Vacuum compatible vertical-laser alignment method based on an oil mirror and air-spaced doublets.

In the field of precision measurement and metrology, a vertical laser is a valuable measurement tool. Its applications include, but are not limited to, the measurement of vertical displacement and attitude in the Kibble balance and joule balance for kilogram realization. A vacuum compatible, vertical-laser alignment method based on an oil mirror and air-spaced doublets is proposed to measure and compensate the vertical deviation angle of the laser beams. Dimethyl silicone oil was selected as the natural direction reference, and the air-spaced doublets were designed as the focusing elements to make the deviation angle correspond to a distance of spots. The corresponding alignment system is vacuum compatible, nonmagnetic, and can be miniaturized. In addition to the mass traceability in the realization of a kilogram, this system can also be applied to the gravity measurements of outer space planets in the field of aerospace science. The off-axis error, which is the highly influential systematic error of the alignment system, is suppressed by replacing the plano-convex lens with a combined optical element-"air-spaced doublets+aperture." The performance of the alignment system has been investigated by experiments. The Type B uncertainty of the alignment system was evaluated to be 19.19 µrad.

Thrombo-Inflammation and Immunological Response in Ischemic Stroke: Focusing on Platelet-Tregs Interaction.

Strokes are mainly caused by thromboembolic obstruction of a major cerebral artery. Major clinical manifestations include paralysis hemiplegia, aphasia, memory, and learning disorders. In the case of ischemic stroke (IS), hyperactive platelets contribute to advancing an acute thrombotic event progression. Therefore, the principal goal of treatment is to recanalize the occluded vessel and restore cerebral blood flow by thrombolysis or mechanical thrombectomy. However, antiplatelets or thrombolytic therapy may increase the risk of bleeding. Beyond the involvement in thrombosis, platelets also contribute to the inflammatory process induced by cerebral ischemia. Platelet-mediated thrombosis and inflammation in IS lie primarily in the interaction of platelet receptors with endothelial cells and immune cells, including T-cells, monocytes/macrophages, and neutrophils. Following revascularization, intervention with conventional antiplatelet medicines such as aspirin or clopidogrel does not substantially diminish infarct development, most likely due to the limited effects on the thrombo-inflammation process. Emerging evidence has shown that T cells, especially regulatory T cells (Tregs), maintain immune homeostasis and suppress immune responses, playing a critical immunomodulatory role in ischemia-reperfusion injury. Hence, considering the deleterious effects of inflammatory and immune responses, there is an urgent need for more targeted agents to limit the thrombotic-inflammatory activity of platelets and minimize the risk of a cerebral hemorrhage. This review highlights the involvement of platelets in neuroinflammation and the evolving role of Tregs and platelets in IS. In response to all issues, preclinical and clinical strategies should generate more viable therapeutics for preventing and managing IS with immunotherapy targeting platelets and Tregs.

Inhalation Aromatherapy via Brain-Targeted Nasal Delivery: Natural Volatiles or Essential Oils on Mood Disorders.

Mood disorders, also often referred to as affective disorders, are a group of psychiatric illnesses that severely impact mood and its related functions. The high medical expenditures have placed a significant financial burden on patients and their families. Aromatherapy is an alternative and complementary treatment that utilizes essential oils (EOs) or volatile oils (VOs) to achieve major therapeutic goals. In general, EOs are volatile chemicals that enter the body primarily through skin absorption and/or nasal inhalation. In addition, they can work through oral administration. Inhalation aromatherapy has shown unique advantages for treating mood disorders, especially depression, anxiety and mental disorders such as sleep disorder, which have been validated over the last decade through clinical and animal studies. Accumulating evidence has shown that EOs or VOs can bypass the blood-brain barrier to target brain tissue through the nasal-brain pathway. Subsequently, they act on the cerebral cortex, thalamus, and limbic system in the brain to improve symptoms of anxiety, depression and improve sleep quality. Here, we review the natural aromatic plants' volatiles or essential oils used commonly as adjuncts to manage mood disorders and illustrate the mechanisms of inhalation aromatherapy, and mainly summarized the application of transnasal inhalation aromatherapy in depression, anxiety, and sleep disorders. We conclude that aromatherapy does not cause side-effects, which is vastly different from commonly used psychotropic drugs. Inhalation aromatherapy via brain-targeted nasal delivery offers potentially efficacious treatment for mental disorders and merits further study.

Copper Nanocomposites In Situ Formed from Metallic Glasses for an Efficient Catalytic Performance.

Metallic glasses (MGs) with the unique long-range disordered and short-range ordered atomic structure have attracted extensive attention in the field of environmental catalysis due to their advanced catalytic capability. Herein, CuZr-based MGs are first proven to exhibit superior catalytic performance toward the degradation of organic pollutants compared to the annealed ribbons with different crystal structures; many Cu nanocomposites are gradually in situ precipitated on the surface of the ribbons. The enhanced catalytic behavior is mainly attributed to the random atomic packing structure accelerating electron transport and providing sufficient active sites. On the other hand, the active species, for example, ·OH, ·O2-, and Cu(III), are generated through an activation reaction between Cu/Cu2O nanocomposites and H2O2 molecules for the catalytic degradation process. Additionally, further investigation indicated that CuZr-based MGs also present superior stability and durability along with an approximate 96% degradation efficiency within 10 min at the 10th run. This research can successfully explain why MGs have a little higher catalytic reactivity than their crystalline counterparts, and more importantly, it will provide a new strategy for the preparation of catalytic materials for wastewater treatment.

A Novel Real-Time Reverse Transcription Loop-Mediated Isothermal Amplification Detection Platform: Application to Diagnosis of COVID-19.

The ongoing Corona virus disease (COVID-19) outbreak has become a huge global health concern. Here, we reported a novel detection platform based on the loop-mediated isothermal amplification (LAMP), termed real-time reverse transcription LAMP (rRT-LAMP) and applied it for the diagnosis of COVID-19 (COVID-19 rRT-LAMP). rRT-LAMP integrates reverse transcription, LAMP amplification, restriction endonuclease cleavage and real-time fluorescence detection into one-pot reaction, and facilitates the diagnosis of COVID-19 at 64°C for only 35 min. The ORF1ab (opening reading frame 1a/b) and NP (nucleoprotein) genes of SARS-CoV-2 were detected for diagnosing COVID-19. The limit of detection (LoD) of COVID-19 rRT-LAMP assay was 14 copies (for each marker) per vessel, and no positive results were obtained from non-SARS-CoV-2 templates. To demonstrate its feasibility, a total of 33 oropharynx swab samples collected from COVID-19 patients also were diagnosed as SARS-CoV-2 infection using COVID-19 rRT-LAMP protocol. No cross-reactivity was yielded from 41 oropharynx swab samples collected from non-COVID-19 patients. These data suggesting that the COVID-19 rRT-LAMP assay is a potential detection tool for the diagnosis of SARS-CoV-2 infection in clinical, field and disease control laboratories, and will be valuable for controlling the COVID-19 epidemic.

Role of Long Non-coding RNAs on Bladder Cancer.

Bladder cancer (BC) is the most common malignant tumor in the urinary system, and its early diagnosis is conducive to improving clinical prognosis and prolonging overall survival time. However, few biomarkers with high sensitivity and specificity are used as diagnostic markers for BC. Multiple long non-coding RNAs (lncRNAs) are abnormally expressed in BC, and play key roles in tumorigenesis, progression and prognosis of BC. In this review, we summarize the expression, function, molecular mechanisms and the clinical significance of lncRNAs on bladder cancer. There are more than 100 dysregulated lncRNAs in BC, which are involved in the regulation of proliferation, cell cycle, apoptosis, migration, invasion, metabolism and drug resistance of BC. Meanwhile, the molecular mechanisms of lncRNAs in BC was explored, including lncRNAs interacting with DNA, RNA and proteins. Additionally, the abnormal expression of thirty-six lncRNAs is closely associated with multiple clinical characteristics of BC, including tumor size, metastasis, invasion, and drug sensitivity or resistance of BC. Furthermore, we summarize some potential diagnostic and prognostic biomarkers of lncRNA for BC. This review provides promising novel biomarkers in early diagnosis, prognosis and monitoring of BC based on lncRNAs.

Effect of Strain Rate on Compressive Behavior of a Zr-Based Metallic Glass under a Wide Range of Strain Rates.

The strain rate effect on the mechanical behavior of amorphous alloys has aroused general interest. Most studies in this area have focused on quasi-static and high strain-rate compressive deformations. However, experimental results have been few, or even non-existent, under a moderate strain-rate loading. This article extends the traditional split Hopkinson pressure bar (SHPB) technique to characterize compressive deformation of an amorphous alloy at medium strain rates. The compressive behavior of Zr65.25Cu21.75Al8Ni4Nb1 amorphous alloy shows a negative strain rate effect on the yield strength with a quasi-static, moderate to high strain-rate range, and the fracture angle increases from 44° at 10-5 s-1 to 60° at 4000 s-1 as strain rate increases. Herein, we introduce a modified cooperative shear model to describe the compressive behavior of the current amorphous alloy under a broad strain rate range. The model predicts that the normalized yield strength will linearly descend with logarithmic strain rate when the strain rate is less than a critical strain rate, however, which rapidly decreases linearly with the square of the strain rate at high strain rates. The predicted data of the model are highly consistent with the current experimental results. These findings provide support for future engineering applications of amorphous alloys.

[Hydrogen water alleviates paraquat-induced lung fibroblast injury in vitro by enhancing Nrf2 expression].

OBJECTIVE: To investigate the effects of hydrogen water on proliferation, differentiation, collagen secretion and Nrf2 expression in paraquat-induced human lung fibroblasts. METHODS: In vitro cultured human lung fibroblasts (HFL1) exposed to 600 µmol/L paraquat (PQ) for 24 h were treated with hydrogen water with or without RNA interference of Nrf2 expression. The changes in the cell proliferation were examined using MTT assay, and the expressions of Col-I, Col-III, α-SMA and Nrf2 in the cells were detected using Western blotting, real-time quantitative PCR and immunofluorescence assay. The contents of SOD, CAT and GSH in the cells were determined with ELISA. RESULTS: Compared with the PQ-exposed cells, the cells with hydrogen water treatment showed significantly lowered expressions of Col-I, Col-III, and α-SMA. Interference of Nrf2 expression obviously attenuated the effect of hydrogen water on PQ-exposed cells. Hydrogen water treatment significantly increased the expression of Nrf2 and promoted the production of the antioxidants in PQ-exposed lung fibroblasts. CONCLUSIONS: Hydrogen water enhances Nrf2 expression to promote the proliferation and production of antioxidants and inhibit the differentiation and collagen secretion in PQ-exposed human lung fibroblasts in vitro.

lncRNA ZFAS1 promotes lung fibroblast-to-myofibroblast transition and ferroptosis via functioning as a ceRNA through miR-150-5p/SLC38A1 axis.

Pulmonary fibrosis (PF) is a lethal fibrotic lung disease. The role of lncRNAs in multiple diseases has been confirmed, but the role and mechanism of lncRNA zinc finger antisense 1 (ZFAS1) in the progression of PF need to be elucidated further. Here, we found that lncRNA ZFAS1 was upregulated in bleomycin (BLM)-induced PF rats lung tissues and transforming growth factor-ß1 (TGF-ß1)-treated HFL1 cells, and positively correlated with the expression of solute carrier family 38 member 1 (SLC38A1), which is an important regulator of lipid peroxidation. Moreover, knockdown of lncRNA ZFAS1 significantly alleviated TGF-ß1-induced fibroblast activation, inflammation and lipid peroxidation. In vivo experiments showed that inhibition of lncRNA ZFAS1 abolished BLM-induced lipid peroxidation and PF development. Mechanistically, silencing of lncRNA ZFAS1 attenuated ferroptosis and PF progression by lncRNA ZFAS1 acting as a competing endogenous RNA (ceRNA) and sponging miR-150-5p to downregulate SLC38A1 expression. Collectively, our studies demonstrated the role of the lncRNA ZFAS1/miR-150-5p/SLC38A1 axis in the progression of PF, and may provide a new biomarker for the treatment of PF patients.

Modeling and design of an overlapped-flexure hinge for joule balance.

In the joule balance experiment, the electromagnetic force and the gravity of the test mass should be aligned along the vertical direction precisely; otherwise, an alignment error will be introduced into the redefinition of the kilogram and the realization of the standard mass. In order to decouple and align those forces, a flexure hinge with an overlapped structure is proposed. The proposed overlapped-flexure hinge contains two flexure hinges, namely, the outer flexure hinge and the inner flexure hinge. The outer flexure hinge is connected to the suspension coil to bear the electromagnetic force, while the inner flexure hinge is connected to the test pan to bear the gravity of the test mass. As the mechanical structure ensures the above hinges coaxial and identical, this hinge can decouple the above-mentioned forces adequately and align these forces along the same vertical line. In this paper, a theoretical compliance model is first established based on Castigliano's second theorem to precisely design the flexure hinge. Second, the key dimension parameters of the overlapped-flexure hinge are designed to satisfy the requirements of the joule balance. Third, finite element analysis simulations and experiments are carried out to validate the performances of the hinge. Finally, in the joule balance experiment, the alignment uncertainty between the electromagnetic force and the gravity of the test mass is proved to be less than 50 ppb by using this overlapped-flexure hinge.

Metals in Occluded Water: A New Perspective for Pollution in Drinking Water Distribution Systems.

Occluded water is water that remains inside corrosion scales within deteriorating distribution pipes. The accumulation of iron and manganese in the occluded water is a potential risk for water quality. Thus, this study investigated the change in metal (iron, manganese, copper and chromium) concentration in occluded water, the effect of these metals on the flowing water, and the source of iron and manganese in the occluded water using a simulation device. The results showed that total iron and total manganese were enriched in the occluded water, while the concentrations of total copper and total chromium in the occluded water gradually decreased over time. The iron and manganese in the occluded water migrate to the flowing water causing pollution in the flowing water. Also, copper and chromium adsorb on the corrosion scales within the pipes. The iron and manganese in the occluded water mainly came from the corrosion of the metal pipes, and the corrosion scales had a certain obstructive effect on the outward migration of iron in the occluded water but had less hindrance to the migration of manganese. Occluded water plays a critical role in the pollution of drinking water, and additional work is needed to control metal accumulation and release.

Design of a tomato classifier based on machine vision.

This paper attempts to design an automated, efficient and intelligent tomato grading method that facilitates the graded selling of the fruit. Based on machine vision, the color images of tomatoes with different morphologies were studied, and the color, shape and size were selected as the key features. On this basis, an automated grading classifier was created based on the surface features of tomatoes, and a grading platform was set up to verify the effect of the classifier. Specifically, the Hue value distributions of tomatoes with different maturities were investigated, and the Hue value ranges were determined for mature, semi-mature and immature tomatoes, producing the color classifier. Next, the first-order Fourier descriptor (1D- FD) was adopted to describe the radius sequence of tomato contour, and an equation was established to compute the irregularity of tomato contour, creating the shape classifier. After that, a linear regression equation was constructed to reflect the relationship between the transverse diameters of actual tomatoes and tomato images, and a classifier between large, medium and small tomatoes was produced based on the transverse diameter. Finally, a comprehensive tomato classifier was built based on the color, shape and size diameters. The experimental results show that the mean grading accuracy of the proposed method was 90.7%. This means our method can achieve automated real-time grading of tomatoes.

Detection of serum long non-coding RNA UCA1 and circular RNAs for the diagnosis of bladder cancer and prediction of recurrence.

Accumulating evidence indicates that long noncoding RNAs (lncRNAs) and circular RNAs (circRNAs) may be biomarkers for the diagnosis and prediction of recurrence in tumor patients because they play an important role in tumorigenesis and progression. In this study, the expression of lncRNA urothelial carcinoma-associated 1 (UCA1) and associated circFARSA, circSHKBP1, and circBANP was investigated in serum specimens from bladder cancer (BC) patients and healthy controls using real-time PCR. When comparing patients with BC to healthy controls, the expression of lncRNA UCA1, circFARSA, and circSHKBP1 was significantly increased. The area under the curve (AUC) of the lncRNA UCA1 and circSHKBP1 signature to distinguish BC patients from controls was 0.804. The diagnostic performance of this signature was more optimal for low volume tumors (AUC = 0.870). Moreover, we determined that the expression of circFARSA, circSHKBP1, and circBANP was higher for recurrent BC than for patients without recurrence. Receiver operating characteristic (ROC) analysis revealed that a combination of circFARSA and circBANP levels was able to discriminate the patients with tumor recurrence from those without, with an area under the ROC curve of 0.737. In conclusion, our results identified an lncRNA UCA1: circSHKBP1 panel and a circFARSA: circBANP panel for BC diagnosis and prognosis, respectively.

Polysulfone foam with high expansion ratio prepared by supercritical carbon dioxide assisted molding foaming method.

Polysulfone (PSU) is considered as an important candidate for the fabrication of high-performance microcellular polymers, but the preparation of PSU foam with a high expansion ratio still remains a big challenge worldwide. In this study, high expansion ratio PSU foam was successfully prepared by a supercritical carbon dioxide (CO2) assisted molding foaming method. The foaming behavior of PSU under supercritical CO2 was systematically studied in various process conditions and different microcellular structures were created in PSU foams. The results showed that foaming temperature and CO2 concentration were the key factors to obtain microcellular foams with tailored microstructures. The cellular structure and expansion ratio of PSU foam obviously changed with different foaming temperatures. The expansion ratio and average cell size firstly increased and then decreased as foaming temperature increased. However, the cell density decreased and then remained stable as foaming temperature increased. The maximum expansion ratio of 11.0 was reached at the optimum foaming temperature of 200 °C. Cellular structure and morphologies of the foam changed obviously at CO2 concentrations below 5% and remained stable at CO2 concentrations above 5%. Finally, the prepared PSU foams exhibit excellent mechanical strength, good thermal conductivity, and superb heat retardancy, thus may have great potential application as a kind of substitute material in the electrical wire and cable industry, railway and steamer transportation, oil and gas platforms, military use and in other fields.

LncRNA UCA1 Promotes Mitochondrial Function of Bladder Cancer via the MiR-195/ARL2 Signaling Pathway.

BACKGROUND/AIMS: This study aims to identify whether Urothelial Cancer Associated 1 (UCA1) regulates mitochondrial metabolic reprogramming in bladder cancer, and to explore how UCA1 participates in mitochondrial metabolism by the UCA1/miR-195/ARL2 signaling pathway; these findings may be aid in the development of tumor diagnostic and therapeutic strategies. METHODS: Bladder tissues were obtained from patients. Stable cell lines were constructed, with ectopic expression of UCA1 in UMUC2 cells and knockdown of UCA1 in 5637 cells. The expression levels of UCA1, miR-195, and ARL2 were detected by real-time PCR, western blotting, and immunohistochemistry Cell viability was detected by Cell Counting Kit-8 (CCK8) assay; mitochondrial DNA copy numbers were tested by realtime PCR; ATP level was evaluated by ATP assay kit; mitochondrial membrane potential was analyzed by 5,5',6,6'-tetrachloro-1,1',3,3'- tetraethylbenzimidazolylcarbocyanine iodide (JC-1) fluorescent probe. miRNAs between UCA1 and ARL2 were predicted by TargetScan and RNAHybrid, and then determined by real-time PCR. Dual-luciferase activity assay and RNA immunoprecipitation (RIP) assay were used to verify the relationship between UCA1 and miR-195. The expression level of ARL2 was silenced by small interfering RNA(siRNA). For in vivo experiments, UCA1-silencing 5637 cells were subcutaneously injected into BALB/C nude mice to evaluate the effects of UCA1 on tumor progression by the regulation of miR-195 and ARL2. RESULTS: We demonstrate here that UCA1 enhances mitochondrial function in bladder cancer cells. UCA1 contributes to ARL2-induced mitochondrial activity, which plays an important role in mitochondrial function. UCA1, as a competing endogenous RNA (ceRNA), regulates mitochondrial function through upregulating ARL2. In this way, it inhibited the miR-195 signaling pathway to enhance mitochondrial function in bladder cancer. Additionally, ARL2 is a direct target of miR-195 and can be repressed by either miR-195 overexpression or UCA1 inhibition. Knockdown of ARL2 was analogous to the inhibition of UCA1 and the upregulation of miR-195. Animal experiments further indicated that UCA1 promoted bladder tumor growth by regulating miR-195 /ARL2. CONCLUSION: These data suggest that UCA1 enhanced mitochondrial function and cell viability through the UCA1/miR-195/ARL2 axis in vitro and in vivo. The elucidation of this signaling network provides a more adequate theoretical basis for understanding the molecular pathology of bladder cancer, and also UCA1 as a potential diagnosis and treatment target for bladder cancer.

System for the measurement of the deviation of a laser beam from the vertical direction.

If a used "vertical beam" is not perfectly vertical in a measurement, a cosine error will be introduced into it. To decrease and compensate for this cosine error, a measurement system is proposed to measure the deviation of the laser beam from the vertical direction. The structure of our measurement system is illustrated, and a model for solving for the deviation angle is established. As the distance of the beam spots on the charge-coupled device is the essential parameter for the measurement results, the acquisition process for this distance is explained. Moreover, the accuracy of the algorithm used in the acquisition process is also tested by experiments. Further, a self-correction module is designed and applied to reduce the error caused by the corner cube reflector in the system. The characteristics of the measurement system such as the resolution, stability, temperature drift, and direction accuracy are analyzed through experiments. The combined uncertainty of the measurement system is calculated to be 11×10-6 rad.

Absolute Position Sensing Based on a Robust Differential Capacitive Sensor with a Grounded Shield Window.

A simple differential capacitive sensor is provided in this paper to measure the absolute positions of length measuring systems. By utilizing a shield window inside the differential capacitor, the measurement range and linearity range of the sensor can reach several millimeters. What is more interesting is that this differential capacitive sensor is only sensitive to one translational degree of freedom (DOF) movement, and immune to the vibration along the other two translational DOFs. In the experiment, we used a novel circuit based on an AC capacitance bridge to directly measure the differential capacitance value. The experimental result shows that this differential capacitive sensor has a sensitivity of 2 × 10(-4) pF/µm with 0.08 µm resolution. The measurement range of this differential capacitive sensor is 6 mm, and the linearity error are less than 0.01% over the whole absolute position measurement range.

Long non-coding RNA UCA1 promotes glycolysis by upregulating hexokinase 2 through the mTOR-STAT3/microRNA143 pathway.

Cancer cells preferentially metabolize glucose through aerobic glycolysis, a phenomenon known as the Warburg effect. Emerging evidence has shown that long non-coding RNAs (lncRNAs) act as key regulators of multiple cancers. However, it remains largely unexplored whether and how lncRNA regulates glucose metabolism in cancer cells. In this study, we show that lncRNA UCA1 promotes glycolysis in bladder cancer cells, and that UCA1-induced hexokinase 2 (HK2) functions as an important mediator in this process. We further show that UCA1 activates mTOR to regulate HK2 through both activation of STAT3 and repression of microRNA143. Taken together, these findings provide the first evidence that UCA1 plays a positive role in cancer cell glucose metabolism through the cascade of mTOR-STAT3/microRNA143-HK2, and reveal a novel link between lncRNA and the altered glucose metabolism in cancer cells.

Urothelial carcinoma associated 1 is a hypoxia-inducible factor-1α-targeted long noncoding RNA that enhances hypoxic bladder cancer cell proliferation, migration, and invasion.

Urothelial carcinoma associated 1 (UCA1) has been identified as an oncogenic long noncoding RNA (lncRNA) that is involved in bladder cancer progression and acts as a diagnostic biomarker for bladder carcinoma. Here, we studied the expression and function of lncRNA-UCA1 in the hypoxic microenvironment of bladder cancer. The expression and transcriptional activity of lncRNA-UCA1 were measured by quantitative real-time polymerase chain reaction and luciferase assays. Cell proliferation and apoptosis were evaluated by MTT assays and flow cytometry. Cell migration and invasion were detected by wound healing, migration, and invasion assays. The binding of hypoxia-inducible factor-1α (HIF-1α) to hypoxia response elements (HREs) in the lncRNA-UCA1 promoter was confirmed by electrophoretic mobility shift assay and chromatin immunoprecipitation. HRE mutations were generated by using a site-directed mutagenesis kit, and HIF-1α knockdown was mediated by small interfering RNA. The effect of HIF-1α inhibition by YC-1 on lncRNA-UCA1 expression was also examined. LncRNA-UCA1 was upregulated by hypoxia in bladder cancer cells. Under hypoxic conditions, lncRNA-UCA1 upregulation increased cell proliferation, migration, and invasion and inhibited apoptosis. The underlying mechanism of hypoxia-upregulated lncRNA-UCA1 expression was that HIF-1α specifically bound to HREs in the lncRNA-UCA1 promoter. Furthermore, HIF-1α knockdown or inhibition could prevent lncRNA-UCA1 upregulation under hypoxia. These findings revealed the mechanism of lncRNA-UCA1 upregulation in hypoxic bladder cancer cells and suggested that effective blocking of lncRNA-UCA1 expression in the hypoxic microenvironment of bladder cancer could be a novel therapeutic strategy.

Upregulation of long non-coding RNA urothelial carcinoma associated 1 by CCAAT/enhancer binding protein α contributes to bladder cancer cell growth and reduced apoptosis.

Long non-coding RNA urothelial carcinoma associated 1 (lncRNA-UCA1) is upregulated in bladder cancer and plays a pivotal role in bladder cancer progression and metastasis. Recent studies and our research found that lncRNA-UCA1 may be an important biomarker and therapeutic target for bladder cancer. However, the molecular mechanism involved in the upregulation of lncRNA-UCA1 in bladder cancer is largely unknown. In the present study, we showed that lncRNA-UCA1 expression in bladder cancer cells was upregulated by transcription factor CCAAT/enhancer binding protein α (C/EBPα), which was the only candidate transcription factor simultaneously predicted by a total of five bioinformatical software programs. Electrophoretic mobility shift assay and chromatin immunoprecipitation assay indicated that C/EBPα bound to the lncRNA-UCA1 core promoter region in vitro and in vivo. The luciferase assays further showed that there was a point mutation (A231G) in the C/EBPα binding site of the lncRNA-UCA1 core promoter in various bladder cancer cell lines, which in turn significantly increased the transcriptional activity of lncRNA-UCA1. We also demonstrated that C/EBPα siRNA treatment contributed to the downregulation of lncRNA-UCA1 expression, whereas overexpression of C/EBPα enhanced lncRNA-UCA1 expression. Furthermore, lncRNA-UCA1 transcriptional repression by C/EBPα siRNA sharply reduced cell viability and induced cell apoptosis in vitro. Collectively, our results provide a novel therapeutic strategy for bladder cancer by effectively interrupting the binding of the lncRNA-UCA1 promoter and certain transcription factors, so as to reverse the upregulation of lncRNA-UCA1 and prevent bladder cancer progression.