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Medical audio classification for lung abnormality diagnosis is a challenging problem owing to comparatively unstructured audio signals present in the respiratory sound clips. To tackle such challenges, we propose an ensemble model by incorporating diverse deep neural networks with attention mechanisms for undertaking lung abnormality and COVID-19 diagnosis using respiratory, speech, and coughing audio inputs. Specifically, four base deep networks are proposed, which include attention-based Convolutional Recurrent Neural Network (A-CRNN), attention-based bidirectional Long Short-Term Memory (A-BiLSTM), attention-based bidirectional Gated Recurrent Unit (A-BiGRU), as well as Convolutional Neural Network (CNN). A Particle Swarm Optimization (PSO) algorithm is used to optimize the training parameters of each network. An ensemble mechanism is used to integrate the outputs of these base networks by averaging the probability predictions of each class. Evaluated using respiratory ICBHI, Coswara breathing, speech, and cough datasets, as well as a combination of ICBHI and Coswara breathing databases, our ensemble model and base networks achieve ICBHI scores ranging from 0.920 to 0.9766. Most importantly, the empirical results indicate that a positive COVID-19 diagnosis can be distinguished to a high degree from other more common respiratory diseases using audio recordings, based on the combined ICBHI and Coswara breathing datasets.

Natural killer (NK) cells can be widely applied for cancer immunotherapy due to their ability to lyse tumor targets without prior sensitization or human leukocyte antigens-matching. Several NK-based therapeutic approaches have been attempted in clinical practice, but their efficacy is not sufficient to suppress tumor development mainly because of lacking specificity. To this end, the engineering of NK cells with T cell receptor along with CD3 subunits (TCR-NK) has been developed to increase the reactivity and recognition specificity of NK cells toward tumor cells. Here, we review recent advances in redirecting NK cells for cancer immunotherapy and discuss the major challenges and future explorations for their clinical applications.

As the largest immune organ of the human body, the intestine also plays a vital role in nutrient digestion and absorption. Some vegetables are considered to have improvement effects on the intestine. This experiment explored the effects of freeze-dried asparagus, broccoli and cabbage powder on the intestinal immune homeostasis and microflora of mice. Thirty-two mice were divided into four groups (n = 8), including control group (fed normal diet), asparagus group (fed normal diet with 5% asparagus power), broccoli group (fed normal diet with 5% broccoli power) and cabbage group (fed normal diet with 5% cabbage power). The experiment lasted 21 days. The results showed that the serum immunoglobulin concentration (IgA and IgM) and intestinal cytokine content (like IFN-γ and TNF-α) were increased after vegetable powder supplement. The experiment also detected that vegetable powder supplementation changed intestinal flora and their metabolites (short-chain fatty acid), which showed that the abundance of Lachnospiraceae and Bacteroides were decreased, while the abundance of Firmicutes and Lactobacillus as well as propionic acid and butyric acid contents were increased. Together, these vegetable powders, especially cabbage, changed the intestinal immune response and microbial activity of mice.

Simple Summary Fusarium crown rot (FCR), caused by a soil-borne fungus Fusarium pseudograminearum, is one of the most destructive diseases of cereal crops, including wheat (Triticum aestivum) in many countries. It is vital to isolate resistance genes for improving crop resistance. Herein, we report the positive function of the wheat DUF26 domain-containing receptor-like kinase TaCRK-7A in the host resistance response to the pathogen F. pseudograminearum attack. The purified TaCRK-7A protein directly inhibited F. pseudograminearum mycelial growth. The TaCRK-7A transcript was elevated upon F. pseudograminearum infection and the transcript induction was higher in resistant wheat genotypes than in susceptible wheat genotypes. Knocking down of TaCRK-7A compromised resistance of wheat to FCR and significantly reduced the transcript levels of defense genes in wheat. This study provides a novel insight into the wheat immune responses to F. pseudograminearum. Abstract The fungus F. pseudograminearum can cause the destructive disease Fusarium crown rot (FCR) of wheat, an important staple crop. Functional roles of FCR resistance genes in wheat are largely unknown. In the current research, we characterized the antifungal activity and positive-regulatory function of the cysteine-rich repeat receptor-like kinase TaCRK-7A in the defense against F. pseudograminearum in wheat. Antifungal assays showed that the purified TaCRK-7A protein inhibited the growth of F. pseudograminearum. TaCRK-7A transcript abundance was elevated after F. pseudograminearum attack and was positively related to FCR-resistance levels of wheat cultivars. Intriguingly, knocking down of TaCRK-7A transcript increased susceptibility of wheat to FCR and decreased transcript levels of defense-marker genes in wheat. Furthermore, the transcript abundances of TaCRK-7A and its modulated-defense genes were responsive to exogenous jasmonate treatment. Taken together, these results suggest that TaCRK-7A can directly inhibit F. pseudograminearum growth and mediates FCR-resistance by promoting the expression of wheat defense genes in the jasmonate pathway. Thus, TaCRK-7A is a potential gene resource in FCR-resistant wheat breeding program.

In the past few decades, biosensors have been gradually developed for the rapid detection and monitoring of human diseases. Recently, functional nucleic-acid (FNA) biosensors have attracted the attention of scholars due to a series of advantages such as high stability and strong specificity, as well as the significant progress they have made in terms of biomedical applications. However, there are few reports that systematically and comprehensively summarize its working principles, classification and application. In this review, we primarily introduce functional modes of biosensors that combine functional nucleic acids with different signal output modes. In addition, the mechanisms of action of several media of the FNA biosensor are introduced. Finally, the practical application and existing problems of FNA sensors are discussed, and the future development directions and application prospects of functional nucleic acid sensors are prospected.

Classical swine fever (CSF) is a highly contagious disease of swine caused by classical swine fever virus (CSFV). For decades the disease has been controlled in China by a modified live vaccine (C-strain) of genotype 1. The emergent genotype 2 strains have become predominant in China in the past years that are genetically distant from the vaccine strain. Here, we aimed to evaluate the current infectious status of CSF, and for this purpose 24 isolates of CSFV were identified from different areas of China during 2016–2018. Phylogenetic analysis of NS5B, E2 and full genome revealed that the new isolates were clustered into subgenotype 2.1d and 2.1b, while subgenotype 2.1d was predominant. Moreover, E2 and Erns displayed multiple variations in neutralizing epitope regions. Furthermore, the new isolates exhibited capacity to escape C-strain-derived antibody neutralization compared with the Shimen strain (genotype 1). Potential positive selection sites were identified in antigenic regions of E2 and Erns, which are related with antibody binding affinity. Recombination events were predicted in the new isolates with vaccine strains in the E2 gene region. In conclusion, the new isolates showed molecular variations and antigenic alterations, which provide evidence for the emergence of vaccine-escaping mutants and emphasize the need of updated strategies for CSF control.

In this research, we propose two Particle Swarm Optimisation (PSO) variants to undertake feature selection tasks. The aim is to overcome two major shortcomings of the original PSO model, i.e., premature convergence and weak exploitation around the near optimal solutions. The first proposed PSO variant incorporates four key operations, including a modified PSO operation with rectified personal and global best signals, spiral search based local exploitation, Gaussian distribution-based swarm leader enhancement, and mirroring and mutation operations for worst solution improvement. The second proposed PSO model enhances the first one through four new strategies, i.e., an adaptive exemplar breeding mechanism incorporating multiple optimal signals, nonlinear function oriented search coefficients, exponential and scattering schemes for swarm leader, and worst solution enhancement, respectively. In comparison with a set of 15 classical and advanced search methods, the proposed models illustrate statistical superiority for discriminative feature selection for a total of 13 data sets.

Alzheimer’s disease (AD) is a neurodegenerative disorder characterized by amyloid beta (Aβ) plaques, neurofibrillary tangles, and neuronal loss. Unfortunately, despite decades of studies being performed on these histological alterations, there is no effective treatment or cure for AD. Identifying the molecular characteristics of the disease is imperative to understanding the pathogenesis of AD. Furthermore, uncovering the key causative alterations of AD can be valuable in developing models for AD treatment. Several alterations have been implicated in driving this disease, including blood–brain barrier dysfunction, hypoxia, mitochondrial dysfunction, oxidative stress, glucose hypometabolism, and altered heme homeostasis. Although these alterations have all been associated with the progression of AD, the root cause of AD has not been identified. Intriguingly, recent studies have pinpointed dysfunctional heme metabolism as a culprit of the development of AD. Heme has been shown to be central in neuronal function, mitochondrial respiration, and oxidative stress. Therefore, dysregulation of heme homeostasis may play a pivotal role in the manifestation of AD and its various alterations. This review will discuss the most common neurological and molecular alterations associated with AD and point out the critical role heme plays in the development of this disease.

The Transmembrane Bax Inhibitor-1 motif (TMBIM)-containing protein family is evolutionarily conserved and has been implicated in cell death susceptibility. The only member with a mitochondrial localization is TMBIM5 (also known as GHITM or MICS1), which affects cristae organization and associates with the Parkinson&rsquo, s disease-associated protein CHCHD2 in the inner mitochondrial membrane. We here used CRISPR-Cas9-mediated knockout HAP1 cells to shed further light on the function of TMBIM5 in physiology and cell death susceptibility. We found that compared to wild type, TMBIM5-knockout cells were smaller and had a slower proliferation rate. In these cells, mitochondria were more fragmented with a vacuolar cristae structure. In addition, the mitochondrial membrane potential was reduced and respiration was attenuated, leading to a reduced mitochondrial ATP generation. TMBIM5 did not associate with Mic10 and Mic60, which are proteins of the mitochondrial contact site and cristae organizing system (MICOS), nor did TMBIM5 knockout affect their expression levels. TMBIM5-knockout cells were more sensitive to apoptosis elicited by staurosporine and BH3 mimetic inhibitors of Bcl-2 and Bcl-XL. An unbiased proteomic comparison identified a dramatic downregulation of proteins involved in the mitochondrial protein synthesis machinery in TMBIM5-knockout cells. We conclude that TMBIM5 is important to maintain the mitochondrial structure and function possibly through the control of mitochondrial biogenesis.

Bexarotene (BEX), a specific retinoic acid X receptor (RXR) agonist granted by Food and Drug Administration (FDA) approval for the clinical treatment of T cell lymphoma, has now been found to exert pharmacological effects in the nervous system, with low bioavailability and poor cerebral distribution limiting its application in treatment on neurological disorders. Pharmaceutical co-crystal was a helpful method to improve the bioavailability and tissue distribution of active pharmaceutical ingredients (APIs). Here, 2bexarotene-ligustrazine (2BEX-LIG), a novel co-crystal system of BEX and ligustrazine (LIG) of which with BEX is an API, was constructed with satisfactory stability and enhanced solubility. The pharmacokinetics characteristics of BEX were detected, and the results showed that the absolute bioavailability and the cerebral concentration of BEX in rats administrated with 2BEX-LIG were enhanced from 22.89% to 42.86% and increased by 3.4-fold, respectively, compared with those in rats administrated an equivalent of BEX. Hence, our present study indicated that the novel co-crystal of 2BEX-LIG contributed to improving BEX oral bioavailability and cerebral distribution, thereby providing significant advantages for clinical application of brain tumors and other neurological diseases.

The use of prebiotics to regulate gut microbiota is a promising strategy to improve gut health. Pectin (PEC) is a prebiotic carbohydrate that enhances the health of the gut by promoting the growth of beneficial microbes. These microbes produce metabolites that are known to improve mucosal immune responses. This study was conducted to better understand effects of PEC on the microbiome and mucosal immunity in pigs. Pigs were fed two diets, with or without 5% apple PEC, for 72 days. Effects of PEC on the microbiota, cytokine expression, short-chain fatty acids (SCFAs) concentration and barrier function were examined in the ileum and cecum of the pigs. An integrative analysis was used to determine interactions of PEC consumption with bacterial metabolites and microbiome composition and host mucosal responses. Consumption of PEC reduced expression of pro-inflammatory cytokines such as IFN-&gamma, IL-6, IL-8, IL-12 and IL-18, and the activation of the pro-inflammatory NF-&kappa, B signaling cascade. Expression of MUC2 and TFF and the sIgA content was upregulated in the mucosa of PEC-fed pigs. Network analysis revealed that PEC induced significant interactions between microbiome composition in the ileum and cecum on mucosal immune pathways. PEC-induced changes in bacterial genera and fermentation metabolites, such as Akkermansia, Faecalibacterium, Oscillibacter, Lawsonia and butyrate, correlated with the differentially expressed genes and cytokines in the mucosa. In summary, the results demonstrate the anti-inflammatory properties of PEC on mucosal immune status in the ileum and cecum effected through modulation of the host microbiome.

The volatile components of milks fermented using traditional starter cultures (Streptococcus thermophilus and Lactobacillus bulgaricus) and probiotics (Lactobacillus lactis, Lactobacillus bifidus, Lactobacillus casei, and Lactobacillus plantarum) were investigated by means of gas chromatography-mass spectrometry (GC-MS) combined with simultaneous distillation extraction (SDE). A total of 53 volatile compounds were detected, being 10 aldehydes, 11 ketones, 10 acids, 11 hydrocarbons, 7 benzene derivatives, and 4 other compounds. The starter culture was found to significantly affect the composition of volatile components in the fermented milks. Ketones and hydrocarbons were the dominant compounds in milk before fermentation, while acids were dominant compounds in the fermented samples. Compared with probiotics, there was greater abundance of volatile components in fermented milks with traditional strains. The importance of each volatile compound was assessed on the basis of odor, thresholds, and odor activity values (OAVs). Of the volatile compounds, 31 of them were found to be odor-active compounds (OAV &gt, 1). The component with the highest OAVs in most samples was (E,E)-2,4-decadienal. Heatmap analysis and principal component analysis were employed to characterize the volatile profiles of milks fermented by different starter cultures. The results could help to better understand the influence of starter cultures on the odor quality of milks.

Vip3Aa, a soluble protein produced by certain Bacillus thuringiensis strains, is capable of inducing apoptosis in Sf9 cells. However, the apoptosis mechanism triggered by Vip3Aa is unclear. In this study, we found that Vip3Aa induces mitochondrial dysfunction, as evidenced by signs of collapse of mitochondrial membrane potential, accumulation of reactive oxygen species, release of cytochrome c, and caspase-9 and -3 activation. Meanwhile, our results indicated that Vip3Aa reduces the ability of lysosomes in Sf9 cells to retain acridine orange. Moreover, pretreatment with Z-Phe-Tyr-CHO (a cathepsin L inhibitor) or pepstatin (a cathepsin D inhibitor) increased Sf9 cell viability, reduced cytochrome c release, and decreased caspase-9 and -3 activity. In conclusion, our findings suggested that Vip3Aa promotes Sf9 cell apoptosis by mitochondrial dysfunction, and lysosomes also play a vital role in the action of Vip3Aa.

A micro-reciprocating piston internal combustion engine with liquid hydrocarbon fuel has the potential to supply ultrahigh density energy to micro electro mechanical system because of its high-density energy, simple structure, and mature energy conversion principle. However, the diagnostic test of the combustion characteristics of the micro reciprocating piston internal combustion engine shows that its combustion characteristics are poor, and the combustion rate was lower with the combustion duration of more than 50 &deg, CA. The mean indicated pressure (Pmi) value was only 0.137 MPa, the combustion stability was very poor, and the cycle variation rate of the Pmi was up to 60%. To improve its combustion performance, the method to enhance combustion in micro-space is explored then. Mechanism studies have shown that the pyrolysis reaction of nitromethane and hydrogen peroxide can produce amounts of free radicals OH, with the possibility of improving the combustion of methanol. Therefore, a method for adjusting the composition of methanol fuel to enhance combustion is proposed, and the method is theoretically confirmed. Finally, based on this method, the test was carried out. The results showed that the combustion rate increased and the combustion duration decreased by 6% after adding nitromethane. The power performance was enhanced, and the Pmi value was increased by 30%. The combustion stability was enhanced, and the cycle variation rate of the Pmi was reduced to 16.9%. Nitromethane has a significant effect on improving the combustion characteristics of methanol, and the enhancement of the latter was mainly reflected in the ignition phase of the combustion process. This study indicates that exploring the fuel additive that can increase the concentration of OH radical in the reaction is an effective method to improve the micro-space combustion, which will facilitate the development of micro-piston internal combustion engine to supply energy to a micro electro mechanical system.

Fire and smoke suppressions of polyvinyl alcohol (PVA) aerogels are urgently required due to the serious fire hazard they present. MXene, a 2D transition-metal carbide with many excellent properties, is considered a promising synergist for providing excellent flame retardant performance. PVA/ammonium polyphosphate (APP)/transition metal carbide (MXene) composite aerogels were prepared via the freeze-drying method to enhance the flame retardancy. Thermogravimetric analysis, limiting oxygen index, vertical burning, and cone calorimeter tests were executed to investigate the thermal stability and flame retardancy of PVA/APP/MXene (PAM) composite aerogels. The results demonstrated that MXene boosted the flame retardancy of PVA-APP, and that PAM-2 (with 2.0 wt% MXene loading) passed the V-0 rating, and reached a maximum LOI value of 42%, Moreover, MXene endowed the PVA-APP system with excellent fire and smoke suppression performance, as the the peak heat release rate and peak smoke production rate were significantly reduced by 55% and 74% at 1.0 wt% MXene loading. The flame retardant mechanism was systematically studied, MXene facilitated the generation of compact intumescent residues via ita catalyst effects, thus further restraining the release of heat and smoke. This work provides a simple route to improve the flame retardancy of PVA aerogels via the synergistic effect of MXene and APP.

A multidrug crystal based on drug combinations was synthesized by the solvent evaporation method. This multicomponent crystal consisted of antidiabetic drugs Glimepiride (Gli) and Metformin (Met), which was performed by single crystal X-ray structure analysis. The results showed an enhancement of the pharmaceutical properties such as lower hygroscopicity and greater accelerated stability than the parent drug Met, and a higher solubility and dissolution rate than Gli.

Marine sediments can reserve many environmental pollutants. Lipophilic marine phycotoxins (LMPs) are natural toxic substances widespread in the marine environment, however, evidence of their existence in sediment is scarce. In the present study, in order to explore the occurrence and distribution characteristics of LMPs in sediment, surface sediment samples collected from a tropical area of Daya Bay (DYB) at different seasons, were analyzed using liquid chromatography with tandem mass spectrometry (LC-MS/MS). According to the results, up to six toxin compounds were detected in sediment samples from DYB, OA and DTX1 had the highest levels, followed by PTX2, homo-YTX, AZA2, and GYM. Although AZA2 and GYM were found in most of the sediment, OA, DTX1, homo-YTX, and PTX2 were the predominant toxin compounds, and PTX2 was the most ubiquitous toxin in sediment. The spatial distribution of LMP components in the sediment fluctuated with sampling times, partially according to the physical&ndash, chemical parameters of the sediment. There are likely several sources for LMPs existing in surface sediments, but it is difficult to determine contributions of a specific toxin-source in the sediment. Therefore, marine sediments may be a toxin reservoir for LMPs accumulation in benthic organisms via food chains.

Discharge regime transition in a single pulse can present the breakdown mechanism of nanosecond pulsed dielectric barrier discharge. In this paper, regime transitions between streamer, diffuse, and surface discharges in nanosecond pulsed dielectric barrier discharge are studied experimentally using high resolution temporal&ndash, spatial spectra and instantaneous exposure images. After the triggering time of 2&ndash, 10 ns, discharge was initiated with a stable initial streamer channel propagation. Then, transition of streamer-diffuse modes could be presented at the time of 10&ndash, 34 ns, and a surface discharge can be formed sequentially on the dielectric plate. In order to analyze the possible reason for the varying discharge regimes in a single discharge pulse, the temporal&ndash, spatial distribution of vibrational population of molecular nitrogen N2 (C3&Pi, u, v = 0,1,2) and reduced electric field were calculated by the temporal&ndash, spatial emission spectra. It is found that at the initial time, a distorted high reduced electric field was formed near the needle electrode, which excited the initial streamer. With the initial streamer propagating to the dielectric plate, the electric field was rebuilt, which drives the transition from streamer to diffuse, and also the propagation of surface discharge.

Background: White adipose tissue (WAT) browning confers beneficial effects on metabolic diseases. However, visceral adipose tissue (VAT) is not as susceptible to browning as subcutaneous adipose tissue (SAT). Aim: Interpreting the heterogeneity of VAT and SAT in brown remodeling and provide promising lipid targets to promote WAT browning. Methods: We first investigated the effects of &beta, 3-adrenergic stimulation by CL316,243 on systemic metabolism. Then, high-coverage targeted lipidomics approach with multiple reaction monitoring (MRM) was utilized to provide extensive detection of lipid metabolites in VAT and SAT. Results: CL316,243 notably ameliorated the systemic metabolism and induced brown remodeling of SAT but browning resistance of VAT. Comprehensive lipidomics analysis revealed browning heterogeneity of VAT and SAT with more dramatic alteration of lipid classes and species in VAT rather than SAT, though VAT is resistant to browning. Adrenergic stimulation differentially affected glycerides content in VAT and SAT and boosted the abundance of more glycerophospholipids species in VAT than in SAT. Besides, CL316,243 increased sphingolipids in VAT without changes in SAT, meanwhile, elevated cardiolipin species more prominently in VAT than in SAT. Conclusions: We demonstrated the browning heterogeneity of WAT and identified potential lipid biomarkers which may provide lipid targets for overcoming VAT browning resistance.

Signal transducer and activator of transcription 3 (STAT3) is a multifunctional factor that regulates inflammation and immunity. Knowledge of its regulatory mechanisms is very limited. Here, we showed that enterovirus 71 (EV71) infection induced the phosphorylation of STAT3 and the expression of its downstream inflammatory regulators. Knockdown of STAT3 with siRNAs significantly restricted viral RNA and protein levels, and also reduced viral titers. With further investigation, we found that importin &alpha, family member Karyopherin-&alpha, 1 (KPNA1) was employed by both STAT1 and STAT3 for their nuclear import. The phosphorylated and un-phosphorylated STAT3 competed with STAT1 for binding to the decreased KPNA1 post infection and repressed downstream ISG expression. STAT3 knockdown alleviated the repressed type I IFN-mediated antiviral response upon infection and led to decreased viral replication. Taken together, our data suggested the role of STAT3 in maintaining the balance of inflammation and antiviral responses in the central nervous system (CNS) upon infection.

&beta, N-Acetyl-d-hexosaminidase from Ostrinia furnacalis (OfHex1) is a new target for the design of insecticides. Although some of its inhibitors have been found, there is still no commercial drug available at present. The residence time of the ligand may be important for its pharmacodynamic effect. However, the unbinding routes of ligands from OfHex1 still remain largely unexplored. In the present study, we first simulated the six dissociation routes of N,N,N-trimethyl-d-glucosamine-chitotriomycin (TMG-chitotriomycin, a highly selective inhibitor of OfHex1) from the active pocket of OfHex1 by steered molecular dynamics simulations. By comparing the potential of mean forces (PMFs) of six routes, Route 1 was considered as the most possible route with the lowest energy barrier. Furthermore, the structures of six different states for Route 1 were snapshotted, and the key amino acid residues affecting the dissociated time were analyzed in the unbinding pathway. Moreover, we also analyzed the &ldquo, open&ndash, close&rdquo, mechanism of Glu368 and Trp448 and found that their conformational changes directly affected the dissociation of TMG-chitotriomycin. Our findings would be helpful to understanding and identifying novel inhibitors against OfHex1 from virtual screening or lead-optimization.

Circular RNA (circRNA), a kind of special endogenous RNA, has been shown to be implicated in crucial biological processes of multiple cancers as a gene regulator. However, the functional roles of circRNAs in breast cancer (BC) remain to be poorly explored, and relatively incomplete knowledge of circRNAs handles the identification and prediction of BC-related circRNAs. Towards this end, we developed a systematic approach to identify circRNA modules in the BC context through integrating circRNA, mRNA, miRNA, and pathway data based on a non-negative matrix factorization (NMF) algorithm. Thirteen circRNA modules were uncovered by our approach, containing 4164 nodes (80 circRNAs, 2703 genes, 63 miRNAs and 1318 pathways) and 67,959 edges in total. GO (Gene Ontology) function screening identified nine circRNA functional modules with 44 circRNAs. Within them, 31 circRNAs in eight modules having direct relationships with known BC-related genes, miRNAs or disease-related pathways were selected as BC candidate circRNAs. Functional enrichment results showed that they were closely related with BC-associated pathways, such as &lsquo, KEGG (Kyoto Encyclopedia of Genes and Genomes) PATHWAYS IN CANCER&rsquo, &lsquo, REACTOME IMMUNE SYSTEM&rsquo, and &lsquo, KEGG MAPK SIGNALING PATHWAY&rsquo, KEGG P53 SIGNALING PATHWAY&rsquo, or &lsquo, KEGG WNT SIGNALING PATHWAY&rsquo, and could sever as potential circRNA biomarkers in BC. Comparison results showed that our approach could identify more BC-related functional circRNA modules in performance. In summary, we proposed a novel systematic approach dependent on the known disease information of mRNA, miRNA and pathway to identify BC-related circRNA modules, which could help identify BC-related circRNAs and benefits treatment and prognosis for BC patients.

The strength of Mg&ndash, Li alloy is greatly improved by the composite strengthening of intermetallic compound YAl2 particles, but the low corrosion resistance of Mg&ndash, Li alloy is still the main factor that restricts the application of the alloy and its composites. In this paper, the effect of YAl2 particles on the corrosion behavior of Mg&ndash, Li alloy was systematically investigated. The results showed that the corrosion resistance of YAl2p/LA143 composite could be significantly improved, accounting for the formation of a transitional interface layer by adding YAl2 particles. The diffusion of yttrium and aluminum atoms from YAl2 particulates improved the stability of the surface film and enhanced the adhesion between the corrosion products and the substrate, which hindered further expansion of pitting.

Background In China, income levels and living standards have improved significantly, but many Chinese citizens still do not feel any happier. This phenomenon may be attributed to increased income inequality. Methods Using data from the 2013 Chinese General Social Survey (CGSS), we employed multilevel structural equation modeling (MSEM) to investigate the impact of county-level income inequality on individual-level happiness in China and multilevel mediation analysis with structural equation modeling (MMSEM) to explore the mechanisms through which income inequality impacted happiness. Results A negative relationship between income inequality and happiness was found. The negative association between them was explained by two psychological mechanisms, i.e., fairness and trust. The findings explained a &ldquo, Chinese puzzle,&rdquo, i.e., why people do not feel happier despite improved income and living standards. Conclusions Our findings may provide a reference for policy makers to implement policies designed to improve individual happiness. What is important now is to reduce income inequality, and to potentially improve perceptions of fairness and trust in China.

In the past decades, we have witnessed dramatic changes in clinical diagnoses and treatments due to the revolutions of genomics and personalized medicine. Undoubtedly we also met many challenges when we use those advanced technologies in drug discovery and development. In this review, we describe when genomic information is applied in personal healthcare in general. We illustrate some case examples of genomic discoveries and promising personalized medicine applications in the area of neurological disease particular. Available data suggest that individual genomics can be applied to better treat patients in the near future.

The radiation effects of three Er3+-doped superfluorescent fiber sources (SFSs), which are based on three segments of Er-doped fibers with different lengths, are studied experimentally. We observed that the radiation-induced attenuation of the signal light of the 1530 nm band for an SFS is less than that of the 1560 nm band. Thus, the trimming technique of the Gauss-like spectra is investigated to reduce the mean wavelength drift. A filter was customized and used in superfluorescent fiber sources. To further reduce output power loss, the method with feedback control of pump power was adopted in the SFS. Then, the trimming spectral SFS with pump feedback control was tested under irradiation environment at the dose rate of 2.988 Gy/h. The experimental results demonstrate that the mean wavelength drift is &lt, 40 ppm and the loss of output power is &lt, 0.2 dB under a total dose higher than 1000 Gy. These findings confirm the significance of the method in improving radiation-resistant capabilities of fiber sources under irradiation environments.

A series of novel chiral nonmetallocene pincer-type rare-earth metal dialkyl complexes bearing the chiral monoanionic tridentate C2-symmetric 1,3-bis(oxazolinymethylidene)isoindoline (BOXMI-H) ligand (BOXMI)Ln(CH2SiMe3)2 1–3 (1: Ln = Sc, yield = 57%; 2: Ln = Lu, yield = 55%; 3: Ln = Y, yield = 62%) have been prepared in moderate yields via the acid-base reaction between the BOXMI ligand and rare-earth metal tri(trimethylsilylmethyl) complexes. The X-ray diffractions show that both of the complexes 1 and 2 contain one BOXMI ligand and two trimethylsilylmethyl ligands, adopting a distorted trigonal bipyramidal configuration. In the presence of a cocatalyst such as borate and AlR3, these complexes 1–3 exhibit high activities of up to 6.8 × 104 (g of polymer)/(molLn h) and high cis-1,4 selectivities of up to 97% in the polymerization of isoprene in toluene, yielding the cis-1,4-polyisoprenes with heavy molecular weights (Mn of up to 710,000 g/mol) and bimodal molecular weight distributions (Mw/Mn = 2.0–4.5).

Astaxanthin (ATX) is a xanthophyll carotenoid which has been approved by the United States Food and Drug Administration (USFDA) as food colorant in animal and fish feed. It is widely found in algae and aquatic animals and has powerful anti-oxidative activity. Previous studies have revealed that ATX, with its anti-oxidative property, is beneficial as a therapeutic agent for various diseases without any side effects or toxicity. In addition, ATX also shows preclinical anti-tumor efficacy both in vivo and in vitro in various cancer models. Several researches have deciphered that ATX exerts its anti-proliferative, anti-apoptosis and anti-invasion influence via different molecules and pathways including signal transducer and activator of transcription 3 (STAT3), nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) and peroxisome proliferator-activated receptor gamma (PPARγ). Hence, ATX shows great promise as chemotherapeutic agents in cancer. Here, we review the rapidly advancing field of ATX in cancer therapy as well as some molecular targets of ATX.

Insulin resistance and obesity is influenced by the retinol binding protein 4 (RBP4) adipokine. This study aims to determine if genetic polymorphisms in RBP4 are associated with the risk of coronary artery disease (CAD) in Chinese patients. RBP4 polymorphisms were analyzed by high resolution melting (HRM) analysis in a case-control study of 392 unrelated CAD patients and 368 controls from China. The Gensini score was used to determine the severity of CAD. The genotypic and allelic frequencies of RBP4 single-nucleotide polymorphisms were evaluated for associations with CAD and severity of disease. The A allele frequency was significantly higher in CAD case groups compared to control groups (16.7% vs. 8.8%) at the RBP4 rs7094671 locus. Compared to the G allele, this allele was associated with a higher risk of CAD (OR = 2.07 (1.50–2.84)). Polymorphisms at rs7094671 were found to associate with CAD using either a dominant or recessive model (OR, 95% CI: 1.97, 1.38–2.81, 3.81, 1.53–9.51, respectively). Adjusting for sex, history of smoking, serum TC, TG, LDL-c, and HDL-c, the risk of CAD for carriers remained significantly higher in both dominant and recessive models (OR, 95% CI: 1.68, 1.12–2.51, 2.74, 1.00–7.52, respectively). However, this SNP was not significantly associated with severity of CAD using angiographic scores in multivariable linear regression models (p = 0.373). The RBP4 rs7094671 SNP is associated with CAD, however, our results do not indicate that this locus is associated with clinical severity of CAD or the extent of coronary lesions.

Both the gene expression and activity of water channel protein can control transmembrane water movement. We have reported the overexpression of CaTIP1-1, which caused a decrease in chilling tolerance in transgenic plants by increasing the size of the stomatal pore. CaTIP1-1 expression was strongly induced by salt and mannitol stresses in pepper (Capsicum annuum). However, its biochemical and physiological functions are still unknown in transgenic tobacco. In this study, transient expression of CaTIP1-1-GFP in tobacco suspension cells revealed that the protein was localized in the tonoplast. CaTIP1-1 overexpressed in radicle exhibited vigorous growth under high salt and mannitol treatments more than wild-type plants. The overexpression of CaTIP1-1 pepper gene in tobacco enhanced the antioxidant enzyme activities and increased transcription levels of reactive oxygen species-related gene expression under osmotic stresses. Moreover, the viability of transgenic tobacco cells was higher than the wild-type after exposure to stress. The pepper plants with silenced CaTIP1-1 in P70 decreased tolerance to salt and osmotic stresses using the detached leaf method. We concluded that the CaTIP1-1 gene plays an important role in response to osmotic stresses in tobacco.

The complete chloroplast genome of Artemisia annua (Asteraceae), the primary source of artemisinin, was sequenced and analyzed. The A. annua cp genome is 150,995 bp, and harbors a pair of inverted repeat regions (IRa and IRb), of 24,850 bp each that separate large (LSC, 82,988 bp) and small (SSC, 18,267 bp) single-copy regions. Our annotation revealed that the A. annua cp genome contains 113 genes and 18 duplicated genes. The gene order in the SSC region of A. annua is inverted; this fact is consistent with the sequences of chloroplast genomes from three other Artemisia species. Fifteen (15) forward and seventeen (17) inverted repeats were detected in the genome. The existence of rich SSR loci in the genome suggests opportunities for future population genetics work on this anti-malarial medicinal plant. In A. annua cpDNA, the rps19 gene was found in the LSC region rather than the IR region, and the rps19 pseudogene was absent in the IR region. Sequence divergence analysis of five Asteraceae species indicated that the most highly divergent regions were found in the intergenic spacers, and that the differences between A. annua and A. fukudo were very slight. A phylogenetic analysis revealed a sister relationship between A. annua and A. fukudo. This study identified the unique characteristics of the A. annua cp genome. These results offer valuable information for future research on Artemisia species identification and for the selective breeding of A. annua with high pharmaceutical efficacy.

Plastome-genome incompatibility (PGI) is prevalent in several plants including the Zantedeschia species, a worldwide commercial flower crop native to South Africa. Generally, hybrids suffering from PGI appear less vigorous and more susceptible than normal plants. Previous reports revealed that the PGI level in interspecific hybrids is correlated with the relatedness of the parental species in the genus Zantedeschia. To provide a basis for utilizing and improving resources in breeding programs, a total of 117 accessions of colored calla lily (Zantedeschia hybrid), collected from New Zealand, the Netherlands and the United States, were genotyped using 31 transferable expressed sequence tags-simple sequence repeats (EST-SSR) markers from the white calla lily (Zantedeschia aethiopica). A moderately high level of genetic diversity was observed, with 111 alleles in total, an observed/expected heterozygosity (Ho/He) of 0.453/0.478, and polymorphism information content (PIC) of 0.26. Genetic distance and STRUCTURE-based analysis further clustered all accessions into four subgroups (G-Ia, G-Ib, G-IIa and G-IIb), which mostly consisted of Zantedeschia pentlandii, Zantedeschia elliotiana, Zantedeschia albomaculata and Zantedeschia rehmannii, respectively. Significant genetic differentiation was observed between all inferred subgroup pairs, with the Fst ranging from 0.142 to 0.281. Finally, the accessions assigned into G-IIb (Z. rehmannii) were recommended as top priority parents in efficient Zantedeschia breeding program designs.

Ligustri Lucidi Fructus (LLF), the fruit of Ligustrum lucidum Ait. (Oleaceae), has been used as a common herbal medicine in clinical practice in China for nearly 2000 years. In most cases, LLF is prescribed in decoctions in the form of processed products rather than crude drugs. In this study, an ultra-high performance liquid chromatography coupled with electrospray ionization-quadrupole-time of flight-mass spectrometry (UHPLC-ESI-Q-TOF-MS) method was established for rapid separation and identification of multiple constituents in the 80% methanol extract of processed-LLF. A total of 50 compounds (one phenylethanoid, seven phenylethanoid glycosides, seven flavonoids, 25 iridoids, nine triterpenoids and one cyclohexanecarboxylic acid) were either unambiguously identified or tentatively characterized with the aid of authentic standards or published data. Luteolin-7-O-rutinoside, oleoside and secologanoside were detected in LLF for the first time. This study enriches the chemical profiling of processed-LLF and could provide valuable information for the quality control and further investigation of processed-LLF and crude LLF.