Identifying TNF and IL6 as potential hub genes and targeted drugs associated with scleritis: A bio-informative report

BackgroundScleritis is a serious inflammatory eye disease that can lead to blindness. The etiology and pathogenesis of scleritis remain unclear, and increasing evidence indicates that some specific genes and proteins are involved. This study aimed to identify pivotal genes and drug targets for scleritis, thus providing new directions for the treatment of this disease.MethodsWe screened candidate genes and proteins associated with scleritis by text-mining the PubMed database using Python, and assessed their functions by using the DAVID database. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were used to identify the functional enrichment of these genes and proteins. Then, the hub genes were identified with CytoHubba and assessed by protein-protein interaction (PPI) network analysis. And the serum from patients with active scleritis and healthy subjects were used for the validation of hub genes. Finally, the DGIdb database was used to predict targeted drugs for the hub genes for treating scleritis.ResultsA total of 56 genes and proteins were found to be linked to scleritis, and 65 significantly altered pathways were identified in the KEGG analysis (FDR < 0.05). Most of the top five pathways involved the categories “Rheumatoid arthritis,” “Inflammatory bowel disease”, “Type I diabetes mellitus,” and “Graft-versus-host disease”. TNF and IL6 were considered to be the top 2 hub genes through CytoHubba. Based on our serum samples, hub genes are expressed at high levels in active scleritis. Five scleritis-targeting drugs were found among 88 identified drugs.ConclusionsThis study provides key genes and drug targets related to scleritis through bioinformatics analysis. TNF and IL6 are considered key mediators and possible drug targets of scleritis. Five drug candidates may play an important role in the diagnosis and treatment of scleritis in the future, which is worthy of the further experimental and clinical study

Black-Box Dissector: Towards Erasing-based Hard-Label Model Stealing Attack

Previous studies have verified that the functionality of black-box models can be stolen with full probability outputs. However, under the more practical hard-label setting, we observe that existing methods suffer from catastrophic performance degradation. We argue this is due to the lack of rich information in the probability prediction and the overfitting caused by hard labels. To this end, we propose a novel hard-label model stealing method termed \emph{black-box dissector}, which consists of two erasing-based modules. One is a CAM-driven erasing strategy that is designed to increase the information capacity hidden in hard labels from the victim model. The other is a random-erasing-based self-knowledge distillation module that utilizes soft labels from the substitute model to mitigate overfitting. Extensive experiments on four widely-used datasets consistently demonstrate that our method outperforms state-of-the-art methods, with an improvement of at most $8.27\%$. We also validate the effectiveness and practical potential of our method on real-world APIs and defense methods. Furthermore, our method promotes other downstream tasks, \emph{i.e.}, transfer adversarial attacks

Association of brain morphology and phenotypic profile in patients with unruptured intracranial aneurysm

IntroductionStudies have found a varying degree of cognitive, psychosocial, and functional impairments in patients with unruptured intracranial aneurysms (UIAs), whereas the neural correlates underlying these impairments remain unknown.MethodsTo examine the brain morphological alterations and white matter lesions in patients with UIA, we performed a range of structural analyses to examine the brain morphological alterations in patients with UIA compared with healthy controls (HCs). Twenty-one patients with UIA and 23 HCs were prospectively enrolled into this study. Study assessment consisted of a brain magnetic resonance imaging (MRI) scan with high-resolution T1-weighted and T2-weighted imaging data, a Montreal Cognitive Assessment (MoCA), and laboratory tests including blood inflammatory markers and serum lipids. Brain MRI data were processed for cortical thickness, local gyrification index (LGI), volume and shape of subcortical nuclei, and white matter lesions.ResultsCompared to the HCs, patients with UIA showed no significant differences in cortical thickness but decreased LGI values in the right posterior cingulate cortex, retrosplenial cortex, cuneus, and lingual gyrus. In addition, decreased LGI values correlated with decreased MoCA score (r = 0.498, p = 0.021) and increased white matter lesion scores (r = −0.497, p = 0.022). The LGI values were correlated with laboratory values such as inflammatory markers and serum lipids. Patients with UIA also showed significant regional atrophy in bilateral thalami as compared to the HCs. Moreover, the LGI values were significantly correlated with thalamic volume in the HCs (r = 0.4728, p = 0.0227) but not in the patients with UIA (r = 0.11, p = 0.6350).DiscussionThe decreased cortical gyrification, increased white matter lesions, and regional thalamic atrophy in patients with UIA might be potential neural correlates of cognitive changes in UIA

Single cell atlas for 11 non-model mammals, reptiles and birds.

The availability of viral entry factors is a prerequisite for the cross-species transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Large-scale single-cell screening of animal cells could reveal the expression patterns of viral entry genes in different hosts. However, such exploration for SARS-CoV-2 remains limited. Here, we perform single-nucleus RNA sequencing for 11 non-model species, including pets (cat, dog, hamster, and lizard), livestock (goat and rabbit), poultry (duck and pigeon), and wildlife (pangolin, tiger, and deer), and investigated the co-expression of ACE2 and TMPRSS2. Furthermore, cross-species analysis of the lung cell atlas of the studied mammals, reptiles, and birds reveals core developmental programs, critical connectomes, and conserved regulatory circuits among these evolutionarily distant species. Overall, our work provides a compendium of gene expression profiles for non-model animals, which could be employed to identify potential SARS-CoV-2 target cells and putative zoonotic reservoirs

Fabrication of Polypyrrole-Decorated Tungsten Tailing Particles for Reinforcing Flame Retardancy and Ageing Resistance of Intumescent Fire-Resistant Coatings

Polypyrrole-decorated tungsten tailing particles (PPY-TTF) were prepared via the in situ polymerization of pyrrole in the presence of tungsten tailing particles (TTF), and then carefully characterized by Fourier transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM) and thermogravimetric analysis (TG) analyses. The effect of PPY-TTF on the flame retardancy, smoke suppression property and ageing resistance of intumescent fire-resistant coatings was investigated by a fire protection test, smoke density test and cone calorimeter test. The results show that PPY-TTF exerts excellent cooperative effect on enhancing the flame retardancy and smoke suppression properties of the intumescent fire-retardant coatings, which is ascribed to the formation of more cross-linking structures in the condense phase that enhance the compactness and thermal stability of intumescent char. The cooperative effect of PPY-TTF in the coatings depends on its content, and the coating containing 3 wt% PPY-TTF exhibits the best cooperative effect among the samples, showing a 10.7% reduction in mass loss and 35.4% reduction in flame-spread rating compared to that with 3% TTF. The accelerated ageing test shows that the presence of PPY-TTF greatly slows down the blistering and powdering phenomenon of the coatings, thus endowing the coating with the super durability of fire resistance and smoke suppression property. This work provides a new strategy for the resource utilization of tungsten tailing in the field of flame-retardant materials