G4LDB 3.0: a database for discovering and studying G-quadruplex and i-motif ligands.

Non-canonical nucleic acid structures, such as G-quadruplex (G4) and i-Motif (iM), have garnered significant research interest because of their unique structural properties and biological activities. Thousands of small molecules targeting G4/iM structures have been developed for various chemical and biological applications. In response to the growing interest in G4-targeting ligands, we launched the first G4 Ligand Database (G4LDB) in 2013. Here, we introduce G4LDB 3.0 (http://www.g4ldb.com), an upgraded version featuring extensive enhancements in content and functionality. The new version includes over 4800 G4/iM ligands and approximately 51 000 activity entries. Key upgrades include advanced search capabilities, dynamic knowledge graphs, enhanced data visualization, along with a new dynamic analysis function that automatically displays ligand structure clustering results and chemical space distribution. With these updates, G4LDB 3.0 further evolves into a comprehensive resource and valuable research tool. The significant improvements address the increasing demand for efficient data handling and user experience, highlighting the critical role of G4LDB in advancing research on G-quadruplexes and i-motifs.

G4LDB 2.2: a database for discovering and studying G-quadruplex and i-Motif ligands.

Noncanonical nucleic acid structures, such as G-quadruplex (G4) and i-Motif (iM), have attracted increasing research interests because of their unique structural and binding properties, as well as their important biological activities. To date, thousands of small molecules that bind to varying G4/iM structures have been designed, synthesized and tested for diverse chemical and biological uses. Because of the huge potential and increasing research interests on G4-targeting ligands, we launched the first G4 ligand database G4LDB in 2013. Here, we report a new version, termed G4LDB 2.2 (http://www.g4ldb.com), with upgrades in both content and function. Currently, G4LDB2.2 contains >3200 G4/iM ligands, ∼28 500 activity entries and 79 G4-ligand docking models. In addition to G4 ligand library, we have also added a brand new iM ligand library to G4LDB 2.2, providing a comprehensive view of quadruplex nucleic acids. To further enhance user experience, we have also redesigned the user interface and optimized the database structure and retrieval mechanism. With these improvements, we anticipate that G4LDB 2.2 will serve as a comprehensive resource and useful research toolkit for researchers across wide scientific communities and accelerate discovering and validating better binders and drug candidates.

Structurally diverse triterpenoid alkaloids from Buxus rugulosa.

Four new nortriterpenoid alkaloids, namely buxrugulines E-H (1-4), along with five known ones (5-9), were isolated from the twigs and leaves of Buxus rugulosa. Their structures were identified based on extensive NMR data and MS spectroscopic analyses. Our bioassays revealed that compounds 5, 6 and 8 exhibited potent cytotoxicity in vitro against MCF-7 cell lines, with IC50 values ranging from 6.70 to 11.00 µM, respectively.

Association of placental PPARα/γ and miR-27b expression with macrosomia in healthy pregnancy.

BACKGROUND: Peroxisomal proliferator-activated receptors (PPARs) and microRNAs (miRNAs) play important roles in the development of fetuses, whereas expression changes of PPARs and three miRNAs (miR-17, miR-27b and miR-34a) and whether these miRNAs regulate PPARs in non-GDM macrosomia placenta is unclear. METHODS: A case-control study was performed to collect information and placental tissues on mothers and newborns of non-GDM macrosomia and normal-birth-weight infants. In vitro HTR8-SVneo cellular model was used to detect the effects of miRNAs on PPARs expression. Quantitative real-time PCR (qRT-PCR) and western blot was applied to examine the expression levels of PPARs, miR-17, miR-27b, and miR-34a in placental tissues and cells. RESULTS: The PPARα/γ mRNA and protein levels were significantly up-regulated and miR-27b was down-regulated in the placenta of macrosomia group compared with in the control group, while no difference was observed in PPARß, miR-17, and miR-34a. After adjusting for confounding factors, low miR-27b and high PPARα/γ mRNA expression still increased the risk of macrosomia. The PPARα/γ protein levels presented a corresponding decrease or increase when cells were transfected with miR-27b mimic or inhibitor. CONCLUSIONS: Placental PPARα/γ and miR-27b expression were associated with non-GDM macrosomia and miR-27b probably promotes the occurrence of non-GDM macrosomia by regulating PPARα/γ protein. IMPACT: Low miR-27b and high PPARα/γ mRNA expression in the placenta were associated with higher risk of macrosomia. In vitro HTR8-SVneo cell experiment supported that miR-27b could negatively regulate the expression of PPARα and PPARγ protein. MiR-27b was probably involved in non-GDM macrosomia through negative regulation of PPARα/γ protein.

Lysobacter lactosilyticus sp. nov., a Novel ß-Galactosidase Producing Bacterial Strain Isolated from Farmland Soil Applied with Amino Acid Fertilizer.

To isolate ß-galactosidase producing bacterial resources, a novel Gram-stain-negative, strictly aerobic bacterial strain designated as A6T was obtained from a farmland soil sample. Cells of the strain were rod-shaped (0.4-0.7 µm × 1.8-2.2 µm) without flagella and motility. Strain A6T grew optimally at 30 °C, pH 7.0 with 0% (w/v) NaCl. Based on phylogenetic analysis, strain A6T clustered within the genus Lysobacter clade and branched with Lysobacter dokdonensis KCTC 12822T (99.5%, 16S rRNA gene sequence similarity) and Lysobacter caseinilyticus KACC 19816T (98.5%). The average nucleotide identity (ANI) and digital DNA-DNA hybridization (dDDH) values between strain A6T and Lysobacter dokdonensis KCTC 12822T were 82.7% and 26.2%, and the values for strain A6T and KACC 19816T were 81.4% and 23.8%, respectively. Iso-C16:0, iso-C15:0, summed feature 9 (C17:1 iso ω9c and/or C16:0 10-methyl) and summed feature 3 (C16:1ω7c and/or C16:1 ω6c) were the major fatty acids, diphosphatidylglycerol, phosphatidylglycerol, and phosphatidylethanolamine were the major polar lipids, and ubiquinone 8 (Q-8) was the major ubiquinone. The genomic DNA G+C content was 67.2 mol%. Furthermore, under the condition of 30 °C, pH 7.0, 4% inoculation with 10.0 g L-1 lactose, the ß-galactosidase activity produced by strain A6T was highest, reaching 95.3 U mL-1, indicating that this strain could be applied as a potential strain for ß-galactosidase production. Strain A6T represents a novel species of the genus Lysobacter, and Lysobacter lactosilyticus sp. nov. is proposed on the basis of phenotypic, genotypic, and chemotaxonomic analysis. The type strain is A6T (=KCTC 82184T=CGMCC 1.18582T).

Relationships between Kazakh elders' disability severity and informal care time in far north-western low-income areas in China: The mediating roles of caregiver health and home-based care quality.

BACKGROUND: Elders' disability severity and caregiver health could predict elders' informal care time, but the mechanism by which the degree of disability in the elderly affects informal care time is unclear. AIM: The aim of this works is to explore the mediating roles of caregiver health and home-based care quality between disability severity of elders and informal care time in far north-western low-income areas in China. METHOD: From September 2017 to February 2018, three hundred fifty-two dyads of Kazakh disabled elders and informal caregivers in Xinjiang were interviewed. Structural equation modelling analyses were applied. RESULTS: Significant positive correlations were observed between elders' disability severity and informal care time, caregiver health and informal care time, elders' disability severity and caregiver health. Significant negative correlations were observed between home-based care quality and informal care time, elders' disability severity and home-based care quality, caregiver health and home-based care quality. Elders' disability severity had 71.94% direct effect on informal care time, 28.06% indirect effect on informal care time mediated by home-based care quality and caregiver health. CONCLUSION: Caregiver health and home-based care quality play mediating roles on the path relationship between the elders' disability severity and informal care time.

Effect of disability severity on home-based care quality among families with Uygur and Kazakh disabled older adults in far western rural China: A cross-sectional study.

AIMS: To explore how family functioning and family resilience mediate the relationship between disability severity and quality of home-based care among families with disabled older adults. METHODS: A cross-sectional survey was conducted with 431 families with Uygur and Kazakh disabled older adults in Xinjiang, China, in 2020. The data were collected using the Katz Activity of Daily Living Scale; Mini-Mental State Examination; Family Adaptation, Partnership, Growth, Affection and Resolve Index Scale; Family Resilience Assessment Scale; and Family Caregiving Consequences Inventory Scale. All mediation effects were estimated in SPSS26.0. RESULTS: Disability severity, family functioning and family resilience were all significantly correlated with home-based care quality. Disability severity had a 46.16% direct effect on home-based care quality and a 53.84% indirect effect on home-based care quality independently and in series through family functioning and family resilience. CONCLUSIONS: Disability severity directly affected home-based care quality and had an indirect influence via family functioning and family resilience. Multidisciplinary care teams should focus on families with disabled older adults and help them improve family functioning and family resilience by implementing targeted interventions, so as to improve home-based care quality.

[Value of capsule endoscopy in children with small intestinal diseases with hematochezia as the chief complaint].

OBJECTIVE: To evaluate the value of capsule endoscopy in children with small intestinal diseases with hematochezia as the chief complaint. METHODS: A retrospective analysis was performed on the clinical data and capsule endoscopy findings of 93 children with hematochezia who were admitted to Children's Hospital of Fudan University from May 2015 to January 2019 and underwent capsule endoscopy. According to the capsule endoscopy findings of the jejunum and the ileum, they were divided into a positive lesion group with 39 patients and a negative lesion group with 54 patients. Related clinical data and the features of lesion on capsule endoscopy were analyzed for the two groups. RESULTS: There were no significant differences in age, sex, duration of capsule endoscopy, gastric transit time, and small intestinal transit time between the positive lesion and negative lesion groups (P>0.05). The positive lesion group had a significantly lower level of hemoglobin than the negative lesion group (P<0.05). Hemoglobin level was negatively correlated with the rate of positive lesions on capsule endoscopy (r=-0.342, P=0.001). Among the 39 patients with positive lesions on capsule endoscopy, the detection of Meckel's diverticulum was the highest (41%), followed by inflammatory bowel disease (21%). CONCLUSIONS: Capsule endoscopy has a certain value in detecting small intestinal diseases, especially diseases in the jejunum and the ileum, in children with lower gastrointestinal hemorrhage.

Cord blood leptin DNA methylation levels are associated with macrosomia during normal pregnancy.

BACKGROUND: We previously demonstrated an association between placental leptin (LEP) methylation levels and macrosomia without gestational diabetes mellitus (non-GDM). This study further explored the association between LEP methylation in cord blood and non-GDM macrosomia. METHOD: We carried out a case-control study of 61 newborns with macrosomia (birth weight ≥4000 g) and 69 newborns with normal birth weight (2500-3999 g). Methylation in the LEP promoter region was mapped by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. RESULTS: Average cord blood LEP methylation levels were lower in macrosomia newborns than in control newborns (P < 0.001). Eleven CpG sites were associated with macrosomia. Multivariate logistic regression revealed that low LEP methylation levels [adjusted odds ratio (AOR) = 2.84, 95% confidence interval (CI): 1.72-4.17], high pre-pregnancy body mass index (AOR = 7.44, 95% CI: 1.99-27.75), long gestational age (AOR = 3.18, 95% CI: 1.74-5.79), high cord blood LEP concentration (AOR = 2.25, 95% CI: 1.34-3.77), and male newborn gender (AOR = 3.91, 95% CI: 1.31-11.69) significantly increased the risk of macrosomia. CONCLUSIONS: Lower cord blood LEP methylation levels and certain maternal and fetal factors are associated with non-GDM macrosomia.

Placental and cord blood brain derived neurotrophic factor levels are decreased in nondiabetic macrosomia.

PURPOSE: To measure levels of placental brain derived neurotrophic factor (BDNF) gene expression and umbilical cord blood BDNF in neonates with nondiabetic macrosomia and determine associations between these levels and macrosomia. METHODS: This case-control study included 58 nondiabetic macrosomic and 59 normal birth weight mother-infant pairs. Data were collected from interviews and our hospital's database. BDNF gene expression was quantified in placental tissues using quantitative real-time polymerase chain reaction (n = 117). Umbilical cord blood BDNF levels were measured by enzyme-linked immunosorbent assay (n = 90). Multivariate logistic regression models were used to evaluate associations between BDNF levels and macrosomia. RESULTS: Placental BDNF gene expression (P = 0.026) and cord blood BDNF (P = 0.008) were lower in neonates with nondiabetic macrosomia than in normal birth weight controls. Cord blood BDNF was significantly lower in vaginally delivered macrosomic neonates than vaginally delivered controls (P = 0.014), but cord BDNF did not differ between vaginal and cesarean section delivery modes in macrosomic neonates. Cord blood BDNF was positively associated with gestational age in control neonates (r = 0.496, P < 0.001), but not in macrosomic neonates. Cord blood BDNF was positively associated with placental BDNF relative expression (r s = 0.245, P = 0.02) in the total group. Higher cord blood BDNF levels were independently associated with protection against nondiabetic macrosomia (adjusted odds ratio 0.992; 95% confidence interval 0.986-0.998). CONCLUSIONS: Both placental BDNF gene expression and cord blood BDNF were downregulated in neonates with nondiabetic macrosomia compared with normal birth weight neonates. Cord BDNF may partly derive from BDNF secreted by the placenta. Higher cord plasma BDNF levels protected against nondiabetic macrosomia.

The relationships among Muslim Uyghur and Kazakh disabled elders' life satisfaction, activity of daily living, and informal family caregiver's burden, depression, and life satisfaction in far western China: A structural equation model.

1 Hypothesis Disabled elders' activities of daily living, caregiver burden, caregiver depression, and caregivers' life satisfaction are significantly related to the life satisfaction of elderly people with disability. 2 Hypothesis There are direct and indirect effects between the life satisfaction of elders, disabled elders' activities of daily living, and family caregivers' factors. This study explored the interrelationships of disabled elders' life satisfaction and activities of daily living, caregivers' factors (burden, depression, and life satisfaction) through a structural equation model. In total, 621 dyads of disabled elders and informal family caregivers completed questionnaires during face-to-face interviews in Xinjiang Uyghur Autonomous Region from September 2013 to January 2014. Activity of daily living exerted a direct effect on life satisfaction of disabled elders and 30.4% indirect effect through caregivers' factors. Caregiver burden had a 60.0% direct effect on life satisfaction of disabled elders and a 40.0% indirect effect through the caregiver depression. Caregiver depression showed 76% direct effect on life satisfaction of disabled elders and 24% indirect effect through caregivers' life satisfaction. Direct relationships between activity of daily living and caregiver burden, caregiver burden and caregiver depression, and caregiver depression and caregivers' life satisfaction were observed. Activity of daily living had a 91.3% indirect effect on caregiver depression mediated by caregiver burden; caregiver burden had a 40.0% indirect effect on caregivers' life satisfaction mediated by caregiver depression. Results provide useful information for nurses and policymakers and shed light on the need to consider caregivers' factors in improving care recipients' life satisfaction.

Effect of Lactobacillus acidophilus and Bifidobacterium bifidum supplementation to standard triple therapy on Helicobacter pylori eradication and dynamic changes in intestinal flora.

To investigate Lactobacillus acidophilus (L. acidophilus) and Bifidobacterium bifidum (B. bifidum) supplementation to triple therapy for Helicobacter pylori (H. pylori) eradication and dynamic changes in intestinal flora in children with H. pylori infection. One hundred H. pylori-infected children were randomly assigned to two groups: treatment group (n = 43), standard triple anti-H. pylori therapy plus probiotics of L. acidophilus and B. bifidum for 2 weeks followed by taking probiotics for another 4 weeks; control group (n = 45), standard triple anti-H. pylori therapy for 6 weeks. After 6-week treatment, ¹³C-urease breath test was performed and side effects were monitored during the observation period. Quantitative PCR with 16S rRNA-gene-targeted species-specific primers was carried out for the analysis of human intestinal B. bifidum, L. acidophilus, and Escherichia coli (E. coli). As expected, treatment group could significantly enhance the H. pylori eradication rate (83.7 vs. 64.4 %, P < 0.05). B. bifidum, L. acidophilus, and E. coli showed no statistical difference before or after therapy in the treatment group. The number of B. bifidum and L. acidophilus was significantly decreased after 2-week treatment in the control group, but after 6-week treatment it significantly increased and nearly returned to the level before treatment. The number of E. coli increased significantly after 2-week treatment, while after 6-week treatment, it nearly decreased to the level before treatment. L. acidophilus and B. bifidum supplementation is effective for H. pylori eradication compared with triple therapy alone.

Re-defining how mRNA degradation is coordinated with transcription and translation in bacteria.

In eukaryotic cells, transcription, translation, and mRNA degradation occur in distinct subcellular regions. How these mRNA processes are organized in bacteria, without employing membrane-bound compartments, remains unclear. Here, we present generalizable principles underlying coordination between these processes in bacteria. In Escherichia coli, we found that co-transcriptional degradation is rare for mRNAs except for those encoding inner membrane proteins, due to membrane localization of the main ribonuclease, RNase E. We further found, by varying ribosome binding sequences, that translation affects mRNA stability not because ribosomes protect mRNA from degradation, but because low translation leads to premature transcription termination in the absence of transcription-translation coupling. Extending our analyses to Bacillus subtilis and Caulobacter crescentus, we established subcellular localization of RNase E (or its homolog) and premature transcription termination in the absence of transcription-translation coupling as key determinants that explain differences in transcriptional and translational coupling to mRNA degradation across genes and species.

Efficacy of exclusive enteral nutrition on the mucosal healing of different gastrointestinal segments in children with Crohn's disease.

OBJECTIVE: To investigate the association between disease location and segmental mucosal healing (SMH) following exclusive enteral nutrition (EEN) in children with Crohn's disease (CD). METHODS: Treatment-naive pediatric patients with endoscopically active CD treated with EEN alone as induction therapy were retrospectively enrolled from January 1, 2017 to June 30, 2022. The simple endoscopic score for CD (SES-CD) was employed to score disease activity in the upper gastrointestinal (GI) tract (esophagus, stomach, duodenum), rectum, left colon, transverse colon, right colon, and terminal ileum. While the Lewis score assessed that of the small bowel from the jejunum to the proximal ileum (except the terminal ileum). The variation in the total scores for each segment and SES-CD subscores for each ileocolonic segment from baseline to 1 year after EEN therapy and the segmental endoscopic outcomes and potential predictors associated with SMH for the segments scored by SES-CD were evaluated. RESULTS: Overall, 82 children with CD were enrolled. Except for the upper GI segment, scores in other segments declined significantly from baseline to EEN completion (all P < 0.001). We analyzed 486 segments (79, 80, 81, 82, 82 and 82 from upper GI tract, terminal ileum, right colon, transverse colon, left colon, and rectum) and found that the segmental SES-CD at baseline (odds ratio [OR] 0.62, 95% confidence interval [CI] 0.55-0.70, P < 0.001) and upper GI location (OR 0.25, 95% CI 0.11-0.55, P = 0.001) were associated with SMH at EEN completion. CONCLUSION: Disease location of the upper GI segment in pediatric CD was associated with SMH following EEN therapy.

Three patients with new mutations in the EPCAM variant gene for congenital tufting enteropathy and a mutation review in China: a case report.

Background: Congenital tufting enteropathy (CTE) is a rare cause of intractable congenital diarrhea in children, always resulting in parenteral nutrition (PN) dependency. We aimed to report novel mutations in Chinese patients and to illustrate the clinical, histopathological, and molecular features of CTE in China. Case Description: We report three cases of CTE diagnosed with whole-exome sequencing (WES) and MOC31 [a monoclonal antibody of epithelial cell adhesion molecule (EPCAM)] immunohistochemistry. The main manifestations in the three patients were watery diarrhea and growth retardation. Upper endoscopy in three patients revealed villous atrophy of the duodenal mucosa. Histological examination revealed villus abnormalities and two patients with focal tufting. All of the three patients revealed a complete absence of EPCAM expression through MOC31 immunohistochemistry. Five novel mutations, including c.319delG, c.505_507delGAG, c.491+1G>C, c.60del (p.F20Lfs*17), and c.353G>A, in EPCAM were identified through molecular analysis. In our review, there were 18 different mutations in 11 patients from nine studies, with 12 mutations reported only once. In China, 73% of the patients were compound heterozygotes, and most of the pathogenic variants were in exon 3. All patients presented with congenital diarrhea and needed PN because of growth retardation, even when diarrhea was improved. Of the 11 patients, 3 (27%) died. Conclusions: CTE is rare and fatal, and lacks characteristic changes during endoscopy. Patients with CTE require early diagnosis via histological examination and genetic detection to improve survival.

Normal and degenerated rabbit nucleus pulposus cells in in vitro cultures: A biological comparison.

This study examined the biological characteristics of normal and degenerated rabbit nucleus pulposus (NP) cells in vitro in order to provide seed cells for intervertebral disc (IVD) tissue engineering. A total of 8 adult New Zealand white rabbits underwent annulus puncture to establish models of intervertebral disc degeneration (IDD). Four weeks later, normal and degenerated NP cells were obtained. Cell morphology was observed by light and electron microscopy. Cell viability was measured by MTT assay. Cell cycle and expression of extracellular matrix (ECM)-related genes (aggrecan and type II collagen) were determined by using flow cytometry and RT-PCR respectively. The growth curve of normal NP cells showed that the cells at passage 4 tended to slowly grow on the fifth day of culture. The density of normal NP cells at passages 5 to 7 was significantly less than that of the first-passage cells 2 or 3 days after seeding (P<0.05). The degenerated NP cells at passage 3 showed slow growth at 4th day. After 5 passages, the degenerated NP cells assumed stagnant growth and the growth seemed to stop at passage 7. The MTT assay revealed that for both normal and degenerated NP cells, the absorbance (A) value at passages 4-7 was obviously decreased as compared with that at passage 1 (P<0.05). Cell cycle analysis showed that the proportion of normal NP cells at Gl phase was 65.4%±3.5%, significantly lower than that of degenerated NP cells at the same cell cycle phase with the value being 77.6%±4.8%. The degenerated NP cells were predominantly arrested at G1 phase and failed to enter S phase. The expression of type II collagen and aggrecan was significantly decreased with passaging. It was concluded that normal NP cells possessed good viability and proliferative capacity by the third passage, and they could secrete large amounts of ECM within this period. The normal NP cells may serve as seed cells for IVD tissue engineering.

High uniformity in angular correlated-color-temperature distribution of white LEDs from 2800K to 6500K.

In this paper, to our best knowledge, it is the first time to present a precise simulation and detailed design of angular correlated color temperature (CCT) distribution of white LEDs covering a range of CCT from 2800K to 6500K. An optimized design of packaging structure with a silicone lens covering a phosphor dome performed an extreme small angular CCT deviation of 105K in the simulation and 182K in a corresponding real sample for a white LED with the CCT near 6500K.

[Factors and neonatal outcomes associated with histologic chorioamnionitis after premature rupture of membranes in the preterms].

OBJECTIVE: To investigate factors and neonatal outcomes associated with histologic chorioamnionitis (HCA) in preterm premature rupture of membranes (PPROM). METHODS: From Jan. 2008 to Jun. 2011, 230 women with PPROM at 28 - 33(+6) weeks of gestation undergoing deliveries in the Second Affiliated Hospital of Wenzhou Medical College were studied retrospectively. According to placental histopathologic findings, those patients were categorized into two groups, including 138 cases in histologic chorioamnionitis (HCA group) and 65 cases in non-chorioamnionitis (control) group. Age, parity, gestational age of PPROM and delivery, latency period, oligohydramnios, white blood cell (WBC) count and serum C-reactive protein (CRP) level at admission and before delivery, the incidence of neonatal respiratory distress syndrome (NRDS), neonatal pneumonia, bronchopulmonary dysplasia, necrotizing enterocolitis, early-onset neonatal sepsis, abnormal brain sonography findings and mortality were compared between two groups. RESULTS: (1) The incidence of HCA was 68.0% (138/203) in all 203 cases with PPROM. (2) The occurring ruptured membrane gestation in HCA group was (31.1 ± 1.5) weeks, which were significantly earlier than (32.0 ± 1.3) weeks in control group (P < 0.05). The level of CRP of (8.2 ± 14.9) mg/L before delivery in HCA group was significantly higher than (5.5 ± 7.2) mg/L in control group (P < 0.05). The rate of oligohydramnios and cesearean sections were 55.1% (76/138) and 45.7% (63/138) in HCA group, which were significantly higher than 30.8% (20/65) and 29.2% (19/65) in control group (P < 0.05). There were no significant difference in patient's age, parity, WBC count and CRP at admission between two groups (P > 0.05). The latency period did not show significant difference between (140 ± 116) hours in HCA group and (129 ± 125) hours in control group (P > 0.05). (3) Using multivariable logistic regression models, oligohydramnios (OR = 2.937), gestational age of PPROM < 32 weeks (OR = 2.352), serum CRP level > 8 mg/L before delivery (OR = 4.923) and latency period > 48 - 168 hours (OR = 4.439) were significantly associated with HCA (P < 0.05). (4) The gestational age of delivery and birth weight of HCA group were significantly lower than those of control group [(32.0 ± 1.5) weeks vs. (32.7 ± 1.5) weeks, (1680 ± 379) g vs. (2017 ± 333) g, respectively, P < 0.05]. The incidence of Apgar < 7, abnormal brain sonograhy findings, neonatal pneumonia, bronchopulmonary dysplasia, early-onset neonatal sepsis and mortality in HCA group were significantly higher than those in control group [20.3% (28/138) vs. 7.7% (5/65), 14.5% (20/138) vs. 4.6% (3/65), 12.3% (17/138) vs. 3.1% (2/65), 5.8% (8/138) vs. 0, 6.5% (9/138) vs. 0, 12.3% (17/138) vs. 3.1% (2/65), respectively, P < 0.05]. The incidence of necrotizing enterocolitis (1.5%, 2/138) in HCA group was higher than that of control group (0) and the incidence of NRDS (18.8%, 26/138) in HCA group did not show statistical difference with 21.4% (14/65) in control group (P > 0.05). CONCLUSIONS: It was found that HCA was significantly correlated with lower gestational age of PPROM, higher serum CRP level before delivery, prolonged latency period and oligohydramnios in PPROM. HCA could increase the neonatal morbidity and mortality.

Relationships Between Placental Lipid Activated/Transport-Related Factors and Macrosomia in Healthy Pregnancy.

To assess associations between infants with macrosomia and placental expression levels of lipid activated/transport-related factors and umbilical cord blood lipid concentrations in healthy pregnancy. We conducted a case-control study of 38 macrosomic neonates (MS group) and 39 normal-birth-weight newborns (NC group) in a healthy pregnancy. Cord blood lipid levels were measured by automatic biochemical analyzer, mRNA and protein expression levels of placental lipid activated/transport-related factors were determined by real-time polymerase chain reaction and western blot, respectively. Compared with NC group, cord blood total cholesterol (TC), low-density lipoprotein cholesterol (LDLC), and non-esterified fatty acid (NEFA) concentrations were decreased in the MS group. The mRNA and protein expression levels of placental peroxisome proliferator-activated receptors (PPARα, PPARγ), plasma membrane fatty acid-binding protein (FABPpm), and fatty acid translocase (FAT/CD36) were significantly higher in the MS group than the NC group. And there was a weak positive correlation between the expression of PPARγ, FABP4, and FABP3 mRNA in the placenta and the HDLC (rs = 0.439; P = 0.005), NEFA (rs = 0.342; P = 0.041), and TG (rs = 0.349; P = 0.034) levels in the cord blood in the MS group, respectively. After multivariate adjustment, the logistic regression analysis showed that high placental PPARα (adjusted odds ratio [AOR] = 3.022; 95% confidence interval [CI] 1.032-8.853) and FAT/CD36 (AOR=2.989; 95%CI 1.029-8.679) and low LDLC concentration in the cord blood (AOR=0.246; 95%CI 0.080-0.759) increased the risk of macrosomia. The increased PPARα and FAT/CD36 expression levels may influence the occurrence of fetal macrosomia through regulating placental lipid transport.

Placental mtDNA copy number and methylation in association with macrosomia in healthy pregnancy.

INTRODUCTION: Fetal growth and development depend on metabolic energy from placental mitochondria. However, the impact of placental mitochondria on the occurrence of macrosomia remains unclear. We aimed to explore the association between macrosomia without gestational diabetes mellitus (non-GDM) and changes in placental mitochondrial DNA (mtDNA) copy number and methylation. METHODS: Fifty-four newborns with macrosomia and 54 normal birthweight controls were enrolled in this study. Placental mtDNA copy number and mRNA expression of nuclear genes related to mitochondrial replication or ATP synthesis-related genes were measured by real-time quantitative polymerase chain reaction (qPCR). Methylation levels of the non-coding regulatory region D-loop and ATP synthesis-related genes were detected by targeted bisulfite sequencing. RESULTS: Newborns with macrosomia had lower placental mtDNA copy number and higher methylation rates of the CpG15 site in the D-loop region (D-CpG15) and CpG6 site in the cytochrome C oxidase III (COX3) gene (COX3-CpG6) than normal birth weight newborns. After adjusting for potential covariates (gestational age, prepregnancy BMI, and infant sex), decreased placental mtDNA copy number (adjusted odds ratio [aOR] = 2.09, 95% confidence interval [CI] 1.03-4.25), elevated methylation rate of D-CpG15 (aOR = 2.06, 95% CI 1.03-4.09) and COX3-CpG6 (aOR = 2.13, 95% CI 1.08-4.20) remained significantly associated with a higher risk of macrosomia. DISCUSSION: Reduced mtDNA copy number and increased methylation levels of specific loci at mtDNA would increase the risk of macrosomia. However, the detailed molecular mechanism needs further identification.