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Aberrant alternative splicing (AS) events have been identified in a variety of cancers. Although somatic mutations of splicing factors and dysregulation of RNA-binding proteins (RBPs) have been linked to AS and tumor malignancy, it remains unclear how upstream mechanisms contribute to cancer development via alternative gene splicing. In this issue of the JCI, Wenrui Zhang and colleagues identified the role of asparagine endopeptidase (AEP), an intracellular cysteine endopeptidase, in promoting solid tumor-associated RNA splicing. The authors demonstrated that tumor environmental factors such as oxygen and nutrient deprivation induce the activity of AEP in a HIFIA-dependent manner. The activated AEP, in turn, cleaves an RNA helicase DDX3X to promote its nuclear retention. The authors further showed that this DDX3X nuclear fraction engages with splicing machinery to induce AS events in several cancer cells. These findings suggest that targeting an AEP-dependent aberrant RNA splicing cascade may facilitate therapeutics for solid tumors., Aberrant RNA splicing in cancers Alternative splicing (AS) is a critical cellular process that contributes to the encoding capacity of transcriptomes of eukaryotic cells (1). Recently, high-throughput sequencing and genome-wide [...]

To achieve the goal of 'carbon neutrality', it is of great significance to accelerate the process of dismantling high-carbon and high-pollution thin-walled cylinder structures such as chimneys and so on. A 183 m ultra-high coaxial thin-walled steel-inner-cylinder reinforced concrete chimney (UCTS-RCC) was successfully demolished for the first time. To successfully dismantle the UCTS-RCC by controlled blasting demolition technology, the necessary structural mechanics theoretical analysis and the critical blasting designs rationality verification were carried out. Based on the equilibrium equation of force and bending moment, a theoretical model of incision angle selection was established to determine the incision design of the steel inner cylinder (SIC). The stability of SIC under the designed incision parameters was verified based on FEM statics analysis. The cutting experimental on the target steel plate was completed with a linear shaped cutter to obtain the cutting effect. The cutting process and the overall collapse process of the UCTS-RCC were simulated by LS-DYNA. Based on the fixed axis rotation differential equation, the synchronous toppling theoretical model were established to study the motion of the UCTS-RCC. The results showed that the maximum stress at the position of the directional window and the stresses of the remaining supports were less than the yield limit of Q235B steel after that several pretreatment windows were carried out, the SIC could maintain the stability of remaining structures. The cutting experimental results of the target steel plate using linear shaped cutter were basically consistent with the cutting simulation and the cutting effect satisfied the design requirements of instantaneous cutting separation of the supports. According to the obvious difference of material properties between Q235B steel and reinforced concrete, the ignition delay time of the SIC was set 2 s earlier than that of the RCC. According to the synchronous collapse simulations, it could be known that the ignition delay time setting was reasonable and the collapse motion state of the UCTS-RCC was approximately fixed axis rotation, which was in line with the established synchronous toppling theory model. The SIC and RCC finally successfully collapsed synchronously. The blasting scheme and the rationality verification methods were applied successfully in this project, which was of great significance to provide a reliable reference for such ultra-high thin-walled cylinder complex structural chimney.

In order to investigate the influence of initial pressures on the propagation characteristics of gas explosion in roadway, the physical model of gas explosion under different initial pressures in roadway is established by the fluid-structure interaction algorithm of ANSYS/LS-DYNA. The pressure of shock wave, the rise rate of pressure and the flame propagation velocity are analyzed when the initial pressure is 0.08, 0.09, 0.10, 0.11, and 0.12 MPa, respectively. The results reveal that the maximum pressure of shock wave at the same position in the roadway increases significantly with the increase of initial pressure, which presents a quadratic function relationship. The time to reach the maximum pressure of shock wave is extended comparatively. In addition, the maximum rise rate of shock wave pressure increases with the increase of the initial pressure, which means that the explosion hazard increases. The flame propagation velocity in the roadway decreases linearly with the increase of initial pressure. When the initial pressure increases by 0.01 MPa, the flame propagation speed will decrease by 2.6%.

3D modeling of wear particles has proven to be a useful tool for monitoring mechanical failure conditions. In this work, a new method for 3D reconstruction of wear particles in uncontaminated oil (healthy oil) and contaminated oil (used oil) was proposed. The image acquisition device can capture multi-view images of moving wear particles in both healthy and used oil by using the reflected light. The images were pretreated first, and the image color inversion was conducted using the Pillow library. The pretreated wear particle images were used for 3D reconstruction using long short-term memory 3D recurrent reconstruction neural network. The current results were verified against existing results, and good agreement can be found. It can be concluded that we can reconstruct the similar 3D wear particle results with fewer images by comparison with other methods. Specifically, only 4–6 image samples were used for the 3D reconstruction of wear particles, and at least 8 image samples were needed for other existing reports. [ABSTRACT FROM AUTHOR]

In thermophotovoltaic (TPV) systems, it is crucial that the selective emitters can tailor emission spectrum to match the bandgap of photovoltaic (PV) cells and largely enhance the system efficiency. In this work, a metamaterial emitter based on the metal-insulator-metal (MIM) structure is proposed to obtain the high energy conversion efficiencies. The geometric parameters of MIM emitter have been investigated to obtain an excellent radiation spectrum of emitter composed of W and HfO2. The excellent emission performance of MIM emitter is attributed to the excitation of surface plasmon polariton (SPP) and cavity resonance, and the structure of MIM emitter is insensitive for different polarization modes. The 21 material combinations of MIM emitters have been screened to obtain the optimal emitter matching GaSb and InGaAsSb cells. This work identifies the crucial role of structure and materials into the emitter of a TPV system. In the evaluation of MIM emitter and TPV System, when the operating temperature of emitter increases from 1400 K to 2000 K, the system efficiency of optimal W/HfO2/W MIM emitter increases from 20.26% to 30.41%, while the output electric power increases from 3.59 kW/m2 to 42.48 kW/m2. The phenomenon indicates that the MIM emitter with the optimal material combinations and geometric parameters can significantly improve the matching degree with GaSb and InGaAsSb cells. Our results will be helpful to expand the optimization scope of metamaterial emitters in TPV systems. [ABSTRACT FROM AUTHOR]

Importance: Pediatric cerebral cavernous malformation (CCM) is a rarely encountered vascular entity. Comparative study on surgical excision and nonsurgical management outcomes of CCM in pediatrics is limited. Objective: To determine the demographic characteristics, hemorrhage rate, and long‐term outcomes of pediatric patients with CCM. Methods: A retrospective study of pediatric patients with CCM in Chinese PLA General Hospital was conducted between January 2004 and January 2019. We compared the clinical characteristics, radiological features, and outcomes of the surgical and nonsurgical groups. Results: Seventy‐nine children were included, with 69.6% being boys, and the average age was 11.8 ± 5.5 years. The annual retrospective hemorrhagic rate was 5.7% per patient per year. Fifty‐six children (70.9%) underwent surgical excision, and they were more likely to present with seizure symptoms (P = 0.011), have a higher proportion of larger lesion size (P = 0.008), less likely to have durations ≤10 days (P = 0.048), and less likely to have supratentorial deep CCM (P = 0.014) compared to children who received nonsurgical management. Total resection was achieved in most surgical cases (55, 98.2%). During the 143.9 ± 50.8 months of follow‐up, 44 patients (78.6%) achieved improvement, 12 patients (17.8%) remained the same, and two (3.6%) experienced worsening. In the nonsurgical management group, 14 children (60.9%) experienced symptom improvement, eight (34.8%) remained the same, and one (4.3%) worsened, with a re‐hemorrhagic risk of 8.7%. Interpretation: Surgical removal of pediatric CCM can eliminate the risk of hemorrhage and lead to satisfactory outcomes. For children undergoing nonsurgical management, long‐term close monitoring is essential due to the life‐long risk of hemorrhage. [ABSTRACT FROM AUTHOR]

Genetically modified intestinal organoids are being explored as potential surrogates of immortalized cell lines and gene-engineered animals. However, genetic manipulation of intestinal organoids is time-consuming, and the efficiency is far beyond satisfactory. To ensure the yield of the genetically modified organoids, large quantity of starting materials is required, and the procedure usually takes more than 10 days. Two major obstacles that restrict the genetic delivery efficiency are the three-dimensional culture condition and that the genetic delivery is carried out in cell suspensions. In the present study, we introduce a novel highly efficient strategy for building genetically modified intestinal organoids in which genetic delivery was performed in freshly established monolayer primary intestinal epithelial cells under two-dimensional conditions and subsequentially transformed into three-dimensional organoids. The total procedure can be finished within 10 hr while displaying much higher efficiency than the traditional methods. Furthermore, this strategy allowed for the selection of transgenic cells in monolayer conditions before establishing high-purity genetically modified intestinal organoids. [ABSTRACT FROM AUTHOR]

The natural environment of cells in vivo is a 3D network in which cellular responses are determined by influences from surrounding cells on all sides. This complex system is hard to be recapitulated in a conventional way. It is highly desirable to replace 2D models with 3D cell culture models. Microfluidic technology offers a variety of advantageous approaches for the long‐term 3D cell culture. Herein, a new cell patterning approach for generating cell clusters of specified size and shape by exploiting induced charge electroosmosis (ICEO) flow at a bipolar electrode array is exploited. Cell or particle clusters can be produced at the edges or centers of bipolar electrodes (BPEs) with controlled organization, by designing electrodes with arbitrary shapes. This platform is further extended to flexibly organize biological units with different properties via the ICEO or dielectrophoresis (DEP) based assembly. Heterotypic cell clusters can be produced at the bipolar electrode (BPE) by adjusting the applied frequencies and the sample injection sequence. This hybrid approach by integrating ICEO flow vortexes and DEP properties of the cells, allows the wireless generation of high‐throughput 3D clusters or spheroids with size adjustability and biocompatibility, which shows great potential in tissue engineering, drug discovery, and tumor research. [ABSTRACT FROM AUTHOR]