A Dual-Bacterial Coupled Fermentation Strategy for Nicotinamide Mononucleotide Synthesis

In this study, a dual-bacterial coupled fermentation system containing nicotinamide nucleoside kinase (NRK) and polyphosphatase (PPK) was constructed, and the application of PPK-based ATP regeneration system in NMN production was achieved. First, engineering strains expressing NRK1 and NRK2 were constructed, and the highly active Escherichia coli BL21 (DE3)-pET28a-NRK1 was selected, with NMN yield and productivity of 5.17 g/L and 77.4%, respectively. Then, the induced expression conditions of NRK1 were optimized, and a low temperature of 16 ℃, an isopropyl-β-D-thiogalactopyranoside (IPTG) concentration of 0.7 mmol/L, an inoculation amount of 3% and an induction duration of 22 h were found to be optimal the soluble expression of NRK1 protein. The optimal synthesis conditions of NMN by E. coli BL21 (DE3)-pET28a-NRK1 were explored. It was found that after 12 h culture at 18 ℃ at an initial cell concentration of 100 g/L and a ratio of ATP to NR of 1:1.5, the highest yield of NMN of 5.73 g/L was obtained with a productivity of 85.78%. Finally, the optimal conditions that provided maximal NMN production (11.81 g/L) by coupled fermentation with E. coli BL21 (DE3) pET28a-PPK and E. coli BL21 (DE3)-pET28a-NRK1 were determined as 1:3.5, 1:2 and 16 h for ATP to NR ratio, initial cell concentration and fermentation time, respectively. The high-density dual-bacterial coupled fermentation strategy established in this study opens up a new pathway for high-efficiency, low-cost and large-scale production of NMN

Epidemiology of invasive group B streptococcal disease in infants from urban area of South China, 2011–2014

YesBackground: Group B Streptococcus (GBS) is a leading cause of morbidity and mortality in infants in both developed and developing countries. To our knowledge, only a few studies have been reported the clinical features, treatment and outcomes of the GBS disease in China. The severity of neonatal GBS disease in China remains unclear. Population-based surveillance in China is therefore required. Methods: We retrospectively collected data of <3 months old infants with culture-positive GBS in sterile samples from three large urban tertiary hospitals in South China from Jan 2011 to Dec 2014. The GBS isolates and their antibiotic susceptibility were routinely identified in clinical laboratories in participating hospitals. Serotyping and multi-locus sequence typing (MLST) were also conducted for further analysis of the neonatal GBS disease. Results: Total 70 cases of culture-confirmed invasive GBS infection were identified from 127,206 live births born in studying hospitals, giving an overall incidence of 0.55 per 1000 live births (95% confidence interval [CI] 0.44–0.69). They consisted of 49 with early-onset disease (EOD, 0.39 per 1000 live births (95% CI 0.29–0.51)) and 21 with late-onset disease (LOD, 0.17 per 1000 live births (95% CI 0.11–0.25)). The incidence of EOD increased significantly over the studying period. Five infants (4 EOD and 1 LOD) died before discharge giving a mortality rate of 7.1% and five infants (7.1%, 2 EOD and 3 LOD) had neurological sequelae. Within 68 GBS isolates from GBS cases who born in the studying hospitals or elsewhere, serotype III accounted for 77.9%, followed by Ib (14.7%), V (4.4%), and Ia (2.9%). MLST analysis revealed the presence of 13 different sequence types among the 68 GBS isolates and ST-17 was the most frequent sequence type (63.2%). All isolates were susceptible to penicillin, ceftriaxone, vancomycin and linezolid, while 57.4% and 51.5% were resistant to erythromycin and clindamycin, respectively. Conclusions: This study gains the insight into the spectrum of GBS infection in south China which will facilitate the development of the guidance for reasonable antibiotics usage and will provide evidence for the implementation of potential GBS vaccines in the future.Supported by medical and health science and technology projects of Health and Family Planning Commission of Guangzhou Municipality (grant number 20151A010034) and Guangdong provincial science and technology planning projects (grant number 2014A020212520)

A Tale of two cities : the economic development of Hong Kong and Singapore.

This project examines the economic developments of Hong Kong and Singapore. Both city-states achieved remarkable economic development although the policies adopted by them differ. Specifically, entrepreneurship, government and government policies and labour of each economy are discussed in this report. The differences in the policies adopted by both economies are highlighted

Clinical features and molecular genetic investigation of infantile-onset ascending hereditary spastic paralysis (IAHSP) in two Chinese siblings caused by a novel splice site ALS2 variation

Abstract Objective ALS2-related disorder involves retrograde degeneration of the upper motor neurons of the pyramidal tracts, among which autosomal recessive Infantile-onset ascending hereditary spastic paralysis (IAHSP) is a rare phenotype. In this study, we gathered clinical data from two Chinese siblings who were affected by IAHSP. Our aim was to assess the potential pathogenicity of the identified variants and analyze their clinical and genetic characteristics. Method Here, Whole-exome sequencing (WES) was performed on proband to identify the candidate variants. Subsequently, Sanger sequencing was used to verify identified candidate variants and to assess co-segregation among available family members. Utilizing both silico prediction and 3D protein modeling, an analysis was conducted to evaluate the potential functional implications of the variants on the encoded protein, and minigene assays were performed to unravel the effect of the variants on the cleavage of pre-mRNA. Results Both patients were characterized by slurred speech, astasia, inability to walk, scoliosis, lower limb hypertonia, ankle clonus, contracture of joint, foot pronation and no psychomotor retardation was found. Genetic analysis revealed a novel homozygous variant of ALS2, c.1815G > T(p.Lys605Asn) in two Chinese siblings. To our knowledge, it is the first confirmed case of a likely pathogenic variant leading to IAHSP in a Chinese patient. Conclusion This study broadens the range of ALS2 variants and has practical implications for prenatal and postnatal screening of IAHSR. Symptom-based diagnosis of IAHSP is frequently difficult for medical practitioners. WES can be a beneficial resource to identify a particular disorder when the diagnosis cannot be determined from the symptoms alone

Coordinated control of distributed renewable energy in bipolar DC microgrid based on modulus transformation

The coupling between the positive and negative poles of the bipolar DC microgrid will influence the voltage control which makes it difficult to compute the parameters of the control loop independently. The unbalanced voltage in the bipolar DC microgrid is a special power quality problem. The suppression of unbalanced voltage is a significant work in operation planning. In this paper, the expressions of voltage unbalance coefficient and distribution line current is deduced to investigate the influence of unbalanced loads on voltage deviation, voltage unbalance coefficient, and current distribution accuracy. On this basis, the common-mode and differential-mode consensus control of the bipolar DC microgrid is proposed to improve the dynamic performance of the control system and reduce the voltage deviation and voltage unbalance coefficient. In addition, the small-signal stability is analyzed in this paper. To verify the effectiveness of the proposed modulus control method in the bipolar DC microgrid, a MATLAB/Simulink simulation platform, and a low-voltage experimental platform are established. The proposed modulus control is better than the droop control in regulating unbalanced voltage. In addition, it is still effective under the influence of load change. Moreover, the unbalanced voltage can be controlled when addition PV and BEMS are added in the bipolar DC microgrid

Etiology and Outcome of non-immune Hydrops Fetalis in Southern China: report of 1004 cases.

Non-immune hydrops fetalis (NIHF) is a complex condition with a high mortality and morbidity rate. Here we report the etiology and outcome of 1004 fetuses with NIHF, in a large single Maternal and Children’s hospital of Southern China, since the year of 2009 to 2016. Among these 1004 fetuses with NIHF, the etiology was identified prenatally in 722 of them (72%). The most common ones were hematologic diseases and chromosomal abnormalities. There were eight spontaneous abortions, 18 intrauterine fetal demise, 672 pregnancy terminations and 87 were lost to follow-up. 219 of the 1004 fetuses were live-born and the overall survival rate was 21.8% at this point. After birth 16 perinatal or early neonatal deaths were encountered and five lost to follow-up. Of the remaining 198 newborns, 153 thrived without apparent morbidity. The most significant factors associated with mortality were prematurity and low birthweight. In conclusion, we described the largest report of underlying causes and outcome of NIHF in Southern China. Etiologies were identified for 72% of 1004 fetuses with NIHF. And two poor prognostic factors for survival are preterm birth at less than 36.5 weeks and birthweight lower than 2575 g respectively

Additional file 1: Figure S1. of Epidemiology of invasive group B streptococcal disease in infants from urban area of South China, 2011–2014

Partial sequence diagram for seven house-keeping genes. adhP gene(A), pheS gene(B), atr gene(C), glnA gene(D), sdhA gene(E), glcK gene(F), tkt gene(G). (DOCX 849 kb