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Leprosy is an infectious disease caused by non‐cultivable bacteria Mycobacterium leprae. Th17 cells play vital roles during pathogenesis of leprosy reactions and IL‐23 is involved in Th17 cell differentiation. Although previous studies have reported the participation of IL‐23 in leprosy patients in peripheral blood, the role of this cytokine in skin has not yet been described for the disease. In this study, we first evaluated IL‐23 expression in the skin of patients with leprosy. Data showed that in keratinocytes, endothelial cells, and macrophages, IL‐23 expression was markedly higher in patients compared to that in the normal skin controls. Also, leprosy patients presented higher percentage of IL‐17A‐producing IL‐23R + CD4 T cells than healthy donors. IL‐23R blocking induced markedly downregulated IL‐17A secretion in leprosy patients but not in healthy donors. Furthermore, TGF‐β expression was significantly elevated after IL‐23R blocking. Overall, this study establishes that Th17 cells produce IL‐17A in an IL‐23 dependent manner in the skin of leprosy patients and provides more focused treatment strategies for Mycobacterium leprae. [ABSTRACT FROM AUTHOR]

The purpose of this study was to investigate the collaborative dialogue patterns of pair programming and their impact on programming self‐efficacy and coding performance for both slow‐ and fast‐paced students. Forty‐six postgraduate students participated in the study. The students were asked to solve programming problems in pairs; those pairs' conversations were recorded when they worked on their tasks. Data analysis methods, including lag sequential analysis, cluster analysis and paired t‐test, were employed, and the results showed that (1) four collaborative dialogue patterns emerged: Lecture, Guide, Question and Answer (Q&A), and Inquiry patterns; (2) Guide and Inquiry patterns significantly increased programming self‐efficacy for both fast‐ and slow‐paced students while Lecture and Q&A patterns significantly increased programming self‐efficacy for slow‐paced students but not for fast‐paced students; (3) Guide and Inquiry patterns played a significant role in improving coding performance for slow‐paced students. The study reveals a complex relationship between collaborative dialogue patterns with programming self‐efficacy and coding performance, critically affecting students' pair programming quality. Further details of the findings are also discussed. Practitioner notesWhat is already known about this topic Pair programming is promising in promoting problem solving and knowledge transfer and is widely used in programming education.There are different patterns observed in the pair programming process.Collaborative dialogue patterns found in "expert‐novice" pair programming were derived from a single programming task.What this paper adds Four collaborative dialogue patterns of pair programming emerged by increasing the different tasks and experiment duration and expanding the sample size, which further verified the stability of the similar patterns in previous studies.Four collaborative dialogue patterns showed different significant impacts on different students' programming self‐efficacy and coding performance.This study presents the finer‐grained characteristics of collaborative interaction in programmer pairs and contributes to the explanation regarding the different effects of pair programming reported in previous studies.Implications for practice and/or policy Four collaborative dialogue patterns can help the teachers understand the collaborative process of pair programming between fast‐ and slow‐paced students.The collaborative dialogue patterns can be used to formulate effective intervention strategies to stimulate the process of collaboration in pairs and applied in future programming education to provide a new path for cultivating and promoting students' programming abilities.It is worth further investigating the impact of collaborative dialogue patterns on students' computational thinking. [ABSTRACT FROM AUTHOR]

Granuloma faciale (GF) is a rare inflammatory skin disorder of unknown etiology, which can cause severe cosmetic impairment.[1] GF presents as asymptomatic, solitary or multiple, erythematous nodules and/or plaques, nearly always limited to the face.[[1], [3]] Due to delayed diagnosis, with delays of up to 15 years reported, the disease may gradually/eventually progress to disseminated or extrafacial GF.[2] Herein, we report an unusual case of GF with extensive lesions (covering 70% of the facial area) and extrafacial involvement, a condition which has rarely been described. Granuloma faciale (GF) is an idiopathic cutaneous disorder of unknown etiology, predominantly affecting the face but may infrequently appear on the trunk, scalp, or extremities.[1] GF usually manifests as localized, well-delimited plaques and nodules at one single site. This suggests that it is still necessary to increase vigilance against the disease and perform skin biopsies on any chronic erythematous plaques or nodules for early diagnosis, so as to avoid the serious consequences of disease progression. [Extracted from the article]

Esophageal squamous cell carcinoma (ESCC) is a malignant tumor with low survival rate, so new therapies are urgently needed. Histone deacetylases (HDACs) play a critical role in tumorigenesis, and HDACs inhibition is a potential therapeutic target in ESSC. In our study, we evaluated the effect and molecular mechanism of MS‐275 (an inhibitor of HDACs) on ESCC cells. We found that HDAC1 and HDAC2 were overexpressed in ESCC tissues and related with clinical pathological features of patients with ESCC. MS‐275 markedly reduced HDAC1 and HDAC2 expression, whereas increased the level of AcH3 and AcH2B. MS‐275 suppressed proliferation and clonogenicity of ESCC cells in a concentration‐dependent manner. In addition, MS‐275 induced apoptosis, arrested cell cycle, and inhibited migration, epithelial–mesenchymal transition, and sphere‐forming ability of ESCC cells in vitro. Moreover, p‐Akt1 and p‐mTOR were downregulated by MS‐275. Finally, MS‐275 significantly inhibited tumor growth in vivo. Taken together, HDAC1 and HDAC2 are associated with the progression of ESCC, and MS‐275 hinders the progression and stemness of ESCC cells by suppressing the PI3K/Akt/mTOR pathway. Our findings show that MS‐275 inhibits ESCC cells growth in vitro and in vivo, which is a potential drug for the ESCC therapy. [ABSTRACT FROM AUTHOR]

Neuronal activity shapes the dendritic arbour; however, most of the molecular players in this process remain to be identified. We observed that depolarization-induced neuronal activity causes an increase in the phosphorylation of glycogen synthase kinase-3 ( GSK-3)α/β on Ser21/9 in cerebellar granule neurons. Using several approaches, including gene knockdown and GSK-3α/βS21A/S21A/S9A/S9A double knockin mice, we demonstrated that both GSK-3β and GSK-3α mediate activity-dependent dendritic growth and that Ser21/9 phosphorylation of GSK-3α/β plays an important role in this process. Collapsin response mediator protein-2 ( CRMP-2), which is crucial for axon development, is phosphorylated at Thr514 and inactivated by GSK-3. We found CRMP-2 was located mainly in the dendrites of cerebellar granule neurons, in contrast to the axonal distribution in hippocampal neurons. Over-expression of CRMP-2 promoted and knockdown of CRMP-2 impaired dendritic growth, suggesting that CRMP-2 is necessary and sufficient for activity-dependent dendritic development. Furthermore, silencing CRMP-2 completely blocked the dendritic growth-promoting effects of GSK-3 knockdown, and expression of Thr514 nonphosphorylated form of CRMP-2 counteracted the inhibitory effect of constitutively active GSK-3. This data indicate that CRMP-2 functions downstream of GSK-3. Together, these findings identify a novel GSK-3/ CRMP-2 pathway that connects neuronal activity to dendritic growth. [ABSTRACT FROM AUTHOR]

Carbon fabric/resin laminated composites (CFRC) are extensively used in aerospace, transportation, and other fields owing to their superiorities of lightweight, high strength, and convenient integral molding. Therefore, strong interlaminar binding and prominent wear resistance are urgent requirements for avoiding premature failure of laminated materials in harsh working environments. To elevate the superficial wear resistance and interlaminar bonding strength of composites simultaneously, the modified composites were obtained by introducing carbon fiber powder (CFP) with different densities on the surface of the composites and between layers. The experimental results indicate that CFP can be evenly distributed in the interlaminar resin enrichment zone of the sample (CFRC‐40) when the deposition density is 40 g/m2. Consequently, CFRC‐40 presents optimal thermal conductivity owing to better heat transfer bridges between layers of the composite established by CFP. At the same time, the mechanical properties such as the tensile, impact, and interlaminar shear strengths of CFRC‐40 are improved by 42.8%, 10.2%, and 8.5%, respectively, compared with the original CFRC, which are attributed to the absorption of crack propagation energy and the inhibition of crack propagation by CFP. Furthermore, the dynamic friction coefficient maintains at a high level after introducing CFP with a density of 40 g/m2, while the wear rate significantly decreases by 61.2% from 12.99 × 10−14 m3(N m)−1 to 5.04 × 10−14 m3(N m)−1. This study proposes an innovative strategy to improve the interlaminar bonding of carbon fabric/resin laminated composite, which is conducive to obtaining composite with excellent mechanical and tribological properties. Highlights: A facile and effectual method was adopted to introduce carbon fiber powder (CFP) into the interlamination and surface of the composites simultaneously.The mechanical properties and abrasive resistance of the composites were obviously strengthened by regulating the content and distribution of CFP.CFP at a certain scale, could not only hinder the propagation of cracks but also alleviate the surface wear and extend the service life of composites. [ABSTRACT FROM AUTHOR]

Previous studies have shown that cancer susceptibility candidate 5 (CASC5) plays important roles in several types of cancer. But its expression and clinical significance in human pan‐cancer remain largely unclear. In the present study, we comprehensively analysed the expression profile and prognostic values of CASC5 in pan‐cancer across 33 cancer types based on the online TCGA analysis databases. CASC5 was found to be abnormally expressed in 16 types of cancer. In addition, dysregulated expression of CASC5 was closely associated with patient overall survival (OS) in kidney renal papillary cell carcinoma (KIRP), lung adenocarcinoma (LUAD), pancreatic adenocarcinoma (PAAD) and thymoma (THYM). By comparative analysis, we found that CASC5 was significantly up‐regulated in LUAD and predicted poor patient OS. High CASC5 expression was closely correlated with tumour advanced stages of patients with LUAD. Through GSEA based on the KEGG database, CASC5 was found to be closely related to DNA replication and microRNA regulation in LUAD. Functionally, knockdown of CASC5 could inhibit cell proliferation of LUAD cells in vitro, rather than affecting cell migration and invasion. Mechanistically, CASC5 promoted proliferation of LUAD cells by targeting miR‐139‐5p. Collectively, our findings reveal that CASC5 is a novel oncogenic gene in LUAD and may be a potential clinical target and (or) biomarker for this human malignancy. Significance of the study: In this study, we for the first time comprehensively analysed the transcriptional level and prognostic significance of CASC5 in human pan‐cancer across 33 cancer types using online TCGA databases. Our study indicates that CASC5 is aberrantly expressed in many tumours and is closely related to the patient overall survival of several tumour types. Our findings reveal that CASC5 is a novel oncogene in LUAD based on bioinformatic analysis and functional experiments. Mechanistically, CASC5 promoted LUAD proliferation by targeting miR‐139‐5p. Results of this study suggest that CASC5 is a potential clinical target and (or) biomarker for LUAD. [ABSTRACT FROM AUTHOR]

Purpose: The prognostic factors for diffuse large B‐cell lymphoma (DLBCL) have been fully explored, but prognostic information for bulky mass DLBCL patients is limited. This study aimed to analyze the prognostic value of MYC protein expression and other biological parameters in bulky mass DLBCL patients. Methods: We defined a bulky mass as a maximum tumor diameter ≥7.5 cm and studied 227 patients with de novo bulky mass DLBCL. Results: In all patients with bulky mass DLBCL, the 1‐year and 3‐year OS rates were 72.7% and 57.1%, respectively, and the 1‐year and 3‐year PFS rates were 52.0% and 42.5%, respectively. The MYC overexpression group (n = 140) showed significantly worse overall survival (OS; p = 0.019) and progression‐free survival (PFS; p = 0.001) than the non‐MYC overexpression group (n = 87). Subgroup analyses demonstrated that the MYC overexpression group was associated with inferior OS and PFS in the subgroups with the International Prognostic Index score of 3–5 (OS: p = 0.011; PFS: p < 0.001), Ann Arbor stage 3–4 (OS: p = 0.014; PFS: p < 0.001) and GCB subtype (OS: p = 0.014; PFS: p = 0.010). Consolidation radiotherapy improved OS and PFS in patients with bulky mass DLBCL (OS: p = 0.008; PFS: p = 0.004) as well as in those with MYC overexpression (OS: p = 0.001; PFS: p = 0.001). The prognostic value of MYC overexpression was maintained in a multivariate model adjusted for the International Prognostic Index. Conclusion: MYC overexpression is a poor predictor for bulky mass DLBCL patients. Consolidation radiotherapy for residual disease after induction therapy may improve outcomes for patients with bulky mass DLBCL. [ABSTRACT FROM AUTHOR]

Keratinocytes are the predominant cell type in the skin epidermis, and they not only protect the skin from the influence of external physical factors but also function as an immune barrier against microbial invasion. However, little is known regarding the immune defence mechanisms of keratinocytes against mycobacteria. Here, we performed single‐cell RNA sequencing (scRNA‐seq) on skin biopsy samples from patients with Mycobacterium marinum infection and bulk RNA sequencing (bRNA‐seq) on M. marinum‐infected keratinocytes in vitro. The combined analysis of scRNA‐seq and bRNA‐seq data revealed that several genes were upregulated in M. marinum‐infected keratinocytes. Further in vitro validation of these genes by quantitative polymerase chain reaction and western blotting assay confirmed the induction of IL‐32 in the immune response of keratinocytes to M. marinum infection. Immunohistochemistry also showed the high expression of IL‐32 in patients' lesions. These findings suggest that IL‐32 induction is a possible mechanism through which keratinocytes defend against M. marinum infection; this could provide new targets for the immunotherapy of chronic cutaneous mycobacterial infections. [ABSTRACT FROM AUTHOR]

Kidney renal clear cell carcinoma (KIRC) is a common malignant tumor in human genitourinary system. Previous studies have shown that the homeobox‐D (HOXD) cluster genes, which belong to the homeobox (HOX) family, are involved in the progression of multiple types of cancer. However, the expression profile and prognostic values of the HOXD genes in KIRC remain largely unknown. Herein, we comprehensively analyzed the transcriptional levels and prognosis of HOXD genes in KIRC using four online The Cancer Genome Atlas analysis databases (GEPIA, UALCAN, starBase v3.0, and LinkedOmics). We found that several members of the HOXD gene family were abnormally expressed in KIRC and correlated with patient prognosis. The messenger RNA levels of HOXD1, HOXD8, and HOXD10 were significantly downregulated in KIRC tissues as compared with the normal tissues. Low expression of HOXD1 or HOXD8 predicted poor overall survival (OS) of KIRC patients, and downregulated HOXD1, HOXD3, or HOXD4 indicated unfavorable patient disease‐free survival (DFS) in KIRC. Through integrated analysis, we found that HOXD1 was lowly expressed in KIRC and correlated with patient OS, DFS and advanced tumor stages. Moreover, gene set enrichment analysis showed that HOXD1 may be mainly implicated in cell cycle regulation, tumor growth factor‐β (TGF‐β) and Wnt signaling pathways in KIRC. Furthermore, both loss‐of‐function and gain‐of‐function experiments demonstrated that HOXD1 inhibited cell proliferation, cell cycle and the TGF‐β signaling in KIRC. Taken together, our findings suggest that HOXD1 is a novel potential tumor suppressor in KIRC. [ABSTRACT FROM AUTHOR]

As far as we know, an ultrasonic evaluation of mycobacterium infection nodules has not yet been reported. I Mycobacterium marinum i is a pathogenic mycobacterium found in skin and soft tissue infections and is associated with fish and bodies of water.1 I Mycobacterium marinum i infections can be divided into four types: a solitary papulonodular lesion, sporotrichoid form, deep infection, and disseminated infection. [Extracted from the article]