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Abstract Background Polycyclic triterpenoids (PTs) are common in plants, and have attracted considerable interest due to their remarkable biological activities. Currently, engineering the ergosterol synthesis pathway in Saccharomyces cerevisiae is a safe and cost-competitive way to produce triterpenoids. However, the strict regulation of ERG1 involved in the epoxidation of squalene limits the triterpenoid production. Results In this study, we found that the decrease in ERG7 protein level could dramatically boost the epoxidation of squalene by improving the protein stability of ERG1. We next explored the potential factors that affected the degradation process of ERG1 and confirmed that ERG7 was involved in the degradation process of ERG1. Subsequently, expression of four different triterpene cyclases utilizing either 2,3-oxidosqualene or 2,3:22,23-dioxidosqualene as the substrate in ERG7-degraded strains showed that the degradation of ERG7 to prompt the epoxidation of squalene could significantly increase triterpenoid production. To better display the potential of the strategy, we increased the supply of 2,3-oxidosqualene, optimized flux distribution between ergosterol synthesis pathway and β-amyrin synthesis pathway, and modified the GAL-regulation system to separate the growth stage from the production stage. The best-performing strain ultimately produced 4216.6 ± 68.4 mg/L of β-amyrin in a two-stage fed-fermentation (a 47-fold improvement over the initial strain). Conclusions This study showed that deregulation of the native restriction in ergosterol pathway was an effective strategy to increase triterpenoid production in yeast, which provided a new insight into triterpenoids biosynthesis.

Purpose: It has previously been reported that repeated exposure to hypoxia increases spleen size and haemoglobin (HGB) level and recent reports on the effect apnoea has on spleen size and haematological parameters are contradictory. Therefore, this study aims to evaluate the effect apnoea training has on spleen size and haematological parameters.Methods: The breath-holding (BH) group was comprised of 12 local student-athletes with no BH exercise experience who performed BH jogging and BH jumping rope dynamic apnoea protocols, five times weekly for 8 weeks. The BH event duration was progressively increased as the apnoea tolerance of the athletes improved (20 to 35 s). The same training task was performed by the control group (n = 10) without BH. Spleen sizes were measured with an ultrasound system and a complete blood cell analysis was performed on the median cubital venous blood.Results: Spleen volume in the BH group increased from 109 ± 13 ml to 136 ± 13 ml (p < 0.001), and bulky platelets decreased from 70.50 ± 5.83 to 65.17 ± 5.87 (p = 0.034), but no changes were recorded for erythrocytes (p = 0.914), HGB (p = 0.637), PLTs (p = 0.346) and WBC (p = 0.532). No changes were recorded for the control group regarding spleen size or haematological parameters.Conclusion: Eight weeks of dry dynamic apnoea training increased spleen size and decreased the number of circulating bulky platelets in the athletes who were assessed in this study. However, the baseline RBC counts and HGB levels of the athletes were not altered by the training programme.

Exercise (Ex) has long been recognized to produce beneficial effects on hypertension (HTN). This coupled with evidence of gut dysbiosis and an impaired gut-brain axis led us to hypothesize that reshaping of gut microbiota and improvement in impaired gut-brain axis would, in part, be associated with beneficial influence of exercise. Male spontaneously hypertensive rats (SHR) and Wistar Kyoto (WKY) rats were randomized into sedentary, trained, and detrained groups. Trained rats underwent moderate-intensity exercise for 12 weeks, whereas, detrained groups underwent 8 weeks of moderate-intensity exercise followed by 4 weeks of detraining. Fecal microbiota, gut pathology, intestinal inflammation, and permeability, brain microglia and neuroinflammation were analyzed. We observed that exercise training resulted in a persistent decrease in systolic blood pressure in the SHR. This was associated with increase in microbial α diversity, altered β diversity, and enrichment of beneficial bacterial genera. Furthermore, decrease in the number of activated microglia, neuroinflammation in the hypothalamic paraventricular nucleus, improved gut pathology, inflammation, and permeability were also observed in the SHR following exercise. Interestingly, short-term detraining did not abolish these exercise-mediated improvements. Finally, fecal microbiota transplantation from exercised SHR into sedentary SHR resulted in attenuated SBP and an improved gut-brain axis. These observations support our concept that an impaired gut-brain axis is linked to HTN and exercise ameliorates this impairment to induce antihypertensive effects.

Objective To explore the safety of the corona mortis of the minimally invasive plate insertion in treatment of the anterior pelvic ring fracture by studying the relationship between the vessel and the position of plate. Method The corona mortis was dissected out of eight adult cadavers and were simulated for the insertion of the anterior ring minimally invasive plate, and the presence of the anastomotic branch (the corona mortis) in the suprapubic branch area was observed. After the Corona mortis stripped off, the data was measured, such as the length, vessel diameter, distance from the pubic tubercle, and the maximum vertical distance between the corona mortis and the pubis. The measured data and the previous literatures were analyzed to study the morphology of the corona mortis and the position relation between the corona mortis and the placement of subperiosteal tunnel through the minimally invasive ilioinguinal approach. Results Out of the 16 unilateral pelvises, the corona mortis were observed on 12 unilateral pelvises with an incidence rate of 75%. Amongst them, there were seven cases of vein anastomosis (incidence of 43.75%), three cases of arterial anastomosis (incidence of 18.75%), and two cases of both arterial anastomosis and vein anastomosis (incidence of 12.5%). The corona mortis length ranged between 24.5 and 37.5 mm (average of 30.7 ± 3.6 mm); the diameter ranged between 1.6 and 3.5 mm (average of 2.5 ± 0.5 mm) and the distance between the vessels and the pubic tubercle was between 53.9 and 65.2 mm (average of 59.0 ± 3.6 mm). Above the pubis, the corona mortis originated from the iliac or the inferior epigastric vessel. It crossed the pubic branch to the dorsal side of the pubis and proceeded downward to anastomize with the obturator vessels near the obturator. Toothless tweezers were used to peel and lift up the corona mortis from the pubic bone. The maximum vertical distance between the corona mortis and the pubis ranged between 8.8 and 18.3 mm (average of 12.6 ± 3.0 mm). Conclusion The corona mortis have a high rate of incidence, with a large number of differences in the type and shape of blood vessels among patients. Following peeling, the movement between the corona mortis and pubic bone is limited. Nevertheless, the plate and bone exfoliator still passed safely. Therefore, when surgeons use the minimally invasive ilioinguinal approach to establish channels, the process of subperiosteal stripping must be performed to avoid any accidental injury.

Objective The treatment of missed Monteggia fracture remains a challenge, despite the various surgical methods described. The purpose of this study was to explore a new surgical technique utilizing external fixator‐assisted ulnar osteotomy and to assess the surgical results in a case series. Methods Thirteen patients with missed Monteggia fractures were treated at our institution using this new surgical technique from August 2012 to January 2016. Our series included 11 boys and 2 girls. The left elbow was involved in 6 patients and the right elbow was involved in 7 patients. According to the Bado classification, 10 fractures were classified as Bado type I with anterior radial head dislocation and 3 were classified as Bado type III with anterolateral dislocation. The average age at the time of surgery was 5 years 8 months (range, 2 years 2 months–10 years). The mean trauma‐to‐surgery interval was 12 months (range, 2–36 months). All patients underwent ulnar osteotomy with angulation and lengthening using a temporary external fixator, plate fixation of the osteotomy, and open reduction of the radial head dislocation without annular ligament reconstruction. Results The average follow‐up was 27 months (range, 16–44 months). The average operation time was 175 min (range, 140–215 min). The average length of distraction was 0.7 cm (range, 0.5–1.2 cm) and the average angulation was 28° (range, 20°–30°) at the ulnar osteotomy site intraoperatively. The elbow performance score (Kim's) was excellent in 10 cases and good in 3 cases. No neurovascular complications, compartment syndrome or implant breakage occurred. No pain in the distal radioulnar joint or limited range of motion of the wrist occurred in any patient. The radial head remained reduced in all patients with no subluxation or redislocation. However, delayed ulnar union occurred in 3 cases, all of which were successfully treated with plaster cast immobilization within approximately 6 months postoperatively. One patient presented with cubitus valgus postoperatively with a carrying angle of 30°, which was 10° greater than the contralateral carrying angle. Conclusions External fixator‐assisted ulnar osteotomy offers substantial flexibility for achieving the optimal positioning of the transected ulna to reduce the radial head prior to the final ulnar osteotomy fixation with a plate, thereby facilitating an effective operative performance. Our procedure is a safe and effective method to treat missed pediatric Monteggia fractures.

Objective: Screening variants underlying the single-gene disorder in the general population can help reduce the incidences of birth defects. To determine the most prevalent pathogenic variants causing autosomal recessive diseases, we investigated the frequencies of these variants in six major geographic ancestry groups from Exome Aggregation Consortium (ExAC) database and 26 populations from the 1,000 Genome Project, including three Chinese ethnic groups. Methods: We selected 64 autosomal recessive diseases and collected corresponding causal genes and variants from ClinVar for the analysis. The RS (reference single-nucleotide polymorphism) IDs of these variants were used to search the corresponding VCF file from the 1,000 Genomes Project and ExAC databases. We calculated the frequencies of heterozygotes of each disease variants in the 1,000 Genomes Project and ExAC samples and compared the distribution of disease alleles among different populations. Results: Our analysis revealed that 1,151/212 variants were carried by 60,706/2,504 individuals sequenced in the ExAC/1,000 Genomes Project. The average number of autosomal recessive disease alleles carried by samples from ExAC and 1,000 Genomes Project were 0.53 and 0.68, respectively. These disease alleles showed differential distribution among populations, and some disease alleles were significantly enriched in certain ethnic groups. In addition, 1–2 main pathogenic variants were identified in each disease. Meanwhile, several ClinVar variants with relatively high frequency (>1%) in the samples were found to be benign instead of “conflicting evaluations of pathogenicity.” Conclusions: Our observations revealed that main pathogenic variants existed in certain autosomal recessive disease, suggesting that screening of disease hypermutations in different populations is valuable in reducing the occurrence of birth defects.

As a large group of cells in a central nervous system, astrocytes have a great influence on ion and energy metabolism in a nervous system. Disorders of neuronal ion and energy metabolism caused by impaired astrocytes play a key role in the pathogenesis of epilepsy. This paper reviews the existing computational models of epileptogenesis resulting from impaired astrocytes and presents several open perspectives with regard to ion and energy metabolism-induced epileptogenesis in a neuron-astrocyte-capillary coupled model. [ABSTRACT FROM AUTHOR]

Previous studies have observed that electromagnetic induction can seriously affect the electrophysiological activity of the nervous system. Considering the role of astrocytes in regulating neural firing, we studied a simple neuron–astrocyte coupled system under electromagnetic induction in response to different types of external stimulation. Both the duration and intensity of the external stimulus can induce different modes of electrical activity in this system, and thus the neuronal firing patterns can be subtly controlled. When the external stimulation ceases, the neuron will continue to fire for a long time and then reset to its resting state. In this study, “delay” is defined as the delayed time from the firing state to the resting state, and it is highly sensitive to changes in the duration or intensity of the external stimulus. Meanwhile, the self-similarity embodied in the aforementioned sensitivity can be quantified by fractal dimension. Moreover, a hysteresis loop of calcium activity in the astrocyte is observed in the specific interval of the external stimulus when the stimulus duration is extended to infinity, since astrocytic calcium or neuron electrical activity in the resting state or during periodic oscillation depends on the initial state. Finally, the regulating effect of electromagnetic induction in this system is considered. It is clarified that the occurrence of “delay” depends purely on the existence of electromagnetic induction. This model can reveal the dynamic characteristics of the neuron–astrocyte coupling system with magnetic induction under external stimulation. These results can provide some insights into the effects of electromagnetic induction and stimulation on neuronal activity. [ABSTRACT FROM AUTHOR]