Association between isolated maternal hypothyroxinemia during the first trimester and adverse pregnancy outcomes in Southern Chinese women: a retrospective study of 7051 cases.

BACKGROUND: The association between isolated maternal hypothyroxinemia (IMH) and adverse pregnancy outcomes is still controversial. This study aimed to evaluate the association between IMH during the first trimester and adverse pregnancy outcomes in southern Chinese women. METHODS: This was a hospital-based, retrospective cohort study. The records of 7051 women, including 1337 IMH women and 5714 euthyroid women who had a singleton pregnancy and accepted routine prenatal service at the Third Affiliated Hospital of Sun Yat-Sen University from January 2015 to September 2018, were extracted from the electronic medical records system in this study. Thyroid functions [thyroid-stimulating hormone (TSH), free thyroxine (fT4) and anti-thyroperoxidase autoantibody (TPO-Ab)] had to be measured before 13 weeks and 6 days of gestation. The chi-square test and multivariate logistic regression analysis were applied to evaluate the association between IMH during the first trimester and adverse pregnancy outcomes. RESULTS: Prepregnancy obesity [prepregnancy body mass index (preBMI) ≥ 25 kg/m2] was found to be more common in the IMH group (11.2% vs. 6.1%) (P < 0.05). The prevalence of gestational diabetes mellitus (GDM), postpartum haemorrhage (PPH), macrosomia and large for gestational age (LGA) was higher in the IMH group. However, after using multivariate logistic regression analysis to adjust for confounders (maternal age, educational levels and preBMI), only LGA was shown to be associated with an increased risk in IMH women [adjusted OR: 1.27 (95% CI 1.044-1.566)]. The prevalence of preterm delivery (either < 37 or < 34 weeks), gestational hypertension, preeclampsia, placenta previa, placental abruption, premature rupture of membrane (PROM), intrauterine growth restriction (IUGR), polyhydramnios, stillbirth, small for gestational age (SGA) and low Apgar score did not increase. CONCLUSION: IMH during the first trimester did not increase any risk of adverse pregnancy outcomes in southern Chinese women except LGA.

Transformation of Biomass DNA into Biodegradable Materials from Gels to Plastics for Reducing Petrochemical Consumption.

Ancient biomass is the main source for petrochemicals including plastics, which are inherently difficult to be degraded, increasingly polluting the earth's ecosystem including our oceans. To reduce the consumption by substituting or even replacing most of the petrochemicals with degradable and renewable materials is inevitable and urgent for a sustainable future. We report here a unique strategy to directly convert biomass DNA, at a large scale and with low cost, to diverse materials including gels, membranes, and plastics without breaking down DNA first into building blocks and without polymer syntheses. With excellent and sometimes unexpected, useful properties, we applied these biomass DNA materials for versatile applications for drug delivery, unusual adhesion, multifunctional composites, patterning, and everyday plastic objects. We also achieved cell-free protein production that had not been possible by petrochemical-based products. We expect our biomass DNA conversion approach to be adaptable to other biomass molecules including biomass proteins. We envision a promising and exciting era coming where biomass may replace petrochemicals for most if not all petro-based products.

First-trimester fasting plasma glucose as a predictor of gestational diabetes mellitus and the association with adverse pregnancy outcomes.

OBJECTIVE: To evaluate the usefulness of a fasting plasma glucose (FPG) at the first trimester in predicting gestational diabetes mellitus (GDM) and the association between FPG and adverse pregnancy outcomes. METHODS: The levels of FPG in women with singleton pregnancies were measured at 9-13+6 weeks. A two hour 75-g oral glucose tolerance test (OGTT) was completed at 24-28 weeks and the International Association of Diabetes and Pregnancy Study Groups (IADPSG) criteria was used. Adverse pregnancy outcomes were assessed and recorded. RESULTS: Among 2112 pregnant women enrolled in the study, 224 (10.6%) subjects were diagnosed with GDM. The AUC for FPG in predicting GDM was 0.63 (95% CI 0.61- 0.65) and the optimal cutoff value was 4.5 mmol/L (sensitivity 64.29% and specificity 56.45%). Higher first-trimester FPG increased the prevalence of GDM, large for gestational age (LGA) and assisted vaginal delivery and/or cesarean section (all P < 0.05). CONCLUSION: FPG at first trimester could be used to predict GDM and higher first-trimester FPG was associated with adverse pregnancy outcomes.

Effect of mildly elevated thyroid-stimulating hormone during the first trimester on adverse pregnancy outcomes.

BACKGROUND: To investigate the effect of a mildly elevated thyroid-stimulating hormone (TSH) concentration between 2.5 and 4.0 mIU/L during the first trimester on pregnancy outcomes in thyroid peroxydase antibody (TPOAb)-negative pregnant women. METHODS: A total of 1858 pregnant women who were TPOAb-negative before 13+ 6 gestational weeks, received regular prenatal services, and delivered in the third affiliated hospital of Sun Yat-Sen University were recruited from June 2016 to June 2017. Measurements of thyroid function (TSH, free T4 [FT4] and TPOAb) and adverse pregnancy outcomes were assessed and recorded. RESULTS: Among the 1858 study participants, the 97.5th percentile for TSH was 3.76 mIU/L, and 142 women (7.6%) had mildly elevated TSH levels between 2.5 and 4.0 mIU/L. No differences in the incidence of adverse pregnancy outcomes were observed between patients with a mildly elevated TSH level and those with a normal TSH level (< 2.5 mIU/L). CONCLUSION: A mildly elevated TSH concentration (2.5-4.0 mIU/L) during the first trimester of pregnancy in TPOAb-negative women was not associated with adverse pregnancy outcomes in our study population. Accordingly, it may be possible to raise the upper limit of the healthy TSH reference range for pregnant women.

Cr:ZnS saturable absorber passively Q-switched mode-locking Tm,Ho:LLF laser.

We first report on a diode-end-pumped passively Q-switched mode-locking Tm,Ho:LLF laser at 2053 nm by using a Cr:ZnS saturable absorber. A stable Q-switched mode-locking pulse train with a nearly 100% modulation depth was achieved. The repetition frequency of the Q-switched pulse envelope increased from 0.5 to 12.3 kHz with increasing pump power from 1 to 4.36 W. The maximum average output power of 145 mW was obtained, and the width of the mode-locked pulse was estimated to be less than 682 ps with a 250 MHz repetition frequency within a Q-switched pulse envelope of about 700 ns.

Characterization and Insights Into the Nano Liposomal Magnetic Gene Vector Used for Cell Co-Transfection.

The development of magnetofection technology has brought a promising method for gene delivery. Here, we develop a novel liposomal magnetofection system, consisted of magnetic nanoparticle and liposome through molecular assembly, was applied to introduce double genes into porcin somatic cells with high co-transfection efficiency. The performace of liposomal magnetic gene nanovectors has been evaluated by involving the micro morphology, diameters distribution, zeta potentials and the capacity of loading DNA molecules. The assembly way among magnetic gene nanovectors and DNA molecules was investigated by atomic force microscopy. Liposomal nano magnetic gene vectors complexes displayed nanoscale assembly and formed compact "fishing-net structure" after combining with plasmid DNA, which is favorable to enhance the loading capacity of DNA molecules.

Diode-end-pumped continuously tunable single frequency Tm, Ho:LLF laser at 2.06 µm.

We report on a laser diode-end-pumped continuously tunable single frequency Tm, Ho:LLF laser near room temperature. For transmission of 5%, the maximum single frequency output power of 221 mW at 2064.4 nm was obtained by using two uncoated etalons. The single frequency Tm, Ho:LLF laser operated on the fundamental transverse mode with an M2 factor of 1.13, and the output frequency could be tuned continuously near 1.5 GHz by angle tuning only of the 1 mm thick etalon. Furthermore, the influence of output coupler transmission on the laser performance was also investigated. The single frequency laser can be used as a seed laser for coherent Doppler lidar and differential absorption lidar systems.

Identifying First-Trimester Risk Factors for SGA-LGA Using Weighted Inheritance Voting Ensemble Learning.

The classification of fetuses as Small for Gestational Age (SGA) and Large for Gestational Age (LGA) is a critical aspect of neonatal health assessment. SGA and LGA, terms used to describe fetal weights that fall below or above the expected weights for Appropriate for Gestational Age (AGA) fetuses, indicate intrauterine growth restriction and excessive fetal growth, respectively. Early prediction and assessment of latent risk factors associated with these classifications can facilitate timely medical interventions, thereby optimizing the health outcomes for both the infant and the mother. This study aims to leverage first-trimester data to achieve these objectives. This study analyzed data from 7943 pregnant women, including 424 SGA, 928 LGA, and 6591 AGA cases, collected from 2015 to 2021 at the Third Affiliated Hospital of Sun Yat-sen University in Guangzhou, China. We propose a novel algorithm, named the Weighted Inheritance Voting Ensemble Learning Algorithm (WIVELA), to predict the classification of fetuses into SGA, LGA, and AGA categories based on biochemical parameters, maternal factors, and morbidity during pregnancy. Additionally, we proposed algorithms for relevance determination based on the classifier to ascertain the importance of features associated with SGA and LGA. The proposed classification solution demonstrated a notable average accuracy rate of 92.12% on 10-fold cross-validation over 100 loops, outperforming five state-of-the-art machine learning algorithms. Furthermore, we identified significant latent maternal risk factors directly associated with SGA and LGA conditions, such as weight change during the first trimester, prepregnancy weight, height, age, and obstetric factors like fetal growth restriction and birthing LGA baby. This study also underscored the importance of biomarker features at the end of the first trimester, including HDL, TG, OGTT-1h, OGTT-0h, OGTT-2h, TC, FPG, and LDL, which reflect the status of SGA or LGA fetuses. This study presents innovative solutions for classifying and identifying relevant attributes, offering valuable tools for medical teams in the clinical monitoring of fetuses predisposed to SGA and LGA conditions during the initial stage of pregnancy. These proposed solutions facilitate early intervention in nutritional care and prenatal healthcare, thereby contributing to enhanced strategies for managing the health and well-being of both the fetus and the expectant mother.

A universal DNA-based protein detection system.

Protein immune detection requires secondary antibodies which must be carefully selected in order to avoid interspecies cross-reactivity, and is therefore restricted by the limited availability of primary/secondary antibody pairs. Here we present a versatile DNA-based protein detection system using a universal adapter to interface between IgG antibodies and DNA-modified reporter molecules. As a demonstration of this capability, we successfully used DNA nano-barcodes, quantum dots, and horseradish peroxidase enzyme to detect multiple proteins using our DNA-based labeling system. Our system not only eliminates secondary antibodies but also serves as a novel method platform for protein detection with modularity, high capacity, and multiplexed capability.

Orthogonally polarized dual-wavelength single-longitudinal-mode Tm,Ho:LLF laser.

We first report a diode-pumped continuous wave orthogonally polarized dual-wavelength single-longitudinal-mode laser with a single c-cut Tm,Ho:LuLiF4 laser crystal. The simultaneous dual-wavelength single-longitudinal-mode laser near 2 µm is realized by using two uncoated intracavity Fabry-Perot etalons. The output wavelengths are 2064 nm in π-polarization and 2066 nm in σ-polarization respectively, which are orthogonal to each other. At the absorbed pump power of 1 W, the maximum single-longitudinal-mode output powers at 2064 and 2066 nm are 76 and 32 mW respectively. The orthogonally polarized dual-wavelength single-longitudinal-mode laser is possible to be applied to the 2 µm differential absorption lidar and the generation of THz radiation.

Diode-pumped continuous wave and passively Q-switched Tm,Ho:LLF laser at 2 µm.

A compact diode-pumped continuous wave and passively Q-switched Tm,Ho:LuLiF(4) laser is demonstrated. The maximal output power of 381 mW at 2069 nm in continuous wave regime is obtained at an absorbed pump power of 1.5 W. By using a Cr(2+):ZnS saturable absorber, the maximum Q-switched average output power of 74 mW is obtained at 2055 nm. The pulse width and pulse energy are almost independent of the absorbed pump power, with the maximal values of 1.2 µs and of 13 µJ respectively. The pulse repetition frequency can be tuned almost linearly from 1 to 5.8 kHz by changing the absorbed pump power. Furthermore, a comparative analysis of laser performances with different output couplers is first carried out.

Diode-pumped actively Q-switched Tm, Ho:GdVO4/BaWO4 intracavity Raman laser at 2533 nm.

A compact diode-end-pumped actively Q-switched intracavity Raman laser with Tm,Ho:GdVO(4) laser gain medium and BaWO(4) Raman gain crystal is demonstrated for the first time. The Raman threshold is as low as 2.0 W of diode power at 802 nm. The highest average output power of 186 mW at the first Stokes wavelength of 2533 nm is obtained at a pulse repetition rate of 1 kHz, and a pump power of 2.8 W, corresponding to a diode-to-Stokes optical conversion efficiency of 6.6%. The pulsewidth and pulse energy are 7.8 ns and 0.19 mJ, respectively.

Portable Paper-Based Nucleic Acid Enrichment for Field Testing.

Point-of-care testing (POCT) can be the method of choice for detecting infectious pathogens; these pathogens are responsible for not only infectious diseases such as COVID-19, but also for certain types of cancers. For example, infections by human papillomavirus (HPV) or Helicobacter pylori (H. pylori) are the main cause of cervical and stomach cancers, respectively. COVID-19 and many cancers are treatable with early diagnoses using POCT. A variety of nucleic acid testing have been developed for use in resource-limited environments. However, questions like unintegrated nucleic acid extraction, open detection systems increase the risk of cross-contamination, and dependence on expensive equipment and alternating current (AC) power supply, significantly limit the application of POCT, especially for on-site testing. In this paper, a simple portable platform is reported capable of rapid sample-to-answer testing within 30 min based on recombinase polymerase amplification (RPA) at a lower temperature, to detect SARS-CoV-2 virus and H. pylori bacteria with a limit of detection as low as 4 × 102 copies mL-1 . The platform used a battery-powered portable reader for on-chip one-pot amplification and fluorescence detection, and can test for multiple (up to four) infectious pathogens simultaneously. This platform can provide an alternative method for fast and reliable on-site diagnostic testing.

Study on the Relationship and Predictive Value of First-Trimester Pregnancy-Associated Plasma Protein-A, Maternal Factors, and Biochemical Parameters in Gestational Diabetes Mellitus: A Large Case-Control Study in Southern China Mothers.

Objective: To investigate the relationship and predictive value of first-trimester pregnancy-associated plasma protein A (PAPP-A), maternal factors, and biochemical parameters with gestational diabetes mellitus (GDM) in southern China mothers. Methods: This study recruited 4872 pregnant women. PAPP-A, the free beta subunit of human chorionic gonadotropin (free ß-HCG), fasting plasma glucose (FPG), total cholesterol (TC), triglycerides (TG), and high- and low-density lipoproteins (HDL, LDL) were measured at 11-13+ weeks of gestation. GDM was diagnosed based on a 75 g oral glucose tolerance test at 24-28 weeks of gestation. We performed stepwise logistic regression analysis to determine the odds ratio (OR) and the 95% confidence interval (CI) of GDM. We used Receiver Operating Characteristic (ROC) curves with the area under the curve (AUC) to evaluate the predictive value of PAPP-A, maternal factors, and biochemical markers. The significance of the differences between the AUC values was assessed using the DeLong test. Results: GDM was diagnosed in 750 (15.39%) women. Independent factors for GDM were age, pre-gestational BMI, GWG before a diagnosis of GDM, previous history of GDM, family history of diabetes, FPG, TG, LDL, PAPP-A, and TC. The AUC of PAPP-A was 0.56 (95% CI 0.53-0.58). The AUC of a model based on combined maternal factors, biochemical markers, and PAPP-A was 0.70 (95% CI 0.68-0.72). Differences in AUC values between PAPP-A alone and the model based on combined maternal factors, biochemical markers, and PAPP-A were statistically significant (Z= 9.983, P<0.001). Conclusion: A Low serum PAPP-A level in the first trimester is an independent risk factor for developing GDM later in pregnancy. However, it is not a good independent predictor although the predictive value of a low serum PAPP-A level increases when combined with maternal factors and biochemical markers.

CHDbase: A Comprehensive Knowledgebase for Congenital Heart Disease-related Genes and Clinical Manifestations.

Congenital heart disease (CHD) is one of themost common causes of major birth defects, with a prevalence of 1%. Although an increasing number of studies have reported the etiology of CHD, the findings scattered throughout the literature are difficult to retrieve and utilize in research and clinical practice. We therefore developed CHDbase, an evidence-based knowledgebase of CHD-related genes and clinical manifestations manually curated from 1114 publications, linking 1124susceptibility genes and 3591 variations to more than 300 CHD types and related syndromes. Metadata such as the information of each publication and the selected population and samples, the strategy of studies, and the major findings of studies were integrated with each item of the research record. We also integrated functional annotations through parsing ∼ 50 databases/tools to facilitate the interpretation of these genes and variations in disease pathogenicity. We further prioritized the significance of these CHD-related genes with a gene interaction network approach and extracted a core CHD sub-network with 163 genes. The clear genetic landscape of CHD enables the phenotype classification based on the shared genetic origin. Overall, CHDbase provides a comprehensive and freely available resource to study CHD susceptibilities, supporting a wide range of users in the scientific and medical communities. CHDbase is accessible at http://chddb.fwgenetics.org.

Impact of Early Pregnancy Subclinical Hypothyroidism on Gestational Diabetes Mellitus: A Retrospective Study of 7,536 Cases.

Background: Maternal subclinical hypothyroidism (SCH) has been associated with adverse pregnancy outcomes. This study aimed to explore whether SCH in the first trimester contributed to the development of gestational diabetes mellitus (GDM). Materials and Methods: A total of 8,777 pregnant women who first visited before 13 weeks and 6 days of gestation and accepted routine prenatal service at the Third Affiliated Hospital of Sun Yat-Sen University from January 2015 to September 2018 were recruited in this study. Thyroid functions (thyroid stimulating hormone [TSH], free T4, and thyroid peroxidase antibody [TPOAb]) were measured before 13 weeks and 6 days of gestation and data of 7,536 subjects with TSH ≥0.1 mIU/L were analyzed. A 2-hour 75-g oral glucose tolerance test was performed between 24 and 28 gestational weeks. Chi-square test and multivariate logistic regression analysis were applied to evaluate the relationship between SCH and GDM. Results: The prevalence of SCH in this population was 7.53%. After stratifying the relationship between SCH and GDM according to TSH concentrations (slightly elevated TSH: ≥2.5, <4.0 mIU/L; moderately elevated TSH: ≥4.0, <10.0 mIU/L) and TPOAb status, a moderately elevated TSH combined with positive TPOAb (23.9% vs. normal 13.0%, chi-square = 6.317, p = 0.012) was found to increase the incidence of GDM. Furthermore, after adjusting for confounders (maternal age, educational levels, parity, and pregestational body mass index [preBMI]), the SCH group still exhibited a higher risk of GDM (relative risk [RR] 1.867, 95% confidence interval [CI] 1.018-3.424). Conclusion: Our findings indicated that SCH during early pregnancy, in the presence of moderately elevated TSH levels and positive TPOAb, might lead to an increased risk of GDM.

Evaluation of association studies and a systematic review and meta-analysis of VDR polymorphisms in type 2 diabetes mellitus risk.

ABSTRACT: Numerous original studies and 4 published meta-analyses have reported the association between the Vitamin D receptor (VDR) BsmI, FokI, ApaI, and TaqI polymorphisms and type 2 diabetes mellitus (T2DM) risk. However, the results were inconsistent. Therefore, an updated meta-analysis was performed to further explore these issues.To further explore the association between the VDR BsmI, FokI, ApaI, and TaqI polymorphisms and T2DM risk.PubMed, EMBASE, Scopus, and Wanfang databases were searched. The following search strategy were used: (VDR OR vitamin D receptor) AND (polymorphism OR variant OR mutation) AND (diabetes OR mellitus OR diabetes mellitus). Pooled crude odds ratios with 95% confidence intervals were applied to evaluate the strength of association in 5 genetic models. Statistical heterogeneity, the test of publication bias, and sensitivity analysis were carried out using the STATA software (Version 12.0). To evaluate the credibility of statistically significant associations, we applied the false-positive report probabilities (FPRP) and Bayesian false discovery probability (BFDP) test.Overall, the VDR BsmI polymorphism was associated with a significantly decreased T2DM risk in Asians; the VDR FokI polymorphism was associated with a significantly decreased T2DM risk in Asians, African countries, and Asian countries; the VDR ApaI polymorphism was associated with a significantly decreased T2DM risk in Caucasians and North American countries.On the VDR ApaI polymorphism, a significantly increased T2DM risk was found in a mixed population. However, when we further performed a sensitivity analysis, FPRP, and BFDP test, less-credible positive results were identified (all FPRP > 0.2 and BFDP > 0.8) in any significant association.In summary, this study strongly indicates that all significant associations were less credible positive results, rather than from true associations.

MiR-101-containing extracellular vesicles bind to BRD4 and enhance proliferation and migration of trophoblasts in preeclampsia.

BACKGROUND: Preeclampsia (PE) is a frequently occurring pregnancy disorder in the placenta, which results in various maternal and fetal complications. The current study aims to evaluate the role of extracellular vesicles (EVs)-encapsulated microRNA (miR)-101 in biological processes of trophoblasts in PE and its underlying mechanism. METHODS: Human umbilical cord mesenchymal stem cell (HUCMSC) and HUCMSC-derived EVs were isolated and cultured, after which EV characterization was carried out using PKH67 staining. In silico analyses were adopted to predict the downstream target genes of miR-101, and dual luciferase reporter gene assay was applied to validate the binding affinity. Furthermore, loss- and gain-of-function approaches were adopted to determine the role of miR-101 and bromodomain-containing protein 4 (BRD4) in trophoblast proliferation and invasion using EDU staining and transwell assay. In addition, a rat model of PE was established to verify the function of EV-encapsulated miR-101 in vivo. RESULTS: Placental tissues obtained from PE patients presented with downregulated miR-101 expression and upregulated BRD4 and CXCL11 expression. EV-encapsulated miR-101 from HUCMSCs could be delivered into the trophoblast HTR-8/SVneo cells, thus enhancing proliferation and migration of trophoblasts. Mechanically, miR-101 targeted and negatively regulated BRD4 expression. BRD4 knockdown promoted the proliferation and migration of trophoblasts by suppressing NF-κB/CXCL11 axis. EV-encapsulated miR-101 from HUCMSCs also reduced blood pressure and 24 h urine protein in vivo, thereby ameliorating PE. CONCLUSION: In summary, EV-encapsulated miR-101 promoted proliferation and migration of placental trophoblasts through the inhibition of BRD4 expression via NF-κB/CXCL11 inactivation.

A PEGDA/DNA Hybrid Hydrogel for Cell-Free Protein Synthesis.

Cell-free protein synthesis (CFPS) has the advantage of rapid expression of proteins and has been widely implemented in synthetic biology and protein engineering. However, the critical problem limiting CFPS industrial application is its relatively high cost, which partly attributes to the overexpense of single-use DNA templates. Hydrogels provide a possible solution because they can preserve and reutilize the DNA templates in CFPS and have great potential in elevating the protein production yield of the CFPS. Here, we presented a low-cost hybrid hydrogel simply prepared with polyethylene glycol diacrylate (PEGDA) and DNA, which is capable of high-efficient and repeated protein synthesis in CFPS. Parameters governing protein production specific to hybrid hydrogels were optimized. Structures and physical properties of the hybrid hydrogel were characterized. Transcription and expression kinetics of solution phase system and gel phased systems were investigated. The results showed that PEGDA/DNA hydrogel can enhance the protein expression of the CFPS system and enable a repeated protein production for tens of times. This PEGDA/DNA hybrid hydrogel can serve as a recyclable gene carrier for either batch or continuous protein expression, and paves a path toward more powerful, scalable protein production and cell-free synthetic biology.

An ultraportable and versatile point-of-care DNA testing platform.

Point-of-care testing (POCT) has broad applications in resource-limited settings. Here, a POCT platform termed POCKET (point-of-care kit for the entire test) is demonstrated that is ultraportable and versatile for analyzing multiple types of DNA in different fields in a sample-to-answer manner. The POCKET is less than 100 g and smaller than 25 cm in length. The kit consists of an integrated chip (i-chip) and a foldable box (f-box). The i-chip integrates the sample preparation with a previously unidentified, triple signal amplification. The f-box uses a smartphone as a heater, a signal detector, and a result readout. We detected different types of DNA from clinics to environment to food to agriculture. The detection is sensitive (<103 copies/ml), specific (single-base differentiation), speedy (<2 hours), and stable (>10 weeks shelf life). This inexpensive, ultraportable POCKET platform may become a versatile sample-to-answer platform for clinical diagnostics, food safety, agricultural protection, and environmental monitoring.