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Corrosion poses a significant threat to the structural integrity of steel rails, especially in an acidic environment. In this study, we evaluate the corrosion properties of U75V-welded joints using potentiodynamic polarization curves, electrochemical impedance measurements, and corrosion morphology studies under simulated acidic conditions. Compared to non-normalized joints, the normalized joints exhibit a higher self-corrosion current (4.65 × 10−5 A/cm2) and a more negative self-corrosion potential (−0.56919 mV). The smaller and more uniform grain size obtained after normalizing provides multiple active sites on the surface for polarization reactions. Furthermore, owing to significant erosion caused on the rail surface by the acidic solutions, normalizing treatment enhances the passivation effects on the surface, resulting in increased corrosion resistance (221.96 Ω cm2). Our findings provide insights into the impact of normalizing treatments on the corrosion mechanism of U75V rail joints under acidic conditions.

Background: Cold environments pose serious threats on human health, with increased risk for myocardial infarction, stroke, frostbite, and hypothermia. Acquired cold acclimation is required to minimize cold-induced injures and to improve metabolic health. However, the underlying mechanisms remain to be fully elucidated. Objective: We aimed to identify critical amino acids involved in cold acclimation and unmask the regulatory mechanisms. Methods: A total of twenty male participants were recruited and followed up after 3 months’ natural cold exposure. Cold-induced vasodilation (CIVD) tests and clinical biochemical analysis were performed at baseline and after 3-months cold exposure, whilst blood samples were collected, and plasma amino acids were analyzed by targeted metabolomics. To further confirm the effect of lysine on cold tolerance and explain the latent mechanism, mice were challenged with chronic cold exposure for 7 days with lysine supplement, then core and local surface temperature as well as thermogenesis activity were detected. Results: Continuous cold exposure shortened the CIVD onset time and increased the average finger temperature. Levels of the plasma lysine and glycine were decreased in both humans and mice. Venn analysis from three datasets revealed that lysine was the only significantly changed plasma amino acid, which strongly correlated with the altered CIVD. Moreover, mice sustained a relatively higher core temperature and surface temperature in the back, tail and paws upon lysine supplementation. Furthermore, lysine supplementation increased the level of histone H3K18cr and promoted the gene and protein expression of Cpt1a, Cpt2 and Cyp27a1 in liver. Conclusion: Our work identified lysine as a critical amino acid for the remodeling of hepatic histone crotonylation that facilitates cold acclimation.

Summary: Emerging evidence highlights the regulatory role of paired-like (PRD-like) homeobox transcription factors (TFs) in embryonic genome activation (EGA). However, the majority of PRD-like genes are lost in rodents, thus prompting an investigation into PRD-like TFs in other mammals. Here, we showed that PRD-like TFs were transiently expressed during EGA in human, monkey, and porcine fertilized embryos, yet they exhibited inadequate expression in their cloned embryos. This study, using pig as the research model, identified LEUTX as a key PRD-like activator of porcine EGA through genomic profiling and found that LEUTX overexpression restored EGA failure and improved preimplantation development and cloning efficiency in porcine cloned embryos. Mechanistically, LEUTX opened EGA-related genomic regions and established histone acetylation via recruiting acetyltransferases p300 and KAT2A. These findings reveal the regulatory mechanism of LEUTX to govern EGA in pigs, which may provide valuable insights into the study of early embryo development for other non-rodent mammals.

Excessive long-term manganese intake can inflict irreversible damage to the nervous system, with a predominant effect on the substantia nigra-striatum pathway. Through a mouse model simulating manganese exposure, we delved into its implications on the central nervous motor system, uncovering autophagy-lysosome dysfunction as a pivotal factor in manganese-induced neurotoxicity. Our research illuminated the molecular mechanisms behind TFEB’s role in manganese-triggered neuronal autophagy dysfunction, offering insights into the cellular and molecular mechanisms of manganese-induced abnormal protein accumulation. This study lays a significant theoretical foundation for future endeavors aimed at safeguarding against manganese neurotoxicity. Furthermore, TFEB emerges as a potential early molecular biomarker for manganese exposure, providing a solid basis for preemptive protection and clinical treatment for populations exposed to manganese.

Aerobic fitness is a critical aspect of overall health and well-being, essential for maintaining a high quality of life. Unfortunately, sedentary behavior has been on the rise among young adults, and this has had a negative impact on their aerobic fitness levels. Therefore, it is crucial to identify enjoyable physical exercise training programs that can play a pivotal role in improving aerobic fitness. The objective of this study was to systematically review the experimental studies concerning the impact of small-sided games (SSGs) training programs, implemented across various team sports, on the enhancement of aerobic fitness in a youth sedentary population. A literature search was conducted in PubMed, Scopus, and the Web of Science on August 01, 2023. Our eligibility criteria focused on studies involving sedentary youth populations (aged

Lamprey underwent biliary atresia (BA) at its metamorphosis stage. In contrast to patients with BA who develop progressive disease, lamprey can grow and develop normally, suggesting that lamprey has several adaptations for BA. Here we show that adaptive changes in bile acid and cholesterol metabolism are produced after lamprey BA. Among 1102 differentially expressed genes (DGEs) after BA in lamprey, many are enriched in gene ontology (GO) terms and pathways related to steroid metabolism. We find that among the DGEs related to bile acids and cholesterol metabolism, the expression of cytochrome P450 family 7 subfamily A member 1 (CYP7A1), sodium-dependent taurine cotransport polypeptide (NTCP) are significantly downregulated, whereas nuclear receptor farnesoid X receptor (FXR), multidrug resistance-associated protein 3 (MRP3), 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR), sterol O-acyltransferase 1 (SOAT1), and ATP binding cassette subfamily A member 1 (ABCA1) are remarkably upregulated. The changes in expression level are also validated by RT-qPCR. Furthermore, the level of high-density lipoprotein-cholesterol (HDL-C) and low-density lipoprotein-cholesterol (LDL-C) in juvenile serum is higher compared to larvae. Taken together, the findings collectively indicate that after BA, lamprey may maintain bile acids and cholesterol homeostasis in liver tissue by inhibiting bile acids synthesis and uptake, promoting its efflux back to circulation, and enhancing cholesterol esterification for storage as lipid droplets and its egress to form nascent HDL (nHDL). Understanding the possible molecular mechanisms of lamprey metabolic adaptation sheds new light on the understanding of the development and treatment of diseases caused by abnormal bile acid and cholesterol metabolism in humans.

Neurotoxicity caused by environmental lead (Pb) pollution is a worldwide public health concern, and developing a therapeutic strategy against Pb-induced neurotoxicity is an important area in the current research. Our prior research has demonstrated the significant involvement of microglia-mediated inflammatory responses in the manifestation of Pb-induced neurotoxicity. Additionally, the suppression of proinflammatory mediator activity significantly mitigated the toxic effects associated with Pb exposure. Recent studies have highlighted the critical role of the triggering receptor expressed on myeloid cells 2 (TREM2) in the pathogenesis of neurodegenerative disorders. TREM2 exerted protective effects on inflammation, but whether TREM2 is involved in Pb-induced neuroinflammation is poorly understood. In the present study, cell culture experiments and animal models were designed to investigate the role of TREM2 in Pb’s neuroinflammation. We examined the impact of pro- and anti-inflammatory cytokines involved in Pb-induced neuroinflammation. Flow cytometry and microscopy techniques were applied to detect microglia phagocytosis and migration ability. Our results showed that Pb treatment significantly downregulated TREM2 expression and altered the localization of TREM2 expression in microglia. The protein expression of TREM2 was restored, and the inflammatory responses provoked by Pb exposure were ameliorated upon the overexpression of TREM2. Furthermore, the phagocytosis and migratory capabilities of microglia, which were impaired due to Pb exposure, were alleviated by TREM2 overexpression. Our in vitro findings were corroborated in vivo, demonstrating that TREM2 regulates the anti-inflammatory functions of microglia, thereby mitigating Pb-induced neuroinflammation. Our results provide insights into the detailed mechanism by which TREM2 alleviates Pb-induced neuroinflammation and suggest that activating the anti-inflammatory functions of TREM2 may represent a potential therapeutic strategy against environmental Pb-induced neurotoxicity.

Emerging evidence suggests that circular RNAs (circRNAs) have crucial roles in various processes, including cancer development and progression. However, the functional roles of circRNAs in breast cancer remain to be elucidated. In this study, we identified a novel circRNA (named circBMPR2) whose expression was lower in breast cancer tissues with metastasis. Moreover, circBMPR2 expression was negatively associated with the motility of breast cancer cells and significantly downregulated in human breast cancer tissues. Functionally, we found that circBMPR2 knockdown effectively enhanced cell proliferation, migration, and invasion. Moreover, circBMPR2 knockdown promoted tamoxifen resistance of breast cancer cells through inhibiting tamoxifen-induced apoptosis, whereas circBMPR2 overexpression led to decreased tamoxifen resistance. Mechanistically, we demonstrated that circBMPR2 could abundantly sponge miR-553 and that miR-553 overexpression could attenuate the inhibitory effects caused by circBMPR2 overexpression. We also found that ubiquitin-specific protease 4 (USP4) was a direct target of miR-553, which functions as a tumor suppressor in breast cancer. Our findings demonstrated that circBMPR2 might function as a miR-553 sponge and then relieve the suppression of USP4 to inhibit the progression and tamoxifen resistance of breast cancer. Targeting this newly identified circRNA may help us to develop potential novel therapies for breast cancer patients. Keywords: breast cancer, circBMPR2, tumor suppressor, tamoxifen resistance, miR-553, USP4

Objective: In view of the poor prognosis and difficulties in the diagnosis of osteosarcoma, and the functionality of microRNA-Let7A in different types of human cancers, our study aimed to explore the diagnostic and prognostic values of microRNA-Let7A for osteosarcoma. Methods: A total of 39 patients with osteosarcoma and 19 normal healthy people were included in this study. All patients received surgical resection, and tumor tissues as well as pericarcinomatous tissues were collected during surgical operation. Venous blood (2 ml) was extracted from each participant. Expression of microRNA-Let7A in tumor tissues and pericarcinomatous tissues, and expression of E2F2 and microRNA-Let7A in blood of each participant was detected by qRT-PCR. ROC analysis was performed to evaluate the diagnostic values of blood E2F2 and microRNA-Let7A for osteosarcoma, and prognostic values of microRNA-Let7A for osteosarcoma was evaluated by survival curve comparisons. Results: Expression level of microRNA-Let7A was significantly lower in tumor tissues than that in pericarcinomatous tissues. MicroRNA-Let7A expression in blood was significantly downregulated in osteosarcoma patients compared with normal control. Expression of microRNA-Let7A was negatively correlated with the expression of E2F2 in blood of osteosarcoma patients. Compared with E2F2, blood microRNA-Let7A can more effectively predict osteosarcoma. Overall survival rate of osteosarcoma patient with low blood expression level of miRNA-let-7a was significantly lower than that of patients with high blood expression level of miRNA-let-7a. Conclusion: Blood microRNA-Let7A is a promising diagnostic and prognostic biomarker for osteosarcoma. Keywords: Osteosarcoma, MicroRNA-Let7A, Venous blood, qRT-PCR, ROC, Pericarcinomatous

Breast cancer (BC) is among the most common malignant diseases and metastasis is the handcuff of treatment. Cancer metastasis is a multistep process associated with the epithelial-mesenchymal transition (EMT) program. Several studies have demonstrated that transcriptional repressor GATA binding 1 (TRPS1) played important roles in development and progression of primary BC. In this study we sought to identify the mechanisms responsible for this function of TRPS1 in the continuum of the metastatic cascade. Here we described that TRPS1 was significantly associated with BC metastasis using public assessable datasets. Clinically, loss of TRPS1 expression in BC was related to higher histological grade. In vitro functional study and bioinformatics analysis revealed that TRPS1 inhibited cell migration and EMT in BC. Importantly, we identified SUZ12 as a novel target of TRPS1 related to EMT program. ChIP assay demonstrated TRPS1 directly inhibited SUZ12 transcription by binding to the SUZ12 promoter. Loss of TRPS1 resulted in increased SUZ12 binding and H3K27 tri-methylation at the CDH1 promoter and repression of E-cadherin. In all, our data indicated that TRPS1 maintained the expression of E-cadherin by inhibiting SUZ12, which might provide novel insight into how loss of TRPS1 contributed to BC progression.

We examined the gut health potential of the brown seaweed Ecklonia radiata and its polysaccharides. Rats consumed an AIN-93G-based diet without addition (control) or containing 5% (w/w) of ground dried whole seaweed (WS) or dried powdered polysaccharide fraction (PF) of the seaweed for 1 wk. The PF consisted largely of fucoidan and alginate. PF treatment increased cecal digesta weight relative to the control (1.36 ± 0.17 vs 0.60 ± 0.06 g/100 g body weight). Beneficial cecal total short chain fatty acids increased in response to WS (213.25 ± 14.40 μmol) and PF (208.59 ± 23.32 μmol) compared with the control (159.96 ± 13.10 μmol). Toxic protein fermentation product levels were decreased by WS and PF. Cecal numbers of bacteria relevant to gut health were determined using quantitative real-time PCR. Relative to the control, numbers of butyrate-producing Faecalibacterium prausnitzii were increased by PF supplementation, whereas WS decreased numbers of potentially pathogenic Enterococcus. In conclusion, E. radiata-derived polysaccharides have promise as prebiotic supplements.

This study investigates the effects of deformation parameters on the second phase and softening behavior of Al–Zn–Mg–Cu alloy. The results are as follows: Firstly, the area fraction of the intermetallic phase fluctuates between 0.704 ± 0.092% and 1.886 ± 0.231% with varying deformation parameters. Secondly, in the temperature range of 270 °C to 430 °C, the area fraction of the η[Mg(Zn, Al, Cu)2] phase first increases and then decreases with rising deformation temperature, and gradually increases with decreasing strain rate. The highest area fraction is 12.613 ± 0.340% at 350 °C/0.001 s−1, and the lowest is 0.366 ± 0.068% at 470 °C/0.001 s−1. Additionally, the coarsening and dissolution of the η[Mg(Zn, Al, Cu)2] phase accelerate the dynamic recovery softening of the alloy. The sample at 350 °C/0.001 s−1 shows a low-angle grain boundary (LAGBs) percentage of 97.83% and a minimum average dislocation density of 8.493 × 102 μm2. Furthermore, at 470 °C/0.001 s−1, the Al7Cu2Fe phase has a weaker effect on stimulating nucleation and recrystallization, while the most significant promotion occurs at 430 °C/0.001 s−1. In the range of 270 °C to 350 °C and 0.1 s−1 to 0.5 s−1, the Al7Cu2Fe phase mainly stimulates the formation of sub-grains. These findings offer valuable insights for refining the grain size of alloys by regulating the content of the second phase during hot deformation.

The present research assessed the impact of dietary valine on nutritional and energy metabolism, as well as muscle development in swimming crabs (Portunus trituberculatus) over a period of six weeks. Swimming crabs, initially weighing around 23.34 ± 0.03 g, were given six diets identical in nitrogen and lipid levels (45 % and 8 % respectively). These diets contained valine contents of 0.99 %, 1.24 %, 1.56 %, 1.69 %, 1.90 %, and 2.20 % respectively. One hundred and eighty crabs were randomized into six treatments, each treatment including three replicates. The results suggested that significant increases were discovered in FW, PWG, as well as SGR of crabs when dietary valine increasing from 0.99 % to 1.69 %, but these measurements decreased when dietary valine increased to 2.20 %. Compare to the control treatment, crabs that were given diets with 1.90 % and 2.20 % valine showed increased level of muscle protein. Crabs that were given the diets containing 1.56 % and 1.69 % valine showed significantly increased concentration of GLU in hemolymph compared to the control group. Additionally, crabs that were given the diets containing 1.69 % valine and 1.90 % valine respectively showed significantly increased concentrations of T-CHO and TG in hepatopancreas. Hepatic glycogen concentration significantly decreased as the level of valine in diets increased from 0.99 % to 1.56 %, but significantly increased as valine level further increased to 2.20 %. Compared with the control group, crabs that were given diets with 1.90 % valine showed increased expression levels of genes associated to amino acid metabolism (pi3k, akt, alt, ast, 4ebp1 and eif4e3) and energy metabolism (pk, cs1, idh, nd1, cytb and cox2). Crabs given diets containing 2.20 % valine showed significantly increased expression level of pepck in hepatopancreas, while crabs given diets containing 1.24 %, 1.56 %, and 1.69 % valine exhibited significantly increased expression level of cpt1 in hepatopancreas. Crabs given the diet with 1.69 % valine had the highest expression levels of tor and pax7 in muscle. Increased dietary valine significantly reduced myofiber density but promoted higher frequency of myofibers in larger diameters. In conclusion, the optimal valine requirement for P. trituberculatus was 1.56 % of diet based on PWG by a quadratic modeling. 1.69–1.90 % valine promoted amino acid metabolism and muscle growth, moreover, enhanced energy metabolism by driving the consumption of glycogen rather than lipids.

Ovarian development is a complex and dynamical process regulated by the coordinated actions of the hepatopancreas and ovary. In mammals, lipids provide necessary energy for oocytes to mature, whereas their regulatory role in crustaceans is not fully understood. This study compares lipid mobilization and deposition in hepatopancreas and ovary of the swimming crab at different stages of ovarian maturation. The results revealed that cholesterol (CHO) and triglyceride (TG) content in hepatopancreas increased with ovary development increased from stage I to Ⅲ, and then decreased at stage V, while those content in ovary significantly increased from stage I to V. Additionally, apolipoprotein (ApoA and ApoB) contents in hepatopancreas and ovary increased significantly during ovary development. Moreover, the highest expression levels of cholesterol transport related genes (srb, ldlr, lrp2 and abcg1) were observed in the hepatopancreas at stage Ⅲ and in the ovary at stage Ⅳ. Furthermore, as ovary development form stage I to Ⅳ, the hepatopancreas up-regulated the expression levels of genes related to lipid anabolism (fas, acc, g6pd, and 6pgd) and fatty acid transport (fabp9 and fatp4). Concurrently, genes related to lipid catabolism (il) and fatty acid β-oxidation (acox2 and acox3) in the hepatopancreas were down-regulated. Differently, with the ovary development increased from stage I to Ⅳ, the ovary up-regulated gene expression levels involved in lipid anabolism (acc, 6pgd, g6pd, dgat1, and gpat3), fatty acid synthesis (elovl and elovl4) and fatty acid β-oxidation (cpt1, cpt2, acox1, and acox3). The mRNA expression levels of lipolysis (tgl) and fatty acid transport (fabp1, fbap9, and fatp4) in ovary were down-regulated. Overall, these findings demonstrate that the hepatopancreas and ovary exhibit different responses to lipid metabolism during ovarian development.

Rearing density is a critical factor for both the productivity and welfare of farmed fish. The present study examined juvenile black sea bream (Acanthopagrus schlegelii) at low (LD), standard (control, CR), moderately high (MD), and high (HD) densities over a 60-day period. The effects of density on physiological aspects of growth, survival, stress response (cortisol), osmosis and ion balance (Na+–K+–ATPase and Ca2+–Mg2+–ATPase), energy metabolism (glucose, lactic acid, and lactic dehydrogenase), digestive enzyme activity (lipase, trypsin, and amylase), antioxidant ability (superoxide dismutase and malondialdehyde), and non-specific immunity (lysozyme) were investigated to evaluate potential physiological improvements in this commercially and ecologically important species under different densities. Both transcriptomic and metabolomics approaches were applied to assess metabolic and transcriptional changes among groups to determine the underlying mechanisms of physiological performance. The results showed that juveniles reared under low density had not only significantly improved growth and survival rate but also significantly reduced energy expense and lower activities of digestive and antioxidant enzymes compared with fish reared under high density. Significantly reduced cortisol and malondialdehyde contents in the LD group indicated less stressful conditions in those fish. Transcriptomic analysis showed that differentially expressed genes (DEGs) were involved in pancreatic secretion, protein digestion and absorption, and protein processing in the endoplasmic reticulum pathway. Metabolomics revealed that significantly different metabolites (SDM) were involved in the biosynthesis of amino acids, ABC transporters, 2-oxocarboxylic acid metabolism, and protein digestion and absorption. A combined analysis of transcriptome and metabolome showed that fish in the LD group exhibited reductions in energy expenditure, osmotic regulation, and antioxidant ability, while fish in the HD group showed higher energy expenditure, digestive ability, and immune regulation. These findings have important implications for the improvement of fish growth and welfare as well as in mechanistic studies of rearing density.

The purpose of present study was to evaluate the effects of vitamin D3 supplementation in high-fat diet on growth performance, calcium and phosphorus in tissue, immunity and lipid metabolism, and to explore whether adding vitamin D3 to high-fat diet can alleviate the adverse effects of high-fat diet on swimming crab (Portunus trituberculatus). The three experimental diets were normal fat diet (NFD, 9.35 % fat, 45.53 % protein), high fat diet (HFD, 14.69 % fat, 44.93 % protein) and high fat diet supplemented with 0.47 mg/kg VD3 (HFD+VD), respectively. A total of 108 healthy swimming crabs with an initial body weight of 9.42±0.13 g were selected for an 8-week feeding trial. The results showed that crabs fed with HFD+VD diet exhibited significantly higher percent weight gain (PWG), specific growth rate (SGR), feed efficiency (FE) and molting rate (MR) compared to those fed with HFD diet (P < 0.05). It was observed from hepatopancreas crude lipid content, TG content and hepatopancreas sections that HFD caused hepatopancreatic cell damage and abnormal lipid accumulation (P < 0.05), however, there were no significant differences in hepatopancreas crude fat content, TG content and hepatopancreas section observation between HFD+VD group and NFD group (P > 0.05). Crabs fed HFD diets with or without VD3 significantly down-regulated the expression of genes related to fatty acid transport, such as fabp9 and lpr1 in hepatopancreas (P < 0.05), moreover, the expression of genes related to fatty acid β-oxidation (cpt2 and acox1) were significantly up-regulated and genes related to lipid synthesis (fas and 6pgd) were significantly down-regulated in the hepatopancreas of the crabs fed with HFD+VD diet compared to those fed with HFD diet (P < 0.05). In conclusion, the results of present study indicated that a high-fat diet can cause deformation and rupture of hepatopancreas cells through abnormal lipid accumulation, thereby causing associated inflammation, leading to large calcium and phosphorus deposits in hemolymph and muscle, however, high fat diet supplemented with vitamin VD3 mainly enhanced the β-oxidation of fatty acids, inhibited lipid synthesis, alleviated abnormal lipid accumulation, and thus maintained the balance of lipid metabolism in hepatopancreas cells and promoted growth performance and feed utilization for swimming crab.

The combustion characteristics of spark assistant compression ignition mode under different loads and fuels were explored, as well as by constructing artificial neural networks(ANN) model, the prediction ability of different algorithms for engine performance was discussed. Burning methanol and n-butanol can help to improve IMEP and induce earlier spontaneous combustion. The knock intensity(KI) of engine fueled with methanol was highest followed by n-butanol and gasoline, but maximum amplitude of filtered pressure oscillation(MAPO) shows the opposite trend. KI showed great positive liner correlation with ignition timing. Methanol showed the most outstanding tolerance on the compression ignition state. Fueled with methanol can decreased equivalent brake specific fuel consumption(ESFC) up to 52.9 % compared with the initial SI gasoline engine. N-butanol can improve BSNOx, BSTHC and BSCO concurrently, however fueled with methanol will worsen BSNOx. ANN model for engine combustion, economy and emissions performance was built. The prediction accuracy of Bayesian regularization algorithm for engine performance predicting was highest, but it have no advantage in the calculating times when the amount of data was large while the Levenberg-Marquardt algorithm would be the ideal efficient. The mean square error of ESFC and emissions parameters under scaled conjugate gradients algorithm always poorest.

The placement of ureteral stents plays a crucial role in the treatment of ureteral strictures, therefore requiring high material performance standards. In addition, depending on the etiology of ureteral strictures, there are significant differences in the retention time of ureteral stents, thus requiring different degradation rates for the stents. Therefore, it is crucial to develop stent materials with high performance and controllable degradation rates. This study explores the potential of Zn-2Cu-0.5Fe-xMn alloy as a ureteral stent material, utilizing the antibacterial effect of copper ions, the strengthening effect of Fe element on Zn-based alloys, and the accelerated degradation effect of Mn element. The research found that with the increase in Mn content, the average grain size of the alloy and the size of (Fe, Mn)Zn13 phase gradually increased, leading to a decrease in hardness. The corrosion rate of the alloy increased with the increase in Mn content, attributed to changes in grain size and standard electrode potential differences between elements. Due to the antibacterial effects of Zn ions and Cu ions, the Zn-2Cu-0.5Fe-xMn alloy exhibits good anti-stone formation capabilities. Furthermore, the alloy also demonstrates acceptable cytotoxicity. Therefore, the Zn-2Cu-0.5Fe-xMn alloy is expected to become an important implant material in urological surgery.

A nanocrystalline alloy, with an iron-based composition (Fe58.5Si16.7B6.5Nb5.1Cu13.2) and a Curie temperature of 570 °C, was investigated for its effectiveness as magnetic shielding films in an induction heating system. The primary focus of the research was to evaluate the shielding performance of the 3-turned (9-layered) shielding films with dimensions of 135 mm × 17 mm × 0.15 mm. Upon winding, these films formed a cylindrical structure that enveloped the coil, with a diameter of 13.9 mm and a height of 17 mm. The results showed that increasing the degree of fragmentation within the nanocrystalline shielding films significantly reduced the magnetic permeability by decreasing the real component from 11,500 to 400 and the imaginary part from 2800 to 20. However, a lower degree of fragmentation led to a 10 % increase in the resistance (Rs) of the heating module, although this effect was less pronounced as the relative permeability continued to increase. Furthermore, observations on preheating time to a set temperature of 400 °C and total energy consumption over a duration of 250s revealed an initial downward trend, followed by a rapid increase that even exceeded the initial values as the magnetic permeability of the nanocrystalline shielding films augmented. Notably, the study emphasized that nanocrystalline shielding films with a relative permeability value of 1000 demonstrated exceptional magnetic shielding performance, resulting in a 12.5 % reduction in preheat time and 7 % less energy consumption during preheating. In addition to empirical findings, the study developed a theoretical model elucidating the shielding mechanism inherent in induction heating systems. This model serves as a robust framework for the application of nanocrystalline shielding materials in such systems, laying the groundwork for enhanced magnetic shielding capabilities in future applications.

High-quality surface reconstruction and texture reconstruction of large-scale scene play a pivotal role in the domains of ancient architecture, cultural heritage preservation, and 3D urban modeling. Given that point cloud data has emerged as a crucial medium for representing three-dimensional spatial information, its utilization for surface and texture reconstruction becomes indispensable. In this research, we propose a novel framework for reconstructing surface and texture from unstructured colorful point clouds without normal information to restore large-scale real-world scenes. Specifically, we first introduce an automatic virtual viewpoint selection method to generate virtual views by rendering the point cloud from multiple viewpoints. Subsequently, we construct a two-step network to facilitate accurate visibility prediction and texture inpainting for each virtual view. Then, the visibility information from multiple perspectives is integrated to solve an optimization problem incorporating visibility constraints, resulting in the generation of a 3D mesh. Subsequently, texture information from various perspectives is integrated, filtering techniques are applied to determine the optimal perspective for texturing, and a texture atlas is generated. Precise texture mapping is then performed, ultimately leading to the production of a comprehensive textured model. In contrast to alternative learning-based methodologies, our framework exclusively learns from two-dimensional images, encompassing the prediction of both visible and invisible points as well as the execution of image inpainting tasks. This approach exhibits exceptional versatility in managing large-scale point clouds while effectively leveraging the color and intensity attributes of the data for precise texture reconstruction. The experimental results demonstrate that our approach achieves a significant improvement of 2.06% in F-scores for outdoor surface reconstruction compared to the current state-of-the-art learning-based methods, while also outperforming them in texture reconstruction.

Purpose: Pure mucinous breast cancer (PMC) is a rare histological type with a favourable prognosis. However, cases with recurrence have been reported and diagnosed in clinical practice. The mechanisms underlying PMC recurrence remain unknown. In this study, we aimed to identify the prognostic factors associated with PMC. Materials and methods: A total of 166 patients diagnosed with PMC were included. We compared the clinicopathological characteristics between patients with and without recurrence. The 21-gene assay was performed in 10 patients with recurrence and 20 TNM stage-matched patients without recurrence. Whole-exon sequencing was performed in 12 PMC primary tumours and four positive lymph nodes (LNs). Results: Tumour size, lymph node status and TNM staging differed significantly between recurrent group and non-recurrent group. And the 21-gene recurrence scores did not differ significantly between recurrent group and its TNM stage-matched non-recurrent group. The most frequently mutated genes in the primary tumours of regional LN-positive PMCs were ADCY10 (3/6) and SHANK3 (3/6), and they more recurrently harboured gains of 15q23, 17q23.2 and 20p11.21, and loss of 21p11.2. And these alterations were not detected in primary tumours of regional LN-negative PMCs. Conclusion: TNM stage is an important prognostic factor in PMC. Although we revealed that regional LN-positive PMCs show increased occurrence of duplication variants at 15q23, 17q23.2 and 20p11.21, and deletion variants at 21p11.2. Further investigation, including multi-omics studies, are needed and may provide additional insights into the nature of PMC.

Glycerol monolaurate (GML) is a common food additive known for its antimicrobial and anti-inflammatory properties. This study aims to assess the impact of GML on experimental colitis, both in vivo and in vitro. The results indicated that GML significantly inhibited the expression of MIP-3α, TNF-α, IL-1β, and IL-6, while upregulating the expression of claudin-3 and claudin-4 in DSS-treated Caco-2 cell monolayers. Oral administration of GML effectively alleviated colitis in mice, as demonstrated by mitigating body weight loss, lowering the DAI score, and improving colon shrinkage. GML significantly suppressed the expression of NF-κB p65, IL-1β, IL-6, TNF-α, and IL-18 in DSS-treated mice. Moreover, GML increased the cecal microbial alpha-diversity index and restored the dysbiosis. GML significantly increased the relative abundance of Lactobacillus, Alistipes, and Bacteroides, which were found to be negatively correlated with the DAI score and pro-inflammatory cytokine expression. In conclusion, the results highlight the potential therapeutic benefits of GML in preventing colitis and emphasize the role of gut microbiota in this process.

ABSTRACT: Macrophages play a crucial role in both innate and adaptive immunity. However, their abnormal activation can lead to undesirable inflammatory reactions. This study aimed to investigate the effects of glycerol monolaurate (GML), a natural monoester known for its anti-inflammatory and immunoregulatory properties, on avian macrophages using the HD11 cell line. The results indicated that a concentration of 10 μg/mL of GML enhanced the phagocytic activity of HD11 cells (P < 0.05) without affecting cell viability (P > 0.05). GML decreased the expression of M1 macrophage polarization markers, such as CD86 and TNF-α genes (P < 0.05), while increasing the expression of M2 macrophage polarization markers, such as TGF-β1 and IL-10 genes (P < 0.05). GML suppressed ROS production, apoptosis, and the expression of proinflammatory genes (IL-1β and IL-6) induced by LPS (P < 0.05). GML also promoted the expression of TGF-β1 and IL-10 (P < 0.05), both in the presence and absence of LPS exposure. Moreover, GML suppressed the gene expression of TLR4 and NF-κB p65 induced by LPS (P < 0.05), as well as the phosphorylation of NF-κB p65 (P < 0.05). In conclusion, GML exhibited regulatory effects on the polarized state of avian macrophages and demonstrated significant anti-apoptotic and anti-inflammatory properties by suppressing intracellular ROS and the NF-κB signaling pathway.

Aim: This study aimed to compare the quality of compressions in supine cardiopulmonary resuscitation (CPR) and prone CPR by performing chest compressions on a manikin. Evaluating the effect of prone CPR using different hand and body position on the quality of manual chest compressions and fatigue of participants. Methods: After completing 2 min of chest compression in the supine position (Supine Group), 25 participants randomly performed three sets of 2-minutes chest compressions on a prone position manikin. Stand + hands overlapped Group: participants stood beside the patient bed with their hands overlapped and placed on the posterior segment of the thoracic spine between the scapulae, Straddle + hands separated Group: participants straddled the patient bed with their hands placed above the scapulae on both sides at the mid-chest level, and Straddle + hands overlapped Group: participants straddled the patient bed with their hands overlapping on the posterior segment of the thoracic spine between the scapulae. Subsequently, the quality of chest compressions and participants fatigue were assessed. Results: Chest compression depth ratio and mean chest compression depth (MCCD) were worse in the three prone CPR groups (Stand + hands overlapped Group: 0.0(0.0,15.6) %, 39.8 ± 1.3 mm; Straddle + hands separated Group: 1.4(0.0,11.7) %, 42.4 ± 1.2 mm; Straddle + hands overlapped Group: 0.0(0.0,9.2) %, 40.9 ± 1.2 mm) than in the Supine group (87.1(68.1,94.0) %; p

Hemopexin as an acute-phase protein binds heme with a high affinity and participates in a variety of processes of physiology and pathology. Hemopexin plays an important role in regulating inflammatory response by regulating pro-/anti-inflammatory cytokines. In this study, the hemopexin gene was identified from black rockfish. The open reading frame of the black rockfish hemopexin (SsHPX) gene was predicted and amplified. The different expression patterns of SsHPX in microbial-challenged tissues and peripheral blood leukocytes (PBLs) were analyzed by RT-qPCR. The results indicated that SsHPX showed high evolutionary conservations in sequence and structure. The expression of SsHPX was significantly induced in a time-dependent manner in black rockfish intestine after Edwardsiella piscicida infection, while the evidently down-regulations were observed in the PBLs following the stimulations of two microbial ligands. The recombinant SsHPX protein (rSsHPX) exhibited microbial binding ability. In addition, rSsHPX could reduce bacterial proliferation with effect, thereby alleviating the inflammatory responses induced by bacteria. Moreover, almost all the expressions of pro-inflammatory cytokines (tnfα, il-1β, il-8 and il-17c) and anti-inflammatory cytokine (IL-10) were inhibited in black rockfish intestine cells stimulated by the mixing solution of LPS + rSsHPX comparing with the group with LPS stimulation. Overall, this study provides a theoretical basis for investigating the key roles of an acute-phase protein hemopexin in bacteriostatic ability and inflammatory regulations in black rockfish during bacterial infection. These findings also contribute to a better understanding of the relatively stable and conserved biological function of hemopexin during species evolution.

Marine ecosystems are undergoing life-history adaptations with impacts on productivity, resilience, and economic value due to Fisheries-Induced Evolution (FIE). Long-term and often intense selective commercial harvesting has led to truncations in population structure and evolutionary changes in key life-history traits. However, the consequences for different functional groups have rarely been evaluated, especially in the context of rebuilding depleted marine stocks. This study uses an individual-based eco-genetic modeling approach to investigate the effects of FIE during shifts in fishing intensity. We focus on functional groups of three types of pelagic fish and three types of demersal fish with different life histories in the China Seas, proposing and evaluating two types of evolving trait response indicators to FIE, and assessing the influence of fishing intensity during the population rebuilding phase. Our results indicate that FIE has a more pronounced impact on biomass recovery in demersal fishes compared to pelagic fishes. The recovery time ranges from 10 to 40 years and strongly correlates with length at 50% vulnerability (L50). Reductions in fishing intensity facilitate biomass recovery, particularly in demersal fishes. In conclusion, our study suggests that adopting a management approach tailored to the needs of distinct functional groups is highly beneficial for promoting the efficient recovery of declining demersal fisheries. This understanding is crucial for developing effective fishery management strategies that integrate the evolutionary responses of different functional groups.

Addressing the challenges in detecting surface defects on ceramic disks, such as difficulty in detecting small defects, variations in defect sizes, and inaccurate defect localization, we propose an enhanced YOLOv5s algorithm. Firstly, we improve the anchor frame structure of the YOLOv5s model to enhance its generalization ability, enabling robust defect detection for objects of varying sizes. Secondly, we introduce the ECA attention mechanism to improve the model's accuracy in detecting small targets. Under identical experimental conditions, our enhanced YOLOv5s algorithm demonstrates significant improvements, with precision, F1 scores, and mAP values increasing by 3.1 %, 3 %, and 4.5 % respectively. Moreover, the accuracy in detecting crack, damage, slag, and spot defects increases by 0.2 %, 4.7 %, 5.4 %, and 1.9 % respectively. Notably, the detection speed improves from 232 frames/s to 256 frames/s. Comparative analysis with other algorithms reveals superior performance over YOLOv3 and YOLOv4 models, showcasing enhanced capability in identifying small target defects and achieving real-time detection.

The study aimed to determine the potential anti-diabetic activities of the hydrolysates of camel milk proteins (CMPH). Camel milk proteins were hydrolyzed independently by using 11 proteases, and their anti-diabetic activities were analyzed by in vitro, and in vivo. The results showed that CMPH-Flavourzyme exhibited the best α-glucosidase and dipeptidyl peptidase-IV inhibitory activity, while CMPH-Papain exhibited the highest α-amylase inhibitory activity, and best proliferative effect on streptozotocin-induced NIT-1 cells in vitro. Furthermore, CMPH-Papain exhibited the most effect in decreasing the serum levels of fasting blood glucose, oral glucose tolerance test, pro-inflammatory factors (IL-1β, IL-6) and triglyceride, as well as increasing insulin levels on in vivo streptozotocin-induced diabetic mice. Peptides identification followed with molecular docking and network pharmacology analysis also found the potential anti-diabetic peptides from CMPH-Flavourzyme and CMPH-Papain. Our results indicated the type of protease used for the treatment significantly influences the anti-diabetic activities of the resulting CMPH.

Background and aim: Prostate cancer is a leading malignant tumor in men, associated with a high rate of mortality. Androgen deprivation therapy is commonly used to treat prostate cancer, which contributes to the progression of castration-resistant prostate cancer (CRPC). The current therapy has a low survival rate in patients with CRPC. Our study aims to develop a novel effective approach for CRPC treatment and improve survival benefits. Experimental procedure: CRPC cell line PC-3-Luc expressing luciferase and the CRPC cell line PC-3-IL6-Luc stably overexpressing IL-6 were used to establish the xenograft tumor mouse model. The tumor was monitored weekly using Bioluminescence imaging. Infiltrated macrophages were quantified by fluorescence-activated cell sorting using flow cytometry. IL6 mRNA level was determined using quantitative real-time PCR. The protein levels of total STAT3 and phosphorylated STAT3 were determined using Western blot. Results and conclusion: Zhoushi Qi Ling decoction (ZQD) treatment significantly reduced PC3 the xenograft tumor progression and the number of infiltrated macrophages when compared with saline treatment. IL6 mRNA level was remarkedly suppressed by ZQD treatment. Notably, the protein level of phosphorylated STAT3 was significantly decreased in PC3 the xenograft tumor treated with ZQD compared to saline treatment. Our findings demonstrated that ZQD treatment significantly reduced the progression of prostate cancer, evidenced by the reduced population of infiltrated macrophages and the inhibition of the IL6/STAT3 pathway.

In the study, a novel method for detecting paeoniflorin (PF), a significant antidepressant drug, is described that makes use of vertically aligned zinc oxide nanorods (ZnO NRs). Vertically aligned zinc oxide (ZnO) nanorods and rGO were electrodeposited on the GCE electrode surface, according to structural investigations performed using field emission scanning electron microscopy (FESEM), X-ray diffraction (XRD), and X-ray photoelectron spectroscopy (XPS). According to electrochemical experiments, ZnO NRs and rGO increase the electron transfer rate and support catalytic activity, making it easier to detect and quantify PF in the electrochemical sensor. The results exhibited that the linear range and sensitivity of ZnO-rGO/GCE were, respectively, 0.1–1305 μg/mL and 0.03792 μA/μg.mL−1. The PF sensor also achieved a low detection limit of 3.4 ng/mL. It was investigated to see how well a PF sensor worked to analyze a sample of human serum. Relative standard deviations (RSD) for sample detections for the proposed PF sensor were all below 4.13 %, according to analytical analyses utilizing the conventional addition approach, with recoveries ranging from 96.00 % to 99.25 %. These findings affirm that the proposed PF sensor exhibits a high degree of accuracy, rendering it well-suited for clinical applications and the analysis of human bodily fluids.

Colorectal cancer (CRC), also known as colon cancer, is the third most common cancer and the fourth most cause of cancer-related death in the world. CRC can be classified into two major subtypes, including microsatellite instability (MSI) and microsatellite stability (MSS), which showed different characteristics in immunotherapy. Low sensitivity of diagnostic biomarkers and metastasis are still the principal cause of mortality, especially in MSI. Here, applying computational programs, we identified recurring expression programs based on single cell RNA sequencing (scRNA-Seq) data of CRC cell lines. Notably, three MSI specific recurring modules were identified by non-negative matrix factorization (NMF). High NMF score genes enriched in the function of metabolism and inflammatory response. Focusing on top specific active transcription factor (TF), RUNX3 (Runt-related transcription factor 3), our results suggest that T cell infiltration was increased in RUNX3 high MSI CRC samples. Unbiased Gene Set Enrichment Analysis (GSEA) showed that RUNX3 was strongly associated with immune and metastasis related functions, such as Interferon Gamma (IFN-γ) and EPITHELIAL MESENCHYMAL TRANSITION (EMT). In addition, RUNX3 shows specific highly activated at epigenetic level in MSI compared with other gastrointestinal carcinomas. Positive correlation between RUNX3 and most immune checkpoints further confirmed RUNX3 might have crucial roles in MSI cancer progression and immunotherapy. Taken together, these results indicate significant tumor heterogeneity of two CRC subtypes at single-cell level and epigenetic modification level. These results also linked transcriptional dysregulation with immune infiltration at single-cell level in MSI, which may advance the application of scRNA-Seq technology in immunotherapy and contribute to developing novel biomarkers of this malignancy.

Background: The prognostic significance of the ratio of activated CD4 T cells to Tregs infiltrating tumor tissues in gastric cancer (GC) remains unknown. Materials and methods: For the quantification of infiltration of immune cells, the ssGSEA algorithm, which is a single sample gene set enrichment analysis, was utilized. Group A was defined as having activated CD4 T cells/Tregs >1, while group B was defined as having activated CD4 T cells/Tregs

Digitalization and informationization are important trends in the development of the sports industry. The study first introduced the sparrow search algorithm to improve the generalization ability of traditional neural networks, optimizing the assignment of initial weights and thresholds of neural networks; Secondly, the chicken swarm algorithm is introduced to optimize the training combination, period, and intensity of athletes based on the evaluation results, improving the subjective limitations of traditional training methods. The results of model performance analysis show that the sparrow search algorithm is better than other intelligent optimization algorithms in finding fitted parameters, and the solution error is less than 0.50. The evaluation model performs well in terms of accuracy, recall, average relative error, and R2 evaluation indicators. The model has high repeatability and is suitable for evaluating track and field training methods. The accuracy and computational speed of the chicken swarm algorithm are relatively good; Compared with other optimization models, the chicken swarm algorithm has better optimization ability and accuracy. Friedman test found significant differences in the chicken swarm algorithm, and the optimized training method has a significant positive impact on the explosive power of athletes, and the training period and intensity arrangement are reasonable and more helpful to the improvement of athletic performance. This study improves the scientific rationality of the development of track and field training methods, which is conducive to optimizing the training effect of track and field sports, and facilitates the risk management and personalized training of athletes. At the same time, it greatly promotes the integration and development of sports and computer disciplines.

During the fault of the wind power collection line of the MMC-HVDC system, the amplitude of the fault current may be limited due to the control of the converter, which leads to the severe limitation of traditional protection. In this paper, based on the difference of negative sequence current accumulation, a new protection scheme for wind farm collection lines is proposed. First, the negative sequence current equivalent circuit of the wind farm collection line is constructed. Then, the distribution characteristics of negative sequence current at different fault locations are identified. On this base, a novel protection scheme based on transient negative sequence current accumulation difference using interconnected blocking signals is proposed. The RTDS simulation results show that the protection scheme can accurately identify faults of different types and locations.

An isolated power grid (IPG) lacks the support of the external power grid, and a single generator or load accounts for a large proportion of the total capacity. Once transient angle instability, the generator and load shedding is not effectively. Phase sequence exchange (PSE) uses power electronic devices to switch the three-phase sequence, thereby reducing the power angle of the generator by 120° and preventing the system from losing stability. This paper proposed a PSE scheme for transient angle instability applied to IPG. The local measurements of IPG are used to identify the critical generator, and the system trajectory is obtained through large-step integration. The stability is assessed by the concavity of the trajectory. Once the trajectory swings from the concave area to the convex area, the IPG loses transient stability, at which point the generators in the critical cluster simultaneously PSE prevent transient instability. Based on Simulink and RTDS platform, the scheme is verified in a 39-bus 10-machine system and an existing IPG system. The results show that the proposed scheme can effectively restore the stability of the IPG, outperforming generators and load shedding.

Abstract Purpose To investigate the feasibility and clinical utility of a compressed-sensing-accelerated subtractionless whole-body MRA (CS-WBMRA) protocol with only contrast injection for suspected arterial diseases, by comparison to conventional dual-pass subtraction-based whole-body MRA (conventional-WBMRA) and available computed tomography angiography (CTA). Materials and methods This prospective study assessed 86 patients (mean age, 56 years ± 16.4 [standard deviation]; 25 women) with suspected arterial diseases from May 2021 to December 2022, who underwent CS-WBMRA (n = 48, mean age, 55.9 years ± 16.4 [standard deviation]; 25 women) and conventional-WBMRA (n = 38, mean age, 48 years ± 17.4 [standard deviation]; 20 women) on a 3.0 T MRI after random group assignment based on the chronological order of enrolment. Of all enrolled patients administered the CS-WBMRA protocol, 35% (17/48) underwent CTA as required by clinical demands. Two experienced radiologists independently scored the qualitative image quality and venous enhancement contamination. Quantitative image assessment was carried out by determining and comparing the apparent signal-to-noise ratios (SNRs) and contrast-to-noise ratios (CNRs) of four representative arterial segments. The total examination time and contrast-dose were also recorded. The independent samples t-test or the Wilcoxon rank sum test was used for statistical analysis. Results The overall scores of CS-WBMRA outperformed those of conventional-WMBRA (3.40 ± 0.60 vs 3.22 ± 0.55, P 0.05) between the two protocols. In the quantitative analysis, overall apparent SNRs were significantly higher in the conventional-WBMRA group than in the CS-WBMRA group (214.98 ± 136.05 vs 164.90 ± 118.05; P 0.05). In the CS-WBMRA group, 7 of 1776 (0.4%) vessel segments were contaminated severely by venous enhancement, while in the convention-WBMRA group, 317 of 1406 (23%) were rated as severe contamination. In the CS-WBMRA group, total examination and reconstruction times were only 7 min and 10 min, respectively, vs 20 min and

The current research on 7-series aluminum alloys mainly focuses on solid solution and aging treatments, as well as the flow stress during the deformation process. There are limited researches on the influence of thermal deformation temperature on the microstructure and properties of the aluminum alloy during multi-pass hot rolling process. In this study, the as-cast 7A04 aluminum alloy was subjected to homogenization treatment, followed by multi-pass hot rolling. The effects of different deformation parameters on dislocation density were analyzed. Microstructural characterization of the deformed alloy was performed using optical microscopy (OM), scanning electron microscopy (SEM) with energy-dispersive spectroscopy (EDS), X-ray diffraction (XRD), and micro-hardness tester. The optimal microstructure of the deformed alloy was selected based on the size of recrystallization. Subsequently, the Deform–3D finite element simulation software was used to analyze the multi-pass hot rolling process. The influence of deformation parameters on the uniformity of equivalent strain distribution within the samples was investigated. The results showed that at the deformation temperature of 430 °C, a significant amount of recrystallized microstructure appeared in the alloy, resulting in the lowest dislocation density and a significant reduction in the quantity of coarse precipitates. Finite element numerical simulation revealed that the deformation temperature had a certain influence on the uniformity of strain distribution within the alloy. However, this influence was mostly eliminated when the deformation temperature exceeded 380 °C. Meanwhile, the distribution of strain within the alloy was found to be related to the temperature distribution.

Objective: In this paper, we present a comprehensive overview of our experience in establishing and leading distinct extracorporeal cardiopulmonary resuscitation (ECPR)-related teams to independently handle ECPR in the early stages in the emergency department. Methods: A retrospective analysis was conducted on the clinical data of 29 patients who underwent ECPR treatment in the emergency room between May 2018 and April 2022. A control group, consisting of 10 patients treated between May 2018 and September 2019 was managed using a standard rescue coordination mode. The 19 patients who received ECPR between October 2019 and April 2022 were treated by members of the department's 24-h extracorporeal life support team. We compared the implementation and operational challenges faced by the two groups, including item preparation, circuit setup, and ECPR initiation times, among other factors. Results: Gender, age, cardiac arrest risk factors, and other baseline data did not significantly differ between the two groups. Extracorporeal membrane oxygenation (ECMO) pipeline prefilling time (from 35.27±10.34 to 13.46±5.32), ECPR establishment time (from 62.35±29.61 to 30.98±13.41), and item preparation time (from 16.42±9.78 to 3.19±1.49) all considerably decreased when compared to the control group. The rate of return of spontaneous circulation recovery rose from 37.50 % to 77.78 % (P

Overlook of chiral consideration in transdermal drug delivery increases administrated dose and risk of side effects, decreasing therapeutical effects. To improve the transdermal delivery efficiency of eutomer, this work focused on investigating the law and mechanism of enantioselective enhancing effects of chiral permeation enhancers on drug enantiomers. Chiral nonsteroidal anti-inflammatory drugs and terpene permeation enhancers were selected as model drug and enhancers. The results indicated that the L-isomer of permeation enhancers increased the skin absorption of S-enantiomer of drug and D-isomer improve the permeation of R-enantiomer, in which the enhancement effect (ER) of L-menthol on S-enantiomer (ER = 3.23) was higher than that on R-enantiomer (ER = 1.49). According to the pharmacokinetics results, L-menthol tended to enhance the permeation of S-enantiomer better than R-enantiomer (2.56 fold), and showed excellent in vitro/in vivo correlations. The mechanism study showed that L-isomer of permeation enhancers improved the permeation of S-enantiomer by increasing the retention, but the D-isomer by improving partition for better permeation. Enantioselective mechanism indicated that the weaker chiral H-bond interaction between drug-chiral enhancers was caused by the enantiomeric conformation. Additionally, stronger chiral enhancers-skin interaction between L-isomer and S-conformation of ceramide produced better enhancing effects. In conclusion, enantioselective interaction of chiral drug-chiral enhancers and chiral enhancers-chiral skin played a critical role in transdermal drug delivery, rational utilization of which contributed to improving the uptake of eutomer and inhibiting distomers to decrease a half of dose and side effects, increasing transdermal therapeutical efficiency.

Neointimal hyperplasia persists as a barrier following vascular interventions. Forkhead Box O1 (FoxO1) is a transcription factor that possesses a distinctive fork head domain and indirectly contributes to various physiological processes. FoxO1 expression and signaling also impact the energy metabolism of vascular smooth muscle cells, potentially influencing neointimal hyperplasia. Our hypothesis is that FoxO1 inhibits neointimal hyperplasia in a rat patch angioplasty model. Four groups were compared in a rat aorta patch angioplasty model: the control group without treatment, patches coated with AS184286 (a FoxO1 inhibitor) in a PLGA matrix, patches coated with FoxO1 in a PLGA matrix, and patches coated with MLN0905 (a PLK1 inhibitor) in a PLGA matrix. The patches were harvested on Day 14 and subjected to analysis. FoxO1-positive and p-FoxO1 cells were observed after patch angioplasty. The addition of FoxO1 through patches coated with exogenous FoxO1 protein in a PLGA matrix significantly inhibited neointimal thickness (p = 0.0012). The treated groups exhibited significantly lower numbers of CD3 (p = 0.0003), CD45 (p

Summary: Background: Lymphocyte telomere length (LTL)-related genetic variants may modulate LTL and affect recurrence of squamous cell carcinoma of the oropharynx (SCCOP). Methods: A total of 1013 patients with incident SCCOP were recruited and genotyped for 16 genome-wide association study (GWAS)-identified TL-related polymorphisms. Of these patients, 489 had tumour HPV16 status determination. Univariate and multivariate analyses were performed to evaluate associations. Findings: Of the 16 TL-related polymorphisms, four were significantly associated with LTL: rs1920116, rs3027234, rs6772228, and rs11125529, and the patients with putatively favourable genotypes had approximately 1.5–3 times the likelihood of shorter LTL compared with patients with the corresponding risk genotypes. Moreover, patients with one to four favourable genotypes of the four combined polymorphisms had approximately 3–11 times the likelihood of shorter LTL compared with patients with no favourable genotype. The four LTL-related polymorphisms were significantly associated with approximately 40% reduced risk (for favourable genotypes) or doubled risk (for risk genotypes) of recurrence, and similar but more pronounced associations were observed in patients with tumour HPV16-positive SCCOP. Similarly, patients with one to four risk genotypes had significantly approximately 2.5–4 times increased recurrence risk compared with patients with no risk genotype, and similar but more pronounced associations were observed in patients with tumour HPV16-positive SCCOP. Interpretation: Four LTL-related polymorphisms individually or jointly modify LTL and risk of recurrence of SCCOP, particularly HPV-positive SCCOP. These LTL-related polymorphisms could have potential to further stratify patients with HPV-positive SCCOP for individualized treatment and better survival. Funding: Not applicable.

Given the difficulties of degrading benzotriazole (BTA), this study used a one-pot hydrothermal method to prepare α-Fe2O3/Cu2O (FC) composites for photoelectrocatalytic (PEC) degradation of BTA. The characterization of FC structure showed that Cu2O in cubic crystals was loaded with circular sheets of Fe2O3. Owing to this structure, FC showed efficient PEC degradation of BTA when exposed to ultraviolet light. The experimental results demonstrated that FC efficiently degraded BTA. When the PEC degradation continued for 60 min, 100% degradation of BTA was achieved because FC enhanced the photoelectron-hole separation and the separation and transfer of articulated carriers. High performance liquid chromatography–mass spectrometry showed that intermediates formed during the PEC degradation of BTA. Finally, various pathways for degradation of BTA were postulated. This FC-based PEC system provides a harmless and effective method for degradation of BTA.