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Hydrogel-based tissue-engineered skin has attracted increased attention due to its potential to restore the structural integrity and functionality of skin. However, the mechanical properties of hydrogel scaffolds and natural skin are substantially different. Here, we developed a polyvinyl alcohol (PVA)/acrylamide based interpenetrating network (IPN) hydrogel that was surface modified with polydopamine (PDA) and termed Dopa-gel. The Dopa-gel exhibited mechanical properties similar to native skin tissue and a superior ability to modulate paracrine functions. Furthermore, a tough scaffold with tensile resistance was fabricated using this hydrogel by three-dimensional printing. The results showed that the interpenetration of PVA, alginate, and polyacrylamide networks notably enhanced the mechanical properties of the hydrogel. Surface modification with PDA endowed the hydrogels with increased secretion of immunomodulatory and proangiogenic factors. In an in vivo model, Dopa-gel treatment accelerated wound closure, increased vascularization, and promoted a shift in macrophages from a proinflammatory M1 phenotype to a prohealing and anti-inflammatory M2 phenotype within the wound area. Mechanistically, the focal adhesion kinase (FAK)/extracellular signal-related kinase (ERK) signaling pathway may mediate the promotion of skin defect healing by increasing paracrine secretion via the Dopa-gel. Additionally, proangiogenic factors can be induced through Rho-associated kinase-2 (ROCK-2)/vascular endothelial growth factor (VEGF)-mediated paracrine secretion under tensile stress conditions. Taken together, these findings suggest that the multifunctional Dopa-gel, which has good mechanical properties similar to those of native skin tissue and enhanced immunomodulatory and angiogenic properties, is a promising scaffold for skin tissue regeneration.

Abstract Background Osteosarcoma is a bone tumor that is characterized by high malignancy and a high mortality rate, and that originates from primitive osteoblastic mesenchymal cells and is most common in rapidly growing long bones. PSMD14, also known as RPN11 or POH1, is a member of the JAMM isopeptidase family, which is able to remove the substrate protein ubiquitination label, thereby regulating the stability and function of the substrate protein. In this study, we explored the expression and potential biological significance of the PSMD14 deubiquitinating enzyme in osteosarcoma. Methods Immunohistochemical methods were used to detect the expression of PSMD14 in biopsies of 91 osteosarcoma patients, and the specimens were classified into high and low PSMD14 expression groups. The correlation between PSMD14 expression and clinical indicators and prognosis was compared.SiRNA was used to downregulate PSMD14 in two osteosarcoma cell lines (HOS and SJSA-1), and the effects of downregulation of PSMD14 on the viability, proliferation, and invasion ability of osteosarcoma cells were analyzed. Results We identified significant differences in recurrence, metastasis, and survival time of the osteosarcoma patients on the basis of PSMD14 expression. High expression of PSMD14 in osteosarcoma patients was associated with a low survival rate and high risk of metastasis and recurrence. Down-regulation of PSMD14 inhibited the viability, proliferation, and invasiveness of osteosarcoma cell lines. Conclusions PSMD14 may be a new prognostic marker and therapeutic target for osteosarcoma.

Objectives: Dihydroartemisinin (DHA), an artemisinin derivative extracted from the traditional Chinese medicinal herb Artemisia annua, has the potential to suppress head and neck squamous cell carcinoma (HNSCC) progression. However, the mechanisms underlying these effects remain unclear. Therefore, we aimed to examine the mechanisms underlying the effects of DHA on tumor invasion and migration. Methods: Human HNSCC cell lines CAL-27 and FaDu were exposed to varying DHA concentrations (0, 5, 20, and 80 μM) for 24 h. Cell proliferation, invasion, and migration were assessed using CCK8, transwell, and wound-healing assays, respectively. Quantitative real-time PCR, western blotting, and immunofluorescence were used to assess the expression levels of the target genes and proteins. Results: DHA suppressed the invasion and migration of CAL-27 and FaDu cells. Additionally, miR-195-5p suppressed the invasion and migration of HNSCC cells. This study revealed significant differences in the expression of miR-195-5p and TENM2 between clinical samples and multiple public databases. DHA treatment and miR-195-5p overexpression significantly reduced TENM2 expression in HNSCC cells, which suggested that miR-195-5p overexpression enhanced the inhibitory effect of DHA on TENM2. Conclusions: This study provides the first evidence that DHA inhibits cell invasion and migration by regulating the miR-195-5p/TENM2 axis in HNSCC cells, suggesting it as a potentially effective treatment strategy for HNSCC.

Abstract Background Long noncoding RNAs (lncRNAs) have been shown to play important roles in the response of plants to various abiotic stresses, including drought, heat and salt stress. However, the identification and characterization of genome-wide salt-responsive lncRNAs in tobacco (Nicotiana tabacum L.) have been limited. Therefore, this study aimed to identify tobacco lncRNAs in roots and leaves in response to different durations of salt stress treatment. Results A total of 5,831 lncRNAs were discovered, with 2,428 classified as differentially expressed lncRNAs (DElncRNAs) in response to salt stress. Among these, only 214 DElncRNAs were shared between the 2,147 DElncRNAs in roots and the 495 DElncRNAs in leaves. KEGG pathway enrichment analysis revealed that these DElncRNAs were primarily associated with pathways involved in starch and sucrose metabolism in roots and cysteine and methionine metabolism pathway in leaves. Furthermore, weighted gene co-expression network analysis (WGCNA) identified 15 co-expression modules, with four modules strongly linked to salt stress across different treatment durations (MEsalmon, MElightgreen, MEgreenyellow and MEdarkred). Additionally, an lncRNA-miRNA-mRNA network was constructed, incorporating several known salt-associated miRNAs such as miR156, miR169 and miR396. Conclusions This study enhances our understanding of the role of lncRNAs in the response of tobacco to salt stress. It provides valuable information on co-expression networks of lncRNA and mRNAs, as well as networks of lncRNAs-miRNAs-mRNAs. These findings identify important candidate lncRNAs that warrant further investigation in the study of plant-environment interactions.

Abstract Pulmonary arterial hypertension (PAH) is a life-threatening condition characterized by a progressive increase in pulmonary vascular resistance leading to right ventricular failure and often death. Here we report that deficiency of transcription factor GATA6 is a shared pathological feature of PA endothelial (PAEC) and smooth muscle cells (PASMC) in human PAH and experimental PH, which is responsible for maintenance of hyper-proliferative cellular phenotypes, pulmonary vascular remodeling and pulmonary hypertension. We further show that GATA6 acts as a transcription factor and direct positive regulator of anti-oxidant enzymes, and its deficiency in PAH/PH pulmonary vascular cells induces oxidative stress and mitochondrial dysfunction. We demonstrate that GATA6 is regulated by the BMP10/BMP receptors axis and its loss in PAECs and PASMC in PAH supports BMPR deficiency. In addition, we have established that GATA6-deficient PAEC, acting in a paracrine manner, increase proliferation and induce other pathological changes in PASMC, supporting the importance of GATA6 in pulmonary vascular cell communication. Treatment with dimethyl fumarate resolved oxidative stress and BMPR deficiency, reversed hemodynamic changes caused by endothelial Gata6 loss in mice, and inhibited proliferation and induced apoptosis in human PAH PASMC, strongly suggesting that targeting GATA6 deficiency may provide a therapeutic advance for patients with PAH.

Abstract Autophagy and cytoskeleton integrity of chondrocytes are a considered as major factors in the progression of osteoarthritis (OA) involving excessive chondrocyte apoptosis and senescence. Nesfatin-1, an adipokine, has been reported to be closely related to cell autophagy and cytoskeleton malfunction. Our previous study found that nesfatin-1 was highly correlated with OA progress in OA patient, and the expression of nesfatin-1 rises in knee articular tissue, serum and chondrocytes. In current study, we aimed to explore the therapeutic effect of nesfatin-1 on OA and its molecular mechanism related to chondrocyte autophagy and cytoskeleton malfunction. We firstly demonstrated that nesfatin-1 effectively suppressed excessive autophagy of OA chondrocytes at both gene and protein levels. Meanwhile, we also found that nesfatin-1 significantly improved cytoskeleton integrity by showing higher F-actin/G-actin ratio, as well as more organized actin fiber structure. Mechanistically, utility of RhoA activator and inhibitor revealed that regulation of autophagy and cytoskeleton integrity via nesfatin-1 was realized via RhoA/ROCK pathway. We also confirmed that nesfatin-1 significantly ameliorated IL-1β induced cartilage degeneration via destabilization of the medial meniscus (DMM) model. Overall, our study indicates that nesfatin-1 might be a promising therapeutic molecule for OA intervention.

Cashmere and wool are both natural animal fibers used in the textile industry, but cashmere is of superior quality, is rarer, and more precious. It is therefore important to distinguish the two fibers accurately and effectively. However, challenges due to their similar appearance, morphology, and physical and chemical properties remain. Herein, a terahertz electromagnetic inductive transparency (EIT) metasurface biosensor is introduced for qualitative and quantitative identification of cashmere and wool. The periodic unit structure of the metasurface consists of four rotationally symmetric resonators and two cross−arranged metal secants to form toroidal dipoles and electric dipoles, respectively, so that its effective sensing area can be greatly improved by 1075% compared to the traditional dipole mode, and the sensitivity will be up to 342 GHz/RIU. The amplitude and frequency shift changes of the terahertz transmission spectra caused by the different refractive indices of cashmere/wool can achieve highly sensitive label−free qualitative and quantitative identification of both. The experimental results show that the terahertz metasurface biosensor can work at a concentration of 0.02 mg/mL. It provides a new way to achieve high sensitivity, precision, and trace detection of cashmere/wool, and would be a valuable application for the cashmere industry.

Due to anthropogenic emissions, the global CO2 concentration increases at a rate of approximately 2 ppm per year. With over 130 countries and regions committing to carbon neutrality goals and continuously reducing anthropogenic CO2 emissions, understanding how atmospheric CO2 concentrations will change globally and in other regions has become an intriguing question. Examining different regions’ efforts to reduce anthropogenic CO2 emissions through atmospheric CO2 observations is also meaningful. We used prior and posterior fluxes to drive the TM5 model. The posterior fluxes were based on the China Carbon Monitoring, Verification and Support System for Global (CCMVS-G), which assimilated the atmospheric CO2 concentration data from ground-based observation and satellite observation. We found that the CO2 concentration obtained using the posterior fluxes was more in line with the actual situation. Then, we presented some experiments to estimate how global and regional CO2 concentrations would change if certain key regions and the whole world achieved net zero emissions of anthropogenic CO2. After removing carbon fluxes from China, North America, and Europe, global CO2 concentrations decreased by around 0.58 ppm, 0.22 ppm, and 0.10 ppm, respectively. The most significant decrease occurred in the regions where fluxes were removed, followed by other areas at the same latitude affected by westerly winds. This indicates that fossil fuel flux is the main factor affecting CO2 concentrations, and that meteorological-driven transportation also significantly impacts CO2 concentrations. Most importantly, using this method, it is possible to quantitatively estimate the impact of achieving carbon neutrality in one region on CO2 concentrations in local regions as well as globally.

Abstract Objective Laryngeal cancer is a common malignancy in otorhinolaryngological head and neck surgery, accounting for approximately one-third of all head and neck malignancies. Terahertz time-domain spectroscopy (THz-TDS) has recently been found to be useful for the detection of tumors. This study was conducted to investigate the application of THz-TDS in the diagnosis of pathological resection margins of laryngeal cancer. Methods Fresh laryngeal cancer tissues from 10 patients with laryngeal cancer were extracted, and after simultaneous HE staining and terahertz imaging, the tumor area, paracancerous area, and normal tissue area of each laryngeal cancer tissue sample were located under a microscope according to the pathological results of HE staining. Results The shape contours of the tumor region revealed by terahertz imaging maps and HE staining were similar. In the terahertz spectrum in the frequency range of 0.5–1.9 THz, both the absorption coefficient and refractive index values followed the order tumor > para cancer > normal tissue, with statistically significant differences (P < 0.01). When the terahertz frequency was 1.5 THz, the absorption coefficient of terahertz light waves by laryngeal cancer tissue and the percentage of nuclei showed an extremely high positive correlation (P < 0.01, r = 0.971). In the frequency ranges of 0.5–1.2 THz and 1.6–1.9 THz, the absorption coefficients of the highly differentiated group were higher than those of the moderately differentiated group. In the frequency range of 1.2–1.6 THz, the results were reversed, with statistically significant differences (P < 0.05). In the frequency range of 0.5–1.9 THz, the highly differentiated group had a higher refractive index than the moderately differentiated group, with a statistically significant difference (P < 0.05). Conclusions THz-TDS can be used to determine the pathological margins of laryngeal cancer based on the absorption coefficient and refractive index, and the magnitudes of the absorption coefficient and refractive index are related to the percentage of nuclei. The degree of differentiation of laryngeal cancer tissue can be assessed by THz-TDS. The study shows that the terahertz time-domain system is promising for applications in the diagnosis of laryngeal cancer, especially for the more accurate identification of intraoperative margins.

Background: Copper as phytonutrient has powerful activity against health diseases. A newly discovered mechanism of cell death that affects energy metabolism by copper (“cuproptosis”) can induce multiple cuproptosis-related genes. Hepatocellular carcinoma (HCC) is a poorly prognosed widespread cancer having danger of advanced metastasis. Therefore, earlier diagnosis followed by the specific targeted therapy are required for improved prognosis. The work herein constructed scoring system built on ten cuproptosis-related genes (CRGs) to predict progression of tumor and metastasis more accurately and test patient reaction toward immunotherapy.Methods: A comprehensive assessment of cuproptosis patterns in HCC samples from two databases and a real-world cohort was performed on ten CRGs, that were linked to immune cell infiltration signatures of TME (tumor microenvironment). Risk signatures were created for quantifying effect of cuproptosis on HCC, and the effects of related genes on cellular function of HCC were investigated, in addition to the effects of immunotherapy and targeted therapy drugs.Results: Two distinct cuproptosis-associated mutational patterns were identified, with distinct immune cell infiltration characteristics and survival likelihood. Studies have shown that assessment of cuproptosis-induced tumor mutational patterns can help predict tumor stage, phenotype, stromal activity, genetic diversity, and patient prognosis. High risk scores are characterized by lower survival and worse treatment with anti-PD-L1/CTAL4 immunotherapy and first-line targeted drugs. Cytological functional assays show that CDKN2A and GLS promote proliferation, migration and inhibit copper-dependent death of HCC cells.Conclusion: HCC patients with high-risk scores exhibit significant treatment disadvantage and survival rates. Cuproptosis plays a non-negligible role in the development of HCC. Quantifying cuproptosis-related designs of tumors will aid in phenotypic categorization, leading to efficient personalized and targeted therapeutics and precise prediction of prognosis and metastasis.

Abstract Background Lycopene epsilon-cyclase (ε-LCY) is a key enzyme in the carotenoid biosynthetic pathway (CBP) of higher plants. In previous work, we cloned two Ntε-LCY genes from allotetraploid tobacco (Nicotiana tabacum), Ntε-LCY2 and Ntε-LCY1, and demonstrated the overall effect of Ntε-LCY genes on carotenoid biosynthesis and stress resistance. However, their genetic and functional characteristics require further research in polyploid plants. Results Here, we used CRISPR/Cas9 to obtain Ntε-LCY2 and Ntε-LCY1 mutants in allotetraploid N.tabacum K326. Ntε-LCY2 and Ntε-LCY1 had similar promoter cis-acting elements, including light-responsive elements. The Ntε-LCY genes were expressed in roots, stems, leaves, flowers, and young fruit, and their highest expression levels were found in leaves. Ntε-LCY2 and Ntε-LCY1 genes responded differently to normal light and high light stress. Both the Ntε-LCY2 and the Ntε-LCY1 mutants had a more rapid leaf growth rate, especially ntε-lcy2-1. The expression levels of CBP genes were increased in the ntε-lcy mutants, and their total carotenoid content was higher. Under both normal light and high light stress, the ntε-lcy mutants had higher photosynthetic capacities and heat dissipation levels than the wild type, and this was especially true of ntε-lcy2-1. The reactive oxygen species content was lower in leaves of the ntε-lcy mutants. Conclusion In summary, the expression patterns and biological functions of the Ntε-LCY genes Ntε-LCY1 and Ntε-LCY2 differed in several respects. The mutation of Ntε-LCY2 was associated with a greater increase in the content of chlorophyll and various carotenoid components, and it enhanced the stress resistance of tobacco plants under high light.

Abstract Background Osteoarthritis (OA) is a debilitating disease that inflicts intractable pain, a major problem that humanity faces, especially in aging populations. Stem cells have been used in the treatment of many chronic diseases, including OA. Cartilage progenitor/stem cells (CPSCs) are a type of stem cells with the ability to self- renew and differentiate. They hold a promising future for the understanding of the progression of OA and for its treatment. Previous studies have reported the relationship between mitochondrial dynamics and mesenchymal stem cell (MSC) proliferation, differentiation and aging. Mitochondrial dynamic and morphology change during stem cell differentiation. Methods This study was performed to access the relationship between mitochondrial dynamics and chondrogenic differentiation of CPSCs. Mitochondrial fusion and fission levels were measured during the chondrogenic differentiation process of CPSCs. After that, we used mitochondrial fusion promoter to induce fusion in CPSCs and then the chondrogenic markers were measured. Transmission electron microscopy (TEM) and confocal microscopy were used to capture the mass and fusion status of mitochondria. Lentiviruses were used to detect the role of mitofusin 2 (Mfn2) in CPSC chondrogenic differentiation. In vivo, Mfn2 was over-expressed in sheets of rat CPSCs, which were then injected intra-articularly into the knees of rats. Results Mitochondrial fusion markers were upregulated during the chondrogenic induction process of CPSCs. The mass of mitochondria was higher in differentiated CPSC, and the fusion status was obvious relative to un-differentiated CPSC. Chondrogenesis of CPSCs was upregulated with the induction by mitochondrial fusion promoter. Mfn2 over-expression significantly increased chondrocyte-specific gene expression and reversed OA through NOTCH2 signal pathway. Conclusions Our study demonstrated that the mitochondrial fusion promotes chondrogenesis differentiation of CPSCs. Mfn2 accelerates the chondrogenesis differentiation of CPSCs through Notch2. In vivo, Mfn2-OE in sheets of rCPSCs ameliorated OA in the rat model.

Proteins of the Nitrate Transporter 1/Peptide Transporter (NPF) family transport a diverse variety of substrates, such as nitrate, peptides, hormones and chloride. In this study, a systematic analysis of the tobacco (Nicotiana tabacum) NPF family was performed in the cultivated ‘K326’. In total, 143 NtNPF genes were identified and phylogenetically classified into eight subfamilies, NPF1 to NPF8, based on the classification of NPF families in other plant species. The chromosomal locations and structures of the NtNPF genes were analyzed. The expression profiles of NtNPF genes under NaCl stress were analyzed to screen the possible NPF genes involving in chloride regulation in tobacco. Most NtNPF6 genes responded to salt stress in the roots and leaves. The expression of NtNPF6.13 was significantly down-regulated after salt stress for 12h. The chloride content was reduced in the roots of ntnpf6.13 mutant. These findings support the participation of NtNPF6.13 in chloride uptake. Several other NtNPF genes that play potential roles in chloride metabolism of tobacco require further study.

The question of at what resolution the large eddy simulations (LESs) of a tropical cyclone (TC) high wind area may converge largely remains unanswered. To address this issue, LESs with five resolutions of 300 m, 100 m, 60 m, 33 m, and 20 m are performed in this study to simulate a high wind area near the radius of maximum wind of Typhoon Chanthu (2021) using the Weather Research and Forecasting (WRF) model. The results show that, for a limited area LES, model grid resolution may alter the local turbulence structure to generate significantly different extreme values of temperature, moisture, and winds, but it only has a marginal impact on the median values of these variables throughout the vertical column. All simulations are able to capture the turbulent roll vortices in the TC boundary layer, but the structure and intensity of the rolls vary substantially in different resolution simulations. Local hectometer-scale eddies with vertical velocities exceeding 10 m s−1 are only observed in the 20 m resolution simulation but not in the coarser resolution simulations. The ratio of the resolved turbulent momentum fluxes and turbulent kinetic energies (TKEs) to the total momentum fluxes and TKEs appears to show some convergence of LESs when the grid resolution reaches 100 m or finer, suggesting that it is an acceptable grid resolution for LES applications in TC simulations.

Solar-heating technology is a promising solution to help China achieve the “3060 double carbon” target as soon as possible. Seasonal thermal storage (STS) can effectively solve the mismatch problem of solar-heating systems between the supply and demand of thermal energy. Due to the instability of solar radiation resources and the heat demand, it is necessary to analyze the dynamic response characteristics and operation strategy optimization of the system in different operation stages. Yet, related studies are still scarce. The aim of this paper is to study the switching mechanism of the operation modes and the transitive relation of the system energy in different operation stages based on a pilot solar-heating system with STS in Huangdicheng, northern China. The impacts of different heating strategies on the system performance were also analyzed with a dynamic simulated method in TRNSYS. The results showed that the solar fraction of the system reached 89.4% in the third year, which was 3.6% higher than that in the first year. The quality–quantity heating operation strategies are effective ways to improve the discharge efficiency of the STS and the system performance without a heat pump. The electricity consumption of the pump on the heating side could be significantly reduced by 44.6% compared with the quality control. Ultimately, the findings in this paper are valuable for the optimization of the operation of solar-heating systems.

Abstract Background Cigar wrapper leaves are the most important raw material of cigars. Studying the genomic information of cigar tobacco is conducive to improving cigar quality from the perspective of genetic breeding. However, no reference genome or full-length transcripts at the genome-wide scale have been reported for cigar tobacco. In particular, anion channels/transporters are of high interest for their potential application in regulating the chloride content of cigar tobacco growing on coastal lands, which usually results in relatively high Cl− accumulation, which is unfavorable. Here, the PacBio platform and NGS technology were combined to generate a full-length transcriptome of cigar tobacco used for cigar wrappers. Results High-quality RNA isolated from the roots, leaves and stems of cigar tobacco were subjected to both the PacBio platform and NGS. From PacBio, a total of 11,652,432 subreads (19-Gb) were generated, with an average read length of 1,608 bp. After corrections were performed in conjunction with the NGS reads, we ultimately identified 1,695,064 open reading frames including 21,486 full-length ORFs and 7,342 genes encoding transcription factors from 55 TF families, together with 2,230 genes encoding long non-coding RNAs. Members of gene families related to anion channels/transporters, including members of the SLAC and CLC families, were identified and characterized. Conclusions The full-length transcriptome of cigar tobacco was obtained, annotated, and analyzed, providing a valuable genetic resource for future studies in cigar tobacco.

Hyper-proliferation of pulmonary arterial vascular smooth muscle cells (PAVSMC) is an important pathological component of pulmonary vascular remodeling in pulmonary arterial hypertension (PAH). Lipogenesis is linked to numerous proliferative diseases, but its role in PAVSMC proliferation in PAH remains to be elucidated. We found that early-passage human PAH PAVSMC had significant up-regulation of key fatty acids synthesis enzymes ATP-citrate lyase (ACLY), acetyl-CoA carboxylase (ACC), and fatty acid synthase (FASN), and increased unstimulated proliferation compared to control human PAVSMC. Treatment with an allosteric ACC inhibitor 5-tetradecyloxy-2-furoic acid (TOFA) significantly decreased proliferation and induced apoptosis of human PAH PAVSMC. Intracellular lipid content and proliferation of PAH PAVSMC were not reduced by incubation in lipid-depleted media but suppressed by a non-metabolizable analog of glucose 2-Deoxy-D-glucose (2-DG) and partially restored by addition of pyruvate. Protein kinase Akt was upregulated in human PAH PAVSMC in a sirtuin 7 (SIRT7)- and c-Jun N-terminal kinase (JNK)-dependent manner. Pharmacological inhibition of Akt down-regulated ACLY and ACC, significantly reduced intracellular lipid content, inhibited proliferation and induced apoptosis of human PAH PAVSMC. Taken together, these data demonstrate that human PAH PAVSMC have up-regulated lipogenesis, which is supported in an Akt- and glycolysis-dependent manner and is required for increased proliferation and survival. Our data suggest that there is a mechanistic link between glycolysis, lipogenesis, and the proliferation of human PAH PAVSMC and call for further studies to determine the potential attractiveness of a SIRT7/JNK-Akt-lipogenesis axis as a target pathway to inhibit PAVSMC hyper-proliferation in PAH.

AbstractThis article describes a simple PCFG induction model with a fixed category domain that predicts a large majority of attested constituent boundaries, and predicts labels consistent with nearly half of attested constituent labels on a standard evaluation data set of child-directed speech. The article then explores the idea that the difference between simple grammars exhibited by child learners and fully recursive grammars exhibited by adult learners may be an effect of increasing working memory capacity, where the shallow grammars are constrained images of the recursive grammars. An implementation of these memory bounds as limits on center embedding in a depth-specific transform of a recursive grammar yields a significant improvement over an equivalent but unbounded baseline, suggesting that this arrangement may indeed confer a learning advantage.

Abstract Long noncoding RNAs (lncRNAs) play crucial roles in regulating a variety of biological processes in lung adenocarcinoma (LUAD). In our study, we mainly explored the functional roles of a novel lncRNA long intergenic non-protein coding RNA 1426 (LINC01426) in LUAD. We applied bioinformatics analysis to find the expression of LINC01426 was upregulated in LUAD tissue. Functionally, silencing of LINC01426 obviously suppressed the proliferation, migration, epithelial–mesenchymal transition (EMT), and stemness of LUAD cells. Then, we observed that LINC01426 functioned through the hedgehog pathway in LUAD. The effect of LINC01426 knockdown could be fully reversed by adding hedgehog pathway activator SAG. In addition, we proved that LINC01426 could not affect SHH transcription and its mRNA level. Pull-down sliver staining and RIP assay revealed that LINC01426 could interact with USP22. Ubiquitination assays manifested that LINC01426 and USP22 modulated SHH ubiquitination levels. Rescue assays verified that SHH overexpression rescued the cell growth, migration, and stemness suppressed by LINC01426 silencing. In conclusion, LINC01426 promotes LUAD progression by recruiting USP22 to stabilize SHH protein and thus activate the hedgehog pathway.

Abstract Background Carotenoids play important roles in photosynthesis, hormone signaling, and secondary metabolism. Phytoene synthase (PSY) catalyzes the first step of the carotenoid biosynthetic pathway. In this study, we aimed to characterize the PSY genes in tobacco and analyze their function. Results In this study, we identified three groups of PSY genes, namely PSY1, PSY2, and PSY3, in four Nicotiana species; phylogenetic analysis indicated that these genes shared a high similarity with those in tomato but not with those in monocots such as rice and maize. The expression levels of PSY1 and PSY2 were observed to be highest in leaves compared to other tissues, and they could be elevated by treatment with certain phytohormones and exposure to strong light. No PSY3 expression was detected under these conditions. We constructed virus-induced PSY1 and PSY2 silencing in tobacco and found that the newly emerged leaves in these plants were characterized by severe bleaching and markedly decreased carotenoid and chlorophyll content. Thylakoid membrane protein complex levels in the gene-silenced plants were also less than those in the control plants. The chlorophyll fluorescence parameters such as Fv/Fm, ΦPSII, qP, and NPQ, which reflect photosynthetic system activities, of the gene-silenced plants were also significantly decreased. We further performed RNA-Seq and metabonomics analysis between gene-silenced tobacco and control plants. RNA-Seq results showed that abiotic stress, isoprenoid compounds, and amino acid catabolic processes were upregulated, whereas the biosynthesis of cell wall components was downregulated. Metabolic analysis results were consistent with the RNA-Seq. We also found the downstream genes in carotenoid biosynthesis pathways were upregulated, and putative transcription factors that regulate carotenoid biosynthesis were identified. Conclusions Our results suggest that PSY can regulate carotenoid contents not only by controlling the first biosynthesis step but also by exerting effects on the expression of downstream genes, which would thereby affect photosynthetic activity. Meanwhile, PSY may affect other processes such as amino acid catabolism and cell wall organization. The information we report here may aid further research on PSY genes and carotenoid biosynthesis.

Aim. This retrospective study is aimed at evaluating the outcomes of a modified peroral endoscopic myotomy (POEM) technique in patients with type II achalasia. Methods. We performed a modified POEM procedure, which involved a shorter (total myotomy length=4 cm), full-thickness myotomy, on 31 patients with type II achalasia. Clinical success rates, technical success rates, pre- and postoperative esophageal manometry results, complications, and reflux-related adverse events were evaluated. Results. The clinical success (Eckardt score≤3) rates were 100% and 88.9% within 2 years and beyond 2 years postoperatively, respectively. The median lower esophageal sphincter pressures (LESP) decreased from 31.6 (26.7-49.7) mmHg preoperatively to 13.4 (10.5-21.6) and 11.8 (7.4-16.7) mmHg (P

Lung adenocarcinomas (LUADs) harbouring epidermal growth factor receptor (EGFR) mutations are generally unable to benefit from immune checkpoint inhibitors (ICIs) due to an immunosuppressive tumour microenvironment (TME) and a lower tumour mutation burden. Currently, no gene signature can comprehensively evaluate the TME and predict the prognosis of patients with EGFR-mutant LUAD. Using the Cancer Genome Atlas database of EGFR-mutant LUAD based on the immune score derived from the ESTIMATE algorithm, we divided 80 patients with EGFR-mutant LUAD samples into high and low immune score groups with different immune microenvironments. Subsequently, we screened 396 differentially expressed immune-related genes with prognostic value. The top Gene Ontology terms were significantly enriched in biological functions related to T cell differentiation, immune response, cell cycle, and cell proliferation, which are closely related to the immune microenvironment of tumours. In addition, the KEGG pathway enrichment analysis mainly focused on cell cycle, cell adhesion molecules, and cytokine-cytokine receptor interaction, which also had a relationship with the immune response. Subsequently, we identified a three-gene signature including BTLA, BUB1B, and CENPE using the LASSO Cox regression model. The three-gene signature could accurately identify patients at risk of EGFR-mutant LUAD in the training and validation sets and high-risk patients from both the sets exhibited significantly shorter overall survival (p=0.0053 and p=0.035, respectively). CIBERSORT was used to evaluate the abundance of immune cell infiltration in the EGFR-mutant LUAD microenvironment. The immune activity of B cells and macrophages was higher in the low-risk group, while the immune activity of natural killer cells and T cells was higher in the high-risk group. Thus, the three-gene signature closely related to immunosuppressive TME could predict the risk and prognosis in patients with EGFR-mutant LUAD.

Abstract. Inner ear hair cells are important for maintaining hearing. Irreversible damage to hair cells is an important cause of sensorineural deafness. Electromagnetic radiation, especially high-power microwave, is an important threat to human health in modern society and war. However, it is not clear whether high-power microwave has an effect on cochlea hair cells. This study aimed to assess the effects of high-power microwave on cochlear hair cells in guinea pigs, and investigate the potential protection of these cells against high-power microwave-induced damage by recombinant adenovirus A20. Based on experimental results, a 65 W/cm2 irradiation density applied to guinea pigs in this study to establish a high-power microwave inner ear injury model. In addition, pAdEeay-1/A20 was injected via a round window into experimental guinea pig cochlea, whereas artificial perilymph was injected into the control group. Auditory function was assessed by testing the auditory brainstem response threshold, and damage to cochlear hair cells was investigated by cell counting and scanning electron microscopy observations of the basilar membrane. Inner ear injury was observed 6hours after 65 W/cm2 of irradiation and the auditory brainstem response threshold was significantly higher in the irradiation group (P

Abstract Background Rotator cuff tears are one of the most frequent upper extremity injuries and lead to pain and disability. Recent studies have implicated fatty infiltration in rotator cuff is a key failure element with the higher re-tear rates and poorer functional prognosis. Therefore, we investigated the differential expression of key genes in each stage of rotator cuff tear. Methods A published expression profile was downloaded from the Gene Expression Omnibus database and analyzed using the Linear Models for Microarray Data (LIMMA) package in R language to identify differentially expressed genes (DEGs) in different stages of injured rotator cuff muscles. Gene ontology (GO) functional and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were performed to annotate the function of the DEGs. Finally, PPI network and module analysis were used to identify hub genes. Results A total of 1089 fatty infiltration-related DEGs were identified, including 733 upregulated and 356 downregulated genes, and GO analyses confirmed that fatty infiltration was strongly associated with inflammatory response, aging, response to lipopolysaccharide, and immune response. Significantly enriched KEGG pathways associated with these DEGs included the phagosome, cell adhesion molecules, tuberculosis, and osteoclast differentiation. Further analyses via a PPI network and module analysis identified a total of 259 hub genes. Among these, Tmprss11d, Ptprc, Itgam, Mmp9, Tlr2, Il1b, Il18, Ccl5, Cxcl10, and Ccr7 were the top ten hub genes. Conclusions Our findings indicated the potential key genes and pathways involved in fatty degeneration in the development of fatty infiltration and supplied underlying therapeutic targets in the future.

Biosensors can convert the concentration of biological analytes into an electrical signal or other signals for detection. They are widely used in medical diagnostics, food safety, process control, and environmental monitoring fields. In recent years, new schemes of stable biosensor interfaces have attracted much attention. Interface design is a vital part of biosensor development, since its stability can be directly related to the quality of sensing performance such as sensitivity, stability, and linearity. This review summarized the latest methods and materials used to construct stable biosensor interfaces and pointed some future perspectives and challenges of them. From the literature, we found that nanomaterials, polymers, and their composites such as chitosan, cellulose, and conducting polymers are the most common materials used in the biosensor interface design. Apart from materials, there are increasing developments in monolayer membrane techniques, three-dimensional constructions, and other interface techniques. This review is a study of the latest progress in biosensor interface stability solutions, which may provide some references and innovative directions of biosensor interface design for researchers in biosensor fields and encourage people to further explore new materials and methods.

Heterotopic ossification (HO) is a pathological condition involved in tendinopathy. Adipokines are known to play a key role in HO of tendinopathy. Nesfatin-1, an 82-amino acid adipokine is closely reportedly associated with diabetes mellitus (DM), which, in turn, is closely related to tendinopathy. In the present study, we aimed to investigate the effects of nesfatin-1 on the osteogenic differentiation of tendon-derived stem cells (TDSCs) and the pathogenesis of tendinopathy in rats. In vitro, TDSCs were incubated in osteogenic induction medium for 14 days with different nesfatin-1 concentration. In vivo, Sprague Dawley rats underwent Achilles tenotomy to evaluate the effect of nesfatin-1 on tendinopathy. Our results showed that the expression of nesfatin-1 expression in tendinopathy patients was significantly higher than that in healthy subjects. Nesfatin-1 affected the cytoskeleton and reduced the migration ability of TDSCs in vitro. Furthermore, nesfatin-1 inhibited the expression of Scx, Mkx, and Tnmd and promoted the expression of osteogenic genes, such as COL1a1, ALP, and RUNX2; these results suggested that nesfatin-1 inhibits cell migration, adversely impacts tendon phenotype, promotes osteogenic differentiation of TDSCs and the pathogenesis of HO in rat tendons. Moreover, we observed that nesfatin-1 suppressed autophagy and activated the mammalian target of rapamycin (mTOR) pathway both in vitro and in vivo. The suppression of the mTOR pathway alleviated nesfatin-1-induced HO development in rat tendons. Thus, nesfatin-1 promotes the osteogenic differentiation of TDSC and the pathogenesis of HO in rat tendons via the mTOR pathway; these findings highlight a new potential therapeutic target for tendinopathy.

BackgroundIn the Xuanwei region of China, lung cancer incidence and mortality are among the highest in China, attributed to severe air pollution generated by combustion of smoky coal. No study has yet comprehensively evaluated the prevalence of epidermal growth factor receptor (EGFR) mutation characteristics in patients with non-small cell lung cancer (NSCLC) in Xuanwei. This meta-analysis was designed to analyze the EGFR mutation pattern in NSCLC patients in Xuanwei region of Yunnan Province in China.MethodsElectronic databases were comprehensively searched and relevant literatures were retrieved. The odds ratio (OR) for EGFR mutations between Xuanwei region and non-Xuanwei region was calculated, and the absolute incidence of EGFR mutations in Xuanwei was pooled by mutation subtype.ResultsSeven studies involving 1,355 patients with NSCLC from Yunnan Province (442 in Xuanwei and 913 in other regions) were included. The EGFR mutation rate ranged between 30.19% and 55.56%. Higher uncommon EGFR mutations (OR: 5.69, 95%CI: 2.23–14.49, P

Background/Aim: Lymph node density is a parameter used to more accurately predict tumor recurrence and patient survival. However, its association with surgical outcome in pyriform sinus carcinoma remains unclear. The purpose of this study was to assess the prognostic value of lymph node density in advanced pyriform sinus carcinoma. Patients and Methods: A total of 87 patients with pyriform sinus carcinoma treated between 2008 and 2015 were enrolled. Then, 5-year overall survival, 5-year disease-specific survival, 5-year disease-free survival, and 5-year regional recurrence-free survival were utilized to assess the prognostic significance of lymph node density. Results: With a median follow-up period of 31.8 months, 5-year overall survival, disease-specific survival, disease-free survival, and regional recurrence-free survival were 37.9%, 46.0%, 41.4%, and 54.0%, respectively. Univariate analysis revealed that lymph node density ≥ 0.093 was a significant predictor of poor 5-year overall survival ( P = .005), disease-specific survival ( P = .008), disease-free survival ( P = .0013), and regional recurrence-free survival ( P = .003). Furthermore, multivariate analysis demonstrated that lymph node density was negatively associated with adverse 5-year overall survival (hazard ratio = 1.62, 95% CI: 1.15-2.29, P = .006), disease-specific survival (hazard ratio = 1.86, 95% CI: 1.24-2.80, P = .003), disease-free survival (hazard ratio = 0.45, 95% CI: 0.24-0.85, P = .014), and regional recurrence-free survival (hazard ratio = 2.97, 95% CI: 1.43-6.17, P = .004). Conclusion: Taken together, these results reveal that lymph node density is a powerful prognostic factor for patients with T3 and T4 pyriform sinus carcinoma, and the median lymph node density cutoff values ≥ 0.093 are associated with a greater risk of recurrence and poorer survival.

In recent years, non-toxic quantum dot has caught the attention of biomedical fields. However, the inherent cytotoxicity of QDs makes its biomedical application painful, and is a major drawback of this method. In this paper, a non-toxic and water-soluble quantum dot AgInZnS-GO using graphene oxide was synthesized. A simple model of state complex was also established, which is produced through a combination of quantum dots and protein. The interaction between AIZS-GO QDs and human serum albumin (HSA) has significant meaning in vivo biological application. Herein, the binding of AIZS-GO QDs and HSA were researched using fluorescence spectra, Uv-visible absorption spectra, FT-IR spectra, and circular dichroism (CD) spectra. The results of fluorescence spectra demonstrate that AIZS-GO QDs have an obvious fluorescence quenching effect on HSA. The quenching mechanism is static quenching, which implies that some type of complex was produced by the binding of QDs and HSA. These results were further proved by Uv-visible absorption spectroscopy. The Stern-Volmer quenching constant Ksv at various temperatures (298 K, 303 K, 308 K) were acquired from analyzing Stern-Volmer plots of the fluorescence quenching information. The Van't Hoff equation could describe the thermodynamic parameters, which demonstrated that the van der Waals and hydrogen bonds had an essential effect on the interaction. FT-IR spectra and CD spectra further indicate that AIZS-GO QDs can alter the structure of HSA. These spectral methods show that the quantum dot can combine well with HSA. The experimental results showed that AgInZn-GO water-soluble quantum dots have good biocompatibility, which can be combined with proteins to form new compounds which have no cytotoxicity and biological practicability. It provides an important basis for the combination of quantum dots and specific proteins as well as fluorescent labeling.

Nitrite is a toxic substance, when excessive nitrite enters the human body, it will be seriously harmful to human. At present, the detection methods of nitrite are complicated to operate and require expensive detection instruments. Therefore, an effective, fast and highly selective nanogold film interdigital electrode sensors that can detect nitrite easily and quickly is developed in the work. Firstly, the variation of the sensitivity of nanogold film nitrite sensors with concentrations (1 mol/L, 10−1 mol/L, 10−2 mol/L, 10−3 mol/L, 10−4 mol/L, and 10−5 mol/L) was measured by experiments. Then, Chrome-black T was modified to the surface of the nanogold film interdigital electrodes by electrochemical polymerization, and the film of chrome-black T had affinity for nitrite ions, so nitrite ions were enriched on the sensor surface. The change law of the impedance signal of the modified nanogold film nitrite sensors after being added to different concentrations of sodium nitrite solution were also concluded. The study demonstrates that the larger the concentration of sodium nitrite solution is added to the modified interdigital electrodes, the smaller impedance and resistance of the modified interdigital electrodes are reflected. Finally, specificity of the modified interdigital electrode sensors has been demonstrated. The novel interdigital electrode sensors can detect the concentration of nitrite solution conveniently and quickly with only 30 s. Therefore, the prospect of applying the novel nanogold film interdigital electrode sensors to the detection of nitrite in blood, body fluid, food and drinking water is promising.

The regulation of transcription level is an important step in gene expression process. Beauveria bassiana is a broad-spectrum insecticidal fungi widely used in the biologic control of arthropod. The regulation of its transcription level is a multilevel complex process. Multiprotein bridging factor 1(MBF1) is a transcriptional co-activator that bridges sequence-specific activators and the TATA-box binding protein(TBP), Little is known about the interaction between MBF1, TBP, and TBP binding to DNA(TATA-sequences)in filamentous fungi of Beauveria bassiana, The binding of TBP to TATA-box and TBP to MBF1 was investigated via electrochemical biosensor. Graphene oxide has an electronic mobility that is unattainable for any metal, so it will be highly sensitive as a test electrode. Hence, we developed a simple, sensitive and specific sensor based on an TBP probe and graphene oxide that successfully detected the interaction of TBP and TATA-box or MBF1. From the electrochemical impedance spectroscopy (EIS), we find that the radius will increase when adding TATA-box or MBF1 buffer to the modified TBP protein electrode. When adding no TATA-box or no MBF1, the radius is relatively unchanged. The interaction between TBP and TATA-box or MBF1 was proved based on the results. These data confirmed the specificity of the interactions, (1) our developed graphene-based electrochemical biosensor can be used for monitoring the interaction between TBP and TATA-box or MBF1, (2) TBP can bind to TATA-box, (3) TBP can bind to MBF1, and (4) TBP mediates the interactions of MBF1 to DNA. Therefore, this work provided a label-free, low-cost and simple detection method for the complex process of eukaryotic gene transcription regulation.

Osteoarthritis (OA) is the most prevalent joint disease and uncontrolled inflammation is now recognized to play vital roles in OA development. Targeting the endogenous counterpart of inflammation may develop new therapeutic approaches in resolving inflammation persistence and treating inflammatory disease including OA. The orphan nuclear receptor 4A1 (NR4A1) is a key negative regulator of inflammatory responses but its role in osteoarthritis remains unclear. In the present study, we found that the NR4A1 expression was elevated in human osteoarthritis cartilage and in vitro OA model, which could be blocked by NF-κB signal inhibitor JSH23. The overexpression of NR4A1 inhibited, whereas knockdown of NR4A1 enhanced IL-1β induced COX-2, iNOS, MMP3, MMP9 and MMP13 expression, and luciferase reporter activity of NF-κB response element. Though NR4A1 was upregulated in inflammatory stimulation and creates a negative feedback loop, persistent inflammatory stimulation inhibited NR4A1 expression and activation. The expression of NR4A1 declined rapidly after an initial peak in conditions of chronic IL-1β stimulation, which could be partially restored by HDACs inhibitor SAHA. The phosphorylation of NR4A1 was increased in human osteoarthritis cartilage, and p38 inhibitor SB203580, JNK inhibitor SP600125 and ERK inhibitor FR180204 could significantly inhibited IL-1β induced NR4A1 phosphorylation. Reactivation of NR4A1 by its agonist cytosporone B could inhibit IL-1β induced chondrocyte inflammation and expression of COX-2, iNOS, MMP3, MMP9, and MMP13. In rat OA model, intra-articular injection of cytosporone B protected cartilage damage and ameliorated osteoarthritis. Thus, our study demonstrated that the NR4A1 is a key endogenous inhibitor of chondrocyte inflammation, which was relatively inactivated under chronic inflammatory stimulation through HDACs mediated transcriptional suppression and MAKP dependent phosphorylation in osteoarthritis. NR4A1 agonist cytosporone B could reactivate and restore the inhibitory regulatory ability of NR4A1, prevent excessive inflammation, and ameliorates osteoarthritis.

Tonotopic differences in the structure and physiological function, e.g., synapse number, membrane properties, Ca2+ channels, Ca2+ dependence of exocytosis and vesicle pool replenishment of inner hair cells (IHCs) along the longitudinal cochlear axis have recently been discovered, suggesting different gene expression patterns of IHCs. To determine whether IHCs present different gene expression patterns along the longitudinal cochlear axis, apical and basal IHCs were collected separately using the suction pipette technique from adult mouse cochleae for RNA-seq and genome-wide transcriptome analysis. We found 689 annotated genes showed more than 2-fold increase in expression. Interestingly, 93.4% of the differentially expressed genes (DEGs) was upregulated in apical IHCs. Although a subset of genes that related to IHC machinery and deafness were found to be differentially expressed, a gradient of gene expression was indeed detected in Ocm, Pvalb, Prkd1, Fbxo32, Nme2, and Sncg, which may play putative roles in the Ca2+ buffering and survival regulation. The expression of these genes was validated by real-time quantitative PCR (RT-qPCR) or immunostaining. We conclude that IHCs from different mouse cochlear longitudinal position have different gene expression profiles. Our data might serve as a valuable resource for exploring the molecular mechanisms underlying different biological properties as well as the survival regulation of IHCs.

We survey research using neural sequence-to-sequence models as compu- tational models of morphological learning and learnability. We discuss their use in determining the predictability of inflectional exponents, in making predictions about language acquisition and in modeling language change. Finally, we make some proposals for future work in these areas.

Abstract Background The CRISPR/Cas9 system is being used for genome editing purposes by many research groups in multiple plant species. Traditional sequencing methods to identify homozygous mutants are time-consuming, laborious and expensive. Results We have developed a method to screen CRISPR/Cas9-induced mutants through Mutation Sites Based Specific Primers Polymerase Chain Reaction (MSBSP-PCR). The MSBSP-PCR method was successfully used to identify homozygous/biallelic mutants in Nicotiana tabacum and Arabidopsis thaliana, and we speculate that it can be used for the identification of CRISPR/Cas9-induced mutants in other plant species. Compared to traditional sequencing methods, MSBSP-PCR is simpler, faster and cheaper. Conclusions The MSBSP-PCR method is simple to implement and can save time and cost in the screening of CRISPR/Cas9-induced homozygous/biallelic mutants.

As the primary active component in tobacco, nicotine affects many aspects of human metabolism. Diet and gut microbiota are key factors that profoundly influence human lipid and glucose metabolism. However, the diet-based differential impacts of nicotine on blood lipid and glucose levels as well as on the gut microbiota are still largely unknown. Here we show that 4-week oral administration of nicotine (2 mg/kg) resulted in bodyweight and fat decrease in both normal-chow (NCD)- and high-fat diet (HFD)-fed mice. But nicotine showed little influence on the plasma levels of lipids, glucose and inflammatory cytokines in NCD-fed mice but moderately deteriorated these parameters in HFD-fed ones. 16S sequencing showed that nicotine perturbed bacterial diversity and community composition of gut microbiota more pronouncedly in HFD mice. At genus level, nicotine dramatically increased Ruminococcaceae UCG-009 in HFD condition but not in NCD feeding. Interestingly, co-treatment with antibiotics (ampicillin + norfloxacin) substantially abolished the lipid-enhancing effect of nicotine in HFD-fed mice, suggesting an important role of gut microbes in the lipid-modulatory effect of nicotine. Together, our results indicate that the harmful effects of nicotine on metabolism and systemic inflammation are diet-dependent. Chronic exposure to nicotine may alter the gut microbiota especially in HFD-fed animals.

Aggrecanase-2 (ADAMTS5) gene is responsible for aggrecan degradation that may contribute to cartilage destruction in a mouse osteoarthritis (OA) model. We aimed to investigate the effects of ADAMTS5 gene polymorphisms on OA risk in a Chinese population. A total of 300 OA patients and 300 controls were recruited and their genotypes for ADAMTS5 gene rs226794 and rs2830585 polymorphisms were determined using a custom-by-design 48-Plex single nucleotide polymorphism Scan™ kit. ADAMTS5-associated genes were identified by co-expression analysis and their functions were investigated by Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses. Bioinformatics analysis showed that ADAMTS5 was significantly related to the components, structural constituent, and organization of the extracellular matrix. The rs2830585 polymorphism, but not rs226794 polymorphism, was significantly associated with an increased risk of knee OA. Stratified analysis further confirmed this significant association in patients at age ≥55 years. In conclusion, the ADAMTS5 rs2830585 polymorphism may be involved in the development of knee OA by destroying the extracellular matrix, but this finding should be further confirmed by larger studies.

Although growing evidence has demonstrated that the long non-coding RNA DLEU1 is involved in the progression of various cancers, its functional role and underlying mechanisms have not been explored in cervical cancer (CC). In this study, we found that DLEU1 was up-regulated in both CC tissues and CC cell lines, and overexpression of DLEU1 was significantly correlated with shorter patient survival. Knockdown of DLEU1 suppressed CC cell proliferation and invasion, whereas overexpression of DLEU1 promoted the proliferation and invasion of CC cells. Bioinformatics analysis was used to elucidate the potential correlation between DLEU1 and miR-381. Moreover, qRT-PCR analysis, luciferase reporter assay and RNA immunoprecipitation assay confirmed that DLEU1 inhibited the expression of miR-381, and revealed a direct interaction between DLEU1 and miR-381. In addition, we demonstrated that miR-381 directly targeted HOXA13 in CC cells. The restoration of HOXA13 expression reversed DLEU1 knockdown or miR-381 overexpression-mediated suppression of cell proliferation and invasion. These results suggested that DLEU1 can promote CC cell proliferation and invasion via the miR-381/HOXA13 axis.

Carotenoids are important pigments in plants that play crucial roles in plant growth and in plant responses to environmental stress. Lycopene β cyclase (β-LCY) functions at the branch point of the carotenoid biosynthesis pathway, catalyzing the cyclization of lycopene. Here, a β-LCY gene from Nicotiana tabacum, designated as Ntβ-LCY1, was cloned and functionally characterized. Robust expression of Ntβ-LCY1 was found in leaves, and Ntβ-LCY1 expression was obviously induced by salt, drought, and exogenous abscisic acid treatments. Strong accumulation of carotenoids and expression of carotenoid biosynthesis genes resulted from Ntβ-LCY1 overexpression. Additionally, compared to wild-type plants, transgenic plants with overexpression showed enhanced tolerance to salt and drought stress with higher abscisic acid levels and lower levels of malondialdehyde and reactive oxygen species. Conversely, transgenic RNA interference plants had a clear albino phenotype in leaves, and some plants did not survive beyond the early developmental stages. The suppression of Ntβ-LCY1 expression led to lower expression levels of genes in the carotenoid biosynthesis pathway and to reduced accumulation of carotenoids, chlorophyll, and abscisic acid. These results indicate that Ntβ-LCY1 is not only a likely cyclization enzyme involved in carotenoid accumulation but also confers salt and drought stress tolerance in Nicotiana tabacum.

The autoimmune regulator (AIRE), a transcriptional regulator expressed in medullary thymic epithelial cells, plays an important role in thymocyte education and negative selection. Several citations studying the association between the rs878081 exon polymorphism of the AIRE gene and the risk of rheumatoid arthritis (RA) in different populations have yielded conflicting findings. Thus, this case-control study involving 300 RA cases and 300 controls was aimed to identify whether such association existed in a Chinese Han population from East China. The rs878081 polymorphism of the AIRE gene was genotyped. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using the chi-squared test, genetic model analysis, and stratification analysis. Genetic model analysis showed significant correlations between the TT genotype and the risk of RA (OR: 1.89, 95%CI: 1.03-3.47 in TT vs CC; OR: 1.84, 95%CI: 1.02-3.31 in TT vs CC+TC). Stratification analyses of sex, age, smoking, and alcoholism suggested that the rs878081 polymorphism of the AIRE gene increased RA risk among non-smokers. In conclusion, rs878081 polymorphism of AIRE gene increases the risk of RA in a Chinese Han population.

Bisphenol A (BPA) is an endocrine disruptor that may lead to reproductive disorder, heart disease, and diabetes. Infants and young children are likely to be vulnerable to the effects of BPA. At present, the detection methods of BPA are complicated to operate and require expensive instruments. Therefore, it is quite vital to develop a simple, rapid, and highly sensitive method to detect BPA in different samples. In this study, we have designed a rapid and highly sensitive biosensor based on an effective self-assembled monolayer (SAM) and alternating current (AC) electrokinetics capacitive sensing method, which successfully detected BPA at nanomolar levels with only one minute. The developed biosensor demonstrates a detection of BPA ranging from 0.028 μg/mL to 280 μg/mL with a limit of detection (LOD) down to 0.028 μg/mL in the samples. The developed biosensor exhibited great potential as a portable BPA biosensor, and further development of this biosensor may also be useful in the detection of other small biochemical molecules.

Digital publishing resources contain a lot of useful and authoritative knowledge. It may be necessary to reorganize the resources by concepts and recommend the related concepts for e-learning. A recommender system is presented in this paper based on the semantic relatedness of concepts computed by texts from digital publishing resources. Firstly, concepts are extracted from encyclopedias. Information in digital publishing resources is then reorganized by concepts. Secondly, concept vectors are generated by skip-gram model and semantic relatedness between concepts is measured according to the concept vectors. As a result, the related concepts and associated information can be recommended to users by the semantic relatedness for learning or reading. History data or users’ preferences data are not needed for recommendation in a specific domain. The technique may not be language-specific. The method shows potential usability for e-learning in a specific domain.

Wet air oxidation (WAO) is one of the most economical and environmentally-friendly advanced oxidation processes. It makes a promising technology for the treatment of refractory organic pollutants in industrial wastewaters. In wet air oxidation aqueous waste is oxidized in the liquid phase at high temperatures (125–320 °C) and pressures (0.5–20 MPa) in the presence of an oxygen-containing gas (usually air). The advantages of the process include low operating costs and minimal air pollution discharges. The present review is concerned about the literature published in the treatment of refractory organic pollutants in industrial wastewaters, such as dyes. Phenolics were taken as model pollutants in most cases. Reports on effect of treatment for the WAO of refractory organic pollutants in industrial wastewaters are reviewed, such as emulsified wastewater, TNT red water, etc. Discussions are also made on the mechanism and kinetics of WAO and main technical parameters influencing WAO. Finally, development direction of WAO is summed up.

Lycopene ε-cyclase (ε-LCY) is a key enzyme that catalyzes the synthesis of α-branch carotenoids through the cyclization of lycopene. Two cDNA molecules encoding ε-LCY (designated Ntε-LCY1 and Ntε-LCY2) were cloned from Nicotiana tabacum. Ntε-LCY1 and Ntε-LCY2 are encoded by two distinct genes with different evolutionary origins, one originating from the tobacco progenitor, Nicotiana sylvestris, and the other originating from Nicotiana tomentosiformis. The two coding regions are 97% identical at the nucleotide level and 95% identical at the amino acid level. Transcripts of Ntε-LCY were detectable in both vegetative and reproductive organs, with a relatively higher level of expression in leaves than in other tissues. Subcellular localization experiments using an Ntε-LCY1-GFP fusion protein demonstrated that mature Ntε-LCY1 protein is localized within the chloroplast in Bright Yellow 2 suspension cells. Under low-temperature and low-irradiation stress, Ntε-LCY transcript levels substantially increased relative to control plants. Tobacco rattle virus (TRV)-mediated silencing of ε-LCY in Nicotiana benthamiana resulted in an increase of β-branch carotenoids and a reduction in the levels of α-branch carotenoids. Meanwhile, transcripts of related genes in the carotenoid biosynthetic pathway observably increased, with the exception of β-OHase in the TRV-ε-lcy line. Suppression of ε-LCY expression was also found to alleviate photoinhibition of Potosystem II in virus-induced gene silencing (VIGS) plants under low-temperature and low-irradiation stress. Our results provide insight into the regulatory role of ε-LCY in plant carotenoid biosynthesis and suggest a role for ε-LCY in positively modulating low temperature stress responses.