L-citrulline is a nonprotein amino acid that plays an important role in human health and has great market demand. Although microbial cell factories have been widely used for biosynthesis, there are still challenges such as genetic instability and low efficiency in the biosynthesis of L-citrulline. In this study, an efficient, plasmid-free, non-inducible L-citrulline-producing strain of Escherichia coli BL21(DE3) was engineered by combined strategies. Firstly, a chassis strain capable of synthesizing L-citrulline was constructed by block of L-citrulline degradation and removal of feedback inhibition, with the L-citrulline titer of 0.43 g/L. Secondly, a push-pull-restrain strategy was employed to enhance the L-citrulline biosynthesis, which realized the L-citrulline titer of 6.0 g/L. Thirdly, the NADPH synthesis and L-citrulline transport were strengthened to promote the synthesis efficiency, which achieved the L-citrulline titer of 11.6 g/L. Finally, fed-batch fermentation was performed with the engineered strain in a 3 L fermenter, in which the L-citrulline titer reached 44.9 g/L. This study lays the foundation for the industrial production of L-citrulline and provides insights for the modification of other amino acid metabolic networks.
Citrulline/biosynthesis* ; Escherichia coli/genetics* ; Metabolic Engineering/methods* ; Fermentation ; NADP/biosynthesis*

Objective To analyze the risk factors and re-intervention strategies for mid- and long-term residual after arterial switch operation (ASO). Methods The clinical data of children with complex congenital heart disease who underwent ASO surgery in Shanghai Children’s Medical Center from January 2006 to June 2022 were retrospectively collected, and the risk factors for mid- and long-term residual after ASO were analyzed. Results A total of 952 children undergoing ASO were enrolled in this study, including 654 males and 298 females with an average age of (102.9±90.1) d and weight of (4.6±1.6) kg. There were 421 patients with D-transposition of the great arteries with intact ventricular septum (D-TGA/IVS), 357 patients with D-transposition of the great arteries with ventricular septal defect (D-TGA/VSD), and 174 patients with right ventricle double outlet combined with subpulmonary ventricular septal defect (Taussig-Bing malformation). Eighty-nine patients died early after the surgery, the mortality rate was 9.3%. The 746 surviving children were regularly followed up after the surgery (follow-up rate 86.4%), with a median follow-up time of 79.4 (12.0-188.0) months. During the follow-up, 53 children underwent surgical re-intervention due to residual, including 33 males and 20 females, with a median age of 62.5 (17.0-214.0) months. The median surgical weight was 19.0 (8.2-86.0) kg, and the mean time of re-intervention was 28.0-170.0 (77.5±45.4) months after the ASO. Residual problems included common trunk and branch stenosis of the pulmonary artery in 23 patients, right ventricular outflow tract (RVOT) obstruction in 11 patients, left ventricular outflow tract obstruction in 6 patients, aortic arch restenosis in 5 patients, aortic insufficiency in 5 patients, residual shunt of ventricular septal defect in 2 patients, and tricuspid valve insufficiency in 1 patient. The early postoperative mortality rate was 3.8% (2/53), with the causes of death being acute myocardial infarction due to coronary artery injury and acute left heart failure, respectively. The mean follow-up time of the surviving children was (52.4±28.6) months, and no mid- and long-term death occurred. Two patients underwent the third operations due to pulmonary restenosis. The multivariate analysis result showed that combined aortic arch surgery and early postoperative RVOT velocity>3 m/s were independent risk factors for mid- and long-term residual after ASO. Conclusion ASO is an ideal procedure for the treatment of D-TGA/IVS, D-TGA/VSD and Taussig-Bing malformations. Combined aortic arch surgery and early postoperative RVOT velocity>3 m/s are independent risk factors for mid- and long-term residual after ASO.

Objective:To investigate the pregnancy outcome and the maternal and infant follow-up in the puer-peral period(42 days after delivery)of cesarean section with SARS-CoV-2 Omicron variant in different periods of pregnancy.Methods:330 pregnant women who were diagnosed with SARS-CoV-2 infection and delivered by ce-sarean section in Guangdong Women and Children Hospital from November 20,2022 to January 25,2023 were selected as the research subjects.They were divided into the early(80 cases),middle(151 cases)and late(99 cases)pregnancy group according to the gestational age of infection.The general information,pregnancy compli-cations and comorbidities,pregnancy outcomes,and postpartum maternal and infant follow-up of each group of pregnant women were compared.Results:The clinical classification of pregnant women was asymptomatic and mild,with 9 cases of asymptomatic and 321 cases of mild.The incidence of gestational diabetes mellitus(GDM)in the early and late group was higher than that in the middle group(P＜0.05).There was no statistically significant difference in the incidence of placental abruption,fetal growth restriction,fetal distress,amniotic fluid contamina-tion,preterm labor,postpartum hemorrhage,macrosomia,low-birth-weight infants and the maternal intensive care unit(MICU)transfer rate,newborn birth weight,neonatal asphyxia rate and NICU transfer rate among the three groups(P＞0.05).The incidence of preterm rupture of membranes in the middle group was higher than that in the late group(P＜0.05).Puerperal follow-up results showed that there was no statistically significant difference in the incidence of poor maternal uterine incision healing,poor uterine involution,vaginal microecological imbal-ance and neonatal acute upper respiratory tract infection,pneumonia,digestive system disease,cardiovascular system disease among the three groups(P＞0.05).Conclusions:The majority of pregnant women with Omicron infection during pregnancy are mild.Omicron infection in different periods of pregnancy has no significant effect on pregnancy outcome and puerperal follow-up of cesarean section.No evidence was found that GDM and prema-ture rupture of membranes are significantly associated with Omicron infection in different periods of pregnancy.

Objective:To investigate the pregnancy outcome and the maternal and infant follow-up in the puer-peral period(42 days after delivery)of cesarean section with SARS-CoV-2 Omicron variant in different periods of pregnancy.Methods:330 pregnant women who were diagnosed with SARS-CoV-2 infection and delivered by ce-sarean section in Guangdong Women and Children Hospital from November 20,2022 to January 25,2023 were selected as the research subjects.They were divided into the early(80 cases),middle(151 cases)and late(99 cases)pregnancy group according to the gestational age of infection.The general information,pregnancy compli-cations and comorbidities,pregnancy outcomes,and postpartum maternal and infant follow-up of each group of pregnant women were compared.Results:The clinical classification of pregnant women was asymptomatic and mild,with 9 cases of asymptomatic and 321 cases of mild.The incidence of gestational diabetes mellitus(GDM)in the early and late group was higher than that in the middle group(P＜0.05).There was no statistically significant difference in the incidence of placental abruption,fetal growth restriction,fetal distress,amniotic fluid contamina-tion,preterm labor,postpartum hemorrhage,macrosomia,low-birth-weight infants and the maternal intensive care unit(MICU)transfer rate,newborn birth weight,neonatal asphyxia rate and NICU transfer rate among the three groups(P＞0.05).The incidence of preterm rupture of membranes in the middle group was higher than that in the late group(P＜0.05).Puerperal follow-up results showed that there was no statistically significant difference in the incidence of poor maternal uterine incision healing,poor uterine involution,vaginal microecological imbal-ance and neonatal acute upper respiratory tract infection,pneumonia,digestive system disease,cardiovascular system disease among the three groups(P＞0.05).Conclusions:The majority of pregnant women with Omicron infection during pregnancy are mild.Omicron infection in different periods of pregnancy has no significant effect on pregnancy outcome and puerperal follow-up of cesarean section.No evidence was found that GDM and prema-ture rupture of membranes are significantly associated with Omicron infection in different periods of pregnancy.

Objective:To investigate the pregnancy outcome and the maternal and infant follow-up in the puer-peral period(42 days after delivery)of cesarean section with SARS-CoV-2 Omicron variant in different periods of pregnancy.Methods:330 pregnant women who were diagnosed with SARS-CoV-2 infection and delivered by ce-sarean section in Guangdong Women and Children Hospital from November 20,2022 to January 25,2023 were selected as the research subjects.They were divided into the early(80 cases),middle(151 cases)and late(99 cases)pregnancy group according to the gestational age of infection.The general information,pregnancy compli-cations and comorbidities,pregnancy outcomes,and postpartum maternal and infant follow-up of each group of pregnant women were compared.Results:The clinical classification of pregnant women was asymptomatic and mild,with 9 cases of asymptomatic and 321 cases of mild.The incidence of gestational diabetes mellitus(GDM)in the early and late group was higher than that in the middle group(P＜0.05).There was no statistically significant difference in the incidence of placental abruption,fetal growth restriction,fetal distress,amniotic fluid contamina-tion,preterm labor,postpartum hemorrhage,macrosomia,low-birth-weight infants and the maternal intensive care unit(MICU)transfer rate,newborn birth weight,neonatal asphyxia rate and NICU transfer rate among the three groups(P＞0.05).The incidence of preterm rupture of membranes in the middle group was higher than that in the late group(P＜0.05).Puerperal follow-up results showed that there was no statistically significant difference in the incidence of poor maternal uterine incision healing,poor uterine involution,vaginal microecological imbal-ance and neonatal acute upper respiratory tract infection,pneumonia,digestive system disease,cardiovascular system disease among the three groups(P＞0.05).Conclusions:The majority of pregnant women with Omicron infection during pregnancy are mild.Omicron infection in different periods of pregnancy has no significant effect on pregnancy outcome and puerperal follow-up of cesarean section.No evidence was found that GDM and prema-ture rupture of membranes are significantly associated with Omicron infection in different periods of pregnancy.

Objective:To investigate the pregnancy outcome and the maternal and infant follow-up in the puer-peral period(42 days after delivery)of cesarean section with SARS-CoV-2 Omicron variant in different periods of pregnancy.Methods:330 pregnant women who were diagnosed with SARS-CoV-2 infection and delivered by ce-sarean section in Guangdong Women and Children Hospital from November 20,2022 to January 25,2023 were selected as the research subjects.They were divided into the early(80 cases),middle(151 cases)and late(99 cases)pregnancy group according to the gestational age of infection.The general information,pregnancy compli-cations and comorbidities,pregnancy outcomes,and postpartum maternal and infant follow-up of each group of pregnant women were compared.Results:The clinical classification of pregnant women was asymptomatic and mild,with 9 cases of asymptomatic and 321 cases of mild.The incidence of gestational diabetes mellitus(GDM)in the early and late group was higher than that in the middle group(P＜0.05).There was no statistically significant difference in the incidence of placental abruption,fetal growth restriction,fetal distress,amniotic fluid contamina-tion,preterm labor,postpartum hemorrhage,macrosomia,low-birth-weight infants and the maternal intensive care unit(MICU)transfer rate,newborn birth weight,neonatal asphyxia rate and NICU transfer rate among the three groups(P＞0.05).The incidence of preterm rupture of membranes in the middle group was higher than that in the late group(P＜0.05).Puerperal follow-up results showed that there was no statistically significant difference in the incidence of poor maternal uterine incision healing,poor uterine involution,vaginal microecological imbal-ance and neonatal acute upper respiratory tract infection,pneumonia,digestive system disease,cardiovascular system disease among the three groups(P＞0.05).Conclusions:The majority of pregnant women with Omicron infection during pregnancy are mild.Omicron infection in different periods of pregnancy has no significant effect on pregnancy outcome and puerperal follow-up of cesarean section.No evidence was found that GDM and prema-ture rupture of membranes are significantly associated with Omicron infection in different periods of pregnancy.

Objective:To investigate the pregnancy outcome and the maternal and infant follow-up in the puer-peral period(42 days after delivery)of cesarean section with SARS-CoV-2 Omicron variant in different periods of pregnancy.Methods:330 pregnant women who were diagnosed with SARS-CoV-2 infection and delivered by ce-sarean section in Guangdong Women and Children Hospital from November 20,2022 to January 25,2023 were selected as the research subjects.They were divided into the early(80 cases),middle(151 cases)and late(99 cases)pregnancy group according to the gestational age of infection.The general information,pregnancy compli-cations and comorbidities,pregnancy outcomes,and postpartum maternal and infant follow-up of each group of pregnant women were compared.Results:The clinical classification of pregnant women was asymptomatic and mild,with 9 cases of asymptomatic and 321 cases of mild.The incidence of gestational diabetes mellitus(GDM)in the early and late group was higher than that in the middle group(P＜0.05).There was no statistically significant difference in the incidence of placental abruption,fetal growth restriction,fetal distress,amniotic fluid contamina-tion,preterm labor,postpartum hemorrhage,macrosomia,low-birth-weight infants and the maternal intensive care unit(MICU)transfer rate,newborn birth weight,neonatal asphyxia rate and NICU transfer rate among the three groups(P＞0.05).The incidence of preterm rupture of membranes in the middle group was higher than that in the late group(P＜0.05).Puerperal follow-up results showed that there was no statistically significant difference in the incidence of poor maternal uterine incision healing,poor uterine involution,vaginal microecological imbal-ance and neonatal acute upper respiratory tract infection,pneumonia,digestive system disease,cardiovascular system disease among the three groups(P＞0.05).Conclusions:The majority of pregnant women with Omicron infection during pregnancy are mild.Omicron infection in different periods of pregnancy has no significant effect on pregnancy outcome and puerperal follow-up of cesarean section.No evidence was found that GDM and prema-ture rupture of membranes are significantly associated with Omicron infection in different periods of pregnancy.

Objective:To investigate the pregnancy outcome and the maternal and infant follow-up in the puer-peral period(42 days after delivery)of cesarean section with SARS-CoV-2 Omicron variant in different periods of pregnancy.Methods:330 pregnant women who were diagnosed with SARS-CoV-2 infection and delivered by ce-sarean section in Guangdong Women and Children Hospital from November 20,2022 to January 25,2023 were selected as the research subjects.They were divided into the early(80 cases),middle(151 cases)and late(99 cases)pregnancy group according to the gestational age of infection.The general information,pregnancy compli-cations and comorbidities,pregnancy outcomes,and postpartum maternal and infant follow-up of each group of pregnant women were compared.Results:The clinical classification of pregnant women was asymptomatic and mild,with 9 cases of asymptomatic and 321 cases of mild.The incidence of gestational diabetes mellitus(GDM)in the early and late group was higher than that in the middle group(P＜0.05).There was no statistically significant difference in the incidence of placental abruption,fetal growth restriction,fetal distress,amniotic fluid contamina-tion,preterm labor,postpartum hemorrhage,macrosomia,low-birth-weight infants and the maternal intensive care unit(MICU)transfer rate,newborn birth weight,neonatal asphyxia rate and NICU transfer rate among the three groups(P＞0.05).The incidence of preterm rupture of membranes in the middle group was higher than that in the late group(P＜0.05).Puerperal follow-up results showed that there was no statistically significant difference in the incidence of poor maternal uterine incision healing,poor uterine involution,vaginal microecological imbal-ance and neonatal acute upper respiratory tract infection,pneumonia,digestive system disease,cardiovascular system disease among the three groups(P＞0.05).Conclusions:The majority of pregnant women with Omicron infection during pregnancy are mild.Omicron infection in different periods of pregnancy has no significant effect on pregnancy outcome and puerperal follow-up of cesarean section.No evidence was found that GDM and prema-ture rupture of membranes are significantly associated with Omicron infection in different periods of pregnancy.

Objective:To investigate the pregnancy outcome and the maternal and infant follow-up in the puer-peral period(42 days after delivery)of cesarean section with SARS-CoV-2 Omicron variant in different periods of pregnancy.Methods:330 pregnant women who were diagnosed with SARS-CoV-2 infection and delivered by ce-sarean section in Guangdong Women and Children Hospital from November 20,2022 to January 25,2023 were selected as the research subjects.They were divided into the early(80 cases),middle(151 cases)and late(99 cases)pregnancy group according to the gestational age of infection.The general information,pregnancy compli-cations and comorbidities,pregnancy outcomes,and postpartum maternal and infant follow-up of each group of pregnant women were compared.Results:The clinical classification of pregnant women was asymptomatic and mild,with 9 cases of asymptomatic and 321 cases of mild.The incidence of gestational diabetes mellitus(GDM)in the early and late group was higher than that in the middle group(P＜0.05).There was no statistically significant difference in the incidence of placental abruption,fetal growth restriction,fetal distress,amniotic fluid contamina-tion,preterm labor,postpartum hemorrhage,macrosomia,low-birth-weight infants and the maternal intensive care unit(MICU)transfer rate,newborn birth weight,neonatal asphyxia rate and NICU transfer rate among the three groups(P＞0.05).The incidence of preterm rupture of membranes in the middle group was higher than that in the late group(P＜0.05).Puerperal follow-up results showed that there was no statistically significant difference in the incidence of poor maternal uterine incision healing,poor uterine involution,vaginal microecological imbal-ance and neonatal acute upper respiratory tract infection,pneumonia,digestive system disease,cardiovascular system disease among the three groups(P＞0.05).Conclusions:The majority of pregnant women with Omicron infection during pregnancy are mild.Omicron infection in different periods of pregnancy has no significant effect on pregnancy outcome and puerperal follow-up of cesarean section.No evidence was found that GDM and prema-ture rupture of membranes are significantly associated with Omicron infection in different periods of pregnancy.

Objective:To investigate the pregnancy outcome and the maternal and infant follow-up in the puer-peral period(42 days after delivery)of cesarean section with SARS-CoV-2 Omicron variant in different periods of pregnancy.Methods:330 pregnant women who were diagnosed with SARS-CoV-2 infection and delivered by ce-sarean section in Guangdong Women and Children Hospital from November 20,2022 to January 25,2023 were selected as the research subjects.They were divided into the early(80 cases),middle(151 cases)and late(99 cases)pregnancy group according to the gestational age of infection.The general information,pregnancy compli-cations and comorbidities,pregnancy outcomes,and postpartum maternal and infant follow-up of each group of pregnant women were compared.Results:The clinical classification of pregnant women was asymptomatic and mild,with 9 cases of asymptomatic and 321 cases of mild.The incidence of gestational diabetes mellitus(GDM)in the early and late group was higher than that in the middle group(P＜0.05).There was no statistically significant difference in the incidence of placental abruption,fetal growth restriction,fetal distress,amniotic fluid contamina-tion,preterm labor,postpartum hemorrhage,macrosomia,low-birth-weight infants and the maternal intensive care unit(MICU)transfer rate,newborn birth weight,neonatal asphyxia rate and NICU transfer rate among the three groups(P＞0.05).The incidence of preterm rupture of membranes in the middle group was higher than that in the late group(P＜0.05).Puerperal follow-up results showed that there was no statistically significant difference in the incidence of poor maternal uterine incision healing,poor uterine involution,vaginal microecological imbal-ance and neonatal acute upper respiratory tract infection,pneumonia,digestive system disease,cardiovascular system disease among the three groups(P＞0.05).Conclusions:The majority of pregnant women with Omicron infection during pregnancy are mild.Omicron infection in different periods of pregnancy has no significant effect on pregnancy outcome and puerperal follow-up of cesarean section.No evidence was found that GDM and prema-ture rupture of membranes are significantly associated with Omicron infection in different periods of pregnancy.