Measurement of the Usage of Web Clips in Underground Economy

In this paper, we study the ecosystem of the abused Web Clips in underground economy. Through this study, we find the Web Clips is wildly used by perpetrators to penetrate iOS devices to gain profit. This work starts with 1,800 user complaint documents about cyber crimes over Web Clips. We firstly look into the ecosystem of abused Web Clips and point out the main participants and workflow. In addition, what is the Web Clips used for is demystified. Then the main participants, including creators, distributors, and operators are deeply studied based on our dataset. We try to reveal the prominent features of the illicit Web Clips and give some mitigation measures. Analysis reveals that 1) SSL certificate is overwhelmingly preferred for signing Web Clips instances compared with certificate issued by Apple. The wildly used SSL certificates can be aggregated into a limited group. 2) The content of the abused Web Clips falls into a few categories, `Gambling', `Fraud', and `Pornography' are among the top categories. 3) Instant messenger (IM) and live streaming platform are the most popular medium to trick victims into deploying the Web Clips. 4) The Web Clips are operated by a small amount of perpetrators, and the perpetrators tend to evade detection by taking technical approach, such as registering domain names through oversea domain name service provider, preferring easy-to-acquire new gTLD (global Top Level Domain), and deploying anti-crawler tricks. Our study gives hints on investigation of cyber crime over Web Clips, we hope that this work can help stakeholders to stay ahead of the threat

Case Report: HAVCR2 mutation-associated Hemophagocytic lymphohistiocytosis

Germline HAVCR2 mutation has been reported to be associated with subcutaneous panniculitis-like T-cell lymphoma (SPTCL) leading to Hemophagocytic lymphohistiocytosis (HLH). Several studies have indicated that HAVCR2 mutation can cause HLH even in the absence of lymphoma, though the exact mechanism remains unclear. In this article, we reported five cases of HAVCR2 mutation-associated HLH. Our analysis revealed an elevated level of IL-1RA in the serum of these patients. Furthermore, we investigated the potential mechanisms underlying HLH associated with HAVCR2 mutation based on changes in cytokine levels. Our findings suggest that HAVCR2 mutation may represent a distinct genetic defect underlying HLH, differing from traditional primary HLH

Different evasion strategies in multiple myeloma

Multiple myeloma is the second most common malignant hematologic malignancy which evolved different strategies for immune escape from the host immune surveillance and drug resistance, including uncontrolled proliferation of malignant plasma cells in the bone marrow, genetic mutations, or deletion of tumor antigens to escape from special targets and so. Therefore, it is a big challenge to efficiently treat multiple myeloma patients. Despite recent applications of immunomodulatory drugs (IMiDS), protease inhibitors (PI), targeted monoclonal antibodies (mAb), and even hematopoietic stem cell transplantation (HSCT), it remains hardly curable. Summarizing the possible evasion strategies can help design specific drugs for multiple myeloma treatment. This review aims to provide an integrative overview of the intrinsic and extrinsic evasion mechanisms as well as recently discovered microbiota utilized by multiple myeloma for immune evasion and drug resistance, hopefully providing a theoretical basis for the rational design of specific immunotherapies or drug combinations to prevent the uncontrolled proliferation of MM, overcome drug resistance and improve patient survival

Causal relationship between the immune cells and ankylosing spondylitis: univariable, bidirectional, and multivariable Mendelian randomization

BackgroundAnkylosing spondylitis (AS) is an autoimmune disease that affects millions of individuals. Immune cells have been recognized as having a crucial role in the pathogenesis of AS. However, their relationship has not been fully explored.MethodsWe chose to employ Mendelian randomization (MR) to investigate the potential correlation between immune cells and AS. We sourced the data on immune cells from the latest genome-wide association studies (GWASs). We obtained data on AS from the FinnGen consortium. Our comprehensive univariable MR analysis covered 731 immune cells to explore its potential causal relationship with AS. The primary analysis method was inverse-variance weighted (IVW). Additionally, we used Cochran’s Q test and the MR-Egger intercept test to assess the presence of pleiotropy and heterogeneity. We examined whether our results could be influenced by individual single-nucleotide polymorphisms (SNPs) using the leave-one-out test. We conducted a bidirectional MR to investigate the reverse relationship. We also applied multivariable MR to decrease the potential influence between the immune cells.ResultsOverall, our univariable MR analysis revealed eight immune cells associated with AS. Among these, four immune cells contributed to an increased risk of AS, while four immune cells were identified as protective factors for AS. However, the Bonferroni test confirmed only one risk factor and one protective factor with a significance level of p < 6.84E−05. CD8 on effector memory CD8+ T cell could increase the risk of AS (p: 1.2302E−05, OR: 2.9871, 95%CI: 1.8289–4.8786). HLA DR on CD33dim HLA DR+ CD11b+ could decrease the risk of AS (p: 1.2301E−06, OR: 0.5446, 95%CI: 0.4260–0.6962). We also identified a bidirectional relationship between CD4 on CD39+ activated CD4 regulatory T cells and AS utilizing the bidirectional MR. To address potential confounding among immune cells, we employed multivariable MR analysis, which revealed that only one immune cell had an independent effect on AS. HLA DR on CD33dim HLA DR+ CD11b+ could decrease the risk of AS (p: 2.113E−06, OR: 0.0.5423, 95%CI: 0.4210–0.6983). Our findings were consistently stable and reliable.ConclusionsOur findings indicated a potential link between immune cells and AS, which could provide a new idea for future research. Nevertheless, the specific underlying mechanisms require further exploration

Factors Underlying Spatiotemporal Variations in Atmospheric PM2.5 Concentrations in Zhejiang Province, China

Fine particulate matter in the lower atmosphere (PM2.5) continues to be a major public health problem globally. Identifying the key contributors to PM2.5 pollution is important in monitoring and managing atmospheric quality, for example, in controlling haze. Previous research has been aimed at quantifying the relationship between PM2.5 values and their underlying factors, but the spatial and temporal dynamics of these factors are not well understood. Based on random forest and Shapley additive explanation (SHAP) algorithms, this study analyses the spatiotemporal variations in selected key factors influencing PM2.5 in Zhejiang Province, China, for the period 2000–2019. The results indicate that, while factors influencing PM2.5 varied significantly during the period studied, SHAP values suggest that there is consistency in their relative importance as follows: meteorological factors (e.g., atmospheric pressure) > socioeconomic factors (e.g., gross domestic product, GDP) > topography and land cover factors (e.g., elevation). The contribution of GDP and transportation factors initially increased but has declined in the recent past, indicating that economic and infrastructural development does not necessarily result in increased PM2.5 concentrations. Vegetation productivity, as indicated by changes in NDVI, is demonstrated to have become more important in improving air quality, and the area of the province over which it constrains PM2.5 concentrations has increased between 2000 and 2019. Mapping of SHAP values suggests that, although the relative importance of industrial emissions has declined during the period studied, the actual area positively impacted by such emissions has actually increased. Despite developments in government policy, greater efforts to conserve energy and reduce emissions are still needed. The study further demonstrates that the combination of random forest and SHAP methods provides a valuable means to identify regional differences in key factors affecting atmospheric PM2.5 values and offers a reliable reference for pollution control strategies

Knowledge atlas of antibody-drug conjugates on CiteSpace and clinical trial visualization analysis

ObjectiveAntibody-drugs conjugates (ADCs) are novel drugs with highly targeted and tumor-killing abilities and developing rapidly. This study aimed to evaluate drug discovery and clinical trials of and explore the hotspots and frontiers from 2012 to 2022 using bibliometric methods.MethodsPublications on ADCs were retrieved between 2012 and 2022 from Web of Science (WoS) and analyzed with CiteSpace 6.1.R2 software for the time, region, journals, institutions, etc. Clinical trials were downloaded from clinical trial.org and visualized with Excel software.ResultsA total of 696 publications were obtained and 187 drug trials were retrieved. Since 2012, research on ADCs has increased year by year. Since 2020, ADC-related research has increased dramatically, with the number of relevant annual publications exceeding 100 for the first time. The United States is the most authoritative and superior country and region in the field of ADCs. The University of Texas MD Anderson Cancer Center is the most authoritative institution in this field. Research on ADCs includes two clinical trials and one review, which are the most influential references. Clinical trials of ADCs are currently focused on phase I and phase II. Comprehensive statistics and analysis of the published literature and clinical trials in the field of ADCs, have shown that the most studied drug is brentuximab vedotin (BV), the most popular target is human epidermal growth factor receptor 2 (HER2), and breast cancer may become the main trend and hotspot for ADCs indications in recent years.ConclusionAntibody-drug conjugates have become the focus of targeted therapies in the field of oncology. The innovation of technology and combination application strategy will become the main trend and hotspots in the future

Amiloride Enhances Antigen Specific CTL by Faciliting HBV DNA Vaccine Entry into Cells

The induction of relatively weak immunity by DNA vaccines in humans can be largely attributed to the low efficiency of transduction of somatic cells. Although formulation with liposomes has been shown to enhance DNA transduction of cultured cells, little, if any, effect is observed on the transduction of somatic tissues and cells. To improve the rate of transduction, DNA vaccine delivery by gene gun and the recently developed electroporation techniques have been employed. We report here that to circumvent requirement for such equipment, amiloride, a drug that is prescribed for hypertension treatment, can accelerate plasmid entry into antigen presenting cells (APCs) both in vitro and in vivo. The combination induced APCs more dramatically in both maturation and cytokine secretion. Amiloride enhanced development of full CD8 cytolytic function including induction of high levels of antigen specific CTL and expression of IFN-γ+perforin+granzymeB+ in CD8+ T cells. Thus, amiloride is a facilitator for DNA transduction into host cells which in turn enhances the efficiency of the immune responses

Environmental regulation, land use efficiency and industrial structure upgrading: Test analysis based on spatial durbin model and threshold effect

Environmental regulation promotes industrial structure change and regional economic transformation through land use adjustment, which gets a new way to explore the path of reforming traditional industrialization and urbanization. Based on the panel data of 128 prefecture-level cities in China 's Yangtze River Economic Belt from 2000 to 2020, this paper uses the spatial Dubin model to analyze the impact of environmental regulation and land use efficiency on the upgrading of industrial structure, and sets the panel threshold model to examine the impact of environmental regulation on the upgrading of industrial structure by affecting land use efficiency. The results show that formal environmental regulation has a significant positive spatial effect on the rationalization and upgrading of industrial structure, which are 0.1734 and 0.2854 respectively. Informal environmental regulation has a negative spillover effect on neighboring provinces but not significant. Heterogeneous environmental regulation has obvious “double threshold effect” on industrial upgrading by affecting land use efficiency. When the threshold of environmental regulation intensity is 0.0315–0.0886, environmental regulation still inhibits land use efficiency and industrial structure upgrading. When the threshold value is greater than 0.0886, environmental regulation has a positive impact on land use efficiency but not significant. With the intensity of environmental regulation from weak to strong, it will produce a double threshold effect of “strong inhibition-weak inhibition-interaction promotion” on the upgrading of manufacturing structure through the adjustment of land use efficiency