Metabolic profiles of children aged 2-5 years born after frozen and fresh embryo transfer: A Chinese cohort study.

BACKGROUND: Frozen embryo transfer (FET) has become a widely employed assisted reproductive technology technique. There have historically been concerns regarding the long-term metabolic safety of FET technology in offspring due to pregnancy-induced hypertension and large for gestational age, both of which are well-recognized factors for metabolic dysfunction of children. Therefore, we aimed to compare the metabolic profiles of children born after frozen versus fresh embryo transfer at 2 to 5 years of age. METHODS AND FINDINGS: This was a prospective cohort study. Using data from the "Assisted Reproductive Technology borned KIDs (ARTKID)," a birth cohort of offspring born from assisted reproductive technology at the Institute of Women, Children and Reproductive Health, Shandong University, China. We included 4,246 singletons born after FET (n = 2,181) and fresh embryo transfer (n = 2,065) enrolled between 2008 and 2019 and assessed the glucose and lipid variables until the age of 2 to 5 years. During a mean follow-up of 3.6 years, no significant differences were observed in fasting blood glucose, fasting insulin, Homeostatic Model Assessment of Insulin Resistance Index, total cholesterol, triglycerides, low-density lipoprotein-cholesterol, and high-density lipoprotein-cholesterol levels between offspring conceived by fresh and frozen embryo transfer in the crude model and adjusted model (adjusted for parental age, parental body mass index, parental education level, paternal smoking, parity, offspring age and sex). These results remained consistent across subgroup analyses considering offspring age, the stage of embryo transfer, and the mode of fertilization. Results from sensitivity analysis on children matched for age within the cohort remains the same. The main limitation of our study is the young age of the offspring. CONCLUSIONS: In this study, the impact of FET on glucose and lipid profiles during early childhood was comparable to fresh embryo transfer. Long-term studies are needed to evaluate the metabolic health of offspring born after FET.

Pulsed electric field-assisted extraction of hesperidin from tangerine peel and its technological optimization through response surface methodology.

BACKGROUND: Tangerine peel is rich in flavonoids, particularly hesperidin, which has anti-inflammatory, antioxidant and anticancer biological activities. However, it is often wasted during citrus processing. The current common extraction method for hesperidin is solvent extraction, which has the characteristics of low extraction rate and high contamination. The aim of this study was to investigate the effect of pulsed electric field-assisted alkali dissolution extraction, followed by an acidification precipitation method, on the extraction rate and structure of hesperidin from tangerine peel. RESULTS: The results showed that the selected factors (material/liquid ratio, electric field intensity and pulse number) had a significant effect on the extraction yield. An optimum condition of 66.00 mL g-1, 4.00 kV cm-1 and 35.00 pulses gave the maximum amount (669.38 µg mL-1), which was consistent with the theoretically predicted value by software (672.10 µg mL-1), indicating that the extraction process was feasible. In addition, the purified extract was further identified as hesperidin from UV and NMR spectra. CONCLUSION: An appropriate strength of pulsed electric field-assisted alkali dissolution extraction followed by an acidification precipitation method can effectively improve the extraction rate of orange peel, and the purity of the extracted orange peel is higher. Compared with the traditional extraction, the pulsed electric field-assisted extraction method may be a potential technology for hesperidin extraction, which is beneficial for the high-value utilization of citrus resources. © 2024 Society of Chemical Industry.

A blood-based, metabolite and demographic characteristic markers panel for the diagnosis of Alzheimer's disease.

Aims: This work was designed to provide early diagnosis strategies for Alzheimer's disease (AD) based on the identification of blood metabolic biomarkers. Patients & methods: A total of 90 subjects aged 60 years or older were included in this study; 45 patients were assigned to the case group and control group, respectively. A total of 31 target metabolites were quantitatively analyzed by parallel reaction monitoring between the two groups. Results & conclusion: Three metabolites were screened out, including cystine, serine and alanine/sarcosine. Logistic regression and random forest analysis were used to establish AD diagnosis models, and the model combining metabolic biomarkers and demographic variables had higher detection efficiency (area under the curve = 0.869). A combination diagnostic model to provide a scientific reference for early screening and diagnosis of AD was constructed.

Immunolocalization of antibacterial peptide S100A7 in mastitis goat mammary gland and lipopolysaccharide induces the expression and secretion of S100A7 in goat mammary gland epithelial cells via TLR4/NFκB signal pathway.

The antimicrobial peptide S100A7, with antimicrobial activities for a broad spectrum of bacteria, has attracted more and more attention for the prevention and treatment of mastitis. However, there is little information about the expression and regulation mechanism of S100A7 in mastitis goats. This study revealed that S100A7 was mainly expressed in the stratified squamous epithelium of teat skin and streak canal, and S100A7 was present weakly in the healthy goat alveolus yet densely in the mastitis goat collapsed alveolus. Goat mammary epithelial cells (MECs) were isolated and treated with 2.5, 5, 10 and 20 µg/mL lipopolysaccharide (LPS) respectively for a different time, S100A7 mRNA expression and protein secretion were upregulated significantly with LPS treatment for 3 h, and the secretion level of S100A7 descended after 48 h treatment for all of these four groups. Moreover, after treatment with LPS, the mRNA levels of Toll-like receptor 4 (TLR4) and MyD88 were up-regulated, and the phosphorylation of p65 was up-regulated markedly. However, adding TLR4 inhibitor TAK-242 or/and NF-κB inhibitor QNZ significantly suppressed the phosphorylation of p65, and then inhibited the expression and secretion of S100A7 induced by LPS treatment. In conclusion, LPS induced the expression and secretion of S100A7 in goat MECs via TLR4/NF-κB signaling pathway.

Long-term cardiometabolic effects of ambient ozone pollution in a large Chinese population.

Limited studies investigated the effects of long-term ozone exposure on cardiometabolic health. We aimed to examine the association of long-term ozone exposure with a range of cardiometabolic diseases, as well as the subclinical indicators in Eastern China. The study included 202,042 adults living in 11 prefecture-level areas in Zhejiang Province between 2014 and 2021. Using a satellite-based model with a 1 × 1 km spatial resolution, we estimated residential 5-year average ozone exposures for each subject. Mixed-effects logistic and linear regression models were applied to explore the associations of ozone exposure with cardiometabolic diseases and subclinical indicators, respectively. We found that a 9% [95% confidence interval (95% CI): 7-12%] higher in odds of cardiometabolic disease per 10 µg/m3 increase in ozone exposure. Specifically, we also found higher prevalence of cardiovascular diseases (15%), stroke (19%), hypertension (7%), dyslipidemia (15%), and hypertriglyceridemia (9%) associated with ozone exposure. However, we did not find significant associations between ozone exposure and coronary heart disease, myocardial infarction, or diabetes mellitus. Long-term ozone exposures were also significantly associated with adverse changes in systolic blood pressure, diastolic blood pressure, total serum cholesterol, triglyceride, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, glucose concentration, and body mass index. Our results showed that people with lower education levels, those over 50 years old, and those who were overweight or obese were more susceptible to the effects of ozone on cardiometabolic diseases. Our findings demonstrated the detrimental effects of long-term ozone exposure on cardiometabolic health, emphasizing the need for ozone control strategies to reduce the burden of cardiometabolic diseases.

Human umbilical cord mesenchymal stem cells conditioned medium exerts anti-tumor effects on KGN cells in a cell density-dependent manner through activation of the Hippo pathway.

BACKGROUND: The conditioned medium from human umbilical cord mesenchymal stem cells (UCMSCs-CM) provides a new cell-free therapy for tumors due to its unique secretome. However, there are many contradictory reports about the effect of UCMSCs-CM on tumor cells. The loss of contact inhibition is a common characteristic of tumor cells. A relationship between the effect of UCMSCs-CM on tumor cells and contact inhibition in tumor cells is rarely concerned. Whether the effect of UCMSCs-CM on tumor cells is affected by cell density? Here, we explored the effect of UCMSCs-CM on granulosa tumor cell line (KGN) cells at low or high density. METHODS: Growth curve and CCK8 assay were used to assess cell proliferation and viability. Scratch wound and matrigel invasion assay were implicated to detect cell motility of KGN cells. UCMSCs-CM effects on cell cycle, apoptosis and pathway-related proteins were investigated by flow cytometry, TUNEL assay, western blot and immunofluorescence analysis respectively. RESULTS: In growth curve analysis, before KGN cells proliferated into confluence, UCMSCs-CM had no effect on cell proliferation. However, once the cells proliferate to contact each other, UCMSCs-CM significantly inhibited proliferation. Meanwhile, when KGN cells were implanted at high density, UCMSCs-CM could induce cell cycle arrest at G1 phase, inhibit cell migration, invasion and promote apoptosis. While it had no similar effect on KGN cells implanted at low density. In mechanism, the UCMSCs-CM treatment activated the Hippo pathway when KGN cells were implanted at high density. Consistently, the MST1/2 inhibitor, XMU-MP-1, inhibited the activation of the Hippo pathway induced by UCMSCs-CM treatment and accordingly declined the anti-tumor effect of UCMSCs-CM on KGN cells. CONCLUSIONS: The effect of UCMSCs-CM on tumor cells is affected by cell density. UCMSCs-CM exerted anti-tumor effect on KGN cells by activating Hippo pathway to restore contact inhibition. Our results suggest that UCMSCs-CM is a promising therapeutic candidate for GCT treatment.

Effects of 4-vinylcyclohexene diepoxide on the cell cycle, apoptosis, and steroid hormone secretion of goat ovarian granulosa cells.

4-Vinylcyclohexene diepoxide (VCD) is a potentially hazardous industrial chemical that may enter a goat's body in various ways during industrial breeding. Ovarian granulosa cells (GCs) play a critical role in supporting follicle development and hormone synthesis. However, there are few studies on the effect of VCD on goat ovarian GCs. In this study, goat ovarian GCs were isolated and treated with VCD. The results showed that treatment with VCD increased the proportion of S phase and G2/M cells, but decreased the proportion of G1 phase. VCD treatment significantly inhibited the expression of cyclin A and cyclin-dependent kinase 2 (CDK2). But the expression levels of p21 and p27 were increased. VCD could induce an apparent increase in the proportion of apoptosis and the level of cleaved caspase 3. Treatment with VCD significantly reduced the progesterone and estrogen concentration in the medium in which goat ovarian GCs were cultured. Correspondingly, the expression level of steroidogenic acute regulatory protein (STAR) was significantly downregulated. Treatment with 0.25 and 0.5 mM VCD, the protein expression level of insulin-like growth factor 1 receptor (IGF1R) and Akt were significantly decreased. Moreover, treatment with 0.25 mM VCD significantly inhibited the phosphorylation of Akt. In conclusion, VCD exposure had cytotoxic effects such as decreased cell viability, disordered cell cycle, increased apoptosis, and interference with steroid hormone synthesis on goat GCs. These cytotoxic effects of VCD on goat GCs may be due to the downregulation of IGF1R and the inhibition of IGF1R/Akt signaling pathway.

Selective capture of toxic anionic dyes of a novel prepared DMDAAC-grafted chitosan/genipin/cellulose hydrogel beads with antibacterial activity.

Novel eco-friendly and green dimethyldiallylammonium chloride (DMDAAC) grafted chitosan/genipin/cellulose hydrogel beads (CCBG-g-PDMDAAC), were fabricated as selective adsorbents for anionic dyes. The physical and chemical structural changes of the prepared hydrogels were evaluated by FTIR, XRD, SEM and TG-DSC analysis. Results showed CCBG-g-PDMDAAC efficiently and selectively adsorb anionic dyes (Reactive Red 195-RR195 and Methyl orange-MO) from mixture of dye solutions. Endowed chitosan-based hydrogels the advantage of acid insolubility and good adsorption. RR195 and MO adsorption process were described better with pseudo-second-order kinetic model and Langmuir isotherm model with a maximum adsorption capacity of 1333.52 and 190.48 mg/g, respectively, indicating that monolayer chemisorption controlled the sorption process. Moreover, the hydrogels exhibited nice reusability and against S. aureus and E. coli. The hydrogels are promising for the potential application in wastewater treatment and antibacterial simultaneously.

Synthesis of Hydrophobic Propionyl Neohesperidin Ester Using an Immobilied Enzyme and Description of Its Anti-proliferative and Pro-apoptotic Effects on MCF-7 Human Breast Cancer Cells.

Neohesperidin (NH) is a natural flavonoid glycoside compound with considerable physiological and pharmacological activities. However, its bioavailability is limited due to poor solubility, and few studies have so far attempted improve the solubility and bioavailability of NH. In this study, we structurally modified NH using an immobilized lipase to improve lipophilicity and therefore expand its applicability in lipophilic media as well as enhance its bioavailability in vivo. In addition, we aimed investigated the pro-apoptoptotic activity of this new compound (propionyl neohesperidin ester, PNHE) in MCF-7 breast cancer cells using a variety of cellular assays, including the MTT (3-(4, 5-dimethyl- 2-thiazolyl)-2, 5-diphenyl-2-h-tetrazolium bromide assay, assessment of intracellular reactive oxygen species (ROS) levels, and flow cytometry. We successfully synthesized PNHE using immobilized lipases, and the esterification of NH was confirmed by Fourier transform-infrared spectroscopy (FT-IR). Compared to NH, HNPE showed higher anti-proliferative and pro-apoptotic in MCF-7 breast cancer cells, which may be explained by its increased lipophilicity compared to neohesperidin, benefiting to the action of NH on the cancer cell wall. The IC50 of PNHE for inducing apoptosis of MCF-7 cells was 185.52 µg/mL. PNHE increased both the proportion of cells in Sub-G1 phase and the cellular ROS content, indicating a certain therapeutic effect of HNPE on breast cancer.

Preparation of crystalline nanocellulose/hydroxypropyl ß cyclodextrin/carboxymethyl cellulose polyelectrolyte complexes and their controlled release of neohesperidin-copper (II) in vitro.

A natural hydrogel film was prepared using carboxymethyl cellulose (CMC), cellulose nanocrystals (CNC), and hydroxypropyl ß cyclodextrin (HP-ß-CD) as reactants and citric acid as the cross-linking agent and used for the controlled release of neohesperidin-copper(II)(NH-Cu (II)). The hydrogel film was characterized by ATR-FTIR, XRD, TGA and DSC. The film showed controlled swelling behavior; the release behavior of NH-Cu(II) from the hydrogel film was also investigated in different solutions including distilled water, various salt solutions including 0.9% NaCl, and solutions having different pH values. Thiazolyl blue tetrazolium bromide assay and relative growth rates were adopted to evaluate the biocompatibility and cytotoxicity of the prepared hydrogel films. The results indicated that the expansion kinetics followed Fickian diffusion and Schott's second-order kinetics model. The hydrogel film exhibited enhanced mechanical properties and improved thermal stability at high temperatures due to the addition of CNC, with the amount of added CNC affecting the swelling ratio, salt sensitivity, and pH sensitivity of the hydrogel film in different solutions. Additionally, the CNC largely improved the loading and encapsulation efficiency of the hydrogel films, with the optimal CNC addition amount being 4% which yielded a loading amount of 753.75 mg/g and an accumulated release rate of 85.08%. The hydrogel film with proven cell compatibility and non-cytotoxicity can potentially be used as a drug delivery and controlled release material.

A Novel and High-Effective Biosynthesis Pathway of Hesperetin-7-O-Glucoside Based on the Construction of Immobilized Rhamnosidase Reaction Platform.

Hesperetin-7-O-glucoside (HMG) is a precursor for synthesizing a sweetener named neohesperidin dihydrochalcone, and the coordination toward flavonoids of metal ions tends to increase the water solubility of flavonoids. In order to achieve effective synthesis of HMG, an immobilized enzyme catalysis platform was constructed using an immobilized rhamnosidase on Fe3O4@graphene oxide (Fe3O4@GO), a novel reaction pathway based on the platform was designed for preparing a hesperidin complex as a soluble substrate, and ammonium hydroxide as a ligand dissociation agent to obtain HMG. The Fe3O4@GO was characterized by Fourier transform infrared (FT-IR), X-ray diffraction (XRD), scanning electron microscope (SEM), and thermal methods (TG/DSC) analysis to evaluate the immobilization matrix properties. The enzyme activity in free and immobilized form at different pH and temperature was optimized. The reusability of immobilized enzyme was also determined. In addition, the kinetic parameters (K m and V max) were computed after experiment. Results indicated that rhamnosidase immobilized on Fe3O4@GO using a green cross-linker of genipin hydrolyzed successfully and selectively the soluble hesperidin-Cu (II) complex into HMG-Cu (II), a permanent magnet helped the separation of immobilized enzyme and hydrolytes, and ammonium hydroxide was an effective ligand dissociation agent of translating HMG-Cu (II) into HMG with high purity determined by ultraviolet-visible (UV-Vis) spectra analysis and time-of-flight mass spectrometry (TOF-MS). As a result, a novel and high-effective biosynthesis pathway of HMG based on a selectively catalytic reaction platform were constructed successfully. The pathway based on the platform has great potential to produce valuable citrus monoglycoside flavonoid HMG, and the designed reaction route are feasible using the hesperidin-Cu (II) complex with good solubility as a reaction substrate and using ammonium water as a dissociation agent.

Development of an orange juice beverage formulated with oat beta-glucan and whey protein isolate.

BACKGROUND: A beverage was developed using beta-glucan and whey protein isolate (WPI). The sensory attributes and changes of the physiochemical properties (pH value, total acidity, total soluble solids, sugar-acid ratio, color, viscosity, turbidity, and browning index) of the beverage during 48-h storage were evaluated by comparison with the commercial product and a blank sample. RESULTS: The sweetness, smoothness, and overall acceptance of the developed beverage were similar to the commercial and blank samples. The suspension stability of the developed beverage was significantly better than that of the commercial products. The total acidity of the beverage decreased considerably after 36-h storage. Regarding color changes, the three samples showed a significant increase in L and b values after 6 h of storage. The viscosity of the developed beverage rose significantly after 24 h of storage. The increase in the concentration of beta-glucan in the mixed hydrocolloid caused a significant elevation in the levels of viscosity. CONCLUSION: The sensory and physicochemical analysis results obtained by the panelists revealed that the developed beverage was acceptable and possessed stable physicochemical attributes. Our present findings indicate that the developed beverage has excellent potential for commercialization. © 2018 Society of Chemical Industry.

The Preciseness in Diagnosing Thyroid Malignant Nodules Using Shear-Wave Elastography.

Our study aimed to identify more accurate results about the diagnostic role of shear-wave elastography (SWE) for thyroid malignant nodules through a meta-analysis. Potential articles were searched in PubMed, Embase, and the Cochrane Library databases. Overall sensitivity and specificity with 95% confidence intervals (CIs) was used to represent the diagnostic accuracy of SWE. Summary receiver operating characteristic (ROC) curve was constructed to illustrate the results. In addition, χ² and I² tests were performed to assess heterogeneity. A value of p≤0.05 indicated significant heterogeneity. All the analysis was conducted in Meta-DiSc version 1.4 software. Twenty studies were included in the analysis. There were a total of 2,907 patients and 3,397 thyroid nodules included in the meta-analysis. Overall sensitivity and specificity were 0.68 (95% CI: 0.66-0.70) and 0.85 (95% CI: 0.84-0.87), respectively. The results showed the area under curve (AUC) was 0.9041, suggesting high accuracy of SWE for differentiating benign and malignant thyroid nodules. SWE showed high accuracy in identifying thyroid malignant nodules, suggesting it could serve as a diagnostic biomarker in thyroid nodules.