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Background Simulation is an increasingly used novel method for the education of medical professionals. This study aimed to systematically review the efficacy of high-fidelity (HF) simulation compared with low-fidelity (LF) simulation or no simulation in advanced life support (ALS) training. Methods A comprehensive search of the PubMed, Chinese Biomedicine Database, Embase, CENTRAL, ISI, and China Knowledge Resource Integrated Database was performed to identify randomized controlled trials (RCTs) that evaluated the use of HF simulation in ALS training. Quality assessment was based on the Cochrane Handbook for Systematic Reviews of Interventions version 5.0.1. The primary outcome was the improvement of knowledge and skill performance. The secondary outcomes included the participants’ confidence and satisfaction at the course conclusion, skill performance at one year, skill performance in actual resuscitation, and patient outcomes. Data were synthesized using the RevMan 5.4 software. Results Altogether, 25 RCTs with a total of 1,987 trainees were included in the meta-analysis. In the intervention group, 998 participants used HF manikins, whereas 989 participants received LF simulation-based or traditional training (classical training without simulation). Pooled data from the RCTs demonstrated a benefit in improvement of knowledge [standardized mean difference (SMD) = 0.38; 95% confidence interval (CI): 0.18–0.59, P =  0.0003 , I 2  = 70%] and skill performance (SMD = 0.63; 95% CI: 0.21–1.04, P = 0.003, I 2  = 92%) for HF simulation when compared with LF simulation and traditional training. The subgroup analysis revealed a greater benefit in knowledge with HF simulation compared with traditional training at the course conclusion (SMD = 0.51; 95% CI: 0.20–0.83, P  = 0.003, I 2  = 61%). Studies measuring knowledge at three months, skill performance at one year, teamwork behaviors, participants’ satisfaction and confidence demonstrated no significant benefit for HF simulation. Conclusions Learners using HF simulation more significantly benefited from the ALS training in terms of knowledge and skill performance at the course conclusion. However, further research is necessary to enhance long-term retention of knowledge and skill in actual resuscitation and patient’s outcomes.

Obesity has become a public health concern due to its positive association with the incidence of many diseases, and coffee components including chlorogenic acid (CGA) and caffeine have been demonstrated to play roles in the suppression of fat accumulation. To investigate the mechanism by which CGA and caffeine regulate lipid metabolism, in the present study, forty mice were randomly assigned to four groups and fed diets containing no CGA or caffeine, CGA, caffeine, or CGA+caffeine for 24 weeks. Body weight, intraperitoneal adipose tissue (IPAT) weight, and serum biochemical parameters were measured, and the activities and mRNA and protein expression of lipid metabolism-related enzymes were analysed. There was a decrease in the body weight and IPAT weight of mice fed the CGA+caffeine diet. There was a significant decrease in the serum and hepatic concentrations of total cholesterol, TAG and leptin of mice fed the CGA+caffeine diet. The activities of carnitine acyltransferase (CAT) and acyl-CoA oxidase (ACO) were increased in mice fed the caffeine and CGA+caffeine diets, while the activity of fatty acid synthase (FAS) was suppressed in those fed the CGA+caffeine diet. The mRNA expression levels of AMP-activated protein kinase (AMPK), CAT and ACO were considerably up-regulated in mice fed the CGA+caffeine diet, while those of PPARγ2 were down-regulated. The protein expression levels of AMPK were increased and those of FAS were decreased in mice fed the CGA+caffeine diet. These results indicate that CGA+caffeine suppresses fat accumulation and body weight gain by regulating the activities and mRNA and protein expression levels of hepatic lipid metabolism-related enzymes and that these effects are stronger than those exerted by CGA and caffeine individually.

Astilbin and neoastilbin are two flavonoid stereoisomers. In the present study, their solubility, stability, and bioavailability were compared in a rat. The results revealed that the water solubility of astilbin and neoastilbin was 132.72 μg/mL and 217.16 μg/mL, respectively. The oil–water distribution coefficient (log P) of astilbin and neoastilbin in simulated gastric fluid (SGF) was 1.57 and 1.39, and in simulated intestinal fluid (SIF) was 1.09 and 0.98, respectively. In SIF, about 78.6% astilbin remained after 4 h of incubation at 37 °C, while this value was 88.3% for neoastilbin. Most of the degraded astilbin and neoastilbin were isomerized into their cis-trans-isomer, namely neoisoastilbin and isoastilbin, respectively, and the decomposed parts were rare. For bioavailability comparison in a rat, an HPLC method for trace amounts of astilbin and neoastilbin determination in plasma was developed, and the pretreatment of plasma was optimized. A pharmacokinetic study showed that the absolute bioavailability of astilbin and neoastilbin in a rat showed no significant difference with values of 0.30% and 0.28%, respectively.

Flavonoids are the main bioactive components responded for the health promoting effects of Rhizoma Smilacis Glabrae (RSG), an herbal material used in many functional food of China. An eco‐friendly method with β‐cyclodextrin (β‐CD)‐assisted extraction and resin adsorption/desorption was developed for total flavonoids purification from RSG. Because of complexes formation between flavonoids and β‐CD, aqueous solution was used for extraction instead of ethanol. The CD‐assisted extraction was optimized through defining optimal CD species, concentration, extraction temperature, and time. The adsorption property of eight macroporous resins on astilbin was compared by adsorption kinetics and capacity. All resins could reach the adsorption equilibrium within 2 hr. Further analyzed by Langmuir and Freundlich models, H103 resin with the best adsorption capacity was selected. The desorption property of different ethanol–water solution was compared. Results showed that by using 75% ethanol, astilbin could be well desorbed from the resin with the recovery of 96.3%. Because of complexes formation, the presence of β‐CD would slightly decrease the adsorption rate and capacity of H103 with concentration dependent. In dynamic adsorption, decreasing the flow rate could minish the effects of β‐CD. The developed method was successfully used for total flavonoids purified from RSG. The yield of purified product was 8.78%, with astilbin and total flavonoids content of 363.8 and 505.7 mg/g, respectively. The purity was 1.74 times increased with the recovery of 94.38% compared with the extract obtained directly through 50% ethanol extraction. An eco‐friendly method with β‐CD‐assisted extraction and resin adsorption/desorption was developed for total flavonoids purification from Rhizoma Smilacis Glabrae sample. The yield of resin purified product was 8.78%, with astilbin and total flavonoids content of 363.8 and 505.7 mg/g, respectively. β‐CD aqueous solution was used for extraction instead of ethanol. Except desorption process, the method needs no organic solvent and is environmentally friendly. Flavonoid peaks in the chromatogram: 1, neoastilbin; 2, astilbin; 3, neoisoastilbin; 4, isoastilbin; 5, engeletin; 6, isoengeletin.

Chalcone-1-deoxynojirimycin heterozygote (DC-5), a novel compound which was designed and synthesized in our laboratory for diabetes treatment, showed an extremely strong in vitro inhibitory activity on α-glucosidase in our previous studies. In the current research, its potential in vivo anti-diabetic effects were further investigated by integration detection and the analysis of blood glucose concentration, blood biochemical parameters, tissue section and gut microbiota of the diabetic rats. The results indicated that oral administration of DC-5 significantly reduced the fasting blood glucose and postprandial blood glucose, both in diabetic and normal rats; meanwhile, it alleviated the adverse symptoms of elevated blood lipid level and lipid metabolism disorder in diabetic rats. Furthermore, DC-5 effectively decreased the organ coefficient and alleviated the pathological changes of the liver, kidney and small intestine of the diabetic rats at the same time. Moreover, the results of 16S rDNA gene sequencing analysis suggested that DC-5 significantly increased the ratio of Firmicutes to Bacteroidetes and improved the disorder of gut microbiota in diabetic rats. In conclusion, DC-5 displayed a good therapeutic effect on the diabetic rats, and therefore had a good application prospect in hypoglycemic drugs and foods.

(Sieb.) Makino ( ) is one species of bamboo distributed in China, Japan and Vietnam. The chemical profile of its leaves and its potential application was unknown yet. The chemical profile of was studied by HPLC and UPLC-DAD-QTOF-MS. The extract was prepared by extraction with 50% aqueous ethanol, followed by H103 macroporous resins adsorption and desorption processes. Pancreatic lipase inhibitory activity was determined using -nitrophenyl palmitate as the substance, which was hydrolyzed by lipase to form coloured nitrophenol. Eighteen compounds were identified in . Most of them were the -glycosylated derivatives of luteolin and apigenin, such as isoorientin, isoorientin-2″- -rhamnoside and isovitexin. Isoorientin-2″- -rhamnoside was the most dominant flavonoid in the sample. extract was prepared through resin adsorption/desorption with yield of 1.12 ± 015% and total flavonoids content of 82 ± 2 mg/g (in term of isoorientin). The extract exhibited pancreatic lipase inhibitory activity with IC50 value of 0.93 mg/mL. The chemical profile of leaves was uncovered for the first time. -glycosyl flavonoids were the main constituents in the plant. The extract exhibited pancreatic lipase inhibitory activity and may have potential for use as a food supplement for controlling obesity.

Three types of calli were induced from Origanum vulgare (O. vulgare) aseptic seedlings, and the friable calli with white appearance and high growth rate were further screened and used to develop cell suspension culture to produce polyphenols. Murashige and Skoog (MS) medium with 3.0 mg/L Kinetin (KT) and 0.5 mg/L 2,4-dichlorophenoxy acetic acid (2,4-D) was suitable for both O. vulgare cells growth and polyphenols accumulation. To further enhance the polyphenols accumulation, O. vulgare cells were treated by phenylalanine (Phe) feeding and salicylic acid (SA) elicitation. Compared with the individual Phe feeding and SA elicitation, SA elicitation combined with Phe feeding showed a much better promotion effect on the polyphenols synthesis in O. vulgare cells, especially rosmarinic acid (RosA) accumulation. With the combined treatment of 200 µM SA and 100 µM Phe, total polyphenols content and yield were 41.36 mg/g and 752.93 mg/L, respectively. RosA content and yield reached 31.25 mg/g and 570.37 mg/L, which were 5.44 and 5.47 times that of the control. Furthermore, the total polyphenols extracted from the cultured cells treated by SA elicitation combined with Phe feeding displayed a much higher antioxidant capacity than that of untreated cells, meanwhile its 1,1-diphenyl-2-trinitrophenyl hydrazine (DPPH) and superoxide anion radical-scavenging activity were much stronger than that of vitamin C. What’s more, our results also showed that RosA was the principal contributor to the fine antioxidant capacity of the total polyphenols extracted from the SA and Phe treated cells. Our research indicated that SA elicitation combined with Phe feeding significantly improved the polyphenols yield and antioxidant capacity of the cultured O. vulgare cells, and therefore has a promising application prospect in natural polyphenols production.

Vacuum cold spraying (VCS) has emerged as an environmentally sustainable method for fabricating ceramic and metal films. A high particle impact velocity is a critical factor in the deposition of metal particles during the VCS process, which can be significantly enhanced through gas preheating. This study employs Computational Fluid Dynamics (CFD) simulations to investigate the substantial impact of gas preheating temperature on particle impact velocity and temperature. Elevating the gas temperature leads to higher particle impact velocity, resulting in severe deformation and the formation of dense copper films. The experimental results indicate improvements in both film compactness and electrical properties with gas preheating. Remarkably, the electrical resistivity of the copper film deposited at a gas preheating temperature of 350 °C was measured at 4.4 × 10−8 Ω·m. This study also examines the evolution of cone-shaped pits on the surface of copper films prepared on rough substrates. VCS demonstrates a self-adaptive repair mechanism when depositing metal films onto rough ceramic substrates, making it a promising method for ceramic surface metallization.

Background Malaria caused by Plasmodium spp. is still a major threat to public health globally. The various approaches to developing new antimalarial agents rely on the understanding of the complex regulatory mechanisms of dynamic gene expression in the life-cycle of these malaria parasites. The nuclear members of the evolutionarily conserved actin-related protein nuclear (ARP) superfamily are the major components of nucleosome remodelling complexes. In the human malaria parasite Plasmodium falciparum , bioinformatics analysis has predicted three ARP orthologues: PfArp1, PfArp4 and PfArp6. However, little is known about the biological functions of putative PfArp4. In this study, we aimed to investigate the function and the underlying mechanisms of PfArp4 gene regulation. Methods A conditional gene knockdown approach was adopted by incorporating the glucosamine-inducible glmS ribozyme sequence into the 3’ UTR of the PfArp4 and PfArp6 genes. The transgenic parasites PfArp4-Ty1-Ribo, PfArp6-Ty1-Ribo and pL6-PfArp4-Ty1::PfArp6-HA were generated by the CRISPR-Cas9 technique. The knockdown effect in the transgenic parasite was measured by growth curve assay and western blot (WB) analysis. The direct interaction between PfArp4 and PfArp6 was validated by co-IFA and co-IP assays. The euchromatic gene expression mediated through H2A.Z (histone H2A variant) deposition and H3K9ac modification at promoters and regulated by PfArp4 , was determined by RNA-seq and ChIP-seq. Results The inducible knockdown of PfArp4 inhibited blood-stage development of P. falciparum . PfArp4 and PfArp6 were colocalized in the nucleus of P. falciparum parasites. PfArp4 gene knockdown altered the global transcriptome. PfArp4 protein colocalized with the histone variant H2A.Z and euchromatic marker H3K9ac in intergenic regions. The inducible downregulation of PfArp4 resulted in the depletion of H2A.Z and lower H3K9ac levels at the upstream regions of eukaryotic genes, thereby repressing the transcriptional abundance of H2A.Z-dependent genes. Conclusions Our findings suggest that PfArp4 regulates the cell cycle by controlling H2A.Z deposition and affecting centromere function, contributing to the understanding the complex epigenetic regulation of gene expression and the development of P. falciparum.

Human genetic and pharmacological studies have demonstrated that voltage-gated sodium channels (VGSCs) are promising therapeutic targets for the treatment of pain. Spider venom contains many toxins that modulate the activity of VGSCs. To date, only 0.01% of such spider toxins has been explored, and thus there is a great potential for discovery of novel VGSC modulators as useful pharmacological tools or potential therapeutics. In the current study, we identified a novel peptide, µ-TRTX-Ca1a (Ca1a), in the venom of the tarantula Cyriopagopus albostriatus . This peptide consisted of 38 residues, including 6 cysteines, i.e. IFECSISCEIEKEGNGKKCKPKKCKGGWKCKFNICVKV. In HEK293T or ND7/23 cells expressing mammalian VGSCs, this peptide exhibited the strongest inhibitory activity on Na v 1.7 (IC 50 378 nM), followed by Na v 1.6 (IC 50 547 nM), Na v 1.2 (IC 50 728 nM), Na v 1.3 (IC 50 2.2 µM) and Na v 1.4 (IC 50 3.2 µM), and produced negligible inhibitory effect on Na v 1.5, Na v 1.8, and Na v 1.9, even at high concentrations of up to 10 µM. Furthermore, this peptide did not significantly affect the activation and inactivation of Na v 1.7. Using site-directed mutagenesis of Na v 1.7 and Na v 1.4, we revealed that its binding site was localized to the DIIS3-S4 linker region involving the D816 and E818 residues. In three different mouse models of pain, pretreatment with Cala (100, 200, 500 µg/kg) dose-dependently suppressed the nociceptive responses induced by formalin, acetic acid or heat. These results suggest that Ca1a is a novel neurotoxin against VGSCs and has a potential to be developed as a novel analgesic.