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Herein, a selective protocol for the complete removal of acetyl protecting groups from carbohydrate derivatives based on copper nanoparticles supported on activated carbon is presented. The deacetylation procedure occurs under neutral conditions, is applicable to a wide range of substrates and tolerates a variety of functional groups (e. g. azido, allyl and silyl groups). Quantitative yields of the deacetylated product were obtained for all evaluated derivatives using catalyst amounts between 1 and 10 mol%. As a special highlight, the dual behavior of the nanocatalyst in both deacetylation and click reactions is reported. [ABSTRACT FROM AUTHOR]

Chitin biomass is the second largest biomass resource on Earth but under-utilized. In this study, pretreated shrimp shells were converted into value-added platform chemical 5-hydroxymethylfurfural (HMF) using microwave hydrothermal treatment. Under the combined pretreatment of acid decalcification at room temperature and microwave-assisted alkali deacetylation, the HMF yield could reach 1.8 wt%. The key process parameters, including the holding temperature, holding time, and pH value, were evaluated and optimised. The highest HMF yield of 6.5 wt% was obtained at 202.6°C at a holding time of 5.8 min and a pH value of 1.5. This result demonstrates the potential of synchronously treating waste and recycling it, thereby offering a highly promising valorisation strategy for chitin-biomass utilisation. [ABSTRACT FROM AUTHOR]

Background: Clear cell renal cell carcinoma (ccRCC) remains one of the most lethal urological malignancies even though a great number of improvements in diagnosis and management have achieved over the past few decades. Accumulated evidence revealed that histone deacetylases (HDACs) play vital role in cell proliferation, differentiation and apoptosis. Nevertheless, the biological functions of histone deacetylation modification related genes in ccRCC remains poorly understood. Method: Bulk transcriptomic data and clinical information of ccRCC patients were obtained from the TCGA database and collected from the Chinese PLA General Hospital. A total of 36 histone deacetylation genes were selected and studied in our research. Univariate cox regression analysis, least absolute shrinkage and selection operator (LASSO) regression, random forest (RF) analysis, and protein-protein interaction (PPI) network analysis were applied to identify key genes affecting the prognosis of ccRCC. The 'oncoPredict' algorithm was utilized for drug-sensitive analysis. Gene Set Enrichment Analysis (GSEA) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis was used to explore the potential biological function. The ssGSEA algorithm was used for tumor immune microenvironment analysis. The expression levels of HDAC10 were validated by RT-PCR and immunohistochemistry (IHC). 5-ethynyl-2′-deoxyuridine (EdU assay), CCK-8 assay, cell transwell migration and invasion assay and colony formation assay were performed to detect the proliferation and invasion ability of ccRCC cells. A nomogram incorporating HDAC10 and clinicopathological characteristics was established to predict the prognosis of ccRCC patients. Result: Two machine learning algorithms and PPI analysis identified four histone deacetylation genes that have a significant association with the prognosis of ccRCC, with HDAC10 being the key gene among them. HDAC10 is highly expressed in ccRCC and its high expression is associated with poor prognosis for ccRCC patients. Pathway enrichment and the experiments of EdU staining, CCK-8 assay, cell transwell migration and invasion assay and colony formation assay demonstrated that HDAC10 mediated the proliferation and metastasis of ccRCC cells and involved in reshaping the tumor microenvironment (TME) of ccRCC. A clinically reliable prognostic predictive model was established by incorporating HDAC10 and other clinicopathological characteristics (https://nomogramhdac10.shinyapps.io/HDAC10%5fNomogram/). Conclusion: Our study found the increased expression of HDAC10 was closely associated with poor prognosis of ccRCC patients. HDAC10 showed a pro-tumorigenic effect on ccRCC and promote the proliferation and metastasis of ccRCC, which may provide new light on targeted therapy for ccRCC. [ABSTRACT FROM AUTHOR]

Idebenone, an antioxidant used in treating oxidative damage-related diseases, has unclear neuroprotective mechanisms. Oxidative stress affects cell and mitochondrial membranes, altering Adp-ribosyl cyclase (CD38) and Silent message regulator 3 (SIRT3) protein expression and possibly impacting SIRT3's ability to deacetylate Tumor protein p53 (P53). This study explores the relationship between CD38, SIRT3, and P53 in H2O2-injured HT22 cells treated with Idebenone. Apoptosis was detected using flow cytometry and terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) staining after determining appropriate H2O2 and Idebenone concentrations. In this study, Idebenone was found to reduce apoptosis and decrease P53 and Caspase3 expression in H2O2-injured HT22 cells by detecting apoptosis-related protein expression. Through bioinformatics methods, CD38 was identified as the target of Idebenone, and it further demonstrated that Idebenone decreased the expression of CD38 and increased the level of SIRT3. An increased NAD+/NADH ratio was detected, suggesting Idebenone induces SIRT3 expression and protects HT22 cells by decreasing apoptosis-related proteins. Knocking down SIRT3 downregulated acetylated P53 (P53Ac), indicating SIRT3's importance in P53 deacetylation. These results supported that CD38 was used as a target of Idebenone to up-regulate SIRT3 to deacetylate activated P53, thereby protecting HT22 cells from oxidative stress injury. Thus, Idebenone is a drug that may show great potential in protecting against reactive oxygen species (ROS) induced diseases such as Parkinson's disease, and Alzheimer's disease. And it might be able to compensate for some of the defects associated with CD38-related diseases. [ABSTRACT FROM AUTHOR]

Eucalyptus branches and bark represent highly abundant and available feedstocks with great potential for obtaining bio-based products. Distinct and integrated pretreatment fractionation strategies for eucalyptus branches and bark were performed for the efficient production of xylooligosaccharides (XOS). By combining pretreatments, a high yield of XOS was obtained from eucalyptus branches and bark. The branches and bark were presoaked in 8% (w/w) sodium hydroxide at 60 °C for 30 min to provide a deacetylation effect. The residues were then hydrothermally treated. The findings revealed that 4.64% of XOS originated from the bark and 6.19% from eucalyptus branches. It has been demonstrated that xylan may be selectively depolymerized during pretreatment by preventing excessive hydrolysis through the use of deacetylation in the first phase of the process. More XOS was produced using hydrothermal treatment, yielding 8.00% (w/w) in the branches and 5.12% in the bark. A significant amount of XOS with DP 2–5 might be obtained in certain experiments, up to 60%, but the most abundant XOS are usually those with DP > 5 (approximately 80% of all XOS). This work provides new insights into the effective generation of XOS under relatively mild conditions by overcoming the recalcitrant structure of eucalyptus branches and bark, representing a noteworthy advancement towards forestry leftover valorization. [ABSTRACT FROM AUTHOR]

The delamination of encapsulants in photovoltaic (PV) modules is a common issue that leads to power loss due to optical losses. Encapsulant debonding is usually examined under monotonic loading conditions subsequent to environmental exposure such as damp heat. Service‐relevant, superimposed environmental‐mechanical fatigue loads are not considered adequately. Hence, the environmental fatigue delamination resistance of thermally toughened double glass laminates with an ethylene vinyl acetate copolymer (EVA) adhesive layer was investigated in this study. Focus was given to the melting range of EVA, in which the non‐crosslinked crystalline phase fraction is already in the partly molten state. Double cantilever beam specimens were tested on an electrodynamic test machine at temperatures of 60, 70, 80, and 90°C and relative humidity (rh) levels of 2%, 30%, 50%, and 80%. The fractured surfaces were characterized by digital microscopy, Fourier transform infrared spectroscopy (FTIR), X‐ray photoelectron spectroscopy (XPS), and differential scanning calorimetry (DSC). The cyclic fatigue tests revealed a decay in delamination resistance at elevated temperature and humidity levels. At 70°C, the delamination resistance was low, regardless of the relative humidity. Most of the laminates failed by debonding. XPS analysis showed a reduction of the C=O and C–O content, along with an increase in Si–O content with increasing relative humidity. For laminates tested at 60 and 70°C, an EVA recrystallization peak was observed in DSC experiments. This peak was shifted to significantly higher temperatures at 80% rh. XPS and DSC indicated local hydrolysis within the porous fracture process zone ahead of the crack tip. Consequently, acetic acid formation led to a decrease in delamination resistance, resulting in lower fatigue threshold values. The investigations confirmed the significant impact of environmental conditions on the fatigue delamination resistance within glass/encapsulant laminates. Notably, acetic acid formation and a significant reduction in delamination properties were observed after around 100 h of environmental fatigue exposure. [ABSTRACT FROM AUTHOR]

SIRT6 owns versatile types of enzymatic activities as a multitasking protein, including ribosyltransferase and deacetylase. To investigate the epigenetic regulations of SIRT6 on MSC fate determination via histone deacetylation, we used allosteric small molecules specifically controlling its histone 3 deacetylation activities. Results showed that enhanced deacetylation of SIRT6 promoted the ossific lineage commitment of MSC and finally achieved anabolic effects on hard tissues. Mechanistically, H3K9ac and H3K56ac, governed by SIRT6, in MSC orchestrated the transcriptions of crucial metabolic genes, mediating MSC fate determination. Most importantly, our data evidenced that modulating the epigenetic regulations of SIRT6, specifically via enhancing its deacetylation of H3K9ac and H3K56ac, was a promising choice to treat bone loss diseases and promote dentin regeneration. In this study, we revealed the specific roles of SIRT6's histone modification in MSC fate determination. These findings endow us with insights on SIRT6 and the promising therapeutic choices through SIRT6's epigenetic functions for hard tissues regeneration. [ABSTRACT FROM AUTHOR]

This study explores the effect of chitosan molecular weight on the formation of chitosan-based films by electrospraying process. The oxidative pathway was employed in chitosan with 220.1 kDa to obtain samples with 124.5 and 52.7 kDa. Both samples of depolymerized chitosan resulted in spheres within electrosprayed chitosan-based films due to a higher deacetylation degree (~85%). The increase in molecular weight (52.7 to 124.5 kDa) resulted in nanospheres (562 nm) within electrosprayed chitosan-based films, enhancing the surface area-to-volume ratio of the material. The electrospraying process maintained the structural integrity and thermal stability of all chitosan-based films while reducing their crystallinity. These findings highlight the impact of chitosan properties, particularly molecular weight, on the physicochemical characteristics of electrosprayed chitosan-based films. For instance, this work provides insights for the application of electrosprayed chitosan-based films in various fields. [ABSTRACT FROM AUTHOR]

To investigate the effect of deacetylated konjac glucomannan (DKGM) on the quality of transglutaminase ( TGase) crosslinking soybean isolate protein ( SPI) gels, different deacetylation konjac glucomannan ( DK-1 = 21. 30%, DK-2 = 36. 28%, DK-3 = 62. 85%, DK-4 = 87. 88% ) were prepared, and the effects of KGM and DKGM on the quality of TGase cross-linking soybean protein isolate gels and dried tofu were investigated. Compared with the blank group, KGM and DKGM improved the textural properties of composite gels of soybean protein isolate, increased the gel strength from 92. 03 g to a maximum of 130. 06 g at 8 h of enzyme cross-linking reaction time, enhanced the whiteness and water-holding properties of composite gels, and reduced the cooking loss rate from 8. 09% to 2. 55% . Compared with KGM, the DKGM treatment resulted in relatively high hardness, chewiness, and adhesiveness in composite gel and dried tofu after baking and sterilization. The thermal denaturation temperature of composite gels with DKGM was increased from 41. 35 ℃ to 44. 67 ℃, while DK-3 had a better effect on the salt content of dried tofu and a more apparent morphology of composite gel. The SEM results showed that S-DK3 composite gel exhibited a more compact and denser complex network structure. Overall, DKGM improved the quality of soybean protein isolate composite gels, and DK-3 was more effective. Therefore, the KGM with moderate deacetylation modification is favorable for the application in the process of dried tofu. [ABSTRACT FROM AUTHOR]

Background: The global outbreak of COVID-19 caused by the SARS-CoV-2 has led to millions of deaths. This unanticipated emergency has prompted virologists across the globe to delve deeper into the intricate dynamicity of the host-virus interface with an aim to identify antiviral targets and elucidate host and viral determinants of severe disease. Aim: The present study was undertaken to analyse the role of histone deacetylase 6 (HDAC6) in regulating SARS-CoV-2 infection. Results: Gradual increase in HDAC6 expression was observed in different SARS-CoV-2-permissive cell lines following SARS-CoV-2 infection. The SARS-CoV-2 nucleocapsid protein (N protein) was identified as the primary viral factor responsible for upregulating HDAC6 expression. Downregulation of HDAC6 using shRNA or a specific inhibitor tubacin resulted in reduced viral replication suggesting proviral role of its deacetylase activity. Further investigations uncovered the interaction of HDAC6 with stress granule protein G3BP1 and N protein during infection. HDAC6-mediated deacetylation of SARS-CoV-2 N protein was found to be crucial for its association with G3BP1. Conclusion: This study provides valuable insights into the molecular mechanisms underlying the disruption of cytoplasmic stress granules during SARS-CoV-2 infection and highlights the significance of HDAC6 in the process. [ABSTRACT FROM AUTHOR]

RNA splicing is crucial in the multilayer regulatory networks for gene expression, making functional interactions with DNA‐ and other RNA‐processing machineries in the nucleus. However, these established couplings are all major spliceosome‐related; whether the minor spliceosome is involved remains unclear. Here, through affinity purification using Drosophila lysates, an interaction is identified between the minor spliceosomal 65K/RNPC3 and ANKRD11, a cofactor of histone deacetylase 3 (HDAC3). Using a CRISPR/Cas9 system, Deletion strains are constructed and found that both Dm65KΔ/Δ and Dmankrd11Δ/Δ mutants have reduced histone deacetylation at Lys9 of histone H3 (H3K9) and Lys5 of histone H4 (H4K5) in their heads, exhibiting various neural‐related defects. The 65K‐ANKRD11 interaction is also conserved in human cells, and the HsANKRD11 middle‐uncharacterized domain mediates Hs65K association with HDAC3. Cleavage under targets and tagmentation (CUT&Tag) assays revealed that HsANKRD11 is a bridging factor, which facilitates the synergistic common chromatin‐binding of HDAC3 and Hs65K. Knockdown (KD) of HsANKRD11 simultaneously decreased their common binding, resulting in reduced deacetylation of nearby H3K9. Ultimately, this study demonstrates that expression changes of many genes caused by HsANKRD11‐KD are due to the decreased common chromatin‐binding of HDAC3 and Hs65K and subsequently reduced deacetylation of H3K9, illustrating a novel and conserved coupling mechanism that links the histone deacetylation with minor spliceosome for the regulation of gene expression. [ABSTRACT FROM AUTHOR]

Charru mussel, an invasive species found along the coastal areas of Baroy, Lanao del Norte, the Philippines, is commonly processed into the local delicacy known as “amahong,” with the shells often discarded as waste from this practice. This study aims to extract chitosan through demineralization of charru mussel shells using 1.25 N HCl, deproteinization using 3% NaOH yielding chitin, and deacetylation of chitin using 45% NaOH. The result shows a chitin yield of 21.27 ± 0.98% and a chitosan yield of 11.07% ± 0.66%. ATR-FTIR analysis confirmed the characteristic bands and functional groups associated with chitosan. SEM imaging revealed an amorphous and uneven particle shape, and TGA results exhibited thermal degradation at 550 °C, at which point chitosan breaks down. The synthesized chitosan displayed antibacterial activity at all concentrations (100, 200, and 300 µg/mL) against S. aureus while ineffective against E. coli. This study underscores the untapped potential of charru mussel shells as a source of chitosan, offering valuable insight for waste management. [ABSTRACT FROM AUTHOR]

Chitosan preparation is a sequential method that involves demineralization and deproteinization followed by deacetylation. In the present study, the effect of different process parameters such as concentration of acid, concentration of alkali, ratio between solid and solvent, reaction time, and temperature for optimization of demineralization and deacetylation processes in chitosan synthesis from Labeo rohita scale was studied. The effects of the above process parameters on chitosan yield (in terms of dry weight and % of moist weight of mass) were carried out using Box–Behnken design (BBD) of response surface methodology (RSM). The optimum condition for demineralization was observed at the ratio of solid to solvent (w/v) of 80 and incubation time of 10 min. Similarly, the optimum condition for deacetylation was revealed at alkali concentration of 15% and incubation time of 20 min. The obtained chitosan is characterized by UV–Visible spectroscopy, FT-IR analysis, SEM, and X-ray diffraction. [ABSTRACT FROM AUTHOR]

Almost one-half of adults have hypertension, and blood pressure is poorly controlled in a third of patients despite the use of multiple drugs, likely because of mechanisms that are not affected by current treatments. Hypertension is linked to oxidative stress; however, common antioxidants are ineffective. Hypertension is associated with inactivation of key intrinsic mitochondrial antioxidant, superoxide dismutase 2 (SOD2), due to hyperacetylation, but the role of specific SOD2 lysine residues has not been defined. Hypertension is associated with SOD2 acetylation at lysine 68, and we suggested that deacetylation mimetic mutation of K68 to arginine in SOD2 inhibits vascular oxidative stress and attenuates hypertension. To test this hypothesis, we have developed a new deacetylation mimetic SOD2-K68R mice. We performed in vivo studies in SOD2-K68R mice using angiotensin II (ANG II) model of vascular dysfunction and hypertension. ANG II infusion in wild-type mice induced vascular inflammation and oxidative stress and increased blood pressure to 160 mmHg. SOD2-K68R mutation completely prevented increase in mitochondrial superoxide, abrogated vascular oxidative stress, preserved endothelial nitric oxide production, protected vasorelaxation, and attenuated ANG II-induced hypertension. ANG II and cytokines contribute to vascular oxidative stress and hypertension. Treatment of wild-type aortas with ANG II and cytokines in organoid culture increased mitochondrial superoxide twofold, which was completely prevented in aortas isolated from SOD2-K68R mice. These data support the important role of SOD2-K68 acetylation in vascular oxidative stress and pathogenesis of hypertension. We conclude that strategies to reduce SOD2 acetylation may have therapeutic potential in the treatment of vascular dysfunction and hypertension. NEW & NOTEWORTHY: Essential hypertension is associated with hyperacetylation of key mitochondrial antioxidant SOD2; however, the pathophysiological role of SOD2 acetylation has not been defined. Our animal study of angiotensin II hypertension model shows that deacetylation mimetic SOD2-K68R mutation prevents pathogenic increase in vascular mitochondrial superoxide, abrogates vascular oxidative stress, preserves endothelial nitric oxide, protects endothelial-dependent vasorelaxation, and attenuates hypertension. These data support the important role of SOD2-K68 acetylation in vascular oxidative stress and the pathogenesis of hypertension. [ABSTRACT FROM AUTHOR]

Cerebral venous thrombosis (CVT) is a neurovascular disease with recently increasing incidence. Aseptic inflammatory responses play an important role in the pathology of CVT. Recent studies report that neutrophil extracellular traps (NETs) are major triggers of thrombosis and inflammation in stroke, but their effect on brain injury in CVT requires further validation. In this study, two CVT animal models were used to simulate superior sagittal sinus thrombosis and cortical vein thrombosis. The effects of brain tissue infiltration of NETs and the molecular mechanisms associated with NET formation were deeply explored in combination with proteomics, histology, and serology. The results showed that the cortical vein thrombosis model could be combined with more severe blood–brain barrier (BBB) disruption and showed more severe cerebral hemorrhage. Decreased Sirtuin 1 (SIRT1) expression promotes high mobility group box 1 (HMGB1) acetylation, causing increased cytosolic translocation and extracellular release, and HMGB1 can promote NET formation and recruitment. In addition, corticocerebral accumulation of NETs contributes to BBB damage. This establishes a vicious cycle between BBB damage and NET accumulation. SIRT1 mediated-HMGB1 deacetylation may play a critical role in attenuating BBB damage following CVT. This study employed a combined validation using models of venous sinus thrombosis and cortical vein thrombosis to investigate the deacetylation role of SIRT1, aiming to offer new insights into the pathological mechanisms of brain injury following CVT. [ABSTRACT FROM AUTHOR]

Abstract Background Clear cell renal cell carcinoma (ccRCC) remains one of the most lethal urological malignancies even though a great number of improvements in diagnosis and management have achieved over the past few decades. Accumulated evidence revealed that histone deacetylases (HDACs) play vital role in cell proliferation, differentiation and apoptosis. Nevertheless, the biological functions of histone deacetylation modification related genes in ccRCC remains poorly understood. Method Bulk transcriptomic data and clinical information of ccRCC patients were obtained from the TCGA database and collected from the Chinese PLA General Hospital. A total of 36 histone deacetylation genes were selected and studied in our research. Univariate cox regression analysis, least absolute shrinkage and selection operator (LASSO) regression, random forest (RF) analysis, and protein-protein interaction (PPI) network analysis were applied to identify key genes affecting the prognosis of ccRCC. The ‘oncoPredict’ algorithm was utilized for drug-sensitive analysis. Gene Set Enrichment Analysis (GSEA) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis was used to explore the potential biological function. The ssGSEA algorithm was used for tumor immune microenvironment analysis. The expression levels of HDAC10 were validated by RT-PCR and immunohistochemistry (IHC). 5-ethynyl-2′-deoxyuridine (EdU assay), CCK-8 assay, cell transwell migration and invasion assay and colony formation assay were performed to detect the proliferation and invasion ability of ccRCC cells. A nomogram incorporating HDAC10 and clinicopathological characteristics was established to predict the prognosis of ccRCC patients. Result Two machine learning algorithms and PPI analysis identified four histone deacetylation genes that have a significant association with the prognosis of ccRCC, with HDAC10 being the key gene among them. HDAC10 is highly expressed in ccRCC and its high expression is associated with poor prognosis for ccRCC patients. Pathway enrichment and the experiments of EdU staining, CCK-8 assay, cell transwell migration and invasion assay and colony formation assay demonstrated that HDAC10 mediated the proliferation and metastasis of ccRCC cells and involved in reshaping the tumor microenvironment (TME) of ccRCC. A clinically reliable prognostic predictive model was established by incorporating HDAC10 and other clinicopathological characteristics ( https://nomogramhdac10.shinyapps.io/HDAC10_Nomogram/ ). Conclusion Our study found the increased expression of HDAC10 was closely associated with poor prognosis of ccRCC patients. HDAC10 showed a pro-tumorigenic effect on ccRCC and promote the proliferation and metastasis of ccRCC, which may provide new light on targeted therapy for ccRCC.

Background and aim: Resveratrol (RSV), is a stilbene-based compound exerting wide biological properties. Its analogue 4,4′-dihydroxy-trans-stilbene (DHS) has shown improved bioavailability and antiproliferative activity in vitro and in vivo. One of the hypotheses on how resveratrol works is based on SIRT1 activation. Since their strict structural similarities, we have explored a potential interaction between DHS and SIRT1, in comparison with the parental molecule. Experimental procedure: Timing of incubation and concentrations of DHS have been determined using MTT assay in normal human lung fibroblasts. Untreated, DHS- or RSV-treated cells were harvested and analysed by Western Blotting or RT-PCR, in order to evaluate SIRT1 levels/activity and expression, and by Cellular Thermal shift assay (CETSA) to check potential DHS or RSV-SIRT1 interaction. Transfection experiments have been performed with two SIRT1 mutants, based on the potential binding pockets identified by Molecular Docking analysis. Results and conclusion: We unexpectedly found that DHS, but not RSV, exerted a time-dependent inhibitory effect on both SIRT1 protein levels and activity, the latter measured as p53 acetylation. At the mRNA level no significant changes were observed, whereas a proteasome-dependent mechanism was highlighted for the reduction of SIRT1 levels by DHS in experiments performed with the proteasome inhibitor MG132. Bioinformatics analysis suggested a higher affinity of RSV in binding all SIRT1 complexes compared to DHS, except comparable results for complex SIRT1-p53. Nevertheless, both CETSA and SIRT1 mutants transfected in cells did not confirm this interaction. In conclusion, DHS reduces SIRT1 protein level, thereby inhibiting its activity through a proteasome-mediated mechanism.

Abstract Background The global outbreak of COVID-19 caused by the SARS-CoV-2 has led to millions of deaths. This unanticipated emergency has prompted virologists across the globe to delve deeper into the intricate dynamicity of the host-virus interface with an aim to identify antiviral targets and elucidate host and viral determinants of severe disease. Aim The present study was undertaken to analyse the role of histone deacetylase 6 (HDAC6) in regulating SARS-CoV-2 infection. Results Gradual increase in HDAC6 expression was observed in different SARS-CoV-2-permissive cell lines following SARS-CoV-2 infection. The SARS-CoV-2 nucleocapsid protein (N protein) was identified as the primary viral factor responsible for upregulating HDAC6 expression. Downregulation of HDAC6 using shRNA or a specific inhibitor tubacin resulted in reduced viral replication suggesting proviral role of its deacetylase activity. Further investigations uncovered the interaction of HDAC6 with stress granule protein G3BP1 and N protein during infection. HDAC6-mediated deacetylation of SARS-CoV-2 N protein was found to be crucial for its association with G3BP1. Conclusion This study provides valuable insights into the molecular mechanisms underlying the disruption of cytoplasmic stress granules during SARS-CoV-2 infection and highlights the significance of HDAC6 in the process.

The nuclear receptor co-repressor (NCoR) complex mediates transcriptional repression dependent on histone deacetylation by histone deacetylase 3 (HDAC3) as a component of the complex. Unexpectedly, we found that signaling by the receptor activator of nuclear factor κB (RANK) converts the NCoR/HDAC3 co-repressor complex to a co-activator of AP-1 and NF-κB target genes that are required for mouse osteoclast differentiation. Accordingly, the dominant function of NCoR/HDAC3 complexes in response to RANK signaling is to activate, rather than repress, gene expression. Mechanistically, RANK signaling promotes RNA-dependent interaction of the transcriptional co-activator PGC1β with the NCoR/HDAC3 complex, resulting in the activation of PGC1β and inhibition of HDAC3 activity for acetylated histone H3. Non-coding RNAs Dancr and Rnu12, which are associated with altered human bone homeostasis, promote NCoR/HDAC3 complex assembly and are necessary for RANKL-induced osteoclast differentiation in vitro. These findings may be prototypic for signal-dependent functions of NCoR in other biological contexts.

Abstract Biodegradable plastics are those subjected easily to a degradation process, in which they can be decomposed after disposal in the environment through microbial activity. 30 bioplastic film formulations based only on chitosan film were used in the current investigation as a positive control together with chitosan film recovered from chitin-waste of locally obtained Aristeus antennatus. Additionally, castor oil was used as a plasticizer. While the yield of chitosan was 18% with 7.65% moisture content and 32.27% ash in the shells, the isolated chitin had a degree of deacetylation (DD) of 86%. The synthesized bioplastic films were characterized via numerous criteria. Firstly, the swelling capacity of these biofilms recorded relatively high percentages compared to polypropylene as synthetic plastic. Noticeably, the FTIR profiles, besides DSC, TGA, and XRD, confirmed the acceptable characteristics of these biofilms. In addition, their SEM illustrated the homogeneity and continuity with a few straps of the chitosan film and showed the homogeneous mixes of chitosan and castor oil with 5 and 20%. Moreover, data detected the antibacterial activity of different bioplastic formulas against some common bacterial pathogens (Enterococcus feacalis, Kelbsiella pnumina, Bacillus subtilis, and Pseudomonas aeruginosa). Amazingly, our bioplastic films have conducted potent antimicrobial activities. So, they may be promising in such a direction. Further, the biodegradability efficacy of bioplastic films formed was proved in numerous environments for several weeks of incubation. However, all bioplastic films decreased in their weights and changed in their colors, while polypropylene, was very constant all the time. The current findings suggest that our biofilms may be promising for many applications, especially in the field of food package protecting the food, and preventing microbial contamination, consequently, it may help in extending the shelf life of products.

Histone deacetylates family proteins have been studied for their function in regulating viral replication by deacetylating non-histone proteins. RIG-I (Retinoic acid-inducible gene I) is a critical protein in RNA virus-induced innate antiviral signaling pathways. Our previous research showed that HDAC8 (histone deacetylase 8) involved in innate antiviral immune response, but the underlying mechanism during virus infection is still unclear. In this study, we showed that HDAC8 was involved in the regulation of vesicular stomatitis virus (VSV) replication. Over-expression of HDAC8 inhibited while knockdown promoted VSV replication. Further exploration demonstrated that HDAC8 interacted with and deacetylated RIG-I, which eventually lead to enhance innate antiviral immune response. Collectively, our data clearly demonstrated that HDAC8 inhibited VSV replication by promoting RIG-I mediated interferon production and downstream signaling pathway. [ABSTRACT FROM AUTHOR]

NAD-dependent deacetylase Sirt2 is involved in mammalian metabolic activities, matching energy demand with energy production and expenditure, and is relevant to a variety of metabolic diseases. Here, we constructed Sirt2 knockout and adeno-associated virus overexpression mice and found that deletion of hepatic Sirt2 accelerated primary obesity and insulin resistance in mice with concomitant hepatic metabolic dysfunction. However, the key targets of Sirt2 are unknown. We identified the M2 isoform of pyruvate kinase (PKM2) as a key Sirt2 target involved in glycolysis in metabolic stress. Through yeast two-hybrid and mass spectrometry combined with multi-omics analysis, we identified candidate acetylation modification targets of Sirt2 on PKM2 lysine 135 (K135). The Sirt2-mediated deacetylation-ubiquitination switch of PKM2 regulated the development of glycolysis. Here, we found that Sirt2 deficiency led to impaired glucose tolerance and insulin resistance and induced primary obesity. Sirt2 severely disrupted liver function in mice under metabolic stress, exacerbated the metabolic burden on the liver, and affected glucose metabolism. Sirt2 underwent acetylation modification of lysine 135 of PKM2 through a histidine 187 enzyme active site-dependent effect and reduced ubiquitination of the K48 ubiquitin chain of PKM2. Our findings reveal that the hepatic glucose metabolism links nutrient state to whole-body energetics through the rhythmic regulation of Sirt2. [ABSTRACT FROM AUTHOR]

Histone deacetylases (HDAC) catalyze the removal of acetylation modifications on histones and non-histone proteins, which regulates gene expression and other cellular processes. HDAC inhibitors (HDACi), approved anti-cancer agents, emerge as a potential new therapy for heart diseases. Cardioprotective effects of HDACi are observed in many preclinical animal models of heart diseases. Genetic mouse models have been developed to understand the role of each HDAC in cardiac functions. Some of the findings are controversial. Here, we provide an overview of how HDACi and HDAC impact cardiac functions under physiological or pathological conditions. We focus on in vivo studies of zinc-dependent classical HDACs, emphasizing disease conditions involving cardiac hypertrophy, myocardial infarction (MI), ischemic reperfusion (I/R) injury, and heart failure. In particular, we review how non-biased omics studies can help our understanding of the mechanisms underlying the cardiac effects of HDACi and HDAC. [ABSTRACT FROM AUTHOR]

Chitosan, a biopolymer obtained from chitin, is known for its remarkable adsorption abilities for dyes, drugs, and fats, and its diverse array of antibacterial characteristics. This study explores the extraction and characterization of chitosan from the mycelium of Amanita phalloides. The moisture content, ash content, water binding capacity, fat binding capacity, and degree of deacetylation of the extracted chitosan were determined. The chitosan exhibited a high yield of 70%, crystallinity of 49.07%, a degree of deacetylation of 86%, and potent antimicrobial properties against both Gram-negative and Gram-positive bacteria. The study also examined the adsorption capabilities of chitosan to remove methylene blue (MB) dye by analysing specific factors like pH, reaction time, and MB concentration using the response surface model. The highest degree of MB dye removal was 91.6% at a pH of 6, a reaction time of around 60 min and an initial dye concentration of 16 ppm. This experimental design can be applied for chitosan adsorption of other organic compounds such as dyes, proteins, drugs, and fats. [ABSTRACT FROM AUTHOR]

Chitosan is cancer cytotoxic. It induces apoptosis/necrosis/autophagy and immuno-responses, and mitigates angiogenic and metastasis tendency of cancer cells. The lower molecular weight chitosan induces apoptosis, whereas the higher molecular weight chitosan exerts apoptosis and necrosis. Transforming chitosan into nanoparticles raises its anti-cancer efficacy with mode of cancer cell death governed by particle size to a greater extent than chitosan molecular weight. The larger nanoparticles tend to exert apoptosis. The smaller nanoparticles mediate necrosis. "Drug-free" small nanoparticles constituted of lower molecular weight chitosan are more cytotoxic than those of larger chitosan molecules/particles in vitro and in vivo, with no clear relationship between the deacetylation degree and zeta potential of nanoparticulate chitosan with anti-cancer activity. "Drug-free" chitosan nanoparticles are potentially as viable as the drug-loaded chitosan nanoparticles but with reduced systemic adverse effects. Their anti-cancer efficacy can be modulated through particle dose adjustment with lower risks of harmful effects than drugs and without processing hurdles faced in the development of drug-loaded chitosan nanoparticles such as low aqueous drug solubility, poor drug encapsulation, premature drug release and drug absorption, and drug instability with toxic metabolite formation. [ABSTRACT FROM AUTHOR]

Chitosan is a polysaccharide resulting from chitin deacetylation. It has demonstrated interesting characteristics in the field of adhesion but loses most of its adhesive resistance in moist environment. A chemical crosslinking of chitosan with genipin has been implemented to improve its adhesive properties in the presence of water. The study of crosslinking kinetics using rheology revealed its dependency on crosslinking rate and chitosan concentration. The capacity of the chitosan-genipin systems for water absorption has been quantified as their Free Swelling Capacity. The cross-linkage of chitosan by genipin (1% w/w) decreased significantly its ability for water absorption. Finally, the adhesive strength of several chitosans be they supplemented or not with genipin and/or glycerol used as plasticizer have been performed on Thick Adherent Shear Test samples of beech wood according to standard EN 204:2016 and EN 205:2016. The chitosan adhesive formulation containing genipin and glycerol exhibits the better adhesive properties on wood and presents higher water resistance compared to the native chitosan formulation. [ABSTRACT FROM AUTHOR]

The study included the extraction of Chitin (Ch) from shrimp shells and preparation of Chitin nanoparticles (NCh) using acid hydrolysis and ultrasound method. In addition, the preparation of chitosan (Chs) and Chitosan nanoparticles (NChs) by Deacetylation method, then we study some of the characteristics, including yield, diameter by Size Analyzer, Field Emission Scanning Electron Microscopy (FESEM), Fourier transform infrared (FTIR) spectroscopy, XRay Diffractometer (X-RD), Viscosity, Water Binding Capacity (WBC) and Fat Binding Capacity (FBC). The results showed, (a) decreased the percentage of yield of NChs to 8.20%, (b) the effective diameter of the natural chitosan using a Size Analyzer and was 28121.5 nm, (c) FESEM analysis revealed that the NChs displayed a nanoscale structure with diameters ranged from 20.93 - 30.20 nm (d) the degree of deacetylation (DD%) using FT-IR spectroscopy device, of NChs was (80.21%) compared to Chs 71.45%, and in addition, from the X-ray spectrum, two peaks in spectra of (Ch, NCh) and (Chs, NChs) were observed at the diffraction angles (2θ) which are (10.70-10.99) and (19.99-20.37). Results show increasing the crystallization coefficient of NCh and NChs, while viscosity, WBC and FBC of NChs decreased compared to Chs. The NChs did not show any toxic effect on human blood cells at concentrations of 100-1000 µg. ml-1. [ABSTRACT FROM AUTHOR]

SUMMARY: Carotenoids are photosynthetic pigments and antioxidants that contribute to different plant colors. However, the involvement of TOPLESS (TPL/TPR)‐mediated histone deacetylation in the modulation of carotenoid biosynthesis through ethylene‐responsive element‐binding factor‐associated amphiphilic repression (EAR)‐containing transcription factors (TFs) in apple (Malus domestica Borkh.) is poorly understood. MdMYB44 is a transcriptional repressor that contains an EAR repression motif. In the present study, we used functional analyses and molecular assays to elucidate the molecular mechanisms through which MdMYB44‐MdTPR1‐mediated histone deacetylation influences carotenoid biosynthesis in apples. We identified two carotenoid biosynthetic genes, MdCCD4 and MdCYP97A3, that were confirmed to be involved in MdMYB44‐mediated carotenoid biosynthesis. MdMYB44 enhanced β‐branch carotenoid biosynthesis by repressing MdCCD4 expression, whereas MdMYB44 suppressed lutein level by repressing MdCYP97A3 expression. Moreover, MdMYB44 partially influences carotenoid biosynthesis by interacting with the co‐repressor TPR1 through the EAR motif to inhibit MdCCD4 and MdCYP97A3 expression via histone deacetylation. Our findings indicate that the MdTPR1‐MdMYB44 repressive cascade regulates carotenoid biosynthesis, providing profound insights into the molecular basis of histone deacetylation‐mediated carotenoid biosynthesis in plants. These results also provide evidence that the EAR‐harboring TF/TPL repressive complex plays a universal role in histone deacetylation‐mediated inhibition of gene expression in various plants. Significance Statement: MdMYB44 regulated carotenoid biosynthesis partially by interacting with co‐repressor TPR1 via EAR motif to inhibit MdCCD4 and MdCYP97A3 expression through histone deacetylation, providing evidence that the EAR‐harboring TF/TPL repressive complex has a universal role in histone deacetylation‐mediated gene expression inhibition in various plants. [ABSTRACT FROM AUTHOR]

Autoimmune diseases (AID) have emerged as prominent contributors to disability and mortality worldwide, characterized by intricate pathogenic mechanisms involving genetic, environmental, and autoimmune factors. In response to this challenge, a growing body of research in recent years has delved into genetic modifications, yielding valuable insights into AID prevention and treatment. Sirtuins (SIRTs) constitute a class of NAD-dependent histone deacetylases that orchestrate deacetylation processes, wielding significant regulatory influence over cellular metabolism, oxidative stress, immune response, apoptosis, and aging through epigenetic modifications. Resveratrol, the pioneering activator of the SIRTs family, and its derivatives have captured global scholarly interest. In the context of AID, these compounds hold promise for therapeutic intervention by modulating the SIRTs pathway, impacting immune cell functionality, suppressing the release of inflammatory mediators, and mitigating tissue damage. This review endeavors to explore the potential of resveratrol and its derivatives in AID treatment, elucidating their mechanisms of action and providing a comprehensive analysis of current research advancements and obstacles. Through a thorough examination of existing literature, our objective is to advocate for the utilization of resveratrol and its derivatives in AID treatment while offering crucial insights for the formulation of innovative therapeutic approaches. [ABSTRACT FROM AUTHOR]

Mitochondrial dysfunction is critically involved in the degeneration of dopamine (DA) neurons in the substantia nigra, a common pathological feature of Parkinson's disease (PD). Previous studies have demonstrated that the NAD+-dependent acetylase Sirtuin 3 (SIRT3) participates in maintaining mitochondrial function and is downregulated in aging-related neurodegenerative disorders. The exact mechanism of action of SIRT3 on mitochondrial bioenergetics in PD pathogenesis, however, has not been fully described. In this study, we investigated the regulatory role of SIRT3-mediated deacetylation of mitochondrial complex II (succinate dehydrogenase) subunit A (SDHA) and its effect on neuronal cell survival in rotenone (ROT)-induced rat and differentiated MN9D cell models. The results revealed that SIRT3 activity was suppressed in both in vivo and in vitro PD models. Accompanying this downregulation of SIRT3 was the hyperacetylation of SDHA, impaired activity of mitochondrial complex II, and decreased ATP production. It was found that the inhibition of SIRT3 activity was attributed to a reduction in the NAD+/NADH ratio caused by ROT-induced inhibition of mitochondrial complex I. Activation of SIRT3 by icariin and honokiol inhibited SDHA hyperacetylation and increased complex II activity, leading to increased ATP production and protection against ROT-induced neuronal damage. Furthermore, overexpression of SDHA also exerted potent protective benefits in cells treated with ROT. In addition, treatment of MN9D cells with the NAD+ precursor nicotinamide mononucleotide increased SIRT3 activity and complex II activity and promoted the survival of cells exposed to ROT. These findings unravel a regulatory SIRT3-SDHA axis, which may be closely related to PD pathology. Bioenergetic rescue through SIRT3 activation-dependent improvement of mitochondrial complex II activity may provide an effective strategy for protection from neurodegeneration. [ABSTRACT FROM AUTHOR]

Schwannomas are benign tumors of the peripheral nervous system arising from the transformation of Schwann cells (SCs). On the whole, these tumors are related to alterations of the neurofibromin type 2 gene, coding for the oncosuppressor merlin, a cytoskeleton‐associated protein belonging to the ezrin–radixin–moesin family. However, the underlying mechanisms of schwannoma onset and progression are not fully elucidated, whereas one of the challenges might be the environment. In this light, the exposure to electromagnetic field (EMF), generated by the use of common electrical devices, has been defiantly suggested as the cause of SCs transformation even if the evidence was mostly epidemiologic. Indeed, insubstantial mechanisms have been so far identified to explain SCs oncotransformation. Recently, some in vitro evidence pointed out alterations in proliferation and migration abilities in SCs exposed to EMF (0.1 T, 50 Hz, 10 min). Here, we used the same experimental paradigma to discuss the involvement of putative epigenetic mechanisms in SCs adaptation to EMF and to explain the occurrence of hypoxic alterations after the exposure. Our findings indicate a set of environmental‐induced changes in SCs, toward a less‐physiological state, which may be pathologically relevant for the SCs differentiation and the schwannoma development. [ABSTRACT FROM AUTHOR]

Despite the importance of spliceosome core components in cellular processes, their roles in cancer development, including hepatocellular carcinoma (HCC), remain poorly understood. In this study, we uncover a critical role for SmD2, a core component of the spliceosome machinery, in modulating DNA damage in HCC through its impact on BRCA1/FANC cassette exons and expression. Our findings reveal that SmD2 depletion sensitizes HCC cells to PARP inhibitors, expanding the potential therapeutic targets. We also demonstrate that SmD2 acetylation by p300 leads to its degradation, while HDAC2-mediated deacetylation stabilizes SmD2. Importantly, we show that the combination of Romidepsin and Olaparib exhibits significant therapeutic potential in multiple HCC models, highlighting the promise of targeting SmD2 acetylation and HDAC2 inhibition alongside PARP inhibitors for HCC treatment. The relevance of spliceosome core components in cancer is less understood. Here the authors show SmD2, a core component of the spliceosome machinery, is under acetylation-dependent regulation, which could be targeted to enhance sensitivity to PARP inhibitors in hepatocellular carcinoma. [ABSTRACT FROM AUTHOR]

Acid mine drainage (AMD) is an environmental issue linked with mining activities, causing the release of toxic water from mining areas. Polyethersulphone (PES) membranes are explored for AMD treatment, but their limited hydrophilicity hinders their performance. Chitosan enhances hydrophilicity, addressing this issue. However, the effectiveness depends on chitosan's degree of deacetylation (DD), determined during the deacetylation process for chitosan production. This study optimized the chitin deacetylation temperature, alkaline (NaOH) concentration, and reaction time, yielding the highest chitosan degree of deacetylation (DD) for PES/chitosan membrane applications. Prior research has shown that high DD chitosan enhances membrane antifouling and hydrophilicity, increasing contaminant rejection and permeate flux. Evaluation of the best deacetylation conditions in terms of temperature (80, 100, 120 °C), NaOH concentration (20, 40, 60 wt.%), and time (2, 4, 6 h) was performed. The highest chitosan DD obtained was 87.11% at 80 °C, 40 wt. %NaOH at 4 h of chitin deacetylation. The PES/0.75 chitosan membrane (87.11%DD) showed an increase in surface hydrophilicity (63.62° contact angle) as compared to the pristine PES membrane (72.83° contact angle). This was an indicated improvement in membrane performance. Thus, presumably leading to high contaminant rejection and permeate flux in the AMD treatment context, postulate to literature. [ABSTRACT FROM AUTHOR]

Purpose: Nuclear accumulation of YAP/TAZ promotes tumorigenesis in several cancers, including melanoma. Although the mechanisms underlying the nuclear retention of YAP are known, those underlying the retention of TAZ remain unclear. Our study investigates a novel acetylation/deacetylation switch in TAZ, governing its subcellular localization in melanoma tumorigenesis. Methods: Immunoprecipitation/Western blot assessed TAZ protein interactions and acetylation. SIRT5 activity was quantified with enzyme-linked immunosorbent assay. Immunofluorescence indicated TAZ nuclear localization. TEAD transcriptional activity was measured through luciferase reporter assays. ChIP detected TAZ binding to the CTGF promoter. Transwell and wound healing assays quantified melanoma cell invasiveness and migration. Metastasis was evaluated using a mouse model via tail vein injections. Clinical relevance was explored via immunohistochemical staining of patient tumors. Results: CBP facilitated TAZ acetylation at K54 in response to epidermal growth factor stimulation, while SIRT5 mediated deacetylation. Acetylation correlated with phosphorylation, regulating TAZ's binding with LATS2 or TEAD. TAZ K54 acetylation enhanced its S89 phosphorylation, promoting cytosolic retention via LATS2 interaction. SIRT5-mediated deacetylation enhanced TAZ-TEAD interaction and nuclear retention. Chromatin IP showed SIRT5-deacetylated TAZ recruited to CTGF promoter, boosting transcriptional activity. In a mouse model, SIRT5 overexpression induced melanoma metastasis to lung tissue following the injection of B16F10 melanocytes via the tail vein, and this effect was prevented by verteporfin treatment. Conclusions: Our study revealed a novel mechanism of TAZ nuclear retention regulated by SIRT5-mediated K54 deacetylation and demonstrated the significance of TAZ deacetylation in CTGF expression. This study highlights the potential implications of the SIRT5/TAZ axis for treating metastatic melanoma. [ABSTRACT FROM AUTHOR]

Sophorolipids (SLs) are a kind of biosurfactants with the highest potential for industrial application, and the degree of acetylation in their sugar chains has an important influence on their surface interface activity, and physicochemical properties. By homologous recombination, the research group constructed the acetyltransferase gene-deficient strain, and nonacetylated SLs was prepared by fermentation with oleic acid and glucose as biphasic carbon sources. In this paper, the structure of nonacetylated SLs was analyzed by high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS), and the physicochemical properties of acetylated SLs produced by wild strains were compared. The results showed that the hydrophobic groups of nonacetylated SLs produced by nonacetylated strains were mainly octadecenoic acid, and the hydrophilic groups were mainly nonacetylated sophoricoside, in which the contents of lipoid, acidic and bolatype SLs were 26. 99%，49. 98% and 23. 03% respectively. The sophorolipids produced by wild strains are mainly acetylated sophorolipids, and the mass fractions of lactone and acid types are 97. 86% and 2. 14% respectively. Its hydrophobic group is mainly octadecenoic acid. The solubility of nonacetylated SLs in water is as high as 485. 8 g/L, which is 14 times higher than acetylated SLs, and it has better foaming performance and foam stability. At the same time, the emulsifying performance of nonacetylated SLs is 26. 7 times higher than acetylated SLs. Due to the increase of hydrophilicity of the missing acetyl group, the surface activity of deacetylation SLs decreased, and the surface tension of aqueous solution was reduced to 41. 0 mN/m, which was higher than that of acetylated sophorolipid (36. 2 mN/m). The hydrophilic and lipophilic balance value is 13, which is higher than that of acetylation SLs (11). Two kinds of sophorolipid have good hard water resistance, but weak acid and alkali resistance. [ABSTRACT FROM AUTHOR]

Biomass and biowastes stand as sustainable and cost-effective environmentally benign alternative feedstock. Chitosan is a biocompatible, bioactive, and biodegradable biopolymer derived from chitin to achieve eight aspects out of the 12 green chemistry principles. Chitosan got significant attention in several fields including chemical analysis, in addition to chemical functionally, which enabled its use as adsorbent and its structural crosslinking using various crosslinkers. The physicochemical, technological, and optical properties of chitosan have been extensively exploited in analysis. Mainly, deacetylation degree and molecular weight are controlling its properties and hence controlling its functions. This review presents a structure, properties, and functions relationships of chitosan. It also aims to provide an overview of the different functions that chitosan can serve in each analytical technique such as supporting matrix, catalyst...etc. The contribution of chitosan in improving the ecological performance is discussed in each technique. [ABSTRACT FROM AUTHOR]

Epigenetic mechanisms are involved in several cellular functions, and their role in the immune system is of prime importance. Histone deacetylases (HDACs) are an important set of enzymes that regulate and catalyze the deacetylation process. HDACs have been proven beneficial targets for improving the efficacy of immunotherapies. HDAC11 is an enzyme involved in the negative regulation of T cell functions. Here, we investigated the potential of HDAC11 downregulation using RNA interference in CAR-T cells to improve immunotherapeutic outcomes against prostate cancer. We designed and tested four distinct short hairpin RNA (shRNA) sequences targeting HDAC11 to identify the most effective one for subsequent analyses. HDAC11-deficient CAR-T cells (shD-NKG2D-CAR-T) displayed better cytotoxicity than wild-type CAR-T cells against prostate cancer cell lines. This effect was attributed to enhanced activation, degranulation, and cytokine release ability of shD-NKG2D-CAR-T when cocultured with prostate cancer cell lines. Our findings reveal that HDAC11 interference significantly enhances CAR-T cell proliferation, diminishes exhaustion markers PD-1 and TIM3, and promotes the formation of T central memory TCM populations. Further exploration into the underlying molecular mechanisms reveals increased expression of transcription factor Eomes, providing insight into the regulation of CAR-T cell differentiation. Finally, the shD-NKG2D-CAR-T cells provided efficient tumor control leading to improved survival of tumor-bearing mice in vivo as compared to their wild-type counterparts. The current study highlights the potential of HDAC11 downregulation in improving CAR-T cell therapy. The study will pave the way for further investigations focused on understanding and exploiting epigenetic mechanisms for immunotherapeutic outcomes. [ABSTRACT FROM AUTHOR]

Silent information regulator two homolog 1 (SIRT1), an NAD + -dependent histone deacetylase, plays a pivotal regulatory role in a myriad of physiological processes. A growing body of evidence suggests that SIRT1 can exert protective effects in metabolic disorders and neurodegenerative diseases by inhibiting endoplasmic reticulum (ER) stress and the nuclear factor-κB (NF-κB) inflammatory signaling pathway. This review systematically elucidates the molecular mechanisms and biological significance of SIRT1 in regulating ER stress and the NF-κB pathway. On one hand, SIRT1 can deacetylate key molecules in the ER stress pathway, such as glucose-regulated protein 78 (GRP78), X-box binding protein 1 (XBP1), PKR-like ER kinase (PERK), inositolrequiring enzyme 1a (IRE1a), and activating transcription factor 6 (ATF6), thereby alleviating ER stress. On the other hand, SIRT1 can directly or indirectly remove the acetylation modification of the NF-κB p65 subunit, inhibiting its transcriptional activity and thus attenuating inflammatory responses. Through these mechanisms, SIRT1 can ameliorate insulin resistance in metabolic diseases, exert cardioprotective effects in ischemia-reperfusion injury, and reduce neuronal damage in neurodegenerative diseases. However, it is important to note that while these findings are promising, the complex nature of the biological systems involved warrants further investigation to fully unravel the intricacies of SIRT1's regulatory mechanisms. Nevertheless, understanding the regulatory mechanisms of SIRT1 on ER stress and the NF-κB pathway is of great significance for expanding our knowledge of the pathogenesis of related diseases and exploring new preventive and therapeutic strategies targeting SIRT1. [ABSTRACT FROM AUTHOR]

Aims: White matter damage (WMD) is linked to both cerebral palsy and cognitive deficits in infants born prematurely. The focus of this study was to examine how caffeine influences the acetylation of proteins within the neonatal white matter and to evaluate its effectiveness in treating white matter damage caused by hypoxia-ischemia. Main methods: We employed a method combining affinity enrichment with advanced liquid chromatography and mass spectrometry to profile acetylation in proteins from the white matter of neonatal rats grouped into control (Sham), hypoxic-ischemic (HI), and caffeine-treated (Caffeine) groups. Key findings: Our findings included 1,999 sites of lysine acetylation across 1,123 proteins, with quantifiable changes noted in 1,342 sites within 689 proteins. Analysis of these patterns identified recurring sequences adjacent to the acetylation sites, notably YKacN, FkacN, and G * * * GkacS. Investigation into the biological roles of these proteins through Gene Ontology analysis indicated their involvement in a variety of cellular processes, predominantly within mitochondrial locations. Further analysis indicated that the acetylation of tau (Mapt), a protein associated with microtubules, was elevated in the HI condition; however, caffeine treatment appeared to mitigate this over-modification, thus potentially aiding in reducing oxidative stress, inflammation in the nervous system, and improving mitochondrial health. Caffeine inhibited acetylated Mapt through sirtuin 2 (SITR2), promoted Mapt nuclear translocation, and improved mitochondrial dysfunction, which was subsequently weakened by the SIRT2 inhibitor, AK-7. Significance: Caffeine-induced changes in lysine acetylation may play a key role in improving mitochondrial dysfunction and inhibiting oxidative stress and neuroinflammation. [ABSTRACT FROM AUTHOR]

This study investigated the influences of crosslinking agent and molecular weight on the surface and comfort properties of cotton fabrics treated by chitosan. Two types of chitosan, with molecular weight (2.6 kDa and 187 kDa), with deacetylation degree (DD) of 75%, were used, along with two types of crosslinking agents: citric acid (CA) and dimethylol dihydroxyethyleneurea (DMDHEU). These agents were applied to cotton fabrics for antibacterial treatments. The treated cotton fabrics were evaluated using several quality indicators related to physico-chemical properties, including whiteness (according to ISO 105 J02), breathability (according to ASTM D737:2004), moisture (according to ASTM D 2495-87), and thermal and moisture resistance under steady-state conditions (according to ISO 11092). Moreover, surface features of treated samples were observed through SEM images. The results showed that the antibacterial treatment of fabrics with lower molecular weight (Mw) chitosan was more favorable for the finishing processes, although the whiteness of the treated samples was quite low. Additionally, cotton fabrics treated with the CA agent exhibited better hygroscopicity and vapor transmission, but tended to have more pronounced yellow color, compared to those treated with the DMDHEU agent. These physico-chemical findings clarified the bonding mechanism of cellulose--crosslinker--chitosan in antibacterial treated cotton fabrics. [ABSTRACT FROM AUTHOR]

The formation of a rigid, tough interface based on a nacre-like structure in carbon fiber (CF) composites is a promising way to eliminate low delamination resistance. An effective method of coating CFs is electrophoretic deposition (EPD), which, in the case of dissimilar components like graphene oxide (GO) and polymeric glue, usually requires chemical bonding/strong interactions. In this work, we focus on chitin nanocrystals (ChNCs), leading to an excellent mechanical performance of artificial nacre, where favorable interactions and bonding with GO are controlled by degrees of deacetylation (5, 15, and 30%). We prepared coatings based on GO/ChNC adducts with 95/5, 90/10, 50/50, and 25/75 ratios using optimized EPD conditions (pH, concentration, voltage, and time). The prepared materials were characterized using FTIR, TEM, XPS, SEM, DLS, and XRD. SEM evaluation indicates the formation of a homogeneous interlayer, which has a fair potential for chemical bonding with the epoxy matrix. Short-beam testing of epoxy matrix composites indicates that the coating does not decrease stiffness and has a relatively low dependence on composition. Therefore, all coatings are promising for a detailed study of delamination resistance using laminate samples. Moreover, facile EPD from the water solution/suspension has a fair potential for industrial applications. [ABSTRACT FROM AUTHOR]

LC3 lipidation plays an important role in the regulation of macroautophagy and LC3-associated microautophagy. The E1-like enzyme ATG7 is one of the core components that are directly involved in LC3 lipidation reaction. Here, we provide evidence showing that acetylation of ATG7 tightly controls its enzyme activity to regulate the induction of macroautophagy and LC3-associated microautophagy. Mechanistically, acetylation of ATG7 disrupts its interaction with the E2-like enzyme ATG3, leading to an inhibition of LC3 lipidation in vitro and in vivo. Functionally, in response to various different stimuli, cellular ATG7 undergoes deacetylation to induce macroautophagy and LC3-associated microautophagy, which are necessary for cells to eliminate cytoplasmic DNA and degrade lysosome membrane proteins, respectively. Taken together, these findings reveal that ATG7 acetylation acts as a critical rheostat in controlling LC3 lipidation and related cellular processes. Abbreviations: AMPK: AMP-activated protein kinase; ATG: autophagy-related; cGAMP: cyclic GMP-AMP; CGAS: cyclic GMP-AMP synthase; CREBBP/CBP: CREB binding protein; EGF: epidermal growth factor; EGFR: epidermal growth factor receptor; EP300/p300: E1A binding protein p300; IFNB1: interferon beta 1; ISD: interferon stimulatory DNA; MAP1LC3/LC3: microtubule associated protein 1 light chain 3; MCOLN1/TRPML1: mucolipin TRP cation channel 1; MEF: mouse embryonic fibroblast; MTOR: mechanistic target of rapamycin kinase; NAM: nicotinamide; PE: phosphatidylethanolamine; PTM: post-translational modification; RB1CC1/FIP200: RB1 inducible coiled-coil 1; SIRT: sirtuin; SQSTM1/p62: sequestosome 1; STING1: stimulator of interferon response cGAMP interactor 1; TSA: trichostatin A; ULK1: unc-51 like autophagy activating kinase 1; WIPI2: WD repeat domain, phosphoinositide interacting 2; WT: wild-type. [ABSTRACT FROM AUTHOR]

Fascin actin‐bundling protein 1 (Fascin) is highly expressed in a variety of cancers, including esophageal squamous cell carcinoma (ESCC), working as an important oncogenic protein and promoting the migration and invasion of cancer cells by bundling F‐actin to facilitate the formation of filopodia and invadopodia. However, it is not clear how exactly the function of Fascin is regulated by acetylation in cancer cells. Here, in ESCC cells, the histone acetyltransferase KAT8 catalyzed Fascin lysine 41 (K41) acetylation, to inhibit Fascin‐mediated F‐actin bundling and the formation of filopodia and invadopodia. Furthermore, NAD‐dependent protein deacetylase sirtuin (SIRT) 7‐mediated deacetylation of Fascin‐K41 enhances the formation of filopodia and invadopodia, which promotes the migration and invasion of ESCC cells. Clinically, the analysis of cancer and adjacent tissue samples from patients with ESCC showed that Fascin‐K41 acetylation was lower in the cancer tissue of patients with lymph node metastasis than in that of patients without lymph node metastasis, and low levels of Fascin‐K41 acetylation were associated with a poorer prognosis in patients with ESCC. Importantly, K41 acetylation significantly blocked NP‐G2‐044, one of the Fascin inhibitors currently being clinically evaluated, suggesting that NP‐G2‐044 may be more suitable for patients with low levels of Fascin‐K41 acetylation, but not suitable for patients with high levels of Fascin‐K41 acetylation. © 2024 The Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

This research work narrates an economically friendly way to synthesize cellulose nanocrystal (CNC) and chitosan (CS) from waste jute bag and shrimp shell, respectively. Different analytical techniques such as X-ray diffraction (XRD), Fourier transform infrared (FT-IR) spectroscopy, and Scanning electron microscopy (SEM) were adopted to characterize diverse chemical and physical properties of the prepared samples, for the confirmation of the identity and assessment of the compatibility of the synthesized specimen for the targeted application. Crystallite size and crystallinity index were accounted for using XRD standard for CNC. The degree of deacetylation was also enumerated using chitosan's FT-IR record which was almost 98 %. The rest of this work is based on the hypothesis that, solely, an adsorbent exhibit either negative or positive net charge and shows affinity towards only oppositely charged dye molecules, while an appropriate hybrid blend of both negatively and positively charged adsorbent may show approximately equal affinity toward both anionic and cationic dye. Based on this concept, the potentiality of blending varying percentages of CNC and CS, as an adsorbent was monitored by executing the adsorption process considering different parameters like adsorbate interaction with adsorbent, pH, influence of initial concentration, contact time and dose of adsorbate with mostly found textile dyes Methylene blue (MB) and Congo red (CR) in wastewater which are cationic and anionic respectively. Cellulose nanocrystal and chitosan in the ratio of 50:50 showed an excellent result in the removal of both dye molecules.

In this research, using a suitable method and in line with the development of green chemistry, chitosan particles were prepared through the process of deacetylation from Persian Gulf shrimp shell waste, and then a copper-based complex was successfully synthesized on a substrate of chitosan particles, and with Techniques such as Fourier Transform Infrared Spectrometry (FT-IR), X-ray Diffraction (XRD), Scanning Electron Microscopy (SEM), X-ray Energy Diffraction Spectroscopy (EDX), Elemental Mapping, and Visible-Ultraviolet Spectroscopy (UV-Vis) was investigated. A wide variety of biaryl compounds were successfully synthesized through the developed catalytic process. The use of chitosan-copper (II) complex catalyst in the synthesis of biphenyl derivatives showed several advantages, including mild reaction conditions and short synthesis time, significant efficiency, avoiding the production of toxic waste, and easy separation of the catalyst. Furthermore, the chitosan-copper(II) complex was easily recovered by filtration and could be reused for five cycles without losing its structural integrity and catalytic activity.

Background Polycystic ovarian syndrome (PCOS) is a prevalent metabolic and endocrine condition in females of reproductive age. This work was to discover the underlying role of Dickkopf 1 (DKK1) and its putative regulating mechanism in P COS.Methods Mice recieved dehydroepiandrosterone (DHEA) injection to establish the in vivo P COS model.Hematoxylin and eosin (H&E) staining was performed for histological analysis. RT-qP CR and Western blotting were used to detect gene and protein expression. CCK-8 and flow cytometry assays were applied to detect cell viability and apoptosis. Co-immunoprecipitation (Co-IP) and immunoprecipitation (IP) were applied to assess association between DKK1 and SIRT2.Results In this work, DKK1 is downregulated in P COS rats. It was revealed that DKK1 knockdown induced apoptosis and suppressed proliferation in KGN cells, whereas DKK1 overexpression had exactly the opposite effects. In addition, DKK1 deactivates the T GF-β1/SMad3 signaling pathway, thereby controlling KGN cell proliferation and apoptosis. Besides, SIRT2 inhibition reversed the impact of DKK1 overexpression on KGN cell proliferation and apoptosis. Furthermore, SIRT2 downregulated DKK1 expression by deacetylating DKK1 in KGN cells.Discussion Altogether, we concluded that SIRT2-induced deacetylation of DKK1 triggers T GF-β1/Smad3 hyperactivation, thereby inhibiting proliferation and promoting apoptosis of KGN cells. The above results indicated that DKK1 might function as a latent target for P COS treatment.