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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.

PurposeElevated concentrations of thyroglobulin eluent is a risk factor for lateral cervical lymph node metastasis (LLNM) in patients with papillary thyroid cancer (PTC). We aimed to develop a practical nomogram based on the distribution of thyroid nodules and the presence of suspicious lateral cervical lymph nodes in fine-needle aspiration biopsies (LN-FNABs), including the cytopathology and the suspicious lateral cervical lymph node (LLN) thyroglobulin eluent (Tg), to predict the possibility of LLNM preoperatively in patients with PTC.MethodsThe clinical data of PTC patients who were admitted to the Third Affiliated Hospital of Soochow University from January 2022 to May 2023 to undergo fine-needle aspiration biopsy (FNAB) were included in this study. A total of 208 patients in 2022 served as the training set (70%), and 89 patients in 2023 served as the validation set (30%). The clinical characteristics and LN-FNAB results were collected to determine the risk factors of LLNM. A preoperative nomogram was developed for predicting LLNM based on the results of the univariate and multivariate analyses. Internal calibration, external calibration, and decision curve analysis (DCA) were performed for these models.ResultsThe multivariate logistic regression analysis showed that the maximum thyroid nodule diameter (Odds Ratio (OR) 2.323, 95% CI 1.383 to 3.904; p = 0.001), Tg level (OR 1.007, 95% CI 1.005 to 1.009; p = 0.000), Tg divided by serum thyroglobulin, (Tg/sTg) [odds ratio (OR) 1.005, 95% CI 1.001 to 1.008; p = 0.009], and cytopathology (OR 9.738, 95% CI 3.678 to 25.783; p = 0.000) (all p < 0.05) had a significant impact on the LLNM of patients with suspicious LLNs. The nomogram showed a better predictive value in both the training cohort [area under the curve, (AUC) 0.937, 95% CI 0.895 to 0.966] and the validation cohort (AUC 0.957, 95% CI 0.892 to 0.989). The nomogram also showed excellent internal and external calibration in predicting LLNM. According to the DCA, the diagnostic performance of this model was dependent on the following variables: maximum thyroid nodule diameter, Tg level, Tg/sTg, and cytopathology.ConclusionBased on the aforementioned risk factors, we believe that it is necessary to establish a personalized LLNM model for patients with PTC. Using this practical nomogram, which combines clinical and Tg risk factors, surgeons could accurately predict the possibility of LLNM preoperatively. The nomogram will also help surgeons to establish personalized treatment plans before surgery.

Nanoscale zero-valent iron particles (NZVI) produced by using green tea (GT) extract as a reductant can remove Cr(VI) from water effectively, which can be utilized in groundwater remediation. In order to define the reaction mechanism and removal effect in the aquifer, in this study, GT-NZVI particles were prepared and measured by some characterization methods to define their surface performance, and then batch and one-dimensional experiments were carried out to reveal the reaction properties of GT-NZVI and Cr(VI) in groundwater. The results showed that the prepared GT-NZVI particles were regular spherical with a diameter of 10–20 nm, which could disperse in water stably. The main component of GT-NZVI was α-Fe with superficial polyphenols as a stabilizer. GT-NZVI suspension had good ability to reduce the Cr(VI) to Cr(III) in water. When the concentration of GT-NZVI was 1 g/L, the removal efficiency of Cr(VI) with an initial concentration of 100 mg/L reached 92.8% in 1 h reaction. In column tests, GT-NZVI passed through the natural sand column successfully with an average outflow percentage of 71.2%. The simulated in-situ reaction zone (IRZ) with GT-NZVI was used to remediate Cr(VI) contaminated groundwater. The outflow concentration of Cr(VI) kept in 0.14–0.32 mg/L corresponding to the outflow rate below 0.32% within 15 days, and the removal efficiency of Cr(VI) by IRZ with GT-NZVI decreased with the increase of aquifer medium particle size, groundwater flow rate and ionic strength. Most of Cr(III) as reduzate was adsorbed or immobilized on the surface or in the lattice of GT-NZVI, which indicated effective immobilization for chromium.

BackgroundAdolescent obesity is associated with impaired inhibitory control. Acute exercise can improve executive function. However, due to the influence of exercise intensity, cognitive test timing, and cardiorespiratory fitness (CF) level, the most effective exercise program remains controversial.MethodsThe current study investigated the time-course effects of moderate-intensity continuous exercise (MICE) and high-intensity interval exercise (HIIE) on inhibitory control (Stroop) and task-related heart rate variability (HRV) in adolescents with different CF. A mixed experimental design of 2 CF levels (high CF, HCF; low CF, LCF) × 3 exercise methods (MICE, HIIE, CON) × 3 test timing (pre, post-0, post-20) was adopted. Heart rate variability (HRV) and Stroop task tests were conducted before exercise (pre), immediately after exercise (post-0), and 20 min after exercise (post-20).ResultsIndividuals with HCF exhibited a positive decrease in Stroop response time immediately and 20 min after MICE and HIIE, compared to pretest response times (RT). Conversely, individuals with LCF showed a slight increase in Stroop task (RT) only immediately after HIIE. All individuals had a slight increase in ACC after MICE and HIIE compared to before exercise. In addition, compared with the control group, the time-domain index (the square root of the mean squared differences of successive NN intervals, RMSSD) of HRV was significantly decreased, the frequency-domain index (the absolute power of the Low-Frequency band/the absolute power of the High-Frequency band ratio, LF/HF) was significantly increased after MICE and HIIE, and the effect of HIIE on RMSSD and LF/HF was significantly greater than that of MICE.ConclusionThe current study found that the acute effects of MICE and HIIE on inhibitory control in obese adolescents were influenced by the interaction of cognitive test timing and cardiorespiratory fitness. Individuals with high cardiorespiratory fitness performed better on the Stroop task than individuals with low cardiorespiratory fitness. The inhibitory control of HIIE in high-cardiorespiratory obese adolescents produced positive effects similar to those in MICE but more lasting, suggesting that HIIE is more beneficial for high-cardiorespiratory obese adolescents. MICE promoted inhibitory control in obese adolescents with low cardiorespiratory fitness, but HIIE impaired inhibitory control in obese adolescents with low cardiorespiratory fitness immediately after exercise, suggesting that low cardiopulmonary fitness obese adolescents may be suitable for MICE rather than HIIE exercise intervention. The shift from balanced HRV to sympathetic dominance after acute exercise reflects increased arousal levels and may be one of the underlying mechanisms by which acute exercise brings benefits to executive function.

IntroductionVariability in the success rates for the endoscopic correction of vesicoureteral reflux (VUR) has prompted a debate regarding the use of routine postoperative voiding cystourethrogram (VCUG). This study examines the predictive performance of intraoperative mound morphology (IMM) and the presence of a postoperative ultrasound mound (PUM) on radiologic success, as well as investigates the role of using these two predictive factors as a composite tool to predict VUR resolution after endoscopic treatment.MethodsThis retrospective study included children with primary VUR who underwent endoscopic correction with a double hydrodistension-implantation technique (HIT) and dextranomer/hyaluronic acid copolymer. IMM was assessed intraoperatively. The presence of a PUM and VUR resolution were assessed by postoperative ultrasound (US) and VCUG, respectively. Radiologic success was defined as VUR resolution.ResultsA total of 70 children (97 ureters) were included in the study. The overall radiologic success rate was 83.5%. There was no statistically significant association between radiologic success and IMM (85.2% with excellent and 87.5% with "other" morphology; p=0.81). The sensitivity and specificity of PUM for radiologic success in this study was 98% and 71%, respectively, while the sensitivity and specificity of the combined prediction model were 81.9% and 85.7%, respectively.ConclusionsWe objectively demonstrated that IMM was a poor predictor of radiologic success and should be used with caution. In addition, the performance of a combined prediction model was inferior to the presence of a PUM alone. As such, selective use of postoperative VCUG may be guided solely by the presence of a PUM.

Postsynaptic NMDARs at spinal synapses are required for postsynaptic long-term potentiation and chronic pain. Here, the authors show that also presynaptic NMDARs in spinal nociceptor terminals modulate synaptic transmission in a nociceptive tone-dependent manner.