Bioinformatics Analysis of Programmed Cell Death in Spinal Cord Injury.

BACKGROUND: Programmed cell death (PCD) in the development of spinal cord injury (SCI) is complicated, including apoptosis, necroptosis, pyroptosis, ferroptosis, cuproptosis, and autophagy. It is necessary to make clear the expression levels of PCD and potential molecular targets after SCI for formulating relevant treatment strategies. METHODS: We downloaded the rats' SCI expression matrix GSE45006, and the ssGSEA method was used to analyze the PCD after SCI. Then the related differentially expressed genes (DEGs) were identified, and the gene ontology (GO) and pathway analysis, protein-protein interaction (PPI) network construction, and HUB genes were identified. Finally, the correlation between HUB genes and PCD was analyzed. RESULTS: Apoptosis, necroptosis, pyroptosis, ferroptosis, and autophagy increased significantly in acute SCI, and then decreased gradually in the subacute and chronic stages; cuproptosis in acute SCI decreased significantly, and then gradually increased. In addition, we also screened 116 DEGs during the development of SCI. GO and pathway analysis showed that DEGs was related to mitosis and cell cycle. The identified hub genes are closely related to cell apoptosis, necroptosis, pyroptosis, ferroptosis after injury, and autophagy. CONCLUSIONS: PCD occurs differently in different stages after SCI. To inhibit apoptosis, necroptosis, pyroptosis, and ferroptosis after injury and induce autophagy may be the therapeutic strategy. In addition, intervention therapy based on related HUB genes may be the therapeutic target of SCI.

Effects of hydrodynamic cavitation on physicochemical structure and emulsifying properties of tilapia (Oreochromis niloticus) myofibrillar protein.

The purpose of this research was to explore the different hydrodynamic cavitation (HC) times (0, 5, 10, 15, 20 min; power 550 W, pressure 0.14 MPa) on the emulsifying properties of tilapia myofibrillar protein (TMP). Results of pH, particle size, turbidity, solubility, surface hydrophobicity, and reactive sulfhydryl (SH) group indicated that HC changed the structure of TMP, as confirmed by the findings of intrinsic fluorescence and circular dichroism (CD) spectra. Furthermore, HC increased the emulsifying activity index (EAI) significantly (P < 0.05) and changed the emulsifying stability index (ESI), droplet size, and rheology of TMP emulsions. Notably, compared with control group, the 10-min HC significantly decreased particle size and turbidity but increased solubility (P < 0.05), resulting in accelerated diffusion of TMP in the emulsion. The prepared TMP emulsion showed the highest ESI (from 71.28 ± 5.50 to 91.73 ± 5.56 min), the smallest droplet size (from 2,754 ± 110 to 2,138 ± 182 nm) and the best rheological properties, as demonstrated by the microstructure photographs. Overall, by showing the effect of HC in improving the emulsifying properties of TMP, the study demonstrated HC as a potential technique for meat protein processing.

Transcriptomic Study on the Lungs of Broilers with Ascites Syndrome.

Although broiler ascites syndrome (AS) has been extensively studied, its pathogenesis remains unclear. The lack of cardiopulmonary function in broilers causes relative hypoxia in the body; hence, the lung is the main target organ of AS. However, the transcriptome of AS lung tissue in broilers has not been studied. In this study, an AS model was successfully constructed, and lung tissues of three AS broilers and three healthy broilers were obtained for RNA sequencing (RNA-seq) and pathological observation. The results showed that 614 genes were up-regulated and 828 genes were down-regulated in the AS group compared with the normal group. Gene Ontology (GO) functional annotation revealed the following up-regulated genes: FABP4, APLN, EIF2AK4, HMOX1, MMP9, THBS1, TLR4, BCL2; and down-regulated genes: APELA, FGF7, WNT5A, CDK6, IL7, IL7R, APLNR. These genes have attracted much attention in cardiovascular diseases such as pulmonary hypertension. Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis showed that multiple metabolic processes were enriched, indicating abnormal lung metabolism of AS in broilers. These findings elucidate the potential genes and signal pathways in the lungs of broilers with AS and provide a potential target for studying the pathogenesis and preventing AS.

Underlying mechanism of Qiling Jiaogulan Powder in the treatment of broiler ascites syndrome.

Broiler ascites syndrome (AS), is a nutritional and metabolic disease that occurs in fast-growing commercial broiler chickens. AS can cause poor growth and a significant increase in the rate of broiler deaths, which has resulted in serious economic losses to the poultry industry. The classic traditional Chinese medicine Qiling Jiaogulan Powder (QLJP) has been demonstrated to have a certain therapeutic effect on broiler AS. However, its pharmacological mechanism remains to be elucidated. This study was performed to investigate the multitarget action mechanism of QLJP in the treatment of broiler AS based on network pharmacology analysis using a broiler AS model. First, all chemical components and targets of QLJP were obtained from the Traditional Chinese Medicine System Pharmacology Analysis Platform (TCMSP). Targets related to broiler AS were further obtained through the GeneCards database and the NCBI Gene sub-database. A protein-protein interaction (PPI) network was constructed. Then, enrichment analyses were performed to predict the potential mechanisms of QLJP in the treatment of broiler AS. Finally, the treatment effect of QLJP on AS was verified in a broiler AS model. Network pharmacology analysis generated 49 active ingredients and 167 core targets of QLJP, and a QLJP-single drug-target-disease network was successfully constructed. Gene enrichment analysis indicated that the core targets have played major roles in the Cell cycle, FOXO signaling pathways, etc. We demonstrated that QLJP improved clinical and organ damage symptoms and significantly reduced the ascites heart index in broilers with AS induced by administration of high-energy, high-protein diets and high-sodium drinking water in a low-temperature environment. QLJP may regulate lung oxidative stress, the cell cycle and apoptosis by activating the FOXO3a signaling pathway to interfere with the occurrence and development of AS in broilers. QLJP administration may be a good clinical strategy for the prevention and treatment of broiler AS.

Antiliquid-Interfering, Antibacteria, and Adhesive Wearable Strain Sensor Based on Superhydrophobic and Conductive Composite Hydrogel.

Conductive hydrogels are promising multifunctional materials for wearable sensors, but their practical applications require combined properties that are difficult to achieve. Herein, we developed a flexible wearable sensor with double-layer structure based on conductive composite hydrogel, which included the outer layer of silicone elastomer (Ecoflex)/silica microparticle composite film and the inner layer of P(AAm-co-HEMA)-MXene-AgNPs hydrogel. Through covalently cross-linking silicone elastomer on the surface of the hydrogel polymer, we bonded a thin Ecoflex film (100 µm) on the P(AAm-co-HEMA)-MXene-AgNPs hydrogel with robust interface, which can easily adhere to the Ecoflex/SiO2 microparticle composite film by silicone glue. The Ecoflex/SiO2 microparticle composite film endows the strain wearable sensor with superhydrophobic function that could maintain the stability under stretching or bending. Moreover, it can effectively resist the interference of water droplets and water flow. The P(AAm-co-HEMA)-MXene-AgNPs hydrogel exhibits outstanding antibacterial activity to inhibit Staphylococcus aureus, Escherichia coli, and even drug-resistant Escherichia coli. In addition, the flexible wearable sensor exhibited good self-adhesive performance by changing the reaction temperature of hydrogel and can adhere strongly onto various materials. The conductive composite hydrogel reported in this work contributes an innovative strategy for the preparation of multifunctional flexible wearable sensor.

Differentiating isoform functions with collaborative matrix factorization.

MOTIVATION: Isoforms are alternatively spliced mRNAs of genes. They can be translated into different functional proteoforms, and thus greatly increase the functional diversity of protein variants (or proteoforms). Differentiating the functions of isoforms (or proteoforms) helps understanding the underlying pathology of various complex diseases at a deeper granularity. Since existing functional genomic databases uniformly record the annotations at the gene-level, and rarely record the annotations at the isoform-level, differentiating isoform functions is more challenging than the traditional gene-level function prediction. RESULTS: Several approaches have been proposed to differentiate the functions of isoforms. They generally follow the multi-instance learning paradigm by viewing each gene as a bag and the spliced isoforms as its instances, and push functions of bags onto instances. These approaches implicitly assume the collected annotations of genes are complete and only integrate multiple RNA-seq datasets. As such, they have compromised performance. We propose a data integrative solution (called DisoFun) to Differentiate isoform Functions with collaborative matrix factorization. DisoFun assumes the functional annotations of genes are aggregated from those of key isoforms. It collaboratively factorizes the isoform data matrix and gene-term data matrix (storing Gene Ontology annotations of genes) into low-rank matrices to simultaneously explore the latent key isoforms, and achieve function prediction by aggregating predictions to their originating genes. In addition, it leverages the PPI network and Gene Ontology structure to further coordinate the matrix factorization. Extensive experimental results show that DisoFun improves the area under the receiver operating characteristic curve and area under the precision-recall curve of existing solutions by at least 7.7 and 28.9%, respectively. We further investigate DisoFun on four exemplar genes (LMNA, ADAM15, BCL2L1 and CFLAR) with known functions at the isoform-level, and observed that DisoFun can differentiate functions of their isoforms with 90.5% accuracy. AVAILABILITY AND IMPLEMENTATION: The code of DisoFun is available at mlda.swu.edu.cn/codes.php?name=DisoFun. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Isoform function prediction based on bi-random walks on a heterogeneous network.

MOTIVATION: Alternative splicing contributes to the functional diversity of protein species and the proteoforms translated from alternatively spliced isoforms of a gene actually execute the biological functions. Computationally predicting the functions of genes has been studied for decades. However, how to distinguish the functional annotations of isoforms, whose annotations are essential for understanding developmental abnormalities and cancers, is rarely explored. The main bottleneck is that functional annotations of isoforms are generally unavailable and functional genomic databases universally store the functional annotations at the gene level. RESULTS: We propose IsoFun to accomplish Isoform Function prediction based on bi-random walks on a heterogeneous network. IsoFun firstly constructs an isoform functional association network based on the expression profiles of isoforms derived from multiple RNA-seq datasets. Next, IsoFun uses the available Gene Ontology annotations of genes, gene-gene interactions and the relations between genes and isoforms to construct a heterogeneous network. After this, IsoFun performs a tailored bi-random walk on the heterogeneous network to predict the association between GO terms and isoforms, thus accomplishing the prediction of GO annotations of isoforms. Experimental results show that IsoFun significantly outperforms the state-of-the-art algorithms and improves the area under the receiver-operating curve (AUROC) and the area under the precision-recall curve (AUPRC) by 17% and 44% at the gene-level, respectively. We further validated the performance of IsoFun on the genes ADAM15 and BCL2L1. IsoFun accurately differentiates the functions of respective isoforms of these two genes. AVAILABILITY AND IMPLEMENTATION: The code of IsoFun is available at http://mlda.swu.edu.cn/codes.php? name=IsoFun. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

NMFGO: Gene Function Prediction via Nonnegative Matrix Factorization with Gene Ontology.

Gene Ontology (GO) is a controlled vocabulary of terms that describe molecule function, biological roles, and cellular locations of gene products (i.e., proteins and RNAs), it hierarchically organizes more than 43,000 GO terms via the direct acyclic graph. A gene is generally annotated with several of these GO terms. Therefore, accurately predicting the association between genes and massive terms is a difficult challenge. To combat with this challenge, we propose an matrix factorization based approach called NMFGO. NMFGO stores the available GO annotations of genes in a gene-term association matrix and adopts an ontological structure based taxonomic similarity measure to capture the GO hierarchy. Next, it factorizes the association matrix into two low-rank matrices via nonnegative matrix factorization regularized with the GO hierarchy. After that, it employs a semantic similarity based k nearest neighbor classifier in the low-rank matrices approximated subspace to predict gene functions. Empirical study on three model species (S. cerevisiae, H. sapiens, and A. thaliana) shows that NMFGO is robust to the input parameters and achieves significantly better prediction performance than GIC, TO, dRW- kNN, and NtN, which were re-implemented based on the instructions of the original papers. The supplementary file and demo codes of NMFGO are available at http://mlda.swu.edu.cn/codes.php?name=NMFGO.

Pump-degenerate phase-sensitive amplification in amorphous silicon waveguides.

We demonstrate phase-sensitive amplification in hydrogenated amorphous silicon photonic waveguides based on pump-degenerate four-wave mixing at continuous-wave (CW) operation, as well as at repetition rates of both 90 MHz and 10 GHz. At 90 MHz pulsed operation, an 11.7 dB phase-sensitive extinction ratio (ER) is achieved with a peak pump power of 1.6 W. At 10 GHz pulsed operation, a 6.6 dB phase-sensitive ER is achieved with a peak pump power of 0.5 W. At CW operation, a 1.6 dB ER is achieved with a pump power of 38 mW.

Wavelength multicasting through four-wave mixing with an optical comb source.

Based on four-wave mixing (FWM) with an optical comb source (OCS), we experimentally demonstrate 26-way or 15-way wavelength multicasting of 10-Gb/s differential phase-shift keying (DPSK) data in a highly-nonlinear fiber (HNLF) or a silicon waveguide, respectively. The OCS provides multiple spectrally equidistant pump waves leading to a multitude of FWM products after mixing with the signal. We achieve error-free operation with power penalties less than 5.7 dB for the HNLF and 4.2 dB for the silicon waveguide, respectively.

Wavelength-agile near-IR optical parametric oscillator using a deposited silicon waveguide.

Using a deposited hydrogenated amorphous silicon (a-Si:H) waveguide, we demonstrate ultra-broad bandwidth (60 THz) parametric amplification via four-wave mixing (FWM), and subsequently achieve the first silicon optical parametric oscillator (OPO) at near-IR wavelengths. Utilization of the time-dispersion-tuned technique provides an optical source with active wavelength tuning over 42 THz with a fixed pump wave.

Non-instantaneous optical nonlinearity of an a-Si:H nanowire waveguide.

We use pump-probe spectroscopy and continuous wave cross-phase and cross-amplitude modulation measurements to study the optical nonlinearity of a hydrogenated amorphous silicon (a-Si:H) nanowire waveguide, and we compare the results to those of a crystalline silicon waveguide of similar dimensions. The a-Si:H nanowire shows essentially zero instantaneous two-photon absorption, but it displays a strong, long-lived non-instantaneous nonlinearity that is both absorptive and refractive. Power scaling measurements show that this non-instantaneous nonlinearity in a-Si:H scales as a third-order nonlinearity, and the refractive component possesses the opposite sign to that expected for free-carrier dispersion.

Multichannel photon-pair generation using hydrogenated amorphous silicon waveguides.

We demonstrate highly efficient photon-pair generation using an 8 mm long hydrogenated amorphous silicon (a-Si:H) waveguide in far-detuned multiple wavelength channels simultaneously, measuring a coincidence-to-accidental ratio as high as 400. We also characterize the contamination from Raman scattering and show it to be insignificant over a spectrum span of at least 5 THz. Our results highlight a-Si:H as a potential high-performance, CMOS-compatible platform for large-scale quantum applications, particularly those based on the use of multiplexed quantum signals.

Highly sensitive ultrafast pulse characterization using hydrogenated amorphous silicon waveguides.

We experimentally demonstrate frequency resolved optical gating (FROG) via four-wave mixing (FWM) in ultrahigh nonlinearity hydrogenated amorphous silicon waveguides. We demonstrate FROG characterization using a FWM architecture that mimics second harmonic generation (SHG) FROG for pulsewidths as low as 360 fs. Additionally, we demonstrate for the first time a FWM architecture analogous to third harmonic generation (THG) FROG and validate its ability to overcome the direction of time ambiguity of the SHG-like architecture. Both architectures allow for sensitivities suitable for future telecommunications signals.

Ultralow-power all-optical processing of high-speed data signals in deposited silicon waveguides.

Utilizing a 6-mm-long hydrogenated amorphous silicon nanowaveguide, we demonstrate error-free (BER < 10(-9)) 160-to-10 Gb/s OTDM demultiplexing using ultralow switching peak powers of 50 mW. This material is deposited at low temperatures enabling a path toward multilayer integration and therefore massive scaling of the number of devices in a single photonic chip.

Ultralow power continuous-wave frequency conversion in hydrogenated amorphous silicon waveguides.

We demonstrate wavelength conversion through nonlinear parametric processes in hydrogenated amorphous silicon (a-Si:H) with maximum conversion efficiency of -13 dB at telecommunication data rates (10 GHz) using only 15 mW of pump peak power. Conversion bandwidths as large as 150 nm (20 THz) are measured in continuous-wave regime at telecommunication wavelengths. The nonlinear refractive index of the material is determined by four-wave mixing (FWM) to be n(2)=7.43×10(-13) cm(2)/W, approximately an order of magnitude larger than that of single crystal silicon.