Identification of Transcriptional Regulators of Immune Evasion Across Cancers: An Alternative Immunotherapeutic Strategy for Cholangiocarcinoma.

Background: Cancer immune evasion is a multifaceted process that synchronizes pro-tumoral immune infiltration, immunosuppressive inflammation, and inhibitory immune checkpoint expression (IC). Current immunotherapies combat this issue by reinstating immunosurveillance of tumors; however, it benefits a limited patient population. Thus, a more effective immunotherapeutic strategy is warranted to cater to specific patient populations.

The Detoxification Effects of Melatonin on Aflatoxin-Caused Toxic Effects and Underlying Molecular Mechanisms.

Aflatoxins (AFTs) are a form of mycotoxins mainly produced by and , which are common contaminants in various agricultural sources such as feed, milk, food, and grain crops. Aflatoxin B1 (AFB1) is the most toxic one among all AFTs. AFB1 undergoes bioactivation into AFB1-8,9-epoxide, then leads to diverse harmful effects such as neurotoxicity, carcinogenicity, hepatotoxicity, reproductive toxicity, nephrotoxicity, and immunotoxicity, with specific molecular mechanisms varying in different pathologies.

A miR-activated hydrogel for the delivery of a pro-chondrogenic microRNA-221 inhibitor as a minimally invasive therapeutic approach for articular cartilage repair.

Articular cartilage has limited capacity for repair (or for regeneration) under pathological conditions, given its non-vascularized connective tissue structure and low cellular density. Our group has successfully developed an injectable hydrogel for cartilage repair, composed of collagen type I (Col I), collagen type II (Col II), and methacrylated-hyaluronic acid (MeHA), capable of supporting chondrogenic differentiation of mesenchymal stem cells (MSCs) towards articular cartilage-like phenotypes. Recent studies have demonstrated that silencing may be an effective approach in promoting improved MSC chondrogenesis.

Interfacial water confers transcription factors with dinucleotide specificity.

Transcription factors (TFs) recognize specific bases within their DNA-binding motifs, with each base contributing nearly independently to total binding energy. However, the energetic contributions of particular dinucleotides can deviate strongly from the additive approximation, indicating that some TFs can specifically recognize DNA dinucleotides. Here we solved high-resolution (<1 Å) structures of MYF5 and BARHL2 bound to DNAs containing sets of dinucleotides that have different affinities to the proteins.

Quorum sensing signals of the grapevine crown gall bacterium, sp. Rr2-17: use of inducible expression and polymeric resin to sequester acyl-homoserine lactones.

Background: A grapevine crown gall tumor strain, sp. strain Rr2-17 was previously reported to accumulate copious amounts of diverse quorum sensing signals during growth. Genome sequencing identified a single luxI homolog in strain Rr2-17, suggesting that it may encode for a AHL synthase with broad substrate range, pending functional validation.

VGLL-fusions define a new class of intraparenchymal CNS schwannoma.

Background: Intracerebral schwannomas are rare tumors resembling their peripheral nerve sheath counterparts but localized in the CNS. They are not classified as a separate tumor type in the 2021 WHO classification. This study aimed to compile and characterize these rare neoplasms morphologically and molecularly.

Monitoring central nervous system tumour metabolism using cerebrospinal fluid.

Central nervous system (CNS) tumours are the most common cancer cause of death in under 40s in the UK, largely because they persist and recur and sometimes metastasise during treatment. Therefore, longitudinal monitoring of patients during and following treatment must be undertaken to understand the course of the disease and alter treatment plans reactively. This monitoring must be specific, sensitive, rapid, low cost, simple, and accepted by the patient.

Altered metabolic function induced by Aβ-oligomers and PSEN1 mutations in iPSC-derived astrocytes.

Altered energy metabolism in Alzheimer's disease (AD) is a major pathological hallmark implicated in the early stages of the disease process. Astrocytes play a central role in brain homeostasis and are implicated in multiple neurodegenerative diseases. Although numerous studies have investigated global changes in brain metabolism, redox status, gene expression and epigenetic markers in AD, the intricate interplay between different metabolic processes, particularly in astrocytes, remains poorly understood.

Protocol for the synthesis and activation of hydrogels with photocaged oligonucleotides.

Hydrogels with spatial-temporal control over chemical and physical properties allow for the creation of cellular niches with controllable properties that better mimic tissue environments. Here, we present a protocol for synthesizing hydrogels incorporating photocaged oligonucleotides that can be activated with non-ultraviolet (UV) wavelengths. We detail the synthesis of bulk hydrogels and spatially defined hydrogels with different chemical functionalities that all share common photocaged DNA.

Early career member highlights from the 22nd ERS Lung Science Conference: development of chronic lung diseases - from life-spanning mechanisms to preventive therapy.

https://bit.ly/4cbMjpS.

A Dynamic Model for Early Prediction of Alzheimer's Disease by Leveraging Graph Convolutional Networks and Tensor Algebra.

Alzheimer's disease (AD) is a neurocognitive disorder that deteriorates memory and impairs cognitive functions. Mild Cognitive Impairment (MCI) is generally considered as an intermediate phase between normal cognitive aging and more severe conditions such as AD. Although not all individuals with MCI will develop AD, they are at an increased risk of developing AD.

The more stars, the brighter! Interview with the ECM award winner 2023.

https://bit.ly/4f0AiVY.

MIBiG 4.0: advancing biosynthetic gene cluster curation through global collaboration.

Specialized or secondary metabolites are small molecules of biological origin, often showing potent biological activities with applications in agriculture, engineering and medicine. Usually, the biosynthesis of these natural products is governed by sets of co-regulated and physically clustered genes known as biosynthetic gene clusters (BGCs). To share information about BGCs in a standardized and machine-readable way, the Minimum Information about a Biosynthetic Gene cluster (MIBiG) data standard and repository was initiated in 2015.

Propelling sustainable energy: Multi-omics analysis of pennycress FATTY ACID ELONGATION1 knockout for biofuel production.

The aviation industry's growing interest in renewable jet fuel has encouraged the exploration of alternative oilseed crops. Replacing traditional fossil fuels with a sustainable, domestically sourced crop can substantially reduce carbon emissions, thus mitigating global climate instability. Pennycress (Thlaspi arvense L.

Advancing tumor microenvironment and lymphoid tissue research through 3D bioprinting and biofabrication.

Cancer progression is significantly influenced by the complex interactions within the tumor microenvironment (TME). Immune cells, in particular, play a critical role by infiltrating tumors from the circulation and surrounding lymphoid tissues in an attempt to control their spread. However, they often fail in this task.

Biofabrication and biomanufacturing in Ireland and the UK.

As we navigate the transition from the Fourth to the Fifth Industrial Revolution, the emerging fields of biomanufacturing and biofabrication are transforming life sciences and healthcare. These sectors are benefiting from a synergy of synthetic and engineering biology, sustainable manufacturing, and integrated design principles. Advanced techniques such as 3D bioprinting, tissue engineering, directed assembly, and self-assembly are instrumental in creating biomimetic scaffolds, tissues, organoids, medical devices, and biohybrid systems.

Major facilitator family transporters specifically enhance caffeyl alcohol uptake during C-lignin biosynthesis.

The mode of transport of lignin monomers to the sites of polymerization in the apoplast remains controversial. C-Lignin is a recently discovered form of lignin found in some seed coats that is composed exclusively of units derived from caffeyl alcohol. RNA-seq and proteome analyses identified a number of transporters co-expressed with C-lignin deposition in the seed coat of Cleome hassleriana.

Investigating the role of elastin and extracellular matrix damage in cardiovascular calcification.

Although calcification in the cardiovascular system is highly studied, the mechanisms behind it are not well understood. Current proposed mechanisms focus on cellular processes leading to, or controlling the unwanted mineralization in soft tissues. However, extracellular components such as collagen and elastin fundamentally regulate the mechanical properties of heart tissues.

Macrophages and the microbiome in chronic obstructive pulmonary disease.

COPD is a heterogeneous disease of the lungs characterised by restricted airflow. Chronic inflammation and recurrent bacterial infections are known to be important driving factors in exacerbations of this disease. Despite a marked increase in the number of alveolar macrophages present in the lungs of COPD patients, there is evidence of reduced clearance of pathogenic bacteria, leading to recurrent infection, exacerbation and subsequent lung function decline.

PROTAC-mediated FTO protein degradation effectively alleviates diet-induced obesity and hepatic steatosis.

Demethylation of N-Methyladenosine (m6A) by fat mass and obesity-associated protein (FTO) occurs in the development of obesity and fatty liver disease. In this study, we synthesized FTO-degradation targeted chimera (FTO-DT), which exhibited excellent lipid-lowering activity at low concentration. At a concentration of 0.

The Potential of Human Wharton's Jelly Mesenchymal Stem Cells Secretome Based Topical Gel for Therapeutic Application.

Background: Diabetic Foot Ulcer (DFU) might be worsened by neuropathy and vascular issues. This condition can cause 14.3% fatality, stressing the need for effective wound healing therapy.