Early Onset Horizontal Gaze Palsy and Progressive Scoliosis Due to a Noncanonical Splicing-Site Variant and a Missense Variant in the ROBO3 Gene

BACKGROUND: Homozygous or compound heterozygous ROBO3 gene mutations cause horizontal gaze palsy with progressive scoliosis (HGPPS). This is an autosomal recessive disorder that is characterized by congenital absence or severe restriction of horizontal gaze and progressive scoliosis. To date, almost 100 patients with HGPPS have been reported and 55 ROBO3 mutations have been identified. METHODS: We described an HGPPS patient and performed whole-exome sequencing (WES) to identify the causative gene. RESULTS: We identified a missense variant and a splice-site variant in the ROBO3 gene in the proband. Sanger sequencing of cDNA revealed the presence of an aberrant transcript with retention of 700 bp from intron 17, which was caused by a variation in the noncanonical splicing site. We identified five additional ROBO3 variants, which were likely pathogenic, and estimated the overall allele frequency in the southern Chinese population to be 9.44 × 10 CONCLUSION: This study has broadened the mutation spectrum of the ROBO3 gene and has expanded our knowledge of variants in noncanonical splicing sites. The results could help to provide more accurate genetic counseling to affected families and prospective couples. We suggest that the ROBO3 gene should be included in the local screening strategy

Long noncoding RNA LINC01088 inhibits esophageal squamous cell carcinoma progression by targeting the NPM1-HDM2-p53 axis

Esophageal squamous cell carcinoma (ESCC) is characterized by extensive metastasis and poor prognosis. Long noncoding RNAs (lncRNAs) have been shown to play important roles in ESCC. However, the specific roles of lncRNAs in ESCC tumorigenesis and metastasis remain largely unknown. Here, we investigate LINC01088 in ESCC. Differentially expressed LINC01088 levels are screened from the GEO database. We find that LINC01088 is expressed at low level in collected clinical samples and is correlated with vascular tumor emboli and poor overall survival time of patients after surgery. LINC01088 inhibits not only ESCC cell migration and invasion in vitro, but also tumorigenesis and metastasis in vivo. Mechanistically, LINC01088 directly interacts with nucleophosmin (NPM1) and increases the expression of NPM1 in the nucleoplasm compared to that in the nucleolar region. LINC01088 decreases mutant p53 (mut-p53) expression and rescues the transcriptional activity of p53 by targeting the NPM1-HDM2-p53 axis. LINC01088 may also interfere with the DNA repair function of NPM1 by affecting its translocation. Our results highlight the potential of LINC01088 as a prognostic biomarker and therapeutic target of ESCC

Numerical Simulation of the Tar Mist and Dust Movement Process in a Low-Temperature Dry Distillation Furnace

In the low-temperature dry distillation of low-rank coal, the important liquid product of coal tar is produced, but its quality and utilization rate are degraded by entrained dust. The movement of coal tar and dust in the furnace is a key factor in causing particles such as dust to mix with coal tar. Therefore, the Euler–Lagrangian method is used to simulate the two-phase motion process of gas, tar, and dust in a furnace. By considering the effects of tar particle size, dust particle size, gas velocity, tar density, and dust density, the motion process mechanism is revealed, enabling the dust content in coal tar to be reduced and the quality improved. The results indicate that tar particles with sizes less than 0.20 mm can be removed from the furnace by gas, and the smaller the particle size is, the shorter the time required for removal. Dust particles greater than 0.18 mm in size cannot be completely removed from the furnace. As the gas velocity increases, the time required for complete removal of the tar mist and dust gradually decreases. When the speed is 0.70 m/s, all tar mist is removed, although some particles remain. Tar mist with a density of more than 900 kg/m3 can be extensively removed, but dust with a density of more than 1400 kg/m3 is difficult to remove and remains in the furnace. Finally, particle size distribution experiments in the product were conducted to verify the accuracy of the numerical simulation

Early onset horizontal gaze palsy and progressive scoliosis due to a noncanonical splicing‐site variant and a missense variant in the ROBO3 gene

Abstract Background Homozygous or compound heterozygous ROBO3 gene mutations cause horizontal gaze palsy with progressive scoliosis (HGPPS). This is an autosomal recessive disorder that is characterized by congenital absence or severe restriction of horizontal gaze and progressive scoliosis. To date, almost 100 patients with HGPPS have been reported and 55 ROBO3 mutations have been identified. Methods We described an HGPPS patient and performed whole‐exome sequencing (WES) to identify the causative gene. Results We identified a missense variant and a splice‐site variant in the ROBO3 gene in the proband. Sanger sequencing of cDNA revealed the presence of an aberrant transcript with retention of 700 bp from intron 17, which was caused by a variation in the noncanonical splicing site. We identified five additional ROBO3 variants, which were likely pathogenic, and estimated the overall allele frequency in the southern Chinese population to be 9.44 × 10−4, by a review of our in‐house database. Conclusion This study has broadened the mutation spectrum of the ROBO3 gene and has expanded our knowledge of variants in noncanonical splicing sites. The results could help to provide more accurate genetic counseling to affected families and prospective couples. We suggest that the ROBO3 gene should be included in the local screening strategy

Pretreatment with Pectoral Nerve Block II Is Effective for Reducing Pain in Patients Undergoing Thoracoscopic Lobectomy: A Randomized, Double-Blind, Placebo-Controlled Trial

Background. Although video-assisted thoracoscopy has a smaller incision than traditional surgery, the postoperative pain is still severe. Ultrasound-guided pectoral nerve block (PECS) II is a new technique that can reduce pain in patients, and it had not been reported in the analgesia after thoracoscopic lobectomy. Methods. 40 patients scheduled for thoracoscopic lobectomy were randomly divided into two groups. Patients in the PECS II group received 0.5% ropivacaine 25 ml before the general anesthesia, while patients in the placebo group received 0.9% saline. Thirty minutes after the block was performed, a pin-prick test was used to analyze the sense of pain of T2-T6 segments. The primary endpoint was the total consumption of fentanyl. Data were collected in the postanesthesia care unit (PACU) and in the ward within 24 hours after operation. Results. The total consumption of fentanyl and the consumption of fentanyl in the intravenous analgesia pump within 24 hours after the operation were significantly lower in the PECS II group compared to the placebo group (p<0.05). The implementation rate of rescue analgesia during operation and in PACU in the PECS II group was significantly lower than that in the placebo group (p<0.05). The numerical rating scale (NRS) in 1 and 4 h after operation was lower in the PECS II group (p<0.05). Mean arterial pressure (MAP) and heart rate (HR) of the PECS II group at chest entering (T1) were significantly lower than those in the placebo group (p<0.05). Conclusion. Preconditioning of PECS II can stabilize the intraoperative circulation and significantly reduce pain and the consumption of opioids after operation

Time is nothing: emotional consistency of autobiographical memory and its neural basis

The emotional aspect of autobiographical memories (AMs) is associated with self-related processing, which plays an important role in mental health. However, the emotional consistency dimension of AMs and its neural underpinnings remain largely unexplored. Twenty-five healthy participants were involved in this study. Participants were first asked to recall important AMs and assess the emotional ratings of each AM. Four weeks later, they were asked to retrieve the details of both positive and negative AMs during functional magnetic resonance imaging (fMRI) scanning. Behavioral results showed that the emotional valence of negative memories changed more strongly than positive memories over time (i.e., lower consistency). fMRI data showed that the activation level of the precuneus was positively correlated with self-rating valence consistency in the positive AM condition. Additionally, the precuneus connected to a key region of the self-referential network, the medial prefrontal cortex, in both the positive and negative AM conditions. Finally, the precuneus showed stronger connections with the inferior parietal lobule when comparing the positive with the negative AM conditions. Our results suggest that the precuneus is a key area of emotional consistency in positive AMs; this brain area may be involved in the maintenance of a positive self-image by strengthening positive AMs

3D nanoporous iridium-based alloy microwires for efficient oxygen evolution in acidic media

Although significant progresses have been achieved recently in developing catalysts for electrochemical oxygen evolution in alkaline electrolytes, high performance catalysts toward oxygen evolution in acidic media have not been realized in spite of the technical importance for the development of promising energy transformation technologies including electrocatalytic water splitting, integrated (photo)electrochemistry cells, rechargeable metal-air batteries, and so on. Here, we synthesized a three-dimensional nanoporous Ir70Ni30-xCox alloy microwires as oxygen evolution reaction electrocatalyst using a dealloying strategy. The three dimensional binder-free np-Ir70Ni15Co15 catalyst in 0.1 M HClO4 shows a low overpotential (220 mV@ η = 10 mA cm−2), low Tafel slope (44.1 mV dec−1) and excellent corrosion resistance, significantly outperforming commercial IrO2 catalysts. The excellent performance is attributed to the nanoporous structure and the alloying effect, which promote the permeation of electrolyte, accelerate the transportation of electrons. More importantly, the high valence Ir oxide species with low-coordination structure in np-Ir70Ni15Co15 alloy are identified for the real catalytic sites of OER process by the XAS results acquired on synchrotron radiation. This work not only provides fundamental understandings of the correlation between surface activity and stability for OER catalysts, but also paves a new way to advanced electrocatalysts working in acidic media