Exploring the impact of lipid nanoparticles on protein stability and cellular proteostasis.

Lipid nanoparticles (LNPs) have become pivotal in advancing modern medicine, from mRNA-based vaccines to gene editing with CRISPR-Cas9 systems. Though LNPs based therapeutics offer promising drug delivery with satisfactory clinical safety profiles, concerns are raised regarding their potential nanotoxicity. Here, we explore the impacts of LNPs on protein stability in buffer and cellular protein homeostasis (proteostasis) in HepG2 cells. First, we show that LNPs of different polyethylene glycol (PEG) molar ratios to total lipid ratio boost protein aggregation propensity by reducing protein stability in cell lysate and blood plasma. Second, in HepG2 liver cells, these LNPs induce global proteome aggregation, as imaged by a cellular protein aggregation fluorescent dye (AggStain). Such LNPs induced proteome aggregation is accompanied by decrease in cellular micro-environmental polarity as quantified by a solvatochromic protein aggregation sensor (AggRetina). The observed local polarity fluctuations may be caused by the hydrophobic contents of LNPs that promote cellular proteome aggregation. Finally, we exploit RNA sequencing analysis (RNA-Seq) to reveal activation of unfolded protein response (UPR) pathway and other proteostasis genes upon LNPs treatment. Together, these findings highlight that LNPs may induce subtle proteome stress by compromising protein stability and proteostasis even without obvious damage to cell viability.

A complex remodeling of cellular homeostasis distinguishes RSV/SARS-CoV-2 co-infected A549-hACE2 expressing cell lines.

Concurrent infections with two or more pathogens with analogous tropism, such as RSV and SARS-CoV-2, may antagonize or facilitate each other, modulating disease outcome. Clinically, discrepancies in the severity of symptoms have been reported in children with RSV/SARS-CoV-2 co-infection. Herein, we propose an in vitro co-infection model to assess how RSV/SARS-CoV-2 co-infection alters cellular homeostasis. To this end, A549-hACE2 expressing cells were either infected with RSV or SARS-CoV-2 alone or co-infected with both viruses. Viral replication was assessed at 72 hours post infection by droplet digital PCR, immunofluorescence, and transmission electron microscopy. Anti-viral/receptor/autophagy gene expression was evaluated by RT-qPCR and confirmed by secretome analyses and intracellular protein production. RSV/SARS-CoV-2 co-infection in A549-hACE2 cells was characterized by: 1) an increase in the replication rate of RSV compared to single infection; 2) an increase in one of the RSV host receptors, ICAM1; 3) an upregulation in the expression/secretion of pro-inflammatory genes; 4) a rise in the number and length of cellular conduits; and 5) augmented autophagosomes formation and/or alteration of the autophagy pathway. These findings suggest that RSV/SARS-CoV-2 co-infection model displays a unique and specific viral and molecular fingerprint and shed light on the viral dynamics during viral infection pathogenesis. This in vitro co-infection model may represent a potential attractive cost-effective approach to mimic both viral dynamics and host cellular responses, providing in future readily measurable targets predictive of co-infection progression.

The role of sirtuin 1 in ageing and neurodegenerative disease: A molecular perspective.

Sirtuin 1 (SIRT1), an NAD+-dependent deacetylase, has emerged as a key regulator of cellular processes linked to ageing and neurodegeneration. SIRT1 modulates various signalling pathways, including those involved in autophagy, oxidative stress, and mitochondrial function, which are critical in the pathogenesis of neurodegenerative diseases. This review explores the therapeutic potential of SIRT1 in several neurodegenerative disorders, including Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD), and Amyotrophic Lateral Sclerosis (ALS). Preclinical studies have demonstrated that SIRT1 activators, such as resveratrol, SRT1720, and SRT2104, can alleviate disease symptoms by reducing oxidative stress, enhancing autophagic flux, and promoting neuronal survival. Ongoing clinical trials are evaluating the efficacy of these SIRT1 activators, providing hope for future therapeutic strategies targeting SIRT1 in neurodegenerative diseases. This review explores the role of SIRT1 in ageing and neurodegenerative diseases, with a particular focus on its molecular mechanisms, therapeutic potential, and clinical applications.

A novel strategy to enhance inhibition of Hela cervical cancer by combining Lentinus ß-glucan and autophagic flux blockage.

Lentinus ß-D-glucan (LNT), derived from artificially cultured mushrooms of Lentinus edodes, shows an important yet incompletely understood biological functions in cancer. In this work, the chemical structure of the refined LNT comprising a ß-D-(1, 6)-branched ß-D-(1,3)-glucan was further clarified via 1D- and 2D-NMR with high resolution, and its drug resistance resulted from autophagy in human cervical cancer (CC) Hela cells besides its anti-cancer function were revealed in vitro and in vivo. In detail, LNT destroyed cellular homeostasis by significantly increasing the intracellular Ca2+ levels and promoted autophagic flux in vitro Hela cells, which was found to at least partially depend on the PI3K/Akt/mTOR-mediated pathway by up-regulating LC3-II levels and down-regulating the expression of p62, PI3K, p-Akt, and mTOR in Hela cells-transplanted BALB/c nude mice. In particular, LNT-induced autophagy led to a drug resistance against LNT-induced proliferation inhibition and apoptosis in Hela cells, and the co-treatment of autophagy inhibitors and LNT significantly enhanced the inhibition of Hela cells and tumor growth in vitro and in vivo. Therefore, the combination of LNT and autophagy inhibitors will be a novel therapeutic strategy to reduce the resistance and improve the prognosis of CC patients in the clinical.

Zinc/Iron-Regulated Transporter-like Protein CsZIP4 Enhances Zinc and Nitrogen Uptake and Alleviates Zinc Stresses with Nitrogen Supply in Camellia sinensis.

Zinc (Zn) and nitrogen (N) are the two crucial nutrients for tea plant growth and development and contribute to the quality formation of tea fresh leaves. In this study, a zinc/iron-regulated transporter-like protein 4 gene (i.e., CsZIP4) was functionally characterized. Expression profiling showed that CsZIP4 could be induced by Zn stresses and a N deficiency. Heterologous expression of CsZIP4 in yeast revealed that CsZIP4 possessed the capacity for Zn transport but not ammonium. Moreover, CsZIP4 overexpression in Arabidopsis thaliana promoted Zn and N uptake and transport and contributed to alleviate Zn stresses by collaborating with N supply, which might be interrelated to the expression of N or Zn metabolism-related genes, such as AtNRT1.1 and AtZIP4. Additionally, CsZIP4 was localized in the plasma membrane and chloroplast, which was helpful in maintaining cellular homeostasis under a Zn excess. Furthermore, silencing of CsZIP4 in tea plants by virus-induced gene silencing increased the chlorophyll content but decreased the Zn content. Finally, the yeast one-hybrid assay demonstrated that CsbZIP2 bound to the CsZIP4 promoter. These results will shed light on the functions of CsZIP4 in the N and Zn interaction in tea plants.

A Dual-Channel Ca2+ Nanomodulator Induces Intracellular Ca2+ Disorders via Endogenous Ca2+ Redistribution for Tumor Radiosensitization.

Tumor cells harness Ca2+ to maintain cellular homeostasis and withstand external stresses from various treatments. Here, a dual-channel Ca2+ nanomodulator (CAP-P-NO) is constructed that can induce irreversible intracellular Ca2+ disorders via the redistribution of tumor-inherent Ca2+ for disrupting cellular homeostasis and thus improving tumor radiosensitivity. Stimulated by tumor-overexpressed acid and glutathione, capsaicin and nitric oxide are successively escaped from CAP-P-NO to activate the transient receptor potential cation channel subfamily V member 1 and the ryanodine receptor for the influx of extracellular Ca2+ and the release of Ca2+ in the endoplasmic reticulum, respectively. The overwhelming level of Ca2+ in tumor cells not only impairs the function of organelles but also induces widespread changes in the gene transcriptome, including the downregulation of a set of radioresistance-associated genes. Combining CAP-P-NO treatment with radiotherapy achieves a significant suppression against both pancreatic and patient-derived hepatic tumors with negligible side effects. Together, the study provides a feasible approach for inducing tumor-specific intracellular Ca2+ overload via endogenous Ca2+ redistribution and demonstrates the great potential of Ca2+ disorder therapy in enhancing the sensitivity for tumor radiotherapy.

KAT8 beyond Acetylation: A Survey of Its Epigenetic Regulation, Genetic Variability, and Implications for Human Health.

Lysine acetyltransferase 8, also known as KAT8, is an enzyme involved in epigenetic regulation, primarily recognized for its ability to modulate histone acetylation. This review presents an overview of KAT8, emphasizing its biological functions, which impact many cellular processes and range from chromatin remodeling to genetic and epigenetic regulation. In many model systems, KAT8's acetylation of histone H4 lysine 16 (H4K16) is critical for chromatin structure modification, which influences gene expression, cell proliferation, differentiation, and apoptosis. Furthermore, this review summarizes the observed genetic variability within the KAT8 gene, underscoring the implications of various single nucleotide polymorphisms (SNPs) that affect its functional efficacy and are linked to diverse phenotypic outcomes, ranging from metabolic traits to neurological disorders. Advanced insights into the structural biology of KAT8 reveal its interaction with multiprotein assemblies, such as the male-specific lethal (MSL) and non-specific lethal (NSL) complexes, which regulate a wide range of transcriptional activities and developmental functions. Additionally, this review focuses on KAT8's roles in cellular homeostasis, stem cell identity, DNA damage repair, and immune response, highlighting its potential as a therapeutic target. The implications of KAT8 in health and disease, as evidenced by recent studies, affirm its importance in cellular physiology and human pathology.

Autophagy and metabolic aging: Current understanding and future applications.

"Metabolic aging" refers to the gradual decline in cellular metabolic function across various tissues due to defective hormonal signaling, impaired nutrient sensing, mitochondrial dysfunction, replicative stress, and cellular senescence. While this process usually corresponds with chronological aging, the recent increase in metabolic diseases and cancers occurring at younger ages in humans suggests the premature onset of cellular fatigue and metabolic aging. Autophagy, a cellular housekeeping process facilitated by lysosomes, plays a crucial role in maintaining tissue rejuvenation and health. However, various environmental toxins, hormones, lifestyle changes, and nutrient imbalances can disrupt autophagy in humans. In this review, we explore the connection between autophagy and cellular metabolism, its regulation by extrinsic factors and its modulation to prevent the early onset of metabolic aging.

UFL1 regulates cellular homeostasis by targeting endoplasmic reticulum and mitochondria in NEFA-stimulated bovine mammary epithelial cells via the IRE1α/XBP1 pathway.

Elevated levels of NEFA caused by negative energy balance in transition cows induce cellular dyshomeostasis. Ubiquitin-like modifier 1 ligating enzyme 1 (UFL1) can maintain cellular homeostasis and act as a critical regulator of stress responses besides functioning in the ubiquitin-like system. The objective of this study was to elucidate the UFL1 working mechanism on promoting cellular adaptations in bovine mammary epithelial cells (BMECs) in response to NEFA challenge, with an emphasis on the ER and mitochondrial function. The results showed that exogenous NEFA and UFL1 depletion resulted in the disorder of ER and mitochondrial homeostasis and the damage of BMEC integrity, overexpression of UFL1 effectively alleviated the NEFA-induced cellular dyshomeostasis. Mechanistically, our study found that UFL1 had a strong interaction with IRE1α and could modulate the IRE1α/XBP1 pathway of unfolded protein response in NEFA-stimulated BMECs, thereby contributing to the modulation of cellular homeostasis. These findings imply that targeting UFL1 may be a therapeutic alternative to relieve NEB-induced metabolic changes in perinatal dairy cows.

Exploring the multifaceted role of GCN1: Implications in cellular responses and disease pathogenesis.

GCN1 is a highly conserved protein present widely across eukaryotes. As an upstream activator of protein kinase GCN2, GCN1 plays a pivotal role in integrated stress responses, such as amino acid starvation and oxidative stress. Through interaction with GCN2, GCN1 facilitates the activation of GCN2, thus initiating downstream signaling cascades in response to cellular stressors. In these contexts, the activation of GCN2 necessitates the presence and action of GCN1. Notably, GCN1 also operates as a ribosome collision sensor, contributing significantly to the translation quality control pathway. These discoveries offer valuable insights into cellular responses to internal stresses, vital for maintaining cellular homeostasis. Additionally, GCN1 exhibits the ability to regulate the cell cycle and suppress inflammation, among other processes, independently of GCN2. Our review outlines the structural characteristics and biological functions of GCN1, shedding light on its significant involvement in the onset and progression of various cancer and non-cancer diseases. Our work underscores the role of GCN1 in the context of drug therapeutic effects, hinting at its potential as a promising drug target. Furthermore, our work delves deep into the functional mechanisms of GCN1, promising innovative avenues for the diagnosis and treatment of diseases in the future. The exploration of GCN1's multifaceted roles not only enhances our understanding of its mechanisms but also paves the way for novel therapeutic interventions. The ongoing quest to unveil additional functions of GCN1 holds the promise of further enriching our comprehension of its mode of action.

Metabolic fingerprinting by nuclear magnetic resonance of hepatocellular carcinoma cells during p53 reactivation-induced senescence.

Cellular senescence is characterized by stable cell cycle arrest. Senescent cells exhibit a senescence-associated secretory phenotype that can promote tumor progression. The aim of our study was to identify specific nuclear magnetic resonance (NMR) spectroscopy-based markers of cancer cell senescence. For metabolic studies, we employed murine liver carcinoma Harvey Rat Sarcoma Virus (H-Ras) cells, in which reactivation of p53 expression induces senescence. Senescent and nonsenescent cell extracts were subjected to high-resolution proton (1H)-NMR spectroscopy-based metabolomics, and dynamic metabolic changes during senescence were analyzed using a magnetic resonance spectroscopy (MRS)-compatible cell perfusion system. Additionally, the ability of intact senescent cells to degrade the extracellular matrix (ECM) was quantified in the cell perfusion system. Analysis of senescent H-Ras cell extracts revealed elevated sn-glycero-3-phosphocholine, myoinositol, taurine, and creatine levels, with decreases in glycine, o-phosphocholine, threonine, and valine. These metabolic findings were accompanied by a greater degradation index of the ECM in senescent H-Ras cells than in control H-Ras cells. MRS studies with the cell perfusion system revealed elevated creatine levels in senescent cells on Day 4, confirming the 1H-NMR results. These senescence-associated changes in metabolism and ECM degradation strongly impact growth and redox metabolism and reveal potential MRS signals for detecting senescent cancer cells in vivo.

Modulating responses of indicator genes in cellular homeostasis, immune defense and apoptotic process in the Macrophthalmus japonicus exposed to di(2-ethylhexyl) phthalate as a plastic additive.

Di(2-ethylhexyl) phthalate (DEHP), have been increasingly used as plasticizers to manufacture soft and flexible materials and ubiquitously found in water and sediments in the aquatic ecosystem. The aim of the present study was to evaluate the effect of DEHP exposure on cellular homeostasis (HSF1 and seven HSPs), immune responses (ILF), and apoptotic responses (p53, BAX, Bcl-2). DEHP exposure upregulated the expression of HSF1 and ILF. Moreover, it altered the expression levels of HSPs (upregulation of HSP70, HSP90, HSP40, HSP83, and HSP67B2 and downregulation of HSP60 and HSP21) in conjunction with HSF1 and ILF in the gills and hepatopancreas of M. japonicus exposed to DEHP. At the protein level, DEHP exposure changed apoptotic signals in both tissues of M. japonicus. These findings indicate that chronic exposures to several DEHP concentrations could disturb cellular balance, damage the inflammatory and immune systems, and induce apoptotic cell death, thereby affecting the survival of M. japonicus.

Small RNA-modulated anaerobic respiration allows bacteria to survive under antibiotic stress conditions.

Despite extensive knowledge of antibiotic-targeted bacterial cell death, deeper understanding of antibiotic tolerance mechanisms is necessary to combat multi-drug resistance in the global healthcare settings. Regulatory RNAs in bacteria control important cellular processes such as cell division, cellular respiration, metabolism, and virulence. Here, we investigated how exposing Escherichia coli to the moderately effective first-generation antibiotic cephalothin alters transcriptional and post-transcriptional dynamics. Bacteria switched from active aerobic respiration to anaerobic adaptation via an FnrS and Tp2 small RNA-mediated post-transcriptional regulatory circuit. From the early hours of antibiotic exposure, FnrS was involved in regulating reactive oxygen species levels, and delayed oxygen consumption in bacteria. We demonstrated that bacteria strive to maintain cellular homeostasis via sRNA-mediated sudden respiratory changes upon sublethal antibiotic exposure.

Evaluation of Mitochondrial Phagy (Mitophagy) in Human Non-small Adenocarcinoma Tumor Cells.

Non-small cell lung cancer (NSCLC) is a predominant form of lung cancer characterized by its aggressive nature and high mortality rate, primarily due to late-stage diagnosis and metastatic spread. Recent studies underscore the pivotal role of mitophagy, a selective form of autophagy targeting damaged or superfluous mitochondria, in cancer biology, including NSCLC. Mitophagy regulation may influence cancer cell survival, proliferation, and metastasis by modulating mitochondrial quality and cellular energy homeostasis. Herein, we present a comprehensive methodology developed in our laboratory for the evaluation of mitophagy in NSCLC tumor cells. Utilizing a combination of immunoblotting, immunocytochemistry, and fluorescent microscopy, we detail the steps to quantify early and late mitophagy markers and mitochondrial dynamics. Our findings highlight the potential of targeting mitophagy pathways as a novel therapeutic strategy in NSCLC, offering insights into the complex interplay between mitochondrial dysfunction and tumor progression. This study not only sheds light on the significance of mitophagy in NSCLC but also establishes a foundational approach for its investigation, paving way for future research in this critical area of cancer biology.

Hepatitis B surface antigen expression impairs endoplasmic reticulum stress-related autophagic flux by decreasing LAMP2.

Background & Aims: Hepatitis B surface antigen (HBsAg) drives hepatocarcinogenesis. Factors and mechanisms involved in this progression remain poorly defined, hindering the development of effective therapeutic strategies. Therefore, the mechanisms involved in the HBsAg-induced transformation of normal liver into hepatocellular carcinoma (HCC) were investigated. Methods: Hemizygous Tg(Alb1HBV)44Bri/J mice were examined for HBsAg-induced carcinogenic events. Gene set-enrichment analysis identified significant signatures in HBsAg-transgenic mice that correlated with endoplasmic reticulum (ER) stress, unfolded protein response, autophagy and proliferation. These events were investigated by western blotting, immunohistochemical and immunocytochemical staining in 2-, 8- and 12-month-old HBsAg-transgenic mice. The results were verified in HBsAg-overexpressing Hepa1-6 cells and validated in human HBV-related HCC samples. Results: Increased BiP expression in HBsAg-transgenic mice indicated induction of the unfolded protein response. In addition, early-phase autophagy was enhanced (increased BECN1 and LC3B) and late-phase autophagy blocked (increased p62) in HBsAg-transgenic mice. Finally, HBsAg altered lysosomal acidification via ATF4- and ATF6-mediated downregulation of lysosome-associated membrane protein 2 (LAMP2) expression. In patients, HBV-related HCC and adjacent tissues showed increased BiP, p62 and downregulated LAMP2 compared to uninfected controls. In vitro, the use of ER stress inhibitors reversed the HBsAg-related suppression of LAMP2. Furthermore, HBsAg promoted hepatocellular proliferation as indicated by Ki67, cleaved caspase-3 and AFP staining in paraffin-embedded liver sections from HBsAg-transgenic mice. These results were further verified by colony formation assays in HBsAg-expressing Hepa1-6 cells. Interestingly, inhibition of ER stress in HBsAg-overexpressing Hepa1-6 cells suppressed HBsAg-mediated cell proliferation. Conclusions: These data showed that HBsAg directly induces ER stress, impairs autophagy and promotes proliferation, thereby driving hepatocarcinogenesis. In addition, this study expanded the understanding of HBsAg-mediated intracellular events in carcinogenesis. Impact and implications: Factors and mechanisms involved in hepatocarcinogenesis driven by hepatitis B surface antigen (HBsAg) are poorly defined, hindering the development of effective therapeutic strategies. This study showed that HBsAg-induced endoplasmic reticulum stress suppressed LAMP2, thereby mediating autophagic injury. The present data suggest that restoring LAMP2 function in chronic HBV infection may have both antiviral and anti-cancer effects. This study has provided insights into the role of HBsAg-mediated intracellular events in carcinogenesis and thereby has relevance for future drug development.

The dance of proteostasis and metabolism: Unveiling the caloristatic controlling switch.

The heat shock response (HSR) is an ancient and evolutionarily conserved mechanism designed to restore cellular homeostasis following proteotoxic challenges. However, it has become increasingly evident that disruptions in energy metabolism also trigger the HSR. This interplay between proteostasis and energy regulation is rooted in the fundamental need for ATP to fuel protein synthesis and repair, making the HSR an essential component of cellular energy management. Recent findings suggest that the origins of proteostasis-defending systems can be traced back over 3.6 billion years, aligning with the emergence of sugar kinases that optimized glycolysis around 3.594 billion years ago. This evolutionary connection is underscored by the spatial similarities between the nucleotide-binding domain of HSP70, the key player in protein chaperone machinery, and hexokinases. The HSR serves as a hub that integrates energy metabolism and resolution of inflammation, further highlighting its role in maintaining cellular homeostasis. Notably, 5'-adenosine monophosphate-activated protein kinase emerges as a central regulator, promoting the HSR during predominantly proteotoxic stress while suppressing it in response to predominantly metabolic stress. The complex relationship between 5'-adenosine monophosphate-activated protein kinase and the HSR is finely tuned, with paradoxical effects observed under different stress conditions. This delicate equilibrium, known as caloristasis, ensures that cellular homeostasis is maintained despite shifting environmental and intracellular conditions. Understanding the caloristatic controlling switch at the heart of this interplay is crucial. It offers insights into a wide range of conditions, including glycemic control, obesity, type 2 diabetes, cardiovascular and neurodegenerative diseases, reproductive abnormalities, and the optimization of exercise routines. These findings highlight the profound interconnectedness of proteostasis and energy metabolism in cellular function and adaptation.

Nonsense-mediated mRNA decay pathway in plants under stress: general gene regulatory mechanism and advances.

MAIN CONCLUSION: Nonsense-mediated mRNA decay in eukaryotes is vital to cellular homeostasis. Further knowledge of its putative role in plant RNA metabolism under stress is pivotal to developing fitness-optimizing strategies. Nonsense-mediated mRNA decay (NMD), part of the mRNA surveillance pathway, is an evolutionarily conserved form of gene regulation in all living organisms. Degradation of mRNA-bearing premature termination codons and regulation of physiological RNA levels highlight NMD's role in shaping the cellular transcriptome. Initially regarded as purely a tool for cellular RNA quality control, NMD is now considered to mediate various aspects of plant developmental processes and responses to environmental changes. Here we offer a basic understanding of NMD in eukaryotes by explaining the concept of premature termination codon recognition and NMD complex formation. We also provide a detailed overview of the NMD mechanism and its role in gene regulation. The potential role of effectors, including ABCE1, in ribosome recycling during the translation process is also explained. Recent reports of alternatively spliced variants of corresponding genes targeted by NMD in Arabidopsis thaliana are provided in tabular format. Detailed figures are also provided to clarify the NMD concept in plants. In particular, accumulating evidence shows that NMD can serve as a novel alternative strategy for genetic manipulation and can help design RNA-based therapies to combat stress in plants. A key point of emphasis is its function as a gene regulatory mechanism as well as its dynamic regulation by environmental and developmental factors. Overall, a detailed molecular understanding of the NMD mechanism can lead to further diverse applications, such as improving cellular homeostasis in living organisms.

Multiple Regulatory Signals and Components in the Modulation of Bicarbonate Transporters.

Bicarbonate transporters are responsible for the appropriate flux of bicarbonate across the plasma membrane to perform various fundamental cellular functions. The functions of bicarbonate transporters, including pH regulation, cell migration, and inflammation, are highlighted in various cellular systems, encompassing their participation in both physiological and pathological processes. In this review, we focused on recently identified modulatory signaling components that regulate the expression and activity of bicarbonate transporters. Moreover, we addressed recent advances in our understanding of cooperative systems of bicarbonate transporters and channelopathies. This current review aims to provide a new, in-depth understanding of numerous human diseases associated with the dysfunction of bicarbonate transporters.

Picky eaters: selective autophagy in plant cells.

Autophagy, a fundamental cellular process, plays a vital role in maintaining cellular homeostasis by degrading damaged or unnecessary components. While selective autophagy has been extensively studied in animal cells, its significance in plant cells has only recently gained attention. In this review, we delve into the intriguing realm selective autophagy in plants, with specific focus on its involvement in nutrient recycling, organelle turnover, and stress response. Moreover, recent studies have unveiled the interesting interplay between selective autophagy and epigenetic mechanisms in plants, elucidating the significance of epigenetic regulation in modulating autophagy-related gene expression and finely tuning the selective autophagy process in plants. By synthesizing existing knowledge, this review highlights the emerging field of selective autophagy in plant cells, emphasizing its pivotal role in maintaining nutrient homeostasis, facilitating cellular adaptation, and shedding light on the epigenetic regulation that governs these processes. Our comprehensive study provides the way for a deeper understanding of the dynamic control of cellular responses to nutrient availability and stress conditions, opening new avenues for future research in this field of autophagy in plant physiology.

Triclosan exposure induces immunotoxic impacts by disrupting the immunometabolism, detoxification, and cellular homeostasis in blood clam (Tegillarca granosa).

Omnipresent presence of triclosan (TCS) in aqueous environment puts a potential threat to organisms. However, it's poorly understood about its immunometabolic impacts of marine invertebrates. In present study, we use a representative bivalve blood clam (Tegillarca granosa) as a model, investigating the effects of TCS exposure at 20 and 200 µg/L for 28 days on immunometabolism, detoxification, and cellular homeostasis to explore feasible toxicity mechanisms. Results demonstrated that the clams exposed to TCS resulting in evident immunotoxic impacts on both cellular and humoral immune responses, through shifting metabolic pathways and substances, as well as suppressing the expressions of genes from the immune- and metabolism-related pathways. In addition, significant alterations in contents (or activity) of detoxification enzymes and the expression of key detoxification genes were detected in TCS-exposed clams. Moreover, exposure to TCS also disrupted cellular homeostasis of clams through increasing MDA contents and caspase activities, and promoting activation of the apoptosis-related genes. These findings suggested that TCS might induce immunotoxic impacts by disrupting the immunometabolism, detoxification, and cellular homeostasis.