Tetracycline (TC) and ciprofloxacin (CF) induce a synergistic effect that alters the biochemical composition, leading to a decrease in the growth and photosynthetic efficiency of microalgae. But the current study provides a novel insight into stress-inducing techniques that trigger a change in macromolecules, leading to an increase in the bioenergy potential and pathogen resistance of Chlorella variabilis biofilm. The study revealed that in a closed system, a light intensity of 167 μmol/m2/s causes 93.5% degradation of TC and 16% degradation of CF after 7 days of exposure, hence availing the products for utilization by C. variabilis biofilm. The resistance to pathogens invasion was linked to 85% and 40% increase in the expression level of photosystem II oxygen-evolving enhancer protein 3 (PsbQ), and mitogen activated kinase (MAK) respectively. The results also indicate that a surge in light intensity triggers 49% increase in the expression level of lysophosphatidylcholine (LPC) (18:2), which is an important lipidomics that can easily undergo transesterification into bioenergy. The thermogravimetric result indicates that the biomass sample of C. variabilis biofilm cultivated under light intensity of 167 μmol/m2/s produces a higher residual mass of 45.5% and 57.5 under air and inert conditions, respectively. The Fourier transform infrared (FTIR) indicates a slight shift in the major functional groups, while the energy-dispersive X-ray spectroscopy (SEM-EDS) and X-ray fluorescence (XRF) indicate clear differences in the morphology and elemental composition of the biofilm biomass in support of the increase bioenergy potential of C. variabilis biofilm. The current study provides a vital understanding of a innovative method of cultivation of C. variabilis biofilm, which is resistant to pathogens and controls the balance between fatty acid and TAG synthesis leading to surge in bioenergy potential and environmental sustainability.

As the most prevalent and reversible internal epigenetic modification in eukaryotic mRNAs, N 6-methyladenosine (m6A) post-transcriptionally regulates the processing and metabolism of mRNAs involved in diverse biological processes. m6A modification is regulated by m6A writers, erasers, and readers. Emerging evidence suggests that m6A modification plays essential roles in modulating the cell-fate transition of embryonic stem cells. Mechanistic investigation of embryonic stem cell maintenance and differentiation is critical for understanding early embryonic development, which is also the premise for the application of embryonic stem cells in regenerative medicine. This review highlights the current knowledge of m6A modification and its essential regulatory contribution to the cell fate transition of mouse and human embryonic stem cells.

Epigenetics refers to heritable changes in gene expression and function that impact nuclear processes associated with chromatin, all without altering DNA sequences. These epigenetic patterns, being heritable traits, are vital biological mechanisms that intricately regulate gene expression and heredity. The application of chemical labeling and single-cell resolution mapping strategies has significantly facilitated large-scale epigenetic modifications in nucleic acids over recent years. Notably, epigenetic modifications can induce heritable phenotypic changes, regulate cell differentiation, influence cell-specific gene expression, parentally imprint genes, activate the X chromosome, and stabilize genome structure. Given their reversibility and susceptibility to environmental factors, epigenetic modifications have gained prominence in disease diagnosis, significantly impacting clinical medicine research. Recent studies have uncovered strong links between epigenetic modifications and the pathogenesis of metabolic cardiovascular diseases, including congenital heart disease, heart failure, cardiomyopathy, hypertension, and atherosclerosis. In this review, we provide an overview of the progress in epigenetic research within the context of cardiovascular diseases, encompassing their pathogenesis, prevention, diagnosis, and treatment. Furthermore, we shed light on the potential prospects of nucleic acid epigenetic modifications as a promising avenue in clinical medicine and biomedical applications.

Drug transporters are critical factors influencing the pharmacokinetics of drugs under hypoxic conditions. Studies have shown significant changes in drug transporter levels in the hypoxic environment. In addition to being regulated by HIF-1, nuclear receptors, and inflammatory factors, hypoxia can also regulate transporters through epigenetic modifications, thereby affecting drug absorption, distribution, metabolism, and excretion. In recent years, increasing attention has been paid to the role of epigenetic modifications in regulating drug transporters under hypoxic conditions at high altitude. In this paper, we comprehensively review the effects of hypoxia on drug transporters and epigenetic modifications and explore the regulatory mechanism of epigenetic modifications on drug transporter expression under hypoxic conditions. The aim is to provide a reference for exploring the epigenetic regulation mechanism of drug transporter expression in the hypoxic environment at high altitude, and then guide the study of pharmacokinetics and promote effective and safe medication at high altitude.

The circulatory system is a closed conduit system throughout the body and consists of two parts as follows: the cardiovascular system and the lymphatic system. Hematological malignancies usually grow and multiply in the circulatory system, directly or indirectly affecting its function. These malignancies include multiple myeloma, leukemia, and lymphoma. O-linked β-N-acetylglucosamine (O-GlcNAc) transferase (OGT) regulates the function and stability of substrate proteins through O-GlcNAc modification. Abnormally expressed OGT is strongly associated with tumorigenesis, including hematological malignancies, colorectal cancer, liver cancer, breast cancer, and prostate cancer. In cells, OGT can assemble with a variety of proteins to form complexes to exercise related biological functions, such as OGT/HCF-1, OGT/TET, NSL, and then regulate glucose metabolism, gene transcription, cell proliferation, and other biological processes, thus affecting the development of hematological malignancies. This review summarizes the complexes involved in the assembly of OGT in cells and the role of related OGT complexes in hematological malignancies. Unraveling the complex network regulated by the OGT complex will facilitate a better understanding of hematologic malignancy development and progression.

Human activities and climate change have resulted in frequent and intense weather fluctuations, leading to diverse abiotic stresses on crops which hampers greatly their metabolic activities. Heat stress, a prevalent abiotic factor, significantly influences cotton plant biological activities resulting in reducing yield and production. We must deepen our understanding of how plants respond to heat stress across various dimensions, encompassing genes, RNAs, proteins, metabolites for effective cotton breeding. Multi-omics methods, primarily genomics, transcriptomics, proteomics, metabolomics, and phenomics, proves instrumental in studying cotton\'s responses to abiotic stresses. Integrating genomics, transcriptomics, proteomics, and metabolomic is imperative for our better understanding regarding genetics and molecular basis of heat tolerance in cotton. The current review explores fundamental omics techniques, covering genomics, transcriptomics, proteomics, and metabolomics, to highlight the progress made in cotton omics research.

BACKGROUND: Fibrogenesis within ovarian endometrioma (endometrioma), mainly induced by transforming growth factor-β (TGF-β), is characterized by myofibroblast over-activation and excessive extracellular matrix (ECM) deposition, contributing to endometrioma-associated symptoms such as infertility by impairing ovarian reserve and oocyte quality. However, the precise molecular mechanisms that underpin the endometrioma- associated fibrosis progression induced by TGF-β remain poorly understood.
METHODS: The expression level of lysine acetyltransferase 14 (KAT14) was validated in endometrium biopsies from patients with endometrioma and healthy controls, and the transcription level of KAT14 was further confirmed by analyzing a published single-cell transcriptome (scRNA-seq) dataset of endometriosis. We used overexpression, knockout, and knockdown approaches in immortalized human endometrial stromal cells (HESCs) or human primary ectopic endometrial stromal cells (EcESCs) to determine the role of KAT14 in TGF-β-induced fibrosis. Furthermore, an adeno-associated virus (AAV) carrying KAT14-shRNA was used in an endometriosis mice model to assess the role of KAT14 in vivo.
RESULTS: KAT14 was upregulated in ectopic lesions from endometrioma patients and predominantly expressed in activated fibroblasts. In vitro studies showed that KAT14 overexpression significantly promoted a TGF-β-induced profibrotic response in endometrial stromal cells, while KAT14 silencing showed adverse effects that could be rescued by KAT14 re-enhancement. In vivo, Kat14 knockdown ameliorated fibrosis in the ectopic lesions of the endometriosis mouse model. Mechanistically, we showed that KAT14 directly interacted with serum response factor (SRF) to promote the expression of α-smooth muscle actin (α-SMA) by increasing histone H4 acetylation at promoter regions; this is necessary for TGF-β-induced ECM production and myofibroblast differentiation. In addition, the knockdown or pharmacological inhibition of SRF significantly attenuated KAT14-mediating profibrotic effects under TGF-β treatment. Notably, the KAT14/SRF complex was abundant in endometrioma samples and positively correlated with α-SMA expression, further supporting the key role of KAT14/SRF complex in the progression of endometrioma-associated fibrogenesis.
CONCLUSIONS: Our results shed light on KAT14 as a key effector of TGF-β-induced ECM production and myofibroblast differentiation in EcESCs by promoting histone H4 acetylation via co-operating with SRF, representing a potential therapeutic target for endometrioma-associated fibrosis.

Postnatal immune activation (PIA) induces persistent glial activation in the brain and causes various neuropathologies in adults. Exercise training improves stress-related mood disorders; however, the role of exercise in psychiatric disorders induced by early-life immune activation and the association between exercise training and glial activation remain unclear. We compared the effects of different exercise intensities on the PIA model, including high-intensity interval training (HIIT) and moderate-intensity continuous training (MICT). Both HIIT and MICT in adolescent mice inhibited neuroinflammation, remodeled synaptic plasticity, and improved PIA-induced mood disorders in adulthood. Importantly, HIIT was superior to MICT in terms of reducing inflammation and increasing body weight. RNA-seq of prefrontal cortex (PFC) tissues revealed a gene expression pattern, confirming that HIIT was more effective than MICT in improving brain glial cell activation through epigenetic modifications of KDM6B. We investigated the role of KDM6B, a specific histone lysine demethylation enzyme - histone 3 lysine 27 demethylase, in inhibiting glial activation against PIA-induced depression and anxiety by regulating the expression of IL-4 and brain-derived neurotrophic factor (BDNF). Overall, our data support the idea that HIIT improves PIA-induced mood disorders by regulating KDM6B-mediated epigenetic mechanisms and indicate that HIIT might be superior to MICT in improving mood disorders with PIA in mice. Our findings provide new insights into the treatment of anxiety and depression disorders.

Extracellular vesicles (EVs), emerging as novel mediators between intercellular communication, encapsulate distinct bioactive cargoes to modulate multiple biological events, such as epigenetic remodeling. In essence, EVs and epigenomic profiles are tightly linked and reciprocally regulated. Epigenetic factors, including histone and DNA modifications, noncoding RNAs, and protein post-translational modifications (PTMs) dynamically regulate EV biogenesis to contribute to EV heterogeneity. Alternatively, EVs actively modify DNA, RNA, and histone profiles in recipient cells by delivering RNA and protein cargoes for downstream epigenetic enzyme regulation. Moreover, EVs display great potential as diagnostic markers and drug-delivery vehicles for therapeutic applications. The combination of parental cell epigenomic modification with single EV characterization would be a promising strategy for EV engineering to enhance the epidrug loading efficacy and accuracy.

Lysine lactylation (Kla) is a kind of novel post-translational modification (PTM) that participates in gene expression and various metabolic processes. Nannochloropsis has a remarkable capacity for triacylglycerol (TAG) production under nitrogen stress. To elucidate the involvement of lactylation in lipid synthesis, we conducted chromatin immunoprecipitation sequencing (ChIP-seq) and mRNA-seq analyses to monitor lactylation modifications and transcriptome alterations in Nannochloropsis oceanica. In all, 2057 genes showed considerable variation between nitrogen deprivation (ND) and nitrogen repletion (NR) conditions. Moreover, a total of 5375 differential Kla peaks were identified, including 5331 gain peaks and 44 loss peaks under ND vs NR. The differential Kla peaks were primarily distributed in the promoter (≤1 kb) (71.07%), 5\'UTR (22.64%), and exon (4.25%). Integrative analysis of ChIP-seq, transcriptome, and previous proteome and lactylome data elucidates the potential mechanism by which lactylation promotes lipid accumulation under ND. Lactylation facilitates autophagy and protein degradation, leading to the recycling of carbon into the tricarboxylic acid (TCA) cycle, thereby providing carbon precursors for lipid synthesis. Additionally, lactylation induces the redirection of carbon from membrane lipids to TAG by upregulating lipases and enhancing the TCA cycle and β-oxidation pathways. This research offers a new perspective for the investigation of lipid biosynthesis in Nannochloropsis.