Identification of FTY720 and COH29 as novel topoisomerase I catalytic inhibitors by experimental and computational studies.

The development of novel topoisomerase I (TOP1) inhibitors is crucial for overcoming the drawbacks and limitations of current TOP1 poisons. Here, we identified two potential TOP1 inhibitors, namely, FTY720 (a sphingosine 1-phosphate antagonist) and COH29 (a ribonucleotide reductase inhibitor), through experimental screening of known active compounds. Biological experiments verified that FTY720 and COH29 were nonintercalative TOP1 catalytic inhibitors that did not induce the formation of DNA-TOP1 covalent complexes. Molecular docking revealed that FTY720 and COH29 interacted favorably with TOP1. Molecular dynamics simulations revealed that FTY720 and COH29 could affect the catalytic domain of TOP1, thus resulting in altered DNA-binding cavity size. The alanine scanning and interaction entropy identified Arg536 as a hotspot residue. In addition, the bioinformatics analysis predicted that FTY720 and COH29 could be effective in treating malignant breast tumors. Biological experiments verified their antitumor activities using MCF-7 breast cancer cells. Their combinatory effects with TOP1 poisons were also investigated. Further, FTY720 and COH29 were found to cause less DNA damage compared with TOP1 poisons. The findings provide reliable lead compounds for the development of novel TOP1 catalytic inhibitors and offer new insights into the potential clinical applications of FTY720 and COH29 in targeting TOP1.

Dynamical analysis of a diffusive population-toxicant model with toxicant-taxis in polluted aquatic environments.

This paper deals with a diffusive population-toxicant model in polluted aquatic environments, with a toxicant-taxis term describing a toxicant-induced behavior change, that is, the population tends to move away from locations with high-level toxicants. The global existence of solutions is established by the techniques of the semigroup estimation and Moser iteration. Based on a detailed study on the properties of the principal eigenvalue for non-self-adjoint eigenvalue problems, we investigated the local and global stability of the toxin-only steady-state solution and the existence of positive steady state, which yields sufficient conditions that lead to population persistence or extinction. Finally, by numerical simulations, we studied the effects of some key parameters, such as toxicant-taxis coefficient, advection rate, and effect coefficient of the toxicant on population growth, on population persistence. Both numerical and analytical results show that a weak chemotaxis effect, a small advection rate of the population, and a weak effect of the toxicant on population growth are favorable for population persistence.

Effects of Sjogren's syndrome and high sugar diet on oral microbiome in patients with rampant caries: a clinical study.

OBJECTIVE: The purpose of this study was to assess the composition of the oral microbial flora of adults with rampant caries in China to provide guidance for treatment. PATIENTS AND METHODS: Sixty human salivary and supragingival plaque samples were collected. They were characterized into four groups: patients with rampant caries with Sjogren's syndrome (RC-SS) or high-sugar diet (RC-HD), common dental caries (DC), and healthy individuals (HP). The 16S rRNA V3-V4 region of the bacterial DNA was detected by Illumina sequencing. PCoA based on OTU with Bray-Curtis algorithm, the abundance of each level, LEfSe analysis, network analysis, and PICRUSt analysis were carried out between the four groups and two sample types. Clinical and demographic data were compared using analysis of variance (ANOVA) or the nonparametric Kruskal-Wallis rank-sum test, depending on the normality of the data, using GraphPad Prism 8 (P < 0.05). RESULTS: OTU principal component analysis revealed a significant difference between healthy individuals and those with RC-SS. In the saliva of patients with rampant caries, the relative abundance of Firmicutes increased significantly at the phylum level. Further, Streptocpccus, Veillonella, Prevotella, and Dialister increased, while Neisseria and Haemophilus decreased at the genus level. Veillonella increased in the plaque samples of patients with rampant caries. CONCLUSION: Both salivary and dental plaque composition were significantly different between healthy individuals and patients with rampant caries. This study provides a microbiological basis for exploring the etiology of rampant caries. CLINICAL RELEVANCE: This study provides basic information on the flora of the oral cavity in adults with rampant caries in China. These findings could serve as a reference for the treatment of this disease.

Preconception Blood Pressure and Adverse Pregnancy Outcomes: A Population-Based Cohort Study.

BACKGROUND: Adverse pregnancy outcomes (APOs) share clinical features and risk factors with cardiovascular disease and there is an increasing prevalence of hypertension among reproductive women. However, the associations between maternal preconception blood pressure (BP) and APOs remain controversial and inconclusive. METHODS: This population-based cohort study used data of 567 127 mother-neonate-father triads from the National Free Preconception Checkup Project in Guangdong Province, China. Maternal BP levels within 1 year before pregnancy were classified using the American College of Obstetricians and Gynecologists definition of hypertension. The primary outcome was a composite of APOs, including preterm birth, small for gestational age, and perinatal infant death. Log-binomial and marginal structural binomial regressions were employed to estimate adjusted risk ratios and absolute risk differences, respectively. RESULTS: Compared with women with normal BP, women with elevated BP (adjusted risk ratio, 1.07 [95% CI, 1.05-1.09]; absolute risk difference, 1.03% [95% CI, 0.72%-1.29%]), hypertension (adjusted risk ratio, 1.25 [95% CI, 1.18-1.32]; and absolute risk difference, 3.42% [95% CI, 1.97%-5.42%]) had a higher risk of a composite of APOs. Compared with women with normal BP, women with elevated BP and hypertension had higher risks of multiple APOs, preterm birth, small for gestational age, and perinatal infant death. However, these associations attenuated with increasing duration of pregnancy preparation and were not statistically significant beyond 90 days of pregnancy preparation. CONCLUSIONS: Women with elevated BP or hypertension before pregnancy were associated with an increased risk of APOs. Preconception hypertension screening and control among women should not be ignored by policymakers, clinicians, and the general population.

Association of maternal preconception blood pressure with preterm birth: a population-based cohort study.

The association between maternal preconception blood pressure (BP) and preterm birth (PTB) is still unclear. The purpose of this study was to investigate the association between maternal preconception BP and PTB. This population-based cohort study included 715 984 Chinese women aged 20-49 years who participated in the National Free Preconception Health Examination Project and successfully had a singleton livebirth during 2014-2019 in Guangdong Province, China. Maternal preconception BP were measured by trained health workers. Multivariate logistic regression models and restricted cubic spline regressions were used to examine the association and dose-response relationship between maternal preconception BP and PTB, respectively. Maternal preconception hypertension was associated with the increased risk of PTB (adjusted odds ratios (aOR): 1.24; 95% CI: 1.14-1.34). Compared to women with normal preconception BP, the aORs for PTB were 1.09 (95% CI: 1.06-1.12), 1.24 (95% CI: 1.13-1.36), and 1.43 (95% CI: 1.15-1.79) for women with preconception elevated BP (120-139/ 80-89 mmHg, stage-1 hypertension (140-159/ 90-99 mmHg, and stage-2 hypertension (160-179/100-109 mmHg), respectively. According to the 2017 American College of Cardiology/American Heart Association criteria, maternal preconception elevated BP and hypertension were also significantly associated with an increased risk of PTB. Preconception systolic and diastolic BP showed a U-shaped (χ2 = 40.54; nonlinear P < 0.001) and linear (χ2 = 6.62; nonlinear P = 0.085) dose-response relationship with PTB, respectively. The association was modified by maternal age and preconception body mass index. These findings identify maternal preconception elevated BP and hypertension as a modifiable risk factor for PTB, providing evidence for future research studies, public health and clinical interventions.

Targeted liposomes encapsulated iridium(III) compound greatly enhance anticancer efficacy and induce cell death via ferroptosis on HepG2 cells.

In this study, ligands 2-phenyl-1H-imidazo[4,5-f][1,10]phenanthroline (PIP), 2-(2-nitrophenyl)-1H-imidazo[4,5-f][1,10]phenanthroline (NPIP), 2-(2-nitronaphthalen-1-yl)-1H-imidazo[4,5-f][1,10]phenanthroline (NNIP) and their iridium(III) metal compounds [Ir(ppy)2(PIP)](PF6) (ppy = 2-phenylpyridine, 1a), [Ir(ppy)2(NPIP)](PF6) (1b), [Ir(ppy)2(NNIP)](PF6) (1c) were designed and synthesized. The anti-cancer activities of 1a, 1b and 1c on BEL-7402, HepG2, SK-Hep1 and non-cancer LO2 were detected using MTT method. 1a shows moderate, 1b and 1c display low or no anti-cancer activities. To elevate the anti-cancer effectiveness, encapsulating the compounds 1a, 1b and 1c into the ordinary or targeted liposomes to produce 1alip, 1blip, 1clip, or targeted 1aTlip, 1bTlip and 1cTlip. The IC50 values of 1alip, 1blip, 1clip, 1aTlip, 1bTlip and 1cTlip against HepG2 cells are 7.9 ± 0.1, 8.6 ± 0.2, 16.9 ± 0.5, 5.9 ± 0.2, 7.3 ± 0.1 and 9.7 ± 0.7 µM, respectively. Specifically, the anti-tumor activity assays in vivo found that the inhibitory rates are 23.24 % for 1a, 61.27 % for 1alip, 76.06 % for 1aTlip. It is obvious that the targeted liposomes entrapped iridium(III) compound greatly enhance anti-cancer efficacy. Additionally, 1alip, 1blip and 1clip or targeted 1aTlip, 1bTlip and 1cTlip can effectively restrain the cell colony and proliferation in the G0/G1 period. 1alip, 1blip, 1clip, 1aTlip, 1bTlip and 1cTlip can increase reactive oxygen species (ROS) concentration, arouse a decline in the mitochondrial membrane potential and promote Ca2+ release. RNA-sequence was applied to examine the signaling pathways. Taken together, the liposomes or targeted liposomes encapsulated compounds trigger cell death by way of apoptosis, autophagy, ferroptosis, disruption of mitochondrial function and PI3K/AKT/mTOR signaling pathways.

Deficiency in AK9 causes asthenozoospermia and male infertility by destabilising sperm nucleotide homeostasis.

BACKGROUND: Asthenozoospermia is the primary cause of male infertility; however, its genetic aetiology remains poorly understood. Adenylate kinase 9 (AK9) is highly expressed in the testes of humans and mice and encodes a type of adenosine kinase that is functionally involved in cellular nucleotide homeostasis and energy metabolism. We aimed to assess whether AK9 is involved in asthenozoospermia. METHODS: One-hundred-and-sixty-five Chinese men with idiopathic asthenozoospermia were recruited. Whole-exome sequencing (WES) and Sanger sequencing were performed for genetic analyses. Papanicolaou staining, Haematoxylin and eosin staining, scanning electron microscopy, and transmission electron microscopy were used to observe the sperm morphology and structure. Ak9-knockout mice were generated using CRISPR-Cas9. Sperm adenosine was detected by liquid chromatography-mass spectrometry. Targeted sperm metabolomics was performed. Intracytoplasmic sperm injection (ICSI) was used to treat patients. FINDINGS: We identified five patients harbouring bi-allelic AK9 mutations. Spermatozoa from men harbouring bi-allelic AK9 mutations have a decreased ability to sustain nucleotide homeostasis. Moreover, bi-allelic AK9 mutations inhibit glycolysis in sperm. Ak9-knockout male mice also presented similar phenotypes of asthenozoospermia. Interestingly, ICSI was effective in bi-allelic AK9 mutant patients in achieving good pregnancy outcomes. INTERPRETATION: Defects in AK9 induce asthenozoospermia with defects in nucleotide homeostasis and energy metabolism. This sterile phenotype could be rescued by ICSI. FUNDING: The National Natural Science Foundation of China (82071697), Medical Innovation Project of Fujian Province (2020-CXB-051), open project of the NHC Key Laboratory of Male Reproduction and Genetics in Guangzhou (KF202004), Medical Research Foundation of Guangdong Province (A2021269), Guangdong Provincial Reproductive Science Institute Innovation Team grants (C-03), and Outstanding Young Talents Program of Capital Medical University (B2205).

Prevalence of preconception TORCH infections and its influential factors: evidence from over 2 million women with fertility desire in southern China.

BACKGROUND: TORCH (Toxoplasma gondii [TOX], Cytomegalovirus [CMV], Rubella virus [RV], and Herpes simplex virus [HSV]) represents pathogens known to traverse the maternal-fetal barrier and cause severe neonatal anomalies. We aimed to assess the prevalence of preconception TOX, CMV, and RV infections among women with fertility desire in southern China, and identify related risk factors. METHODS: Data were obtained from a population-based cross-sectional study conducted as part of the National Free Preconception Health Examination Project. Women planning to conceive within the next 6 months in Guangdong Province were enrolled between 2014 and 2019. Information on sociodemographic, gynecological, and obstetric characteristics was collected. Sera were analyzed for TOX IgG, CMV IgG, and RV IgG antibodies using an enzyme-linked immunosorbent assay. Descriptive, univariate, and multivariate logistic regression analyses were performed to assess the association between TORCH infections and related factors. RESULTS: Among 2,409,137 participants, the prevalence of IgG antibodies for TOX, CMV, and RV was 3.20% (95% CI: 3.18-3.22%), 77.67% (95% CI: 77.62-77.71%) and 76.03% (95% CI: 75.98-76.07%), respectively. Of all participants, 141,047 women (5.85%, 95% CI:5.83-5.88%) reported a history of immunization for RV. Women living in the Pearl River Delta, a more developed region, have significantly lower vaccination rates than those living in other regions. The seropositivity of TOX IgG was highest among women aged 35 years and above, with primary or lower education levels, and rural registration. Factors such as being older, having a higher educational level, and being of other ethnicities were associated with a higher prevalence of naturally acquired CMV and RV infections. Women living in the Pearl River Delta showed a higher risk of TOX, CMV, and RV infections, with aORs of 2.21, 4.45, and 1.76, respectively. A history of pregnancy, gynecological diseases, and sexually transmitted infections were potentially associated with TORCH infections, but this association varied across pathogens. CONCLUSION: The findings of this study update the baseline of preconception TORCH infections among women with fertility desire in southern China, helping to estimate the risk of congenital infection and guide the development and implementation of effective prevention measures for preconception TORCH infections.

Identification of N-(3-(methyl(3-(orotic amido)propyl)amino)propyl) oleanolamide as a novel topoisomerase I catalytic inhibitor by rational design, molecular dynamics simulation, and biological evaluation.

DNA topoisomerase I (TOP1) catalytic inhibitors are a promising class of antitumor agents. Oleanolic acid derivatives are potential TOP1 catalytic inhibitors. However, their inhibitory activity still needs to be enhanced, and the stability and hotspot residue sites of their interaction with TOP1 remain to be elucidated. Herein, a novel oleanolic acid derivative, OA4 (N-(3-(methyl(3-(orotic amido)propyl)amino)propyl)oleanolamide), was identified by rational design. Subsequently, molecular dynamics simulations were performed to explore the stability and conformational dynamics of the TOP1-OA4 complex. The molecular mechanics/generalized Born surface area method calculated the binding free energy and predicted Arg488, Ile535, and His632 to be hotspot residues. Biological experiments verified that OA4 is a nonintercalative TOP1 catalytic inhibitor. OA4 exhibits better proliferation inhibitory activity against tumor cells than normal cells. Furthermore, OA4 can induce apoptosis and effectively suppress the proliferation and migration of cancer cells. This work provides new insights for the development of novel TOP1 catalytic inhibitors.

Single-cell RNA sequencing reveals the local cell landscape in mouse epididymal initial segment during aging.

BACKGROUND: Morphological and functional alterations in aging reproductive organs result in decreased male fertility. The epididymis functions as the transition region for post-testicular sperm maturation. And we have previously demonstrated that the epididymal initial segment (IS), a region of the reproductive tract essential for sperm maturation and capacitation, undergoes considerable histological changes and chronic immune activation in mice during aging. However, the local aging-associated cellular and molecular changes in the aged epididymal IS are poorly understood. RESULTS: We conducted single-cell RNA sequencing analysis on the epididymal IS of young (3-month-old) and old (21-month-old) mice. In total, 10,027 cells from the epididymal IS tissues of young and old mice were obtained and annotated. The cell composition, including the expansion of a principal cell subtype and Ms4a4bHiMs4a6bHi T cells, changed with age. Aged principal cells displayed multiple functional gene expression changes associated with acrosome reaction and sperm maturation, suggesting an asynchronous process of sperm activation and maturation during epididymal transit. Meanwhile, aging-related altered pathways in immune cells, especially the "cell chemotaxis" in Cx3cr1Hi epididymal dendritic cells (eDCs), were identified. The monocyte-specific expression of chemokine Ccl8 increased with age in eDCs. And the aged epididymal IS showed increased inflammatory cell infiltration and cytokine secretion. Furthermore, cell-cell communication analysis indicated that age increased inflammatory signaling in the epididymal IS. CONCLUSION: Contrary to the general pattern of lower immune responses in the male proximal genital tract, we revealed an inflammaging status in mouse epididymal initial segment. These findings will allow future studies to enable the delay of male reproductive aging via immune regulation.

Activating Blood Circulation, Anti-Inflammatory and Diuretic Effects of Leonurus japonicus Extract on a Rat Model of Trauma Blood Stasis and Its Phytochemical Profiling.

Leonurus japonicus Houtt. has been traditionally used to treat many ailments. This study evaluated the activating blood circulation, anti-inflammatory, and diuretic effects of L. japonicus extract (LJ) and identified its phytochemicals. In this work, the phytochemicals in LJ were identified using liquid chromatography mass spectrometry. Rats were randomly assigned to three groups (n=8): Control group was treated with saline, while the Model group (saline) and LJ group (426 mg/kg) had induced traumatic injury. All rats were treated with once by daily oral gavage for one week. The biochemical indices and protein expression were measured. Herein, 79 constituents were identified in LJ, which were effective in elevating body weight, food consumption, water intake, and urinary excretion volume, as well as in ameliorating traumatic muscle tissues in model rats. In addition, LJ prominently decreased the contents of plasma viscosity, platelet aggregation rate, thrombin time, prothrombin time, activated partial thromboplastin time, fibrinogen, thromboxane B2 (TXB2), TXB2/6-keto-prostaglandin F1α (6-keto-PGF1α), urokinase-type plasminogen activator (u-PA), plasminogen activator inhibitor 1 (PAI-1), PAI-1/tissue-type PA (t-PA), and PAI-1/u-PA, while significantly increasing antithrombin III, 6-keto-PGF1α, and t-PA contents. Furthermore, LJ notably inhibited tumor necrosis factor alpha, interleukin 6 (IL-6), IL-8, angiotensin II, antidiuretic hormone, aldosterone, aquaporin 1 (AQP1), AQP2, and AQP3 levels, and markedly elevating IL-10 and natriuretic peptide levels. Finally, LJ markedly reduced the protein expression of AQP1, AQP2, and AQP3 compared to the model group. Collectively, LJ possessed prominent activating blood circulation, anti-inflammatory, and diuretic effects, thus supporting the clinical application of L. japonicus.

Preconception syphilis seroprevalence and association with duration of marriage and age among married individuals in Guangdong Province, China: A population-based cross-sectional study.

BACKGROUND: Duration of marriage (DoM) and age are important characteristics of married individuals, who are the critical population for eliminating mother-to-child transmission (MTCT) of syphilis. A deep understanding of the preconception syphilis seroprevalence (PSS) and its distribution among this population may be able to help to eliminate MTCT. However, few population-based epidemiological studies have been focused on this group, and the association of DoM and age with PSS remains unclear. METHODOLOGY/PRINCIPAL FINDINGS: This study used data from 4,826,214 married individuals aged 21-49 years who participated in the National Free Preconception Health Examination Project in Guangdong Province, China, between 2014 and 2019. Syphilis was screened using the rapid plasma reagin (RPR) test. The seroprevalence time series, seroprevalence map, and hot spot analysis (HSA) were employed to visualize the spatiotemporal distribution. The restricted cubic spline (RCS) based on multivariate logistic regression was used to model the association of DoM and age with PSS. The interactions on the additive scale of DoM and age were also assessed. The PSS was 266.61 per 100,000 persons (95% CI: 262.03-271.24) and the burden was higher in economically underdeveloped area within the province. A strong J-shaped non-linearity association was observed between age and PSS. Specifically, the risk of seropositivity was relatively flat until 27 years of age among men and increased rapidly afterwards, with an adjusted odds ratio (aOR) of 1.13 (95% CI: 1.12-1.13) per unit. Among women, the risk of seropositivity was relatively flat until 25 years of age and increased rapidly afterwards with an aOR of 1.08 (95% CI: 1.08-1.09) per unit. DoM was negatively associated with PSS among married individuals. Moreover, the combined effects of age and DoM appeared to be synergistic. CONCLUSIONS/SIGNIFICANCE: Our findings suggest that attention should be paid to preventing syphilis in underdeveloped areas and that syphilis screening in newly married individuals who are in their late 20s or older should be recommended. Additionally, early syphilis prevention strategies should be implemented among young people as early as possible.

Novel mutations of PMFBP1 in a man with acephalic spermatozoa defects.

BACKGROUND: Acephalic spermatozoa (AS) is a serious but rare reproductive genetic disorder that causes infertility in men. To date, only a few genes associated with AS defects have been identified, including the polyamine modulated factor 1 binding protein 1 (PMFBP1) gene. Consistent with this, PMFBP1 localizes to the head-neck connection, which bridges the implantation fossa and basal body. METHODS: A male patient was diagnosed as having an AS defect. Blood samples from all family members and a sample of the patient's semen were collected to determine the genetic causes of his infertility. RESULTS: Compound heterozygote mutation in the PMFBP1 gene, which is associated with AS defects in the present case: two loss-of-function mutations, with one a nonsense mutation c.361C > T p.Gln121Ter, and another a splice donor mutation c.414 + 1G > T. The current study, together with previous studies, suggests that the nonsense mutation is responsible for a truncated PMFBP1 protein during its formation; a splice donor mutation c.414 + 1G > T might lead to new open reading frames, from which the dysfunction of an abnormal PMFBP1 protein might be predicted. Additionally, the expression of outer dense fiber 1 (ODF1) and ODF2 proteins has been experimentally shown to be regulated by the truncated PMFBP1 protein. CONCLUSION: We herein present a case with AS defects associated with heterozygote mutations of PMFBP1, which have been shown to be rare and pathogenic; the association with an AS defect is a monogenic disorder with a recessive inherited pattern in the patient's family.

Effect of hydrophile-lipophile balance of the linker in Gal/GalNAc ligands on high-affinity binding of galactosylated liposomes by the asialoglycoprotein receptor.

In this study, we explored the effect of the hydrophile-lipophile balance (HLB) in the linker unit of Galactose (Gal)/N-acetylgalactosamine (GalNAc) ligands on their affinity toward asialoglycoprotein receptors (ASGPRs). Two Gal/GalNAc ligands with lipophilic linkers-{(5-cholesten-3b-ol)[(2-acetamido-2-deoxy-d-galactopyranose-6-o)sebacate]} (CHS-6-GalNAc) and {(5-cholesten-3b-ol)[(d-galactopyranose-6-o)sebacate]} (CHS-6-Gal)-and two with hydrophilic linkers-{(5-cholesten-yl)[(4-O-b-D-galactopyranosyl)-D-glucitol-6-yl]sebacate} (CHS-1-Gal) and {(5-cholesten-3a-ol)[(2-acetamido-2-deoxy-d-galactopyranose-6-o)3,6-dioxa-octanedioate]} (CHS-PEG2-6-GalNAc)-were synthesized by enzymatic catalysis. Compared with unmodified liposomes, all Gal/GalNAc ligand-modified liposomes showed higher efficiency toward the hepatocyte target as evaluated by weighted-average overall drug-targeting efficiency (Te*) in vivo and HepG2 cell uptake efficiency in vitro. The ligands containing linkers with high HLB values (i.e., CHS-PEG2-6-GalNAc and CHS-1-Gal) exhibited higher ASGPR affinity than those containing linkers with low HLB values (i.e., CHS-6-GalNAc and CHS-6-Gal). We used molecular-dynamics (MD) simulations to investigate the structure-activity relationship between the HLB value of the linker in a ligand and ASGPR affinity. MD simulation results indicated that a Gal/GalNAc ligand with a more hydrophilic linker (i.e., higher HLB value) unit tended to have a higher solvent-accessible surface area (SASA), leading to lower steric hindrance for effective ASGPR recognition. The results of this study will provide an improved design for Gal/GalNAc ligand-based surface-modified liposomes with high ASGPR affinity.

Comprehensive Analysis of circRNAs, miRNAs, and mRNAs Expression Profiles and ceRNA Networks in Decidua of Unexplained Recurrent Spontaneous Abortion.

The diagnosis and treatment of unexplained recurrent spontaneous abortion (URSA) are subject to debate, because the exact underlying mechanisms remain unclear. To address this issue, we elucidated the expression profiles of dysregulated circRNAs, miRNAs, and mRNAs and constructed circRNA-associated competitive endogenous RNA (ceRNA) networks by comparing the decidua of URSA with that of normal early pregnancy (NEP) using RNA-sequencing. In total, 550 mRNAs, 88 miRNAs, and 139 circRNAs were differentially expressed (DE) in decidua of URSA. Functional annotation revealed that DE mRNAs as well as potential target genes of DE miRNAs and DE circRNAs are mainly involved in immunologic function, such as antigen processing and presentation, allograft rejection, and T cell receptor signaling pathway. In addition, the top hub genes, including CCL4, DDX58, CXCL10, CXCL9, MX1, CD44, RPS2, SOCS3, RPS3A, and CXCL11, were identified. The mRNAs involved in ceRNA network were enriched in complement and coagulation cascades and protein processing in the endoplasmic reticulum. We found that circRNAs in the ceRNA network, which acted as decoys for hsa-miR-204-5p, were positively correlated with MFGE8 expression. Collectively, the results demonstrated that circRNAs, miRNAs, and mRNAs were aberrantly expressed in the decidua of patients with URSA and played a potential role in the development of URSA. Thus, the establishment of the ceRNA network may profoundly affect the diagnosis and therapy of URSA in the future.

Design and Implementation of Obstetric Central Monitoring System Based on Medical Image Segmentation Algorithm.

At present, the incidence of emergencies in obstetric care environment is gradually increasing, and different obstetric wards often have a variety of situations. Therefore, it can provide great help in clinical medicine to give early warning and plan coping plans according to different situations. This paper studied an obstetrics central surveillance system based on a medical image segmentation algorithm. Images obtained by central obstetrics monitoring are segmented, magnified in detail, and image features are extracted, collated, and trained. The normal distribution rule is used to classify the features, which are included in the feature library of the obstetric central monitoring system. In the gray space of the medical image, the statistical distribution of gray features of the medical image is described by the mixture model of Rayleigh distribution and Gaussian distribution. In the gray space of the medical image, Taylor series expansion is used to describe the linear geometric structure of medicine. The eigenvalues of Hessian matrix are introduced to obtain high-order multiscale features of medicine. The multiscale feature energy function is introduced into Markov random energy objective function to realize medical image segmentation. Compared with other segmentation algorithms, the accuracy and sensitivity of the proposed algorithm are 87.98% and 86.58%, respectively, which can clearly segment small medical features.

Global dynamics of a generalist predator-prey model in open advective environments.

This paper deals with a system of reaction-diffusion-advection equations for a generalist predator-prey model in open advective environments, subject to an unidirectional flow. In contrast to the specialist predator-prey model, the dynamics of this system is more complex. It turns out that there exist some critical advection rates and predation rates, which classify the global dynamics of the generalist predator-prey system into three or four scenarios: (1) coexistence; (2) persistence of prey only; (3) persistence of predators only; and (4) extinction of both species. Moreover, the results reveal significant differences between the specialist predator-prey system and the generalist predator-prey system, including the evolution of the critical predation rates with respect to the ratio of the flow speeds; the take-over of the generalist predator; and the reduction in parameter range for the persistence of prey species alone. These findings may have important biological implications on the invasion of generalist predators in open advective environments.

Homozygous mutation in DNALI1 leads to asthenoteratozoospermia by affecting the inner dynein arms.

Asthenozoospermia is the most common cause of male infertility. Dynein protein arms play a crucial role in the motility of sperm flagella and defects in these proteins generally impair the axoneme structure and affect sperm flagella function. In this study, we performed whole exome sequencing for a cohort of 126 infertile patients with asthenozoospermia and identified homozygous DNALI1 mutation in one patient from a consanguineous family. This identified homozygous mutation was verified by Sanger sequencing. In silico analysis showed that this homozygous mutation is very rare, highly pathogenic, and very conserved. Sperm routine analysis confirmed that the motility of the spermatozoa from the patient significantly decreased. Further sperm morphology analysis showed that the spermatozoa from the patient exhibited multiple flagella morphological defects and a specific loss in the inner dynein arms. Fortunately, the patient was able to have his child via intracytoplasmic sperm injection treatment. Our study is the first to demonstrate that homozygous DNALI1 mutation may impair the integration of axoneme structure, affect sperm motility and cause asthenoteratozoospermia in human beings.

Global view on virus infection in non-human primates and implications for public health and wildlife conservation.

Viruses can be transmitted from animals to humans (and vice versa) and across animal species. As such, host-virus interactions and transmission have attracted considerable attention. Non-human primates (NHPs), our closest evolutionary relatives, are susceptible to human viruses and certain pathogens are known to circulate between humans and NHPs. Here, we generated global statistics on VI-NHPs based on a literature search and public data mining. In total, 140 NHP species from 12 families are reported to be infected by 186 DNA and RNA virus species, 68.8% of which are also found in humans, indicating high potential for crossing species boundaries. The top 10 NHP species with high centrality in the NHP-virus network include two great apes (Pan troglodytes, Pongo pygmaeus) and eight Old World monkeys (Macaca mulatta, M. fascicularis, M. leonina, Papio cynocephalus, Cercopithecus ascanius, C. erythrotis, Chlorocebus aethiops, and Allochrocebus lhoesti). Given the wide distribution of Old World monkeys and their frequent contact with humans, there is a high risk of virus circulation between humans and such species. Thus, we suggest recurring epidemiological surveillance of NHPs, specifically Old World monkeys that are in frequent contact with humans, and other effective measures to prevent potential circulation and transmission of viruses. Avoidance of false positives and sampling bias should also be a focus in future work.