Clinical and biological significance of RNA N6-methyladenosine regulators in Alzheimer disease.

RNA N6-methyladenosine (m6A) regulators are essential for a variety of biological functions, such as early development, viral infections, and cancer. However, their roles in Alzheimer disease (AD) are still not very clear. Here, 16 significant m6A regulators were identified using difference analysis between AD patients and non-demented controls based on the GSE132903 dataset from the Gene Expression Omnibus database. Using these 16 m6A regulators, a nomogram model was established to predict the prevalence of AD. We found that patients could obtain a good clinical benefit based on this model. In addition, we revealed 2 distinct m6A patterns and 2 distinct m6A gene patterns in AD and demonstrated their prognostic and risk assessment significance. This present work comprehensively evaluated the functions of m6A regulators in the diagnosis and subtype classification of AD. These results suggested they have potential prognostic and risk assessment significance in AD.

TJZYF Improves Endometrial Receptivity through Regulating VEGF and PI3K/AKT Signaling Pathway.

The endometrium receptivity was impaired by controlled ovarian hyperstimulation (COH), which would then lead to fertility issues and increased abortion clinically. In the present study, to explore the effectiveness of Tiaojing Zhuyun Formula (TJZYF) in improving endometrial receptivity of COH rats and the possible active ingredients and mechanisms, an approach of network pharmacology was performed and a COH animal model was established. As analyzed, stigmasterol and quercetin may be the active ingredients of TJZYF on improving endometrial receptivity and positive regulation of ion transport, the cytokine-mediated signaling pathway, and endocrine process, and vascular endothelial growth factor receptor signaling pathway may be involved. Eighty female rats were divided into four groups randomly: control, model, TJZYF, and TJZYF+si-VEGFA. COH rat models were constructed by injecting with human menopausal gonadotropin (HMG) and human chorionic gonadotropin (HCG). We found that both endometrial thickness and number of embryo implantations in model were substantially reduced vs. control. The gene and protein expressions of VEGF, PI3K, and p-Akt in the uterus were significantly reduced. TJZYF could increase the endometrial thickness and number of embryo implantations and enhance the expressions of VEGF, PI3K, and p-Akt in the uterus. In the TJZYF+si-VEGFA group, the effect of TJZYF was impaired. Generally, TJZYF could improve the endometrium receptivity and facilitate embryo implantation of COH rats by upregulating VEGF and enhancing the PI3K/Akt signaling pathway.

Electroacupuncture improves endometrial receptivity through miRNA-223-3p-mediated regulation of leukemia inhibitory factor / signal transducer and activator of transcription 3 signaling pathway.

Ovulation-inducing drugs such as endogenous steroids could reduce endometrial receptivity during the implantation window, resulting in lower clinical pregnancy rates and higher miscarriage rates. The present study employed electroacupuncture therapy along with different frequencies on elevating impaired endometrial receptivity to elucidate the mechanism therein. The rats were split up into seven groups of normal, model, low-frequency electroacupuncture (LF-EA), high-frequency electroacupuncture (HF-EA), LF-EA+anti-miRNA, HF-EA+anti-miRNA, and anti-miRNA. PCR assays were used to detect miR-223-3p expressions. The effects of electroacupuncture and miR-223-3p on rats' endometrial membrane cell-drinking process in a manner of scanning electron microscopy were recorded. After that we observed on the electroacupuncture effects on the conditions of adhesion molecules and LIF/STAT3 signaling pathway with assays of immunofluorescence and Western Blot. This study was end up with dual luciferase assay, where combination of miR-233-3p onto the 3'-UTR sequence of LIF was determined. PCR assay demonstrated that HF-EA procured an inhibition in miR-223-3p expression, whereas scanning electron microscopy turned out that both electroacupuncture and miR-223-3p were capable of raising the amount of intrauterine pinocytosis and the number of blastocyst implantation in rats. Additionally, assays of Western Blot and immunofluorescence showed that therapy of electroacupuncture brought about decreasing expressions in adhesion molecules of E-cadherin, ß-catenin and claudin-1 (CLDN1). We found that both electroacupuncture and miR-223-3p were able to fortify LIF/STAT3 signaling pathway, then the fact of miR-223-3p combination to LIF 3'-UTR sequence was validated via our dual-luciferase assay. Electroacupuncture therapy inhibited the miR-223-3p expression upon LIF/STAT3 signaling pathway to elevate endometrial receptivity.

High-frequency electroacupuncture improves endometrial receptivity via regulating cell adhesion molecules and leukemia inhibitory factor / signal transducer and activator of transcription signaling pathway.

Controlled ovarian hyperstimulation (COH) impairs the endometrium receptivity during the implantation window, resulting in a lower clinical pregnancy rate and a higher abortion rate. Our study explored the effect of electroacupuncture on the endometrial receptivity of COH rats. Female rats were randomly divided into normal treatment (Normal), model treatment (Model), low-frequency electroacupuncture treatment (LF-EA) and high-frequency electroacupuncture treatment (HF-EA). Rats in the Model, LF-EA, and HF-EA treatment groups were injected with pregnant mare serum gonadotropin (PMSG) and human chorionic gonadotropin (HCG) to establish a model of COH rats. Compared with the Normal, the endometrial thickness, the number of pinopodes and amount of blastocyst implantation in the Model group were significantly reduced. Among them, the endometrial thickness and the amount of blastocyst implantation in the Model group were substantially decreased than those in the HF-EA group. High-frequency electroacupuncture treatment could markedly reduce the protein expression levels of E-cadherin, ß-catenin and claudin-1 (CLDN1). During HF-EA treatment, the LIF/STAT3 signaling pathway of COH rats was enhanced. In conclusion, electroacupuncture could improve the endometrium receptivity and promote the blastocyst implantation in COH rats by reducing cell adhesion molecules and enhancing the LIF/STAT3 signaling pathway.Highlights High-frequency electroacupuncture could effectively improve endometrial receptivity and blastocyst implantation amount in COH rats.Electroacupuncture, especially high-frequency electroacupuncture, could significantly increase endometrial thickness and the number of pinopodes.High-frequency electroacupuncture significantly reduced the protein expression levels of E-cadherin, ß-catenin and CLDN1 adhesion molecules in COH rats.High-frequency electroacupuncture could markedly enhance the LIF/STAT3 signaling pathway in COH rats.

microRNA-203 Targets Insulin-Like Growth Factor Receptor 1 to Inhibit Trophoblast Vascular Remodeling to Augment Preeclampsia.

OBJECTIVE: Preeclampsia (PE) is a pregnancy-specific condition featured by high blood pressure, edema, and proteinuria. Research about the role of microRNA (miR)-203 in PE remains insufficient. This experiment is designed to investigate the specific role of miR-203 in trophoblasts in PE. STUDY DESIGN: miR-203 expression in placenta tissues of normal pregnant women and PE patients was examined to analyze the relevance between miR-203 and PE diagnostic efficiency and between miR-203 and blood pressure (systolic pressure and diastolic pressure) and proteinuria of PE patients. miR-203 expression was downregulated in hypoxia-cultured trophoblasts using miR-203 inhibitor to assess matrix metalloproteinase-9 (MMP-9) level. Then, the angiogenesis of trophoblasts with different treatments was determined. Subsequently, the target relation between miR-203 and insulin-like growth factor receptor 1 (IGF-1R) was predicted and verified. Additionally, the effect of IGF-1R in the mechanism of miR-203 modulating trophoblast vascular remodeling was detected. RESULTS: miR-203 was overexpressed in the placenta of PE patients and it acted as a promising diagnostic indicator for PE. Moreover, miR-203 was positively associated with blood pressure (systolic pressure and diastolic pressure) and proteinuria of PE patients. miR-203 silencing in hypoxia-cultured trophoblasts enhanced trophoblast vascular remodeling. Mechanically, miR-203 bound to IGF-1R to suppress its transcription. IGF-1R downregulation counteracted the promotive effect of miR-203 silencing on trophoblast vascular remodeling. CONCLUSION: miR-203 was overexpressed in PE, and it targeted IGF-1R to limit trophoblast vascular remodeling. KEY POINTS: · miR-203 is overexpressed in the placenta of PE patients.. · miR-203 acts as a potential diagnostic marker for PE.. · miR-203 targets IGF-1R to reduce trophoblast vascular remodeling in PE..

Maternal and Neonatal Outcomes of Pregnant Women With Coronavirus Disease 2019 (COVID-19) Pneumonia: A Case-Control Study.

BACKGROUND: The ongoing pandemic of coronavirus disease 2019 (COVID-19) has caused serious concerns about its potential adverse effects on pregnancy. There are limited data on maternal and neonatal outcomes of pregnant women with COVID-19 pneumonia. METHODS: We conducted a case-control study to compare clinical characteristics and maternal and neonatal outcomes of pregnant women with and without COVID-19 pneumonia. RESULTS: During the period 24 January-29 February 2020, there were 16 pregnant women with confirmed COVID-19 pneumonia and 18 suspected cases who were admitted to labor in the third trimester. Two had vaginal delivery and the rest were cesarean delivery. Few patients presented respiratory symptoms (fever and cough) on admission, but most had typical chest computed tomographic images of COVID-19 pneumonia. Compared to the controls, patients with COVID-19 pneumonia had lower counts of white blood cells (WBCs), neutrophils, C-reactive protein (CRP), and alanine aminotransferase on admission. Increased levels of WBCs, neutrophils, eosinophils, and CRP were found in postpartum blood tests of pneumonia patients. Three (18.8%) of the mothers with confirmed COVID-19 pneumonia and 3 (16.7%) with suspected COVID-19 pneumonia had preterm delivery due to maternal complications, which were significantly higher than in the control group. None experienced respiratory failure during their hospital stay. COVID-19 infection was not found in the newborns, and none developed severe neonatal complications. CONCLUSIONS: Severe maternal and neonatal complications were not observed in pregnant women with COVID-19 pneumonia who had vaginal or cesarean delivery. Mild respiratory symptoms of pregnant women with COVID-19 pneumonia highlight the need of effective screening on admission.

Fungal-specific subunits of the Candida albicans mitochondrial complex I drive diverse cell functions including cell wall synthesis.

Our published research has focused on the role of Goa1p, an apparent regulator of the Candida albicans mitochondrial complex I (CI). Lack of Goa1p affects optimum cell growth, CI activity and virulence. Eukaryotic CI is composed of a core of 14 alpha-proteobacterial subunit proteins and a variable number of supernumerary subunit proteins. Of the latter group of proteins, one (NUZM) is fungal specific and the other (NUXM) is found in fungi, algae and plants, but is not a mammalian CI subunit protein. We have established that NUXM is orf19.6607 and NUZM is orf19.287 in C. albicans. Herein, we validate both subunit proteins as NADH:ubiquinone oxidoreductases (NUO) and annotate their gene functions. To accomplish these objectives, we compared null mutants of each with wild type (WT) and gene-reconstituted strains. Genetic mutants of genes NUO1 (orf19.6607) and NUO2 (orf19.287), not surprisingly, each had reduced oxygen consumption, decreased mitochondrial redox potential, decreased CI activity, increased reactive oxidant species (ROS) and decreased chronological ageing in vitro. Loss of either gene results in disassembly of CI. Transcriptional profiling of both mutants indicated significant down-regulation of genes of carbon metabolism, as well as up-regulation of mitochondrial-associated gene families that may occur to compensate for the loss of CI activity. Profiling of both mutants also demonstrated a loss of cell wall ß-mannosylation but not in a conserved CI subunit (ndh51Δ). The profiling data may indicate specific functions driven by the enzymatic activity of Nuo1p and Nuo2p. Of importance, each mutant is also avirulent in a murine blood-borne, invasive model of candidiasis associated with their reduced colonization of tissues. Based on their fungal specificity and roles in virulence, we suggest both as drug targets for antifungal drug discovery.

Homogeneous tritylation of cellulose in 1-allyl-3-methylimidazolium chloride and subsequent acetylation: the influence of base.

Homogeneous tritylation of cellulose in 1-allyl-3-methylimidazolium chloride (AmimCl) ionic liquid with triphenylmethy chloride as regents, pyridine or 1-butylimidazole (BIM) as base was investigated, and subsequent acetylation of the 6-O-functionalized products was further studied. The structure of products was analyzed by FTIR and (13)C NMR spectroscopy and base influences on the structure were discussed as well. The solution with pyridine as base underwent heterogeneous-homogeneous-heterogeneous process and the obtained trityl cellulose (TC) had organized structure with trityl group located completely at C-6 position of cellulose with maximum DS(trityl) of nearly 1. In the case of BIM as base, the solution was homogeneous for the whole reaction, but the highest DS(trityl) was about 0.22, with trityl group located not only at position 6 but also partially at position 2. Subsequent acetylation of the TC led to products with a preferred functionalization of the unprotected secondary OH-groups.

Direct visualization of solution morphology of cellulose in ionic liquids by conventional TEM at room temperature.

Taking advantage of the negligible vapor pressure and dissolving features of ionic liquids (ILs), the solution morphology and dissolution process of cellulose in ILs have been visualized directly by conventional transmission electron microscopy (TEM) at room temperature for the first time.

Cysteine and pH-responsive hydrogel based on a saccharide derivative with an aldehyde group.

For the development of chemoresponsive hydrogel, a new saccharide-derived hydrogelator 1 [methyl-4,6-O-(4'-aldehydephenylidene)-alpha-D-glucopyranoside] was synthesized and characterized. The resulting hydrogel not only shows thermal responsiveness but also exhibits cysteine and pH responsiveness due to the presence of aldehyde and acetal groups in 1. The release of guest molecules from the hydrogel of 1 was examined by employing compound 2 (fluorescein disodium) and compound 3 [methyl-4,6-O-(2'-pyrenylidene)-alpha-D-glucopyranoside] as guest molecules. The results indicate that the release of compound 2 from the hydrogel of 1 is controlled by the diffusion process, while the release of compound 3 from the hydrogel of 1 is facilitated by the presence of cysteine. These results demonstrate (1) the proof of principle to design chemoresponsive gels by incorporating reactive groups into the gelators and (2) it is possible to stimulate the release of guest molecules from hydrogels upon addition of reactive chemicals by manipulating the intermolecular interactions among the hydrogelators and guest molecules.

Thermoplastic cellulose-graft-poly(L-lactide) copolymers homogeneously synthesized in an ionic liquid with 4-dimethylaminopyridine catalyst.

An effective method for grafting L-lactide (LA) from unmodified cellulose by ring-opening polymerization (ROP) in homogeneous mild conditions is presented. By using 4-dimethylaminopyridine (DMAP) as an organic catalyst, cellulose-graft-poly(L-lactide) (cellulose-g-PLLA) copolymers with a molar substitution (MS(PLLA)) of PLLA in a range of 0.99-12.28 were successfully synthesized in ionic liquid 1-allyl-3-methylimidazolium chloride (AmimCl) at 80 degrees C. The amount and length of grafted PLLA in cellulose-g-PLLA copolymers were controlled by adjusting the molar ratios of LA monomer to cellulose. The structure and thermal properties of cellulose-g-PLLA copolymers were characterized by (1)H NMR, (13)C NMR, wide-angle X-ray powder diffraction (WAXD), differential scanning calorimetry (DSC), thermogravimetric analysis (TGA), and optical microscopy. The DSC results revealed that the copolymers exhibited a single glass transition temperature, T(g), which sharply decreased with the increase of MS(PLLA) up to MS(PLLA) = 8.28 (DS(PLLA) = 2.19) and increased a little with a further increase of the lactyl content. When MS(PLLA) was above 4.40, the graft copolymers exhibited thermoplastic behavior, indicating the intermolecular and intramolecular hydrogen bonds in cellulose molecules had been effectively destroyed. By using a conventional thermal processing method, fibers and disks of cellulose-g-PLLA copolymers were prepared.

Dendritic effect on supramolecular self-assembly: organogels with strong fluorescence emission induced by aggregation.

A novel class of dumbbell-shaped dendritic molecules with a p-terphenylene core was synthesized, and their self-assembling properties were investigated. The incorporation of bulky dendritic wedges to the central stiff aromatic scaffolds could finely tune their solubility in many organic solvents. Unlike the self-assembly behavior of p-terphenylen-1,4"-ylenebis(dodecanamide), the p-terphenylene cored different generation dendritic molecules could form gels in several kinds of organic solvents through a cooperative effect of the pi-pi stacking, hydrogen-bonding, and van der Waals forces. Interestingly, significant fluorescence enhancement was observed after gelation. Extensive investigations with atomic force microscopy (AFM), scanning electron microscopy (SEM), transmission electron microscopy (TEM), theological measurements, UV-vis absorption spectroscopy, FT-IR spectroscopy, 1H NMR, and X-ray powder diffraction (XRD) revealed that these dendritic molecules self-assembled into elastically interpenetrating one-dimensional nanostructures in organogels.