Prepregnancy body mass index and other risk factors for early-onset and late-onset haemolysis, elevated liver enzymes and low platelets (HELLP) syndrome: a population-based retrospective cohort study in British Columbia, Canada.

BACKGROUND: Obesity increases risk of pre-eclampsia, but the association with haemolysis, elevated liver enzymes and low platelets (HELLP) syndrome is understudied. OBJECTIVE: To examine the association between prepregnancy body mass index (BMI) and HELLP syndrome, including early-onset versus late-onset disease. STUDY DESIGN: A retrospective cohort study using population-based data. SETTING: British Columbia, Canada, 2008/2009-2019/2020. POPULATION: All pregnancies resulting in live births or stillbirths at ≥20 weeks' gestation. METHODS: BMI categories (kg/m2) included underweight (<18.5), normal (18.5-24.9), overweight (25.0-29.9) and obese (≥30.0). Rates of early-onset and late-onset HELLP syndrome (<34 vs ≥34 weeks, respectively) were calculated per 1000 ongoing pregnancies at 20 and 34 weeks' gestation, respectively. Cox regression was used to assess the associations between risk factors (eg, BMI, maternal age and parity) and early-onset versus late-onset HELLP syndrome. MAIN OUTCOME MEASURES: Early-onset and late-onset HELLP syndrome. RESULTS: The rates of HELLP syndrome per 1000 women were 2.8 overall (1116 cases among 391 941 women), and 1.9, 2.5, 3.2 and 4.0 in underweight, normal BMI, overweight and obese categories, respectively. Overall, gestational age-specific rates of HELLP syndrome increased with prepregnancy BMI. Obesity (compared with normal BMI) was more strongly associated with early-onset HELLP syndrome (adjusted HR (AHR) 2.24 (95% CI 1.65 to 3.04) than with late-onset HELLP syndrome (AHR 1.48, 95% CI 1.23 to 1.80) (p value for interaction 0.025). Chronic hypertension, multiple gestation, bleeding (<20 weeks' gestation and antepartum) also showed differing AHRs between early-onset versus late-onset HELLP syndrome. CONCLUSIONS: Prepregnancy BMI is positively associated with HELLP syndrome and the association is stronger with early-onset HELLP syndrome. Associations with early-onset and late-onset HELLP syndrome differed for some risk factors, suggesting possible differences in aetiological mechanisms.

Complex effects of testosterone level on ectoparasite load in a ground squirrel: an experimental test for the immunocompetence handicap hypothesis.

BACKGROUND: The immunocompetence handicap hypothesis suggests that males with a higher testosterone level should be better at developing male secondary traits, but at a cost of suppressed immune performance. As a result, we should expect that males with an increased testosterone level also possess a higher parasite load. However, previous empirical studies aimed to test this prediction have generated mixed results. Meanwhile, the effect of testosterone level on parasite load in female hosts remains poorly known. METHODS: In this study, we tested this prediction by manipulating testosterone level in Daurian ground squirrels (Spermophilus dauricus), a medium-sized rodent widely distributed in northeast Asia. S. dauricus is an important host of ticks and fleas and often viewed as a considerable reservoir of plague. Live-trapped S. dauricus were injected with either tea oil (control group) or testosterone (treatment group) and then released. A total of 10 days later, the rodents were recaptured and checked for ectoparasites. Fecal samples were also collected to measure testosterone level of each individual. RESULTS: We found that testosterone manipulation and sex of hosts interacted to affect tick load. At the end of the experiment, male squirrels subjected to testosterone implantation had an averagely higher tick load than males from the control group. However, this pattern was not found in females. Moreover, testosterone manipulation did not significantly affect flea load in S. dauricus. CONCLUSIONS: Our results only lent limited support for the immunocompetence handicap hypothesis, suggesting that the role of testosterone on regulating parasite load is relatively complex, and may largely depend on parasite type and gender of hosts.

Effect of beta-cypermethrin on the reproductive capacity of female mice in advanced age.

The aim of the present study was to investigate whether exposure to pesticides beta-cypermethrin (ß-CYP) harms the reproductive capacity of advanced-age female mice. The results evidenced that peri-implantation ß-CYP exposure significantly reduced the number of fetuses per advanced-age female in the first litter, and the number and weight of implantation sites. The levels of decidualization markers were significantly reduced in ß-CYP-administered advanced-age mice. Lower expression of Pcna, Cdk6, Foxo1, Ki67, and p62 protein and mRNA was found in the decidua of ß-CYP-treated advanced-age mice. The levels of Bax, cleaved caspase-3, Lc3a/b, Atg, mTOR, and p-mTOR protein, and the ratio of p-mTOR/mTOR protein expression were clearly downregulated by peri-implantation ß-CYP exposure. These results indicated that peri-implantation ß-CYP exposure may elevate the decline in reproductive capacity of early pregnant mice in advanced age.

Obesity, Twin Pregnancy, and the Role of Assisted Reproductive Technology.

Importance: The prevalence of overweight and obesity (body mass index [BMI] ≥25) has increased globally, and high BMI has been linked to higher rates of twin birth. However, evidence from large population-based studies is lacking; the issue needs careful study, as women with obesity are also more likely to use assisted reproductive technology (ART), which frequently results in twin pregnancy. Objective: To examine the association between BMI and twin birth and the role of ART as a potential mediator in this association. Design, Setting, and Participants: This retrospective cohort study included all live births and stillbirths with gestational age of 20 weeks or longer in British Columbia, Canada, from 2008 to 2020, using data from the British Columbia Perinatal Database Registry. Data analysis was conducted from November 2022 to June 2023. Exposures: Prepregnancy BMI, calculated as weight in kilograms divided by height in meters squared, and use of ART. Main Outcomes and Measures: The study assessed whether prepregnancy BMI is associated with the rate of twin vs singleton delivery and whether this association is explained by the differential use of ART in women with obesity. Results: A total of 524 845 deliveries at 20 weeks' or longer gestation occurred in British Columbia during the study period, and 392 046 women had complete data on prepregnancy BMI. The median (IQR) age was 31.4 (27.7-35.0) years, approximately half were nulliparous (243 443 [46.4%]) and less than 10% smoked during pregnancy (36 894 [7.1%]). Overall, 8295 women had a twin delivery (15.8 per 1000 deliveries), and rates per 1000 deliveries by prepregnancy BMI categories were 11.9 (underweight), 15.1 (normal), 16.0 (overweight), 16.0 (obesity class I), 16.7 (obesity class II), and 18.9 (obesity class III). After adjustment for other covariates, women with underweight had relatively 16% fewer twins compared with women with normal BMI (adjusted risk ratio [aRR], 0.84; 95% CI, 0.74-0.95), while women with overweight, class I obesity, class II obesity, and class III obesity had 14% (aRR, 1.14; 95% CI, 1.07-1.21), 16% (aRR, 1.16; 95% CI, 1.06-1.27), 17% (aRR, 1.17; 95% CI, 1.02-1.34), and 41% higher rates (aRR, 1.41; 95% CI, 1.19-1.66), respectively. The proportion of women who conceived by ART increased with increasing BMI, and ART was associated with nearly a 12-fold higher rate of twin delivery (aRR, 11.80; 95% CI 11.10-12.54). ART explained about a quarter of the association between obesity class I and II and twin delivery (eg, obesity class I, 23% mediated; 95% CI, 7%-39% mediated), but none of this association was mediated by ART in women with class III obesity. Conclusions and relevance: In this cohort study of 524 845 births, the rate of twin birth increased with increasing prepregnancy BMI. In women with a BMI between 30 and 40, approximately one-quarter of this association was explained by higher use of ART; however, there was no evidence of such mediation in women with BMI of 40 or greater.

Interfering TRIB3 protects the blood brain barrier through PI3K/Akt pathway to alleviate cerebral ischemia-reperfusion injury in diabetes mellitus mice.

This study aimed to treat diabetic cerebral ischemia-reperfusion injury (CI/RI) by affecting blood brain barrier (BBB) permeability and integrity. The CI/RI model in DM mice and a high glucose (HG) treated oxygen and glucose deprivation/reoxygenation (OGD/R) brain endothelial cell model were established for the study. Evans blue (EB) staining was used to evaluate the permeability of BBB in vivo. TTC staining was used to analyze cerebral infarction. The location and expression of tribbles homolog 3 (TRIB3) in endothelial cells were detected by immunofluorescence. Western blotting was used to detect the protein expressions of TRIB3, tight junction molecules, adhesion molecules, phosphorylated protein kinase B (p-AKT) and AKT. The levels of pro-inflammatory cytokines were detected by qRT-PCR. Trans-epithelial electrical resistance (TEER) and fluorescein isothiocyanate (FITC)-dextran were used to measure vascular permeability in vitro. TRIB3 ubiquitination and acetylation levels were detected. Acetyltransferase bound to TRIB3 were identified by immunoprecipitation. TRIB3 was localized in cerebral endothelial cells and was highly expressed in diabetic CI/R mice. The BBB permeability in diabetic CI/R mice and HG-treated OGD/R cells was increased, while the junction integrity was decreased. Interference with TRIB3 in vitro reduces BBB permeability and increases junction integrity. In vivo interfering with TRIB3 reduced cerebral infarction volume, BBB permeability and inflammation levels, and upregulated p-AKT levels. The phosphatidylinositol 3-kinase (PI3K) inhibitor wortmannin reversed the effects of TRIB3-interfering plasmid. In vitro HG treatment induced TRIB3 acetylation through acetyltransferase p300, which in turn reduced ubiquitination and stabilized TRIB3. Interfering TRIB3 protects BBB by activating PI3K/AKT pathway and alleviates brain injury, which provides a new target for diabetic CI/RI.

Cerebral venous thrombosis caused by spontaneous intracranial hypotension due to spontaneous spinal cerebrospinal fluid leakage in the high cervical region: a case report.

Spontaneous intracranial hypotension (SIH) may lead to cerebral venous thrombosis (CVT). This case report describes the diagnostic and treatment processes used for a patient with CVT caused by SIH due to spontaneous spinal cerebrospinal fluid (CSF) leakage in the high cervical region. Clinical data were collected from a 37-year-old man with an initial symptom of spontaneous posterior cervical pain. The diagnostic and treatment processes of SIH-induced CVT were described. A magnetic resonance imaging (MRI) study showed superior sagittal sinus thrombosis, and a lumbar puncture revealed a low initial CSF pressure of less than 60 mmH2O. The patient underwent anticoagulation and fluid rehydration therapies. No abnormalities were observed in the thoracic MRI scan, but a cervical MRI scan revealed a spontaneous CSF leak. An epidural blood patch with autologous blood was performed, and symptoms completely resolved 3 days after the procedure. This report proposes a diagnostic procedure for detecting rare cases of SIH-induced CVT, thereby preventing future misdiagnoses and delayed treatment. When a patient presenting with CVT in conjunction with intracranial hypotension has no history of trauma or piercing, SIH caused by spontaneous spinal CSF leakage should be considered as a potential cause of secondary low intracranial pressure. For detection of CSF leaks at rare sites, an MRI of the whole spine rather than a localized MRI of the spine needs to be performed to avoid misdiagnosis. An epidural blood patch should be performed as soon as possible as it may shorten the length of hospitalization and improve prognosis.

[Multicenter Prospective Study of Different Induction Regimens of Azacytidine in Treatment of Elderly Patients with Acute Myeloid Leukemia].

OBJECTIVE: To observe the efficacy and safety of different induction regimens of same total dosage of azacitidine (Aza), including standard dose (standard dose group) and low-dose long-term (adjusted dose group), in the treatment of elderly acute myeloid leukemia (AML). METHODS: A total of 103 elderly patients with AML (non-acute promyelocytic leukemia) from January 2020 to June 2021 were enrolled. Aza was administered at the standard dose of 75 mg/(m2·d) for 7 days in the standard dose group (50 cases), while at 100 mg/d for 7-12 days in the adjusted dose group (53 cases). The administration days in adjusted dose group was calculated based on the total standard dose of the patient's single course of treatment. The efficacy and safety between standard dose group and adjusted dose group were compared. Subgroup analysis were performed in the two groups for Aza alone, Aza combined with BCL-2 inhibitor, and Aza combined with low-dose chemotherapy for efficacy and safety. RESULTS: There were no significant differences in overall response rate (ORR), incidence of adverse reaction, and 1-year overall survival (OS) rate between standard dose group and adjusted dose group (P >0.05). The ORR of combination was higher than that of Aza alone (P < 0.05), while there was no significant difference in ORR between Aza combined with BCL-2 inhibitor and Aza combined with low-dose chemotherapy (P >0.05). The combination of BCL-2 inhibitor did not increase the incidence of adverse reactions compared wtih Aza alone. There was a higher risk of myelosuppression and pulmonary infection with a combination of low-dose chemotherapy than with a combination of BCL-2 inhibitor and Aza alone (P <0.05). No significant difference was observed in 1-year OS between Aza alone, Aza combined with BCL-2 inhibitor, and Aza combined with low-dose chemotherapy (P >0.05). CONCLUSIONS: Both two induction regimens can be used in elderly AML patients who cannot tolerate intensive chemotherapy with similar overall effectiveness and safety. Aza combined with low-dose chemotherapy may result in increased ORR and an increased incidence of serious adverse reactions, and may not result in longer survival compared with Aza alone. Aza combined with BCL-2 inhibitor not only has similar effect in complete remission, objective response rate, and OS compared with Aza combined with low-dose chemotherapy, but also has higher safety.

Regulatory considerations for paediatric drug evaluation in China.

The regulatory guidelines for the research and development of paediatric drugs are still evolving in China. The formulation of the guidelines started from learning and borrowing existing experience, and gradually changed to the exploration and improvement of local guidelines, which was not only in line with international standards but also had breakthroughs, innovations and Chinese characteristics. In this paper, the current setting of paediatric drug research and development in China and corresponding technical guidelines have been introduced from regulatory perspectives, and the accessibility of further improvement in regulatory strategies has also been discussed.

Pre-pregnancy body mass index and adverse maternal and perinatal outcomes in twins: A population retrospective cohort study.

OBJECTIVE: To examine the association between pre-pregnancy BMI and severe maternal morbidity (SMM), perinatal death and severe neonatal morbidity in twin pregnancies. METHODS: All twin births at ≥ 20 weeks gestation in British Columbia, Canada, from 2000 to 2017 were included. We estimated rates of SMM, a perinatal composite of death and severe morbidity, and its components per 10,000 pregnancies. Confounder-adjusted rate ratios (aRR) between pre-pregnancy BMI and outcomes were estimated using robust Poisson regression. RESULTS: Overall, 7770 (368 underweight, 1704 overweight, and 1016 obese) women with twin pregnancy were included. The rates of SMM were: 271.1, 320.4, 270.0, and 225.9 in underweight, normal BMI, overweight and obese women, respectively. There was little association between obesity and any of the primary outcomes (e.g., aRR = 1.09, 95% CI = 0.85, 1.38 for composite perinatal outcome). Underweight women had higher rates of the composite perinatal adverse outcome (aRR = 1.79, 95% CI = 1.32-2.43), driven by increased rates of severe respiratory distress syndrome, and neonatal death. CONCLUSIONS: There was no evidence of elevated risk of adverse outcomes among twin pregnancies of women who were overweight or obese. Risk was higher in underweight women, who may require specific care when carrying twins.

Toxicity mechanism of peri-implantation pesticide beta-cypermethrin exposure on endometrial remodeling in early pregnant mice.

Beta-cypermethrin (ß-CYP) is a universally used pyrethroid pesticide with adverse effects on human health. ß-CYP may impair endometrial remodeling in mice; however, the mechanism remains largely unknown. Endometrial remodeling plays a vital role in embryonic development and the maintenance of pregnancy. Therefore, we explored the mechanism by which peri-implantation ß-CYP administration reduces uterine remodeling in pregnant mice. The C57BL/6 J pregnant mice were administered a dose of 20 mg/kg.bw. d ß-CYP via oral gavage once daily from day 1 of gestation (GD1) to GD7. Molecular markers of endometrial remodeling, stromal cell proliferation, cell cycle regulation, and the PI3K/Akt/mTOR signaling pathway were evaluated in the decidual tissue of the uterus on GD7. An in vivo pseudopregnancy mouse model, a pregnant mouse model treated with an mTOR activator and an mTOR inhibitor and an in vitro decidualization model of mouse endometrial stromal cells were used to confirm ß-CYP-induced defective endometrial remodeling and the key molecules expression of PI3K/Akt/mTOR signaling pathway. The results showed that ß-CYP decreased the expression of the endometrial remodeling markers MMP9 and LIF in the uterine decidua. Peri-implantation ß-CYP treatment markedly downregulated the expression of endometrial proliferation markers PCNA and Ki67 and decreased decidua thickness. Correspondingly, peri-implantation ß-CYP exposure upregulated the expression of FOXO1, P57 and p-4E-BP1 in the decidua. Further experiments showed ß-CYP significantly inhibited key molecules in the PI3K/Akt/mTOR pathway: PI3K, p-Akt/Akt, p-mTOR, and p-P70S6K in the uterine decidua. Additional experiments showed that aberrant endometrial remodeling induced by ß-CYP was aggravated by rapamycin (an mTOR inhibitor) and partially reversed by MHY1485 (an mTOR agonist). In summary, our results indicated that a reduction in the PI3K/Akt/mTOR pathway may enhance defective endometrial remodeling by downregulating the proliferation and differentiation of endometrial stromal cells in early pregnant mice exposed to ß-CYP. Our study elucidates the mechanism of defective endometrial remodeling induced by peri-implantation ß-CYP exposure.

Combined effects of light pollution and vegetation height on behavior and body weight in a nocturnal rodent.

At a global scale, organisms are under threat due to various kinds of environmental changes, such as artificial light at night (ALAN), noise, climatic change and vegetation destruction. Usually, these changes co-vary in time and space and may take effect simultaneously. Although impacts of ALAN on biological processes have been well documented, our knowledge on the combined effects of ALAN and other environmental changes on animals remains limited. In this study, we conducted field experiments in semi-natural enclosures to explore the combined effects of ALAN and vegetation height on foraging behavior, vigilance, activity patterns and body weight in dwarf striped hamsters (Cricetulus barabensis), a nocturnal rodent widely distributed in East Asia. We find that ALAN and vegetation height affected different aspects of behavior. ALAN negatively affected search speed and positively affected handling speed, while vegetation height negatively affected giving-up density and positively affected body weight. ALAN and vegetation height also additively shaped total time spent in a food patch. No significant interactive effect of ALAN and vegetation height was detected. C. barabensis exposed to ALAN and short vegetation suffered a significant loss in body weight, and possessed a much narrower temporal niche (i.e. initiated activity later but became inactive earlier) than those under other combinations of treatments. The observed behavioral responses to ALAN and changes in vegetation height may bring fitness consequences, as well as further changes in structure and functioning of local ecosystems.

[Effects of Different Colored Polycarbonate Plastics on Growth and Community Structure of Periphytic Algae].

Periphytic algae are important primary producers in water bodies, which play an important role in maintaining ecological function and water purification. Previous studies have shown that plastic is a good substrate for periphytic algae, and different plastic materials have different effects on the colonization of periphytic algae; however, there are few reports on the effects of plastic color on the growth of periphytic algae. In this study, polycarbonate plastic (PC) of various colors were used as the substrate to study the effects of different colors on the growth and community structure of periphytic algae by measuring the biomass, photosynthetic activity, and community composition. The results showed that the growth of periphytic algae was inhibited by the brown PC plastic, and the contents of chlorophyll a and dry weight in this group were significantly lower than those in other groups. Green PC plastic inhibited the photosynthetic activity of periphytic algae, and the actual photosynthetic efficiency (Yield) of the group was significantly lower than that of the other groups. The influence of PC plastic with different colors on periphytic algae occurred mainly in the early colonization/development stage but was not significant in the late community maturity stage. On day seven of the experiment, the community composition of periphytic algae was significantly different between the transparent PC plastic group and the green PC plastic group. By contrast, on days 25 and 40, there were no significant differences in the community structure of periphytic algae. In the early stage of the experiment, the dominant genus was Pseudoranea (Cyanophyta), and in the middle and mature stages, the dominant genus was Mougeotia (Chlorophyta). In this study, the effects of different colors of polycarbonate plastics on periphytic algae were investigated, which provided new insights for selecting suitable substrates for water pollution treatment by using periphyton biotechnology.

Genetic variation in placental insufficiency: What have we learned over time?

Genetic variation shapes placental development and function, which has long been known to impact fetal growth and pregnancy outcomes such as miscarriage or maternal pre-eclampsia. Early epidemiology studies provided evidence of a strong heritable component to these conditions with both maternal and fetal-placental genetic factors contributing. Subsequently, cytogenetic studies of the placenta and the advent of prenatal diagnosis to detect chromosomal abnormalities provided direct evidence of the importance of spontaneously arising genetic variation in the placenta, such as trisomy and uniparental disomy, drawing inferences that remain relevant to this day. Candidate gene approaches highlighted the role of genetic variation in genes influencing immune interactions at the maternal-fetal interface and angiogenic factors. More recently, the emergence of molecular techniques and in particular high-throughput technologies such as Single-Nucleotide Polymorphism (SNP) arrays, has facilitated the discovery of copy number variation and study of SNP associations with conditions related to placental insufficiency. This review integrates past and more recent knowledge to provide important insights into the role of placental function on fetal and perinatal health, as well as into the mechanisms leading to genetic variation during development.

Ecological correlates of ectoparasite load in a rodent: Complex roles of seasonality.

Understanding the mechanisms driving parasite distributions is not only important for understanding ecosystem functioning, but also crucial for disease control. Previous studies have documented the important roles of host sex, host body size, host behavioral trait (such as boldness and trappability), and seasonality in shaping parasite load. However, few studies have simultaneously assessed the roles of these factors, as well as their interactions. In spring and summer of 2021, we conducted live trapping in Hohhot, China, to collect ectoparasites on Daurian ground squirrel (Spermophilus dauricus), a small rodent widely distributed in East Asian grassland. We then used generalized linear models to explore the effects of several biological factors (sex, body weight, trappability, and reproductive status) and seasonality on the abundance of ticks and fleas in S. dauricus. Significant but inconsistent seasonal effects were observed: tick load was significantly greater in summer than in spring, while flea load was greater in spring than in summer. Seasons also significantly interacted with host trappability and body weight to affect tick abundance. Our results highlight the importance of considering seasonal changes in parasitism, as well as interactions between season and host biological traits in shaping parasite distributions.

lncRNA MEG3 restrained the M1 polarization of microglia in acute spinal cord injury through the HuR/A20/NF-κB axis.

The M1 polarization of microglia and neuroinflammation restrict the treatment of acute spinal cord injury (ASCI), and long non-coding ribonucleic acid (lncRNA) maternally expressed gene 3 (MEG3) expression is lessened in ASCI. However, the function and mechanism of lncRNA MEG3 in the M1 polarization of microglia and neuroinflammation in ASCI are unclear. The expressions of lncRNA MEG3 in ASCI mouse spinal cord tissues and lipopolysaccharide (LPS)-treated primary microglia and BV2 cells were quantified through a quantitative real-time polymerase chain reaction. In-vitro assays were conducted to explore the function of lncRNA MEG3 in the M1 polarization of microglia and neuroinflammation in ASCI. RNA degradation, RNA immunoprecipitation, RNA pull-down, cycloheximide-chase, and ubiquitination analyses were carried out to probe into the mechanism of lncRNA MEG3 in the M1 polarization of microglia and neuroinflammation in ASCI. The lncRNA MEG3 expression was lessened in the ASCI mouse spinal cord tissues and LPS-treated primary microglia and BV2 cells, and the overexpression of lncRNA MEG3 restrained the M1 polarization of microglia and the neuroinflammation by regulating the NF-κB signaling pathway. For the investigation of the potential mechanism of such, the overexpression of lncRNA MEG3 restrained the M1 polarization of microglia through the HuR/A20/NF-κB axis and boosted the motor function recovery and neuroinflammation relief in the mice with SCI. The overexpression of lncRNA MEG3 restrained the M1 polarization of microglia through the HuR/A20/NF-κB axis.

Smart Self-Healing Capability of Asphalt Material Using Bionic Microvascular Containing Oily Rejuvenator.

It has become one of the research directions of intelligent materials for self-healing asphalt pavements to use a bionic microvascular containing oily rejuvenator. The rejuvenator in a microvascular can carry out the healing of asphalt micro-cracks, thus reducing the damage to and prolonging the life of asphalt pavement. The aim of this work was to investigate the smart self-healing capability of an asphalt/microvascular material through its microstructure and mechanical properties. Microstructure observation indicated no interface separation between the microvasculars and bitumen matrix. Micro-CT images showed that microvasculars dispersed in asphalt samples without accumulation or tangles. The phenomenon of microcracks healing without intervention was observed, which proved that the fractured asphalt sample carried out the self-healing process with the help of rejuvenator diffusing out from the broken microvasculars. The self-healing efficiency of asphalt samples was also evaluated through a tensile test considering the factors of microvasculars content, healing time and healing temperature. It was found that the tensile strength of the asphalt samples was greatly enhanced by the addition of microvasculars under a set test condition. Self-healing efficiency was enhanced with more broken microvasculars in the rupture interface of the asphalt sample. During two self-healing cycles, the self-healing efficiency of the asphalt sample with three microvascular per 1 cm2 of a broken interface were able to reach 80% and 86%. This proves that microvasculars containing rejuvenator play a practical role in the self-healing process of asphalt. With an increase in temperature from 0 to 30 °C, the self-healing capability of the asphalt samples increased dramatically. An increase in time increased the self-healing capability of the bitumen samples. At last, a preliminary mathematical model also deduced that the self-healing efficiency was determined by the individual healing steps, including release, penetration and diffusion of the rejuvenator agent.

Regulation of subsoiling tillage on the grain filling characteristics of maize varieties from different eras.

Grain filling is the key stage for achieving high grain yield. Subsoiling tillage, as an effective conservation tillage, has been widely used in the maize planting region of China. This study was conducted to explore the effects of subsoiling on the grain filling characteristics of maize varieties of different eras. Five typical maize varieties from different eras (1970s, 1980s, 1990s, 2000s and 2010s) were used as experimental materials with two tillage modalities (rotation tillage and subsoiling tillage). The characteristic parameters (Tmax: the time when the maximum grouting rate was reached, Wmax: the grain weight at the maximum filling rate, Rmax: the maximum grouting rate, P: the active grouting stage, Gmean: the average grouting rate; A: the ultimate growth mass) and rate parameters (T1: the grain filling duration of the gradually increasing stage, V1: the average grain filling rate of the gradually increasing stage, T2: he grain filling duration of the rapidly increasing stage, V2: the average grain filling rate of the rapidly increasing stage, T3: the grain filling duration of the slowly increasing stage, V3: the average grain filling rate of the slowly increasing stage) of grain filling of two tillage modalities were analyzed and compared. The results showed that the filling parameters closely correlated with the 100-kernel weight were significantly different among varieties from different eras, and the grain filling parameters of the 2010s variety were better than those of the other varieties, the P and Tmax prolonged by 4.06-19.25%, 5.88-27.53% respectively, the Rmax and Gmean improved by 5.68-14.81%, 4.76-12.82% and the Wmax increased by 10.14-32.58%. Moreover, the 2010s variety helped the V2 and V3 increase by 6.49-13.89%, 4.55-15.00%. In compared with rotation tillage, the grain yield of maize varieties from different eras increased by 4.28-7.15% under the subsoiling condition, while the 100-kernel weight increased by 3.53-5.06%. Under the same contrast conditions, subsoiling improved the Rmax, Wmax and Gmean by 1.23-4.86%, 4.01-5.96%, 0.25-2.50% respectively, delayed the Tmax by 4.04-5.80% and extended the P by 1.19-4.03%. These differences were major reasons for the significant increases in 100-kernel dry weight under the subsoiling condition. Moreover, subsoiling enhanced the V2 and V3 by 0.70-4.29%, 0.00-2.44%. The duration of each filling stage and filling rate of maize varieties from different eras showed different responses to subsoiling. Under the subsoiling condition, the average filling rate of the 1970-2010s varieties were improved by 1.18%, 0.34%, 0.57%, 1.57% and 2.69%. In the rapidly increasing period, the grain filling rate parameters of the 2010s variety were more sensitive to subsoiling than those of the other varieties. The rapidly increasing and slowly increasing period are the key period of grain filling. Since the 2010s variety and subsoiling all improve the grain filling rate parameters of two periods, we suggest that should select the variety with higher grain filling rate in the rapidly increasing and slowly increasing period, and combine subsoiling measures to improve the grain filling characteristic parameters of maize in production, so as to achieve the purpose of increasing 100 grain weight and yield.

Incidence and risk factors for severe preeclampsia, hemolysis, elevated liver enzymes, and low platelet count syndrome, and eclampsia at preterm and term gestation: a population-based study.

BACKGROUND: The majority of previous studies on severe preeclampsia, eclampsia, and hemolysis, elevated liver enzymes, and low platelet count syndrome were hospital-based or included a relatively small number of women. Large, population-based studies examining gestational age-specific incidence patterns and risk factors for these severe pregnancy complications are lacking. OBJECTIVE: This study aimed to assess the gestational age-specific incidence rates and risk factors for severe preeclampsia, hemolysis, elevated liver enzymes, and low platelet count syndrome, and eclampsia. STUDY DESIGN: We carried out a retrospective, population-based cohort study that included all women with a singleton hospital birth in Canada (excluding Quebec) from 2012 to 2016 (N=1,078,323). Data on the primary outcomes (ie, severe preeclampsia, hemolysis, elevated liver enzymes, and low platelet count syndrome, and eclampsia) were obtained from delivery hospitalization records abstracted by the Canadian Institute for Health Information. A Cox regression was used to assess independent risk factors (eg, maternal age and chronic comorbidity) for each primary outcome and to assess differences in the effects at preterm vs term gestation (<37 vs ≥37 weeks). RESULTS: The rates of severe preeclampsia (n=2533), hemolysis, elevated liver enzymes, and low platelet count syndrome (n=2663), and eclampsia (n=465) were 2.35, 2.47, and 0.43 per 1000 singleton pregnancies, respectively. The cumulative incidence of term-onset severe preeclampsia was lower than that of preterm-onset severe preeclampsia (0.87 vs 1.54 per 1000; rate ratio, 0.57; 95% confidence intervals, 0.53-0.62), the rates of hemolysis, elevated liver enzymes, and low platelet count syndrome were similar (1.32 vs 1.23 per 1000; rate ratio, 0.93; 95% confidence interval, 0.86-1.00), and the preterm-onset eclampsia rate was lower than the term-onset rate (0.12 vs 0.33 per 1000; rate ratio, 2.64; 95% confidence interval, 2.16-3.23). For each primary outcome, chronic comorbidity and congenital anomalies were stronger risk factors for preterm- vs term-onset disease. Younger mothers (aged <25 years) were at higher risk for severe preeclampsia at term and for eclampsia at all gestational ages, whereas older mothers (aged ≥35 years) had elevated risks for severe preeclampsia and hemolysis, elevated liver enzymes, and low platelet count syndrome. Regardless of gestational age, nulliparity was a risk factor for all outcomes, whereas socioeconomic status was inversely associated with severe preeclampsia. CONCLUSION: The risk for severe preeclampsia declined at term, eclampsia risk increased at term, and hemolysis, elevated liver enzymes, and low platelet count syndrome risk was similar for preterm and term gestation. Young maternal age was associated with an increased risk for eclampsia and term-onset severe preeclampsia. Prepregnancy comorbidity and fetal congenital anomalies were more strongly associated with severe preeclampsia, hemolysis, elevated liver enzymes, and low platelet count syndrome, and eclampsia at preterm gestation.

LncRNA-Fendrr protects against the ubiquitination and degradation of NLRC4 protein through HERC2 to regulate the pyroptosis of microglia.

OBJECTIVES: Targeted inhibition of inflammatory response can reduce diabetic cerebral ischemia-reperfusion (I/R) injure. Pyroptosis is characterized by caspase-1 dependence and the release of a large number of pro-inflammatory factors. LncRNA-Fendrr is associated with a variety of diseases, but Fendrr has not been studied in diabetic cerebral I/R. NLR-family CARD-containing protein 4 (NLRC4) regulate the pyroptosis of microglia cells. This study was designed to investigate whether Fendrr is involved in the effects of diabetic cerebral I/R injury. METHODS: The diabetic brain I/R model in mice was constructed. Mouse microglia cell line BV-2 cells were exposed to high glucose followed by hypoxia/reoxygenation (H/R). Fendrr and some pyroptosis-associated proteins were detected by qRT-PCR, western blot or ELISA. HE staining was used to detect pathological changes. Microglia pyroptosis was detected by TUNEL staining. RNA pull-down and RNA Immunoprecipitation were used to detect binding of Fendrr to HERC2 (E3 ubiquitin ligase), and CO-IP detected binding of HERC2 to NLRC4. The ubiquitination of NLRC4 was detected by ubiquitination experiments. RESULTS: Fendrr was significantly increased in the diabetic cerebral I/R model, and NLRC4 inflammatory complex and pyroptosis mediated inflammatory factors were increased. NLRC4 and inflammatory cytokines associated with pyroptosis were decreased in the high glucose-treated hypoxia/reoxygenation (H/R)-induced microglia after Fendrr knockdown. Fendrr bound to HERC2 protein, and HERC2 bound to NLRC4. Meanwhile, Fendrr could inhibit the ubiquitination of NLRC4, HERC2 promoted the ubiquitination of NLRC4 protein. Moreover, the effect of Fendrr overexpression in the diabetic cerebral I/R model of microglia can be reversed by HERC2 overexpression. CONCLUSION: Fendrr can protect against the ubiquitination and degradation of NLRC4 protein through E3 ubiquitin ligase HERC2, thereby accelerating the pyroptosis of microglia.

Orexin-A differentially modulates inhibitory and excitatory synaptic transmission in rat inner retina.

In this work, modulation by orexin-A of the release of glutamate and GABA from bipolar and amacrine cells respectively was studied by examining the effects of the neuropeptide on miniature excitatory postsynaptic currents (mEPSCs) and miniature inhibitory postsynaptic currents (mIPSCs) of rat retinal ganglion cells (GCs). Using RNAscope in situ hybridization in combination with immunohistochemistry, we showed positive signals for orexin receptor-1 (OX1R) mRNA in the bipolar cell terminals and those for orexin receptor-2 (OX2R) mRNA in the amacrine cell terminals. With whole-cell patch-clamp recordings in rat retinal slices, we demonstrated that application of orexin-A reduced the interevent interval of mEPSCs of GCs through OX1R. However, it increased the interevent interval of mIPSCs, mediated by GABAA receptors, through OX2R. Furthermore, orexin-A-induced reduction of mEPSC interevent interval was abolished by the application of PI-PLC inhibitors or PKC inhibitors. In contrast, orexin-A-induced increase of GABAergic mIPSC interevent interval was mimicked by 8-Br-cAMP or an adenylyl cyclase activator, but was eliminated by PKA antagonists. Finally, application of nimodipine, an L-type Ca2+ channel blocker, increased both mEPSC and mIPSC interevent interval, and co-application of orexin-A no longer changed the mEPSCs and mIPSCs. We conclude that orexin-A increases presynaptic glutamate release onto GCs by activating L-type Ca2+ channels in bipolar cells, a process that is mediated by an OX1R/PI-PLC/PKC signaling pathway. However, orexin-A decreases presynaptic GABA release onto GCs by inhibiting L-type Ca2+ channels in amacrine cells, a process that is mediated by an OX2R/cAMP-PKA signaling pathway.