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In this investigation, we explored the corrosion inhibition mechanism of an imidazoline quaternary ammonium salt (IQA) on J55 steel in simulated annulus environment through a series of experiments, including electrochemical testing, stress corrosion immersion experiments, and hydrogen permeation testing. Our findings reveal that IQA functions as a mixed-type inhibitor, exerting its inhibitory action through chemical adsorption. Notably, it exhibits a stronger inhibitory effect on the anodic dissolution reaction compared to the cathodic hydrogen evolution reaction. Despite the minor influence of tensile plastic strain on the average inhibition efficiency, it notably exacerbates pitting and initiates stress corrosion cracking. This underscores the limitation of average inhibition efficiency in accurately assessing IQA's efficacy against stress corrosion. Additionally, hydrogen permeation experiments and electrochemical testing demonstrate that plastic strain diminishes IQA's inhibitory effect on the cathodic hydrogen evolution reaction, facilitating hydrogen diffusion into the steel substrate and thereby exacerbating stress corrosion in J55 steel. Consequently, at low IQA inhibitor concentrations (as in this study, 12.5 mg L−1), despite high average inhibition efficiency, it proves ineffective in mitigating stress corrosion.

Cytochrome P450 (CYP450) enzymes comprise a highly diverse superfamily of heme-thiolate proteins that responsible for catalyzing over 90 % of enzymatic reactions associated with xenobiotic metabolism in humans. Accurately predicting whether chemicals are substrates or inhibitors of different CYP450 isoforms can aid in pre-selecting hit compounds for the drug discovery process, chemical toxicology studies, and patients treatment planning. In this work, we investigated in silico studies on CYP450s specificity over past twenty years, categorizing these studies into structure-based and ligand-based approaches. Subsequently, we utilized 100 of the most frequently prescribed drugs to test eleven machine learning-based prediction models which were published between 2015 and 2024. We analyzed various aspects of the evaluated models, such as their datasets, algorithms, and performance. This will give readers with a comprehensive overview of these prediction models and help them choose the most suitable one to do prediction. We also provide our insights for future research trend in both structure-based and ligand-based approaches in this field.

Tyrosine phosphorylation is crucial for controlling normal cell growth, survival, intercellular communication, gene transcription, immune responses, and other processes. protein tyrosine phosphatase (PTP) and protein tyrosine kinases (PTK) can achieve this goal by regulating multiple signaling pathways. Oedaleus decorus asiaticus is an important pest that infests the Mongolian Plateau grassland. We aimed to evaluate the survival rate, growth rate, overall performance, and ovarian developmental morphology of the 4th instar nymphs of O. decorus asiaticus while inhibiting the activity of protein tyrosine phosphatase-1B (PTP1B) and PTK. In addition, the expression and protein phosphorylation levels of key genes in the MAPK signaling pathway and antioxidant enzyme activity were assessed. The results showed no significant differences in survival rate, growth rate, or overall performance between PTP1B inhibitor treatment and control. However, after PTK inhibitor treatment, these indexes were significantly lower than those in the control. The ovarian size of female larvae after 15 days of treatment with PTK inhibitors showed significantly slower development, while female larvae treated with PTP1B exhibited faster ovarian growth than the control group. In comparison to controls and nymphs treated with PTK inhibitors, the expression and phosphorylation levels of key genes in the MAPK signaling pathway under PTP1B inhibitor treatments were significantly higher in 4th instar nymphs. However, reactiveoxygen (ROS) species levels and the activities of NADPH oxidase and other antioxidant enzymes were considerably reduced, although they were significantly greater in the PTK inhibitor treatment. The results suggest that PTP1B and PTK feedback inhibition in the mitogen-activated-protein kinases (MAPK) signal transfer can regulate the physiological metabolism of the insect as well as its developmental rate. These findings can facilitate future uses of PTP1B and PTK inhibitors in controlling insect development to help control pest populations.

Tumor cells voraciously consume nutrients from their environment to facilitate rapid proliferation, necessitating effective strategies to manage nutrient scarcity during tumor growth and progression. A pivotal regulatory mechanism in this context is the Integrated Stress Response (ISR), which ensures cellular homeostasis under conditions such as endoplasmic reticulum stress, the unfolded protein response, and nutrient deprivation. Within the ISR framework, the kinase GCN2 is critical, orchestrating a myriad of cellular processes including the inhibition of protein synthesis, the enhancement of amino acid transport, autophagy initiation, and angiogenesis. These processes collectively enable tumor survival and adaptation under nutrient-limited conditions. Furthermore, GCN2-mediated pathways may induce apoptosis, a property exploited by specific therapeutic agents. Leveraging extensive datasets from TCGA, GEO, and GTEx projects, we conducted a pan-cancer analysis to investigate the prognostic significance of GCN2 expression across diverse cancer types. Our analysis indicates that GCN2 expression significantly varies and correlates with both adverse and favorable prognoses depending on the type of cancer, illustrating its complex role in tumorigenesis. Importantly, GCN2 also modulates the tumor immune microenvironment, influencing immune checkpoint expression and the functionality of immune cells, thereby affecting immunotherapy outcomes. This study highlights the potential of targeting GCN2 with specific inhibitors, as evidenced by their efficacy in preclinical models to augment treatment responses and combat resistance in oncology. These findings advocate for a deeper exploration of GCN2′s multifaceted roles, which could pave the way for novel targeted therapies in cancer treatment, aiming to improve clinical outcomes.

This study presents a novel method for synthesizing carbon nanodots (BC-CNDs) from Bombax ceiba leaf extract via microwave assistance, yielding cost-effective, biodegradable, and water-soluble nanomaterials. Spectroscopic analysis, including FT-IR, UV–Vis, and fluorescence emission spectrophotometry, revealed the distinctive characteristics of BC-CNDs. Additionally, an anti-corrosive coating (BC-CNDs-C) was formulated by blending BC-CNDs with a plasticizer and binder. Quantitative evaluation of BC-CNDs-C showed an impressive inhibitory rate of 92.55% against corrosion. Electrochemical measurements indicated a notable increase in polarization resistance (Rp values: 1782.2 Ω cm2 for P1 to 4778.3 Ω cm2 for P4) and a decrease in corrosion current density (Icorr values: 0.065 μA/cm2 for P1 to 0.010 μA/cm2 for P4) with the incorporation of BC-CNDs, highlighting their effectiveness in enhancing corrosion resistance. Additionally, structural analyses via scanning electron microscopy (SEM) and atomic force microscopy (AFM) confirmed the reliability of BC-CNDs-C as a corrosion barrier. This research contributes to the development of sustainable materials for corrosion protection, addressing corrosion-related challenges in various industrial applications.

The aim of the present work is to optimize the corrosion inhibition process of low-carbon steel in 2.5 M phosphoric acid at different temperatures and inhibitor concentrations. The weight loss method is used to evaluate the corrosion rate in the absence or presence of a corrosion inhibitor. Taguchi dynamic (L16), mathematical regression, and artificial neural networks (ANN) are used during the data processing. The outcomes showed that the %IE increased with inhibitor concentration and temperature up to 50 °C. The Taguchi method showed that the optimum conditions for the corrosion inhibition temperature were found to be 50 °C and a 0.05 M KI concentration. Two mathematical models are proposed to construct a relationship between %IE and independent variables: the exponent model (EM) and the polynomial model (PM). PM was more accurate than EM, with a significant correlation coefficient approaching 0.9851. Temperature had a greater effect on the %IE than inhibitor concentration, which was consistent with Taguchi's findings. In ANN analyses, five networks were suggested: linear, a generalized regression neural network (GRNN), radial basis functions (RBF), and two multi-layer perceptron (MLP) networks. The highest correlation coefficient (0.996) and lower absolute error (0.126) were achieved by MLP 2:2-9-4-1:1.

Background: Angiotensin-converting enzyme 2 (ACE2) is a pivotal molecular nexus linking novel coronavirus disease to breast cancer. In-silico investigations have repurposed carnosine for both these conditions based on its potential ACE2 inhibitory properties. Methods: Utilizing an ACE2 inhibitor screening kit, we determined the inhibitory range of carnosine doses. Subsequently, we examined the effect of carnosine on ACE2 expression in supernatants from various breast cancer cell lines (MCF-7, MDA-MB-231, and EMT-6). Additionally, we compared ACE2 activity in cell line pellets with and without carnosine and a putative ACE2 activator using a fluorometric activity assay kit. Finally, we performed a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay across overlapping concentrations. Results: Carnosine exhibited dose-dependent ACE2 inhibition within the 100–300 mM range. ACE2 expression significantly diminished after exposure to carnosine for 2 and 24 h in MDA-MB-231 and MCF-7 cell lines, respectively. MTT assay unveiled notable antiproliferative effects in MDA-MB-231 (50 % survival at approximately 265 mM) and EMT-6 cell lines (unquantifiable 50 % survival dose). Conversely, the MCF-7 cell line displayed a modest increase in proliferation (Effective concentration 50–186 mM, ∼40 % increased survival). Conclusion: This pioneering study delineates evident dose-dependent ACE2 inhibition by carnosine. Moreover, it unveils the modulatory impact of this ACE2 inhibitor in breast cancer cell lines. Carnosine demonstrated a significant antiproliferative effect on aggressive cell lines while sparing luminal cell lines from substantial toxic or proliferative effects.

As a global metabolic disease, the control and treatment of diabetes have always been the focus of medical research. α-Glucosidase is a key enzyme in regulating blood glucose levels and has important applications in the treatment of diabetes. This review aims to explore the enzyme activity of α-glucosidase and its inhibition mechanism and evaluate the efficacy and limitations of existing inhibitor screening methods. First, the chemical structure, biological activity, and influencing factors of α-glucosidase on diabetes are discussed in detail. Then, the various methods that have been used to screen α-glucosidase inhibitors in recent years are reviewed, including in vivo animal experiments, in vitro experiments, and virtual molecular docking. The experimental principles, advantages, and limitations of each method and their application in discovering new inhibitors are also discussed. Finally, this review emphasizes the importance of developing efficient and safe α-glucosidase inhibitors, summarizes the advantages and disadvantages of various screening models, and proposes future research directions. This review comprehensively examines the enzyme activity of α-glucosidase and the screening methods for α-glucosidase inhibitors, provides an important perspective in the field of diabetes drug discovery and development, and provides a reference for future research.

Sphingosine-1 phosphate (S1P) is a lipid metabolite regulating diverse biological processes, including proliferation, differentiation, migration, and apoptosis, highlighting its physiological and therapeutic significance. Current S1P-based therapeutic approaches primarily focus on modulating the downstream signalling via targeting S1P receptors, however, this is challenged by incomplete receptor internalisation. Sphingosine-1-phosphate lyase (SPL) is a highly conserved enzyme that “gatekeeps” the final step of S1P degradation. Cognisant of the complex ligand and receptor interaction and dynamic metabolic networks, the selective modulation of SPL activity presents a new opportunity to regulate S1P biosynthesis and reveal its role in various systems. Over the past decade, an evolving effort has been made to identify new molecules that could block SPL activity in vitro or in vivo. This review focuses on summarising the current understanding of the reported SPL inhibitors identified through various screening approaches, discussing their efficacy in diverse model systems and the possible mechanism of action. Whilst effective modulation of S1P levels via inhibiting SPL is feasible, the specificity of those inhibitors remains inconclusive, presenting a clear challenge for future implications. Yet, none of the currently available SPL inhibitors is proven effective in elevating S1P levels within the central nervous system. This review article embraces future research focusing on investigating selective SPL inhibitors with high potency and possibly blood-brain-barrier permeability, which would aid the development of new S1P-based therapeutics for neurological disorders.

Hyperuricemia is with growing incidence and of high risk to develop into gout and other metabolic diseases. The key enzyme catalyzing uric acid synthesis, xanthine oxidoreductase (XOR) is a vital target for anti-hyperuricemic drugs, while XOR inhibitors characterized as both potent and safe are currently in urgent need. In this study, a novel small molecule compound, CC15009, was identified as a specific XOR inhibitor. CC15009 exerted strongest in vitro XOR inhibitory activity among current XOR inhibitors. It also showed favorable dose-dependent uric acid-lowering effects in two different XOR substrate-induced hyperuricemic mouse models, which was significantly superior than the current first-line drug, allopurinol. Mechanically, the direct binding of CC15009 against XOR was confirmed by molecular docking and SPR analysis. The inhibition mode was competitive and reversible. Besides, the potential antioxidant activity of CC15009 was indicated by its strong inhibitory activity against the oxidized isoform of XOR, which reduced ROS generation as the byproduct. Regarding the safety concerns of current XOR inhibitors, especially in cardiovascular risks, the safety of CC15009 was comprehensively evaluated. No significant abnormality was observed in the acute, subacute toxicity tests and mini-AMES test. Notably, there was no obvious inhibition of CC15009 against cardiac ion channels, including hERG, Nav1.5, Cav1.2 at the concentration of 30 μM, indicating its lower cardiovascular risk. Taken together, our results supported CC15009 as a candidate of high efficacy and safety profile to treat hyperuricemia through direct XOR inhibition.

Pancreatic cancer, one of the most aggressive malignancies, has no effective treatment due to the lack of targets and drugs related to tumour metastasis. SIRT6 can promote the migration of pancreatic cancer and could be a potential target for antimetastasis of pancreatic cancer. However, highly selective and potency SIRT6 inhibitor that can be used in vivo is yet to be discovered. Here, we developed a novel SIRT6 allosteric inhibitor, compound 11e, with maximal inhibitory potency and an IC50 value of 0.98 ± 0.13 μmol/L. Moreover, compound 11e exhibited significant selectivity against other histone deacetylases (HADC1‒11 and SIRT1‒3) at concentrations up to 100 μmol/L. The allosteric site and the molecular mechanism of inhibition were extensively elucidated by cocrystal complex structure and dynamic structural analyses. Importantly, we confirmed the antimetastatic function of such inhibitors in four pancreatic cancer cell lines as well as in two mouse models of pancreatic cancer liver metastasis. To our knowledge, this is the first study to reveal the in vivo effects of SIRT6 inhibitors on liver metastatic pancreatic cancer. It not only provides a promising lead compound for subsequent inhibitor development targeting SIRT6 but also provides a potential approach to address the challenge of metastasis in pancreatic cancer.

Anaplastic lymphoma kinase (ALK) is an attractive therapeutic target for the treatment of anaplastic large cell lymphoma (ALCL). We identified novel deuterated 2,4-diarylamino pyrimidine compounds as potent ALK inhibitors. The compound 9 (AMX6001) showed better in vitro activity against ALK and NPM-ALK kinase and significantly inhibited proliferation of Karpas299 and SU-DHL-1 cell lines. In vivo efficacy of compound 9 was better than reference standard ceritinib in ALCL Karpas299 mice models. Daily oral treatment of compound 9 (25 mg/kg) induced tumor suppression TGI up to 95.8 % in ALCL models.

The scientific community has long been interested in capsaicin, and the extensive hunt for AChE and BChE enzyme inhibitors is still ongoing. In this investigation analogs of capsaicin, such as the pharmaceutical nonivamide, which is preferred in clinical settings for the topical treatment of pain, were explored in the search for appropriate inhibitors. Thus, to test their inhibitory effect on AChE and BChE, we synthesized a short series of derivatives derived from vanillylamide. Consequently, it was discovered that compounds 12, 34, and 35, which have Ki values in the sub-micromolar concentration range, are especially effective inhibitors. Compound 12 demonstrated dual mixed-type (competitive/uncompetitive) inhibitory activity for both enzymes; compound 34 showed selective mixed-type inhibitory activity for AChE, and compound 35 was found to have selective uncompetitive activity for AChE.

Nsp14 is an RNA methyltransferase (MTase) encoded by all coronaviruses. In fact, many viral families, including DNA viruses, encode MTases that catalyze the methylation of the RNA precap structure, resulting in fully capped viral RNA. This capping is crucial for efficient viral RNA translation, stability, and immune evasion. Our previous research identified nsp14 inhibitors based on the chemical scaffold of its methyl donor − the S-adenosyl methionine (SAM) − featuring a modified adenine base and a substituted arylsulfonamide. However, the binding mode of these inhibitors was based only on docking experiments. To uncover atomic details of nsp14 inhibition we solved the crystal structure of nsp14 bound to STM957. The structure revealed the atomic details of nsp14 inhibition such that the 7-deaza-adenine moiety of STM957 forms specific interactions with Tyr368, Ala353, and Phe367, while the arylsulfonamide moiety engages with Asn388 and Phe506. The large aromatic substituent at the 7-deaza position displaces a network of water molecules near the adenine base. Surprisingly, this was recently observed in the case of an unrelated monkeypox MTase VP39, where the 7-deaza modified SAH analogs also displaced water molecules from the vicinity of the active site.

A small library of arylsulfonamido-alkyl sulfamates was prepared by a two-step synthesis from readily available starting materials. The compounds were tested for their ability to inhibit bovine carbonic anhydrase II. Several of them were found as good competitive inhibitors holding Ki values as low as Ki = 0.9 μM (compound 47b). The activity was influenced by the substitution pattern of the arylsulfonamide moiety as well as the length of the spacer to the distal sulfamate group. Molecular docking studies were used to substantiate these findings. For the aryl-substituted analogues, the increase in inhibitory activity for compounds with a shorter spacer can be explained by stabilization via aromatic π-interactions. For the cyclopropyl or methylsulfonyl substituted analogues, their inhibitory activity can be attributed to their reduced steric hindrance. These results provide a basis for designing effective CA II inhibitors.

Background: Isolated acquired clotting factor deficiencies (ACFDs) are mainly caused by the existence of anti-factor antibodies or adsorption of clotting factors onto substances such as amyloid. Besides acquired factor (F)VIII deficiency (acquired hemophilia A), the remaining factor deficiencies are rare and diverse, posing challenges in both diagnosis and management. Objectives: To describe different features of isolated ACFDs to improve our understanding of these diseases and provide practical recommendations for their management. Methods: Clinical characteristics of patients with isolated acquired FII, FV, FIX, FX, FXI, FXII, FXIII, and von Willebrand factor deficiencies were collected from a single center between July 1997 and December 2021 and analyzed retrospectively. Results: A total of 54 rare isolated ACFD patients were enrolled in our study, mainly including 20 acquired FV deficiency patients and 16 acquired FX deficiency patients. The median age at diagnosis of all rare isolated ACFD patients was 55 years. The median time to diagnose all rare isolated ACFD patients was 60 days. Ten (18.5%) rare isolated ACFD patients had no bleeding and 2 (3.7%) rare isolated ACFD patients showed venous thromboembolism. Hemostatic treatment was applied to 41 (41/54; 75.9%) rare isolated ACFD patients. Thirty-seven (68.5%) rare isolated ACFD patients received immunosuppressive therapy, and 10 (18.5%) rare isolated ACFD patients received chemotherapy targeting primary diseases. Twenty-two (61.9%) rare isolated ACFD patients achieved complete remission, and 9 (21.4%) rare isolated ACFD patients died. Conclusion: Rare isolated ACFDs are underestimated, associated with delayed diagnosis, and lack effective therapy. Clinicians should raise awareness for recognizing and managing rare isolated ACFD patients to avoid morbidity and mortality.

Diabetes mellitus (DM) is a metabolic disorder characterized by hyperglycemia, with its prevalence linked to both genetic predisposition and environmental factors. Epigenetic modifications, particularly through histone deacetylases (HDACs), have been recognized for their significant influence on DM pathogenesis. This review focuses on the classification of HDACs, their role in DM and its complications, and the potential therapeutic applications of HDAC inhibitors. HDACs, which modulate gene expression without altering DNA sequences, are categorized into four classes with distinct functions and tissue specificity. HDAC inhibitors (HDACi) have shown efficacy in various diseases, including DM, by targeting these enzymes. The review highlights how HDACs regulate β-cell function, insulin sensitivity, and hepatic gluconeogenesis in DM, as well as their impact on diabetic cardiomyopathy, nephropathy, and retinopathy. Finally, we suggest that targeted histone modification is expected to become a key method for the treatment of diabetes and its complications. The study of HDACi offers insights into new treatment strategies for DM and its associated complications.

The development of new anticancer agents is one of the most urgent topics in drug discovery. Inhibition of molecular chaperone Hsp90 stands out as an approach that affects various oncogenic proteins in different types of cancer. These proteins rely on Hsp90 to obtain their functional structure, and thus Hsp90 is indirectly involved in the pathophysiology of cancer. However, the most studied ATP-competitive inhibition of Hsp90 at the N-terminal domain has proven to be largely unsuccessful clinically. Therefore, research has shifted towards Hsp90 C-terminal domain (CTD) inhibitors, which are also the focus of this study. Our recent discovery of compound C has provided us with a starting point for exploring the structure-activity relationship and optimising this new class of triazole-based Hsp90 inhibitors. This investigation has ultimately led to a library of 33 analogues of C that have suitable physicochemical properties and several inhibit the growth of different cancer types in the low micromolar range. Inhibition of Hsp90 was confirmed by biophysical and cellular assays and the binding epitopes of selected inhibitors were studied by STD NMR. Furthermore, the most promising Hsp90 CTD inhibitor 5x was shown to induce apoptosis in breast cancer (MCF-7) and Ewing sarcoma (SK-N-MC) cells while inducing cause cell cycle arrest in MCF-7 cells. In MCF-7 cells, it caused a decrease in the levels of ERα and IGF1R, known Hsp90 client proteins. Finally, 5x was tested in zebrafish larvae xenografted with SK-N-MC tumour cells, where it limited tumour growth with no obvious adverse effects on normal zebrafish development.

Aminoalcohols were converted into the corresponding enantiomeric phenylsulfonamide sulfamates. These compounds proved to be inhibitors of carbonic anhydrase II. Interestingly, a sulfamate derived from (S)-tryptophan was no inhibitor at all while its (R) configurated enantiomer was an excellent inhibitor of carbonic anhydrase II (CA II). A rationale can be deduced from molecular modeling studies. The sulfamates derived from (R) or (S) proline held very low inhibition constants for this enzyme as Ki = 0.77 μM and 0.70 μM, respectively.

Hematopoietic cell kinase (Hck), a non-receptor tyrosine kinase belonging to the Src kinase family, is intricately linked to the pathogenesis of numerous human diseases, with a particularly pronounced association with cancer. Hck not only directly impacts the proliferation, migration, and apoptosis of cancer cells but also interacts with JAK/STAT, MEK/ERK, PI3K/AKT, CXCL12/CXCR4, and other pathways. Hck also influences the tumor microenvironment to facilitate the onset and progression of cancer. This paper delves into the functional role and regulatory mechanisms of Hck in various solid tumors. Additionally, it explores the implications of Hck in hematological malignancies. The review culminates with a summary of the current research status of Hck inhibitors, the majority of which are in the pre-clinical phase of investigation. Notably, these inhibitors are predominantly utilized in the therapeutic management of leukemia, with their combinatorial potential indicating promising avenues for future research. In conclusion, this review underscores the significance of the mechanism of Hck in solid tumors. This insight is crucial for comprehending the current research trends regarding Hck: targeted therapy against Hck shows great promise in both diagnosis and treatment of malignant tumors. Further investigation into the role of Hck in cancer, coupled with the development of specific inhibitors, has the potential to revolutionize approaches to cancer treatment.

Neuroimmune and neurodegenerative ailments impose a substantial societal burden. Neuroimmune disorders involve the intricate regulatory interactions between the immune system and the central nervous system. Prominent examples of neuroimmune disorders encompass multiple sclerosis and neuromyelitis optica. Neurodegenerative diseases result from neuronal degeneration or demyelination in the brain or spinal cord, such as Alzheimer's disease, Parkinson's disease, Huntington's disease, and amyotrophic lateral sclerosis. The precise underlying pathogenesis of these conditions remains incompletely understood. Ferroptosis, a programmed form of cell death characterised by lipid peroxidation and iron overload, plays a pivotal role in neuroimmune and neurodegenerative diseases. In this review, we provide a detailed overview of ferroptosis, its mechanisms, pathways, and regulation during the progression of neuroimmune and neurodegenerative diseases. Furthermore, we summarise the impact of ferroptosis on neuroimmune-related cells (T cells, B cells, neutrophils, and macrophages) and neural cells (glial cells and neurons). Finally, we explore the potential therapeutic implications of ferroptosis inhibitors in diverse neuroimmune and neurodegenerative diseases.

To investigate the mechanism of inhibition of spontaneous combustion of coal by degradation of white-rot fungus, the changes of macroscopic oxidizing characteristics and microstructure of the degraded coal were investigated by the programmed temperature-raising test and the in situ Fourier-transform infrared spectroscopy experiments. The difference in gas production between the degraded coal and the blank samples indicated that the degradation inhibited the oxidation process of coal, and the intensity of the inhibition effect was different at different oxidation stages. The strongest inhibition effect was found in the accelerated oxidation stage, i.e. 80–140 °C. To further analyze the micro-mechanism of the degradation of Phanerochaete chrysosporium affecting the spontaneous combustion of coal, the relative contents of active functional groups in coal samples were compared. The results showed that the degradation affected the relative contents of hydroxyl, aliphatic hydrocarbon, and oxygenated functional groups in coal. Among them, the most significant changes of –OH and –CO- were observed at 80–140 °C. Thus, it was analyzed that Phanerochaete chrysosporium could degrade the macromolecular structure of coal by generating biological enzymes to reduce the number of oxidizable functional groups such as –OH, –CH2, –CH3, –CO-, and so on, thus reducing the risk of spontaneous combustion of coal.

Triggering receptor expressed on myeloid cells 1 (TREM1) is a cell surface receptor expressed on neutrophils, monocytes and some tissue macrophages, where it functions as an immunoregulator that controls myeloid cell responses. The activation of TREM1 is suggested to be an upregulation-based, ligands-induced and structural multimerization-mediated process, in which damage- and pathogen-associated molecular patterns play important roles. Activated TREM1 initiates an array of downstream signaling pathways that ultimately result in the production of pro-inflammatory cytokines and chemokines, whereby it functions as an amplifier of inflammation and is implicated in the pathogenesis of many inflammation-associated diseases. Over the past decade, there has been growing evidence for the involvement of TREM1 overactivation in tumor stroma inflammation and cancer progression. Indeed, it was shown that TREM1 promotes tumor progression, immunosuppression, and resistance to therapy by activating tumor-infiltrating myeloid cells. TREM1-deficiency or blockade provide protection against tumors and reverse the resistance to anti-PD-1/PD-L1 therapy and arginine-deprivation therapy in preclinical models. Here, we first review the structure, activation modes and signaling pathways of TREM1 and emphasize the role of soluble TREM1 as a biomarker of infection and cancer. We then focus on the role of TREM1 in cancer and systematically summarize its expression patterns, upregulation mechanisms and functions in tumor development and progression. Lastly, we discuss the therapeutic prospects of TREM1 inhibition, via effective pharmacological inhibitors, in treating cancer and other diseases.

Eukaryotic elongation factor 1A (eEF1A) is among the most abundant proteins in eukaryotic cells. Evolutionarily conserved across species, eEF1A is in charge of translation elongation for protein biosynthesis as well as a plethora of non-translational moonlighting functions for cellular homeostasis. In malignant cells, however, eEF1A becomes a pleiotropic driver of cancer progression via a broad diversity of pathways, which are not limited to hyperactive translational output. In the past decades, mounting studies have demonstrated the causal link between eEF1A and carcinogenesis, gaining deeper insights into its multifaceted mechanisms and corroborating its value as a prognostic marker in various cancers. On the other hand, an increasing number of natural and synthetic compounds were discovered as anticancer eEF1A-targeting inhibitors. Among them, plitidepsin was approved for the treatment of multiple myeloma whereas metarrestin was currently under clinical development. Despite significant achievements in these two interrelated fields, hitherto there lacks a systematic examination of the eEF1A protein in the context of cancer research. Therefore, the present work aims to delineate its clinical implications, molecular oncogenic mechanisms, and targeted therapeutic strategies as reflected in the ever expanding body of literature, so as to deepen mechanistic understanding of eEF1A-involved tumorigenesis and inspire the development of eEF1A-targeted chemotherapeutics and biologics.

A by-product of the making of essential oil from Melaleuca leaves can be re-extracted to produce an inhibitor. Melaleuca leaves extract (MLE), as an alternative corrosion inhibitor, was employed to protect low-carbon steel (LCS) in a sulfuric acid medium. Adsorption and corrosion inhibition were examined using electrochemical tests. MLE functioned as a mixed-type inhibitor with an optimal inhibitory efficacy of 98.99%. The inhibition by MLE on LCS was based on the Temkin adsorption isotherm and physisorption. The study demonstrated the potential of MLE derived from biomass by-product as a nature-friendly corrosion inhibitor that offers new insights and opportunities.

The corrosion inhibitory effect of banana peel extract on mild steel in a CO2 corrosion environment is studied using weight loss method. The corrosion mechanism is studied with respect to process parameters such as the concentration of the extract, pH, temperature, and immersion time. The extract production is done using maceration method, while FTIR analysis is used to confirm the constituents of the chemical functional groups. The morphology of the corroded coupons’ surface examines SEM microscopy. The results show that the respective corrosion rate increase of 0.184–0.347 mgcm−2h−1 and 0.128–0.354 mgcm−2h−1 are obtained when temperature and immersion time increased from 35 to 75 °C and 48 to 240 h, respectively. Also, a decrease in corrosion rate of 1.01–0.128 mgcm−2h−1 and 0.035–0.0 is noted when the concentration and pH increased from 0.0001 to 1.0 g/l and 3–12, respectively. Changes in these respective experimental parameters yielding corrosion inhibitory efficiencies of (98.0–95.1), (99.1–96.0), (96.1–98.0) and (99.1–100) %. FTIR analysis confirmed the presence of electron copious functional groups such as alkane, amine, alcohol, carboxylic acid, ester and nitro compound that contain O2 and N2 atoms that can donate lone pair electrons and bind metal ions. The SEM micrographs indicated that more severity of the corrosion effects is associated with low pH and high temperature conditions. That is in good agreement with corrosion test results. Hence, a strong correlation is established between the process conditions and the corrosion mechanism. It therefore concludes that banana peel has potential for CO2 corrosion mitigation.

The SARS-CoV-2, responsible for the COVID-19 pandemic, poses a significant threat to global healthcare. Peptide and peptide-based inhibitors, known for their safety, efficacy, and selectivity, have recently emerged as promising candidates for treating late-developing viral infections. In this study, three peptides were selected to target different stages of viral invasion, specifically ACE2 and S protein binding, as well as membrane fusion. The objective was to assess their ability to impede the entry of the SARS-CoV-2 Spike pseudotyped virus. Our findings revealed that a combination of these three peptides demonstrated enhanced antiviral effects. This outcome substantiates the feasibility of developing effective peptide combinations to combat diseases related to SARS-CoV-2. Moreover, the three-peptide combinations, designed to target multiple aspects of SARS-CoV-2 viral entry, exhibited heightened viral inhibition and broad-spectrum antiviral properties.

Sirtuins (SIRTs) represent a class of nicotinamide adenine dinucleotide (NAD+)-dependent protein deacetylases that exert a crucial role in cellular signal transduction and various biological processes. The mammalian sirtuins family encompasses SIRT1 to SIRT7, exhibiting therapeutic potential in counteracting cellular aging, modulating metabolism, responding to oxidative stress, inhibiting tumors, and improving cellular microenvironment. These enzymes are intricately linked to the occurrence and treatment of diverse pathological conditions, including cancer, autoimmune diseases, and cardiovascular disorders. Given the significance of histone modification in gene expression and chromatin structure, maintaining the equilibrium of the sirtuins family is imperative for disease prevention and health restoration. Mounting evidence suggests that modulators of SIRTs play a crucial role in treating various diseases and maintaining physiological balance. This review delves into the molecular structure and regulatory functions of the sirtuins family, reviews the classification and historical evolution of SIRTs modulators, offers a systematic overview of existing SIRTs modulation strategies, and elucidates the regulatory mechanisms of SIRTs modulators (agonists and inhibitors) and their clinical applications. The article concludes by summarizing the challenges encountered in SIRTs modulator research and offering insights into future research directions.

Myocardial fibrosis is a significant pathological basis of heart failure. Overactivation of the ERK1/2 and JNK1/2 signaling pathways of MAPK family members synergistically promotes the proliferation of myocardial fibroblasts and accelerates the development of myocardial fibrosis. In addition to some small molecule inhibitors and Western drugs, many Chinese medicines can also inhibit the activity of ERK1/2 and JNK1/2, thus slowing down the development of myocardial fibrosis, and are generally safe and effective. However, the specific biological mechanisms of ERK1/2 and JNK1/2 signaling pathways in myocardial fibrosis still need to be fully understood, and there is no systematic review of existing drugs and methods to inhibit them from improving myocardial fibrosis. This study aims to summarize the roles and cross-linking mechanisms of ERK1/2 and JNK1/2 signaling pathways in myocardial fibrosis and to systematically sort out the small-molecule inhibitors, Western drugs, traditional Chinese medicines, and non-pharmacological therapies that inhibit ERK1/2 and JNK1/2 to alleviate myocardial fibrosis. In the future, we hope to conduct more in-depth research from the perspective of precision-targeted therapy, using this as a basis for developing new drugs that provide new perspectives on the prevention and treatment of heart failure.

Urinary extracellular vesicles (uEVs) play important roles in physiologic condition and various renal/urological disorders. However, their roles in kidney stone disease remain unclear. This study aimed to examine modulatory effects of large and small uEVs derived from normal human urine on calcium oxalate (CaOx) crystals (the main component in kidney stones). After isolation, large uEVs, small uEVs and total urinary proteins (TUPs) with equal (protein equivalent) concentration were added into various crystal assays to compare with the control (without uEVs or TUPs). TUPs strongly inhibited CaOx crystallization, growth, aggregation and crystal-cell adhesion. Large uEVs had lesser degree of inhibition against crystallization, growth and crystal-cell adhesion, and comparable degree of aggregation inhibition compared with TUPs. Small uEVs had comparable inhibitory effects as of TUPs for all these crystal assays. However, TUPs and large uEVs slightly promoted CaOx invasion through extracellular matrix, whereas small uEVs did not affect this. Matching of the proteins reported in six uEVs datasets with those in the kidney stone modulator (StoneMod) database revealed that uEVs contained 18 known CaOx stone modulators (mainly inhibitors). These findings suggest that uEVs derived from normal human urine serve as CaOx stone inhibitors to prevent healthy individuals from kidney stone formation.

Earlier studies had shown the potential of modified pentacyclic triterpenes as possible inhibitors of carbonic anhydrase II (CA II). In an extension of our earlier studies, betulin, betulinic acid and, for comparison purposes, glycyrrhetinic acid, ursolic acid and oleanolic acid were therefore converted into the respective acetates and linked to either taurinamide or de-acetylated acetazolamide via a variable linker. In particular, the derivatives 8 and 18 derived from betulinic acid or betulin and provided with a long spacer were found to be strong competitive inhibitors of CA II, thereby holding Ki = 1.27 and 0.20 μM, respectively.

Tea polyphenols possess anti-obesity properties and reduce TMAO levels. However, the variability of tea polyphenols under different processing methods and their preventive efficacy requires further exploration. This study systematically evaluated the antioxidant, hypoglycemic, and hypolipotropic enzyme capacities of GT, YT and DT through UPLC-ESI-MS/MS analysis of catechin profiles. OPLS, correlation analysis, and molecular docking were employed to investigate the compounds and inhibitory mechanisms targeting hypoglycemic, hypolipidemic, and TMAO-producing enzymes. GT exhibited significantly lower IC50 values for biological activity and higher catechins contents compared to YT and DT (p

Sulphuric acid (H2SO4) is widely used in various industrial processes, including fertilizer production. However, its highly corrosive nature poses a significant challenge to the materials used for transport and storage, particularly metals and alloys. This review provides an overview of corrosion types in iron and nickel-based alloys, commonly employed for handling sulphuric acid. The paper discusses alloy selection based on their corrosion behavior in different H2SO4 concentrations, temperatures, and harsh conditions such as erosion-corrosion and presence of contaminants. Additionally, it highlights the use of inhibitors and polymeric coatings for corrosion protection. Finally, the paper outlines future research directions for corrosion protection of alloys in sulphuric acid environments.

JAK2 transmits signals of several important cytokines, such as growth hormone and erythropoietin. The interest toward the therapeutic targeting of JAK2 was boosted in 2005, when the somatic JAK2 V617F mutation, responsible for the majority of myeloproliferative neoplasms (MPNs) was discovered. JAK2 inhibitors have been approved for MPN therapy and they are effective in alleviating symptoms and improving the quality of life of the patients, but they do not lead to molecular remission. This calls for the discovery of new compounds for JAK2-targeted therapeutic approaches. Here we describe the development of a fluorescence-based activity assay for the screening of versatile inhibitor types against JAK2. The assay was utilized to screen a diverse set of small molecule weight natural products and the assay performance was compared to that of differential scanning fluorimetry. We identified 37 hits and further analysis of the most potent hits revealed that most of them displayed non-ATP competitive binding modes. The hits were profiled against other JAK family members and showed distinctive selectivity profiles. The developed assay is consistent, simple and inexpensive to use, and can be utilized for inhibitor screening of diverse compound classes against all JAK family members.

Corrosion induced by aqueous environments containing carbon dioxide (CO2) is a well-documented issue in the oil and gas industries, particularly affecting transportation via steel pipelines. Operational conditions during transportation, including temperature, flow rate, and solution chemistry, significantly influence the corrosion inhibition mechanism. In this study, the corrosion inhibition behavior of API 5L X52 steel in a 3.5 wt% NaCl brine solution saturated with carbon dioxide was investigated using 1, 3-diazole glyoxaline (DG) as an organic inhibitor. Both gravimetric and electrochemical methods were employed to assess corrosion rates and inhibitor efficiency across various temperatures, inhibitor concentrations, and rotational speeds. The outcomes showed that inhibition efficiency increased with inhibitor concentration and temperature. From weight loss measurements, the maximum inhibition efficiency was 98.58 % at 3 × 10−4 M of DG and 60 °C. The polarization investigations showed a reduction in the anodic and cathodic curves in the presence of the inhibitor. This suggested a mixed-type inhibition mechanism. The electrochemical impedance spectroscopy results showed an improvement in charge transfer resistance due to the formation of a protective layer on the metal surface. In addition, AFM, SEM, contact angle, hardness, and roughness measurements proved the enhancement in surface morphology due to the presence of DG.

Resveratrol is a natural phenolic compound that belongs to stilbenoid group found in diverse plants. Health benefits and therapeutic potentials of resveratrol have been widely recognized in various diseases. In kidney stone disease, it can alleviate oxalate-induced hyperproduction of free radicals in renal epithelial cells. Nevertheless, its direct effects on calcium oxalate (CaOx) crystal, which is the major stone component, remained unclear. This study therefore addressed the direct effects of resveratrol (at 1, 10 or 100 μM) on each step of CaOx kidney stone formation. The results revealed that resveratrol had no significant effects on CaOx crystallization. However, resveratrol significantly decreased CaOx crystal growth and adhesion to renal epithelial cells at all concentrations, and induced crystal internalization into the cells (a process related to crystal degradation by endolysosomes) in a concentration-dependent manner. On the other hand, resveratrol promoted crystal aggregation. These data indicate that resveratrol serves as a dual modulator on CaOx stone formation. While it inhibits CaOx stone development by reducing crystal growth and adhesion to renal cells and by inducing crystal internalization into the cells, resveratrol promotes crystal aggregation, which is one of the mechanisms leading to kidney stone formation.

In this study the firstly study reported on the use of plum, cherry, nectarine and apple pomace extract as corrosion inhibitors of steel in water solution. Potentiodynamic polarization study showed that extracts act as a mixed type inhibitors with dominant cathodic effect. Linear polarization resistance method (LRP) assesses the time-related effect of inhibitors during open circuit potential corrosion. The results show that the inhibitory efficiency of our extract increases with increasing time formation protective film to reach 99 % in a concentration of 500 ppm. LC - MS and FTIR spectroscopy techniques can be concluded that several water-soluble interaction products of chemical reaction in NaCl are identified namely flavanol–anthocyanin and flavanol-aldehyde adducts. Subsequently, the iron-mediated complexation and oxidation of the extract components (flvonoids) in the aqueous solution were explored using UV-spectrophotometric and HPLC methods. With the passage of time, iron-mediated oxidative degradation and coupling reactions occurred, resulting in the production of hydroxybenzoic acid derivatives. Consequently, the inhibition decreased after 24 h. The chemisorption type of interaction of the product formed in the inhibited solution forming the adsorption-polymerization layer with the steel surface is established. Based on the quantum-chemically calculated parameters of the electronic structure of flavanol–anthocyanin and flavanol-aldehyde adducts, it was established for the first time that the combination of reactive fragments in them, which are spatially located in different planes with a higher quantity of hydroxyl groups, increases their adsorption activity and, as a result, their inhibitory capacity.

ABSTRACT: Chicken diet essentially relies on soybean as the major source of proteins but there are increasing efforts to identify other protein-rich feedstuffs. Of these, some pea cultivars constitute interesting sources of proteins, although some of them contain antinutritional factors that may compromise the digestibility of their protein content. Consequently, chickens exhibit low performance, while undigested compounds rejected in feces have a negative environmental impact. In this article, we analyzed the intestinal content of chickens fed a pea diet (Pisum sativum) to decipher the mechanisms that could explain such a low digestibility. Using gelatin zymography, we observed that the contents of chicken fed the pea diet exhibit altered proteolytic activities compared with intestinal contents from chickens fed a rapeseed, corn, or soybean diet. This pea-specific profile parallels the presence of a 34 kDa protein band that resists proteolysis during the digestion process. Using mass spectrometry analysis, we demonstrated that this band contains the pea-derived Bowman-Birk protease inhibitor (BBI) and 3 chicken proteases, the well-known chymotrypsinogen 2-like (CTRB2) and trypsin II-P39 (PRSS2), and the yet uncharacterized trypsin I-P38 (PRSS3). All 3 proteases are assumed to be protease targets of BBI. Molecular modeling of the interaction of pea BBI with PRSS2 and PRSS3 trypsins reveals that electrostatic features of PRSS3 may favor the formation of a BBI-PRSS3 complex at physiological pH. We hypothesize that PRSS3 is specifically expressed and secreted in the intestinal lumen to form a complex with BBI, thereby limiting its inhibitory effects on PRSS2 and chymotrypsinogen 2-like proteases. These data clearly demonstrate that in chickens, feedstuff containing active pea BBI affects intestinal proteolytic activities. Further studies on the effects of BBI on the expression of PRSS3 by digestive segments will be useful to better appreciate the impact of pea on intestine physiology and function. From these results, we suggest that PRSS3 protease may represent an interesting biomarker of digestive disorders in chickens, similar to human PRSS3 that has been associated with gut pathologies.

The role of inhibitor behavior in abnormal growth of Goss grains during secondary recrystallization was studied in combination with experimental observation and phase-field model simulation in grain-oriented silicon steel. The frequency advantages of both HE (high energy) and CSL (coincidence site lattice) grain boundaries around Goss grains over the matrix were identified, with frequency advantages of ∼15% and ∼2% respectively. The HE grain boundary was supposed to play a more important role in abnormal grain growth over CSL grain boundary in this study. The boundary character distribution was necessary but not sufficient for the abnormal growth of Goss grains. Appropriate inhibitor behavior was a prerequisite for secondary recrystallization. The initial content and stability of inhibitor played a key role in stabilizing the matrix, which guaranteed beneficial fine grains around Goss grains. While if the inhibitor force rapidly declined, matrix grains might grow obviously, resulting in coarsened grain colonies with Cube, {112}, {111}, {411}and {210} orientation, which further hindered the abnormal growth of Goss grains. The candidate Goss grains with different misorientations competed with each other during secondary recrystallization and the exact Goss grain exhibited an obvious growth advantage. Only with an appropriate pinning force and grain boundary character, perfect secondary recrystallization can be achieved. The present findings can provide guidance to understand and precise control of abnormal grain growth phenomenon.

A series of chromone-thiazolidine-2,4-dione derivatives (e1 ∼ 28) were synthesized and screened for their α-glucosidase inhibitory. All synthetic derivatives presented excellent α-glucosidase inhibitory with IC50 values ranging from 2.40 ± 0.11 to 5.66 ± 0.15 μM, comparing to positive control acarbose (IC50 value: 640.57 ± 5.13 μM). Among them, compound e28 displayed the strongest α-glucosidase inhibitory (IC50 value: 2.40 ± 0.11), ∼267 times stronger than positive control acarbose. Kinetic studies revealed that compound e28 was a reversible non-competitive inhibitor. CD spectra and 3D fluorescence spectra results explained that compound e28 changed the conformational changes of α-glucosidase. Molecular docking simulated the binding between compound e28 and α-glucosidase. In vitro cytotoxicity assay ascertained the good security of e28.

TET proteins (methylcytosine dioxygenases) play an important role in the regulation of gene expression. Dysregulation of their activity is associated with many serious pathogenic states such as oncological diseases. Regulation of their activity by specific inhibitors could represent a promising therapeutic strategy. Therefore, this review describes various types of TET protein inhibitors in terms of their inhibitory mechanism and possible applicability. The potential and possible limitations of this approach are thoroughly discussed in the context of TET protein functionality in living systems. Furthermore, possible therapeutic strategies based on the inhibition of TET proteins are presented and evaluated, especially in the field of oncological diseases.

The acyl-acyl carrier protein synthetase enzyme enables some bacteria to scavenge free fatty acids from the environment for direct use in lipids. This fatty acid recycling pathway can help pathogens circumvent fatty acid synthase (FAS) inhibition with established antibiotics and those in clinical development. AasS enzymes are surprisingly hard to identify as they show high sequence similarity to other adenylate forming enzymes, and only a handful have been correctly annotated to date. Four recently discovered AasS enzymes from Gram negative bacteria, Chlamydia trachomatis, Neisseria gonorrhoeae, and Alistipes finegoldii, form distinct clusters in protein sequence similarity networks and have varying substrate preferences. We previously synthesized C10-AMS, an inhibitor of AasS that mimics the acyl-AMP reaction intermediate. Here we tested its ability to be broadly applicable to enzymes in this class, and found it inhibits all four newly annotated AasS enzymes. C10-AMS therefore provides a tool to study the role of AasS in fatty acid recycling in pathogenic bacteria as well as offers a platform for antibiotic development.

In the marine high-pressure low-temperature environment, it is difficult to regulate the low-temperature rheology of the drilling fluid, and the spilled natural gas is easy to generate solid gas hydrate in the wellbore, causing problems such as wellbore blockage and increasing the risk of safe drilling operations. Although there are many researches on the invasion process of drilling fluid and the development of new hydrate inhibition, there is still a lack of research on the inhibition system suitable for drilling fluid. Therefore, this paper uses the self-developed hydrate formation evaluation experimental device to simulate and analyze the effect of inhibitors in reservoir environment and optimize the scheme of drilling fluid inhibition system. The results show that: (1) Through the improvement of the experimental device of water bath methane hydrate (MH) evaluation, the accuracy and parallel control of the equipment are enhanced, and the methane hydrate formed by sea water (SW) is less than that of distilled water (DW), and the structure of methane hydrate formed by distilled water is more compact. (2) Through the evaluation experiment of single inhibitor A3, PAC and CMC inhibition system, it was found that A3 had the best inhibition effect, and when the inhibitor concentration was 1.5 wt%, it had the best inhibition effect. (3) The influence of clay types on the formation of methane hydrate is also significantly different. Bentonite soil Red (BSR) has better inhibition performance than Bentonite soil Yellow (BSY), and its ' hut ' structure formed at low temperature is the reason for the formation of methane hydrate. (4) The inhibition ability of A3 inhibitor in BSY system and BSR system solution in general, the addition of KCl can play a strong synergistic inhibition ability with A3 in BSR system, and its electric field reduces the activation energy of water molecules as well as the consumption of free water is the reason to reduce the generation of methane hydrate.

Protection performance of admixed citronella and myrrh essential oil extract (CNM) on the corrosion resistance of high carbon steel (HCS) in 3 M of CH3COOH and C6H8O7 solution was evaluated by potentiodynamic polarization, open circuit potential measurement, weight loss measurement, x-ray diffractometry and ATF-FTIR spectroscopy. Results showed CNM performed effectively in CH3COOH with optimal inhibition of 87.47% and 80.12% at 1.67% concentration from potentiodynamic polarization and weight loss. CNM performed poorly in C6H8O7 solution with highest value of 41.29% and 43.81% at 1.67% CNM concentration from both tests. In both acids inhibition efficiency increased with increase in CNM concentration coupled with the exhibition of mixed-type inhibition effect. Open circuit potential plots show CNM significantly reduces the activation barrier for HCS to corrode wherewith the plots in the presence of CNM extract where significantly electropositive compared to the plot from C6H8O7 solution without CNM. In CH3COOH, the action of protonated CNM molecules and CH3CO2− anions results in the formation of complexes that increases the reactivity of HCS surface and its thermodynamic tendency to corrode despite effective inhibition performance. X-ray diffractometry shows admixed extract caused significant decrease in intensity/counts for diffraction peaks of Fe2O3 and Fe3O4 compounds on the spectrum plots compared to the plots without the extracts. ATF-FTIR spectroscopy shows significant reduction in transmittance at specific range of wavenumbers occurred within CNM/CH3COOH solution after corrosion, and on HCS surface after corrosion in the presence of the extracts compared to CNM/CH3COOH before corrosion. This contrast the results obtained from CNM/C6H8O7 solution.

In order to break through the bottleneck of high energy consumption in the production of traditional grain-oriented electrical steel, this paper creatively proposes a new composition system of grain-oriented electrical steel with Cu-rich precipitates as main inhibitor. In this research, the microstructure, texture, precipitates and decarburization effect of the primary recrystallization samples are analyzed in the process of decarburization annealing treatment at 850–900 °C for different time. The results show that with Cu-rich precipitates as main inhibitor, the annealing temperature has a great influence on the decarburization effect. The decarburization effect at 850 °C is the best, followed by 875 and 900 °C. The residual carbon content decreases first and then tends to level off with the increasing decarburization time. The optimal process is decarburization annealing at 850 °C for 6 min, in which case the carbon content can be reduced to less than 40 ppm, and the average grain diameter is about 16.1 μm. The primary recrystallized textures mainly include {111}, {111}, {114}, {112} and a small number of Goss-oriented grains. In the decarburized annealed matrix, the Cu-rich precipitates are about 10–50 nm in size, with a distribution density of about 5.06 × 109/cm2, and thus can be used as an effective inhibitor for grain-oriented electrical steel. When the sample is annealed at a high temperature, above 1000 °C, the large-scale secondary recrystallized macrostructure of the steel is formed, more importantly, there is no need for a long purification heat treatment at 1200 °C.

In this study, machine learning algorithm was used to model measurements of corrosion rates of stainless steel Type 904 in 0.5 M H2SO4 media as a function of exposure time, and temperature, when corrosion inhibitors are added in different dosage. Hyper-parameter optimization of the adaptive neuro-fuzzy inference system (ANFIS) and artificial neural network (ANN) was carried out to select the best model that accurately predicts the corrosion rate. A range of 1–10 neurons in a single hidden layer neural network with varying prominent training algorithms and activation functions was tested. The FCM-clustered ANFIS model tested a range of 2–20 cluster numbers. The models’ performance was evaluated using correlation determination (R2), root mean square error (RMSE), mean absolute percentage error (MAPE), and mean absolute deviation (MAD). The experiments show that the FCM-clustered ANFIS model with 20 clusters outperformed all other models with MAPE, MAD, RMSE, and R2 values of 1.9222, 0.5543, 0.7317, and 0.9308 at the testing phase respectively, and 0.5457, 0.3943, 2.9258 and 0.9993 at the training phase respectively. The entire FCM-ANFIS model produced the optimum prediction with a 96.40% level of robustness and accuracy. Therefore, ANFIS and ANN can be used to predict corrosion inhibition using agricultural waste in acidic media with great degree of success. These models are reliable, cheap, fast, efficient, and effective tools for corrosion inhibition prediction.

The use of blended green concrete with improved performance has significantly increased in the industrial sector owing to the CO2 gas emissions and carbon footprint caused by the production of ordinary Portland cement. Although improvements have been continuously made, the deterioration of concrete structures in seawater poses a serious concern. The long term performance of green concretes in seawater environment are scarcely studied. Here we report the long-term strength, durability and anti-fouling properties of a novel blended eco-friendly concrete made with ordinary Portland cement, fly ash, nanoparticles, and corrosion inhibitor in natural seawater for one year. The mechanical strength, alkalinity, free chloride concentrations, biofouling attachment, and total viability count are studied. After a year of exposure to seawater, the ternary blended green concrete showed improved mechanical strength, a significantly lower chloride penetration and water penetration depth, a 70% reduction in free chloride content, a high calcium silicate hydrate content, and a four-order reduction in the total biomass. Our results suggest that the new concrete mix is promising for applications in seawater environments because of its improved mechanical properties, durability, and biofouling resistance.

The Keap1-Nrf2 pathway has been established as a therapeutic target for Alzheimer's disease (AD). Directly inhibiting the protein-protein interaction (PPI) between Keap1 and Nrf2 has been reported as an effective strategy for treating AD. Our group has validated this in an AD mouse model for the first time using the inhibitor 1,4-diaminonaphthalene NXPZ-2 with high concentrations. In the present study, we reported a new phosphodiester containing diaminonaphthalene compound, POZL, designed to target the PPI interface using a structure-based design strategy to combat oxidative stress in AD pathogenesis. Our crystallographic verification confirms that POZL shows potent Keap1-Nrf2 inhibition. Remarkably, POZL showed its high in vivo anti-AD efficacy at a much lower dosage compared to NXPZ-2 in the transgenic APP/PS1 AD mouse model. POZL treatment in the transgenic mice could effectively ameliorate learning and memory dysfunction by promoting the Nrf2 nuclear translocation. As a result, the oxidative stress and AD biomarker expression such as BACE1 and hyperphosphorylation of Tau were significantly reduced, and the synaptic function was recovered. HE and Nissl staining confirmed that POZL improved brain tissue pathological changes by enhancing neuron quantity and function. Furthermore, it was confirmed that POZL could effectively reverse Aβ-caused synaptic damage by activating Nrf2 in primary cultured cortical neurons. Collectively, our findings demonstrated that the phosphodiester diaminonaphthalene Keap1-Nrf2 PPI inhibitor could be regarded as a promising preclinical candidate of AD.