Using quasi-bound states in the continuum in an all-dielectric metasurface array to enhance terahertz fingerprint sensing.

The terahertz absorption fingerprint spectrum is crucial for qualitative spectral analysis, revealing the rotational or vibrational energy levels of numerous biological macromolecules and chemicals within the THz frequency range. However, conventional sensing in this band is hindered by weak interactions with trace analytes, leading to subtle signals. In this Letter, an all-dielectric metasurface array is proposed to enhance the absorption fingerprint spectrum using quasi-bound states in the continuum (BIC) resonance. The observable quasi-BIC resonance is achieved by breaking the symmetry of the C2v structure. The periodic dimensions of the structure are adjusted to excite quasi-BIC resonances at different frequencies, thereby enhancing the fingerprint spectra of four different substances. By exploiting the correlation between the Q-factor and absorption across different frequencies, calibration of the molecular absorption fingerprint spectrum obtained through metasurface sensing yields precise enhanced absorption fingerprint spectra for various substances within the 0.55-1.6 THz range. Our Letter introduces a novel, to the best of our knowledge, strategy for trace sensing in the THz frequency range, demonstrating the promising potential for enhanced absorption fingerprint spectrum sensing.

Coupling-Based Multiple Bound States in the Continuum and Grating-Assisted Permittivity Retrieval in the Terahertz Metasurface.

The terahertz (THz) metasurfaces that support bound states in the continuum (BICs) provide a promising platform for various applications due to their high Q-factor resonance. In this study, we experimentally demonstrate multiple BICs with different resonance symmetries in the THz metasurface based on mode coupling. The proposed metasurface is composed of 2 × 2 split ring resonators (SRRs) metamolecules. The SRRs of two different gap angles in the metamolecule lattice provide intrinsic resonance with different frequencies, and the coupling between them exhibits high transmission quasi-BIC resonance, which can be tuned by varying the gap angle. The arrangement of SRRs in the 2 × 2 metamolecule lattice determines the types of coupling that govern the resonance symmetry of quasi-BIC. More interestingly, the multiple quasi-BICs enabled by different couplings can be simultaneously achieved in a metasurface. Apart from tuning the gap angles, the permittivity in the vicinity of SRRs also changes the resonance frequency. Consequently, quasi-BIC can be artificially formed by deliberately constructing the permittivity difference of the dielectric environment on the SRRs. In view of this, we introduce the scheme of permittivity retrieval for the dispersive analyte, assisted by the fixed-permittivity gratings. In addition, we experimentally demonstrate the metasurface in combination with the microfluidic chip for the sensing of the glucose solution concentration. Our findings offer a possible strategy for the existing manufactured metasurface to achieve quasi-BIC resonance and provide a promising candidate for approaching the spectral analysis of the biochemical.

Observation of the bound states in the continuum supported by mode coupling in a terahertz metasurface.

Metasurface supporting bound states in the continuum (BIC) provides a unique approach for the realization of intense near-field enhancement and high quality factor (Q-factor) resonance, which promote the advancement of various applications. Here we experimentally demonstrate a Friedrich-Wintgen BIC based on the mode coupling in the terahertz metasurface, which produces BIC by the coupling of the LC mode and dipole mode resonances. The transition from ideal BIC to quasi-BIC is caused by the mismatch of the coupling, and the mode decay rate during this process is analyzed by temporal coupled mode theory. The Q-factor and the electric field enhancement of the quasi-BIC resonance are significantly increased, which provides enormous potential in sensing, nonlinear optics, and topological optics.

Exosome as potential biomarkers for gastrointestinal tumors.

INTRODUCTION: Exosomes are polyvesicles that are formed by invagination of intracellular lysosomal particles, and are released into the extracellular matrix after the fusion of polyvesicular outer membrane and cell membrane. In the body, immune response, antigen presentation, cell migration, cell differentiation and tumor invasion are closely related to tumorigenesis and tumor progression. This study aimed to conduct a meta-analysis for evaluating the clinicopathological, diagnostic and prognostic significance of exosomal expression in gastrointestinal tumors. METHODS: The original English articles were systematically searched in the online databases. The diagnostic accuracy, prognostic utility and clinicopathological correlation of gastrointestinal tumors were investigated. The quality assessment for studies of diagnostic accuracy II and Newcastle-Ottawa scale were used for quality evaluation, and the data was strictly extracted to judge the deviation of the study. RESULTS: A total of 14 studies with 1837 gastrointestinal tumor patients were included. The change in exosomal expression showed significant correlation with poor clinicopathological parameters (tumor diameter: combined P = .00024394; differentiation: combined P = 2.796e-08; lymphatic metastasis: P = 9.610e-07; distant metastasis: combined P = .00017326; pathological classification: combined P = .00875213; invasion depth: combined P = 3.504e-08) carcinoembryonic antigen (combined P = . 04458857) and tumor location (combined P = .00145983). The difference in the area under the curve between gastrointestinal tumor patients and healthy people showed an area under the curve of 0.89 (95%Cl 0.85-0.91) and heterogeneity of 0.59, 95% CI=[0.55-0.68]. The sensitivity was 0.88 (95%Cl 0.83 mi 0.91), the specificity was 0.72 (95%Cl 0.63 mi 0.80), and the diagnostic odds ratio was 18 (10-33). The results of survival analysis revealed that the abnormally expressed exosomes were significantly correlated with poor overall survival (hazard ratio =2.81, 95% CI: 2.02-3.93, P=0.013∗ 62.7%∗). CONCLUSION: The abnormally expressed exosomes might act as auxiliary biomarkers in diagnosing gastrointestinal tumors and demonstrated good prognostic significance in predicting the survival of patients with gastrointestinal tumors.

Microbiome characterization and re-design by biologic agents for inflammatory bowel disease insights.

The therapeutic effect of inflammatory bowel disease has improved in the past decades, but most of patients cannot tolerate, do not respond to drugs, or relapse after treating with conventional therapy. Therefore, new and more effective treatment methods are still needed in treatment of IBD. In this review, we will discuss the relevant mechanisms and the latest research progress of biologics (anti-TNF treatments, interleukin inhibitors, integrin inhibitors, antisense oligonucleotide, and JAK inhibitors) for IBD, focus on the efficacy and safety of drugs for moderate-to-severe IBD, and summarize the clinical status and future development direction of biologics in IBD.

Comparative investigation of coarse and fine wool sheep skin indicates the early regulators for skin and wool diversity.

The hair follicle is an excellent mini-system illustrating the mechanisms governing organogenesis and regeneration. Although the general mechanisms modulating skin and hair follicle development are widely studied in mouse and chicken models, the delicate network regulating skin and hair diversity remains largely unclear. Sheep is an additional model to address the various wool characteristics observed in nature. The coarse and fine wool sheep with diverse fibers were examined to show differences in the primary wool follicle size and skin thickness. The molecular dynamics in skin staged at the primary wool follicle induction between two sheep lines were investigated by RNA-sequencing analyses to generate 1994 differentially expressed genes revealing marker genes for epithelium (6 genes), dermal condensate (38 genes) and dermal fibroblast (58 genes) highly correlated with skin and wool follicle morphological differences. The DEGs were enriched in GO terms represented by epithelial cell migration and differentiation, regulation of hair follicle development and ectodermal placode formation, and KEGG pathways typified by WNT and Hedgehog signaling pathways governing the differences of skin structure. The qPCR detection of 9 genes confirmed the similar expression tendency with RNA-sequencing profiles. This comparative study of coarse and fine wool sheep skin reveals the presence of skin and wool follicle differences at primary wool follicle induction stage, and indicates the potential effectors (APCDD1, FGF20, DKK1, IGFBP3 and SFRP4) regulating the skin compartments during the early morphogenesis of primary wool follicles to shape the variable wool fiber thickness in later developmental stages.

Transcriptome Reveals Long Non-coding RNAs and mRNAs Involved in Primary Wool Follicle Induction in Carpet Sheep Fetal Skin.

Murine primary hair follicle induction is driven by the communication between the mesenchyme and epithelium and mostly governed by signaling pathways including wingless-related integration site (WNT), ectodysplasin A receptor (EDAR), bone morphogenetic protein (BMP), and fibroblast growth factor (FGF), as observed in genetically modified mouse models. Sheep skin may serve as a valuable system for hair research owing to the co-existence of sweat glands with wool follicles in trunk skin and asynchronized wool follicle growth pattern similar to that of human head hair follicles. However, the mechanisms underlying wool follicle development remain largely unknown. To understand how long non-coding RNAs (lncRNAs) and mRNAs function in primary wool follicle induction in carpet wool sheep, we conducted high-throughput RNA sequencing and revealed globally altered lncRNAs (36 upregulated and 26 downregulated), mRNAs (228 elevated and 225 decreased), and 80 differentially expressed novel transcripts. Several key signals in WNT (WNT2B and WNT16), BMP (BMP3, BMP4, and BMP7), EDAR (EDAR and EDARADD), and FGF (FGFR2 and FGF20) pathways, and a series of lncRNAs, including XLOC_539599, XLOC_556463, XLOC_015081, XLOC_1285606, XLOC_297809, and XLOC_764219, were shown to be potentially important for primary wool follicle induction. GO and KEGG analyses of differentially expressed mRNAs and potential targets of altered lncRNAs were both significantly enriched in morphogenesis biological processes and transforming growth factor-ß, Hedgehog, and PI3K-Akt signaling, as well as focal adhesion and extracellular matrix-receptor interactions. The prediction of mRNA-mRNA and lncRNA-mRNA interaction networks further revealed transcripts potentially involved in primary wool follicle induction. The expression patterns of mRNAs and lncRNAs of interest were validated by qRT-PCR. The localization of XLOC_297809 and XLOC_764219 both in placodes and dermal condensations was detected by in situ hybridization, indicating important roles of lncRNAs in primary wool follicle induction and skin development. This is the first report elucidating the gene network of lncRNAs and mRNAs associated with primary wool follicle early development in carpet wool sheep and will shed new light on selective wool sheep breeding.

Defining Key Genes Regulating Morphogenesis of Apocrine Sweat Gland in Sheepskin.

The apocrine sweat gland is a unique skin appendage in humans compared to mouse and chicken models. The absence of apocrine sweat glands in chicken and murine skin largely restrains further understanding of the complexity of human skin biology and skin diseases, like hircismus. Sheep may serve as an additional system for skin appendage investigation owing to the distributions and histological similarities between the apocrine sweat glands of sheep trunk skin and human armpit skin. To understand the molecular mechanisms underlying morphogenesis of apocrine sweat glands in sheepskin, transcriptome analyses were conducted to reveal 1631 differentially expressed genes that were mainly enriched in three functional groups (cellular component, molecular function and biological process), particularly in gland, epithelial, hair follicle and skin development. There were 7 Gene Ontology (GO) terms enriched in epithelial cell migration and morphogenesis of branching epithelium that were potentially correlated with the wool follicle peg elongation. An additional 5 GO terms were enriched in gland morphogenesis (20 genes), gland development (42 genes), salivary gland morphogenesis and development (8 genes), branching involved in salivary gland morphogenesis (6 genes) and mammary gland epithelial cell differentiation (4 genes). The enriched gland-related genes and two Kyoto Encyclopedia of Genes and Genomes pathway genes (WNT and TGF-ß) were potentially involved in the induction of apocrine sweat glands. Genes named BMPR1A, BMP7, SMAD4, TGFB3, WIF1, and WNT10B were selected to validate transcript expression by qRT-PCR. Immunohistochemistry was performed to localize markers for hair follicle (SOX2), skin fibroblast (PDGFRB), stem cells (SOX9) and BMP signaling (SMAD5) in sheepskin. SOX2 and PDGFRB were absent in apocrine sweat glands. SOX9 and SMAD5 were both observed in precursor cells of apocrine sweat glands and later in gland ducts. These results combined with the upregulation of BMP signaling genes indicate that apocrine sweat glands were originated from outer root sheath of primary wool follicle and positively regulated by BMP signaling. This report established the primary network regulating early development of apocrine sweat glands in sheepskin and will facilitate the further understanding of histology and pathology of apocrine sweat glands in human and companion animal skin.

A bi-cistronic baculovirus expression vector for improved recombinant protein production.

Baculoviruses are one of the most studied insect viruses both in basic virology research and in biotechnology applications. Incorporating an internal ribosome entry site (IRES) into the baculovirus genome generates bi-cistronic baculoviruses expression vectors that produce two genes of interest. The bi-cistronic baculoviruses also facilitate recombinant virus isolation and titer determination when the green fluorescent protein was co-expressed. Furthermore, when the secretion proteins were co-expressed with the cytosolic green fluorescent protein, the cell lysis and cytosolic protein released into the culture medium could be monitored by the green fluorescence, thus facilitating purification of the secreted proteins.

Functional expression of rat neuroligin-1 extracellular fragment by a bi-cistronic baculovirus expression vector.

The interaction between the synaptic adhesion molecules neuroligins and neurexins is essential for connecting the pre- and post-synaptic neurons, modulating neuronal signal transmission, and facilitating neuronal axogenesis. Here, we describe the simultaneous expression of the extracellular domain of rat neuroligin-1 (NL1) proteins along with the enhanced green fluorescent protein (EGFP) using the bi-cistronic baculovirus expression vector system (bi-BEVS). Recombinant rat NL1 protein, fused with signal sequence derived from human Azurocidin gene (AzSP), was secreted into the culture medium and the optimum harvest time for NL1 protein before the lysis of infected cells was determined through the release of cytosolic EGFP. The NL1 protein (0.129±0.013 mg/8×10(7) High Five cells; ~96% purity by metal affinity chromatography) was obtained from the supernatant of the recombinant virus-infected insect cells. A novel chip was employed to address whether the recombinant NL1 is functional in axogenesis. The purified rat NL1 promoted and enhanced the growth rate (137.07±9.74 µm/day) of the axon on NL1/PLL (poly-L-lysine)-coated fine lines on the chip compared to those lines that were coated with PLL alone (105.53±4.53 µm/day). These results were confirmed by fluorescence immunocytochemistry and demonstrated that the recombinant protein can be purified by a one-step process using IMAC combined with monitoring of cell lysis by bi-BEVS. This technique along with our novel chip offers a simple, cost-effective and useful platform for understanding the roles of NL1 protein in neuronal regeneration and synaptic formation studies.

Expression of recombinant human interferon-γ with antiviral activity in the bi-cistronic baculovirus-insect/larval system.

A bi-cistronic baculovirus-insect/larval system containing a polyhedron promoter, an internal ribosome entry site (IRES), and an egfp gene was developed as a cost-effective platform for the production of recombinant human interferon gamma (rhIFN-γ). There was no significant difference between the amounts of rhIFN-γ produced in the baculovirus-infected Spodoptera frugiferda 21 cells grown in serum-free medium and the serum-supplemented medium, while the Trichoplusia ni (T. ni) and Spodoptera exigua (S. exigua) larvae afforded rhIFN-γ amounting to 1.08±0.04 and 9.74±0.35 µg/mg protein respectively. The presence of non-glycosylated and glycosylated rhIFN-γ was confirmed by immunoblot and lectin blot. The immunological activity of purified rhIFN-γ, with 96% purity by Nickel (II)-nitrilotriacetic acid (Ni-NTA) affinity chromatography, was similar to that commercially available. Moreover, the rhIFN-γ protein from T. ni had more potent antiviral activity. These findings suggest that this IRES-based expression system is a simple and inexpensive alternative for large-scale protein production in anti-viral research.

Cell-based analysis of Chikungunya virus membrane fusion using baculovirus-expression vectors.

Chikungunya virus infection has emerged in many countries over the past decade. There are no effective drugs for controlling the disease. To develop cell-based system for screening anti-virus drugs, a bi-cistronic baculovirus expression system was utilized to co-express viral structural proteins C (capsid), E2 and E1 and the enhanced green fluorescence protein (EGFP) in Spodoptera frugiperda insect cells (Sf21). The EGFP-positive Sf21 cells fused with each other and with uninfected cells to form a syncytium, allowing characterization of cholesterol and low pH requirements for syncytium formation. Western blot analysis showed three structural proteins were expressed in baculovirus infected cells. The structural proteins of Chikungunya virus that is required for cell fusion was determined with various recombinant baculoviruses bearing different lengths of the viral structural protein genes. Protein E1 was required for cell fusion and indicating that Chikungunya viral membrane fusion was a class II membrane fusion. It was also demonstrated that the heterologous expression of alphavirus monomeric E1 can induce insect cell fusions. Furthermore, this cell-based system provides a model for studying class II viral membrane fusion.

Development of a prokaryotic-like polycistronic baculovirus expression vector by the linkage of two internal ribosome entry sites.

Recombinant baculoviruses are suitable for the high-level production of large multi-protein complexes. A tri-cistronic expression vector was constructed by the inclusion of two internal ribosome entry sites (IRESs). In this novel polycistronic vector, one single polyhedrin promoter controlled the transcription of a tri-cistronic transcript. Also, the first cistron was translated through a cap-dependent mechanism, while the second and third cistrons were translated by the IRESs derived from the 5' UTR of Rhopalosiphum padi virus (RhPV) and Perina nuda virus (PnV), respectively. The ratio of tri-cistronic gene expression levels produced by the three translational initiation modules is about 2:1:1 (cap:PnV IRES:RhPV IRES). This study indicates that polycistronic genes can be co-expressed at the translational level as in prokaryotic expression system by baculovirus biotechnology.