Increased local DNA methylation disorder in AMLs with DNMT3A-destabilizing variants and its clinical implication.

The mechanistic link between the complex mutational landscape of de novo methyltransferase DNMT3A and the pathology of acute myeloid leukemia (AML) has not been clearly elucidated so far. Motivated by a recent discovery of the significance of DNMT3A-destabilizing mutations (DNMT3A) in AML, we here investigate the common characteristics of DNMT3A AML methylomes through computational analyses. We present that methylomes of DNMT3A AMLs are considerably different from those of DNMT3A AMLs in that they exhibit increased intratumor DNA methylation heterogeneity in bivalent chromatin domains.

Dynamic supramolecular snub cubes.

Mimicking the superstructures and properties of spherical biological encapsulants such as viral capsids and ferritin offers viable pathways to understand their chiral assemblies and functional roles in living systems. However, stereospecific assembly of artificial polyhedra with mechanical properties and guest-binding attributes akin to biological encapsulants remains a formidable challenge. Here we report the stereospecific assembly of dynamic supramolecular snub cubes from 12 helical macrocycles, which are held together by 144 weak C-H hydrogen bonds.

Electrochemical Three-Component C-H Functionalization of Indoles with Sodium Bisulfite and Alcohols to Access Indole-Containing Sulfonate Esters.

Herein, an efficient electrochemical three-component C-H functionalization of indoles with sodium bisulfite and alcohols is described, providing a sustainable and convenient synthetic route for the construction of structurally valuable indole-containing sulfonate esters in moderate to good yields. This protocol proceeds in an undivided cell without any metal catalysts or oxidants, features a broad substrate scope, and has an excellent functional group tolerance. Preliminary mechanistic studies suggest that a radical-radical pathway may be involved in this three-component reaction system.

Mechanistic Investigation of the Ce(III) Chloride Photoredox Catalysis System: Understanding the Role of Alcohols as Additives.

Photocatalytic C-H activation is an emerging area of research. While cerium chloride photocatalysts have been extensively studied, the role of alcohol additives in these systems remains a subject of ongoing discussion. It was demonstrated that the photocatalyst [NEt][CeCl] () produces •Cl and added alcohols exhibit zero-order kinetics.

2,3 : 6,7-Naphthalenediimide-Based Chiral Triangular Macrocycle: Self-Assembled Helix, Outer π-Surface Directed Co-Assembly and Circularly Polarized Luminescence.

Here, we report the synthesis and self-assembly of a novel chiral 2,3 : 6,7-naphthalenediimide-based triangular macrocycle (NDI-Δ) and its chiroptical properties. The enantiomeric NDI-Δ is synthesized by condensation of (RR) or (SS)-trans-1,2-cyclohexanediamine and 2,3,6,7-naphthalenetetracarboxylic 2,3 : 6,7-dianhydride, in which the chirality of the macrocycles is controlled by the diamine. With the rigid outer π-surface, the macrocycle exhibits unique chiroptical properties and self-assembly modes.

Rh(III)-Catalyzed Double C-H Activation toward Peptide-Benzazepine Conjugates.

We herein report the efficient synthesis of peptide-benzazepine conjugates from Lys-based peptides and acroleins via Rh(III)-catalyzed double C-H activation. This reaction features mild reaction conditions, broad scope, high atom and step economies, and excellent chemo- and site selectivity. The synthetic utility of this strategy is further demonstrated by scale-up experiments and product derivatizations, including diverse late-stage ligations based on the aldehyde moiety.

Palladium-Catalyzed Fluorinated Olefination of Aromatics.

Palladium-mediated, ligand-promoted C-H fluorinated olefination of aromatic derivatives is reported employing 2-bromo-3,3,3-trifluoropropene (BTP) as the fluorinating reagent. Bioactive compounds, such as Isatin, exhibited excellent compatibility with this reaction, underscoring the significance of this methodology for the synthesis of important derivatives.

Synthetic Breast Ultrasound Images: A Study to Overcome Medical Data Sharing Barriers.

The vast potential of medical big data to enhance healthcare outcomes remains underutilized due to privacy concerns, which restrict cross-center data sharing and the construction of diverse, large-scale datasets. To address this challenge, we developed a deep generative model aimed at synthesizing medical data to overcome data sharing barriers, with a focus on breast ultrasound (US) image synthesis. Specifically, we introduce CoLDiT, a conditional latent diffusion model with a transformer backbone, to generate US images of breast lesions across various Breast Imaging Reporting and Data System (BI-RADS) categories.

Real-world impact of luspatercept on red blood cell transfusions among patients with myelodysplastic syndromes: A United States healthcare claims database study.

Myelodysplastic syndromes (MDS) are associated with anemia and the need for blood transfusions. In clinical trials, luspatercept reduced transfusion dependency among patients with lower-risk MDS. This United States (US) study describes real-world clinical outcomes pre- and post-luspatercept initiation among patients with MDS.

Rhodium-catalyzed C-H α-fluoroalkenylation/annulation of β-ketosulfoxonium ylides with 2,2-difluorovinyl tosylate/oxadiazolones.

A Rh(III)-catalyzed C-H α-fluoroalkenylation/annulation of β-ketosulfoxonium ylides with 2,2-difluorovinyl tosylate/oxadiazolones was realized, which afforded various -fluoroalkenylation β-ketosulfoxonium ylides with high -selectivity and diverse oxadiazolone fused-isoquinolines. This protocol featured mild conditions, broad substrate scope, and functional-group compatibility. In addition, scale-up synthesis, related applications and preliminary mechanistic explorations were also accomplished.

Dual impacts of serine/glycine-free diet in enhancing antitumor immunity and promoting evasion via PD-L1 lactylation.

The effect of the serine/glycine-free diet (-SG diet) on colorectal cancer (CRC) remains unclear; meanwhile, programmed death-1 (PD-1) inhibitors are less effective for most CRC patients. Here, we demonstrate that the -SG diet inhibits CRC growth and promotes the accumulation of cytotoxic T cells to enhance antitumor immunity. Additionally, we also identified the lactylation of programmed death-ligand 1 (PD-L1) in tumor cells as a mechanism of immune evasion during cytotoxic T cell-mediated antitumor responses, and blocking the PD-1/PD-L1 signaling pathway is able to rejuvenate the function of CD8+ T cells recruited by the -SG diet, indicating the potential of combining the -SG diet with immunotherapy.

Coffee consumption is associated with intestinal Lawsonibacter asaccharolyticus abundance and prevalence across multiple cohorts.

Although diet is a substantial determinant of the human gut microbiome, the interplay between specific foods and microbial community structure remains poorly understood. Coffee is a habitually consumed beverage with established metabolic and health benefits. We previously found that coffee is, among >150 items, the food showing the highest correlation with microbiome components.

Deep learning-based algorithm for automatic quantification of nigrosome-1 and Parkinsonism classification using susceptibility map-weighted MRI.

Background And Purpose: To develop and validate a deep learning-based automatic quantification for nigral hyperintensity and a classification algorithm for neurodegenerative parkinsonism using susceptibility map-weighted imaging (SMwI).

Materials And Methods: We retrospectively collected 450 participants (210 with idiopathic Parkinson's disease [IPD] and 240 individuals in the control group) for training data between November 2022 and May 2023, and 237 participants (168 with IPD, 58 with essential tremor, and 11 with drug-induced Parkinsonism) for validation data between July 2021 and January 2022. SMwI data were reconstructed from multi-echo GRE.

Enantioselective Propargylic C(sp)-H Acyloxylation Enabled by Photoexcited Copper Catalysis.

Direct C-H bond functionalization is an efficient method for modifying organic molecules. However, achieving high enantioselectivity and regioselectivity in asymmetric C-H functionalization, particularly of C(sp)-H bonds, remains challenging. This study introduces an enantioselective propargylic C(sp)-H acyloxylation using photoexcited copper catalysis.

Mild-Condition Photocatalytic Reforming of Methanol-Water by a Hierarchical, Asymmetry Carbon Nitride.

As a reproducible intermediate for hydrogen (H) and carbon cycling, methanol mixed with water (HO) in a ratio of 1 : 1 can multiply the outcome of green H generation via Photocatalytic reforming of methanol-HO (PRMW). Hitherto, low-energy and mild-condition PRMW remains a serious challenge. Here, the amino acid-derived carbon nitrides (ACN) were synthesized supramolecular precursor strategy for PRMW and achieved excellent performance (H, 35.

CAR-Macrophage Therapy Alleviates Myocardial Ischemia-Reperfusion Injury.

Background: Given the growing acknowledgment of the detrimental effects of excessive myocardial fibrosis on pathological remodeling after myocardial ischemia-reperfusion injury (I/R), targeting the modulation of myocardial fibrosis may offer protective and therapeutic advantages. However, effective clinical interventions and therapies that target myocardial fibrosis remain limited. As a promising chimeric antigen receptor (CAR) cell therapy, whether CAR macrophages (CAR-Ms) can be used to treat I/R remains unclear.

Steerable Structural Evolvement and Adsorption Behavior of Metastable Polyoxovanadate-Based Metal-Organic Polyhedra.

Promoting the advancement of the structure and function of metastable substances is challenging but worthwhile. In particular, how to harness the entangled state and evolution path of labile porous structures has been at the forefront of research in molecular self-assembly. In this work, the metastable structures of polyoxovanadate-based metal-organic polyhedra (VMOPs) can be manually regulated, including separation of the interlocked aggregate by a ligand-widening approach as well as transformation from a tetrahedral to capsule-like scaffold via a vertice-remodeling strategy.

Enantioselective Electrocatalysis for Cross-Dehydrogenative Heteroarylation with Indoles, Pyrroles, and Furans.

Oxidative cross-dehydrogenative C-H/C-H functionalizations represent an exemplary approach for synthesizing carbonyl compounds via α-heteroarylation. Here we present the development of a direct anodic oxidative coupling process between 2-acylimidazoles and divergent heterocyclic systems including indole, pyrrole, and furan, facilitated by ferrocene-assisted asymmetric nickel electrocatalysis with high levels of enantioselectivity. Mechanistic investigations indicate that the reaction initially involves the formation of a chiral Ni-bound α-carbonyl radical, which is then captured by the heteroarene radical cation via intermolecular stereoselective radical/radical cation coupling.

Benzylic C-H Radical Sulfation by Persulfates.

Sulfation is a highly valuable pathological and physiological process, yet it is often underappreciated considering the rather difficult accessibility of organosulfates. O-sulfonation (O-SO), a conventional and still common way to make organosulfates, restricts its applicability to hydroxyl compounds and therein lies a major challenge of library construction. Here, we describe a benzylic C-H radical sulfation with persulfates via C-O bond formation.

Visible-Light Photoredox-Catalyzed Direct Carboxylation of Tertiary C(sp)-H Bonds with CO: Facile Synthesis of All-Carbon Quaternary Carboxylic Acids.

Direct carboxylation of C-H bonds with CO represents an attractive strategy to synthesize valuable carboxylic acids with high atom, step, and redox economy. Although great progress has been achieved in this field, catalytic carboxylation of tertiary C(sp)-H bonds still remains challenging due to their inherent inertness and significant steric hindrance. Herein, we report a direct carboxylation of tertiary benzylic C(sp)-H bonds with CO via visible-light photoredox catalysis.

Tumor draining lymph nodes connected to cold triple-negative breast cancers are characterized by Th2-associated microenvironment.

Tumor draining lymph nodes (TDLN) represent a key component of the tumor-immunity cycle. There are few studies describing how TDLNs impact lymphocyte infiltration into tumors. Here we directly compare tumor-free TDLNs draining "cold" and "hot" human triple negative breast cancers (TDLN and TDLN).

Isolated Pt Atoms Stabilized by GaO Clusters Confined in ZSM-5 for Nonoxidative Activation of Ethane.

Selective activation of light alkanes is an essential reaction in the petrochemical industry for producing commodity chemicals, such as light olefins and aromatics. Because of the much higher intrinsic activities of noble metals in comparison to non-noble metals, it is desirable to employ solid catalysts with low noble metal loadings to reduce the cost of catalysts. Herein, we report the introduction of a tiny amount of Pt (at levels of hundreds of ppm) as a promoter of the GaO clusters encapsulated in ZSM-5 zeolite, which leads to ∼20-fold improvement in the activity for ethane dehydrogenation reaction.