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Objective: This paper mainly studied the effects and regulation of exogenous addition of pyruvate, overexpression of pyruvate kinase and acetyl-CoA synthase on the synthesis of Bacillomycin D. Methods: In this study, B. amyloliquefaciens fmbJ was used as the initial strain. Firstly, the effect of exogenous pyruvate with different concentrations on the yield of Bacillomycin D was detected by HPLC. The regulation of pyruvate in this process was detected by RT-PCR. Then, pyruvate kinase (pyk) and acetyl-CoA synthase (acs) overexpression strains B. amyloliquefaciens fmbJ-pyk and fmbJ-acs were constructed by electrotransformation, and their Bacillomycin D production induced by different concentrations of IPTG was studied. Results: 0.075% pyruvate could increase the yield on Bacillomycin D to 1.41-fold that of the control group. The upregulation of Bacillomycin D synthesis gene also verified this enhancement. In addition, pyruvate could up-regulate the expression of regulatory factors such as comA, comP, comQ, sigH, sigM, degU, degQ, spo0A and codY, down-regulate the expression of rapC and abrB, promote the production of acetyl CoA synthase, and finally jointly promote the synthesis of Bacillomycin D. Under the induction of 50 mg/L IPTG, the yield of Bacillomycin D of fmbJ-acs and fmbJ-pyk increased to 1.16-fold and 1.34-fold that of fmbJ, respectively. Conclusion: This study found that exogenous addition of pyruvate and overexpression of acs or pyk could promote the synthesis of Bacillomycin D, clarified the regulation of pyruvate in the synthesis of Bacillomycin D, and widened a new research idea for promoting the efficient production of Bacillomycin D.

Abstract Background To evaluate the effectiveness of individualized-dose polyethylene glycol recombinant human growth hormone (PEG-rhGH) for short stature. Methods This real-world study enrolled children with short stature in 19 hospitals throughout China. They were treated with PEG-rhGH for 6 months. The starting dosage ranged from 0.10 to 0.20 mg/kg/week. The primary outcome was the change in height standard deviation score (ΔHt SDS). Results Five hundred and ten patients were included and grouped based on dosage as A (0.10–0.14 mg/kg/week), B (0.15–0.16 mg/kg/week), C (0.17–0.19 mg/kg/week), and D (0.20 mg/kg/week). The mean 6-month ΔHt SDS for the total cohort was 0.49 ± 0.27, and the means differed among the four dose groups (P = 0.002). The ΔHt SDS was lower in group A than in groups B (LSM difference [95%CI], -0.09 [-0.17, -0.01]), C (LSM difference [95%CI], -0.10 [-0.18, -0.02]), and D (LSM difference [95%CI], -0.13 [-0.21, -0.05]) after adjusting baseline covariates. There were no significant differences among groups B, C, and D. When the baseline IGF-1 was 0 SDS, the △Ht SDS was not different among the four groups (P = 0.931 and P = 0.400). In children with baseline IGF-1 SDS of -2 ~ 0 SDS, a higher dosage was associated with a better treatment effect (P = 0.003), and the △Ht SDS was lower in older children than in younger ones (P

Lead (Pb) contamination has been affecting public health for decades. As a plant-derived medicine, the safety and effectiveness of Emblica officinalis (E. officinalis) fruit extract has been emphasized. The current study focused on mitigating the adverse effects of lead (Pb) exposure in reducing its toxicity worldwide. According to our findings, E. officinalis significantly improved weight loss and colon length shortening (p

Abstract. Background:. Compared to adult studies, studies which involve the treatment of pediatric congenital hypogonadotropic hypogonadism (CHH) are limited and no universal treatment regimen is available. The aim of this study was to evaluate the feasibility of human chorionic gonadotropin (hCG)/human menopausal gonadotropin (hMG) therapy for treating male adolescents with CHH. Methods:. Male adolescent CHH patients were treated with hCG/hMG (n = 20) or a gonadotropin-releasing hormone (GnRH) pump (n = 21). The treatment was divided into a study phase (0–3 months) and a follow-up phase (3–12 months). The testicular volume (TV), penile length (PL), penis diameter (PD), and sex hormone levels were compared between the two groups. The TV and other indicators between the groups were analyzed using a t-test (equal variance) or a rank sum test (unequal variance). Results:. Before treatment, there was no statistical difference between the two groups in terms of the biochemistry, hormones, and other demographic indicators. After 3 months of treatment, the TV of the hCG/hMG and GnRH groups increased to 5.1 ± 2.3 mL and 4.1 ± 1.8 mL, respectively; however, the difference was not statistically significant (P > 0.05, t = 1.394). The PL reached 6.9 ± 1.8 cm and 5.1 ± 1.6 cm (P 0.05, t = 0.314). After 9 to 12 months of treatment, the T level was higher in the hCG/hMG group. Other parameters did not exhibit a statistical difference. Conclusions:. The hCG/hMG regimen is feasible and effective for treating male adolescents with CHH. The initial 3 months of treatment may be a window to optimally observe the strongest effects of therapy. Furthermore, results from the extended time-period showed positive outcomes at the 1-year mark; however, the long-term effectiveness, strengths, and weaknesses of the hCG/hMG regimen require further research. Trial Registration:. ClinicalTrials.gov, NCT02880280; https://clinicaltrials.gov/ct2/show/NCT02880280.

Congenital hypogonadotropic hypogonadism (CHH) can be divided into Kallmann syndrome (KS) and normosmic HH (nHH). The clinical and genetic characteristics of CHH have been studied in adults, but less in pre-adults. The medical records of patients with CHH in our gonad disease database from 2008 to 2020 were evaluated. In total, 125 patients aged 0 to 18 years were enrolled in our study. KS patients had a higher incidence of micropenis compared with nHH (86.2% vs. 65.8%, p=0.009), and 7 patients (5.6%) had hypospadias. Among the 39 patients with traceable family history, delayed puberty, KS/nHH, and olfactory abnormalities accounted for 56.4%, 17.9%, and 15.4%, respectively. In total, 65 patients completed the hCG prolongation test after undergoing the standard hCG test, and the testosterone levels of 24 patients (22.9%) were still lower than 100 ng/dL. In 77 patients, 25 CHH-related genes were identified, including digenic and trigenic mutations in 23 and 3 patients, respectively. The proportion of oligogenic mutations was significantly higher than that in our previous study (27.7% vs. 9.8%). The most common pathogenic genes were FGFR1, PROKR2, CHD7 and ANOS1. The incidence rate of the genes named above was 21.3%, 18.1%, 12.8% and 11.7%, respectively; all were higher than those in adults (

Abstract Background Wolf-Hirschhorn syndrome is a well-characterized genomic disorder caused by 4p16.3 deletions. Wolf-Hirschhorn syndrome patients exhibit characteristic facial dysmorphism, growth retardation, developmental delay, intellectual disability and seizure disorders. Recently, NSD2 gene located within the 165 kb Wolf-Hirschhorn syndrome critical region was identified as the key causal gene responsible for most if not all phenotypes of Wolf-Hirschhorn syndrome. So far, eight NSD2 loss of function variants have been reported in patients from different parts of the world, all were de novo variants. Methods In our study, we performed whole exome sequencing for two patients from one family. We also reviewed more NSD2 mutation cases in pervious literature. Results A novel loss of function NSD2 variant, c.1577dupG (p.Asn527Lysfs*14), was identified in a Chinese family in the proband and her father both affected with intellectual disability. After reviewing more NSD2 mutation cases in pervious literature, we found none of them had facial features that can be recognized as Wolf-Hirschhorn syndrome. In addition, we have given our proband growth hormone and followed up with this family for 7.5 years. Conclusions Here we reported the first familial NSD2 variant and the long-term effect of growth hormone therapy for patients. Our results suggested NSD2 mutation might cause a distinct intellectual disability and short stature syndrome.

The multimodal magnetic resonance imaging (MRI) technique has been extensively studied over the past few years since it offers complementary information that can increase diagnostic accuracy. Simple methods to synthesize contrast agents are necessary for the development of multimodal MRI. Herein, uniformly distributed Fe3O4/Gd2O3 nanocubes for T1–T2 dual-mode MRI contrast agents were successfully designed and synthesized. In order to increase hydrophilicity and biocompatibility, the nanocubes were coated with nontoxic 3,4-dihydroxyhydrocinnamic acid (DHCA). The results show that iron (Fe) and gadolinium (Gd) were homogeneously distributed throughout the Fe3O4/Gd2O3-DHCA (FGDA) nanocubes. Relaxation time analysis was performed on the images obtained from the 3.0 T scanner. The results demonstrated that r1 and r2 maximum values were 67.57 ± 6.2 and 24.2 ± 1.46 mM−1·s−1, respectively. In vivo T1- and T2-weighted images showed that FGDA nanocubes act as a dual-mode contrast agent enhancing MRI quality. Overall, these experimental results suggest that the FGDA nanocubes are interesting tools that can be used to increase MRI quality, enabling accurate clinical diagnostics.

Macrophages play important roles in angiogenesis; however, previous studies on macrophage angiogenesis have focused on traditional 2D cultures. In this study, we established a 3D culture system for macrophages using collagen microcarriers and assessed the effect of 3D culture on their angiogenic capabilities. Macrophages grown in 3D culture displayed a significantly different morphology and arrangement under electron microscopy compared to those grown in 2D culture. Tube formation assays and chick embryo chorioallantoic membrane assays further revealed that 3D-cultured macrophages were less angiogenic than those in 2D culture. Whole-transcriptome sequencing showed that nearly 40% of genes were significantly differently expressed, including nine important angiogenic factors of which seven had been downregulated. In addition, the expression of almost all genes related to two important angiogenic pathways was decreased in 3D-cultured macrophages, including the two key angiogenic factors, VEGFA and ANG2. Together, the findings of our study improve our understanding of angiogenesis and 3D macrophage culture in tissues, and provide new avenues and methods for future research on macrophages.

Abstract Background Obesity is associated with many chronic diseases including cortisol rhythm disorder and low testosterone. Furthermore, studies on obese children are quite limited and no concordance results have been obtained, especially for boys in puberty. Moreover, the sample sizes of previous studies were small, and were not representative. Methods We conducted a cross-sectional survey including 1148 boys aged 6–14 years, they were divided into overweight/obesity (OW/OB) group and normal weight (NW) group. Puberty status was assessed according to Tanner scale and testicular volume. Serum levels of pregnenolone, 17-OH progesterone, corticosterone, dehydroepiandrosterone (DHEA), and androstenedione were detected by LC-MS. Serum free testosterone and sex hormone-binding globulin (SHBG) levels were measured by chemiluminescence immunoassay. Results The 17-OH progesterone, DHEA, androstenedione and free testosterone levels of OW/OB boys at prepubertal stage or at the age 6 =

Osteochondral defect regeneration was a great challenge because of limited self-repaired ability for its sophisticated hierarchical inner structure. Hereon, the bi-layer hydrogel with robust osteochondral interfacial bonding was formulated under fully physical crosslinking, which was consisted of polyvinyl alcohol/collagen II for cartilage layer and polyvinyl alcohol/biphasic calcium phosphate/carbon nanotubes for bone layer. The bi-layer hydrogel with irregular pore distribution showed decreased pore size from top to bottom. The tensile modulus of bi-layer hydrogel reached to 7.14 ± 3 MPa and the stretched fracture surfaces were always appeared in the upper hydrogels, proving bi-layer hydrogels' well interfacial bonding strength. Furthermore, hydrogels' biocompatibility was evaluated using two kinds of cells in vitro, and the repair performance was also assessed in vivo test. The results demonstrated the bi-layer hydrogel owned favorable cytocompatibility and could induce the formation of osteochondral regeneration. Additionally, the max load at defect section reached to 67.24 ± 36.06 N after 12 weeks regeneration, verifying well bonding strength between the neotissue and native adjacent tissues. This work revealed the favorable bi-layer hydrogel owed great potential in repairing osteochondral defects.

Abstract The localization of sensor node is an essential problem for many economic forecasting applications in wireless sensor networks. Considering that the mobile sensors change their locations frequently over time, Monte Carlo localization algorithm utilizes the moving characteristics of nodes and employs the probability distribution function (PDF) in the previous time slot to estimate the current location by using a weighted particle filter. However, it also has the problem of insufficient number of valid samples, which further affects the node’s localization accuracy. In this paper, differential evolution method is introduced into the Monte Carlo localization algorithm. The sample weight is taken as the objective function, and differential evolution algorithm is implemented in sample stage. Finally, the node position is estimated by making the sample close to the actual location of the node instead of being filtered out. The simulation results demonstrate that the proposed algorithm provides a better position estimation with less localization error.

Dempster–Shafer evidence theory (DS theory) has some superiorities in uncertain information processing for a large variety of applications. However, the problem of how to quantify the uncertainty of basic probability assignment (BPA) in DS theory framework remain unresolved. The goal of this paper is to define a new belief entropy for measuring uncertainty of BPA with desirable properties. The new entropy can be helpful for uncertainty management in practical applications such as decision making. The proposed uncertainty measure has two components. The first component is an improved version of Dubois–Prade entropy, which aims to capture the non-specificity portion of uncertainty with a consideration of the element number in frame of discernment (FOD). The second component is adopted from Nguyen entropy, which captures conflict in BPA. We prove that the proposed entropy satisfies some desired properties proposed in the literature. In addition, the proposed entropy can be reduced to Shannon entropy if the BPA is a probability distribution. Numerical examples are presented to show the efficiency and superiority of the proposed measure as well as an application in decision making.

Objective. To characterize the genotype and phenotype of Chinese patients with congenital hyperinsulinism (CHI) caused by activating mutations in GLUD1, the gene that encodes mitochondrial enzyme glutamate dehydrogenase (GDH). Methods. The clinical data of glutamate dehydrogenase hyperinsulinism (GDH-HI) patients were reviewed, and gene mutations were confirmed by whole exome sequencing (WES) and Sanger DNA sequencing. Results. Twenty-six patients with GDH-HI heterozygous missense mutations were identified from 240 patients diagnosed as congenital hyperinsulinism over past 15 years. The median age at onset was 8 months (range: 1 day of life to 3 years). Seizure disorder was common in our cohort of patients (23/26). Four patients had normal serum ammonia levels; the median serum concentration was 101 μmol/L (range: 37–190 μmol/L). Hypoglycemic symptoms could be triggered by fasting or protein meals in all patients while blood glucose could be well controlled in all patients with diazoxide. Dosage of diazoxide could be reduced by protein restriction. Attempts to lower ammonia levels failed with different therapies such as protein restriction, benzoate, or N-carbamoyl glutamate. In follow-up, 15 of 26 patients had normal intelligence. Eleven patients developed epilepsy at the age of 6 months to 11 years. De novo mutations in GLUD1 were found in 24 cases, and dominant inheritance was observed in the other two; all were heterozygous. A total of 35% (9/26) patients carried c.1493C>T (p.S445L) mutation. Conclusions. Phenotypic heterogeneity of GDH-HI patients was observed within the Chinese cohort in the present study. The fact that most patients had a GLUD1 p. S445L mutation implies that this site could be a hotspot in Chinese patients. A high frequency of GDH-HI with normal ammonia has been reported in this study. Hence, GLUD1 mutational analysis may be an important method to differential diagnosis of GDH-HI from other diazoxide-responsive CHI in Chinese patients.

Economic high-quality and low-carbon development stand as strategic priorities for urban advancement within the context of dual carbon goals. Administrative territorial adjustments have emerged as a robust instrument in China's urbanization drive over recent decades. Nevertheless, scant attention has been given to its impact on urban low-carbon development. This paper employs a multi-period DID model to investigate the effect of the "City-County Merger" policy (CCMP) on urban carbon emissions, while also exploring potential channels and heterogeneity characteristics. The findings of this study are unequivocal: the implementation of the CCMP has proven to be a potent strategy in effectively curbing urban carbon emissions. This conclusion remains robust after a series of robustness tests. Furthermore, the study identifies certain channels that play a pivotal role in moderating the nexus between the CCMP and urban carbon emissions, including enhancing government intervention, optimizing urban energy structure, and improving urban (green) technology innovation. The heterogeneity analysis shows that CCMP yields heightened effectiveness in small and medium-sized cities, non-resource-based cities, and cities in the eastern and western regions. This study serves to provide nuanced insights, offering both theoretical underpinnings and pragmatic recommendations to propel the effective implementation of the CCMP. [ABSTRACT FROM AUTHOR]