Tertiary Lymphoid Structures are Linked to Enhanced Antitumor Immunity and Better Prognosis in Muscle-Invasive Bladder Cancer.

The prognosis for muscle-invasive bladder cancer (MIBC) remains poor, and reliable prognostic markers have yet to be identified. Tertiary lymphoid structures (TLS) have been associated with favorable outcomes in certain cancers. However, the relationship between TLS and MIBC remains unclear.

Self-improving generative foundation model for synthetic medical image generation and clinical applications.

In many clinical and research settings, the scarcity of high-quality medical imaging datasets has hampered the potential of artificial intelligence (AI) clinical applications. This issue is particularly pronounced in less common conditions, underrepresented populations and emerging imaging modalities, where the availability of diverse and comprehensive datasets is often inadequate. To address this challenge, we introduce a unified medical image-text generative model called MINIM that is capable of synthesizing medical images of various organs across various imaging modalities based on textual instructions.

Structural insight into Okazaki fragment maturation mediated by PCNA-bound FEN1 and RNaseH2.

PCNA is a master coordinator of many DNA-metabolic events. During DNA replication, the maturation of Okazaki fragments involves at least four DNA enzymes, all of which contain PCNA-interacting motifs. However, the temporal relationships and functional modulations between these PCNA-binding proteins are unclear.

Stereoselective Construction of the ABCDE Pentacyclic Motif of Phainanoids via Norrish-Yang Photocyclization Reaction.

A Norrish-Yang photocyclization reaction has been applied to regio- and stereoselective construction of the ABCDE pentacyclic motif of natural product phainanoids. The observed substrate conformation control implicates this powerful reaction could be applied to the construction of structurally diverse natural product scaffolds.

Siderophore interactions drive the ability of spp consortia to protect tomato against .

The soil-borne bacterial pathogen causes significant losses in Solanaceae crop production worldwide, including tomato, potato, and eggplant. To efficiently prevent outbreaks, it is essential to understand the complex interactions between pathogens and the microbiome. One promising mechanism for enhancing microbiome functionality is siderophore-mediated competition, which is shaped by the low iron availability in the rhizosphere.

Promoter DNA methylation and transcription factor condensation are linked to transcriptional memory in mammalian cells.

The regulation of genes can be mathematically described by input-output functions that are typically assumed to be time invariant. This fundamental assumption underpins the design of synthetic gene circuits and the quantitative understanding of natural gene regulatory networks. Here, we found that this assumption is challenged in mammalian cells.

Alkaline ceramidase 1-mediated platelet ceramide catabolism mitigates vascular inflammation and abdominal aortic aneurysm formation.

Abdominal aortic aneurysm (AAA) is a highly lethal vascular disease. The role of platelets in AAA remains incompletely understood. Here we show that platelet ceramides, rather than other phospholipids, were elevated in an angiotensin II (AngII)-induced AAA murine model and in patients with AAA by using targeted lipidomic analysis.

DNA polymerase δ subunit Pol32 binds histone H3-H4 and couples nucleosome assembly with Okazaki fragment processing.

During lagging strand chromatin replication, multiple Okazaki fragments (OFs) require processing and nucleosome assembly, but the mechanisms linking these processes remain unclear. Here, using transmission electron microscopy and rapid degradation of DNA ligase Cdc9, we observed flap structures accumulated on lagging strands, controlled by both Pol δ's strand displacement activity and Fen1's nuclease digestion. The distance between neighboring flap structures exhibits a regular pattern, indicative of matured OF length.

A replisome-associated histone H3-H4 chaperone required for epigenetic inheritance.

Faithful transfer of parental histones to newly replicated daughter DNA strands is critical for inheritance of epigenetic states. Although replication proteins that facilitate parental histone transfer have been identified, how intact histone H3-H4 tetramers travel from the front to the back of the replication fork remains unknown. Here, we use AlphaFold-Multimer structural predictions combined with biochemical and genetic approaches to identify the Mrc1/CLASPIN subunit of the replisome as a histone chaperone.

A generalized AI system for human embryo selection covering the entire IVF cycle via multi-modal contrastive learning.

fertilization (IVF) has revolutionized infertility treatment, benefiting millions of couples worldwide. However, current clinical practices for embryo selection rely heavily on visual inspection of morphology, which is highly variable and experience dependent. Here, we propose a comprehensive artificial intelligence (AI) system that can interpret embryo-developmental knowledge encoded in vast unlabeled multi-modal datasets and provide personalized embryo selection.

Hunting for the Intermolecular Diels-Alderase.

ConspectusThe Diels-Alder reaction is well known as a concerted [4 + 2] cycloaddition governed by the Woodward-Hoffmann rules. Since Prof. Otto Diels and his student Kurt Alder initially reported the intermolecular [4 + 2] cycloaddition between cyclopentadiene and quinone in 1928, it has been recognized as one of the most powerful chemical transformations to build C-C bonds and construct cyclic structures.

Chrysomycins, Anti-Tuberculosis C-Glycoside Polyketides from sp. MS751.

A new dimeric C-glycoside polyketide chrysomycin F (), along with four new monomeric compounds, chrysomycins G (), H (), I (), J (), as well as three known analogues, chrysomycins A (), B (), and C (), were isolated and characterised from a strain of sp. obtained from a sediment sample collected from the South China Sea. Their structures were determined by detailed spectroscopic analysis.

Author Correction: Gel-like inclusions of C-terminal fragments of TDP-43 sequester stalled proteasomes in neurons.

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Structure and topography of the synaptic V-ATPase-synaptophysin complex.

Synaptic vesicles are organelles with a precisely defined protein and lipid composition, yet the molecular mechanisms for the biogenesis of synaptic vesicles are mainly unknown. Here we discovered a well-defined interface between the synaptic vesicle V-ATPase and synaptophysin by in situ cryo-electron tomography and single-particle cryo-electron microscopy of functional synaptic vesicles isolated from mouse brains. The synaptic vesicle V-ATPase is an ATP-dependent proton pump that establishes the proton gradient across the synaptic vesicle, which in turn drives the uptake of neurotransmitters.

Regioselective Syntheses of 1,4- and 1,6-Dicarbonyl Compounds via Photoredox-Based Oxidative Heterocoupling of Enolsilanes with Oxygen as an Oxidant.

A photoredox-based oxidative heterocoupling of enolsilanes to the corresponding 1,4- and 1,6-dicarbonyl compounds was developed by using Mes-AcrBF as the photocatalyst, and oxygen was used as the oxidant. This newly developed chemistry adheres to the principles of atom economy, step economy, and redox economy, making it a concise and efficient method.

Development of a Strategy for the Total Synthesis of Alkaloids via the Cyclobutenone-Based PET-Initiated Cationic Radical-Driven [2+2]/Retro-Mannich Reaction.

A novel strategy for the synthesis of alkaloids has been achieved via a photoredox-initiated [2+2]/retro-Mannich reaction of tryptamine-substituted enaminones as a key step. The developed chemistry has been applied to the construction of the core tetracycle of alkaloids (±)-aspidospermidine and (±)-limaspermidine.

Enzymatic Degradation of Deoxynivalenol with the Engineered Detoxification Enzyme Fhb7.

In the era of global climate change, the increasingly severe head blight (FHB) and deoxynivalenol (DON) contamination have caused economic losses and brought food and feed safety concerns. Recently, an FHB resistance gene coding a glutathione-S transferase (GST) to degrade DON by opening the critical toxic epoxide moiety was identified and opened a new window for wheat breeding and DON detoxification. However, the poor stability of Fhb7 and the elusiveness of the catalytic mechanism hinder its practical application.

Exo-Selective Diels-Alder Reactions.

The Diels-Alder reaction stands as one of the most pivotal transformations in organic chemistry. Its efficiency, marked by the formation of two carbon-carbon bonds and up to four new stereocenters in a single step, underscores its versatility and indispensability in synthesizing natural products and pharmaceuticals. The most significant stereoselectivity feature is the "endo rule".

Total Synthesis of Penicibilaenes Enabled by a Tandem Double Conia-ene Type Reaction.

The total syntheses of penicibilaenes A and B are described. The key step is the BuOK/DMSO-mediated tandem 5-- Conia-ene type reaction and 6-- Conia-ene type reaction to install the tricyclic [6.3.

Near telomere-to-telomere genome of the model plant Physcomitrium patens.

The model plant Physcomitrium patens has played a pivotal role in enhancing our comprehension of plant evolution and development. However, the current genome harbours numerous regions that remain unfinished and erroneous. To address these issues, we generated an assembly using Oxford Nanopore reads and Hi-C mapping.