A facile and on-site sensing strategy for phenolic compounds based on a novel nanozyme with high polyphenol oxidase-like activity.

Phenolic compounds (PCs) are diverse in nature and undergo complex migration and transformations in the environment, making it challenging to use techniques such as chromatography and other traditional methods to determine the concentration of PCs by separation, individual monitoring and subsequent addition. To address this issue, a facile and on-site strategy was developed to measure the concentration of PCs using a novel nanozyme with polyphenol oxidase-like activity. First, the nanozyme was designed by coordinating the asymmetric ligand nicotinic acid with copper to mimic the structure of mononuclear and trinuclear copper clusters of natural laccases. Subsequently, by introducing 2-mercaptonicotinic acid to regulate the valence state of copper, the composite nanozyme CuNA10S was obtained with significantly enhanced activity. Interestingly, CuNA10S was shown to have a broad substrate spectrum capable of catalyzing common PCs. Building upon the superior performance of this nanozyme, a method was developed to determine the concentration of PCs. To enable rapid on-site sensing, we designed and prepared CuNA10S-based test strips and developed a tailored smartphone sensing platform. Using paper strip sensors combined with a smartphone sensing platform with RGB streamlined the sensing process, facilitating rapid on-site analysis of PCs within a range of 0-100 µM. Our method offers a solution for the quick screening of phenolic wastewater at contaminated sites, allowing sensitive and quick monitoring of PCs without the need for standard samples. This significantly simplifies the monitoring procedure compared to more cumbersome large-scale instrumental methods.

Palmitic acid impairs human and mouse placental function by inhibiting trophoblast autophagy through induction of acyl-coenzyme A-binding protein (ACBP) upregulation.

STUDY QUESTION: Can exposure to palmitic acid (PA), a common saturated fatty acid, modulate autophagy in both human and mouse trophoblast cells through the regulation of acyl-coenzyme A-binding protein (ACBP)? SUMMARY ANSWER: PA exposure before and during pregnancy impairs placental development through mechanisms involving placental autophagy and ACBP expression. WHAT IS KNOWN ALREADY: High-fat diets, including PA, have been implicated in adverse effects on human placental and fetal development. Despite this recognition, the precise molecular mechanisms underlying these effects are not fully understood. STUDY DESIGN, SIZE, DURATION: Extravillous trophoblast (EVT) cell line HTR-8/SVneo and human trophoblast stem cell (hTSC)-derived EVT (hTSCs-EVT) were exposed to PA or vehicle control for 24 h. Female wild-type C57BL/6 mice were divided into PA and control groups (n = 10 per group) and subjected to a 12-week dietary intervention. Afterward, they were mated with male wild-type C57BL/6 mice and euthanized on Day 14 of gestation. Female ACBPflox/flox mice were also randomly assigned to control and PA-exposed groups (each with 10 mice), undergoing the same dietary intervention and mating with ACBPflox/floxELF5-Cre male mice, followed by euthanasia on Day 14 of gestation. The study assessed the effects of PA on mouse embryonic development and placental autophagy. Additionally, the role of ACBP in the pathogenesis of PA-induced placental toxicity was investigated. PARTICIPANTS/MATERIALS, SETTING, METHODS: The findings were validated using real-time PCR, Western blot, immunofluorescence, transmission electron microscopy, and shRNA knockdown approaches. MAIN RESULTS AND THE ROLE OF CHANCE: Exposure to PA-upregulated ACBP expression in both human HTR-8/SVneo cells and hTSCs-EVT, as well as in mouse placenta. PA exposure also induced autophagic dysfunction in HTR-8/SVneo cells, hTSCs-EVT, and mouse placenta. Through studies on ACBP placental conditional knockout mice and ACBP knockdown human trophoblast cells, it was revealed that reduced ACBP expression led to trophoblast malfunction and affected the expression of autophagy-related proteins LC3B-II and P62, thereby impacting embryonic development. Conversely, ACBP knockdown partially mitigated PA-induced impairment of placental trophoblast autophagy, observed both in vitro in human trophoblast cells and in vivo in mice. LARGE SCALE DATA: N/A. LIMITATIONS, REASONS FOR CAUTION: Primary EVT cells from early pregnancy are fragile, limiting research use. Maintaining their viability is tough, affecting data reliability. The study lacks depth to explore PA diet cessation effects after 12 weeks. Without follow-up, understanding postdiet impacts on pregnancy stages is incomplete. Placental abnormalities linked to elevated PA diet in embryos lack confirmation due to absence of control groups. Clarifying if issues stem solely from PA exposure is difficult without proper controls. WIDER IMPLICATIONS OF THE FINDINGS: Consuming a high-fat diet before and during pregnancy may result in complications or challenges in successfully carrying the pregnancy to term. It suggests that such dietary habits can have detrimental effects on the health of both the mother and the developing fetus. STUDY FUNDING/COMPETING INTEREST(S): This work was supported in part by the National Natural Science Foundation of China (82171664, 82301909) and the Natural Science Foundation of Chongqing Municipality of China (CSTB2022NS·CQ-LZX0062, cstc2019jcyj-msxmX0749, and cstc2021jcyj-msxmX0236). The authors declare that they have no conflict of interest. TRIAL REGISTRATION NUMBER: N/A.

Metabolic landscape and pathogenic insights: a comprehensive analysis of high ovarian response in infertile women undergoing in vitro fertilization.

BACKGROUND: In the realm of assisted reproduction, a subset of infertile patients demonstrates high ovarian response following controlled ovarian stimulation (COS), with approximately 29.7% facing the risk of Ovarian Hyperstimulation Syndrome (OHSS). Management of OHSS risk often necessitates embryo transfer cancellation, leading to delayed prospects of successful pregnancy and significant psychological distress. Regrettably, these patients have received limited research attention, particularly regarding their metabolic profile. In this study, we aim to utilize gas chromatography-mass spectrometry (GC-MS) to reveal these patients' unique serum metabolic profiles and provide insights into the disease's pathogenesis. METHODS: We categorized 145 infertile women into two main groups: the CON infertility group from tubal infertility patients and the Polycystic Ovary Syndrome (PCOS) infertility group. Within these groups, we further subdivided them into four categories: patients with normal ovarian response (CON-NOR group), patients with high ovarian response and at risk for OHSS (CON-HOR group) within the CON group, as well as patients with normal ovarian response (PCOS-NOR group) and patients with high ovarian response and at risk for OHSS (PCOS-HOR group) within the PCOS group. Serum metabolic profiles were analyzed using GC-MS. The risk criteria for OHSS were: the number of developing follicles > 20, peak Estradiol (E2) > 4000pg/mL, and Anti-Müllerian Hormone (AMH) levels > 4.5ng/mL. RESULTS: The serum metabolomics analysis revealed four different metabolites within the CON group and 14 within the PCOS group. Remarkably, 10-pentadecenoic acid emerged as a discernible risk metabolite for the CON-HOR, also found to be a differential metabolite between CON-NOR and PCOS groups. cysteine and 5-methoxytryptamine were also identified as risk metabolites for the PCOS-HOR. Furthermore, KEGG analysis unveiled significant enrichment of the aminoacyl-tRNA biosynthesis pathway among the metabolites differing between PCOS-NOR and PCOS-HOR. CONCLUSION: Our study highlights significant metabolite differences between patients with normal ovarian response and those with high ovarian response and at risk for OHSS within both the tubal infertility control group and PCOS infertility group. Importantly, we observe metabolic similarities between patients with PCOS and those with a high ovarian response but without PCOS, suggesting potential parallels in their underlying causes.

Study on the optimal time limit of frozen embryo transfer and the effect of a long-term frozen embryo on pregnancy outcome.

In this retrospective study conducted at Sichuan Jinxin Xinan Women and Children's Hospital spanning January 2015 to December 2021, our objective was to investigate the impact of embryo cryopreservation duration on outcomes in frozen embryo transfer. Participants, totaling 47,006 cycles, were classified into 3 groups based on cryopreservation duration: ≤1 year (Group 1), 1 to 6 years (Group 2), and ≥6 years (Group 3). Employing various statistical analyses, including 1-way ANOVA, Kruskal-Wallis test, chi-square test, and a generalized estimating equation model, we rigorously adjusted for confounding factors. Primary outcomes encompassed clinical pregnancy rate and Live Birth Rate (LBR), while secondary outcomes included biochemical pregnancy rate, multiple pregnancy rate, ectopic pregnancy rate, early and late miscarriage rates, preterm birth rate, neonatal birth weight, weeks at birth, and newborn sex. Patient distribution across cryopreservation duration groups was as follows: Group 1 (40,461 cycles), Group 2 (6337 cycles), and Group 3 (208 cycles). Postcontrolling for confounding factors, Group 1 exhibited a decreased likelihood of achieving biochemical pregnancy rate, clinical pregnancy rate, and LBR (OR < 1, aOR < 1, P < .05). Furthermore, an elevated incidence of ectopic pregnancy was observed (OR > 1, aOR > 1), notably significant after 6 years of freezing time [aOR = 4.141, 95% confidence intervals (1.013-16.921), P = .05]. Cryopreservation exceeding 1 year was associated with an increased risk of early miscarriage and preterm birth (OR > 1, aOR > 1). No statistically significant differences were observed in birth weight or sex between groups. However, male infant birth rates were consistently higher than those of female infants across all groups. In conclusion, favorable pregnancy outcomes align with embryo cryopreservation durations within 1 year, while freezing for more than 1 year may diminish clinical pregnancy and LBRs, concurrently elevating the risk of ectopic pregnancy and preterm birth.

A new metal ion chelator attenuates human tau accumulation-induced neurodegeneration and memory deficits in mice.

Neuronal neurofibrillary tangles containing Tau hyperphosphorylation proteins are a typical pathological marker of Alzheimer's disease (AD). The level of tangles in neurons correlates positively with severe dementia. However, how Tau induces cognitive dysfunction is still unknown, which leads to a lack of effective treatments for AD. Metal ions deposition occurs with tangles in AD brain autopsy. Reduced metal ion can improve the pathology of AD. To explore whether abnormally phosphorylated Tau causes metal ion deposition, we overexpressed human full-length Tau (hTau) in the hippocampal CA3 area of mice and primary cultured hippocampal neurons (CPHN) and found that Tau accumulation induced iron deposition and activated calcineurin (CaN), which dephosphorylates glycogen synthase kinase 3 beta (GSK3ß), mediating Tau hyperphosphorylation. Simultaneous activation of CaN dephosphorylates cyclic-AMP response binding protein (CREB), leading to synaptic deficits and memory impairment, as shown in our previous study; this seems to be a vicious cycle exacerbating tauopathy. In the current study, we developed a new metal ion chelator that displayed a significant inhibitory effect on Tau phosphorylation and memory impairment by chelating iron ions in vivo and in vitro. These findings provide new insight into the mechanism of memory impairment induced by Tau accumulation and develop a novel potential treatment for tauopathy in AD.

miR-181d-5p, which is upregulated in fetal growth restriction placentas, inhibits trophoblast fusion via CREBRF.

PURPOSE: Fetal growth restriction (FGR) is a common complication characterized by impaired placental function and unfavorable pregnancy outcomes. This study aims to elucidate the expression pattern of miR-181d-5p in FGR placentas and explore its effects on trophoblast fusion. METHODS: The expression pattern of miR-181d-5p in human FGR placentas were evaluated using qRT-PCR. Western blot, qRT-PCR, and Immunofluorescence analysis were performed in a Forskolin (FSK)-induced BeWo cell fusion model following the transfection of miR-181d-5p mimic or inhibitor. Potential target genes for miR-181d-5p were identified by screening miRNA databases. The interaction between miR-181d-5p and Luman/CREB3 Recruitment Factor (CREBRF) was determined through a luciferase assay. Moreover, the effect of CREBRF on BeWo cell fusion was examined under hypoxic conditions. RESULTS: Aberrant up-regulation of miR-181d-5p and altered expression of trophoblast fusion makers, including glial cell missing 1 (GCM1), Syncytin1 (Syn1), and E-cadherin (ECAD), were found in human FGR placentas. A down-regulation of miR-181d-5p expression was observed in the FSK-induced BeWo cell fusion model. Transfection of the miR-181d-5p mimic resulted in the inhibition of BeWo cell fusion, characterized by a down-regulation of GCM1 and Syn1, accompanied by an up-regulation of ECAD. Conversely, the miR-181d-5p inhibitor promoted BeWo cell fusion. Furthermore, miR-181d-5p exhibited negative regulation of CREBRF, which was significantly down-regulated in the hypoxia-induced BeWo cell model. The overexpression of CREBRF was effectively ameliorated the impaired BeWo cell fusion induced by hypoxia. CONCLUSIONS: Our study demonstrated that miR-181d-5p, which is elevated in FGR placenta, inhibited the BeWo cell fusion through negatively regulating the expression of CREBRF.

Maternal Hepatitis B Virus Infection and Pregnancy Outcomes of Freeze-Thaw Embryo Transfer.

This cohort study assesses the association of maternal hepatitis B virus (HBV) serostatus with pregnancy outcomes in women undergoing freeze-thaw embryo transfer (FET).

[Isolation and quantification of a 17-epi-dammarane triterpenoid rhuslactone from roots of Rhus chinensis and its preventive effects on coronary heart disease and thrombosis in zebrafish].

Based on mass spectrometry(MS)-guided separation strategy, compound 1 was obtained from the roots of Rhus chinensis. By comprehensive analysis of high resolution-electrospray ionization-mass spectrometry(HR-ESI-MS), nuclear magnetic resonance(NMR) data, and quantum chemical calculation of NMR(qcc-NMR) parameters, compound 1 was elucidated as rhuslactone, a 17-epi-dammarane triterpenoid with a rare 17α-side chain. An HPLC-ELSD method for its quantification in R. chinensis was established and adopted for the quantification of rhuslactone in different batches of R. chinensis. Rhuslactone displayed a good linear relationship within the range of 0.021 3-1.07 µmol·mL~(-1 )(r=0.997 6), and the average recovery was 99.34% [relative standard deviation(RSD) 2.9%). Moreover, the results of the evaluation test of the preventive effects of rhusalctone on coronary heart disease(CHD) and thrombosis showed that rhuslactone(0.11 nmol·mL~(-1)) significantly alleviated heart enlargement and venous congestion and increased cardiac output(CO), blood flow velocity(BFV), and heart rate, thereby reducing thrombus formation in zebrafish with CHD. The effects of rhuslactone on CO and BFV were superior to that of digoxin(1.02 nmol·mL~(-1)), and its effect on improving heart rate was comparable to that of digoxin. This study provides experimental references for the isolation, identification, quality control, and application of rhuslactone from R. chinensis against CHD. It is worth mentioning that this study has discussed some omissions in the determination of the stereochemistry of C-17 in dammarane triterpenoids in the present coursebook Chemistry of Chinese Medicine and some research papers, that is, the compound may be 17-epi-dammarane triterpenoid. This paper has also proposed steps for the establishment of C-17 stereochemistry.

Effects of COVID-19 home quarantine on pregnancy outcomes of patients with gestational diabetes mellitus: a retrospective cohort study.

OBJECTIVE: This study aimed to evaluate the effects of the home quarantine on pregnancy outcomes of gestational diabetes mellitus (GDM) patients during the COVID-19 outbreak. METHODS: The complete electronic medical records of patients with GDM with home quarantine history were collected and classified into the home quarantine group from 24 February 2020 to 24 November 2020. The same period of patients with GDM without home quarantine history were included in the control group from 2018 to 2019. The pregnant outcomes of the home quarantine and control groups were systematically compared, such as neonatal weight, head circumference, body length, one-minute Apgar score, fetal macrosomia, and pre-term delivery. RESULTS: A total of 1358 patients with GDM were included in the analysis, including 484 in 2018, 468 in 2019, and 406 in 2020. Patients with GDM with home quarantine in 2020 had higher glycemic levels and adverse pregnancy outcomes than in 2018 and 2019, including higher cesarean section rates, lower Apgar scores, and higher incidence of macrosomia and umbilical cord around the neck. More importantly, the second trimester of home quarantine had brought a broader impact on pregnant women and fetuses. CONCLUSION: Home quarantine has aggravated the condition of GDM pregnant women and brought more adverse pregnancy outcomes during the COVID-19 outbreak. Therefore, we suggested governments and hospitals strengthen lifestyle guidance, glucose management, and antenatal care for patients with GDM with home quarantine during public health emergencies.

Potential antiplatelet aggregation metabolites from the discarded sorghum (Sorghum bicolor L.) root.

Sorghum (Sorghum bicolor L.) is the fifth largest crop in the world and has potential health benefits, but vast quantities of sorghum roots are discarded after harvest. Based on the previous antiplatelet aggregation for this species, two new multi-substituted 3H-indole alkaloids sorghumine A (1) and sorghumine B (2), together with 14 known compounds (3-16), were found from the water extract of sorghum roots. Compounds 1-2 were identified by analyzing their spectroscopic data and physic and chemical properties, and the absolute configuration was further determined by electronic circular dichroism (ECD) analysis and calculations. 1-2, 4, 6-8 and 13-15 showed significant inhibition of platelet aggregation induced by adenosine diphosphate. 2-4, 6-9 and 11 showed significant inhibition of platelet aggregation induced by collagen. 4-6, 8, 10-11 and 16 showed significant inhibition on platelet aggregation induced by thrombin. Furthermore, molecular docking showed that active compounds can bind to P2Y12 and COX-1 receptors in platelet.

The effect of varied exercise intensity on antioxidant function, aortic endothelial function, and serum lipids in rats with non-alcoholic fatty liver disease / El efecto del ejercicio de intensidad variada sobre la función antioxidante, la función endotelial aórtica y los lípidos séricos en ratas con enfermedad del hígado graso no alcohólico

Abstract This study aimed to compare the effects of diet and exercise of different intensities on antioxidant function, aortic endothelial cell function and serum lipids in NAFLD (nonalcoholic fatty liver disease) rats. Fifty Sprague-Dawley (SD) rats (180-220g) were randomly divided into two experimental groups and fed either a standard rodent chow diet (CON; n=10) or a high-fat diet (HFD; n=40). After 16 weeks, the animals that received the HFD were randomly separated into a high-fat control group (HFC; n=10) or three exercise training groups: HFD and low-intensity exercise (LE; n=10), HFD and moderate-intensity exercise (ME; n=10), and HFD and incremental intensity exercise (IE; n=10). These experimental rats keep sedentary or trained for the next six weeks. A detection kit was used to detect nitric oxide synthase (NOs), nitric oxide (NO), malondialdehyde (MDA) and other markers of aortic oxidative stress. The expression levels of endothelial nitric oxide synthase (e-NOS) and endothelin-1 (ET-1) were detected by immunohistochemistry. TC, TG, and other lipid metabolism parameters were detected by an automatic analyzer. Exercise with different intensities could improve lipid metabolism, enhance antioxidant function, reduce MDA (P<0.01), increase NO (P<0.01), and improve the expression of e-NOS and ET-1 (P<0.01) protein levels in NAFLD rats. Decreased blood lipids were exhibited in all exercise groups. Notably, the moderate-intensity exercise demonstrated more effect on increasing glutathione (GSH) contents (P<0.01) and decreased the expression of ET-1 protein levels (P<0.01). The results showed that exercise at different intensities improved lipid metabolism and enhanced anti-oxidation function. Moderate exercise could improve the function of aortic endothelial cells.

Resumen Este estudio tuvo como objetivo comparar los efectos de la dieta y el ejercicio a diferentes intensidades sobre la función antioxidante, la función de las células endoteliales aórticas y los lípidos séricos en ratas NAFLD (con enfermedad del hígado graso no alcohólico) y alimentados con una dieta estándar para roedores (CON; n = 10) o con una dieta alta en grasas (HFD; n = 40). Después de 16 semanas, los animales que recibieron HFD se separaron aleatoriamente en un grupo de control alto en grasas (HFC; n=10) o tres grupos de entrenamiento físico: HFD y ejercicio de baja intensidad (LE; n=10), HFD y ejercicio de intensidad moderada (ME; n=10), y HFD y ejercicio de intensidad incremental (IE; n=10). Estas ratas experimentales se mantuvieron sedentarias o entrenadas durante las próximas seis semanas. Se utilizó un kit de detección para determinar óxido nítrico sintetasa (NO), óxido nítrico (NO), malondialdehído (MDA) y otros marcadores de estrés oxidativo aórtico. Los niveles de expresión de la óxido nítrico sintetasa endotelial (e-NOS) y endotelina-1 (ET-1) se detectaron mediante inmunohistoquímica. El analizador automático detectó TC, TG y otros parámetros del metabolismo de los lípidos. El ejercicio con diferente intensidad mejoró el metabolismo de los lípidos, mejoró la función antioxidante, redujo la MDA (P <0,01), aumentó el NO (P <0,01) y mejoró la expresión de los niveles de proteína e-NOS y ET-1 (P <0,01) en ratas NAFLD. Se observó una disminución de los lípidos en sangre en todos los grupos de ejercicio. En particular, el ejercicio de intensidad moderada demostró un mayor efecto en el aumento del contenido de glutatión (GSH) (P<0,01) y disminuyó la expresión de los niveles de proteína ET-1 (P<0,01). Los resultados mostraron que el ejercicio a diferentes intensidades mejoró el metabolismo de los lípidos y mejoró función antioxidante. El ejercicio moderado podría mejorar la función de las células endoteliales aórticas.

[HADHA Inhibits the Migration and Invasion of HTR-8/SVneo Cells by Regulating PI3K/AKT Signaling Pathway].

Objective: To explore the effects of hydroxyacyl-CoA dehydrogenase alpha subunit (HADHA) on the migration and invasion of HTR-8/SVneo cells, a human trophoblast cell line, and its potential mechanism of action. Methods: Immunofluorescence staining was done to evaluate the expression levels of HADHA in samples of normal villi and recurrent spontaneous abortion (RSA) villi at 6-8 weeks. Lentiviral infection system was used to construct stable HTR-8/SVneo cell lines with HADHA overexpression and knockdown. Western blot, qRT-PCR, Wound-healing assay, and Transwell assay were used to determine the effect of HADHA on the migration and invasion of HTR-8/SVneo cells and the expression of relevant genes. Transcriptome sequencing and bioinformatics analysis were done to screen for the potential target genes and signaling pathways regulated by HADHA. The specific molecular mechanism of how HADHA regulates the migration and invasion of HTR-8/SVneo cells was examined by adding the inhibitor of protein kinase B (PKB/AKT). Results: HADHA was highly expressed in extravillous trophoblasts (EVT) of RSA villus samples as compared with samples from the normal control group. In HTR-8/SVneo cells overexpressing HADHA, the expression levels of migration and invasion-related genes, including HLA-G, MMP2, MMP9, and NCAD, were decreased (P<0.01,P<0.05), and the migration and invasion abilities of HTR-8/SVneo cells were weakened (P<0.05). HADHA knockdown increased the expression levels of HLA-G, MMP2, MMP9, and NCAD (P<0.01, P<0.05), and promoted the migration and invasion of HTR-8/SVneo cells (P<0.05). In addition, HADHA overexpression decreased the phosphorylation levels of PI3K and AKT (P<0.05) and inhibited the PI3K/AKT signaling pathway. HADHA knockdown activated the PI3K/AKT signaling pathway. When MK-2206, an AKT inhibitor, was added to stable HTR-8/SVneo cell lines with HADHA knockdown, the migration and invasion of the cells were significantly reduced. Conclusion: HADHA inhibits the migration and invasion of HTR-8/SVneo cells by inhibiting the PI3K/AKT signaling pathway.

MicroRNA cargo of extracellular vesicles released by skeletal muscle fibro-adipogenic progenitor cells is significantly altered with disuse atrophy and IL-1ß deficiency.

Fibro-adipogenic progenitor cells (FAPs) are a population of stem cells in skeletal muscle that play multiple roles in muscle repair and regeneration through their complex secretome; however, it is not well understood how the FAP secretome is altered with muscle disuse atrophy. Previous work suggests that the inflammatory cytokine IL-1ß is increased in FAPs with disuse and denervation. Inflammasome activation and IL-1ß secretion are also known to stimulate the release of extracellular vesicles (EVs). Here, we examined the microRNA (miRNA) cargo of FAP-derived, platelet-derived growth factor receptor A (PDGFRα+) EVs from hindlimb muscles of wild-type and IL-1ß KO mice after 14 days of single-hindlimb immobilization. Hindlimb muscles were isolated from mice following the immobilization period, and PDGFRα+ extracellular vesicles were isolated using size-exclusion chromatography and immunoprecipitation. Microarrays were performed to detect changes in miRNAs with unloading and IL-1ß deficiency. Results indicate that the PDGFRα+, FAP-derived EVs show a significant increase in miRNAs, such as miR-let-7c, miR-let-7b, miR-181a, and miR-124. These miRNAs have previously been demonstrated to play important roles in cellular senescence and muscle atrophy. Furthermore, the expression of these same miRNAs was not significantly altered in FAP-derived EVs isolated from the immobilized IL-1ß KO. These data suggest that disuse-related activation of IL-1ß can mediate the miRNA cargo of FAP-derived EVs, contributing directly to the release of senescence- and atrophy-related miRNAs. Therapies targeting FAPs in settings associated with muscle disuse atrophy may therefore have the potential to preserve muscle function and enhance muscle recovery.

Metabolic response of earthworms (Pheretima guillemi) to silver nanoparticles in sludge-amended soil.

Silver nanoparticles (AgNPs) can enter soils via the application of sludge and pose risks to soil invertebrates. However, current knowledge regarding the toxicity of AgNPs at environmentally relevant concentration is insufficient, especially at the molecular level. Therefore, we examined the effects of low-level AgNPs (7.2 mg kg-1, dry weight) on the bioaccumulation, pathology and metabolism of earthworms (Pheretima guillemi). After exposure for 28 d, earthworms were dissected into digestive system and the rest of the body to explore the response of different body parts to AgNPs. Ag concentration in the digestive system of exposed group (2.5 mg kg-1, dry weight) was significantly higher than that of the control group (0.5 mg kg-1, dry weight). AgNPs exposure had no significant effects on the survival and growth, but induced intestinal damage and metabolic interference to earthworms relative to the control. Metabolomics analysis showed that AgNPs exposure disturbed the glycerophospholipid metabolism, glutathione metabolism and energy metabolism in the digestive system and the energy metabolism in the rest of the body. AgNPs exposure also induced lipid peroxidation in the digestive system. The different metabolic responses between two body parts highlighted the importance of the uptake routes of Ag. These results provide a biochemical insight for the risk assessment of low-level AgNPs in terrestrial environment.

A decrease in cluster of differentiation 2 expression on natural killer cells is associated with polycystic ovary syndrome but not influenced by metformin in a mouse model†.

PROBLEM: Natural killer (NK) cells from the peripheral blood and spleen represent the source from which various tissues replenish their immune cell populations. Hyperandrogenism and high interleukin-2 (IL-2) levels are factors present in polycystic ovary syndrome (PCOS). These factors and metformin, one of the commonest medications used in treating PCOS, may have an impact on NK cells. However, this is presently unknown. Here, we aimed to assess the distribution of peripheral blood and splenic NK cells and their CD2 and CD94 expression patterns in a PCOS mouse model and test whether metformin could reverse these effects. METHOD OF STUDY: Four mouse groups were designed as follows (n = 15/group): control, PCOS, PCOS plus vehicle, PCOS plus metformin. Dehydroepiandrosterone and a high-fat diet were administered to induce the PCOS mouse model. Flow cytometry was used to analyze the expressions of CD2 and CD94 on peripheral blood and splenic NK cells. RESULTS: PCOS mice had a low surface-density of CD2 on peripheral blood NK cells and a decreased percentage of CD2+ splenic NK cells. Metformin administration did not significantly influence these changes; however, it reduced the splenic NK cell counts. CONCLUSIONS: Our findings proved the association of PCOS with an altered expression of CD2 on peripheral blood and splenic NK cells and that of metformin with a lowered splenic NK cell reserve in PCOS conditions. These findings could further unlock key mechanisms in PCOS pathophysiology and in the mechanism of action of metformin, towards improving PCOS management.

Study on the university students' satisfaction of the wisdom tree massive open online course platform based on parameter optimization intelligent algorithm.

INTRODUCTION: Curriculum learning through the wisdom tree massive open online course platform not only gets rid of the limitations of specialty, school and region, eliminates the limitations of time and space in traditional teaching, but also effectively solves the problem of educational equity. OBJECTIVES: This paper proposes an intelligent algorithm combining decision tree, support vector machine, and simulated annealing to obtain the best classification accuracy and decision rules for university students' satisfaction with the wisdom tree massive open online course platform. METHODS: This study takes the university students in Fuzhou city information management department as the survey object, and adopts the electronic questionnaire survey method. A total of 1136 formal questionnaires were responded, and 1028 valid questionnaires were obtained after data cleaning and deleting invalid questionnaires (the effective rate was 90.49%). In this paper, the reliability and validity of the questionnaire were tested by IBM SPSS-20.0 software, and six explanatory variables including function, achievement, exercise, quality, richness, and interaction were obtained by principal component analysis. Then, the questionnaire data is converted to CSV (comma separated values) format for analysis. This paper proposes an intelligent algorithm combining decision tree, support vector machine, and simulated annealing to obtain the best classification accuracy and decision rules for university students' satisfaction with the wisdom tree massive open online course platform. In this paper, the proposed algorithm is compared with decision tree, random forest, k-nearest neighbor, and support vector machine to verify its performance. RESULTS: The experimental results show that training set classification accuracy of decision tree, random forest, k-nearest neighbor, only support vector machine and the proposed algorithm (simulated annealing + support vector machine) are 92.21%, 96.10%, 95.67%, 97.29%, and 99.58%, respectively. CONCLUSION: The proposed algorithm simulated annealing + support vector machine does increase the classification accuracy. At the same time, the 11 decision rules generated by simulated annealing + decision tree can provide useful information for decision makers.

Iodothyronine deiodinase 2 (DiO2) regulates trophoblast cell line cycle, invasion and apoptosis; and its downregulation is associated with early recurrent miscarriage.

INTRODUCTION: Trophoblast development is a crucial event in placentation and pregnancy complications but its underlying mechanisms remain unclear. Thus, we aimed at investigating the role of DiO2 in trophoblast cell line decisions and assessing its placental villous expression in early recurrent miscarriage (ERM) patients. METHODS: The placental villous expression of DiO2 was determined with immunofluorescence. Cell proliferation was measured with the CCK8 kit while cell-cycle and apoptosis were studied with flow-cytometry. Cell migration and invasion were measured with wound-healing and transwell assays, respectively. Gene expression was then assessed with RT-qPCR and western blotting. RESULTS: DiO2 is expressed in the CTB, PCT, DCT and STB of the placenta. Its overexpression arrested trophoblast cell line proliferation at the G1 phase of the cell-cycle by downregulating cyclin-D1 and PCNA, while promoting apoptosis via increased caspase-3 activity and inhibition of the AKT and ERK1/2 signaling pathways. Also, it augmented trophoblast cell line migration and invasion via the upregulation of N-cadherin, vimentin, fascin-1, twist-1 and other epithelial-mesenchymal transition genes. DiO2 knockdown elicited the opposite effects. Surprisingly, each of these effects of DiO2 manipulation was not mediated by thyroid hormone metabolism. Assessment of the ERM placental villi revealed a downregulation of DiO2, N-cadherin, vimentin, fascin-1 and twist-1. The expression of E-cadherin remained unchanged in these placentae. DISCUSSION: During placentation, DiO2 may inhibit trophoblast proliferation while facilitating their differentiation into an invasive phenotype; and that its downregulation may contribute to the shallow trophoblast invasion that precedes ERM. Hence, DiO2 is a potential therapeutic target against ERM.

THBS1 regulates trophoblast fusion through a CD36-dependent inhibition of cAMP, and its upregulation participates in preeclampsia.

Preeclampsia is a pregnancy complication which threatens the survival of mothers and fetuses. It originates from abnormal placentation, especially insufficient fusion of the cytotrophoblast cells to form the syncytiotrophoblast. In this study, we found that THBS1, a matricellular protein that mediates cell-to-cell and cell-to-matrix interactions, is downregulated during the fusion of primary cytotrophoblast and BeWo cells, but upregulated in the placenta of pregnancies complicated by preeclampsia. Also, THBS1 was observed to interact with CD36, a membrane signal receptor and activator of the cAMP signaling pathway, to regulate the fusion of cytotrophoblast cells. Overexpression of THBS1 inhibited the cAMP signaling pathway and reduced the BeWo cells fusion ratio, while the effects of THBS1 were abolished by a CD36-blocking antibody. Our results suggest that THBS1 signals through a CD36-mediated cAMP pathway to regulate syncytialization of the cytotrophoblast cells, and that its upregulation impairs placental formation to cause preeclampsia. Thus, THBS1 can serve as a therapeutic target regarding the mitigation of abnormal syncytialization and preeclampsia.