Targeting O-GlcNAcylated METTL3 impedes MDS/AML progression via diminishing SRSF1 mA modification.

N6-methyladenosine (mA) modification, primarily regulated by methyltransferase-like protein 3 (METTL3), plays a pivotal role in RNA metabolism and leukemogenesis. However, the post-translational mechanisms governing METTL3 stability and function remain incompletely understood. Given the widespread occurrence of O-GlcNAcylation on nuclear and cytosolic proteins, we hypothesized that METTL3 might undergo O-GlcNAcylation, thereby influencing its stability and oncogenic function in myeloid malignancies.

Forms of chitin-polysaccharide cross-linking in the Coprinopsis cinerea stipe cell wall.

The fungal cell wall provides the cell with enough strength to withstand turgor pressure and keeps adequate plasticity to extend the cell wall size under turgor pressure for cell growth. The cell walls of apical growing hyphae and budding growth yeast have been studied in detailed which share common components of chitin and β-1,3-glucan in their scaffold structures while other polysaccharide components vary on species. In contrast, the cell walls of elongating growth mushroom stipe remains poorly studied.

O-GlcNAcylated FTO promotes m6A modification of SOX4 to enhance MDS/AML cell proliferation.

Fat mass and obesity-associated protein (FTO) was the first m6A demethylase identified, which is responsible for eliminating m6A modifications in target RNAs. While it is well-established that numerous cytosolic and nuclear proteins undergo O-GlcNAcylation, the possibility of FTO being O-GlcNAcylated and its functional implications remain unclear. This study found that a negative correlation between FTO expression and O-GlcNAcylation in patients with myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML).

Immobilization of glycosyltransferase into a hydrophilic metal-organic framework for efficient biosynthesis of chondroitin sulfate.

Chondroitin sulfate (CS) is a structurally complex anionic polysaccharide widely used in medical, cosmetic and food applications. Enzymatic catalysis is an important strategy for synthesizing CS with uniform chain lengths and well-defined structures. However, the industrial application of glycosyltransferases is hindered by limitations such as low expression yields, poor stability, and challenges in reuse.

Design, synthesis, and molecular docking of 4‑Thiol‑N‑acetylhexosamine uridine diphosphate donors for glycan synthesis.

Unnatural chemically modified nucleotide sugars UDP-4-SH-GalNAc was synthesized for the first time from a previously reported Benzyl 2-Amino-glucoypranoside derivative, with a total yield of 18.6%. UDP-4-SH-GalNAc was smaller in size than UDP-GalNAc calculated by Multiwfn, and its binding capability with glycosyltransferase was stronger than that of UDP-GalNAc and glycosyltransferase, which means the unnatural nucleotide sugars is equally well recognized by the enzyme and doped into the sugar chains.

Stereoselective Total Synthesis of Natural Decanolides Bellidisin C and Pinolidoxin.

A divergent total synthesis of bioactive, naturally occurring decanolides, pinolidoxin and bellidisin C, was accomplished by taking advantage of chiral templates -ribose and -malic acid. In particular, bellidisin C, which is the first total synthesis so far, was achieved through a cascade reaction of reductive elimination and nucleophilic addition in a one-pot process and a sodium-alkoxide-promoted intramolecular lactonization as the key steps.

Photocatalytic fluoroalkylation by ligand-to-metal charge transfer.

Trifluoromethyl (CF) and other fluoroalkyl groups are of great significance in the fields of pharmaceutical chemistry and agricultural chemicals. Fluoroalkyl acids, especially trifluoroacetic acid (TFA) is considered the most ideal fluoroalkylation reagent due to its low cost and easy availability. However, the extremely high oxidation potential requirement of TFA limits its wide application.

Low Carbon Loss from Long-Term Manure-Applied Soil during Abrupt Warming Is Realized through Soil and Microbiome Interplay.

Manure application is a global approach for enhancing soil organic carbon (SOC) sequestration. However, the response of SOC decomposition in manure-applied soil to abrupt warming, often occurring during diurnal temperature fluctuations, remains poorly understood. We examined the effects of long-term (23 years) continuous application of manure on SOC chemical composition, soil respiration, and microbial communities under temperature shifts (15 vs 25 °C) in the presence of plant residues.

Catalytic System-Controlled Regioselective 1,2- and 1,4-Carboannulations of [60]Fullerene.

Selective functionalization of fullerenes is an important but challenging topic in fullerene chemistry and synthetic chemistry. Here we present the first example of catalytic system-controlled regioselective 1,2- and 1,4-addition reactions for the flexible and efficient synthesis of novel 1,2- and 1,4-carbocycle-fused fullerenes via a palladium-catalyzed decarboxylative carboannulation process.

Pathogenesis of diabetic complications: Exploring hypoxic niche formation and HIF-1α activation.

Hypoxia is a common feature of diabetic tissues, which highly correlates to the progression of diabetes. The formation of hypoxic context is induced by disrupted oxygen homeostasis that is predominantly driven by vascular remodeling in diabetes. While different types of vascular impairments have been reported, the specific features and underlying mechanisms are yet to be fully understood.

Spatially Segregated MOF Bioreactor Enables Versatile Modular Glycoenzyme Assembly for Hierarchical Glycan Library Construction.

The multienzyme cascade has received growing attention to obtain structurally defined glycans . However, due to poor enzyme stability and low compatibility between glycoenzymes, artificially designed multienzyme pathways to access glycans are often inefficient. Herein, based on the strategy "Modular-Enzymes Assembly by Spatial Segregation" (MASS), we developed a universal immobilization platform to assemble multiple glycoenzymes in compartmentalized MOF particles, inside and outside, significantly reducing the undesired interference and cross-inhibitions.

Diabetes-Induced Autophagy Dysregulation Engenders Testicular Impairment via Oxidative Stress.

Testes produce sperms, and gamete generation relies on a proper niche environment. The disruption of hierarchical regulatory homeostasis in Leydig or Sertoli cells may evoke a sterile phenotype in humans. In this study, we recapitulated type 2 diabetes mellitus by using a high-fat diet- (HFD-) fed mouse model to identify the phenotype and potential mechanism of diabetes-induced testicular impairment.

Organocatalytic Cloke-Wilson Rearrangement: Carbocation-Initiated Tandem Ring Opening/Cyclization of Cyclopropanes under Neutral Conditions.

We report a metal-, acid-, and base-free 2-(bromomethyl)naphthalene (2-BMN)-promoted organocatalytic Cloke-Wilson rearrangement of chain doubly activated cyclopropanes for the construction of 2,3-dihydrofurans via a carbocation-initiated tandem intramolecular ring-opening/recyclization process. The strategy is especially suitable for the construction of furan units in complex molecules, providing a solution to the problem of heavy-metal residues in dihydrofuran-containing drugs synthesized by traditional metal-based protocols. Thus, it is of potential interest in synthetic and medicinal chemistry.

Synthetic K Channels Constructed by Rebuilding the Core Modules of Natural K Channels in an Artificial System.

Different types of natural K channels share similar core modules and cation permeability characteristics. In this study, we have developed novel artificial K channels by rebuilding the core modules of natural K channels in artificial systems. All the channels displayed high selectivity for K over Na and exhibited a selectivity sequence of K ≈Rb during the transport process, which is highly consistent with the cation permeability characteristics of natural K channels.

Clinical Application of Shock Wave in the Treatment of Avascular Necrosis of the Femoral Head in the Early and Middle Stages.

In order to observe the clinical efficacy of shock waves in the treatment of avascular necrosis of the femoral head in the early and middle stages, a clinical application method of a shock wave in the treatment of avascular necrosis of the femoral head in the early and middle stages was proposed. The method combines the CT image segmentation technology to further segment the hip joint image, thereby speeding up the treatment speed and achieving a better treatment effect. Experimental results show that CT image segmentation takes 10.

Investigating bacterial coupled assimilation of fertilizer‑nitrogen and crop residue‑carbon in upland soils by DNA-qSIP.

Microbial immobilization of fertilizer nitrogen (N) can effectively reduce N losses in soil. However, the effects of crop residue on microbial assimilation of fertilizer-N and the underlying microbial mechanisms in upland soils are unclear. We evaluated the influence of maize residue (C) addition on the microbial assimilation of ammonium-N (N) in DNA from fertilizer, and quantified the bacterial C or N assimilation by quantitative stable isotope probing (DNA-qSIP).

Keystone microbial taxa drive the accelerated decompositions of cellulose and lignin by long-term resource enrichments.

Lignin and cellulose are the most important component of crop straw entering arable soil. The decomposition of lignin and cellulose are related to carbon sequestration and soil fertility. The keystone microbes decomposing lignin and cellulose in cropland and their impact on agricultural management, however, remains largely unclear.

MAPK CcSakA of the HOG Pathway Is Involved in Stipe Elongation during Fruiting Body Development in .

Mitogen-activated protein kinase (MAPK) pathways, such as the high-osmolarity glycerol mitogen-activated protein kinase (HOG) pathway, are evolutionarily conserved signaling modules responsible for transmitting environmental stress signals in eukaryotic organisms. Here, we identified the MAPK homologue in the HOG pathway of which was named CcSakA. Furthermore, during the development of the fruiting body, CcSakA was phosphorylated in the fast elongating apical part of the stipe, which meant that CcSakA was activated in the apical elongating stipe region of the fruiting body.

Transfer of IGF2BP3 Through Ara-C-Induced Apoptotic Bodies Promotes Survival of Recipient Cells.

Cytosine arabinoside (Ara-C) has been the standard therapeutic agent for myelodysplastic syndromes (MDS) and adult acute myeloid leukemia (AML) patients for decades. Considerable progress has been made in development of new treatments for MDS/AML patients, but drug resistance remains a major clinical problem. Apoptotic bodies (ABs), produced by late apoptotic cells, can enclose bioactive components that affect cell-cell interactions and disease progression.

Fabrication of pH-sensitive magnetic metal-organic framework for controlled-release of heparin.

Heparin, the most widely used anticoagulant drug in the world today, suffers from the risk of overdose and a short serum half-life, limiting its clinical applications. Concerning the controlled, sustained, and targeted release of heparin, a delivery system was fabricated in this research using the layered composites of FeO magnetic particles and pH-sensitive metal-organic framework, FeO@ZIF-8. The composite demonstrated a high loading capacity for the heparin, 66.

A Facile and Cost-Effective Method to Prepare Biodegradable Poly(ester urethane)s with Ordered Aliphatic Hard-Segments for Promising Medical Application as Long-Term Implants.

The article below describes a simple methodology to prepare cost-effective biodegradable poly(ester urethane)s (PEUs) with ordered hard segments (OHS) for medical application as long-term implants. A low-cost diurethane diol (1,4-butanediol-hexanediisocyanate-1,4-butanediol, BHB) was first designed and synthesized. Consequently, the BHB was employed as a chain extender to react with NCO-terminated poly(-caprolactone) to obtain PEUs.

Molecular Mechanism by Which the GATA Transcription Factor CcNsdD2 Regulates the Developmental Fate of under Dark or Light Conditions.

Coprinopsis cinerea has seven homologs of the Aspergillus nidulans transcription factor NsdD. Of these, CcNsdD1 and CcNsdD2 from show the best identities of 62 and 50% to A. nidulans NsdD, respectively.

HIF-1 Activation Promotes Luteolysis by Enhancing ROS Levels in the Corpus Luteum of Pseudopregnant Rats.

The increase of oxidative stress is one of the important characteristics of mammalian luteal regression. Previous investigations have revealed the essential role of reactive oxygen species (ROS) in luteal cell death during luteolysis, while it is unknown how ROS is regulated in this process. Considering the decrease of blood flow and increase of PGF during luteolysis, we hypothesized that the HIF-1 pathway may be involved in the regulation of ROS in the luteal cell of the late corpus luteum (CL).

Rhodium-Catalyzed Denitrogenative Transannulation of -Sulfonyl-1,2,3-triazoles with Glycals Giving Pyrroline-Fused -Glycosides.

Described here is a selective synthesis of 2,3-dihydropyrrole-fused -glycosides through rhodium-catalyzed denitrogenative transannulation of -sulfonyl-1,2,3-triazoles with glycals. A series of pyrroline-fused -glycosides are afforded in moderate to excellent yields with exclusive regioselectivity and stereoselectivity. Functional application of such a resultant product by oxidative addition and epoxidation is also explored.