Development of interactive biological web applications with R/Shiny.

Development of interactive web applications to deposit, visualize and analyze biological datasets is a major subject of bioinformatics. R is a programming language for data science, which is also one of the most popular languages used in biological data analysis and bioinformatics. However, building interactive web applications was a great challenge for R users before the Shiny package was developed by the RStudio company in 2012. By compiling R code into HTML, CSS and JavaScript code, Shiny has made it incredibly easy to build web applications for the large R community in bioinformatics and for even non-programmers. Over 470 biological web applications have been developed with R/Shiny up to now. To further promote the utilization of R/Shiny, we reviewed the development of biological web applications with R/Shiny, including eminent biological web applications built with R/Shiny, basic steps to build an R/Shiny application, commonly used R packages to build the interface and server of R/Shiny applications, deployment of R/Shiny applications in the cloud and online resources for R/Shiny.

LIRBase: a comprehensive database of long inverted repeats in eukaryotic genomes.

Small RNAs (sRNAs) constitute a large portion of functional elements in eukaryotic genomes. Long inverted repeats (LIRs) can be transcribed into long hairpin RNAs (hpRNAs), which can further be processed into small interfering RNAs (siRNAs) with vital biological roles. In this study, we systematically identified a total of 6 619 473 LIRs in 424 eukaryotic genomes and developed LIRBase (https://venyao.xyz/lirbase/), a specialized database of LIRs across different eukaryotic genomes aiming to facilitate the annotation and identification of LIRs encoding long hpRNAs and siRNAs. LIRBase houses a comprehensive collection of LIRs identified in a wide range of eukaryotic genomes. In addition, LIRBase not only allows users to browse and search the identified LIRs in any eukaryotic genome(s) of interest available in GenBank, but also provides friendly web functionalities to facilitate users to identify LIRs in user-uploaded sequences, align sRNA sequencing data to LIRs, perform differential expression analysis of LIRs, predict mRNA targets for LIR-derived siRNAs, and visualize the secondary structure of candidate long hpRNAs encoded by LIRs. As demonstrated by two case studies, collectively, LIRBase bears the great utility for systematic investigation and characterization of LIRs and functional exploration of potential roles of LIRs and their derived siRNAs in diverse species.

Enantioseparation by zeolitic imidazolate framework-8-silica hybrid monolithic column with sulfobutylether-ß-cyclodextrin as a chiral additive in capillary electrochromatography.

A zeolitic imidazolate framework (ZIF)-8-silica hybrid monolithic column was prepared by one-step sol-gel method. The stationary phase in the monolithic column was characterized by Fourier-transform infrared spectra, X-ray diffraction, thermogravimetric analysis, nitrogen adsorption/desorption, and zeta potential. The results showed that ZIF-8-silica hybrid monolithic materials had abundant functional groups, good crystallinity, large specific surface area, and good thermal stability. A capillary electrochromatography (CEC) chiral separation system was for the first time constructed with ZIF-8-silica hybrid monolithic column and sulfobutylether-ß-cyclodextrin (SBE-ß-CD) as a chiral additive and was applied to separate the selected single and mixed chiral compounds (13 natural amino acids and 5 chiral pesticides). Under the optimized CEC conditions, all the single analytes achieved baseline separation with resolution of 2.14-5.94 and selectivity factor of 1.06-1.49 in less than 6 min, and the mixed amino acids with similar properties were also simultaneously enantioseparated (Rs ≥ 1.82). Relative standard deviations (RSDs) of migration time and column efficiency were lower than 4.26% and did not change significantly after 200 runs, evidencing excellent reproducibility and stability. These results demonstrate that the application of SBE-ß-CD as a chiral additive for ZIF-8-silica hybrid monolithic columns is a promising method for the separation of chiral compounds.

Genome-Wide Identification and Functional Analysis of Nitrate Transporter Genes (NPF, NRT2 and NRT3) in Maize.

Nitrate is the primary form of nitrogen uptake in plants, mainly transported by nitrate transporters (NRTs), including NPF (NITRATE TRANSPORTER 1/PEPTIDE TRANSPORTER FAMILY), NRT2 and NRT3. In this study, we identified a total of 78 NPF, seven NRT2, and two NRT3 genes in maize. Phylogenetic analysis divided the NPF family into eight subgroups (NPF1-NPF8), consistent with the results in Arabidopsis thaliana and rice. The NRT2 family appears to have evolved more conservatively than the NPF family, as NRT2 genes contain fewer introns. The promoters of all NRTs are rich in cis-acting elements responding to biotic and abiotic stresses. The expression of NRTs varies in different tissues and developmental stages, with some NRTs only expressed in specific tissues or developmental stages. RNA-seq analysis using Xu178 revealed differential expression of NRTs in response to nitrogen starvation and nitrate resupply. Moreover, the expression patterns of six key NRTs genes (NPF6.6, NPF6.8, NRT2.1, NRT2.5 and NRT3.1A/B) varied in response to alterations in nitrogen levels across distinct maize inbred lines with different nitrogen uptake rates. This work enhances our understanding of the structure and expression of NRTs genes, and their roles in nitrate response, paving the way for improving maize nitrogen efficiency through molecular breeding.

Phospholipase D-derived phosphatidic acid promotes root hair development under phosphorus deficiency by suppressing vacuolar degradation of PIN-FORMED2.

Root hair development is crucial for phosphate absorption, but how phosphorus deficiency affects root hair initiation and elongation remains unclear. We demonstrated the roles of auxin efflux carrier PIN-FORMED2 (PIN2) and phospholipase D (PLD)-derived phosphatidic acid (PA), a key signaling molecule, in promoting root hair development in Arabidopsis thaliana under a low phosphate (LP) condition. Root hair elongation under LP conditions was greatly suppressed in pin2 mutant or under treatment with a PLDζ2-specific inhibitor, revealing that PIN2 and polar auxin transport and PLDζ2-PA are crucial in LP responses. PIN2 was accumulated and degraded in the vacuole under a normal phosphate (NP) condition, whereas its vacuolar accumulation was suppressed under the LP or NP plus PA conditions. Vacuolar accumulation of PIN2 was increased in pldζ2 mutants under LP conditions. Increased or decreased PIN2 vacuolar accumulation is not observed in sorting nexin1 (snx1) mutant, indicating that vacuolar accumulation of PIN2 is mediated by SNX1 and the relevant trafficking process. PA binds to SNX1 and promotes its accumulation at the plasma membrane, especially under LP conditions, and hence promotes root hair development by suppressing the vacuolar degradation of PIN2. We uncovered a link between PLD-derived PA and SNX1-dependent vacuolar degradation of PIN2 in regulating root hair development under phosphorus deficiency.

Controllable assembly of a novel cationic gemini surfactant containing a naphthalene and amide spacer with ß-cyclodextrin.

A novel cationic gemini surfactant (C12NDDA) with a spacer containing naphthalene and amides was successfully synthesized. The assembly of C12NDDA with ß-cyclodextrin (ß-CD) was investigated using various techniques including transmission electron microscopy, proton nuclear magnetic resonance (1H NMR), and scanning electron microscopy. Tuning the C12NDDA concentration and the C12NDDA/ß-CD molar ratio allowed the production of different assembled aggregate morphologies such as micelles, vesicles, nanowires, nanorods, and hydrogels. Investigation of the inclusion mechanisms of C12NDDA and ß-CD by 1H NMR revealed that hydrophobic interactions, hydrogen bonding, π-π stacking, and electrostatic forces play key roles in the assembly process. The antimicrobial activities of the C12NDDA/xß-CD (x = 0-4) inclusion complexes were tested against Gram-negative bacteria (Escherichia coli and Salmonella) and Gram-positive bacteria (Staphylococcus aureus and Streptococcus), and very low minimum inhibitory concentrations of 0.078-0.31 µg mL-1 were observed. Thus, this newly synthesized gemini surfactant and its inclusion complexes exhibit potential as superior broad-spectrum disinfectants for various biomedical and biotechnological applications.

Green synthesis of up- and down-conversion photoluminescent carbon dots from coffee beans for Fe3+ detection and cell imaging.

Carbon dots (CDs) are a developing stable, conductive, and environmentally friendly fluorescent nanomaterial with potential applications in biomedicine and sensing. In this study, CDs with up- and down-conversion photoluminescence characteristics were prepared via a one-pot hydrothermal method using coffee beans as the sole raw material. Fourier transform infrared spectra and X-ray photoelectron spectroscopy showed the presence of nitrogen and oxygen functional groups on the CDs surfaces. Transmission electron microscopy showed that the CDs were spherical with an average size of 4.6 nm. The CDs precursor and synthesis process are environmentally benign, and the resulting CDs exhibit excellent photostability, reversible fluorescence response to temperature, and good ionic-strength tolerance. Moreover, these CDs can be used as efficient fluorescence probes in selective and sensitive Fe3+ detection by a dual-readout assay. The down- and up-conversion fluorescence measurements from the CDs were in the linear range for 0-0.10 mM Fe3+ with the detection limits of 15.4 and 16.3 nM, respectively. Furthermore, the CDs were successfully applied to intracellular sensing and imaging Fe3+ ions, indicating their potential use in bioscience applications.

Large-scale fabrication of 3D hierarchical MoSe2 hollow sphere arrays with like-Pacific Plate architecture for high-performance hydrogen evolution reaction.

Optimizing of electrocatalytic hydrogen evolution reaction (HER) activity is still a gigantic challenge for improving catalysts in renewable energy field. In this research, large-scale neoteric three-dimensional (3D) hierarchical MoSe2 hollow sphere arrays with like-Pacific Plate architecture were triumphantly prepared via a facile and reliable approach. The like-Pacific Plate architecture consists of many 3D MoSe2 arrays plates with the dimensions of 10-35 µm, which is assembled by plentiful closely connecting hierarchical MoSe2 hollow spheres with the outer diameter, hierarchically secondary unit size and shell thickness of 450 nm, 25 nm and 10 nm, respectively. The products exhibited remarkable HER performance with small Tafel slope (58.5 mV dec-1), low overpotential (169.8 mV) at 10 mA cm-2, high conductivity and durable stability, which are attribute to the mechanisms (1) 3D hollow framework furnishes large specific surface area, (2) hierarchical structure generates more active sites, (3) like-Pacific Plate architecture facilitates the touch of electrolyte and catalyst, and (4) closely packed arrays expedite the migration of electron. The current work indicates that unique 3D hierarchical hollow sphere arrays with like-Pacific Plate architecture will be a potential candidate for effective electrocatalytic water splitting catalyst material with energy source application.

A chiral BINOL-based Gemini amphiphilic gelator and its specific discrimination of native arginine by gelation in water.

A novel axially chiral cationic Gemini amphiphile gelator (S1) derived from (S)-BINOL has been synthesized and characterized by 1H NMR, 13C NMR, ESI-MS and FT-IR analyses. The critical micelle concentration (CMC) of S1 was determined to be 0.21 mM in water at room temperature. A transparent hydrogel with S1 at 43 mM was obtained at room temperature and characterized using various methods including SEM, CD, fluorescence, 1H NMR, FT-IR, and XRD. The results indicate that the hydrophobic effect of long alkyl chains, π-π stacking of naphthalene rings, and intermolecular hydrogen-bonding of the amide groups of S1 should be responsible for the hydrogel formation. Moreover, an 8.5 mM aqueous solution of S1 could gel by the addition of l-arginine, whereas it failed to gel in the presence of other 15 amino acids, respectively. It is suggested that S1 could discriminate native arginine by hydrogel formation, mainly due to the electrostatic interaction and hydrogen bonding effects between S1 and l-arginine molecules.

A 4,5-quinolimide-based fluorescent sensor for the turn-on detection of Cd2+ with live-cell imaging.

A 4,5-quinolimide derivative, BNA, bearing the amide-DPA receptor, was synthesized as a turn-on fluorescent sensor for Cd2+. Under physiological conditions, BNA could distinguish Cd2+ from Zn2+, showing turn-on fluorescence behaviour and an increased fluorescence lifetime. BNA and Cd2+ formed a 1 : 1 stoichiometric complex, and the detection limit was measured to be as low as 11 nM. Furthermore, BNA was utilized for fluorescence imaging of Cd2+ in live cells. To the best of our knowledge, it is the first 4,5-quinolimide-based sensor for the detection of metal ions.

A Ratiomeric Fluorescent Sensor for Zn2+ Based on N,N'-Di(quinolin-8-yl)oxalamide.

A new ratiometric fluorescent sensor (DQO) based on N,N'-Di(quinolin-8-yl) oxalamide has been designed and synthesized for selective detection of Zn2+. The fluorescence ratio (I 536 nm/I 450 nm) of DQO was enhanced 10-fold when Zn2+ was present in a buffer aqueous solution at pH 8.66. The sensor showed linear response toward Zn2+ in the concentration range 0-15 µM, and the detection limit was calculated to be 2.4 µM. A Job's plot implied the formation of a DQO/Zn2+ complex with 1:1 stoichiometry, and the apparent association constant of DQO/Zn2+ complex was computed to be 1.5 × 104 M-1.

Downregulated serum miR-223 servers as biomarker in Alzheimer's disease.

Alzheimer's disease (AD) is an age-related neurodegenerative disorder that is characterized by progressive memory loss and deteriorated higher cognitive functions. An economical, rapid and noninvasive biomarker for AD has not been identified. We aimed to investigate the diagnostic value of serum miR-223 and miR-519 in AD. The expressions of miR-223 and miR-519, with previously reported AD-associated miR-29 and miR-125b, were measured by quantitative reverse transcription polymerase chain reaction in the serum of 84 probable sporadic AD patients (age onset > 65 years) and 62 healthy control populations in China. Analyses were undertaken to assess the specificity and sensitivity of miRNAs to predict AD. In addition, the relationship between miRNAs and mini mental state examination (MMSE) scores in AD patients was also assessed. Serum miR-29, miR-125b and miR-223 were significantly decreased, but serum miR-519 was significantly increased in AD patients compared with healthy blood donors. In addition, serum miR-223 was strongly positively correlated with MMSE score in AD patients but serum miR-519 was not. Importantly, the receiver operating characteristic (ROC) result of serum miR-223 for prediction of AD was 0.786, higher than those of serum miR-29 (0.734) or miR-125b (0.726). The combination of serum miR-223 and miR-125b gave improved sensitivity/specificity for AD prediction (area under the ROC curve, 0.879) than either miRNA alone. Our preliminary findings indicate that serum miR-223 might be a potential biomarker for AD evaluation. Copyright © 2016 John Wiley & Sons, Ltd.

Garcinol Upregulates GABAA and GAD65 Expression, Modulates BDNF-TrkB Pathway to Reduce Seizures in Pentylenetetrazole (PTZ)-Induced Epilepsy.

BACKGROUND Epilepsy is the most predominant neurological disorder characterized by recurrent seizures. Despite treatment with antiepileptic drugs, epilepsy still is a challenge to treat, due to the associated adverse effects of the drugs. Previous investigations have shown critical roles of BDNF-TrkB signalling and expression of glutamic acid decarboxylase 65 (GAD65) and GABAA in the brain during epilepsy. Thus, drugs that could modulate BDNF-TrkB signal and expression of GAD65 and GABAA could aid in therapy. Recent experimental data have focussed on plant-derived compounds in treatments. Garcinol (camboginol), is a polyisoprenylated benzophenone derived from the fruit of Garcinia indica. We investigated the effects of garcinol in pentylenetetrazole (PTZ)-induced epileptic models. MATERIAL AND METHODS Seizure scores were measured in epilepsy kindled mice. Neuronal degeneration and apoptosis were assessed by Nissl staining, TUNEL assay, and Fluoro-Jade B staining. Immunohistochemistry was performed to evaluate cleaved caspase-3 expressions. Expression of BDNF, TrkB, GABAA, GAD65, Bad, Bcl-2, Bcl-xL, and Bax were determined by western blots. RESULTS Significantly reduced seizure scores and mortality rates were observed with pretreatment with garcinol. Elevated expression of apoptotic proteins and caspase-3 in kindled mice were effectively downregulated by garcinol. Epileptogenic mice presented increased BDNF and TrkB with considerably decreased GABAA and GAD65 expression. Garcinol significantly enhanced GABAA and GAD65 while it suppressed BDNF and TrkB. Garcinol enhanced the performance of mice in Morris water maze tests. CONCLUSIONS Garcinol exerts neuroprotective effects via supressing apoptosis and modulating BDNF-TrkB signalling and GAD65/GABAA expressions and also enhanced cognition and memory of the mice.

Bi-8-carboxamidoquinoline derivatives for the fluorescent recognition of Zn2+.

Three fluorescent sensors which were composed of a phendiol (o-, m-, p-isomers) and two carboxamidoquinolines have been synthesized and characterized. Research on the Zn(2+)-sensing properties of the three sensors was carried out, and the results showed a significant difference in the recognition performance for Zn(2+). The fluorescence intensity (I(510 nm)) of ortho isomeric sensor binding to Zn(2+) was enhanced 23-fold, the meta 15-fold, the para 8-fold. As the distance between two carboxamidoquinolines became longer, the fluorescence enhancement decreased. In addition, the selectivity of sensors got poor and the detection limit became higher with rising the distance between two receptors.

Circulating miR-145 is associated with plasma high-sensitivity C-reactive protein in acute ischemic stroke patients.

Stroke is a major cerebrovascular disease threatening human health and life with high morbidity, disability and mortality. We aimed to find effective biomarkers for the early diagnosis on stroke. Nine previously reported stroke-associated miRNAs (miR-21, miR-23a, miR-29b, miR-124, miR-145, miR-210, miR-221, miR-223 and miR-483-5p) were measured by quantitative real time-PCR, and plasma high-sensitivity C-reactive protein (hs-CRP) and serum interleukin 6 (IL-6), the pro-inflammation markers in brain injury, were examined by enzyme-linked immunosorbent assay in 146 acute ischemic stroke patients and 96 healthy blood donors. We found that serum miR-145 was significantly increased within 24 h after stroke onset and serum miR-23a and miR-221 were decreased in patients. Moreover, serum miR-145 was strong positively correlated with plasma hs-CRP and moderate positively correlated with serum IL-6. Meanwhile, serum miR-23a and miR-221 were moderate negatively correlated with plasma hs-CRP but not serum IL-6. Importantly, the combination of hs-CRP and serum miR-145 gained a better sensitivity/spectivity for prediction of acute ischemia stroke (area under receiver operating characteristic curve from 0.794 to 0.896). Conclusively, our preliminary findings indicate that serum miR-145 upregulated in acute ischemic stroke might be a new biomarker for acute ischemia stroke evaluation.

Overexpression of FOXC1 correlates with poor prognosis in gastric cancer patients.

AIMS: The aim of this study was to determine FOXC1 expression in gastric tissues, and the clinical significance of FOXC1 in the development, progression and metastasis of gastric cancer (GC). METHODS AND RESULTS: We screened GCs for the expression of FOXC1 using the Affymetrix U133 plus 2.0 Gene Chip Array, and found that expression was significantly higher in GC tissues than in controls. Furthermore, we validated the expression levels of FOXC1 using real-time quantitative RT-PCR (qRT-PCR), and of FOXC1 using immunohistochemistry (IHC). Our study showed that expression levels of FOXC1 mRNA and FOXC1 in GC tissues were significantly higher than those in corresponding non-tumour tissues. High FOXC1 expression correlated with the degree of histological differentiation (P < 0.01), TNM stage (P < 0.001), invasive depth (P < 0.05), lymph node metastasis (P < 0.05), and distant metastasis (P < 0.01). Survival analysis revealed that patients with high FOXC1 expression had shorter overall survival than those with low expression (P < 0.001). Multivariate analysis showed that high FOXC1 expression was an independent prognostic factor for GC patients (P < 0.01). CONCLUSIONS: Overexpression of FOXC1 may play a key role in the progression of GC, and FOXC1 expression may serve as a useful marker for predicting the outcome of patients with GC.

Preparation and characterization of mesoporous Ag/VO(x)-TiO2 employed for catalytic hydroxylation of benzene.

The V-based complex oxides were found to exhibit good catalytic reactivity for the selective oxidation of benzene to phenol. In order to understand the effect of the catalyst on the reaction, a series of Ag/VO(x)-TiO2 catalysts with different Ag loadings were prepared. Data from the X-ray diffraction (XRD), N2-adsorption isotherms, scanning electron microscopy (SEM), transmission electron microscopy (TEM), H2 temperature-programmed reduction (H2-TPR), and X-ray photoelectron spectroscopy (XPS) showed the formation of complex oxides with phases of silver and vanadates, and the increased redox ability of vanadium species. The results from H2-TPR revealed that the addition of Ag promoted the reduction of vanadium species in the complex catalysts. The presence of Ag and Ag+ ions at the catalyst surface were proved independently by XPS measurements. The Ag and Ag+ ions also effectively strengthened the thermostability of the Ag/VO(x)-TiO2 catalyst, and the Ag species also made a strong contribution to the monodispersion of vanadium on the surface of the TiO2 carrier. The reactivity for the selective oxidation of benzene was evaluated by using a liquid-phase reaction unit, and was correlated with the surface redox property of the catalysts.

A bicarboxaminoquinoline-based ratiometric fluorescent sensor for the sequential detection of Zn2+ and PPi.

A new ratiometric fluorescent sensor (LP) based on bicarboxaminoquinoline was designed and synthesized for sequentially recognizing Zn2+ and PPi. In aqueous solution, LP exhibited the ratiometric fluorescence response towards Zn2+, along with the about 4-folds enhancement of fluorescence quantum yield. Subsequently, the LP-Zn2+ complex displayed the fluorescence recovery upon adding PPi through the displacement strategy. And the LODs of LP and its Zn2+ complex for sensing Zn2+ and PPi were found to be 15 nM and 5.5 nM, respectively. Notably, the reversibility of LP for sequentially sensing Zn2+ and PPi had been employed to construct the INHIBIT logic gate. Moreover, LP and its Zn2+ complex had been successfully utilized for the detection of Zn2+ and PPi in two real water samples and cells imaging.

Genetic history of esophageal cancer group in southwestern China revealed by Y-chromosome STRs and genomic evolutionary connection analysis.

Genetic and environmental factors play crucial roles in the development of esophageal cancer (EC) and contribute uniquely or cooperatively to human cancer susceptibility. Sichuan is located in the interior of southwestern China, and the northern part of Sichuan is one of the regions with a high occurrence of EC. However, the factors influencing the high incidence rate of EC in the Sichuan Han Chinese population and its corresponding genetic background and origins are still poorly understood. Here, we utilized genome-wide single nucleotide polymorphisms (SNPs) and Y-chromosome short tandem repeats (Y-STRs) to characterize the genetic structure, connection, and origin of cancer groups and general populations. We generated Y-STR-based haplotype data from 214 Sichuan individuals, including the Han Chinese EC population and a control group of Han Chinese individuals. Our results, obtained from Y-STR-based population statistical methods (analysis of molecular variance (AMOVA), principal component analysis (PCA), and phylogenetic analysis), demonstrated that there was a genetic substructure difference between the EC population in the high-incidence area of northern Sichuan Province and the control population. Additionally, there was a strong genetic relationship between the EC population in the northern Sichuan high-incidence area and those at high risk in both the Fujian and Chaoshan areas. In addition, we obtained high-density SNP data from saliva samples of 60 healthy Han Chinese individuals from three high-prevalence areas of EC in China: Sichuan Nanchong, Fujian Quanzhou, and Henan Xinxiang. As inferred from the allele frequency of SNPs and sharing patterns of haplotype segments, the evolutionary history and admixture events suggested that the Han population from Nanchong in northern Sichuan Province shared a close genetic relationship with the Han populations from Xinxiang in Henan Province and Quanzhou in Fujian Province, both of which are regions with a high prevalence of EC. Our study illuminated the genetic profile and connection of the Northern Sichuan Han population and enriched the genomic resources and features of the Han Chinese populations in China, especially for the Y-STR genetic data of the Han Chinese EC population. Populations living in different regions with high incidences of EC may share similar genetic backgrounds, which offers new insights for further exploring the genetic mechanisms underlying EC.