CRISPR/Cas9-assisted gene editing reveals that EgPKS, a polyketide synthase, is required for the biosynthesis of preussomerins in Edenia gomezpompae SV2.

Edenia gomezpompae, an endophytic fungus derived from plants, produced a diverse array of preussomerins, a type of spirobisnaphthalenes featuring two spiroketal groups, which exhibited significant antibacterial, antifungal, and cytotoxic activities. Structurally, the biosynthesis of preussomerins might be related to the biosynthesis of 1,8-dihydroxynaphthalene (DHN), a precursor of DHN-melanin. However, the absence of efficient gene-editing tools for E.

CD36 Promotes Iron Accumulation and Dysfunction in CD8+ T Cells via the p38-CEBPB-TfR1 Axis in Early-stage Hepatocellular Carcinoma.

Background: The identification of factors that lead to CD8⁺ T cell dysfunction within the tumor microenvironment (TME) holds great promise for the development of innovative immunotherapies. However, the precise mechanisms underlying the exhausted phenotype of CD8⁺ T cells infiltrating early-stage hepatocellular carcinoma (HCC) tumors remains unclear.

Methods: Single-cell RNA sequencing was performed using a murine HCC model.

Dicoumarol sensitizes hepatocellular carcinoma cells to ferroptosis induced by imidazole ketone erastin.

Introduction: Ferroptosis, an iron-dependent form of regulated cell death, is characterized by the lethal accumulation of lipid peroxides on cellular membranes. It not only inhibits tumor growth but also enhances immunotherapy responses and overcomes drug resistance in cancer therapy. The inhibition of the cystine-glutamate antiporter, system Xc-, induces ferroptosis.

Identification of a functional vitamin D response element in the promoter of goose anti-Müllerian hormone gene.

Anti-Müllerian hormone (AMH) plays an important role in avian ovarian follicle development. The high mRNA expression of AMH in avian ovarian prehierarchical follicles helps prevent premature granulosa cell differentiation. Vitamin D3 was reported to downregulate AMH mRNA expression in granulosa cells of prehierarchical follicles in hens; however, the underlying molecular mechanism remains unknown.

Mechanistic role of mesencephalic astrocyte-derived neurotrophic factor in myocardial ischemia/reperfusion injury.

Mesencephalic astrocyte-derived neurotrophic factor (MANF) is a protein crucial for cellular stress response and survival, particularly in the nervous and cardiovascular systems. Unlike traditional neurotrophic factors, MANF primarily regulates endoplasmic reticulum (ER) stress and protects cells by reducing ER stress-induced apoptosis. MANF operates both inside and outside cells, influencing key pathways like JAK/STAT and NF-κB to enhance cell survival during stress.

Dual Frequency-Regulated Magnetic Vortex Nanorobots Empower Nattokinase for Focalized Microvascular Thrombolysis.

Magnetic nanorobots are emerging players in thrombolytic therapy due to their noninvasive remote actuation and drug loading capabilities. Although the nanorobots with a size under 100 nm are ideal to apply in microvascular systems, the propulsion performance of nanorobots is inevitably compromised due to the limited response to magnetic fields. Here, we demonstrate a nattokinase-loaded magnetic vortex nanorobot (NK-MNR) with an average size around 70 nm and high saturation magnetization for mechanical propelling and thermal responsive thrombolysis under a magnetic field with dual frequencies.

Selective recognition of PTRE1 transcripts mediated by protein-protein interaction between the mA reader ECT2 and PTRE1.

N-methyladenosine (mA) is a prevalent internal post-transcriptional modification in eukaryotic RNAs executed by mA-binding proteins known as "readers." Our previous research demonstrated that the Arabidopsis mA reader ECT2 positively regulates transcript levels of the proteasome regulator PTRE1 and several 20S proteasome subunits, thereby enhancing 26S proteasome activity. However, mechanism underlying the selective recognition of mA targets by readers, such as ECT2, remains elusive.

Inhibition of ferroptosis rescues M2 macrophages and alleviates arthritis by suppressing the HMGB1/TLR4/STAT3 axis in M1 macrophages.

Ferroptosis is a type of programmed cell death driven by iron-dependent lipid peroxidation. The TNF-mediated biosynthesis of glutathione has been shown to protect synovial fibroblasts from ferroptosis in the hyperplastic synovium. Ferroptosis induction provides a novel therapeutic approach for rheumatoid arthritis (RA) by reducing the population of synovial fibroblasts.

Potential mechanism of tea for treating osteoporosis, osteoarthritis, and rheumatoid arthritis.

Osteoporosis (OP), osteoarthritis (OA), and rheumatoid arthritis (RA) are common bone and joint diseases with a high incidence and long duration. Thus, these conditions can affect the lives of middle-aged and elderly people. Tea drinking is a traditional lifestyle in China, and the long-term intake of tea and its active ingredients is beneficial to human health.

Circadian clock gene BMAL1 regulates STAR expression in goose ovarian preovulatory granulosa cells.

The ovarian circadian clock plays a regulatory role in the avian ovulation-oviposition cycle. However, little is known regarding the ovarian circadian clock of geese. In this study, we investigated rhythmic changes in clock genes over a 48-h period and identified potential clock-controlled genes involved in progesterone synthesis in goose ovarian preovulatory granulosa cells.

Impact of Airborne Pathogen-Derived Extracellular Vesicles on Macrophages Revealed by Raman Spectroscopy and Multiomics.

Long-term exposure to the indoor environment may pose threats to human health due to the presence of pathogenic bacteria and their byproducts. Nanoscale extracellular vesicles (EVs) extensively secreted from pathogenic bacteria can traverse biological barriers and affect physio-pathological processes. However, the potential health impact of EVs from indoor dust and the underlying mechanisms remain largely unexplored.

Diverse functional genes harboured in extracellular vesicles from environmental and human microbiota.

Exchange of mobile functional genes within microbiota benefits the microbial community. However, the status of the mobile gene pool in environment is still largely unclear, impeding the understanding on the process of gene transfer in natural microbial communities. The release of extracellular vesicles (EVs) by diverse organisms has been proposed to be a vital way in the complex networks of interactions between microbes and their habitats.

Inhibition of ferroptosis and iron accumulation alleviates pulmonary fibrosis in a bleomycin model.

Idiopathic pulmonary fibrosis (IPF) is a chronic progressive disease characterized by excessive proliferation of fibroblasts and excessive accumulation of extracellular matrix (ECM). Ferroptosis is a novel form of cell death characterized by the lethal accumulation of iron and lipid peroxidation, which is associated with many diseases. Our study addressed the potential role played by ferroptosis and iron accumulation in the progression of pulmonary fibrosis.

Deep Learning-Enabled Raman Spectroscopic Identification of Pathogen-Derived Extracellular Vesicles and the Biogenesis Process.

Pathogenic bacterial infections, exacerbated by increasing antimicrobial resistance, pose a major threat to human health worldwide. Extracellular vesicles (EVs), secreted by bacteria and acting as their "long-distance weapons", play an important role in the occurrence and development of infectious diseases. However, no efficient methods to rapidly detect and identify EVs of different bacterial origins are available.

Effects of soil protists on the antibiotic resistome under long term fertilization.

Soil protists are key in regulating soil microbial communities. However, our understanding on the role of soil protists in shaping antibiotic resistome is limited. Here, we considered the diversity and composition of bacteria, fungi and protists in arable soils collected from a long-term field experiment with multiple fertilization treatments.

Widespread of Potential Pathogen-Derived Extracellular Vesicles Carrying Antibiotic Resistance Genes in Indoor Dust.

Extracellular vesicles (EVs) are newly recognized as important vectors for carrying and spreading antibiotic resistance genes (ARGs). However, the ARGs harbored by EVs in ambient environments and the transfer potential are still unclear. In this study, the prevalence of ARGs and mobile genetic elements (MGEs) in EVs and their microbial origins were studied in indoor dust from restaurants, kindergarten, dormitories, and vehicles.

TNF antagonist sensitizes synovial fibroblasts to ferroptotic cell death in collagen-induced arthritis mouse models.

Ferroptosis is a nonapoptotic cell death process that requires cellular iron and the accumulation of lipid peroxides. In progressive rheumatoid arthritis (RA), synovial fibroblasts proliferate abnormally in the presence of reactive oxygen species (ROS) and elevated lipid oxidation. Here we show, using a collagen-induced arthritis (CIA) mouse model, that imidazole ketone erastin (IKE), a ferroptosis inducer, decreases fibroblast numbers in the synovium.

Oncogenic Activation of YAP Signaling Sensitizes Ferroptosis of Hepatocellular Carcinoma ALOXE3-Mediated Lipid Peroxidation Accumulation.

Ferroptosis, a form of programmed cell death process driven by iron-dependent lipid peroxidation, plays an important role in tumor suppression. Although previous study showed that intracellular Merlin-Hippo signaling suppresses ferroptosis of epithelial tumor cells through the inactivation of YAP signaling, it remains elusive if the proto-oncogenic transcriptional co-activator YAP could serve as a potential biomarker to predict cancer cell response to ferroptosis-inducing therapies. In this study, we show that both total YAP staining and nuclear YAP staining were more prevalent in HCC tissues than in nontumorous regions.

NMN recruits GSH to enhance GPX4-mediated ferroptosis defense in UV irradiation induced skin injury.

Oxidative stress and lipid peroxidation are major causes of skin injury induced by ultraviolet (UV) irradiation. Ferroptosis is a form of regulated necrosis driven by iron-dependent peroxidation of phospholipids and contributes to kinds of tissue injuries. However, it remains unclear whether the accumulation of lipid peroxides in UV irradiation-induced skin injury could lead to ferroptosis.

PERK mediates resistance to BRAF inhibition in melanoma with impaired PTEN.

Targeting mutant BRAF in patients with melanomas harboring this oncogene has been highly successful as a first-line treatment, but other mutations may affect its efficacy and alter the route of acquired resistance resulting in recurrence and poor prognosis. As an evolving strategy, melanoma treatment needs to be expanded to include targets based on newly discovered emerging molecules and pathways. We here show that PERK plays a critical role in BRAF inhibitor-acquired resistance in melanoma with impaired PTEN.