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Cells employ diverse strategies to repair double-strand breaks (DSBs), a dangerous form of DNA damage that threatens genome integrity. Eukaryotic nuclei consist of different chromatin environments, each displaying distinct molecular and biophysical properties that can significantly influence the DSB-repair process. DSBs arising in the compact and silenced heterochromatin domains have been found to move to the heterochromatin periphery in mouse and Drosophila to prevent aberrant recombination events. However, it is poorly understood how chromatin components, such as histone post-translational modifications, contribute to these DSB movements within heterochromatin. Using irradiation as well as locus-specific DSB induction in Drosophila tissues and cultured cells, we find enrichment of histone H3 lysine 9 acetylation (H3K9ac) at DSBs in heterochromatin but not euchromatin. We find this increase is mediated by the histone acetyltransferase dGcn5, which rapidly localizes to heterochromatic DSBs. Moreover, we demonstrate that in the absence of dGcn5, heterochromatic DSBs display impaired recruitment of the SUMO E3 ligase Nse2/Qjt and fail to relocate to the heterochromatin periphery to complete repair. In summary, our results reveal a previously unidentified role for dGcn5 and H3K9ac in heterochromatic DSB repair and underscore the importance of differential chromatin responses at heterochromatic and euchromatic DSBs to promote safe repair.

Heparan sulfate (HS) is degraded in lysosome by a series of glycosidases. Before the glycosidases can act, the terminal glucosamine of HS must be acetylated by the integral lysosomal membrane enzyme heparan-α-glucosaminide N-acetyltransferase (HGSNAT). Mutations of HGSNAT cause HS accumulation and consequently mucopolysaccharidosis IIIC, a devastating lysosomal storage disease characterized by progressive neurological deterioration and early death where no treatment is available. HGSNAT catalyzes a unique transmembrane acetylation reaction where the acetyl group of cytosolic acetyl-CoA is transported across the lysosomal membrane and attached to HS in one reaction. However, the reaction mechanism remains elusive. Here we report six cryo-EM structures of HGSNAT along the reaction pathway. These structures reveal a dimer arrangement and a unique structural fold, which enables the elucidation of the reaction mechanism. We find that a central pore within each monomer traverses the membrane and controls access of cytosolic acetyl-CoA to the active site at its luminal mouth where glucosamine binds. A histidine-aspartic acid catalytic dyad catalyzes the transfer reaction via a ternary complex mechanism. Furthermore, the structures allow the mapping of disease-causing variants and reveal their potential impact on the function, thus creating a framework to guide structure-based drug discovery efforts.

BACKGROUND: Tau is aberrantly acetylated in various neurodegenerative conditions, including Alzheimers disease, frontotemporal lobar degeneration (FTLD), and traumatic brain injury (TBI). Previously, we reported that reducing acetylated tau by pharmacologically inhibiting p300-mediated tau acetylation at lysine 174 reduces tau pathology and improves cognitive function in animal models. METHODS: We investigated the therapeutic efficacy of two different antibodies that specifically target acetylated lysine 174 on tau (ac-tauK174). We treated PS19 mice, which harbor the P301S tauopathy mutation that causes FTLD, with anti-ac-tauK174 and measured effects on tau pathology, neurodegeneration, and neurobehavioral outcomes. Furthermore, PS19 mice received treatment post-TBI to evaluate the ability of the immunotherapy to prevent TBI-induced exacerbation of tauopathy phenotypes. Ac-tauK174 measurements in human plasma following TBI were also collected to establish a link between trauma and acetylated tau levels, and single nuclei RNA-sequencing of post-TBI brain tissues from treated mice provided insights into the molecular mechanisms underlying the observed treatment effects. RESULTS: Anti-ac-tauK174 treatment mitigates neurobehavioral impairment and reduces tau pathology in PS19 mice. Ac-tauK174 increases significantly in human plasma 24 h after TBI, and anti-ac-tauK174 treatment of PS19 mice blocked TBI-induced neurodegeneration and preserved memory functions. Anti-ac-tauK174 treatment rescues alterations of microglial and oligodendrocyte transcriptomic states following TBI in PS19 mice. CONCLUSIONS: The ability of anti-ac-tauK174 treatment to rescue neurobehavioral impairment, reduce tau pathology, and rescue glial responses demonstrates that targeting tau acetylation at K174 is a promising neuroprotective therapeutic approach to human tauopathies resulting from TBI or genetic disease.

Regular exercise promotes whole-body health and prevents disease, but the underlying molecular mechanisms are incompletely understood1-3. Here, the Molecular Transducers of Physical Activity Consortium4 profiled the temporal transcriptome, proteome, metabolome, lipidome, phosphoproteome, acetylproteome, ubiquitylproteome, epigenome and immunome in whole blood, plasma and 18 solid tissues in male and female Rattus norvegicus over eight weeks of endurance exercise training. The resulting data compendium encompasses 9,466 assays across 19 tissues, 25 molecular platforms and 4 training time points. Thousands of shared and tissue-specific molecular alterations were identified, with sex differences found in multiple tissues. Temporal multi-omic and multi-tissue analyses revealed expansive biological insights into the adaptive responses to endurance training, including widespread regulation of immune, metabolic, stress response and mitochondrial pathways. Many changes were relevant to human health, including non-alcoholic fatty liver disease, inflammatory bowel disease, cardiovascular health and tissue injury and recovery. The data and analyses presented in this study will serve as valuable resources for understanding and exploring the multi-tissue molecular effects of endurance training and are provided in a public repository ( https://motrpac-data.org/ ).

Mammalian polynucleotide kinase 3'-phosphatase (PNKP), a DNA end-processing enzyme with 3'-phosphatase and 5'-kinase activities, is involved in multiple DNA repair pathways, including base excision (BER), single-strand break (SSBR), and double-strand break repair (DSBR). However, little is known as to how PNKP functions in such diverse repair processes. Here we report that PNKP is acetylated at K142 (AcK142) by p300 constitutively but at K226 (AcK226) by CBP, only after DSB induction. Co-immunoprecipitation analysis using AcK142 or AcK226 PNKP-specific antibodies showed that AcK142-PNKP associates only with BER/SSBR, and AcK226 PNKP with DSBR proteins. Despite the modest effect of acetylation on PNKP's enzymatic activity in vitro, cells expressing non-acetylable PNKP (K142R or K226R) accumulated DNA damage in transcribed genes. Intriguingly, in striatal neuronal cells of a Huntington's Disease (HD)-based mouse model, K142, but not K226, was acetylated. This is consistent with the reported degradation of CBP, but not p300, in HD cells. Moreover, transcribed genomes of HD cells progressively accumulated DSBs. Chromatin-immunoprecipitation analysis demonstrated the association of Ac-PNKP with the transcribed genes, consistent with PNKP's role in transcription-coupled repair. Thus, our findings demonstrate that acetylation at two lysine residues, located in different domains of PNKP, regulates its distinct role in BER/SSBR versus DSBR.

Primary familial brain calcification (PFBC) is characterized by calcium deposition in the brain, causing progressive movement disorders, psychiatric symptoms, and cognitive decline. PFBC is a heterogeneous disorder currently linked to variants in six different genes, but most patients remain genetically undiagnosed. Here, we identify biallelic NAA60 variants in ten individuals from seven families with autosomal recessive PFBC. The NAA60 variants lead to loss-of-function with lack of protein N-terminal (Nt)-acetylation activity. We show that the phosphate importer SLC20A2 is a substrate of NAA60 in vitro. In cells, loss of NAA60 caused reduced surface levels of SLC20A2 and a reduction in extracellular phosphate uptake. This study establishes NAA60 as a causal gene for PFBC, provides a possible biochemical explanation of its disease-causing mechanisms and underscores NAA60-mediated Nt-acetylation of transmembrane proteins as a fundamental process for healthy neurobiological functioning.

A major barrier to the impact of genomic diagnosis in patients with congenital malformations is the lack of understanding regarding how sequence variants contribute to disease pathogenesis and whether this information could be used to generate patient-specific therapies. Congenital diaphragmatic hernia (CDH) is among the most common and severe of all structural malformations; however, its underlying mechanisms are unclear. We identified loss-of-function sequence variants in the epigenomic regulator gene SIN3A in two patients with complex CDH. Tissue-specific deletion of Sin3a in mice resulted in defects in diaphragm development, lung hypoplasia, and pulmonary hypertension, the cardinal features of CDH and major causes of CDH-associated mortality. Loss of SIN3A in the lung mesenchyme resulted in reduced cellular differentiation, impaired cell proliferation, and increased DNA damage. Treatment of embryonic Sin3a mutant mice with anacardic acid, an inhibitor of histone acetyltransferase, reduced DNA damage, increased cell proliferation and differentiation, improved lung and pulmonary vascular development, and reduced pulmonary hypertension. These findings demonstrate that restoring the balance of histone acetylation can improve lung development in the Sin3a mouse model of CDH.

Cell senescence is an anti-cancer strategy following DNA repair and apoptosis, which is associated with the initiation, progression, and treatment of ovarian cancer. The CDK4/6 inhibitor alters cell cycle and induces cell senescence dependent on retinoblastoma (RB) family proteins. Objective Herein, we aimed to explore the effects of Palbociclib (a CDK4/6 inhibitor) on cellular senescence of high-grade serous ovarian cancer (HGSOC). Cell viability and cell cycle were evaluated by cell counting kit-8 and flow cytometry. Cell senescence was analyzed using the SA-β-gal staining assay. The senescence-associated secretory phenotype was assessed using quantitative PCR (qPCR). Senescence-related markers were tested using western blot. The role of Palbociclib in vivo was clarified using xenograft tumor. Acetylation of p53 was evaluated by qPCR and western blot. The results showed that Palbociclib inhibited cell viability, blocked cell cycle at G0/G1 phase, and induced cell senescence. A rescue study indicated that knockdown of p53 reversed the effects on cell cycle and senescence induced by Palbociclib. Moreover, we found that Palbociclib promotes P300-mediated p53 acetylation, thus increasing p53 stability and transcription activity. Moreover, Palbociclib suppressed tumor growth in vivo with increased p53 and acetylated p53 levels. In conclusion, Palbociclib induced cell senescence of HGSOC through P300-mediated p53 acetylation, suggesting that Palbociclib may have the effect of treating HGSOC. [ABSTRACT FROM AUTHOR]

Acetylation is a breakthrough in wood modification and has been established on industrial scale. However, concerns have been raised regarding the stability of acetylated wood under elevated temperatures, particularly during post hot-pressing processes to manufacture products such as laminated veneer lumber (LVL). At around 150 °C, the added acetyl groups might cleave off ("de-acetylation") and by that release sorption sites for water. This would increase the moisture uptake of the modified wood. In this study, the impact of hot-pressing at 150 °C on the stability of acetylated beech veneers and LVL was investigated. Fourier transform infrared (FTIR) spectroscopy showed that the chemical composition of acetylated veneers seemed to be unaffected after the heat treatment. Dynamic vapor sorption (DVS) analysis and long-term storing over saturated salt-solutions in miniature climate chambers, indicated no de-acetylation on the basis of negligible changes in wood-water interactions. The number of hydroxyl groups of heat-treated acetylated samples was similar to that of not heat-treated ones, indicating the persistence of the effects of acetylation. By the present study, a certain resilience of acetylated wood towards elevated temperature, like it may occur during hot-pressing of acetylated veneers, became apparent and illustrated the thermal stability of this chemical modification approach. [ABSTRACT FROM AUTHOR]

In this study, a DABCO-based ionic liquid containing cobalt metal ([(DABCO)2C3H5OH]·CoCl4) was successfully synthesized through a simple method combined with DABCO, 1,3-dichloropropan-2-ol and CoCl2. The structure of this reagent was investigated via various analytical methods including Fourier transform infrared spectroscopy (FT-IR), thermal analysis (TGA), X-ray diffraction pattern (XRD), energy dispersive X-ray analysis (EDX), and field emission scanning electron microscopy (FESEM). The catalytic performance of the prepared Lewis acidic catalyst was evaluated for the reduction of nitroarenes, and aromatic aldehydes and also one-pot reductive acetylation of aldehydes using NaBH4 and CH3COCl as the hydrogen donor and acetylating agent, respectively. Ease of preparation, reusability of the catalyst, short reaction times and excellent yields of the obtained compounds are among the salient features of this process. [ABSTRACT FROM AUTHOR]

Post-translational modifications (PTMs), as epigenetic modifications, are significant in the interaction between virus and its host. However, it is unclear whether rotavirus (RV) causes changes in both the host cell epigenetic protein modification and the regulatory mechanism of viral replication. Here, we analyzed the proteome of Caco-2 cells to determine if acetylation modification occurred within the cells after RV infection. We found that glyceraldehyde-3-phosphate dehydrogenase (GAPDH), a protein involved in glycolysis, was deacetylated at lysine 219 via histone deacetylase 9 (HDAC9) in 50 h after the RV infection. Remarkably, the deacetylation of GAPDH promoted RV replication. Finally, we found that glycolysis was alterable in Caco-2 cells by RV or the deacetylation of GAPDH lysine 219, using the Seahorse XF Glycolysis Stress Test. In conclusion, our results demonstrate for the first time that RV infection promoted deacetylation of GAPDH at lysine 219 in order to increase its own viral replication in Caco-2 cells. [ABSTRACT FROM AUTHOR]

Paper-based separator for lithium-ion battery application has attracted great attention due to its good electrolyte affinity and thermal stability. To avoid the short circuit by the micron-sized pores of paper and improve the electrochemical properties of paper-based separator, cellulose fibers were acetylated followed by wet papermaking and metal-organic framework coating. Due to the strong intermolecular interaction between acetylated cellulose fibers and N,N-dimethylformamide, the resulting separator exhibited compact microstructure. The zeolitic imidazolate framework-8 coating endowed the separator with enhanced electrolyte affinity (electrolyte contact angle of 0°), ionic conductivity (1.26 mS·cm−1), interfacial compatibility (284 Ω), lithium ion transfer number (0.61) and electrochemical stability window (4.96 V). The assembled LiFePO4/Li battery displayed an initial discharge capacity of 146.10 mAh·g−1 at 0.5 C with capacity retention of 99.71% after 100 cycles and good rate performance. Our proposed strategy would provide a novel perspective for the design of high-performance paper-based separators for battery applications. [ABSTRACT FROM AUTHOR]

Highlights: OC2 knockout promotes apoptosis in HCC cells. OC2 knockout significantly inhibits tumor growth. OC2 promotes SKP2 transcriptional activation. OC2 knockout promotes p53 acetylation activation. Onecut2 (OC2) plays a vital regulatory role in tumor growth, metastasis and angiogenesis. In this study, we report the regulatory role and specific molecular mechanism of OC2 in the apoptosis of hepatocellular carcinoma (HCC) cells. We found that OC2 knockout via the CRISPR/CAS9 system not only significantly inhibited the proliferation and angiogenesis of HCC cells but also significantly promoted apoptosis. The apoptosis rate of the OC2 knockout HCC cell line reached 30.514%. In a mouse model, the proliferation inhibition rate of tumor cells reached 98.8%. To explore the mechanism of apoptosis, ChIP-Seq and dual-luciferase reporter assays were carried out. The results showed that OC2 could directly bind to the promotor of SKP2 and regulate its expression. Moreover, downregulating the expression of OC2 and SKP2 could release p300, promote the acetylation of p53, increase the expression of p21 and p27, and promote the apoptosis of HCC cells. Moreover, the overexpression of OC2 or SKP2 in the knockout HCC cell line clearly inhibited the acetylation level of p53 and reduced cell apoptosis. This study revealed that OC2 could regulate the apoptosis of HCC cells through the SKP2/p53/p21 axis, which may provide some therapeutic targets for HCC in the clinic. [ABSTRACT FROM AUTHOR]

Substituting solid acid for liquid acid to catalyze the cellulose acetylation can simplify the conventional production process and make it environmentally friendly, but the related technique remains at the research stage. The unclear reaction behavior of solid acid catalytic cellulose acetylation results in limited success of previous efforts and measures. In the present work, SO42−/TiO2 solid acid was used as the research object in comparison with H2SO4. Various characterization results demonstrate that the reaction behavior of cellulose acetylation catalyzed by SO42−/TiO2 is completely different from that by H2SO4. SO42−/TiO2 is limited to the outer surface of cellulose for catalytic acetylation through solid-to-solid contact, while H2SO4 can penetrate into the cellulose interior for internal and external simultaneous acetylation. The superficial cellulose molecular chains undergo partial acetylation by SO42−/TiO2 catalysis and subsequently dissolve in acetate acid, followed by being further catalytic acetylated. The subsurface cellulose molecular chains are exposed to interact with SO42−/TiO2 for subsequent round of acetylation till the depletion of the celluloses. Based on the present research result of reaction behavior, it is clarified that the efficiency of solid acid catalytic cellulose acetylation is mainly determined by the micron-scale morphological limitation between solid acid and cellulose rather than the intrinsic catalytic activity of solid acid. [ABSTRACT FROM AUTHOR]

Cellulose is the most abundant and renewable biopolymers on earth. The hydrophilic nature of cellulose endows cellulosic materials with good compatibility with polar matrices, but it also leads to their poor dispersion in non-polar matrices. Regulating the surface hydrophobicity of cellulosic materials via surface esterification can greatly extend their applications. However, the existing surface esterification methods for cellulosic materials are time-consuming and costly, which makes them less attractive for practical application. Here we found that when vinyl esters were used as esterifying agents, various alkalis can be used to catalyze the ultrafast surface esterification of cellulose materials in aqueous media at room temperature within seconds or minutes, which is highly attractive for the surface esterification of nanocellulose in suspension state. Surface acetylated cellulose nanofibers (ACNF) and surface acetylated cellulose nanocrystals (ACNC) with acetyl group content (Ac%) up to 10.7% and 6.5%, respectively, were successfully prepared within 5 min in aqueous diethylamine solution. Additionally, this method can also be used to achieve the rapid acetylation of phenol hydroxy group in aqueous media. [ABSTRACT FROM AUTHOR]

Background/Objectives. The presence of anti-citrullinated peptide/protein antibodies (ACPAs), anti-carbamylated peptide/protein antibodies (anti-CarPs), and anti-acetylated peptide/protein antibodies (AAPAs), collectively termed as anti-modified peptide/protein antibodies (AMPAs), is a hallmark of rheumatoid arthritis. These autoantibodies play a crucial role in the complex autoimmune responses observed in patients. Understanding the interplay between them is essential for early diagnosis and effective management of the disease. Methods. In this work, we investigate IgG, IgM, and IgA levels of ACPAs, anti-CarPs, and AAPAs in two cohorts: patients with established RA disease and healthy blood donors, using a unique peptide antigenic backbone. Results. Our results showed that antibody levels of anti-citrullinated peptide (CFFCP) and anti-homocitrullinated peptide (CFFHP) were significantly higher in RA patients compared to healthy blood donors in the three isotypes analyzed, IgG, IgA, and IgM. Fine specificities were more frequent when using the CFFCP antigen. Regarding the reactivity to the acetyl-lysine modified peptide (CFFAP), the correlation between IgA and IgG/IgM was very weak. CCFAP was highly specific for isotypes IgG and IgA, but its sensitivity was low for both isotypes. Anti-CarP and AAPA are significant in the context of RA, particularly concerning their IgA isotypes. Conclusions. Their inclusion in diagnostics assessments for RA, especially for anti-citrulline negative cases, presents a potential advance in the field; however, they do not replace yet traditional markers like rheumatoid factor (RF) and ACPAs. [ABSTRACT FROM AUTHOR]

HBO1, also known as KAT7 or MYST2, is a crucial histone acetyltransferase with diverse cellular functions. It typically forms complexes with protein subunits or cofactors such as MEAF6, ING4, or ING5, and JADE1/2/3 or BRPF1/2/3, where the BRPF or JADE proteins serve as the scaffold targeting histone H3 or H4, respectively. The histone acetylation mediated by HBO1 plays significant roles in DNA replication and gene expression regulation. Additionally, HBO1 catalyzes the modification of proteins through acylation with propionyl, butyryl, crotonyl, benzoyl, and acetoacetyl groups. HBO1 undergoes ubiquitination and degradation by two types of ubiquitin complexes and can also act as an E3 ubiquitin ligase for the estrogen receptor α (ERα). Moreover, HBO1 participates in the expansion of medullary thymic epithelial cells (mTECs) and regulates the expression of peripheral tissue genes (PTGs) mediated by autoimmune regulator (AIRE), thus inducing immune tolerance. Furthermore, HBO1 influences the renewal of hematopoietic stem cells and the development of neural stem cells significantly. Importantly, the overexpression of HBO1 in various cancers suggests its carcinogenic role and potential as a therapeutic target. This review summarizes recent advancements in understanding HBO1's involvement in acylation modification, DNA replication, ubiquitination, immunity, and stem cell renewal. [ABSTRACT FROM AUTHOR]

Petroleum-derived single-use plastics have dominated a range of material applications, including packaging and service ware (e.g., water bottles, food containers, and drinking straws). However, despite their short-lived service life, the inherent durability, and stability of these plastics have resulted in significant environmental accumulation and spill, contaminating both aquatic and land ecosystems. Consequently, there is a surging interest in the development of bioplastics as a sustainable alternative to petrochemical derived plastics that align with circular economy principles. Among potential materials, cellulose acetate (CA) showcases impressive mechanical properties, optical characteristics, melt processability, and compostability. However, due to its hygroscopic behavior, inferior barrier properties, and lack of dimensional stability, CA applications in the packaging industry are minimal. In this research, the acetylation of lignin and its use as a functional filler for CA matrix was studied. The impact of varying lignin loadings (up to 30 wt.%) on the tensile, morphological, barrier, and viscoelastic properties of the resulting materials was investigated. A thorough characterization of the compression-molded acetylated lignin-CA films revealed a reduction in water uptake (by 59% over baseline), up to a 41.5% reduction in water vapor permeability, and enhanced tensile properties with melt flowability. In summary, the examined films displayed favorable characteristics for use in food and other packaging applications. Consequently, they serve as low carbon footprint, and eco-friendly substitutes for conventional petrochemical-based packaging materials. [ABSTRACT FROM AUTHOR]

The cAMP response element binding protein (CREB)‐binding protein (CBP) is a histone acetyltransferase that plays an indispensable role in regulating the acetylation of histone and non‐histone proteins. Recently, it has been discovered that chemical inhibitors A485 and C646 can bind to Bombyx mori's CBP (BmCBP) and inhibit its acetyltransferase activity. Notably, the binding ability of A485 with BmCBP showed a very low Kd value of 48 nM by surface plasmon resonance (SPR) test. Further identification showed that both A485 and C646 can decrease the acetylation level of known substrate H3K27 and only 1 μM of A485 can almost completely inhibit the acetylation of H3K27, suggesting that A485 is an effective inhibitor of BmCBP's acetyltransferase activity. Moreover, it was confirmed that A485 could downregulate the expression of acetylated Bm30K‐24 protein at a post‐translational level through acetylation modification by BmCBP. Additionally, it was found that A485 can downregulate the stability of Bm30K‐24 and improve its ubiquitination level, suggesting that the acetylation modification by BmCBP could compete with ubiquitination modification at the same lysine site on Bm30K‐24, thereby affecting its protein stability. Here, we predict that A485 may be a potent CBP acetyltransferase inhibitor which could be utilized to inhibit acetyltransferase activity in insects, including silkworms. [ABSTRACT FROM AUTHOR]

Efficient DNA double strand break (DSB) repair is necessary for genomic stability and determines efficacy of DNA damaging cancer therapeutics. Spatiotemporal dynamics and post-translational modifications of repair proteins at DSBs dictate repair efficacy. Here, we identified a non-canonical function of GCN5 in regulating both HR and NHEJ repair post genotoxic stress. Mechanistically, genotoxic stress induced GCN5 recruitment to DSBs. GCN5 PARylation by PARP1 was essential for its recruitment, acetyltransferase activity and DSB repair function. Liquid chromatography-mass spectrometry (LC–MS) identified DNA-PKcs as part of GCN5 interactome. In-vitro acetyltransferase assays revealed that GCN5 acetylates DNA-PKcs at K3241 residue, a prerequisite for DNA-PKcs S2056 phosphorylation and DSB recruitment. Alongside, ChIP-qPCR revealed GCN5 mediates transcription of PRKDC via H3K27Ac acetylation in its promoter region (− 710 to − 554). Genetic perturbation of GCN5 also decreased CHEK1, NBN1, TP53BP1, POL-L transcription and abrogated ATM, BRCA1 activation. Accordingly, GCN5 loss led to persistent ɣ-H2AX foci formation, compromised in-vivo HR-NHEJ and caused GBM radio-sensitization. Importantly, PARP1 inhibition phenocopied GCN5 loss. Together, this study identifies an untraversed DSB repair function of GCN5 and provides mechanistic insights into transcriptional as well as post-translational regulation of pivotal HR-NHEJ factors. Alongside, it highlights the translational importance of PARP1-GCN5 axis in mediating GBM radio-resistance. [ABSTRACT FROM AUTHOR]

Activation of the Toll-like receptor 4 (TLR4) by bacterial endotoxins in macrophages plays a crucial role in the pathogenesis of sepsis. However, the mechanism underlying TLR4 activation in macrophages is still not fully understood. Here, we reveal that upon lipopolysaccharide (LPS) stimulation, lysine acetyltransferase CBP is recruited to the TLR4 signalosome complex leading to increased acetylation of the TIR domains of the TLR4 signalosome. Acetylation of the TLR4 signalosome TIR domains significantly enhances signaling activation via NF-κB rather than IRF3 pathways. Induction of NF-κB signaling is responsible for gene expression changes leading to M1 macrophage polarization. In sepsis patients, significantly elevated TLR4-TIR acetylation is observed in CD16+ monocytes combined with elevated expression of M1 macrophage markers. Pharmacological inhibition of HDAC1, which deacetylates the TIR domains, or CBP play opposite roles in sepsis. Our findings highlight the important role of TLR4-TIR domain acetylation in the regulation of the immune responses in sepsis, and we propose this reversible acetylation of TLR4 signalosomes as a potential therapeutic target for M1 macrophages during the progression of sepsis. Synopsis: Activation of macrophage TLR4 by bacterial endotoxins is important for the progression of sepsis, but the underlying mechanisms remain unknown. This study demonstrates that lipopolysaccharide (LPS) stimulation induces acetylation of the TLR4 signalosome TIR domains, which plays an important role in M1 macrophage polarization. LPS induces CBP-mediated acetylation of the TIR domains of TLR4, Mal, and MyD88 in the TLR4 signalosome complex. TIR domain acetylation in the TLR4 complex enhances NF-κB activation, leading to pro-inflammatory gene expression in M1 macrophages during sepsis. Inhibition of the primary TIR domain acetyltransferase CBP or deacetylase HDAC1 has opposite effects on the progression of sepsis. LPS-induced acetylation of the TLR4 complex TIR domains induces NF-κB signaling, leading to macrophage polarization. [ABSTRACT FROM AUTHOR]

This study investigates the impact of acetylation treatment on Enterolobium cyclocarpum (Parota) starch, focusing Morphological, Physico‐chemical and thermal impact induced by varying acetylation levels. The research employed scanning electron microscopy (SEM), differential scanning calorimetry (DSC), and thermogravimetric analysis (TGA) to examine the structural and thermal alterations resulting from acetylation. These analyses also evaluated the starch's thermal stability. Through titration, the degree of substitution and acetyl group content were quantified, demonstrating significant morphological transformations in the starch, such as increased particle size and the appearance of surface cracks on the granules. The study revealed that the degree of substitution, which changes with the duration of acetylation, markedly influences the starch's physicochemical properties, including hydrophobicity and thermal stability. Initially, acetylation reduced the gelatinization temperature, suggesting a decrease in the energy required for gelatinization. Over longer acetylation periods, however, the gelatinization temperature increased, likely due to enhanced crystallinity or molecular reorganization. These findings indicate that acetylated Parota starch has potential applications in the food industry as an encapsulating agent and in the thermoplastics industry as a plasticizer, dependent on the level of acetylation. This research underscores the utility of specific chemical modifications to adapt starch properties for various industrial applications. [ABSTRACT FROM AUTHOR]

Crotonylation is a recently discovered protein acyl modification that shares many enzymes with acetylation. However, it possesses a distinct regulatory mechanism and biological function due to its unique crotonyl structure. Since the discovery of crotonylation in 2011, numerous crotonylation sites have been identified in both histones and other proteins. In recent studies, crotonylation was found to play a role in various diseases and biological processes. This paper reviews the initial discovery and regulatory mechanisms of crotonylation, including various writer, reader, and eraser proteins. Finally, we emphasize the relationship of dysregulated protein crotonylation with eight common malignancies, including cervical, prostate, liver, and lung cancer, providing new potential therapeutic targets. [ABSTRACT FROM AUTHOR]

Cyclin‐dependent kinase 9 (CDK9), a catalytic subunit of the positive transcription elongation factor b (P‐TEFb) complex, is a global transcriptional elongation factor associated with cell proliferation. CDK9 activity is regulated by certain histone acetyltransferases, such as p300, GCN5 and P/CAF. However, the impact of males absent on the first (MOF) (also known as KAT8 or MYST1) on CDK9 activity has not been reported. Therefore, the present study aimed to elucidate the regulatory role of MOF on CDK9. We present evidence from systematic biochemical assays and molecular biology approaches arguing that MOF interacts with and acetylates CDK9 at the lysine 35 (i.e. K35) site, and that this acetyl‐group can be removed by histone deacetylase HDAC1. Notably, MOF‐mediated acetylation of CDK9 at K35 promotes the formation of the P‐TEFb complex through stabilizing CDK9 protein and enhancing its association with cyclin T1, which further increases RNA polymerase II serine 2 residues levels and global transcription. Our study reveals for the first time that MOF promotes global transcription by acetylating CDK9, providing a new strategy for exploring the comprehensive mechanism of the MOF–CDK9 axis in cellular processes. [ABSTRACT FROM AUTHOR]

[Display omitted] • Ginsenoside fraction from Panax ginseng decreased the acetylated protein levels of spliceosome in cardiomyocytes. • Ginsenoside Rb2 inhibited SF3A2 acetylation at lysine 10 to promote mitochondrial function against myocardial ischemic/reperfusion injury. • Ginsenoside Rb2 promoted Fscn1 alternative splicing to enhance mitochondrial respiration. • The decreased acetylation of SF3A2 (K 10) by ginsenoside Rb2 was mediated by p300 inhibition. Ginsenosides (GS) derived from Panax ginseng can regulate protein acetylation to promote mitochondrial function for protecting cardiomyocytes. However, the potential mechanisms of GS for regulating acetylation modification are not yet clear. This study aimed to explore the potential mechanisms of GS in regulating protein acetylation and identify ginsenoside monomer for fighting myocardial ischemia-related diseases. The 4D-lable free acetylomic analysis was employed to gain the acetylated proteins regulated by GS pretreatment. The co-immunoprecipitation assay, immunofluorescent staining, and mitochondrial respiration measurement were performed to detect the effect of GS or ginsenoside monomer on acetylated protein level and mitochondrial function. RNA sequencing, site-specific mutation, and shRNA interference were used to explore the downstream targets of acetylation modificationby GS. Cellular thermal shift assay and surface plasmon resonance were used for identifying the binding of ginsenoside with target protein. In the cardiomyocytes of normal, oxygen glucose deprivation and/or reperfusion conditions, the acetylomic analysis identified that the acetylated levels of spliceosome proteins were inhibited by GS pretreatment and SF3A2 acetylation at lysine 10 (K 10) was significantly decreased as a potential target of GS. Ginsenoside Rb2 was identified as one of the active ginsenoside monomers for reducing the acetylation of SF3A2 (K 10), which enhanced mitochondrial respiration against myocardial ischemic injury in in vivo and in vitro experiments. RNA-seq analysis showed that ginsenoside Rb2 promoted alternative splicing of mitochondrial function-related genes and the level of fascin actin-bundling protein 1 (Fscn1) was obviously upregulated, which was dependent on SF3A2 acetylation. Critically, thermodynamic, kinetic and enzymatic experiments demonstrated that ginsenoside Rb2 directly interacted with p300 for inhibiting its activity. These findings provide a novel mechanism underlying cardiomyocyte protection of ginsenoside Rb2 by inhibiting p300-mediated SF3A2 acteylation for promoting Fscn1 expression, which might be a promising approach for the prevention and treatment of myocardial ischemic diseases. [ABSTRACT FROM AUTHOR]

Background/Objectives: Typhoid and paratyphoid fever together are responsible for millions of cases and thousands of deaths per year, most of which occur in children in South and Southeast Asia. While typhoid conjugate vaccines (TCVs) are licensed, no vaccines are currently available against S. Paratyphi A. Here we describe the design of a S. Paratyphi A conjugate. Methods: The serovar-specific O-antigen (O:2) was linked to the CRM197 carrier protein (O:2–CRM197) and a panel of conjugates differing for structural characteristics were compared in mice and rabbits. Results: We identified the O-antigen molecular size, polysaccharide to protein ratio, conjugate cross-linking, and O:2 O-acetylation level as critical quality attributes and identified optimal design for a more immunogenic vaccine. Conclusions: This work guides the development of the O:2–CRM197 conjugate to be combined with TCV in a bivalent formulation against enteric fever. [ABSTRACT FROM AUTHOR]

Cervical cancer, CC, is one of the malignant cancers in women worldwide. Many studies about the genesis and progression of CC have been done at genomic, transcriptional, translational, and epigenetic levels. However, much less is done at post-translational modification (PTM) level. We first used pan-PTM antibodies to compare the pan PTM levels between clinical normal cervical tissues and CC tissues; we then sent the selected samples for label-free identification of acetylation sites. Next, we employed WT or K119A mutant PARP1-EGFP-STREPII plasmid transfection in Hela cells and examined various indexes including colony formation, wound healing, ROS generation, early apoptosis, and immunofluorescence and quantification of proliferation markers (Ki67, PCNA, and p-P53). Last, we examined the levels of multiple important kinases regulating cervical cancer progression. We found that pan-acetylation was the most downregulated in clinical CC samples, whereas the acetylation of PARP1, Poly(ADP-ribose) polymerase-1, was upregulated at K119. Next, we showed that PARP1-WT overexpression significantly suppressed the proliferation and progression in CC cell line Hela, while K119A overexpression didn't show any impact. Finally, PARP1-WT overexpression significantly decreased p-ERK1/2 while didn't affect the phosphorylation levels of other important kinases such as AKT, MTOR, and RPS6. This study discovered a new type of PTM of PARP1 in CC, and showed that PARP1 acetylation at K119 is essential in regulating the proliferation and progression of CC through ERK1/2. Further studies are required to investigate how PARP1 acetylation impact its function. [ABSTRACT FROM AUTHOR]

Sirtuin 7 (SIRT7) is a member of the sirtuin family and has emerged as a key player in numerous cellular processes. It exhibits various enzymatic activities and is predominantly localized in the nucleolus, playing a role in ribosomal RNA expression, DNA damage repair, stress response and chromatin compaction. Recent studies have revealed its involvement in diseases such as cancer, cardiovascular and bone diseases, and obesity. In cancer, SIRT7 has been found to be overexpressed in multiple types of cancer, including breast cancer, clear cell renal cell carcinoma, lung adenocarcinoma, prostate adenocarcinoma, hepatocellular carcinoma, and gastric cancer, among others. In general, cancer cells exploit SIRT7 to enhance cell growth and metabolism through ribosome biogenesis, adapt to stress conditions and exert epigenetic control over cancer-related genes. The aim of this review is to provide an in-depth understanding of the role of SIRT7 in cancer carcinogenesis, evolution and progression by elucidating the underlying molecular mechanisms. Emphasis is placed on unveiling the intricate molecular pathways through which SIRT7 exerts its effects on cancer cells. In addition, this review discusses the feasibility and challenges associated with the development of drugs that can modulate SIRT7 activity. [ABSTRACT FROM AUTHOR]

Zinc plays a pivotal role in tissue regeneration and maintenance being as a central cofactor in a plethora of enzymatic activities. Hypozincemia is commonly seen with chronic liver disease and is associated with an increased risk of liver fibrosis development and hepatocellular carcinoma. Previously favorable effects of zinc supplementation on liver fibrosis have been shown. However, the underlying mechanism of this effect is not elucidated. Liver fibrosis was induced in mice by using CCl4 injection, followed by treatment with zinc chloride (ZnCl2) both at fibrotic and sham groups, and their hepatocytes were isolated. Our results showed that the administration of ZnCl2 restored the depleted cytosolic zinc levels in the hepatocytes isolated from the fibrotic group. Also, alpha-smooth muscle actin (αSMA) expression in hepatocytes was decreased, indicating a reversal of the fibrotic process. Notably, ZIP14 expression significantly increased in the fibrotic group following ZnCl2 treatment, whereas in the sham group ZIP14 expression decreased. Chromatin immunoprecipitation (ChIP) experiments revealed an increased binding percentage of Metal-regulatory transcription factor 1 (MTF1) on ZIP14 promoter in the hepatocytes isolated from fibrotic mice compared to the sham group after ZnCl2 administration. In the same group, the binding percentage of the histone deacetylase HDAC4 on ZIP14 promoter decreased. Our results suggest that the ZnCl2 treatment ameliorates liver fibrosis by elevating intracellular zinc levels through MTF1-mediated regulation of ZIP14 expression and the reduction of ZIP14 deacetylation via HDAC4. The restoration of intracellular zinc concentrations and the modulation of ZIP14 expression by zinc orchestrated through MTF1 and HDAC4, appear to be essential determinants of the therapeutic response in hepatic fibrosis. These findings pave the way for potential novel interventions targeting zinc-related pathways for the treatment of liver fibrosis and associated conditions. [ABSTRACT FROM AUTHOR]

α‐substituted ketones are important chemical targets as synthetic intermediates as well as functionalities in natural products and pharmaceuticals. We report the α‐acetylation of C(sp3)−H substrates R−H with arylmethyl ketones ArC(O)Me to provide α‐alkylated ketones ArC(O)CH2R at RT with tBuOOtBu as oxidant via copper(I) β ${\beta }$ ‐diketiminato catalysts. Proceeding via alkyl radicals R•, this method enables α‐substitution with bulky substituents without competing elimination that occurs in more traditional alkylation reactions between enolates and alkyl electrophiles. DFT studies suggest the intermediacy of copper(II) enolates [CuII](CH2C(O)Ar) that capture alkyl radicals R• to give R−CH2C(O)Ar outcompeting dimerization of the copper(II) enolate to give the 1,4‐diketone ArC(O)CH2CH2C(O)Ar. [ABSTRACT FROM AUTHOR]

ABSTRACT The acetylation of histones H2A on lysine 5 (H2AacK5) and H3 on lysine 27 (H3AcK27) modulate several cellular mechanisms through the p300 enzyme in pathological lesions; however, their role in odontogenic lesions has not been addressed. This study aims to evaluate the immunoexpression of p300, H2AacK5, and H3AcK27 in samples of ameloblastoma (AMB) (n = 30), odontogenic keratocyst (OK) (n = 15), adenomatoid odontogenic tumor (AOT) (n = 10), odontogenic fibroma (OF) (n = 8), calcifying odontogenic cyst (COC) (n = 8), odontogenic myxoma (MIX) (n = 10), and ameloblastic fibroma (AF) (n = 06). The percentage of p300‐positive cells was higher in AOT and decreased in COC, OK, AMB, AF, OF, and MIX. H2AacK5‐positive cells were higher in AF and decreased in AOT, COC, OK, OF, AMB, and MIX, whereas H3acK27‐positive cells were higher in AOT and decreased in COC, OK, AF, OF, AMB, and MIX. The expression of these proteins was higher in nonaggressive lesions in comparison to aggressive lesions. There was a positive correlation between p300 and H2AacK5, and H3acK27 in AMB, MIX, and OF, whereas there was a positive correlation between p300 and H2AacK5 in AOT and COC. The histone acetylation may be involved in the biological behavior of these lesions, which could be used to improve their diagnosis and treatment. [ABSTRACT FROM AUTHOR]

Aim Methods Results Conclusion Duchenne muscular dystrophy is a progressive muscle‐wasting disease caused by mutations in the dystrophin gene. Despite progress in dystrophin‐targeted gene therapies, it is still a fatal disease requiring novel therapeutics that can be used synergistically or alternatively to emerging gene therapy. Defective autophagy and disorganized microtubule networks contribute to dystrophic pathogenesis, yet the mechanisms by which microtubule alterations regulate autophagy remain elusive. The present study was designed to uncover possible mechanisms underpinning the role of microtubules in regulating autophagy in dystrophic mice.Mdx mice were also supplemented with Tubastatin A, a pharmacological inhibitor of histone deacetylase 6, and pathophysiology was assessed. Mdx mice with a genetic deletion of the Nox‐2 scaffolding subunit p47phox were used to assess redox dependence on tubulin acetylation.Our data show decreased acetylation of α‐tubulin with enhanced histone deacetylase 6 expression. Tubastatin A increases tubulin acetylation and Q‐SNARE complex formation but does not alter microtubule organization or density, indicating improved autophagosome–lysosome fusion. Tubastatin A increases the acetylation of peroxiredoxin and protects it from hyper‐oxidation, hence modulating intracellular redox status in mdx mice. Tubastatin A reduces muscle damage and enhances force production. Genetic down regulation of Nox2 activity in the mdx mice promotes autophagosome maturation but not autolysosome formation.Our data highlight that autophagy is differentially regulated by redox and acetylation in mdx mice. By improving autophagy through promoting tubulin acetylation, Tubastatin A decreases the dystrophic phenotype and improves muscle function, suggesting a great potential for clinical translation and treating dystrophic patients. [ABSTRACT FROM AUTHOR]

Tauopathies, including Alzheimer's disease (AD), are a class of neurodegenerative diseases characterized by the presence of insoluble tau inclusions. Tau phosphorylation has traditionally been viewed as the dominant post-translational modification (PTM) controlling tau function and pathogenesis in tauopathies. However, we and others have identified tau acetylation as a primary PTM regulating both normal tau function as well as abnormal pathogenic features including aggregation. Prior work showed robust tau acetylation in aggregation hotspots located within the 2nd and 3rd repeat regions of tau (residues K280 and K311) in tauopathy brains, including AD, compared to non-tauopathy controls. By screening thousands of hybridoma clones, we generated site-specific and modification-specific monoclonal antibodies targeting acetylated tau at residues K280 or K311. To validate these antibodies in a bona fide neuronal system, we targeted the acetyltransferase CBP to the cytoplasm of neurons to promote tau acetylation. Several antibody clones specifically detected CBP-acetylated tau and co-localized with ac-tau in neurons. Additionally, our lead optimal anti-acetylated-tau monoclonal antibodies detected robust tau pathology in tangles and neuritic plaques of human AD brains. Given the now emerging interest in acetylated tau as critical regulator of tau functions, these sensitive and highly specific tools will allow us to further unravel the tau PTM code and, importantly, could be deployed as diagnostic or disease-modifying agents. [ABSTRACT FROM AUTHOR]

The aberrant acetylation of mitochondrial proteins is involved in the pathogenesis of multiple diseases including neurodegenerative diseases and cerebral ischemic injury. Previous studies have shown that depletion of mitochondrial NAD+, which is necessary for mitochondrial deacetylase activity, leads to decreased activity of mitochondrial deacetylase and thus causes hyperacetylation of mitochondrial proteins in ischemic brain tissues, which results in altered mitochondrial dynamics. However, it remains largely unknown about how mitochondrial dynamics-related protein Drp1 is acetylated in ischemic neuronal cells and brain tissues. Here, we showed that Drp1 and GCN5L1 expression was up-regulated in OGD-treated neuronal cells and ischemic brain tissues induced by dMCAO, accompanied by the increased mitochondrial fission, mtROS accumulation, and cell apoptosis. Further, we confirmed that ischemia/hypoxia promoted Drp1 interaction with GCN5L1 in neuronal cells and brain tissues. GCN5L1 knockdown attenuated, while its overexpression enhanced Drp1 acetylation and mitochondrial fission, indicating that GCN5L1 plays a crucial role in ischemia/hypoxia-induced mitochondrial fission by acetylating Drp1. Mechanistically, ischemia/hypoxia induced Drp1 phosphorylation by CDK5 upregulation-mediated activation of AMPK in neuronal cells, which in turn facilitated the interaction of GCN5L1 with Drp1, thus enhancing Drp1 acetylation and mitochondrial fission. Accordingly, inhibition of AMPK alleviated ischemia/hypoxia- induced Drp1 acetylation and mitochondrial fission and protected brain tissues from ischemic damage. These findings provide a novel insight into the functional roles of GCN5L1 in regulating Drp1 acetylation and identify a previously unrecognized CDK5-AMPK-GCN5L1 pathway that mediates the acetylation of Drp1 in ischemic brain tissues. [ABSTRACT FROM AUTHOR]

RNA modification is an important type of epigenetic modification, which refers to the addition of chemical modifying groups to the bases or ribose of RNA molecules, and can occur in a variety of RNAs, such as messenger RNAs (mRNAs), transfer RNAs (tRNAs), ribosomal RNAs (rRNAs), and cyclic RNAs (circRNAs), etc. RNA methylation and acetylation are two of the key types of modifications that perform important biological functions by regulating the genetic information of organisms. Both modifications are dynamically and reversibly regulated by three types of regulators, namely writers, erasers and readers, which have a crucial impact on different RNA metabolic processes such as RNA splicing, translocation, translation, transport and degradation. In recent years, with the development of RNA modification detection technologies, numerous studies have identified new RNA modification sites in plants and confirmed that methylation and acetylation modifications of RNAs play key roles in plant growth and development as well as in response to biotic and abiotic stresses. This paper firstly outlines the types of RNA modifications and their biological properties, and on this basis focuses on reviewing the research progress on RNA methylation and acetylation regulators in recent years, and finally summarizes the functions of RNA methylation and acetylation in plant growth and development and in response to stresses, and looks forward to some new research directions for RNA modifications in plants, with a view to providing theoretical basis and new ideas for further research related to RNA methylation and acetylation modification in plants. [ABSTRACT FROM AUTHOR]

The Allis group identified Gcn5 as the first transcriptionrelated lysine acetyltransferase in 1996, providing a molecular "missing link" between chromatin organization and gene regulation. This review will focus on functions subsequently identified for Gcn5 and the closely related PCAF protein, in the context of two major complexes, SAGA and ATAC, and how the study of these enzymes informs long standing questions regarding the importance of lysine acetylation. [ABSTRACT FROM AUTHOR]

Background: Infertility is a global reproductive health burden. Assisted reproductive technologies (ARTs) have been widely used to help patients become pregnant. Few embryos develop to the blastocyst stage with ARTs, leading to relatively low live birth rates. Protein modifications play crucial roles in nearly every aspect of cell biology, including reproductive processes. The aim of this study was to explore the characteristics of protein modifications during embryonic development. Methods: Proteomic data from humans and mice were acquired from the integrated proteome resources (iProX) of ProteomeXchange (PXD024267) and a tandem mass tag (TMT)‐mass spectrometry dataset. Gene ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis were applied for functional annotation. Protein–protein interactions (PPIs) of the modification‐related genes were revealed by the STRING database. Modified proteins during mouse embryogenesis were visualized through heatmaps of hierarchically clustering using k‐means. Results: We identified modification‐related proteins in human embryo development and characterized them through heatmaps, GO analysis, KEGG analysis, and PPI network analysis. We found that the 4‐cell stage to the 8‐cell stage might be the demarcation period for modification‐related protein expression patterns during embryo development. Using quantitative mass spectrometry, we elucidated the methylation, acetylation, and ubiquitination events that occur during mouse embryogenesis to validate our findings in human embryonic development to some extent. Conclusions: The results of our study suggest that the posttranslational modifications (PTMs) of human preimplantation embryos might exhibit the same trends as those in mice to exert synergistic and fine‐tuned regulatory effects during embryonic development. [ABSTRACT FROM AUTHOR]

Lysine acetylation, an evolutionarily conserved post‐translational protein modification, is reversibly catalyzed by lysine acetyltransferases and lysine deacetylases. Lysine acetylation, which was first discovered on histones, mainly functions to configure the structure of chromatin and regulate gene transcriptional activity. Over the past decade, with advances in high‐resolution mass spectrometry, a vast and growing number of non‐histone proteins modified by acetylation in various plant species have been identified. Lysine acetylation of non‐histone proteins is widely involved in regulating biological processes in plants such as photosynthesis, energy metabolism, hormone signal transduction and stress responses. Moreover, in plants, lysine acetylation plays crucial roles in regulating enzyme activity, protein stability, protein interaction and subcellular localization. This review summarizes recent progress in our understanding of the biological functions and mechanisms of non‐histone protein acetylation in plants. Research prospects in this field are also noted. [ABSTRACT FROM AUTHOR]

With the aim of improving the uncertainties associated with the correct diagnosis of seronegative rheumatoid arthritis (RA) and identifying those at risk of developing interstitial lung disease (ILD), we have designed new peptide antigens bearing three post-translational modifications (PTMs) (citrulline, homocitrulline and acetyl-lysine) related to RA that could complement existing tests based on anti-citrullinated peptide/protein antibodies (ACPAs). Several chimeric peptides were synthesized and comparatively tested as antigens in ELISAs with two cohorts of sera: 178 RAs and 110 healthy blood donors. The results indicated that although chimeric peptides containing all three PTMs and vimentin and enolase domains do not significantly outperform existing ACPA tests in terms of sensitivity and specificity, they show potential to complement current assays, especially when detecting antibodies in some seronegative patients. Furthermore, the presence of these autoantibodies significantly identified patients with RA and ILD. We can conclude that the identification of specific autoantibody profiles using synthetic antigens containing peptide domains derived from proteins present in the human joint could help in the early detection of the risk of ILD in patients with RA and be useful for adapting follow-up strategies and guiding decisions during treatment. [ABSTRACT FROM AUTHOR]

The interest in natural fibres and biopolymers for developing bio-composites has greatly increased in recent years, motivated by the need to reduce the environmental impact of traditional synthetic, fossil fuel-derived materials. However, several limitations associated with the use of natural fibres and polymers should be addressed if they are to be seriously considered mainstream fibre reinforcements. These include poor compatibility of natural fibres with polymer matrices, variability, high moisture absorption, and flammability. Various surface treatments have been studied to tackle these drawbacks, such as alkalisation, silane treatment, acetylation, plasma treatment, and polydopamine coating. This review paper considers the classification, properties, and limitations of natural fibres and biopolymers in the context of bio-composite materials. An overview of recent advancements and enhancement strategies to overcome such limitations will also be discussed, with a focus on mechanical performance, moisture absorption behaviour, and flammability of composites. The limitations of natural fibres, biopolymers, and their bio-composites should be carefully addressed to enable the widespread use of bio-composites in various applications, including electronics, automotive, and construction. [ABSTRACT FROM AUTHOR]

This study aimed to investigate the effects of acid or alkali modification of isolated cassava starch (ICS) on its physicochemical properties. Acetic acid concentrations of 5%, 10%, and 20% v/v (0.87, 1.73, and 3.46 M, respectively) and calcium hydroxide concentrations of 0.15%, 0.20%, and 0.30% w/w (0.02, 0.025, and 0.04 M, respectively) were tested independently and compared with untreated isolated starch. The scanning electron microscope (SEM) shows starches with polyhedral and semispherical shapes; these modifications do not change the surface of the starch granules. Nanocrystals with orthorhombic crystal structure were extracted from ICS. Transmission electron microscopy (TEM) shows crystallites with a size (two‐dimensional) of 20 ± 5 nm in length and 10 ± 2 nm in width and reveals that this starch contains nanocrystals with orthorhombic crystal structure. The X‐ray patterns show that these nanocrystals are unaffected by acidic or alkaline treatments. The Ca+2 and CH3COO− ions do not interact with these nanocrystals. The alkaline treatment only affects the gelatinization temperature at a Ca(OH)2 concentration of 0.30%. Low concentrations of acidic and alkaline treatments affect the ability of cassava starch to absorb water and reduce the peak and final viscosity. The infrared spectra show that the modifications lead to C–H and C═C bond formations. ICS‐B 0.30 can modify the amorphous regions of the starch, and the acid treatment leads to acetylation, which was confirmed by the presence of an IR band at 1740 cm−1. [ABSTRACT FROM AUTHOR]

A mild strategy was developed for efficient preparation of acetylsalicylic acid (ASA) from the acetylation of salicylic acid (SA) and acetic anhydride (AA) assisted ultrasonic over Y-immobilized cation exchange resin (Y-CER). With this strategy, an ASA yield of 95.2% was obtained. The results showed that the increased yield was due to Lewis acidic sites (LAS) combined with ultrasonic assistance. The process reduced the AA reagent feed while lowering the reaction temperature. The characterization results showed that metal Y species were dispersedly anchored on the CER surface through S-O-Y triple-dentate bonds, resulting in abundant LAS and stable catalytic activity. Comparative experiments revealed that LAS was more favorable for the formation of ASA than Bronsted acidic sites (BAS). Furthermore, a plausible mechanism for the acetylation of SA and AA by Y-CER has been proposed. This work provided a practical protocol for improving ASA yield and reducing acid wastewater discharge, with potential application prospects. [ABSTRACT FROM AUTHOR]

As a treasure trove of natural products (NPs), various fungal species possess great potential as cell factories for valuable NPs bioproduction. However, they have many silent biosynthetic gene clusters (BGCs), and activation of BGCs expression is critical to the discovery of their indetectable NPs, especially secondary metabolites, in which epigenetic regulation plays a significant role. Thanks to the development of sequencing technologies, more and more epigenetic regulators have been characterized and adopted for boosting fungal NPs production. In this review, at first we summarize various kinds of epigenetic regulation and relevant strategies for triggering fungal NPs biosynthesis. Then, we discuss the limitations of the current strategies, and propose future trends in the discovery of fungi derived NPs by manipulating epigenetics. • Epigenetic regulation plays a significant role in discovery of the undetectable natural products from fungal species. • Manipulating histone-modifying proteins is a novel manner to activate the expression of biosynthetic gene clusters. • This work provides a systematical view on triggering fungal natural products biosynthesis by epigenetic regulation. [ABSTRACT FROM AUTHOR]

Main conclusion: This review focuses on HATs and HDACs that modify non-histone proteins, summarizes functional mechanisms of non-histone acetylation as well as the roles of HATs and HDACs in rice and Arabidopsis. The growth and development of plants, as well as their responses to biotic and abiotic stresses, are governed by intricate gene and protein regulatory networks, in which epigenetic modifying enzymes play a crucial role. Histone lysine acetylation levels, modulated by histone acetyltransferases (HATs) and histone deacetylases (HDACs), are well-studied in the realm of transcriptional regulation. However, the advent of advanced proteomics has unveiled that non-histone proteins also undergo acetylation, with its underlying mechanisms now being clarified. Indeed, non-histone acetylation influences protein functionality through diverse pathways, such as modulating protein stability, adjusting enzymatic activity, steering subcellular localization, influencing interactions with other post-translational modifications, and managing protein–protein and protein–DNA interactions. This review delves into the recent insights into the functional mechanisms of non-histone acetylation in plants. We also provide a summary of the roles of HATs and HDACs in rice and Arabidopsis, and explore their potential involvement in the regulation of non-histone proteins. [ABSTRACT FROM AUTHOR]

This work aimed to isolate cellulose nanofibers (CNF) from sisal fibers and to impart hydrophobic characteristics through acetylation with acetic anhydride. The sisal fibers were pre-treated using alkaline hydrogen peroxide (AHP) followed by acetylation using acetic anhydride. Acetylated and non-acetylated CNF were then isolated by mechanical defibrillation of pre-treated fibers using a high-speed blender. Both resulting CNF were evaluated using attenuated total reflection Fourier transform infrared spectroscopy (ATR-FTIR), X-ray diffraction (XRD), transmissions electron microscopy (TEM), thermogravimetric analysis (TGA), and water contact angle measurement. ATR-FTIR results revealed the substitution of hydroxyl groups by some acetyl groups as indicated by the presence of carbonyl and methyl groups for the acetylated CNF (ACNF). The yield of ACNF and CNF obtained in this work was 90% and 86%, respectively. The dispersion studies exhibited that ACNF formed a more stable suspension and dispersed better in acetone than CNF. XRD analysis indicated that the acetylation process decreased the crystallinity index of CNF from 79 to 66%. The average diameter distribution of ACNF and CNF was 5.59 ± 1.45 nm and 6.22 ± 1.97, respectively. Furthermore, without lowering the thermal stability of CNF, ACNF exhibited higher hydrophobicity as high as 87° compared with that of CNF with a 12° contact angle. The resulting ACNF extracted from sisal fibers had great potential application as reinforcement for nanocomposites with a nonpolar polymer matrix. [ABSTRACT FROM AUTHOR]

METTL3 methylates RNA and regulates the fate of mRNA through its methyltransferase activity. METTL3 enhances RNA translation independently of its catalytic activity. However, the underlying mechanism is still elusive. Here, we report that METTL3 is both interacted with and acetylated at lysine 177 by the acetyltransferase PCAF and deacetylated by SIRT3. Neither the methyltransferase activity nor the stability of METTL3 is affected by its acetylation at K177. Importantly, acetylation of METTL3 blocks its interaction with EIF3H, a subunit of the translation initiation factor, thereby reducing mRNA translation efficiency. Interestingly, acetylation of METTL3 responds to oxidative stress. Mechanistically, oxidative stress enhances the interaction of PCAF with METTL3, increases METTL3 acetylation, and suppresses the interaction of METTL3 with EIF3H, thereby decreasing the translation efficiency of ribosomes and inhibiting cell proliferation. Altogether, we suggest a mechanism by which oxidative stress regulates RNA translation efficiency by the modulation of METTL3 acetylation mediated by PCAF. [ABSTRACT FROM AUTHOR]

Abstract HBO1, also known as KAT7 or MYST2, is a crucial histone acetyltransferase with diverse cellular functions. It typically forms complexes with protein subunits or cofactors such as MEAF6, ING4, or ING5, and JADE1/2/3 or BRPF1/2/3, where the BRPF or JADE proteins serve as the scaffold targeting histone H3 or H4, respectively. The histone acetylation mediated by HBO1 plays significant roles in DNA replication and gene expression regulation. Additionally, HBO1 catalyzes the modification of proteins through acylation with propionyl, butyryl, crotonyl, benzoyl, and acetoacetyl groups. HBO1 undergoes ubiquitination and degradation by two types of ubiquitin complexes and can also act as an E3 ubiquitin ligase for the estrogen receptor α (ERα). Moreover, HBO1 participates in the expansion of medullary thymic epithelial cells (mTECs) and regulates the expression of peripheral tissue genes (PTGs) mediated by autoimmune regulator (AIRE), thus inducing immune tolerance. Furthermore, HBO1 influences the renewal of hematopoietic stem cells and the development of neural stem cells significantly. Importantly, the overexpression of HBO1 in various cancers suggests its carcinogenic role and potential as a therapeutic target. This review summarizes recent advancements in understanding HBO1’s involvement in acylation modification, DNA replication, ubiquitination, immunity, and stem cell renewal.

Introduction: Ginsenosides (GS) derived from Panax ginseng can regulate protein acetylation to promote mitochondrial function for protecting cardiomyocytes. However, the potential mechanisms of GS for regulating acetylation modification are not yet clear. Objectives: This study aimed to explore the potential mechanisms of GS in regulating protein acetylation and identify ginsenoside monomer for fighting myocardial ischemia-related diseases. Methods: The 4D-lable free acetylomic analysis was employed to gain the acetylated proteins regulated by GS pretreatment. The co-immunoprecipitation assay, immunofluorescent staining, and mitochondrial respiration measurement were performed to detect the effect of GS or ginsenoside monomer on acetylated protein level and mitochondrial function. RNA sequencing, site-specific mutation, and shRNA interference were used to explore the downstream targets of acetylation modificationby GS. Cellular thermal shift assay and surface plasmon resonance were used for identifying the binding of ginsenoside with target protein. Results: In the cardiomyocytes of normal, oxygen glucose deprivation and/or reperfusion conditions, the acetylomic analysis identified that the acetylated levels of spliceosome proteins were inhibited by GS pretreatment and SF3A2 acetylation at lysine 10 (K10) was significantly decreased as a potential target of GS. Ginsenoside Rb2 was identified as one of the active ginsenoside monomers for reducing the acetylation of SF3A2 (K10), which enhanced mitochondrial respiration against myocardial ischemic injury in in vivo and in vitro experiments. RNA-seq analysis showed that ginsenoside Rb2 promoted alternative splicing of mitochondrial function-related genes and the level of fascin actin-bundling protein 1 (Fscn1) was obviously upregulated, which was dependent on SF3A2 acetylation. Critically, thermodynamic, kinetic and enzymatic experiments demonstrated that ginsenoside Rb2 directly interacted with p300 for inhibiting its activity. Conclusion: These findings provide a novel mechanism underlying cardiomyocyte protection of ginsenoside Rb2 by inhibiting p300-mediated SF3A2 acteylation for promoting Fscn1 expression, which might be a promising approach for the prevention and treatment of myocardial ischemic diseases.

Objective To investigate the molecular mechanism of translocation of heterogeneous nuclear ribonucleoprotein A2B1 (hnRNPA2B1) to the cytoplasm after glucose starvation and the effects of increased cytoplasmic translocation of hnRNPA2B1 on the survival of prostate cancer PC3 cells. Methods Human prostate cancer PC3 cells were divided into normal control group (cultured conventionally with glucose-containing medium, RPMI 1640 Medium) and glucose starvation group (cultured with glucose-free medium, RPMI 1640 Medium). The 2 types of cells were treated with deacetylase inhibitor, trichostatin A (TSA) combined with nicotinamide (NAM), AKT inhibitor BEZ235, si-NC transfection, and si-hnRNPA2B1 transfection, respectively. Cytoplasmic and nuclear protein separation, immunoprecipitation and Western blotting were used to detect changes in hnRNPA2B1 acetylation, total AKT protein and its phosphorylation level, and expression levels of hnRNPA2B1 in the cytoplasm and nucleus. CCK-8 assay was employed to observe cell survival in each group. Results After 3~5 h of glucose starvation treatment, the acetylation of hnRNPA2B1 protein was reduced (P < 0.01), and its cytoplasmic translocation was increased in PC3 cells (P < 0.01), which was accompanied by enhanced AKT phosphorylation and activation of the AKT signaling pathway. TSA/NAM treatment, BEZ235 treatment, and si-hnRNPA2B1 transfection all resulted in obvious increase in acetylation of hnRNPA2B1 protein when compared with glucose starvation treated cells (P < 0.01), which could inhibit the glucose starvation-mediated cytoplasmic translocation of hnRNPA2B1, suppress AKT phosphorylation, and consequently decrease the cell survival rate after glucose starvation (P < 0.01). Conclusion Glucose starvation can maintain the survival of PC3 cells by inducing the activation of the Ac-hnRNPA2B1-AKT signaling pathway.