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Bombyx mori nucleopolyhedrovirus (BmNPV) is a serious threat to sericulture. Nevertheless, no effective control strategy is currently available. The innate immunity of silkworm is critical in the antiviral process. Exploring its molecular mechanism provides theoretical support for the prevention and treatment of BmNPV. Insect hormone receptors play an essential role in regulating host immunity. We found a correlation between Bombyx mori ecdysone receptor B1 (BmEcR-B1) and BmNPV infection, whereas the underlying mechanism remains unclear. In this study, the expression patterns and sequence characteristics of BmEcR-B1 and its isoform, BmEcR-A, were initially analyzed. BmEcR-B1 was found to be more critical than BmEcR-A in silkworm development and responses to BmNPV. Moreover, RNAi and an overexpression in BmN cells showed BmEcR-B1 had antiviral effects in the presence of 20-hydroxyecdysone (20E); Otherwise, it had no antiviral activity. Furthermore, BmEcR-B1 was required for 20E-induced apoptosis, which significantly suppressed virus infection. Finally, feeding 20E had no significant negative impacts on larval growth and the cocoon shell, suggesting the regulation of this pathway has practical value in controlling BmNPV in sericulture. The findings of this study provide important theoretical support for understanding the mechanism of the silkworm innate immune system in response to BmNPV infection.

Agile Product Line Engineering (APLE), a relatively new approach combining the two successful methods of Agile Software Development (ASD) and Software Product Lines (SPLs), makes product lines more responsive to ever-changing customer needs or market changes. However, SPLs often fail to keep up with market demand due to high coordination costs, slow development processes, and long release cycles in the case of frequent changes in business requirements; in agile software projects, the lack of a unified specification for describing requirements leads to high coordination costs and inconvenient requirement management. Some studies in the literature have proposed optimized approaches to integrate ASD and SPLs, but they still have not covered all aspects of APLE’s characteristics, and software resource reuse is rarely considered in these approaches during product line development. In view of this, we propose a collaborative framework of agile product line engineering for software resource reuse, namely ScrumOntoSPL. The ScrumOntoSPL approach efficiently merges ASD and SPL based on the agile method Scrum, SPL architecture, and ontology technology. In ScrumOntoSPL, uniform requirement specification is constructed by utilizing ontology, and the Matching Requirement with Component (MRC) process is designed to match product new requirements and software resources stored in a resource pool. In addition, we evaluated the proposed framework and approach with CMMI. In the end, a case study of a software development tool called IMC-Tool based on ScrumOntoSPL for a universal Instrument Microcontroller Chip (IMC) is discussed. The IMC-Tool case illustrates that the ScrumOntoSPL has the advantages of dynamically managing demand changes, enhancing software resource reuse, reducing coordination costs, and reducing time to market.

Supplementary Materials and Figure Legends 1-2 from Inhibition of Growth and Metastasis of Human Hepatocellular Carcinoma by Antisense Oligonucleotide Targeting Signal Transducer and Activator of Transcription 3

Purpose: Hepatocellular carcinoma (HCC) is an aggressive malignancy and is a devastating clinical complication of chronic liver disease. Therapeutic options are limited mainly because the genetic and biochemical understanding of this disease remains fragmented. We intended to study the role of signal transducer and activator of transcription 3 (STAT3) aberrant signaling in HCC malignancy, and the therapeutic potential of inhibition of STAT3 expression for HCC.Experimental Design: A 2′-O-methoxyethylribose–modified phosphorothioate antisense oligonucleotide (ASO) was used to knock down STAT3 expression in different human HCC cell lines, including the highly metastatic HCCLM3 derived from orthotopic implantation and subsequent lung metastasis in athymic mice. The effects of STAT3 ASO treatment on HCC cells, metastasis, and animal survival following HCCLM3 orthotopic implantation were evaluated.Results: Specific suppression of phosphorylated STAT3 reduced its DNA-binding activity, inhibited the expression of vascular endothelial growth factor, survivin, matrix metalloproteinases 2 and 9, reduced cell proliferation and migratory potential, induced apoptosis in vitro, and inhibited intradermal angiogenesis and s.c. tumorigenesis upon injection in mice. In mice bearing orthotopically implanted HCCLM3, STAT3 inhibition following therapeutic treatment with STAT3 ASO reduced circulating vascular endothelial growth factor and basic fibroblast growth factor, decreased intratumor CD34-positive microvessel density, intrahepatic and intraperitoneal transmission, and lung metastasis. HCC tumor volume and weight were reduced and the survival time of mice bearing orthotopically xenografted HCC was approximately doubled in STAT3 ASO–treated mice (P < 0.05).Conclusions: Constitutively activated STAT3 is essential for the growth, survival, and metastasis of HCC, suggesting that STAT3-targeted therapy may have utility for HCC.

Supplementary Figures 1-2 from Inhibition of Growth and Metastasis of Human Hepatocellular Carcinoma by Antisense Oligonucleotide Targeting Signal Transducer and Activator of Transcription 3

In recent years, the tourism industry in traditional villages has been developing rapidly due to the national call to vigorously advocate for and promote traditional culture, but there are plenty of problems and challenges facing the protection and development of traditional villages. The GPS action tracking method was adopted in this study to investigate the trajectory of tourists in typical traditional villages of Huizhou and to screen out different spatial sites with different characteristics based on the kernel density analysis. Thereby, people’s behavior in different spatial sites were analyzed in depth using the method of behavior observation, and ultimately, the relevance between the spatial environment of traditional villages, the characteristics of tourists’ actions, and their staying preferences were discussed, and hence an improvement strategy of spatial optimization was put forward accordingly. The research shows that, in Huizhou traditional villages, different scales and forms of space will affect tourists’ tour paths; the unreasonable distribution of commercial formats leads to the uneven distribution of village vitality; and traditional elements and landscape facilities are more likely to cause tourists to demonstrate a variety of behaviors. These findings provide (1) a basis for further understanding the spatial characteristics of traditional villages in Huizhou; (2) a basis for the spatial optimization of traditional villages; and (3) a new research perspective and feasible technical route for the protection, renewal, and sustainable development of traditional villages in other regions.

Spermatogenesis is a cyclical process in which different generations of spermatids undergo a series of developmental steps at a fixed time and finally produce spermatids. Here, we report that overexpression of PD-L1 (B7 homolog1) in the testis causes sperm developmental disorders and infertility in male mice, with severe malformation and sloughing during spermatid development, characterized by disorganized and collapsed seminiferous epithelium structure. PD-L1 needs to be simultaneously expressed on Sertoli cells and spermatogonia to cause spermatogenesis failure. After that, we excluded the influence of factors such as the PD-L1 receptor and humoral regulation, confirming that PD-L1 has an intrinsic function to interact with PD-L1. Studies have shown that PD-L1 not only serves as a ligand but also plays a receptor-like role in signal transduction. PD-L1 interacts with PD-L1 to affect the adhesive function of germ cells, causing malformation and spermatid sloughing. Taken together, these results indicate that PD-L1 can interact with PD-L1 to cause germ cell detachment and male infertility.

With the continuous development of mobile Internet and educational technology, the deep integration of education and Internet has a great impact on the education concept and teaching mode. The mixed teaching based on Rain Classroom is the specific application of new educational technology in the teaching of Internet plus education. Most of the students in ethnic universities come from the central and western ethnic regions. In addition, the evaluation of blended classroom teaching reform effect is looked as the classical multiple attribute decision making (MADM). We extend the dual MSM (DMSM) operator with fuzzy number intuitionistic fuzzy numbers (FNIFNs) to build the fuzzy number intuitionistic fuzzy dual MSM (FNIFDMSM) operator and fuzzy number intuitionistic fuzzy weighted DMSM (FNIFWDMSM) equation in this study. A few MADM operators are built with FNIFWDMSM operator. Finally, taking blended classroom teaching reform effect evaluation as an useful example, this paper illustrates the depicted approach.

CIPK protein family is a key protein family in Ca

Both traditional teaching and online teaching advocate individualized education. One of the difficulties on exploring possible improvements of instructional design is the challenging process of data collection. Existing research mainly focuses on the exam score of students but pays little attention to students' daily practice. As an effective method to handle time-series dataset, the generalized estimating equations (GEE) have not been used in this research field. Considering above issues, we first propose an experimental paradigm of programming performance analysis based on the performance record of students’ daily practice-exam and finish collecting a complete time-series dataset in one semester, including students’ individual attributes, learning behavior, and learning performance. Then, we propose an approach that analyzes practice-exam time-series dataset based on GEE to study the influence of individual attributes and learning behavior on learning performance. It is the first time to apply the GEE method for ordinal multinomial responses in this research field, by which we conclude several results that gender or major does have a certain difference on the programming learning. The longer the answer time and the less the cost time, the better the students' performance. Regardless of gender, students tend to cram for the exam and perform a little worse in the daily exercise. Finally, targeting at two important individual attributes, we give corresponding teaching mode decisions that university should teach students programming by major and teacher should give different teaching methods to students of different genders at different time points.

In this work, a new type of Au-tetrahedral DNA nanostructure (Au-TDN) was originally proposed and successfully applied in an electrochemiluminescence aptasensor to detect organophosphorus pesticides (Ops).

As multifunctional luminescence sensor, EU MOF has good thermal stability and water stability. It is used for the detection of Fe3+, Cr2O72−, CrO42− and aspartic acid in water system with low detection limit. And it has good recycling performance.

The massive use of organophosphorus pesticides (OPs) poses a great threat to food safety, human health and environmental protection. As there are many kinds of pesticides, their detection is facing a severe challenge. The simultaneous detection of multiple organophosphorus pesticides in one test is a problem to be solved at present. In this paper, a time-resolved fluorescent immunochromatographic (TRFIA) strip is prepared by using broad-specificity antibodies (Abs) of OPs as the recognition element. Abs were connected to europium oxide latex microspheres using sheep anti-mouse antibodies (SaMIgG) to form an indirect probe. This strategy could effectively realize signal amplification, and could save the amount and protect the activity of Abs. After the detection, the color change of the test line (T-line) was observed to make qualitative judgment under UV-light (365 nm). Then, the images of the positive sample were analyzed by using ImageJ to complete the quantitative detection. Under optimal construction and operating conditions, the limit of detection of the strip could reach 0.53 ng g

Persistent luminescence nanoparticles (PLNPs) possess advantages for high-sensitivity bioimaging and continuous photodynamic therapy (PDT) because they can emit persistent luminescence (PerL) after excitation ceases. However, PLNPs are limited to single-wavelength emission, which can only efficiently realize one of the functions of bioimaging or PDT. In addition, most PLNPs are excited by shallow tissue penetrating excitation light, which makes it difficult to achieve repeatable

In this work, by the introduction of a new kernel function composed of exponent functions with several parameters, and using the method of weight coefficient, Hermite-Hadamard’s inequality, and some other techniques of real analysis, a more accurate half-discrete Hilbert-type inequality including both the homogeneous and non-homogeneous cases is established. Furthermore, by introducing the Bernoulli number and the rational fraction expansion of tangent function, some special and interesting Hilbert-type inequalities and their equivalent hardy-type inequalities are presented at the end of the paper.

Background：Scribble, a master scaffold in apical-basal polarity, proliferation and epithelial integrity. Current knowledge about the biological function of Scribble in the colonic epithelial plasticity/regeneration during intestinal inflammation is limited. Here, we explore the unexpected role of Scribble in IBD. Results：We showed that Scribble level are decreased in IBD patients and mice with DSS-induced colitis. Our study suggested that ScribΔIEC mice develops severe acute colitis by disrupting epithelial barrier integrity and impairing the function of crypt stem cells. Here, we confirmed that Scribble KO may contribute to the dysregulated autophagy level due to the deletion of Atg16L1, and led to an accumulation of mitochondrial ROS both in intestinal stem cells and epithelial cells. Mechanistically, Scribble suppressed the process of autophagy by modulating the stability of caspase-dependent degradation of Atg16L1 by directly interacting with Atg16L1 in a LRR domain-dependent manner in IECs. Moreover, when ScribΔIEC organoids were treated with autophagy activator Rapa, the ROS signal in the organoids was significantly reduced, which indicates that the specific association of Scribble and Atg16L1 are crucial signaling molecules in oxidative stress response of intestinal inflammation. In addition, further study indicates that dietary sphingomyelin alleviates DSS-induced colitis by increase the expression of Scribble, which suggests that Scribble may be the critical marker of IBD. Conclusions：Our study firstly shows that Scribble deficiency maybe associated with the dysregulated autophagy and impaired maintenance of colonic stemness, and it may be a target for diagnosis and treatment of inflammatory bowel disease.