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Abstract The effective isolation of rare target cells, such as circulating tumor cells, from whole blood is still challenging due to the lack of a capturing surface with strong target-binding affinity and non-target-cell resistance. Here we present a solution leveraging the flexibility of bacterial virus (phage) nanofibers with their sidewalls displaying target circulating tumor cell-specific aptamers and their ends tethered to magnetic beads. Such flexible phages, with low stiffness and Young’s modulus, can twist and adapt to recognize the cell receptors, energetically enhancing target cell capturing and entropically discouraging non-target cells (white blood cells) adsorption. The magnetic beads with flexible phages can isolate and count target cells with significant increase in cell affinity and reduction in non-target cell absorption compared to magnetic beads having rigid phages. This differentiates breast cancer patients and healthy donors, with impressive area under the curve (0.991) at the optimal detection threshold (>4 target cells mL−1). Immunostaining of captured circulating tumor cells precisely determines breast cancer subtypes with a diagnostic accuracy of 91.07%. Our study reveals the power of viral mechanical attributes in designing surfaces with superior target binding and non-target anti-fouling.

With the rapid development of the livestock industry, finding new sources of feed has become a critical issue that needs to be addressed urgently. China is one of the top five sunflower producers in the world and generates a massive amount of sunflower stalks annually, yet this resource has not been effectively utilized. Therefore, in order to tap into the potential of sunflower stalks for animal feed, it is essential to explore and develop efficient methods for their utilization.In this study, various proportions of alfalfa and sunflower straw were co-ensiled with the following mixing ratios: 0:10, 2:8, 4:6, 5:5, 6:4, and 8:2, denoted as A0S10, A2S8, A4S6, A5S5, A6S4, and A8S2, respectively. The nutrient composition, fermentation quality, microbial quantity, microbial diversity, and broad-spectrum metabolomics on the 60th day were assessed. The results showed that the treatment groups with more sunflower straw added (A2S8, A4S6) could start fermentation earlier. On the first day of fermentation, Weissella spp.dominated overwhelmingly in these two groups. At the same time, in the early stage of fermentation, the pH in these two groups dropped rapidly, which could effectively reduce the loss of nutrients in the early stage of fermentation.In the later fermentation period, a declining trend in acetic acid levels was observed in A0S10, A2S8, and A4S6, while no butyric acid production was detected in A0S10 and A2S8 throughout the process. In A4S6, butyric acid production was observed only after 30 days of fermentation. From the perspective of metabolites, compared with sunflower ensiling alone, many bioactive substances such as flavonoids, alkaloids, and terpenes are upregulated in mixed ensiling.

Exosome-derived long non-coding RNAs (lncRNAs) are extensively engaged in recovery and repair of the injured spinal cord, through different mechanisms. However, to date no study has systematically evaluated the differentially expressed lncRNAs involved in the development of spinal cord injury. Thus, the aim of this study was to identify key circulating exosome-derived lncRNAs in a rat model of spinal cord injury and investigate their potential actions. To this end, we established a rat model of spinal cord hemisection. Circulating exosomes were extracted from blood samples from spinal cord injury and control (sham) rats and further identified through Western blotting and electron microscopy. RNA was isolated from the exosomes and sequenced. The enrichment analysis demonstrated that there were distinctively different lncRNA and mRNA expression patterns between the two groups. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis and Gene Ontology (GO) functional analysis were performed to determine the possible involvements of upregulated and downregulated lncRNAs in various pathways and different biological processes, as well as their cellular locations and molecular functions. Furthermore, quantitative reverse transcription-polymerase chain reaction showed that the expression of five lncRNAs––ENSRN0T00000067908, XR_590093, XR_591455, XR_360081, and XR_346933––was increased, whereas the expression of XR_351404, XR_591426, XR_353833, XR_590076, and XR_590719 was decreased. Of note, these 10 lncRNAs were at the center of the lncRNA-miRNA-mRNA coexpression network, which also included 198 mRNAs and 41 miRNAs. Taken together, our findings show that several circulating exosomal lncRNAs are differentially expressed after spinal cord injury, suggesting that they may be involved in spinal cord injury pathology and pathogenesis. These lncRNAs could potentially serve as targets for the clinical diagnosis and treatment of spinal cord injury.

The development of gel electrophoresis-based biodetection assays for point-of-care analysis are highly demanding. In this work, we proposed a ratiometric gel electrophoresis-based biosensing platform by employing catalytic hairpin assembly (CHA) process functions as both the signal output and the signal amplification module. Two types of nucleic acids, DNA and miRNA, are chosen for demonstration. The proposed strategy indeed provides a new paradigm for the design of a portable detection platform and may hold great potential for sensitive diagnoses.

In this paper, an output dynamic game model of intertwined supply chains operating in two different countries is established. The Nash equilibrium point of the model and its stable region are obtained using nonlinear dynamic principles. The complex properties of the system, such as stability, period-doubling bifurcations, and chaos, are investigated using numerical simulations. Our results suggest that the level of output and the system’s profits undergo bifurcation and chaos with an increase in the output adjustment speed. An interesting phenomenon occurs in that higher tariffs lead to the expansion of the stable range of the supply chain in the product-exporting country. The chaotic behavior of the system is sensitive to the value of the initial level of output. In supply chain competition, each supply chain firm should make suitable adjustments to the speed of output. To maintain the stability of domestic markets, excessive tariffs should be avoided. It is essential that each supply chain firm evaluates the potential impacts of different initial output values when making initial decisions. Using the method of delayed feedback control, the chaotic behavior of the system can effectively be controlled. These findings offer valuable and novel insight into inter-chain competition in supply chain networks.

Super-rational aspiration induced strategy updating with exit rights has been considered in some previous studies, in which the players adjust strategies in line with their payoffs and aspirations, and they have access to exit the game. However, exit payoffs for exiting players are automatically allocated, which is clearly contrary to reality. In this study, evolutionary cooperation dynamics with super-rational aspiration and asymmetry in the Prisoner's Dilemma game is investigated, where exit payoffs are implemented by local peers. The results show that for different population structures, the asymmetry of the system is always contributive to the participation of the players. Furthermore, we show that under different exit payoffs, super-rationality and asymmetry are conductive to the evolution of cooperation.

Solanum xanthocarpum is used for the treatment of rheumatic arthritis, toothache, sore throats, carbuncle, furuncle, and other inflammatory diseases in traditional Chinese medicine and Ayurvedic medical system, with the phenolic compounds being one of its principal components. In this study, 51 phenolic compounds including seven new compounds 1, 2, 9, 13, 17, 22, and 40 were isolated from the fruits of Solanum xanthocarpum. 40 known compounds 3–8, 10–12, 14–16, 18–21, 23–25, 28–32, 35–39, 41–51 were firstly isolated from Solanum xanthocarpum. Their structures were determined by comprehensive spectroscopic analyses, X-ray crystallography, NMR calculations, chemical methods, and comparisons of spectroscopic data. The results of anti-inflammatory assays indicated that most isolated compounds (3–7, 11–30, 32–37, 39, 40, 42, 43, 45, and 48–51) possessed significant inhibitory activities of the NO release of LPS-induced RAW 264.7 cells, with IC50 values ranging from 10.46 to 47.59 μM. Further analysis by molecular docking implied that most bioactive compounds could interact with the amino acid residues of iNOS proteins, supporting the anti-inflammatory activity of the compounds. Especially, compounds 17–20, 26–27, 32, and 34 showed strong affinities with iNOS proteins. The bioinformatic analysis further revealed the potential anti-inflammatory targets of the phenolic compounds isolated from the fruits of Solanum xanthocarpum.

Abstract Background Glioma, the most frequent primary tumor of the central nervous system, has poor prognosis. The epidermal growth factor receptor (EGFR) pathway and angiogenesis play important roles in glioma growth, invasion, and recurrence. The present study aimed to use proteomic methods to probe into the role of the EGF‐EGFR‐angiogenesis axis in the tumorigenesis of glioma and access the therapeutic efficacy of selumetinib on glioma. Methods Proteomic profiling was used to characterize 200 paired EGFR‐positive and EGFR‐negative glioma tissues of all pathological types. The quantitative mass spectrometry data were used for systematic analysis of the proteomic profiles of 10 EGFR‐positive and 10 EGFR‐negative glioma cases. Consensus‐clustering analysis was used to screen target proteins. Immunofluorescence analysis, cell growth assay, and intracranial xenograft experiments were used to verify and test the therapeutic effect of selumetinib on glioma. Results Advanced proteomic screening demonstrated that the expression of EGF‐like domain multiple 7 (EGFL7) was higher in EGFR‐positive tumor tissues than in EGFR‐negative tumor tissues. In addition, EGFL7 could act as an activator in vitro and in vivo to promote glioma cell proliferation. EGFL7 was associated strongly with EGFR and prognosis. EGFL7 knockdown effectively suppressed glioma cell proliferation. Selumetinib treatment showed tumor reduction effect in EGFR‐positive glioblastoma xenograft mouse model. Conclusions EGFL7 is a potential diagnostic biomarker and therapeutic target of glioma. Selumetinib could target the EGFR pathway and possibly improve the prognosis of EGFR‐positive glioma.

Apiculture has been greatly developed in recent years in China. Beekeeping cooperatives and honey manufacturing enterprises have increased rapidly. As a result, a variety of honey products have entered the market, adding vitality to the food economy; however, the adulteration of honey products is on the rise in China. Previous attempts to control the adulteration of honey products mostly relied on technical, product-specific measures, and there was a lack of modeling research to guide the supervision of the honey product industry. In order to help local governments to better control the adulteration of honey products from a management perspective, this paper establishes an evolutionary game model composed of beekeeping cooperatives, honey product enterprises, and local governments. Through stability analysis and model simulation, we found that local government subsidies to cooperatives have little impact on the game system. Local government penalties to cooperatives and price adjustments of unadulterated raw honey by cooperatives are effective management tools to reduce the adulteration behavior of cooperatives. Local government penalties for enterprises are an effective management tool to reduce the adulteration behavior of enterprises. This research provides useful information for government agencies to design appropriate policies/business modes so as to promote sustainability and the healthy development of the honey product industry in China.

Elesesterpenes A–K (1–11), eleven new lupane-type triterpenoids, triterpenoid glycosides, and nortriterpenoid were isolated from the leaves of Eleutherococcus sessiliflorus. Their structures and relative configurations were completely elucidated by a combination of diverse methods including physical, spectroscopic data. The absolute configuration of elesesterpenes A–B (1–2) was defined by single-crystal X-ray diffraction. Meanwhile, all the isolates were evaluated for anti-inflammatory activities on lipopolysaccharide-induced nitric oxide production in BV2 microglial cells, and antiproliferative activities against human hepatoma (HepG2), human lung adenocarcinoma (A549), and human glioma cells (LN229) in vitro. It was found that some of them exhibited obvious anti-inflammatory activities and potent antiproliferative activities.

Butyrate is widely accepted as a proliferation inhibitor in colon cancer but less thoroughly characterized in the colonic epithelium of objects with type 2 diabetes mellitus. The present study investigated the regulatory effect of butyrate on proliferation, the related molecule high-mobility group box 1 (HMGB1) and the receptor for advanced glycation end products (RAGE) in the colon of db/db type 2 diabetic model mice and non-cancerous NCM460 colon cells. Proliferation and the expression of HMGB1 and RAGE were increased and could be partially reversed by butyrate treatment in the colon of db/db mice, which were consistent in NCM460 cells under a high glucose state. In NCM460 cells, under the normal glucose state, proliferation increased by overexpression of HMGB1. Under a high glucose state, increased expression of HMGB1 was accompanied with a release from cell nuclei into the cytoplasm and extracellular matrix. Down-regulation of HMGB1 could lower the expression of RAGE and attenuate the abnormally increased proliferation. And overexpression of HMGB1 reversed the suppressing effect of butyrate on abnormally increased proliferation. Conclusively, butyrate suppressed the abnormally increased proliferation in colonic epithelial cells under diabetic state by targeting HMGB1. Keywords: Diabetes, Butyrate, Proliferation, HMGB1, Colonic epithelial cells

Piwi-interacting RNAs (piRNAs), a class of small non-coding RNAs (ncRNAs), play pivotal roles in maintaining the genomic stability and modulating biological processes such as growth and development via the regulation of gene expression. However, the piRNAs in the Asian honeybee (Apis cerana) are still largely unknown at present. In this current work, on the basis of previously gained high-quality small RNA-seq datasets, piRNAs in the larval gut of Apis cerana cerana, the nominated species of A. cerana, were identified for the first time, followed by an in-depth investigation of the regulatory roles of differentially expressed piRNAs (DEpiRNAs) in the developmental process of the A. c. cerana. Here, a total of 621 piRNAs were identified in A. c. cerana larval guts, among which 499 piRNAs were shared by 4-(Ac4 group), 5-(Ac5 group), and 6-day-old (Ac6 group) larval guts, while the numbers of unique ones equaled 79, 37, and 11, respectively. The piRNAs in each group ranged from 24 nucleotides (nt) to 33 nt in length, and the first base of the piRNAs had a cytosine (C) bias. Additionally, five up-regulated and five down-regulated piRNAs were identified in the Ac4 vs. Ac5 comparison group, nine of which could target 9011 mRNAs; these targets were involved in 41 GO terms and 137 pathways. Comparatively, 22 up-regulated piRNAs were detected in the Ac5 vs. Ac6 comparison group, 21 of which could target 28,969 mRNAs; these targets were engaged in 46 functional terms and 164 pathways. The results suggested an overall alteration of the expression pattern of piRNAs during the developmental process of A. c. cerana larvae. The regulatory network analysis showed that piR-ace-748815 and piR-ace-512574 in the Ac4 vs. Ac5 comparison group as well as piR-ace-716466 and piR-ace-828146 in the Ac5 vs. Ac6 comparison group were linked to the highest number of targets. Further investigation indicated that targets of DEpiRNAs in the abovementioned two comparison groups could be annotated to several growth and development-associated pathways, such as the Jak/STAT, TGF-β, and Wnt signaling pathways, indicating the involvement of DEpiRNAs in modulating larval gut development via these crucial pathways. Moreover, the expression trends of six randomly selected DEpiRNAs were verified using a combination of stem-loop RT-PCR and RT-qPCR. These results not only provide a novel insight into the development of the A. c. cerana larval gut, but also lay a foundation for uncovering the epigenetic mechanism underlying larval gut development.

Eight new inositol derivatives, solsurinositols A–H (1–8), were isolated from the 70% EtOH extract of the leaves of Solanum capsicoides Allioni. Careful isolation by silica gel column chromatography followed by preparative high-performance liquid chromatography (HPLC) allowed us to obtain analytically pure compounds 1–8. They shared the same relative stereochemistry on the ring but have different acyl groups attached to various hydroxyl groups. This was the first time that inositol derivatives have been isolated from this plant. The chemical structures of compounds 1–8 were characterized by extensive 1D nuclear magnetic resonance (NMR) and 2D NMR and mass analyses. Meanwhile, the in vitro anti-inflammatory activity of all compounds was determined using lipopolysaccharide (LPS)-induced BV2 microglia, and among the isolates, compounds 5 (IC50 = 11.21 ± 0.14 µM) and 7 (IC50 = 14.5 ± 1.22 µM) were shown to have potential anti-inflammatory activity.

As a new target protein for Alzheimer’s disease (AD), the triggering receptor expressed on myeloid Cells 2 (TREM2) was expressed on the surface of microglia, which was shown to regulate neuroinflammation, be associated with a variety of neuropathologic, and regarded as a potential indicator for monitoring AD. In this study, a novel recognition system based on surface plasmon resonance (SPR) for the TREM2 target spot was established coupled with quadrupole time-of-flight tandem mass spectrometry (UPLC-MS), in order to screen the active ingredients targeting TREM2 from Datura metel seeds. The results showed that four lignan-amides were discovered as candidate compounds by SPR biosensor-UPLC/MS recognition analysis. According to the guidance of the active ingredients discovered by the system, the lignin-amides from Datura metel seeds (LDS) were preliminarily identified as containing 27 lignan-amides, which were enriched compositions by the HP-20 of Datura metel seeds. Meanwhile, the anti-inflammatory activity of LDS was evaluated in BV2 microglia induced by LPS. Our experimental results demonstrated that LDS could reduce NO release in LPS-treated BV2 microglia cells and significantly reduce the expression of the proteins of inducible Nitric Oxide Synthase (iNOS), cyclooxygenase 2 (COX-2), microtubule-associated protein tau (Tau), and ionized calcium-binding adapter molecule 1 (IBA-1). Accordingly, LDS might increase the expression of TREM2/DNAX-activating protein of 12 kDa (DAP12) and suppress the Toll-like receptor SX4 (TLR4) pathway and Recombinant NLR Family, Pyrin Domain Containing Protein 3 (NLRP3)/cysteinyl aspartate specific proteinase-1 (Caspase-1) inflammasome expression by LDS in LPS-induced BV2 microglial cells. Then, the inhibitory release of inflammatory factors Interleukin 1 beta (IL-1β), Interleukin 6 (IL-6), and Tumor necrosis factor-alpha (TNFα) inflammatory cytokines were detected to inhibit neuroinflammatory responses. The present results propose that LDS has potential as an anti-neuroinflammatory agent against microglia-mediated neuroinflammatory disorders.

Watershed urbanization leads to dramatic changes in draining streams, with urban streams receiving a high frequency of scouring flows, together with the nutrient, contaminant, and thermal pollution associated with urbanization. These changes are known to cause significant losses of sensitive insect and fish species from urban streams, yet little is known about how these changes affect the composition and function of stream microbial communities. Over the course of two years, we repeatedly sampled sediments from eight central North Carolina streams affected to varying degrees by watershed urbanization. For each stream and sampling date, we characterized both overall and denitrifying bacterial communities and measured denitrification potentials. Denitrification is an ecologically important process, mediated by denitrifying bacteria that use nitrate and organic carbon as substrates. Differences in overall and denitrifying bacterial community composition were strongly associated with the gradient in urbanization. Denitrification potentials, which varied widely, were not significantly associated with substrate supply. By incorporating information on the community composition of denitrifying bacteria together with substrate supply in a linear mixed-effects model, we explained 45% of the variation in denitrification potential (p-value