Gestational diabetes mellitus and risk of long-term all-cause and cardiac mortality: a prospective cohort study.

BACKGROUND: To investigate the association between gestational diabetes mellitus (GDM) without subsequent overt diabetes and long-term all-cause and cardiac mortality. METHODS: This prospective cohort study included 10,327 women (weighted population: 132,332,187) with a pregnancy history from the National Health and Nutrition Examination Survey (2007 to 2018). Participants were divided into three groups (GDM alone, overt diabetes, and no diabetes). Mortality data was linked from the National Death Index up to December 31, 2019. Multivariable Cox regression analysis was performed to examine the association between GDM alone and overt diabetes with all-cause mortality and cardiac mortality. Data analysis was performed from October 2022 to April 2023. RESULTS: Among the participants, 510 (weighted 5.3%) had GDM alone and 1862 (weighted 14.1%) had overt diabetes. Over a median follow-up period of 6.7 years (69,063 person-years), there were 758 deaths. The GDM group did not show an increased risk of all-cause mortality (hazard ratio [HR] 0.67; 95% CI, 0.25-1.84), while the overt diabetes group had a significantly higher risk (HR 1.95; 95% CI, 1.62-2.35). Similarly, the GDM group did not exhibit an elevated risk of cardiac mortality (HR 1.48; 95% CI, 0.50-4.39), whereas the overt diabetes group had a significantly higher risk (HR 2.37; 95% CI, 1.69-3.32). Furthermore, sensitivity analysis focusing on women aged 50 or above showed that the HR of GDM history for all-cause mortality was 1.14 (95% CI, 0.33-3.95) and the HR for cardiac mortality was 1.74 (95% CI, 0.49-6.20). CONCLUSIONS: GDM alone was not associated with an increased risk of all-cause and cardiac mortality, while overt diabetes was significantly associated with both types of mortality.

Comprehensive transcriptome profiling and transcription factor identification in early/late leaf senescence grafts in potato.

Potato (Solanum tuberosum L.) is recognized globally as the most significant non-cereal staple crop. Leaf senescence, which significantly impacts tuber yield, serves as a critical indicator of potato maturity. Despite its importance, the molecular mechanisms regulating this process remain largely unknown. In a previous study, we grafted the early-maturing variety 'Zhongshu 5' (Z5) onto the late-maturing variety 'Zhongshu 18' (Z18), and demonstrated that the rootstock's leaves displayed physiological characteristics suggestive of early senescence. Here, we analyzed the transcriptome data of the Z5 and Z18 grafts to conduct weighted gene co-expression network and gene expression clustering analysis. Differentially expressed genes in cluster 9, as well as the floralwhite module, exhibited markedly elevated expression levels during the onset of leaf senescence. These genes were found to be enriched in several senescence related processes, such as chloroplast organization, electron transport chain, and chlorophyll metabolic process. Furthermore, we constructed transcription factor correlation networks and hub gene co-expression networks. By monitoring the expression patterns of these genes throughout the whole growth period, we identified two candidate genes, StWRKY70 and StNAP, which may play pivotal roles in leaf senescence. This study contributes valuable genetic resources for further investigations into the regulatory mechanism governing potato leaf senescence, with implications for genetic improvements, particularly in terms of maturity and yield.

Novel LDLR variants affecting low density lipoprotein metabolism identified in familial hypercholesterolemia.

BACKGROUND: Familial hypercholesterolemia (FH) is an autosomal dominant disease of lipid metabolism mainly caused by mutations in the low-density lipoprotein receptor (LDLR) gene. Genetic detection of patients with FH help with precise diagnosis and treatment, thus reducing the risk of coronary heart disease (CHD) and other related diseases. The study aimed to identify the causative gene mutations in a Chinese FH family and reveal the pathogenicity and the mechanism of these mutations. METHODS AND RESULTS: Whole exome sequencing was performed in a patient with severe lipid metabolism dysfunction seeking fertility guidance from a Chinese FH family. Two LDLR variants c.1875 C > G (p.N625K; novel variant) and c.1448G > A (p.W483*) were identified in the family. Wildtype and mutant LDLR constructs were established by the site-direct mutagenesis technique. Functional studies were carried out by cell transfection to evaluate the impact of detected variants on LDLR activity. The two variants were proven to affect LDL uptake and binding, resulting in cholesterol clearance reduction to different degrees. According to The American College of Medical Genetics and Genomics (ACMG) Standards and Guidelines, the W483* variant was classified as "Pathogenic", while the N625K variant as "VUS". CONCLUSIONS: Our results provide novel experimental evidence of functional alteration by LDLR variants identified in our study and expand the mutational spectrum of LDLR mutation induced FH.

The Impact of Empowerment Education on Discharge Readiness and Care Burden of Caregivers of Children with Congenital Heart Disease.

Context: Care burden refers to the physical burden that caregivers bear during the process of caring for children with congenital heart disease (CHD), and discharge readiness mainly refers to the confidence of the main caregivers in taking care of patients. Empowerment education's influence on the discharge readiness and caregivers' burden is unknown for children with CHD. Objective: The study intended to explore the impact of empowerment education on the discharge readiness and care burden of caregivers of children with CHD. Design: The research team conducted a prospective cohort study. Setting: The study took place at Anhui Provincial Children's Hospital in Hefei City, China. Participants: Participants were 163 caregivers of children who underwent surgery for CHD at the hospital between January 2019 and August 2021. Interventions: The research team divided participants into two groups using convenience sampling: (1) a control group, with 82 participants who received routine nursing education and intervention, and (2) an intervention group, with 81 participants who received empowered nursing education. Outcome Measures: Postintervention, the research team evaluated the caregivers': (1) readiness for the child's discharge and (2) burden level. Results: Postintervention, the intervention group's: (1) total score for discharge readiness and scores on the personal status and adaptability dimensions were significantly higher than those of the control group (all P < .05), and (2) care burden level was significantly lower than that of the control group (P < .05). Conclusions: Empowerment education can help caregivers of children with congenital defects of the heart to build awareness of the need to participate in disease management, improve disease-related knowledge and skills, reduce their negative emotions, and improve their level of preparation for their children's discharge and reduce their level of care burden. The therapy is worth further investigation and popularization.

Association of inactivated COVID-19 vaccination with maternal coagulation function in early pregnancy.

Reports of rare but severe thrombotic events after receiving some COVID-19 vaccines brought concerns for the possibility of vaccine-induced coagulation abnormality. However, no study has reported the impacts of COVID-19 vaccination on coagulation function in pregnant women. We aimed to explore whether vaccination with inactivated COVID-19 vaccines before pregnancy was associated with coagulation changes in pregnant women. We conducted a retrospective cohort study in a tertiary-care hospital in Shanghai, China. A total of 5166 pregnant women were included, of whom 2721 (52.7%) completed vaccination before conception. Compared with unvaccinated women, the mean serum levels of prothrombin time (PT) and fibrinogen (FIB) were lower in vaccinated women by 0.09 (ß = -0.09, 95% confidence interval [CI], -0.13, -0.05) mg/L and 0.11 (ß = -0.11, 95% CI, -0.15, -0.07) mg/L, and the mean D-Dimer (D-D) levels were higher by 0.12 (ß = 0.12, 95% CI, 0.09, 0.15) mg/L. However, no significant association was observed between COVID-19 vaccination and serum levels of activated partial thromboplastin time (APTT), fibrinogen degradation product (FDP) or thrombin time (TT). Our findings suggested that inactivated COVID-19 vaccination before conception resulted in a small change in maternal coagulation function, but this might not have clinical significance.

No association of vaccination with inactivated COVID-19 vaccines before conception with pregnancy complications and adverse birth outcomes: A cohort study of 5457 Chinese pregnant women.

Data on the safety of inactivated COVID-19 vaccines in pregnant women is limited and monitoring pregnancy outcomes is required. We aimed to examine whether vaccination with inactivated COVID-19 vaccines before conception was associated with pregnancy complications or adverse birth outcomes. We conducted a birth cohort study in Shanghai, China. A total of 7000 healthy pregnant women were enrolled, of whom 5848 were followed up through delivery. Vaccine administration information was obtained from electronic vaccination records. Relative risks (RRs) of gestational diabetes mellitus (GDM), hypertensive disorders in pregnancy (HDP), intrahepatic cholestasis of pregnancy (ICP), preterm birth (PTB), low birth weight (LBW), and macrosomia associated with COVID-19 vaccination were estimated by multivariable-adjusted log-binomial analysis. After exclusion, 5457 participants were included in the final analysis, of whom 2668 (48.9%) received at least two doses of an inactivated vaccine before conception. Compared with unvaccinated women, there was no significant increase in the risks of GDM (RR = 0.80, 95% confidence interval [CI], 0.69, 0.93), HDP (RR = 0.88, 95% CI, 0.70, 1.11), or ICP (RR = 1.61, 95% CI, 0.95, 2.72) in vaccinated women. Similarly, vaccination was not significantly associated with any increased risks of PTB (RR = 0.84, 95% CI, 0.67, 1.04), LBW (RR = 0.85, 95% CI, 0.66, 1.11), or macrosomia (RR = 1.10, 95% CI, 0.86, 1.42). The observed associations remained in all sensitivity analyses. Our findings suggested that vaccination with inactivated COVID-19 vaccines was not significantly associated with an increased risk of pregnancy complications or adverse birth outcomes.

Association of COVID-19 vaccination before conception with maternal thyroid function during early pregnancy: A single-center study in China.

Despite the high vaccination coverage, potential COVID-19 vaccine-induced adverse effects, especially in pregnant women, have not been fully characterized. We examined the association between COVID-19 vaccination before conception and maternal thyroid function during early pregnancy. We conducted a retrospective cohort study in Shanghai, China. A total of 6979 pregnant women were included. Vaccine administration was obtained from electronic vaccination records. Serum levels of thyroid hormone were measured by fluorescence and chemiluminescence immunoassays. Among the 6979 included pregnant women, 3470 (49.7%) received at least two doses of an inactivated vaccine. COVID-19 vaccination had a statistically significant association with both maternal serum levels of free thyroxine (FT4) and thyroid stimulating hormone (TSH). Compared with unvaccinated pregnant women, the mean FT4 levels were lower in pregnant women who had been vaccinated within 3 months before the date of conception by 0.27 pmol/L (ß = -0.27, 95% confidence interval [CI], -0.42, -0.12), and the mean TSH levels were higher by 0.08 mIU/L (ß = 0.08, 95% CI, 0.00, 0.15). However, when the interval from vaccination to conception was prolonged to more than 3 months, COVID-19 vaccination was not associated with serum FT4 or TSH levels. Moreover, we found that COVID-19 vaccination did not significantly associate with maternal hypothyroidism. Our study suggested that vaccination with inactivated COVID-19 vaccines before conception might result in a small change in maternal thyroid function, but this did not reach clinically significant levels.

Real-world effectiveness of Azvudine versus nirmatrelvir-ritonavir in hospitalized patients with COVID-19: A retrospective cohort study.

Chinese guidelines prioritize the use of Azvudine and nirmatrelvir-ritonavir in COVID-19 patients. Nevertheless, the real-world effectiveness of Azvudine versus nirmatrelvir-ritonavir is still lacking, despite clinical trials showing their effectiveness compared with matched controls. To compare the effectiveness of Azvudine versus nirmatrelvir-ritonavir treatments in real-world clinical practice, we identified 2118 hospitalized COVID-19 patients, with a follow-up of up to 38 days. After exclusions and propensity score matching, we included 281 Azvudine recipients and 281 nirmatrelvir-ritonavir recipients who did not receive oxygen therapy at admission. The lower crude incidence rate of composite disease progression outcome (7.83 vs. 14.83 per 1000 person-days, p = 0.026) and all-cause death (2.05 vs. 5.78 per 1000 person-days, p = 0.052) were observed among Azvudine recipients. Azvudine was associated with lower risks of composite disease progression outcome (hazard ratio [HR]: 0.55; 95% confidence interval [CI]: 0.32-0.94) and all-cause death (HR: 0.40; 95% CI: 0.16-1.04). In subgroup analyses, the results of composite outcome retained significance among patients aged <65 years, those having a history of disease, those with severe COVID-19 at admission, and those receiving antibiotics. These findings suggest that Azvudine treatment showed effectiveness in hospitalized COVID-19 patients compared with nirmatrelvir-ritonavir in terms of composite disease progression outcome.

Multifunctional Textiles with Flame Retardant and Antibacterial Properties: A Review.

It is well known that bacterial infections and fire-hazards are potentially injurious in daily life. With the increased security awareness of life and properties as well as the improvement of living standards, there has been an increasing demand for multifunctional textiles with flame retardant and antibacterial properties, especially in the fields of home furnishing and medical protection. So far, various treatment methods, including the spray method, the dip-coating method, and the pad-dry-cure method, have been used to apply functional finishing agents onto fabrics to achieve the functionalization in the past exploration stage. Moreover, in addition to the traditional finishing technology, a number of novel technologies have emerged, such as layer-by-layer (LBL) deposition, the sol-gel process, and chemical grafting modification. In addition, some natural biomasses, including chitin, chitosan (CS), and several synthetic functional compounds that possess both flame-retardant and bacteriostatic properties, have also received extensive attention. Hence, this review focuses on introducing some commonly used finishing technologies and flame retardant/antibacterial agents. At the same time, the advantages and disadvantages of different methods and materials were summarized, which will contribute to future research and promote the development and progress of the industry.

The length of stay and inpatient burden in inpatients with different psoriasis subtypes.

Background: Heavy disease burden of psoriasis has been indicated by previous studies. However, the cost of care and length of stay (LOS) in inpatients with different psoriasis subtypes were rarely addressed. This study aimed to investigate the cost of care and LOS in Chinese patients with different psoriasis types and to clarify the independent factors affecting LOS. Methods: We conducted a cross-sectional study by enrolling patients with psoriasis who were hospitalized between 13 Feb 2017 and 29 Mar 2021. Demographic and clinical characteristics of the patients were collected by reviewing their Electronic Medical Records. Multivariate linear regression was used to estimate the associations with adjustments. Results: A total of 310 adult patients with psoriasis were included (mean cost of care: 13.0±22.3 kCNY; mean LOS: 7.9±4.3 days). Statistically significant differences were found among patients with different psoriasis subtypes in LOS (P<0.001) but not in the cost of care (P=0.530). Relative to psoriasis vulgaris, pustular psoriasis (Adjusted coefficient: 2.37, 95% confidence interval (CI): 0.87-3.87) and erythrodermic psoriasis (Adjusted coefficient: 2.92, 95%CI: 1.38-4.47) were significantly associated with an increased LOS. Meanwhile, respiratory tract infections (Adjusted coefficient: 1.60, 95%CI: 0.11-3.10) also significantly increased the LOS. On the contrary, a decreased LOS was found in psoriatic arthritis patients treated with TNF-alpha inhibitors (Adjusted coefficient: -2.21, 95%CI: -4.37 to -0.05). Conclusions: LOS differed significantly among different psoriasis subtypes while the inpatient burden for a single hospitalization was alike. Infection is an important factor associated with a longer LOS. TNF-alpha inhibitors evidently reduced the total hospital stay period for patients with psoriatic arthritis.

Gestational exposure to BDE-209 induces placental injury via the endoplasmic reticulum stress-mediated PERK/ATF4/CHOP signaling pathway.

Several epidemiological studies have reported significant associations between prenatal polybrominated diphenyl ethers (PBDEs) exposure and adverse birth outcomes. Placental injury is thought to mediate these associations. However, few study has investigated the adverse effects of PBDEs exposure on placental growth and development. We examined the impacts of gestational exposure to BDE-209, the most abundant PBDE conger detected in human samples, on placental structure and function, and its model of action in vivo and in vitro. Pregnant mice were exposed to 0, 2, 20, 200 mg/kg/day of BDE-209 by gavages from gestational day (GD) 0 to GD18. Results showed that gestational BDE-209 exposure significantly reduced placental weight, impaired placental vascular development and induced placental cell apoptosis. In addition, gestational BDE-209 exposure impaired placental transport and endocrine function as demonstrated by markedly downregulated expression of Glut1, Znt1, Pgf and Igf2 in BDE-209-treated placentas. Mechanistically, gestational exposure to BDE-209 upregulated the expression of GRP78, and 3 downstream proteins (p-eIF2α, ATF4 and CHOP) of the PERK signaling, suggesting the activation of endoplasmic reticulum (ER) stress and PERK signaling pathway in mouse placentas. Further in vitro study showed that PERK siRNA pretreatment markedly reversed BDE-209-induced cell apoptosis in human JEG-3 cells. Collectively, our results suggest that the activation of the ER stress-mediated PERK/ATF4/CHOP signaling pathway played a role in BDE-209-induced placental injury. Our findings provide new insight into the mechanisms of BDE-209 induced reproductive and developmental toxicity.

Iron Metabolism and Ferroptosis in Physiological and Pathological Pregnancy.

Iron is a vital element in nearly every living organism. During pregnancy, optimal iron concentration is essential for both maternal health and fetal development. As the barrier between the mother and fetus, placenta plays a pivotal role in mediating and regulating iron transport. Imbalances in iron metabolism correlate with severe adverse pregnancy outcomes. Like most other nutrients, iron exhibits a U-shaped risk curve. Apart from iron deficiency, iron overload is also dangerous since labile iron can generate reactive oxygen species, which leads to oxidative stress and activates ferroptosis. In this review, we summarized the molecular mechanism and regulation signals of placental iron trafficking under physiological conditions. In addition, we revealed the role of iron metabolism and ferroptosis in the view of preeclampsia and gestational diabetes mellitus, which may bring new insight to the pathogenesis and treatment of pregnancy-related diseases.

The N6-Methyladenosine Regulator ALKBH5 Mediated Stromal Cell-Macrophage Interaction via VEGF Signaling to Promote Recurrent Spontaneous Abortion: A Bioinformatic and In Vitro Study.

Successful conception requires the synchrony of multiple systems and organs. Dysregulation of stromal cell-immune cell interactions has been proposed to be associated with recurrent spontaneous abortion. However, the mechanism of this regulation has not been well elucidated. N6-methyladenosine is one of the most common RNA modifications, and is involved in many pathological processes. Our group has demonstrated that abnormal patterns of m6A modification inhibit trophoblast invasion and contribute to adverse pregnancy outcomes. The association between m6A regulators and stromal cell-immune cell interactions is unclear. We obtained RNA-seq profiles from a GEO dataset and identified differentially expressed m6A regulators between healthy controls and patients with a recurrent spontaneous abortion history. ROC curves, functional enrichment and subclassification analysis were applied to elucidate the role of m6A regulators in pregnancy. We verified the expression of m6A regulators and constructed an overexpression cell line in a coculture system to reveal ALKBH5 function in stromal cell-macrophage interactions. We identified 11 differentially expressed m6A regulators between healthy controls and patients with a recurrent spontaneous abortion history. Then, we identified the correlation between "eraser" genes and "writer" genes. We tested the predictive abilities of the 11 m6A regulators based on another dataset and verified their expression in primary human endometrial stromal cells. We then subclassified three distinct patterns using the 11 genes and visualized genes related to immune infiltration and macrophage function in each cluster. ALKBH5 was proven to be correlated with recurrent spontaneous abortion. To verify the role of ALKBH5 in RSA, we constructed an ALKBH5-overexpression cell line. Finally, we cocultured the overexpression cell line with THP-1 cells. A decrease in M2 differentiation was observed, and this bias could be attributed to the hyposecretion of VEGF in stromal cells. N6-methyladenosine regulators play a pivotal role in stromal cell-immune cell interactions at the maternal-fetal interface. Overexpression of the m6A "eraser" gene ALKBH5 in stromal cells resulted in the hyposecretion of VEGF. Dysregulation of VEGF might impair macrophage recruitment and M2 differentiation, which could be the potential cause of recurrent spontaneous abortion.

Fine Mapping and Candidate Gene Prediction of Tuber Shape Controlling Ro Locus Based on Integrating Genetic and Transcriptomic Analyses in Potato.

Tuber shape is one of the most important quality traits in potato appearance. Since poor or irregular shape results in higher costs for processing and influences the consumers' willingness to purchase, breeding for shape uniformity and shallow eye depth is highly important. Previous studies showed that the major round tuber shape controlling locus, the Ro locus, is located on chromosome 10. However, fine mapping and cloning of tuber shape genes have not been reported. In this study, the analyses of tissue sectioning and transcriptome sequencing showed that the developmental differences between round and elongated tuber shapes begin as early as the hook stage of the stolon. To fine map tuber shape genes, a high-density genetic linkage map of the Ro region on chromosome 10 based on a diploid segregating population was constructed. The total length of the genetic linkage map was 25.8 cM and the average marker interval was 1.98 cM. Combined with phenotypic data collected from 2014 to 2017, one major quantitative trait locus (QTL) for tuber shape was identified, which explained 61.7-72.9% of the tuber shape variation. Through the results of genotyping and phenotypic investigation of recombinant individuals, Ro was fine mapped in a 193.43 kb interval, which contained 18 genes. Five candidate genes were preliminarily predicted based on tissue sections and transcriptome sequencing. This study provides an important basis for cloning Ro gene(s).

Regulation of the innate immune cells during pregnancy: An immune checkpoint perspective.

The foetus can be regarded as a half-allograft implanted into the maternal body. In a successful pregnancy, the mother does not reject the foetus because of the immune tolerance mechanism at the maternal-foetal interface. The innate immune cells are a large part of the decidual leukocytes contributing significantly to a successful pregnancy. Although the contributions have been recognized, their role in human pregnancy has not been completely elucidated. Additionally, the accumulated evidence demonstrates that the immune checkpoint molecules expressed on the immune cells are co-inhibitory receptors regulating their activation and biological function. Therefore, it is critical to understand the immune microenvironment and explore the function of the innate immune cells during pregnancy. This review summarizes the classic immune checkpoints such as PD-1, CTLA-4 and some novel molecules recently identified, including TIM-3, CD200, TIGIT and the Siglecs family on the decidual and peripheral innate immune cells during pregnancy. Furthermore, it emphasizes the role of the immune checkpoint molecules in pregnancy-associated complications and reproductive immunotherapy.

Decreased nitric oxide content mediated by asymmetrical dimethylarginine and protein l-arginine methyltransferase 3 in macrophages induces trophoblast apoptosis: a potential cause of recurrent miscarriage.

STUDY QUESTION: Is the protein l-arginine methyltransferase 3 (PRMT3)/asymmetrical dimethylarginine (ADMA)/nitric oxide (NO) pathway involved in the development of recurrent miscarriage (RM), and what is the potential mechanism? SUMMARY ANSWER: Elevated levels of PRMT3 and ADMA inhibit NO formation in the decidua, thereby impairing the functions of trophoblast cells at the maternal-foetal interface. WHAT IS KNOWN ALREADY: Decreased NO bioavailability is associated with RM. ADMA, an endogenous inhibitor of nitric oxide synthase (NOS), is derived from the methylation of protein arginine residues by PRMTs and serves as a predictor of mortality in critical illness. STUDY DESIGN, SIZE, DURATION: A total of 145 women with RM and 149 healthy women undergoing elective termination of an early normal pregnancy were enrolled. Ninety-six female CBA/J, 24 male DBA/2 and 24 male BALB/c mice were included. CBA/J × DBA/2 matings represent the abortion group, while CBA/J × BALB/c matings represent the normal control group. The CBA/J pregnant mice were then categorised into four groups: (i) normal + vehicle group (n = 28), (ii) abortion + vehicle group (n = 28), (iii) normal + SGC707 (a PRMT3 inhibitor) group (n = 20) and (iv) abortion + SGC707 group (n = 20). All injections were made intraperitoneally on Days 0.5, 3.5 and 6.5 of pregnancy. Decidual tissues were collected on Days 8.5, 9.5 and 10.5 of gestation. The embryo resorption rates were calculated on Day 9.5 and Day 10.5 of gestation. PARTICIPANTS/MATERIALS, SETTING, METHODS: NO concentration, ADMA content, NOS activity, expression levels of NOS and PRMTs in decidual tissues were determined using conventional assay kits or western blotting. PRMT3 expression was further analysed in decidual stromal cells, macrophages and natural killer cells. A co-culture system between decidual macrophages (DMs) and HTR-8/SVneo trophoblasts was constructed to study the roles of the PRMT3/ADMA/NO signalling pathway. Trophoblast apoptosis was analysed via Annexin V-fluorescein isothiocyanate/propidium iodide staining. CBA/J × DBA/2 mouse models were used to investigate the effects of SGC707 on embryo resorption rates. MAIN RESULTS AND THE ROLE OF CHANCE: Our results show that NO concentration and NOS activity were decreased, but ADMA content and PRMT3 expression were increased in the decidua of RM patients. Moreover, compared with the normal control subjects, PRMT3 expression was significantly up-regulated in the macrophages but not in the natural killer cells or stromal cells of the decidua from RM patients. The inhibition of PRMT3 results in a significant decrease in ADMA accumulation and an increase in NO concentration in macrophages. When co-cultured with DMs, which were treated with SGC707 and ADMA, trophoblast apoptosis was suppressed and induced, respectively. In vivo experiments revealed that the administration of SGC707 reduced the embryo resorption rate of CBA/J × DBA/2 mice. LIMITATIONS, REASONS FOR CAUTION: All sets of experiments were not performed with the same samples. The main reason is that each tissue needs to be reserved for clinical diagnosis and only a small piece of each tissue can be cut and collected for this study. WIDER IMPLICATIONS OF THE FINDINGS: Our results indicate that the PRMT3/ADMA/NO pathway is a potential marker and target for the clinical diagnosis and therapy of RM. STUDY FUNDING/COMPETING INTEREST(S): This study was supported by the National Key Research and Development Program of China (2017YFC1001401), National Natural Science Foundation of China (81730039, 82071653, 81671460, 81971384 and 82171657) and Shanghai Municipal Medical and Health Discipline Construction Projects (2017ZZ02015). The authors have declared no conflict of interest. TRIAL REGISTRATION NUMBER: N/A.

Natural killer cells: functional differences in recurrent spontaneous abortion†.

Recurrent spontaneous abortion (RSA) is one of the major pregnancy disorders and poses a serious risk to both the mother and the fetus. Although a number of research efforts have been conducted, therapeutic advances for treating RSA have not lived up to their expectations. Hence, other treatments should be explored. The important role of natural killer (NK) cells in immunotherapy is attracting increasing attention, both as a pharmaceutical target and for cell therapies. NK cells are abundant in the endometrium and play a role in implantation and placentation in normal pregnancy. As research progresses, NK cells are increasingly regarded as playing essential roles in the emergence and development of RSA. In this article, I review recent findings on the role of uterine NK cells in the pathophysiology of RSA. These cells may become therapeutic NK cell-related targets. In conclusion, although several issues regarding NK cells in RSA remain unresolved and require further investigation, extensive evidence is available for the treatment of RSA.

A high-throughput BAC end analysis protocol (BAC-anchor) for profiling genome assembly and physical mapping.

Traditional approaches for sequencing insertion ends of bacterial artificial chromosome (BAC) libraries are laborious and expensive, which are currently some of the bottlenecks limiting a better understanding of the genomic features of auto- or allopolyploid species. Here, we developed a highly efficient and low-cost BAC end analysis protocol, named BAC-anchor, to identify paired-end reads containing large internal gaps. Our approach mainly focused on the identification of high-throughput sequencing reads carrying restriction enzyme cutting sites and searching for large internal gaps based on the mapping locations of both ends of the reads. We sequenced and analysed eight libraries containing over 3 200 000 BAC end clones derived from the BAC library of the tetraploid potato cultivar C88 digested with two restriction enzymes, Cla I and Mlu I. About 25% of the BAC end reads carrying cutting sites generated a 60-100 kb internal gap in the potato DM reference genome, which was consistent with the mapping results of Sanger sequencing of the BAC end clones and indicated large differences between autotetraploid and haploid genotypes in potato. A total of 5341 Cla I- and 165 Mlu I-derived unique reads were distributed on different chromosomes of the DM reference genome and could be used to establish a physical map of target regions and assemble the C88 genome. The reads that matched different chromosomes are especially significant for the further assembly of complex polyploid genomes. Our study provides an example of analysing high-coverage BAC end libraries with low sequencing cost and is a resource for further genome sequencing studies.

Downregulation of HDAC8 expression decreases CD163 levels and promotes the apoptosis of macrophages by activating the ERK signaling pathway in recurrent spontaneous miscarriage.

Recurrent spontaneous miscarriage (RSM) is a systemic disorder that has been defined as two or more pregnancies lost before the 20th week of gestation. Although the impaired function of macrophages at the maternal-fetal interface has been reported to be associated with RSM, the underlying mechanisms have not been fully elucidated. Here, we revealed that HDAC8 plays a critical role in RSM. Our results show that the mRNA and protein expression of HDAC8 was decreased in decidual macrophages from RSM patients. Moreover, the knockdown of HDAC8 resulted in a significant decrease in CD163 expression and an increase in apoptosis in dTHP-1 macrophages. Mechanistically, the ERK signaling pathway was activated in HDAC8-knockdown macrophages. When HDAC8-knockdown cells were pretreated with the ERK inhibitor U0126, expression levels of CD163, activated caspases 3, 7 and 9, and the apoptosis rate, were rescued. Taken together, our current results suggest that HDAC8 plays an important role in macrophage activation and apoptosis and may contribute to maintaining normal pregnancy by increasing the expression of M2 marker genes and inhibiting the apoptosis of macrophages at the maternal-fetal interface.

Design, synthesis, and biological activity of a novel series of benzofuran derivatives against oestrogen receptor-dependent breast cancer cell lines.

A docking study of a novel series of benzofuran derivatives with ERα was conducted. In this study, we report the synthesis of a novel series of benzofuran derivatives and evaluation of their anticancer activity in vitro against MCF-7 human breast cancer cells, as well as their potential toxicity to ER-independent MDA-MB-231 breast cancer cells, human renal epithelial HEK-293 cells, and human immortal keratinocytes (HaCaT cells) by using the MTT colorimetric assay. The screening results indicated that the target compounds exhibited anti-breast cancer activity. The target compound 2-benzoyl-3-methyl-6-[2-(morpholin-4-yl)ethoxy]benzofuran hydrochloride (4e) exhibited excellent activity against anti-oestrogen receptor-dependent breast cancer cells and low toxicity. The preliminary structure-activity relationships of the target benzofuran derivatives have been summarised. In conclusion, the novel benzofuran scaffold may be a promising lead for the development of potential oestrogen receptor inhibitors.