Search

Under the background of "Internet +", the development mode of enterprises has gradually moved from internalization to socialization, and the interaction between enterprises and customers has become more frequent. Under the background of industrial integration, the boundaries of enterprises have gradually disappeared, and cross-border operations have become the norm. As a new strategic resource, the Internet has been widely integrated into the economic and social system, promoting industrial restructuring and business model reform. The Internet has changed the transaction process of traditional commerce, connecting purchase and sale information, products and services, and providing conditions for the innovation of business models. This paper points out that value is the core of business model innovation through the relevant theoretical research of business model, analyzes the components of business model from the perspective of value, and proposes the types of business model innovation based on value. Based on the background of Internet development and precise marketing model, this paper analyzes the innovation path of business model.

The evaluation of overall thermal comfort in non-uniform thermal environments has not been fully clarified; it was therefore studied in this paper. For this aim, a series of experiments were conducted under non-uniform thermal environments with local cooling, where subjects’ thermal responses were surveyed by questionnaires. The correlations between the overall thermal comfort, the overall thermal sensation and the local thermal comfort were explored under both steady and unsteady states. As well, the relationship between the overall thermal comfort and the local thermal comfort was examined under steady-state conditions. The results indicated that the overall thermal comfort was dependent on the overall thermal sensation and also on the local thermal comfort at the body parts exposed to local cooling, whether in steady or transient states. Considering the two factors, the overall thermal comfort models were proposed for steady and unsteady states. Also, the overall thermal comfort was approximated by the average of the maximum and minimum local thermal comfort under steady states. Another overall thermal comfort model was therefore proposed. The two overall thermal comfort models for the steady state were verified by experimental results.

The purpose of this study was to detect the missing heritability of patients with KIF11-related retinopathy and to describe their clinical and genetic characteristics. We enrolled 10 individuals from 7 unrelated families harboring a pathogenic monoallelic variant in KIF11. All subjects underwent ophthalmic assessment and extraocular phenotype evaluations, as well as comprehensive molecular genetic analyses using next-generation sequencing. Minigene assays were performed to observe the effects of one novel deep intron variant (DIV) and one novel synonymous variant on pre-mRNA splicing. We detected 6 novel different disease-causing variants of KIF11 in the seven pedigrees. Co-segregation analysis and ultra-deep sequencing results indicated that 5 variants arose de novo in 5 families (71%). Functional validation revealed that the synonymous variant leads to an exon skip, while the DIV causes a pseudoexon (PE) inclusion. The patients presented with high variations in their phenotype, and two families exhibited incomplete penetrance. Ocular manifestations and characteristic facial features were observed in all patients, as well as microcephaly in seven patients, intellectual disability in five patients, and lymphedema in one patient. The key retinal features for KIF11-related retinopathy were retinal folds, tractional retinal detachment, and chorioretinal dysplasia. All seven probands had more severe visual detects than other affected family members. Our findings widen the genetic spectrum of KIF11 variants. DIV explained rare unresolved cases with KIF11-related retinopathy. The patients displayed a variable phenotype expressivity and incomplete penetrance, indicating the importance of genetic analysis for patients with KIF11-related retinopathy.

To identify the missing heritability of patients with Wolfram syndrome 1 (WFS1) in a Chinese cohort and to report their clinical and genetic features.We recruited 24 unrelated patients with suspected WFS1 who carried at least one variant in WFS1. All patients underwent ophthalmic examinations and comprehensive molecular genetic analyses, including Sanger-DNA sequencing of WFS1 and next-generation sequencing of the whole WFS1 sequence.We identified 38 distinct pathogenic variants of WFS1 in the 24 probands, comprising 23 patients with biallelic variants and one patient with a monoallelic variant. Sanger-DNA sequencing of WFS1 initially detected 35 variants, and subsequent whole genome sequencing revealed three missing variants: one novel deep intronic variant (DIV), one copy number variant (CNV), and one variant in the promoter region. Minigene assays showed that the DIV activated cryptic splice sites, leading to the insertion of pseudoexons. Optic atrophy was observed in all patients, and diabetes mellitus (DM) was revealed in 21 patients (91.3%), hearing loss in nine patients (39.1%), renal tract abnormalities in nine patients (39.1%), and diabetes insipidus in five patients (21.7%). The mean onset age for DM was significantly younger in the patients with biallelic null variants than in the patients with biallelic missense variants.Our results extend the pathogenic variant spectrum of WFS1. DIVs and CNVs explained rare unresolved Chinese cases with WFS1. The patients showed a wide and variable clinical spectrum, supporting the importance of genetic analysis for patients with atypical WFS1.

We report for the first time the use of experimental electron density (ED) as training data for the generation of drug-like three-dimensional molecules based on the structure of a target protein pocket. Similar to a structural biologist building molecules based on their ED, our model functions with two main components: a generative adversarial network (GAN) to generate the ligand ED in the input pocket and an ED interpretation module for molecule generation. The model was tested on three targets including kinase (HPK1), protease (Covid19-3CL), and nuclear receptor (VDR), and evaluated with a reference dataset composed of over 8,000 compounds that have their activities reported in the literature. The evaluation examined the chemical validity, chemical space distribution-based diversity, and similarity with reference active compounds concerning the molecular structure and pocket-binding mode. Our model can reproduce classical active compounds and can also generate novel molecules with similar binding modes as active compounds, making it a promising tool for library generation supporting high-throughput virtual screening. Our model is available as an online service to academic users via https://edmg.stonewise.cn/#/create.

Skin temperature is an important physiological parameter that reflects human thermal sensation. However, it is uncertain whether it can evaluate overall thermal sensation in non-uniform thermal environments. This study aims to explore the feasibility of using skin temperature to predict overall thermal sensation in non-uniform environments. The overall thermal sensation votes and skin temperatures were obtained in a non-uniform thermal environment with local cooling on the chest in a climate chamber. The predictive power of the representative skin temperature (RST) estimated from five different methods was examined by analysing its sensitivity and the correlation between the overall thermal sensation and the RST. The RSTs estimated from the 7-point method with the measurement site of trunk assigned on the chest and the 1-point method with a measurement site at the centre of the chest had high sensitivity and coefficients of determination. They could reflect overall thermal sensation in the non-uniform environments with local cooling on the chest. The results imply that skin temperature could be used to evaluate overall thermal sensation in non-uniform environments. The overall thermal sensation in non-uniform environments can be evaluated by the RST if, when determining the RST, the measuring site exposed to local cooling is involved and given a high weight.

This paper proposes the TransE-CBA (TransE Based On Improved Bernoulli And Adam) model, an improved TransE model. We used an improved Bernoulli distribution sampling method to improve the accuracy of negative samples, and used the Adam algorithm to update the gradient to improve the performance of the algorithm. Experiment result shows that, on the FB13 and WN18 datasets, the TransE-CBA model has a lower average ranking score (MeanRank) than TransE as a whole, and the proportion of the top ten triples (HITS@10) Higher, better sorting effect.

It is reported that Ischemia and reperfusion damage (I/R damage) can lead to retinal ganglion cell (RGC) death and neurodegeneration, which in turn can lead to irreversible vision loss. In this study, we sought to understand the neuroprotective effect of resveratrol, the important activator of sirtuin1 (SIRT1), on RGC survival in I/R damage model and the molecular mechanism that mediate this effect. Our results show that resveratrol could reverse axonal swelling, holes, and the chaos of the nucleus in axons of RGCs caused by I/R. At the same time, resveratrol could also reverse the activation of retinal astrocytes and the loss of RGCs caused by I/R. Resveratrol increased the expression of SIRT1 while decreasing the phosphorylation of N-terminal kinase (JNK). SP600125(JNK inhibitor) decreased the phosphorylation of JNK while increasing the expression of SIRT1, indicating that SIRT1 and JNK can interact with each other. Simultaneous administration of resveratrol and sirtinol (SIRT1 inhibitor) neither increased the expression of SIRT1 nor decreased the phosphorylation of JNK, indicating that resveratrol affects the phosphorylation of JNK by SIRT1. In total, our research shows that resveratrol treatment significantly reduces apoptosis and axonal degeneration of RGCs, and this protection is partly mediated through the SIRT1-JNK pathway.