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BackgroundIn secondary spinal cord injury (SCI), the immune microenvironment of the injured spinal cord plays an important role in spinal regeneration. Among the immune microenvironment components, macrophages/microglia play a dual role of pro-inflammation and anti-inflammation in the subacute stage of SCI. Therefore, discovering the immune hub genes and targeted therapeutic drugs of macrophages/microglia after SCI has crucial implications in neuroregeneration. This study aimed to identify immune hub genes and targeted therapeutic drugs for the subacute phase of SCI.MethodsBulk RNA sequencing (bulk-RNA seq) datasets (GSE5296 and GSE47681) and single-cell RNA sequencing (scRNA-seq) dataset (GSE189070) were obtained from the Gene Expression Omnibus database. In the bulk RNA-seq, the R package ‘limma,’ ‘WGCNA,’ and ‘CIBERSORT’ were used to jointly screen key immune genes. Subsequently, the R package ‘Seurat’ and the R package ‘celldex’ were used to divide and annotate the cell clusters, respectively. After using the Autodock software to dock immune hub genes and drugs that may be combined, the effectiveness of the drug was verified using an in vivo experiment with the T9 SCI mouse model.ResultsIn the bulk-RNA seq, B2m, Itgb5, and Vav1 were identified as immune hub genes. Ten cell clusters were identified in scRNA-seq, and B2m and Itgb5 were mainly located in the microglia, while Vav1 was mainly located in macrophages. Molecular docking results showed that the proteins corresponding to these immune genes could accurately bind to decitabine. In decitabine-treated mice, the pro-inflammatory factor (TNF-α, IL-1β) levels were decreased while anti-inflammatory factor (IL-4, IL-10) levels were increased at 2 weeks post-SCI, and macrophages/microglia transformed from M1 to M2. At 6 weeks post-SCI, the neurological function score and electromyography of the decitabine treatment group were also improved.ConclusionIn the subacute phase of SCI, B2m, Itgb5, and Vav1 in macrophages/microglia may be key therapeutic targets to promote nerve regeneration. In addition, low-dose decitabine may promote spinal cord regeneration by regulating the polarization state of macrophages/microglia.

As a result of the trend toward economic globalization, the vigorous development of cross-border e-commerce has attracted many scholars to study this field, involving many related fields, such as consumer behavior, advertising, information systems, and supply chain management. Throughout the existing literature, it can be found that most of the research focuses on certain influencing factors of the development of cross-border e-commerce, and there is no systematic and macro- overview of the development trend of research in this field in recent years, nor the integration and analysis of keywords. Given that the research in the field of cross-border e-commerce is fragmented to a large extent, to effectively explore the research trend in this field, we must understand the current situation of cross-border e-commerce. Systematic bibliometric analysis can solve this problem by providing publishing trends and information on various topics. Therefore, based on the scientific database web, this study collected 198 references related to cross-border e-commerce from 2016 to 2021, briefly introduced the current situation and development trend of cross-border e-commerce, visually analyzed and refined the journals, authors, research institutions, countries, publication years, keywords, citations of academic publications in this field, and other key information, and summarized the development trend and path of CEBC in the existing research. It is helpful for researchers to solve the current research gap, understand the future research direction in this field, and help academia establish a strict knowledge system.

BackgroundPsoriasis is an immune-related skin disease notable for its chronic inflammation of the entire system. Alzheimer’s disease (AD) is more prevalent in psoriasis than in the general population. Immune-mediated pathophysiologic processes may link these two diseases, but the mechanism is still unclear. This article aimed to explore potential molecular mechanisms in psoriasis and AD.MethodsGene expression profiling data of psoriasis and AD were acquired in the Gene Expression Omnibus (GEO) database. Gene Set Enrichment Analysis (GSEA) and single-sample GSEA (ssGSEA) were first applied in two datasets. Differentially expressed genes (DEGs) of two diseases were identified, and common DEGs were selected. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis was performed to explore common biological pathways. Signature transcription factors (STFs) were identified and their diagnostic values was calculated by receiver operating characteristic (ROC) curve analysis in the exploration cohort and verified in the validation cohort. The expression levels of STFs were further investigated in the validation cohort and the GTEx Portal Database. Additionally, four kinds of interaction analysis were performed: correlation analysis among STFs, gene-gene, chemical-protein, and protein-ligand interaction analyses. In the end, we predicted the transcription factor that potentially regulates STFs.ResultsBiosynthesis and metabolic pathways were enriched in GSEA analysis. In ssGSEA analysis, most immunoreaction gene lists exhibited differential enrichment in psoriasis cases, whereas three receptor-related gene lists did in AD. The KEGG analysis of common DEGs redetermined inflammatory and metabolic pathways essential in both diseases. 5 STFs (PPARG, ZFPM2, ZNF415, HLX, and ANHX) were screened from common DEGs. The ROC analysis indicated that all STFs have diagnostic values in two diseases, especially ZFPM2. The correlation analysis, gene-gene, chemical-protein, and protein-ligand interaction analyses suggested that STFs interplay and involve inflammation and aberrant metabolism. Eventually, ZNF384 was the predicted transcription factor regulating PPARG, ZNF415, HLX, and ANHX.ConclusionsThe STFs (PPARG, ZFPM2, ZNF415, HLX, and ANHX) may increase the morbidity rate of AD in psoriasis by initiating a positive feedback loop of excessive inflammation and metabolic disorders. ZNF384 is a potential therapeutic target for psoriasis and AD by regulating PPARG, ZNF415, HLX, and ANHX.

The novel coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has spread worldwide, and the WHO declared it a pandemic on March 11, 2020. Clinical characteristics and epidemiology features of patients infected with SARS-CoV-2 have been explored in the previous study. However, little is known about the combinative association of liver dysfunction and abnormal interleukins (ILs) in severe patients with COVID-19. This study was designed to estimate whether liver dysfunction and abnormal ILs could predict the severity of COVID-19. This study integrated liver function data and ILs data in patients with COVID-19 and found that liver injury and two ILs, interleukin-2 receptor (IL-2R) and interleukin-6 (IL-6), were closely related to the prognosis of patients with COVID-19. This study may give more exact information to clinicians about the prognosis of patients with COVID-19. In addition, this correlational study between liver disorder and ILs may provide a new vision to diagnosis and treatment in patients.

Psoriasis is a multifactorial immune-mediated disease. The highly effective and eligible treatment for psoriasis is limited, for its specific pathogenesis is incompletely elucidated. Skin microbiota is a research hotspot in the pathogenesis of immune-mediated inflammatory skin diseases nowadays, and it may have significant involvement in the provocation or exacerbation of psoriasis with broadly applicable prospects. It is postulated that skin microbiota alternation may interplay with innate immunity such as antimicrobial peptides and Toll-like receptors to stimulate T-cell populations, resulting in immune cascade responses and ultimately psoriasis. Achieving a thorough understanding of its underlying pathogenesis is crucial. Herein, we discuss the potential immunopathogenesis of psoriasis from the aspect of skin microbiota in an attempt to yield insights for novel therapeutic and preventive modalities for psoriasis.

BackgroundThe four ERBB tyrosine kinase family members [ERBB1 (epidermal growth factor receptor, EGFR), ERBB2 (HER2), ERBB3 (HER3), and ERBB4 (HER4)] (ERBB receptor family) have been shown, according to previous studies, to be related to the cutaneous melanoma. ERBB3 is the only member of the ERBBs that lacks tyrosine kinase activity and thus needs to dimer with other tyrosine kinases receptors to trigger the signaling pathway, while ERBB3 may dimer with all members of the ERBB family. Melanoma progression depends on activation of ERBB signaling, especially the ERBB3/ERBB2 cascade. There are lymphocytes and T cell infiltrates in melanoma. Numerous pieces of evidences indicate that local immune status plays an important role in the formation of anti-tumor immune responses. However, the relationship between the ERBBs and prognosis and immune infiltration in cutaneous melanoma is not completely clear.MethodsThe expression of the ERBBs was analyzed through the Oncomine database, Gene Expression Profiling Interactive Analysis (GEPIA), respectively. Immunohistochemistry of ERBBs was obtained from the Human Protein Atlas is increased before HPA database. ERBBs genes expression and mutation analysis in cutaneous melanoma from the cBioPortal. Functional annotation and Kyoto Encyclopedia of Genes and Genomes is increased before KEGG pathway enrichment analysis from the Metascape. Correlations between ERBBs and 31 genes that were close to each other and frequently altered were explored by GEPIA. Using the GEPIA database, we also investigated the relationship between ERBBs and myeloid-derived suppressor cells (MDSC) in cutaneous melanoma. The disease-free survival and different tumor stages of ERBBs were evaluated by GEPIA. The correlation of ERBBs and tumor-infiltrating immune cells and prognostic(5 years survival rates) was tested by the Tumor Immune Estimation Resource (TIMER).ResultsIn general, the expression levels of ERBB1/2 in cutaneous melanoma were lower than those in normal skin tissue. By contrast, the ERBB3 expression level was higher in cutaneous melanoma than in normal skin tissue. Low expression of ERBB1/2 and high expression of ERBB3 were detrimental to the 5 years survival of cutaneous melanoma patients (ERBB1: log-rank P: 0.03; ERBB2: log-rank P: 0.008; ERBB3: log-rank P: 0.039). ERBB4 expression may not affect the prognosis of patients with cutaneous melanoma. ERBBs may not play a role in the tumor stage and disease-free survival in cutaneous melanoma patients. The relationship between the ERBB family and 31 genes that were close to each other and frequently altered is demonstrated as the genes regulated by the ERBB family being mainly concentrated in the RAS/RAF/MEK/ERK signaling pathway. ERBB2 can induce infiltration of CD8+ T cells and B cells, while ERBB3 can induce infiltration of CD4+ T cells, CD8+ T cells, and Neutrophil cells. ERBBs are more significantly associated with M1 macrophages, dendritic cells, Th1, Th2, Th17, and Treg cellular immune markers (Cor > 0.2). ERBB2/3 were related to MDSC in cutaneous melanoma, including human mononuclear myeloid-derived suppressor cells (M-MDSC) and polymorphonuclear myeloid-derived suppressor cells (PMN-MDSC), and may influence the progression of cutaneous melanoma through MDSC, but the conclusion needs further probing.ConclusionThis study investigated the prognosis and immune infiltration of the ERBB family in cutaneous melanoma. Our results suggest that ERBB1/2/3 may serve as early prognostic markers and potential therapeutic targets in cutaneous melanoma.

Background: D-dimer is a small protein fragment and high levels of D-dimer have been associated with increased mortality in patients presenting to emergency departments with infection. Previous studies have reported increased levels of D-dimer in COVID-19; however, it is unclear whether an increased D-dimer level provides early warning of poor prognosis. Therefore, this study aimed to assess the usefulness of D-dimer as an early indicator of prognosis in patients with coronavirus disease (COVID-19).Methods: We conducted a retrospective study of patients with COVID-19 admitted to Leishenshan Hospital in Wuhan, China, from February 15 to March 30, 2020. The final date of follow-up was April 11, 2020.Results: Of the 1,643 patients with COVID-19, 691 had elevated D-dimer levels. Their median age was 65 years. Of the patients with elevated D-dimer levels, 45% had comorbidities, with cardiovascular disease (205 [29.7%]) being the most common. Patients with elevated D-dimer were more likely to require treatment with high-flow oxygen, anticoagulation, antibiotics, and admission to the intensive care unit They were also more likely to have increased interleukin-6, monocytes, and lymphocytes. Patients with elevated D-dimer levels had significantly higher mortality than those with normal or low D-dimer levels.Conclusion: In patients with COVID-19, elevated D-dimer was associated with abnormal immunity, underlying disease, increased disease severity, and increased mortality. Taken together, D-dimer may be a marker for the early warning of disease severity and increased risk of death. These findings provide insights into the potential risk of elevated D-dimer in patients with COVID-19.

From a variety of yield stress fluid models, an elastoviscoplastic Herschel-Bulkley (EVPHB) model written in 3D is selected and coupled with a Finite Element Method with Lagrangian Integration Points (FEMLIP) to solve boundary value problems with large deformation process. By tracing the historical variables of a material point, it is verified that in a time-independent flow the elastic strain and viscous strain rate could be accurately reproduced by EVPHB model. For a time-dependent flow, because of the addition of elasticity, the EVPHB model makes the material experience a deformation process which is significantly distinctive from that produced by a pure regularized Herschel-Bulkley model. Benchmarks also show that in FEMLIP the yielded and unyielded zones could be easily defined by EVPHB model according to the stress of a material point. Lastly, it is shown that EVPHB model also induces a stress relaxation process for materials under constant strain. The suitability of FEMLIP to model elastoviscoplastic fluid is verified.

The capillary component and adsorptive component of matric suction differently impact the soil strength. Due to the cavitation effects of pore water, the adsorption effect dominates the behavior of soil when matric suction exceeds the cavitation tension. Based on the binary medium theory, a compression-shear strength model for unsaturated soils considering both capillary effect and adsorption effect is established. Compared with test data, the proposed compression-shear strength model has better prediction performance on the compression-shear strength of soil over a range of wide suction. The soil failure depends both on tension-shear stress and compression-shear stress. The tension-shear coupling mechanism in the soil is first investigated. A concept of closed stress point is introduced to divide the two zones of tension-shear coupling stress and compression-shear stress. According to the compression-shear strength model and tension-shear failure mechanism, the tension-shear and compression-shear joint strength model applicable to plane stress conditions is then established. Compared with test data, the proposed model in this article can better predict the nonlinear strength characteristics of clays and has better applicability. Finally, using the user material subroutine (UMAT), the secondary development of the joint strength model is conducted in ABAQUS and then applied to the slope stability analysis. The calculation results show that the established strength model presents a reasonable description of the development of the tension-shear coupling plastic zone in slope and gives an accurate safety factor.