Generation of a Human Induced Pluripotent Stem Cell Line Expressing a Magnetic Resonance Imaging Reporter Gene.

The objective of the current study is to develop a new method for tracking transplanted human induced pluripotent stem cells-derived cardiomyocytes (hiPSC-CMs) using magnetic resonance imaging (MRI). The CRISPR/dCas9 activation system is employed to overexpress ferritin heavy chain (FHC) in hiPSC-CMs. The mRNA and protein expression of FHC in hiPSC and hiPSC-CMs significantly increased after transfection. Iron chloride does not affect the cell viability in a concentration range from 0 to 2000 µm. hiPSCs overexpressing FHC (hiPSC- FHCOE) and hiPSC-CMs overexpressing FHC (hiPSC-CM-FHCOE) significantly enhanced cellular uptake of iron chloride but with no changes in electrophysiological properties compared to hiPSC-CM-Control. Furthermore, hiPSC-CM-FHCOE presented robust contrast and lower T2* values, signifying their potential as highly effective candidates for cardiac MRI. Next, hiPSC-CM-FHCOE is injected into mouse hearts and after 3 days of transplantation, MR images are obtained. hiPSC-CM-FHCOE cells exhibited clear signals in the hearts with lower T2* and rapid signal decay. Collectively, data from this proof-of-concept study demonstrated that endogenous labeling with FHC in hiPSC-CMs can be a potent strategy for enhancing the accuracy of cardiac MRI. This technology represents a significant step forward in tracking the transplanted hiPSC-CMs in the hearts of live animals.

Associations of maternal serum concentration of iron-related indicators with birth outcomes in Chinese: a pilot prospective cohort study.

BACKGROUND: Previous studies of maternal iron and birth outcomes have been limited to single indicators that do not reflect the comprehensive relationship with birth outcomes. We aimed to investigate the relationship between maternal iron metabolism and neonatal anthropometric indicators using comprehensive iron-related indicators. METHODS: A total of 914 Chinese mother-child dyads were enrolled in this prospective study. Subjects' blood samples were collected at ≤ 14 weeks of gestation. Serum concentrations of iron-related indicators were measured by enzyme-linked immunosorbent assay (ELISA). Femur length was measured by B-ultrasound nearest delivery. Neonatal anthropometric indicators were collected from medical records. RESULTS: After adjustment for potential covariates, higher iron (per one standard deviation, SD increase) was detrimentally associated with - 0.22 mm lower femur length, whereas higher transferrin (per one SD increase) was associated with 0.20 mm higher femur length. Compared with normal subjects (10th-90th percentiles), subjects with extremely high (> 90th percentile) iron concentration were detrimentally associated with lower femur length, birth weight, and chest circumference, and a higher risk of low birth weight, LBW (HR: 3.92, 95%CI: 1.28, 12.0). Subjects with high concentration of soluble transferrin receptor, sTFR and transferrin (> 90th percentile) were associated with higher femur length. Subjects with low concentration of iron and ferritin concentrations (< 10th percentile) were associated with a higher risk of LBW (HR: 4.10, 95%CI: 1.17, 14.3) and macrosomia (HR: 2.79, 95%CI: 1.06, 7.35), respectively. CONCLUSIONS: Maternal iron overload in early pregnancy may be detrimentally associated with neonatal anthropometric indicators and adverse birth outcomes.

Factors and outcomes for placental anomalies: An umbrella review of systematic reviews and meta-analyses.

Background: Placental anomalies, including placenta previa (PP), placenta accreta spectrum disorders (PAS), and vase previa (VP), are associated with several adverse foetal-neonatal and maternal complications. However, there is still a lack of robust evidence on the pathogenesis and adverse outcomes of the diseases. Through this umbrella review, we aimed to systematically review existing meta-analyses exploring the factors and outcomes for pregnancy women with placental anomalies. Methods: We searched PubMed, Embase, Web of Science, and the Cochrane Library from inception to February 2023. We used AMSTAR 2 to assess the quality of the reviews and estimated the pooled risk and 95% confidence intervals (CIs) for each meta-analysis. Results: We included 34 meta-analyses and extracted 55 factors (27 for PP, 22 for PAS, and 6 for VP) and 16 outcomes (12 for PP, and 4 for VP) to assess their credibility. Seven factors (maternal cocaine use (for PP), uterine leiomyoma (for PP), prior abortion (spontaneous) (PP), threatened miscarriage (PP), maternal obesity (PP), maternal smoking (PAS), male foetus (PAS)) had high epidemiological evidence. Twelve factors and six outcomes had moderate epidemiological evidence. Twenty-two factors and eight outcomes showed significant association, but with weak credibility. Conclusions: We found varying levels of evidence for placental anomalies of different factors and outcomes in this umbrella review. Registration: PROSPERO: CRD42022300160.

Peptide-Guided Nanoparticle Drug Delivery for Cardiomyocytes.

BACKGROUND: Nanoparticles (NPs) have been extensively utilized as a drug delivery system to control the release of therapeutic agents to treat cardiac injuries. However, despite the advantages of utilizing NP-based drug delivery for treating heart diseases, the current delivery system lacks specificity in targeting the cardiac tissue, thus limiting its application. METHODS: We created three linear peptides, each consisting of 16-24 amino acids. These peptides were conjugated on the surface of NPs, resulting in the formation of cardiac targeting peptide (CTP)-NPs (designated as CTP-NP1, CTP-NP2, and CTP-NP3). To assess their effectiveness, we compared the binding efficiency of these three CTP-NPs to human and mouse cardiomyocytes. Additionally, we determined their distribution 24 h after injecting the CTP-NPs intravenously into adult C57BL/6J mice. RESULTS: When compared to control NPs without CTP (Con-NPs), all three CTP-NPs exhibited significantly increased binding affinity to both human and mouse cardiomyocytes in vitro and enhanced retention in mouse hearts in vivo. A thorough assessment of the heart sections demonstrated that the binding specificity of CTP-NP3 to cardiomyocytes in vivo was significantly greater than that of Con-NPs. None of the three CTP-NPs were proven to cause cardiomyocyte apoptosis. CONCLUSIONS: Biocompatible and safe CTP-NP3 can target the heart via binding to cardiomyocytes. This approach of targeting specific molecules-coated NPs may help in delivering therapeutic compounds to cardiomyocytes for the treatment of heart diseases with high efficacy and low toxicity to other tissues.

Toward Smart, Flexible, and Omnidirectional Self-Powered Photodetection by an All-Solution-Processed In2O3/Pbl2 Heterojunction.

Amorphous In2O3 film is emerging as a promising oxide semiconductor for next-generation electronics and optoelectronics owing to high mobility and wide band gap. However, the persistent photocurrent phenomenon and high carrier concentration in amorphous In2O3 film are challenging the photodetection performances, resulting in a long response time and low Ilight/Idark ratio. In this work, the In2O3/PbI2 heterojunction is constructed by an all-solution synthesis process to inhibit the persistent photocurrent phenomenon and large dark current. Benefiting from the built-in electric field at the heterojunction interface, the In2O3/PbI2 heterojunction photodetector exhibits excellent self-powered photodetection performances with an ultralow dark current of 10-12 A, a high Ilight/Idark ratio of 104, and fast response times of 0.6/0.6 ms. Furthermore, the entire solution synthesis process and amorphous characteristics enable the fabrication of an In2O3/PbI2 heterojunction photodetector on arbitrary substrates to realize specific functions. When configured onto the polyimide substrate, the In2O3/PbI2 heterojunction photodetector shows excellent mechanical flexibility, bending endurance, and photoresponse stability. When implanted onto the transparent substrate, the In2O3/PbI2 heterojunction photodetector exhibits an outstanding omnidirectional self-powdered photodetection performance and imaging capability. All results pave the way for an all-solution-processed amorphous In2O3 film in advanced high-performance photodetectors.

Tunable Contacts of Bi2 O2 Se Nanosheets MSM Photodetectors by Metal-Assisted Transfer Approach for Self-Powered Near-Infrared Photodetection.

Owing to the Fermi pinning effect arose in the metal electrodes deposition process, metal-semiconductor contact is always independent on the work function, which challenges the next-generation optoelectronic devices. In this work, a metal-assisted transfer approach is developed to transfer Bi2 O2 Se nanosheets onto the pre-deposited metal electrodes, benefiting to the tunable metal-semiconductor contact. The success in Bi2 O2 Se nanosheets transfer is contributed to the stronger van der Waals adhesion of metal electrodes than that of growth substrates. With the pre-deposited asymmetric electrodes, the self-powered near-infrared photodetectors are realized, demonstrating low dark current of 0.04 pA, high Ilight /Idark ratio of 380, fast rise and decay times of 4 and 6 ms, respectively, under the illumination of 1310 nm laser. By pre-depositing the metal electrodes on polyimide and glass, high-performance flexible and omnidirectional self-powered near-infrared photodetectors are achieved successfully. This study opens up new opportunities for low-dimensional semiconductors in next-generation high-performance optoelectronic devices.

Associations of early pregnancy serum uric acid levels with risk of gestational diabetes and birth outcomes: a retrospective cohort study.

BACKGROUND: Previous evidence suggests that higher blood uric acid (UA) levels are associated with adverse cardiovascular outcomes during pregnancy and subsequent birth outcomes. However, it has been relatively unclear whether these associations persist in normotensive pregnant women. METHODS: The study was based on a retrospective analysis of 18,250 mother-infant pairs in a large obstetric center in China. Serum UA concentrations in early pregnancy (median: 17.6, IQR: 16.3, 18.6 gestational weeks) were assessed. Hyperuricemia was defined as ≥ one standard deviation (SD) of the reference value for the corresponding gestational age. Outcomes of gestational diabetes mellitus (GDM), preterm birth (PB), low birth weight (LBW), macrosomia, small for gestational age (SGA) and large for gestational age (LGA) were extracted from the medical records. RESULTS: The mean maternal UA level was 0.22 ± 0.05 mmol/L, and 2,896 (15.9%) subjects had hyperuricemia. After adjustment for several covariates, UA was associated with several adverse outcomes. The ORs (95%CI) per one SD increase in serum UA concentration were 1.250 (1.136, 1.277) for GDM, 1.137 (1.060, 1.221) for PB, 1.134 (1.051, 1.223) for LBW, and 1.077 (1.020, 1.137) for SGA, respectively. Similar adverse associations were found between hyperuricemia and GDM, PB (ORs: 1.394 and 1.385, P < 0.001), but not for LBW, macrosomia, SGA, and LGA. Adverse associations tended to be more pronounced in subjects with higher BMI for outcomes including PB, LBW, and SGA (P interaction = 0.001-0.028). CONCLUSION: Higher UA levels in early pregnancy were associated with higher risk of GDM, PB, LBW, and SGA in normotensive Chinese women.

Role of breastfeeding on maternal and childhood cancers: An umbrella review of meta-analyses.

Background: Multiple studies and meta-analyses have claimed that breastfeeding is inversely correlated with maternal and childhood cancers. These results could either be causal or confounded by shared risk factors. By conducting an umbrella review, we aimed to consolidate the relationship between breastfeeding and maternal and childhood cancers. Methods: We searched PubMed, Embase, Web of Science, Elsevier ScienceDirect, and Cochrane Library databases from inception to December 2022. Two reviewers independently extracted the data and assessed the quality of the studies using standardised forms. We considered two types of breastfeeding comparisons ("ever" vs "never" breastfeeding; and "longest" vs "shortest" duration). We estimated the pooled risk and 95% confidence interval (CI) for each meta-analysis. Results: We included seventeen meta-analyses with 55 comparisons. There was an inverse correlation between breastfeeding and childhood leukaemia (pooled risk = 0.90, 95% CI = 0.81-0.99), neuroblastoma (pooled risk = 0.81, 95% CI = 0.71-0.93), maternal ovarian cancer (pooled risk = 0.76, CI = 0.71-0.81), breast cancer (pooled risk = 0.85, 95% CI = 0.82-0.88), and oesophageal cancer (pooled risk = 0.67, 95% CI = 0.54-0.81) for "ever" vs "never" breastfeeding; and with childhood leukaemia (pooled risk = 0.94, 95% CI = 0.89-0.98), and maternal ovarian cancer (pooled risk = 0.84, 95% CI = 0.78-0.90) and breast cancer (pooled risk = 0.92, 95% CI = 0.89-0.96) for "longest" vs "shortest" breastfeeding duration. Conclusions: We found evidence that breastfeeding may reduce the risk of maternal breast cancer, ovarian cancers, and childhood leukaemia, suggesting positive implications for influencing women's decision in breastfeeding. Registration: PROSPERO (CRD42021255608).

Associations of serum concentrations of metal nutrients with postpartum anemia among pregnant Chinese women: A large retrospective cohort study.

Background and Aims: The association between serum concentrations of metal nutrients in pregnancy and postpartum anemia has not been widely studied. This study aimed to determine this association in a large retrospective cohort study. Methods: We included 14,829 Chinese women with singleton pregnancies. Serum concentrations of metals before 28 weeks of gestation, the occurrence of postpartum anemia and other potential covariates were obtained from their laboratory or medical records. Cox regression and restricted cubic spline regression models were used to explore the relationship between serum concentrations of metal nutrients in pregnancy and postpartum anemia. Results: After adjustment for covariates, higher concentrations of iron (Fe), magnesium (Mg) and zinc (Zn) and lower concentrations of copper (Cu) were associated with a lower risk of postpartum anemia. Compared with those whose serum concentrations of metal nutrients were in the bottom quintile (Q1), the hazard ratios (HRs) of those whose serum concentrations of metal nutrients were in the top quintile (Q5) were 0.57 (95% confidence interval (CI): 0.50, 0.64) for Fe, 0.67 (95% CI: 0.60, 0.76) for Mg, 0.82 (95% CI: 0.73, 0.93) for Zn, and 1.44 (95% CI: 1.28, 1.63) for Cu. L-shaped curve relationships were found between increasing concentrations of Fe, Mg, and Zn and incidence of postpartum anemia. Higher serum concentrations of Cu were associated with an increased risk of postpartum anemia. Serum concentrations of Fe in Q5 were associated with a lower risk of postpartum anemia when they coincided with serum concentrations of Mg in Q5, Zn in Q5, or Cu in Q1. Conclusion: Higher serum concentrations of Fe, Mg, and Zn, and lower serum concentrations of Cu were associated with a lower risk of postpartum anemia among pregnant women.

Prediction of vaginal birth after cesarean in China.

OBJECTIVE: This study aimed to develop and validate a prediction model of vaginal birth after cesarean delivery (VBAC) in China. METHODS: A nomogram for effective prediction of VBAC of singleton, cephalic and one previous low-transverse cesarean section deliveries was created by comparing the combinations of ultrasonographic and non-ultrasonographic factors from five hospitals between 2018 and 2019. RESULTS: A total of 1066 women were included. Of the women who underwent trial of labor after cesarean (TOLAC), 854 (80.1%) had a VBAC. Ultrasound factors included reached a higher area under the curve (AUC) combined with non-ultrasonographic factors. Of the three ultrasonographic factors analyzed, the best predictive factor for successful TOLAC was fetal abdominal circumference. A nomogram was generated with eight validated factors, including maternal age, gestational week, height, previous vaginal delivery, Bishop score, dilatation of the cervix at the time of admission, body mass index at delivery, and fetal abdominal circumference by ultrasound. The trained and validated AUC were 0.719 (95% confident interval 0.674-0.764) and 0.774 (95% confident interval 0.712-0.837), respectively. CONCLUSION: Our VBAC nomogram based on obstetric factors and fetal abdominal circumference obtained by ultrasound could be used to counsel women who are considering TOLAC.

Relationship between family cohesion/adaptability and postpartum depressive symptoms: A single-center retrospective study.

BACKGROUND: Depression is the most common mental illness in postpartum mothers, and the etiology of postpartum depression remains poorly understood. Over the past several decades, studies have reported that postpartum depression is caused by multiple factors, such as genetic, psychological, pregnancy, and environmental factors, with the family environment being an important environmental factor. The theory of family cohesion and adaptability put forward by Olson is a classic model that describes the level of family function. However, to date, this model has not been examined regarding its applicability to patients with postpartum depression. AIM: To investigate the relationship between family cohesion and adaptability and the risk of postpartum depressive symptoms. METHODS: We retrospectively analyzed 1446 patients admitted to the postpartum healthcare clinic of the Affiliated Foshan Maternity and Child Healthcare Hospital from April 2021 to December 2021. Patients were grouped according to whether postpartum depression symptoms were reported (symptoms, n = 454; no symptoms, n = 992). All patients completed the Edinburgh Postpartum Depression Scale and the Chinese version of the Family Cohesion and Adapt-ability Assessment Scale II. Baseline and clinical data were compared between groups. Univariate regression analysis was used to investigate the association between different types of family cohesion and postpartum depressive symptoms and the association between different family adaptability types and postpartum depressive symptoms. RESULTS: After adjusting for age, education, occupation, gravidity, parity, and mode of delivery, disengaged [adjusted odds ratio (AOR) = 3.36, 95%CI: 1.91-5.91], and separated (AOR = 1.97, 95%CI: 1.34-2.90) family cohesion types showed a higher risk of postpartum depression than the connection type, whereas the enmeshed type (AOR = 0.38, 95%CI: 0.28-0.51) protected against postpartum depressive symptoms. Rigid (AOR = 4.41, 95%CI: 3.02-6.43) and structured families (AOR = 1.88, 95%CI: 1.34-2.63) had a higher risk of postpartum depressive symptoms than flexible families, whereas chaotic families (AOR = 0.35, 95%CI: 0.24-0.51) protected against postpartum depressive symptoms. CONCLUSION: Family cohesion and adaptability are influencing factors for postpartum depressive symptoms, with higher family cohesion and adaptability being associated with a lower risk of postpartum depressive symptoms.

Optimal gestational weight gain in women with twin pregnancies and gestational diabetes mellitus: a population-based study in the United States.

BACKGROUND: There is limited evidence regarding optimal gestational weight gain in women with twin pregnancies and gestational diabetes mellitus. OBJECTIVE: This study aimed to examine the association between gestational weight gain and perinatal outcomes among women with gestational diabetes mellitus and twin pregnancies and to explore the gestational weight gain targets by prepregnancy body mass index category. STUDY DESIGN: A national population-based cohort study of twin pregnancies with gestational diabetes mellitus was conducted between 2014 and 2020. Women with gestational diabetes mellitus aged between 18 and 45 years with live-born twins without congenital malformations between 24 and 42 weeks of gestation were included in the analysis. Two approaches were used to determine the optimal gestational weight gain targets by body mass index category: an interquartile range method to calculate targets in low-risk gestational diabetes mellitus pregnancies and a logistic model method to identify the odds ratio targets at which a composite adverse outcome decreased. RESULTS: Of 29,308 women with gestational diabetes mellitus and twin pregnancies, 8239 (28.1%) were normal-weight, 7626 (26.0%) were overweight, and 13,443 (45.9%) were obese. The continuous standardized gestational weight gain by 36 weeks was associated with preterm birth <36 weeks, large-for-gestational-age infants, small-for-gestational-age infants, and gestational hypertensive disorders. The interquartile range targets were 13.6 to 20.9 kg, 10.9 to 20.4 kg, and 7.7 to 17.7 kg for normal-weight, overweight, and obese women, respectively. The odds ratio targets were 14.1 to 20.0 kg, 12.1 to 16.0 kg, and 6.1 to 12.0 kg for normal-weight, overweight, and obese women, respectively. Gestational weight gain outside these targets was associated with preterm birth <36 weeks, large-for-gestational-age and small-for-gestational-age infants, and gestational hypertensive disorders, and exhibited significant population attributable fractions for preterm birth <36 weeks, large-for-gestational-age infants, and gestational hypertensive disorders across body mass index categories. CONCLUSION: Compared with the Institute of Medicine guidelines, more stringent gestational weight gain targets would be beneficial for improved perinatal outcomes in women with gestational diabetes mellitus and twin pregnancies.

Association between gut microbiota and preeclampsia-eclampsia: a two-sample Mendelian randomization study.

BACKGROUND: Several recent observational studies have reported that gut microbiota composition is associated with preeclampsia. However, the causal effect of gut microbiota on preeclampsia-eclampsia is unknown. METHODS: A two-sample Mendelian randomization study was performed using the summary statistics of gut microbiota from the largest available genome-wide association study meta-analysis (n=13,266) conducted by the MiBioGen consortium. The summary statistics of preeclampsia-eclampsia were obtained from the FinnGen consortium R7 release data (5731 cases and 160,670 controls). Inverse variance weighted, maximum likelihood, MR-Egger, weighted median, weighted model, MR-PRESSO, and cML-MA were used to examine the causal association between gut microbiota and preeclampsia-eclampsia. Reverse Mendelian randomization analysis was performed on the bacteria that were found to be causally associated with preeclampsia-eclampsia in forward Mendelian randomization analysis. Cochran's Q statistics were used to quantify the heterogeneity of instrumental variables. RESULTS: Inverse variance weighted estimates suggested that Bifidobacterium had a protective effect on preeclampsia-eclampsia (odds ratio = 0.76, 95% confidence interval: 0.64-0.89, P = 8.03 × 10-4). In addition, Collinsella (odds ratio = 0.77, 95% confidence interval: 0.60-0.98, P = 0.03), Enterorhabdus (odds ratio = 0.76, 95% confidence interval: 0.62-0.93, P = 8.76 × 10-3), Eubacterium (ventriosum group) (odds ratio = 0.76, 95% confidence interval: 0.63-0.91, P = 2.43 × 10-3), Lachnospiraceae (NK4A136 group) (odds ratio = 0.77, 95% confidence interval: 0.65-0.92, P = 3.77 × 10-3), and Tyzzerella 3 (odds ratio = 0.85, 95% confidence interval: 0.74-0.97, P = 0.01) presented a suggestive association with preeclampsia-eclampsia. According to the results of reverse MR analysis, no significant causal effect of preeclampsia-eclampsia was found on gut microbiota. No significant heterogeneity of instrumental variables or horizontal pleiotropy was found. CONCLUSIONS: This two-sample Mendelian randomization study found that Bifidobacterium was causally associated with preeclampsia-eclampsia. Further randomized controlled trials are needed to clarify the protective effect of probiotics on preeclampsia-eclampsia and their specific protective mechanisms.

Perinatal outcomes among twin pregnancies with gestational diabetes mellitus: A nine-year retrospective cohort study.

Objective: To compare the outcomes between gestational diabetes mellitus (GDM) vs. non-GDM twin gestations. Methods: A retrospective cohort study of 2,151 twin pregnancies was performed in a tertiary hospital in Foshan, China, 2012-2020. Pregnancy and neonatal outcomes were compared between women with vs. without GDM using 1:1 propensity score matching (PSM) and multivariable logistic models. For neonatal outcomes, generalized estimating equation (GEE) approach was used to address the intertwin correlation. Results: Of the 2,151 participants, 472 women (21.9%) were diagnosed with GDM. Women with GDM were older and more likely to be overweight or obese, and more likely have chronic hypertension, assisted pregnancies and dichorionic twins. In the PSM cohort of 942 pregnancies, there was no statistical difference when comparing GDM twin pregnancies and non-GDM in any of the perinatal outcomes, especially in terms of preterm birth (PTB) <37 weeks (P = 0.715), large for gestational age (LGA) (P = 0.521) and neonatal respiratory distress (NRDS) (P = 0.206). In the entire cohort, no significant adjusted ORs for these outcomes were obtained from logistic regression models adjusted for confounders (aOR for PTB < 37 weeks: 1.25, 95% CI: 0.98-1.58; aOR for LGA: 1.26, 95% CI: 0.88-1.82; and aOR for NRDS, 1.05, 95% CI: 0.68-1.64). Conclusion: Twin pregnancies with GDM and adequate prenatal care have comparable perinatal outcomes to those without.

First Report of Fusarium falciforme Causing Leaf Blight in Acacia mangium in China.

Acacia mangium Willd. is an important economic tree species with diverse uses and high ecological value, used in agriculture, restoration of degraded lands, for ornamental purposes, and commercial forestry (Leroy et al. 2009). This tree is widely cultivated in tropical and subtropical regions of China, such as Hainan, Guangdong, and Guangxi Provinces. In July 2021, a leaf blight of A. mangium saplings was observed with widespread distribution in the cultivation base of Hainan University (20° 3' 33″ N, 110°18' 56″ E) in Hainan Province, China. The initial symptoms were brown-to-black, irregular-shaped lesions on the leaf margin or tip. The entire leaf wilted and turned brown, leading to death and defoliation in the later periods of the disease (Fig. 1A-C). Of the 50 trees surveyed, the incidence rate was 68%. Small pieces of diseased tissue were collected from six different infected trees. The tissue surface was disinfested with 75% ethanol for 30 s, and 1% mercury chloride for 1 min, then rinsed three times with sterile distilled water. Infected tissues were placed onto potato dextrose agar (PDA) containing 0.01% streptomycin and incubated at 25°C for 7 days. Seventeen isolates were obtained by single-spore isolation on fresh PDA plates, and 15 isolates were identified morphologically as Fusarium spp. (Leslie et al. 2006). The colony surface was white, and the reverse side yellowish (Fig. 1D-E). Microconidia were oval or kidney-shaped, 6.2 to 9.6 × 2.5 to 6.3 µm (n=60). Macroconidia were sickle-shaped, with three to five septa, 19.5 to 41.2 × 3.7 to 6.8 µm (n=60) (Fig. 1F). For molecular identification, genomic DNA of three isolates (HNKFS01, HNKFS02, and HNKFS03) was extracted using E.Z.N.A.® HP Plant DNA kit (Omega Bio-Tek) and the internal transcribed spacer of rDNA (ITS), translation elongation factor 1-α (EF1-α), RNA polymerase II beta subunit (RPB2), and ß-tubulin (TUB) regions were amplified and sequenced using primers ITS1F/ITS4, EF-1/EF-2, RPB2-5F2/11aR, and T1/T2, respectively (O'Donnell et al. 2010; O'Donnell and Cigelnik 1997; White et al. 1990). Sequences were deposited in GenBank for ITS (OM289152 to OM289154), EF1-α (OM289155 to OM289157), RPB2 (ON193365 to ON193367), and TUB (ON193314 to ON193316). Using BLASTn, ITS sequences matched 98.88% (532/538 bp) to F. falciforme (MT114705), EF1-α sequences matched 99.58% (703/706 bp; MK752502), RPB2 sequences matched 98.31% (988/1005 bp; MW691193), and TUB gene sequences matched 99.10% (332/335 bp; OK087483). Polyphasic identification with ITS, EF1-α, RPB2, and TUB sequences revealed a 98.51% match with F. falciforme (NRRL 32729) sequences in Fusarium-ID databases. Pathogenicity of 15 isolates was determined by using healthy one-year-old A. mangium seedlings. Three leaves from each seedling were selected to test. Mycelial plugs of each isolate were inoculated on one leaf (three plugs per leaf). An agar plug without the fungus was placed on a leaf as a control. The pathogenicity tests were repeated twice. After 7 days of incubation in a greenhouse, all leaves inoculated with the pathogen showed black lesions with white flocculent hyphae (Fig. 1H), while control leaves were asymptomatic (Fig. 1G). Typical colonies of F. falciforme were isolated from all inoculated leaves, and identified by morphology and ITS, EF1-α, RPB2, and TUB sequence analysis, fulfilling Koch´s postulates. To our knowledge, this is the first report of F. falciforme causing leaf blight in A. mangium in China and the world. This disease can lead to death of A. mangium, which seriously restricts commercialization, requiring that management strategies be adopted.

Association between serum total bilirubin and Alzheimer's disease: A bidirectional Mendelian randomization study.

Oxidative stress plays an important role in the pathogenesis of Alzheimer's disease (AD). As a potent antioxidant, serum bilirubin is decreased in AD and may be related to its pathogenesis, but the causal association between serum bilirubin and AD has not been reported. This was investigated in the present study by bidirectional two-sample Mendelian randomization (MR) analysis. Genetic instruments at the genome-wide significance level (P < 5 × 10-8) were selected from the United Kingdom Biobank (n = 342,829). Summary-level AD data were obtained from a large-scale genome-wide association study (n = 63,926). Causal estimates were evaluated using the inverse variance weighted (IVW) approach and other five complementary methods. MR-Egger, IVW and MR pleiotropy residual sum and outlier (MR-PRESSO) methods were used for sensitivity analyses. The results showed that there was no significant association between serum total bilirubin and AD (odds ratio=1.003, 95% confidence interval: 0.967-1.041, P = 0.865). Inverse MR revealed that serum total bilirubin was increased in AD (beta = 0.009, SE = 0.003, P = 0.010). These results indicate that serum total bilirubin is not causally associated with AD and cannot be used for screening or diagnosis, but can potentially serve as a biomarker of disease severity, and it needs further clinical studies.

Association of Optimal Gestational Weight Gain Ranges With Perinatal Outcomes Across Body Mass Index Categories in Twin Pregnancies.

Importance: The existing gestational weight gain (GWG) recommendations for twin pregnancies are lacking for underweight individuals and are not stratified by obesity class. Objective: To identify optimal GWG ranges associated with reduced adverse perinatal outcomes stratified by prepregnancy body mass index (BMI) categories in twin pregnancies. Design, Setting and Participants: This population-based cohort study of twin pregnancies using data from the National Center for Health Statistics was conducted between January 1, 2014, and December 31, 2018. Statistical analysis was performed from October 24, 2021, to May 7, 2022. The study population comprised 262 604 individuals between 18 and 45 years of age with live-born twins without congenital malformation between 24 and 42 weeks of gestation. Two approaches were used to determine the optimal GWG ranges: a statistics-based approach calculating IQRs of GWG in a low-risk population, and an outcome-based approach identifying GWG thresholds below or above which an adverse perinatal outcome increased. Exposure: Gestational weight gain. Main Outcomes and Measures: Preterm birth less than 36 weeks, gestational hypertensive disorders, small for gestational age status, large for gestational age status, and a composite outcome defined as any occurrence of the individual outcomes. Results: The main sample comprised 200 810 individuals with twin pregnancies (mean [SD] maternal age, 30.4 [5.5] years; 1624 [0.8%] American Indian or Alaska Native, 13 031 [6.5%] Asian or Pacific Islander, 36 423 [18.1%] Black, and 149 732 [74.6%] White; and 137 409 [68.4%] multiparous). In the low-risk subgroup (n = 61 794), the IQRs of the total GWG after 36 weeks of gestation as assessed using a statistics-based approach and based on BMI group were 15.9 to 22.7 kg for underweight, 15.4 to 22.7 kg for normal weight, 12.7 to 22.2 kg for overweight, 10.0 to 20.0 kg for class 1 obesity, 7.7 to 18.1 kg for class 2 obesity, and 5.9 to 16.3 kg for class 3 obesity. The absolute risk of the composite outcome showed U-shaped associations with GWG across BMI categories. The optimal GWG ranges by 36 weeks identified using an outcome-based approach and BMI group were 17.5 to 24.9 kg for underweight, 15.0 to 24.9 kg for normal weight, 15.0 to 24.9 kg for overweight, 10.0 to 19.9 kg for class 1 obesity, 7.5 to 17.4 kg for class 2 obesity, and 5.0 to 9.9 kg for class 3 obesity. The multivariable logistic models assessed using the validation sample (n = 49 275) showed that GWG defined outside those optimal ranges was associated with preterm birth at less than 36 weeks, gestational hypertensive disorders, and small or large for gestational age. Conclusions and Relevance: This population-based cohort study found that optimal GWG ranges were similar for individuals with underweight and normal weight but decreased with increasing severity of obesity. The current US Institute of Medicine GWG recommendations may be too high for individuals with moderate or severe obesity.

Identification of metabolic pathways underlying FGF1 and CHIR99021-mediated cardioprotection.

Acute myocardial infarction is a leading cause of death worldwide. We have previously identified two cardioprotective molecules - FGF1 and CHIR99021- that confer cardioprotection in mouse and pig models of acute myocardial infarction. Here, we aimed to determine if improved myocardial metabolism contributes to this cardioprotection. Nanofibers loaded with FGF1 and CHIR99021 were intramyocardially injected to ischemic myocardium of adult mice immediately following surgically induced myocardial infarction. Animals were euthanized 3 and 7 days later. Our data suggested that FGF1/CHIR99021 nanofibers enhanced the heart's capacity to utilize glycolysis as an energy source and reduced the accumulation of branched-chain amino acids in ischemic myocardium. The impact of FGF1/CHIR99021 on metabolism was more obvious in the first three days post myocardial infarction. Taken together, these findings suggest that FGF1/CHIR99021 protects the heart against ischemic injury via improving myocardial metabolism which may be exploited for treatment of acute myocardial infarction in humans.

Assessment of different thresholds of birthweight discordance for early neonatal outcomes: retrospective analysis of 2348 twin pregnancies.

BACKGROUND: The optimal threshold of birthweight discordance (BWD) remains controversial. This study aimed to evaluate the associations between BWD at different thresholds and early neonatal outcomes and to assess their predictive accuracy. METHODS: This was a retrospective cohort study using a birthweight data with the chorionicity information of 2348 liveborn twin pairs at a gestational age of ≥26 weeks, from 2012 to 2018. The percentage of BWD was calculated by dividing the actual birthweight difference by the weight of the larger twin and multiplying by 100. Outcomes of interest included neonatal intensive care unit (NICU) admission, neonatal respiratory distress syndrome (NRDS), ventilator support and a composite outcome combining major morbidities and neonatal death. Logistic regression models were performed to estimate the association between neonatal outcomes and BWD with different thresholds (≥15.0%, ≥20.0%, ≥25% and ≥ 30%). Generalized estimated equation (GEE) models were used to address intertwin correlation. Restrictive cubic spline (RCS) models were established to draw the dose-response relationship between BWD and the odds ratios of outcomes. Clustered receiver operating characteristic (ROC) curve analyses were performed to assess the predictive accuracy. RESULTS: Of 2348 twin pairs, including 1946 dichorionic twin pairs and 402 monochorionic twin pairs, BWD was significantly associated with NICU admission, regardless of the thresholds used. The incidence of NRDS, ventilator support and the composite outcome were significantly higher when a threshold of ≥20% or greater was chosen. The dose-response relationship showed nonlinear growth in the risk of adverse neonatal outcomes with increasing BWD. ROC analyses showed a low significant AUROC of 0.569 (95% CI: 0.526-0.612) for predicting NICU admission but no significant AUROCs for predicting other outcomes. A BWD of ≥30% provided a moderate increase in the likelihood of NICU admission [positive likelihood ratio (LR+) = 5.77]. CONCLUSION: Although BWD is independently associated with adverse neonatal outcomes, it is not a single predictor for neonatal outcomes given the weak discriminative ability to predict neonatal outcomes. A cutoff of 30% is more practical for risk stratification among twin gestations.

Associations between thyroid function and gestational diabetes mellitus in Chinese pregnant women: a retrospective cohort study.

BACKGROUND: Thyroid function is known to be closely linked with type 2 diabetes, but data on the association between thyroid function and gestational diabetes mellitus (GDM) are inconsistent. METHODS: A total of 2849 pregnant women were included in this retrospective study. Serum concentrations of thyroid indicators (free tetraiodothyronine, FT4; thyroid-stimulating hormone, TSH; and thyroid peroxidase antibody, TPO Ab) were obtained from a clinical laboratory. The presence of GDM were drawn from medical records. The clinical subtypes of thyroid function (euthyroidism, subclinical hypothyroidism, hyperthyroidism, and isolated hypothyroxinemia) were categorized according to the thresholds of the 2.5th/97.5th and 10th/90th percentiles of TSH and FT4 concentrations. A concentration of > 34 IU/L was defined as indicating TPO Ab-positivity. RESULTS: Two hundred and thirty-five (8.25%) of the 2849 women were TPO Ab-positive. Higher serum concentrations of FT4 (top vs. bottom tertiles) was found to be negatively associated with the risk of GDM. The corresponding odds (OR) values (top tertile vs. bottom tertile) were 0.71 [95% confidence interval (CI): 0.54, 0.93]. No significant associations were observed between the extremely 2.5th/97.5th or 10th/90th percentiles of FT4 concentration, TSH concentration, thyroid function subtypes (vs. euthyroidism), TPO Ab-positivity (vs. -negativity), and the GDM risk. The corresponding results remained similar when TPO Ab-positive subjects were excluded. CONCLUSIONS: A negative association with the risk of GDM was observed for the highest FT4 concentrations tertile. No significant associations were found between the TSH concentration, thyroid function subtypes, TPO Ab positivity, and the GDM risk.