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Oxygen reduction reaction (ORR) is an important half-reaction in various energy devices such as fuel cells. Here, 2D dendritic Fe/N co-doped carbon-based nanosheet composites (L-Fe-CNT@NCS-900) were obtained by high-temperature calcination using ZIF-L generated in the aqueous phase as a precursor and Vitamin C as a modifier. It is found that the catalysts calcined at 900℃ possessed the large specific surface area and the pore size distribution graphs showed a narrow micropore size distribution centered at about 1.8 nm. Furthermore, the Fe-N-C species was detected, which further improved the ORR performance as an active center. Thus, the L-Fe-CNT@NCS-900 calcined at 900 °C achieved the best ORR performance with a half-wave potential (E1/2) of 0.85 V, and the hydrogen peroxide yield is only about 4% during the ORR process. Meanwhile, L-Fe-CNT@NCS-900 exhibited outstanding methanol resistance. This work proposes a new strategy for constructing an efficient electrocatalysts for oxygen reduction reaction. [ABSTRACT FROM AUTHOR]

Electric eel is an excellent example to harness ion-concentration gradients for sustainable power generation. However, current strategies to create electric-eel-inspired power sources commonly involve manual stacking of multiple salinity-gradient power source units, resulting in low efficiency, unstable contact, and poor flexibility. Here we propose a consecutive multimaterial printing strategy to efficiently fabricate biomimetic ionic hydrogel power sources with a maximum stretchability of 137%. The consecutively-printed ionic hydrogel power source filaments showed seamless bonding interface and can maintain stable voltage outputs for 1000 stretching cycles at 100% strain. With arrayed multi-channel printhead, power sources with a maximum voltage of 208 V can be automatically printed and assembled in parallel within 30 min. The as-printed flexible power source filaments can be woven into a wristband to power a digital wristwatch. The presented strategy provides a tool to efficiently produce electric-eel-inspired ionic hydrogel power sources with great stretchability for various flexible power source applications. Electric eels are an excellent example of harnessing ion-concentration gradient for power generation. Here, authors demonstrate an automatic and high-throughput consecutive multi-material printing strategy to fabricate electric-eel-inspired ionic hydrogel power sources with high stretchability. [ABSTRACT FROM AUTHOR]

Exploration of highly efficient non-noble metal oxygen reduction reaction (ORR) catalysts is essential for the widespread industrial utilization of fuel cells. Herein, we demonstrated a hierarchical porous catalyst (denoted as Fe-NC-Gs) using a simple stirring and one-step pyrolysis method. ZIF-8-derived N-doped carbon framework loaded on graphene oxide, on which Fe3O4 and FeS nanoparticles are uniformly dispersed. In the composite nanostructure, a high surface area (470.58 m2 g−1) and hierarchical porous structure were observed. The obtained Fe-NC-G-2 exhibits superior ORR properties. The half-wave potential (E1/2) and the limiting current density in alkaline media were up to 0.85 V and − 5.39 mA cm−2, respectively, comparable to the commercially available Pt/C. The four-electron-dominated process was exhibited in the ORR catalysis. It also manifests a better methanol tolerance and electrochemical stability during the chronoamperometry measurement in 0.1 M KOH. These results suggest that the proposed strategy provides a new pathway to construct efficient electrocatalysts for ORR. [ABSTRACT FROM AUTHOR]

Background: Babesia orientalis is an intra-erythrocytic protozoan parasite that causes babesiosis in water buffalo. The genome of B. orientalis has been reported and various genes have been accurately annotated, including heat shock proteins (HSP). Three B. orientalis HSPs (HSP90, HSP70 and HSP20) have been previously identified as potential antigenic targets. Here, a new validation strategy for the chaperone activities and cell protection characteristics of the three HSPs was developed in vitro. Methods: BoHSP20, BoHSP70 and BoHSP90B were amplified from cDNA, followed by cloning them into the pEGFP-N1 vector and transfecting the vector plasmid separately into 293T and Hela mammalian cells. Their expression and localization were determined by fluorescence microscopy. The biological functions and protein stability were testified through an analysis of the fluorescence intensity duration. Their role in the protection of cell viability from heat-shock treatments was examined by MTT assay (cell proliferation assay based on thiazolyl blue tetrazolium bromide). Results: Fusion proteins pEGFP-N1-BoHSP20, pEGFP-N1-BoHSP70, and pEGFP-N1-BoHSP90B (pBoHSPs: pBoHSP20; pBoHSP70 and pBoHSP90B) were identified as 47 kDa/97 kDa/118 kDa with a 27 kDa GFP tag, respectively. Prolonged fluorescent protein half-time was observed specifically in pBoHSPs under heat shock treatment at 55 °C, and BoHSP20 showed relatively better thermotolerance than BoHSP70 and BoHSP90B. Significant difference was found between pBoHSPs and controls in the cell survival curve after 2 h of 45 °C heat shock. Conclusion: Significant biological properties of heat stress-associated genes of B. orientalis were identified in eukaryote by a new strategy. Fusion proteins pBoHSP20, pBoHSP70 and pBoHSP90B showed good chaperone activity and thermo-stability in this study, implying that BoHSPs played a key role in protecting B. orientalis against heat-stress environment during parasite life cycle. In conclusion, the invitro model explored in this study provides a new way to investigate the biological functions of B. orientalis proteins during the host–parasite interaction. [ABSTRACT FROM AUTHOR]

Gene editing technology is regarded as a good news to save patients with genetic diseases because of its significant function of specifically changing genetic information. From zinc-finger proteins to transcription activator-like effector protein nucleases gene editing tools are constantly updated. At the same time, scientists are constantly developing a variety of new gene editing therapy strategies, in order to promote gene editing therapy from various aspects and realize the maturity of the technology as soon as possible. In 2016, CRISPR-Cas9-mediated CAR-T therapy was the first to enter the clinical trial stage, indicating that the use of CRISPR-Cas system as the blade of the genetic lancet to save patients is officially on the schedule. The first challenge to achieve this exciting goal is to improve the security of the technology. This review will introduce the gene security issues faced by the CRISPR system as a clinical treatment tool, the current safer delivery methods and the newly developed CRISPR editing tools with higher precision. Many reviews summarize the means of improving the security of gene editing therapy and the comprehensive delivery method, while few articles focus on the threat of gene editing to the genomic security of the treatment target. Therefore, this review focuses on the risks brought by gene editing therapy to the patient genome, which provides a broader perspective for exploring and improving the security of gene editing therapy from two aspects of delivery system and CRISPR editing tools. [ABSTRACT FROM AUTHOR]

Previous studies on the association between metals and dyslipidemia are not completely consistent. There are few studies investigating the relationship between mixed metal exposure and dyslipidemia as well as the effects of metals on dyslipidemia in community-dwelling elderly. To evaluate the correlations and interaction effect between the urinary concentrations of metals and the risk of dyslipidemia in community-dwelling elderly. We designed a case–control study to assess the correlation between urine metals and dyslipidemia in elderly people in the Yinchuan. The urinary levels of 13 metals, including calcium, vanadium, iron, cobalt, zinc, copper, arsenic, selenium, molybdenum, cadmium, tellurium, and thallium, were measured by inductively coupled plasma–mass spectrometry (ICP-MS), and the blood biochemical analyzer was used to measure the blood lipid levels of 3384 senior individuals from four different areas of Yinchuan city. Logistic regression and restricted cubic splines (RCS) were used to explore the correlation and dose–response relationship between urinary metals and the risk of dyslipidemia. Least absolute shrinkage and selection operator (LASSO) regression was used to select metals, and then weighted quantile sum (WQS) regression was used to explore the weight of each metal in mixed metals. Bayesian kernel machine regression (BKMR) was used to explore the interactions between metals on dyslipidemia risk. (1) After selection by LASSO regression, in the multi-metal model, compared with the lowest quartile, the adjusted ORs (95%CI) of the highest quartiles were 0.47 (0.37–0.60) for Fe, 1.43 (1.13–1.83) for Zn, 1.46 (1.11–1.92) for As, 0.59 (0.44–0.80) for Se, 1.53 (1.18–2.00) for Mo, and 1.36 (1.07–1.73) for Te. (2) In the WQS regression model, Fe and Mo accounted for the largest weight in the negative and positive effects of dyslipidemia, respectively. (3) In the BKMR model, there may be a positive interaction between Te and Se on dyslipidemia. Among the mixed metals, Fe, As, Se, Mo, and Te were associated with the prevalence of dyslipidemia, with Fe and Mo contributing the most. There may be certain interactions between Te and Se. [ABSTRACT FROM AUTHOR]

Occult hepatitis B virus (HBV) infection (OBI) refers to the presence of replication-competent HBV DNA in the liver, with or without HBV DNA in the blood, in individuals who tested negative for HBV surface antigen (HBsAg). In this peculiar phase of HBV infection, the covalently closed circular DNA (cccDNA) is in a low state of replication. Several advances have been made toward clarifying the mechanisms involved in such a suppression of viral activity, which seems to be mainly related to the host's immune control and epigenetic factors. Although the underlying mechanisms describing the genesis of OBI are not completely known, the presence of viral cccDNA, which remains in a low state of replication due to the host's strong immune suppression of HBV replication and gene expression, appears to be the causative factor. Through this review, we have provided an updated account on the role of HBV cccDNA in regulating OBI. We have comprehensively described the HBV cell cycle, cccDNA kinetics, current regulatory mechanisms, and the therapeutic methods of cccDNA in OBI-related diseases. [ABSTRACT FROM AUTHOR]

Vitamin B3 is an essential vitamin that the human body cannot synthesize in sufficient amounts. Thus, it must be supplemented through food and medicine. The vitamin B3 content of foods and drugs must therefore be determined to identify its main sources. However, vitamin B3 is a strongly polar substance, and its detection in complex actual samples has certain challenges. In this study, a double column tandem method was established for the determination of vitamin B3 in fruit and drug samples. The chromatographic retention of the vitamin was investigated using different chromatographic single-column and double-column tandem models. The best separation and determination effect was obtained under a dual-column tandem mode consisting of a C18 short column and a HILIC column. The chromatographic conditions for vitamin B3 detection were as follows: 10:90 (v:v) acetonitrile–0.1% acetic acid water solution mobile phase, 30 ℃ column temperature, 0.4 mL/min flow rate, and 262 nm detection wavelength. This method was used to detect vitamin B3 in three fruits and two drugs. The detected content ranged between 1.50×102 and 1.35×103 mg/kg, and the recovery for spiked samples was 85–102%. This high performance liquid chromatography with two columns tandem can effectively determine vitamin B3. [ABSTRACT FROM AUTHOR]

Planar super-oscillatory lens (SOL), a far-field subwavelength-focusing diffractive device, holds great potential for achieving sub-diffraction-limit imaging at multiple wavelengths. However, conventional SOL devices suffer from a numerical-aperture-related intrinsic tradeoff among the depth of focus (DoF), chromatic dispersion and focusing spot size. Here, we apply a multi-objective genetic algorithm (GA) optimization approach to design an apochromatic binary-phase SOL having a prolonged DoF, customized working distance (WD), minimized main-lobe size, and suppressed side-lobe intensity. Experimental implementation demonstrates simultaneous focusing of blue, green and red light beams into an optical needle of ~0.5λ in diameter and DOF > 10λ at WD = 428 μm. By integrating this SOL device with a commercial fluorescence microscope, we perform, for the first time, three-dimensional super-resolution multicolor fluorescence imaging of the "unseen" fine structures of neurons. The present study provides not only a practical route to far-field multicolor super-resolution imaging but also a viable approach for constructing imaging systems avoiding complex sample positioning and unfavorable photobleaching. Conventional super-oscillatory devices suffer from numerical-aperture related issue including depth of focus, chromatic dispersion, and focusing, Here, the authors utilised multi-objective genetic algorithm to optimise the design and experimentally demonstrated lens with an extended depth of focus, ultra-large working distance and suppressed side-lobes. [ABSTRACT FROM AUTHOR]

Although metal exposure has been associated with hypertension, the conclusions remain controversial, and studies investigating the predictive effect of multiple metals on hypertension are limited. In this study, we aimed to evaluate the nonlinear dose–response relationship between a single urinary metal and the risk of hypertension, and to assess the predictive effect of multiple urinary metals on hypertension. Of the Yinchuan community-dwelling elderly cohort launched in 2020, 3,733 participants (803 with hypertension and 2,930 without hypertension) were analysed in this study, and the concentrations of 13 metal elements in urine were measured. We found that urinary vanadium (odds ratio (OR): 1.16, 95% confidence interval [CI]: 1.08–1.25), molybdenum (OR: 1.08, 95% CI: 1.01–1.16), and tellurium (OR: 1.14, 95% CI: 1.06–1.22) were associated with higher risk of hypertension, whereas iron (OR: 0.92, 95% CI: 0.85–0.98) and strontium (0.92, 95% CI: 0.85–0.99) were significantly associated with lower risk of hypertension. Restricted cubic splines analysis was conducted in patients with iron concentrations of ≥ 15.48 μg/g and ≤ 399.41 μg/g and a strontium concentration of ≤ 69.41 μg/g, results showed that the risk of hypertension decreased gradually as the urinary concentrations of these metals increased. With an increase in the vanadium concentration in urine, the risk of hypertension gradually increased. In patients with a molybdenum concentration of ≥ 56.82 μg/g and a tellurium concentration of ≥ 21.98 μg/g, the risk of hypertension gradually decreased as the urinary concentrations of these metals increased. Predictive scores based on the 13 metallic elements were significantly associated with a higher risk of hypertension (OR: 1.34 (95% CI: 1.25–1.45). After additionally including urinary metal concentrations as a parameter variable in the traditional hypertension risk assessment model, integrated discrimination and net reclassification increased by 8.00% (P < 0.001) and 2.41% (P < 0.001), respectively. Urinary vanadium, Mo, and Te concentrations were associated with a higher risk of hypertension, while iron and strontium concentrations were associated with a lower risk of hypertension. Multiple urinary metal concentrations can significantly improve the predictive ability of traditional hypertension risk-assessment models. [ABSTRACT FROM AUTHOR]

The rational construction and preparation of efficient, stable, and economic electrocatalysts for the oxygen reduction reaction (ORR) are necessary for fuel cells. In this work, we fabricated a porous carbon skeleton structure consisting of bimetallic organic framework (BMMOF)-derived N-doped microspheres linked with graphene oxide (GO) conducting network (denoted as UA-Co/RSC@NGF, where "UA" stands for ultrasound-assisted, "RSC" stands for resin microspheres, and "NGF" stands for N-doped graphene framework) as an efficient ORR catalyst by an ultrasound-assisted and one-step pyrolysis method. In this configuration, benefiting from the support of carbon microspheres and the strong synergistic coupling with GO, the structure of UA-Co/RSC@NGF is stabilized, and the large specific surface area enhances the density of active sites. With UA-Co/RSC@NGF as the catalyst, significant ORR properties were achieved with a high half-wave potential (E1/2, 0.90 V), an onset potential (Eonset, 1.03 V), and a large limited current density (5.37 mA cm−2). The durability and methanol resistance of UA-Co/RSC@NGF in alkaline media outperform commercially available Pt/C. This study may open a pathway for rationally designing multidimensional composite-structured carbon-based ORR catalysts for energy-related applications. [ABSTRACT FROM AUTHOR]

In order to improve the accuracy of cross-modal retrieval tasks and achieve flexible retrieval between different modalities, we propose a Dual Discriminant Adversarial cross-modal Retrieval (DDAC) method in this paper. First, DDAC integrates adversarial learning and minimization of feature projection distances and introduces label information in it. It can eliminate the same semantic heterogeneity between modalities while maintaining the distinguishability of different semantic features between modalities. Then, cosine distance is used to minimize and maximize the inter-modal distance of features with the same and different labels respectively to solve the inter-modal discrimination problem. Different from the general method, DDAC performs dual discrimination in the label space and solves the intra-modal discrimination problem from two perspectives of probability distribution and distance. Extensive experiments carried out on three public datasets validate that the proposed DDAC outperforms the state-of-the-art methods. [ABSTRACT FROM AUTHOR]

A selective method for the determination of myosmine (a tobacco alkaloid) was developed using molecularly imprinted polymers (MIPs) based on Fe3O4@SiO2 and PAMAM dendrimers. Fe3O4@SiO2 with excellent magnetism and rapid separation performance was chosen as carrier for the MIPs. Moreover, the MIPs modified with PAMAM dendrimers exhibited a regular structure and abundant functional groups, which improve the efficiency of imprinting sites. The myosmine concentration was measured by HPLC with PDA detector, and the UV detection wavelength was set to 200 nm. The linear range of this assay was 13.2–400 mg/L with a correlation coefficient of 0.999, and the detection limit was 4.0 mg/L (S/N = 3). The MIPs have been used for the determination of myosmine in cigarettes, and the recovery range was 84.2–93.5%, with RSD values in the range 0.41–3.1%. In conclusion, our MIPs combine advantages of simple preparation and remarkable selectivity, which gives them excellent application prospects for the sensitive determination of trace myosmine in tobacco products. [ABSTRACT FROM AUTHOR]

Hydraulic fracturing is an essential technique to increase reservoir permeability and enhance the production of shale gas. When the dip angle is steep and geological condition is complex, hydraulic fractures may behave complexly, and research on this topic is critical for the shale gas industry. This paper reports a case study of hydraulic fracturing in a shale reservoir with a steep dip angle. We monitored pump data, including the injection rate and fluid pressure. Microseismic monitoring was also used to record the seismic events and monitor the hydraulic fracture propagation. Our results validated that microseismic monitoring is a feasible technique to monitor the hydraulic fracture propagation in shale reservoirs with steep dip angles. Moreover, the variation in depth of shale reservoir induces significant alternation of local in situ stress states, in which cases the fracture propagation pathway is more complex, and where microseismic monitoring is necessary to acquire the hydraulic fracture distribution. Besides, all sound sources, including quarries and rivers, should be eliminated during microseismic station arrangement to improve accuracy of microseismic signals. Moreover, the relationship between the maximum magnitude of seismic event and fluid injection volume was validated further in this study. Finally, unexpected faults and aquifers may affect hydraulic fracture propagation due to the steep dip angle of the target shale reservoir. Thus, a comprehensive geological survey is essential for better hydraulic fracturing design. Our results provide first-hand in situ hydraulic fracturing data and provide important implications for shale gas development, especially for those shale reservoirs with steep dip angles. [ABSTRACT FROM AUTHOR]

This document is a correction notice for an article titled "Super-resolution multicolor fluorescence microscopy enabled by an apochromatic super-oscillatory lens with extended depth-of-focus" published in Nature Communications. The correction addresses errors in the introduction, results, discussion, and supplementary information sections of the original article. The errors include incorrect measurements and references. The corrected versions of the article have been updated in both the PDF and HTML versions. The document also provides the names of the authors involved in the research. [Extracted from the article]

Immunostimulatory therapies based on pattern recognition receptors (PRRs) have emerged as an effective approach in the fight against cancer, with the ability to recruit tumor-specific lymphocytes in a low-immunogenicity tumor environment. The agonist cyclic dinucleotides (CDNs) of the stimulator of interferon gene (STING) are a group of very promising anticancer molecules that increase tumor immunogenicity by activating innate immunity. However, the tumor immune efficacy of CDNs is limited by several factors, including relatively narrow cytokine production, inefficient delivery to STING, and rapid clearance. In addition, a single adjuvant molecule is unable to elicit a broad cytokine response and thus cannot further amplify the anticancer effect. To address this problem, two or more agonist molecules are often used together to synergistically enhance immune efficacy. In this work, we found that a combination of the STING agonist CDGSF and the Toll-like receptor 7/8 (TLR7/8) agonist 522 produced a broader cytokine response. Subsequently, we developed multicomponent nanovaccines (MCNVs) consisting of a PC7A polymer as a nanocarrier encapsulating the antigen OVA and adjuvant molecules. These MCNVs activate bone marrow-derived dendritic cells (BMDCs) to produce multiple proinflammatory factors that promote antigen cross-presentation to stimulate specific antitumor T-cell responses. In in vivo experiments, we observed that MCNVs triggered a strong T-cell response in tumor-infiltrating lymphocytes, resulting in significant tumor regression and, notably, a 100% survival rate in mice through 25 days without other partnering therapies. These data suggest that our nanovaccines have great potential to advance cancer immunotherapy with increased durability and potency. [ABSTRACT FROM AUTHOR]

Nerve growth factor (NGF) is a protective factor of neural cells; the possible relationship between the NGF and the pathogenesis of amyotrophic lateral sclerosis (ALS) hasn't been completely known. In this study, we observed and analyzed the expression and distribution of NGF, as well as the possible relationship between the NGF expression and distribution and the neural cell death in both SOD1 wild-type (WT) and Tg(SOD1*G93A)1Gur (TG) mice applying the fluorescence immunohistochemistry method. The results showed that the expression and distribution of NGF in the anterior horn (AH), the lateral horn (LH), and the surrounding central canal (CC) significantly increased at the supper early stage of ALS (Pre-onset stage) and the early stage (Onset stage), but the NGF expression and distribution in the AH, the LH, and the surrounding CC significantly reduced at the progression stage. The astrocyte, neuron, and oligodendrocyte produced the NGF and the neural precursor cells (NPCs) produced the NGF. The neural cell death gradually increased accompanying with the reduction of NGF expression and distribution. Our data suggested that the NGF was a protective factor of neural cells, because the neural cells in the AH, the LH, and the surrounding CC produced more NGF at the supper early and early stage of ALS; moreover, the NPCs produced the NGF. It implied that the NGF exerted the protective effect of neural cells, prevented from the neural cell death and aroused the potential of self-repair in the development of ALS. [ABSTRACT FROM AUTHOR]

SNP rs3755955 (major/minor allele: G/A) located in Iduronidase-Alpha-L- (IDUA) gene was reported to be significant for human bone mineral density (BMD). This follow-up study was to uncover the underlying association mechanism through molecular and cellular functional assays relevant to bone. We tested the effects of single nucleotide polymorphisms (SNP) rs3755955 (defined allele G as wild-type and allele A as variant-type) on osteoblastic and osteoclastic functions, as well as protein phosphorylation in stably transfected human fetal osteoblast (hFOB) cell and mononuclear-macrophage (RAW264.7) cell. In hFOB cells, transfection with variant-type IDUA significantly decreased osteoblastic gene expression (OPN, COL1A1 and RANKL) (p < 0.01), impeded cell proliferation (p < 0.05), stimulated cell apoptosis (p < 0.001) and decreased ALP enzyme activity, as compared with that of wild-type IDUA transfection. In RAW264.7 cells, transfection with variant-type IDUA significantly inhibited cell apoptosis (p < 0.01), promoted osteoclastic precursor cell migration (p < 0.0001), growth (p < 0.01), osteoclastic gene expression (TRAP, RANK, Inte-αv and Cath-K) (p < 0.05) and TRAP enzyme activity (p < 0.001), as compared with that of wild-type IDUA transfection. In both hFOB and RAW264.7 cells, the total protein and IDUA protein-specific phosphorylation levels were significantly reduced by variant IDUA transfection, as compared with that of wild-type IDUA transfection (p < 0.05). Variant allele A of phosSNP rs3755955 in IDUA gene regulates protein phosphorylation, inhibits osteoblast function and promotes osteoclastic activity. The SNP rs3755955 could alter IDUA protein phosphorylation, significantly regulates human osteoblastic and osteoclastic gene expression, and influences the growth, differentiation and activity of osteoblast and osteoclast, hence to affect BMD. [ABSTRACT FROM AUTHOR]

Introduction: Gut microbiota is now considered to be a hidden organ that interacts bidirectionally with cellular responses in numerous organs belonged to the immune, bone, and nervous systems. Here, we aimed to investigate the relationships between gut microbiota and complex diseases by utilizing multiple publicly available genome-wide association. Materials and methods: We applied a novel microbiota-related gene set enrichment analysis approach to detect the associations between gut microbiota and complex diseases by processing genome-wide association studies (GWASs) data sets of six autoimmune diseases (including celiac disease (CeD), inflammatory bowel diseases (IBD), multiple sclerosis (MS), primary biliary cirrhosis (PBC), type 1 diabetes (T1D) and primary sclerosing cholangitis (PSC)) and osteoporosis (OP). Results: The family Oxalobacteraceae and genus Candidatus_Soleaferrea were found to be correlated with all of the six autoimmune diseases (FDR adjusted P < 0.05). Moreover, we observed that the six autoimmune diseases except PBC shared 3 overlapping features (including family Peptostreptococcaceae, order Gastranaerophilales and genus Romboutsia). For all of the six autoimmune diseases and BMDs (LS-BMD and TB-BMD), an association signal was observed for genus Candidatus_Soleaferrea (FDR adjusted P < 0.05). Notably, FA / FN-BMD shared the maximum number of overlapping microbial features (e.g., genus Ruminococcaceae_UCG009, Erysipelatoclostridium and Ruminococcaceae_UCG013). Conclusion: Our study found that part of the gut microbiota could be novel regulators of BMDs and autoimmune diseases via the effects of its metabolites and may lead to a better understanding of the role played by gut microbiota in the communication of the microbiota-skeletal/immune-gut axis. [ABSTRACT FROM AUTHOR]

Strain sensors with good stability are vital to the development of wearable healthcare monitoring systems. However, the design of strain sensor with both duration stability and environmental stability is still a challenge. In this work, we propose an ultra-stable and washable strain sensor by embedding a coupled composite film of carbon nanotube (CNT) and Ti3C2Tx MXene into polydimethylsiloxane (PDMS) matrix. The composite strain sensor with embedded microstructure and uneven surface makes it conformal to skin, while the CNT/MXene sensing layer exhibits a resistance sensitive to strain. This sensor shows reliable responses at different frequencies and with long-term cycling durability (over 1,000 cycles). Meanwhile, the CNT/MXene/PDMS composite strain sensor provides the advantages of superior anti-interference to temperature change and water washing. The results demonstrate less than 10% resistance changes as the temperature rises from −20 to 80 °C or after sonication in water for 120 min, respectively. The composite sensor is applied to monitor human joint motions, such as bending of finger, wrist and elbow. Moreover, the simultaneous monitoring of the electrocardiogram (ECG) signal and joint movement while riding a sports bicycle is demonstrated, enabling the great potential of the as-fabricated sensor in real-time human healthcare monitoring. [ABSTRACT FROM AUTHOR]

White Spot Syndrome Virus (WSSV) is the most harmful and pathogenic infectious agent in shrimp aquaculture. Vp28, a protein used to protect hosts against this virus, has successfully been expressed in nine hosts since 2004; however, to date, it has not been used commercially. We constructed transgenic Synechococcus elongatus PCC 7942 expressing vp28 and enhanced green fluorescent protein (egfp) genes simultaneously to enable the easy detection of vp28 expression. GFP has been expressed in cyanobacteria previously and was used in this study to construct transgenic cyanobacteria that can easily be detected. The optimal growth conditions for the transgenic cyanobacteria were determined using a liquid-phase oxygen electrode. At the optimum light intensity, the net photosynthetic rate of the transgenic cyanobacteria increased by 12.6% compared with that of the wild-type. Furthermore, Synechococcus sp. PCC 7942 harboring vp28 and vp28-egfp were fed to shrimp in order to protect them against WSSV infection. The cumulative survival rate of the groups fed with transgenic cyanobacteria was 75%. [ABSTRACT FROM AUTHOR]

Granite residual soil presents a strong disintegration phenomenon when it encounters water, thus contributing to geological disasters such as collapsing erosion. Disintegration characteristics are closely related to the initial moisture content and temperature. However, the relevant quantitative assessment is still lacking. In this study, the disintegration of granite residual soil in the collapsing erosion zone of southern China was analyzed. Disintegration tests were performed to measure the total disintegration time after the soil samples had been soaked in water. The disintegration process was captured by measuring the weight change over time. Based on the disintegration rate and characteristics of the disintegrative deposit, the effects of dry density, initial moisture content, and temperature on granite residual soil disintegration were evaluated. The results show that the effects of dry density on the disintegration rate are not obvious, and an increase in dry density only delays the time when the soil sample enters the rapid disintegration stage. The initial moisture content has a considerable effect on the disintegration rate, and the disintegration rate increases as the initial moisture content increases. Furthermore, as the temperature increases, the disintegration rate increases. An increase in temperature greatly accelerates the entry of water molecules into the soil sample, thus potentially damaging the aggregation between particles and increasing the disintegration rate. [ABSTRACT FROM AUTHOR]

Objective: To investigate the mechanistic basis for the attenuation of bone degeneration by edible bird's nest (EBN) in ovariectomized rats. Methods: Forty-two female Sprage-Dawley rats were randomized into 7 groups (6 in each group). The ovariectomized (OVX) and OVX + 6%, 3%, and 1.5% EBN and OVX +estrogen groups were given standard rat chow alone, standard rat chow +6%, 3%, and 1.5% EBN, or standard rat chow +estrogen therapy (0.2mg/kg per day), respectively. The sham-operation group was surgically opened without removing the ovaries. The control group did not have any surgical intervention. After 12 weeks of intervention, blood samples were taken for serum estrogen, osteocalcin, and osteoprotegerin, as well as the measurement of magnesium, calcium abd zinc concentrations. While femurs were removed from the surrounding muscles to measure bone mass density using the X-ray edge detection technique, then collected for histology and estrogen receptor (ER) immunohistochemistry. Results: Ovariectomy altered serum estrogen levels resulting in increased food intake and weight gain, while estrogen and EBN supplementation attenuated these changes. Ovariectomy also reduced bone ER expression and density, and the production of osteopcalcin and osteorotegerin, which are important pro-osteoplastic hormones that promote bone mineraliztion and density. Conversely, estrogen and EBN increased serum estrogen levels leading to increased bone ER expression, pro-osteoplastic hormone production and bone density (all P<0.05). Conclusion: EBN could be used as a safe alternative to hormone replacement therapys for managing menopausal complications like bone degeneration. [ABSTRACT FROM AUTHOR]

Quantitative inversion of reservoir properties plays a crucial role in the efficient development of tight sandstone reservoirs. Based on the theories of statistical rock physics and extended elastic impedance (EEI), a complete workflow for quantitative prediction of reservoir properties is developed and the key steps thereof are provided here. The square of S-velocity to P-velocity ratio (K), which is consistent with geological setting of a study area, is obtained from statistics of well data, the value of angle χ most relevant to lithology and porosity is produced automatically by evaluating correlations of reservoir parameters with EEI, and the formulas that fit EEI with clay volume and with porosity are obtained. Then, angle χ is applied to relevant EEI reflection coefficient data from amplitude variation with offset attribute cubes, the EEI related to clay volume and porosity is obtained through model-based constrained inversion on these data cubes, fitting formulas from well analysis are used to convert EEI data cubes to clay volume and porosity data cubes, and finally, the parameters of a tight sandstone reservoir are predicted quantitatively. The prediction results are consistent with production data from existing wells, indicating that the method proposed here is reliable. [ABSTRACT FROM AUTHOR]

All-trans retinoic acid (ATRA), a ligand of retinoic acid receptors, could regulate various biological processes by activating retinoic acid signals. Recent studies suggested that ATRA displays multiple neuroprotective effects and thereby alleviates the disease progression in a variety of neurological diseases. Our previous studies found that the impaired retinoic acid signal decreased ALDH1A2, an essential synthetase of ATRA, in the spinal cord of ALS mice. Here, we evaluated the neuroprotective and neurorestorative effects of ATRA in a SOD1-G93A transgenic mice model of ALS. We administrated ATRA(3 mg/kg) daily from the onset stage to the progression stage for 5 weeks. Behavioral tests showed that ATRA improved the forelimb grip strength in ALS mice and may slow the disease progression, but not the body weight. ATRA could completely reverse the impaired retinoic acid receptor alpha (RARα) signal in the spinal cord of ALS mice. This effect was accompanied by enhancing the degradation of misfolded proteins via the ubiquitin-proteasome system, regulating the oxidative stress, inhibiting the astrocyte activation, and promoting the neurotrophic signal recovery. Our findings are the first to indicate that the damaged retinoic acid signal is involved in the pathogenesis of ALS, and ATRA could induce the functional neuroprotection via repairing the damaged retinoic acid signal. [ABSTRACT FROM AUTHOR]

The heat flux loaded on the divertor is an important issue in tokamaks. At present, the heat flux on the divertor is calculated from the divertor surface temperature measured by the infrared (IR) camera. However, the movement of the field of view and the geometrical distortion are present in the IR images. Small movements occur with machine shaking during normal discharges, while large ones often arise at disruptions or the rapid variations in the magnetic field. As a result, it is difficult to obtain the real temperature evolution on the specified divertor surface from the IR images. In this paper, the scale invariant feature transform descriptors and K-means clustering have been applied for vibration correction on the IR videos in EAST. The projective transformation is used to correct the geometrical distortion in the IR images. The experimental results show that the proposed methods are efficient in compensating for image translations brought about by vibrations and for perspective distortions in the images, thereby allowing assignment of the IR emission-derived surface temperatures to the correct locations on the divertor surface. [ABSTRACT FROM AUTHOR]

Chemical reactivity hazards of organic peroxides are major concerns of the chemical industry due to many serious incidents every year. Thermal hazard assessment for organic peroxides is of great importance for safe operations in chemical process industries. A new hazard evaluation method based on quantitative structure–property relationship (QSPR) was proposed to assess thermal hazard of organic peroxides from their molecular structures. Optimal molecular descriptors were determined to characterize thermal hazard parameters, including onset temperature (To), time to maximum rate under adiabatic condition (TMRad) and heat of reaction (ΔH), respectively. Both the probability and severity of the thermal risk were considered to evaluate the thermal hazards of organic peroxides comprehensively. To and TMRad were employed to describe the probability of thermal risk, while ΔH was used to describe the severity. Then, the thermal hazard rating was developed based on the molecular descriptors and a corresponding ranking criterion was also proposed with the thermal hazards being divided into five levels. After comparing and verifying with previously developed evaluation methods, the proposed assessment method in this work would be reasonably expected to provide an accurate ranking of the thermal hazards for organic peroxides. [ABSTRACT FROM AUTHOR]

Geopolymers, such as phosphate-based geopolymer, are promising materials that have drawn extensive attentions as wave-transparent candidates with low dielectric loss factor. In this paper, multilayer SiO2 fibers are introduced into phosphate-based geopolymer matrix to prepare composites. Crack generation and fracture behaviors during the three-point bending tests in as-prepared SiO2f/phosphate geopolymer composites are clarified by in situ observation. Before high-temperature treatment, composite with 17 vol% fiber content exhibits the best mechanical properties. A decreasing mechanical strength is observed after being treated at higher temperature, which is attributed to the stronger interface binging between fibers and phosphate-based geopolymer matrix. Most importantly, the presence of SiO2 fibers can strengthen mechanical properties of phosphate-based geopolymer matrix but shows negligible impact on its dielectric properties, achieving dielectric loss factor as low as 3.53 × 10−3 after being treated at 700 °C. [ABSTRACT FROM AUTHOR]

Flexible strain sensors exhibit outstanding advantages in terms of sensitivity and stability by detecting changes in physical signals. It can be easily attached to human skin and clothed to achieve monitoring of human motion and health. However, general sensing materials shows low stretchability and cannot respond to signals under large deformation. In this work, a highly stretchable polymer composite was developed by adding small amount (0.17 wt.%) of silver nanowires (AgNWs) in stretchable conductive polymer materials. The conductivity of polymer/AgNWs composite is 1.3 S/m with the stretchability up to 500%. The stretchable strain sensor based on the polymer/AgNWs composite can respond to strain signals in real time, even for 1% strain response, and shows excellent stability over 1,000 loading/unloading cycles. Moreover, the strain sensor can be attached to human skin and clothed to monitor joints, throat and pulse of the human body. The human body electrocardiogram (ECG) signal was detected successfully with the polymer/AgNWs electrode, which is comparable to the signal obtained by the commercial electrode. Overall, the sensors enable monitoring of human movement and health. These advantages make it a potential application in wearable devices and electronic skin. [ABSTRACT FROM AUTHOR]

Polycystic ovary syndrome (PCOS) is a hormonal disorder common among women of reproductive age. Although much is understood concerning the pathology of PCOS, further investigation into the influence of microribonucleic acids (miRNAs) on the proliferation of ovarian granulosa cells (GCs) is needed. This study investigated the role of specific miRNAs in ovarian dysfunction of PCOS and its effect on the proliferation of GCs. Initially, miRNA profiling was performed on the ovarian cortexes of 15 rats in which PCOS had been induced and 15 rats without PCOS (non-PCOS). This mechanical study was performed on ovarian GCs extracted from human chorionic gonadotrophin (hCG)-induced rats. Insulin was used to treat GCs to establish the PCOS cell model. Increased Equus caballus mir-9119 expression was observed and confirmed in the insulin-induced model of PCOS in GCs (GC-PCOS) as well as in the hCG-induced rats when compared to non-PCOS rats and cells. Observation and confirmation were carried out through both miRNA array and quantitative PCR. In contrast, downregulation of the nuclear factor kappa B (NFκB) p65 was observed in the PCOS cell model. Additionally, annexin V, FITC, and propidium iodide flow cytometry showed overexpression of miR-9119-induced apoptosis. In this study, we revealed that miR-9119 inhibition regulates p65 expression levels in insulin-treated GCs by binding to the 3′-untranslated of p65. Additionally, regulation of p65 expression was positively correlated with the expression of the double-stranded RNA endoribonuclease DICER. Moreover, RNA silencing/overexpression of p65 affected the functional role of miR-9119. In conclusion, GCs of PCOS, the expression of miR-9119, and targeted NFκB/p65-DICER axis are upregulated in order to maintain cell viability and prevent apoptosis, thereby promoting Anti-Müllerian hormone production in GCs. This study may provide a new understanding of the mechanism of GC dysfunction. [ABSTRACT FROM AUTHOR]

In current work, a red-emitting phosphor K2TiF6:Mn4+ was prepared by a facile method using H2O to replace high toxic HF as solvent at room temperature. Its structure and morphology were characterized by the XRD and SEM measurement. The obtained K2Ti0.96F6:0.04Mn4+ presents intense excitation band in the blue-light region and narrow-band emission with high color purity. Meanwhile, this sample is of the excellent thermal-quenching resistance and its emission intensity at 160 °C is still higher than that at 20 °C. The white light-emitting diode (wLED) fabricated with the commercial Y3Al5O12:Ce3+ and K2Ti0.96F6:0.04Mn4+ shows excellent photoelectric performances (the color rendering index of 88.4, the color temperature of 4138 K, and the luminous efficiency of 178.5 lm/W). So this as-synthesized phosphor may be find application on wLEDs. [ABSTRACT FROM AUTHOR]

Circulating exosomes are promising biomarker source in various diseases. Exosomal constituents can stably exist in the circulating plasma and serum thus making them ideal biomarkers for a number of clinical applications. Exosomes can also mediate the occurrence of many types of diseases, including distal cancerous metastasis and tumour enlargement, through encapsulated proteins or RNAs, which regulate interactions among tissues. While performing these actions, exosomes show tissue specificity. However, the mechanism for such selection is not clear. For non-small cell lung cancer (NSCLC), molecular diagnostic markers and mechanisms of exosome-mediated tumour metastasis are not well understood. Therefore, in this study, we characterized LLC exosomal proteins and mRNAs by analysing their molecular profiles, laying a foundation for exploring diagnostic markers of lung cancer. Furthermore, the interactions between exosomal membrane proteins and their target proteins were analysed and revealed a possible tissue propensity of LLC cell-derived exosomes. These findings provide a theoretical basis for studying exosome-mediated tissue targeting and distal lung cancer metastasis. [ABSTRACT FROM AUTHOR]

In this paper, the cobalt-substituted aluminophosphate CoAPO-11 was prepared and utilized for the adsorption of phenol in cigarette smoke. XRD, XPS, SEM, TPD and N2-sorption results suggested that the product possessed highly crystallized AEL topology with mesoporous structure, and the existence of Co in the framework provided acid sites and base sites to the sample. The adsorption kinetic data were modeled through the pseudo-first-order and pseudo-second-order kinetic equations using linear and non-linear methods, and the result demonstrated that the adsorption character of phenol on CoAPO-11 obeyed the pseudo-second-order kinetic model and the adsorption process occurred via film and intra-particle diffusion. The CoAPO-11's adsorption capacity for phenol was generally positively correlated with its specific surface area and pore volume, and it could reduce the content of phenol in the cigarette smoke by 23%. In addition, it was effective for reducing HCN and croton aldehyde, which evidenced it an excellent multifunctional adsorbent for cigarette smoke. [ABSTRACT FROM AUTHOR]

To identify PBMC-expressed genes significant for RA, and to ascertain their upstream regulatory factors, as well as downstream functional effects relevant to RA pathogenesis. We performed peripheral blood mononuclear cells (PBMCs) transcriptome-wide mRNA expression profiling in a case–control discovery sample. Differentially expressed genes (DEGs) were identified and validated in PBMCs in independent samples. We also generated genome-wide SNP genotyping data, and collected miRNA expression data and DNA methylation data from PBMCs of the discovery sample. Pearson correlation analyses were conducted to identify miRNAs/DNA methylations influencing DEG expression. Association analyses were conducted to identify expression-regulating SNPs. The key DEG, SAMD9, which was reported to function as a tumor suppressor gene, was assessed for its effects on T cell proliferation, apoptosis, and inflammatory cytokine expression. A total of 181 DEGs (Fold Change ≥ 2.0, Bonferroni adjusted p ≤ 0.05) were discovered in PBMCs. Four DEGs (SAMD9, CKLF, PARP9, and GUSB), upregulated with RA, were validated independently in PBMCs. Specifically, SAMD9 mRNA expression level was significantly upregulated in PHA-activated Jurkat T cells in vitro, and correlated with 8 miRNAs and associated with 22 SNPs in PBMCs in vivo. Knockdown of SAMD9 could transiently promote Jurkat T cell proliferation within 48 h and significantly induce TNF-α and IL-8 expression in T cells. SAMD9 expression is (epi-) genetically regulated, and significantly upregulated in PBMCs in RA patients and in activated T cells in vitro. SAMD9 might serve as a T cell activation marker but act as an anti-inflammatory factor. [ABSTRACT FROM AUTHOR]

One major function of lncRNA is to regulate the expression of mRNA, but the patterns of their interactions were largely unknown. We attempted to construct lncRNA-mRNA interaction modules at a genome-wide scale. We performed a genome-wide lncRNA-mRNA eQTL analysis in peripheral blood mononuclear cells of 43 individuals, followed by weighted gene co-expression network analysis and functional enrichment analysis which sought to detect functional modules. There were 4627 significant cis lnc-eQTL pairs (P < 1.4 × 10−6) and 1,587,128 significant trans lnc-eQTL pairs (P < 3.46 × 10−9). We detected 11 eQTL modules for the lnc-eQTL networks. Among them, five modules showed significant enrichments in GO terms, and three modules showed significant enrichments in specific KEGG pathways (e.g., Toll-like receptor, PI3K-Akt, NF-kappa B, and TNF signaling pathways). lncRNA-protein interaction analysis showed that some well-known functional lncRNAs (HOTAIR, CCDC26, RHPN1-AS1, WT1-AS, and TCL6) in the eQTL module interacted with genes in focal adhesion and PI3K-Akt signaling pathway. We identified biologically functional lncRNA-mRNA interaction modules by integrating eQTL and weighted gene co-expression network analysis. Integrative analysis of lncRNA and mRNA data by applying eQTL analysis and weighted gene co-expression network analysis methods could be helpful for functional annotation of lncRNAs. [ABSTRACT FROM AUTHOR]

Babesia gibsoni (B. gibsoni), an intracellular apicomplexan protozoan, poses great threat to canine health. Currently, little information is available about the B. gibsoni (WH58) endemic to Wuhan, China. Here, the mitochondrial (mt) genome of B. gibsoni (WH58) was amplified by five pairs of primers and sequenced and annotated by alignment with the reported mt genome sequences of Babesia canis (B. canis, KC207822), Babesia orientalis (KF218819), Babesia bovis (AB499088), and Theileria equi (AB499091). The evolutionary relationships were analyzed with the amino acid sequences of cytochrome c oxidase I (cox1) and cytochrome b (cob) genes in apicomplexan parasite species. Additionally, the mt genomes of Babesia, Theileria, and Plasmodium spp. were compared in size, host infection, form, distribution, and direction of the protein-coding genes. The full size of the mt genome of B. gibsoni (WH58) was 5865 bp with a linear form, containing terminal-inverted repeats on both ends, six large subunit ribosomal RNA fragments, and three protein-coding genes: cox1, cob, and cytochrome c oxidase III (cox3). Babesia, Theileria, and Plasmodium spp. had a similar mt genome size of about 6000 bp. The mt genomes of parasites that cause canine babesiosis showed a slightly smaller size than the other species. Moreover, Babesia microti (R1 strain) was about 11,100 bp in size, which was twice larger than that of the other species. The mt form was linear for Babesia and Theileria spp. but circular for Plasmodium falciparum and Plasmodium knowlesi. Additionally, all the species contained the three protein-coding genes of cox1, cox3, and cob except Toxoplasma gondii (RH strain) which only contained the cox1 and cob genes. The phylogenetic analysis indicated that B. gibsoni (WH58) was more identical to B. gibsoni (AB499087), B. canis (KC207822), and Babesia rossi (KC207823) and most divergent from Babesia conradae in Babesia spp. Despite the highest similarity to B. gibsoni (AB499087) reported in Japan, B. gibsoni (WH58) showed notable differences in the sequence of nucleotides and amino acids and the property in virulence to host and in vitro cultivation. This study compared the mt genomes of the two B. gibsoni isolates and other parasites in the phylum Apicomplexa and provided new insights into their differences and evolutionary relationships. [ABSTRACT FROM AUTHOR]

k-median and facility location problems are classical NP-hard combinatorial optimization problems. Although there are many experimental studies on them, their theoretical results are relatively few. This paper mainly contributes to investigating the approximation performance of two evolutionary algorithms for the k-median and facility location problems from a theoretical perspective. For k-median problem, we show that the evolutionary algorithms with standard bit mutation (SBM) operator can obtain approximation ratios 5 and 3+2/p in expected polynomial time while the evolutionary algorithm with somatic contiguous hypermutation (CHM) operator cannot obtain them. For facility location problem, we show that the evolutionary algorithms with SBM operator can obtain approximation ratio 3 in expected polynomial time while the evolutionary algorithm with CHM operator cannot obtain it. Further, we prove that on a facility location instance the evolutionary algorithm with CHM operator greatly outperforms the evolutionary algorithm with SBM operator. [ABSTRACT FROM AUTHOR]

Hydraulic fracturing (HF) is indispensable in shale gas, but there are also problems existed in high ratio of energy consumption and low ratio of energy utilization. Based on hydraulic fracturing and pulsating jet, pulse hydraulic fracturing (PHF) has been widely used and achieved good results in the coal-bed methane. This paper attempts to study the mechanism of pulse wave propagation and attenuation during PHF in shale reservoirs, which provides theoretical support for application. On the basis of the motion equation and continuity equation, the two-dimensional propagation and attenuation equation with damping and fissure width during PHF is established and fracture network is simulated based on DFN discrete random model. The mathematical and physical model is verified by laboratory experiment The study of PHF superiority, PHF waveform effect, PHF propagation and attenuation characters are also performed. Results indicate that PHF propagation has two stages: The first is the pressure fluctuation is sharp in the process of the initial fracturing. The second is a stable state is appeared after a period of time. Compared with HF, PHF can pressurize obviously the pressure gradient of pulse waveform, which is an important parameter of affecting pulse pressure: the greater pressure gradient, the more obvious water hammer and supercharging effect. In the process of PHF propagation, pressure distribution complicates under the supercharging. Pressure wave has different attenuation characteristics in two steps. These research results will provide guidance for optimizing technical parameters for using PHF technology in shale reservoirs. [ABSTRACT FROM AUTHOR]

Irisin, a myokine produced by skeletal muscle in response to physical exercise, promotes trans-differentiation of white adipose tissue into brown adipose tissue. Recent evidences suggested that irisin also plays an important role in the control of bone metabolism. This study aimed to ascertain the relationship between plasma irisin and bone mineral density (BMD) in Chinese population by adoption of an extreme sampling method. Based on a large and screened Chinese elderly population (N = 6308), two subgroups with extremely high and low hip BMD were selected for discovery (N = 80, high vs. low BMD = 44:36) and validation (N = 60, high vs. low BMD = 30:30), respectively. Plasma irisin, P1NP, and β-CTx were measured using commercially available ELISA kits. Other metabolic parameters (e.g., blood glucose, total cholesterol and triglycerides) were collected. Student's t test and Spearman correlation analyses were conducted in SPSS. Significant difference was discovered for plasma irisin between females and age-matched males (N = 80, male vs. female = 42:38, P = 0.002). The plasma irisin levels were significantly higher in high BMD subjects than in low BMD subjects, which was observed in both discovery (P = 0.012) and validation samples (P = 0.022). However, such observation was limited to males only. Further correlation analyses in males showed that plasma irisin was correlated with BMD (r = 0.362, P = 0.025) and triglyceride (r = - 0.354, P = 0.032). Plasma irisin levels were associated with hip BMD in Chinese elderly men. This study represented the first effort of investigating the relationship of plasma irisin and BMD in elderly population. The positive correlation between plasma irisin and BMD hints intrinsic communication between muscle and bone. [ABSTRACT FROM AUTHOR]

Two new furan-2-carboxylic acids, 5-(3-hydroxy-5-(hydroxymethyl)-4-methoxyphenyl)-3-methylfuran-2-carboxylic acid (1) and 5-(4-hydroxy-5-methoxy-2-methylphenyl)-3-methylfuran-2-carboxylic acid (2), together with two known furan-2-carboxylic acids (3 and 4) were isolated from the roots of Nicotiana tabacum. Their structures were determined by means of HR-ESI-MS and extensive 1D and 2D NMR spectroscopic studies. Compounds 1 and 2 were tested for their anti-tobacco mosaic virus (TMV) and cytotoxicity activities. The results revealed that compounds 1 and 2 showed high anti-TMV activity with inhibition rate of 35.8 and 32.6%. These rates are close to that of positive control. Compounds 1 and 2 also showed moderate to weak inhibitory activities against some tested human tumor cell lines with IC50 values in the range of 1.5-6.0 μM. [ABSTRACT FROM AUTHOR]

Two new benzolactones, 4-methoxy-6-(2-oxopropyl)isobenzofuran-1(3H)-one (1) and 4-methyl-6-(2-oxopropyl)isobenzofuran-1(3H)-one (2), were isolated from the leaves of Yunnan local sun cured tobacco. Their structures were determined by means of HR-ESI-MS and extensive 1D and 2D NMR spectroscopic studies. Compounds 1 and 2 were tested for their anti-tobacoo mosaic virus (TMV) activities and cytotoxicity activities. The results revealed that compounds 1 and 2 showed high anti-TMV activity with inhibition rates of 32.6 and 30.2%. These rates are close to that of positive control. Compounds 1 and 2 also showed weak inhibitory activities against some tested human tumor cell lines. [ABSTRACT FROM AUTHOR]

Extended homozygosity is a genomic region in which the copies inherited from parents are identical, and has obvious inter-individual differences in length and frequency. Runs of homozygosity (ROHs), regarded as a type of structure variations, may have potential capacity in regulating gene transcription. To learn more about the genome-wide distribution of ROH regions in humans and understand the potential roles, this study applied ROH-based approach to quantify and characterize ROHs in 41 Chinese Han female subjects, and test potential associations between ROHs and mRNA expressions by eQTL analysis to ascertain whether ROHs are relevant to gene transcription in peripheral blood mononuclear cells (PBMCs). 10,884 ROH regions were identified in human genome. The average cumulative length of ROH regions was 217,250 ± 20,241 kb. The number of core segments in each chromosome generally matched the total length of corresponding chromosome, i.e., the longer the chromosome, the more the core segments. Genes located in the core regions of ROH were significantly enriched in multiple basic metabolism pathways. A total of 226 cis-eQTLs and 178 trans-eQTLs were identified. The cis-effect size was mainly concentrated at ± 0.5; and the trans-effect size was mainly concentrated at −1.5 and 1.0. Genes with eQTL effects were significantly enriched in functions related to protein binding, cytosol, nucleoplasm, nuclear membrane, protein binding and citrate metabolic process. This study described comprehensive distributions and characteristics of ROH in Han female Chinese, and recognized the significant role of ROH associated with gene transcription in human PBMC. [ABSTRACT FROM AUTHOR]

MicroRNAs (miRNAs) can regulate gene expression through binding to complementary sites in the 3′-untranslated regions of target mRNAs, which will lead to existence of correlation in expression between miRNA and mRNA. However, the miRNA–mRNA correlation patterns are complex and remain largely unclear yet. To establish the global correlation patterns in human peripheral blood mononuclear cells (PBMCs), multiple miRNA–mRNA correlation analyses and expression quantitative trait locus (eQTL) analysis were conducted in this study. We predicted and achieved 861 miRNA–mRNA pairs (65 miRNAs, 412 mRNAs) using multiple bioinformatics programs, and found global negative miRNA–mRNA correlations in PBMC from all 46 study subjects. Among the 861 pairs of correlations, 19.5% were significant (P < 0.05) and ~70% were negative. The correlation network was complex and highlighted key miRNAs/genes in PBMC. Some miRNAs, such as hsa-miR-29a, hsa-miR-148a, regulate a cluster of target genes. Some genes, e.g., TNRC6A, are regulated by multiple miRNAs. The identified genes tend to be enriched in molecular functions of DNA and RNA binding, and biological processes such as protein transport, regulation of translation and chromatin modification. The results provided a global view of the miRNA–mRNA expression correlation profile in human PBMCs, which would facilitate in-depth investigation of biological functions of key miRNAs/mRNAs and better understanding of the pathogenesis underlying PBMC-related diseases. [ABSTRACT FROM AUTHOR]

DNA methylation is an important regulator on the mRNA expression. However, a genome-wide correlation pattern between DNA methylation and mRNA expression in human peripheral blood mononuclear cells (PBMCs) is largely unknown. The comprehensive relationship between mRNA and DNA methylation was explored by using four types of correlation analyses and a genome-wide methylation-mRNA expression quantitative trait locus (eQTL) analysis in PBMCs in 46 unrelated female subjects. An enrichment analysis was performed to detect biological function for the detected genes. Single pair correlation coefficient ( r ) between methylation level and mRNA is moderate (−0.63-0.62) in intensity, and the negative and positive correlations are nearly equal in quantity. Correlation analysis on each gene (T4) found 60.1% genes showed correlations between mRNA and gene-based methylation at P < 0.05 and more than 5.96% genes presented very strong correlation ( R > 0.8). Methylation sites have regulation effects on mRNA expression in eQTL analysis, with more often observations in region of transcription start site (TSS). The genes under significant methylation regulation both in correlation analysis and eQTL analysis tend to cluster to the categories (e.g., transcription, translation, regulation of transcription) that are essential for maintaining the basic life activities of cells. Our findings indicated that DNA methylation has predictive regulation effect on mRNA with a very complex pattern in PBMCs. The results increased our understanding on correlation of methylation and mRNA and also provided useful clues for future epigenetic studies in exploring biological and disease-related regulatory mechanisms in PBMC. [ABSTRACT FROM AUTHOR]

Grammatical evolution (GE) is a combination of genetic algorithm and context-free grammar, evolving programs for given problems by breeding candidate programs in the context of a grammar using genetic operations. As far as the representation is concerned, classical GE as well as most of its existing variants lacks awareness of both syntax and semantics, therefore having no potential for parallelism of various evaluation methods. To this end, we have proposed a novel approach called model-based grammatical evolution (MGE) in terms of grammar model (a finite state transition system) previously. It is proved, in the present paper, through theoretical analysis and experiments that semantic embedded syntax taking the form of regex (regular expression) over an alphabet of simple cycles and paths provides with potential for parallel evaluation of fitness, thereby making it possible for MGE to have a better performance in coping with more complex problems than most existing GEs. [ABSTRACT FROM AUTHOR]