"Comparative study of adipose-derived stem cells from localized scleroderma patients and healthy donors in treating skin fibrosis".

BACKGROUND: Localized scleroderma (LoS) is an autoimmune disease characterized by fibrosis of the skin and atrophy of the subcutaneous fat tissue. Adipose-derived mesenchymal stem cells (ASCs) is a promising treatment approach for LoS. However, ASCs from scleroderma patients (LoS-ASCs) have been shown to exhibit altered characteristics compared to ASCs from healthy donors (healthy-ASCs). This study aimed to compare the abilities of LoS-ASCs and healthy-ASCs in treating skin fibrosis. METHODS: The paracrine ability of ASCs was tested with cytokine array. Bleomycin-challenged mice models received subcutaneous injection of LoS-ASCs and healthy-ASCs. Pathological staining and western blotting of COL1, α-SMA was performed. Fibroblasts derived from LoS lesions (LoS-FB) was co-cultured with ASCs, and subjected to RNA sequencing to further explore the similarities and differences in the treatment mechanism. RESULTS: In vivo comparison revealed that healthy ASCs had a stronger proliferation ability and secreted higher levels of growth factors and cytokines, including VEGFA, PDGFB, and IL-10. Pathological staining of the skin in mice models treated with ASCs demonstrated that healthy ASCs were more effective in reducing dermal thickness and collagen deposition, while increasing microvessel density and the proportion of M2 macrophages. Co-culture with both healthy-ASCs and LoS-ASCs reduced the proliferation and migration abilities of LoS-FB, as well as the protein expression of α-SMA and COL1. RNA sequencing and validation revealed potential difference in the canonical Wnt pathway. CONCLUSIONS: Healthy-ASCs exhibited stronger proliferation, paracrine, anti-fibrosis, pro-angiogenesis, and immunomodulation abilities in treating skin fibrosis in scleroderma mouse models. CLINICAL RELEVANCE STATEMENT: Allogenic ASCs obtained from healthy donors are more efficient in treating skin fibrosis, and could serve as a potential alternative for patients who are not suitable candidates for liposuction surgery in the future.

Human Adipose Tissue-Derived Stromal Cells Ameliorate Adriamycin-Induced Nephropathy by Promoting Angiogenesis.

This study is to investigate the therapeutical effect and mechanisms of human-derived adipose mesenchymal stem cells (ADSC) in relieving adriamycin (ADR)-induced nephropathy (AN). SD rats were separated into normal group, ADR group, ADR+Losartan group (20 mg/kg), and ADR + ADSC group. AN rats were induced by intravenous injection with adriamycin (8 mg/kg), and 4 d later, ADSC (2 × 105 cells/mouse) were administrated twice with 2 weeks interval time (i.v.). The rats were euthanized after the 6 weeks' treatment. Biochemical indicators reflecting renal injury, such as blood urea nitrogen (BUN), neutrophil gelatinase alpha (NGAL), serum creatinine (Scr), inflammation, oxidative stress, and pro-fibrosis molecules, were evaluated. Results demonstrated that we obtained high qualified ADSCs for treatment determined by flow cytometry, and ADSCs treatment significantly ameliorated renal injuries in DN rats by decreasing BUN, Scr and NGAL in peripheral blood, as well as renal histopathological injuries, especially protecting the integrity of podocytes by immunofluorescence. Furthermore, ADSCs treatment also remarkably reduced the renal inflammation, oxidative stress, and fibrosis in DN rats. Preliminary mechanism study suggested that the ADSCs treatment significantly increased renal neovascularization via enhancing proangiogenic VEGF production. Pharmacodynamics study using in vivo imaging confirmed that ADSCs via intravenous injection could accumulate into the kidneys and be alive at least 2 weeks. In a conclusion, ADSC can significantly alleviate ADR-induced nephropathy, and mainly through reducing oxidative stress, inflammation and fibrosis, as well as enhancing VEGF production.

TNFAIP2 confers cisplatin resistance in head and neck squamous cell carcinoma via KEAP1/NRF2 signaling.

BACKGROUND: Drug resistance limits the treatment effect of cisplatin-based chemotherapy in head and neck squamous cell carcinoma (HNSCC), and the underlying mechanism is not fully understood. The aim of this study was to explore the cause of cisplatin resistance in HNSCC. METHODS: We performed survival and gene set variation analyses based on HNSCC cohorts and identified the critical role of tumor necrosis factor alpha-induced protein 2 (TNFAIP2) in cisplatin-based chemotherapy resistance. Half-maximal inhibitory concentration (IC50) examination, colony formation assays and flow cytometry assays were conducted to examine the role of TNFAIP2 in vitro, while xenograft models in nude mice and 4-nitroquinoline N-oxide (4NQO)-induced HNSCC models in C57BL/6 mice were adopted to verify the effect of TNFAIP2 in vivo. Gene set enrichment analysis (GSEA) and coimmunoprecipitation coupled with mass spectrometry (Co-IP/MS) were performed to determine the mechanism by which TNFAIP2 promotes cisplatin resistance. RESULTS: High expression of TNFAIP2 is associated with a poor prognosis, cisplatin resistance, and low reactive oxygen species (ROS) levels in HNSCC. Specifically, it protects cancer cells from cisplatin-induced apoptosis by inhibiting ROS-mediated c-JUN N-terminal kinase (JNK) phosphorylation. Mechanistically, the DLG motif contained in TNFAIP2 competes with nuclear factor-erythroid 2-related factor 2 (NRF2) by directly binding to the Kelch domain of Kelch-like ECH-associated protein 1 (KEAP1), which prevents NRF2 from undergoing ubiquitin proteasome-mediated degradation. This results in the accumulation of NRF2 and confers cisplatin resistance. Positive correlations between TNFAIP2 protein levels and NRF2 as well as its downstream target genes were validated in HNSCC specimens. Moreover, the small interfering RNA (siRNA) targeting TNFAIP2 significantly enhanced the cisplatin treatment effect in a 4NQO-induced HNSCC mouse model. CONCLUSIONS: Our results reveal the antioxidant and cisplatin resistance-regulating roles of the TNFAIP2/KEAP1/NRF2/JNK axis in HNSCC, suggesting that TNFAIP2 might be a potential target in improving the cisplatin treatment effect, particularly for patients with cisplatin resistance.

The thelytokous strain of the parasitoid Neochrysocharis formosa outperforms the arrhenotokous strain in reproductive capacity and biological control of agromyzid leafminers.

BACKGROUND: Both arrhenotoky (sexual reproduction of females and asexual reproduction of males) and thelytoky (asexual reproduction of females) occur within the order Hymenoptera. The existence of both thelytokous and arrhenotokous strains within one species provides an opportunity to compare the biocontrol efficiency between two reproductive modes. The parasitoid Neochrysocharis formosa (Westwood) (Hymenoptera: Eulophidae) has thelytokous and arrhenotokous strains with sympatric distributions. This parasitoid is used to control invasive leafminers through feeding, stinging, and parasitization. To compare the biocontrol efficiency of the two strains, we analyzed life tables and host-killing parameters of these two strains reared on the leafminer Liriomyza sativae Blanchard using the age-stage, two-sex life table and the CONSUME-MSChart software. RESULTS: Our results showed that the intrinsic rate of increase (r), finite rate of increase (λ), and net reproduction rate (R0 ) of the thelytokous strain were significantly higher than those of the arrhenotokous strain. The thelytokous females also performed better than the arrhenotokous females for the net host-feeding rate, net host-stinging rate, and net host-killing rate, but not the finite parasitism rate. Conclusively, the finite host-killing rate of the thelytokous strain (0.8720 ± 0.0516) was significantly higher than that of the arrhenotokous strain (0.5914 ± 0.0832). CONCLUSION: We concluded that thelytokous N. formosa is a better candidate as a biocontrol agent than arrhenotokous N. formosa to control leafminers. Our results shed light on how to choose a better biocontrol agent for integrated pest management (IPM) based on biological control, especially for co-occurring thelytokous and arrhenotokous parasitoids. © 2022 Society of Chemical Industry.

Cytoplasmic eIF6 promotes OSCC malignant behavior through AKT pathway.

BACKGROUND: Eukaryotic translation initiation factor 6 (eIF6), also known as integrin ß4 binding protein, is involved in ribosome formation and mRNA translation, acting as an anti-association factor. It is also essential for the growth and reproduction of cells, including tumor cells. Yet, its role in oral squamous cell carcinoma (OSCC) remains unclear. METHODS: The expression characteristics of eIF6 in 233 samples were comprehensively analyzed by immunohistochemical staining (IHC). Effects of eIF6 over-expression and knockdown on cell proliferation, migration and invasion were determined by CCK-8, wound healing and Transwell assays. Western blot, immunofluorescence (IF) and co-immunoprecipitation (co-IP) were performed for mechanical verification. RESULTS: We found that cytoplasmic eIF6 was abnormally highly expressed in OSCC tissues, and its expression was associated with tumor size and the clinical grade. Amplification of eIF6 promoted the growth, migration and invasion capabilities of OSCC cell lines in vitro and tumor growth in vivo. Through Western blot analysis, we further discovered that eIF6 significantly promotes epithelial-mesenchymal transformation (EMT) in OSCC cells, while depletion of eIF6 can reverse this process. Mechanistically, eIF6 promoted tumor progression by activating the AKT signaling pathway. By performing co-immunoprecipitation, we discovered a direct interaction between endogenous eIF6 and AKT protein in the cytoplasm. CONCLUSION: These results demonstrated that eIF6 could be a new therapeutic target in OSCC, thus providing a new basis for the prognosis of OSCC patients in the future. Video abstract.

Mechanisms and biomarkers of airway epithelial cell damage in asthma: A review.

Bronchial asthma is a heterogeneous disease with complex pathological mechanisms representing different phenotypes, including severe asthma. The airway epithelium is a major site of complex pathological changes in severe asthma due, in part, to activation of inflammatory and immune mechanisms in response to noxious agents. Current imaging procedures are unable to accurately measure epithelial and airway remodeling. Damage of airway epithelial cells occurs is linked to specific phenotypes and endotypes which provides an opportunity for the identification of biomarkers reflecting epithelial, and airway, remodeling. Identification of patients with more severe epithelial disruption using biomarkers may also provide personalised therapeutic opportunities and/or markers of successful therapeutic intervention. Here, we review the evidence for ongoing epithelial cell dysregulation in the pathogenesis of asthma, the sentinel role of the airway epithelium and how understanding these molecular mechanisms provides the basis for the identification of candidate biomarkers for asthma prediction, prevention, diagnosis, treatment and monitoring.

A coma-free super-high resolution optical spectrometer using 44 high dispersion sub-gratings.

Unlike the single grating Czerny-Turner configuration spectrometers, a super-high spectral resolution optical spectrometer with zero coma aberration is first experimentally demonstrated by using a compound integrated diffraction grating module consisting of 44 high dispersion sub-gratings and a two-dimensional backside-illuminated charge-coupled device array photodetector. The demonstrated super-high resolution spectrometer gives 0.005 nm (5 pm) spectral resolution in ultra-violet range and 0.01 nm spectral resolution in the visible range, as well as a uniform efficiency of diffraction in a broad 200 nm to 1000 nm wavelength region. Our new zero-off-axis spectrometer configuration has the unique merit that enables it to be used for a wide range of spectral sensing and measurement applications.

Clinical characteristics of re-positive COVID-19 patients in Huangshi, China: A retrospective cohort study.

A cluster of patients with coronavirus disease 2019 (COVID-19) underwent repeated positive severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA tests after they were discharged from the hospital. We referred to them as re-positive (RP) patients in this study. We aimed to describe the clinical characteristics of these patients in a retrospective cohort study. After being treated for COVID-19, the patients underwent 14 days of quarantine following their discharge from the Huangshi Hospital of Traditional Chinese Medicine and the Huangshi Hospital of Youse. Two additional sequential SARS-CoV-2 RNA tests were performed at the end of quarantine. The median age of the 368 patients was 51 years, and 184 (50%) patients were female. A total of 23 RP patients were observed at follow-up. Using multivariate Cox regression analysis, risk factors associated with RP included a higher ratio of lymphocyte/white blood cell on admission (adjusted HR 7.038; 95% CI, 1.911-25.932; P = 0.0034), lower peak temperature during hospitalization (adjusted HR, 0.203; 95% CI, 0.093-0.443; P<0.0001), and the presence of comorbidities, particularly hypertension or chronic diseases in the respiratory system (adjusted HR, 3.883; 95% CI, 1.468-10.273; P = 0.0063). Antivirus treatment with arbidol was associated with a lower likelihood of re-positive outcomes (adjusted HR, 0.178; 95% CI, 0.045-0.709; P = 0.0144).

High Cancer Susceptibility Candidate 8 Expression Is Associated With Poor Prognosis of Pancreatic Adenocarcinoma: Validated Analysis Based on Four Cancer Databases.

OBJECTIVE: The aim of this study was to explore the association between the expression of a long non-coding RNA (lncRNA), cancer susceptibility candidate 8 (CASC8), and pancreatic adenocarcinoma (PAAD). MATERIALS AND METHODS: starBase database was used to perform differential expression, survival, and competing endogenous RNA (ceRNA) network and H19/miR-671 correlation analyses for CASC8 in 178 PAAD samples. Using the cBioPortal database website, we analyzed the alteration in CASC8 expression and its correlation with the overall survival in PAAD. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were also performed using the circlncRNAnet database. Analysis of CASC8 polymorphisms was performed using the UCSC Xena database. Finally, the expression of CASC8 in Chinese PAAD tissues was validated by qPCR. RESULTS: The expression of CASC8 was observed to be high in 178 PAAD samples [fold change = 8.71, P = 0.0014, false discovery rate (FDR) = 0.04] and was related with poor prognosis, but not in pancreatic neuroendocrine tumor (pNET). CASC8 amplification was noted in 6% of the PAAD patients; however, the gene amplification did not affect the expression of CASC8 but was involved with the overall survival time of PAAD patients. Network analysis indicated that H19 is the ceRNA pair of CASC8 and that CASC8 competitively binds to miR-671 and might participate in the process of epithelial-to-mesenchymal transition (EMT). The correlation analysis showed that CASC8 was significantly negatively correlated with SMAD7. The analysis of CASC8 polymorphism showed that high copy number segment (CNS) of CASC8 is associated with low survival. Validation using PAAD tissues from Chinese patients was consistent with the in silico findings. CONCLUSION: CASC8 is specifically expressed at a high level in PAAD and associated with poor prognosis, which might be through its interaction with H19, miR-671, and SMAD7. These results indicate that CASC8 could serve as a novel marker for predicting the prognosis and as a potential target for the therapy of PAAD.

Identification of the Novel Target Genes for Osteosarcoma Therapy Based on Comprehensive Bioinformatic Analysis.

Osteosarcoma is one of the most common primary malignant tumors of the bone and tends to develop in teenage years. Although multitreatments for the diagnosis and therapy of osteosarcoma have been developed, there are still needs of new methods to prevent and treat the osteosarcoma. Here, we performed bioinformatic analysis to screen for the key genes, molecules, and pathways involved in osteosarcoma survival. Four microarray data sets (GSE99671, GSE87624, GSE65071, and GSE28423), which include data from human bone and osteosarcoma samples, were downloaded from the Gene Expression Omnibus (GEO) database. Differentially expressed mRNAs and miRNAs were identified. Kyoto Encyclopedia of Genes and Genomes enriched pathways, miRNA-mRNA target, gene/disease relationship, and overall survival was elucidated using related websites and software according to bioinformatic analysis protocols. We found three critical genes miR-29c, blood vessel epicardial substance (BVES), and proteasome 20S subunit beta 2 (PSMB2) through the GEO database and predicting miRNA-mRNA target. Among these genes, BVES and PSMB2 presented a high expression level in osteosarcoma based on GSE99671 and GSE87624 data sets, while miR-29c showed a low expression level in osteosarcoma based on GSE65071 and GSE28423 data sets. Furthermore, we found that the high expression level of miR-29c and BVES associated with better prognosis, while highly expressed PSMB2 associated with poor prognosis. The abnormally expressed mRNAs and miRNAs, which were identified by integrated bioinformatic analysis, provided insights into the molecular mechanisms of osteosarcoma. Notably, we found three critical genes that could be used as novel therapeutic targets for preventing or diagnosing osteosarcoma. Finally, PSMB2 may be the target of miR-29c.

CCN6 mutation detection in Chinese patients with progressive pseudo-rheumatoid dysplasia and identification of four novel mutations.

BACKGROUND: No formal diagnostic criteria for progressive pseudo-rheumatoid dysplasia (PPD) are available because of insufficient clinical data, which results in that PPD is often misdiagnosed with other diseases. Whole exome sequencing (WES) and Sanger sequencing were employed to reveal the novel mutations on CCN6 of five patients with PPD from China in order to increase the clinical data of PPD. METHODS: Four suspected PPD pedigrees containing five patients in total were collected from 1998 to 2018 in our medical center. The phenotypes of each suspected PPD case were recorded in detail, and peripheral blood samples were collected for subsequent sequencing. Genomic DNA was extracted from peripheral blood samples, and Agilent liquid phase chip capture system was utilized for efficient enrichment of whole exome region DNA. After acquiring raw sequenced reads of whole exome region, bioinformatics analysis was completed in conjunction with reference or genome sequence (GRCh37/hg19). Sanger sequencing was performed to identify the results of WES. RESULTS: In total, four novel PPD-related mutation sites in CCN6 gene were identified including (CCN6):c.643 + 2T>C, (CCN6):c.1064_1065dupGT(p.Gln356ValfsTer33), (CCN6):c.1064G > A), and exon4:c.670dupA:p.W223fs. CONCLUSION: Our findings increase the clinical data of PPD including the CCN6 mutation spectrum, the clinical symptoms and signs. Moreover, the study highlights the utility of WES in reaching definitive diagnoses for PPD.

Transcriptome-wide Sequencing Reveals Molecules and Pathways Involved in Neurofibromatosis Type I Combined With Spinal Deformities.

MINI: We identified differentially expressed genes (DEGs) that may be involved in the development of neurofibromatosis type I by whole-transcriptional sequencing. Seven hundred eighty DEGs were identified which include protein coding genes, miRNAs, and lncRNAs. The enrichment analysis may reveal pathways that these DEGs involved. A total of 383 protein-pairs for DEGs may unfold the possible mechanism how the disease is developed. STUDY DESIGN: This is a clinical basic study on neurofibromatosis type I (NF-1) with spinal deformity. OBJECTIVE: The current research focuses on screening key molecules affecting NF-1 with spinal deformity by transcriptome sequencing and discovering its underlying molecular biological mechanisms. SUMMARY OF BACKGROUND DATA: NF-1 is a complex multisystem human disorder, which is often found in spinal deformities patients. The success rate of orthopedic surgery for neurofibromatosis type I combined with spinal deformities patients was low because of the lack of molecular pathology. METHODS: In our study, the transcriptome-wide sequencing was preformed to identify the differentially expressed genes (DEGs) involved in this disease. RESULTS: Seven hundred eighty DEGs were identified which include protein coding genes, miRNAs, and lncRNAs. The DO, GO, KEGG and Reactome enrichment analysis may reveal pathways that these DEGs involved. And the 383 protein-pairs for DEGs that are involved in NF-1 combined with spinal deformities may unfold the possible mechanism how this disease is developed. CONCLUSION: The differentially expressed miRNAs and lncRNAs may contribute the ceRNA network. We focused on three key DEGs: FGFR2, MAP3K1 and STAT4. FGFR2 and MAP3K1 are members of the RAS/RAF/MEK/ERK-signaling pathway, and STAT4 were involved in the JAK/STAT pathway. The expression changes were verified by other researches and the functional cross-talk between the Ras/MAPK and JAK/STAT pathways may contribute in the disease development. This study took insight of the molecular mechanism of this disease. More detailed interactions between these factors are needed to be further explored. These key DEGs and involved pathways may provide clues in the clinical process for patients with NF-1, especially in prognosis prediction. LEVEL OF EVIDENCE: N/A.

This is a clinical basic study on neurofibromatosis type I (NF-1) with spinal deformity. The current research focuses on screening key molecules affecting NF-1 with spinal deformity by transcriptome sequencing and discovering its underlying molecular biological mechanisms. NF-1 is a complex multisystem human disorder, which is often found in spinal deformities patients. The success rate of orthopedic surgery for neurofibromatosis type I combined with spinal deformities patients was low because of the lack of molecular pathology. In our study, the transcriptome-wide sequencing was preformed to identify the differentially expressed genes (DEGs) involved in this disease. Seven hundred eighty DEGs were identified which include protein coding genes, miRNAs, and lncRNAs. The DO, GO, KEGG and Reactome enrichment analysis may reveal pathways that these DEGs involved. And the 383 protein-pairs for DEGs that are involved in NF-1 combined with spinal deformities may unfold the possible mechanism how this disease is developed. The differentially expressed miRNAs and lncRNAs may contribute the ceRNA network. We focused on three key DEGs: FGFR2, MAP3K1 and STAT4. FGFR2 and MAP3K1 are members of the RAS/RAF/MEK/ERK-signaling pathway, and STAT4 were involved in the JAK/STAT pathway. The expression changes were verified by other researches and the functional cross-talk between the Ras/MAPK and JAK/STAT pathways may contribute in the disease development. This study took insight of the molecular mechanism of this disease. More detailed interactions between these factors are needed to be further explored. These key DEGs and involved pathways may provide clues in the clinical process for patients with NF-1, especially in prognosis prediction. Level of Evidence: N/A.

Five Novel Genes Related to the Pathogenesis and Progression of Pancreatic Neuroendocrine Tumors by Bioinformatics Analysis With RT-qPCR Verification.

OBJECTIVE: To explore novel related genes and potential biomarkers of pancreatic neuroendocrine tumors (PanNETs). MATERIALS AND METHODS: Two data sets from ICGC and two from the NCBI GEO database were used to identify the differentially expressed genes (DEGs) in PanNETs. The common DEGs among the four sources were analyzed; furthermore, the relationship of these gene expression patterns with different PanNET grades, their mutation status and corresponding impact on prognosis, the interaction network, and the relationship with three known PanNET genes (ATRX, DAXX, and MEN1) were analyzed by two other GEO data and cBioPortal database. Finally, the expressions of novel DEGs were validated in Chinese PanNET tissues by RT-qPCR. RESULTS: Five new DEGs (ABCC8, PCSK2, IL13RA2, KLKB1, and PART1) and one confirmed DEG-ISL1 were identified. The mutation counts of DEGs increased with the tumor grade increasing from G1 to G3, and PanNET patients present vascular invasion or are deceased. These DEG expression patterns in PanNETs are quite different from that of pancreatic ductal adenocarcinoma and are related to A-D-M (ATRX-DAXX-MEN1) mutation. ABCC8 and KLKB1 are co-occurrence with the A-D-M axis in PanNETs. Importantly, patients with DEG mutations have a lower survival rate. RT-qPCR verification results of KLKB1 (P < 0.01), IL13RA2 (P < 0.01), ABCC8 (P < 0.01), and PART1 (P < 0.0001) expressions in Chinese PanNET tissues are consistent with our database analysis, which were significantly up-regulated. However, the expression of PCSK2 (P < 0.01) was contrary to our bioinformatics analysis, which was significantly down-regulated, suggesting that the expression trend of PCSK2 may be different among different races. These results indicated that these five genes may play an important role in the occurrence and progression of PanNETs. CONCLUSION: Five novel common DEGs identified are related to the development and prognosis of PanNETs and may serve as specific biomarkers and therapeutic targets.

Prognostic roles of MAGE family members in breast cancer based on KM-Plotter Data.

Breast cancer is the second leading cause of cancer-associated mortality among women worldwide, and the prevalence and mortality rates associated with this disease are high in Western countries. The melanoma-associated antigen (MAGE) family proteins are well-known tumor-specific antigens; this family includes >60 proteins that serve an important part in cell cycle withdrawal, neuronal differentiation and apoptosis. The aim of the present study was to identify a biomarker within the MAGE family that is specific for breast cancer. In the present study, the prognostic role of MAGE mRNA expression was investigated in patients with breast cancer using the Kaplan-Meier plotter database. The prognostic value of MAGE members in the different intrinsic subtypes of breast cancer was further investigated, as well as the clinicopathological features of the disease. The results of the present study indicated that patients with breast cancer that had high mRNA expression levels of MAGEA5, MAGEA8, MAGEB4 and MAGEB6 had an improved relapse-free survival, whereas those with high mRNA expression levels of MAGEB18 and MAGED4 did not. These results suggested that MAGEA5, MAGEA8, MAGEB4 and MAGEB6 may have roles as tumor suppressors in the occurrence and development of breast cancer, whereas MAGEB18 and MAGED4 may possess carcinogenic potential. MAGED2, MAGED3 and MAGEF1 had different effects depending on the type of breast cancer. In particular, high MAGEC3 mRNA expression was associated with worse RFS in lymph node-positive breast cancer, but with improved RFS in lymph node-negative breast cancer. In patients with wild-type TP53 and patients with different pathological grades of breast cancer, MAGEE2, MAGEH1 and MAGEL2 were more worthy of attention as potential prognostic factors. The results of the present study may help to elucidate the role of MAGE family members in the development of breast cancer, and may promote further research that identifies MAGE-targeting reagents for the treatment of breast cancer.

Identification of LCN1 as a Potential Biomarker for Breast Cancer by Bioinformatic Analysis.

The biological functions of lipocalin-1 (LCN1) are involved in innate immune responses and act as a physiological scavenger of potentially harmful lipophilic molecules. However, the relevance of LCN1 with cancer is rarely concerned currently. The aim of this study is to address the relevance of LCN1 with BRCA by bioinformatics. In this study, we found that the expressions of LCN1 increased significantly in various cancerous tissues, including BRCA, compared with their adjacent normal tissues through the TIMER database. Furthermore, UALCAN database analysis showed that the expression of LCN1 increased gradually from stage 1 to stage 4 and was upregulated in BRCA patients with different races and subtypes compared with that in the normal. In addition, those patients with perimenopause and postmenopause status displayed higher LCN1 expression. Importantly, LCN1 genetic alterations, including copy number amplification, deep deletion, and missense mutation, could be found, and the alteration frequency showed difference in various invasive BRCA through cBioPortal database. Moreover, a positive correlation between LCN1 somatic copy number alterations and immune cell enrichments was revealed in basal like BRCA by GISTIC 2.0. Finally, analysis on prognostic value of LCN1 by Kaplan-Meier plotter showed that low LCN1 expression correlated with poor prognosis for relapse-free survival in all types of BRCA, overall survival in luminal B BRCA, distant metastasis free survival in human epithelial growth factor receptor-2 (HER2) positive BRCA, and postprogression survival (PPS) in luminal A BRCA. But high LCN1 expression also displayed poor prognosis for PPS in HER2 positive BRCA. The results together verified the significance of LCN1 in BRCA, suggesting that it may be a potential biomarker for BRCA diagnosis.

Ultrahigh-resolution spectrometer based on 19 integrated gratings.

Optical spectrometers play a key role in acquiring rich photonic information in both scientific research and a wide variety of applications. In this work, we present a new spectrometer with an ultrahigh resolution of better than 0.012 nm/pixel in the 170-600 nm spectral region using a grating-integrated module that consists of 19 subgratings without any moving parts. By using two-dimensional (2D) backsideilluminated complementary metal-oxide-semiconductor (BSI-CMOS) array detector technology with 2048 × 2048 pixels, a high data acquisition speed of approximately 25 spectra per second is achieved. The physical photon-sensing size of the detector along the one-dimensional wavelength direction is enhanced by a factor of 19 to approximately 428 mm, or 38912 pixels, to satisfy the requirement of seamless connection between two neighboring subspectral regions without any missing wavelengths throughout the entire spectral region. As tested with a mercury lamp, the system has advanced performance capabilities characterized by the highest k parameter reported to date, being approximately 3.58 × 104, where k = (working wavelength region)/(pixel resolution). Data calibration and analysis as well as a method of reducing background noise more efficiently are also discussed. The results presented in this work will stimulate further research on precision spectrometers based on advanced BSI-CMOS array detectors in the future.

Identification of differentially expressed long noncoding RNAs in human knee osteoarthritis.

Long noncoding RNAs (lncRNAs) are considered a novel class of regulatory factors in many diseases, but their biological function and the signaling pathway involved in osteoarthritic (OA) remain unknown. To identify the lncRNAs specifically expressed in OA cartilage, the expression of lncRNAs in OA cartilage was measured using an illumina sequencing platform. Furthermore, differentially expressed transcripts of uncertain coding potential (TUCPs) and messenger RNAs (mRNAs) were identified. The colocated target genes and the possible role of lncRNAs as a competing endogenous RNA (ceRNA) were predicted. Based on 19 samples from osteoarthritis patients of knees, 580 significantly dysregulated lncRNAs as well as differently expressed TUCPs and mRNAs were identified. Four differently expressed lncRNAs (SNHG5, ZFAS1, GAS5, and DANCR) involved in OA cartilage were analyzed by protein-protein interactions network and ceRNA regulatory network. Part of our results were consistent with previous studies, and 96 novel differently expressed lncRNAs were identified in OA. These results could expand our knowledge of the OA mechanism.

How hsa-miR-495 performed in the tumorigenesis of pancreatic adenocarcinoma by bioinformatics analysis.

INTRODUCTION: Pancreatic adenocarcinoma (PAAD) is one of the most fatal cancers in the world for early metastasis, extensive invasion, and poor prognosis with a 5-year survival rate less than 5%. However, the underlying mechanisms are poorly understood. Therefore, it is urgent to explore molecular markers for early diagnosis or therapy target to improve the outcome of PAAD. METHODS: We retrieved transcriptome data as well as clinical information from patients with PAAD in The Cancer Genome Altas (TCGA) database. Survival time associated microRNAs (miRNAs) and messenger RNAs (mRNAs) were initially identified, followed by enrichment analysis (Gene Ontology [GO] and pathway). The relationship between survival time associated miRNAs-mRNAs was also investigated to discover putative transcriptional control mechanisms of PAAD. Finally, by consulting the literature and retrieving the database, we found that hsa-miR-495 might have played an important role in PAAD. RESULTS: In total, 146 miRNAs from 378 miRNAs and 580 mRNA from 17 100 mRNA, including 328 risk mRNA and 252 protective mRNA, were found to be associated with the survival time of PAAD. Eight hundred eighty-eight mRNA-miRNA pairs were related to the survival time of PAAD, involving in 755 mRNAs and 35 miRNAs. We chose 13 miRNAs predicted by target gene in the miRanda database for further research. Among these 13 miRNAs, hsa-miR-495 was identified as a good biomarker. Through GO and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis, the significantly enriched pathways involved in focal adhesion, Staphylococcus aureus infection, and Intestinal immune network for immunoglobulin A production. And four target genes and 87 pathways of the hsa-miR-495 were enriched in PAAD. Interestingly, we found hsa-miR-495 with a low expression having a poor overall survival and significantly different recurrence rate within 5 years. CONCLUSION: Hsa-miR-495 and its target genes may serve as a prognostic and predictive marker in PAAD. Further research on the function of the hsa-miR-495 and its target genes in the KEGG pathway may provide references for treatment of PAAD.

miR-93-5p may be an important oncogene in prostate cancer by bioinformatics analysis.

INTRODUCTION: Prostate adenocarcinoma is one of the most prevalent causes of cancer-related deaths in males worldwide. However, the underlying mechanisms remain poorly understood. Hence, it is important to identify specific and effective therapeutic targets, to be able to determine appropriate therapy and management. So, this study aimed to predict that miR-93-5p is an important oncogene in prostate cancer by bioinformatics analysis. METHODS: In this study, initially we identified differentially expressed genes (DEGs) and differently expressed miRNAs (DEMs) in the The Cancer Genome Atlas (TCGA) database, performed Gene Ontology (GO) and pathway enrichment analysis, then investigated the relationship between DEGs and DEMs, and finally through consulting the literature and retrieving the database, we found that miR-93-5p may play a major role in prostate cancer, so we predicted the expression and survival of miR-93-5p and its isomers by bioinformatics analysis, meanwhile, evaluated the function of miR-93-5p in vitro. RESULTS: In total, 104 DEMs were differently expressed between prostate cancer and normal samples, including 56 downregulated ones and 48 upregulated ones; miR-93-5p (upregulated) was identified as a good biomarker. And 1904 DEGs were retrieved, including 794 downregulated ones and 1110 upregulated ones. We also obtained 1254 DEGs of the DEMs. In GO and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis, the significantly enriched pathways involved pathway in focal adhesion, vascular smooth muscle contraction, and regulation of actin cytoskeleton. By the KEGG pathway, we got 16 target genes and 92 pathways of the miR-93-5p in prostate cancer. We also found that the miR-93-5p and its isomers can express in prostate cancer, and which with a high expression had a poor overall survival and a significant difference recurrence rate within 5 years. Further in vitro verification results demonstrated that the low expression of miR-93-5p can inhibit cell proliferation, migration, invasion, change cell cycle, and promote early apoptosis of PC-3 cells. CONCLUSION: The miR-93-5p and its target genes were used to define important molecular targets that could serve as a prognostic and predictive marker in the treatment of prostate cancer. Further research on the function of the miR-93-5p and its target genes in the KEGG pathway could provide references for the treatment of prostate cancer.

A High-Performance Spectrometer with Two Spectral Channels Sharing the Same BSI-CMOS Detector.

Optical spectrometers play an important role in modern scientific research. In this work, we present a two-channel spectrometer with a pixel resolution of better than 0.1 nm/pixel in the wavelength range of 200 to 950 nm and an acquisition speed of approximately 25 spectra per second. The spectrometer reaches a high k factor which characterizes the spectral performance of the spectrometer as k = (working wavelength region)/(pixel resolution) = 7500. Instead of using mechanical moving parts in traditional designs, the spectrometer consists of 8 integrated sub-gratings for diffracting and imaging two sets of 4-folded spectra on the upper and lower parts, respectively, of the focal plane of a two-dimensional backside-illuminated complementary metal-oxide-semiconductor (BSI-CMOS) array detector, which shows a high peak quantum efficiency of approximately 90% at 400 nm. In addition to the advantage of being cost-effective, the compact design of the spectrometer makes it advantageous for applications in which it is desirable to use the same two-dimensional array detector to simultaneously measure multiple spectra under precisely the same working conditions to reduce environmental effects. The performance of the finished spectrometer is tested and confirmed with an Hg-Ar lamp.