DSEATM: drug set enrichment analysis uncovering disease mechanisms by biomedical text mining.

Disease pathogenesis is always a major topic in biomedical research. With the exponential growth of biomedical information, drug effect analysis for specific phenotypes has shown great promise in uncovering disease-associated pathways. However, this method has only been applied to a limited number of drugs. Here, we extracted the data of 4634 diseases, 3671 drugs, 112 809 disease-drug associations and 81 527 drug-gene associations by text mining of 29 168 919 publications. On this basis, we proposed a 'Drug Set Enrichment Analysis by Text Mining (DSEATM)' pipeline and applied it to 3250 diseases, which outperformed the state-of-the-art method. Furthermore, diseases pathways enriched by DSEATM were similar to those obtained using the TCGA cancer RNA-seq differentially expressed genes. In addition, the drug number, which showed a remarkable positive correlation of 0.73 with the AUC, plays a determining role in the performance of DSEATM. Taken together, DSEATM is an auspicious and accurate disease research tool that offers fresh insights.

Enhancing intracellular mRNA precise imaging-guided photothermal therapy with a nucleic acid-based polydopamine nanoprobe.

Despite significant advancements in cancer research, real-time monitoring and effective treatment of cancer through non-invasive techniques remain a challenge. Herein, a novel polydopamine (PDA) nucleic acid nanoprobe has been developed for imaging signal amplification of intracellular mRNA and precise photothermal therapy guidance in cancer cells. The PDA nucleic acid nanoprobe (PDA@DNA) is constructed by assembling an aptamer hairpin (H1) labeled with the Cy5 fluorophore and another nucleic acid recognition hairpin (H2) onto PDA nanoparticles (PDA NPs), which have exceptionally high fluorescence quenching ability and excellent photothermal conversion properties. The nanoprobe could facilitate cellular uptake of DNA molecules and their protection from nuclease degradation. Upon recognition and binding to the intracellular mRNA target, a catalytic hairpin assembly (CHA) reaction occurs. The stem of H1 unfolds upon binding, allowing the exposed H1 to hybridize with H2, forming a flat and sturdy DNA double-stranded structure that detaches from the surface of PDA NPs. At the same time, the target mRNA is displaced and engages in a new cyclic reaction, resulting in the recovery and significant amplification of Cy5 fluorescence. Using thymidine kinase1 (TK1) mRNA as a model mRNA, this nanoprobe enables the analysis of TK1 mRNA with a detection limit of 9.34 pM, which is at least two orders of magnitude lower than that of a non-amplifying imaging nucleic acid probe. Moreover, with its outstanding performance for in vitro detection, this nanoprobe excels in precisely imaging tumor cells. Through live-cell TK1 mRNA imaging, it can accurately distinguish between tumor cells and normal cells. Furthermore, when exposed to 808-nm laser irradiation, the nanoprobe fully harnesses exceptional photothermal conversion properties of PDA NPs. This results in a localized temperature increase within tumor cells, which ultimately triggers apoptosis in these tumor cells. The integration of PDA@DNA presents innovative prospects for tumor diagnosis and image-guided tumor therapy, offering the potential for high-precision diagnosis and treatment of tumors.

Rational design of a near-infrared dual-emission fluorescent probe for ratiometric imaging of glutathione in cells.

Sensors for which the output signal is an intensity change for a single-emission peak are easily disturbed by many factors, such as the stability of the instrument, intensity of the excitation light, and biological background. However, for ratiometric fluorescence sensors, the output signal is a change in the intensity ratio of two or more emission peaks. The fluorescence intensity of these emission peaks is similarly affected by external factors; thus, these sensors have the ability to self-correct, which can greatly improve the accuracy and reliability of the detection results. To accurately image glutathione (GSH) in cells, gold nanoclusters (AuNCs) with intrinsic double emission at wavelengths of 606 nm and 794 nm were synthesized from chloroauric acid. With the emission peak at 606 nm as the recognition signal and the emission peak at 794 nm as the reference signal, a near-infrared dual-emission ratio fluorescence sensing platform was constructed to accurately detect changes in the GSH concentration in cells. In vitro and in vivo analyses showed that the ratiometric fluorescent probe specifically detects GSH and enables ultrasensitive imaging, providing a new platform for the accurate detection of active small molecules.

Sound source direction-of-arrival estimation method for microphone array based on ultra-weak fiber Bragg grating distributed acoustic sensor.

A sound source direction-of-arrival (DOA) estimation method for microphone array based on ultra-weak fiber Bragg grating (UW-FBG) distributed acoustic sensor is proposed. The principle of acoustic signal demodulation is introduced, the sound pressure sensitivity and frequency response range of a single UW-FBG microphone are analyzed, and a series linear array with three UW-FBG microphones is designed. Combined with convolutional recurrent neural networks, the DOA estimation method is developed. Log-Mel spectral features and SCOT/PHAT joint weighting generalized cross correlation features are used for DOA estimation. The corresponding system is established and experimentally verified. Results show that the measured sound pressure sensitivity of the UW-FBG microphone is in the range of 0.1032-3.306 rad/Pa within the frequency range of 1000-3000 Hz, and the peak sound pressure sensitivity is about 3.306 rad/Pa. The estimated mean error of 2D DOA estimation is about 2.85°, and the error of 3D DOA estimation is about 5.465°. This method has good application prospects in distributed sound source localization.

Bilayer Two-Orbital Model of La_{3}Ni_{2}O_{7} under Pressure.

The newly discovered Ruddlesden-Popper bilayer La_{3}Ni_{2}O_{7} reaches a remarkable superconducting transition temperature T_{c}≈80 K under a pressure of above 14 GPa. Here we propose a minimal bilayer two-orbital model of the high-pressure phase of La_{3}Ni_{2}O_{7}. Our model is constructed with the Ni-3d_{x^{2}-y^{2}}, 3d_{3z^{2}-r^{2}} orbitals by using Wannier downfolding of the density functional theory calculations, which captures the key ingredients of the material, such as band structure and Fermi surface topology. There are two electron pockets, α, ß, and one hole pocket, γ, on the Fermi surface, in which the α, ß pockets show mixing of two orbitals, while the γ pocket is associated with Ni-d_{3z^{2}-r^{2}} orbital. The random phase approximation spin susceptibility reveals a magnetic enhancement associated with the d_{3z^{2}-r^{2}} state. A higher energy model with O-p orbitals is also provided for further study.

A Novel Fluorescent Aptamer Sensor with DNAzyme Signal Amplification for the Detection of CEA in Blood.

Carcinoembryonic antigen (CEA) is a tumor-specific biomarker; however, its low levels in the early stages of cancer make it difficult to detect. To address the need for analysis of ultra-low-level substances, we designed and synthesized a fluorescent aptamer sensor with DNAzyme signal amplification and used it for the detection of CEA in blood. In the presence of the target protein, the aptamer sequence in the recognition probe binds to the target protein and opens the hairpin structure, hybridizes with the primer and triggers a polymerization reaction in the presence of polymerase to generate double-stranded DNA with two restriction endonuclease Nb.BbvCl cleavage sites. At the same time, the target protein is displaced and continues to bind to another recognition probe, triggering a new round of polymerization reaction, forming a cyclic signal amplification triggered by the target. The experimental results show that the blood detection with CEA has a high sensitivity and a wide detection range. The detection range: 10 fg/mL~10 ng/mL, with a detection limit of 5.2 fg/mL. In addition, the sensor can be used for the analysis of complex biological samples such as blood.

Two new meroterpenoids from the bark of Cinnamomum cassia and their antioxidant activity.

Two new (1 and 2) meroterpenoids were isolated from the bark of Cinnamomum cassia. Their structures were determined by spectroscopic analyses and chemical methods. Antioxidant activities of 1 and 2 were evaluated by the ORAC and DPPH radical scavenging assays, and the results revealed that compound 2 displayed oxygen radical absorbance capacity. The discovery of compounds 1 and 2 added new members of this kind of natural product.

Fabrication of Ag-CaCO3 Nanocomposites for SERS Detection of Forchlorfenuron.

In this study, Ag-CaCO3 nanocomposites were synthesized using silver nitrate as the precursor solution based on calcium carbonate nanoparticles (CaCO3 NPs). The synthesis involved the reaction of calcium lignosulphonate and sodium bicarbonate. The properties of Ag-CaCO3 nanocomposites were studied by various technologies, including an ultraviolet-visible spectrophotometer, a transmission electron microscope, and a Raman spectrometer. The results showed that Ag-CaCO3 nanocomposites exhibited a maximum UV absorption peak at 430 nm, the surface-enhanced Raman spectroscopy (SERS) activity of Ag-CaCO3 nanocomposites was evaluated using mercaptobenzoic acid (MBA) as the marker molecule, resulting in an enhancement factor of 6.5 × 104. Additionally, Ag-CaCO3 nanocomposites were utilized for the detection of forchlorfenuron. The results demonstrated a linear relationship in the concentration range of 0.01 mg/mL to 2 mg/mL, described by the equation y = 290.02x + 1598.8. The correlation coefficient was calculated to be 0.9772, and the limit of detection (LOD) was determined to be 0.001 mg/mL. These findings highlight the relatively high SERS activity of Ag-CaCO3 nanocomposites, making them suitable for analyzing pesticide residues and detecting toxic and harmful molecules, thereby contributing to environmental protection.

Astramalabaricosides A-T, Highly Oxygenated Malabaricane Triterpenoids with Migratory Inhibitory Activity from Astragalus membranaceus var. mongholicus.

Twenty new malabaricane triterpenoids, astramalabaricosides A-T (1-20), were isolated from the roots of Astragalus membranaceus var. mongholicus (Astragali Radix). Their structures were determined by spectroscopic analysis, and the use of the circular dichroism exciton chirality method, quantum chemical calculations, and chemical methods. Malabaricane triterpenoids, an unusual group with the 6-6-5-tricyclic core, are distributed in plants (e.g., Simaroubaceae, Polypodiaceae, and Fabaceae), a marine sponge, and fungi, and their number obtained to date is limited. Compounds 1-20 were characterized as glycosides with a highly oxygenated side chain, and 13-20 were the first cyclic carbonate derivatives among the malabaricane triterpenoids. The stereocluster formed from the continuous hydroxylated chiral carbons in each highly oxygenated side chain and the 6-6-5-tricyclic core system were entirely segregated, and the independent identification of their stereoconfigurations required considerable effort. The migratory inhibitory and antiproliferative activities of 1-20 were evaluated by wound-healing and cell-viability assays, respectively. Most compounds showed significant migratory inhibitory activity, and a preliminary structure-activity relationship was developed. Malabaricane triterpenoids are being reported in the genus Astragalus for the first time.

Bioactive phenylpropanoid derivatives from the fruits of Lycium ruthenicum Murr.

Eight new (1-7 and 15) and 18 known (8-14 and 16-26) phenylpropanoid derivatives were isolated from the fruits of Lycium ruthenicum Murr. (black wolfberry). Their structures were determined by comprehensive spectroscopic analyses, chemical methods, and comparisons of spectroscopic data. Four known compounds (16, 17, 24, and 26) were firstly isolated from the genus Lycium. Interestingly, compounds 1/2 and 4/5 were isolated as two pairs of inseparable anomers owing to the tautomerism of the free hemiacetal at C-1'' in solution. The antioxidant, α-glucosidase inhibitory, and acetylcholinesterase (AChE) inhibitory activities of compounds 1-26 were evaluated. Some compounds possessed DPPH radical scavenging activity, and all compounds (1-26) exhibited different levels of oxygen radical absorbance capacity (ORAC). One compound displayed α-glucosidase inhibitory activity with potency close to that of the positive control (acarbose).

SAGD: a comprehensive sex-associated gene database from transcriptomes.

Many animal species present sex differences. Sex-associated genes (SAGs), which have female-biased or male-biased expression, have major influences on the remarkable sex differences in important traits such as growth, reproduction, disease resistance and behaviors. However, the SAGs resulting in the vast majority of phenotypic sex differences are still unknown. To provide a useful resource for the functional study of SAGs, we manually curated public RNA-seq datasets with paired female and male biological replicates from the same condition and systematically re-analyzed the datasets using standardized methods. We identified 27,793 female-biased SAGs and 64,043 male-biased SAGs from 2,828 samples of 21 species, including human, chimpanzee, macaque, mouse, rat, cow, horse, chicken, zebrafish, seven fly species and five worm species. All these data were cataloged into SAGD, a user-friendly database of SAGs (http://bioinfo.life.hust.edu.cn/SAGD) where users can browse SAGs by gene, species, drug and dataset. In SAGD, the expression, annotation, targeting drugs, homologs, ontology and related RNA-seq datasets of SAGs are provided to help researchers to explore their functions and potential applications in agriculture and human health.

Fortification of set yogurt with passion fruit juice: Effects on fermentation kinetics, physicochemical properties, and functionality.

With the purpose of developing an alternative set yogurt with high consumer acceptability, passion fruit juice, at levels that varied from 0 to 10%, was incorporated into set yogurt, and the effects on the fermentation kinetics, physicochemical properties, and functionality of set yogurt were evaluated. The results showed that the addition of passion fruit juice was simultaneously propitious for milk acidification in earlier fermentation stages and reduced the fermentation rate at later stages of fermentation. The phenolic compounds and pectin in passion fruit juice interacted with caseins to form soluble complexes, enhancing the gel strength of set yogurts by 7.5%. The aroma and flavor of the set yogurt was improved as well. However, with the addition of 10% passion fruit juice, the gel structure was destroyed, and the quality of the set yogurt was very degraded. More importantly, the addition of passion fruit juice increased the polyphenol content and significantly enhanced the antioxidant activity of the set yogurt. This investigation demonstrated the feasibility of fabricating passion fruit juice-enriched set yogurt and its superior quality compared with the corresponding normal product.

pyMeSHSim: an integrative python package for biomedical named entity recognition, normalization, and comparison of MeSH terms.

BACKGROUND: Many disease causing genes have been identified through different methods, but there have been no uniform annotations of biomedical named entity (bio-NE) of the disease phenotypes of these genes yet. Furthermore, semantic similarity comparison between two bio-NE annotations has become important for data integration or system genetics analysis. RESULTS: The package pyMeSHSim recognizes bio-NEs by using MetaMap which produces Unified Medical Language System (UMLS) concepts in natural language process. To map the UMLS concepts to Medical Subject Headings (MeSH), pyMeSHSim is embedded with a house-made dataset containing the main headings (MHs), supplementary concept records (SCRs), and their relations in MeSH. Based on the dataset, pyMeSHSim implemented four information content (IC)-based algorithms and one graph-based algorithm to measure the semantic similarity between two MeSH terms. To evaluate its performance, we used pyMeSHSim to parse OMIM and GWAS phenotypes. The pyMeSHSim introduced SCRs and the curation strategy of non-MeSH-synonymous UMLS concepts, which improved the performance of pyMeSHSim in the recognition of OMIM phenotypes. In the curation of 461 GWAS phenotypes, pyMeSHSim showed recall > 0.94, precision > 0.56, and F1 > 0.70, demonstrating better performance than the state-of-the-art tools DNorm and TaggerOne in recognizing MeSH terms from short biomedical phrases. The semantic similarity in MeSH terms recognized by pyMeSHSim and the previous manual work was calculated by pyMeSHSim and another semantic analysis tool meshes, respectively. The result indicated that the correlation of semantic similarity analysed by two tools reached as high as 0.89-0.99. CONCLUSIONS: The integrative MeSH tool pyMeSHSim embedded with the MeSH MHs and SCRs realized the bio-NE recognition, normalization, and comparison in biomedical text-mining.

Anti-masculinization induced by aromatase inhibitors in adult female zebrafish.

BACKGROUND: Early sex differentiation genes of zebrafish remain an unsolved mystery due to the difficulty to distinguish the sex of juvenile zebrafish. However, aromatase inhibitors (AIs) could direct juvenile zebrafish sex differentiation to male and even induce ovary-to-testis reversal in adult zebrafish. RESULTS: In order to determine the transcriptomic changes of sex differentiation in juvenile zebrafish and early sex-reversal in adult zebrafish, we sequenced the transcriptomes of juvenile and adult zebrafish treated with AI exemestane (EM) for 32 days, when juvenile zebrafish sex differentiation finished. EM treatment in females up-regulated the expression of genes involved in estrogen metabolic process, female gamete generation and oogenesis, including gsdf, macf1a and paqr5a, while down-regulated the expression of vitellogenin (vtg) genes, including vtg6, vtg2, vtg4, and vtg7 due to the lower level of Estradiol (E2). Furthermore, EM-juveniles showed up-regulation in genes related to cell death and apoptosis, such as bcl2l16 and anax1c, while the control-juveniles exhibited up-regulation of genes involved in positive regulation of reproductive process and oocyte differentiation such as zar1 and zpcx. Moreover, EM-females showed higher enrichment than control females in genes involved in VEGF signaling pathway, glycosaminoglycan degradation, hedgehog signaling pathway, GnRH signaling pathway and steroid hormone biosynthesis. CONCLUSIONS: Our study shows anti-masculinization in EM-treated adult females but not in EM-treated juveniles. This may be responsible for the lower sex plasticity in adults than juveniles.

Deformation detection of a double-clamped beam according to ultra-weak fiber Bragg grating.

Metal beam strain detection may offer valuable insight into health monitoring for large-scale steel structures. This research presents, to the best of our knowledge, the first implementation of ultra-weak fiber Bragg gratings for the deformation detection of a double-clamped beam because of their higher multiplexing and denser detection points compared to fiber Bragg gratings. The measured values are entirely consistent with those determined by strain gauges applied for reference and demonstrate that the strain of each sensing point increases linearly with the load at the middle of the beam. The errors of different loads at different load points between inversion maximum deflection and measured displacement are less than 9.59%.

Hyperspectral Leaf Image-Based Cucumber Disease Recognition Using the Extended Collaborative Representation Model.

Collaborative representation (CR)-based classification has been successfully applied to plant disease recognition in cases with sufficient training samples of each disease. However, collecting enough training samples is usually time consuming and labor-intensive. Moreover, influenced by the non-ideal measurement environment, samples may be corrupted by variables introduced by bad illumination and occlusions of adjacent leaves. Consequently, an extended collaborative representation (ECR)-based classification model is presented in this paper. Then, it is applied to cucumber leaf disease recognition, which constructs a pure spectral library consisting of several representative samples for each disease and designs a universal variation spectral library that deals with linear variables superimposed on samples. Thus, each query sample is encoded as a linear combination of atoms from these two spectral libraries and disease identity is determined by the disease of minimal reconstruction residuals. Experiments are conducted on spectral curves extracted from normal leaves and the disease lesions of leaves infected with cucumber anthracnose and brown spot. The diagnostic accuracy is higher than 94.7% and the average online diagnosis time is short, about 1 to 1.3 ms. The results indicate that the ECR-based classification model is feasible in the fast and accurate diagnosis of cucumber leaf diseases.

Preparation of "Ion-Imprinting" Difunctional Magnetic Fluorescent Nanohybrid and Its Application to Detect Cadmium Ions.

In this work, we have fabricated a novel difunctional magnetic fluorescent nanohybrid (DMFN) for the determination of cadmium ions (Cd2+) in water samples, where the "off-on" model and "ion-imprinting" technique were incorporated simultaneously. The DMFN were composed of CdTe/CdS core-shell quantum dots (QD) covalently linked onto the surface of polystyrene magnetic microspheres (PMM) and characterized using ultraviolet-visible spectroscopy (UV-Vis), fluorescence spectroscopy, and transmission electron microscopy (TEM). Based on the favorable magnetic and fluorescent properties of the DMFN, the chemical etching of ethylene diamine tetraacetic acid (EDTA) at the surface produced specific Cd2+ recognition sites and quenched the red fluorescence of outer CdTe/CdS QD. Under optimal determination conditions, such as EDTA concentration, pH, and interfering ions, the working curve of determining Cd2+ was obtained; the equation was obtained Y = 34,759X + 254,894 (R = 0.9863) with a line range 0.05-8 µM, and the detection limit was 0.01 µM. Results showed that synthesized magnetic fluorescent microspheres had high sensitivity, selectivity, and reusability in detection. Moreover, they have significant potential value in fields such as biomedicine, analytical chemistry, ion detection, and fluorescence labeling.

Cycloartane-type triterpenoids from the root of Astragalus membranaceus var. mongholicus.

Three new (1-3) and 11 known (4-14) cycloartane-type triterpenoids were isolated from the root of Astragalus membranaceus var. mongholicus. Their structures were determined by spectroscopic analyses and chemical methods. Cycloartane-type triterpenoids are a class of major bioactive constituents in the root of A. membranaceus var. mongholicus, and the discovery of compounds 1-3 added new members of this kind of natural product. [Formula: see text].

Accurity: accurate tumor purity and ploidy inference from tumor-normal WGS data by jointly modelling somatic copy number alterations and heterozygous germline single-nucleotide-variants.

Motivation: Tumor purity and ploidy have a substantial impact on next-gen sequence analyses of tumor samples and may alter the biological and clinical interpretation of results. Despite the existence of several computational methods that are dedicated to estimate tumor purity and/or ploidy from The Cancer Genome Atlas (TCGA) tumor-normal whole-genome-sequencing (WGS) data, an accurate, fast and fully-automated method that works in a wide range of sequencing coverage, level of tumor purity and level of intra-tumor heterogeneity, is still missing. Results: We describe a computational method called Accurity that infers tumor purity, tumor cell ploidy and absolute allelic copy numbers for somatic copy number alterations (SCNAs) from tumor-normal WGS data by jointly modelling SCNAs and heterozygous germline single-nucleotide-variants (HGSNVs). Results from both in silico and real sequencing data demonstrated that Accurity is highly accurate and robust, even in low-purity, high-ploidy and low-coverage settings in which several existing methods perform poorly. Accounting for tumor purity and ploidy, Accurity significantly increased signal/noise gaps between different copy numbers. We are hopeful that Accurity is of clinical use for identifying cancer diagnostic biomarkers. Availability and implementation: Accurity is implemented in C++/Rust, available at http://www.yfish.org/software/. Supplementary information: Supplementary data are available at Bioinformatics online.

Fast-switching high-voltage porous-tip electrospray ionization mass spectrometry for rapid detection of antirheumatic drugs in adulterated herbal dietary supplements.

RATIONALE: Herbal dietary supplements (HDSs) adulterated with undeclared synthetic drugs can lead to serious health problems METHODS: A fast-switching positive/negative high-voltage (+/- HV) was developed to apply on electrospray ionization mass spectrometry (ESI-MS) with porous tips for rapid screening of five antirheumatic drugs in antirheumatic HDSs. The fast-switching (switch-time: 100 ms) negative and positive ions were alternately generated to perform full-MS and tandem-MS analysis, providing an effective method for rapid detection of analytes in whichever mode of detection was most suitable (negative or positive ion mode). The use of different tips and solvents was also optimized in this work. RESULTS: The limits of detection of the five antirheumatic drugs were found to be less than 0.1 ng/g (S/N > 3). The reproducibility of the five drugs was measured to be 10.0-23.3% (n = 5). A single sample analysis could be completed within 1 min. Rapid screening of a total of 28 real HDS samples collected from the market was examined by the fast-switching HV substrate-tip ESI-MS method, and the screening result was further validated by conventional liquid chromatography/mass spectrometry. CONCLUSIONS: Overall, our results demonstrated that fast-switching HV substrate-tip ESI-MS is a rapid, reliable, and effective method for simultaneous screening of various analytes in complex samples.