Synergistic Enhancement of Ferroptosis via Mitochondrial Accumulation and Photodynamic-Controlled Release of an Organogold(I) Cluster Prodrug.

Effective delivery and controlled release of metallo-prodrugs with sustained activation and rapid response feed the needs of precise medicine in metal chemotherapeutics. However, gold-based anticancer drugs often suffer from detoxification binding and extracellular transfer by sulfur-containing peptides. To address this challenge, we integrate a thiol-activated prodrug strategy of newly prepared hypercoordinated carbon-centered gold(I) clusters (HCGCs) with their photosensitization character to augment the mitochondrial release of Au(I) in tumors.

Complex hierarchical structures analysis in single-cell data with Poincaré deep manifold transformation.

Single-cell RNA sequencing (scRNA-seq) offers remarkable insights into cellular development and differentiation by capturing the gene expression profiles of individual cells. The role of dimensionality reduction and visualization in the interpretation of scRNA-seq data has gained widely acceptance. However, current methods face several challenges, including incomplete structure-preserving strategies and high distortion in embeddings, which fail to effectively model complex cell trajectories with multiple branches.

Flexible deformation and special interface structure in nanoparticle-stabilized Pickering bubbles strengthen the immunological response as adjuvant.

Adjuvants can enhance an immunological response, which is an important part of vaccine research. Pickering bubbles have been a mega-hit for biomedical applications, including visualization and targeted drug delivery. However, there have been no studies on Pickering bubbles as an immunological adjuvant, and the special properties and structures of Pickering bubbles may play an important role in immunization.

Multi-Label Zero-Shot Learning Via Contrastive Label-Based Attention.

Multi-label zero-shot learning (ML-ZSL) strives to recognize all objects in an image, regardless of whether they are present in the training data. Recent methods incorporate an attention mechanism to locate labels in the image and generate class-specific semantic information. However, the attention mechanism built on visual features treats label embeddings equally in the prediction score, leading to severe semantic ambiguity.

The role of lnc‑MAPKAPK5‑AS1 in immune cell infiltration in hepatocellular carcinoma: Bioinformatics analysis and validation.

The oncogenic and tumor suppressor roles of lnc-MAPKAPK5-AS1 in multiple cancers suggest its complexity in modulating cancer progression. The expression and promoter methylation level of lnc-MAPKAPK5-AS1 in hepatocellular carcinoma (HCC) was investigated through data mining from The Cancer Genome Atlas and Gene Expression Omnibus and its significance in prognosis and immunity was explored. lnc-MAPKAPK5-AS1 was co-expressed with its protein-coding gene MAPKAPK5 in HCC and exhibited upregulation in HCC tissues as a result of hypomethylation of its promoter region.

Overexpression of miR‑424‑5p reduces cisplatin resistance by downregulating SMURF1 in gastric cancer.

Chemoresistance is a major obstacle in the treatment of gastric cancer (GC). Notably, aberrant expression of microRNAs (miRs) is closely related to tumor development and progression. In the present study, the role of miR-424-5p in the chemoresistance of GC was investigated.

The prognostic importance of the negative regulators of ferroptosis, GPX4 and HSPB1, in patients with colorectal cancer.

The prognostic value of negative regulators of ferroptosis in patients with colorectal cancer (CRC) has not yet been fully elucidated. The present study performed a systematic identification and selection of candidate negative regulators of ferroptosis using The Cancer Genome Atlas data cohort (n=367), followed by clinical validation through immunohistochemistry of samples from patients with CRC (n=166) and further evaluation. analysis identified specific light-chain subunit of the cystine/glutamate antiporter, AIFM2, NFE2L2, FTH1, GLS2, glutathione peroxidase 4 (GPX4) and heat shock protein β-1 (HSPB1) genes as possible candidates.

Biosynthesis of Lysosomally Escaped Apoptotic Bodies Inhibits Inflammasome Synthesis in Macrophages.

Hyperglycemia and bacterial colonization in diabetic wounds aberrantly activate Nod-like receptor protein 3 (NLRP3) in macrophages, resulting in extensive inflammatory infiltration and impaired wound healing. Targeted suppression of the NLRP3 inflammasome shows promise in reducing macrophage inflammatory disruptions. However, challenges such as drug off-target effects and degradation via lysosomal capture remain during treatment.

Bioceramic Surface Topography Regulating Immune Osteogenesis.

This study aims to clarify the effects of bioceramic interface cues on macrophages. Recently, there have been many researches exploring the effects of interface topography cues on macrophage polarization and cytokine secretion. However, the effects and underlying mechanisms of bioceramic interface cues on macrophages still need exploring.

Microsomal glutathione transferase 1 confers cisplatin resistance of non-small cell lung cancer via interaction with arachidonate lipoxygenase 5 to repress ferroptosis.

Objectives: Cisplatin (DDP) resistance remains a primary cause of chemotherapy failure and recurrence of non-small cell lung cancer (NSCLC). Abnormal high microsomal glutathione transferase 1 (MGST1) expression has been found in DDP-resistant NSCLC cells. This study aimed to explore the function and mechanism of MGST1 in DDP resistance of NSCLC cells.

Mass production of ultrasmall MnO nanoparticles for glutathione responsive off-on / switching magnetic resonance imaging and tumor theranostics.

Individual theranostics with an integrated multifunction holds considerable promise for clinical application compared with multicomponent regimes. MnO nanoparticles with an ultrasmall size (4 nm) and mass production capability were developed with dual function of integrated tumor magnetic resonance imaging (MRI) and therapy. The high valence state of MnO nanocrystals enables a sensitive reaction with the glutathione (GSH) molecule and favorable decomposition ability, which further induces a unique, favorable, variable turn-off and turn-on MRI property.

Emoquine-1: A Hybrid Molecule Efficient against Multidrug-Resistant Parasites, Including the Artemisinin-Resistant Quiescent Stage, and Also Active In Vivo.

To challenge the multidrug resistance of malaria parasites, new hybrid compounds were synthesized and evaluated against laboratory strains and multidrug-resistant clinical isolates. Among these hybrids, emoquine-1 was the most active on proliferative , with IC values in the range of 20-55 nM and a high selectivity index with respect to mammalian cells. This drug retained its activity on several multiresistant field isolates from Cambodia and Guiana, exhibited no cross-resistance to artemisinin, and is also very active against the quiescent stage of the artemisinin-resistant parasites, three features that constitute the gold standard for new antimalarial drugs.

Enhancing High-Level Food-Grade Expression of Glutamate Decarboxylase and Its Application in the Production of γ-Aminobutyric Acid.

Gamma-aminobutyric acid (GABA), a non-proteinogenic amino acid, exhibits diverse physiological functions and finds extensive applications in food, medicine, and various industries. Glutamate decarboxylase (GAD) can effectively convert L-glutamic acid (L-Glu) or monosodium glutamate (MSG) into GABA. However, the low food-grade expression of GAD has hindered large-scale GABA production.

Acid-Promoted Phosphorylation of Ynones for the Synthesis of Phosphoryl Enones.

An efficient phospha-aldol/Meyer-Schuster rearrangement cascade reaction between propargylic aldehydes and phosphine oxides has been developed in which various phosphoryl enones were obtained in moderate to excellent yields. A comprehensive series of mechanistic experiments, including the identification of key intermediates and the application of O isotope labeling, has confirmed that this cascade reaction proceeds through a phospha-aldol followed by Meyer-Schuster rearrangement cascade reaction.

Spiny CoO@Hollow Carbon Spheres─Polyacrylonitrile/Carbon Black Fiber-Based Bifunctional Air Electrodes.

In the realm of zinc-air batteries, high bifunctional catalytic efficacy is intimately tied to the evaluation of catalysts. Consequently, the pursuit of proficient bifunctional catalysts that can efficiently catalyze both the oxygen reduction reaction (ORR) and oxygen evolution reaction (OER) remains a paramount objective in this research area. In this study, the spiny cobalt tetroxide (CoO) encapsulated hollow carbon spheres (HCSs) are constructed by anchoring CoO onto HCS via hydrothermal or annealing treatment.

Giant low-grade myofibroblastic sarcoma of the male breast: case report and literature review.

Low-grade myofibroblastic sarcoma is an uncommon malignancy that can be difficult to identify and for which there is no unified treatment protocol. We report herein a case of an 81-year-old male who presented with a giant irregular breast mass and was diagnosed with low-grade myofibroblastic sarcoma. In this study we summarise the clinicopathological features of 13 reported cases of myofibroblastic sarcoma arising in the breast, present the diagnostic process and treatment procedure of our case, and discuss the differential diagnosis from other similar diseases, to provide constructive information and promote deep understanding of myofibroblastic sarcoma in the future.

Predicting TNFRSF4 expression and prognosis in head and neck squamous cell carcinoma tissue: a pathological image analysis approach.

Head and neck squamous cell carcinoma (HNSCC) exhibits a poor 5-year survival rate. TNFRSF4 is gaining attention in tumor therapy. The objective of this study was to forecast the expression of TNFRSF4 in HNSCC tissue using analysis of pathological images and investigate its possible molecular mechanisms.

Coherent Exciton Spin Relaxation Dynamics and Exciton Polaron Character in Layered Two-Dimensional Lead-Halide Perovskites.

The quantum-well-like two-dimensional lead-halide perovskites exhibit strongly confined excitons due to the quantum confinement and reduced dielectric screening effect, which feature intriguing excitonic effects. The ionic nature of the perovskite crystal and the "softness" of the lattice induce the complex lattice dynamics. There are still open questions about how the soft lattices decorate the nature of excitons in these hybrid materials.

Neutrophil-macrophage hybrid membrane-coated prussian blue nanozyme for ulcerative colitis treatment and mechanistic insights.

Background: Ulcerative colitis (UC) is a chronic and recurrent digestive tract disease that can lead to significant morbidity and mortality. The pathogenesis of UC is intricately associated with the presence of reactive oxygen species (ROS). Prussian blue (PB), an inorganic nanozyme with potent antioxidant properties, has been extensively applied in the treatment of various inflammatory conditions and tumors.

Increased nerve density adversely affects outcome in colorectal cancer and denervation suppresses tumor growth.

Background: The colon and rectum are highly innervated, with neural components within the tumor microenvironment playing a significant role in colorectal cancer (CRC) progression. While perineural invasion (PNI) is associated with poor prognosis in CRC, the impact of nerve density and diameter on tumor behavior remains unclear. This study aims to evaluate the prognostic value of nerve characteristics in CRC and to verify the impact of nerves on tumor growth.

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).

Synergistic anti-oxidative/anti-inflammatory treatment for acute lung injury with selenium based chlorogenic acid nanoparticles through modulating Mapk8ip1/MAPK and Itga2b/PI3k-AKT axis.

Oxidative stress and inflammatory dysregulation play crucial roles in pathogenesis of acute lung injury (ALI), and their cyclic synergy drives excessive inflammatory responses and further exacerbates ALI. Therefore, new effective strategies to treat ALI are urgently needed. Herein, a novel synergistic selenium based chlorogenic acid nanoparticle was developed to disrupt the cyclic synergistic effect between oxidative stress and inflammatory response in ALI.

Mortality-related risk factors of carbapenem-resistant Enterobacteriaceae infection with focus on antimicrobial regimens optimization: a real-world retrospective study in China.

Objectives: To determine the mortality-related risk factors for carbapenem-resistant Enterobacteriaceae (CRE) infection in hospitalized patients and to compare the clinical efficacy of different antimicrobial regimen.

Methods: Data were retrospectively collected from a 3,500-bed regional medical center between January 2021 and June 2022. Mortality-related risk factors were analyzed by the Cox proportional regression model for multivariate analysis.

-Functionalization of Pillar[4]arene[1]benzoquinone Monoxime via Selective 1,4-Addition of Grignard Reagents.

-functionalization of pillar[]arenes has been a formidable challenge, partially due to the fragility of their macrocyclic skeletons. In this concise report, we describe a facile synthetic method for monoarylation/alkylation at the position to the oxime functionality in pillar[4]arene[1]benzoquinone monoxime () via addition of Grignard reagents. The described method enables the creation of various mono--alkyl/aryl-substituted pillar[5]arene derivatives that were previously inaccessible.

A Dual-Pathway Responsive Mechanophore for Intelligent Luminescent Polymer Materials.

Mechanoluminescent units, when integrated into polymer matrices, undergo structural transformations in response to mechanical force, resulting in changes in fluorescence. This phenomenon holds considerable promise for the development of stress-sensing materials. Despite the high demand for robust, tunable mechanoluminescent mechanophores for force assessment and smart force-responsive materials, strategies for their design and synthesis remain underdeveloped.