Multifaceted functions of RNA-binding protein vigilin in gene silencing, genome stability, and autism-related disorders.

RNA-binding proteins (RBPs) are emerging as important players in regulating eukaryotic gene expression and genome stability. Specific RBPs have been shown to mediate various chromatin-associated processes ranging from transcription to gene silencing and DNA repair. One of the prominent classes of RBPs is the KH domain-containing proteins. Vigilin, an evolutionarily conserved KH domain-containing RBP has been shown to be associated with diverse biological processes like RNA transport and metabolism, sterol metabolism, chromosome segregation, and carcinogenesis. We have previously reported that vigilin is essential for heterochromatin-mediated gene silencing in fission yeast. More recently, we have identified that vigilin in humans plays a critical role in efficient repair of DNA double-stranded breaks and functions in homology-directed DNA repair. In this review, we highlight the multifaceted functions of vigilin and discuss the findings in the context of gene expression, genome organization, cancer, and autism-related disorders.

The mTORC1-G9a-H3K9me2 axis negatively regulates autophagy in fatty acid-induced hepatocellular lipotoxicity.

Defective autophagy and lipotoxicity are the hallmarks of nonalcoholic fatty liver disease. However, the precise molecular mechanism for the defective autophagy in lipotoxic conditions is not fully known. In the current study, we elucidated that activation of the mammalian target of rapamycin complex 1 (mTORC1)-G9a-H3K9me2 axis in fatty acid-induced lipotoxicity blocks autophagy by repressing key autophagy genes. The fatty acid-treated cells show mTORC1 activation, increased histone methyltransferase G9a levels, and suppressed autophagy as indicated by increased accumulation of the key autophagic cargo SQSTM1/p62 and decreased levels of autophagy-related proteins LC3II, Beclin1, and Atg7. Our chromatin immunoprecipitation analysis showed that decrease in autophagy was associated with increased levels of the G9a-mediated repressive H3K9me2 mark and decreased RNA polymerase II occupancy at the promoter regions of Beclin1 and Atg7 in fatty acid-treated cells. Inhibition of mTORC1 in fatty acid-treated cells decreased G9a-mediated H3K9me2 occupancy and increased polymerase II occupancy at Beclin1 and Atg7 promoters. Furthermore, mTORC1 inhibition increased the expression of Beclin1 and Atg7 in fatty acid-treated cells and decreased the accumulation of SQSTM1/p62. Interestingly, the pharmacological inhibition of G9a alone in fatty acid-treated cells decreased the H3K9me2 mark at Atg7 and Beclin1 promoters and restored the expression of Atg7 and Beclin1. Taken together, our findings have identified the mTORC1-G9a-H3K9me2 axis as a negative regulator of the autophagy pathway in hepatocellular lipotoxicity and suggest that the G9a-mediated epigenetic repression is mechanistically a key step during the repression of autophagy in lipotoxic conditions.

Vigilin protein Vgl1 is required for heterochromatin-mediated gene silencing in Schizosaccharomyces pombe.

Heterochromatin is a conserved feature of eukaryotic genomes and regulates various cellular processes, including gene silencing, chromosome segregation, and maintenance of genome stability. In the fission yeast Schizosaccharomyces pombe, heterochromatin formation involves methylation of lysine 9 in histone H3 (H3K9), which recruits Swi6/HP1 proteins to heterochromatic loci. The Swi6/HP1-H3K9me3 chromatin complex lies at the center of heterochromatic macromolecular assemblies and mediates many functions of heterochromatin by recruiting a diverse set of regulators. However, additional factors may be required for proper heterochromatin organization, but they are not fully known. Here, using several molecular and biochemical approaches, we report that Vgl1, a member of a large family of multiple KH-domain proteins, collectively known as vigilins, is indispensable for the heterochromatin-mediated gene silencing in S. pombe ChIP analysis revealed that Vgl1 binds to pericentromeric heterochromatin in an RNA-dependent manner and that Vgl1 deletion leads to loss of H3K9 methylation and Swi6 recruitment to centromeric and telomeric heterochromatic loci. Furthermore, we show that Vgl1 interacts with the H3K9 methyltransferase, Clr4, and that loss of Vgl1 impairs Clr4 recruitment to heterochromatic regions of the genome. These findings uncover a novel role for Vgl1 as a key regulator in heterochromatin-mediated gene silencing in S. pombe.

Spiropyrrolidine/spiroindolizino[6,7-b]indole heterocyclic hybrids: Stereoselective synthesis, cholinesterase inhibitory activity and their molecular docking study.

A regio and stereo- selective synthesis of hitherto unexplored hybrid heterocyclic system comprising spiropyrrolidine, indolizino[6,7-b]indole units in good to excellent yields, has been developed via three component 1,3-dipolar cycloaddition and concomitant trifluoroacetic acid catalyzed Pictet-Spengler cyclization with paraformaldehyde. The newly synthesized compounds were evaluated for their in vitro acetylcholinesterase (AChE) and butylcholinesterase (BChE) enzyme inhibitory activities. Most of the synthesized compounds showed good inhibitory activity, among them, compounds 4d and 4g displayed highest potency against AChE (IC50 1.88 and 1.98 µM), and BChE (IC50 18.32 and 10.21 µM) enzyme, respectively than the standard drug, galanthamine. Molecular modeling simulation was investigated for the most active compounds 4d and 4g on AChE and BChE enzymes to disclose the binding and orientation of these molecules into active site of respective receptors.

Synthesis, Structural Characterization and Antimicrobial Activity of Cu(II) and Fe(III) Complexes Incorporating Azo-Azomethine Ligand.

We are reporting a novel azo-azomethine ligand, HL and its complexes with Cu(II) and Fe(III) ions. The ligand and its complexes are characterized by various physico-chemical techniques using C,H,N analyses, FT-IR, ¹H-NMR, ESI-MS and UV-Vis studies. TGA analyses reveal complexes are sufficiently stable and undergo two-step degradation processes. The redox behavior of the complexes was evaluated by cyclic voltammetry. Furthermore, the ligand and its complexes were tested for antimicrobial activity against bacterial and fungal strains by determining inhibition zone, minimal inhibitory concentration (MIC) and minimal bactericidal concentration (MBC). The complexes showed moderate antimicrobial activity when tested against Gram +ve and Gram -ve bacterial strains. To obtain insights into the structure of ligand, DFT studies are recorded. The results obtained are quite close to the experimental results. In addition, the energy gap, chemical hardness, softness, electronegativity, electrophilic index and chemical potential were calculated using HOMO, LUMO energy value of ligand.

Role of Inner Nuclear Membrane Protein Complex Lem2-Nur1 in Heterochromatic Gene Silencing.

Heterochromatin in the fission yeast Schizosaccharomyces pombe is clustered at the nuclear periphery and interacts with a number of nuclear membrane proteins. However, the significance and the factors that sequester heterochromatin at the nuclear periphery are not fully known. Here, we report that an inner nuclear membrane protein complex Lem2-Nur1 is essential for heterochromatin-mediated gene silencing. We found that Lem2 is physically associated with another inner nuclear membrane protein, Nur1, and deletion of either lem2 or nur1 causes silencing defect at centromeres, telomeres, and rDNA loci. We analyzed the genome-wide association of Lem2 using ChIP sequencing and we found that it binds to the central core region of centromeres, in striking contrast to Chp1, a component of pericentromeric heterochromatin, which binds H3K9me-rich chromatin in neighboring sequences. The recruitment of Lem2 and Nur1 to silent regions of the genome is dependent on H3K9 methyltransferase, Clr4. Finally, we show that the Lem2-Nur1 complex regulates the local balance between the underln]Snf2/HDAC-containing repressor complex (SHREC) histone deacetylase complex and the anti-silencing protein Epe1. These findings uncover a novel role for Lem2-Nur1 as a key functional link between localization at the nuclear periphery and heterochromatin-mediated gene silencing.

Synthesis, Spectroscopic, X-ray Diffraction and DFT Studies of Novel Benzimidazole Fused-1,4-Oxazepines.

A series of benzimidazole-tethered oxazepine heterocyclic hybrids has been synthesized in good to excellent yields from an N-alkylated benzimidazole 2-carboxaldehyde, which in turn was accomplished from o-phenylenediamine in three good yielding steps. The calculated molecular structure of compounds 2-methyl-4-(2-((phenylimino)methyl)-1H-benzo-[d]imidazol-1-yl)-butan-2-ol 9 and 10 3,3-dimethyl-N-phenyl-1,2,3,5-tetrahydrobenzo-[4,5]imidazo[2,1-c][1,4]oxazepin-5-amine using the B3LYP/6-31 G(d, p) method were found to agree well with their X-ray structures. The charge distributions at the different atomic sites were computed using the natural bond orbital (NBO) method. The regions of electrophilic and nucleophilic reactivity were shown using a molecular electrostatic potential (MEP) map. In addition, the frontier molecular orbitals of these compounds were discussed at the same level of theory. Nonlinear optical (NLO) properties have also been investigated by computational hyperpolarizability studies, and it was found that Compound 9 is the best candidate for NLO applications.

A Sustainable Approach to the Stereoselective Synthesis of Diazaheptacyclic Cage Systems Based on a Multicomponent Strategy in an Ionic Liquid.

The microwave-assisted three-component reactions of 3,5-bis(E)-arylmethylidene]tetrahydro-4(1H)-pyridinones, acenaphthenequinone and cyclic α-amino acids in an ionic liquid, 1-butyl-3-methylimidazolium bromide, occurred through a domino sequence affording structurally intriguing diazaheptacyclic cage-like compounds in excellent yields.

The halotolerant exopolysaccharide-producing Rhizobium azibense increases the salt tolerance mechanism in Phaseolus vulgaris (L.) by improving growth, ion homeostasis, and antioxidant defensive enzymes.

Globally, agricultural productivity is facing a serious problem due to soil salinity which often causes osmotic, ionic, and redox imbalances in plants. Applying halotolerant rhizobacterial inoculants having multifarious growth-regulating traits is thought to be an effective and advantageous approach to overcome salinity stress. Here, salt-tolerant (tolerating 300 mM NaCl), exopolysaccharide (EPS) producing Rhizobium azibense SR-26 (accession no. MG063740) was assessed for salt alleviation potential by inoculating Phaseolus vulgaris (L.) plants raised under varying NaCl regimes. The metabolically active cells of strain SR-26 produced a significant amount of phytohormones (indole-3-acetic acid, gibberellic acid, and cytokinin), ACC deaminase, ammonia, and siderophore under salt stress. Increasing NaCl concentration variably affected the EPS produced by SR-26. The P-solubilization activity of the SR-26 strain was positively impacted by NaCl, as demonstrated by OD shift in NaCl-treated/untreated NBRIP medium. The detrimental effect of NaCl on plants was lowered by inoculation of halotolerant strain SR-26. Following soil inoculation, R. azibense significantly (p ≤ 0.05) enhanced seed germination (10%), root (19%) shoot (23%) biomass, leaf area (18%), total chlorophyll (21%), and carotenoid content (32%) of P. vulgaris raised in soil added with 40 mM NaCl concentration. Furthermore, strain SR-26 modulated the relative leaf water content (RLWC), proline, total soluble protein (TSP), and sugar (TSS) of salt-exposed plants. Moreover, R. azibense inoculation lowered the concentrations of oxidative stress biomarkers; MDA (29%), H2O2 content (24%), electrolyte leakage (31%), membrane stability (36%) and Na+ ion uptake (28%) when applied to 40 mM NaCl-treated plants. Further, R. azibense increases the salt tolerance mechanism of P. vulgaris by upregulating the antioxidant defensive responses. Summarily, it is reasonable to propose that EPS-synthesizing halotolerant R. azibense SR-26 should be applied as the most cost-effective option for increasing the yields of legume crops specifically P. vulgaris in salinity-challenged soil systems.

Exploring the mechanism of interaction of glipizide with DNA: Combined in vitro and bioinformatics approach.

DNA, vital for biological processes, encodes hereditary data for protein synthesis, shaping cell structure and function. Since revealing its structure, DNA has become a target for various therapeutically vital molecules, spanning antidiabetic to anticancer drugs. These agents engage with DNA-associated proteins, DNA-RNA hybrids, or bind directly to the DNA helix, triggering diverse downstream effects. These interactions disrupt vital enzymes and proteins essential for maintaining cell structure and function. Analysing drug-DNA interactions has significantly advanced our understanding of drug mechanisms. Glipizide, an antidiabetic drug, is known to cause DNA damage in adipocytes. However, its extract mechanism of DNA interaction is unknown. This study delves into the interaction between glipizide and DNA utilizing various biophysical tools and computational technique to gain insights into the interaction mechanism. Analysis of UV-visible and fluorescence data reveals the formation of complex between DNA and glipizide. The binding affinity of glipizide to DNA was of moderate strength. Examination of thermodynamic parameters at different temperatures suggests that the binding was entropically spontaneous and energetically favourable. Various experiments such as thermal melting assays, viscosity measurement, and dye displacement assays confirmed the minor grove nature of binding of glipizide with DNA. Molecular dynamics studies confirmed the glipizide forms stable complex with DNA when simulated by mimicking the physiological conditions. The binding was mainly favoured by hydrogen bonds and glipizide slightly reduced nucleotide fluctuations of DNA. The study deciphers the mechanism of interaction of glipizide with DNA at molecular levels.

Trichoderma Inoculation Alleviates Cd and Pb-Induced Toxicity and Improves Growth and Physiology of Vigna radiata (L.).

Heavy metals (HMs) pose a serious threat to agricultural productivity. Therefore, there is a need to find sustainable approaches to combat HM stressors in agriculture. In this study, we isolated Trichoderma sp. TF-13 from metal-polluted rhizospheric soil, which has the ability to resist 1600 and 1200 µg mL-1 cadmium (Cd) and lead (Pb), respectively. Owing to its remarkable metal tolerance, this fungal strain was applied for bioremediation of HMs in Vigna radiata (L.). Strain TF-13 produced siderophore, salicylic acid (SA; 43.4 µg mL-1) and 2,3-DHBA (21.0 µg mL-1), indole-3-acetic acid, ammonia, and ACC deaminase under HM stressed conditions. Increasing concentrations of tested HM ions caused severe reduction in overall growth of plants; however, Trichoderma sp. TF-13 inoculation significantly (p ≤ 0.05) increased the growth and physiological traits of HM-treated V. radiata. Interestingly, Trichoderma sp. TF-13 improved germination rate (10%), root length (26%), root biomass (32%), and vigor index (12%) of V. radiata grown under 25 µg Cd kg-1 soil. Additionally, Trichoderma inoculation showed a significant (p ≤ 0.05) increase in total chlorophyll, chl a, chl b, carotenoid content, root nitrogen (N), and root phosphorus (P) of 100 µg Cd kg-1 soil-treated plants over uninoculated treatment. Furthermore, enzymatic and nonenzymatic antioxidant activities of Trichoderma inoculated in metal-treated plants were improved. For instance, strain TF-13 increased proline (37%), lipid peroxidation (56%), catalase (35%), peroxidase (42%), superoxide dismutase (27%), and glutathione reductase (39%) activities in 100 µg Pb kg-1 soil-treated plants. The uptake of Pb and Cd in root/shoot tissues was decreased by 34/39 and 47/38% in fungal-inoculated and 25 µg kg-1 soil-treated plants. Thus, this study demonstrates that stabilizing metal mobility in the rhizosphere through Trichoderma inoculation significantly reduced the detrimental effects of Cd and Pb toxicity in V. radiata and also enhanced development under HM stress conditions.

Genome wide nucleosome landscape shapes 3D chromatin organization.

The hierarchical chromatin organization begins with formation of nucleosomes, which fold into chromatin domains punctuated by boundaries and ultimately chromosomes. In a hierarchal organization, lower levels shape higher levels. However, the dependence of higher-order 3D chromatin organization on the nucleosome-level organization has not been studied in cells. We investigated the relationship between nucleosome-level organization and higher-order chromatin organization by perturbing nucleosomes across the genome by deleting Imitation SWItch (ISWI) and Chromodomain Helicase DNA-binding (CHD1) chromatin remodeling factors in budding yeast. We find that changes in nucleosome-level properties are accompanied by changes in 3D chromatin organization. Short-range chromatin contacts up to a few kilo-base pairs decrease, chromatin domains weaken, and boundary strength decreases. Boundary strength scales with accessibility and moderately with width of nucleosome-depleted region. Change in nucleosome positioning seems to alter the stiffness of chromatin, which can affect formation of chromatin contacts. Our results suggest a biomechanical "bottom-up" mechanism by which nucleosome distribution across genome shapes 3D chromatin organization.

Early use of oral cholera vaccines as a prime control measure during outbreaks: Necessary but not sufficient.

INTRODUCTION: Despite being a preventable and treatable disease, cholera remains a public health problem in Sudan. The objective of the outbreak investigation was to identify associated risk factors that would help institute appropriate control measures. MATERIAL AND METHODS: A case control study design was chosen to identify the risk factors for cholera in Gadarif State. RESULTS: Multi-variate analysis of identified two risk factors and three preventive factors for cholera in Gadarif City. RISK FACTORS: Buying foods or drinks from street vendors (OR = 71.36), 95 % CI: 16.58-307.14), living in an urban setting (Gadarif City) (OR = 5.38), 95 % CI: 2.10-13.81); and the preventive factors were: Washing hands with water after defecation but without soap (OR = 0.16), 95 % CI: 0.04-0.63) or with soap (OR = 0.01), 95 % CI: 0.00-0.03), washing hands before eating (OR = 0.15), 95 % CI: 0.05-0.51) and taking Oral Cholera Vaccine (OCV) (OR = 0.19, 95 % CI: 0.08-0.44). The effectiveness of OCV (VE) was (Unadjusted VE: 80 %, 95 % CI: 69 %-87 %) or (Adjusted VE = 81.0 %, 95 % CI: 56.0 %-92.0 %). DISCUSSION: Cholera outbreaks, especially in the setting of a complex humanitarian crises, can spread rapidly, resulting in many deaths, and quickly become a public health crisis. Implementation of a community-wide vaccination campaign using OCV as early as possible during the outbreak while implementing other control measures to target hotspots and at-risk populations would expedite halting outbreaks of cholera and save lives.

Management of virulence in Pseudomonas aeruginosa and Serratia marcescens using environmentally-friendly titanium dioxide nanoparticles.

Antimicrobial resistance (AMR), a condition in which the efficacy of antimicrobial drugs in fighting microorganisms is reduced, has become a global challenge. Multidrug resistance (MDR) has been developing in microorganisms, where they can resist multiple medications. In particular, there has been a rise in MDR as well as extensively drug-resistant (XDR) strains of Pseudomonas aeruginosa in some regions, with prevalence rates ranging from 15% to 30%. The application of nanotechnology ranges from diagnostics to drug-delivery systems, revolutionizing healthcare, and improving disease treatment. We aimed to investigate the efficacy of titanium dioxide nanoparticles (TiO2-NPs) against various virulent traits of P. aeruginosa and S. marcescens. More than 50% reduction in the production of virulent pigments of P. aeruginosa was recorded following the treatment of TiO2-NPs. Additionally, elastases and exoproteases were inhibited by 58.21 and 74.36%, respectively. A similar result was observed against the rhamnolipid production and swimming motility of P. aeruginosa. The effect of TiO2-NPs was also validated against another opportunistic pathogen, S. marcescens, where the production of prodigiosin was reduced by 64.78%. Also, a roughly 75% attenuation of proteolytic activity and more than 50% reduction in swarming motility were found. In the control group, the cell surface hydrophobicity was 77.72%, which decreased to 24.67% with the addition of 64 µg ml-1 TiO2-NPs in culture media. The hydrophobicity index of microorganisms is crucial for their initial attachment and the formation of biofilms. In conclusion, TiO2-NPs demonstrated potential in a multi-target approach against P. aeruginosa and S. marcescens, suggesting their advantages in the prevention and treatment of infections. These nanomaterials could have vital importance in the development of novel antibacterial agents to combat drug-resistant bacteria.

Construction and Activity Testing of a Modular Fusion Peptide against Enterococcus faecalis.

The emergence of antibiotic resistance in enterococci is a great concern encountered worldwide. Almost all enterococci exhibit significant levels of resistance to penicillin, ampicillin, semi-synthetic penicillin and most cephalosporins, primarily due to the expression of low-affinity penicillin-binding proteins. The development of new and novel antibacterial agents against enterococci is a significant need of the hour. In this research, we have constructed a modular peptide against Enterococcus faecalis. The enzymatic domain of the constructed peptide BP404 is from the bacteriocin BacL1 and the cell wall binding domain from endolysin PlyV12 of phage ϕ1. The protein BP404 was found to be active against two tested strains of Enterococcus faecalis, with a reduction in cell density amounting to 85% and 65%. The cell wall binding assay confirms the binding of the protein to Enterococcus faecalis, which was not seen towards the control strain Escherichia coli, invariably pointing to the specificity of BP404. To the best of our knowledge, this is one of the first instances of the development of a chimeric peptide against Enterococcus faecalis. This study points out that novel proteins can be genetically engineered against clinically relevant enterococci.

An Enzybiotic Cocktail Effectively Disrupts Preformed Dual Biofilm of Staphylococcus aureus and Enterococcus faecalis.

Multidrug-resistant bacterial infections are on the rise around the world. Chronic infections caused by these pathogens through biofilm mediation often complicate the situation. In natural settings, biofilms are often formed with different species of bacteria existing synergistically or antagonistically. Biofilms on diabetic foot ulcers are formed predominantly by two opportunistic pathogens, Staphylococcus aureus and Enterococcus faecalis. Bacteriophages and phage-based proteins, including endolysins, have been found to be active against biofilms. In this study, we evaluated the activity of two engineered enzybiotics either by themselves or as a combination against a dual biofilm formed by S. aureus and E. faecalis in an inert glass surface. An additive effect in rapidly disrupting the preformed dual biofilm was observed with the cocktail of proteins, in comparison with mono treatment. The cocktail-treated biofilms were dispersed by more than 90% within 3 h of treatment. Apart from biofilm disruption, bacterial cells embedded in the biofilm matrix were also effectively reduced by more than 90% within 3 h of treatment. This is the first instance where a cocktail of engineered enzybiotics has been effectively used to impede the structural integrity of a dual biofilm.

The Bcl-2 family protein bid interacts with the ER stress sensor IRE1 to differentially modulate its RNase activity.

IRE1 is a transmembrane signalling protein that activates the unfolded protein response under endoplasmic reticulum stress. IRE1 is endowed with kinase and endoribonuclease activities. The ribonuclease activity of IRE1 can switch substrate specificities to carry out atypical splicing of Xbp1 mRNA or trigger the degradation of specific mRNAs. The mechanisms regulating the distinct ribonuclease activities of IRE1 have yet to be fully understood. Here, we report the Bcl-2 family protein Bid as a novel recruit of the IRE1 complex, which directly interacts with the cytoplasmic domain of IRE1. Bid binding to IRE1 leads to a decrease in IRE1 phosphorylation in a way that it can only perform Xbp1 splicing while mRNA degradation activity is repressed. The RNase outputs of IRE1 have been found to regulate the homeostatic-apoptotic switch. This study, thus, provides insight into IRE1-mediated cell survival.

Deep Eutectic Solvent (DES)-Mediated One-Pot Multicomponent Green Approach for Naphthalimide-Centered Acridine-1,8-dione Derivatives and Their Photophysical Properties.

An efficient and green methodology to assemble various functionalized naphthalimide-centered acridine-1,8-dione derivatives involving a one-pot multicomponent protocol has successfully been developed. Herein, a variety of aromatic aldehydes, 1,3-diketones, 1,8-naphthanoic anhydride, and hydrazine hydrate have been condensed under a reusable, inexpensive, and biodegradable deep eutectic solvent (DES) of N,N'-dimethyl urea and l-(+)-tartaric acid to obtain the desired targets under operationally mild reaction conditions with outstanding conversions. Strikingly, in this strategy, the DES plays a dual role of a catalyst and solvent and was recycled efficiently in four consecutive runs with no substantial drop in the yield of the desired product. Interestingly, the easy recovery and high reusability of the DES make this simple yet efficient protocol environmentally desirable. Moreover, the preliminary photophysical properties of thus-prepared valuable molecules have also been investigated by ultraviolet-visible (UV-vis) and fluorescence spectroscopy.

Development of Metallo (Calcium/Magnesium) Polyurethane Nanocomposites for Anti-Corrosive Applications.

Long-term corrosion protection of metals might be provided by nanocomposite coatings having synergistic qualities. In this perspective, rapeseed oil-based polyurethane (ROPU) and nanocomposites with calcium and magnesium ions were designed. The structure of these nanocomposites was established through Fourier-transform infrared spectroscopy (FT-IR). The morphological studies were carried out using scanning electron microscopy (SEM) as well as transmission electron microscopy (TEM). Their thermal characteristics were studied using thermogravimetric analysis (TGA). Electrochemical experiments were applied for the assessment of the corrosion inhibition performance of these coatings in 3.5 wt. % NaCl solution for 7 days. After completion of the test, the results revealed a very low icorr value of 7.73 × 10-10 A cm-2, a low corrosion rate of 8.342 × 10-5 mpy, impedance 1.0 × 107 Ω cm2, and phase angle (approx 90°). These findings demonstrated that nanocomposite coatings outperformed ordinary ROPU and other published methods in terms of anticorrosive activity. The excellent anti-corrosive characteristic of the suggested nanocomposite coatings opens up new possibilities for the creation of advanced high-performance coatings for a variety of metal industries.

Heat-induced SIRT1-mediated H4K16ac deacetylation impairs resection and SMARCAD1 recruitment to double strand breaks.

Hyperthermia inhibits DNA double-strand break (DSB) repair that utilizes homologous recombination (HR) pathway by a poorly defined mechanism(s); however, the mechanisms for this inhibition remain unclear. Here we report that hyperthermia decreases H4K16 acetylation (H4K16ac), an epigenetic modification essential for genome stability and transcription. Heat-induced reduction in H4K16ac was detected in humans, Drosophila, and yeast, indicating that this is a highly conserved response. The examination of histone deacetylase recruitment to chromatin after heat-shock identified SIRT1 as the major deacetylase subsequently enriched at gene-rich regions. Heat-induced SIRT1 recruitment was antagonized by chromatin remodeler SMARCAD1 depletion and, like hyperthermia, the depletion of the SMARCAD1 or combination of the two impaired DNA end resection and increased replication stress. Altered repair protein recruitment was associated with heat-shock-induced γ-H2AX chromatin changes and DSB repair processing. These results support a novel mechanism whereby hyperthermia impacts chromatin organization owing to H4K16ac deacetylation, negatively affecting the HR-dependent DSB repair.