Reduced expression of CXCL16/CXCR6 is involved in the pathogenesis of hidradenitis suppurativa.

Mutations in the γ-secretase complex have been well-described in familial hidradenitis suppurativa (HS). No gene mutations have been identified in sporadic HS, which comprises 60%-70% of all HS cases. Obesity and smoking are risk factors for HS and are closely related to DNA methylation, an essential epigenetic phenomenon. Hence, we hypothesized that epigenetic modifications might be involved in sporadic HS. To investigate genes with aberrant methylation in sporadic HS cases and assess their expression in skin lesions and blood from patients with HS. Skin lesion samples and corresponding normal skin were obtained from three patients with HS and subjected to whole-genome DNA methylation sequencing. Blood samples were collected from 20 patients with HS and 20 healthy controls (HCs). The HS mouse model was established by applying tamoxifen to NcstnΔKC mice. Target gene expression was analysed by immunohistochemistry, immunofluorescence, western blotting, enzyme-linked immunosorbent assay (ELISA) and semiquantitative real-time polymerase chain reaction (RT-qPCR). Among 10 807 differentially methylated genes, we filtered 2101 genes with hypermethylated promoter regions, and following bioinformatics analyses, we focused on CXC chemokine ligand 16 (CXCL16). Subsequent functional experiments confirmed the downregulation of CXCL16 and its receptor, CXC chemokine receptor (CXCR) 6, in skin tissue from HS patients and NcstnΔKC mice. Serum CXCL16 concentrations were also significantly decreased in patients with HS. Our data revealed the downregulation of CXCL16 and CXCR6 in HS.

Performance of novel deep learning network with the incorporation of the automatic segmentation network for diagnosis of breast cancer in automated breast ultrasound.

OBJECTIVE: To develop novel deep learning network (DLN) with the incorporation of the automatic segmentation network (ASN) for morphological analysis and determined the performance for diagnosis breast cancer in automated breast ultrasound (ABUS). METHODS: A total of 769 breast tumors were enrolled in this study and were randomly divided into training set and test set at 600 vs. 169. The novel DLNs (Resent v2, ResNet50 v2, ResNet101 v2) added a new ASN to the traditional ResNet networks and extracted morphological information of breast tumors. The accuracy, sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), area under the receiver operating characteristic (ROC) curve (AUC), and average precision (AP) were calculated. The diagnostic performances of novel DLNs were compared with those of two radiologists with different experience. RESULTS: The ResNet34 v2 model had higher specificity (76.81%) and PPV (82.22%) than the other two, the ResNet50 v2 model had higher accuracy (78.11%) and NPV (72.86%), and the ResNet101 v2 model had higher sensitivity (85.00%). According to the AUCs and APs, the novel ResNet101 v2 model produced the best result (AUC 0.85 and AP 0.90) compared with the remaining five DLNs. Compared with the novice radiologist, the novel DLNs performed better. The F1 score was increased from 0.77 to 0.78, 0.81, and 0.82 by three novel DLNs. However, their diagnostic performance was worse than that of the experienced radiologist. CONCLUSIONS: The novel DLNs performed better than traditional DLNs and may be helpful for novice radiologists to improve their diagnostic performance of breast cancer in ABUS. KEY POINTS: • A novel automatic segmentation network to extract morphological information was successfully developed and implemented with ResNet deep learning networks. • The novel deep learning networks in our research performed better than the traditional deep learning networks in the diagnosis of breast cancer using ABUS images. • The novel deep learning networks in our research may be useful for novice radiologists to improve diagnostic performance.

γ-Secretase Genetics of Hidradenitis Suppurativa: A Systematic Literature Review.

BACKGROUND: Acne inversa/hidradenitis suppurativa (HS) is a chronic, recurrent inflammatory disease of the skin that can significantly affect patients' quality of life. The etiology and pathogenesis of HS are unclear and gene mutations might play a role. SUMMARY: The primary focus of the review is on aggregating the gene mutations reported, summarizing the structure of γ-secretase and analyzing and speculating about the mechanism and the underlying relations between gene mutation and functional changes of protein. The systematic literature review was done by searching the PubMed, Embase, and Web of Science databases. γ-Secretase is an intramembrane protease complex responsible for the intramembranous cleavage of more than 30 type-1 transmembrane proteins including amyloid precursor protein and Notch receptors. The protein complex consists of four hydrophobic proteins: presenilin, presenilin enhancer-2 (PSENEN), nicastrin, and anterior pharynx defective 1 (APH1). To date, 57 mutations of γ-secretase genes have been reported in 70 patients or families worldwide, including 39 in NCSTN, 14 in PSENEN, and 4 in PSEN1, of which 17 are frameshifts, 15 result in nonsense mutations, 13 in missense mutations, and 12 are splice site mutations. Given the structure of γ-secretase and analysis of related mutation loci of NCSTN, PSENEN, and PSEN1, mutations in γ-secretase genes could affect activation of presenilin, prevent substrate binding, and hinder intramembrane cleavage of select proteins.

Peripheral blood mononuclear cell microRNA profiles in syphilitic patients with serofast status.

Syphilis is a chronic sexually transmitted disease caused by infection with Treponema pallidum, which can invade various system organs, leading to clinical manifestations such as neurosyphilis, ocular syphilis, and cardiovascular syphilis and seriously endangering human health. Serofast status is a common outcome after syphilis treatment that presents an important clinical problem. At present, the etiology of serofast status remains unknown. A systematic investigation of the microRNA (miRNA) expression profiles in peripheral blood mononuclear cells (PBMCs) of patients with serofast status or secondary syphilis and of healthy control subjects was conducted using small RNA-seq. The expression of miRNAs was further confirmed by real-time fluorescence quantitative PCR (qPCR) assays. The data reveal a specific miRNA expression profile that was displayed in cells from patients with serofast status. Known and novel predicted (np)-miRNAs were also identified and verified, such as miR-338-5p, np-miR-163, np-miR-128, np-miR-244, and np-miR-5, which together may be used as indicators for treatment evaluation. The functions of genes targeted by the miRNAs differentially expressed in serofast status patients were further analyzed; these genes were found to be involved in various biological functions, such as T-cell receptor signaling pathways, metabolism, and growth. Our study presents the first systematic landscape of miRNAs in PBMCs from patients with serofast status and proposes specific miRNAs linked with serofast status. Our results provide further evidence that serofast status is closely related to host immune function. Additionally, the miRNA expression profile in PBMCs of patients with serofast status generated by this work offers insight into the complex immune network in humans. We hope our results can provide new insights into the pathogenesis of serofast status.

Comprehensive Analysis of Competing Endogenous RNA (ceRNA) Network Based on RNAs Differentially Expressed in Lung Adenocarcinoma Using The Cancer Genome Atlas (TCGA) Database.

BACKGROUND The aim of this study was to explore a comprehensive analysis of the competing endogenous (ceRNA) network of lung adenocarcinoma and predict its regulatory mechanism and prognosis correlation based on The Cancer Genome Atlas (TCGA) database. MATERIAL AND METHODS The genes expression data from 535 lung adenocarcinoma cases and 59 normal tissue cases were acquired and downloaded from TCGA database, and differentially expressed messenger RNA (mRNA), long noncoding RNA (lncRNA) and microRNA (miRNA) were selected primarily by "edgeR" package in R software, which further constructs lncRNA-miRNA-mRNA ceRNA network. We then proceed to carry out Gene Ontology enrichment analysis, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis, and Kaplan-Meier survival analysis of the mRNAs involved in the ceRNA network. RESULTS There are 3 mRNAs (ANLN, IGFBP1, and TFAP2A) in differentially expressed genes, 4 lncRNAs (AC015923.1, FGF12-AS2, LINC00211, and MED4-AS1), and 2 miRNAs (miR-31 and miR-490) associated with the prognostic of lung adenocarcinoma. Besides, LINC00461 and has-mir-139 as key nodes were found in the ceRNA network. Significantly, miR-31 shows the greatest prognostic value related to the adverse effect of the prognostic of lung adenocarcinoma (P<0.001). CONCLUSIONS By analyzing the expression data of lung adenocarcinoma in TCGA database, we found that 3 mRNAs, 4 lncRNAs, and 2 miRNAs were screened as potential prognostic factors for lung adenocarcinoma. In addition, LINC00461 and has-mir-139 are 2 important regulatory network nodes in lung adenocarcinoma ceRNA.

Serological response to therapy following retreatment of serofast early syphilis patients with benzathine penicillin.

Background: Some syphilitic patients remain in a serologically positive state after the recommended therapy. Although we often retreat patients in clinical practice, the optimal treatment protocol remains uncertain due to the paucity of data regarding serological response to retreatment and long-term outcomes. Methods: We examined rapid plasma reagin serological test results of 70 serofast early syphilis cases who were retreated with 2.4 million units of benzathine penicillin weekly for 3 weeks. Serological retreatment success was defined as a minimum 4-fold decrease in baseline rapid plasma reagin test antibody titre within 6 months. Results: Thirty-four (48.6%) of the patients who failed to achieve serological cure at 6 months after initial therapy achieved serological cure at 12 months. Patients who had higher non-treponemal titres at baseline and at 6 months were more likely to exhibit serological cure after retreatment than those with lower titres. Conclusions: Our results suggest that the incremental benefit of retreating serofast patients with early syphilis is moderate, considering the almost 1:1 ratio of serological response to serofast state at follow-up.

Comprehensive binding analysis of glycated myosin with furan derivatives via glucose by means of multi-spectroscopy techniques and molecular docking simulation.

Myosin is an ideal binding receptor for aroma compounds and its functional properties are easily affected by glucose. The study comprehensively clarified the effects of glucose glycation-induced structural modifications of myosin on its binding ability with furan derivatives, including 2-methylfuran, 2-furfural, and 2-furfurylthiol. The results demonstrated that the binding levels of furan derivatives were obviously affected by the glycation levels of myosin due to the changes of myosin structure and surface. The increased glycation levels caused the unfolding of myosin structure and accelerated the aggregation, as were exhibited by the data of zeta potential, particle size, microstructure, and secondary structure. The glycated myosin with wrinkled surfaces favored the significant increase of hydrophobic interactions (31.59-69.50 µg), the more exposure of amino acid residues (3459-6048), the formation of free sulfhydryl groups (16.37-20.58 mmol/104g) and hydrogen bonds. These key (non)covalent linkages accounted for the generation of glycated myosin-odorants complex, including 2-furfurylthiol (29.17-47.87 %), thus enhancing the resultant binding ability as evidenced by the free furan derivatives concentrations, fluorescence quenching and molecular docking simulation analysis. The glycated myosin for 8 h bound highest concentrations of furan derivatives. The results will provide comprehensive data on the retention of aroma compounds in meat products.

Electrical stimulation towards melanoma therapy via liquid metal printed electronics on skin.

BACKGROUND: We proposed a method of using electrical stimulation for treatment of malignant melanoma through directly spray-printing liquid metal on skin as soft electrodes to deliver low intensity, intermediate frequency electric fields. METHODS: With patterned conductive liquid metal components on mice skin and under assistance of a signal generator, a sine wave electrical power with voltage of 5 V and 300 kHz could be administrated on treating malignant melanoma tumor. FINDINGS: The experiments demonstrated that tumor volume was significantly reduced compared with that of the control group. Under the designed parameters (signal: sine wave, signal amplitude Vpp: 5 V and Vpp: 4 V, frequency: 300 kHz) of Tumor treating fields (TTFields) with the sprayed liquid metal electrode, four mice tumor groups became diminishing after 1 week of treatment. The only device-related side effect as seen was a mild to moderate contact dermatitis underneath the field delivering electrodes. The SEM images and pathological analysis demonstrated the targeted treating behavior of the malignant melanoma tumor. Further, thermal infrared imaging experiments indicated that there occur no evident heating effects in the course of treatment. Besides, the liquid metal is easy to remove through medical alcohol. CONCLUSIONS: Tumor treating fields through liquid metal electrode could offer a safe, straightforward and effective treatment modality which evidently slows down tumor growth in vivo. These promising results also raised the possibility of applying spray-printing TTFields as an easy going physical way for future cancer therapy.