The epithelial-mesenchymal transition (EMT) is a key hallmark of cancer which promotes malignant progression, especially during the process of cancer invasion. A better understanding of EMT will help elucidate the molecular mechanism underlying colorectal cancer (CRC) metastasis and may provide new insights into the identification of potential biomarkers and therapeutic targets.

Abnormal expression of noncoding RNA molecules such as circRNA plays an important role in the development of malignant tumors. circRNAs are stable in structure and can be useful as ideal tumor markers. Advanced bladder cancer has poor treatment options and prognosis. Thus, we examined circRNAs to further understand the pathogenesis and development of bladder cancer and to identify molecular markers for the early diagnosis of bladder carcinoma. We found that hsa_circ_0018069 was differentially expressed in our RNA sequencing data. We used qRT-PCR to detect its expression in T24 and Biu-87 cell lines and in 41 paired samples of bladder cancer and adjacent normal tissue and analyzed the correlation between expression of hsa_circ_0018069 and the clinical characteristics of patients with bladder cancer. We then performed a bioinformatics analysis to reveal the mechanism of hsa_circ_0018069 in tumorigenesis of bladder cancer. The expression of hsa_circ_0018069 was significantly reduced in T24 and Biu-87 cells and was also significantly downregulated in bladder cancer tissues. Decreased expression of hsa_circ_0018069 was related to the grade stage (P=0.024), T stage (P=0.027), and muscular invasion depth (P=0.022) of bladder cancer. Bioinformatics analysis showed that hsa_circ_0018069 was coexpressed with protein-coding mRNAs that participate in cytoskeletal protein binding and cell-substrate junction assembly and play an anticancer role through focal adhesion and calcium signaling pathways. ceRNA analysis showed that hsa_circ_0018069 functions in ErbB, Ras, FoxO, and the focal adhesion signaling pathway by harboring miR-23c, miR-34a-5p, miR-181b-5p, miR-454-3p, and miR-3666. hsa_circ_0018069 may thus play an important role in the occurrence and progression of bladder cancer and serve as a valuable biomarker for the early diagnosis of this disease.

Preeclampsia (PE) is a pregnancy-specific hypertension syndrome and is one of the leading causes of maternal and perinatal morbidity and mortality. Long noncoding RNAs (lncRNAs) have been reported to be abnormally expressed in many diseases, including preeclampsia. The present study is aimed at identifying the key genes and lncRNA-associated competing endogenous RNA (ceRNA) networks in early-onset preeclampsia (EOPE).

Gestational trophoblastic neoplasia (GTN) originates from placental tissue and exhibits the potential for invasion and metastasis. Gene alterations in GTN have not been extensively studied because of a lack of qualified tumor specimens after chemotherapy. GTN has a rapid growth rate and is highly metastatic, which makes circulating tumor DNA (ctDNA) sequencing a promising modality for gene profiling. Accordingly, in this study, we performed targeted next-generation sequencing (NGS) of 559 tumor-associated genes using circulating cell-free DNA (cfDNA) collected prior to chemotherapy from 11 patients with GTN. All sequenced genes were associated with oncogenesis, progression, and targeted therapy. The average cfDNA level was 0.43 ± 0.22 ng/μL. Significant correlations were found between cfDNA concentration and maximum lesion diameter (r = 0.625, p=0.040) and time for human chorionic gonadotropin beta subunit (β-HCG) recovering to normal level (r = 0.609, p=0.047). There were no significant correlations between cfDNA concentrations and β-HCG expression level or lung metastasis. ctDNA mutations were detected in all patients, and 73 mutant genes were detected in 11 patients. BMPR1A (27.3%), LRP1B (27.3%), ERCC4 (18.2%), FGF14 (18.2%), HSP90AA1 (18.2%), KAT6A (18.2%), KMT2D (18.2%), MAP3K1 (18.2%), RANBP2 (18.2%), and ZNF217 (18.2%) mutations were detected as overlapping mutations. The mRNA and protein levels of bone morphogenetic protein receptor type 1A were significantly downregulated in human JAR and JEG-3 choriocarcinoma cells (p < 0.0001), whereas mRNA and protein levels of mitogen-activated protein kinase kinase kinase 1 were upregulated in these two cell lines (p=0.0128, p=0.0012, respectively). These genes may play important roles in GTN initiation and progression and may be candidate targets for GTN treatment. These findings suggested that cfDNA levels could provide potential assessment value in disease severity of GTN and that ctDNA sequencing was a promising approach for identifying gene mutations in GTN.

Alcoholic liver injury is a major global public health concern at present. The ADAM9 gene plays a crucial role in the occurrence and development of various liver diseases, but its role in acute alcoholic liver injury remains ambiguous. In this study, a chimeric single-guide RNA targeting the genomic regions of mouse ADAM9 was designed using the clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein 9 (Cas9) technology. Next, the role of ADAM9 in acute alcoholic liver injury in vitro in cultured mouse cells and in vivo in a hydrodynamic injection-based alcoholic liver injury mouse model was documented. The findings of this study suggest that ADAM9 induces by regulating cell proliferation, apoptosis, and stress metabolism in mice. Thus, inhibiting the expression of ADAM9 gene using CRISPR/Cas9 can attenuate alcohol-induced acute liver injury in mice.

Inadequate oxygen availability at high altitude leads to oxidative stress, resulting in hippocampal neurodegeneration and memory impairment. In our previous study, we found that the cognitive dysfunction occurred when male SD rat was rapidly exposed to 4200 m of high altitude for 3 days. And we also found that crocin showed a cognitive protective effect under hypoxia by regulating SIRT1/PGC-1α pathways in rat's hippocampus. In this article, focused on factors related to SIRT1/PGC-1α pathways, we proposed to further elucidate crocin's pharmacological mechanism. Adult male Sprague-Dawley rats were randomly divided into five groups: control group, hypoxia group (rats were rapidly transported to high altitude of 4200 m for 72 h), and crocins+hypoxia groups (pretreatment with crocin of 25, 50, and 100 mg/kg/d for 3 days). The learning and memory ability was tested by Morris water maze analysis. Hippocampal histopathological changes were observed by HE staining and Nissl staining. The expression of NRF1, TFAM, Bcl-2, Bax, and caspase-3 was detected by immunohistochemistry, RT-PCR, and western blotting test. The contents of malondialdehyde (MDA), superoxide dismutase (SOD), glutathione (GSH), and glutathione peroxidase (GSHPx) were detected by the TBA, WST, and colorimetry method. Neuronal apoptosis was observed by TUNEL staining. After crocin pretreatment, the traveled distance was significantly reduced and the percentage of time in the target quadrant was significantly increased tested by Morris water maze. And neuronal damage in the hippocampus was also significantly ameliorated based on HE staining and Nissl staining. Furthermore, in hippocampus tissue, mitochondrial biosynthesis-related factors of NRF1, TFAM expression was increased; oxidative stress factors of SOD, GSH, and GSHPx expression level were increased, and MDA and glutathione disulfide (GSSG) level were decreased; antiapoptotic protein Bcl-2 expression was increased, and proapoptotic proteins Bax and caspase-3 expression were decreased, with a manner of crocin dose dependent. Therefore, the cognitive protective mechanism of crocin in rat under acute hypoxia was related to promoting mitochondrial biosynthesis, ameliorating oxidative stress injury, and decreasing neuronal apoptosis.

New high-throughput technique ChIP-seq, coupling chromatin immunoprecipitation experiment with high-throughput sequencing technologies, has extended the identification of binding locations of a transcription factor to the genome-wide regions. However, the most existing motif discovery algorithms are time-consuming and limited to identify binding motifs in ChIP-seq data which normally has the significant characteristics of large scale data. In order to improve the efficiency, we propose a fast cluster motif finding algorithm, named as FCmotif, to identify the (l,  d) motifs in large scale ChIP-seq data set. It is inspired by the emerging substrings mining strategy to find the enriched substrings and then searching the neighborhood instances to construct PWM and cluster motifs in different length. FCmotif is not following the OOPS model constraint and can find long motifs. The effectiveness of proposed algorithm has been proved by experiments on the ChIP-seq data sets from mouse ES cells. The whole detection of the real binding motifs and processing of the full size data of several megabytes finished in a few minutes. The experimental results show that FCmotif has advantageous to deal with the (l,  d) motif finding in the ChIP-seq data; meanwhile it also demonstrates better performance than other current widely-used algorithms such as MEME, Weeder, ChIPMunk, and DREME.

The K+ transporter/high-affinity K+/K+ uptake (KT/HAK/KUP) transporters dominate K+ uptake, transport, and allocation that play a pivotal role in mineral homeostasis and plant adaptation to adverse abiotic stresses. However, molecular mechanisms towards K+ nutrition in forest trees are extremely rare, especially in willow. In this study, we identified 22 KT/HAK/KUP transporter genes in purple osier willow (designated as SpuHAK1 to SpuHAK22) and examined their expression under K+ deficiency, drought, and salt stress conditions. Both transcriptomic and quantitative real-time PCR (qRT-PCR) analyses demonstrated that SpuHAKs were predominantly expressed in stems, and the expression levels of SpuHAK1, SpuHAK2, SpuHAK3, SpuHAK7, and SpuHAK8 were higher at the whole plant level, whereas SpuHAK9, SpuHAK11, SpuHAK20, and SpuHAK22 were hardly detected in tested tissues. In addition, both K+ deficiency and salt stress decreased the tissue K+ content, while drought increased the tissue K+ content in purple osier plant. Moreover, SpuHAK genes were differentially responsive to K+ deficiency, drought, and salt stresses in roots. K+ deficiency and salt stress mainly enhanced the expression level of responsive SpuHAK genes. Fifteen putative cis-acting regulatory elements, including the stress response, hormone response, circadian regulation, and nutrition and development, were identified in the promoter region of SpuHAK genes. Our findings provide a foundation for further functional characterization of KT/HAK/KUP transporters in forest trees and may be useful for breeding willow rootstocks that utilize potassium more efficiently.

Lung cancer is the most important cause of cancer mortality worldwide, but the underlying mechanisms of this disease are not fully understood. Copy number variations (CNVs) are promising genetic variations to study because of their potential effects on cancer.

Mycosis fungoides (MF) is the most common T-cell lymphoma, with indolent biologic behavior in the early stage and features of invasive in the tumor stage. The diagnosis of MF is still ambiguous and difficult. We focused on the proteomic profiling change in the pathogenesis of early MF and identified candidate biomarkers for early diagnosis.