changes induced by KME + CHO ingestion following glycogen-lowering exercise are insufficient to enhance subsequent endurance time trial performance. Full article

Hyperthermia accelerates dehydration and can lead to a glycolysis malfunction. Therefore, to deeply understand the relationship between dehydration and hyperthermia during exercise, as well as in the recovery time, there might be important factors to improve athletic performance. A systematic review was carried out in different databases using the words “hydration” OR “dehydration” AND “glycogen” OR “glycogenesis” OR “glycogenolysis” AND “muscle” OR “muscle metabolism” OR “cardiovascular system” and adding them to the “topic section” in Web of Science, to “Title/Abstract” in PubMed and to “Abstract” in SPORTDiscus. A total of 18 studies were included in the review and 13 in the meta-analysis. The free statistical software Jamovi was used to run the meta-analysis (version 1.6.15). A total sample of 158 people was included in the qualitative analysis, with a mean age of 23.5 years. Ten studies compared muscle glycogen content after hydration vs. remaining dehydrated (SMD −4.77 to 3.71, positive 80% of estimates, \hat{\mu} = 0.79 (95% CI: −0.54 to 2.12), z = 1.17, p = 0.24, Q-test (Q(9) = 66.38, p < 0.0001, tau² = 4.14, I² = 91.88%). Four studies examined the effect of temperature on postexercise muscle glycogen content (SMD −3.14 to −0.63, 100% of estimates being negative, \hat{\mu} = −1.52 (95% CI: −2.52 to −0.53), (z = −3.00, p = 0.003, Q-test (Q(3) = 8.40, p = 0.038, tau² = 0.68, I² = 66.81%). In conclusion, both hyperthermia and dehydration may contribute to elevated glycogenolysis during exercise and poor glycogen resynthesis during recovery. Although core and muscle hyperthermia are the key factors in glycogen impairments, they are also directly related to dehydration. Full article

Airway epithelium repair after infection consists of wound repair, re-synthesis of the extracellular matrix (ECM), and tight junction proteins. In humans, EPs^® 7630 obtained from Pelargonium sidoides roots reduces the severity and duration of acute respiratory tract infections. The effect of EPs^® 7630 on tissue repair of rhinovirus-16 (RV-16) infected and control human airway epithelial cells was assessed for: (i) epithelial cell proliferation by manual cell counts, (ii) epithelial wound repair by “scratch assay”, (iii) ECM composition by Western-blotting and cell-based ELISA, and (iv) epithelial tight junction proteins by Western-blotting. EPs^® 7630 stimulated cell proliferation through cAMP, CREB, and p38 MAPK. EPs^® 7630 significantly improved wound repair. Pro-inflammatory collagen type-I expression was reduced by EPs^® 7630, while fibronectin was increased. Virus-binding tight junction proteins desmoglein2, desmocollin2, ZO-1, claudin1, and claudin4 were downregulated by EPs^® 7630. The RV16-induced shift of the ECM towards the pro-inflammatory type was prevented by EPs^® 7630. Most of the effects of EPs^® 7630 on tissue repair and regeneration were sensitive to inhibition of cAMP-induced signaling. The data suggest that EPs^® 7630-dependent modification of epithelial cell metabolism and function might underlie the faster recovery time from viral infections, as reported by others in clinical studies. Full article

The aim of this study was to investigate the possible effects of chronic nitrate supplementation on the metabolites of energy metabolism during high-intensity, high-volume intermittent training (HIHVT). In this placebo-controlled double-blind study, 17 participants exercised 3 times a week on a cycle ergometer. Sodium nitrate or sodium chloride as the placebo was supplemented daily at 8.5 mg/kg body weight for 10 days. The training exercise consisted of a warm-up, a 45-min interval period, and a post-exercise period. Oxygen uptake, respiratory exchange ratio, and various parameters were measured in the venous blood and plasma. During training, the oxygen uptake and respiratory exchange ratio did not differ between the nitrate and the placebo group. Venous plasma concentrations of nitrate and nitrite were significantly increased in the nitrate group (p < 0.001 and p = 0.007, respectively). Triglyceride concentrations were significantly lower in the nitrate group than in the placebo group (p = 0.010). The concentration of free fatty acids in the plasma did not change upon nitrate supplementation and no significant differences were observed in the contribution of fat to energy metabolism during exercise. An increase in plasma ammonia concentration was observed in the nitrate group during and after exercise (p = 0.048). Metabolites of energy-rich phosphates did not differ between the nitrate and chloride groups, suggesting no improvement in efficiency through the supplemented nitrate. It was concluded that nitrate supplementation did not reduce oxygen uptake and adenosine triphosphate resynthesis by hydrolysis or through creatine kinase activity during high-intensity, high-volume intermittent exercise. Although, lipid metabolism as well as amino acid metabolism might be affected by nitrate supplementation during HIHVT. Full article

Mitochondrial DNA (mtDNA) is particularly vulnerable to somatic mutagenesis. Potential mechanisms include DNA polymerase γ (POLG) errors and the effects of mutagens, such as reactive oxygen species. Here, we studied the effects of transient hydrogen peroxide (H₂O₂ pulse) on mtDNA integrity in cultured HEK 293 cells, applying Southern blotting, ultra-deep short-read and long-read sequencing. In wild-type cells, 30 min after the H₂O₂ pulse, linear mtDNA fragments appear, representing double-strand breaks (DSB) with ends characterized by short GC stretches. Intact supercoiled mtDNA species reappear within 2–6 h after treatment and are almost completely recovered after 24 h. BrdU incorporation is lower in H₂O₂-treated cells compared to non-treated cells, suggesting that fast recovery is not associated with mtDNA replication, but is driven by rapid repair of single-strand breaks (SSBs) and degradation of DSB-generated linear fragments. Genetic inactivation of mtDNA degradation in exonuclease deficient POLG p.D274A mutant cells results in the persistence of linear mtDNA fragments with no impact on the repair of SSBs. In conclusion, our data highlight the interplay between the rapid processes of SSB repair and DSB degradation and the much slower mtDNA re-synthesis after oxidative damage, which has important implications for mtDNA quality control and the potential generation of somatic mtDNA deletions. Full article

The CIGS (Cu(In, Ga)Se₂) thin film solar cell sputtering process utilizes only 30% of the original target. The remaining 70% of the target must be recycled to achieve In, Ga, and Se rare metal sustainable use. It is, therefore, very important to establish spent CIGS target recycling technology to reduce environmental damage. CIGS is a tetrahedrally bonded semiconductor with a chalcopyrite crystal structure. Chalcopyrite is resistant to attack by the oxidants used in dissolution due to forming a passivation surface layer. Therefore, increasing the reaction temperature, lixiviating agent, and oxidant concentrations is necessary to enhance CIGS dissolution. The oxidation roasting pretreatment effects on the recovery and leaching of spent CIGS targets are investigated in this study. The results indicated that the proper oxidation roasting pretreatment process could significantly enhance CIGS leaching, reducing costs and increasing the reaction rate. This can be explained by the fact that the chalcopyrite structure was decomposed and transformed into easier dissolvable Cu₂SeO₄, In₂O_3, and amorphous Ga₂O₃ after roasting in the air. Cu, In, and Ga recoveries can reach above 99.9% by leaching CIGS roasted at 500 °C in 1 M H₂SO₄ at 60 °C for 1 h. As the roasting temperature was increased to 600 °C, the Ga recovery rate decreased due to the formation of difficult dissolvable β-Ga₂O₃. Mono-dispersed, near-stoichiometric CIGS nanoparticles with a mean crystallite size of 9 nm can be obtained using a direct recycling process combining oxidation, leaching, and re-synthesis processes. Full article

High-performance MgO-CaO-Fe₂O₃ clinker was prepared using magnesite from Xinjiang (with high calcium and low silica), calcium oxide, and ferric oxide as raw materials. Microstructural analysis and thermogravimetric analysis, combined with HSC chemistry 6 software simulations, were used to investigate the synthesis mechanism of MgO-CaO-Fe₂O₃ clinker and the effect of firing temperature on the properties of MgO-CaO-Fe₂O₃ clinker. The results show that MgO-CaO-Fe₂O₃ clinker with a bulk density of 3.42 g·cm⁻³, water absorption of 0.7%, and excellent physical properties can be formed by firing at 1600 °C for 3 h. In addition, the crushed and reformed specimens can be refired at temperatures of 1300 °C and 1600 °C to achieve compressive strengths of 17.9 MPa and 39.1 MPa, respectively. The main crystalline phase of the MgO-CaO-Fe₂O₃ clinker is the MgO phase; the 2CaO·Fe₂O₃ phase generated by the reaction is distributed between the MgO grains to form a cemented structure with a small quantity of 3CaO·SiO₂ and 4CaO·Al₂O₃·Fe₂O₃ also distributed between the MgO grains. A series of decomposition and resynthesis chemical reactions occurred during the firing of the MgO-CaO-Fe₂O₃ clinker, and the liquid phase appeared in the system once the firing temperature exceeded 1250 °C. The presence of the liquid phase promoted intergranular mass transfer between the MgO grains, ensuring the continuous growth of the MgO grains and furthering the densification of the MgO-CaO-Fe₂O₃ clinker. Full article

Fenugreek extracts possess promising physiological and pharmacological properties in human and animal models. This review aims to provide a scientific and comprehensive analysis of the literature on the effects of fenugreek extracts on muscle performance. An extensive online search was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement guidelines. The main medical and scientific engines were searched for articles from May 1981 to May 2021 to capture all scientific studies focused on the effect of fenugreek on muscle and exercise or sport. Out of 81 studies acquired, six eligible randomized controlled trials (RCTs) were included in the qualitative analysis. Four RCTs observed that fenugreek supplementation had significantly improved muscle strength, repetitions to failure (muscle endurance), submaximal performance index, lean body mass, and reduced body fat. Among the remaining two trials, one reported the significant effect of fenugreek extracts on the rate of muscle glycogen resynthesis during post-exercise recovery; however, the other failed to do so. Those two trials were weak, with a minimal sample size (<10). Further, fenugreek glycoside supplementation with sapogenins and saponins reported substantial anabolic and androgenic activity, influencing testosterone levels and muscle performance. It was useful during eight weeks of resistance training without any clinical side effects. Fenugreek with creatine supplementation improved creatine uptake without the necessity of high carbohydrate intake. Hence, fenugreek extracts can be a helpful natural supplement and ergogenic aid for athletes. However, it is better to be aware of doping and liver and kidney damage before using the fenugreek supplement. Full article

Volatile global oil prices, owing to the scarcity of fossil resources, have impacted the cost of producing petrochemicals. Therefore, there is a need to seek novel, renewable chemicals from biomass feedstocks that have comparable properties to petrochemicals. In this study, synthesis, thermal and mechanical properties, and degradability studies of a novel series of sustainable thiophene-based copolyesters like poly(hexylene 2,5-thiophenedicarboxylate-co-bis(2-hydroxyethoxybenzene) (PTB_xH_y) were conducted via a controlled melt polymerization method. Fourier-transform infrared (FTIR) and nuclear magnetic resonance (¹H NMR) spectroscopy techniques elucidated the degree of randomness and structural properties of copolyesters. Meanwhile, gel permeation chromatography (GPC) analysis showed a high average molecular weight in the range of 67.4–78.7 × 10³ g/mol. The glass transition temperature (T_g) was between 69.4 and 105.5 °C, and the melting point between 173.7 and 194.2 °C. The synthesized polymers outperformed poly(ethylene 2,5-thiophenedicarboxylate) (PETF) and behaved similarly to polyethylene terephthalate. The copolyesters exhibited a high tensile strength of 46.4–70.5 MPa and a toughness of more than 600%, superior to their corresponding homopolyesters. The copolyesters, which ranged from 1,4-bis(2-hydroxyethyl)benzene thiophenedicarboxylate (TBB)-enriched to hexylene thiophenedicarboxylate (THH)-enriched, offered significant control over crystallinity, thermal and mechanical properties. Enzymatic hydrolysis of synthetized polymers using porcine pancreatic lipase (PP-L) over a short period resulted in significant weight losses of 9.6, 11.4, 30.2, and 35 wt%, as observed by scanning electron microscopy (SEM), with perforations visible on all surfaces of the films. Thus, thiophene-based polyesters with cyclic aromatic structures similar to terephthalic acid (TPA) show great promise as PET mimics. At the same time, PP-L appears to be a promising biocatalyst for the degradation of bioplastic waste and its recycling via re-synthesis processes. Full article

To explore the molecular mechanisms underlying the anti-inflammatory activity of (R)-(-)-carvone, we evaluated its ability to inhibit the signaling pathways involving the mitogen-activated protein kinases (MAPKs) and the transcription factor, nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB). (R)-(-)-carvone significantly decreased c-Jun N-terminal kinase (JNK) 1phosphorylation, but not that of the other MAPKs, induced by bacterial lipopolysaccharides (LPS) in the RAW 264.7 macrophage cell line. Although (R)-(-)-carvone significantly inhibited resynthesis of the inhibitor of NF-κB (IκB)-α induced by LPS, it did not interfere with the canonical NF-κB activation pathway, suggesting that it may interfere with its transcriptional activity. (R)-(-)-carvone also showed a tendency to decrease the levels of acetylated NF-κB/p65 in the nucleus, without affecting the activity and protein levels of Sirtuin-1, the major NF-κB/p65 deacetylating enzyme. Interestingly, the nuclear protein levels of the transcription factor, nuclear factor (erythroid-derived 2)-like 2 (Nrf2) and the expression of its target,, heme oxygenase-1 (HO-1), an antioxidant enzyme, also showed a tendency to increase in the presence of (R)-(-)-carvone. Taken together, these results suggest that the ability of (R)-(-)-carvone to inhibit JNK1 and to activate Nrf2 can underlie its capacity to inhibit the transcriptional activity of NF-κB and the expression of its target genes. This study highlights the diversity of molecular mechanisms that can be involved in the anti-inflammatory activity of monoterpenes. Full article

With the increasing bandwidths of servo control systems and decreasing mode frequencies, aeroservoelastic (ASE) stability evaluation has become an essential part of flight vehicle design. However, the theoretical method is limited by the modeling errors of numerical models, and the dry wind tunnel method is limited by the complex design of force controllers. Given these limitations, a novel ASE stability evaluation method for slender vehicles based on the ground frequency response test (FRT) is proposed in this paper. FRTs are implemented for a slender vehicle to obtain the frequency response functions (FRFs) of the real structure and servo control systems. The low-order unsteady aerodynamic FRFs established in physical coordinates are calculated by the quasi-steady aerodynamic derivative method. An ASE open-loop FRF is established for stability evaluation via the Nyquist criterion. Comparison with the theoretical results shows that the proposed method is feasible and accurate for different positions of the inertial measurement unit, different control laws, and different Mach numbers. To deal with the unavoidable influence of hanging supports in the test, an FRF fitting and resynthesis method is used to remove the hanging modes and provide an accurate ASE open-loop FRF with free–free boundary conditions. Full article

Despite aggressive treatment and androgen-deprivation therapy, most prostate cancer patients ultimately develop castration-resistant prostate cancer (CRPC), which is associated with high mortality rates. However, the mechanisms governing the development of CRPC are poorly understood, and androgen receptor (AR) signaling has been shown to be important in CRPC through AR gene mutations, gene overexpression, co-regulatory factors, AR shear variants, and androgen resynthesis. A growing number of non-AR pathways have also been shown to influence the CRPC progression, including the Wnt and Hh pathways. Moreover, non-coding RNAs have been identified as important regulators of the CRPC pathogenesis. The present review provides an overview of the relevant literature pertaining to the mechanisms governing the molecular acquisition of castration resistance in prostate cancer, providing a foundation for future, targeted therapeutic efforts. Full article