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A Novel cold-active chitin deacetylase from Shewanella psychrophila WP2 (SpsCDA) was overexpressed in Escherichia coli BL21 and employed for deacetylation of chitin to chitosan. The produced chitosan was characterized, and its antifungal activity was investigated against Fusarium oxysporum. The purified recombinant SpsCDA appeared as a single band on SDS-PAGE at approximately 60 kDa, and its specific activity was 92 U/mg. The optimum temperature and pH of SpsCDA were 15 °C and 8.0, respectively, and the enzyme activity was significantly enhanced in the presence of NaCl. The bioconversion of chitin to chitosan by SpsCDA was accomplished in 72 h, and the chitosan yield was 69.2%. The solubility of chitosan was estimated to be 73.4%, and the degree of deacetylation was 78.1%. The estimated molecular weight of the produced chitosan was 224.7 ± 8.4 kDa with a crystallinity index (CrI) value of 18.75. Moreover, FTIR and XRD spectra revealed the characteristic peaks for enzymatically produced chitosan compared with standard chitosan, indicating their structural similarity. The produced chitosan inhibited spore germination of F. oxysporum with a minimum inhibitory concentration (MIC) of 1.56 mg/mL. The potential antifungal effect of chitosan is attributed to the inhibition of spore germination accompanied by ultrastructural damage of membranes and leakage of cellular components, as evidenced by transmission electron microscopy (TEM), and accumulation of reactive oxygen species (ROS) that was confirmed by fluorescence microscopy. This study shed light on the cold-active chitin deacetylase from S. psychrophila and provides a candidate enzyme for the green preparation of chitosan. [ABSTRACT FROM AUTHOR]

Lysine deacetylases (KDACs or HDACs) are metal‐dependent enzymes that regulate lysine acetylation, a post‐translational modification that is present on thousands of human proteins, essential for many cellular processes, and often misregulated in diseases. The selective inhibition of KDACs would allow for understanding of the biological roles of individual KDACs and therapeutic targeting of individual enzymes. Recent studies have suggested that purportedly specific KDAC inhibitors have significant off‐target binding, but the biological consequences of off‐target binding were not evaluated. We compared the effects of treatment with two of the reportedly most KDAC‐selective inhibitors, Tubastatin A and PCI‐34051, in HT1080 cells in which the endogenous KDAC6 or KDAC8 gene has been mutated to inactivate enzyme catalysis while retaining enzyme expression. Genetic inactivation results in much stronger deacetylation defects on known targets compared to inhibitor treatment. Gene expression analysis revealed that both inhibitors have extensive and extensively overlapping off‐target effects in cells, even at low inhibitor doses. Furthermore, Tubastatin A treatment led to increased histone acetylation, while inactivation of KDAC6 or KDAC8 did not. Genetic inactivation of KDAC6, but not KDAC8, impaired tumor formation in a xenograft model system, in contrast to previous reports with KDAC inhibitors suggesting the reverse. We conclude that the majority of observed biological effects of treatment with KDAC inhibitors are due to off‐target effects rather than the intended KDAC inhibition. Developing a truly specific KDAC6 inhibitor could be a promising therapeutic avenue, but it is imperative to develop new inhibitors that selectively mimic genetic inactivation of individual KDACs. [ABSTRACT FROM AUTHOR]

Background: The NOD-like receptor protein (NLRP)3 inflammasome is at the signaling hub center to instigate inflammation in response to pathogen infection or oxidative stress, and its tight control is pivotal for immune defense against infection while avoiding parallel intensive inflammatory tissue injury. Acetylation of NLRP3 is critical for the full activation of NLRP3 inflammasome, while the precise regulation of the acetylation and deacetylation circuit of NLRP3 protein remained to be fully understood. Methods: The interaction between histone deacetylase 10 (HDAC10) and NLRP3 was detected by immunoprecipitation and western blot in the HDAC10 and NLRP3 overexpressing cells. The role of HDAC10 in NLRP3 inflammasome activation was measured by immunofluorescence, real-time PCR and immunoblotting assay in peritoneal macrophages and bone marrow-derived macrophages after the stimulation with LPS and ATP. To investigate the role of HDAC10 in NLRP3-involved inflammatory diseases, the Hdac10 knockout (Hdac10−/−) mice were used to construct the LPS-induced acute endotoxemia model and folic acid-induced acute tubular necrosis model. Tissue injury level was analyzed by hematoxylin and eosin staining, and the serum level of IL-1β was measured by enzyme-linked immunosorbent assay (ELISA). The conservative analysis and immunoprecipitation assay were performed to screen the precise catalytic site regulated by HDAC10 responsible for the switching from the acetylation to ubiquitination of NLRP3. Results: Here we demonstrated that HDAC10 directly interacted with NLRP3 and induced the deacetylation of NLRP3, thus leading to the inhibition of NLRP3 inflammasome and alleviation of NLRP3 inflammasome-mediated acute inflammatory injury. Further investigation demonstrated that HDAC10 directly induced the deacetylation of NLRP3 at K496 residue, thus switching NLRP3 acetylation to the ubiquitination modification, resulting in the proteasomal degradation of NLRP3 protein. Thus, this study identified HDAC10 as a new eraser for NLRP3 acetylation, and HDAC10 attenuated NLRP3 inflammasome involved acute inflammation via directly deacetylating NLRP3. Conclusions: This study indicated that HDAC10 switched NLRP3 modification from acetylation to ubiquitination and attenuated acute inflammatory diseases, thus it provided a potential therapeutic strategy for NLRP3 inflammasome-associated diseases by targeting HDAC10. Plain English summary: The NOD-like receptor protein (NLRP)3 inflammasome is the core signaling hub and key instigator of acute inflammation in response to infection and oxidative stress to promote inflammatory cascade responses. Although inflammasome activation protects against infection and injury, excessive NLRP3 inflammasome activity yields excessive cytokine secretion and a pathological hyperinflammatory state. Of increasing interest is the critical contribution of NLRP3 inflammasome to acute inflammatory injury. Thus, the activation of NLRP3 inflammasome must be tightly controlled to ensure its efficient biological function without excessive side effect. NLRP3 protein is rich in lysine and susceptible to both acetylation and ubiquitination modification, while these two modifications usually had opposing effects on the protein degradation and stability. Various post-translational modifications in inflammasome signaling can be cross-regulated by each other, whereas the machinery involved in their spatial coordination during the process of NLRP3 inflammasome activation remains to be fully understood. Here we demonstrated that HDAC10 negatively regulated NLRP3 inflammasome by switching from acetylation to ubiquitination modification, leading to the proteasome-mediated degradation of the NLRP3 protein and attenuation of NLRP3 inflammasome activation. The further ubiquitination and acetylation analysis revealed that the Lys496 residue of NLRP3 protein is the pivotal convergence point involved in this PTM switch, indicating the critical switching node effect of this lysine residue. Altogether, our work suggested a novel fine-tuned regulatory mechanism of NLRP3 inflammasome activation by HDAC10, and provided a potential therapeutic target for NLRP3 inflammasome-associated diseases. [ABSTRACT FROM AUTHOR]

Summary Tiller is an important factor in determining rice yield. Currently, researches mainly focus on the outgrowth of low‐order tiller (LOT), while the regulation mechanism of high‐order tiller (HOT) outgrowth has remained unknown. In this study, we detected one OsNL1 mutant, nl1, exhibiting HOT numbers increase, and found that OsNL1 interacts with OsTOPLESS2, which was mediated by the core motif of nine amino acids VDCTLSLGT within the HAN domain of OsNL1. The topless2 mutant exhibits similar HOT number increase as in the nl1. Through ChIP‐seq analysis, we revealed that OsNL1 recruits OsTOPLESS2 to conduct histone deacetylation in the promoters of OsMOC1 and OsMOC3 to regulate HOT outgrowth. Moreover, we showed that the HAN domain is essential for OsNL1 function as a repressor. In summary, our study reveals partial mechanism of HOT outgrowth in rice and deciphers the molecular biology function of the HAN domain. This will contribute to the comprehensive understanding of tiller outgrowth and the role of HAN‐domain‐containing genes. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Elaborated conditions for lipase‐catalyzed preferential monoacetylation enabled the large‐scale preparation of hydroquinone monoacetate. This product was then applied to the synthesis of tournefolin B, a highly oxygenated prenylated hydroquinone of plant origin (Tournefortia sarmentosa Lam.). During the course of the synthetic transformations, lipase‐catalyzed deacetylation under mild conditions was demonstrated. [ABSTRACT FROM AUTHOR]

In recent years, research has extensively explored the broad industrial potential of chitosan, with the degree of deacetylation being a pivotal chemical attribute that significantly influences its physical and biological properties crucial for its various applications. Numerous methods have been developed to determine the degree of deacetylation: linear potentiometric titration, infrared spectroscopy, nuclear magnetic resonance spectroscopy, pyrolysis-mass spectrometry, UV spectroscopy, and titrimetry. The challenge for researchers lies in selecting an appropriate method due to factors like time consumption, costliness (notably nuclear magnetic resonance spectroscopy), and the potential for sample destruction inherent in certain methods. Among these, infrared spectroscopy has emerged as a preferred method due to its speed and non-destructive nature. This study investigated the use of experimental equations, as documented in the literature, to determine the degree of chitosan deacetylation under laboratory conditions using three chitosan samples differing in viscosity, each having a documented degree of deacetylation above 75 %. Three distinct methods — potentiometric titration, acid-base titration, and Fourier transform infrared spectroscopy — were employed to calculate chitosan's deacetylation degree. While acid-base and potentiometric titration showcased simplicity in terms of equipment, the latter proved more time-consuming. In contrast, infrared spectroscopy demands more intricate instrumentation but requires only minimal samples, ensuring rapid analysis. The results showed that the methods of infrared spectroscopy and acid-base titration, using reported experimental equations, can be used to determine the degree of chitosan deacetylation. However, potentiometric titration did not validate its efficacy for this purpose. [ABSTRACT FROM AUTHOR]

High mobility group protein B1 (HMGB1) acts as a pathogenic inflammatory response to mediate ranges of conditions such as epilepsy, septic shock, ischemia, traumatic brain injury, Parkinson's disease, Alzheimer's disease and mass spectrometry. HMGB1 promotes inflammation during sterile and infectious damage and plays a crucial role in disease development. Mobilization from the nucleus to the cytoplasm is the first important step in the release of HMGB1 from activated immune cells. Here, we demonstrated that Sirtuin 2 (SIRT2) physically interacts with and deacetylates HMGB1 at 43 lysine residue at nuclear localization signal locations, strengthening its interaction with HMGB1 and causing HMGB1 to be localized in the cytoplasm. These discoveries are the first to shed light on the SIRT2 nucleoplasmic shuttle, which influences HMGB1 and its degradation, hence revealing novel therapeutic targets and avenues for neuroinflammation treatment. [ABSTRACT FROM AUTHOR]

New FOXM1‐specific inhibitors with the potential to be used for therapeutic purposes are under extensive research. We hypothesized that deacetylation of FOXM1 would decrease protein expression, thus providing novel therapeutic management of colon cancers. Immunostaining was used to determine FOXM1 and SIRT2 expressions in human colon cancer tissue microarrays (n = 90) from Stage I to Stage IV. SIRT2‐FOXM1 interaction was evaluated in colon cancer cells using immunoprecipitation. Deacetylation of FOXM1 via SIRT2 was determined using in vitro deacetylation assays. FOXM1 could be hyper‐acetylated when p300 and pCAF histone acetyltransferases were administered alongside deacetylase inhibitors. We detected that SIRT2 and FOXM1 physically interacted, and SIRT2 deacetylated FOXM1 in vitro. SIRT2 overexpression led to a significant decrease while knockdown of SIRT2 increased the FOXM1 expression in HCT116 human colon carcinoma cells. In the analysis of 90 human colorectal cancer samples, high SIRT2 expression was observed in about 49% of colorectal cancer, intermediate in 29%, and low or no staining in 22%. Strong SIRT2 expression was found to be negatively associated with the FOXM1 staining in our clinical cohort. This study reveals a molecular interaction and association between SIRT2 and FOXM1 expression in colon cancer cell lines and human colon cancer samples, and suggests that targeting SIRT2 activity using small molecule modulators may be a promising therapeutic approach for colorectal cancer. Highlights: Upregulation of FOXM1 may be an early molecular signal required for cancerSIRT2 and FOXM1 physically interacted, and SIRT2 deacetylated FOXM1 in vitroStrong SIRT2 expression was negatively associated with the FOXM1 staining in the TMAResveratrol, berberine and quercetin decreased FOXM1 expression in colorectal cancer cells [ABSTRACT FROM AUTHOR]

Chitosan, a cationic polysaccharide derived from the deacetylation of chitin, is widely distributed in nature. Its antibacterial activity, biocompatibility, biodegradability, and non-toxicity have given it extensive uses in medicine, food, and cosmetics. However, the significant impact of variations in the physicochemical properties of chitosan extracted from different sources on its application efficacy, as well as the considerable differences in its antimicrobial mechanisms under varying conditions, limit the full realization of its biological functions. Therefore, this paper provides a comprehensive review of the structural characteristics of chitosan, its preparation methods from different sources, its antimicrobial mechanisms, and the factors influencing its antimicrobial efficacy. Furthermore, we highlight the latest applications of chitosan and its derivatives across various fields. We found that the use of microbial extraction shows promise as a new method for producing high-quality chitosan. By analyzing the different physicochemical properties of chitosan from various sources and the application of chitosan-based materials (such as nanoparticles, films, sponges, and hydrogels) prepared using different methods in biomedicine, food, agriculture, and cosmetics, we expect these findings to provide theoretical support for the broader utilization of chitosan. [ABSTRACT FROM AUTHOR]

Abstract Background The NOD-like receptor protein (NLRP)3 inflammasome is at the signaling hub center to instigate inflammation in response to pathogen infection or oxidative stress, and its tight control is pivotal for immune defense against infection while avoiding parallel intensive inflammatory tissue injury. Acetylation of NLRP3 is critical for the full activation of NLRP3 inflammasome, while the precise regulation of the acetylation and deacetylation circuit of NLRP3 protein remained to be fully understood. Methods The interaction between histone deacetylase 10 (HDAC10) and NLRP3 was detected by immunoprecipitation and western blot in the HDAC10 and NLRP3 overexpressing cells. The role of HDAC10 in NLRP3 inflammasome activation was measured by immunofluorescence, real-time PCR and immunoblotting assay in peritoneal macrophages and bone marrow-derived macrophages after the stimulation with LPS and ATP. To investigate the role of HDAC10 in NLRP3-involved inflammatory diseases, the Hdac10 knockout (Hdac10 −/−) mice were used to construct the LPS-induced acute endotoxemia model and folic acid-induced acute tubular necrosis model. Tissue injury level was analyzed by hematoxylin and eosin staining, and the serum level of IL-1β was measured by enzyme-linked immunosorbent assay (ELISA). The conservative analysis and immunoprecipitation assay were performed to screen the precise catalytic site regulated by HDAC10 responsible for the switching from the acetylation to ubiquitination of NLRP3. Results Here we demonstrated that HDAC10 directly interacted with NLRP3 and induced the deacetylation of NLRP3, thus leading to the inhibition of NLRP3 inflammasome and alleviation of NLRP3 inflammasome-mediated acute inflammatory injury. Further investigation demonstrated that HDAC10 directly induced the deacetylation of NLRP3 at K496 residue, thus switching NLRP3 acetylation to the ubiquitination modification, resulting in the proteasomal degradation of NLRP3 protein. Thus, this study identified HDAC10 as a new eraser for NLRP3 acetylation, and HDAC10 attenuated NLRP3 inflammasome involved acute inflammation via directly deacetylating NLRP3. Conclusions This study indicated that HDAC10 switched NLRP3 modification from acetylation to ubiquitination and attenuated acute inflammatory diseases, thus it provided a potential therapeutic strategy for NLRP3 inflammasome-associated diseases by targeting HDAC10.

Objective: Post-resuscitation brain injury is a common sequela after cardiac arrest (CA). Increasing sirtuin1 (SIRT1) has been involved in neuroprotection in oxygen-glucose deprivation (OGD) neurons, and we investigated its mechanism in post-cardiopulmonary resuscitation (CPR) rat brain injury by mediating p65 deacetylation modification to mediate hippocampal neuronal ferroptosis. Methods: Sprague-Dawley rat CA/CPR model was established and treated with Ad-SIRT1 and Ad-GFP adenovirus vectors, or Erastin. Rat postoperative neurological function, and cognitive and learning abilities were assessed by neurological deficit score and Morris water maze test. Hippocampal neuronal pathological changes and injury were evaluated by H&E and TUNEL staining. Serum brain injury biomarkers and hippocampal inflammatory factors and SIRT1 mRNA levels were determined by ELISA and RT-qPCR. OGD/reoxygenation (OGD/R) rat hippocampal neuron (H19-7) model was established. Cell viability and injury, nuclear factor-kappa B (NF-κB) p65 localization, iron content, and levels of glutathione, malondialdehyde, reactive oxygen species, SIRT1, Ac NF-κB p65 (Lys310), NF-κB p65, ACSL4, glutathione peroxidase 4 and SLC7A11 were measured. Results: In CA/CPR rats, SIRT1 was down-regulated, and SIRT1 overexpression alleviated cerebral injury. SIRT1 overexpression inhibited OGD/R-induced H19-7 cell ferroptosis to ameliorate cell injury, and inactivated the NF-κB pathway by reducing p65 acetylation to hinder its entry into the nucleus. Inactivating the NF-κB pathway reduced OGD/R-induced ferroptosis and alleviated cell injury. SIRT1 alleviated cerebral injury by mediating p65 deacetylation to inhibit hippocampal neuronal ferroptosis mediated by the NF-κB pathway. Conclusions: SIRT1 inhibited the NF-κB signaling pathway-mediated hippocampal neuronal ferroptosis by mediating p65 deacetylation modification, thereby alleviating brain injury in CA/CPR rats. [ABSTRACT FROM AUTHOR]

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 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.

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.

Chitosan is a non-toxic, high molecular weight, biodegradable polymer that closely resembles cellulose, a plant fiber. The main difference between chitosan and cellulose is the presence of an amine group (-NH2) in chitosan, as opposed to the hydroxyl group (-OH) found in cellulose. The aim of the study is the effect of nanochitosan production in Iran and Iraq on bacteria. Chitosan is derived from chitin, a substance found abundantly in the shells of shellfish such as crabs, lobsters, and shrimp. Extracting chitin from natural sources involves a process of demineralization and deproteinization. The purified chitin is then treated with concentrated alkaline compounds, such as sodium hydroxide, in a process known as deacetylation, resulting in chitosan. Chitosan exhibits enhanced antimicrobial properties when formed into nanoparticles and used as a coating material. Chitosan nanoparticles. These chitosan nanoparticle derivatives were evaluated for their antibacterial activity against Escherichia coli using methods such as well diffusion and microtiter method. The results showed the highest inhibition zone against Escherichia coli, the characteristics of nanochitosan, including its charge and size, ranged from 20-100 nm. The particle size of the nanochitosan was measured by (TEM) analyze the physical properties and morphology of nanochitosan. Microbiological investigations: Microbiological investigations were carried out to evaluate the antimicrobial properties of nanochitosan. Determination of MIC of nanochitosan was determined for some pathogenic bacteria, providing insights into their efficacy as antimicrobial agents. The results showed that among the nanostructures studied, the nanochitosan made from seashells from Iraq and Iran was the most effective. The results showed that the nanochitosan that appeared under the electron microscope and was characterized by its spherical shape had more antimicrobial properties compared to the nanochitosan that was characterized by its tubular shape due to its small size and its ability to penetrate bacterial cells easily. [ABSTRACT FROM AUTHOR]

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 is the most abundant natural polysaccharide and is produced annually almost as much as cellulose. Chitin is deactylated to obtain chitosan. It has become of great interest not only as an underutilized resource, but also as a new functional material of high potential in various fields. Exoskeletons of shrimp were used for chitin extraction and chitosan was obtained by deacetylation. Physiochemical analysis and applications of chitin and chitosan were studied. Physiochemical analysis such as determination of moisture content, organic matter and organic carbon, degree of deacetylation of chitosan and FTIR analysis were carried out. Chitin as a biofertilizer in plant growth analysis, use of chitosan in food preservation and as an adsorbent for dye removal were also studied. The results obtained indicate that shrimp shell waste can be a valuable resource for Chitin and Chitosan and further these biopolymers can be used for their varied appicatios. [ABSTRACT FROM AUTHOR]

Chitosan, an important and abundant natural-based polymer, was extracted for the first time from the pupal exuviae (PE) of Hippotion celerio L., reared and fed with an invasive plant species, Colocasia esculenta (L.) Schott. In this study, we investigated the safety and biotechnological potential of insect-based chitosan. Demineralization and deproteinization were performed with 1 M hydrochloric acid at 25°C for 3 hours at 300 RPM and 1 M sodium hydroxide (NaOH) for 4 hours at 100°C, respectively. The extracted chitin was converted into chitosan via deacetylation using 50% NaOH for 4 hours at 80°C. Both chitin and chitosan were characterized by Fourier Transform Infrared Spectroscopy (FTIR) to determine its purity and Scanning Electron Microscopy (SEM) to examine its surface morphology. For the acute toxicity study, a single dose of three concentrations of 300, 2000, and 5000 mg/kg bw of chitosan were administered orally using a gavage to healthy female Swiss albino mice. The chitin and chitosan yield of the dry weight were 21.74±2.15% and 58.26±4.24%, respectively. Additionally, the degree of deacetylation (DD) was found to be 85%, higher compared to the commercial chitosan obtained from the shrimp with 83%. Scanning Electron Microscope (SEM) exposed smooth, porous, and fibrous surfaces, suggesting its use in biotechnology. LD50 value for chitosan in Swiss albino mice was greater than 5000 mg/kg bw. Thus, this study suggests that chitosan extracted from the pupal exuviae of H. celerio L. is safe and could be used in future applications in tissue engineering, biomedicine, and textile industry. [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]

Mannosylerythritol lipids (MELs), a glycolipid biosurfactant, possess great potential in many high‐value‐added fields. However, its water‐insolubility is an important obstacle to its wide application, especially in home and personal care fields. In this study, a new strategy "killing two birds with one stone" based on the chemical modification of natural MELs was developed for the preparation of hydrophilic MELs. These newly prepared MELs can be efficiently isolated from the reacted solution via stepwise extraction with a methanol/n‐hexane system. 88% of hydrophilic MELs were recovered from natural MELs, with a corresponding yield of 50%. This is mainly attributed to the esterification of fatty acids, representing the main and relatively‐difficult‐to‐remove impurities in fermentative‐produced MELs, facilitating separation from the MEL product via extraction. Moreover, these new MELs presented comparable surface activities to natural MELs while exhibiting enhanced water solubility and biocompatibility. This originates from the generation of MEL‐D, resulting from the deacetylation of natural MELs and the formation of new hydrophilic MELs containing just one hydrophobic chain (named "MEL‐G"). Hence, the present strategy is not only beneficial for the removal of impurities (fatty acids) but also for the preparation of MELs with improved hydrophilicity. [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 degree of deacetylation, DDA is the most important characteristic for a specific chitosan sample as it mainly influences its chemical and biological properties. Several natural wastes may be used as sources for chitin as for example crabs' and shrimps' exoskeletons, and the yield of chitosan extraction is generally small and depends on the chitin extraction and the deacetylation step. The simultaneous maximization of yield and deacetylation degree DDA pointed out some optimal operating conditions of the deacetylation procedure. The maximum yield and maximum DDA can be obtained working with higher NaOH concentrations and longer duration of this step. [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]

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]

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]

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.

ABSTRACTEnterohemorrhagic Escherichia coli (EHEC) O157:H7 is a common food-borne pathogen that can cause acute diseases. Lysine acetylation is a post-translational modification (PTM) that occurs in various prokaryotes and is regulated by CobB, the only deacetylase found in bacteria. Here, we demonstrated that CobB plays an important role in the virulence of EHEC O157:H7 and that deletion of cobB significantly decreased the intestinal colonization ability of bacteria. Using acetylation proteomic studies, we systematically identified several proteins that could be regulated by CobB in EHEC O157:H7. Among these CobB substrates, we found that acetylation at the K44 site of CesA, a chaperone for the type-III secretion system (T3SS) translocator protein EspA, weakens its binding to EspA, thereby reducing the stability of this virulence factor; this PTM ultimately attenuating the virulence of EHEC O157:H7. Furthermore, we showed that deacetylation of the K44 site, which is deacetylated by CobB, promotes the interaction between CesA and EspA, thereby increasing bacterial virulence in vitro and in animal experiments. In summary, we showed that acetylation influences the virulence of EHEC O157:H7, and uncovered the mechanism by which CobB contributes to bacterial virulence based on the regulation of CesA deacetylation.

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.

Histone deacetylases (HDACs) are proteases that play a key role in chromosome structural modification and gene expression regulation, and the involvement of HDACs in cancer, the nervous system, and the metabolic and immune system has been well reviewed. Our understanding of the function of HDACs in the vascular system has recently progressed, and a significant variety of HDAC inhibitors have been shown to be effective in the treatment of vascular diseases. However, few reviews have focused on the role of HDACs in the vascular system. In this study, the role of HDACs in the regulation of the vascular system mainly involving endothelial cells and vascular smooth muscle cells was discussed based on recent updates, and the role of HDACs in different vascular pathogenesis was summarized as well. Furthermore, the therapeutic effects and prospects of HDAC inhibitors were also addressed in this review.

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 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]