Learning Attentive Pairwise Interaction for Fine-Grained Classification

Fine-grained classification is a challenging problem, due to subtle differences among highly-confused categories. Most approaches address this difficulty by learning discriminative representation of individual input image. On the other hand, humans can effectively identify contrastive clues by comparing image pairs. Inspired by this fact, this paper proposes a simple but effective Attentive Pairwise Interaction Network (API-Net), which can progressively recognize a pair of fine-grained images by interaction. Specifically, API-Net first learns a mutual feature vector to capture semantic differences in the input pair. It then compares this mutual vector with individual vectors to generate gates for each input image. These distinct gate vectors inherit mutual context on semantic differences, which allow API-Net to attentively capture contrastive clues by pairwise interaction between two images. Additionally, we train API-Net in an end-to-end manner with a score ranking regularization, which can further generalize API-Net by taking feature priorities into account. We conduct extensive experiments on five popular benchmarks in fine-grained classification. API-Net outperforms the recent SOTA methods, i.e., CUB-200-2011 (90.0%), Aircraft(93.9%), Stanford Cars (95.3%), Stanford Dogs (90.3%), and NABirds (88.1%).Comment: Accepted at AAAI-202

Relationship between occupational stress and job burnout among rural-to-urban migrant workers in Dongguan, China: a cross-sectional study

Objectives: In China, there have been an increasing number of migrant workers from rural to urban areas, and migrant workers have the highest incidence of occupational diseases. However, few studies have examined the impact of occupational stress on job burnout in these migrant workers. This study aimed to investigate the relationship between occupational stress and job burnout among migrant workers. Design: This study used a cross-sectional survey. Setting: This investigation was conducted in Dongguan city, Guangdong Province, China. Participants: 3806 migrant workers, aged 18–60 years, were randomly selected using multistage sampling procedures. Primary and secondary outcome measures: Multistage sampling procedures were used to examine demographic characteristics, behaviour customs and jobrelated data. Hierarchical linear regression and logistic regression models were constructed to explore the relationship between occupational stress and burnout. Results: Demographics, behaviour customs and jobrelated characteristics significantly affected on burnout. After adjusting for the control variable, a high level of emotional exhaustion was associated with high role overload, high role insufficiency, high role boundary, high physical environment, high psychological strain, high physical strain, low role ambiguity, low responsibility and low vocational strain. A high level of depersonalisation was associated with high role overload, high role ambiguity, high role boundary, high interpersonal strain, high recreation, low physical environment and low social support. A low level of personal accomplishment was associated with high role boundary, high role insufficiency, low responsibility, low social support, low physical environment, low self-care and low interpersonal strain. Compared to the personal resources, the job strain and personal strain were more likely to explain the burnout of rural-to-urban migrant workers in our study. Conclusions: The migrant workers have increased job burnouts in relation to occupational stress. Relieving occupational stress and maintaining an appropriate quantity and quality of work could be important measures for preventing job burnout among these workers

Epimorphin Regulates Bile Duct Formation via Effects on Mitosis Orientation in Rat Liver Epithelial Stem-Like Cells

Understanding how hepatic precursor cells can generate differentiated bile ducts is crucial for studies on epithelial morphogenesis and for development of cell therapies for hepatobiliary diseases. Epimorphin (EPM) is a key morphogen for duct morphogenesis in various epithelial organs. The role of EPM in bile duct formation (DF) from hepatic precursor cells, however, is not known. To address this issue, we used WB-F344 rat epithelial stem-like cells as model for bile duct formation. A micropattern and a uniaxial static stretch device was used to investigate the effects of EPM and stress fiber bundles on the mitosis orientation (MO) of WB cells. Immunohistochemistry of liver tissue sections demonstrated high EPM expression around bile ducts in vivo. In vitro, recombinant EPM selectively induced DF through upregulation of CK19 expression and suppression of HNF3α and HNF6, with no effects on other hepatocytic genes investigated. Our data provide evidence that EPM guides MO of WB-F344 cells via effects on stress fiber bundles and focal adhesion assembly, as supported by blockade EPM, β1 integrin, and F-actin assembly. These blockers can also inhibit EPM-induced DF. These results demonstrate a new biophysical action of EPM in bile duct formation, during which determination of MO plays a crucial role

Comprehensive analysis of the prognosis and immune effect of the oncogenic protein Four Jointed Box 1

BackgroundThe Four Jointed Box 1 (FJX1) gene has been implicated in the upregulation of various cancers, highlighting its crucial role in oncology and immunity. In order to better understand the biological function of FJX1 and identify new immunotherapy targets for cancer, we conducted a comprehensive analysis of this gene.MethodsWe analyzed the expression profiles and prognostic value of FJX1 using data from The Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression (GTEx). Copy number alterations (CNAs), mutations, and DNA methylation were analyzed through cBioPortal. The Immune Cell Abundance Identifier (ImmuCellAI) was used to examine the correlation between FJX1 expression and immune cell infiltration. The relationship between FJX1 expression and immune-related genes and immunosuppressive pathway-related genes was analyzed using The Tumor Immune Estimation Resource version 2 (TIMER2). Tumor mutational burden (TMB) and microsatellite instability (MSI) were obtained from TCGA pan-cancer data. The effect of immunotherapy and the IC50 were assessed using IMvigor210CoreBiologies and Genomics For Drug Sensitivity in Cancer (GDSC). Finally, we evaluated the impact of FJX1 on colon cancer cell proliferation and migration through in vitro functional experiments.ResultsOur study indicated that FJX1 expression was high in most cancers and was significantly associated with poor prognosis. High FJX1 expression was also linked to significant alterations in CNA, DNA methylation, TMB, and MSI. Positive correlations were found between FJX1 expression and tumor-associated macrophages (TAMs) and with immune-related genes such as TGFB1 and IL-10 and immunosuppressive pathway-related genes such as TGFB1 and WNT1. On the other hand, FJX1 expression showed a negative relationship with CD8+ T cells. Furthermore, high FJX1 expression led to reduced effectiveness of immunotherapy and drug resistance. In colon cancer cells, FJX1 knockdown was found to decrease cell proliferation and migration.ConclusionOur research findings demonstrate that FJX1 is a new prognostic factor with a significant role in tumor immunity. Our results highlight the importance of further exploring the potential of targeting FJX1 as a therapeutic strategy in cancer

Overcoming Drug Resistance in Colon Cancer by Aptamer-Mediated Targeted Co-Delivery of Drug and siRNA Using Grapefruit-Derived Nanovectors

Background/Aims: Multidrug resistance (MDR) is the most common cause of chemotherapy failure. Upregulation of P-glycoprotein (P-gp) is one of the main mechanisms underlying MDR. Methods: In this study, we developed a targeted drug and small interfering (si)RNA co-delivery system based on specific aptamer-conjugated grapefruit-derived nanovectors (GNVs) that we tested in MDR LoVo colon cancer cells. The internalization of nanovectors in cancer cells was tested by fluorescence microscopy and flow cytometry. The anti-cancer activity in vitro was determined by colony formation and cell apoptosis assays. The biodistribution of nanovectors was analyzed by live imaging and the anti-cancer activity in vivo was observed. Results: GNVs loaded with aptamer increased doxorubicin (Dox) accumulation in MDR LoVo cells, an effect that was abolished by pretreatment with DNase. The LA1 aptamer effectively promoted nanovector internalization into cells at 4°C and increased the targeted delivery of Dox to tumors. Constructs harboring Dox, LA1, and P-gp siRNA more effectively inhibited proliferation and enhanced apoptosis in cultured MDR LoVo cells while exhibiting more potent anti-tumor activity in vivo than free Dox or GNVs loaded with Dox alone or in conjunction with LA1, an effect that was associated with downregulation of P-gp expression. Conclusion: This GNV-based system may be an effective strategy for overcoming MDR in clinical settings

Spatial-temporal clustering of an outbreak of SARS-CoV-2 Delta VOC in Guangzhou, China in 2021

BackgroundIn May 2021, the SARS-CoV-2 Delta variant led to the first local outbreak in China in Guangzhou City. We explored the epidemiological characteristics and spatial-temporal clustering of this outbreak.MethodsBased on the 153 cases in the SARS-CoV-2 Delta variant outbreak, the Knox test was used to analyze the spatial-temporal clustering of the outbreak. We further explored the spatial-temporal clustering by gender and age groups, as well as compared the changes of clustering strength (S) value between the two outbreaks in Guangzhou.ResultsThe result of the Knox analysis showed that the areas at short distances and brief periods presented a relatively high risk. The strength of clustering of male-male pairs was higher. Age groups showed that clustering was concentrated in cases aged ≤ 18 years matched to 18–59 years and cases aged 60+ years. The strength of clustering of the outbreak declined after the implementation of public health measures. The change of strength of clustering at time intervals of 1–5 days decreased greater in 2021 (S = 129.19, change rate 38.87%) than that in 2020 (S = 83.81, change rate 30.02%).ConclusionsThe outbreak of SARS-CoV-2 Delta VOC in Guangzhou has obvious spatial-temporal clustering. The timely intervention measures are essential role to contain this outbreak of high transmission

Discovery of first-in-class inhibitors of ASH1L histone methyltransferase with anti-leukemic activity

ASH1L histone methyltransferase plays a crucial role in the pathogenesis of different diseases, including acute leukemia. While ASH1L represents an attractive drug target, developing ASH1L inhibitors is challenging, as the catalytic SET domain adapts an inactive conformation with autoinhibitory loop blocking the access to the active site. Here, by applying fragment-based screening followed by medicinal chemistry and a structure-based design, we developed first-in-class small molecule inhibitors of the ASH1L SET domain. The crystal structures of ASH1L-inhibitor complexes reveal compound binding to the autoinhibitory loop region in the SET domain. When tested in MLL leukemia models, our lead compound, AS-99, blocks cell proliferation, induces apoptosis and differentiation, downregulates MLL fusion target genes, and reduces the leukemia burden in vivo. This work validates the ASH1L SET domain as a druggable target and provides a chemical probe to further study the biological functions of ASH1L as well as to develop therapeutic agents

New genetic loci link adipose and insulin biology to body fat distribution.

Body fat distribution is a heritable trait and a well-established predictor of adverse metabolic outcomes, independent of overall adiposity. To increase our understanding of the genetic basis of body fat distribution and its molecular links to cardiometabolic traits, here we conduct genome-wide association meta-analyses of traits related to waist and hip circumferences in up to 224,459 individuals. We identify 49 loci (33 new) associated with waist-to-hip ratio adjusted for body mass index (BMI), and an additional 19 loci newly associated with related waist and hip circumference measures (P < 5 × 10(-8)). In total, 20 of the 49 waist-to-hip ratio adjusted for BMI loci show significant sexual dimorphism, 19 of which display a stronger effect in women. The identified loci were enriched for genes expressed in adipose tissue and for putative regulatory elements in adipocytes. Pathway analyses implicated adipogenesis, angiogenesis, transcriptional regulation and insulin resistance as processes affecting fat distribution, providing insight into potential pathophysiological mechanisms

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

Research on High-Temperature Evaluation Indexes and Performance of Qingchuan Rock-SBS Composite Modified Asphalt

The phenomenon of structural destabilization damage to asphalt pavement is becoming increasingly serious as a result of high temperatures and heavy traffic. Considering the advantages of Qingchuan rock asphalt (QRA) in its durability, high-temperature rutting resistance, and good compatibility with asphalt, it was proposed to compound rock asphalt with SBS to ameliorate the high-temperature performance of asphalt. In this study, DSR and BBR were used to determine the rheological properties of Qingchuan rock-modified asphalt (QRMA) and Qingchuan rock–SBS-modified asphalt (QRA-SBSMA), and the optimum blending amount of rock asphalt was determined based on the PG classification results. Secondly, four different structures of ‘30 mm AC-10 upper layer (70-A, QRMA, SBSMA, QRA-SBSMA) + 50 mm AC-16 lower layer (70-A)’ double-layer composite specimens were prepared. Multiple high-temperature performance evaluation indexes (G*/sinδ, Ds, rutting depth, micro-strain, Fn, modulus) were used to assess the improvement effect of QRA. Finally, using a 1/3 scale accelerated loading testing machine, we simulated high-temperature, water, and high-temperature coupled environments to assess the impact of high temperature and water on the performance of QRMA and QRA-SBSMA, respectively. The findings demonstrated that QRA can increase the PG classification of 70-A and SBSMA as well as its resistance to high-temperature deformation. Multi-index comprehensive evaluation methods were used to consummate the asphalt high-temperature evaluation system. The QRA-SBSMA had the smallest rutting depth and creep rate and the largest dynamic modulus, characterizing its ability to optimally resist high-temperature rutting and deformation