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Aim Design Data Sources Review Method Results Conclusion Implications Impact Reporting Method Patient or Public Contribution To critically evaluate missed care measurement approaches and their application in long‐term aged care (LTAC) settings.Systematic review using Tawfik's guideline.PubMed, Scopus, Web of Science, CINAHL and ProQuest were searched. Supplemental searching was from reference lists of retrieved records, first authors' ORCID homepages and Google advanced search for grey literature. Search limitations were English language, published between 1 January 2001 and 31 December 2022.COVIDENCE was utilized for screening, data extraction and quality appraisal. JBI Critical Appraisal Tools and COSMIN Risk of Bias Tool were used for quality appraisal. Data were summarized and synthesized using narrative analysis.Twenty‐four publications across 11 regions were included, with two principal methods of missed care measurement: modified standard scales and tailored specific approaches. They were applied inconsistently and generated diverse measurement outcomes. There were challenges even with the most commonly used tool, the BERNCA‐NH, including absence of high‐quality verification through comparative analysis against an established ‘gold standard’, reliance on self‐administration, incomplete assessment of constructs and inadequate exploration of psychometric properties.Globally, there are deficiencies in the effectiveness and comprehensiveness of the instruments measuring missed care in LTAC settings. Further research on theoretical and practical perspectives is required.Findings highlighted a critical need to establish a standardized, validated approach to measure missed care in LTAC settings. This review calls for collaborative efforts by researchers, clinical staff and policymakers to develop and implement evidence‐based practices as a way of safeguarding the well‐being of older clients living in LTAC settings.Measurements of missed care in LTAC settings rely on adapting acute care tools. There is a critical gap in measuring missed care in LTAC settings. Developing a new tool could improve care quality and safety in LTAC settings globally.Adhered to PRISMA guideline.No patient or public contribution. [ABSTRACT FROM AUTHOR]

Hyperuricemia, i.e., increased plasma uric acid concentration, is a common problem in clinical practice, leading to gout or nephrolithiasis, and is associated with other disorders, such as metabolic syndrome, cardiovascular disease, and chronic renal disease. Xanthine oxidoreductase (XOR) is a critical rate-limiting enzyme involved in uric acid synthesis and a promising target for hyperuricemia therapy. However, XOR inhibitors currently face clinical problems such as a short half-life and side effects. Here, we found that specifically targeting liver Xor with GalNAc-siRNAs had a good therapeutic effect on hyperuricemia. First, siRNAs were designed to target various sites in the homologous region between Homo sapiens and Mus musculus Xor mRNA and were screened in primary mouse hepatocytes. Then, the siRNAs were modified to increase their stability in vivo and conjugated with GalNAc for liver-specific delivery. The effects of GalNAc-siRNAs were evaluated in three hyperuricemia mouse models, including potassium oxonate and hypoxanthine administration in WT and humanized XDH mice and Uox knockout mice. Febuxostat, a specific XOR inhibitor used for hyperuricemia treatment, was used as a positive control. Targeting liver Xor with GalNAc-siRNAs by subcutaneous administration reduced plasma uric acid levels, uric acid accumulation in the kidney, renal inflammation, and fibrosis, thereby alleviating kidney damage in hyperuricemia mouse models without hepatoxicity. The results demonstrated that targeting liver Xor with GalNAc-siRNAs was a promising strategy for hyperuricemia therapy. [ABSTRACT FROM AUTHOR]

Introduction: Combined forceps and cryoprobe biopsy during bronchoscopy are increasingly used. However, the adult standard cuffed endotracheal tube (SCETT) is can be limited by general anaesthesia and neuromuscular blockade. An adult uncuffed endotracheal tube (UCETT) might provide simple and safe airway support in stable patients during forceps and cryoprobe biopsy under spontaneous respiration. Methods: A retrospective review of stable patients undergoing forceps and cryoprobe biopsy was performed. They were divided into a UCETT group (N = 33) and a SCETT group (N = 27). The primary technical outcome was the successful intubation and completion of bronchoscopy. The primary safety outcome was the incidence of desaturation events. Recovery time and side effects were also recorded. Results: UCETTs and SCETTs were successfully inserted, and bronchoscopic procedures were completed in all patients. Only 3/33 (9.1%) patients in the UCETT group exhibited a drop of SPO2 < 90% during the bronchoscopy, compared to 2/27 (7.4%) patients in the SCETT group (P = 0.545). Patients recovered faster in the UCETT group than those in the SCETT group. Major bleeding, laryngospasm and major arrhythmias did not occur in either group. Incidences of sinus tachycardia, incidences of vomiting, minor and moderate bleeding and premature atrial contractions were not significantly different between the two groups. Nausea occurred in 5/33 (15.2%) patients in the UCETT group, compared to 11/27 (40.7%) in the SCETT group. Conclusion: This study suggests that UCETT under spontaneous respiration can provide satisfactory airway support and a shorter recovery time in stable patients; thus, it may be an option to assist forceps and cryoprobe biopsy. [ABSTRACT FROM AUTHOR]

Objective. To evaluate the changes of rectus abdominis thickness and inter-rectus distance before and after delivery with high-frequency ultrasound. Methods. A total of 148 pregnant women at 12 weeks of gestation who underwent prenatal examination in our hospital from January 2019 to March 2020 were selected, and 140 of them cooperated with rectus abdominis examination. According to the results of rectus abdominis examination 42 days after delivery, 97 patients were divided into the DRA group with rectus abdominis isolated and 43 patients were divided into the normal group with rectus abdominis not isolated. At 12 weeks, 24 weeks, and 37 weeks of pregnancy, 3 days and 42 days after delivery, the thickness and spacing of the left and right rectus abdominis muscle were measured by high-frequency ultrasound along the white linea at three positions: 5 cm above the navel, 3 cm below the umbilical edge, and 3 cm below the navel. Results. The thickness of rectus abdominis at 5 cm above the navel, 3 cm below the navel, and at the navel margin of the abdominal white line in the pregnant women of the two groups was gradually decreased with the increase of the pregnancy cycle and gradually recovered after delivery. At 42 days after delivery, the thickness of rectus abdominis in the DRA group was significantly lower than that in the normal group, which was 5 cm above the umbilicus, 3 cm below the umbilicus, and the umbilical margin of the abdominal white line (P < 0.05). The space between rectus abdominis 5 cm above the navel, 3 cm below the navel, and the navel margin of the abdominal white line in the pregnant women of the two groups was gradually increased with the increase of the pregnancy cycle and gradually recovered after delivery. At 37 weeks of pregnancy, 3 days after delivery, and 42 days after delivery, the space of rectus abdominis along the umbilicus 5 cm above, 3 cm below the umbilicus, and the umbilicus border of the abdominal white line in the DRA group was significantly larger than that of the normal group (P < 0.05). Conclusion. Ultrasound can accurately measure the inter-rectus distance and rectus thickness, accurately evaluate the degree of DRA, and realize the one-stop evaluation from prenatal diagnosis and prediction to postpartum rehabilitation monitoring, so as to intervene during pregnancy and reduce the risk of postpartum DRA. [ABSTRACT FROM AUTHOR]

Purpose: This review aims to systematically evaluate the effects of Paro on older adults and provide a stronger basis for the rational application of Paro in aged care facilities. Methods: Articles published between January 2003 and January 2020 via five databases (PubMed, Web of Science, EMBASE, Cochrane Library, Cumulative Index to Nursing and Allied Health Literature (CINAHL), and Chinese database SinoMed) were searched. The Cochrane collaboration tool for randomized controlled trials was used to assess the quality of all included studies. Results: Nine articles were included in this systematic review. All articles were summarized according to three themes: quality of life, and biopsychological conditions, and drug usage. Conclusions: The review demonstrated that interaction with Paro can be beneficial for improving quality of life (QOL), biopsychological conditions, and reducing psychotropic and pain medical usage. Since the differences of the study design and low to moderate quality of these studies, however, we should be cautious to make positive comments on the role of Paro. Implications of nursing practice: The implications of Paro in aged care facilities have positive effects on nursing outcomes. This review helps caregivers understand the advantages and disadvantages of care robots, and promotes the integration of intelligent technology and manual services in nursing practice. [ABSTRACT FROM AUTHOR]

Family with sequence similarity 134 member B (FAM134B)/RETREG1/JK1 is a novel gene with recently reported roles in various diseases. Understanding the function and mechanism of action of FAM134B is necessary to develop disease therapies. Notably, emerging data are clarifying the molecular mechanisms of FAM134B function in organelle membrane morphogenesis and the regulation of signaling pathways, such as the Wnt and AKT signaling pathways. In addition, transcription factors, RNA N6‐methyladenosine‐mediated epigenetic regulation, microRNA, and small molecules are involved in the regulation of FAM134B expression. This review comprehensively considers recent studies on the role of FAM134B and its potential mechanisms in neurodegenerative diseases, obesity, viral diseases, cancer, and other diseases. The functions of FAM134B in maintaining cell homeostasis by regulating Golgi morphology, endoplasmic reticulum autophagy, and mitophagy are also highlighted, which may be the underlying mechanism of FAM134B gene mutation‐induced diseases. Moreover, the molecular mechanisms of the FAM134B function during numerous biological processes are discussed. This review provides novel insights into the functions and mechanisms of FAM134B in various diseases, which will inform the development of effective drugs to treat diseases. [ABSTRACT FROM AUTHOR]

Summary: Obesity, defined as excessive fat accumulation, is strongly associated with metabolic diseases and cancer, and its prevalence is rising worldwide. Thus, understanding the molecular mechanism of adipogenesis is of fundamental significance. Epigenetic modifications play important roles in regulating adipogenesis. N6‐methyladenosine (m6A), the most prevalent and abundant mRNA modification in eukaryotic cells, modulates multiple aspects of RNA metabolism, including mRNA stability, translation, splicing and export. Recent studies indicate that m6A methylation plays important roles in modulating gene expression and signal pathways in various physiologic processes and diseases. Notably, the significant function and regulatory mechanisms of m6A in adipogenesis are now emerging. In this review, we summarize recent studies that elucidate the vital roles of m6A modifications in regulating adipogenesis and adipose tissue expansion. Furthermore, we highlight the nutritional regulation of m6A methylation and adipogenesis, which may prove a novel therapeutic strategy to fight against obesity. [ABSTRACT FROM AUTHOR]

ABSTRACT Let G be a graph and be n copies of G. Connecting each corresponding vertices of and for by a , we get a new graph denoted by. In this paper, we give the spectrum of graph by the spectrum of G. This generalizes the classical results about odd path and linear hexagon. [ABSTRACT FROM AUTHOR]

Purpose: With technological progress, the integration of aged care with technology is a new challenge. This study developed a theoretical model of smart aged care in the community to meet the diverse needs of community‐dwelling older adults. Methods: This qualitative study recruited 22 participants from three communities in Chongqing, China. Through semi‐structured interviews and grounded theory, this study analyzed the needs of community‐dwelling older adults for smart aged care and identified strategies. Results: Nine categories were identified, including five need categories, three important factors, and one outcome objective. Furthermore, four health provider topics were proposed. Conclusions: Although the application of information technology has enhanced convenience and possibilities, its popularity and satisfaction are low. Information technology can be successfully introduced into the lives of community‐dwelling older adults only by truly understanding their needs. Implications of nursing practice: Smart aged care in the community has positive effects on nursing outcomes for older adults. This study's findings can help caregivers understand the various dimensions of the needs of community‐dwelling older adults and relevant influencing factors under smart aged care to increase its popularity and satisfaction. Furthermore, this can promote the integration of intelligent technology and manual services in nursing practice. [ABSTRACT FROM AUTHOR]

• An ultrasensitive multicolor electrochromic platform for visual sensing of Pseudomonas aeruginosa established on a closed bipolar electrode (BPE). • The cathode and anode of BPE were individually used as sensing interface and signal interface. • The magnetic separation technology applied in the enrichment of Pseudomonas aeruginosa greatly reduces the detection time. • Impedance measurement realized the quantitative detection of Pseudomonas aeruginosa. Pseudomonas aeruginosa (P. aeruginosa) is an opportunistic infection-causing pathogen that threatens human health. Accordingly, a rapid and ultrasensitive analytical method is required urgently. Herein, an ultrasensitive multicolor electrochromic sensing platform was established on the basis of a closed bipolar electrode (BPE). Prussian blue (PB), the blue spot that can be easily electrodeposited, was selected as an electrochromic indicator at the closed BPE cathode. Integrating with the anodic emitter, Ru(bpy) 3 2+, which emitted optical red light, visualized multicolor electrochromism was achieved on closed BPE. Particularly, physical separation between the positive and negative poles of the closed BPE greatly prevented mutual interference between Ru(bpy) 3 2+ and PB. Consequently, the sensitivity and accuracy of the proposed biosensor considerably improved. Notably, owing to magnetic-separation technology, the closed BPE surface required no modification. Without any complex pretreatment, the entire experiment time could be greatly shortened because the PA@MBs completely captured P. aeruginosa in food matrix within only 20 min. By comparing the visual electrochromic colors, ultrasensitive screening of P. aeruginosa was accomplished within 1–108 CFU mL−1. Combining the merits of closed BPE, electrochemiluminescence (ECL), and electrochromic, this strategy provided an accurate and intrinsic way for visual detection of P. aeruginosa , as well as great potential in measuring other pathogens. [ABSTRACT FROM AUTHOR]

Background: In light of the worldwide shortage of nurses and to maximize the effectiveness of the nursing care available, it is important to investigate the components of the care regularly provided by nursing assistants (NAs) to older adults. Well-organized allocation of NA care activities is directly linked to the quality of care provided to nursing home (NH) residents and their quality of life. However, relevant knowledge about the actual time allocation of NAs in this context is lacking, as previous related studies have focused only on the duration necessary for NAs to complete nursing activities. Purpose: This study was designed to investigate the time allocation of NAs in completing job tasks necessary to meet the needs of residents in nursing care units at an NH in China. Methods: A time–motion method and nonparticipatory observations were used to collect data. Two postgraduate students observed 15 NAs' time expenditure and nursing content simultaneously during day shifts for 3 weeks as the NAs provided care to residents in four different nursing care levels. Data on nursing time and activity frequency were collected using a worklist based on the Zuluaga–Raysmith model. Results: The 119.6 hours of observation included 8,907 discrete observed activities. In terms of the care provided to meet the needs of residents, the most time-consuming activities were physical health care (26.8%) and communication care (18.3%), followed by mental, emotional, social, and spiritual health care (14.1%) and protection and security care (12.6%). The higher the level of care, the higher the proportion of somatic nursing time and nursing activity frequency. However, the time and frequency of psychological and spiritual care showed an opposite trend. Conclusions: Because of their lack of formal nursing training and skills, NAs pay more attention to meeting the physiological needs of residents while ignoring their mental needs. Moreover, their effectiveness in providing spiritual care tends to be quite low. Furthermore, the NA nursing activity classification system based on the Zuluaga–Raysmith model developed in this study is applicable for designing nursing work tasks, organizing NH units, and improving the quality of life of residents, as this model accurately reflects the essence of NA work. [ABSTRACT FROM AUTHOR]

Fat Mass and Obesity-associated protein (FTO), associated with obesity, is proved to demethylate N6-methyladenosine (m 6 A), which raises questions regarding whether m 6 A plays vital roles in adipogenesis. To prove this, overexpression and knockdown of FTO and METTL3, as well as the chemical treatment in procine adipocytes were conducted. The results showed FTO negatively regulated m 6 A levels and positively regulated adipogenesis, while METTL3 positively correlated with m 6 A levels and negatively with adipogenesis. To remove the potential effect of FTO and METTL3 gene, chemical reagents of methylation inhibitor cycloleucine and methyl donor betaine were used to test the regulation effect of m 6 A on adipogenesis. The results showed the inverse effect of m 6 A on lipid accumulation in porcine adipocytes. These findings provide compelling evidence that m 6 A plays a critical role in the regulation of adipogenesis. [ABSTRACT FROM AUTHOR]

Obesity may result from altered fatty acid (FA) disposal. Altered FA distribution in obese individuals is poorly understood. Lean wild-type C57BL/6J and obese C57BL/6Job/ob mice received an oral dose of [1-14C]18:1n-9 (oleic acid), and the radioactivity in tissues was evaluated at various time points. The 14C concentration decreased rapidly in gastrointestinal tract but gradually increased and peaked at 96 h in adipose tissue, muscle and skin in lean mice. The 14C concentration was constant in adipose tissue and muscle of obese mice from 4h to 168h. 14C-label content in adipose tissue was significantly affected by genotype, whereas muscle 14C-label content was affected by genotype, time and the interaction between genotype and time. There was higher total 14C retention (47.7%) in obese mice than in lean mice (9.0%) at 168 h (P<0.05). The 14C concentrations in the soleus and gastrocnemius muscle were higher in obese mice than in lean mice (P<0.05). Perirenal adipose tissue contained the highest 14C content in lean mice, whereas subcutaneous adipose tissue (SAT) had the highest 14C content and accounted for the largest proportion of total radioactivity among fat depots in obese mice. More lipid radioactivity was recovered as TAG in SAT from obese mice than from lean mice (P<0.05). Gene expression suggested acyl CoA binding protein and fatty acid binding protein are important for FA distribution in adipose tissue and muscle. The FA distribution in major tissues was altered in ob/ob mice, perhaps contributing to obesity. Understanding the disparity in FA disposal between lean and obese mice may reveal novel targets for the treatment and prevention of obesity. [ABSTRACT FROM AUTHOR]

Fatty liver disease is regularly observed in cultured large yellow croaker, and the disease leads to lower growth rates and reduced harvest yields. The goal of this study was to achieve a more detailed understanding of the physiological and molecular changes in response to high-fat diet-induced fatty liver in large yellow croaker. Large yellow croaker fed a high-fat diet ( HFD) for 9 weeks developed hepatic steatosis characterized by histological observation and significantly increased plasma triglyceride levels and serum alanine aminotransferase ( ALT) activities. However, no significant differences in serum total protein, glucose, cholesterol, non-esterified free fatty acids ( NEFA), aspartate aminotransferase, high-density lipoprotein and low-density lipoprotein were observed between the normal diet and the high-fat diet ( HFD) group. The fatty acid composition of tissue lipids was not affected significantly by dietary lipid levels. Gene expression analysis demonstrated that the HFD decreased fatty acid synthase expression and increased PPARγ expression, but had no effect on lipoprotein lipase and PPARα expression. These results suggest that the HFD-induced physiological changes and fatty liver may be due to the alteration of related gene expression. As such, further investigations of the metabolic pathways and differentially expressed genes are of particular significance in the mechanistic study and understanding of HFD-induced fatty liver disease. [ABSTRACT FROM AUTHOR]

BACKGROUND In order to improve the antioxidant and anti-fatigue capacities of whey protein for wider utilization, it was hydrolyzed by chymotrypsin ( EC 3.4.21.1) to produce whey protein hydrolysate ( WPH). Fractions of WPH with different molecular weight ( MW) were separated by ultrafiltration. Kunming mice in various treatment groups were orally administered (1.5 g kg−1 body weight) whey protein isolate ( WPI), WPH or WPHs with different MW (<5, 5-10, 10-30 or >30 kDa) for 6 weeks to explore whether different MW fractions of WPH affected mice fatigue. RESULTS Compared with the control group (orally administered 9 g kg−1 saline) or the WPI group, low- MW (<10 kDa) WPH groups showed prolonged swimming time ( P < 0.05) and had higher concentrations ( P < 0.05) of glucose, non-esterfied fatty acid, liver glycogen, superoxide dismutase and glutathione peroxidase and lower concentration of lactate. Low- MW (<10 kDa) WPHs had higher hydroxyl- and α, α-diphenyl- β-picrylhydrazyl-scavenging abilities and ferrous-chelating capacity than WPI. CONCLUSION The results proved that low- MW (<10 kDa) WPHs with higher anti-fatigue capacity showed higher free radical-scavenging and ferrous-chelating activities. © 2013 Society of Chemical Industry [ABSTRACT FROM AUTHOR]

The present study aimed to elucidate how Atlantic salmon adipocytes pre-enriched with palmitic (16:0, PA), oleic (18:1n−9, OA), or eicosapentaenoic (20:5n−3, EPA) acid respond to a fasting condition mimicked by nutrient deprivation and glucagon. All experimental groups were supplemented with radiolabeled PA to trace secreted lipids and distribution of radioactivity in different lipid classes. There was a higher content of intracellular lipid droplets in adipocytes pre-enriched with OA than in adipocytes pre-enriched with PA or EPA. In the EPA group, the radiolabeled PA was mainly esterified in phospholipids and triacylglycerols, whereas in the OA and PA groups, the radioactivity was mainly recovered in phospholipids and cholesterol-ester. By subjecting the experimental groups to nutrient-deprived media supplemented with glucagon, lipolysis occurred in all groups, although to a lower extent in the OA group. The lipids were mainly secreted as esterified lipids in triacylglycerols and phospholipids, indicating mobilization in lipoproteins. A significant proportion was secreted as free fatty acids and glycerol. Leptin secretion was reduced in all experimental groups in response to fasting, while the mitochondria area responded to changes in the energy supply and demand by increasing after 3 h of fasting. Overall, different lipid classes in adipocytes influenced their mobilization during fasting. [ABSTRACT FROM AUTHOR]

Purpose: This study aims to solve the problem of high output voltage fluctuation and low efficiency caused by the misalignment of the magnetic coupling structure in the wireless charging system for electric vehicles. To address these issues, this paper proposes a dual LCC-S wireless power transfer (WPT) system based on the double-D double-layer quadrature (DDDQ) coil, which can realize the anti-misalignment constant voltage output of the system. Design/methodology/approach: First, this paper establishes the equivalent circuit of a WPT system based on dual LCC-S compensation topology and analyzes its constant-voltage output characteristics and the relationship between system transmission efficiency and coupling coefficient. 1. Quadruple D (Ahmad et al., 2019) and double-D quadrature pad (DDQP) (Chen et al., 2019) coils have good anti-misalignment in the transverse and longitudinal directions, but the magnetic induction intensity in the center of the coils is weak, making it difficult for the receiving coil to effectively couple to the magnetic field energy. 2. Based on the double-D quadrature (DDQ) structure coil that can eliminate the mutual inductance between coupling coils and cross-coupling, Gong et al. (2022a) proposed a parameter optimized LCC-LC series-parallel hybrid topology circuit, which ensures that the output current fluctuation is controlled within 5% only when the system is misaligned within the 50% range along the X direction, achieving constant current output with anti-misalignment. The magnetic coupling structure's finite element simulation model is established to analyze the change in magnetic induction intensity and the system's anti-misalignment characteristics when the coil offsets along the x and y axes. Finally, an experimental prototype is developed to verify the constant voltage output performance and anti-misalignment performance of the system, and the proposed anti-misalignment system is compared with the systems in existing literature, highlighting the advantages of this design. Findings: The experimental results show that the system can achieve a constant voltage output of 48V under a time-varying load, and the output voltage fluctuates within ±5% of the set value within the range of ±60 mm lateral misalignment and ±72 mm longitudinal misalignment. Originality/value: Based on the dual LCC-S WPT system, the mutual inductance between the same side coils is reduced by adding decoupling coils, and the anti-misalignment characteristics and output power of the system are improved in a certain range. It is aimed at improving the stability of the system output and transmission efficiency. [ABSTRACT FROM AUTHOR]

Purpose: To simplify the circuit design and control complexity of the magnetic coupling resonant wireless charging system, the radio energy transmission constant current and constant voltage charging is realized. Design/methodology/approach: The purpose of this study is to simplify the circuit design and control complexity of the magnetic coupling resonance wireless charging system, in order to achieve constant current and constant voltage charging for wireless energy transmission. First, the principle of LCC/S-S compensation structure is analyzed, and the equivalent mathematical model is established; then, the system characteristics under constant current and constant voltage mode are analyzed, and the design method of system parameters is given; finally, a simulation and experimental system is built to verify the correctness and feasibility of the theoretical analysis. Findings: The results show that the proposed hybrid topology can achieve a constant current output of 2 A and a constant voltage output of 30 V under variable load conditions, and effectively suppress the current distortion problem under light load conditions. The waveform distortion rate of the inverter current is reduced from 33.97% to 10.45%. Originality/value: By changing the high-order impedance characteristics of the compensation structure, the distortion of the current waveform under light load is suppressed, and the overall stability and efficiency of the system are improved. [ABSTRACT FROM AUTHOR]

Purpose: This paper aims to solve the problems of large hard switching loss and unclear resonant parameter design in the existing inverter power supply topology. Design/methodology/approach: This paper proposes a simple and reliable two-stage isolated inverter composed of series quasi-resonant push-pull and external freewheeling diode full-bridge inverter. The power supply topology is analyzed, the topology mode is analyzed, the mathematical model of the converter is established and the DC gain of the converter is deduced. The relationship between the load and the output gain of the resonant tank is presented, a new resonant parameter design method is proposed, and the parameter design of the resonant element of the converter is clarified. Findings: The resonant components of the converter are designed according to the proposed resonant parameter design method, and the correctness of the method is verified by simulation and the development and testing of a 500 W experimental prototype. After experimental tests, the peak efficiency of the experimental prototype can reach 94%. Because the experimental prototype achieves soft switching, the heat generation of the switch is greatly reduced, so the heavy heat sink is removed, and the volume is reduced by about 30% compared with the traditional power supply, and the total harmonic distortion of the output voltage is about 2%. Originality/value: The feasibility of the scheme is verified by experiments, which is of great significance for improving the efficiency of the inverter power supply and parameter optimization. [ABSTRACT FROM AUTHOR]

In this paper, the authors establish the boundedness of parametrized Littlewood–Paley area integral and g λ ∗ -function, and their high-order commutators on Herz-type Hardy spaces with variable exponent. These results are also new even for classical Herz-type Hardy space. [ABSTRACT FROM AUTHOR]

High-rise buildings often use mechanical systems to assist ventilation to maintain the stability of their internal environments, and the energy consumption of mechanical ventilation poses a great challenge to urban environments and energy systems. The ventilation system of termite mounds with a combination of internal main and attached chambers is one of the classic examples of nature's bionic approach to maintaining a stable internal ventilation environment for large-volume structures. In this study, based on the inspiration of the internal ventilation chamber structure of bionic termite mounds, we constructed seven high-rise building chamber ventilation models based on the chamber structure of termite mounds with main chambers, main chambers plus single-attached chambers (three types), and main chambers plus double-attached chambers (three types) under natural ventilation conditions, aiming at obtaining the optimal low-energy and high-efficiency chamber ventilation model for bionic termite mounds in high-rise buildings. (1) The wind speed and wind pressure of the high-rise building with the addition of the bionic termite mound chamber structure is higher than that of the traditional chamber-free high-rise building in the sample floors, the maximal difference of the wind speed between the two models is 0.05 m/s, and the maximal difference of the wind speed of the single building is 0.14 m/s, with the maximal difference of the wind speed of the single building being 0.14 m/s; and the natural ventilation environment can be satisfied by a high-rise building with a chamber. (2) After increasing the single-attached chamber structure of the bionic termite mound, the difference in wind speed of different floors is 0.15 m/s, which is 0.10 m/s higher than that of the high-rise building model with the main chamber only. (3) Under the bionic termite mound chamber high-rise building double-attached chamber model, the maximum difference in wind speed of each floor sampling point can reach 0.19 m/s, while the wind pressure cloud map shows a stable wind environment system. (4) Two attached chambers are added at A and B of the high-rise building to form the a4 model of the chamber of the high-rise building with a double-chamber bionic termite mound. According to the results, it can be seen that the model of the nine floor sampling points of the maximum wind speed difference has six places for the highest value, and the single building wind speed difference for the minimum value of 0.10 m/s. The study aims to optimize the connectivity and ventilation performance of high-rise buildings under natural ventilation conditions and to promote the green and sustainable design of high-rise buildings. [ABSTRACT FROM AUTHOR]

A new alginate lyase gene of algl17 was cloned from an alginate-degrading marine bacterium Microbulbifer sp. ALW1. The gene contained 2220 bp and encoded a 739-amino acid protein classified into the PL-17 family. The recombinant alginate lyase AlgL17 was overexpressed and purified from Escherichia coli BL21 (DE3) with a molecular mass of 84.9 kDa. This enzyme showed activities towards sodium alginate, polyM and alginate oligosaccharide, but very low activity towards polyG. These results indicate that AlgL17 is a polyM-specific oligoalginate lyase. When sodium alginate was used as a substrate, the optimum reaction temperature and pH for the enzyme were 35 °C and pH 8.0, respectively. Recombinant AlgL17 was stable at 25 °C, but not stable at 30 °C and 35 °C. It showed good stability over a pH range of 5.0–8.0. The enzyme activity was increased to 1.7 times by adding NaCl to a final concentration of 0.7 M. The ability of the recombinant AlgL17 producing 4-deoxy-L- erythro -5-hexoseulose uronic acid (DEH) from sodium alginate and polyM block indicates that AlgL17 is an exo-type alginate lyase. • A new alginate lyase from a marine bacterium Microbulbifer sp. ALW1 was overexpressed in Escherichia coli BL21 (DE3). • The recombinant enzyme was identified to be an exo -oligoalginate lyase. • We identified the enzymatic hydrolysates and their antioxidant activities. [ABSTRACT FROM AUTHOR]

Background: Intramuscular fat (IMF) content is a critical indicator of pork quality, and abnormal IMF is also relevant to human disease as well as aging. Although N6-methyladenosine (m6A) RNA modification was recently found to regulate adipogenesis in porcine intramuscular fat, however, the underlying molecular mechanisms was still unclear. Results: In this work, we collected 20 longissimus dorsi muscle samples with high (average 3.95%) or low IMF content (average 1.22%) from a unique heterogenous swine population for m6A sequencing (m6A-seq). We discovered 70 genes show both differential RNA expression and m6A modification from high and low IMF group, including ADIPOQ and SFRP1, two hub genes inferred through gene co-expression analysis. Particularly, we observed ADIPOQ, which contains three m6A modification sites within 3′ untranslated and protein coding region, could promote porcine intramuscular preadipocyte differentiation in an m6A-dependent manner. Furthermore, we found the YT521‑B homology domain family protein 1 (YTHDF1) could target and promote ADIPOQ mRNA translation. Conclusions: Our study provided a comprehensive profiling of m6A methylation in porcine longissimus dorsi muscle and characterized the involvement of m6A epigenetic modification in the regulation of ADIPOQ mRNA on IMF deposition through an m6A-YTHDF1-dependent manner. [ABSTRACT FROM AUTHOR]

Alginate lyases can depolymerize alginate to oligomers with potential applications in many fields. Here a new alginate lyase, namely AlgL6, was characterized from Microbulbifer sp. ALW1, phylogenetically classified into the polysaccharide lyase family 6 (PL6). The recombinant alginate lyase AlgL6 exerted enzymatic activities towards polymannuronate, polyguluronate, and sodium alginate in an exolytic manner. AlgL6 had an optimum temperature of 35 °C and good stability at 30 °C or below. Its optimum pH was 8.0, and it had good stability over the pH range of 5.0–9.0. AlgL6 exhibited excellent halo-stability against Na+, and its activity can be increased up to about 1.8 times by 0.5 M NaCl. AlgL6 also showed strong stability in the presence of some nonionic detergents such as Tween 20 and Tween 80. The degradation products of sodium alginate by AlgL6 exhibited more effective antioxidant activities than the undigested polysaccharides. Structure analysis illustrated the catalytic mechanism defined by the coordination of the acid/base residues Arg269 and Lys248 of AlgL6. The replacement of Ca2+-interacting amino acid residues in AlgL6 and depletion of Ca2+ suggested the involvement of Ca2+ in the enzyme's catalytic activity. These properties of AlgL6 supply support to its industrial application for development of alginate bioresource. • AlgL6 exhibits excellent halo-stability against Na+. • AlgL6 has calcium-dependence catalysis property. • AlgL6 has a great potential as an exo-type tool to produce bioactive AOS. [ABSTRACT FROM AUTHOR]

Obesity has become a health threat and hard enough to deal with. Evidences show that metformin could inhibit adipogenesis and combat obesity, while its mechanisms remain to be elucidated more comprehensively. In this study, we found that administration of metformin could combat obesity of mice induced by high-fat diet (HFD), indicated by strikingly decreased body weight and weight of inguinal white adipose tissue (iWAT) and epidydimal white adipose tissue (eWAT) compared with the control group. Mechanically, we revealed that metformin could inhibit protein expression of FTO, leading to increased m6A methylation levels of cyclin D1 (Ccnd1) and cyclin dependent kinase 2 (Cdk2), two crucial regulators in cell cycle. Ccnd1 and Cdk2 with increased m6A levels were recognised by YTH m6A RNA binding protein 2 (YTHDF2), causing an YTHDF2-dependent decay and decreased protein expressions. In consequence, mitotic clonal expansion (MCE) process was blocked and adipogenesis was inhibited. [ABSTRACT FROM AUTHOR]

Abstract: Breast cancer stem cells (BCSCs), which can fully recapitulate the tumor origin and are often resistant to chemotherapy and radiotherapy, are currently considered as a major obstacle for breast cancer treatment. To achieve the goal of both targeting BCSCs and bulk breast cancer cells, we developed 8-hydroxyquinoline-loaded hyaluronan modified mesoporous silica nanoparticles (MSN)-supported lipid bilayers (HA-MSS) and docetaxel-loaded MSS. The results showed that the size of all the nanoparticles was smaller than 200 nm. BCSCs were enriched from MCF-7 cells by a sphere formation method and identified with the CD44+/CD24− phenotype. Quantitative and qualitative analysis demonstrated that HA promotes the uptake of HA-MSS in CD44-overexpressing MCF-7 mammospheres, revealing the mechanism of receptor-mediated endocytosis. DTX or DTX-loaded MSS showed much enhanced cytotoxicity against MCF-7 cells compared with MCF-7 mammospheres, whereas 8-HQ or 8-HQ-loaded HA-MSS showed much enhanced cytotoxicity against MCF-7 mammospheres compared with MCF-7 cells. In the MCF-7 xenografts in mice, the combination therapy with DTX-loaded MSS plus 8-HQ-loaded HA-MSS produced the strongest antitumor efficacy, with little systemic toxicity (reflecting by loss of body weight) in mice. Thus, this combination therapy may provide a potential strategy to improve the therapy of breast cancer by eradication of breast cancer cells together with BCSCs. [Copyright &y& Elsevier]

Background: Obesity leads to a decline in the exercise capacity of skeletal muscle, thereby reducing mobility and promoting obesity-associated health risks. Dietary intervention has been shown to be an important measure to regulate skeletal muscle function, and previous studies have demonstrated the beneficial effects of docosahexaenoic acid (DHA; 22:6 ω-3) on skeletal muscle function. At the molecular level, DHA and its metabolites were shown to be extensively involved in regulating epigenetic modifications, including DNA methylation, histone modifications, and small non-coding microRNAs. However, whether and how epigenetic modification of mRNA such as N6-methyladenosine (m6A) mediates DHA regulation of skeletal muscle function remains unknown. Here, we analyze the regulatory effect of DHA on skeletal muscle function and explore the involvement of m6A mRNA modifications in mediating such regulation. Results: DHA supplement prevented HFD-induced decline in exercise capacity and conversion of muscle fiber types from slow to fast in mice. DHA-treated myoblasts display increased mitochondrial biogenesis, while slow muscle fiber formation was promoted through DHA-induced expression of PGC1α. Further analysis of the associated molecular mechanism revealed that DHA enhanced expression of the fat mass and obesity-associated gene (FTO), leading to reduced m6A levels of DNA damage-induced transcript 4 (Ddit4). Ddit4 mRNA with lower m6A marks could not be recognized and bound by the cytoplasmic m6A reader YTH domain family 2 (YTHDF2), thereby blocking the decay of Ddit4 mRNA. Accumulated Ddit4 mRNA levels accelerated its protein translation, and the consequential increased DDIT4 protein abundance promoted the expression of PGC1α, which finally elevated mitochondria biogenesis and slow muscle fiber formation. Conclusions: DHA promotes mitochondrial biogenesis and skeletal muscle fiber remodeling via FTO/m6A/DDIT4/PGC1α signaling, protecting against obesity-induced decline in skeletal muscle function. [ABSTRACT FROM AUTHOR]

Context Nondigestible fermentable carbohydrates (NDFCs) can be fermented by microbiota, thereby yielding metabolites that have a beneficial role in the prevention and treatment of obesity and its complications. However, to our knowledge, no meta-analysis has been conducted to evaluate the effects of NDFCs on obesity. Objective To conduct a meta-analysis of randomized controlled trials (RCTs) to summarize existing evidence on the effects of numerous NDFCs on adiposity and cardiovascular risk factors in adults with overweight or obesity with ≥2 weeks of follow-up. Data Sources The following databases were searched: MEDLINE, Embase, and CINAHL. Data Extraction Seventy-seven RCTs with 4535 participants were identified for meta-analysis from the 3 databases. Data Analysis The findings suggest that increased intake of NDFCs is significantly effective in reducing body mass index by 0.280 kg/m2, weight by 0.501 kg, hip circumference by 0.554 cm, waist circumference by 0.649 cm, systolic blood pressure by 1.725 mmHg, total cholesterol by 0.36 mmol/L, and low-density lipoprotein by 0.385 mmol/L, with evidence of moderate-to-high quality. Conclusion Convincing evidence from meta-analyses of RCTs indicates that increased NDFC intake improves adiposity, blood lipid levels, and systolic blood pressure in people with overweight and obesity. [ABSTRACT FROM AUTHOR]

To obtain the relation between spark discharges and the topography of electrode surfaces, some models, such as a micro-initial model of cone and spherical head cylinder, generated from the scanning of a scanning electron microscope are introduced. Based on the principles of energy conservation and thermal equilibrium, the second-order non-homogeneous differential equation is established. The relationships between the temperature of the cathode surface and the distance from the top of micro-protrusions, the cone angle, and the radius of the ball head are derived from a set of second-order non-homogeneous differential equations. When introduced electron emission theory, the main emission type at the initial stage of the discharge is electron field emission. As the discharge progresses, the Joule heat generated by the emission current will cause thermionic emission. During this progress, the emission current density gradually increases. When the temperature of the cathode surface reaches the melting point of the cathode metal, the current density will increase sharply. Observed from the discharge, the temperature of the cathode surface is inversely proportional to the cone angle and the radius of the ball head maintains a gradually decreasing slope. It is proportional to micro-protrusions maintaining a gradually increasing slope. When the cone angle is less than 12° and the radius of the ball head is less than 0.04 µm, the temperature of the cathode surface changes more dramatically. Through this study, a further understanding of factors that affect the density of cathode current emission can be obtained, which is of great significance to improve the capacity of cathode emission. [ABSTRACT FROM AUTHOR]

The two-electron reduction of molecular oxygen represents an effective strategy to enable the green, mild and on-demand synthesis of hydrogen peroxide. Its practical viability, however, hinges on the development of advanced electrocatalysts, preferably composed of non-precious elements, to selectively expedite this reaction, particularly in acidic medium. Our study here introduces 2H-MoTe2 for the first time as the efficient non-precious-metal-based electrocatalyst for the electrochemical production of hydrogen peroxide in acids. We show that exfoliated 2H-MoTe2 nanoflakes have high activity (onset overpotential ∼140 mV and large mass activity of 27 A g−1 at 0.4 V versus reversible hydrogen electrode), great selectivity (H2O2 percentage up to 93%) and decent stability in 0.5 M H2SO4. Theoretical simulations evidence that the high activity and selectivity of 2H-MoTe2 arise from the proper binding energies of HOO* and O* at its zigzag edges that jointly favor the two-electron reduction instead of the four-electron reduction of molecular oxygen. [ABSTRACT FROM AUTHOR]

Cellular long‐chain fatty acids' (LCFAs) uptake is a crucial physiological process that regulates cellular energy homeostasis. AMPK has been shown to modulate LCFAs uptake in several kinds of cells, but whether it exerts an impact on intestinal LCFAs uptake is not quite clear. In the current study, we found that AMPK reinforced LCFAs uptake in intestinal epithelial cells (IECs). Moreover, intestinal epithelium‐specific AMPK deletion impaired intestinal LCFAs absorption and protected mice from high‐fat diet‐induced obesity. Mechanistically, we discovered that AMPK deletion reduced the CD36 protein level by upregulating Parkin‐mediated polyubiquitination of CD36 in IECs. Furthermore, our results revealed that AMPK affected PARK2 (gene name of Parkin) mRNA stability in a YTHDF2‐dependent manner through FTO‐dependent demethylation of N6‐methyladenosine (m6A). Besides, AMPK promoted the translocation of CD36 to the plasma membrane in IECs, but the inhibition of AKT signaling suppressed this effect, which also halted the accelerated fatty acid uptake induced by AMPK. These results suggest that AMPK facilitates the intestinal LCFAs uptake by upregulating CD36 protein abundance and promoting its membrane translocation simultaneously. Such findings shed light on the role of AMPK in the regulation of intestinal LCFAs uptake. [ABSTRACT FROM AUTHOR]

Obesity has become a major health crisis in the past decades. Branched-chain amino acids (BCAA), a class of essential amino acids, exerted beneficial health effects with regard to obesity and its related metabolic dysfunction, although the underlying reason is unknown. Here, we show that BCAA supplementation alleviates high-fat diet (HFD)-induced obesity and insulin resistance in mice and inhibits adipogenesis in 3T3-L1 cells. Further, we find that BCAA prevent the mitotic clonal expansion (MCE) of preadipocytes by reducing cyclin A2 (CCNA2) and cyclin-dependent kinase 2 (CDK2) expression. Mechanistically, BCAA decrease the concentration of nicotinamide adenine dinucleotide phosphate (NADPH) in adipose tissue and 3T3-L1 cells by reducing glucose-6-phosphate dehydrogenase (G6PD) expression. The reduced NADPH attenuates the expression of fat mass and obesity-associated (FTO) protein, a well-known m6A demethylase, to increase the N 6-methyladenosine (m6A) levels of Ccna2 and Cdk2 mRNA. Meanwhile, the high m6A levels of Ccna2 and Cdk2 mRNA are recognized by YTH N 6-methyladenosine RNA binding protein 2 (YTHDF2), which results in mRNA decay and reduction of their protein expressions. Overall, our data demonstrate that BCAA inhibit obesity and adipogenesis by reducing CDK2 and CCNA2 expression via an NADPH-FTO-m6A coordinated manner in vivo and in vitro , which raises a new perspective on the role of m6A in the BCAA regulation of obesity and adipogenesis. [Display omitted] [ABSTRACT FROM AUTHOR]

N6‐methyladenosine (m6A), as the most abundant RNA epigenetic modifications, has been shown to play critical roles in various biological functions. Research about enzymes that can catalyze and remove m6A have revealed its comprehensive roles in messenger RNA (mRNA) metabolism and other physiological processes. The "readers" including YTH domain‐containing proteins, hnRNPC, hnRNPG, hnRNPA2B1, IGF2BP1, IGF2BP2, and IGF2BP3, which can affect the fates of mRNA in an m6A‐dependent manner. In this review, we focus on recent advances in the research of the m6A modifications, especially about the latest functions of its writers, erasers, readers in RNA metabolism, cancer, and lipid metabolism. In the end, we provide insights into the underlying molecular mechanisms of m6A modifications. In this review, we focus on recent advances in the research of the m6A modifications, especially about the latest functions of its writers, erasers, readers in RNA metabolism, cancer, and lipid metabolism. In the end, we provide insights into the underlying molecular mechanisms of m6A modifications. [ABSTRACT FROM AUTHOR]

Bacterial infection causes nutrient malabsorption in small intestine. KR-32, a kind of synthetic antimicrobial peptide, has the bacteriostatic effect. In the present study, 2 experiments were designed to analyze the effects of KR-32 on fat absorption of piglets with or without Escherichia coli infection. In Exp. 1, 12 weaning piglets (21 d old) were allocated to 2 groups: piglets with an intraperitoneal (i.p.) injection of antimicrobial peptide KR-32 (APK) and piglets with an i.p. injection of an equivalent volume (1 mL) of phosphate-buffered saline (PBS) (CON-1). Results showed that after 7 d of growth, KR-32 did not significantly change growth performance and apparent total tract digestibility (ATTD) of feed nutrients of normal pigs. To confirm whether KR-32 affects those of enterotoxigenic Escherichia coli (ETEC) K88–challenged pigs, we performed Exp. 2, in which 18 piglets (28 d old) were divided into the following 3 groups: 1) piglets orally challenged with 1 × 1010 cfu ETEC K88 on day 1 followed by an i.p. injection of 0.6 mg/kg KR-32 (K88 + APK); 2) piglets orally challenged with 1 × 1010 cfu ETEC K88 on day 1 followed by an i.p. injection of an equivalent volume (1 mL) of PBS (K88); and 3) piglets with an oral administration of fresh Luria–Bertani broth (50 mL) followed by an i.p. injection of an equivalent volume of PBS (CON-2). Results showed that ETEC K88 challenge led to poor ADFI, ADG, and G:F in piglets; decreased ATTD of feed nutrients, especially CP and ether extract (EE); and intestinal morphology disorder. After i.p. injection of KR-32, ADG and ATTD of CP and EE were greatly increased, G:F was significantly reduced (P < 0.05), and, especially, ATTD of EE returned to a normal level compared with group CON-2. Fatty acid absorption also highly increased after KR-32 injection. Then we focused on fat digestion and fatty acid uptake. The pH in the intestine and pancreas lipase showed no difference among the 3 treatment groups, whereas fatty acid transporter protein 4 (FATP4) expression was remarkably improved (P < 0.05) and the epithelial barrier was recovered after i.p. injection of KR-32. In conclusion, KR-32, given to ETEC K88–challenged piglets, improved growth performance, ATTD of EE, fatty acid absorption, and intestinal morphology, which indicated that KR-32 was likely to improve the expression of FATP4 and by repairing the epithelial barrier, thereby alleviating fatty acid malabsorption. [ABSTRACT FROM AUTHOR]

N6‐methyladenosine (m6A) mRNA modification plays an important role in adipogenesis, but its role on single gene remains unexplored. Family with Sequence Similarity 134, Member B (FAM134B) is a cis‐Golgi transmembrane protein that known to be necessary for the long‐term survival of nociceptive and autonomic ganglion neurons. Recent work has shown that FAM134B plays a pivotal role in lipid homeostasis and was identified as its significant m6A level difference between Chinese local Jinhua pigs and Landrace through RNA‐sequence. Here, we construct the non‐m6A FAM134B coding sequence (CDS) plasmid (FAM134B‐MUT) and found one important m6A site on its CDS. Expression of FAM134B‐MUT was more effective in promoting porcine preadipocytes adipogenic differentiation and lipid deposition than wild‐type FAM134B (FAM134B‐WT) both in early and ultimate differentiation stage. FAM134B‐MUT functions better in promoting fat deposition by upregulating peroxisome proliferator‐activated receptor γ (PPARγ) and CCAAT/enhancer‐binding protein (C/EBPα) level. The m6A reader protein YTH m6A RNA binding protein 2 (YTHDF2) interacts with FAM134B mRNA and down regulated its protein level. These results demonstrate that FAM134B was the target of YTHDF2, which may recognize and binds the m6A site of FAM134B to reduce its mRNA lifetime and reduce its protein abundance. © 2018 IUBMB Life, 71(5):580–586, 2019 [ABSTRACT FROM AUTHOR]

Family with sequence similarity 134, Member B (FAM134B), is a cis-Golgi transmembrane protein that is known to be necessary for the long-term survival of nociceptive and autonomic ganglion neurons. Recent work has shown that FAM134B plays a pivotal role in autophagy-mediated turnover of endoplasmic reticulum (ER) membranes, tumor inhibition and lipid homeostasis. In this study, we provide mechanistic links between FAM134B and ARF-related protein 1 (ARFRP1) and further show that FAM134B resides in the Golgi apparatus. Here, we found that FAM134B increased lipid accumulation in adipocytes. Transport vehicle number and ADP-ribosylation factor (ARF) family gene expression were also increased by FAM134B overexpression, suggesting that vesicular transport activity enhanced lipid accumulation. ARF-related protein 1 (ARFRP1) is a GTPase that promotes protein trafficking. We show that FAM134B regulates the expression of ARFRP1, and the knockdown of ARFRP1 abolishes enhancement on lipid accumulation caused by FAM134B. In addition, FAM134B upregulates the PAT family protein (PAT), which associates with the lipid droplets (LDs) surface and promotes lipolysis by recruiting adipocyte triglyceride lipase (ATGL). These findings indicate that FAM134B promotes lipid accumulation and adipogenic differentiation by increasing vesicle transport activity in the Golgi apparatus and inhibiting the lipolysis of LDs. [ABSTRACT FROM AUTHOR]

Abstract Dysregulated activation of inflammation is associated with the development and progression of many diseases. Generation of reactive oxygen species (ROS) has been shown to promote an inflammatory response. Cathelicidin peptides not only defend against the invasion of various microbes but also play an important role in regulating immune responses. The objective of this study was to investigate the effects and mechanisms of Cathelicidin-WA (CWA) on the inflammatory response and oxidative stress in macrophages. Our results showed that CWA efficiently attenuated lipopolysaccharide (LPS)-stimulated inflammation and oxidative stress both in vivo and in vitro. Mechanistically, we found that CWA significantly reduced the LPS-induced nuclear translocation of NF-κB, thus decreasing the production of the pro-inflammatory cytokines TNF-α and IL-6 in macrophages. On the other hand, CWA markedly promoted the nuclear translocation of Nrf2 via the AKT pathway and p38 signaling. This resulted in increased expression of the anti-oxidative genes NQO-1 and HO-1 and alleviated oxidative stress in LPS-stimulated macrophages. Interestingly, the effects of CWA were diminished when AMPK was knocked down. Consistently, we noticed that CWA failed to ameliorate the LPS-induced inflammatory response and oxidative stress in AMPK knockout mice. Furthermore, we discovered that LKB1 was essential for AMPK activation by CWA. These data demonstrated for the first time that CWA attenuated LPS-stimulated inflammation and redox imbalance through regulating LKB1-AMPK signaling. Such knowledge provides new insights into the mechanisms through which Cathelicidin peptides modulate immune responses. Graphical abstract fx1 Highlights • CWA suppressed LPS-induced nuclear translocation of NF-κB in macrophages. • CWA promoted nuclear expression of Nrf2 in LPS-stimulated macrophages. • CWA activated LKB1-AMPK signaling in macrophages. • AMPK knockout diminished the effect of CWA on alleviating inflammation in mice. • AMPK was essential for the action of CWA on ameliorating oxidative stress in mice. [ABSTRACT FROM AUTHOR]

Abstract N6-methyladenosine (m6A) is the most prevalent internal mRNA modification in eukaryotes. Loss of m6A demethylase FTO increases m6A levels and inhibits adipogenesis of preadipocytes. However, its underlying mechanism remains elusive. Here, we demonstrated that silencing FTO inhibited adipogenesis of preadipocytes through impairing cell cycle progression at the early stage of adipogenesis. FTO knockdown markedly decreased the expression of CCNA2 and CDK2, crucial cell cycle regulators, leading to delayed entry of MDI-induced cells into G2 phase. Furthermore, the m6A levels of CCNA2 and CDK2 mRNA were significantly upregulated following FTO knockdown. m6A-binding protein YTHDF2 recognized and decayed methylated mRNAs of CCNA2 and CDK2, leading to decreased protein expression, thereby prolonging cell cycle progression and suppressing adipogenesis. Our work unravels that FTO regulates adipogenesis by controlling cell cycle progression in an m6A-YTHDF2 dependent manner, which provides insights into critical roles of m6A methylation in adipogenesis. Highlights • Loss of FTO delays entry of MDI-induced 3T3-L1 preadipocytes into G2 phase. • FTO demethylates CCNA2 and CDK2 mRNA and enhance their expression. • YTHDF2 recognizes and destabilizes m6A-modified CCNA2 and CDK2 mRNA. • The FTO/m6A/YTHDF2 signaling is critical for 3T3-L1 preadipocytes adipogenesis and cell cycle progression. [ABSTRACT FROM AUTHOR]

1. This study aimed to investigate the pharmacokinetic interaction of the three ingredients in a traditional Chinese herbal formulation, Sini Decoction, and provide evidence for its compatibility mechanism. 2. First, the effect of liquiritin and 6-gingerol on the pharmacokinetic parameters of aconitine was investigated in rats by using a sensitive and reliable LC–MS/MS method. Then the Caco-2 cell monolayer model and Rhodamine-123 uptake assay were used to investigate the effect of liquiritin and 6-gingerol on the absorption of aconitine and the activity ofP-gp. 3. TheCmaxof aconitine increased significantly (p < 0.05) from 10.34 ± 1.99 to 17.68 ± 2.65 ng/mL with the pretreatment of liquiritin (20 mg/kg), and to 17.43 ± 0.96 ng/mL with 6-gingerol (20 mg/kg). When aconitine was co-administered with liquiritin and 6-gingerol, theCmaxandAUC(0–t)of aconitine increased approximately twofold, and whilet1/2only increased 1.2-fold. The Caco-2 cell monolayer model and Rhodamine-123 uptake assay indicated that both liquiritin and 6-gingerol could increase the absorption of aconitine by inhibiting the activity ofP-gp. 4. These results indicated that both liquiritin and 6-gingerol could promote the absorption of aconitine and increase its drug concentration in blood by inhibiting the activity ofP-gp, and it could also provide evidence for compatibility mechanism of the traditional Chinese herbal formula, Sini Decoction. [ABSTRACT FROM AUTHOR]

Porous carbon materials doped with nano-sized transition metal carbides and/or metal-nitrogen coordinative sites are promising oxygen reduction electrocatalysts. The doping of such functionalities in carbon materials with desirable concentration, ultra-small size and stable configuration is still a challenge. In this paper, by grinding and pyrolyzing solid mixtures of an amino acid, an iron salt, and a mesoporous silica template, we demonstrate a solvent-free assembly approach to directly anchor both Fe 3 C nanoclucters and FeN x sites into nitrogen-doped ordered mesoporous graphitic carbon materials. The carbonaceous electrocatalysts are imparted with several fascinating features, namely, highly dispersed ultra-small Fe 3 C nanoclusters of 1–3 nm, well-anchored FeN x sites, nitrogen-doped well-graphitized carbon frameworks, and ordered mesopores (∼5.4 nm) and high surface areas (>1000 m 2 /g), respectively. The combination of these features makes these electrocatalysts exceptional for oxygen reduction reaction under both alkaline and acidic electrolytes, i.e. superior catalytic activities (e.g. onset and half-wave potentials up to 1.00 and 0.89 V vs. the reversible hydrogen electrode in alkaline solution), outstanding stabilities and excellent methanol tolerance, respectively. An in-depth study has been conducted to identify and characterize the key active sites in these electrocatalysts and to elucidate several important influencing factors to optimize the catalytic performance. [ABSTRACT FROM AUTHOR]

The development of nonprecious metal-based electrocatalysts for the oxygen reduction reaction holds the decisive key to many energy conversion devices. Among several potential candidates, transition metal and nitrogen co-doped carbonaceous materials are the most promising, yet their activity and stability are still insufficient to meet the needs of practical applications. In this study, a core-shell hybrid electrocatalyst is developed via the self-polymerization of dopamine and cobalt on carbon nanotubes (CNTs), followed by high-temperature pyrolysis. The polymer-derived carbonaceous shell contains abundant structural defects and facilitates the formation of CoN/C active sites, whereas the graphitic carbon nanotube core provides high electrical conductivity and corrosion resistance. These two components separately fulfill different functionalities, and jointly afford the catalyst with excellent electrochemical performance. In 1 m KOH, CoN/CNT exhibits a positive half-wave potential of ≈0.91 V, low peroxide yield of <7%, as well as great stability. When used as the air catalyst of primary Zn-air and Al-air batteries, this hybrid electrocatalyst enables large discharge current density, high peak power density, and prolonged operation stability. [ABSTRACT FROM AUTHOR]

Co-delivery of clodronate-liposomes and doxorubicin-liposomes inhibited hepatic progenitor activation and increased drug concentrations in tumor cells by depleting macrophages, thereby inhibiting hepatocellular carcinoma development and progression. [Display omitted] • Co-delivery of clodronate-liposomes and doxorubicin-liposomes by intra-spleen injection. • Combination of doxorubicin-liposomes and clodronate-liposomes inhibited the occurrence and progression of primary hepatocellular carcinoma effectively and feasibly in DEN-induced rat HCC model without evident damage on vital organs. • Delivery of clodronate-liposomes accompanied with doxorubicin-liposomes inhibited the activation of hepatic progenitor cells, improve the tumor microenvironment and increased drug concentrations in the plasma by depleting macrophages in the liver and spleen. Macrophages in the liver have capacities of capturing and phagocytosing nanocarriers. Macrophages also play an important role in the inflammatory microenvironment and in the tumorigenesis, development and progression of hepatocellular carcinoma (HCC). Several studies have shown that depletion of macrophages is a viable strategy for drug delivery and tumor microenvironment regulation. We prepared liposomes containing doxorubicin and clodronate using an ammonium sulfate gradient and thin film hydration method. The repressive therapeutic effects of liposomes were compared by intrasplenic injection at different stages of a primary HCC model induced by diethylnitrosamine (DEN) in rats. Doxorubicin-liposome (DOX-LIP) and clodronate-liposome (CL-LIP) about 180–200 nm were successfully prepared and characterized. We found that DOX-LIP combined with CL-LIP could effectively inhibit the occurrence and development of liver cancer without major organ damage and side effects. The combination of doxorubicin and clodronate liposomes notably decreased hepatic CD68 + macrophages, enriched DOX in plasma and accumulated it for a long time in the liver and spleen, thus improving the tumor microenvironment, inhibiting the activation of hepatic progenitor cells (HPCs) and promoting the apoptosis of tumor cells, and finally producing the inhibitory and therapeutic effects of HCC in rats. Results of this study were expected to provide a new prospect for the chemotherapy of HCC. [ABSTRACT FROM AUTHOR]

Co-delivery of clodronate-liposomes and doxorubicin-liposomes inhibited hepatic progenitor activation and increased drug concentrations in tumor cells by depleting macrophages, thereby inhibiting hepatocellular carcinoma development and progression. [Display omitted] • Co-delivery of clodronate-liposomes and doxorubicin-liposomes by intra-spleen injection. • Combination of doxorubicin-liposomes and clodronate-liposomes inhibited the occurrence and progression of primary hepatocellular carcinoma effectively and feasibly in DEN-induced rat HCC model without evident damage on vital organs. • Delivery of clodronate-liposomes accompanied with doxorubicin-liposomes inhibited the activation of hepatic progenitor cells, improve the tumor microenvironment and increased drug concentrations in the plasma by depleting macrophages in the liver and spleen. Macrophages in the liver have capacities of capturing and phagocytosing nanocarriers. Macrophages also play an important role in the inflammatory microenvironment and in the tumorigenesis, development and progression of hepatocellular carcinoma (HCC). Several studies have shown that depletion of macrophages is a viable strategy for drug delivery and tumor microenvironment regulation. We prepared liposomes containing doxorubicin and clodronate using an ammonium sulfate gradient and thin film hydration method. The repressive therapeutic effects of liposomes were compared by intrasplenic injection at different stages of a primary HCC model induced by diethylnitrosamine (DEN) in rats. Doxorubicin-liposome (DOX-LIP) and clodronate-liposome (CL-LIP) about 180–200 nm were successfully prepared and characterized. We found that DOX-LIP combined with CL-LIP could effectively inhibit the occurrence and development of liver cancer without major organ damage and side effects. The combination of doxorubicin and clodronate liposomes notably decreased hepatic CD68 + macrophages, enriched DOX in plasma and accumulated it for a long time in the liver and spleen, thus improving the tumor microenvironment, inhibiting the activation of hepatic progenitor cells (HPCs) and promoting the apoptosis of tumor cells, and finally producing the inhibitory and therapeutic effects of HCC in rats. Results of this study were expected to provide a new prospect for the chemotherapy of HCC. [ABSTRACT FROM AUTHOR]

There has been a continuous call for active, durable, and low-cost electrocatalysts for a range of energy applications. Among many different nonprecious metal based candidates, transition metal nanoparticles encapsulated in graphene layers have gained increasing attention over recent years. In this study, it is demonstrated that metallic cobalt nanoparticles sheathed by multilayered nitrogen-enriched graphene shells can be facilely prepared using cobalt-containing Prussian blue colloids as the single precursor. These metallic cobalt cores can be readily leached out by HCl treatment, resulting in hollow graphene spheres. Products with or without acid leaching exhibit great bifunctional activities for electrocatalytic oxygen reduction and hydrogen evolution in both alkaline and acidic electrolytes. Most importantly, it is found that the removal of the metallic cores does not deteriorate but rather enhances the electrocatalytic performance. Based on this and other experimental observations, Co-N-C moieties are proposed as the catalytically active sites. At last, it is shown that these catalysts can be employed as the air catalyst of primary zinc-air batteries with excellent current density, power density, and operation durability. [ABSTRACT FROM AUTHOR]

Aims The present study examined the effect of the antimicrobial peptide cathelicidin-BF (CBF) on LPS-induced mucosal injury and intestinal epithelial barrier dysfunction in a rat model and in the porcine intestinal epithelial cell line. Main methods Changes in barrier integrity were assessed in intestinal epithelium and IPEC-J2 monolayers by measuring nutrient absorption and transepithelial electrical resistance (TER), and the permeability of intestinal epithelium was examined by measuring plasma d -lactate and diamine oxidase levels. The expression levels of tight junction (TJ) proteins were quantified by real-time PCR, and immunofluorescence was used to analyse the location and distribution of TJs in cells. Key findings In vivo , CBF improved epithelial barrier function through attenuating the alterations of the mucosal structure, nutrient absorption and TER in the jejunum, and preventing the down-regulation of TJ proteins in LPS-induced rat intestinal epithelium. In vitro , CBF prevented the disruption and the re-distribution of ZO-1 and occludin, and suppressed the increase in inflammatory cytokine levels in LPS-induced IPEC-J2. The CBF-induced upregulation of zonula occludens-1 and occludin was prevented by U0126 or SB203580, suggesting the involvement of the MEK and p38 MAPK pathways in the CBF-induced changes in tight junctions. Significance Our results showed that CBF prevents LPS-induced intestinal epithelial barrier dysfunction, suggesting its potential as a therapeutic agent for the prevention of LPS-mediated intestinal diseases. We found that exogenous CBF had protective effects on LPS-induced intestinal epithelial barrier disruption in rats and on epithelial damage in IPEC-J2 cells. [ABSTRACT FROM AUTHOR]