Genome-wide identification of functional enhancers and their potential roles in pig breeding

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.

Enhancers and hindrances to doctor-nurse interdisciplinary collaborative practice in Nigeria

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.

Novel chemical permeation enhancers for transdermal drug delivery

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.

Influence of chemical penetration enhancers on skin permeability of ellagic acid-loaded niosomes

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 4
C.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.

The enhancing effect and promoting mechanisms of the stereoisomeric monoterpene alcohol esters as enhancers for drugs with different physicochemical properties

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.

The untold story between enhancers and skeletal muscle development

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.

Potential of Essential Oils as Alternative Permeation Enhancers for Transdermal Delivery

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.

Enhanced structural damage behavior of liquid-filled tank by reactive material projectile impact

A series of ballistic experiments were performed to investigate the damage behavior of high velocity reactive material projectiles(RMPs) impacting liquid-filled tanks,and the corresponding hydrodynamic ram(HRAM) was studied in detail.PTFE/Al/W RMPs with steel-like and aluminum-like densities were prepared by a pressing/sintering process.The projectiles impacted a liquid-filled steel tank with front aluminum panel at approximately 1250 m/s.The corresponding cavity evolution characteristics and HRAM pressure were recorded by high-speed camera and pressure acquisition system,and further compared to those of steel and aluminum projectiles.Significantly different from the conical cavity formed by the inert metal projectile,the cavity formed by the RMP appeared as an ellipsoid with a conical front.The RMPs were demonstrated to enhance the radial growth velocity of cavity,the global HRAM pressure amplitude and the front panel damage,indicating the enhanced HRAM and structural damage behavior.Furthermore,combining the impact-induced fragmentation and deflagration characteristics,the cavity evolution of RMPs under the combined effect of kinetic energy impact and chemical energy release was analyzed.The mechanism of enhanced HRAM pressure induced by the RMPs was further revealed based on the theoretical model of the initial impact wave and the impulse analysis.Finally,the linear correlation between the deformation-thickness ratio and the non-dimensional impulse for the front panel was obtained and analyzed.It was determined that the enhanced near-field impulse induced by the RMPs was the dominant reason for the enhanced structural damage behavior.

Loss of LBP triggers lipid metabolic disorder through H3K27 acetylation-mediated C/EBPβ-SCD activation in non-alcoholic fatty liver disease

Non-alcoholic fatty liver disease(NAFLD)is associated with mutations in lipopolysaccharide-binding protein(LBP),but the underlying epigenetic mechanisms remain understudied.Herein,LBP^(-/-)rats with NAFLD were established and used to conduct integrative targetingactive enhancer histone H3 lysine 27 acetylation(H3K27ac)chromatin immunoprecipitation coupled with high-throughput and transcriptomic sequencing analysis to explore the potential epigenetic pathomechanisms of active enhancers of NAFLD exacerbation upon LBP deficiency.Notably,LBP^(-/-)reduced the inflammatory response but markedly aggravated high-fat diet(HFD)-induced NAFLD in rats,with pronounced alterations in the histone acetylome and regulatory transcriptome.In total,1128 differential enhancer-target genes significantly enriched in cholesterol and fatty acid metabolism were identified between wild-type(WT)and LBP^(-/-)NAFLD rats.Based on integrative analysis,CCAAT/enhancer-binding proteinβ(C/EBPβ)was identified as a pivotal transcription factor(TF)and contributor to dysregulated histone acetylome H3K27ac,and the lipid metabolism gene SCD was identified as a downstream effector exacerbating NAFLD.This study not only broadens our understanding of the essential role of LBP in the pathogenesis of NAFLD from an epigenetics perspective but also identifies key TF C/EBPβand functional gene SCD as potential regulators and therapeutic targets.

Steering Against Wind： A New Network of NamiRNAs and Enhancers

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.

Effect of paracellular permeation enhancers on intestinal permeability of two peptide drugs,enalaprilat and hexarelin, in rats

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.

Liquid injectivity in a SAG foam process:Effect of permeability

Foam is utilized in enhanced oil recovery and CO_(2) sequestration.Surfactant-alternating-gas(SAG)is a preferred approach for placing foam into reservoirs,due to it enhances gas injection and minimizes corrosion in facilities.Our previous studies with similar permeability cores show that during SAG injection,several banks occupy the area near the well where fluid exhibits distinct behaviour.However,underground reservoirs are heterogeneous,often layered.It is crucial to understand the effect of permeability on fluid behaviour and injectivity in a SAG process.In this work,coreflood experiments are conducted in cores with permeabilities ranging from 16 to 2300 mD.We observe the same sequence of banks in cores with different permeabilities.However,the speed at which banks propagate and their overall mobility can vary depending on permeability.At higher permeabilities,the gas-dissolution bank and the forced-imbibition bank progress more rapidly during liquid injection.The total mobilities of both banks decrease with permeability.By utilizing a bank-propagation model,we scale up our experimental findings and compare them to results obtained using the Peaceman equation.Our findings reveal that the liquid injectivity in a SAG foam process is misestimated by conventional simulators based on the Peaceman equation.The lower the formation permeability,the greater the error.

Evaluating Ignition and Combustion Performance with Al-Metal- Organic Frameworks and Nano-Aluminum in HTPB Fuel

Incorporating aluminum metal-organic frameworks(Al-MOFs)as energetic additives for solid fuels presents a promising avenue for enhancing combustion performance.This study explores the potential benefits of Al-MOF(MIL-53(Al))energetic additive on the combustion performance of hydroxyl-terminated polybutadiene(HTPB)fuel.The HTPB-MOF fuel samples were manufactured using the vacuum-casting technique,followed by a comprehensive evaluation of their ignition and combustion properties using an opposed flow burner(OFB)setup utilizing gaseous oxygen as an oxidizer.To gauge the effectiveness of Al-MOFs as fuel additives,their impact is compared with that of nano-aluminum(nAl),another traditional additive in HTPB fuel.The results indicate that the addition of 15%(mass fraction)nAl into HTPB resulted in the shortest ignition delay time(136 ms),demonstrating improved ignition performance compared to pure HTPB(273 ms).The incorporation of Al-MOF in HTPB also reduced ignition delay times to 227 ms and 189 ms,respectively.Moreover,under high oxidizer mass flux conditions(79—81 kg/(m^(2)s)),HTPB fuel with 15%nAl exhibited a substantial 83.2%increase in regression rate compared to the baseline HTPB fuel,highlighting the positive influence of nAl on combustion behavior.In contrast,HTPB-MOF with a 15%Al-MOF additive showed a 32.7%increase in regression rate compared to pure HTPB.These results suggest that HTPB-nAl outperforms HTPB-MOF in terms of regression rates,indicating a more vigorous and rapid burning behavior.

Advances in All-Solid-State Lithium-Sulfur Batteries for Commercialization

Solid-state batteries are commonly acknowledged as the forthcoming evolution in energy storage technologies.Recent development progress for these rechargeable batteries has notably accelerated their trajectory toward achieving commercial feasibility.In particular,all-solid-state lithium-sulfur batteries(ASSLSBs)that rely on lithium-sulfur reversible redox processes exhibit immense potential as an energy storage system,surpassing conventional lithium-ion batteries.This can be attributed predominantly to their exceptional energy density,extended operational lifespan,and heightened safety attributes.Despite these advantages,the adoption of ASSLSBs in the commercial sector has been sluggish.To expedite research and development in this particular area,this article provides a thorough review of the current state of ASSLSBs.We delve into an in-depth analysis of the rationale behind transitioning to ASSLSBs,explore the fundamental scientific principles involved,and provide a comprehensive evaluation of the main challenges faced by ASSLSBs.We suggest that future research in this field should prioritize plummeting the presence of inactive substances,adopting electrodes with optimum performance,minimizing interfacial resistance,and designing a scalable fabrication approach to facilitate the commercialization of ASSLSBs.

Broadband Dual-Input Doherty Power Amplifier Design Based on a Simple Adaptive Power Dividing Ratio Function

In this paper,a simple adaptive power dividing function for the design of a dual-input Doherty power amplifier(DPA)is presented.In the presented approaches,the signal separation function(SSF)at different frequency points can be characterized by a polynomial.And in the practical test,the coefficients of SSF can be determined by measuring a small number of data points of input power.Same as other dualinput DPAs,the proposed approach can also achieve high output power and back-off efficiency in a broadband operation band by adjusting the power distribution ratio flexibly.Finally,a 1.5-2.5 GHz highefficiency dual-input Doherty power amplifier is implemented according to this approach.The test results show that the peak power is 48.6-49.7d Bm,and the 6-d B back-off efficiency is 51.0-67.0%,and the saturation efficiency is 52.4-74.6%.The digital predistortion correction is carried out at the frequency points of 1.8/2.1GHz,and the adjacent channel power ratio is lower than-54.5d Bc.Simulation and experiment results can verify the effectiveness and correctness of the proposed method.

Ground threat prediction-based path planning of unmanned autonomous helicopter using hybrid enhanced artificial bee colony algorithm

Unmanned autonomous helicopter(UAH)path planning problem is an important component of the UAH mission planning system.Aiming to reduce the influence of non-complete ground threat information on UAH path planning,a ground threat prediction-based path planning method is proposed based on artificial bee colony(ABC)algorithm by collaborative thinking strategy.Firstly,a dynamic threat distribution probability model is developed based on the characteristics of typical ground threats.The dynamic no-fly zone of the UAH is simulated and established by calculating the distribution probability of ground threats in real time.Then,a dynamic path planning method for UAH is designed in complex environment based on the real-time prediction of ground threats.By adding the collision warning mechanism to the path planning model,the flight path could be dynamically adjusted according to changing no-fly zones.Furthermore,a hybrid enhanced ABC algorithm is proposed based on collaborative thinking strategy.The proposed algorithm applies the leader-member thinking mechanism to guide the direction of population evolution,and reduces the negative impact of local optimal solutions caused by collaborative learning update strategy,which makes the optimization performance of ABC algorithm more controllable and efficient.Finally,simulation results verify the feasibility and effectiveness of the proposed ground threat prediction path planning method.

Finesse measurement for high-power optical enhancement cavity

Finesse is a critical parameter for describing the characteristics of an optical enhancement cavity(OEC). This paper first presents a review of finesse measurement techniques, including a comparative analysis of the advantages, disadvantages, and potential limitations of several main methods from both theoretical and practical perspectives. A variant of the existing method called the free spectral range(FSR) modulation method is proposed and compared with three other finesse measurement methods, i.e., the fast-switching cavity ring-down(CRD) method, the rapidly swept-frequency(SF) CRD method, and the ringing effect method. A high-power OEC platform with a high finesse of approximately 16000 is built and measured with the four methods. The performance of these methods is compared, and the results show that the FSR modulation method and the fast-switching CRD method are more suitable and accurate than the other two methods for high-finesse OEC measurements. The CRD method and the ringing effect method can be implemented in open loop using simple equipment and are easy to perform. Additionally, recommendations for selecting finesse measurement methods under different conditions are proposed, which benefit the development of OEC and its applications.

PAPS: Progressive Attention-Based Pan-sharpening

Pan-sharpening aims to seek high-resolution multispectral(HRMS) images from paired multispectral images of low resolution(LRMS) and panchromatic(PAN) images, the key to which is how to maximally integrate spatial and spectral information from PAN and LRMS images. Following the principle of gradual advance, this paper designs a novel network that contains two main logical functions, i.e., detail enhancement and progressive fusion, to solve the problem. More specifically, the detail enhancement module attempts to produce enhanced MS results with the same spatial sizes as corresponding PAN images, which are of higher quality than directly up-sampling LRMS images.Having a better MS base(enhanced MS) and its PAN, we progressively extract information from the PAN and enhanced MS images, expecting to capture pivotal and complementary information of the two modalities for the purpose of constructing the desired HRMS. Extensive experiments together with ablation studies on widely-used datasets are provided to verify the efficacy of our design, and demonstrate its superiority over other state-of-the-art methods both quantitatively and qualitatively. Our code has been released at https://github.com/JiaYN1/PAPS.

Facile electrochemical surface-alloying and etching of Au wires to enable high-performance substrates for surface enhanced Raman scattering

Surface-enhanced Raman Spectroscopy(SERS)is a nondestructive technique for rapid detection of analytes even at the single-molecule level.However,highly sensitive and reliable SERS substrates are mostly fabricated with complex nanofabrication techniques,greatly restricting their practical applications.A convenient electrochemical method for transforming the surface of commercial gold wires/foils into silver-alloyed nanostructures is demonstrated in this report.Au substrates are treated with repetitive anodic and cathodic bias in an electrolyte of thiourea,in a one-pot one-step manner.X-rays absorption fine structure(XAFS)spectroscopy confirms that the AuAg alloy is induced at the surface.The unique AuAg alloyed surface nanostructures are particularly advantageous when served as SERS substrates,enabling a remarkably sensitive detection of Rhodamine B(a detection limit of 10^(-14)M,and uniform strong response throughout the substrates at 10^(-12)M).

Atomically Substitutional Engineering of Transition Metal Dichalcogenide Layers for Enhancing Tailored Properties and Superior Applications

Transition metal dichalcogenides(TMDs)are a promising class of layered materials in the post-graphene era,with extensive research attention due to their diverse alternative elements and fascinating semiconductor behavior.Binary MX2 layers with different metal and/or chalcogen elements have similar structural parameters but varied optoelectronic properties,providing opportunities for atomically substitutional engineering via partial alteration of metal or/and chalcogenide atoms to produce ternary or quaternary TMDs.The resulting multinary TMD layers still maintain structural integrity and homogeneity while achieving tunable(opto)electronic properties across a full range of composition with arbitrary ratios of introduced metal or chalcogen to original counterparts(0–100%).Atomic substitution in TMD layers offers new adjustable degrees of freedom for tailoring crystal phase,band alignment/structure,carrier density,and surface reactive activity,enabling novel and promising applications.This review comprehensively elaborates on atomically substitutional engineering in TMD layers,including theoretical foundations,synthetic strategies,tailored properties,and superior applications.The emerging type of ternary TMDs,Janus TMDs,is presented specifically to highlight their typical compounds,fabrication methods,and potential applications.Finally,opportunities and challenges for further development of multinary TMDs are envisioned to expedite the evolution of this pivotal field.