Hsa-miR-125b suppresses bladder cancer development by down-regulating oncogene SIRT7 and oncogenic long non-coding RNA MALAT1

AbstractMicroRNAs mainly inhibit coding genes and long non-coding RNA expression. Here, we report that hsa-miR-125b and oncogene SIRT7/oncogenic long non-coding RNA MALAT1 were inversely expressed in bladder cancer. Hsa-miR-125b mimic down-regulated, whereas hsa-miR-125b inhibitor up-regulated the expression of SIRT7 and MALAT1. Binding sites were confirmed between hsa-miR-125b and SIRT7/MALAT1. Up-regulation of hsa-miR-125b or down-regulation of SIRT7 inhibited proliferation, motility and increased apoptosis. The effects of up-regulation of hsa-miR-125b were similar to that of silencing MALAT1 in bladder cancer as we had previously described. These data suggest that hsa-miR-125b suppresses bladder cancer development via inhibiting SIRT7 and MALAT1

TiEV: The Tongji Intelligent Electric Vehicle in the Intelligent Vehicle Future Challenge of China

TiEV is an autonomous driving platform implemented by Tongji University of China. The vehicle is drive-by-wire and is fully powered by electricity. We devised the software system of TiEV from scratch, which is capable of driving the vehicle autonomously in urban paths as well as on fast express roads. We describe our whole system, especially novel modules of probabilistic perception fusion, incremental mapping, the 1st and the 2nd planning and the overall safety concern. TiEV finished 2016 and 2017 Intelligent Vehicle Future Challenge of China held at Changshu. We show our experiences on the development of autonomous vehicles and future trends

Veterinarians in the UK on the use of non-steroidal anti-inflammatory drugs (NSAIDs) for post-disbudding analgesia of calves

<p>Top 20 down-regulated genes after DAPT treatment in P0 Lfng-GFP⁺ cells.</p

Novel bi-allelic variants of CHMP1A contribute to pontocerebellar hypoplasia type 8: additional clinical and genetic evidence

Pontocerebellar hypoplasia type 8(PCH8) is a rare neurodegenerative disorder, reportedly caused by pathogenic variants of the CHMP1A in autosomal recessive inheritance, and CHMP1A variants have also been implicated in other diseases, and yet none of the prenatal fetal features were reported in PCH8. In this study, we investigated the phenotype and genotype in a human subject with global developmental delay, including clinical data from the prenatal stage through early childhood. Prenatally, the mother had polyhydramnios, and the bilateral ventricles of the fetus were slightly widened. Postnatally, the infant was observed to have severely delayed psychomotor development and was incapable of visual tracking before 2 years old and could not fix on small objects. The young child had hypotonia, increased knee tendon reflex, as well as skeletal malformations, and dental crowding; she also had severe and recurrent pulmonary infections. Magnetic resonance imaging of the brain revealed a severe reduction of the cerebellum (vermis and hemispheres) and a thin corpus callosum. Through whole exome sequencing and whole genomics sequencing, we identified two novel compound heterozygous variations in CHMP1A [c.53 T &gt; C(p.Leu18Pro)(NM_002768.5) and exon 1 deletion region (NC_000016.10:g.89656392_89674382del)]. cDNA analysis showed that the exon1 deletion region led to the impaired expression, and functional verification with zebrafish embryos using base edition indicated variant c.53 T &gt; C (p.Leu18Pro), causing dysplasia of the cerebellum and pons. These results provide further evidence that CHMP1A variants in a recessive inheritance pattern contribute to the clinical characteristics of PCH8 and further expand our knowledge of the phenotype and genotype spectrum of PCH8

Endurance exercise accelerates myocardial tissue oxygenation recovery and reduces ischemia reperfusion injury in mice

Exercise training offers cardioprotection against ischemia and reperfusion (I/R) injury. However, few essential signals have been identified to underscore the protection from injury. In the present study, we hypothesized that exercise-induced acceleration of myocardial tissue oxygenation recovery contributes to this protection. C57BL/6 mice (4 weeks old) were trained on treadmills for 45 min/day at a treading rate of 15 m/min for 8 weeks. At the end of 8-week exercise training, mice underwent 30-min left anterior descending coronary artery occlusion followed by 60-min or 24-h reperfusion. Electron paramagnetic resonance oximetry was performed to measure myocardial tissue oxygenation. Western immunoblotting analyses, gene transfection, and myography were examined. The oximetry study demonstrated that exercise markedly shortened myocardial tissue oxygenation recovery time following reperfusion. Exercise training up-regulated Kir6.1 protein expression (a subunit of ATP-sensitive K(+)channel on vascular smooth muscle cells, VSMC sarc-K(ATP)) and protected the heart from I/R injury. In vivo gene transfer of dominant negative Kir6.1AAA prolonged the recovery time and enlarged infarct size. In addition, transfection of Kir6.1AAA increased the stiffness and reduced the relaxation capacity in the vasculature. Together, our study demonstrated that exercise training up-regulated Kir6.1, improved tissue oxygenation recovery, and protected the heart against I/R injury. This exercise-induced cardioprotective mechanism may provide a potential therapeutic intervention targeting VSMC sarc-K(ATP) channels and reperfusion recovery

Nanoarchitectonic Engineering of Thermal-Responsive Magnetic Nanorobot Collectives for Intracranial Aneurysm Therapy

Stent-assisted coiling is a main treatment modality for intracranial aneurysms (IAs) in clinics, but critical challenges remain to be overcome, such as exogenous implant-induced stenosis and reliance on antiplatelet agents. Herein, we report an endovascular approach for IA therapy without stent grafting or microcatheter shaping, enabled by active delivery of thrombin (Th) to target aneurysms using innovative phase-change material (PCM)-coated magnetite-thrombin (Fe3O4-Th@PCM) FTP nanorobots. The nanorobots are controlled by an integrated actuation system of dynamic torque-force hybrid magnetic fields. With robust intravascular navigation guided by real-time ultrasound imaging, nanorobotic collectives can effectively accumulate and retain in model aneurysms constructed in vivo, followed by controlled release of the encapsulated Th for rapid occlusion of the aneurysm upon melting the protective PCM (thermally responsive in a tunable manner) through focused magnetic hyperthermia. Complete and stable aneurysm embolization was confirmed by postoperative examination and 2-week postembolization follow-up using digital subtraction angiography (DSA), contrast-enhanced ultrasound (CEUS) and histological analysis. The safety of the embolization therapy was assessed through biocompatibility evaluation and histopathology assays. Our strategy, seamlessly integrating secure drug packaging, agile magnetic actuation and clinical interventional imaging, avoids possible exogenous implant rejection, circumvents cumbersome microcatheter shaping, and offers a promising option for IA therapy

Solenoid-free current drive via ECRH in EXL-50 spherical torus plasmas

As a new spherical tokamak (ST) designed to simplify engineering requirements of a possible future fusion power source, the EXL-50 experiment features a low aspect ratio (A) vacuum vessel (VV), encircling a central post assembly containing the toroidal field coil conductors without a central solenoid. Multiple electron cyclotron resonance heating (ECRH) resonances are located within the VV to improve current drive effectiveness. Copious energetic electrons are produced and measured with hard X-ray detectors, carry the bulk of the plasma current ranging from 50kA to 150kA, which is maintained for more than 1s duration. It is observed that over one Ampere current can be maintained per Watt of ECRH power issued from the 28-GHz gyrotrons. The plasma current reaches Ip>80kA for high density (>5e18me-2) discharge with 150kW ECHR heating. An analysis was carried out combining reconstructed multi-fluid equilibrium, guiding-center orbits of energetic electrons, and resonant heating mechanisms. It is verified that in EXL-50 a broadly distributed current of energetic electrons creates smaller closed magnetic-flux surfaces of low aspect ratio that in turn confine the thermal plasma electrons and ions and participate in maintaining the equilibrium force-balance

Tonicity-responsive microRNAs contribute to the maximal induction of osmoregulatory transcription factor OREBP in response to high-NaCl hypertonicity

Osmotic response element binding protein (OREBP) is a Rel-like transcription factor critical for cellular osmoresponses. Previous studies suggest that hypertonicity-induced accumulation of OREBP protein might be mediated by transcription activation as well as posttranscriptional mRNA stabilization or increased translation. However, the underlying mechanisms remain incompletely elucidated. Here, we report that microRNAs (miRNAs) play critical regulatory roles in hypertonicity-induced induction of OREBP. In renal medullary epithelial mIMCD3 cells, hypertonicity greatly stimulates the activity of the 3′-untranslated region of OREBP (OREBP-3′UTR). Furthermore, overexpression of OREBP-3′UTR or depletion of miRNAs by knocking-down Dicer greatly increases OREBP protein expression. On the other hand, significant alterations in miRNA expression occur rapidly in response to high NaCl exposure, with miR-200b and miR-717 being most significantly down-regulated. Moreover, increased miR-200b or miR-717 causes significant down-regulation of mRNA, protein and transcription activity of OREBP, whereas inhibition of miRNAs or disruption of the miRNA–3′UTR interactions abrogates the silencing effects. In vivo in mouse renal medulla, miR-200b and miR-717 are found to function to tune OREBP in response to renal tonicity alterations. Together, our results support the notion that miRNAs contribute to the maximal induction of OREBP to participate in cellular responses to osmotic stress in mammalian renal cells