Associations of COVID-19 lockdown with birth weight in China.

Background: During the special period of the global spread of COVID-19, pregnant women are sensitive groups to the impacts of COVID-19 epidemic. However, the effects of lockdown measures implemented in response to the COVID-19 on fetal birthweight remain unclear. Objectives: This study investigated the associations of COVID-19 lockdown with birth weight in Chinese population. Methods: We collected 730,153 data of participants from hospitals of five cities in the south of China, we defined the time period of level I response (1/23-2/24/2020) as level I lockdown, and women who were pregnant during level I lockdown as the exposure group. Women who were pregnant during the same calendar month from 2015 to 2019 were defined as the unexposed group. We quantitatively estimate the individual cumulative exposure dose by giving different weights to days with different emergency response levels. Generalized linear regression models were used to estimate the association between COVID-19 lockdown exposure with birth weight and risk of low birth weight (<2,500 g) and macrosomia (>4,000 g). Results: The birth weight of the exposed group is heavier than the unexposed group (3,238.52 vs. 3,224.11 g: adjusted ß = 24.39 g [95% CI: 21.88, 26.91 g]). The exposed group had a higher risk of macrosomia (2.8% vs. 2.6%; adjusted OR = 1.17 [95% CI: 1.12, 1.22]). More obvious associations were found between COVID-19 lockdown and macrosomia in women who experienced the lockdown in their early pregnancy. Women who experienced the lockdown at their 4-7 weeks of pregnancy showed statistically significant heavier birth weight than unexposed group (after adjustment): ß = 1.28 (95% CI: 1.11, 1.46) g. We also observed a positive association between cumulative exposure dose of COVID-19 lockdown in all pregnant women and birth weight, after divided into four groups, Q1: ß = 32.95 (95% CI: 28.16, 37.75) g; Q2: ß = 18.88 (95% CI: 14.12, 23.64) g; Q3: ß = 19.50 (95% CI: 14.73, 24.28) g; Q4: ß = 21.82 (95% CI: 17.08, 26.56) g. However, there was no statistically significant difference in the risk of low birth weight between exposed and unexposed groups. Conclusions: The COVID-19 lockdown measures were associated with a heavier birth weight and a higher risk of macrosomia. Early pregnancy periods may be a more susceptible exposure window for a heavier birth weight and a higher risk of macrosomia. We also observed a positive association between cumulative exposure dose of COVID-19 lockdown and birth weight. The government and health institutions should pay attention to the long-term health of the infants born during the COVID-19 lockdown period, and follow up these mothers and infants is necessary.

The fatty acid 2-hydroxylase CsSCS7 is a key hyphal growth factor and potential control target in Colletotrichum siamense.

SCS7 is a fatty acid 2-hydroxylase required for the synthesis of inositol phosphorylceramide but is not essential for normal growth in Saccharomyces cerevisiae. Here, we demonstrate that the Colletotrichum siamense SCS7 homolog CsSCS7 plays a key role in hyphal growth. The CsSCS7 deletion mutant showed strong hyphal growth inhibition, small conidia, and marginally reduced sporulation and also resulted in a sharp reduction in the full virulence and increasing the fungicide sensitivity. The three protein domains (a cytochrome b5 domain, a transmembrane domain, and a hydroxylase domain) are important to CsSCS7 protein function in hyphal growth. The fatty acid assay results revealed that the CsSCS7 gene is important for balancing the contents of multiple mid-long- and short-chain fatty acids. Additionally, the retarded growth and virulence of C. siamense ΔCsSCS7 can be recovered partly by the reintroduction of homologous sequences from Magnaporthe oryzae and Fusarium graminearum but not SCS7 of S. cerevisiae. In addition, the spraying of C. siamense with naked CsSCS7-double-stranded RNA (dsRNAs), which leads to RNAi, increases the inhibition of hyphal growth and slightly decreases disease lesions. Then, we used nano material Mg-Al-layered double hydroxide as carriers to deliver dsRNA, which significantly enhanced the control effect of dsRNA, and the lesion area was obviously reduced. These data indicated that CsSCS7 is an important factor for hyphal growth and affects virulence and may be a potential control target in C. siamense and even in filamentous plant pathogenic fungi.IMPORTANCECsSCS7, which is homologous to yeast fatty acid 2-hydroxylase SCS7, was confirmed to play a key role in the hyphal growth of Colletotrichum siamense and affect its virulence. The CsSCS7 gene is involved in the synthesis and metabolism of fatty acids. Homologs from the filamentous fungi Magnaporthe oryzae and Fusarium graminearum can recover the retarded growth and virulence of C. siamense ΔCsSCS7. The spraying of double-stranded RNAs targeting CsSCS7 can inhibit hyphal growth and reduce the disease lesion area to some extent. After using nano material Mg-Al layered double hydroxide as carrier, the inhibition rates were significantly increased. We demonstrated that CsSCS7 is an important factor for hyphal growth and affects virulence and may be a potential control target in C. siamense and even in filamentous plant pathogenic fungi.

Association of COVID-19 Lockdown With Gestational Diabetes Mellitus.

Importance: The ongoing pandemic of COVID-19 is still affecting our life, but the effects of lockdown measures on gestational diabetes mellitus (GDM) in pregnant women remain unclear. Aim: To investigate the association between COVID-19 lockdown and GDM. Subjects and Methods: Medical records of 140844 pregnant women during 2015-2020 were extracted from 5 hospitals in Guangdong Province, China. Pregnant women who underwent the COVID-19 Level I lockdown (1/23 - 2/24/2020) during pregnancy were defined as the exposed group (N=20472) and pregnant women who underwent the same calendar months during 2015-2019 (1/23 - 2/24) were defined as the unexposed group (N=120372). Subgroup analyses were used to explore the potential susceptible exposure window of COVID-19 lockdown on GDM. Cumulative exposure is quantitatively estimated by assigning different weights to response periods with different exposure intensities. A logistic regression model was used to estimate the association between COVID-19 lockdown exposure and GDM. Results: The rates of GDM in the exposed and unexposed groups were 15.2% and 12.4%, respectively. The overall analyses showed positive associations (odds ratio, OR=1.22, 95%CI: 1.17, 1.27) between lockdown exposure and GDM risk in all pregnant women. More pronounced associations were found in women who underwent the COVID-19 lockdown in their first four months of pregnancy, and the adjusted OR values ranged from 1.24 (95%CI: 1.10, 1.39) in women with 5-8 gestational weeks (GWs) to 1.35 (95%CI: 1.20, 1.52) with < 5 GWs. In addition, we found a positive exposure-response association of cumulative lockdown exposure with the risk of GDM. Conclusions: The COVID-19 lockdown was associated with an increased risk of GDM, and the first four months of pregnancy may be the window for sensitive exposure.

Associations of COVID-19 lockdown with gestational length and preterm birth in China.

BACKGROUND: The effects of COVID-19 lockdown measures on maternal and fetal health remain unclear. We examined the associations of COVID-19 lockdown with gestational length and preterm birth (PTB) in a Chinese population. METHODS: We obtained medical records of 595,396 singleton live infants born between 2015 and 2020 in 5 cities in Guangdong Province, South China. The exposed group (N = 101,900) included women who experienced the COVID-19 Level I lockdown (1/23-2/24/2020) during pregnancy, while the unexposed group (N = 493,496) included women who were pregnant during the same calendar months in 2015-2019. Cumulative exposure was calculated based on days exposed to different levels of emergency responses with different weighting. Generalized linear regression models were applied to estimate the associations of lockdown exposure with gestational length and risk of PTB (< 37 weeks). RESULTS: The exposed group had a shorter mean gestational length than the unexposed group (38.66 vs 38.74 weeks: adjusted ß = - 0.06 week [95%CI, - 0.07, - 0.05 week]). The exposed group also had a higher risk of PTB (5.7% vs 5.3%; adjusted OR = 1.08 [95%CI, 1.05, 1.11]). These associations seemed to be stronger when exposure occurred before or during the 23rd gestational week (GW) than during or after the 24th GW. Similarly, higher cumulative lockdown exposure was associated with a shorter gestational length and a higher risk of PTB. CONCLUSIONS: The COVID-19 lockdown measures were associated with a slightly shorter gestational length and a moderately higher risk of PTB. Early and middle pregnancy periods may be a more susceptible exposure window.

The Mediating Role of Placental Weight Change in the Association Between Prenatal Exposure to Thallium and Birth Weight: A Prospective Birth Cohort Study.

Background: Previous studies have demonstrated the embryotoxicity and fetotoxicity of thallium (Tl). However, the effects of prenatal exposure to Tl on birth weight and placental weight and the mediating role of placental weight in the association of Tl with birth weight remain unclear. Methods: We recruited 2,748 participants from the ongoing Prenatal Environment and Offspring Health Cohort (PEOH Cohort) study, which was initiated in 2016 in Guangzhou, China. The Tl concentrations in maternal urine samples collected during the first and third trimester were determined by inductively coupled plasma mass spectrometry. Birth weight and placental weight were extracted from maternal medical records. Results: Pregnant women exposed to the highest tertile of Tl in the first trimester (ß = -42.7 g, 95% CI: -82.3, -3.1 g) and third trimester (ß = -50.6 g, 95% CI: -99.0, -2.3 g) had babies with lower birth weights than those exposed to the lowest tertile. We also found significant negative associations of exposure to Tl concentrations in the first and third trimester with placental weight. Mediation analyses showed that 50.3% (95% CI: 15.9, 79.2%) and 33.5% (95% CI: 1.3, 80.3%) of the effects of Tl exposure in the first and third trimester on birth weight were mediated by decreased placental weight. Conclusion: Our results suggest that prenatal exposure to Tl is negatively associated with birth weight and that this association may be mediated by decreased placental weight.

PROGRESSION OF MYOPIC MACULOPATHY IN CHINESE CHILDREN WITH HIGH MYOPIA: A Long-Term Follow-Up Study.

PURPOSE: To investigate the progression of myopic maculopathy and associated factors in highly myopic Chinese children. METHODS: In this retrospective observational case series, biometric fundus features were morphometrically measured on photographs. Myopic maculopathy was defined as recommended by the Meta-analysis of Pathologic Myopia Study Group. RESULTS: The study included 274 children (mean age: 11.7 ± 2.5 years; mean refractive error: -7.66 ± 1.87 diopters [D]) with a mean follow-up of 4.9 ± 1.2 years. Myopic maculopathy progression was detected in 52 eyes (18.9%; 95% confidence interval [CI]: 14.3-23.7%). In multivariable analysis, myopic maculopathy progression was associated with a decrease in refractive error (odds ratio [OR]: 0.72; 95% CI: 0.56-0.92; P < 0.001) (i.e., higher myopization) and enlargement of parapapillary gamma zone (OR: 7.68; 95% CI: 1.63-36.2; P = 0.002). Incident peripapillary diffuse choroidal atrophy, noted in 47 of 236 eyes (20.0%; 95% CI: 14.8-25.2%), was correlated with a decrease in refractive error (OR: 0.70; 95% CI: 0.54-0.92; P = 0.009) (i.e., higher myopization) and greater gamma zone enlargement (OR: 8.28; 95% CI: 1.33-51.7; P = 0.02). CONCLUSION: Myopia in schoolchildren may have a considerable risk of progressing to myopic maculopathy. Enlargement of parapapillary gamma zone was a main independent risk factor.

Outdoor Jogging and Myopia Progression in School Children From Rural Beijing: The Beijing Children Eye Study.

PURPOSE: To assess the influence of an outdoor program on myopia progression in school children. METHODS: The prospective interventional school-based study included 373 students aged 6 to 7 years (grade 1 or 2) who were examined annually between 2012 and 2016. Between 2012 and 2013, the children in the study group (n = 157) performed a 30-minute jogging exercise every school day, while the children in the control school (n = 216) did not. All children underwent a comprehensive ocular examination, including biometry. RESULTS: At 1 year after baseline, axial elongation and progression of myopic refractive error were significantly lower in the study group than in the control group. Study group and control group differed in axial elongation only in the subgroup of children nonmyopic at baseline, while axial elongation in the children myopic at baseline did not differ between both groups. At 1 and 2 years after the outdoor program stopped, increase in axial length was significantly larger in the study group. At 4 years after baseline, study group and control group did not differ significantly in total axial elongation and total change in refractive error. CONCLUSIONS: An outdoor program of 30 minutes performed every school day for 1 year temporarily reduced myopia progression in schoolchildren nonmyopic at baseline, with a complete rebound effect after the program ended within the 3 following years. TRANSLATIONAL RELEVANCE: An outdoor program of 30 minutes performed every school day for 1 year temporarily reduced the progression of myopia in schoolchildren nonmyopic at baseline for the period when the program was carried out.

A superparamagnetic Fe3O4-loaded polymeric nanocarrier for targeted delivery of evodiamine with enhanced antitumor efficacy.

The aim of this study was to design and synthesize a polymeric nanocarrier system loaded with both superparamagnetic iron oxide nanoparticles (SPIONs) and the anticancer drug evodiamine through a solvent evaporation technique. The hydrodynamic diameter of the prepared SPION-evodiamine-loaded nanocarrier was approximately 261nm, and the drug-loading content and encapsulation efficiency were 8.61±0.73% and 40.36±3.42%, respectively. The nanocarrier exhibited good superparamagnetism and an iron content of approximately 9.34%. In vitro drug release experiments showed a sustained release profile over 70h. Staining with Prussian blue confirmed that the nanocarrier could be effectively internalized into HeLa cells. MTT assays indicated that the SPION-evodiamine-loaded nanocarrier showed cytotoxicity comparable to that of free evodiamine. If an external magnetic field was applied, the SPION-loaded nanocarrier accumulated at the targeted sites and demonstrated a magnetic force-mediated targeting property with the aid of a magnetic field. Furthermore, the SPION-evodiamine-loaded nanocarrier exhibited a much higher in vivo antitumor efficacy than free evodiamine. Together, these results indicate that the SPION-evodiamine-loaded nanocarrier could effectively inhibit tumor growth both in vitro and in vivo with reduced toxicity, and therefore is a promising candidate to achieve enhanced therapeutic efficacy for clinical development.

Enhanced in vitro antitumor efficacy and strong anti-cell-migration activity of a hydroxycamptothecin-encapsulated magnetic nanovehicle.

A 10-hydroxycamptothecin-encapsulated magnetic nanovehicle (HEMN) was fabricated by coencapsulating Fe(3)O(4) nanoparticles and 10-hydroxycamptothecin (HCPT) into a micelle core self-assembled from the amphiphilic copolymer methoxy-poly(ethylene glycol)-poly(d,l-lactide-co-glycolide) through a facile dialysis method. A satisfactory drug-loading content of (9.03 ± 0.67) % and a relatively high encapsulation efficiency of (53.52 ± 6.46) % were achieved. In vitro drug release was performed by membrane dialysis and a pH-dependent release behavior was observed. In comparison with free HCPT dissolved in dimethylsulfoxide, HEMNs showed a greatly improved in vitro antitumor efficacy against three different human cancer cell lines-HeLa, A549, and HepG2-and lower IC(50) values were measured. The mechanism of cell death was investigated, and it was clearly demonstrated that the apoptosis process was triggered. An in vitro wound-healing assay and a transwell assay indicated that HEMNs exerted much stronger activity in inhibiting HeLa cell migration. The cellular uptake of HEMNs in a desired area can be significantly enhanced by an external magnetic field. These results demonstrate HCPT-encapsulated magnetic nanovehicles might have important potential in clinical applications for inhibiting tumor metastasis and for targeted drug delivery.

A double-targeted magnetic nanocarrier with potential application in hydrophobic drug delivery.

A double-targeted magnetic nanocarrier based with potential applications in the delivery of hydrophobic drugs has been developed. It consists of magnetite (Fe(3)O(4)) nanoparticles encapsulated in self-assembled micelles of the amphiphilic copolymer MPEG-PLGA [methoxy poly (ethylene glycol)-poly (d,l-lactide-co-glycolide)], and was fabricated using the solvent-evaporation technique. The magnetic nanocarrier has a very stable core-shell structure and is superparamagnetic. Its cytotoxicity was evaluated using the MTT assay with three cell lines-HeLa, MCF-7, and HT1080; it exhibited no cytotoxicity against any tested line at concentrations of up to 400 µg/mL after incubation for 24 h. Its cellular uptake was studied by Prussian blue staining and by fluorescence microscopy after encapsulating a fluorescent probe (hydrophobic quantum dots) into the nanocarrier. Finally, the magnetic targeting property of the magnetic nanocarrier was confirmed by an in vitro test. Overall, the results obtained demonstrate the potential of the double-targeted nanocarrier for the intracellular delivery of hydrophobic drugs.