Upper tract urothelial carcinoma (UTUC), including renal, pelvic, and ureteral carcinoma, has a high incidence rate in Taiwan, which is different from that in Western countries. Therefore, it is ...imperative to elucidate the mechanisms underlying UTUC growth and metastasis. To explore the function of miR-145-5p in UTUC, we transfected the BFTC909 cell line with miR-145-5p mimics and analyzed the differences in protein levels by performing two-dimensional polyacrylamide gel electrophoresis. Real-time polymerase chain reaction and Western blot analysis were used to analyze 5-aminoimidazole-4-carboxamide ribonucleotide formyltransferase/inositol monophosphate cyclohydrolase (ATIC) messenger RNA and protein levels. A dual-luciferase assay was performed to identify the target of miR-145-5p in ATIC. The effects of miR-145-5p and ATIC expression by cell transfection on cell proliferation, migration, and invasion were also assessed. miR-145-5p downregulated ATIC protein expression. High ATIC expression is associated with tumor stage, metastasis, recurrence, and a poor prognosis in patients with UTUC. Cell function assays revealed that ATIC knockdown inhibited the proliferation, migration, and invasive abilities of UTUC cells. In contrast, miR-145-5p affected the proliferation, migration, and invasive abilities of UTUC cells by directly targeting the 3'-untranslated regions of ATIC. Furthermore, we used RNA sequencing and Ingenuity Pathway Analysis to identify possible downstream genes regulated by ATIC and found that miR-145-5p regulated the protein levels of fibronectin 1, Slug, cyclin A2, cyclin B1, P57, and interferon-induced transmembrane 1 via ATIC. ATIC may be a valuable predictor of prognosis and a potential therapeutic target for UTUC.
ABSTRACT
Innovations in genomics have enabled the development of low‐cost, high‐resolution, single nucleotide polymorphism (SNP) genotyping arrays that accelerate breeding progress and support basic ...research in crop science. Here, we developed and validated the SoySNP618K array (618,888 SNPs) for the important crop soybean. The SNPs were selected from whole‐genome resequencing data containing 2,214 diverse soybean accessions; 29.34% of the SNPs mapped to genic regions representing 86.85% of the 56,044 annotated high‐confidence genes. Identity‐by‐state analyses of 318 soybeans revealed 17 redundant accessions, highlighting the potential of the SoySNP618K array in supporting gene bank management. The patterns of population stratification and genomic regions enriched through domestication were highly consistent with previous findings based on resequencing data, suggesting that the ascertainment bias in the SoySNP618K array was largely compensated for. Genome‐wide association mapping in combination with reported quantitative trait loci enabled fine‐mapping of genes known to influence flowering time, E2 and GmPRR3b, and of a new candidate gene, GmVIP5. Moreover, genomic prediction of flowering and maturity time in 502 recombinant inbred lines was highly accurate (>0.65). Thus, the SoySNP618K array is a valuable genomic tool that can be used to address many questions in applied breeding, germplasm management, and basic crop research.
To accelerate breeding progress and support basic research in soybean, the customized SoySNP618K array contains 618,888 SNPs selected from > 2,000 diverse, re‐sequenced soybean genomes. SoySNP618K is a valuable genomic tool to address questions in applied breeding, germplasm management, and basic research.
A facile and cost-efficient synthesis method for fabricating the low-spin Fe redox-based Prussian blue electrochromic thin film and device, which can selectively and independently modulate the ...visible and near-infrared spectral ranges. The remarkable electrochromic performance, energy storage performance and optical memory effect satisfy the demand for practical smart windows.
Display omitted
Dual-band electrochromic materials (DBEMs) are of utmost importance for smart windows to realize independent control of the visible (VIS) and near-infrared (NIR) light. However, very few single-component DBEMs are capable of independently and effectively controlling both VIS and NIR light. Here, we present Prussian blue (PB) with remarkable performance to replace the composite DBEMs that require deliberate design and complicated preparation. Excellent durability and capacity were achieved simultaneously due to the activated low-spin Fe in PB. A dual-band electrochromic device (DBED) by using PB thin films as electrochromic layers was constructed, exhibiting superior dual-band electrochromic performance, energy storage performance and memory effect. We show that the energy-saving DBED can be bleached without applying any external bias potential, and can be colored by using a commercial photovoltaic solar panel under ambient solar irradiation. The stored energy during coloration can be further used to light up the lights. Finally, the coloration mechanism of the DBED was studied by the density functional theory calculations, to shed light on the large optical transmittance modulation in both VIS and NIR regions. The new insights will advance the design of efficient and durable DBEMs and the development of bi-functional smart windows.
Bone healing in tooth extraction sockets occurs in a complex environment containing saliva and many microorganisms and is affected by many factors. Endoplasmic reticulum (ER) stress affects bone ...metabolism, but the role of ER stress in bone healing after tooth extraction remains unclear. We utilized a rat tooth extraction model, in which we promoted wound healing by using salubrinal to regulate the ER stress response. Western blot analysis showed increased expression of p‐eIF2α/eIF2α, Runx2 and alkaline phosphatase (ALP) in bone tissue, and histological assays showed irregularly arranged and new bone with more collagen fibres 14 days after tooth extraction and after modulating the degree of ER stress. Micro‐CT showed that modulating ER stress to an appropriate degree increases bone filling in regards to the density in the bottom and the surrounding bone wall of the tooth extraction wounds. Transmission electron microscopy showed rough ER expansion and newly formed collagen fibrils in osteoblasts after modulating ER stress to an appropriate degree. We also used different concentrations of salubrinal to evaluate the resistance to tunicamycin‐induced ER stress in an osteogenic induction environment. Salubrinal restored the tunicamycin‐induced decrease in the viability of primary calvarial osteoblasts and increased the expression of Runx2 and ALP, and decreased p‐eIF2α/eIF2α in a dose‐dependent manner. Taken together, the results demonstrate that ER stress occurred after tooth extraction, and regulating the degree of ER stress can promote bone healing in tooth extraction sockets, providing clinical evidence for bone healing.
•4150 blood and 4232 urine samples were collected from 1748 pregnant women.•Urinary 8-OHdG, HNE-MA and 8-isoPGF2α varied greatly across pregnancy.•Blood THMs were positively associated with urinary ...8-OHdG and HNE-MA.•Urinary HAAs were positively associated with 8-OHdG, HNE-MA, and 8-isoPGF2α.
Toxicological studies have demonstrated that disinfection by-products (DBPs) can induce oxidative stress, a proposed mechanism that is relevant to adverse birth outcomes.
To examine the associations of blood trihalomethanes (THMs) and urinary haloacetic acids (HAAs) with urinary biomarkers of oxidative stress among pregnant women.
From 2015 to 2017, a total of 4150 blood and 4232 urine samples were collected from 1748 Chinese women during pregnancy. We determined concentrations of 4 blood THMs chloroform (TCM), bromodichloromethane (BDCM), dibromochloromethane (DBCM), and bromoform (TBM) and 2 urinary HAAs dichloroacetic acid (DCAA) and trichloroacetic acid (TCAA). The summary measures of exposure for brominated THMs (Br-THMs; a molar sum of BDCM, DBCM, and TBM) and total THMs (TTHMs; a molar sum of TCM and Br-THMs) were also calculated. Associations of categorical (i.e., tertiles) and continuous measures of DBPs with urinary concentrations of oxidative stress (OS) biomarkers, 8-hydroxy-2-deoxyguanosine (8-OHdG), 4-hydroxy-2-nonenal-mercapturic acid (HNE-MA), and 8-iso-prostaglandin F2α (8-isoPGF2α), were assessed using linear mixed regression models.
After adjusting for relevant confounding factors, we observed positive dose-response relationships between blood Br-THM tertiles and urinary HNE-MA (P for trend < 0.001). We also found positive associations between tertiles of blood TCM and TTHMs and urinary 8-OHdG and HNE-MA (all P for trend < 0.05). Urinary HAAs were also positively associated with 8-OHdG, HNE-MA, and 8-isoPGF2α in a dose-response manner (all P for trend < 0.001). These associations were further confirmed when we modeled DBP exposures as continuous variables in linear mixed regression models, as well as in penalized regression splines based on generalized additive mixed models.
Exposure to DBPs during pregnancy may increase maternal OS status.
Neuropeptides are ubiquitous intercellular signaling molecules in the CNS and play diverse roles in modulating physiological functions by acting on specific G-protein coupled receptors (GPCRs). Among ...them, the elevenin signaling system is now believed to be present primarily in protostomes. Although elevenin was first identified from the L11 neuron of the abdominal ganglion in mollusc Aplysia californica, no receptors have been described in Aplysia, nor in any other molluscs. Here, using two elevenin receptors in annelid Platynereis dumerilii, we found three putative elevenin GPCRs in Aplysia. We cloned the three receptors and tentatively named them apElevR1, apElevR2, and apElevR3. Using an inositol monophosphate (IP1) accumulation assay, we demonstrated that Aplysia elevenin with the disulfide bond activated the three putative receptors with low EC50 values (ranging from 1.2 to 25 nM), supporting that they are true receptors for elevenin. In contrast, elevenin without the disulfide bond could not activate the receptors, indicating that the disulfide bond is required for receptor activity. Using alanine substitution of individual conserved residues other than the two cysteines, we showed that these residues appear to be critical to receptor activity, and the three different receptors had different sensitivities to the single residue substitution. Finally, we examined the roles of those residues outside the disulfide bond ring by removing these residues and found that they also appeared to be important to receptor activity. Thus, our study provides an important basis for further study of the functions of elevenin and its receptors in Aplysia and other molluscs.
Patients with Philadelphia chromosome‐like acute lymphoblastic leukaemia (Ph‐like ALL) often face a grim prognosis, with PDGFRB gene fusions being commonly detected in this subgroup. Our study has ...unveiled a newfound fusion gene, TERF2::PDGFRB, and we have found that patients carrying this fusion gene exhibit sensitivity to dasatinib. Ba/F3 cells harbouring the TERF2::PDGFRB fusion display IL‐3‐independent cell proliferation through activation of the p‐PDGFRB and p‐STAT5 signalling pathways. These cells exhibit reduced apoptosis and demonstrate sensitivity to imatinib in vitro. When transfused into mice, Ba/F3 cells with the TERF2::PDGFRB fusion gene induce tumorigenesis and a shortened lifespan in cell‐derived graft models, but this outcome can be improved with imatinib treatment. In summary, we have identified the novel TERF2::PDGFRB fusion gene, which exhibits oncogenic potential both in vitro and in vivo, making it a potential therapeutic target for tyrosine kinase inhibitors (TKIs).
Beta-transducin repeat containing E3 ubiquitin protein ligase (BTRC) is crucial for the degradation of IκBα. Our previous transcriptome sequencing analysis revealed that tetraspanin 15 (TSPAN15) was ...significantly upregulated in clinical oesophageal squamous cell carcinoma (OSCC) tissues. Here, we show that high TSPAN15 expression in OSCC tissues is significantly associated with lymph node and distant metastasis, advanced clinical stage, and poor prognosis. Elevated TSPAN15 expression is, in part, caused by the reduction of miR-339-5p. Functional studies demonstrate that TSPAN15 promotes metastatic capabilities of OSCC cells. We further show that TSPAN15 specifically interacts with BTRC to promote the ubiquitination and proteasomal degradation of p-IκBα, and thereby triggers NF-κB nuclear translocation and subsequent activation of transcription of several metastasis-related genes, including ICAM1, VCAM1, uPA, MMP9, TNFα, and CCL2. Collectively, our findings indicate that TSPAN15 may serve as a new biomarker and/or provide a novel therapeutic target to OSCC patients.
Epigenetic modifications such as histone modifications and cytosine hydroxymethylation are linked to tumorigenesis. Loss of 5‐hydroxymethylcytosine (5 hmC) by ten‐eleven translocation 1 (TET1) ...down‐regulation facilitates tumor initiation and development. However, the mechanisms by which loss of TET1 knockdown promotes malignancy development remains unclear. Here, we report that TET1 knockdown induced epithelial‐mesenchymal transition (EMT) and increased cancer cell growth, migration, and invasion in DLD1 cells. Loss of TET1 increased EZH2 expression and reduced UTX‐1 expression, thus increasing histone H3K27 tri‐methylation causing repression of the target gene E‐cadherin. Ectopic expression of the H3K27 demethylase UTX‐1 or EZH2 depletion both impeded EZH2 binding caused a loss of H3K27 methylation at epithelial gene E‐cadherin promoter, thereby suppressing EMT and tumor invasion in shTET1 cells. Conversely, UTX‐1 depletion and ectopic expression of EZH2 enhanced EMT and tumor metastasis in DLD1 cells. These findings provide insight into the regulation of TET1 and E‐cadherin and identify EZH2 as a critical mediator of E‐cadherin repression and tumor progression.
TET1 depletion promoted cancer cell proliferation, migration, and invasion in DLD1 cells. TET1 depletion induced epithelial‐mesenchymal transition (EMT) in DLD1 cells. Modulation of H3K27me3 as a result of TET1 knockdown promotes DLD1 cancer cell migration.
Tomato (Lycopersicon esculentum Miller) cv. Jiahe No. 9 (a salinity-resistant cultivar) and cv. Shuangfeng 87-5 (a salinity-sensitive cultivar) were used as experimental materials to investigate the ...effects of exogenous selenium (Na₂SeO₃ 0.05 mM) on plant growth, chlorophyll fluorescence, photosynthetic rate, and antioxidative metabolism of chloroplasts in tomato seedlings under NaCl (100 mM) stress. Salt stress significantly inhibited plant growth, net photosynthetic rate (P ₙ), maximum quantum yield of PSII (F ᵥ/F ₘ), actual photochemical efficiency of PSII (Φ PSII), photochemical quenching coefficient (q P), and non-photochemical quenching coefficient (q N) of both cultivars, whereas application of Se reversed the negative effects of salt stress. Furthermore, application of Se significantly decreased the levels of hydrogen peroxide (H₂O₂) and malondialdehyde. Application of Se increased the activities of superoxidase dismutase, glutathione reductase, dehydroascorbate reductase, monodehydroascorbate reductase, glutathione peroxidase, and thioredoxin reductase, and the contents of ascorbate, glutathione (GSH) and NADPH, and the ratios of GSH/GSSH, AsA/DHA, and NADPH/ NADP⁺ in the salt-stressed chloroplasts of both cultivars. These results suggest that Se alleviates salt-induced oxidative stress through regulating the antioxidant defense systems in the chloroplasts of tomato seedlings, which is associated with the improvement of the photochemical efficiency of PSII, thereby maintaining higher photosynthetic rates. In addition, the salt tolerance of Jiahe No. 9 is closely related with high reactive oxygen species scavenging activity and reducing power levels in the chloroplasts.
PDF
