The potential role of transcription factor sterol regulatory element binding proteins (SREBPs) in Alzheimer's disease.

Sterol regulatory element binding proteins (SREBPs) are a series of cholesterol-related transcription factors. Their role in regulating brain cholesterol biosynthesis, amyloid accumulation, and tau tangles formation has been intensively studied in protein-protein interaction analysis based on genes in clinical databases. SREBPs play an important role in maintaining cholesterol homeostasis in the brain.

Discovery of ZJCK-6-46: A Potent, Selective, and Orally Available Dual-Specificity Tyrosine Phosphorylation-Regulated Kinase 1A Inhibitor for the Treatment of Alzheimer's Disease.

Targeting dual-specificity tyrosine phosphorylation-regulated kinase 1A (DYRK1A) has been verified to regulate the progression of tau pathology as a promising treatment for Alzheimer's disease (AD), while the research progress on DYRK1A inhibitors seemed to be in a bottleneck period. In this work, we identified () as the most potential DYRK1A inhibitor (IC = 0.68 nM) through rational design, systematic structural optimization, and comprehensive evaluation.

Identification of Differentially Expressed mRNAs and miRNAs and Related Regulatory Networks in Cumulus Oophorus Complexes Associated with Fertilization.

Cumulus oophorus complexes (COCs) are the first extracellular barriers that sperm must pass through to fuse with oocytes, which have an important role in oocyte maturation and fertilization. However, little is known about the molecular mechanisms of COCs involved in fertilization. In this study, COCs were collected and then randomly divided into a test group that interacted with sperm and a control group that did not interact with sperm.

Discovery of novel harmine derivatives as GSK-3β/DYRK1A dual inhibitors for Alzheimer's disease treatment.

Multitarget-directed ligands (MTDLs) have recently attracted significant interest due to their superior effectiveness in multifactorial Alzheimer's disease (AD). Combined inhibition of two important AD targets, glycogen synthase kinase-3β (GSK-3β) and dual-specificity tyrosine phosphorylation-regulated kinase 1A (DYRK1A), may be a breakthrough in the treatment of AD. Based on our previous work, we have designed and synthesized a series of novel harmine derivatives, investigated their inhibition of GSK-3β and DYRK1A, and evaluated a variety of biological activities.

Clinical and neonatal outcomes of using a modified micro cryotube for cryopreservation of small numbers of spermatozoa for TESA-ICSI cycles.

Cryopreservation of a small number of human spermatozoa is still a major challenge for embryologists. The aim of this study was to evaluate the clinical pregnancy and neonatal outcomes of intracytoplasmic sperm injection (ICSI) using a modified micro cryotube as freezing carrier for freezing small numbers of human spermatozoa collected by testicular sperm aspiration (TESA). We conducted a retrospective study to analyses the ICSI outcomes of using frozen-thawed few testicular spermatozoa in males with obstructive azoospermia (OA) from June 2017 to June 2021.

Discovery of novel β-carboline-1,2,3-triazole hybrids as AChE/GSK-3β dual inhibitors for Alzheimer's disease treatment.

Alzheimer's disease (AD) is characterized by progressive cognitive impairment and mental behavior. The combination inhibition of two essential AD targets, acetylcholinesterase (AChE) and glycogen synthase kinase-3β (GSK-3β), might be a breakthrough in the discovery of therapeutic success. Herein, 17 β-carboline-1,2,3-triazole hybrids were designed, synthesized, and evaluated for their AChE and GSK-3β inhibitory potential.

Design, synthesis and biological evaluation of novel coumarin derivatives as multifunctional ligands for the treatment of Alzheimer's disease.

Multi-targeted directed ligands (MTDLs) are emerging as promising Alzheimer's disease (AD) therapeutic possibilities. Coumarin is a multifunctional backbone with extensive bioactivity that has been utilized to develop innovative anti-neurodegenerative properties and is a desirable starting point for the construction of MTDLs. Herein, we explored and synthesized a series of novel coumarin derivatives and assessed their inhibitory effects on cholinesterase (AChE, BuChE), GSK-3β, and BACE1.

Pyranone Derivatives With Antitumor Activities, From the Endophytic Fungus sp. YN02-P-3.

Two new pyranone derivatives phomapyrone A (2) and phomapyrone B (3), one new coumarin 11 13-(+)-phomacumarin A (1), three known pyranones (4-6), together with three known amide alkaloids fuscoatramides A-C (7-9), as well as 9 11-(+)-ascosalitoxin (10) were isolated from the endophytic fungus sp. YN02-P-3, which was isolated from the healthy leaf tissue of a Paulownia tree in Yunnan Province, China. Their structures were elucidated using extensive NMR spectroscopic and HRESIMS data and by comparing the information with literature data.

Discovery of novel α-carboline derivatives as glycogen synthase kinase-3β inhibitors for the treatment of Alzheimer's disease.

Alzheimer's disease (AD) is a chronic and progressive neurodegenerative disease, characterized by irreversible cognitive impairment, memory loss, and behavioral disturbances, ultimately resulting in death. The critical roles of glycogen synthase kinase-3β (GSK-3β) in tau pathology have also received considerable attention. Based on molecular docking studies, a series of novel α-carboline derivatives were designed, synthesized, and evaluated as GSK-3β inhibitors for their various biological activities.

Exploration of 4-(1H-indol-3-yl)cyclohex-3-en-1-amine analogues as HDAC inhibitors: Design, synthesis, biological evaluation and modelling studies.

Epigenetics regulate the gene expression and chromatin organization associated with the development and occurrence of cancer. Histone deacetylase inhibitors (HDACis) have been proved to be an effective epigenetic targeting drug for cancer treatment. The structures of most HDACis were divided into four parts, including cap group, connection unit, linker region and zinc binding group.

Discovery of novel benzofuro[3,2-b]quinoline derivatives as dual CDK2/Topo I inhibitors.

Uncontrolled cell proliferation is a hallmark of cancer. The major regulator of the cell cycle, cyclin dependent kinase 2 (CDK2), has become a mature target for cancer treatment. Herein, we describe our efforts toward the discovery of a series of benzofuro[3,2-b]quinoline alkaloid derivatives as CDK2 inhibitors through a scaffold hopping strategy.

Discovery of novel β-carboline derivatives as selective AChE inhibitors with GSK-3β inhibitory property for the treatment of Alzheimer's disease.

The natural product harmine, a representative β-carboline alkaloid from the seeds of Peganum harmala L. (Zygophyllaceae), possesses a broad spectrum of biological activities. In this study, a novel series of harmine derivatives containing N-benzylpiperidine moiety were identified for the treatment of Alzheimer's disease (AD).

A Technique to Reduce the Early Recurrence of Intussusception in Ultrasound-Guided Hydrostatic Reduction.

Objectives: Ultrasound-guided saline enema is highly successful in treating pediatric intussusception; however, early recurrence-within 48 hours-is possible. This study aimed to explore effective methods of reducing early recurrence.

Methods: This study included patients aged 0 to 14 years diagnosed with ileocolic intussusception with a symptom duration of <48 hours from January 2019 to March 2021.

Laser-assisted selection of immotile spermatozoa has no effect on obstetric and neonatal outcomes of TESA-ICSI pregnancies.

Background: Azoospermic patients have benefited from both epididymal and testicular spermatozoa intracytoplasmic sperm injection (ICSI) treatment and lasers have been used to identify viable, immotile spermatozoa before the procedure. There are limited studies on the safety of laser-assisted selection of immotile spermatozoa. The aim of this study was to investigate the impact of laser-assisted selection of immotile spermatozoa on the obstetric and neonatal outcomes after ICSI.

Does longer storage of blastocysts with equal grades in a cryopreserved state affect the perinatal outcomes?

Aim: Although mammalian embryos could be preserved in liquid nitrogen for thousands of years in theoretical models, the viability of cryopreserved blastocyst with varying grades remains to be speculated. In this study, we aimed to determine whether the longer storage time of blastocysts with equal grades could negatively affect the perinatal outcomes.

Materials And Methods: Single vitrified-warmed blastocyst was divided into four grades (AA, AB/BA, BB, BC/CB) according to the blastocyst score when freezing, and each grade of blastocyst was categorized into four storage duration categories: 28 days-1 year, 1-3 years, 3-5 years, and ≥5 years.

Design, synthesis and biological evaluation of harmine derivatives as potent GSK-3β/DYRK1A dual inhibitors for the treatment of Alzheimer's disease.

Alzheimer's disease (AD) is a chronic and progressive neurodegenerative disease, characterized by irreversible cognitive impairment, memory loss and behavioral disturbances, ultimately leading to death. Glycogen synthase kinase 3β (GSK-3β) and dual-specificity tyrosine phosphorylation regulated kinase1A (DYRK1A) have gained a lot of attention for its role in tau pathology. To search for potential dual GSK-3β/DYRK1A inhibitors, we focused on harmine, a natural β-carboline alkaloid, which has been extensively studied for its various biological effects on the prevention of AD.

Choosing the optimal blastocyst by morphology score versus developmental rate in frozen-thawed embryo transfer cycles.

The aim of this study was to provide guidance for better management in the selection of blastocyst to warm in frozen-thawed embryo transfer (FET) cycles. A retrospective cohort follow-up study was conducted that included single autologous frozen blastocyst transfer cycles performed in our Reproductive Medicine Unit from January 2009 to December 2016. The live birth rate (LBR), clinical pregnancy rate (cPR) were increased as blastocyst morphology scores increased, but the miscarriage rate decreased in all groups.

A point of confusion for embryologists in the identification of viable spermatozoa by the eosin-nigrosin test.

A viable spermatozoon is a prerequisite for fertilization in intracytoplasmic sperm injection (ICSI). Thus, it is crucial to select viable but immotile spermatozoa on the day of ICSI. We report conflicting results in the identification of viable but immotile spermatozoa between the eosin-nigrosin staining and the laser test, which resulted in confusion for embryologists during assisted reproductive technology (ART).

[Identification and selection of completely immotile but viable spermatozoa for assisted reproductive technology].

Intracytoplasmic sperm injection (ICSI) remains the most effective method for severe male infertility patients to obtain their genetic offspring. A viable spermatozoon is the prerequisite for initiating fertilization in ICSI. Motility is the primary sign of sperm viability.

Cumulus oophorus complexes favor physiologic selection of spermatozoa for intracytoplasmic sperm injection.

Objective: To investigate the effectiveness of cumulus oophorus complexes (COCs) in the physiologic selection of spermatozoa for intracytoplasmic sperm injection (ICSI).

Design: A prospective sibling oocytes study.

Setting: Center of reproductive medicine.

A new insight into male fertility preservation for patients with completely immotile spermatozoa.

Background: Sperm cryopreservation is the most effective method to preserve male fertility but this is normally used for motile spermatozoa. Thus, only motile spermatozoa are used for cryopreservation in most reproductive medicine centers worldwide. The immotile spermatozoa from some problematic patients are usually discarded, resulting in a missed opportunity of sterility cryopreservation for future assisted reproductive treatments.

Effect of different artificial shrinkage methods, when applied before blastocyst vitrification, on perinatal outcomes.

Background: In recent years, single blastocyst transfer combined with vitrification has been applied widely, which can maximize the cumulative pregnancy rate in per oocyte retrieval cycles and minimize the multiple pregnancy rate. Thus, the guarantee for these is the effectiveness of vitrified blastocyst. Studies has shown that AS of the blastocoel cavity prior to vitrification can reduce injuries, increase the thawed blastocyst survival rate and implantation rate.

A successful pregnancy using completely immotile but viable frozen-thawed spermatozoa selected by laser.

The aim of this study was to report a successful pregnancy using completely immotile frozen-thawed spermatozoa selected by laser. A single laser shot was used to detect the presence of viable immotile spermatozoa in fresh and frozen-thawed testicular spermatozoa. The viability rate was 55.

Blastocoele re-expansion time in vitrified-warmed cycles is a strong predictor of clinical pregnancy outcome.

Aim: To assess the predictive value of blastocoele re-expansion time in clinical pregnancy outcome in vitrified-warmed cycles.

Methods: Data on 468 single vitrified-thawed blastocyst transfer cycles (in patients aged <38 years) carried out from January 2012 through December 2012, at the Reproductive Medicine Center, Maternal and Child Health Hospital of Guangxi Zhuang Autonomous Region, were analyzed. Vitrified-warmed blastocysts were divided into three groups according to blastocoele re-expansion time: group A, <1 h; group B, 1-2 h; and group C, >2 h, and the clinical pregnancy outcomes (i.

Flow cytometric and near-infrared Raman spectroscopic investigation of quality in stained, sorted, and frozen-thawed buffalo sperm.

Flow cytometry and Laser Tweezers Raman spectroscopy have been used to investigate Nili-Ravi buffalo (Bubalus bubalis) sperm from different samples (fresh, stained, sorted and frozen-thawed) of the flow-sorting process to optimize sperm sex sorting procedures. During the sorting and freezing-thawing processes, the two detection methods both indicated there were differences in mitochondrial activity and membrane integrity. Moreover, a dispersive-type NIR (Near Infrared Reflection) use of the Raman system resulted in the ability to detect a variety of sperm components, including relative DNA, lipid, carbohydrates and protein contents.