Analysis of the Effect of Co-Branding of “Electronic Games + Museum” Components

With the development of the digital era, Electronic Games, as an emerging form of entertainment, have become an indispensable part of people's lives. And the museum is also an important place for people to know history and culture. In order to attract more young people to visit museums, the integration of Electronic Games and museums has become a trend. Therefore, it has become a new marketing strategy to jointly launch a "Electronic Games + museum" component brand. Based on this, this paper analyses the branding effect of a game and a museum for reference

Tumor-Derived Exosomal Protein Tyrosine Phosphatase Receptor Type O Polarizes Macrophage to Suppress Breast Tumor Cell Invasion and Migration

Tumor-derived exosomes, containing multiple nucleic acids and proteins, have been implicated to participate in the interaction between tumor cells and microenvironment. However, the functional involvement of phosphatases in tumor-derived exosomes is not fully understood. We and others previously demonstrated that protein tyrosine phosphatase receptor type O (PTPRO) acts as a tumor suppressor in multiple cancer types. In addition, its role in tumor immune microenvironment remains elusive. Bioinformatical analyses revealed that PTPRO was closely associated with immune infiltration, and positively correlated to M1-like macrophages, but negatively correlated to M2-like macrophages in breast cancer tissues. Co-cultured with PTPRO-overexpressing breast cancer cells increased the proportion of M1-like tumor-associated macrophages (TAMs) while decreased that of M2-like TAMs. Further, we observed that tumor-derived exosomal PTPRO induced M1-like macrophage polarization, and regulated the corresponding functional phenotypes. Moreover, tumor cell-derived exosomal PTPRO inhibited breast cancer cell invasion and migration, and inactivated STAT signaling in macrophages. Our data suggested that exosomal PTPRO inhibited breast cancer invasion and migration by modulating macrophage polarization. Anti-tumoral effect of exosomal PTPRO was mediated by inactivating STAT family in macrophages. These findings highlight a novel mechanism of tumor invasion regulated by tumor-derived exosomal tyrosine phosphatase, which is of translational potential for the therapeutic strategy against breast cancer

Normal-weight central obesity: implications for diabetes mellitus

BackgroundCurrent guidelines for obesity prevention and control focus on body mass index (BMI) and rarely address central obesity. Few studies have been conducted on the association between normal-weight central obesity and the risk of diabetes mellitus (DM).Methods26,825 participants from the National Health and Nutrition Examination Survey (NHANES) were included in our study. A weighted multivariate logistic regression model was used to analyze the relationship between different obesity patterns and the risk of DM.ResultsOur results suggest that normal-weight central obesity is associated with an increased risk of DM (OR: 2.37, 95% CI: 1.75–3.23) compared with normal-weight participants without central obesity. When stratified by sex, men with normal-weight central obesity, obesity and central obesity were found to have a similar risk of DM (OR: 3.83, 95% CI: 2.10–5.97; OR: 4.20, 95% CI: 3.48–5.08, respectively) and a higher risk than all other types of obesity, including men who were overweight with no central obesity (OR: 1.21, 95% CI: 0.96–1.51) and obese with no central obesity (OR: 0.53, 95% CI: 0.30–0.91).ConclusionOur results highlight the need for more attention in people with central obesity, even if they have a normal BMI

Selection, characterization and application of new RNA HIV gp 120 aptamers for facile delivery of Dicer substrate siRNAs into HIV infected cells

The envelope glycoprotein of human immunodeficiency virus (HIV) consists of an exterior glycoprotein (gp120) and a trans-membrane domain (gp41) and has an important role in viral entry into cells. HIV-1 entry has been validated as a clinically relevant anti-viral strategy for drug discovery. In the present work, several 2′-F substituted RNA aptamers that bind to the HIV-1BaL gp120 protein with nanomole affinity were isolated from a RNA library by the SELEX (Systematic Evolution of Ligands by EXponential enrichment) procedure. From two of these aptamers we created a series of new dual inhibitory function anti-gp120 aptamer–siRNA chimeras. The aptamers and aptamer–siRNA chimeras specifically bind to and are internalized into cells expressing HIV gp160. The Dicer-substrate siRNA delivered by the aptamers is functionally processed by Dicer, resulting in specific inhibition of HIV-1 replication and infectivity in cultured CEM T-cells and primary blood mononuclear cells (PBMCs). Moreover, we have introduced a ‘sticky’ sequence onto a chemically synthesized aptamer which facilitates attachment of the Dicer substrate siRNAs for potential multiplexing. Our results provide a set of novel inhibitory agents for blocking HIV replication and further validate the use of aptamers for delivery of Dicer substrate siRNAs

Novel loci and pathways significantly associated with longevity

Only two genome-wide significant loci associated with longevity have been identified so far, probably because of insufficient sample sizes of centenarians, whose genomes may harbor genetic variants associated with health and longevity. Here we report a genome-wide association study (GWAS) of Han Chinese with a sample size 2.7 times the largest previously published GWAS on centenarians. We identified 11 independent loci associated with longevity replicated in Southern-Northern regions of China, including two novel loci (rs2069837-IL6; rs2440012-ANKRD20A9P) with genome-wide significance and the rest with suggestive significance (P < 3.65 × 10(−5)). Eight independent SNPs overlapped across Han Chinese, European and U.S. populations, and APOE and 5q33.3 were replicated as longevity loci. Integrated analysis indicates four pathways (starch, sucrose and xenobiotic metabolism; immune response and inflammation; MAPK; calcium signaling) highly associated with longevity (P ≤ 0.006) in Han Chinese. The association with longevity of three of these four pathways (MAPK; immunity; calcium signaling) is supported by findings in other human cohorts. Our novel finding on the association of starch, sucrose and xenobiotic metabolism pathway with longevity is consistent with the previous results from Drosophilia. This study suggests protective mechanisms including immunity and nutrient metabolism and their interactions with environmental stress play key roles in human longevity

Novel loci and pathways significantly associated with longevity

Only two genome-wide significant loci associated with longevity have been identified so far, probably because of insufficient sample sizes of centenarians, whose genomes may harbor genetic variants associated with health and longevity. Here we report a genome-wide association study (GWAS) of Han Chinese with a sample size 2.7 times the largest previously published GWAS on centenarians. We identified 11 independent loci associated with longevity replicated in Southern-Northern regions of China, including two novel loci (rs2069837-IL6; rs2440012-ANKRD20A9P) with genome-wide significance and the rest with suggestive significance (P < 3.65 × 10⁻⁵). Eight independent SNPs overlapped across Han Chinese, European and U.S. populations, and APOE and 5q33.3 were replicated as longevity loci. Integrated analysis indicates four pathways (starch, sucrose and xenobiotic metabolism; immune response and inflammation; MAPK; calcium signaling) highly associated with longevity (P ≤ 0.006) in Han Chinese. The association with longevity of three of these four pathways (MAPK; immunity; calcium signaling) is supported by findings in other human cohorts. Our novel finding on the association of starch, sucrose and xenobiotic metabolism pathway with longevity is consistent with the previous results from Drosophilia. This study suggests protective mechanisms including immunity and nutrient metabolism and their interactions with environmental stress play key roles in human longevity.This is the publisher’s final pdf. The published article is copyrighted by the author(s) and published by Nature Publishing Group. The published article can be found at: http://www.nature.com/articles/srep2124

Effects of temporal and sequential stimulus presentations on logistic models from Sniff Olfactometer (SO) data

An unanswered question in smell perception is "How does the brain represent a stimulus intensity?". A recent study (Ni, et al. 2022) showed that when human subjects are presented with odorant puffs in a sequentially increasing or decreasing order, as would be the case in the usual "stair-case method" (e.g.,1-2-3 and then 4-5-6), the data produced questionable models with enormous confidences intervals (CIs). However, when the concentrations were interlaced (e.g.,1-3-5 and then 2-4-6), the models were more robust and reproducible with CIs < 10% of the stimulus intensity. One consequence of interlacing is that the difference between adjacent odorants is much greater. We hypothesized that the brain is "recording" the difference between adjacent pairs, rather than their difference from a fixed standard. If true, this may have two consequences; 1) A noticeable difference is required for the brain to relate two stimuli, and 2) The interstimulus difference (ISD) should affect the CIs. The experiments reported here were designed to determine the effect of varying the ISDs between stimuli on the CI of the resulting logistic functions. Six concentrations ranging across the subject's threshold were grouped in two triads, and the probability of perception of an odor was used to model a threshold function from the six concentrations. The ISDs were increased from 1 minute to 1 day, 2 days, and 7 days; however, increasing the ISDs did not affect the threshold's robustness, reproducibility, or CIs

A Low Creatinine to Body Weight Ratio Predicts the Incident Nonalcoholic Fatty Liver Disease in Nonelderly Chinese without Obesity and Dyslipidemia: A Retrospective Study

Aim. A lower ratio of creatinine to body weight (Cr/BW) is considered the independent risk factor for incident nonalcoholic fatty liver disease (NAFLD). However, the relationship between the Cr/BW ratio and NAFLD among individuals without obesity and dyslipidemia and how this relationship is impacted by age are still ambiguous. Therefore, we explored the effect of the Cr/BW ratio on the incident NAFLD among Chinese without obesity and dyslipidemia of different age groups. Methods. A total of 9756 participants without NAFLD at baseline were included and grouped by the median value (1.32) of the Cr/BW ratio. Then, a further analysis was stratified by age (60 years old). The primary outcome was new-onset NAFLD. Results. After a median follow-up of 2.76 years, 844 (8.7%) participants developed NAFLD. The elderly had a higher person-years incidence rate and cumulative incidence rate than the nonelderly. A high Cr/BW ratio showed a lower cumulative incidence compared to a low Cr/BW ratio for the whole population (P=0.039) and the nonelderly group (P=0.008). After being adjusted for multivariate variables, the lower Cr/BW ratio was the independent risk factor for incident NAFLD in the nonelderly (HR 0.718, 95% CI 0.548-0.942), instead of the elderly. Conclusions. The Cr/BW ratio has a negative relationship with incident NAFLD among nonobese Chinese without dyslipidemia before the age of 60

Whole Exome Sequencing Identified a Novel Heterozygous Mutation in HMBS Gene in a Chinese Patient With Acute Intermittent Porphyria With Rare Type of Mild Anemia

Acute intermittent porphyria (AIP) is a rare hereditary metabolic disease with an autosomal dominant mode of inheritance. Germline mutations of HMBS gene causes AIP. Mutation of HMBS gene results into the partial deficiency of the heme biosynthetic enzyme hydroxymethylbilane synthase. AIP is clinically manifested with abdominal pain, vomiting, and neurological complaints. Additionally, an extreme phenotypic heterogeneity has been reported in AIP patients with mutations in HMBS gene. Here, we investigated a Chinese patient with AIP. The proband is a 28-year-old Chinese male manifested with severe stomach ache, constipation, nausea and depression. Proband’s father and mother is normal. Proband’s blood sample was collected and genomic DNA was extracted. Whole exome sequencing and Sanger sequencing identified a heterozygous novel single nucleotide deletion (c.809delC) in exon 12 of HMBS gene in the proband. This mutation leads to frameshift followed by formation of a truncated (p.Ala270Valfs∗2) HMBS protein with 272 amino acids comparing with the wild type HMBS protein of 361 amino acids. This mutation has not been found in proband’s unaffected parents as well as in 100 healthy normal control. According to the variant interpretation guidelines of American College of Medical Genetics and Genomics (ACMG), this variant is classified as “likely pathogenic” variant. Our findings expand the mutational spectra of HMBS gene related AIP which are significant for screening and genetic diagnosis for AIP