Conditional Protein Structure Generation with Protpardelle-1c.

We present Protpardelle-1c, a collection of protein structure generative models with robust motif scaffolding and support for multi-chain complex generation under hotspot-conditioning. Enabling sidechain-conditioning to a backbone-only model increased Protpardelle-1c's MotifBench score from 4.97 to 28.

The global genomic landscape of hypervirulent from 1932 to 2021.

The global spread of hypervirulent (hvKp) poses a serious public health threat. In this study, we conducted genomic epidemiology analysis on 2097 global hvKp isolates, including our 900 isolates sequenced through the Illumina platform (177 of them fully sequenced through PacBio platform), representing the most comprehensive genomic analysis of hvKp to date. Our results identified six dominant clonal groups (CGs), particularly including CG23 and CG258, and 17 major virulence determinant combinations (VDCs) comprising 10 virulence gene profiles (VGPs), four types of virulence plasmids, four ICE variants, Tn, and _island.

Research progress on NAT10-mediated acetylation in normal development and disease.

N4-acetylcytidine (ac4C) is an evolutionarily conserved RNA modification catalyzed by the acetyltransferase NAT10. It regulates RNA stability, translation, and post-transcriptional processes. Meanwhile, NAT10 functions as a dual-function enzyme exhibiting both protein acetyltransferase and RNA acetylase activities.

MERS-related coronavirus circulating in pangolins exhibits strong fusogenicity in human cells and high sensitivity to fusion inhibitors.

Unlike preceding MERS-related coronaviruses, the recently identified MjHKU4r-CoV-1 strain can directly infect human cells. Nonetheless, its potential pathogenic attributes and underlying molecular mechanisms remain unclear. We find that MjHKU4r-CoV-1 induces significant inflammation, including interleukin (IL)-6 and tumor necrosis factor alpha (TNF-α), and exhibits pronounced fusogenicity mediated by its spike (S) protein, leading to extensive syncytium formation.

Assessing generative model coverage of protein structures with SHAPES.

Recent advances in generative modeling enable efficient sampling of protein structures, but their tendency to optimize for designability imposes a bias toward idealized structures at the expense of loops and other complex structural motifs that are critical for function. We introduce SHAPES (structural and hierarchical assessment of proteins with embedding similarity) to evaluate five state-of-the-art generative models of protein structures. Using structural embeddings across multiple structural hierarchies, ranging from local geometries to global protein architectures, we reveal substantial undersampling of the observed protein structure space by these models.

MedSAGE: Bridging Generative AI and Medicinal Chemistry for Structure-Based Design of Small Molecule Drugs.

While generative AI is transforming the design of proteins, its effectiveness for structure-based design of small molecules remains limited. Current methods, including diffusion models, often produce small molecules with difficult-to-synthesize structures, poor medicinal chemistry properties, and limited target selectivity. To address these limitations, we introduce MedSAGE, a novel generative AI framework that adapts diffusion models specifically for small-molecule design.

YY1-induced DDX18 modulates EMT via the AKT/mTOR pathway in esophageal cancer: a novel therapeutic target.

Background: Esophageal cancer is the 11th most common malignancy and the 7th leading cause of cancer-related death globally. Identifying key molecules and underlying mechanisms in the progression of esophageal cancer represents an effective strategy for developing novel therapeutic approaches.

Methods: DDX18 expression in clinical specimens was evaluated by immunohistochemistry and western blot analysis.

Numerical Investigation of Perovskite/Silicon Heterojunction Tandem Solar Cell with a Dual-Functional Layer of MoO.

This study proposed a novel perovskite/silicon heterojunction (SHJ) tandem device structure without an interlayer, represented as ITO/NiO/perovskite/SnO/MoO/i-a-Si:H/n-c-Si/i-a-Si:H/n-a-Si:H/Ag, which was investigated by Silvaco TCAD software. The recombination layer in this structure comprises the carrier transport layers of SnO and MoO, where MoO serves dual functions, acting as the emitter for the SHJ bottom cell and as part of the recombination layer in the tandem cell. First, the effects of different recombination layers are analyzed, and the SnO/MoO layer demonstrates the best performance.

Anti-S2 antibodies responsible for the SARS-CoV-2 infection-induced serological cross-reactivity against MERS-CoV and MERS-related coronaviruses.

Sarbecoviruses, such as SARS-CoV-2, utilize angiotensin-converting enzyme 2 (ACE2) as the entry receptor; while merbecoviruses, such as MERS-CoV, use dipeptidyl peptidase 4 (DPP4) for viral entry. Recently, several MERS-related coronaviruses, NeoCoV and PDF-2180, were reported to use ACE2, the same receptor as SARS-CoV-2, to enter cells, raising the possibility of potential recombination between SARS-CoV-2 and MERS-related coronaviruses within the co-infected ACE2-expressing cells. However, facing this potential recombination risk, the serum and antibody cross-reactivity against MERS/MERS-related coronaviruses after SARS-CoV-2 vaccination and/or infection is still elusive.

Contrast-enhanced MRI-based intratumoral heterogeneity assessment for predicting lymph node metastasis in resectable pancreatic ductal adenocarcinoma.

Objectives: To develop and validate a contrast-enhanced MRI-based intratumoral heterogeneity (ITH) model for predicting lymph node (LN) metastasis in resectable pancreatic ductal adenocarcinoma (PDAC).

Methods: Lesions were encoded into different habitats based on enhancement ratios at arterial, venous, and delayed phases of contrast-enhanced MRI. Habitat models on enhanced ratio mapping and single sequences, radiomic models, and clinical models were developed for evaluating LN metastasis.

Pan-cancer analysis shapes the understanding of cancer biology and medicine.

Advances in multi-omics datasets and analytical methods have revolutionized cancer research, offering a comprehensive, pan-cancer perspective. Pan-cancer studies identify shared mechanisms and unique traits across different cancer types, which are reshaping diagnostic and treatment strategies. However, continued innovation is required to refine these approaches and deepen our understanding of cancer biology and medicine.

Assessing Generative Model Coverage of Protein Structures with SHAPES.

Recent advances in generative modeling enable efficient sampling of protein structures, but their tendency to optimize for designability imposes a bias toward idealized structures at the expense of loops and other complex structural motifs critical for function. We introduce SHAPES (Structural and Hierarchical Assessment of Proteins with Embedding Similarity) to evaluate five state-of-the-art generative models of protein structures. Using structural embeddings across multiple structural hierarchies, ranging from local geometries to global protein architectures, we reveal substantial undersampling of the observed protein structure space by these models.

High-Density Polyethylene Janus Fibrous Membrane with Enhanced Breathability and Moisture Permeability via PDA Assisted Hydrophilic Modification.

Functional fibrous membranes with high mechanical properties are intensively developed for different application fields. In this study, to enhance moisture and air permeability without compromising mechanical strength, a facile float-surface modification strategy is employed to fabricate Janus fibrous membranes with distinct hydrophobicity/hydrophilicity using the high-density polyethylene (HDPE) fibrous membranes. By coating one side of the HDPE fibrous membranes with polydopamine (PDA) and a superhydrophilic polyelectrolyte, the obtained Janus HDPE fibrous membranes demonstrate an excellent water transmission rate (577.

Improvement of silage characteristics of HMC4 and improvement of silage quality of king grass.

The effect of HMC4 produced by protoplast fusion on silage was studied. The silage formula was composed of heterozygote HMC4 (Group C), parent Lactobacillus (Group A) and a combination of two parents (Group B). The fermentation quality and microbial composition of each batch of silage were evaluated.

DEAD-box helicase family proteins: emerging targets in digestive system cancers and advances in targeted drug development.

Cancer has become one of the major diseases threatening human health in the twenty-first century due to its incurability. In 2022, new cases of esophageal and gastrointestinal cancers accounted for 17.1% of all newly diagnosed cancer cases worldwide.

Reticulophagy promotes EMT-induced fibrosis in offspring's lung tissue after maternal exposure to carbon black nanoparticles during gestation by a mC-dependent manner.

Accumulating evidence indicates that maternal exposure to carbon black nanoparticles (CBNPs) during gestation can induce multiple system abnormalities in offspring, whereas its potential mechanism in respiratory disease is still largely unknown. In order to explore the effect of maternal exposure to CBNPs on offspring's lung and latent pathogenesis, we respectively established in vivo model of pregnant rats exposed to CBNPs and ex vivo model of lung epithelial cells treated with pups' serum of pregnant rats exposed to CBNPs. After maternal exposure to CBNPs, epithelial-mesenchymal transition (EMT) and fibrosis levels increased as a result of DDRGK1-mediated reticulophagy upregulated in offspring's lung.

Modulation of AAV transduction and integration targeting by topoisomerase poisons.

Adeno-associated virus (AAV) is a widely used vehicle for gene delivery, lending interest to developing methods for enhancing AAV transduction and transgene expression. Here, we profile the function of several topoisomerase poisons, which are small molecules that stabilize topoisomerase enzymatic intermediates, where topoisomerase enzymes are covalently bound at chromosomal DNA breaks. As previously observed, we found that the topoisomerase poisons camptothecin (CPT), doxorubicin (DOX), and etoposide (ETO) increased AAV transduction in cultured cell models.

Ultrasound-Assisted Remote Benzylic C(sp)-H Alkylation of -Fluoroamides with Enol Silanes.

We have developed an ultrasound-assisted remote benzylic C(sp)-H alkylation of -fluorobenzamides with enol silanes; a series of β-aryl substituted propiophenones was generated in good to high yields. This reaction represents a C(sp)-C(sp) coupling and features simplicity, high efficiency, and wide substrate scope in a multiple-step sequential process, which involves N-F homolysis, 1,5-hydrogen atom transfer, benzylic radical addition, oxidation by copper(II) salt, and removal of the trimethylsilyl group. Also, DFT theoretical calculations and Marcus theory were employed to consolidate the proposed reaction mechanism.