Global Profiling of Protein Lactylation in Human Hippocampi.

Purpose: The hippocampus has long been associated with cognition and memory function, the implications of lysine lactylation (Kla), a recently identified post-translational modification (PTM), in the role of the hippocampus remain largely unexplored.

Experimental Design: An LC-MS/MS bottom-up proteomics analysis of three human hippocampal tissue samples was applied to profile the lactylation map in human hippocampi under normal physiological conditions.

Results: We identified 2579 quantifiable Class I lactylated sites in 853 proteins, of which contained four types of modification motifs.

Systolic blood pressure variability in late-life predicts cognitive trajectory and risk of Alzheimer's disease.

Background: The relationship of systolic blood pressure variability (SBPV) with Alzheimer's disease (AD) remains controversial. We aimed to explore the roles of SBPV in predicting AD incidence and to test the pathways that mediated the relationship of SBPV with cognitive functions.

Methods: Longitudinal data across 96 months (T to T) were derived from the Alzheimer's disease Neuroimaging Initiative cohort.

Early results of the integrative epigenomic-transcriptomic landscape of colorectal adenoma and cancer.

Background: Aberrant methylation is common during the initiation and progression of colorectal cancer (CRC), and detecting these changes that occur during early adenoma (ADE) formation and CRC progression has clinical value.

Aim: To identify potential DNA methylation markers specific to ADE and CRC.

Methods: Here, we performed SeqCap targeted bisulfite sequencing and RNA-seq analysis of colorectal ADE and CRC samples to profile the epigenomic-transcriptomic landscape.

Absolute Configuration of 12-Deoxynortryptoquivaline from Ascidian-Derived Fungus Determined by Anisotropic NMR and Chiroptical Spectroscopy.

Tryptoquivalines are highly toxic metabolites initially isolated from the fungus . The relative and absolute configuration of tryptoquivaline derivates was primarily established by comparison of the chemical shifts, NOE data, and ECD calculations. A de novo determination of the complete relative configuration using NMR spectroscopy was challenging due to multiple spatially separated stereocenters, including one nonprotonated carbon.

Role of sleep in asthenospermia induced by di (2-ethyl-hexyl) phthalate.

Di (2-ethyl-hexyl) phthalate (DEHP) mainly enters the human body through the digestive tract, respiratory tract, and skin. At the same time, it has reproductive and developmental toxicity, neurotoxicity, and so on, which can cause the decrease of sperm motility. Asthenospermia is also known as low sperm motility, and the semen quality of men in some areas of China is declining year by year.

A mutation-sensitive, multiplexed and amplification-free detection of nucleic acids by stretching single-molecule tandem hairpin probes.

The detection of nucleic acid sequences in parallel with the discrimination of single nucleotide variations (SNVs) is critical for research and clinical applications. A few limitations make the detection technically challenging, such as too small variation in probe-hybridization energy caused by SNVs, the non-specific amplification of false nucleic acid fragments and the few options of dyes limited by spectral overlaps. To circumvent these limitations, we developed a single-molecule nucleic acid detection assay without amplification or fluorescence termed THREF (hybridization-induced tandem DNA hairpin refolding failure) based on multiplexed magnetic tweezers.

The RNA polymerase II subunit B (RPB2) functions as a growth regulator in human glioblastoma.

Glioblastoma multiforme (GBM) is the most common and aggressive brain tumor with a poor prognosis. The growth of GBM cells depends on the core transcriptional apparatus, thus rendering RNA polymerase (RNA pol) complex as a candidate therapeutic target. The RNA pol II subunit B (POLR2B) gene encodes the second largest subunit of the RNA pol II (RPB2); however, its genomic status and function in GBM remain unclear.

Electroacupuncture and manual acupuncture at LR3 and ST36 have attenuating effects on hypertension and subsequent cognitive dysfunction in spontaneously hypertensive rats: A preliminary resting-state functional magnetic resonance imaging study.

Introduction: Chronic hypertension may have a contributory role toward cognitive impairment. Acupuncture exerts protective effects on cognitive functions while controlling the blood pressure. However, the neural mechanism underlying the dual attenuating effect of acupuncture remains unclear.

Colonic mechanism of serum NAD depletion induced by DEHP during pregnancy.

Di (2-ethylhexyl) phthalate (DEHP) is a widely used plasticizer in polyvinyl chloride products such as feed piping, packing bag, and medical consumable. Our previous studies have demonstrated that DEHP exposure reduced the concentration of nicotinamide adenine dinucleotide (NAD) in pregnant mice serum, which cuts off the source of NAD to placenta and results fetal growth restriction. However, the mechanism of serum NAD depletion by DEHP remains elusive.

Effects of non-invasive brain stimulation on motor function after spinal cord injury: a systematic review and meta-analysis.

Background: In recent years, non-invasive brain stimulation (NIBS) has been used for motor function recovery. However, the effects of NIBS in populations with spinal cord injury (SCI) remain unclear. This study aims to conduct a meta-analysis of the existing evidence on the effects and safety of NIBS against sham groups for motor dysfunction after SCI to provide a reference for clinical decision-making.

5-Methyl-cytosine stabilizes DNA but hinders DNA hybridization revealed by magnetic tweezers and simulations.

5-Methyl-cytosine (5mC) is one of the most important DNA modifications and plays versatile biological roles. It is well known that 5mC stabilizes DNA duplexes. However, it remains unclear how 5mC affects the kinetics of DNA melting and hybridization.

The BRD4 Inhibitor dBET57 Exerts Anticancer Effects by Targeting Superenhancer-Related Genes in Neuroblastoma.

Neuroblastoma (NB) is the most common solid tumor of the neural crest cell origin in children and has a poor prognosis in high-risk patients. The oncogene MYCN was found to be amplified at extremely high levels in approximately 20% of neuroblastoma cases. In recent years, research on the targeted hydrolysis of BRD4 to indirectly inhibit the transcription of the MYCN created by proteolysis targeting chimaera (PROTAC) technology has become very popular.

Fecal microbiota transplantation relieves abdominal bloating in children with functional gastrointestinal disorders via modulating the gut microbiome and metabolome.

Objective: To evaluate the efficacy and safety of fecal microbiota transplantation (FMT) in functional gastrointestinal disorders (FGIDs) in children with abdominal bloating and changes in their gut microbiome and metabolome.

Methods: Twelve pediatric FGID patients with predominant abdominal bloating who underwent FMT were enrolled in the study. Fourteen healthy controls and four stool donors were included for analysis.

Explore the multitarget mechanism of tetrahydrocurcumin preventing on UV-induced photoaging mouse skin.

UV induced photoaging is the main external factor of skin aging. In this study, we tested the protective effects of tetrahydrocurcumin on UV-induced skin photoaging of KM mice and researched the multi-target mechanism through RNA sequencing technology. Mouse experiments show that tetrahydrocurcumin strongly changed in skin appearance, epidermal thickness, and wrinkle-related parameters in UV-irradiated mice.

Compartmentalized regulation of NAD by Di (2-ethyl-hexyl) phthalate induces DNA damage in placental trophoblast.

Di (2-ethyl-hexyl) phthalate (DEHP) is a wildly used plasticizer. Maternal exposure to DEHP during pregnancy blocks the placental cell cycle at the G2/M phase by reducing the efficiency of the DNA repair pathways and affects the health of offsprings. However, the mechanism by which DEHP inhibits the repair of DNA damage remains unclear.

Super-enhancer profiling identifies novel critical and targetable cancer survival gene LYL1 in pediatric acute myeloid leukemia.

Background: Acute myeloid leukemia (AML) is a myeloid neoplasm makes up 7.6% of hematopoietic malignancies. Super-enhancers (SEs) represent a special group of enhancers, which have been reported in multiple cell types.

Weizhouochrones: Gorgonian-Derived Symmetric Dimers and Their Structure Elucidation Using Anisotropic NMR Combined with DP4+ Probability and CASE-3D.

Natural product dimers have intriguing structural features and often have remarkable pharmacological activities. We report here two uncommon marine gorgonian-derived symmetric dimers, weizhouochrones A () and B (), with indenone-derived monomers, that were isolated from the coral collected from the South China Sea. These dimers are difficult targets for structure elucidation that solely relies upon conventional NMR data such as NOEs and -couplings.

Echinococcosis Is Associated with the Increased Prevalence of Intestinal Infection in Tibetans and Host Susceptibility to the in Mice.

Blastocystis is a common human intestinal protozoan parasite. Little is known about its prevalence in echinococcosis. This study tested whether Echinococcus multilocularis infection would increase host susceptibility to Blastocystis.

BRD4 inhibitor GNE987 exerts anti-cancer effects by targeting super-enhancers in neuroblastoma.

Background: Neuroblastoma (NB) is a common extracranial malignancy with high mortality in children. Recently, super-enhancers (SEs) have been reported to play a critical role in the tumorigenesis and development of NB via regulating a wide range of oncogenes Thus, the synthesis and identification of chemical inhibitors specifically targeting SEs are of great urgency for the clinical therapy of NB. This study aimed to characterize the activity of the SEs inhibitor GNE987, which targets BRD4, in NB.

SAPCD2 promotes neuroblastoma progression by altering the subcellular distribution of E2F7.

Recent studies uncovered the emerging roles of SAPCD2 (suppressor anaphase-promoting complex domain containing 2) in several types of human cancer. However, the functions and underlying mechanisms of SAPCD2 in the progression of neuroblastoma (NB) remain elusive. Herein, through integrative analysis of public datasets and regulatory network of GSK-J4, a small-molecule drug with anti-NB activity, we identified SAPCD2 as an appealing target with a high connection to poor prognosis in NB.

CEBPG promotes acute myeloid leukemia progression by enhancing EIF4EBP1.

Background: Acute myeloid leukemia (AML) is a myeloid neoplasm accounts for 7.6% of hematopoietic malignancies. AML is a complex disease, and understanding its pathophysiology is contributing to the improvement in the treatment and prognosis of AML.

MI-773, a breaker of the MDM2/p53 axis, exhibits anticancer effects in neuroblastoma via downregulation of INSM1.

Neuroblastoma (NB) is a common pediatric malignancy associated with poor outcomes. Recent studies have shown that murine double minute2 homolog (MDM2) protein inhibitors are promising anticancer agents. MI-773 is a novel and specific antagonist of MDM2, however, the molecular mechanism of its anti-NB activity remains unclear.