The widespread use of mobile internet and social media has driven the creation and development of the micro-marketing model. Micro-influencers utilize marketing techniques that have a small and ...highly targeted reach, which in turn affects the psychology and perception of the target population. In the process of micromarketing, a very important influencing factor is interpersonal relationships. Therefore, this paper takes interpersonal relationships as an entry point, analyzes several aspects of interpersonal relationships participation in micro-marketing, the current situation of interpersonal relationships among micro-influencers, and the influence of interpersonal relationships on marketing strategy, which is of great significance in exploring the influence of interpersonal relationships on micro-marketing from the perspective of social influence. The author analyzes some micro-marketing strategies on the Chinese social platform Red Booklet. The empirical study shows that the more interaction between micro-influencers and the target population, the stronger the influence on the target population; compared with unilateral promotion by celebrities, micro-influencers have a stronger influence on the target population.
Region proposal network (RPN) based object detection, such as Faster Regions with CNN (Faster R-CNN), has gained considerable attention due to its high accuracy and fast speed. However, it has room ...for improvements when used in special application situations, such as the on-board vehicle detection. Original RPN locates multiscale anchors uniformly on each pixel of the last feature map and classifies whether an anchor is part of the foreground or background with one pixel in the last feature map. The receptive field of each pixel in the last feature map is fixed in the original faster R-CNN and does not coincide with the anchor size. Hence, only a certain part can be seen for large vehicles and too much useless information is contained in the feature for small vehicles. This reduces detection accuracy. Furthermore, the perspective projection results in the vehicle bounding box size becoming related to the bounding box position, thereby reducing the effectiveness and accuracy of the uniform anchor generation method. This reduces both detection accuracy and computing speed. After the region proposal stage, many regions of interest (ROI) are generated. The ROI pooling layer projects an ROI to the last feature map and forms a new feature map with a fixed size for final classification and box regression. The number of feature map pixels in the projected region can also influence the detection performance but this is not accurately controlled in former works. In this paper, the original faster R-CNN is optimized, especially for the on-board vehicle detection. This paper tries to solve these above-mentioned problems. The proposed method is tested on the KITTI dataset and the result shows a significant improvement without too many tricky parameter adjustments and training skills. The proposed method can also be used on other objects with obvious foreshortening effects, such as on-board pedestrian detection. The basic idea of the proposed method does not rely on concrete implementation and thus, most deep learning based object detectors with multiscale feature maps can be optimized with it.
Avian influenza, particularly the H9N2 subtype, presents significant challenges to poultry health, underscoring the need for effective antiviral interventions. This study explores the antiviral ...capabilities of Belamcanda extract, a traditional Chinese medicinal herb, against H9N2 Avian influenza virus (AIV) in specific pathogen-free (SPF) chicks. Through a comprehensive approach, we evaluated the impact of the extract on cytokine modulation and crucial immunological signaling pathways, essential for understanding the host-virus interaction. Our findings demonstrate that Belamcanda extract significantly modulates the expression of key inflammatory cytokines, including tumor necrosis factor alpha (TNF-α), interleukin-1 (IL-1), interleukin-2 (IL-2), and interleukin-6 (IL-6), which are pivotal to the host's response to H9N2 AIV infection. Western blot analysis further revealed that the extract markedly reduces the expression of critical immune signaling molecules such as toll-like receptor 3 (TLR3), TIR-domain-containing adapter-inducing interferon-β (TRIF), and nuclear factor kappa B (NF-κB). These insights into the mechanisms by which Belamcanda extract influences host immune responses and hinders viral replication highlight its potential as an innovative antiviral agent for poultry health management. The study advances our comprehension of natural compounds' antiviral mechanisms and lays the groundwork for developing strategies to manage viral infections in poultry. The demonstrated ability of Belamcanda extract to modulate immune responses and inhibit viral replication establishes it as a promising candidate for future antiviral therapy development, especially in light of the need for effective treatments against evolving influenza virus strains and the critical demand for enhanced poultry health management strategies.
Flash point is one of the major physical and chemical properties used to determine the fire and explosion hazards of liquids; therefore, the prediction of flash points is an important safety ...consideration. In this paper, flash point prediction methods based on vapor pressure, molecular structure, composition range, and boiling point of flammable liquids are reviewed, respectively. Le Chatelier’s rule and Antoine equations are used in the correlation between vapor pressure and flash point. Research on the correlations between flash point and composition range of the mixture has focused on flash point predictions for binary and ternary solutions, and further investigation for multicomponent solutions is required in the future. With regard to the correlation between molecular structure and flash point, some key breakthroughs have been made through quantitative structure−property relationship (QSPR) analysis. In particular, the artificial neural network (ANN) in QSPR is one possible correlation technique because of its nonlinear property and high accuracy and has the potential for wide application.
In the past decade, enormous progress has been made in understanding the role of stem cells in physiologic tissue renewal and in pathologic processes such as cancer. These findings have shed light on ...the identity and biological properties of such cells and the intrinsic and extrinsic signals that balance stem cell self-renewal with differentiation. With its astonishing self-renewal capacity, the intestinal epithelium has provided a unique model to study stem cell biology, lineage specification, and cancer. Here we review the role of Notch signaling in physiologic cell renewal and differentiation in the intestine as well as during its malignant transformation.
Background & Aims Ablation of Notch signaling within the intestinal epithelium results in loss of proliferating crypt progenitors due to their conversion into postmitotic secretory cells. We aimed to ...confirm that Notch was active in stem cells (SCs), investigate consequences of loss of Notch signaling within the intestinal SC compartment, and identify the physiologic ligands of Notch in mouse intestine. Furthermore, we investigated whether the induction of goblet cell differentiation that results from loss of Notch requires the transcription factor Krüppel-like factor 4 (Klf4). Methods Transgenic mice that carried a reporter of Notch1 activation were used for lineage tracing experiments. The in vivo functions of the Notch ligands Jagged1 (Jag1), Delta-like1 (Dll1), Delta-like4 (Dll4), and the transcription factor Klf4 were assessed in mice with inducible, gut-specific gene targeting (Vil-Cre-ERT2 ). Results Notch1 signaling was found to be activated in intestinal SCs. Although deletion of Jag1 or Dll4 did not perturb the intestinal epithelium, inactivation of Dll1 resulted in a moderate increase in number of goblet cells without noticeable effects of progenitor proliferation. However, simultaneous inactivation of Dll1 and Dll4 resulted in the complete conversion of proliferating progenitors into postmitotic goblet cells, concomitant with loss of SCs (Olfm4+ , Lgr5+ , and Ascl2+ ). Klf4 inactivation did not interfere with goblet cell differentiation in adult wild-type or in Notch pathway–deficient gut. Conclusions Notch signaling in SCs and progenitors is activated by Dll1 and Dll4 ligands and is required for maintenance of intestinal progenitor and SCs. Klf4 is dispensable for goblet cell differentiation in intestines of adult Notch-deficient mice.
Mesangial cells are specialized pericyte/smooth muscle cells that surround and constrain the vascular network within the glomerulus of the kidney. They are derived from the stromal mesenchyme, a ...progenitor population distinct from nephron stem cells. Whether mesangial cells have a distinct origin from vascular smooth muscle cells (VSMCs) and the pathways that govern their specification are unknown. Here we show that Notch signaling in stromal progenitors is essential for mesangial cell formation but is dispensable for the smooth muscle and interstitial cell lineages. Deletion of RBPjk, the common DNA-binding partner of all active Notch receptors, with Foxd1(tgCre) results in glomerular aneurysm and perinatal death from kidney failure. This defect occurs early in glomerular development as stromal-derived, desmin-positive cells fail to coalesce near forming nephrons and thus do not invade the vascular cleft of the S-shaped body. This is in contrast to other mutants in which the loss of the mesangium was due to migration defects, and suggests that loss of Notch signaling results in a failure to specify this population from the stroma. Interestingly, Pdgfrb-positive VSMCs do not enter the vascular cleft and cannot rescue the mesangial deficiency. Notch1 and Notch2 act redundantly through γ-secretase and RBPjk in this process, as individual mutants have mesangial cells at birth. Together, these data demonstrate a unique origin of mesangial cells and demonstrate a novel, redundant function for Notch receptors in mesangial cell specification, proliferation or survival during kidney development.
The isotopic composition of lithium (Li) in clinopyroxene (Cpx), determined via in situ micro‐analysis, has been employed as a potential geochemical tool for studying various geological processes ...such as crust‐mantle recycling, silicate weathering and fluid‐rock interaction. To obtain precise and accurate Li isotopic compositions in Cpx by LA‐MC‐ICP‐MS, synthetic Cpx matrix‐matched reference materials (RMs) were prepared in this study. Six Cpx‐matrix RMs were prepared by mixing metallic oxides with GSP‐2 (granodiorite) or pure L‐SVEC solution and melting them into glasses (GSP‐2 + oxide; L‐SVEC + oxide). Two representative synthetic glasses, CPXA01 and CPXB01, were subjected to a series of analyses to investigate the possible qualification of the RMs for in situ Li isotope measurement by LA‐MC‐ICP‐MS, including elemental homogeneity analysis (elemental mapping analysis and spot analysis), Li isotopic homogeneity analysis and accurate Li isotopic determination. The applicability of the synthetic Cpx‐matrix RMs was highlighted by comparing the δ7Li values of three natural Cpx calibrated against the synthetic Cpx‐matrix RMs and other commonly used RMs with different matrices (NIST SRM 612, BCR‐2G, GOR128‐G, StHs6/80‐G, KL2‐G and T1‐G), respectively. Additionally, CPXB01‐05 RMs with the same matrix but different Li contents were prepared to explore the Li content mismatch effect, which is significant for accurate determination of in situ Li isotopic composition by LA‐MC‐ICP‐MS. The results of the cross‐calibration of Li isotopes in CPXA01 and CPXB01 suggested no obvious Li isotopic fractionation between the two types of glasses (GSP‐2 + oxide; L‐SVEC + oxide). Thus, the two methods of producing Cpx‐matrix RMs are suitable for preparing the matrix‐matched RMs for in situ microanalysis for Li isotopes.
Key points
Synthetic clinopyroxene‐matrix glass.
Li isotopic homogeneity measured by LA‐MC‐ICP‐MS.
Application of synthetic reference material on natural samples, using existing reference materials for comparsion.
Programmed death ligand-1 (PD-L1) is highly expressed in a variety of cancer cells and suggests a poorer prognosis for patients. The natural compound isorhamnetin (ISO) shows promise in treating ...cancers and causing damage to canine mammary tumor (CMT) cells. We investigated the mechanism of ISO in reducing PD-L1 expression in CMT cells. Clustered, regularly interspaced short palindromic repeat-associated protein 9 (CRISPR/Cas9) was used to mediate
knockout in U27 cells. Then, monoclonal cells were screened and cultured. Nucleotide sequencing and expression of PD-L1 were detected. Additionally, we examined cell migration, invasion, and damage. Immunofluorescent staining of PD-L1 was examined in U27 cells. The signaling pathways were measured by Western blotting. Murine xenotransplantation models and murine immunocompetent allograft mammary tumor models were established to evaluate the effect of ISO therapy. Expression of Ki-67, caspase3, and PD-L1 were analyzed by immunohistochemistry. A pull-down assay was used to explore which proteins could bind to ISO. Canine EGFR protein was purified and used to detect whether it directly binds to ISO using a surface plasmon resonance assay. ISO inhibited the EGFR-STAT3-PD-L1 signaling pathway and blocked cancer growth, significantly increasing the survival rate of healthy cells. The cell membrane receptor EGFR was identified as a direct target of ISO. ISO could be exploited as an antineoplastic treatment of CMT by targeting EGFR to suppress PD-L1 expression.
Lung development is the result of complex interactions between four tissues: epithelium, mesenchyme, mesothelium and endothelium. We marked the lineages experiencing Notch1 activation in these four ...cellular compartments during lung development and complemented this analysis by comparing the cell fate choices made in the absence of RBPjκ, the essential DNA binding partner of all Notch receptors. In the mesenchyme, RBPjκ was required for the recruitment and specification of arterial vascular smooth muscle cells (vSMC) and for regulating mesothelial epithelial-mesenchymal transition (EMT), but no adverse affects were observed in mice lacking mesenchymal RBPjκ. We provide indirect evidence that this is due to vSMC rescue by endothelial-mesenchymal transition (EnMT). In the epithelium, we show that Notch1 activation was most probably induced by Foxj1-expressing cells, which suggests that Notch1-mediated lateral inhibition regulates the selection of Clara cells at the expense of ciliated cells. Unexpectedly, and in contrast to Pofut1-null epithelium, Hes1 expression was only marginally reduced in RBPjκ-null epithelium, with a corresponding minimal effect on pulmonary neuroendocrine cell fate selection. Collectively, the primary roles for canonical Notch signaling in lung development are in selection of Clara cell fate and in vSMC recruitment. These analyses suggest that the impact of γ-secretase inhibitors on branching in vitro reflect a non-cell autonomous contribution from endothelial or vSMC-derived signals.
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