Enhanced glycolysis is a main feature of pluripotent stem cells (PSCs) and is proposed to be important for the maintenance and induction of pluripotency. The molecular mechanism underlying enhanced glycolysis in PSCs is not clear. Using Dgcr8 À/À mouse embryonic stem cells (ESCs) that lack mature miRNAs, we found that miR-290 cluster of miRNAs stimulates glycolysis by upregulating glycolytic enzymes Pkm2 and Ldha, which are also essential for the induction of pluripotency during reprogramming. Mechanistically, we identified Mbd2, a reader for methylated CpGs, as the target of miR-290 cluster that represses glycolysis and reprogramming. Furthermore, we discovered Myc as a key target of Mbd2 that controls metabolic switch in ESCs. Importantly, we demonstrated that miR-371 cluster, a human homolog of miR-290 cluster, stimulates glycolysis to promote the reprogramming of human fibroblasts. Hence, we identified a previously unappreciated mechanism by which miR-290/371 miRNAs orchestrate epigenetic, transcriptional and metabolic networks to promote pluripotency in PSCs and during reprogramming.
The molecular mechanism controlling the dismantling of naive pluripotency is poorly understood. Here we show that microRNAs (miRNAs) have important roles during naive to primed pluripotency transition. Dgcr8−/− embryonic stem cells (ESCs) failed to completely silence the naive pluripotency program, as well as to establish the primed pluripotency program during differentiation. miRNA profiling revealed that expression levels of a large number of miRNAs changed dynamically and rapidly during naive to primed pluripotency transition. Furthermore, a miRNA screen identified numerous miRNAs promoting naive to primed pluripotency transition. Unexpectedly, multiple miRNAs from miR-290 and miR-302 clusters, previously shown as pluripotency-promoting miRNAs, demonstrated the strongest effects in silencing naive pluripotency. Knockout of both miR-290 and miR-302 clusters but not either alone blocked the silencing of naive pluripotency program. Mechanistically, the miR-290/302 family of miRNAs may facilitate the exit of naive pluripotency in part by promoting the activity of MEK pathway and through directly repressing Akt1. Our study reveals miRNAs as an important class of regulators potentiating ESCs to transition from naive to primed pluripotency, and uncovers context-dependent functions of the miR-290/302 family of miRNAs at different developmental stages.
Purpose An automatic evaluation technology based on artificial intelligence and three‐dimensional ultrasonography (3D US) is proposed for hip US inspection plane selection. This study aimed to evaluate the consistency of the α angle as measured using 3D US to select the section plane and two‐dimensional ultrasonography (2D US) to manually select the Graf image, as well as to explore the feasibility of diagnosing developmental dysplasia of the hip (DDH) using 3D US and reconstruction technology. Methods A total of 216 infant hips were included and assessed by doctors using 3D US layer‐by‐layer. The researchers used a computer to identify the coronal images that met the Graf standard and then compared the αX values obtained with the αG values measured artificially by 2D US. Results Compared with 2D US, 3D US more clearly showed the relative positions of the ilium, ischia, and pubis. The measured α value of the optimal section obtained by 3D US showed good agreement with the measured α value of the standard Graf section. Conclusion The artificial intelligence and 3D US‐based automatic evaluation technology for section selection and inspection for DDH showed good agreement with the Graf method based on standard sections.
Background Neuromuscular choristomas (NMCs), are extremely rare developmental lesions that, have been previously established associated with recurrent fibromatosis after surgery, leading to several operations or even amputation. However, reports on the ultrasound imaging features and clinical conditions of NMCs are rare. The purpose of this study is to describe the ultrasound features and clinical analysis of NMCs to provide suggestions to identify the optimal management strategy. Methods From September 2020 to September 2021, 7 patients with a confirmed diagnosis of NMC who underwent ultrasound examination in our department were enrolled in our study. Physical examinations were performed to detect motor deficits, sensory deficits, neuropathic pain, limb undergrowth, muscular atrophy, cavus foot and bone dysplasia. Ultrasound imaging was performed and investigated both in affected nerves and neuromuscular choristomas associated desmoid-type fibromatosis (NMC-DTF). All patients had a definite history and regular follow-up. The clinical course, physical examinations, ultrasound features and pathologic results of NMC patients were analyzed. Results Seven patients with an average age of 7.0 ± 7.2 years (range: 2–22 years) were enrolled in our study. The affected nerves included the sciatic nerve (6 cases) and the brachial plexus (1 case). Six patients (85.7%) presented with limb undergrowth, 6 (85.7%) with muscular atrophy, and 5 (71.4%) with cavus foot deformity. Based on ultrasound findings, all the visibly affected nerve segments presented with hypoechoic and fusiform enlargement with intraneural skeletal muscle elements. Five patients (71.4%) had NMC-DTFs at the site of the affected nerve. All NMC-DTFs were shown as hypoechoic solid lesions adjacent to the nerve and were well circumscribed. In the subset of the surgery group, all 5 patients presented with progression to NMC-DTFs at the site of the NMCs. No fibromatosis was detected in the other two nonsurgical patients. Conclusions Understanding the typical ultrasound features and clinically associated conditions would support the early diagnosis of this rare disease. When a potential diagnosis is determined, an invasive procedure such as biopsy or resection might not be a good choice given the frequent occurrence of complications such as aggressive recurrence.
This thesis takes practical enterprise internal investigation of the consulting company for instance, thoroughly introducing the aim, content, method, analysis as well as report of this investigation. This investigation group conducted a thorough and systematic investigation to the internal management through the methods of desk research, materials consultation, on-the-spot investigation, anonymous questionnaire survey, post readme, in-depth interview, and visiting customers and the suppliers and displayed present situations and reform suggestions at aspects on company's strategic management, corporate culture, human resources management, production and quality management, sales management, financial management and management system.
The 1Cr18Ni9Ti stainless steel was brazed in the argon shield and впр7 as the filler metal. The spreadability and clearance fillability of впр7 on 1Cr18Ni9Ti stainless steel was evaluated at different temperatures and the optimum brazing temperature was clearly demonstrated as 1170~1190°C. Scanning electron microscope (SEM) study combined with energy dispersive spectrometer (EDS) showed the presence of many undissolved elements and voids in the joints while the brazing clearance is 0.15mm, which directly caused a low joint shearing strength. Almost no undissolved brittle compounds were observed while the brazing clearance stands in a range of 0.01mm~0.10mm. Therefore, a Ni-based solid solution with good performance was obtained in the joint. Those brazing parameters matching with the holding time 8~10min could bring the joint a typical performance which fully satisfies Russian standard. These conclusions had been proved by joint stress-rupture and low cycle fatigue tests.
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