Threshold of hyperglycaemia associated with mortality in critically ill patients: a multicentre, prospective, observational study using continuous glucose monitoring.

AIMS/HYPOTHESIS: Continuous glucose monitoring (CGM) provides comprehensive information on the exposure to dysglycaemia. This study aimed to investigate the threshold of hyperglycaemia related to mortality risk in critically ill patients using CGM technology. METHODS: A total of 293 adult critically ill patients admitted to intensive care units of five medical centres were prospectively included between May 2020 and November 2021. Participants wore intermittently scanned CGM for a median of 12.0 days. The relationships between different predefined time above ranges (TARs), with the thresholds of hyperglycaemia ranging from 7.8 to 13.9 mmol/l (140-250 mg/dl), and in-hospital mortality risk were assessed by multivariate Cox proportional regression analysis. Time in ranges (TIRs) of 3.9 mmol/l (70 mg/dl) to the predefined hyperglycaemic thresholds were also assessed. RESULTS: Overall, 66 (22.5%) in-hospital deaths were identified. Only TARs with a threshold of 10.5 mmol/l (190 mg/dl) or above were significantly associated with the risk of in-hospital mortality, after adjustment for covariates. Furthermore, as the thresholds for TAR increased from 10.5 mmol/l to 13.9 mmol/l (190 mg/dl to 250 mg/dl), the hazards of in-hospital mortality increased incrementally with every 10% increase in TARs. Similar results were observed concerning the associations between TIRs with various upper thresholds and in-hospital mortality risk. For per absolute 10% decrease in TIR 3.9-10.5 mmol/l (70-190 mg/dl), the risk of in-hospital mortality was increased by 12.1% (HR 1.121 [95% CI 1.003, 1.253]). CONCLUSIONS/INTERPRETATION: A glucose level exceeding 10.5 mmol/l (190 mg/dl) was significantly associated with higher risk of in-hospital mortality in critically ill patients.

The Slack Channel Regulates Anxiety-Like Behaviors via Basolateral Amygdala Glutamatergic Projections to Ventral Hippocampus.

Anxiety disorders are a series of mental disorders characterized by anxiety and fear, but the molecular basis of these disorders remains unclear. In the present study, we find that the global Slack KO male mice exhibit anxious behaviors, whereas the Slack Y777H male mice manifest anxiolytic behaviors. The expression of Slack channels is rich in basolateral amygdala (BLA) glutamatergic neurons and downregulated in chronic corticosterone-treated mice. In addition, electrophysiological data show enhanced excitability of BLA glutamatergic neurons in the Slack KO mice and decreased excitability of these neurons in the Slack Y777H mice. Furthermore, the Slack channel deletion in BLA glutamatergic neurons is sufficient to result in enhanced avoidance behaviors, whereas Kcnt1 gene expression in the BLA or BLA-ventral hippocampus (vHPC) glutamatergic projections reverses anxious behaviors of the Slack KO mice. Our study identifies the role of the Slack channel in controlling anxious behaviors by decreasing the excitability of BLA-vHPC glutamatergic projections, providing a potential target for anxiolytic therapies.SIGNIFICANCE STATEMENT Anxiety disorders are a series of mental disorders characterized by anxiety and fear, but the molecular basis of these disorders remains unclear. Here, we examined the behaviors of loss- and gain-of-function of Slack channel mice in elevated plus maze and open field tests and found the anxiolytic role of the Slack channel. By altering the Slack channel expression in the specific neuronal circuit, we demonstrated that the Slack channel played its anxiolytic role by decreasing the excitability of BLA-vHPC glutamatergic projections. Our data reveal the role of the Slack channel in the regulation of anxiety, which may provide a potential molecular target for anxiolytic therapies.

Epigenetic Application of ATAC-Seq Based on Tn5 Transposase Purification Technology.

Background: Assays of transposase accessible chromatin sequencing (ATAC-seq) is an efficient assay to investigate chromatin accessibility, which depends on the activity of a robust Tn5 transposase to fragment the genome while cutting in the sequencing adapters. Methods: We propose reliable approaches for purifying hyperactive Tn5 transposase by chitin magnetic bead sorting. Double-stranded DNA of J76 cells and 293T cells were digested and subjected to tagmentation as test samples with Tn5 transposase, and libraries were established and sequenced. Sequencing data was then analyzed for peak calling, GO enrichment, and motif analysis. Results: We report a set of rapid, efficient, and low-cost methods for ATAC-seq library construction and data analysis, through large-scale and rapid sequencing. These methods can provide a reference for the study of epigenetic regulation of gene expression.

Application of Multi-Electrode Resistivity Method on Semi-Diagenesis Rocks in Freezing Area and Its' Implications.

Recently, with the development of geophysical exploration technology, geophysical engineering instruments and methods have also improved. The multi-electrode resistivity method is widely used in engineering exploration. In this paper, multi-electrode resistivity tests were carried out in a seasonal frozen soil area in Heilongjiang Province, to provide an optimized multi-electrode resistivity method under the conditions of frozen soil. Combined with shear wave velocity tests and standard penetration tests, multi-electrode resistivity tests were used to comprehensively analyze and evaluate the physical and mechanical properties of Tertiary semi-diagenesis rocks. The results show that the high resistivity due to the frozen surface layer acting as a shield can be eliminated by technical means. It is feasible to test the resistivity through the frozen surface layer. The multi-electrode resistivity method can visually reflect the interface between saturated sand and semi-diagenetic rocks. Dividing the interface between saturated sand and semi-diagenetic rocks is advantageous as the morphology of the resistivity curve has a significant curvature change. There is a strong correlation between the resistance and shear wave velocity of a strata in which the Pearson correlation coefficient is as high as 0.99. The multi-electrode resistivity method test used in combination with the shear wave velocity test and the standard penetration test could give the bearing capacity and frictional resistance of semi-diagenetic rocks, which saves a lot of time and material costs in engineering exploration.

Predominant role of gut-vagus-brain neuronal pathway in postoperative nausea and vomiting: evidence from an observational cohort study.

BACKGROUND: Postoperative nausea and vomiting (PONV) as a clinically most common postoperative complication requires multimodal antiemetic medications targeting at a wide range of neurotransmitter pathways. Lacking of neurobiological mechanism makes this 'big little problem' still unresolved. We aim to investigate whether gut-vagus-brain reflex generally considered as one of four typical emetic neuronal pathways might be the primary mediator of PONV. METHODS: Three thousand two hundred twenty-three patients who underwent vagus nerve trunk resection (esophagectomy and gastrectomy) and non-vagotomy surgery (hepatectomy, pulmonary lobectomy and colorectomy) from December 2016 to January 2019 were enrolled. Thirty cases of gastrectomy with selective resection on the gastric branch of vagus nerve were also recruited. Nausea and intensity of vomiting was recorded within 24 h after the operation. RESULTS: PONV occurred in 11.9% of 1187 patients who underwent vagus nerve trunk resection and 28.7% of 2036 non-vagotomy patients respectively. Propensity score matching showed that vagotomy surgeries accounted for 19.9% of the whole PONV incidence, much less than that observed in the non-PONV group (35.1%, P <  0.01). Multivariate logistic regression result revealed that vagotomy was one of underlying factor that significantly involved in PONV (OR = 0.302, 95% CI, 0.237-0.386). Nausea was reported in 5.9% ~ 8.6% vagotomy and 12 ~ 17% non-vagotomy patients. Most vomiting were mild, being approximately 3% in vagotomy and 8 ~ 13% in non-vagotomy patients, while sever vomiting was much less experienced. Furthermore, lower PONV occurrence (10%) was also observed in gastrectomy undergoing selective vagotomy. CONCLUSION: Patients undergoing surgeries with vagotomy developed less PONV, suggesting that vagus nerve dependent gut-brain signaling might mainly contribute to PONV.

Ethylene regulates post-germination seedling growth in wheat through spatial and temporal modulation of ABA/GA balance.

This study aimed to gain insights into the molecular mechanisms underlying the role of ethylene in regulating germination and seedling growth in wheat by combining pharmacological, molecular, and metabolomics approaches. Our study showed that ethylene does not affect radicle protrusion but controls post-germination endospermic starch degradation through transcriptional regulation of specific α-amylase and α-glucosidase genes, and this effect is mediated by alteration of endospermic bioactive gibberellin (GA) levels, and GA sensitivity via expression of the GA signaling gene, TaGAMYB. Our data implicated ethylene as a positive regulator of embryo axis and coleoptile growth through transcriptional regulation of specific TaEXPA genes. These effects were associated with modulation of GA levels and sensitivity, through expression of GA metabolism (TaGA20ox1, TaGA3ox2, and TaGA2ox6) and signaling (TaGAMYB) genes, respectively, and/or the abscisic acid (ABA) level and sensitivity, via expression of specific ABA metabolism (TaNCED2 or TaCYP707A1) and signaling (TaABI3) genes, respectively. Ethylene appeared to regulate the expression of TaEXPA3 and thereby root growth through its control of coleoptile ABA metabolism, and root ABA signaling via expression of TaABI3 and TaABI5. These results show that spatiotemporal modulation of ABA/GA balance mediates the role of ethylene in regulating post-germination storage starch degradation and seedling growth in wheat.

Responses of the proteome in testis of mice exposed chronically to environmentally relevant concentrations of Microcystin-LR.

Microcystin-LR (MC-LR), a widespread environmental contaminant, has been shown to have potent acute testicular toxicity. However, magnitudes of toxic effects, induced by MCs, depend on route and magnitude of exposure to the toxin. In the present study, male mice were orally exposed 1, 10 or 100 µg/L MC-LR for 90 or 180 days, and pathological approach and the isobaric tags for relative and absolute quantitation (iTRAQ)-based proteomics were employed with testes. Proteomics revealed that a number of differentially altered proteins may be involved in MC-LR-induced chronic testicular toxicity. The biological process analysis indicated the altered proteins played an important role in biological adhesion, cellular process, response to stimulus or rhythmic process. The cellular component analysis revealed that most of the proteins with altered expression associated with cell part, extracellular region, extracellular region part, membrane, membrane part, organelle or organelle part. The molecular function showed that these proteins were critical in molecular transducer activity. Integrity analyses provide first compelling evidence that MC-LR significantly cause dysfunction of blood-testis barrier (BTB) through affecting tight junctions and gap junctions. Moreover, phosphatidylinositol 3-kinase (PI3K)/AKT eventually contributed to injury result from chronic low-level MC-LR treatment. Identification of proteins in testis responsive to MC-LR provides insights into molecular mechanisms of chronic toxicity of MCs.

Preoperative Sleep Disturbance Exaggerates Surgery-Induced Neuroinflammation and Neuronal Damage in Aged Mice.

Postoperative cognitive dysfunction (POCD) is defined as new cognitive impairment (memory impairment and impaired performance) after surgery, especially in aged patients. Sleep disturbance is a common phenomenon before surgery that has been increasingly thought to affect patient recovery. However, little is known about the functional impact of preoperative sleep disturbance on POCD. Here, we showed that tibial fracture surgery induced cognitive deficit and production of proinflammatory cytokines interleukin-6 (IL-6) and IL-1ß, along with microglia and astrocyte activation, neuronal damage, and blood-brain barrier (BBB) disruption. Preoperative sleep disturbance enhanced the surgery-induced neuroinflammation, neuronal damage, BBB disruption, and memory impairment 24 h after surgery. Taken together, these results demonstrated that preoperative sleep disturbance aggravated postoperative cognitive function in aged mice and the mechanism may be related to central nervous system (CNS) inflammation and neuronal damage.

Degradation of phenol by coal-based carbon membrane integrating sulfate radicals-based advanced oxidation processes.

Phenol, as a representative organic pollutant in aquatic environments, has posed a serious threat to humans and ecosystem. In this work, a novel integration system combined coal-based carbon membrane with sulfate radicals-based advanced oxidation processes (SR-AOPs) was designed for degradation of phenol. The integrated system achieved 100% removal efficiency under the optimal condition (peroxydisulfate dosage is 0.2 g/L, at alkaline condition with 2 mL/min flow velocity). The quenching experiments revealed that the efficient removal of phenol by the integrated system were attributed to the co-existence of radical and nonradical mechanisms. This study proposes a green and efficient technique for the removal of phenol.

Comparison of the nephrotoxic effects of iodixanol versus iohexol in patients with chronic heart failure undergoing coronary angiography or angioplasty.

OBJECTIVES: The aim of this clinical trial is to compare iodixanol with iohexol for the incidence of contrast-induced nephropathy in patients with chronic heart failure with reduced ejection fraction who are currently undergoing coronary angiography or angioplasty. METHODS: The clinical trial included 220 consecutive patients with chronic heart failure with reduced ejection fraction undergoing coronary angiography or angioplasty. Study participants were administered either iodixanol (n = 110) or iohexol (n = 110). The primary study endpoint was the incidence of contrast-induced nephropathy within 72 h after the procedure. The secondary endpoints were to determine the peak increase in serum creatinine levels and Cystatin C, and the peak decrease in estimated glomerular filtration rate at 72 h post-contrast medium. RESULTS: Baseline demographic and clinical characteristics of the patients were similar between the two groups. Our study showed that the overall incidence of contrast induced nephropathy in patients with chronic heart failure was 20.9%. The incidence of contrast induced nephropathy was significantly lower in iodixanol group than in iohexol group (29.1% vs 12.7%, P = 0.041). The peak increase in serum creatinine levels and the peak decrease in estimated glomerular filtration rate after the procedure were statistically significant between the two groups. Moreover, there was statistically significance in the peak increase of Cystatin C levels after the procedure. CONCLUSIONS: In patients with chronic heart failure with reduced ejection fraction who are currently undergoing coronary angiography with or without percutaneous coronary intervention, the iso-osmolar contrast iodixanol was associated with a lower incidence of contrast induced nephropathy than low-osmolar contrast iohexol.

Effects of RAGE-Specific Inhibitor FPS-ZM1 on Amyloid-ß Metabolism and AGEs-Induced Inflammation and Oxidative Stress in Rat Hippocampus.

An increased level of advanced glycation end products (AGEs) is observed in brains of patients with Alzheimer's disease (AD). AGEs and receptor for AGEs (RAGE) play important roles in the pathogenesis of AD. FPS-ZM1 is a high-affinity RAGE-specific blocker that inhibits amyloid-ß binding to RAGE, neurological damage and inflammation in the APP(sw/0) transgenic mouse model of AD. FPS-ZM1 is not toxic to mice and can easily cross the blood-brain barrier. In this study, an AGEs-RAGE-activated rat model were established by intrahippocampal injection of AGEs, then these rats were treated with intraperitoneal administration of FPS-ZM1 and the possible neuroprotective effects were investigated. We found that AGEs administration induced an-regulation of Abeta production, inflammation, and oxidative stress, and an increased escape latency of rats in the Morris water maze test, all of these are significantly reduced by FPS-ZM1 treatment. Our results suggest that the AGEs-RAGE pathway is responsible for cognitive deficits, and therefore may be a potential treatment target. FPS-ZM1 might be a novel therapeutic agent to treat AD patients.

Reproductive toxicity of JJH201501 in rats: Perinatal study.

INTRODUCTION: In this study, JJH201501 was examined for reproductive toxicity during the perinatal period to support its safety as a novel serotonergic agent (5-HT) antidepressant. Pregnant Sprague-Dawley rats (F0, n = 24/group) were continuously exposed to 0 (control), 6, 18, and 60 mg/kg body weight/day of JJH201501 by intragastric administration from gestation day 15 to lactation day 21. METHODS: During this period, maternal toxicity was evaluated based on clinical signs, body weight, feed intake, delivery condition, litter parameters, and necropsy, with body weight, sex ratios, malformation incidence, physical, and neurodevelopmental assessments conducted on all offspring rats. Ten pups (male:female 1:1) from each dam within each dose group on postnatal day 4 (PND4) were randomly selected. One pair was evaluated for behavior evaluations (F1a) after PND35, one for reproduction performance (F1b) after 10 weeks, and three for organ weight and deformities (F1c) on PND35. After successful mating, F1b male rats were weighed and dissected to assess reproductive organ weight and sperm motility. Pregnant F1b rats were weighed and monitored for food intake twice weekly until laparotomy on GD14, which recorded live/dead fetuses, resorptions, implantations, corpora lutea, and uterine weight. Some statistical differences were found between the JJH-treated and control groups in maternal weight, food consumption, and F1 body weight and water maze performance. RESULTS: Autopsy results showed that JJH201501 had a low cardiac index effect in F0, with no significant histopathological changes detected. Only one F1 offspring died in the high-dose group throughout the experiment. Due to the lack of dose-dependent effects and the consistent growth pattern of these alterations, the study findings do not suggest any toxicological significance for the observed results. CONCLUSION: In conclusion, the no-observed-adverse-effect level of JJH201501 for perinatal rats is about 60 mg/kg b.w./day.

SRSF10 regulates migration of neural progenitor cells and granule cells and affects the formation of dentate gyrus during the development of mouse hippocampus.

Hippocampus is a critical component of the central nervous system. SRSF10 is expressed in central nervous system and plays important roles in maintaining normal brain functions. However, its role in hippocampus development is unknown. In this study, using SRSF10 conditional knock-out mice in neural progenitor cells (NPCs), we found that dysfunction of SRSF10 leads to developmental defects in the dentate gyrus of hippocampus, which manifests as the reduced length and wider suprapyramidal blade and infrapyramidal blade.Furthermore, we proved that loss of SRSF10 in NPCs caused inhibition of the differentiation activity and the abnormal migration of NPCs and granule cells, resulting in reduced granule cells and more ectopic granule cells dispersed in the molecular layer and hilus. Finally, we found that the abnormal migration may be caused by the radial glia scaffold and the reduced DISC1 expression in NPCs. Together, our results indicate that SRSF10 is required for the cell migration and formation of dentate gyrus during the development of hippocampus.

Offspring's own serotonin transporter genotype, independently from the maternal one, increases anxiety- and depression-like behavior and alters neuroplasticity markers in rats.

INTRODUCTION: Developmental changes due to early life variations in the serotonin system affect stress-related behavior and neuroplasticity in adulthood. These outcomes can be caused both by offspring's own and maternal serotonergic genotype. We aimed to dissociate the contribution of the own genotype from the influences of mother genotype. METHODS: Sixty-six male homozygous (5-HTT-/-) and heterozygous (5-HTT+/-) serotonin transporter knockout and wild-type rats from constant 5-HTT genotype mothers crossed with varying 5-HTT genotype fathers were subjected to tests assessing anxiety- and depression-like behaviors. Additionally, we measured plasma corticosterone levels and mRNA levels of BDNF, GABA system and HPA-axis components in the prelimbic and infralimbic cortex. Finally, we assessed the effect of paternal 5-HTT genotype on these measurements in 5-HTT+/- offspring receiving their knockout allele from their mother or father. RESULTS: 5-HTT-/- offspring exhibited increased anxiety- and depression-like behavior in the elevated plus maze and sucrose preference test. Furthermore, Bdnf isoform VI expression was reduced in the prelimbic cortex. Bdnf isoform IV and GABA related gene expression was also altered but did not survive false discovery rate (FDR) correction. Finally, 5-HTT+/- offspring from 5-HTT-/- fathers displayed higher levels of anxiety- and depression-like behavior and changes in GABA, BDNF and HPA-axis related gene expression not surviving FDR correction. LIMITATIONS: Only male offspring was tested. CONCLUSIONS: Offspring's own 5-HTT genotype influences stress-related behaviors and Bdnf isoform VI expression, independently of maternal 5-HTT genotype. Paternal 5-HTT genotype separately influenced these outcomes. These findings advance our understanding of the 5-HTT genotype dependent susceptibility to stress-related disorders.

Risk factor analysis of postoperative complications in patients undergoing emergency abdominal surgery.

Purpose: To investigate the relationship between intraoperative anesthesia-related factors and postoperative complications in patients undergoing emergency abdominal surgery, and to identify risk factors for these postoperative complications. Methods: We retrospectively analyzed 942 emergency surgery patients who underwent general anesthesia and emergency abdominal operations at Jiangsu Province Hospital during the period September 2015 to December 2016. Logistic regression analysis was performed to analyze the association between preoperative or intraoperative parameters and postoperative complications. Results: Among the 942 patients whose data were analyzed, 226 (24.0%) had major postoperative complications within 30 days after surgery. The most common postoperative complications were respiratory complications (31.8% of those experiencing complications). After adjusting for the role of multiple confounding factors, multivariable analysis showed that the independent risk factors for postoperative complications were patient age (OR 1.648; 95% CI 1.352-2.008), the ASA classification (OR 3.220; 95% CI 2.492-4.162), intraoperative hypotension lasting more than 20 min (OR 2.031; 95% CI 1.256-3.285), intraoperative tachyarrhythmias (OR 2.205; 95% CI 1.114-4.365), and the surgical level (i.e. type and difficulty level) [OR 1.895; 95% CI 1.306-2.750]. Conclusion: Prolonged intraoperative hypotension (>20 min) and the occurrence of tachyarrhythmias are independent risk factors for postoperative complications in patients who undergo emergency abdominal surgery. During hemodynamic management of these patients, systolic blood pressure should be controlled to within 20% of the baseline value to reduce the risk of postoperative complications. In addition, a higher patient age, higher ASA grade, and a higher surgical classification level also significantly increase the risk of postoperative complications.

Monitoring the Relationship between Social Network Status and Influenza Based on Social Media Data.

BACKGROUND: This article aims to analyze the relationship between user characteristics on social networks and influenza. METHODS: Three specific research questions are investigated: (1) we classify Weibo updates to recognize influenza-related information based on machine learning algorithms and propose a quantitative model for influenza susceptibility in social networks; (2) we adopt in-degree indicator from complex networks theory as social media status to verify its coefficient correlation with influenza susceptibility; (3) we also apply the LDA topic model to explore users' physical condition from Weibo to further calculate its coefficient correlation with influenza susceptibility. From the perspective of social networking status, we analyze and extract influenza-related information from social media, with many advantages including efficiency, low cost, and real time. RESULTS: We find a moderate negative correlation between the susceptibility of users to influenza and social network status, while there is a significant positive correlation between physical condition and susceptibility to influenza. CONCLUSIONS: Our findings reveal the laws behind the phenomenon of online disease transmission, and providing important evidence for analyzing, predicting, and preventing disease transmission. Also, this study provides theoretical and methodological underpinnings for further exploration and measurement of more factors associated with infection control and public health from social networks.

Microglia participate in postoperative cognitive dysfunction by mediating the loss of inhibitory synapse through the complement pathway.

BACKGROUND: Elderly patients after surgery are prone to cognitive decline known as postoperative cognitive dysfunction (POCD). Several studies have shown that the microglial activation and the increase of complement protein expression in hippocampus induced by surgery may be related to the pathogenesis of POCD. The purpose of this study was to determine whether microglia and complement system were involved in cognitive dysfunction in aged mice. METHODS: The POCD model was established by exploratory laparotomy in 15-month-old male C57BL/6J mice and animal behavioral tests were performed to test hippocampal-dependent memory capacity. Minocycline was used to suppress the activation of microglia, and complement 3 receptor inhibitor was used to suppress the association between microglia and complement 3. Western blot and immunofluorescence were used to detect the microglial activation, complement protein, and synaptic protein expressions. RESULTS: Operation induced hippocampal-dependent memory impairment (P < 0.01), which was accompanied by microglial activation (P < 0.01). There was also a significant reduction in inhibitory synaptic protein expression in the hippocampus of mice in the surgery group (P < 0.01). However, minocycline, a microglia inhibitor, rescued all the above changes. In addition, C3RI intervention inhibited the phagocytosis of inhibitory synapses by microglia (P < 0.05) and improved the cognitive function of mice (P < 0.01). CONCLUSION: Microglia participate in postoperative cognitive dysfunction by mediating inhibitory synaptic loss through the complement pathway.

Sensitive and rapid detection of tetrodotoxin based on gold nanoflower-and latex microsphere-labeled monoclonal antibodies.

Tetrodotoxin (TTX) could result in serious diseases due to its extremely high neurotoxicity. Thus, it is of great importance to measure TTX for food safety. In this study, an anti-TTX monoclonal antibody with good specificity and high affinity was used to develop the immunochromatographic test strips (ICTS). Gold nanoflower (AuNF) with multiple branches and latex microsphere (LM) with large particle size as signal reporters were employed for improving the sensitivity of test strips. Both AuNF and LM probes are stable, and the developed ICTS were specific to TTX, demonstrating no cross-reactivity with other marine toxins. The linear range of AuNF- and LM-based strips for TTX was 9.49-330.98 ng/mL and 5.40-443.19 ng/mL, respectively. The limit of detection (LOD) of AuNF- and LM-based strips was determined to be 9.49 ng/mL and 5.40 ng/mL, respectively. In summary, the developed ICTS based on AuNF and LM signal probes displayed enhancement of sensitivity and provided rapid and specific detection of TTX.

SRSF10 regulates proliferation of neural progenitor cells and affects neurogenesis in developing mouse neocortex.

Alternative pre-mRNA splicing plays critical roles in brain development. SRSF10 is a splicing factor highly expressed in central nervous system and plays important roles in maintaining normal brain functions. However, its role in neural development is unclear. In this study, by conditional depleting SRSF10 in neural progenitor cells (NPCs) in vivo and in vitro, we found that dysfunction of SRSF10 leads to developmental defects of the brain, which manifest as abnormal ventricle enlargement and cortical thinning anatomically, as well as decreased NPCs proliferation and weakened cortical neurogenesis histologically. Furthermore, we proved that the function of SRSF10 on NPCs proliferation involved the regulation of PI3K-AKT-mTOR-CCND2 pathway and the alternative splicing of Nasp, a gene encoding isoforms of cell cycle regulators. These findings highlight the necessity of SRSF10 in the formation of a structurally and functionally normal brain.

Intestinal Ultrasound Combined with Blood Inflammatory Markers Is a More Efficient Tool in Evaluating Severity of Crohn's Disease: A Pilot Study.

Background and Aims: Intestinal ultrasound (IUS) is considered a nonirradiating, noninvasive, well-tolerated, and valuable tool for objectively assessing Crohn's disease (CD) activity. However, there is no widely accepted intestinal ultrasound scoring system. This study is aimed at evaluating the efficacy of IUS key parameters, the International Bowel Ultrasound Activity Score (IBUS-SAS), and IBUS-SAS combined with blood inflammatory markers in assessing CD activity. Methods: 40 CD patients were reviewed in this retrospective study and were divided into the moderate-severe group (n = 25) and nonmoderate-severe group (n = 15) based on a simplified endoscopic score of Crohn's disease (SES-CD). Double-balloon enteroscopy/colonoscopy were reviewed by three gastroenterologists. A transabdominal ultrasound was performed by two ultrasound specialists. Blood inflammatory markers were measured from morning samples. Results: In evaluating moderate to severe CD patients, (1) IBUS-SAS had a good predictive effect with an area-under-the-curve (AUC) of 0.855 (P < 0.001); (2) IUS key parameters (including BWT, CDS, BWS, and I-fat) yielded good predictive effects with AUC of 0.811, 0.731, 0.724, and 0.747, respectively (P < 0.001); (3) blood inflammatory markers (including ESR, CRP, PLR, MLR, and NLR) also had good predictive effects with AUC of 0.771, 0.837, 0.728, 0.743, and 0.775, respectively (P < 0.001); (4) IBUS-SAS combined with ESR and CRP exerted the best predictive effect with the highest AUC of 0.912 (95% CI: 0.823-1.000), and the sensitivity and specificity were 88.0% and 80.0%, respectively (P < 0.001). Conclusion: IBUS-SAS combined with ESR and CRP is a more efficient tool than IBUS-SAS alone or inflammatory markers alone in evaluating CD patients with moderate to severe disease activity.