Association of the podocyte phenotype with extracapillary hypercellularity in patients with diabetic kidney disease.

BACKGROUND: Extracapillary hypercellularity was recently identified as a poor prognostic factor for diabetic kidney disease (DKD), but its nature, pathogenesis, and relationship with glomerular sclerosis are still unclear. METHODS: We retrospectively studied 107 patients with biopsy-proven DKD, recruited from January 2018 through December 2020. We compared the clinicopathologic characteristics of 25 patients with extracapillary hypercellularity lesions (the extracapillary hypercellularity group) to those of 82 patients without extracapillary hypercellularity (the control group). Multiple cell-specific markers were used for immunohistochemical staining to analyse the types of cells that exhibited extracapillary hypercellularity. Podocyte phenotype changes were evaluated via immunohistochemical staining for Synaptopodin and Nephrin, and foot process width was measured via transmission electron microscopy. RESULTS: Patients with extracapillary hypercellularity lesions had more severe clinical features than patients without extracapillary hypercellularity in DKD, as indicated by elevated proteinuria and serum creatinine levels, and decreased serum albumin. Pathologically, extracapillary hypercellularity was accompanied by increased mesangial hyperplasia and interstitial fibrosis. Severe obliterative microvascular disease was observed more frequently in the extracapillary hypercellularity group than in the control group. At cell type analysis, 25 patients in the DKD-extracapillary hypercellularity group showed that a mixture of cells expressed either Wilm's tumor-1 or paired box protein 2. Furthermore, DKD-extracapillary hypercellularity patients had significant loss of podocyte phenotype and severe foot process effacement. Cells in extracapillary hypercellularity had increased hypoxia-induced factor-1 alpha expression. CONCLUSIONS: Extracapillary hypercellularity is associated with severe renal dysfunction and renal sclerosis. Vascular damage is closely related to severe podocyte hypoxia injury and requires additional attention in future research.

Exploring the potential prompting role of cervical human papilloma virus detection in vulvar lesions: a cross-sectional study in China.

Introduction: The etiology and clinical presentation of vulvar carcinomas, especially vulvar lesions, are not fully understood. Because the vulva and cervix are anatomically connected, human papillomavirus (HPV) is the main cause of cervical lesions. Thus, this study explored the potential characteristics and effects of specific HPV infection types across vulvar lesions and concurrent cervical lesions. Methods: This retrospective, cross-sectional study analyzed patients with cervical HPV or cytological results and concurrent vulvar biopsy who were seen in our hospital colposcopy clinic in Shanxi Province, China, between 2013 and 2023. Data on age, menopause status, vulvar manifestations, and cytology and HPV infection testing results were collected. Attributable fractions and multinominal logistic models were used to evaluate HPV genotyping and clinical characteristics across vulvar lesions. Results: Among the 1,027 participants, 83 (8.1%) had vulvar intraepithelial neoplasia (VIN) of high grade or worse (VIN2+), and 127 (12.4%) had non-neoplastic epithelial disorders of the vulva (NNEDV). A total of 175 patients had either VIN2+ or cervical intraepithelial neoplasia (CIN) lesions of grade 2 or worse (CIN2+). The most common HPV genotypes for VIN2+ or concurrent VIN2+/CIN2+ were HPV16, HPV52, and HPV58, although attributable fractions differed among lesions. Patients with normal cytological or histopathological result were more likely to have NNEDV detected, while abnormal cervical diagnosis was associated with higher detection of VIN2+. Multinominal logistic modeling showed that age and HPV16 infection were risk factors for VIN2+ or concurrent VIN2+/CIN2+; however, only vulvar presentation with depigmentation was a risk factor for NNEDV. Among patients with low-grade CIN1/VIN1, compared with those who were HPV16 negative, those who were HPV16 positive were at 6.63-fold higher risk of VIN2+/CIN2+ [95% confidence interval (CI): 3.32, 13.21]. Vulvar depigmentation was also associated with increased risk of NNEDV (odds ratio: 9.98; 95% CI: 3.02, 33.04). Conclusions: Chinese women may be at specific, high risk for HPV infection types associated with VIN or CIN. The use of cervical cell HPV detection along with vulvar presentation during cervical cancer screening may also contribute to vulvar lesion detection.

Time-resolved fluorescence nanoprobe of acetylcholinesterase based on ZnGeO:Mn luminescence nanorod modified with metal ions.

A novel time-resolved fluorescence nanoprobe (PBMO, PLNR-BSA-Mn2+-OPD) is fabricated for the label-free determination of acetylcholinesterase (AChE). The ZnGeO:Mn persistent luminescence nanorod (PLNR) and Mn(II) are, respectively, exploited as the signal molecule and quencher to construct the PBMO nanopobe using bovine serum albumin (BSA) as the surface-modified shell and o-phenylenediamine (OPD) as the reducing agent. In the presence of H2O2, the persistent luminescence of PBMO at 530 nm is enhanced remarkably within 30 s due to the oxidation of Mn(II). H2O2 can react with thiocholine (TCh), which is produced through the enzymatic degradation of acetylcholine (ATCh) by AChE. The PBMO nanoprobe is successfully applied to the determination of AChE in the linear range of 0.08-10 U L-1, with a detection limit of 0.03 U L-1 (3σ/s). The practicability of this PBMO nanoprobe is confirmed by accurately monitoring AChE contents in human serum samples, giving rise to satisfactory spiking recoveries of 96.2-103.6%.

A diagnosis model of parental care: How parents optimize their provisioning strategy in brood reduction?

Altricial birds often display biased preferences in providing parental care for their dependent offspring, especially during food shortages. During this process, such inflexible rules may result in provisioning errors. To demonstrate how parents optimize their provisioning strategies, we proposed a "diagnosis model" of parental care to posit that parents will undergo a diagnosis procedure to test whether selecting against some particular offspring based on phenotype is an optimal strategy. We tested this model in an asynchronous hatching bird, the Azure-winged Magpie Cyanopica cyanus, based on 10 years of data about demography and parental provisioning behaviors. Given their higher daily survival rates, core offspring (those hatched on the first day) merits an investment priority compared with their marginal brood mates (those hatched on later days). However, a marginal offspring also merited a priority if it displayed greater weight gain than the expected value at the early post-hatching days. Parents could detect such a marginal offspring via a diagnosis strategy, in which they provisioned the brood at the diagnosis stage by delivering food to every nestling that begged, then biased food toward high-value nestlings at the subsequent decision stage by making a negative response to the begging of low-value nestlings. In this provisioning strategy, the growth performance of a nestling became a more reliable indicator of its investment value than its hatching order or competitive ability. Our findings provide evidence for this "diagnosis model of parental care" wherein parents use a diagnosis method to optimize their provisioning strategy in brood reduction.

Clouclip combined with a questionnaire on the influence factors of myopia in children.

Purpose: To evaluate eye use behavior in myopic and non-myopic children objectively using Clouclip M2 device and subjectively using questionnaire and compare the results. The study also aimed to assess the relationships between ocular biometric parameters and refractive status. Methods: Clouclip M2 was used in monitoring eye use behavior and visual environment in children aged 9-11 years. The participants were monitored for 7 days. On the eighth day, data stored in the device were collected, relevant eye examination were conducted and survey questionnaire was administered. The paired sample t-test was used to compare the eye use behavior obtained objectively and subjectively. The relationships between ocular biometric parameters and refractive status were assessed using the Pearson's Correlation analysis. Results: Spherical equivalent refraction was significantly correlated with axial length, axial length to corneal radius, anterior chamber depth, lens thickness, and corneal radius (P < 0.05). The average time per day spent on near work, the maximum time for single near work, and the average near working distance were significantly lower, and the average total time spent on outdoor activities was significantly longer as determined by questionnaire method than that found using Clouclip M2. Logistic regression analysis revealed that prolonged near work, shorter working distance, presence of parental myopia, and lesser outdoor activities were significant risk factors for myopia. Conclusions: The childhood myopia is influenced by eye use behavior, eye use environment, and parental myopia. Results from this study further support that biometric and optical parameters of the eye determine refractive status. Being an objective method, Clouclip M2 provides an independent eye use behavior data which potentially are more reliable than obtained from subjective method. Our study provided a theoretical basis for myopia prevention and control in clinical practice.

Responses of a resident group to an outsider in the blue-breasted quail: A paradigm for studying social resettlement of dispersers.

Dispersal is an individual life-history trait that can influence the ecological and evolutionary dynamics of both the source and recipient populations. Current studies of animal dispersal have paid little attention to how the responses of residents in a recipient population affect the social resettlement of dispersers into a new habitat. We addressed this question in the blue-breasted quail Synoicus chinensis by designing an outsider introduction experiment to simulate a scenario of interaction between residents and dispersers. In the experiment, we introduced an unfamiliar quail into a group of 3 differently ranked residents and then examined their behavioral responses to the arrival of the outsider. We found that all residents made negative responses by pecking at the outsider to maintain their pecking order, in which high-ranked residents displayed significantly greater intensity than those of lower ranks. This result highlighted that adverse behavioral responses of residents would prevent outsiders from obtaining hierarchical dominance in the recipient group. Moreover, the residents' sex ratio, their relative ages to the outsiders, and whether outsiders counter-pecked at the residents all influenced the probability of outsiders prevailing against the residents. Those outsiders that displayed counter-peck courage were more likely to gain higher dominance and hence resettle into the recipient group successfully. Our findings suggest that resident groups may impose a selection among dispersers via adverse behavioral responses. Therefore, social factors that can influence the resettlement step of dispersers in a new habitat should be accounted for in future studies of animal dispersal.

Gender-specific association of SLC19A1 and MTHFR genetic polymorphism with oxidative stress biomarkers and plasma folate levels in older adults.

BACKGROUND: Plasma folate levels are closely related to antioxidant capacity and are regulated by folate pathway gene polymorphism. However, few studies have explored the gender-specific association of folate pathway gene polymorphism with oxidative stress biomarkers. The present study was designed to explore the gender-specific independent and combined impacts of solute carrier family 19 member 1 (SLC19A1) and methylenetetrahydrofolate reductase (MTHFR) genetic polymorphisms on oxidative stress biomarkers in older adults. METHODS: A total of 401 subjects were recruited, including 145 males and 256 females. Demographic characteristics of the participants were collected by using a self-administered questionnaire. Fasting venous blood samples were taken for folate pathway gene genotyping, circulating lipids parameters and erythrocyte oxidative stress biomarkers measurement. The difference of genotype distribution and the Hardy-Weinberg equilibrium was calculated by the Chi-square test. The general linear model was applied to compare the plasma folate levels and erythrocyte oxidative stress biomarkers. Multiple linear regression was used to explore the correlation between genetic risk scores and oxidative stress biomarkers. Logistic regression was used to explore the association of genetic risk scores of folate pathway gene with folate deficiency. RESULTS: The male subjects have lower plasma folate and HDL-C levels than the female ones, and the male carrying MTHFR rs1801133 (CC) or MTHFR rs2274976 (GA) genotypes have higher erythrocyte SOD activity. The plasma folate levels, erythrocyte SOD and GSH-PX activities were negatively correlated with genetic risk scores in the male subjects. A positive correlation between the genetic risk scores and folate deficiency was observed in the male subjects. CONCLUSIONS: There was association between folate pathway gene polymorphism of Solute Carrier Family 19 Member 1 (SLC19A1) and Methylenetetrahydrofolate Reductase (MTHFR) with erythrocyte SOD and GSH-PX activities, and folate levels in male but not in female aging subjects. Genetic variant of genes involved in folate metabolism has strong impact on plasma folate levels in the male aging subjects. Our data demonstrated that there was a potential interaction of gender and its genetic background in affecting the body's antioxidant capacity and the risk of folate deficiency in aging subjects.

Predicting the current and future distributions of Pennisetum alopecuroides (L.) in China under climate change based on the MaxEnt model.

Pennisetum alopecuroides (L.), one of the important exotic plants, gives great economic value to animal husbandry in China. In order to study the distribution of Pennisetum alopecuroides (L.) in China and its response to climate change, based on the distribution records of Pennisetum alopecuroides (L.), our study used the Maximum Entropy (MaxEnt) model and geographic information system (GIS) methods, combined with environmental factors such as climate and terrain, to predict the potential distribution areas suitable for Pennisetum alopecuroides (L.) under current and future climate scenarios. The results showed that annual precipitation was the most important factor affecting the distribution of Pennisetum alopecuroides (L.). In current climate scenario, the total area of suitable for Pennisetum alopecuroides (L.) growth was about 576.5 km2, accounting for about 60.5% of the total land area of China. Among all the suitable areas, the area of low, middle and high fitness areas accounted for 5.69%, 20.55% and 33.81% of the total area respectively. In future climate scenarios (RCP4.5), the suitable area of Pennisetum alopecuroides (L.) would decrease with climate change, showing a clear trend of northward expansion in China. A concentrated and contiguous distribution region for Pennisetum alopecuroides (L.) would appear in northeast China. The model was tested by the receiver operating characteristic curve (ROC), and the average area under the curve of ROC of the training set was 0.985, which was reliable. This work provided an important reference and theoretical basis for the efficient utilization and plant regionalization of Pennisetum alopecuroides (L.) in future.

Adult tiger beetles Cicindela gemmata modify their foraging strategy in different hunting contexts.

Predator-prey interaction has long been an interesting item in the research of animal behaviors. Given that live prey can damage their predators, predators must trade foraging efficiency for safety while hunting, but the extent of this trade-off is not yet clear. Tiger beetles display diversity in their diets and hunting strategies, and hence, they become an ideal system to address how self-security affects foraging efficiency. We addressed this question in captive adult tiger beetles Cicindela gemmata. By offering several types of arthropod and plant foods, we confirmed that C. gemmata is carnivorous. We found that C. gemmata hunt by either ambushing or chasing their prey, and that they switch between strategies based on differences in the number of prey, the prey status and encounter rate, and the number of predators. Ambushing success increased with the number of prey but decreased with prey encounter rate. Chasing success decreased as prey body size and encounter rate increased. Foraging Cicindela gemmata often gave up an attack when it was nonfatal. This active giving up of hunting may be a consequence of a trade-off between foraging efficiency and self-security. Therefore, it is an adaptive response to the risk of injury when hunting for larger live prey.

How does workplace event criticality spur employees' proactivity? The roles of work engagement and mindfulness.

This paper aims to generate insights about whether, how, and when workplace event criticality spurs employee proactivity. We conducted multilevel analyses with a three-wave time-lagged survey of 179 employees and their 55 direct leaders in China to test our proposed model. The findings indicate that workplace event criticality is conducive to stimulating proactive work behavior through improving employee engagement. Further, employee mindfulness amplifies the positive relationship between workplace event criticality and work engagement. Despite the increasingly unavoidable influence of events in the workplace on employee proactivity, empirical research around the relationship and its underlying mechanism has been rather sparse. Our event-oriented research advances this knowledge by unpacking the salient motivating role of workplace events' criticality in employee work engagement and proactivity. It also increases our understanding by illustrating that employee mindfulness will amplify and intensify the motivational potential of workplace event criticality for work engagement.

Nobiletin Inhibits Hypoxia-Induced Placental Damage via Modulating P53 Signaling Pathway.

In this study, we aimed to evaluate the effect of Nobiletin (NOB) on the placenta of Sprague-Dawley (SD) rats that had undergone reduced uterine perfusion pressure (RUPP) surgery and to evaluate the safety of NOB intervention during pregnancy. The results showed that NOB alleviated placental hypoxia, attenuated placental cell apoptosis, and inhibited placental damage in RUPP rats. No side effect of NOB intervention during pregnancy was observed. BeWo cell lines with P53 knockdown were then constructed using lentiviral transfection, and the P53 signaling pathway was found to be essential for NOB to reduce hypoxia-induced apoptosis of the BeWo cell lines. In summary, NOB attenuated hypoxia-induced placental damage by regulating the P53 signaling pathway, and those findings may contribute some insights into the role of NOB in placental development and the prevention of placental-related diseases.

Antiosteoporosis Effects, Pharmacokinetics, and Drug Delivery Systems of Icaritin: Advances and Prospects.

Osteoporosis is a systemic skeletal disorder affecting over 200 million people worldwide and contributes dramatically to global healthcare costs. Available anti-osteoporotic drug treatments including hormone replacement therapy, anabolic agents, and bisphosphonates often cause adverse events which limit their long-term use. Therefore, the application of natural products has been proposed as an alternative therapy strategy. Icaritin (ICT) is not only an enzyme-hydrolyzed product of icariin but also an intestinal metabolite of eight major flavonoids of the traditional Chinese medicinal plant Epimedium with extensive pharmacological activities, such as strengthening the kidney and reinforcing the bone. ICT displays several therapeutic effects, including osteoporosis prevention, neuroprotection, antitumor, cardiovascular protection, anti-inflammation, and immune-protective effect. ICT inhibits bone resorption activity of osteoclasts and stimulates osteogenic differentiation and maturation of bone marrow stromal progenitor cells and osteoblasts. As for the mechanisms of effect, ICT regulates relative activities of two transcription factors Runx2 and PPARγ, determines the differentiation of MSCs into osteoblasts, increases mRNA expression of OPG, and inhibits mRNA expression of RANKL. Poor water solubility, high lipophilicity, and unfavorable pharmacokinetic properties of ICT restrict its anti-osteoporotic effects, and novel drug delivery systems are explored to overcome intrinsic limitations of ICT. The paper focuses on osteogenic effects and mechanisms, pharmacokinetics and delivery systems of ICT, and highlights bone-targeting strategies to concentrate ICT on the ideal specific site of bone. ICT is a promising potential novel therapeutic agent for osteoporosis.

Insufficient Fruit and Vegetable Intake and Low Potassium Intake Aggravate Early Renal Damage in Children: A Longitudinal Study.

Insufficient fruit and vegetable intake (FVI) and low potassium intake are associated with many non-communicable diseases, but the association with early renal damage in children is uncertain. We aimed to identify the associations of early renal damage with insufficient FVI and daily potassium intake in a general pediatric population. We conducted four waves of urine assays based on our child cohort (PROC) study from October 2018 to November 2019 in Beijing, China. We investigated FVI and other lifestyle status via questionnaire surveys and measured urinary potassium, ß2-microglobulin (ß2-MG), and microalbumin (MA) excretion to assess daily potassium intake and renal damage among 1914 primary school children. The prevalence of insufficient FVI (<4/d) was 48.6% (95% CI: 46.4%, 50.9%) and the estimated potassium intake at baseline was 1.63 ± 0.48 g/d. Short sleep duration, long screen time, lower estimated potassium intake, higher ß2-MG and MA excretion were significantly more frequent in the insufficient FVI group. We generated linear mixed effects models and observed the bivariate associations of urinary ß2-MG and MA excretion with insufficient FVI (ß = 0.012, 95% CI: 0.005, 0.020; ß = 0.717, 95% CI: 0.075, 1.359), and estimated potassium intake (ß = −0.042, 95% CI: −0.052, −0.033; ß = −1.778, 95% CI: −2.600, −0.956), respectively; after adjusting for age, sex, BMI, SBP, sleep duration, screen time and physical activity. In multivariate models, we observed that urinary ß2-MG excretion increased with insufficient FVI (ß = 0.011, 95% CI: 0.004, 0.018) and insufficient potassium intake (<1.5 g/d) (ß = 0.031, 95% CI: 0.023, 0.038); and urinary MA excretion increased with insufficient FVI (ß = 0.658, 95% CI: 0.017, 1.299) and insufficient potassium intake (ß = 1.185, 95% CI: 0.492, 1.878). We visualized different quartiles of potassium intake showing different renal damage with insufficient FVI for interpretation and validation of the findings. Insufficient FVI and low potassium intake aggravate early renal damage in children and underscores that healthy lifestyles, especially adequate FVI, should be advocated.

Time-resolved fluorescence determination of albumin using ZnGeO:Mn luminescence nanorods modified with polydopamine nanoparticles.

A novel time-resolved fluorescence (TRF) pobe is constructed to detect human serum albumin (HSA) by exploiting ZnGeO:Mn persistent luminescence nanorods (ZnGeO:Mn PLNRs) and polydopamine nanoparticles (PDA NPs). HSA-induced dynamic quenching leads to the fluorescence decrease of ZnGeO:Mn PLNRs, providing the basis for quantitative analysis of HSA. The excellent photo-thermal conversion performance of PDA NPs is helpful to the collision process between ZnGeO:Mn PLNRs and HSA, inducing significant improvement of sensitivity. HSA is quantified by measuring time-resolved fluorescence at 540 nm under excitation of 250-nm light. Under optimal conditions, HSA in the linear range 0.1-100 ng mL-1 are detected by this PDA-mediated ZnGeO:Mn probe with high sensitivity and selectivity, and the detection limit is 36 pg mL-1 (3σ/s). The RSD for the quantification of HSA (5 ng mL-1, n = 11) is 5.2%. The practicability of this TRF probe is confirmed by accurate monitoring HSA contents in urine samples, giving rise to satisfactory spiking recoveries of 96.2-106.0%.

IMUP and GPRC5A: two newly identified risk score indicators in pancreatic ductal adenocarcinoma.

BACKGROUND: Pancreatic cancer has been a threateningly lethal malignant tumor worldwide. Despite the promising survival improvement in other cancer types attributing to the fast development of molecular precise medicine, the current treatment situation of pancreatic cancer is still woefully challenging since its limited response to neither traditional radiotherapy and chemotherapy nor emerging immunotherapy. The study is to explore potential responsible genes during the development of pancreatic cancer, thus identifying promising gene indicators and probable drug targets. METHODS: Different bioinformatic analysis were used to interpret the genetic events in pancreatic cancer development. Firstly, based on multiple cDNA microarray profiles from Gene Expression Omnibus (GEO) database, the genes with differently mRNA expression in cancer comparing to normal pancreatic tissues were identified, followed by being grouped based on the difference level. Then, GO and KEGG were performed to separately interpret the multiple groups of genes, and further Kaplan-Meier survival and Cox Regression analysis assisted us to scale down the candidate genes and select the potential key genes. Further, the basic physicochemical properties, the association with immune cells infiltration, mutation or other types variations besides expression gap in pancreatic cancer comparing to normal tissues of the selected key genes were analyzed. Moreover, the aberrant changed expression of key genes was validated by immunohistochemistry (IHC) experiment using local hospital tissue microarray samples and the clinical significance was explored based on TCGA clinical data. RESULTS: Firstly, a total of 22,491 genes were identified to express differently in cancer comparing to normal pancreatic tissues based on 5 cDNA expression profiles, and the difference of 487/22491 genes was over eightfold, and 55/487 genes were shared in multi profiles. Moreover, after genes interpretation which showed the > eightfold genes were mainly related to extracellular matrix structural constituent regulation, Kaplan-Meier survival and Cox-regression analysis were performed continually, and the result indicated that of the 55 extracellular locating genes, GPRC5A and IMUP were the only two independent prognostic indicators of pancreatic cancer. Further, detailed information of IMUP and GPRC5A were analyzed including their physicochemical properties, their expression and variation ratio and their association with immune cells infiltration in cancer, as well as the probable signaling pathways of genes regulation on pancreatic cancer development. Lastly, local IHC experiment performed on PAAD tissue array which was produced with 62 local hospital patients samples confirmed that GPRC5A and IMUP were abnormally up-regulated in pancreatic cancer, which directly associated with worse patients both overall (OS) and recurrence free survival (RFS). CONCLUSIONS: Using multiple bioinformatic analysis as well as local hospital samples validation, we revealed that GPRC5A and IMUP expression were abnormally up-regulated in pancreatic cancer which associated statistical significantly with patients survival, and the genes' biological features and clinical significance were also explored. However, more detailed experiments and clinical trials are obligatory to support their further potential drug-target role in clinical medical treatment.

Vitamin D3 alleviates cognitive impairment through regulating inflammatory stress in db/db mice.

Patients with type 2 diabetes mellitus (T2DM) have a higher risk to develop cognitive impairment. Several studies reported the potential roles of vitamin D in prevention of cognitive impairment, but the mechanism remains unclear. The present study aims to investigate the protective effects of vitamin D3 on cognitive impairment in db/db mice and to explore the possible mechanism. Twelve-week-old male db/db mice were randomly administrated with low, medium, and high dose of vitamin D3 (LVD, MVD, and HVD groups, respectively) and equivalent volume vitamin D3 solvent (corn oil, DM group) intragastrically. Eight age-matched db/m mice were given equivalent volume corn oil as normal group. After 16 weeks of vitamin D3 treatment, the concentrations of fasting serum glucose in three vitamin D3 groups (especially the 1,000 IU/kg·bw dose) were significantly decreased compared with DM group. Pathology revealed that the neuron damage was reduced in vitamin D3 groups. MVD intervention significantly shortened the escape latency on day 5 and extended time in the target quadrant. Mice in HVD group had significantly higher exploration time and discrimination index compared with the DM group mice. Moreover, vitamin D3 treatment has increased the phosphorylation of cAMP-response element-binding protein and the expression of brain-derived neurotrophic factor and vitamin D receptor. This treatment, meanwhile, has decreased the expression of tumor necrosis factor-α, the phosphorylation of inhibitor kappa Bα (IκBα), and nuclear factor-κB p65 (NF-κB p65) in the hippocampus of db/db mice. These results suggest that vitamin D3 alleviated cognitive impairment in the hippocampus of db/db mice. Down-regulation of the NF-κB signaling pathway-related proteins IκBα and p65 might be one of the possible mechanisms.

Comprehensive Analysis of circRNA Expression Profiles During Cervical Carcinogenesis.

Circular RNAs (circRNAs) are regulatory molecules that participate in the occurrence, development and progression of tumors. To obtain a complete blueprint of cervical carcinogenesis, we analyzed the temporal transcriptomic landscapes of mRNAs and circRNAs. Microarrays were performed to identify the circRNA and mRNA expression profiles of cervical squamous cell carcinoma (CSCC) and high-grade squamous intraepithelial lesion (HSIL) patients compared with normal controls (NC). Short time-series expression miner (STEM) was utilized to characterize the time-course expression patterns of circRNAs and mRNAs from NC to HSIL and CSCC. A total of 3 circRNA profiles and 3 mRNA profiles with continuous upregulated patterns were identified and selected for further analysis. Furthermore, functional annotation showed that the mRNAs were associated with DNA repair and cell division. The protein-protein interaction (PPI) network analysis revealed that the ten highest-degree genes were considered to be hub genes. Subsequently, a competing endogenous RNA (ceRNA) network analysis and real-time PCR validation indicated that hsa_circ_0001955/hsa-miR-6719-3p/CDK1, hsa_circ_0001955/hsa-miR-1277-5p/NEDD4L and hsa_circ_0003954/hsa-miR-15a-3p/SYCP2 were highly correlated with cervical carcinogenesis. Silencing of hsa_circ_0003954 inhibited SiHa cell proliferation and perturb the cell cycle in vitro. This study provides insight into the molecular events regulating cervical carcinogenesis, identifies functional circRNAs in CSCC, and improves the understanding of the pathogenesis and molecular biomarkers of CSCC and HSIL.

Fitness consequences of divorce in the azure-winged magpie depends on the breeding experience of a new mate.

Sexual conflict in producing and raising offspring is a critical issue in evolutionary ecology research. Individual experience affects their breeding performance, as measured by such traits of provisioning of offspring and engagement in extra-pair copulations, and may cause an imbalance in sexual conflict. Thus, divorce is hypothesized to occur within aged social pairs, irrespective of current reproductive success. This concept was explored in the azure-winged magpie Cyanopica cyanus by investigating the divorce of a social pair and its relationship to their changes in breeding performance with prior experience. Females engaging in extra-pair copulation may intensify sexual conflicts and may be the main reason for divorce. Once divorced, females repairing with an inexperienced male realized higher reproductive success than that repairing with an experienced male; males repairing with an experienced female realized higher reproductive success than that repairing with an inexperienced female. This finding indicates that the fitness consequence of divorce depends on the breeding experience of new mates. Divorced females can obtain more extra-pair copulations, whereas divorced males cannot, when they repair with inexperienced breeders. Divorced females provisioned a brood at lower rates than inexperienced females whereas divorced males had no such difference. It appears that divorced females can obtain an advantage in sexual conflicts with inexperienced mates in future reproduction. Consequently, females are probably more active than males in divorcing their aged mates so as to select an inexperienced male as a new mate. Azure-winged magpies thus provide novel insights into the implications of sexual conflict in birds.

Mediating effects of platelet-derived extracellular vesicles on PM2.5-induced vascular endothelial injury.

At present, PM2.5 exposure has been considered as a major risk factor for cardiovascular disease. Most studies have focused on the toxic mechanism of PM2.5 in direct contact with cells or biomolecules, only few studies have reported the toxic mechanism of PM2.5 mediated by intercellular communication. Extracellular vesicles are the main carriers of intercellular communication and signal transduction in vivo, and play a vital role in the occurrence and development of cardiovascular disease. Therefore, the present research aimed to determine whether platelets-derived extracellular vesicles (P-EVs) secreted from PM2.5-exposed platelets are transferred into the human umbilical vein endothelial cells (HUVECs) and mediated the PM2.5-induced vascular endothelial injury by affecting normal cellular function. The result showed that P-EVs secreted from PM2.5-exposed platelets significantly reduced the proliferation promoting effect of normal P-EVs on vascular endothelium by decreasing the effective factors promoting vascular endothelial growth. Meanwhile, the levels of intercellular adhesion molecules, proinflammatory factors (ICAM-1, IL-6, and TNF-α) and the ROS level of HUVECs were markedly elevated. In addition, the apoptotic rate was increased via up-regulating the protein level of cytochrome-C(Cyt C), Bax, cleaved caspase-3 and down-regulating Bcl-2 in HUVECs, indicating that mitochondrial apoptotic pathway was activated by P-EVs secreted from PM2.5-exposed platelets. Further, the expression level of P-EVs targeted miRNAs in HUVECs was altered, indicating that miRNAs released from P-EVs were transferred to HUVECs and regulated the cellular function, while PM2.5 could inhibit this regulatory effect. In summary, these results demonstrate that the P-EVs secreted from PM2.5-exposed platelets can enter the HUVECs, which mediate the PM2.5-induced vascular endothelial injury. These findings provide a new perspective and theoretical basis for further exploring the mechanism of cardiovascular damage caused by PM2.5 exposure.