Background:The pig is an economically important livestock species and is a widely applied large animal model in medical research.Enhancers are critical regulatory elements that have fundamental functions in evolution,...Background:The pig is an economically important livestock species and is a widely applied large animal model in medical research.Enhancers are critical regulatory elements that have fundamental functions in evolution,development and disease.Genome-wide quantification of functional enhancers in the pig is needed.Results:We performed self-transcribing active regulatory region sequencing(STARR-seq)in the porcine kidney epithelial PK15 and testicular ST cell lines,and reliably identified 2576 functional enhancers.Most of these enhancers were located in repetitive sequences and were enriched within silent and lowly expressed genes.Enhancers poorly overlapped with chromatin accessibility regions and were highly enriched in chromatin with the repressive histone modification H3K9me3,which is different from predicted pig enhancers detected using ChIP-seq for H3K27ac or/and H3K4me1 modified histones.This suggests that most pig enhancers identified with STARR-seq are endogenously repressed at the chromatin level and may function during cell type-specific development or at specific developmental stages.Additionally,the PPP3CA gene is associated with the loin muscle area trait and the QKI gene is associated with alkaline phosphatase activity that may be regulated by distal functional enhancers.Conclusions:In summary,we generated the first functional enhancer map in PK15 and ST cells for the pig genome and highlight its potential roles in pig breeding.展开更多
The effects of some commonly used penetration enhancers such as laurocapram (AZ), oleic acid (OA), poloxamer (POL) and propylene glycol (PG) on the in vitro transdermal iontophoretic delivery of insulin through fu...The effects of some commonly used penetration enhancers such as laurocapram (AZ), oleic acid (OA), poloxamer (POL) and propylene glycol (PG) on the in vitro transdermal iontophoretic delivery of insulin through full-thickness mouse skin were investigated. The results showed that AZ had a synergistic effect on iontophoretic ability to enhance skin permeation of insulin, and PG could further increase this effect. 5% AZ / PG increased the iontophoretic steady state flux of insulin by a factor of 2.75 compared to that treated with iontophoresis alone. OA did not further enhance iontophoretic effect to increase skin permeation of insulin. The combination of iontophoresis and some enhancer provided a novel idea and possibility for transdermal delivery of insulin.展开更多
The purpose of this study was to identify factors that enhance and hinder interdisciplinary collaborative practice (ICP) among doctors and nurses at the Nnamdi Azikiwe teaching hospital, Nnewi, southeast Nigeria. The ...The purpose of this study was to identify factors that enhance and hinder interdisciplinary collaborative practice (ICP) among doctors and nurses at the Nnamdi Azikiwe teaching hospital, Nnewi, southeast Nigeria. The study was a cross-sectional descriptive survey and the quantitative method of data collection was employed. The population was all doctors irrespective of area of specialty and all nurses employed and working in the hospital as at the time of study. Proportionate stratified and convenience sampling methods were used to select study participants according to their categories. Using validated structured questionnaire, data were collected from 110 doctors and 95 nurses in the teaching hospital on their perception on ICP and factors that enhance/hinder ICP. Data were analyzed using both descriptive and inferential statistics. Specifically, frequencies, percentages, standard deviation and graphic presentation were used for descriptive analysis of scores while the unpaired t test of mean score using Graph Pad Prism, Version 5.30 was used to determine the influence of profession, gender, and years of experience on perception of ICP at 0.05 level of significance. The study found that both doctors and nurses have positive perception on ICP. Their years of experience have significant influence on their perception. Clear individual roles and good working relationships enhance ICP while giving priority to professional status rather than expertise was seen as a prominent hindrance to ICP. The study recommends collaborative continuing education for doctors and nurses to enhance ICP in patient care. In addition, the inclusion of interdisciplinary collaborative practice programmme into the curriculum of medical and nursing students (where it does not exist) would go a long way to strengthen ICP and decrease hindrances when they graduate.展开更多
In recent decades, a growing worldwide trend of developing the biodegradable lubricants has been prevailing to form a specific field of green chemistry and green engineering. Enhancement of biodegradability of unreadi...In recent decades, a growing worldwide trend of developing the biodegradable lubricants has been prevailing to form a specific field of green chemistry and green engineering. Enhancement of biodegradability of unreadily biodegradable petroleum-based lubricants has as such become an urgent must. For over a decade the authors have been focusing on the improvement of biodegradability of unreadily biodegradable lubricants such as petroleum-based lubricating oils and greases. A new idea of lubricant biodegradation enhancer was put forward by the authors with the aim to stimulate the biodegradation of unreadily biodegradable lubricants by incorporating the enhancer into the lubricants in order to turn the lubricants into greener biodegradable ones and to help in situ bioremediation of lubricant-contaminated environment. This manuscript summarizes our recent efforts relating to the chemistry and technology of biodegradation enhancers for lubricants. Firstly, the chemistry of lubricant biodegradation enhancers was designed based on the principles of bioremediation for the treatment of hydrocarbon contaminated environment. Secondly, the ability of the designed biodegradation enhancers for increasing the biodegradability of unreadily biodegradable industrial lubricants was investigated through biodegradability evaluation tests, microbial population analysis, and biodegradation kinetics modeling. Finally, the impact of biodegradation enhancers on some crucial performance characteristics of lubricants such as lubricity and oxidation stability was tested via tribological evaluation and oxidation determinations. Our results have shown that the designed chemistry of nitrogenous and/or phosphorous compounds such as lauroyl glutamine, oleoyl glycine, oleic diethanolamide phosphate and lauric diethanolamide borate was outstanding in boosting biodegradation of petroleum-based lubricants which was ascribed to increase the microbial population and decrease the oil-water interfacial tension during the biodegradation process. Lubricants doped with the biodegradation enhancers exhibited much better biodegradability and higher biodegradation rate in the surrounding soils which could be well modeled by the exponential biodegradation kinetics. Furthermore, as lubricant dopants, the biodegradation enhancers also provided excellent capability in reducing friction and wear and in retarding oxidation of lubricants. In the nature of things, lubricant biodegradation enhancers, which are multi-functional not only in the improvement of biodegradability, but also in the fortification of lubricity and in the inhibition of oxidation of lubricants, are expected to be promising as a new category of lubricant additives.展开更多
Our previous studies had confirmed that the essential oil from Zanthoxylum bungeanum Maxim. （Z. bungeanum oil） could effectively enhance the percutaneous permeation of drug molecules as a natural transdermal penetra...Our previous studies had confirmed that the essential oil from Zanthoxylum bungeanum Maxim. （Z. bungeanum oil） could effectively enhance the percutaneous permeation of drug molecules as a natural transdermal penetration enhancer. The aim of the present study is to investigate and compare the skin penetration enhancement effect of Z. bungeanum oil and its main components on traditional Chinese medicine （TCM） active components. Toxicities of Z. bungeanum oil and three selected terpene compounds （terpinen-4-ol, 1,8-cineole, and limonene） in epidermal keratinocytes （HaCaT） and dermal flbroblast （CCC-ESF-1） cell lines were measured using an MTT （3-（4,5-dimethylthiazol-2-yl）-2,5-diphenyltetrazolium bromide） assay. Five model drugs in TCM external preparations, namely osthole （OT）, tetramethylpyrazine （TMP）, ferulic acid （FA）, puerarin （PR）, and geniposide （GP）, which were selected based on their lipophilicity denoted by IogKo^w, were tested using in vitro permeation studies in which vertical Franz diffusion ceils and rat abdominal skin were employed. The secondary structure changes of skin stratum corneum （SC） and drug thermodynamic activities were investigated to understand their mechanisms of action using Fourier transform infrared （FTIR） spectroscopy and saturation solubility studies, respectively. It was found that Z. bungeanum oil showed lower toxicities in both HaCaT cells and CCC-ESF-1 cells compared with three terpene compounds used alone. The enhancement permeation capacities by all tested agents were in the following increasing order： terpinen-4-ol=1,8-cineole〈limonene〈Z, bungeanum oil. The mechanisms of permeation enhancement suggested that these enhancers promoted the skin permeation of drugs mainly by affecting SC lipids. These results indicated that Z. bungeanum oil exhibited better performance in enhancing the skin permeation of active components in TCM preparations.展开更多
To explore the structure-activity connections of amphiphilic permeation enhancers containing the length of the hydrophobic chains as well as the properties of the polar head,O-acylgeraniol and O-acylnerol derivatives ...To explore the structure-activity connections of amphiphilic permeation enhancers containing the length of the hydrophobic chains as well as the properties of the polar head,O-acylgeraniol and O-acylnerol derivatives were synthesized from geraniol/nerol(cis-isomer of geraniol) and pharmaceutical excipient acids in this research. Their promotion of the percutaneous absorption of three drugs as the model, flurbiprofen(FP), isosorbide dinitrate(ISDN) and donepezil(DNP), which were selected based on their physicochemical properties,was tested by in vitro skin penetration and in vivo. Molecular simulation, ATR-FTIR, CLSM and histological observation were implement to evaluate the mode of action of the enhancers.The results indicated that(E)-3,7-dimethyl-2,6-octadien-1-yl tetradecanoate(GER-C14, trans-)achieved the highest enhancement ability for the three drugs;additionally, the in vivo results obtained were in good correlation with the in vitro data. Molecular docking results suggested that enhancers loosen the hydrogen bonds between ceramides, and the results of molecular simulation indicated that GER-C14, NER-C14 could insert into the middle of the lipid bilayer to form an independent phase. According to ATR-FTIR and histological evaluation, the enhancers extracted lipids and influenced the protein region, thereby disturbing the skin array. In addition, CLSM described the dynamic effects of enhancers on lipids between stratum corneum(SC) cells. In conclusion, GER-C14 had a better penetration promotion effect, which broadened our understanding of stereoisomeric penetration enhancers.展开更多
Transdermal drug delivery has been accepted as a potential non-invasive route of drug administration,with advantages of prolonged therapeutic action,decreased side effect,easy use and better patient compliance.However...Transdermal drug delivery has been accepted as a potential non-invasive route of drug administration,with advantages of prolonged therapeutic action,decreased side effect,easy use and better patient compliance.However,development of transdermal products is primarily hindered by the low permeability of the skin.To overcome this barrier effect,numerous new chemicals have been synthesized as potential permeation enhancers for transdermal drug delivery.In this review,we presented an overview of the investigations in this field,and further implications on selection or design of suitable permeation enhancers for transdermal drug delivery were also discussed.展开更多
This study aimed to develop niosomes of ellagic acid(EA),a potent antioxidant phytochemical substance,for dermal delivery and to investigate the influence of chemical penetration enhancers on the physicochemical prope...This study aimed to develop niosomes of ellagic acid(EA),a potent antioxidant phytochemical substance,for dermal delivery and to investigate the influence of chemical penetration enhancers on the physicochemical properties of EA-loaded niosomes.The EA niosomes were prepared by reverse phase evaporation method using Span 60,Tween 60 and cholesterol as vesicle forming agents and Solulan C24 as a steric stabilizer.Polyethylene glycol 400(PEG)was used as a solubilizer while dimethylsulfoxide(DMSO)or Nmethyl-2-pyrrolidone(NMP)was used as a skin penetration enhancer.It was found that the mean particle sizes of EA-loaded niosomes were in the range of 312e402 nm with PI values of lower than 0.4.The niosomes were determined to be spherical multilamellar vesicles as observed by transmission electron microscope and optical microscopy.All niosomes were stable after 4 months storage at 4C.In vitro skin permeation through human epidermis revealed that the skin enhancers affected the penetration of EA from the niosomes at 24 h.The DMSO niosomes showed the highest EA amount in epidermis;whereas the NMP niosomes had the highest EA amount in the acceptor medium.Concomitantly,the skin distribution by confocal laser scanning microscopy showed the high fluorescence intensity of the DMSO niosomes and NMP niosomes at a penetration depth of between 30e90 mm(the epidermis layer)and 90e120 mm(the dermis layer)under the skin,respectively.From the results,it can be concluded that the DMSO niosomes are suitable for epidermis delivery of EA while the NMP niosomes can be used for dermis delivery of EA.展开更多
Currently,enhancers have key transcriptional regulatory roles in muscle development.Skeletal muscle formation involves various molecules,and in animals,enhancers are one of the main types of transcriptional regulatory...Currently,enhancers have key transcriptional regulatory roles in muscle development.Skeletal muscle formation involves various molecules,and in animals,enhancers are one of the main types of transcriptional regulatory regions that are of great importance to regulate myogenic gene expression.In muscle development,enhancers can generate enhancer RNAs(eRNAs)that are involved in the regulation of gene transcription.The regulation of gene expression by eRNAs offers great potential in improving animal production traits.Herein we comprehensively review the roles of enhancers in muscle formation and its potential function in skeletal muscle development.This review will describe the future application of enhancers in skeletal muscle development and discuss the prospects that enhancer studies offer for agriculture,biotechnology,and animal breeding.展开更多
Estrogen-Related Receptor Alpha(ESRRA)is an orphan nuclear receptor that plays a pivotal role in regulating cellular metabolism,mitochondrial biogenesis,and energy homeostasis through transcriptional control.It has be...Estrogen-Related Receptor Alpha(ESRRA)is an orphan nuclear receptor that plays a pivotal role in regulating cellular metabolism,mitochondrial biogenesis,and energy homeostasis through transcriptional control.It has been implicated in diverse physiological processes and diseases,including cancer.However,the transcriptional programs governed by ESRRA and the underlying molecular mechanisms remain incompletely understood.Here,we demonstrate that ESRRA serves as a central regulator in orchestrating the transcriptional activation of estrogen receptorα(ERα)-occupied super enhancers(ERSEs)and cognate ERα-target genes.In parallel,ESRRA represses the expression of cytosolic RNA sensors RIG1 and MDA5,thereby attenuating type I interferon(IFN)signaling and type I IFN-stimulated genes.In terms of mechanism,ESRRA is recruited to ERSEs together with ERαin response to estrogen and their binding to ERSEs occurs in a mutually dependent manner.In contrast,ESRRA directly binds to the promoter regions of RIG1 and MDA5 to suppress their expression.Consistent with these findings,pharmacological inhibition of ESRRA using its inverse agonist XCT790 suppressed estrogen/ERα-induced gene transcription while enhancing type I IFN pathway and antitumor immunity,thereby restraining ERα-positive breast cancer cell growth both in vitro and in vivo.Combination treatment with XCT790 and endocrine therapies,including the ERαantagonist Tamoxifen or degrader Fulvestrant,produced synergistic antitumor effects.Furthermore,co-treatment with XCT790 and tamoxifen re-sensitized Tamoxifen-resistant ERα-positive breast cancer cells to Tamoxifen treatment.In addition,XCT790 treatment augmented the therapeutic efficacy of chemotherapeutic agents such as Doxorubicin in suppressing ERα-positive breast cancer cell growth both in vitro and in vivo.In summary,our findings reveal that ESRRA is a pivotal regulator of ERSEs and estrogen/ERα-target gene activation,as well as the type I IFN signaling pathway,highlighting its potential as a promising therapeutic target in ERα-positive breast cancer in the clinic.展开更多
MicroRNAs (miRNAs) are a class of endogenous non-coding RNAs with regulatory functions. Traditionally, miRNAs are thought to play a negative regulatory role in the cytoplasm by binding to the YUTR of target genes to d...MicroRNAs (miRNAs) are a class of endogenous non-coding RNAs with regulatory functions. Traditionally, miRNAs are thought to play a negative regulatory role in the cytoplasm by binding to the YUTR of target genes to degrade mRNA or inhibit translation. However, it remains a challenge to interpret the potential function of many miRNAs located in the nucleus. Recently, we reported a new type of miRNAs present in the nucleus, which can activate gene expres- sion by binding to the enhancer, and named them nuclear activating miRNAs (NamiRNAs). The discovery of NamiRNAs showcases a complementary regulatory mechanism of miRNA, demon- strating their differential roles in the nucleus and cytoplasm. Here, we reviewed miRNAs in nucleus to better understand the function of NamiRNAs in their interactions with the enhancers. Accord- ingly, we propose a NamiRNA--enhancer-target gene activation network model to better under- stand the crosstalk between NamiRNAs and enhancers in regulating gene transcription. Moreover, we hypothesize that NamiRNAs may be involved in cell identity or cell fate determina- tion during development, although further study is needed to elucidate the underlying mechanisms in detail.展开更多
Transdermal drug delivery plays a significant part in the drug delivery system when compared to other routes of drug administration.The function of the stratum corneum(SC)is a barrier.Recently,numerous methods have be...Transdermal drug delivery plays a significant part in the drug delivery system when compared to other routes of drug administration.The function of the stratum corneum(SC)is a barrier.Recently,numerous methods have been thrived to improve the perforation of drugs across the skin.The most effective method is to use enhancers since these agents enhance skin permeability.Natural penetration enhancers like essential oils demonstrate higher enhancement activity and are more widely accepted than synthetic penetration enhancers.High potential in the expansion and interaction with the SC intercellular lipids has led to an increasing interest in these oils as penetration enhancers.This article gives an overview of a few essential oils,including their mode of action and important parameters for permeation improvement.The present work can provide essential oils as alternative enhancers,and this could be useful in transdermal administration.展开更多
Transcellular permeation enhancers are known to increase the intestinal permeability of enalaprilat,a 349 Da peptide,but not hexarelin(887 Da).The primary aim of this paper was to investigate if paracellular permeabil...Transcellular permeation enhancers are known to increase the intestinal permeability of enalaprilat,a 349 Da peptide,but not hexarelin(887 Da).The primary aim of this paper was to investigate if paracellular permeability enhancers affected the intestinal permeation of the two peptides.This was investigated using the rat single-pass intestinal perfusion model with concomitant blood sampling.These luminal compositions included two paracellular permeation enhancers,chitosan(5 mg/mL) and ethylenediaminetetraacetate(EDTA,1 and 5 mg/mL),as well as low luminal tonicity(100 mOsm) with or without lidocaine.Effects were evaluated by the change in lumen-to-blood permeability of hexarelin and enalaprilat,and the blood-to-lumen clearance of ^(51)chromium-labeled EDTA(CL_(Cr-EDTA)),a clinical marker for mucosal barrier integrity.The two paracellular permeation enhancers increased the mucosal permeability of both peptide drugs to a similar extent.The data in this study suggests that the potential for paracellular permeability enhancers to increase intestinal absorption of hydrophilic peptides with low molecular mass is greater than for those with transcellular mechanism-of-action.Further,the mucosal blood-to-lumen flux of ^(51)Cr-EDTA was increased by the two paracellular permeation enhancers and by luminal hypotonicity.In contrast,luminal hypotonicity did not affect the lumen-to-blood transport of enalaprilat and hexarelin.This suggests that hypotonicity affects paracellular solute transport primarily in the mucosal crypt region,as this area is protected from luminal contents by a constant water flow from the crypts.展开更多
A dual-phase synergistic enhancement method was adopted to strengthen the Al-Mn-Mg-Sc-Zr alloy fabricated by laser powder bed fusion(LPBF)by leveraging the unique advantages of Er and TiB_(2).Spherical powders of 0.5w...A dual-phase synergistic enhancement method was adopted to strengthen the Al-Mn-Mg-Sc-Zr alloy fabricated by laser powder bed fusion(LPBF)by leveraging the unique advantages of Er and TiB_(2).Spherical powders of 0.5wt%Er-1wt%TiB_(2)/Al-Mn-Mg-Sc-Zr nanocomposite were prepared using vacuum homogenization technique,and the density of samples prepared through the LPBF process reached 99.8%.The strengthening and toughening mechanisms of Er-TiB_(2)were investigated.The results show that Al_(3)Er diffraction peaks are detected by X-ray diffraction analysis,and texture strength decreases according to electron backscatter diffraction results.The added Er and TiB_(2)nano-reinforcing phases act as heterogeneous nucleation sites during the LPBF forming process,hindering grain growth and effectively refining the grains.After incorporating the Er-TiB_(2)dual-phase nano-reinforcing phases,the tensile strength and elongation at break of the LPBF-deposited samples reach 550 MPa and 18.7%,which are 13.4%and 26.4%higher than those of the matrix material,respectively.展开更多
Geneupregulation through genome editing is important for plant research and breeding.Targeted insertion of short transcriptional enhancers(STEs)into gene promoters may offer a universal solution akin to transgene-medi...Geneupregulation through genome editing is important for plant research and breeding.Targeted insertion of short transcriptional enhancers(STEs)into gene promoters may offer a universal solution akin to transgene-mediated overexpression while avoiding the drawbacks associated with transgenesis.Here,we introduce an“in locus activation”technique in rice that leverages well-characterized STEs for refined,heritable,and multiplexed gene upregulation.To address the scarcity of potent enhancers,we developed a large-scale mining approach and discovered a suite of STEs that are capable of enhancing gene expression in rice protoplasts.The in locus integration of these STEs into eight rice genes resulted in substantial tran-scriptional upregulation in the edited plants,with up to 869.1-fold increases in their transcript levels.Em-ploying a variety of STEs,we achieved delicate control of gene expression,enabling the fine-tuning of key phenotypic traits such as plant height.Our approach also enabled efficient multiplexed gene upregu-lation,with up to four genes activated simultaneously,significantly enhancing the nicotinamide mononucleotide metabolic pathway.Importantly,heritability studies from the To to T3 generations confirmed the stable and heritable nature of STE-driven gene activation.Collectively,our work demon-strates that coupled with STE mining,leveraging genome editing for in locus activation and gene upregu-lation holds great promise to be widely adopted in fundamental plant research and crop breeding.展开更多
Enhancers are often mutated and dysregulated in various diseases such as cancer.By integrating the function annotation of the mammalian genome(FANTOM)enhancers expression profiles and RNA-seq data from The Cancer Geno...Enhancers are often mutated and dysregulated in various diseases such as cancer.By integrating the function annotation of the mammalian genome(FANTOM)enhancers expression profiles and RNA-seq data from The Cancer Genome Atlas(TCGA)of 13 cancers and their corresponding para-cancerous tissues,we systematically identified a total of 4702 significantly differentially expressed(DE)enhancers.Furthermore,a total of 1036 DE genes regulated by DE enhancerswere identified.Itwas found that in these 13 cancers,most(61.13%)enhancers were ubiquitously expressed,whereas DE enhancers were more likely to be tissue-specific expressed,and the DE genes regulated by DE enhancers were significantly enriched in cancer-related pathways.Finally,it was manifested that 74 single nucleotide polymorphisms(SNPs)were located in 37 DE enhancers,and these SNPs affected the gain and loss of functional transcription factor binding sites of 758 transcription factors,which were shown to be highly correlated with tumorigenesis and development.展开更多
To study the durability of concrete in harsh environments in Northwest China,concrete was prepared with various durability-improving materials such as concrete anti-erosion inhibitor(SBT-TIA),acrylate polymer(AP),supe...To study the durability of concrete in harsh environments in Northwest China,concrete was prepared with various durability-improving materials such as concrete anti-erosion inhibitor(SBT-TIA),acrylate polymer(AP),super absorbent resin(SAP).The erosion mode and internal deterioration mechanism under salt freeze-thaw cycle and dry-wet cycle were explored.The results show that the addition of enhancing materials can effectively improve the resistance of concrete to salt freezing and sulfate erosion:the relevant indexes of concrete added with X-AP and T-AP are improved after salt freeze-thaw cycles;concrete added with SBTTIA shows optimal sulfate corrosion resistance;and concrete added with AP displays the best resistance to salt freezing.Microanalysis shows that the increase in the number of cycles decreases the generation of internal hydration products and defects in concrete mixed with enhancing materials and improves the related indexes.Based on the Wiener model analysis,the reliability of concrete with different lithologies and enhancing materials is improved,which may provide a reference for the application of manufactured sand concrete and enhancing materials in Northwest China,especially for the study of the improvement effects and mechanism of enhancing materials on the performance of concrete.展开更多
In a series of experiments,Phelps et al.1provided novel data linking moderate-to-vigorous physical activity (MVPA),gut microbiota composition changes and the release of the short chain fatty acid (SCFA) formate,and en...In a series of experiments,Phelps et al.1provided novel data linking moderate-to-vigorous physical activity (MVPA),gut microbiota composition changes and the release of the short chain fatty acid (SCFA) formate,and enhanced antitumor immunity via the transcription factor Nuclear factor erythroid 2-related factor 2 (Nrf2) pathway in cytotoxic CD8+T cells.These data support the growing awareness that the clinical benefits of MVPA are achieved at least in part through enhanced immunity with support from the gut microbiome.展开更多
Incorporating ceramic particles into metal matrices is a proven strategy for boosting mechanical properties and wear resistance.The reinforcement potential of tungsten carbide(WC)particles in 316L stainless steel is r...Incorporating ceramic particles into metal matrices is a proven strategy for boosting mechanical properties and wear resistance.The reinforcement potential of tungsten carbide(WC)particles in 316L stainless steel is revealed,utilizing selective laser melting(SLM)to fabricate composites with 5 and 10 vol.%WC.The WC incorporation markedly alters the composite’s microstructure and mechanical attributes.Notably,5 vol.%WC-316L composite exhibits a refined submicron cellular structure,averaging 0.67μm in grain size.Elemental diffusion at WC-316L interface formed a 0.8μm gradient transition layer enriched with M_(2)C carbides(Fe,Cr,W),ensuring robust metallurgical bonding.Compared with unreinforced 316L,5%WC composite exhibits a 70%increase in tensile strength,reaching 1012.6 MPa,and a 25.3%rise in hardness,while maintaining acceptable ductility.10%WC composite achieves a 70.8%hardness enhancement,albeit with reduced elongation.Friction coefficient is reduced by up to 17.3%,and the wear mechanism shifts from adhesive to abrasive,significantly improving wear resistance.展开更多
基金supported by the National Natural Science Foundation of China(32100502)the Ministry of Agriculture of China(2016ZX08009003-006)Science&Technology Department of Yunnan Province(202102AE090039).
文摘Background:The pig is an economically important livestock species and is a widely applied large animal model in medical research.Enhancers are critical regulatory elements that have fundamental functions in evolution,development and disease.Genome-wide quantification of functional enhancers in the pig is needed.Results:We performed self-transcribing active regulatory region sequencing(STARR-seq)in the porcine kidney epithelial PK15 and testicular ST cell lines,and reliably identified 2576 functional enhancers.Most of these enhancers were located in repetitive sequences and were enriched within silent and lowly expressed genes.Enhancers poorly overlapped with chromatin accessibility regions and were highly enriched in chromatin with the repressive histone modification H3K9me3,which is different from predicted pig enhancers detected using ChIP-seq for H3K27ac or/and H3K4me1 modified histones.This suggests that most pig enhancers identified with STARR-seq are endogenously repressed at the chromatin level and may function during cell type-specific development or at specific developmental stages.Additionally,the PPP3CA gene is associated with the loin muscle area trait and the QKI gene is associated with alkaline phosphatase activity that may be regulated by distal functional enhancers.Conclusions:In summary,we generated the first functional enhancer map in PK15 and ST cells for the pig genome and highlight its potential roles in pig breeding.
文摘The effects of some commonly used penetration enhancers such as laurocapram (AZ), oleic acid (OA), poloxamer (POL) and propylene glycol (PG) on the in vitro transdermal iontophoretic delivery of insulin through full-thickness mouse skin were investigated. The results showed that AZ had a synergistic effect on iontophoretic ability to enhance skin permeation of insulin, and PG could further increase this effect. 5% AZ / PG increased the iontophoretic steady state flux of insulin by a factor of 2.75 compared to that treated with iontophoresis alone. OA did not further enhance iontophoretic effect to increase skin permeation of insulin. The combination of iontophoresis and some enhancer provided a novel idea and possibility for transdermal delivery of insulin.
文摘The purpose of this study was to identify factors that enhance and hinder interdisciplinary collaborative practice (ICP) among doctors and nurses at the Nnamdi Azikiwe teaching hospital, Nnewi, southeast Nigeria. The study was a cross-sectional descriptive survey and the quantitative method of data collection was employed. The population was all doctors irrespective of area of specialty and all nurses employed and working in the hospital as at the time of study. Proportionate stratified and convenience sampling methods were used to select study participants according to their categories. Using validated structured questionnaire, data were collected from 110 doctors and 95 nurses in the teaching hospital on their perception on ICP and factors that enhance/hinder ICP. Data were analyzed using both descriptive and inferential statistics. Specifically, frequencies, percentages, standard deviation and graphic presentation were used for descriptive analysis of scores while the unpaired t test of mean score using Graph Pad Prism, Version 5.30 was used to determine the influence of profession, gender, and years of experience on perception of ICP at 0.05 level of significance. The study found that both doctors and nurses have positive perception on ICP. Their years of experience have significant influence on their perception. Clear individual roles and good working relationships enhance ICP while giving priority to professional status rather than expertise was seen as a prominent hindrance to ICP. The study recommends collaborative continuing education for doctors and nurses to enhance ICP in patient care. In addition, the inclusion of interdisciplinary collaborative practice programmme into the curriculum of medical and nursing students (where it does not exist) would go a long way to strengthen ICP and decrease hindrances when they graduate.
基金the financial support provided by the National Natural Science Foundation of China (project Nos.50975282 and 50275147)the Natural Science Foundation of Chongqing, China (project No. CSTC 2008BA4037)
文摘In recent decades, a growing worldwide trend of developing the biodegradable lubricants has been prevailing to form a specific field of green chemistry and green engineering. Enhancement of biodegradability of unreadily biodegradable petroleum-based lubricants has as such become an urgent must. For over a decade the authors have been focusing on the improvement of biodegradability of unreadily biodegradable lubricants such as petroleum-based lubricating oils and greases. A new idea of lubricant biodegradation enhancer was put forward by the authors with the aim to stimulate the biodegradation of unreadily biodegradable lubricants by incorporating the enhancer into the lubricants in order to turn the lubricants into greener biodegradable ones and to help in situ bioremediation of lubricant-contaminated environment. This manuscript summarizes our recent efforts relating to the chemistry and technology of biodegradation enhancers for lubricants. Firstly, the chemistry of lubricant biodegradation enhancers was designed based on the principles of bioremediation for the treatment of hydrocarbon contaminated environment. Secondly, the ability of the designed biodegradation enhancers for increasing the biodegradability of unreadily biodegradable industrial lubricants was investigated through biodegradability evaluation tests, microbial population analysis, and biodegradation kinetics modeling. Finally, the impact of biodegradation enhancers on some crucial performance characteristics of lubricants such as lubricity and oxidation stability was tested via tribological evaluation and oxidation determinations. Our results have shown that the designed chemistry of nitrogenous and/or phosphorous compounds such as lauroyl glutamine, oleoyl glycine, oleic diethanolamide phosphate and lauric diethanolamide borate was outstanding in boosting biodegradation of petroleum-based lubricants which was ascribed to increase the microbial population and decrease the oil-water interfacial tension during the biodegradation process. Lubricants doped with the biodegradation enhancers exhibited much better biodegradability and higher biodegradation rate in the surrounding soils which could be well modeled by the exponential biodegradation kinetics. Furthermore, as lubricant dopants, the biodegradation enhancers also provided excellent capability in reducing friction and wear and in retarding oxidation of lubricants. In the nature of things, lubricant biodegradation enhancers, which are multi-functional not only in the improvement of biodegradability, but also in the fortification of lubricity and in the inhibition of oxidation of lubricants, are expected to be promising as a new category of lubricant additives.
基金supported by the Beijing Natural Science Foundation(No.7132127)the Innovative Research Team in Beijing University of Chinese Medicine(No.2011-CXTD-13),China
文摘Our previous studies had confirmed that the essential oil from Zanthoxylum bungeanum Maxim. （Z. bungeanum oil） could effectively enhance the percutaneous permeation of drug molecules as a natural transdermal penetration enhancer. The aim of the present study is to investigate and compare the skin penetration enhancement effect of Z. bungeanum oil and its main components on traditional Chinese medicine （TCM） active components. Toxicities of Z. bungeanum oil and three selected terpene compounds （terpinen-4-ol, 1,8-cineole, and limonene） in epidermal keratinocytes （HaCaT） and dermal flbroblast （CCC-ESF-1） cell lines were measured using an MTT （3-（4,5-dimethylthiazol-2-yl）-2,5-diphenyltetrazolium bromide） assay. Five model drugs in TCM external preparations, namely osthole （OT）, tetramethylpyrazine （TMP）, ferulic acid （FA）, puerarin （PR）, and geniposide （GP）, which were selected based on their lipophilicity denoted by IogKo^w, were tested using in vitro permeation studies in which vertical Franz diffusion ceils and rat abdominal skin were employed. The secondary structure changes of skin stratum corneum （SC） and drug thermodynamic activities were investigated to understand their mechanisms of action using Fourier transform infrared （FTIR） spectroscopy and saturation solubility studies, respectively. It was found that Z. bungeanum oil showed lower toxicities in both HaCaT cells and CCC-ESF-1 cells compared with three terpene compounds used alone. The enhancement permeation capacities by all tested agents were in the following increasing order： terpinen-4-ol=1,8-cineole〈limonene〈Z, bungeanum oil. The mechanisms of permeation enhancement suggested that these enhancers promoted the skin permeation of drugs mainly by affecting SC lipids. These results indicated that Z. bungeanum oil exhibited better performance in enhancing the skin permeation of active components in TCM preparations.
基金The Natural Science Foundation of Hebei Province [grant numbers H2019209254]North China University of Science and Technology Foundation for Distinguished Young Scholars[grant numbers JQ201713]Distinguished Young Scholars of Hebei Province。
文摘To explore the structure-activity connections of amphiphilic permeation enhancers containing the length of the hydrophobic chains as well as the properties of the polar head,O-acylgeraniol and O-acylnerol derivatives were synthesized from geraniol/nerol(cis-isomer of geraniol) and pharmaceutical excipient acids in this research. Their promotion of the percutaneous absorption of three drugs as the model, flurbiprofen(FP), isosorbide dinitrate(ISDN) and donepezil(DNP), which were selected based on their physicochemical properties,was tested by in vitro skin penetration and in vivo. Molecular simulation, ATR-FTIR, CLSM and histological observation were implement to evaluate the mode of action of the enhancers.The results indicated that(E)-3,7-dimethyl-2,6-octadien-1-yl tetradecanoate(GER-C14, trans-)achieved the highest enhancement ability for the three drugs;additionally, the in vivo results obtained were in good correlation with the in vitro data. Molecular docking results suggested that enhancers loosen the hydrogen bonds between ceramides, and the results of molecular simulation indicated that GER-C14, NER-C14 could insert into the middle of the lipid bilayer to form an independent phase. According to ATR-FTIR and histological evaluation, the enhancers extracted lipids and influenced the protein region, thereby disturbing the skin array. In addition, CLSM described the dynamic effects of enhancers on lipids between stratum corneum(SC) cells. In conclusion, GER-C14 had a better penetration promotion effect, which broadened our understanding of stereoisomeric penetration enhancers.
基金National Natural Science Foun-dation of China(No:30973654 and No:81173007).
文摘Transdermal drug delivery has been accepted as a potential non-invasive route of drug administration,with advantages of prolonged therapeutic action,decreased side effect,easy use and better patient compliance.However,development of transdermal products is primarily hindered by the low permeability of the skin.To overcome this barrier effect,numerous new chemicals have been synthesized as potential permeation enhancers for transdermal drug delivery.In this review,we presented an overview of the investigations in this field,and further implications on selection or design of suitable permeation enhancers for transdermal drug delivery were also discussed.
基金This project is supported by the Office of the High Education Commission and Mahidol University under the National Research Universities Initiative.
文摘This study aimed to develop niosomes of ellagic acid(EA),a potent antioxidant phytochemical substance,for dermal delivery and to investigate the influence of chemical penetration enhancers on the physicochemical properties of EA-loaded niosomes.The EA niosomes were prepared by reverse phase evaporation method using Span 60,Tween 60 and cholesterol as vesicle forming agents and Solulan C24 as a steric stabilizer.Polyethylene glycol 400(PEG)was used as a solubilizer while dimethylsulfoxide(DMSO)or Nmethyl-2-pyrrolidone(NMP)was used as a skin penetration enhancer.It was found that the mean particle sizes of EA-loaded niosomes were in the range of 312e402 nm with PI values of lower than 0.4.The niosomes were determined to be spherical multilamellar vesicles as observed by transmission electron microscope and optical microscopy.All niosomes were stable after 4 months storage at 4C.In vitro skin permeation through human epidermis revealed that the skin enhancers affected the penetration of EA from the niosomes at 24 h.The DMSO niosomes showed the highest EA amount in epidermis;whereas the NMP niosomes had the highest EA amount in the acceptor medium.Concomitantly,the skin distribution by confocal laser scanning microscopy showed the high fluorescence intensity of the DMSO niosomes and NMP niosomes at a penetration depth of between 30e90 mm(the epidermis layer)and 90e120 mm(the dermis layer)under the skin,respectively.From the results,it can be concluded that the DMSO niosomes are suitable for epidermis delivery of EA while the NMP niosomes can be used for dermis delivery of EA.
基金This work was supported by the Key R&D Programmes of Guangdong Province,China(2018B020203003)the National Natural Science Foundation of China(31830090)+1 种基金the Shenzhen Science Technology and Innovation Commission,China(JCYJ20170307160516413)and the Science and Technology Innovation Program of the Chinese Academy of Agricultural Sciences(CAAS-ZDRW202006).We appreciate Postdoctoral Fellow AdeyinkaAbiolaAdetula,for grammar checking and suggestions.
文摘Currently,enhancers have key transcriptional regulatory roles in muscle development.Skeletal muscle formation involves various molecules,and in animals,enhancers are one of the main types of transcriptional regulatory regions that are of great importance to regulate myogenic gene expression.In muscle development,enhancers can generate enhancer RNAs(eRNAs)that are involved in the regulation of gene transcription.The regulation of gene expression by eRNAs offers great potential in improving animal production traits.Herein we comprehensively review the roles of enhancers in muscle formation and its potential function in skeletal muscle development.This review will describe the future application of enhancers in skeletal muscle development and discuss the prospects that enhancer studies offer for agriculture,biotechnology,and animal breeding.
基金supported by the National Natural Science Foundation of China(82125028,U22A20320,31871319,91953114,and 82303108)the Ministry of Science and Technology of China(2020YFA0112300 and 2020YFA0803600)+1 种基金the Shenzhen Science and Technology Program(JCYJ20230807091159001)the Fundamental Research Funds for the Central University(20720190145 and 20720220003).
文摘Estrogen-Related Receptor Alpha(ESRRA)is an orphan nuclear receptor that plays a pivotal role in regulating cellular metabolism,mitochondrial biogenesis,and energy homeostasis through transcriptional control.It has been implicated in diverse physiological processes and diseases,including cancer.However,the transcriptional programs governed by ESRRA and the underlying molecular mechanisms remain incompletely understood.Here,we demonstrate that ESRRA serves as a central regulator in orchestrating the transcriptional activation of estrogen receptorα(ERα)-occupied super enhancers(ERSEs)and cognate ERα-target genes.In parallel,ESRRA represses the expression of cytosolic RNA sensors RIG1 and MDA5,thereby attenuating type I interferon(IFN)signaling and type I IFN-stimulated genes.In terms of mechanism,ESRRA is recruited to ERSEs together with ERαin response to estrogen and their binding to ERSEs occurs in a mutually dependent manner.In contrast,ESRRA directly binds to the promoter regions of RIG1 and MDA5 to suppress their expression.Consistent with these findings,pharmacological inhibition of ESRRA using its inverse agonist XCT790 suppressed estrogen/ERα-induced gene transcription while enhancing type I IFN pathway and antitumor immunity,thereby restraining ERα-positive breast cancer cell growth both in vitro and in vivo.Combination treatment with XCT790 and endocrine therapies,including the ERαantagonist Tamoxifen or degrader Fulvestrant,produced synergistic antitumor effects.Furthermore,co-treatment with XCT790 and tamoxifen re-sensitized Tamoxifen-resistant ERα-positive breast cancer cells to Tamoxifen treatment.In addition,XCT790 treatment augmented the therapeutic efficacy of chemotherapeutic agents such as Doxorubicin in suppressing ERα-positive breast cancer cell growth both in vitro and in vivo.In summary,our findings reveal that ESRRA is a pivotal regulator of ERSEs and estrogen/ERα-target gene activation,as well as the type I IFN signaling pathway,highlighting its potential as a promising therapeutic target in ERα-positive breast cancer in the clinic.
基金supported by the National Natural Science Foundation of China (Grant No. 31671308)the Ministry of Science and Technology of China (Grant No. 2016YFC0900300)
文摘MicroRNAs (miRNAs) are a class of endogenous non-coding RNAs with regulatory functions. Traditionally, miRNAs are thought to play a negative regulatory role in the cytoplasm by binding to the YUTR of target genes to degrade mRNA or inhibit translation. However, it remains a challenge to interpret the potential function of many miRNAs located in the nucleus. Recently, we reported a new type of miRNAs present in the nucleus, which can activate gene expres- sion by binding to the enhancer, and named them nuclear activating miRNAs (NamiRNAs). The discovery of NamiRNAs showcases a complementary regulatory mechanism of miRNA, demon- strating their differential roles in the nucleus and cytoplasm. Here, we reviewed miRNAs in nucleus to better understand the function of NamiRNAs in their interactions with the enhancers. Accord- ingly, we propose a NamiRNA--enhancer-target gene activation network model to better under- stand the crosstalk between NamiRNAs and enhancers in regulating gene transcription. Moreover, we hypothesize that NamiRNAs may be involved in cell identity or cell fate determina- tion during development, although further study is needed to elucidate the underlying mechanisms in detail.
文摘Transdermal drug delivery plays a significant part in the drug delivery system when compared to other routes of drug administration.The function of the stratum corneum(SC)is a barrier.Recently,numerous methods have been thrived to improve the perforation of drugs across the skin.The most effective method is to use enhancers since these agents enhance skin permeability.Natural penetration enhancers like essential oils demonstrate higher enhancement activity and are more widely accepted than synthetic penetration enhancers.High potential in the expansion and interaction with the SC intercellular lipids has led to an increasing interest in these oils as penetration enhancers.This article gives an overview of a few essential oils,including their mode of action and important parameters for permeation improvement.The present work can provide essential oils as alternative enhancers,and this could be useful in transdermal administration.
文摘Transcellular permeation enhancers are known to increase the intestinal permeability of enalaprilat,a 349 Da peptide,but not hexarelin(887 Da).The primary aim of this paper was to investigate if paracellular permeability enhancers affected the intestinal permeation of the two peptides.This was investigated using the rat single-pass intestinal perfusion model with concomitant blood sampling.These luminal compositions included two paracellular permeation enhancers,chitosan(5 mg/mL) and ethylenediaminetetraacetate(EDTA,1 and 5 mg/mL),as well as low luminal tonicity(100 mOsm) with or without lidocaine.Effects were evaluated by the change in lumen-to-blood permeability of hexarelin and enalaprilat,and the blood-to-lumen clearance of ^(51)chromium-labeled EDTA(CL_(Cr-EDTA)),a clinical marker for mucosal barrier integrity.The two paracellular permeation enhancers increased the mucosal permeability of both peptide drugs to a similar extent.The data in this study suggests that the potential for paracellular permeability enhancers to increase intestinal absorption of hydrophilic peptides with low molecular mass is greater than for those with transcellular mechanism-of-action.Further,the mucosal blood-to-lumen flux of ^(51)Cr-EDTA was increased by the two paracellular permeation enhancers and by luminal hypotonicity.In contrast,luminal hypotonicity did not affect the lumen-to-blood transport of enalaprilat and hexarelin.This suggests that hypotonicity affects paracellular solute transport primarily in the mucosal crypt region,as this area is protected from luminal contents by a constant water flow from the crypts.
基金Shaanxi Province Qin Chuangyuan“Scientist+Engineer”Team Construction Project(2022KXJ-071)2022 Qin Chuangyuan Achievement Transformation Incubation Capacity Improvement Project(2022JH-ZHFHTS-0012)+8 种基金Shaanxi Province Key Research and Development Plan-“Two Chains”Integration Key Project-Qin Chuangyuan General Window Industrial Cluster Project(2023QCY-LL-02)Xixian New Area Science and Technology Plan(2022-YXYJ-003,2022-XXCY-010)2024 Scientific Research Project of Shaanxi National Defense Industry Vocational and Technical College(Gfy24-07)Shaanxi Vocational and Technical Education Association 2024 Vocational Education Teaching Reform Research Topic(2024SZX354)National Natural Science Foundation of China(U24A20115)2024 Shaanxi Provincial Education Department Service Local Special Scientific Research Program Project-Industrialization Cultivation Project(24JC005,24JC063)Shaanxi Province“14th Five-Year Plan”Education Science Plan,2024 Project(SGH24Y3181)National Key Research and Development Program of China(2023YFB4606400)Longmen Laboratory Frontier Exploration Topics Project(LMQYTSKT003)。
文摘A dual-phase synergistic enhancement method was adopted to strengthen the Al-Mn-Mg-Sc-Zr alloy fabricated by laser powder bed fusion(LPBF)by leveraging the unique advantages of Er and TiB_(2).Spherical powders of 0.5wt%Er-1wt%TiB_(2)/Al-Mn-Mg-Sc-Zr nanocomposite were prepared using vacuum homogenization technique,and the density of samples prepared through the LPBF process reached 99.8%.The strengthening and toughening mechanisms of Er-TiB_(2)were investigated.The results show that Al_(3)Er diffraction peaks are detected by X-ray diffraction analysis,and texture strength decreases according to electron backscatter diffraction results.The added Er and TiB_(2)nano-reinforcing phases act as heterogeneous nucleation sites during the LPBF forming process,hindering grain growth and effectively refining the grains.After incorporating the Er-TiB_(2)dual-phase nano-reinforcing phases,the tensile strength and elongation at break of the LPBF-deposited samples reach 550 MPa and 18.7%,which are 13.4%and 26.4%higher than those of the matrix material,respectively.
基金supported by the National Key R&D Program of China(2021YFD1201300 to Y.L.and 2021YFA1300404 to J.-K.Z.)the Shanghai Agricultural Science and Technology Innovation Program of China(K2023001 to Y.L.)the National Natural Science Foundation of China(32070396 to Y.L.and 32188102 to J.-K.Z.).
文摘Geneupregulation through genome editing is important for plant research and breeding.Targeted insertion of short transcriptional enhancers(STEs)into gene promoters may offer a universal solution akin to transgene-mediated overexpression while avoiding the drawbacks associated with transgenesis.Here,we introduce an“in locus activation”technique in rice that leverages well-characterized STEs for refined,heritable,and multiplexed gene upregulation.To address the scarcity of potent enhancers,we developed a large-scale mining approach and discovered a suite of STEs that are capable of enhancing gene expression in rice protoplasts.The in locus integration of these STEs into eight rice genes resulted in substantial tran-scriptional upregulation in the edited plants,with up to 869.1-fold increases in their transcript levels.Em-ploying a variety of STEs,we achieved delicate control of gene expression,enabling the fine-tuning of key phenotypic traits such as plant height.Our approach also enabled efficient multiplexed gene upregu-lation,with up to four genes activated simultaneously,significantly enhancing the nicotinamide mononucleotide metabolic pathway.Importantly,heritability studies from the To to T3 generations confirmed the stable and heritable nature of STE-driven gene activation.Collectively,our work demon-strates that coupled with STE mining,leveraging genome editing for in locus activation and gene upregu-lation holds great promise to be widely adopted in fundamental plant research and crop breeding.
基金This work was supported by Basic Research Cultivation Support Programof Fundamental Research Funds for the Central Universities(Grant No.2682021ZTPY016)the National Science and Technology Major Project of Infectious Diseases(Grant No.R111320H01004).
文摘Enhancers are often mutated and dysregulated in various diseases such as cancer.By integrating the function annotation of the mammalian genome(FANTOM)enhancers expression profiles and RNA-seq data from The Cancer Genome Atlas(TCGA)of 13 cancers and their corresponding para-cancerous tissues,we systematically identified a total of 4702 significantly differentially expressed(DE)enhancers.Furthermore,a total of 1036 DE genes regulated by DE enhancerswere identified.Itwas found that in these 13 cancers,most(61.13%)enhancers were ubiquitously expressed,whereas DE enhancers were more likely to be tissue-specific expressed,and the DE genes regulated by DE enhancers were significantly enriched in cancer-related pathways.Finally,it was manifested that 74 single nucleotide polymorphisms(SNPs)were located in 37 DE enhancers,and these SNPs affected the gain and loss of functional transcription factor binding sites of 758 transcription factors,which were shown to be highly correlated with tumorigenesis and development.
基金Funded by the National Natural Science Foundation of China(No.52178216)the Research on the Durability and Application of High-performance Concrete for Highway Engineering in the Cold and Arid Salt Areas of Northwest China(No.2022-24)the Construction Project of the Scientific Research Platform of Provincial Enterprises Supported by the Capital Operating Budget of Gansu Province(No.2023GZ018)。
文摘To study the durability of concrete in harsh environments in Northwest China,concrete was prepared with various durability-improving materials such as concrete anti-erosion inhibitor(SBT-TIA),acrylate polymer(AP),super absorbent resin(SAP).The erosion mode and internal deterioration mechanism under salt freeze-thaw cycle and dry-wet cycle were explored.The results show that the addition of enhancing materials can effectively improve the resistance of concrete to salt freezing and sulfate erosion:the relevant indexes of concrete added with X-AP and T-AP are improved after salt freeze-thaw cycles;concrete added with SBTTIA shows optimal sulfate corrosion resistance;and concrete added with AP displays the best resistance to salt freezing.Microanalysis shows that the increase in the number of cycles decreases the generation of internal hydration products and defects in concrete mixed with enhancing materials and improves the related indexes.Based on the Wiener model analysis,the reliability of concrete with different lithologies and enhancing materials is improved,which may provide a reference for the application of manufactured sand concrete and enhancing materials in Northwest China,especially for the study of the improvement effects and mechanism of enhancing materials on the performance of concrete.
文摘In a series of experiments,Phelps et al.1provided novel data linking moderate-to-vigorous physical activity (MVPA),gut microbiota composition changes and the release of the short chain fatty acid (SCFA) formate,and enhanced antitumor immunity via the transcription factor Nuclear factor erythroid 2-related factor 2 (Nrf2) pathway in cytotoxic CD8+T cells.These data support the growing awareness that the clinical benefits of MVPA are achieved at least in part through enhanced immunity with support from the gut microbiome.
基金supported by Opening funding of National Key Laboratory of Aerospace Liquid Propulsion(HTKJ2024KL011004)Aeronautical Science Fund of China(ASFC-20240042070001)+2 种基金Opening funding of State Key Laboratory of Metal Forming Technology and Heavy Equipment(B2408100.W05)National Key R&D Program of China(2022YFB4601804)National Natural Science Foundation of China(52250287,52275375).
文摘Incorporating ceramic particles into metal matrices is a proven strategy for boosting mechanical properties and wear resistance.The reinforcement potential of tungsten carbide(WC)particles in 316L stainless steel is revealed,utilizing selective laser melting(SLM)to fabricate composites with 5 and 10 vol.%WC.The WC incorporation markedly alters the composite’s microstructure and mechanical attributes.Notably,5 vol.%WC-316L composite exhibits a refined submicron cellular structure,averaging 0.67μm in grain size.Elemental diffusion at WC-316L interface formed a 0.8μm gradient transition layer enriched with M_(2)C carbides(Fe,Cr,W),ensuring robust metallurgical bonding.Compared with unreinforced 316L,5%WC composite exhibits a 70%increase in tensile strength,reaching 1012.6 MPa,and a 25.3%rise in hardness,while maintaining acceptable ductility.10%WC composite achieves a 70.8%hardness enhancement,albeit with reduced elongation.Friction coefficient is reduced by up to 17.3%,and the wear mechanism shifts from adhesive to abrasive,significantly improving wear resistance.
