Disruption of splicing-regulatory elements using CRISPR/Cas9 to rescue spinal muscular atrophy in human iPSCs and mice

We here report a genome-editing strategy to correct spinal muscular atrophy (SMA). Rather than directly targeting the pathogenic exonic mutations, our strategy employed Cas9 and guide-sgRNA for the targeted disruption of intronic splicing-regulatory elements. We disrupted intronic splicing silencers (ISSs, including ISS-N1 and ISS + 100) of survival motor neuron (SMN) 2, a key modifier gene of SMA, to enhance exon 7 inclusion and full-length SMN expression in SMA iPSCs. Survival of splicing-corrected iPSC-derived motor neurons was rescued with SMN restoration. Furthermore, co-injection of Cas9 mRNA from Streptococcus pyogenes (SpCas9) or Cas9 from Staphylococcus aureus (SaCas9) alongside their corresponding sgRNAs targeting ISS-N1 into zygotes rescued 56% and 100% of severe SMA transgenic mice (Smn , SMN2 ). The median survival of the resulting mice was extended to >400 days. Collectively, our study provides proof-of-principle for a new strategy to therapeutically intervene in SMA and other RNA-splicing-related diseases. -/- tg/

Shipping sustainability : ship recycling must be safe and environmentally friendly

There has been a growing emphasis on green shipping practices in the maritime industry. The ship recycling sector contributes to sustainability in shipping as majority of the ship material can be recycled and reused in secondary markets. However, the ship dismantling process is relatively dangerous and there are many safety and environmental concerns that needs to be addressed. The method of ship recycling differs between countries depending on the level of economic development and infrastructure. There are various issues associated with ship dismantling, such as high accident rates at shipyards, pollution due to disposal of hazardous substances and health problems from toxic working environment. These issues are more pervasive in developing countries in the Indian Subcontinent that are less industrialised and rely heavily on manual labour. In order to raise the standards of ship recycling as a whole, it is crucial to adopt safe working practices, green ship recycling solutions and relevant technology. Existing ship recycling Conventions set guidelines and standards for the stakeholders involved and should be taken into serious consideration when implementing new solutions. This study seeks to explore current and potential solutions that could address the safety and environmental concerns in the ship recycling sector.Bachelor of Science (Maritime Studies

Treatment of Pediatric Inflammatory Myofibroblastic Tumor: The Experience from China Children’s Medical Center

Background: Inflammatory myofibroblastic tumor (IMT) is a rare mesenchymal tumor with intermediate malignancy that tends to affect children primarily. To date, no standardized therapies exist for the treatment of IMT. This study aimed to share experience from China Children’s Medical Center for the explorative treatment of IMT. Methods: Patients with newly diagnosed IMT between January 2013 and December 2018 were included. Patients were grouped according to surgical margins and Intergroup Rhabdomyosarcoma Study Group (IRSG) staging. The clinical characteristic, therapeutic schedules, treatment response and clinical outcome were described. Results: Six patients were enrolled in this study, including two boys and four girls, with a median age of 57 months (range 10–148 months). Among them, five patients were anaplastic lymphoma kinase positive. Four patients achieved complete remission and two patients attained partial remission after treatment with this protocol. All patients were alive after a median follow-up of 4 years (range 3–7 years). The most common treatment-related adverse reaction was myelosuppression. Conclusion: In this study, we demonstrated that IMT has a good prognosis and the treatment selected according to risk stratification was effective and feasible

Study on the Effect of Rock Mass Structure on CO₂ Transient Fissure Excavation

As a new rock breaking method, CO2 transient cracking has been widely used in rock excavation projects in recent years. However, in the actual construction process, there are often situations where the fracturing effect varies due to different rock mass structures. Through theoretical analysis and on-site cracking tests, this article studies the effect of CO2 transient cracking under the control of different rock mass structures. The results show that: (1) the dynamic compressive strength of rock directly determines the number and range of dynamic impact fractures; the original fractures of rock mass and those caused by dynamic impact in the first stage jointly determine the effect of high-pressure gas expansion in the second stage. (2) The arrangement of holes along the strata is conducive to the action of high-pressure expanding gas along the soft structural plane in the rock mass, which is conducive to the fracturing of the rock mass; the amount of crack formation is small, but the influence range is large. (3) The cracking effect of carbon dioxide transient cracking applied to massive rock mass is better than that of monolithic rock mass, while the cracking effect of layered rock mass with soil interlayer is poor. The research results are of great significance for improving the effectiveness of carbon dioxide transient-induced cracking excavation and guiding actual construction

Metabolic and Transcriptomic Analyses Reveal Different Metabolite Biosynthesis Profiles between Purple and Green Pak Choi

Pak choi is one of the most important leafy vegetables planted in East Asia and provides essential nutrients for the human body. Purple pak choi differs mainly in leaf colour but exhibits distinct nutritional profiles from green pak choi. In this study, we performed metabolic and transcriptomic analyses to uncover the mechanisms underlying the differences in metabolite biosynthesis profiles between the two pak choi varieties. Metabolite profiling revealed significant differences in the levels of metabolites, mainly amino acids and their derivatives and flavonoids. Furthermore, 34 flavonoids significantly differed between green and purple pak choi leaves, and cyanidin and its derivative anthocyanins were abundant in purple pak choi. In addition, we found that the structural genes CHS, DFR, ANS, and UGT75C1, as well as the transcription factor MYB2, play a major role in anthocyanin synthesis. These results provide insight into the molecular mechanisms underlying leaf pigmentation in pak choi and offer a platform for assessing related varieties

An Improved Detection Algorithm for Ischemic Stroke NCCT Based on YOLOv5

Cerebral stroke (CS) is a heterogeneous syndrome caused by multiple disease mechanisms. Ischemic stroke (IS) is a subtype of CS that causes a disruption of cerebral blood flow with subsequent tissue damage. Noncontrast computer tomography (NCCT) is one of the most important IS detection methods. It is difficult to select the features of IS CT within computational image analysis. In this paper, we propose AC-YOLOv5, which is an improved detection algorithm for IS. The algorithm amplifies the features of IS via an NCCT image based on adaptive local region contrast enhancement, which then detects the region of interest via YOLOv5, which is one of the best detection algorithms at present. The proposed algorithm was tested on two datasets, and seven control group experiments were added, including popular detection algorithms at present and other detection algorithms based on image enhancement. The experimental results show that the proposed algorithm has a high accuracy (94.1% and 91.7%) and recall (85.3% and 88.6%) rate; the recall result is especially notable. This proves the excellent performance of the accuracy, robustness, and generalizability of the algorithm

Wettability and Spreading Behavior of Sn–Ti Alloys on Si₃N₄

The purpose of this study was to investigate the wetting behavior and interfacial reactions of Sn-Ti alloys, which has been widely applied to join ceramics with metals, on Si3N4 substrates. The isothermal wetting process of Sn-xTi alloys (x = 0.5, 1.0, 1.5, 2.0 and 2.5 wt.%) on Si3N4 was systematically studied from 1223 K to 1273 K through sessile drop methods. The microstructures of the interface were characterized by X-ray diffraction (XRD) and microscope (SEM). The active Ti element remarkably enhanced the wettability of Sn-xTi melts on Si3N4 substrates because of the formation of metallic reaction layers (Ti5Si3 and TiN). With the Ti content rising, thicker Ti5Si3 layer formed on the TiN phase inducing a lower equilibrium contact angle. The value of the lowest contact angle was 6°, which was obtained in the Sn-2.0Ti/Si3N4 system at 1273 K. Larger Ti5Si3 grains were found in Sn-2.5Ti melt and a higher final contact angle was obtained. Lower temperature increased the final contact angle and slowed down the spreading rate. The formation of reaction products was calculated thematically, and the spreading kinetics was calculated according to the reaction-driven theory. The spreading behavior of Sn-Ti alloy on Si3N4 ceramic was composed of rapid-spreading stage and sluggish-spreading stage. The calculated activity energy of spreading was 395 kJ/mol. Eventually, the wetting process of Sn-2.0Ti/Si3N4 system was successfully elucidated. These results provide significant guidance information for the brazing between metals and Si3N4 ceramic

Association of Neutrophil–Lymphocyte Ratio and the Presence of Neonatal Sepsis

The neutrophil–lymphocyte ratio (NLR) is an emerging risk factor of sepsis that is receiving increasing attention. However, the relationship between NLR and the presence of sepsis in neonates is poorly studied. Here, we retrospectively recruited 1480 neonates and collected and analyzed relevant clinical and laboratory data. According to the International Pediatric Sepsis Consensus, 737 neonates were diagnosed with sepsis, and 555 neonates were suspected for having infection. Neonates with hyperbilirubinemia (n=188) served as controls. Neonates with sepsis had significantly elevated neutrophil counts and NLR (P1.88 group (P<0.001). Multiple logistic regression analysis showed that NLR was an independent risk factor for the presence of neonatal sepsis. Receiver operating characteristic (ROC) curve analysis showed that the optimal cut-off value NLR for predicting the presence of neonatal sepsis was 1.62 (area under curve AUC=0.63, 95% CI 0.60–0.66, P<0.001). In conclusion, our data suggest that elevated NLR levels are associated with a higher neonatal sepsis risk