Single-cell transcriptomics reveals heterogeneity and prognostic markers of myeloid precursor cells in acute myeloid leukemia.

Background: Acute myeloid leukemia (AML) is a hematologic tumor with poor prognosis and significant clinical heterogeneity. By integrating transcriptomic data, single-cell RNA sequencing data and independently collected RNA sequencing data this study aims to identify key genes in AML and establish a prognostic assessment model to improve the accuracy of prognostic prediction.

Materials And Methods: We analyzed RNA-seq data from AML patients and combined it with single-cell RNA sequencing data to identify genes associated with AML prognosis.

Enhanced engraftment of human haematopoietic stem cells via mechanical remodelling mediated by the corticotropin-releasing hormone.

The engraftment of haematopoietic stem and progenitor cells (HSPCs), particularly in cord-blood transplants, remains challenging. Here we report the role of the corticotropin-releasing hormone (CRH) in enhancing the homing and engraftment of human-cord-blood HSPCs in bone marrow through mechanical remodelling. By using microfluidics, intravital two-photon imaging and long-term-engraftment assays, we show that treatment with CRH substantially enhances HSPC adhesion, motility and mechanical remodelling, ultimately leading to improved bone-marrow homing and engraftment in immunodeficient mice.

Aging and head and neck cancer insights from single cell and spatial transcriptomic analyses.

Background: Head and neck squamous cell carcinoma(HNSCC) is the sixth most common malignancy worldwide, with more than 890,000 new cases and 450,000 deaths annually. Its major risk factors include smoking, alcohol abuse, aging, and poor oral hygiene. Due to the lack of early and effective detection and screening methods, many patients are diagnosed at advanced stages with a five-year survival rate of less than 50%.

Multi-modal transcriptomics: integrating machine learning and convolutional neural networks to identify immune biomarkers in atherosclerosis.

Background: Atherosclerosis, a complex chronic vascular disorder with multifactorial etiology, stands as the primary culprit behind consequential cardiovascular events, imposing a substantial societal and economic burden. Nevertheless, our current understanding of its pathogenesis remains imprecise. In this investigation, our objective is to establish computational models elucidating molecular-level markers associated with atherosclerosis.

Immunomodulatory activity and molecular mechanisms of action of peptides derived from casein hydrolysate by alcalase and flavourzyme based on virtual screening.

This study aimed to screen novel immunomodulatory peptides from casein hydrolysates (CH) using alcalase and flavorzyme by virtual screening, and their molecular mechanism were further studied. Based on the primary structural characteristics of immunomodulatory peptides, along with their hydrophobicity and isoelectric point, 3 novel immunomodulatory peptides (ALPMHIR, AMKPWIQPK, NPWDQVKR) were quickly found using virtual screening. These peptides exhibited strong interactions with TLR2/TLR4 through hydrogen bonding and hydrophobic interactions.

Bioinformatics Identification and Validation of Ferroptosis-Related Key Genes and Therapeutic Compounds in Septic Lung Injury.

Background: Septic lung injury (SLI) is a severe condition with high mortality, and ferroptosis, a form of programmed cell death, is implicated in its pathogenesis. However, the explicit mechanisms underlying this condition remain unclear. This study aimed to elucidate and validate key ferroptosis-related genes involved in the pathogenesis of SLI through bioinformatics analysis and experimental validation.

Therapeutic strategies for ypT1 rectal cancer after neoadjuvant chemoradiotherapy: a retrospective cohort study.

Purpose: The optimal treatment of ypT1 rectal cancer after neoadjuvant chemoradiotherapy (nCRT) remains controversial. This study aimed to determine whether local excision is non-inferior to radical surgery and whether adjuvant chemotherapy (ACT) would improve survival in patients with ypT1 rectal cancer after nCRT.

Methods: We enrolled 1212 and 91 patients with ypT1 rectal cancer underwent nCRT followed by radical surgery from the SEER database (2004-2018) and the Zhejiang Cancer Hospital (ZJCH) (2010-2022), respectively.

Molecular Design of Phthalocyanine-Based Drug Coassembly with Tailored Function.

Coassemblies with tailored functions, such as drug loading, tissue targeting and releasing, therapeutic and/or imaging purposes, and so on, have been widely studied and applied in biomedicine. design of these coassemblies hinges on an integrated approach involving synergy between various design strategies, ranging from structure screening of combinations of "phthalocyanine-chemotherapeutic drug" molecules for molecular scaffolds, exploration of related fabrication principles to verification of intended activity of specific designs. Here, we propose an integrated approach combining computation and experiments to design from scratch coassembled nanoparticles.

Time-Lapse Acquisition of Both Freely Secreted Proteome and Exosome Encapsulated Proteome in Live Organoids' Microenvironment.

Proteomic communications in neighboring microenvironments during early organ development is a dynamic process that continuously reshapes human embryonic stem cells (hESCs) developmental fate. Such dynamic proteomic alteration in the microenvironment consists of both freely secreted proteome and exosome-encapsulated proteome. Simultaneous monitoring of the time-lapse shift of both proteomes with live organoids remains technically challenging.

Deciphering the role of NcRNAs in Pancreatic Cancer immune evasion and drug resistance: a new perspective for targeted therapy.

Pancreatic cancer (PC) is a very aggressive digestive system tumor, known for its high mortality rate, low cure rate, low survival rate and poor prognosis. In particular, pancreatic ductal adenocarcinoma (PADC), which accounts for more than 90% of PC cases, has an overall 5-year survival rate of only 5%, which is an extremely critical situation. Early detection and effective treatment of PC is extremely difficult, which leads many patients to despair.

A noncoding variant confers pancreatic differentiation defect and contributes to diabetes susceptibility by recruiting RXRA.

Human genetics analysis has identified many noncoding SNPs associated with diabetic traits, but whether and how these variants contribute to diabetes is largely unknown. Here, we focus on a noncoding variant, rs6048205, and report that the risk-G variant impairs the generation of PDX1+/NKX6-1+ pancreatic progenitor cells and further results in the abnormal decrease of functional β cells during pancreatic differentiation. Mechanistically, this risk-G variant greatly enhances RXRA binding and over-activates FOXA2 transcription, specifically in the pancreatic progenitor stage, which in turn represses NKX6-1 expression.

The two-sided battlefield of tumour-associated macrophages in glioblastoma: unravelling their therapeutic potential.

Gliomas are the most common primary malignant tumours of the central nervous system (CNS), which are highly aggressive, with increasing morbidity and mortality rates year after year, posing a serious threat to the quality and expected survival time of patients. The treatment of gliomas is a major challenge in the field of neuro-oncology, especially high-grade gliomas such as glioblastomas (GBMs). Despite considerable progress in recent years in the study of the molecular and cellular mechanisms of GBMs, their prognosis remains bleak.

Integrative biomarker discovery and immune profiling for ulcerative colitis: a multi-methodological approach.

Background We aimed to pinpoint biomarkers, create a diagnostic model for ulcerative colitis (UC), and delve into its immune features to better understand this autoimmune condition. Methods The sequencing data for both the UC and the control groups were obtained from GEO, including both bulk and single-cell data. Using GSE87466 as training group, we applied differential analysis, WGCNA, PPI, LASSO, RF, and SVM-RFE for biomarker selection.

Multi-modal transcriptomic analysis reveals metabolic dysregulation and immune responses in chronic obstructive pulmonary disease.

Chronic obstructive pulmonary disease (COPD), a progressive inflammatory condition of the airways, emerges from the complex interplay between genetic predisposition and environmental factors. Notably, its incidence is on the rise, particularly among the elderly demographic. Current research increasingly highlights cellular senescence as a key driver in chronic lung pathologies.

Sono-Triggered Biomimetically Nanoantibiotics Mediate Precise Sequential Therapy of MRSA-Induced Lung Infection.

Bacterial-induced lower respiratory tract infections are a growing global health concern, exacerbated by the inefficacy of conventional antibiotics and delivery methods to effectively target the lower respiratory tract, leading to suboptimal therapeutic outcomes. To address this challenge, this work engineers PBP2a antibody-presenting membrane nanovesicles (AMVs) specifically designed to target the penicillin-binding protein variant on the surface of methicillin-resistant Staphylococcus aureus (MRSA). Concurrently, this work develops pure ciprofloxacin nanoparticles (NanoCip) that, for the first time, exhibits exceptional self-generated sonodynamic properties, attributed to hydrogen-bond-driven self-assembly, while maintaining their inherent pharmacological efficacy.

A multichannel microfluidic device for revealing the neurotoxic effects of Bisphenol S on cerebral organoids under low-dose constant exposure.

Bisphenol S is a widely used plasticizer in manufacturing daily supplies, while little was known about its adverse effect on human health, especially on fetal brain development. Due to the complexity and subtlety of the brain, it remains challenging to reveal the hazardous effects of environmental pollution on human fetal brain development. Taking advantage of stem cell application, cerebral organoids generated from stem cells are becoming powerful tools for understanding brain development and drug toxicity testing models.

New Insights into the Structure-Activity Relationship of a Novel Immunomodulatory Peptide (HPHPHLSF) from Casein Hydrolyzed by JY-1: Molecular Docking, Interaction Evaluation, and HOMO Analysis.

Casein is rich in immunomodulatory peptides. In this study, the release of casein-derived immunomodulatory peptides by JY-1 was investigated for the first time, and an immunosuppressive mouse model was used to evaluate the immunomodulatory activity in the casein hydrolysate. The results showed that the cellular and humoral immunity of immunosuppressed mice could be significantly enhanced by casein hydrolysate.

Facile and Reconfigurable Opaque Droplet-based Photomask for Photolithography.

Photolithography is a widely used technology in microfabrication, where photomasks are mostly indispensable. The fabrication of photomasks is generally costly, irreversible, and time-consuming, which limits the prompt delivery of photolithography especially in low-resource settings. Herein, we introduce a facile technique for green and reversible photomask fabrication with opaque droplets, termed as "droplet-based photomask.