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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]

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]

Oleanolic acid, a naturally occurring triterpenoid compound, has garnered significant attention in the scientific community due to its diverse pharmacological properties. Continuing our previous work on the synthesis of oleanolic acid dimers (OADs), a simple, economical, and safe acetylation reaction was performed. The newly obtained derivatives (AcOADs, 3a–3n) were purified using two methods. The structures of all acetylated dimers (3a–3n) were determined based on spectral methods (IR, NMR). For all AcOADs (3a–3n), the relationship between the structure and the expected directions of pharmacological activity was determined using a computational method (QSAR computational analysis). All dimers were also tested for their cytotoxic activity on the SKBR-3, SKOV-3, PC-3, and U-87 cancer cell lines. HDF cell line was applied to evaluate the Selectivity Index of the tested compounds. All cytotoxic tests were performed with the application of the MTT assay. Finally, all dimers of oleanolic acid were subjected to DPPH and CUPRAC tests to evaluate their antioxidant activity. The obtained results indicate a very high level of cytotoxic activity (IC50 for most AcOADs below 5.00 µM) and a fairly high level of antioxidant activity (Trolox equivalent in some cases above 0.04 mg/mL). [ABSTRACT FROM AUTHOR]

We have already proven that thiazolylketol acetates, synthetised by addition of 2-lithiothiazole to sugar lactones followed by acetylation, are efficient glycosyl donors in the presence of O-, N-, and P-nucleophiles. We describe here their first use in the C-glycosidation using trimetylsilyl cyanide as the acceptor in order to prepare, after thiazole-to-formyl unmasking and reduction, the corresponding C-ketosides. [ABSTRACT FROM AUTHOR]

Cellular senescence is a permanent condition of cell cycle arrest caused by a progressive shortening of telomeres defined as replicative senescence. Stem cells may also undergo an accelerated senescence response known as premature senescence, distinct from telomere shortening, as a response to different stress agents. Various treatment protocols have been developed based on epigenetic changes in cells throughout senescence, using different drugs and antioxidants, senolytic vaccines, or the reprogramming of somatic senescent cells using Yamanaka factors. Even with all the recent advancements, it is still unknown how different epigenetic modifications interact with genetic profiles and how other factors such as microbiota physiological conditions, psychological states, and diet influence the interaction between genetic and epigenetic pathways. The aim of this review is to highlight the new epigenetic modifications that are involved in stem cell senescence. Here, we review recent senescence-related epigenetic alterations such as DNA methylation, chromatin remodeling, histone modification, RNA modification, and non-coding RNA regulation outlining new possible targets for the therapy of aging-related diseases. The advantages and disadvantages of the animal models used in the study of cellular senescence are also briefly presented. [ABSTRACT FROM AUTHOR]

UV-B stress destroys the photosynthetic system of Rhododendron chrysanthum Pall. (R. chrysanthum), as manifested by the decrease of photosynthetic efficiency and membrane fluidity, and also promotes the accumulation of lignin. The MYB (v-myb avian myeloblastosis viral oncogene homolog) family of transcription factors can be involved in the response to UV-B stress through the regulation of lignin biosynthesis. This study indicated that both the donor and recipient sides of the R. chrysanthum were significantly damaged based on physiological index measurements made using OJIP curves under UV-B stress. The analysis of bioinformatics data revealed that the RcTRP5 transcription factor exhibits upregulation of acetylation at the K68 site, directly regulating the biosynthesis of lignin. Additionally, there was upregulation of the K43 site and downregulation of the K83 site of the CAD enzyme, as well as upregulation of the K391 site of the PAL enzyme. Based on these findings, we conjectured that the RcTRP5 transcription factor facilitates acetylation modification of both enzymes, thereby indirectly influencing the biosynthesis of lignin. This study demonstrated that lignin accumulation can alleviate the damage caused by UV-B stress to R. chrysanthum, which provides relevant ideas for improving lignin content in plants, and also provides a reference for the study of the metabolic regulation mechanism of other secondary substances. [ABSTRACT FROM AUTHOR]

Applications of millet bran dietary fiber (MBDF) in the food industry are limited by its poor hydration properties. Herein, MBDF was modified by heating, xylanase and cellulase treatment separately combined with carboxymethylation, acetylation, and phosphate crosslinking, and the effects of the modified MBDFs on heat-induced egg white protein gel (H-EWG) were studied. The results showed that three composite modifications, especially heating and dual enzymolysis combined with carboxymethylation, increased the surface area, soluble fiber content, and hydration properties of MBDF (p < 0.05). MBDF and the modified MBDFs all made the microstructure of H-EWG denser and decreased its α-helix content. Three composite modifications, especially heating and dual enzymolysis combined with carboxymethylation, enhanced the improving effect of MBDF on the WRA (from 24.89 to 35.53 g/g), pH, hardness (from 139.93 to 323.20 g), chewiness, and gumminess of H-EWPG, and enhanced the gastric stability at 3–5 g/100 g. MBDFs modified with heating and dual enzymolysis combined with acetylation or crosslinking were more effective in increasing the antioxidant activity of the gastrointestinal hydrolysates of H-EWG than MBDF (p < 0.05). Overall, heating, xylanase and cellulase treatment separately combined with carboxymethylation, acetylation and crosslinking can enhance the hydration properties and the improving effect of millet bran fibers on H-EWG properties. [ABSTRACT FROM AUTHOR]

The aim of this work was to develop a kinetic model based on the power law to describe the evolution of glycerol conversion and product distribution in the crude glycerol (G) acetylation reaction with acetic acid (AA) without the use of a catalyst. For this purpose, experimental tests were carried out with analytical glycerol under different reaction conditions (T = 80–160 °C, AA/G = 1–9 molar ratio, t = 0.25–2 h). The results showed the formation of mono- (MAG), di- (DAG) and tri- (TAG) acetylglycerols, liquid products with multiple applications in the chemical industry. From these results, a kinetic model based on the power law was implemented, which could acceptably estimate the experimental concentrations with an average relative error of 14.9%. Then, crude glycerol samples from different biodiesel industries were characterized by identifying and quantifying the impurities present in them (H2O, CH3OH, NaOH, NaCOOH, MONG and NaCl), and employed as reactants in the reaction tests. Given the significant differences observed in the glycerol conversion values compared to those obtained with analytical glycerol, further reaction tests were conducted to elucidate the effect of each impurity over the glycerol conversion. In these tests, the different impurities were added individually, maintaining the same concentration range as that of the crude glycerol samples. From the results obtained, global activity factors were introduced, which allowed us to modify the kinetic model to estimate glycerol conversions in the crude glycerol samples with an average relative error of 7%. It is hoped that this kinetic model will be a powerful tool useful for designing reactors on an industrial scale. [ABSTRACT FROM AUTHOR]

An imbalance in estrogen signaling is a critical event in breast tumorigenesis. The majority of breast cancers (BCs) are hormone-sensitive; they majorly express the estrogen receptor (ER+) and are activated by 17β-estradiol (E2). The steroidogenic acute regulatory protein (StAR) mediates the rate-limiting step in steroid biosynthesis. The dysregulation of the epigenetic machinery, modulating E2 levels, is a primary occurrence for promoting breast tumorigenesis. StAR expression, concomitant with E2 synthesis, was reported to be aberrantly high in human and mouse hormone-dependent BC cells compared with their non-cancerous counterparts. However, the mechanism of action of StAR remains poorly understood. We discovered StAR as an acetylated protein and have identified a number of lysine (K) residues that are putatively acetylated in malignant and non-malignant breast cells, using LC-MS/MS (liquid chromatography–tandem mass spectrometry), suggesting they differently influence E2 synthesis in mammary tissue. The treatment of hormone-sensitive MCF7 cells with a variety of histone deacetylase inhibitors (HDACIs), at therapeutically and clinically relevant doses, identified a few additional StAR acetylated lysine residues. Among a total of fourteen StAR acetylomes undergoing acetylation and deacetylation, K111 and K253 were frequently recognized either endogenously or in response to HDACIs. Site-directed mutagenesis studies of these two StAR acetylomes, pertaining to K111Q and K253Q acetylation mimetic states, resulted in increases in E2 levels in ER+ MCF7 and triple negative MB-231 BC cells, compared with their values seen with human StAR. Conversely, these cells carrying K111R and K253R deacetylation mutants diminished E2 biosynthesis. These findings provide novel and mechanistic insights into intra-tumoral E2 regulation by elucidating the functional importance of this uncovered StAR post-translational modification (PTM), involving acetylation and deacetylation events, underscoring the potential of StAR as a therapeutic target for hormone-sensitive BC. [ABSTRACT FROM AUTHOR]

Post-translational modifications (PTMs) affecting proteins during or after their synthesis play a crucial role in their localization and function. The modification of these PTMs under pathophysiological conditions, i.e., their appearance, disappearance, or variation in quantity caused by a pathological environment or a mutation, corresponds to post-translational variants (PTVs). These PTVs can be directly or indirectly involved in the pathophysiology of diseases. Here, we present the PTMs and PTVs of four major amyotrophic lateral sclerosis (ALS) proteins, SOD1, TDP-43, FUS, and TBK1. These modifications involve acetylation, phosphorylation, methylation, ubiquitination, SUMOylation, and enzymatic cleavage. We list the PTM positions known to be mutated in ALS patients and discuss the roles of PTVs in the pathophysiological processes of ALS. In-depth knowledge of the PTMs and PTVs of ALS proteins is needed to better understand their role in the disease. We believe it is also crucial for developing new therapies that may be more effective in ALS. [ABSTRACT FROM AUTHOR]

This study aimed to explore the capacity of immobilized lipases on the acetylation of six aglycon flavonoids, namely myricetin, quercetin, luteolin, naringenin, fisetin and morin. For this purpose, lipase B from Candida antarctica (CaLB) and lipase from Thermomyces lanuginosus (TLL) were immobilized onto the surface of ZnOFe nanoparticles derived from an aqueous olive leaf extract. Various factors affecting the conversion of substrates and the formation of monoesterified and diesterified products, such as the amount of biocatalyst and the molar ratio of the substrates and reaction solvents were investigated. Both CaLB and TLL-ZnOFe achieved 100% conversion yield of naringenin to naringenin acetate after 72 h of reaction time, while TLL-ZnOFe achieved higher conversion yields of quercetin, morin and fisetin (73, 85 and 72% respectively). Notably, CaLB-ZnOFe displayed significantly lower conversion yields for morin compared with TLL-ZnOFe. Molecular docking analysis was used to elucidate this discrepancy, and it was revealed that the position of the hydroxyl groups of the B ring on morin introduced hindrances on the active site of CaLB. Finally, selected flavonoid esters showed significantly higher antimicrobial activity compared with the original compound. This work indicated that these lipase-based nanobiocatalysts can be successfully applied to produce lipophilic derivatives of aglycon flavonoids with improved antimicrobial activity. [ABSTRACT FROM AUTHOR]

Simple Summary: The incidence of obstructive sleep apnea in children is increasing year by year, and its occurrence and related metabolic and endocrine lesions may be related to hypothalamic dysfunction. Lysine acetylation is a common post-translational modification that is essential for metabolism. The aim of this study was to determine the effects of chronic intermittent hypoxia-induced lysine acetylation on hypothalamic function in an infant mice model, simulating pediatric obstructive sleep apnoea patients. Our study revealed the lysine acetylome and proteomic profile of the hypothalamus induced by chronic intermittent hypoxia in juvenile mice. Differentially acetylated proteins were involved in endocrine metabolism, the citrate cycle (TCA cycle), synapse function, and circadian entrainment. Our findings suggest that chronic intermittent hypoxia may induce metabolic and endocrine dysregulation through modulation of hypothalamic lysine acetylation. Paediatric obstructive sleep apnoea (OSA) is a highly prevalent sleep disorder resulting in chronic intermittent hypoxia (CIH) that has been linked to metabolism and endocrine impairment. Protein acetylation, which is a frequently occurring posttranslational modification, plays pivotal roles in the regulation of hypothalamic processes. However, the effects of CIH-induced global protein acetylation on hypothalamic function and endocrine metabolism remain poorly understood. To bridge this knowledge gap, we conducted a study utilizing liquid chromatography–mass spectrometry to analyse the lysine acetylome and proteome of the hypothalamus in healthy infantile mice exposed to 3 weeks of intermittent hypoxia (as a CIH model) compared to normoxic mice (as controls). Our analysis identified and quantified 2699 Kac sites in 2453 proteins. These acetylated proteins exhibited disruptions primarily in endocrine metabolism, the citrate cycle (TCA cycle), synapse function, and circadian entrainment. Additionally, we observed significant down-regulation of proteins that are known to be involved in endocrine hormone secretion. This study aimed to elucidate the molecular mechanisms underlying CIH-induced alterations in protein acetylation within the hypothalamus. By providing valuable insights into the pathophysiological processes associated with CIH and their impacts on hypothalamic function, our findings contribute to a deeper understanding of the consequences stemming from CIH-induced changes in protein acetylation within the hypothalamus as well as its potential role in endocrine impairment. [ABSTRACT FROM AUTHOR]

Phosphoglycerylation is a non-enzymatic protein modification in which a phosphoglyceryl moiety is covalently bound to the ε-amino group of lysine. It is enriched in glycolytic enzymes from humans and mice and is thought to provide a feedback mechanism for regulating glycolytic flux. We report the first proteomic analysis of this post-translational modification in bacteria by profiling phosphoglyceryl-lysine during the growth of Streptococcus pyogenes in different culture media. The identity of phosphoglyceryl-lysine was confirmed by a previously unknown diagnostic cyclic immonium ion generated during MS/MS. We identified 370 lysine phosphoglycerylation sites in 123 proteins of S. pyogenes. Growth in a defined medium on 1% fructose caused a significant accumulation of phosphoglycerylation compared to growth in a rich medium containing 0.2% glucose. Re-analysis of phosphoproteomes from 14 bacterial species revealed that phosphoglycerylation is generally widespread in bacteria. Many phosphoglycerylation sites were conserved in several bacteria, including S. pyogenes. There was considerable overlap between phosphoglycerylation, acetylation, succinylation, and other acylations on the same lysine residues. Despite some exceptions, most lysine phosphoglycerylations in S. pyogenes occurred with low stoichiometry. Such modifications may be meaningless, but it is also conceivable that phosphoglycerylation, acetylation, and other acylations jointly contribute to the overall regulation of metabolism. [ABSTRACT FROM AUTHOR]

Nanocomposites made via electrospinning were constructed of polyvinyl alcohol (PVA) and chitin. Chitin was extracted from a natural source (Fomes fomentarius), which allowed for precise control of the chemical properties of the resulting material. Chitin was chosen as a filler due to its low cost and widespread availability. Increasing the degree of acetylation of the chitin increased the Young's Modulus of the resulting fiber mats but only at relatively high levels. While composites at lower acetylation levels were stable, no increase in the Young's Modulus was observed, presumably due to decreased intermolecular bonding among fibers. The results suggest that precise control of the degree of acetylation of chitin, more than the loading amount and dispersibility, significantly impacts composite formation. [ABSTRACT FROM AUTHOR]

Flavonoids, a class of natural compounds with anticancer activity, exhibit varying biological activities and potencies based on their structural differences. Acylation, including acetylation of flavonoids, generally increases their structural diversity, which is closely related to the diversity of bioactivity within this group of compounds. However, it remains largely unknown how acetylation affects the bioactivity of many flavonoids. Based on our previous findings that O-acetylation enhances quercetin's bioactivity against various cancer cells, we synthesized 12 acetylated flavonoids, including seven novel compounds, to investigate their anticancer activities in the MDA-MB-231, HCT-116, and HepG2 cell lines. Our results showed that acetylation notably enhanced the cell proliferation inhibitory effect of quercetin and kaempferol across all cancer cell lines tested. Interestingly, while the 5,7,4′-O-triacetate apigenin (3Ac-A) did not show an enhanced the effect of inhibition of cell proliferation through acetylation, it exhibited significantly strong anti-migration activity in MDA-MB-231 cells. In contrast, the 7,4′-O-diacetate apigenin (2Ac-Q), which lacks acetylation at the 5-position hydroxy group, showed enhanced cell proliferation inhibitory effect but had weaker anti-migration effects compared to 3Ac-A. These results indicated that acetylated flavonoids, especially quercetin, kaempferol, and apigenin derivatives, are promising for anticancer applications, with 3Ac-A potentially having unique anti-migration pathways independent of apoptosis induction. This study highlights the potential application of flavonoids in novel chemopreventive strategies for their anti-cancer activity. [ABSTRACT FROM AUTHOR]

The effectiveness of coronavirus disease 2019 (COVID-19) vaccines against the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) strain rapidly wanes over time. Growing evidence from epidemiological studies suggests that influenza vaccination is associated with a reduction in the risk of SARS-CoV-2 infection and COVID-19 severity. However, the underlying mechanisms remain elusive. Here, we investigate the cross-reactive immune responses of influenza vaccination to SARS-CoV-2 spike protein peptides based on in vitro study. Our data indicate enhanced activation-induced-marker (AIM) expression on CD4+ T cells in influenza-vaccination (IV)-treated peripheral blood mononuclear cells (PBMCs) upon stimulation with spike-protein-peptide pools. The fractions of other immune cell subtypes, including CD8+ T cells, monocytes, NK cells, and antigen-presenting cells, were not changed between IV-treated and control PBMCs following ex vivo spike-protein-peptide stimulation. However, the classical antiviral (IFN-γ) and anti-inflammatory (IL-1RA) cytokine responses to spike-protein-peptide stimulation were still enhanced in PBMCs from both IV-immunized adult and aged mice. Decreased expression of proinflammatory IL-1β, IL-12p40, and TNF-α is associated with inhibited levels of histone acetylation in PBMCs from IV-treated mice. Remarkably, prior immunity to SARS-CoV-2 does not result in modification of histone acetylation or hemagglutinin-protein-induced cytokine responses. This response is antibody-independent but can be mediated by manipulating the histone acetylation of PBMCs. These data experimentally support that influenza vaccination could induce modification of histone acetylation in immune cells and reveal the existence of potential cross-reactive immunity to SARS-CoV-2 antigens, which may provide insights for the adjuvant of influenza vaccine to limit COVID-19-related inflammatory responses. [ABSTRACT FROM AUTHOR]

This study highlights the advantages of employing acetylation to enhance the morphology and thermal properties of cellulose nanocrystals (CNCs) derived from maize stalks. Utilizing a green synthesis approach for CNC extraction, this research presents a novel comparison between green extracted CNCs, and their acid hydrolysed, followed by their acetylated counterparts (ACCNCs). This comparison reveals significant improvements in the properties of acetylated CNCs over those produced through conventional acid hydrolysis. The study employs advanced characterization techniques, including Fourier Transform Infrared (FTIR) spectroscopy, X-ray Diffraction (XRD), Scanning Electron Microscopy (SEM), and Thermogravimetric Analysis (TGA), to analyze untreated maize stalk extracted cellulose, green extracted CNCs, and acetylated CNCs. FTIR spectroscopy identifies changes in functional groups, underscoring the efficacy of the extraction and modification processes. XRD analysis demonstrates a beneficial transformation from cellulose I to cellulose II allomorphs post-acetylation, with increased crystallinity index values indicating effective removal of amorphous regions. SEM imaging reveals the preservation of rod-like structures in CNCs, while acetylated CNCs exhibit advantageous morphological changes, such as reduced nanocrystal length and increased branching. TGA results show superior thermal stability in green extracted CNCs and favorable thermal degradation behavior in acetylated CNCs. Overall, this study underscores the potential of acetylation to develop sustainable nanomaterials with tailored properties, offering significant advancements for various applications. Emphasizing the advantages of the prepared ACCNCs and the green synthesis method over traditional acid hydrolysis extraction, this research paves the way for innovative applications in diverse fields. [ABSTRACT FROM AUTHOR]

The goal of this study is to comprehensively evaluate the natural weathering performance of three wood species representing hardwood and softwood modified with the acetylation process. Alder (Alnus glutinosa L.), beech (Fagus sylvatica L.), and radiata pine (Pinus radiata D. Don) were characterised by various techniques to determine the aesthetical, chemical, and physical changes. The overall aesthetic performance of the investigated species was similar, with all showing a change in appearance after 9 months of exposure. However, the multi-sensor approach used for characterisation revealed differences in weathering behaviour related to surface erosion, wettability, and changes in chemical composition between the investigated species. An increase in the surface roughness observed for both hardwoods was associated with the erosion of the wood surface and the leaching of photodegraded chemical components. On the contrary, values of Sa remained relatively constant for acetylated radiata pine. Acetylated pine wood exhibited lower susceptibility to bleaching at the initial stage of the weathering process (3 months) and represented a more constant CIE L* compared to the investigated hardwood species. The contact angle measured with water gradually decreased in the case of acetylated radiata pine for up to six months, then it plateaued with a slight oscillation around 15°. For both hardwood species, the big drop was observed already after three months, followed by rather similar values. The PCA of IR spectra highlighted different mechanisms in the weathering of acetylated softwood and hardwood. The acetylated hardwood samples showed higher thermal stability than acetylated radiata pine. Experimental findings provide a comprehensive understanding of the long-term performance of acetylated wood, which directly influences its practical applications by enhancing design strategies, maintenance planning, product development, market acceptance, and overall sustainability. Performed tests have demonstrated the potential of underutilised hardwood species, enhanced through the acetylation process, to serve as alternative cladding materials to commonly used acetylated radiata pine. [ABSTRACT FROM AUTHOR]

Epigenetic modulation, including histone modification, alters gene expression and controls cell fate. Histone deacetylases (HDACs) are identified as important regulators of dental pulp cell (DPC) mineralisation processes. Currently, there is a paucity of information regarding the nature of histone modification and HDAC expression in the dentine–pulp complex during dentinogenesis. The aim of this study was to investigate post-translational histone modulation and HDAC expression during DPC mineralisation and the expression of Class I/II HDACs during tooth development and in adult teeth. HDAC expression (isoforms −1 to −6) was analysed in mineralising primary rat DPCs using qRT-PCR and Western blot with mass spectrometry being used to analyse post-translational histone modifications. Maxillary molar teeth from postnatal and adult rats were analysed using immunohistochemical (IHC) staining for HDACs (1–6). HDAC-1, -2, and -4 protein expression increased until days 7 and 11, but decreased at days 14 and 21, while other HDAC expression increased continuously for 21 days. The Class II mineralisation-associated HDAC-4 was strongly expressed in postnatal sample odontoblasts and DPCs, but weakly in adult teeth, while other Class II HDACs (-5, -6) were relatively strongly expressed in postnatal DPCs and adult odontoblasts. Among Class I HDACs, HDAC-1 showed high expression in postnatal teeth, notably in ameloblasts and odontoblasts. HDAC-2 and -3 had extremely low expression in the rat dentine–pulp complex. Significant increases in acetylation were noted during DPC mineralisation processes, while trimethylation H3K9 and H3K27 marks decreased, and the HDAC-inhibitor suberoylanilide hydroxamic acid (SAHA) enhanced H3K27me3. These results highlight a dynamic alteration in histone acetylation during mineralisation and indicate the relevance of Class II HDAC expression in tooth development and regenerative processes. [ABSTRACT FROM AUTHOR]

Lysine acetylation of proteins plays a critical regulatory function in plants. A few advances have been made in the study of plant acetylproteome. However, until now, there have been few data on Rhododendron chrysanthum Pall. (R. chrysanthum). We analyzed the molecular mechanisms of photosynthesis and stress resistance in R. chrysanthum under UV−B stress. We measured chlorophyll fluorescence parameters of R. chrysanthum under UV−B stress and performed a multi−omics analysis. Based on the determination of chlorophyll fluorescence parameters, R. chrysanthum Y(NO) (Quantum yield of non−photochemical quenching) increased under UV−B stress, indicating that the plant was damaged and photosynthesis decreased. In the analysis of acetylated proteomics data, acetylated proteins were found to be involved in a variety of biological processes. Notably, acetylated proteins were significantly enriched in the pathways of photosynthesis and carbon fixation, suggesting that lysine acetylation modifications have an important role in these activities. Our findings suggest that R. chrysanthum has decreased photosynthesis and impaired photosystems under UV−B stress, but NPQ shows that plants are resistant to UV−B. Acetylation proteomics revealed that up- or down-regulation of acetylation modification levels alters protein expression. Acetylation modification of key enzymes of the Calvin cycle (Rubisco, GAPDH) regulates protein expression, making Rubisco and GAPDH proteins expressed as significantly different proteins, which in turn affects the carbon fixation capacity of R. chrysanthum. Thus, Rubisco and GAPDH are significantly differentially expressed after acetylation modification, which affects the carbon fixation capacity and thus makes the plant resistant to UV−B stress. Lysine acetylation modification affects biological processes by regulating the expression of key enzymes in photosynthesis and carbon fixation, making plants resistant to UV−B stress. [ABSTRACT FROM AUTHOR]

Cytochrome c (Cytc) is important for both mitochondrial respiration and apoptosis, both of which are altered in cancer cells that switch to Warburg metabolism and manage to evade apoptosis. We earlier reported that lysine 53 (K53) of Cytc is acetylated in prostate cancer. K53 is conserved in mammals that is known to be essential for binding to cytochrome c oxidase and apoptosis protease activating factor-1 (Apaf-1). Here we report the effects of this acetylation on the main functions of cytochrome c by expressing acetylmimetic K53Q in cytochrome c double knockout cells. Other cytochrome c variants analyzed were wild-type, K53R as a control that maintains the positive charge, and K53I, which is present in some non-mammalian species. Intact cells expressing K53Q cytochrome c showed 49% decreased mitochondrial respiration and a concomitant increase in glycolytic activity (Warburg effect). Furthermore, mitochondrial membrane potential was decreased, correlating with notably reduced basal mitochondrial superoxide levels and decreased cell death upon challenge with H2O2 or staurosporine. To test for markers of cancer aggressiveness and invasiveness, cells were grown in 3D spheroid culture. K53Q cytochrome c-expressing cells showed profoundly increased protrusions compared to WT, suggesting increased invasiveness. We propose that K53 acetylation of cytochrome c is an adaptive response that mediates prostate cancer metabolic reprogramming and evasion of apoptosis, which are two hallmarks of cancer, to better promote tumor survival and metastasis. [ABSTRACT FROM AUTHOR]

High-temperature vapour-phase acetylation (HTVPA) is a simultaneous acetylation and heat treatment process for wood modification. This study was the first investigation into the impact of HTVPA treatment on the resistance of wood to biological degradation. In the termite resistance test, untreated wood exhibited a mass loss (MLt) of 20.3%, while HTVPA-modified wood showed a reduced MLt of 6.6–3.2%, which decreased with an increase in weight percent gain (WPG), and the termite mortality reached 95–100%. Furthermore, after a 12-week decay resistance test against brown-rot fungi (Laetiporus sulfureus and Fomitopsis pinicola), untreated wood exhibited mass loss (MLd) values of 39.6% and 54.5%, respectively, while HTVPA-modified wood exhibited MLd values of 0.2–0.9% and −0.2–0.3%, respectively, with no significant influence from WPG. Similar results were observed in decay resistance tests against white-rot fungi (Lenzites betulina and Trametes versicolor). The results of this study demonstrated that HTVPA treatment not only effectively enhanced the decay resistance of wood but also offered superior enhancement relative to separate heat treatment or acetylation processes. In addition, all the HTVPA-modified wood specimens prepared in this study met the requirements of the CNS 6717 wood preservative standard, with an MLd of less than 3% for decay-resistant materials. [ABSTRACT FROM AUTHOR]

Post-translational modifications (PTMs) are essential for regulating protein functions, influencing various fundamental processes in eukaryotes. These include, but are not limited to, cell signaling, protein trafficking, the epigenetic control of gene expression, and control of the cell cycle, as well as cell proliferation, differentiation, and interactions between cells. In this review, we discuss protein PTMs that play a key role in the malaria parasite biology and its pathogenesis. Phosphorylation, acetylation, methylation, lipidation and lipoxidation, glycosylation, ubiquitination and sumoylation, nitrosylation and glutathionylation, all of which occur in malarial parasites, are reviewed. We provide information regarding the biological significance of these modifications along all phases of the complex life cycle of Plasmodium spp. Importantly, not only the parasite, but also the host and vector protein PTMs are often crucial for parasite growth and development. In addition to metabolic regulations, protein PTMs can result in epitopes that are able to elicit both innate and adaptive immune responses of the host or vector. We discuss some existing and prospective results from antimalarial drug discovery trials that target various PTM-related processes in the parasite or host. [ABSTRACT FROM AUTHOR]

Quercetin, a flavonoid polyphenol found in many plants, has garnered significant attention due to its potential cancer chemoprevention. Our previous studies have shown that acetyl modification of the hydroxyl group of quercetin altered its antitumor effects in HepG2 cells. However, the antitumor effect in other cancer cells with different gene mutants remains unknown. In this study, we investigated the antitumor effect of quercetin and its methylated derivative 3,3′,4′,7-O-tetramethylquercetin (4Me-Q) and acetylated derivative 3,3′,4′,7-O-tetraacetylquercetin (4Ac-Q) on two human breast cancer cells, MCF-7 (wt-p53, caspase-3-ve) and MDA-MB-231 (mt-p53, caspase-3+ve). The results demonstrated that 4Ac-Q exhibited significant cell proliferation inhibition and apoptosis induction in both MCF-7 and MDA-MB-231 cells. Conversely, methylation of quercetin was found to lose the activity. The human apoptosis antibody array revealed that 4Ac-Q might induce apoptosis in MCF-7 cells via a p53-dependent pathway, while in MDA-MB-231 cells, it was induced via a caspase-3-dependent pathway. Furthermore, an evaluation using a superoxide inhibitor, MnTBAP, revealed 4Ac-Q-induced apoptosis in MCF-7 cells in a superoxide-independent manner. These findings provide valuable insights into the potential of acetylated quercetin as a new approach in cancer chemoprevention and offer new avenues for health product development. [ABSTRACT FROM AUTHOR]

The aim of the presented research was to determine the suitability of both non-modified and modified buckwheat husk (BH) as a filler for urea–formaldehyde adhesive in plywood production. The effect of two modification methods, acetylation and silanization, was investigated. Infrared spectroscopy outcomes confirmed that both acetylation and silanization of the filler had occurred. Based on the results, it was found that the introduction of BH had a significant effect on both the adhesive properties and the characteristics of the manufactured plywood. The application of non-modified husks led to a reduction in viscosity and an extension of the gelation time, and the produced plywood boards were characterized by reduced bonding quality and increased delamination. Modification of the husk surface by acetylation and silanization with 3-aminopropyltriethoxysilane contributed to the noticeable improvement in the resin properties. On the other hand, the improvement in plywood properties, consisting of the increase in bonding quality and reduced delamination, was observed only in the case of the silanized husk. Furthermore, the use of non-modified and acetylated husk did not significantly influence the formaldehyde emission. The reduction in the investigated emission of formaldehyde was observed only in the case of variants containing 15 and 20% of silanized buckwheat husk. [ABSTRACT FROM AUTHOR]

Simple Summary: A significant number of prostate cancers (PC) recur in patients despite treatment with chemotherapy or radiotherapy. While HOXB13 contributes to resistance to anti-androgen treatment, its role in radio resistance is unknown. Herein, we show that HOXB13 assembles at DNA damage sites and colocalizes with γH2AX at double strand breaks despite Androgen Receptor antagonism. Functionally, ablation of HOXB13 sensitizes PC cells to either radiotherapy or anti-androgen Enzalutamide as well as combination therapies. Resistance to these agents is mediated by acetylation of HOXB13 at lysine 13, which acts as an interaction module for the Switch deficient Sucrose Nonfermenting (SWI/SNF) chromatin remodeling complex. K13-acetylated HOXB13 is required for effective DNA replication following DNA damage and for the formation of nuclear puncta. Our results reveal a hitherto unknown but critical role for HOXB13 in ensuring genomic integrity in PC. Advanced localized prostate cancers (PC) recur despite chemotherapy, radiotherapy and/or androgen deprivation therapy. We recently reported HOXB13 lysine (K)13 acetylation as a gain-of-function modification that regulates interaction with the SWI/SNF chromatin remodeling complex and is critical for anti-androgen resistance. However, whether acetylated HOXB13 promotes PC cell survival following treatment with genotoxic agents is not known. Herein, we show that K13-acetylated HOXB13 is induced rapidly in PC cells in response to DNA damage induced by irradiation (IR). It colocalizes with the histone variant γH2AX at sites of double strand breaks (DSBs). Treatment of PCs with the Androgen Receptor (AR) antagonist Enzalutamide (ENZ) did not suppress DNA-damage-induced HOXB13 acetylation. In contrast, HOXB13 depletion or loss of acetylation overcame resistance of PC cells to ENZ and synergized with IR. HOXB13K13A mutants show diminished replication fork progression, impaired G2/M arrest with significant cell death following DNA damage. Mechanistically, we found that amino terminus regulates HOXB13 nuclear puncta formation that is essential for proper DNA damage response. Therefore, targeting HOXB13 acetylation with CBP/p300 inhibitors in combination with DNA damaging therapy may be an effective strategy to overcome anti-androgen resistance of PCs. [ABSTRACT FROM AUTHOR]

The chromatin organization and its dynamic remodeling determine its accessibility and sensitivity to DNA damage oxidative stress, the main source of endogenous DNA damage. We studied the role of the VRK1 chromatin kinase in the response to oxidative stress. which alters the nuclear pattern of histone epigenetic modifications and phosphoproteome pathways. The early effect of oxidative stress on chromatin was studied by determining the levels of 8-oxoG lesions and the alteration of the epigenetic modification of histones. Oxidative stress caused an accumulation of 8-oxoG DNA lesions that were increased by VRK1 depletion, causing a significant accumulation of DNA strand breaks detected by labeling free 3′-DNA ends. In addition, oxidative stress altered the pattern of chromatin epigenetic marks and the nuclear phosphoproteome pathways that were impaired by VRK1 depletion. Oxidative stress induced the acetylation of H4K16ac and H3K9 and the loss of H3K4me3. The depletion of VRK1 altered all these modifications induced by oxidative stress and resulted in losses of H4K16ac and H3K9ac and increases in the H3K9me3 and H3K4me3 levels. All these changes were induced by the oxidative stress in the epigenetic pattern of histones and impaired by VRK1 depletion, indicating that VRK1 plays a major role in the functional reorganization of chromatin in the response to oxidative stress. The analysis of the nuclear phosphoproteome in response to oxidative stress detected an enrichment of the phosphorylated proteins associated with the chromosome organization and chromatin remodeling pathways, which were significantly decreased by VRK1 depletion. VRK1 depletion alters the histone epigenetic pattern and nuclear phosphoproteome pathways in response to oxidative stress. The enzymes performing post-translational epigenetic modifications are potential targets in synthetic lethality strategies for cancer therapies. [ABSTRACT FROM AUTHOR]

An enzyme-promoted addition of nitromethane to the appropriate phosphorylated imine (aza-Henry reaction) intended to be used in the synthesis of the title phosphoemeriamine, a phospha-analog of emeriamine (aminocarnitine), failed due to the tautomerization of the imine to the corresponding enamine. Nevertheless, both enantiomers of phosphoemeriamine were synthesized in high yield and enantiomeric purity using another chemoenzymatic approach, starting with a crucial step involving a CAL-B-mediated acetylation of the appropriate racemic precursor—diethyl 2-amino-3-dimethylaminopropylphosphonate—under kinetic resolution conditions. The enzymatic reaction was very efficient and provided each enantiomeric product in acceptable yield and with enantiomeric excess of 91 and 92%. The following appropriate chemical transformations led to the desired enantiomers of phosphoemeriamine in the form of phosphoemeriamine sesquichloride with enantiomeric excess up to 90%. [ABSTRACT FROM AUTHOR]

The trichothecene biosynthesis in Fusarium begins with the cyclization of farnesyl pyrophosphate to trichodiene, followed by subsequent oxygenation to isotrichotriol. This initial bicyclic intermediate is further cyclized to isotrichodermol (ITDmol), a tricyclic precursor with a toxic trichothecene skeleton. Although the first cyclization and subsequent oxygenation are catalyzed by enzymes encoded by Tri5 and Tri4, the second cyclization occurs non-enzymatically. Following ITDmol formation, the enzymes encoded by Tri101, Tri11, Tri3, and Tri1 catalyze 3-O-acetylation, 15-hydroxylation, 15-O-acetylation, and A-ring oxygenation, respectively. In this study, we extensively analyzed the metabolites of the corresponding pathway-blocked mutants of Fusarium graminearum. The disruption of these Tri genes, except Tri3, led to the accumulation of tricyclic trichothecenes as the main products: ITDmol due to Tri101 disruption; a mixture of isotrichodermin (ITD), 7-hydroxyisotrichodermin (7-HIT), and 8-hydroxyisotrichodermin (8-HIT) due to Tri11 disruption; and a mixture of calonectrin and 3-deacetylcalonectrin due to Tri1 disruption. However, the ΔFgtri3 mutant accumulated substantial amounts of bicyclic metabolites, isotrichotriol and trichotriol, in addition to tricyclic 15-deacetylcalonectrin (15-deCAL). The ΔFgtri5ΔFgtri3 double gene disruptant transformed ITD into 7-HIT, 8-HIT, and 15-deCAL. The deletion of FgTri3 and overexpression of Tri6 and Tri10 trichothecene regulatory genes did not result in the accumulation of 15-deCAL in the transgenic strain. Thus, the absence of Tri3p and/or the presence of a small amount of 15-deCAL adversely affected the non-enzymatic second cyclization and C-15 hydroxylation steps. [ABSTRACT FROM AUTHOR]

This study aims to enhance value addition to agricultural byproducts to produce composites by the solution casting technique. It is well known that PLA is moisture-sensitive and deforms at high temperatures, which limits its use in some applications. When blending with plant-based fibers, the weak point is the poor filler–matrix interface. For this reason, surface modification was carried out on hemp and flax fibers via acetylation and alkaline treatments. The fibers were milled to obtain two particle sizes of <75 μm and 149–210 μm and were blended with poly (lactic) acid at different loadings (0, 2.5%, 5%, 10%, 20%, and 30%) to form a composite film The films were characterized for their spectroscopy, physical, and mechanical properties. All the film specimens showed C–O/O–H groups and the π–π interaction in untreated flax fillers showed lignin phenolic rings in the films. It was noticed that the maximum degradation temperature occurred at 362.5 °C. The highest WVPs for untreated, alkali-treated, and acetylation-treated composites were 20 × 10−7 g·m/m2 Pa·s (PLA/hemp30), 7.0 × 10−7 g·m/m2 Pa·s (PLA/hemp30), and 22 × 10−7 g·m/m2 Pa·s (PLA/hemp30), respectively. Increasing the filler content caused an increase in the color difference of the composite film compared with that of the neat PLA. Alkali-treated PLA/flax composites showed significant improvement in their tensile strength, elongation at break, and Young's modulus at a 2.5 or 5% filler loading. An increase in the filler loadings caused a significant increase in the moisture absorbed, whereas the water contact angle decreased with an increasing filler concentration. Flax- and hemp-induced PLA-based composite films with 5 wt.% loadings showed a more stable compromise in all the examined properties and are expected to provide unique industrial applications with satisfactory performance. [ABSTRACT FROM AUTHOR]

Pseudomonas syringae pv. tomato DC3000 (Pst DC3000) is able to infect many economically important crops and thus causes substantial losses in the global agricultural economy. Pst DC3000 can be divided into virulent lines and avirulent lines. For instance, the pathogen effector avrRPM1 of avirulent line Pst-avrRpm1 (Pst DC3000 avrRpm1) can be recognized and detoxified by the plant. To further compare the pathogenicity mechanisms of virulent and avirulent Pst DC3000, a comprehensive analysis of the acetylome and succinylome in Arabidopsis thaliana was conducted following infection with virulent line Pst DC3000 and avirulent line Pst-avrRpm1. In this study, a total of 1625 acetylated proteins encompassing 3423 distinct acetylation sites were successfully identified. Additionally, 229 succinylated proteins with 527 unique succinylation sites were detected. A comparison of these modification profiles between plants infected with Pst DC3000 and Pst-avrRpm1 revealed significant differences. Specifically, modification sites demonstrated inconsistencies, with a variance of up to 10% compared to the control group. Moreover, lysine acetylation (Kac) and lysine succinylation (Ksu) displayed distinct preferences in their modification patterns. Lysine acetylation is observed to exhibit a tendency towards up-regulation in Arabidopsis infected with Pst-avrRpm1. Conversely, the disparity in the number of Ksu up-regulated and down-regulated sites was not as pronounced. Motif enrichment analysis disclosed that acetylation modification sequences are relatively conserved, and regions rich in polar acidic/basic and non-polar hydrophobic amino acids are hotspots for acetylation modifications. Functional enrichment analysis indicated that the differentially modified proteins are primarily enriched in the photosynthesis pathway, particularly in relation to light-capturing proteins. In conclusion, this study provides an insightful profile of the lysine acetylome and succinylome in A. thaliana infected with virulent and avirulent lines of Pst DC3000. Our findings revealed the potential impact of these post-translational modifications (PTMs) on the physiological functions of the host plant during pathogen infection. This study offers valuable insights into the complex interactions between plant pathogens and their hosts, laying the groundwork for future research on disease resistance and pathogenesis mechanisms. [ABSTRACT FROM AUTHOR]

Sugar beet flakes, a by-product of the sugar industry, were used as a source for pectin extraction that was performed using conventional citric acid extraction (CE) and two non-conventional extraction techniques—microwave-assisted extraction (MAE) and pulsed ultrasound-assisted extraction (PUAE). The influence of extraction conditions was studied for each technique based on pectin yield and galacturonic acid content, and spectroscopic, chromatographic and colorimetric methods were used for pectin characterization. Better results for pectin yield were achieved through CE (20.80%), while higher galacturonic acid content was measured in pectin extracted using PUAE (88.53 g/100 g). Pectin extracted using PUAE also presented a higher degree of methylation and acetylation. A significant increase in the molecular weight of pectin was observed for the PUAE process (7.40 × 105 g/mol) by comparison with conventional extraction (1.18 × 105 g/mol). Hydrogels and cryogels prepared with pectin from sugar beet flakes also showed differences in physicochemical parameters determined by the method of pectin extraction. Hydrogels had higher bulk density values irrespective of the pectin extraction method, and overall lower values of the textural parameters. Cryogels prepared with pectin from CE showed higher values of the textural parameters of hardness, adhesiveness, cohesiveness, gumminess and chewiness, while gels obtained with pectin from MAE and PUAE had higher thermal stability. The results of this study prove that sugar beet flakes can be considered a potential source for pectin production, and the extracted pectin is suitable for obtaining hydrogels and cryogels with physicochemical parameters comparable to the commercial citrus and apple pectin available on the market. [ABSTRACT FROM AUTHOR]

Background: Obesity, a chronic metabolic disorder, is related to cardiovascular diseases, diabetes, cancer, and reproductive disorders. The relationship between obesity and male infertility is now well recognized, but the mechanisms involved are unclear. We aimed to observe the effect of obesity on spermatogenesis and to investigate the role of histone ubiquitination and acetylation modifications in obesity-induced spermatogenesis disorders. Methods: Thirty male C57BL/6J mice were randomly divided into two groups. The control group was fed with a general maintenance diet (12% fat), while a high-fat diet (HFD) group was fed with 40% fat for 10 weeks; then, they were mated with normal females. The fertility of male mice was calculated, testicular and sperm morphology were observed, and the expression levels of key genes and the levels of histone acetylation and ubiquitination modification during spermatogenesis were detected. Results: The number of sperm was decreased, as well as the sperm motility, while the number of sperm with malformations was increased. In the testes, the mRNA and protein expression levels of gonadotropin-regulated testicular RNA helicase (GRTH/DDX25), chromosome region maintenance-1 protein (CRM1), high-mobility group B2 (HMGB2), phosphoglycerate kinase 2 (PGK2), and testicular angiotensin-converting enzyme (tACE) were decreased. Furthermore, obesity led to a decrease in ubiquitinated H2A (ubH2A) and reduced levels of histone H3 acetylation K18 (H3AcK18) and histone H4 acetylation K5, K8, K12, and K16 (H4tetraAck), which disrupted protamine 1 (Prm1) deposition in testis tissue. Conclusion: These results suggest that low levels of histone ubiquitination and acetylation are linked with obesity-induced disorders during spermatogenesis, contributing to a better understanding of obesity-induced damage to male reproduction. [ABSTRACT FROM AUTHOR]

Cytochrome c (Cytc) has both life-sustaining and cellular death-related functions, depending on subcellular localization. Within mitochondria, Cytc acts as a single electron carrier as part of the electron transport chain (ETC). When released into the cytosol after cellular insult, Cytc triggers the assembly of the apoptosome, committing the cell to intrinsic apoptosis. Due to these dual natures, Cytc requires strong regulation by the cell, including post-translational modifications, such as phosphorylation and acetylation. Six phosphorylation sites and three acetylation sites have been detected on Cytc in vivo. Phosphorylations at T28, S47, Y48, T49, T58, and Y97 tend to be present under basal conditions in a tissue-specific manner. In contrast, the acetylations at K8, K39, and K53 tend to be present in specific pathophysiological conditions. All of the phosphorylation sites and two of the three acetylation sites partially inhibit respiration, which we propose serves to maintain an optimal, intermediate mitochondrial membrane potential (ΔΨm) to minimize reactive oxygen species (ROS) production. Cytc phosphorylations are lost during ischemia, which drives ETC hyperactivity and ΔΨm hyperpolarization, resulting in exponential ROS production thus causing reperfusion injury following ischemia. One of the acetylation sites, K39, shows a unique behavior in that it is gained during ischemia, stimulating respiration while blocking apoptosis, demonstrating that skeletal muscle, which is particularly resilient to ischemia-reperfusion injury compared to other organs, possesses a different metabolic strategy to handle ischemic stress. The regulation of Cytc by these post-translational modifications underscores the importance of Cytc for the ETC, ΔΨm, ROS production, apoptosis, and the cell as a whole. [ABSTRACT FROM AUTHOR]

Histone deacetylase 6 (HDAC6) plays a crucial role in the acetylation of non-histone proteins and is notably implicated in angiogenesis, though its underlying mechanisms were previously not fully understood. This study conducted transcriptomic and proteomic analyses on vascular endothelial cells with HDAC6 knockdown, identifying endoglin (ENG) as a key downstream protein regulated by HDAC6. This protein is vital for maintaining vascular integrity and plays a complex role in angiogenesis, particularly in its interaction with bone morphogenetic protein 9 (BMP9). In experiments using human umbilical vein endothelial cells (HUVECs), the pro-angiogenic effects of BMP9 were observed, which diminished following the knockdown of HDAC6 and ENG. Western blot analysis revealed that BMP9 treatment increased SMAD1/5/9 phosphorylation, a process hindered by HDAC6 knockdown, correlating with reduced ENG expression. Mechanistically, our study indicates that HDAC6 modulates ENG transcription by influencing promoter activity, leading to increased acetylation of transcription factor SP1 and consequently altering its transcriptional activity. Additionally, the study delves into the structural role of HDAC6, particularly its CD2 domain, in regulating SP1 acetylation and subsequently ENG expression. In conclusion, the present study underscores the critical function of HDAC6 in modulating SP1 acetylation and ENG expression, thereby significantly affecting BMP9-mediated angiogenesis. This finding highlights the potential of HDAC6 as a therapeutic target in angiogenesis-related processes. [ABSTRACT FROM AUTHOR]

Simple Summary: This study provides insights into the regulation of Sox2, specifically focusing on the acetylation of Sox2 K75 residue and O-GlcNAcylation of S246 residue. These post-translational modifications (PTM) are orchestrated through interactions with ACSS2/p300 for acetylation and miR29a/HDAC4 for deacetylation, respectively. These findings shed light on the significance of these PTMs in the development and progression of colorectal cancer. Aberrant expression of the pluripotency-associated transcription factor Sox2 is associated with poor prognosis in colorectal cancer (CRC). We investigated the regulatory roles of major post-translational modifications in Sox2 using two CRC cell lines, SW480 and SW620, derived from the same patient but with low and high Sox2 expression, respectively. Acetylation of K75 in the Sox2 nuclear export signal was relatively increased in SW480 cells and promotes Sox2 nucleocytoplasmic shuttling and proteasomal degradation of Sox2. LC-MS-based proteomics analysis identified HDAC4 and p300 as binding partners involved in the acetylation-mediated control of Sox2 expression in the nucleus. Sox2 K75 acetylation is mediated by the acetyltransferase activity of CBP/p300 and ACSS3. In SW620 cells, HDAC4 deacetylates K75 and is regulated by miR29a. O-GlcNAcylation on S246, in addition to K75 acetylation, also regulates Sox2 stability. These findings provide insights into the regulation of Sox2 through multiple post-translational modifications and pathways in CRC. [ABSTRACT FROM AUTHOR]

Post-translational modifications (PTMs) are crucial mechanisms that underlie the intricacies of biological systems and disease mechanisms. This review focuses on the latest advancements in the design of heterobifunctional small molecules that hijack PTM machineries for target-specific modifications in living systems. A key innovation in this field is the development of proteolysis-targeting chimeras (PROTACs), which promote the ubiquitination of target proteins for proteasomal degradation. The past decade has seen several adaptations of the PROTAC concept to facilitate targeted (de)phosphorylation and acetylation. Protein fusion tags have been particularly vital in these proof-of-concept studies, aiding in the investigation of the functional roles of post-translationally modified proteins linked to diseases. This overview delves into protein-tagging strategies that enable the targeted modulation of ubiquitination, phosphorylation, and acetylation, emphasizing the synergies and challenges of integrating heterobifunctional molecules with protein tags in PTM research. Despite significant progress, many PTMs remain to be explored, and protein tag-assisted PTM-inducing chimeras will continue to play an important role in understanding the fundamental roles of protein PTMs and in exploring the therapeutic potential of manipulating protein modifications, particularly for targets not yet addressed by existing drugs. [ABSTRACT FROM AUTHOR]

RhoA-regulated gene transcription by serum response factor (SRF) and its transcriptional cofactor myocardin-related transcription factors (MRTFs) signaling pathway has emerged as a promising therapeutic target for pharmacological intervention in multiple diseases. Altered mitochondrial metabolism is one of the major hallmarks of cancer, therefore, this upregulation is a vulnerability that can be targeted with Rho/MRTF/SRF inhibitors. Recent advances identified a novel series of oxadiazole-thioether compounds that disrupt the SRF transcription, however, the direct molecular target of these compounds is unclear. Herein, we demonstrate the Rho/MRTF/SRF inhibition mechanism of CCG-203971 and CCG-232601 in normal cell lines of human lung fibroblasts and mouse myoblasts. Further studies investigated the role of these molecules in targeting mitochondrial function. We have shown that these molecules hyperacetylate histone H4K12 and H4K16 and regulate the genes involved in mitochondrial function and dynamics. These small molecule inhibitors regulate mitochondrial function as a compensatory mechanism by repressing oxidative phosphorylation and increasing glycolysis. Our data suggest that these CCG molecules are effective in inhibiting all the complexes of mitochondrial electron transport chains and further inducing oxidative stress. Therefore, our present findings highlight the therapeutic potential of CCG-203971 and CCG-232601, which may prove to be a promising approach to target aberrant bioenergetics. [ABSTRACT FROM AUTHOR]

To improve the application potential of pomelo peel insoluble dietary fiber (PIDF) in emulsion systems, acetylation (PIDF-A), cellulase hydrolysis (PIDF-E), and wet ball milling (PIDF-M) were investigated in this paper as methods to change the emulsification properties of PIDF. The impact of the methods on PIDF composition, structure, and physicochemical properties was also assessed. The results demonstrated that both acetylation modification and cellulase hydrolysis could significantly improve the emulsification properties of PIDF. The emulsions stabilized with PIDF-A and PIDF-E could be stably stored at 25 °C for 30 d without phase separation at particle concentrations above 0.8% (w/v) and had higher storage stability: The D4,3 increments of PIDF-A- and PIDF-E-stabilized emulsions were 0.98 μm and 0.49 μm, respectively, at particle concentrations of 1.2% (w/v), while the storage stability of PIDF-M-stabilized emulsion (5.29 μm) significantly decreased compared with that of PIDF (4.00 μm). Moreover, PIDF-A showed the highest water retention capacity (21.84 g/g), water swelling capacity (15.40 mL/g), oil retention capacity (4.67 g/g), and zeta potential absolute (29.0 mV) among the PIDFs. In conclusion, acetylation modification was a promising method to improve the emulsifying properties of insoluble polysaccharides. [ABSTRACT FROM AUTHOR]

Chitosan-based materials have broad applications, from biotechnology to pharmaceutics. Recent experiments showed that the degree and pattern of acetylation along the chitosan chain modulate its biological and physicochemical properties; however, the molecular mechanism remains unknown. Here, we report, to the best of our knowledge, the first de novo all-atom molecular dynamics (MD) simulations to investigate chitosan's self-assembly process at different degrees and patterns of acetylation. Simulations revealed that 10 mer chitosan chains with 50% acetylation in either block or alternating patterns associate to form ordered nanofibrils comprised of mainly antiparallel chains in agreement with the fiber diffraction data of deacetylated chitosan. Surprisingly, regardless of the acetylation pattern, the same intermolecular hydrogen bonds mediate fibril sheet formation while water-mediated interactions stabilize sheet–sheet stacking. Moreover, acetylated units are involved in forming strong intermolecular hydrogen bonds (NH–O6 and O6H–O7), which offers an explanation for the experimental observation that increased acetylation lowers chitosan's solubility. Taken together, the present study provides atomic-level understanding the role of acetylation plays in modulating chitosan's physiochemical properties, contributing to the rational design of chitosan-based materials with the ability to tune by its degree and pattern of acetylation. Additionally, we disseminate the improved molecular mechanics parameters that can be applied in MD studies to further understand chitosan-based materials. [ABSTRACT FROM AUTHOR]

Sirtuins (SIRTs) are stress-responsive proteins that regulate several post-translational modifications, partly by acetylation, deacetylation, and affecting DNA methylation. As a result, they significantly regulate several cellular processes. In essence, they prolong lifespan and control the occurrence of spontaneous tumor growth. Members of the SIRT family have the ability to govern embryonic, hematopoietic, and other adult stem cells in certain tissues and cell types in distinct ways. Likewise, they can have both pro-tumor and anti-tumor effects on cancer stem cells, contingent upon the specific tissue from which they originate. The impact of autophagy on cancer stem cells, which varies depending on the specific circumstances, is a very intricate phenomenon that has significant significance for clinical and therapeutic purposes. SIRTs exert an impact on the autophagy process, whereas autophagy reciprocally affects the activity of certain SIRTs. The mechanism behind this connection in cancer stem cells remains poorly understood. This review presents the latest findings that position SIRTs at the point where cancer cells and autophagy interact. Our objective is to highlight the various roles of distinct SIRTs in cancer stem cell-related functions through autophagy. This would demonstrate their significance in the genesis and recurrence of cancer and offer a more precise understanding of their treatment possibilities in relation to autophagy. [ABSTRACT FROM AUTHOR]

This paper presents an experimental study where the mechanical behaviour of single-dowel timber connections made of acetylated Scots pine is compared with the behaviour of connections made from untreated Scots pine. The main aim was to evaluate the influence of the acetylation on the connection brittleness and also to compare the experimental results to the design provisions of the current European structural timber code, Eurocode 5 (EC5). The experiments included embedment tests and tests with connections loaded parallel and perpendicular to the grain, and, for the latter tests, applying different end and edge distances. The acetylated wood showed a 2% increase in density and a 31% increase in embedment strength compared to the untreated wood. For tests on connections loaded parallel to the grain, all specimens made from acetylated wood failed in a brittle manner, while the connections made from untreated wood and complying with minimum end distance of the EC5 design provisions failed due to embedment failure followed by splitting involving cracking along the grain. The connections made of acetylated wood showed a 13–15% higher capacity than the corresponding specimens made from untreated wood. Thus, to fully utilize the potential of the increased embedment strength parallel to the grain, it is concluded that reinforcement of the joint, e.g., by self-tapping screws or externally applied sheet reinforcement would be necessary if the minimum end distances of EC5 are applied. The current design provisions for loading perpendicular to the grain overestimated the capacities severely with predicted characteristic values being 20–50% higher than mean values from tests for the recommended minimum edge distances. Finally, it was found that the splitting capacity in loading perpendicular to the grain was 10–18% lower for the specimens made from acetylated wood compared to the untreated wood. [ABSTRACT FROM AUTHOR]

Numerous studies indicate that reversible Nε-lysine acetylation in bacteria may play a key role in the regulation of metabolic processes, transcription and translation, biofilm formation, virulence, and drug resistance. Using appropriate mutant strains deficient in non-enzymatic acetylation and enzymatic acetylation or deacetylation pathways, we investigated the influence of protein acetylation on cell viability, protein aggregation, and persister formation in Escherichia coli. Lysine acetylation was found to increase protein aggregation and cell viability under the late stationary phase. Moreover, increased lysine acetylation stimulated the formation of persisters. These results suggest that acetylation-dependent aggregation may improve the survival of bacteria under adverse conditions (such as the late stationary phase) and during antibiotic treatment. Further experiments revealed that acetylation-favorable conditions may increase persister formation in Klebsiella pneumoniae clinical isolate. However, the exact mechanisms underlying the relationship between acetylation and persistence in this pathogen remain to be elucidated. [ABSTRACT FROM AUTHOR]

Transketolase (TKT) is an essential thiamine diphosphate (ThDP)-dependent enzyme of the non-oxidative branch of the pentose phosphate pathway, with the glucose-6P flux through the pathway regulated in various medically important conditions. Here, we characterize the brain TKT regulation by acylation in rats with perturbed thiamine-dependent metabolism, known to occur in neurodegenerative diseases. The perturbations are modeled by the administration of oxythiamine inhibiting ThDP-dependent enzymes in vivo or by reduced thiamine availability in the presence of metformin and amprolium, inhibiting intracellular thiamine transporters. Compared to control rats, chronic administration of oxythiamine does not significantly change the modification level of the two detected TKT acetylation sites (K6 and K102) but doubles malonylation of TKT K499, concomitantly decreasing 1.7-fold the level of demalonylase sirtuin 5. The inhibitors of thiamine transporters do not change average levels of TKT acylation or sirtuin 5. TKT structures indicate that the acylated residues are distant from the active sites. The acylations-perturbed electrostatic interactions may be involved in conformational shifts and/or the formation of TKT complexes with other proteins or nucleic acids. Acetylation of K102 may affect the active site entrance/exit and subunit interactions. Correlation analysis reveals that the action of oxythiamine is characterized by significant negative correlations of K499 malonylation or K6 acetylation with TKT activity, not observed upon the action of the inhibitors of thiamine transport. However, the transport inhibitors induce significant negative correlations between the TKT activity and K102 acetylation or TKT expression, absent in the oxythiamine group. Thus, perturbations in the ThDP-dependent catalysis or thiamine transport manifest in the insult-specific patterns of the brain TKT malonylation and acetylations. [ABSTRACT FROM AUTHOR]

Androgen receptor (AR) transcriptional activity significantly influences prostate cancer (PCa) progression. In addition to ligand stimulation, AR transcriptional activity is also influenced by a variety of post-translational modifications (PTMs). A number of oncogenes and tumor suppressors have been observed leveraging PTMs to influence AR activity. Subjectively targeting these post-translational modifiers based on their impact on PCa cell proliferation is a rapidly developing area of research. This review elucidates the modifiers, contextualizes the effects of these PTMs on AR activity, and connects these cellular interactions to the progression of PCa. [ABSTRACT FROM AUTHOR]

Influenza A virus (IAV) is one of the most circulated human pathogens, and influenza disease, commonly known as the flu, remains one of the most recurring and prevalent infectious human diseases globally. IAV continues to challenge existing vaccines and antiviral drugs via its ability to evolve constantly. It is critical to identify the molecular determinants of IAV pathogenesis to understand the basis of flu severity in different populations and design improved antiviral strategies. In recent years, acetylation has been identified as one of the determinants of IAV pathogenesis. Acetylation was originally discovered as an epigenetic protein modification of histones. But, it is now known to be one of the ubiquitous protein modifications of both histones and non-histone proteins and a determinant of proteome complexity. Since our first observation in 2007, significant progress has been made in understanding the role of acetylation during IAV infection. Now, it is becoming clearer that acetylation plays a pro-IAV function via at least three mechanisms: (1) by reducing the host's sensing of IAV infection, (2) by dampening the host's innate antiviral response against IAV, and (3) by aiding the stability and function of viral and host proteins during IAV infection. In turn, IAV antagonizes the host deacetylases, which erase acetylation, to facilitate its replication. This review provides an overview of the research progress made on this subject so far and outlines research prospects for the significance of IAV-acetylation interplay. [ABSTRACT FROM AUTHOR]

O2 is essential for the life of eukaryotic cells. The ability to sense oxygen availability and initiate a response to adapt the cell to changes in O2 levels is a fundamental achievement of evolution. The key switch for adaptation consists of the transcription factors HIF1A, HIF2A and HIF3A. Their levels are tightly controlled by O2 through the involvement of the oxygen-dependent prolyl hydroxylase domain-containing enzymes (PHDs/EGNLs), the von Hippel–Lindau tumour suppressor protein (pVHL) and the ubiquitin–proteasome system. Furthermore, HIF1A and HIF2A are also under the control of additional post-translational modifications (PTMs) that positively or negatively regulate the activities of these transcription factors. This review focuses mainly on two PTMs of HIF1A and HIF2A: phosphorylation and acetylation. [ABSTRACT FROM AUTHOR]

In this research, acetylation was applied under industrial conditions to improve the properties of Turkey oak and Pannonia poplar wood. Both species are potential "climate winners" in Hungary, yet they are currently underused due their low durability and poor dimensional stability. The acetylation modification process may be a suitable method to improve their properties. In order to verify the effectiveness of the process, comparative chemical analyses (cellulose, hemicelluloses, lignin, extractives, ash, buffering capacity, and pH) of the untreated and acetylated heartwood and sapwood were carried out for both species for the first time. Diffuse reflectance infrared Fourier transform (DRIFT) spectroscopy was also used to support the evaluation of the chemical analyses. The weight percent gain was 11.54% for poplar and 0.94% for Turkey oak, indicating poor treatment efficiency for the latter. The cellulose, hemicelluloses, and lignin contents changed significantly in poplar, with the highest change (+81%) induced by acetylating the hemicelluloses. Only the alpha-cellulose content decreased significantly in Turkey oak, presumably due to the degradation of the non-crystalline part of the cellulose. Acetylation may improve the resistance of Pannonia poplar against moisture, weather, decay, and wood-boring insects, but the process parameters need to be optimized in order to prevent degradation and discoloration in poplar. Turkey oak was found to be less suitable for acetylation due to its low permeability and tendency to crack. [ABSTRACT FROM AUTHOR]

Biodegradable polymers have recently become attractive and have been increasingly used as matrix materials to replace fossil plastics due to concerns about the environmental issue. However, their application areas are limited due to their high costs and natural properties. In this study, we fabricated ecofriendly and economical polybutylene adipate terephthalate (PBAT) composites loaded with various concentrations of wood flour (WF) to investigate the effects on the PBAT and WF interfaces as well as the physical properties of the WF/PBAT biocomposites. Then, WF was acetylated with acetic anhydride, and the effect of WF acetylation on the mechanical and thermal properties of the biocomposites were investigated. The results showed that the tensile strength, tensile modulus, flexural strength and flexural modulus increased with WF loading in the composites, and acetylation could not only further increase these properties, but also increase the impact strength and elongation at break. The incorporation of WF would weaken the thermal stability of PBAT, but the thermal stability of the biocomposite could be improved after WF acetylation. The cold crystallization temperature and hydrophobicity of the WF/PBAT samples would be increased with the increasing load of the WF, while the melting enthalpy and the crystallinity of the samples reduced gradually. A morphological analysis of the modified composites revealed that the matrix exhibited greater interfacial interactions with the WF compared to the WF/PBAT. Considering the much lower cost of WF compared to PBAT, the improved properties of WF/PBAT biocomposites will make it economically competitive with other commercial polymers, and these biocomposites should have much wider application areas. [ABSTRACT FROM AUTHOR]