ADDP: Anomaly Detection based on Denoising Pretraining

    Acquiring labels in anomaly detection tasks is expensive and challenging. Therefore, as an effective way to improve efficiency, pretraining is widely used in anomaly detection models， which enriches the model's representation capabilities, thereby enhancing both performance and efficiency in anomaly detection. In most pretraining methods, the decoder is typically randomly initialized. Drawing inspiration from the diffusion model, this paper proposed to use denoising as a task to pretrain the decoder in anomaly detection, which is trained to reconstruct the original noise-free input. Denoising requires the model to learn the structure, patterns, and related features of the data, particularly when training samples are limited. This paper explored two approaches on anomaly detection: simultaneous denoising pretraining for encoder and decoder, denoising pretraining for only decoder. Experimental results demonstrate the effectiveness of this method on improving model’s performance. Particularly, when the number of samples is limited, the improvement is more pronounced

Bis[1-hydroxy­ethyl­idenediphosphon­ato(1−)](1,10-phenanthroline)nickel(II) mono­hydrate

In the mononuclear title compound, [Ni(C2H6O7P2)2(C12H8N2)]·H2O, the NiII atom (site symmetry 2) is bonded to two phosphate-based O,O′-bidentate chelate ligands and one N,N′-bidentate 1,10-phenanthroline ligand, resulting in a slightly distorted cis-NiN2O4 octa­hedral geometry. In the crystal structure, pairs of complexes are linked by double hydrogen bonds, forming a one-dimensional chain-like structure. Aromatic π–π stacking inter­actions [centroid–centroid separation = 3.768 (2) Å] and further hydrogen bonds generate a two-dimensional structure. The water O atom also lies on a crystallographic twofold axis

Changes of Acylating Stimulating Protein (ASP) and Blood Lipid in Patients with Acute Myocardial Infarction

Objective: To study the changes of acylating stimulating protein (ASP) and blood lipid in patients with acute myocardial infarction. Method: There were three groups,25 cases of acute myocardial infarction patients (acute myocardial infarction group), 32 cases of coronary heart disease patients without myocardial infarction (CHD group) and 30 cases of healthy people (control group). They respectively detected the ASP, low density lipoprotein cholesterol (LDL-C), triglyceride (TG), total cholesterol (TC) and high-density lipoprotein cholesterol (HDL-C), and analyzed the correlation between them. Results: (1) ASP, TG, TC and LDL-C of acute myocardial infarction group and coronary heart disease group were significantly higher than those of control group, while HDL-C was lower than control group, the difference was statistically significant (P < 0.05). (2) TG in coronary heart disease group was higher than that in acute myocardial infarction group, while ASP, TC, LDL-C and HDL-C had no significant difference. Conclusion: ASP and blood lipid are risk factors of CHD, ASP can be used as risk index of CHD. There was no significant difference in plasma ASP between patients with acute myocardial infarction and patients with coronary heart disease without myocardial infarction. ASP cannot be used as a surrogate marker of acute myocardial infarction

Effects of lncRNA PKD2-2-3 on cell proliferation, clone formation, migration, and invasion of lung adenocarcinoma

Background and purpose: Long non-coding RNA (lncRNA) is abnormally expressed in lung adenocarcinoma patients, and closely related to tumor occurrence, development and chemotherapy resistance. In this study, we mainly investigated the biological function of lncRNA PKD2-2-3 and verified its effect on the proliferation, colony formation, migration and invasion in lung adenocarcinoma. Methods: Three pairs of lung adenocarcinoma tissues and adjacent tissues were analyzed based on expression profiling Affymetrix® GeneChip Human Transcriptome Array 2.0 (HTA2.0), and we focused on lncRNA PKD2-2-3 that showed most significant difference between lung adenocarcinoma issues and adjacent tissues. Besides, we found the upregulated expression of lncRNA PKD2-2-3 in lung adenocarcinoma tissues and suggested the relation of lncRNA PKD2-2-3 expression with prognosis by using GSE19188 and GSE30219 data in Gene Expression Omnibus (GEO) database. Real-time fluorescence quantitative polymerase chain reaction (RTFQ-PCR) was used to detect the expression of lncRNA PKD2-2-3 in cell lines including HBE, A549 and PC9. After using siRNAs to decrease the expression of lncRNA PKD2-2-3 in A549 and PC9, we detected cell proliferation and colony formation by cell counting kit-8 (CCK-8) assay and colony formation assay. Effects of lncRNA PKD2-2-3 on migration and invasion in lung adenocarcinoma cells were detected by wound-healing assay and transwell assay, respectively. Moreover, we detected expression levels of E-cadherin and N-cadherin that were epithelial-mesenchymal transition (EMT) related genes by Western blot. The effect of lncRNA PKD2-2-3 on the formation and growth of lung adenocarcinoma in vivo was verified by subcutaneous transplantation tumor model. Results: LncRNA PKD2-2-3 was highly expressed in lung adenocarcinoma tissue, and was positively associated with poor prognosis of lung adenocarcinoma patients. Compared with human bronchial epithelial cells (HBE), lncRNA PKD2-2-3 was overexpressed in A549 and PC9. The proliferation, colony formation, migration and invasion of lung adenocarcinoma cells were significantly inhibited when decreasing the expression level of lncRNA PKD2-2-3. Western blot also showed that the expression level of E-cadherin was increased, while the level of N-cadherin was decreased after lncRNA PKD2-2-3 knockdown. Subcutaneous tumor transplantation experiments showed that lncRNA PKD2-2-3 knockdown inhibited the growth of lung adenocarcinoma in vivo. Conclusion: LncRNA PKD2-2-3 expression was upregulated in lung adenocarcinoma tissues, and it was associated with poor prognosis of lung adenocarcinoma patients. Overexpression of lncRNA PKD2-2-3 promoted the proliferation, colony formation, migration and invasion of lung adenocarcinoma cells. LncRNA PKD2-2-3 level was closely related to EMT process in lung adenocarcinoma in vitro and in vivo

Missense-depleted regions in population exomes implicate ras superfamily nucleotide-binding protein alteration in patients with brain malformation.

Genomic sequence interpretation can miss clinically relevant missense variants for several reasons. Rare missense variants are numerous in the exome and difficult to prioritise. Affected genes may also not have existing disease association. To improve variant prioritisation, we leverage population exome data to identify intragenic missense-depleted regions (MDRs) genome-wide that may be important in disease. We then use missense depletion analyses to help prioritise undiagnosed disease exome variants. We demonstrate application of this strategy to identify a novel gene association for human brain malformation. We identified de novo missense variants that affect the GDP/GTP-binding site of ARF1 in three unrelated patients. Corresponding functional analysis suggests ARF1 GDP/GTP-activation is affected by the specific missense mutations associated with heterotopia. These findings expand the genetic pathway underpinning neurologic disease that classically includes FLNA. ARF1 along with ARFGEF2 add further evidence implicating ARF/GEFs in the brain. Using functional ontology, top MDR-containing genes were highly enriched for nucleotide-binding function, suggesting these may be candidates for human disease. Routine consideration of MDR in the interpretation of exome data for rare diseases may help identify strong genetic factors for many severe conditions, infertility/reduction in reproductive capability, and embryonic conditions contributing to preterm loss

KMT2A promotes melanoma cell growth by targeting hTERT signaling pathway.

Melanoma is an aggressive cutaneous malignancy, illuminating the exact mechanisms and finding novel therapeutic targets are urgently needed. In this study, we identified KMT2A as a potential target, which promoted the growth of human melanoma cells. KMT2A knockdown significantly inhibited cell viability and cell migration and induced apoptosis, whereas KMT2A overexpression effectively promoted cell proliferation in various melanoma cell lines. Further study showed that KMT2A regulated melanoma cell growth by targeting the hTERT-dependent signal pathway. Knockdown of KMT2A markedly inhibited the promoter activity and expression of hTERT, and hTERT overexpression rescued the viability inhibition caused by KMT2A knockdown. Moreover, KMT2A knockdown suppressed tumorsphere formation and the expression of cancer stem cell markers, which was also reversed by hTERT overexpression. In addition, the results from a xenograft mouse model confirmed that KMT2A promoted melanoma growth via hTERT signaling. Finally, analyses of clinical samples demonstrated that the expression of KMT2A and hTERT were positively correlated in melanoma tumor tissues, and KMT2A high expression predicted poor prognosis in melanoma patients. Collectively, our results indicate that KMT2A promotes melanoma growth by activating the hTERT signaling, suggesting that the KMT2A/hTERT signaling pathway may be a potential therapeutic target for melanoma

JAG1 is correlated to suppressive immune microenvironment and predicts immunotherapy resistance in lung adenocarcinoma

BackgroundThe current exploration of the tumor immune microenvironment is enthusiastic, but few studies explored the impact of angiogenesis on the immune microenvironment. Immunotherapy combined with anti-angiogenesis therapy has become one of the first-line treatment for lung adenocarcinoma. Our study aimed to explore the reasons for resistance of immunotherapy, and explore markers for immunotherapy combined with anti-angiogenesis therapy.MethodsFirst, by unsupervised clustering of 36 angiogenesis-related genes in lung adenocarcinoma patients from TCGA database, AGS1 and AGS2 groups were distinguished with significantly different clinical outcomes. Secondly, the immune microenvironment and metabolic characteristics were analyzed. Next, we used the GDSC and GEO database to analyze therapeutic responses. Then, through multivariate Cox regression, the hub gene: JAG1, significantly related to prognosis was selected, and further verified by multi-omics data. Finally, we validated that patient with high JAG1 expression had a low immune-infiltrating tumor microenvironment through single-cell transcriptomic data.ResultsCompared with the AGS1 group, AGS2 showed an immune “cold” phenotype with lower lymphocyte infiltration, and was associated with worse prognoses. At the same time, the immunosuppressive TGF-β response was significantly higher in AGS2. Furthermore, the glycolysis ability of the AGS2 was stronger than AGS1. The expression of JAG1 was significantly higher in the AGS2, and was significantly negatively correlated with the degree of immune infiltration, accompanying with higher glycolytic capacity. The above results indicate that patients with high expression of JAG1 may lead to immunosuppressive phenotype due to its strong glycolytic capacity, thus making immunotherapy resistance.ConclusionPatients with high expression of JAG1 enhanced glycolytic capacity was likely to cause suppressed immune microenvironment. JAG1 may be a marker for resistance of immunotherapy. Combining anti-angiogenesis therapy could be considered to improve the prognosis of those patients