New corrosion inhibitor derived from coumarin-3-amine namely 3-((2-chlorobenzylidene)amino)coumarin was synthesized and characterized by CHN elemental analysis in addition to Fourier transform infrared and nuclear magnetic resonance techniques. The anti-corrosion ability of 3-((2-chlorobenzylidene)amino)coumarin to inhibit the impacts of corrosion has been demonstrated and damage reduction of the mild steel also. 3-((2-chlorobenzylidene)amino)coumarin, has been employed as a good corrosion inhibitor for mild steel in HCL solution. The efficiency of the inhibition was figured according to weight loss method and it was 74.6%.

Corrosion inhibitors are the natural or synthetic compounds that have the ability to inhibit the average of corrosion and reduce the damage of the mild steel. Enormous organic inhibitors nowadays employed in the corrosion domain but excluded due to costly. Comparatively cheap, and stable organic compound, namely 3-((4-nitrobenzylidene)amino)coumarin, have been utilized as an excellent corrosion inhibitor in hydrochloric acid for mild steel. The inhibition efficiency has been figured regarding to weight loss method. The corrosion inhibitor was identified according to spectroscopic techniques namely Fourier transform infrared and nuclear magnetic resonance in addition to micro-elemental analysis. Inhibition efficiency for the studied inhibitor was 71.4% that, at the highest studied concentration.

This research aims to explore the use of sodium benzoate C6H5-COOH as corrosion inhibitor added to the mixing water of concrete, and test the mechanical performances of five types of concretes over several time periods, 7, 28, 56 and 90 days, in the absence and in the presence of limestone fillers. Hence the results confirm the increase in this resistance over time. Through this, tests were carried out cement paste after addition of sodium benzoate and limestone fillers, we see clearly that the start and the and setting time of cement shift out considerably which indicates that sodium benzoate aims to delay start and end setting time of cement. In addition, Abrams cone slump tests on concrete in the fresh state were carried out in order to see the influence of the addition of sodium benzoate and tests on the cement consistencies in the absence and presence of superplasticizing adjuvant “ORAFLOW THM 17200” which has the main role of improving the workability and quality of the concrete while comparing with ordinary concrete.

The Voltammetric and polarographic methods are proposed to determine the short time corro-sion rates of brass in 1N HCl solution. It should be noted that it is also possible to determine the corrosion rates of each species present in the solution, simultaneously like Cu (II) and Zn (II) in brass. Samples extracted from bark of Babul (ESBB) is used as corrosion inhibitors. The corrosion inhibition efficiency is 96% at 24h after the test started. These results are compared with the av-erage corrosion rates obtained by using gravimetric (PIT) and some electrochemical methods i.e. galvanostatic and potentiodynamic polarization measurements.

In this study, we investigated the inhibiting effect of Dioscorea spp leaf extracts on the corrosion of mild steel in selected media using the weight loss method. The mild steel samples were pre-weighed and immersed in NaOH, NaCl and H₂SO₄ solutions respectively containing the leaf extracts, with the control samples immersed in solutions of the media containing no extract. The samples were allowed to stand for 672 hours, with a set of samples from each environment withdrawn at intervals of 168 hours for corrosion characterization. The results obtained from all the environments indicate that the corrosion rate increased as concentrations of Dioscorea spp increased. Results also confirmed that the extract was an effective and excellent inhibitor in the alkaline, salt, and acidic media. Conclusively it was proven that the higher concentration of Dioscorea spp leaf extracts in the media had the best inhibition characteristic on the mild steel in the selected environments. The results show good potential for application in manufacturing industries. The microstructure analysis of the various test coupons in the test media should be carried out to reveal the influence of adding the leaf extracts to the stimulated media on the grain structure distribution of the mild steel.

This work aims to follow the corrosion behavior of copper in 3 wt% NaCl solution in the presence of a bio-oily extract. Spent coffee grounds (SCG), a highly recyclable and usable biomass - often thrown away and becoming a serious threat to the environment - , has a fraction of oils (12%) that we have opted to use as a corrosion inhibitor for copper. The extraction was carried out using n-hexane as the solvent for the decoction. The oily fraction was analyzed by Fourier transform infrared spectroscopy (FTIR) and thermogravimetric analysis (TGA). Potentiodynamic polarization measurements have revealed SCG extract acts as a cathode-type inhibitor for copper in saline media, mainly preventing the diffusion of oxygen molecules toward the substrate. As the extract concentration increased, the inhibition efficiency has improved as well, reaching 95.78 % with 0.6 g/L of SCG extract. The obtained results by electrochemical impedance spectroscopy (EIS) are in accordance with the order of inhibitory efficiency obtained by potentiodynamic polarization. We have found that the SCG extract adsorption process on copper surface is spontaneous and complies with Langmuir isotherm.

To provide carbon steel a long corrosion protection effect in NaCl solution with various pH, a pH-controlled intelligent inhibitor based on poly-acrylamide (PAM) and oleate imidazoline (OIM) was synthesized. SEM, FT-IR and TGA results indicating the OIM inhibitor was successfully loaded into PAM hydrogel with a very high content (39.64 wt%). The OIM release behavior from hydrogel structure have two stages, quickly release and sustained release. The pH of solution could affect the initial release kinetics of OIM inhibitor and the diffusion path in hydrogel structure. Weight loss measurement of L80 steel in different pH solution with OIM@PAM proved the inhibitor responsive release mechanism and an-ti-corrosion performance. The inhibition efficiency of OIM@PAM can maintain over 80% after long term immersion in harsh corrosive environment (pH 3), which is much higher than the inhibition efficiency of inhibitor in moderate corrosive solution.

This paper studies the use of zinc oxide nanoparticles (ZnO-NPs) synthesized using an extract of convolvulus leaves and expired ZnCl₂, as an efficient inhibitor for carbon steel corrosion in 1M HCl solution. ZnO-NPs are characterized by Fourier-transform infrared spectrophotometer (FTIR) and UV–Vis analysis. The technique of weight loss, potentiodynamic polarization, and electrochemical impedance spectroscopy (EIS) has also been used to investigate the prevention of carbon steel corrosion in 1M HCl. The results showed that the efficiency of restraint increased when the concentration of ZnO-NPs was raised to 91% and that the inhibition efficiency is still high despite its decrease at high temperature, and it acts as a mixed-type inhibitor A sample of carbon steel with the protective inhibitor layer on top was immersed for 20 hours and observed; an increase in the charge transfer resistance (Rct) and stability of the inhibitor was noticed after 6 hours. Adsorption isotherm models demonstrated that the inhibitor adsorption mechanism on the carbon steel surface followed Langmuir, more than Freundlich and Temkin, behavior. The thermodynamic parameters showed that the adsorption process is a mixed adsorption, spontaneous, and exothermic. The results illustrated that the acid medium was a strong inhibitor of carbon steel corrosion. Scanning electron microscope (SEM) showed that the ZnO-NPs formed a good protective film on the carbon steel surface.

Severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) continues to be a global threat due to its ability to evolve and generate new subvariants, leading to new waves of infection. Additionally, other coronaviruses like Middle East respiratory syndrome coronavirus (MERS-CoV, formerly known as hCoV-EMC) which first emerged in 2012, persists and continues to present a threat of severe illness to humans. The continued identification of novel coronaviruses, coupled with the potential for genetic recombination between different strains, raises the possibility of new coronavirus clades of global concern emerging. As a result, there is a pressing need for pan-CoV therapeutic drugs and vaccines. After extensive optimization of an HCV protease inhibitor screening hit, a novel 3CLPro inhibitor (MK-7845) was discovered and subsequently profiled. MK-7845 exhibited nanomolar in vitro potency with broad spectrum activity against a panel of clinical SARS-CoV-2 subvariants and MERS-CoV. Furthermore, when administered orally, MK-7845 demonstrated a notable reduction of viral burdens by >6 log orders in the lungs of transgenic mice infected with SARS-CoV-2 (K18-hACE2 mice) and MERS-CoV (K18-hDDP4 mice).

Improvement of hydrophysical properties and corrosion resistance of self-compacting concrete to the effects of alternate freezing-thawing and aggressive soils of southern and central Kazakhstan is of interest to a wide range of researchers from the side of practical application of the obtained results in construction practice. It is proposed to form a spatially reinforced fine crystalline structure of cement matrix with maximum dense packing by using a complex modifier (Hyperplasticiser + Polymer + Microsilica + Fibro fibers) in the composition of self-compacting concretes (SCC). The introduction of the calculated amount of the above additives increases the operational reliability of the current SCC compositions, increasing the water resistance to W16, frost resistance to F=500, increasing the compressive strength by 20%, reducing the mass loss of samples during corrosion leaching to 50%. It has been experimentally established that the proposed addition of complex modifier (Hyperplasticiser + Polymer + Microsilica + Fiber fibers) to the SCC composition allows obtaining self-compacting concrete of high quality with improved performance characteristics (compressive strength, water resistance, frost resistance and corrosion resistance). Studies have shown that the complex modifier-modified SCC compositions have a high degree of resistance in aggressive environments and leaching corrosion. Based on the results of the conducted tests, it is possible to recommend the obtained SCC compositions for production of building products working in the zone of alternating freezing-thawing and aggressive soils.

Programmed cell death 4 (Pdcd4) is a tumor suppressor, which has been demonstrated to efficiently suppress tumorigenesis. Biochemically, Pdcd4 binds with translation initiation factor 4A and represses protein translation. Beyond its role in tumor suppression, increasing evidence indicates that Pdcd4 enhances the chemosensitivity of several chemotherapeutic drugs. To date, several translational targets of Pdcd4 have been identified. These targets govern important signal transduction pathways, and their attenuation may enhance chemosensitivity or overcome drug resistance. This review will discuss the signal transduction pathways regulated by Pdcd4 and the potential mechanisms through which Pdcd4 enhances chemosensitivity or counteracts drug resistance.

Present worldwide difficulties in healthcare and the environment have motivated the investigation and research of novel materials in an effort to find novel techniques to address the current chal-lenges and requirements. In particular, the use of nanomaterials has demonstrated a significant promise in the fight against bacterial infections and the problem of antibiotic resistance. Metal na-noparticles and carbon-based nanomaterials in particular have been highlighted for their excep-tional abilities to inhibit many types of bacteria and pathogens. In order for these materials to be as effective as possible, synthetic techniques are crucial. Therefore, in this review article, we high-light some recent developments in the design and synthesis of various nanomaterials, including metal nanoparticles (e.g., Ag, Zn, or Cu), metal hybrid nanomaterials, and the synthesis of mul-ti-metallic hybrid nanostructured materials. Following that, examples of these materials’ applica-tions in antimicrobial performance targeted at eradicating multi-drug resistant bacteria, material protection such as microbiologically influenced corrosion (MIC), or additives in construction ma-terials have been described.

Structural and functional materials are subjected to harsh oxidizing environments that lead to a rapid decline in their surface chemical stability. At high-temperatures, the diffusion of atoms is erratic; thus, the reactive elements (REs) get a chance to migrate to the surface and look for oxygen-reactive sites. Their migration from the lattice sites creates vacancies in the matrix and thus weakens the bond, making the material prone to environmental degrading factors. Subsequently, the inward diffusion of oxygen, sulfur, nitrogen, or carbon may occupy these vacancies, resulting in undesired precipitation at the grain boundary, which is usually brittle. The solubility and dissociation of attacking species and corrosion products play the most critical role in corrosion in high-temperature water. To evade such situations, Ti, Al, and Cr are added in Ni/Fe-based alloys, forming a dense oxide layer on the surface that impedes further surface migration of ions. The stability of the alloys is then determined by the capability of these oxide layers to heal or reform during spalling/cracking. This review attempts to understand the migration of REs at the interfaces to prepare structural materials in any unexpected set of oxidizing service conditions. This review will also try to establish the interaction mechanism of REs novel/conventionally added in the alloys with the oxidizing elements in the environments to design better degradation-resistant high-temperature alloys.

Governments worldwide are actively committed to achieving their carbon emission reduction targets, and one avenue under exploration is harnessing the potential of hydrogen. Blending hydrogen with natural gas is emerging as a promising strategy to reduce carbon emissions, as it burns cleanly without emitting carbon dioxide. This blending could significantly contribute to emissions reduction in both residential and commercial settings. However, a critical challenge associated with this approach is the potential for Hydrogen Embrittlement (HE), a phenomenon wherein the mechanical properties of pipe steels degrade due to the infiltration of hydrogen atoms into the metal lattice structure. This can result in sudden and sever failures when the steel is subjected to mechanical stress. To effectively implement hydrogen-natural gas blending, it is imperative to gain a comprehensive understanding of how hydrogen affects the integrity of pipe steel. This necessitates the development of robust experimental methodologies capable of monitoring the presence and impact of hydrogen within the microstructures of steel. Key techniques employed for this assessment include microscopic observation, hydrogen permeation tests, and tensile and fatigue testing. In this study, samples from two distinct types of pipeline steels used in the natural gas distribution network underwent rigorous examination. To induce hydrogen absorption, an electrochemical charging process is employed in a solution rich in H+ ions. This charging process, accomplished by a potentiostat applying a constant current, prompts the hydrogen evolution reaction at the steel specimen, acting as the cathode of the charging cell. Immediate tensile and fatigue testing following the charging process enables the evaluation of mechanical properties in comparison to non-charged samples. Different charging current densities are employed to simulate various hydrogen blend scenarios. The findings from this research indicate that charged samples exhibit a discernible decline in fatigue and tensile properties. This deterioration is attributed to embrittlement and reduced ductility stemming from the infiltration of hydrogen into the steel matrix. The extent of degradation in fatigue properties is correlated not only to the hydrogen content but also to the hydrogen permeability and diffusion rate influenced by steel’s microstructural features, with higher charging current densities indicating a more significant presence of hydrogen in the natural gas pipeline blend.

A series of waterborne polyurethane (WBPU)/modified lignin amine (MLA) adhesives was prepared using modified lignin amine (MLA) as a chain extender by a prepolymer mixing process. A successful Mannich reaction was achieved during the synthesis of MLA by reacting lignin with bis(3-aminopropyl)amine. Higher tensile strength, Young’s modulus and thermal stability were recorded for WBPU/MLA adhesives with higher MLA contents. The WBPU/MLA adhesive materials were used to coat PVC substrates. The adhesive strength increased with increasing MLA content. More importantly, the MLA also enhanced the WBPU/MLA coating in terms of adhesive strength at moderately high temperatures as well as under natural weather exposed conditions. The adhesive strength was essentially unaffected with 6.48 mole% MLA in the WBPU/MLA coating after exposure to natural weather conditions for 180 days.

The apicomplexan parasite, Sarcocystis neurona causes the degenerative neurological equine protozoal myeloencephalitis (EPM) disease of horses. Due to its host range expansion, S. neurona is an emerging threat that requires close monitoring. In apicomplexans, protein kinases (PKs) have been implicated in a myriad of critical functions such as host cell invasion, cell cycle progression and host immune responses evasion. Here, we used various bioinformatics methods to define the kinome of S. neurona and phylogenetic relatedness of its PKs to other apicomplexans. Further, three-dimensional (3D) homology models for selected S. neurona putative PKs were constructed and evaluated for inhibitor docking. We identified 92 putative PKs clustering within the AGC, CAMK, CK1, CMGC, STE, TKL, aPK and OPK groups. Although containing the universally conserved PKA (AGC group), S. neurona kinome was devoid of PKB and PKC, but contained the six apicomplexan conserved CDPKs (CAMK group). The OPK group was represented by ROPKs 19A, 27, 30, 33, 35 and 37, but was devoid of the virulence-associated ROPKs 5, 6, 18 and 38. Two out of the three S. neurona CK1 enzymes had high sequence similarities to T. gondii TgCK1-α and TgCK1-β and the Plasmodium PfCK1. Docking of four inhibitors onto homology models of putative ROP27 and PKA indicated that inhibition of S. neurona PKs is feasible, but needs to be experimentally tested. The essentiality of apicomplexan PKs makes the elucidation of S. neurona kinome a key milestone for development of novel therapeutics for EPM.

The Bax inhibitor-1 (BI-1) gene family, which is required for plant growth, development, and stress tolerance, remains largely unexplored in cauliflower. In this study, we identified and characterized cauliflower BI-1 family genes. On the basis of aligned homologous sequences and collinearity with Arabidopsis genes, we identified nine cauliflower BI-1 genes, which encoded proteins that varied regarding length, molecular weight, isoelectric point, and subcellular localization (i.e., Golgi apparatus, plasma membrane, cell membrane, and chloroplast). Phylogenetic analyses detected evolutionary conservation and divergence among these genes. Ten structural motifs were identified, with Motif 5 crucial for inhibiting apoptosis. According to the cis-regulatory elements in their promoters, these genes likely influence hormone signaling and stress responses. Expression profiles among tissues highlighted the diversity in the functions of these genes, which were significantly expressed in the silique and root. Focusing on BobBIL4, we investigated its role in brassinosteroid (BR)-mediated root development and salt stress tolerance. BobBIL4 expression levels increased in response to BR and salt treatments. The functional characterization of this gene in Arabidopsis revealed it enhances root growth and salinity tolerance. These findings provide insights into BI-1 gene functions in cauliflower, while also highlighting the potential utility of BobBIL4 for improving crop stress resistance.

The key question for the understanding of corrosion phenomena of Si3N4-SiC material in Al reduction cell – whether corrosion by gases (and oxidation in particular) opens way for the corrosion by molten cryolite, or corrosion of Si3N4-SiC by cryolite plays its own role in degradation of the material in service. More probably the reactions of silicon carbide and silicon nitride with molten cryolite go after the stage of pre oxidation to silicon dioxide. The corrosion of Si3N4-SiC material in the reduction cell may take place by “gas-solid” reaction and by “liquid-solid” reaction. There are several variants of lab corrosion test for the evaluation of corrosion resistance of Si3N4-SiC material to cryolite. The results of investigation of Si3N4-SiC lab corrosion test give no direct evidence of selective dissolution of specific phase (Si3N4 or SiC, α-Si3N4 or β-Si3N4) in cryolite. The existing variants of lab corrosion testing require clarification.

For better understanding the corrosion and corrosion products behavior in the primary circuit of lead-bismuth eutectic (LBE) coolant reactor, the concentration distribution of soluble impurities and the transport of solid particles are investigated through finite-element method. An axisymmetric model of the primary circuit of LBE reactor was constructed to accelerate the calculation the thermal hydraulic filed of circuit. The saturation concentration of solute Fe, Cr and Ni in LBE coolant are identified through the equilibrium of their oxides and PbO. And the very different saturation concentrations of Fe/Cr/Ni in LBE will lead to significant element selective corrosion. The migration of solid oxides particles in the primary circuit is also investigated by the Euler-Lagrange tracing model. The simulation shows that driving force for the movement of particles >100 μm is buoyancy, which lets particles float on a free surface, while particles <10 μm tend to suspend in coolant. However, the behavior of particles also depends on the formation position, the particles formed above the core have the high possibility of re-entering in the core.

Today, legislative framework addresses the metal alloys’ corrosion issues, demanding the re-striction of use of the probable carcinogenic, mutagenic and toxic for reproduction at humans (CMG) metals, like nickel, cobalt and chromium, and demand to develop new biomaterials. Therefore, the aim of this research is to evaluate and compare ion release of standard dental alloys and their hypoallergenic equivalents. Six types of orthodontic alloy wires (nickel-titanium (NiTi), coated NiTi, stainless steel (SS), Ni-free SS, cobalt-chromium (CoCr), and titanium-molybdenum (TMA) were immersed into artificial saliva of pH 5.5 and 6.6. Release of metal ions was measured by inductively coupled plasma-mass-spectrometry (ICP-MS) after 3, 7, 14 and 28 days. Data analyses were done using analysis of variance, results with P

Despite the high quality of soybean protein, raw soybeans and soybean meal cannot be directly included into animal feed mixtures due to the presence of Kunitz (KTi) and Bowman Birk protease inhibitors (BBi) which reduces animal performance. Heat treatment can substantially inactivate trypsin and chymotrypsin inhibitors (BBi) but such treatment is energy intensive, adds expense, and negatively impact the quality of seed proteins. As an alternative approach we have employed CRISPR/Cas9 gene editing to create mutations in BBi genes to drastically lower the protease inhibitor content in soybean seed. Agrobacterium-mediated transformation was used to generate several stable transgenic soybean events. These independent CRISPR/Cas9 events were examined in comparison to wild type plants using Sanger sequencing, proteomic analysis, trypsin/chymotrypsin inhibitor activity assays and q15RT-PCR. Collectively, our results demonstrate the creation of an allelic series of loss of function mutations affecting the major BBi gene in soybean. Mutations in two of the highly expressed seed specific BBi genes lead to substantial reductions in both trypsin and chymotrypsin inhibitor activities.

Fe-(9, 19, 28, 37)wt.% Cr alloys were corroded at 700 and 800 ^oC for 70 h under 1 atm of N₂, 1 atm of N₂/3.2%H₂O-mixed gas, and 1 atm of N₂/3.1%H₂O/2.42%H₂S-mixed gas. The corrosion rate of Fe-9Cr alloy increased with the addition of H₂O, and furthermore with the addition of H₂S in N₂ gas. Fe-9Cr alloy was always nonprotective. In contrast, Fe-(19, 28, 37) wt.%Cr alloys were protective in N₂ and N₂/H₂O-mixed gas because of formation of the Cr₂O₃ layer. They were, however, nonprotective in N₂/H₂O/H₂S-mixed gas because sulfidation dominated to form the outer FeS layer and the inner Cr₂S₃ layer containing some FeCr₂S₄.

As high strength and ultra-high strength steels are widely used in all kinds of modern welded constructions, a lot of research is carried out to investigate the mechanical properties of weldments of these steels but there is a scarce information on such important characteristic as their corrosion behaviour. This research focuses on the corrosion behaviour of weld metal of weldments of S906QL and S700MC steels. Weld metal was tested electrochemically in a 3,5% NaCl aqueous solution via potentiodynamic scan to determine corrosion rate and its dependence on welding gap. No influence of welding gap on corrosion rate was found but the experimental results suggested that corrosion rate depended on the chemical composition of filler material and the microstructure of weld metal.

The landscape of clinical management for metastatic melanoma (MM) and other solid tumors has been modernized by the advent of immune checkpoint inhibitors (ICI), including programmed cell death-1 (PD-1), programmed cell death-ligand 1 (PD-L1), and cytotoxic T lymphocyte antigen 4 (CTLA-4) inhibitors. While these agents demonstrate efficacy in suppressing tumor growth, they also lead to immune-related adverse events (irAEs), resulting in exacerbation of autoimmune diseases such as Rheumatoid arthritis (RA), Ulcerative colitis (UC), and Crohn’s disease (CD). The immune checkpoint inhibitors offer promising advancements in the treatment of melanoma and other cancers, but they also present significant challenges related to irAEs and autoimmune diseases. Ongoing research is crucial to better understand these challenges and develop strategies for mitigating adverse effects while maximizing therapeutic benefits. In this manuscript, we addressed this challenge using network-based approaches by constructing and analyzing molecular and signaling networks associated with tumor-immune cross-talk.. Our analysis revealed that IL6 is the key regulator responsible for irAEs during ICI therapies. Furthermore, we conducted an integrative network and molecular-level analysis, including virtual screening, of drug libraries, such as the Collection of Open Natural Products (COCONUT) and the Zinc15 FDA-approved library, to identify potential IL-6 inhibitors.. Subsequently, the compound amprenavir was identified as the best molecule that may disrupt essential interactions between IL6 and IL6R responsible for initiating signaling cascades underlying irAEs in ICI therapies.

Although various atmospheric corrosion simulation models have been developed that give good results, industrial environments are still challenging. This paper aims to investigate the effect industrial atmospheres in Bor on the mechanical properties of structural steel S235JR and to create a constitutive model and also laboratory experimental conditions that will give the best results as an accelerated corrosion test. Atmospheric corrosion tests lasted six months, using sites close to the Electrolytic Refining Plant and Sulphuric Acid Plant, as well as air quality monitoring stations at a remote location in the city of Bor. The laboratory experiments included a salt chamber test lasting 120 h and 240 h and immersing the specimen in the electrolyte from the Electrolytic Refining Plant for 30 days. The results were compared with the standard specimens stored in the laboratory. The X-ray diffraction (XRD) method was used to identify the composition of corrosion products. The scanning electron microscopy (SEM) analysis was applied to analyze the fracture surfaces of the specimens. The use of the Complete Gurson Model (CGM) described the tensile characteristics of the corroded specimens. The study has shown that an enhanced acceleration model and conditions could be developed using numerical analysis of the test results.

This comprehensive review delves into cancer's complexity, focusing on adhesion, metastasis, and inhibition. It explores the pivotal role of these factors in disease progression and therapeutic strategies. This review covers cancer cell migration, invasion, and colonization of distant organs, emphasizing the significance of cell adhesion and the intricate metastasis process. Inhibition approaches targeting adhesion molecules, such as integrins and cadherins, are discussed. Overall, this review contributes significantly to advancing cancer research and developing targeted therapies, holding promise for improving patient outcomes worldwide. Exploring different inhibition strategies revealed promising therapeutic targets to alleviate adhesion and metastasis of cancer cells. The effectiveness of integrin-blocking antibodies, small molecule inhibitors targeting FAK and the TGF-β pathway, and combination therapies underscores their potential to disrupt focal adhesions and control epithelial-mesenchymal transition processes. The identification of as FAK, Src, β-catenin and SMAD4 offers valuable starting points for further research and the development of targeted therapies. The complex interrelationships between adhesion and metastatic signaling networks will be relevant to the development of new treatment approaches.

Hypertension is a frequent risk factor for cardiovascular diseases and the prevalence rate is continuously rising. Multiple pathophysiological mechanisms are responsible for hypertension, necessitating a combination of drugs from different classes for best management. Combination therapy is five times more effective in decreasing blood pressure compared to escalating the dose of a single agent. As per the ACCOMPLISH trial analysis, coupling a renin-angiotensin system inhibitor with a calcium channel blocker is more effective than the combination of a renin-angiotensin system inhibitor with diuretics in reducing major cardiovascular events, cardiovascular-related mortality, and the progression of chronic kidney disease. The renin-angiotensin system can be suppressed by inhibiting the angiotensin-converting enzyme or angiotensin type 1 receptor (AT1R), resulting, in decreased vascular smooth muscle contraction, heart performance, and reduced aldosterone synthesis. Calcium channel blockers work by inhibiting L-type calcium channels, reducing heart performance via negative inotropic, chronotropic, and bathmotropic effects, along with reducing vascular smooth muscle contraction. Diuretics exert their antihypertensive impact by changing body fluid volume and electrolytes. Initially, hypertension treatment commences with a single medication but often, different classes of two or more antihypertensive medications are necessary for achieving the target blood pressure goal. Sometimes, for Resistant hypertension four different classes of antihypertensive medications are necessary to reach the target blood pressure goal.

Retroviruses perpetuate their survival by incorporating a copy of their genome into the host cell, a critical step catalyzed by the virally encoded integrase. The viral capsid plays an important role during the viral life-cycle, including nuclear importation in case of lentiviruses and integration targeting events, hence, targeting the integrase and the viral capsid is a favorable therapeutic strategy. While integrase strand transfer inhibitors (INSTIs) are recommended as first-line regimens given their high efficacy and tolerability, lenacapavir is the first capsid inhibitor and the newest addition to the HIV treatment arsenal. These inhibitors are however designed for treatment of HIV-1 infection, and their efficacy against HIV-2 remains widely understudied and inconclusive, supported only by few limited phenotypic susceptibility studies. We therefore carried out inhibition profiling of a panel of second-generation INSTIs and lenacapavir against HIV-2 in cell culture, utilizing pseudovirion inhibition profiling assays. Our results show that the tested INSTIs and lenacapavir exerted excellent efficacy against ROD-based HIV-2 integrase, and interestingly, raltegravir also showed modest antiviral activity against the SARS-CoV-2 Omicron variant in antiviral assays carried out in Vero E6 cells.

This study introduces a novel nanocomposite coating composed of PANI/CeO2 nanocomposite films, aimed at addressing corrosion protection needs. Analysis through FTIR spectra and XRD patterns confirms the successful formation of the nanocomposite films. Notably, the PANI/CeO2 nanocomposite films exhibit a hydrophilic nature. The bandgap energy of the PANI composite film measures at 3.74 eV, while the introduction of CeO2 NPs into the PANI matrix reduces the bandgap energy to 3.67 eV. Furthermore, the electrical conductivity of the PANI composite film is observed to be 0.40 S.cm-1, with the incorporation of CeO2 NPs leading to an increase in electrical conductivity to 1.07 S.cm-1. To evaluate its efficacy, electrochemical measurements were conducted to assess the corrosion protection performance. Results indicate a high protection efficiency of 92.25% for the PANI/CeO2 nanocomposite film.

Portland cement emits large amounts of CO2 in production. Given proposals for "carbon peaking and carbon neutralization" studying alternative low-carbon cementitious materials to reduce emissions is extremely important. Alkali-activated slag (AAS) cement, a new green cementitious material, has high application potential. The chemical corrosion resistance of AAS concrete is important for ensuring durability and prolonging service life. Studying the chemical corrosion mechanism of AAS concrete and understanding its influence on performance provides important theoretical foundations for application in different environments.

This paper employs the Finite Element Method (FEM) to simulate and analyze the effects of corrosion defect parameters on the stress and failure pressure of pipelines. It investigates how the boundary conditions of the pipeline model influence stress and examines the sensitivity of failure pressure to corrosion defect parameters. A nonlinear regression equation has been developed from a dataset obtained through simulation experiments to predict the failure pressure of corroded pipelines. To validate the effects of corrosion defect parameters on failure pressure, a hydrostatic test platform for an API 5L X65 pipeline with corrosion defects was established to measure stress levels and failure pressures across varying corrosion defects. The study reveals that failure pressure is negatively correlated with corrosion length and depth, while positively correlated with corrosion width. Among these parameters, corrosion depth exerts a more significant influence on the pipeline's failure pressure than corrosion length and width. Within the range of corrosion defect parameters examined, the maximum deviation of the prediction equation's results from the simulation results is 8.71%, with an average deviation of 5.81%. The standard deviation of the fitted residuals is 0.01837. Additionally, the maximum deviation between the predicted results and experimental measurements is 8.39%, with an average deviation of 7.77%. The strong agreement between the predicted results from the equation and the actual measured data underscores the effectiveness of the nonlinear regression equation.

Caveolin-1 (Cav-1) is 22 kDa caveolae protein, acts as a scaffold within caveolar membranes. It interacts with alpha subunits of G-protein and thereby regulates their activity. Earlier studies reported elevated or up-regulated levels of caveolin-1 in the serum of prostate cancer patients. Secreted Cav-1 promotes angiogenesis, cell proliferation and anti-apoptotic activities in prostate cancer patients. Cav-1 upregulation is mainly related to prostate cancer metastasis. Keeping above facts in view, the present study was designed to explore Cav-1 as a target for prostate cancer therapy using computational approach. Molecular docking, structural base molecular modelling and molecular dynamics simulations were performed to investigate Cav-1 inhibitors. A predictive model was generated and validated to establish a stable structure. ZINC database of biogenic compounds was used for induced fit docking (IFD) and high throughput virtual screening. The H-bond interactions of the compounds with active site residues of Cav-1 were estimated by IFD and 100 ns long molecular dynamic simulations. The reported compounds showed significant binding and thus can be considered as potent therapeutic inhibitors of Cav-1. This study provides a valuable insight into biochemical interactions of Cav-1 for therapeutic applications and warrants for experimental validation of the predicted ‘active(s)’.

In this work, the inhibition properties of new bio-based lignine ILs on the corrosion of mild steel in an aqueous solution of 0.01 M NaCl were investigated by Potentiostatic Electrochemical Impedance Spectroscopy (PEIS), Cyclic Potentiodynamic Polarization (CPP). Moreover, the surface was characterized using SEM, EDS, and optical profilometry. The influence of cation and anion on the inhibitor properties and a possible synergistic effect were investigated. The IL choline syringate showed a promising performance, reducing the corrosion current after 24-hour immersion in 0.01 M sodium chloride, from 1.66 µA/cm2 for the control to 0.066 µA/cm2 with 10 mM of the IL present. In addition to the performance as a corrosion inhibitor, both components of this IL also meet or exceed current additional desired properties of such compounds, being readily available, economically efficient, and well tolerated in organisms and the environment.

This study delves into the atmospheric corrosion behavior of chromium-free complex-phase steel (CP), specifically investigating the influence of wet/dry frequency and ratio in cyclic corrosion tests (CCT). The study employs a modified ISO 14993 standard CCT method, which involves salt spray, dry, and wet stages. After 15 and 30 CCT cycles, mass loss, maximum corrosion depth, and corrosion products were analyzed to gain insights into corrosion mechanisms. In general, increasing the frequency and wet/dry stage ratio in CCT extends the time for autocatalytic reactions to occur, leading to accelerated localized CP corrosion and increased pitting factors. However, as the rust layer thickens, uniform corrosion may also intensify, so careful considerations are necessary. This study underscores the importance of controlling the frequency and ratio of wet/dry stages in CCT for effectively analyzing localized corrosion behavior in specimens.

This review paper aims to understand the current processing plant maintenance systems and further identify on-stream phased array corrosion mapping (PACM) to reduce turnaround maintenance (TAM) activity during plant operations. Reducing the TAM duration and extending the TAM interval are common goals of most researchers. Thus, a detailed review was performed to understand the maintenance systems and the problems faced. Furthermore, a review of the current PACM application and the possibility of applying it during on-stream inspection was also per-formed. PACM has better detectability for localized corrosion, and the results can be obtained for a range of thicknesses, which is the main advantage of this method. The challenge is to apply it to a surface with high temperatures, owing to the greater probe contact and the limitation of ultrasonic properties. This literature review provides a more precise direction for future research to evaluate PACM on piping that can be utilized in inspection during plant operation at elevated temperatures. Detecting and monitoring corrosion growth without shutdown.

Triple negative breast cancer (TNBC) is associated with a generally poor prognosis due to its highly aggressive and metastatic nature, lack of targetable receptors, as well as the frequent development of resistance to chemotherapy. We previously reported that AU1, a small molecule developed as an inhibitor of BPTF (bromodomain PHD finger containing transcription factor), was capable of sensitizing preclinical models of triple negative breast cancer to chemotherapy, in part via the promotion of autophagy. In studies reported here, we identify an additional property of this compound, specifically that sensitization is associated with inhibition of the P-glycoprotein efflux pump. In silico molecular docking studies indicate that AU1 binds to active regions of the efflux pump, in a manner consistent with inhibition of pump function. This work identifies a novel chemical structure that can influence multidrug efflux, an established mechanism of drug resistance in triple negative breast cancer, that has not yet been successfully addressed by clinical efforts.

Aluminum base alloys containing chromium (Cr) and zinc (Zn) were produced using extrusion and heat treated powder metallurgy. Cr addition ranged between 5 to 10 wt. % while Zn was added in an amount between 0 to 20 wt. %. Heat treatment processes were performed during powder metallurgy process at different temperatures followed by water quenching. Similar alloys were extruded, with an extrusion ratio of 4.6 to get proper densification. Optical microscopy was used for microstructure investigations of the produced alloys. The element distribution microstructure study was carried out using the Energy Dispersive X-ray analysis method. Hardness and tensile properties of the investigated alloys have been examined. Wear resistance tests were carried out and the results were compared with these of the Al-based bulk alloys. Results showed that the aluminum base alloys containing 10wt. % Chromium and heat treated at 500°C for one hour followed by water quenching exhibited the highest wear resistance and better mechanical properties.

Beginning in December 2019, a novel coronavirus known as SARS-CoV-2 has caused an international outbreak of respiratory illness termed COVID-19. This disease may cause mild to moderate respiratory illness. However, older individuals and those with underlying medical conditions like diabetes, cancer, and cardiovascular disease are more likely to develop serious illnesses (progressive pneumonia, multi-organ failure, and even death) (1). The main target for antiviral therapy for COVID-19 is the 3CL protease (3CLpro, Main protease, Mpro, Nsp5). The 3CL protease plays an integral role in viral replication and is often known as the “Achilles heel” of the SARS-CoV-2 virus (2). Thus, NLC Pharma utilized a unique and novel technology termed Quantum Core Technology (QCT) to design a mechanism-based potent inhibitor against the SARS-Cov-2 3CL protease. 3CL Pharma has designed an oral anti-viral for COVID-19 called Tollovir. Biochemical assays have revealed that 40uM of Tollovir in PBS can achieve 90% maximum inhibition of 3CL protease. Furthermore, the oral anti-viral has completed clinical trial phase 2b/3. Tollovir has proven to be safe and significantly decreases mortality rates of hospitalized patients with COVID-19 infection.

The corrosion inhibition behavior of cetyl pyridinium chloride (CPC) on mild steel (MS) in 0.5 M H₂SO₄ solution was examined using the weight loss method and potentiodynamic polarization method. The experimented MS surface was characterized by Fourier Transform Infrared Spectroscopy (FTIR), Field Emission Scanning Electron Microscopy (FESEM), and Atomic Force Microscopy (AFM). Corrosion rate and corrosion efficiency was calsulated via weight loss and potentiodynamic polarization methods where the corrosion rate in 0.5 M H₂SO₄ , 0.000192 M, and 0.0077 M of CPC solution was 12.09×10^-3, 8.23×10^-3, 6.63×10^-5 (mm/Year), respectively and the inhibition efficiency of 94.42% and 98.54%. FESEM studies demonstrated the corrosion attack on MS surface. Also, the EDX showed the presence of nitrogen of CPC. Thus, CPC acts as an important corrosion inhibitor.

To enhance the corrosion resistance of molybdenum metal in molten zinc, this study successfully fabricated TiB2 coatings on molybdenum substrates using the molten salt electrophoretic deposition technique and investigated their corrosion resistance in molten zinc. Initially, TiB2 nanoparticles with a size ranging from 50 to 150 nm were synthesized using the borothermal reduction method in NaF-AlF3 molten salts at 1238 K. Subsequently, electrophoretic deposition experiment was conducted by applying a cell voltage of 1.2 V (corresponding to an electric field of 0.6V/cm) for 1 h in the molten salts containing TiB2 nanoparticles, resulting in a uniform, continuous, and dense TiB2 coating with a thickness of 35 μm on the molybdenum substrate. Moreover, the corrosion resistance of the TiB2 coated molybdenum metal to molten zinc was tested through continuous immersion. After 120 h of immersion, the TiB2 coating showed no signs of cracking or peeling off, successfully protecting the molybdenum metal substrate from corrosion by molten zinc. The results confirm that the molten salt electrophoretic deposition technique can be used to prepare TiB2 coatings with good resistance to molten zinc corrosion on molybdenum metal.

Information taken from David A. Scott’s book “Copper and Bronze in Art” was crucial for research on copper corrosion products in Stuttgart. Examples discussed are the nature and variability of ‘Black Spots’ (aka ‘Brown Fuzzies’); cupric hydroxide by cleaning, patination, and pigment synthesis; the wondrous phenomenon of curly malachite; chalconatronite formed by contact to soda glass; the formation of copper formates by glass-induced metal corrosion; and synthesis and X-ray diffraction of basic copper acetates (‘verdigris’).

Menaquinone is one of the major lipoquinones involved in the respiratory chains of bacteria, which includes ubiquinone. Menaquinone is an essential component in the electron transfer process and ATP synthesis especially in some Gram-positive bacteria including Mycobacterium tuberculosis (M. Tb). However, mammals utilize ubiquinone in the analogous electron transfer processes, and do not synthesize menaquinone. In the biosynthesis of menaquinone, MenA is an important enzyme, which is involved in the conversion of 1,4-dihydroxy-2-napthoate to demethylmenaquinone via prenyl transferase activity. Therefore MenA is chosen as a drug target in determining the inhibitor. While designing and screening MenA inhibitors we observed that benzophenone derivatives showed high coordination with enzymes in transition state and interrupted the growth of M. Tb moderately. In addition, diphenyl ether derivatives also showed moderate MIC and IC50 results. Therefore, to improve the biological activity we synthesized a polymeric compound having both benzophenone and diphenyl ether groups. In addition, a hydrophilic functional group was introduced into the polymeric compound to enhance the biological activity. The synthesized polymeric inhibitor showed improved MIC and IC50 values to inhibit the M. tb infection.

it still undergoes corrosion when exposed to corrosive environments. This paper proposes an evaluation method for assessing the corrosion level of SPCC steel specimens using traditional eddy current testing (ECT), along with two different machine learning approaches. The objective is to classify the corroded state of the specimens into two states: a less corroded state (state-1) and a highly corroded state (state-2). Generative and discriminative models were implemented for classification. The generative classifier was based on the Gaussian mixture model (GMM), while the discriminative model was based on the logistic regression model. The models used features based on the absolute maximum of the perturbation magnetic field components at two different frequencies. The performance of the classifiers was evaluated using metrics such as absolute error, accuracy, precision, recall, and F1 score. The results indicate that high classification accuracy can be achieved based on both methods using traditional eddy current testing.

Nano-titanium has excellent corrosion resistance and can be widely used in the field of corrosion resistant coatings. This paper introduces nano-weight titanium modified phenolic resin coatings and their anti-corrosion properties to explore the principle of nano-titanium modification and the mechanism of anti-corrosion to further develop more advanced corrosion resistant coatings. The article uses scanning electron microscopy, Fourier transform infrared spectroscopy, Raman spectroscopy and UV-Vis spectrophotometer to characterise the morphology and structure of the nano-titanium modified phenolic resin coatings and to determine the corrosion resistance properties of the modified phenolic resin coatings. The results show that the 4% nano-titanium modified phenolic resin coating, nano-titanium powder and phenolic resin will maximize the dispersion and combination, and the structure is good; nano-titanium grafted on phenolic resin, the successful preparation of nano-titanium modified phenolic resin; modified nano-titanium added to improve the coating's ability of UV absorption. The corrosion resistance of the coating is much better than that of the unmodified phenolic resin coating.

Plasma Electrolytic Oxidation (PEO) is a surface treatment, similar to anodizing, that produces thick oxide films on the surface of metals. In the present work, PEO coatings were obtained on zinc-aluminized (ZA) carbon steel using as electrolyte a solution containing sodium silicate and potassium hydroxide, and working with high current densities and short treatment times in DC mode. The surface morphology resulted the typical one of PEO layers, with the presence of a lot of pores and micro-cracks. Considering the cross section, the thickness of the coating was strongly influenced by the process parameters, with different dissolution grades of the ZA layer depending on the current density and treatment time. The PEO layer resulted mainly composed by aluminum and zinc oxides and silicates. The corrosion resistance was remarkable increased in the samples with the PEO coating.

Cholesterol homeostasis is pivotal for cellular function. Acyl-coenzyme A:cholesterol acyltransferase 1 (ACAT1), also abbreviated as SOAT1, is an enzyme catalyzing the storage of excess cholesterol to cholesteryl esters. ACAT1 is an emerging target to treat diverse diseases including atherosclerosis, cancer, and neurodegenerative diseases. F12511 is a high affinity ACAT1 inhibitor. Previously, we developed a stealth liposome-based nanoparticle to encapsulate F12511 to enhance its delivery to the brain and showed its efficacy in treating a mouse model for Alzheimer’s disease (AD). In this study, we introduce F26, a close derivative of F12511 metabolite in rats. F26 was encapsulated in the same DSPE-PEG2000/phosphatidylcholine (PC) liposome-based nanoparticle system. We employed various in vitro and in vivo methodologies to assess F26's efficacy and toxicity compared to F12511. Results demonstrate that F26 is more effective and durable than F12511 in inhibiting ACAT1, in both mouse embryonic fibroblasts (MEFs) and in multiple mouse tissues including the brain tissues, without exhibiting any overt systemic or neurotoxic effects. This study demonstrates the superior pharmacokinetic and safety profile of F26 in wild-type mice, and suggests its therapeutic potential against various neurodegenerative diseases including AD.

This article utilized electrodeposition technology to fabricate Zn and Zn-Y₂O₃-Al₂O₃ composite coatings on Q235 steel plates. The composite coatings were obtained by adding Y₂O₃/Al₂O₃ nanoparticles (0, 5, 10, and 15 g/L) to acidic chloride solutions. This study then examined the impact of these nanoparticles on the microstructure, morphology, microhardness, hydrophobicity, and corrosion resistance of the composite coatings. The results indicate that the addition of the nanoparticles increased the nucleation sites on the surface of the coating, thereby refining the grain size and reducing the roughness of the coating surface. When 10g/L of Y₂O₃ and 10g/L of Al₂O₃ nanoparticles were added, the hardness of the composite coating (369 Hv) was 2.49 times higher than that of the pure Zn coating (148 Hv), which was attributed to the dispersion strengthening and grain refinement effects of the nanoparticles. The corrosion resistance of the Zn and Zn-Y₂O₃-Al₂O₃ composite coatings was studied using linear sweep voltammetry and AC impedance spectroscopy. The addition of the nanoparticles improved the corrosion resistance of the composite coating, and the composite coating prepared in an electrolyte containing 10 g/L of Y₂O₃ and 10 g/L of Al₂O₃ nanoparticles exhibited the best corrosion resistance. Meanwhile, the composite coating exhibited good hydrophobicity, with a contact angle of 120.9°, 1.94 times that of the pure Zn coating (62.2°). The Zn-Y₂O₃-Al₂O₃ nanocomposite coating material has significant potential advantages in the field of steel corrosion.

The 70/30 copper–nickel alloy is mainly used in critical parts with more demanding conditions in marine settings. There is a need for innovative methods that offer fast production and cost-effectiveness to supplement current copper–nickel alloy manufacturing processes. In this study, we employ wire-arc additive manufacturing (WAAM) to fabricate the 70/30 copper–nickel alloy. The as-built microstructure is characterized by columnar grains with prominent dendrites and chemical segregation in the inter-dendritic area. The aspect ratio of the columnar grain increases with increasing travel speed (TS) at the same wire feed speed (WFS). This is in contrast to an equiaxed grain structure with a more random orientation of conventional sample. The sample built with a WFS of 8 m/min, TS of 1000 mm/min, and a track distance of 3.85 mm exhibits superior corrosion properties in the 3.5 wt% NaCl solution compared to the conventional one, as evidenced by a higher film resistance and breakdown potential, along with a lower passive current density of the WAAM sample. The corrosion morphology reveals the critical roles played by the nickel element unevenly distributed between the dendrite core and inter-dendritic area.

The study’s objective is to analyse the mechanical properties of steel pipe piles as a part of a trestle bridge subjected to five years of natural marine corrosion degradation. Sixteen tensile specimens were extracted from the steel pipe piles in the splash, tidal, and immersion zones. The experimental tensile test results are used to establish regression equations defining elastic modulus, yield strength, strain hardening index, and strength coefficient for the true stress-strain curves of the three regions. A non-linear time-dependent mathematical model is exploited to identify the corrosion degradation using the data from one single corrosion degradation measurement campaign. The analysis indicated that the splash zone experiences the most severe corrosion degradation, and there are progressive losses in the mechanical properties of each zone as the corrosion degradation progresses. The established relationships of the mechanical properties, as a function of the ratio of corroded plate thickness to the as-built one, can be used as a fast-engineering approach to identify the mechanical properties of severely corroded piles. The corrosion degradation allowance is also defined using the First Order Reliability Method, accounting for existing uncertainties covered by the partial safety factors. By examining the impact of marine corrosion on the mechanical properties of marine structures and developing predictive models to assess the corrosion’s effect on material strength and corrosion allowance, the study aims to improve offshore structures’ safety, design, and maintenance.

The development of Al-Ni alloys with a controlled microstructure has had a great impact on the field of study of aluminum-based alloys. In the present research, the influence of thermal parameters on the grain structures resulting from the directional solidification process of Al-Ni alloys with different alloy content has been studied. It has also been evaluated how different structures and the distribution of second phases influence the corrosion behavior and microhardness of alloys. The columnar-to-equiaxed transition (CET) was observed to occur when the temperature gradient in the melt decreased to values between 1.3 to 2.9 ° C/cm. In addition, a small increase in the microhardness values was observed as a function of the Ni-content. When the Ni-content increase, the resistance to polarization decreases for samples with equiaxed grain structure, throughout the range of compositions studied. Furthermore, the equiaxed grain structure presents higher resistance to polarization values than the columnar grain zone, for alloys with a composition equal to or lower than the eutectic composition.

In the present study, the corrosion resistance of amorphous coating and composite coatings in 3.5 wt.% NaCl, 0.5 M H₂SO₄ and 10 wt.% NaOH solution were studied. The composite coatings exhibit superior corrosion resistance. When the content of AT13 （Al₂O₃–13 wt.% TiO₂）was 15 wt.%, the composite coating has the lowest corrosion current density (1.75×10^-6 A cm^-2), which is 5.14×10^-5 A cm^-2 for Fe-based metallic glassy coating, and the highest corrosion potential (-411 mV), which is -580 mV for Fe-based metallic glassy coating. The breakdown potential of the passivation film in 3.5 wt.% NaCl solution was much higher than that of 316L.The long-time immersion corrosion tests carried out on different coatings showed that the corrosion protection effect of coating was enhanced with the increase of the amount of AT13 added.

Repair mortar is commonly used to rehabilitate reinforced concrete structures or components that exhibit a relatively high level of distresses. Yet, this repair mortar can be contaminated by salt from its service environment. This work employs a two-dimensional finite element model to investigate the transport behavior of ionic species in salt-contaminated and water-saturated repair mortar under an externally applied electric field. The model was experimentally validated and then utilized to evaluate the effectiveness of electrochemical chloride extraction (ECE) with or without electrical injection of corrosion inhibitor (EICI). In the case study, both the ECE alone and the ECE+EICI treatment was found effective in decontaminating the zone in front of the steel rebar. In both techniques, the magnitude of current density has a significant effect on removing chloride out of the mortar and increasing the pH of the pore solution near the rebar, whereas the treatment time any not have a significant effect under some scenarios. The injection of the organic corrosion inhibitor significantly slowed down the removal of chloride. Changes in the ionic distribution in the mortar were generally beneficial in reducing the corrosion risk of the steel rebar and thus extending the service life of the repair mortar.

Cellular automata (CA) models have emerged as a valuable tool in corrosion management. This manuscript provides an overview of the application of cellular automata models in corrosion research, highlighting their benefits and contributions to understanding the complex nature of corrosion processes. Cellular automata models offer a computational approach to simulate corrosion behavior at the microscale, capturing the intricate interactions between electrochemical reactions, material properties, and environmental factors generating a new vision of predictive maintenance. It discusses the key features of cellular automata, such as the grid-based representation of the material surface, the definition of state variables, and the rules governing cell-state transitions. The ability to model local interactions and emergent global behavior makes cellular automata particularly suitable for simulating corrosion processes. Finally, cellular automata models offer a powerful and versatile approach to studying corrosion processes, expanding models that can continue to enhance our understanding of corrosion and contribute to the development of effective corrosion prevention and control strategies.

Neuroblastoma (NB) is a childhood cancer with heterogeneous characteristics, posing challenges to effective treatment. NBs express somatostatin receptors that facilitates the use of somatostatin analogs (SSTAs) as tumor-seeking agents for diagnosis and therapy. High-risk (HR) NBs often have gain-of-function mutations in the receptor tyrosine kinase anaplastic lymphoma kinase (ALK). Despite intensive multimodal treatment, survival rates remain below 40% for children with HR-NB. The aim of this work was to investigate the combined effect of the SSTA 177Lu-octreotide with the ALK inhibitor lorlatinib. Mice bearing human HR-NB CLB-BAR tumors were treated with lorlatinib, 177Lu-octreotide, combination of these pharmaceuticals or saline (control). Tumor volume was monitored and tumor samples were evaluated for cleaved caspase-3 and expression of 84 human genes involved in apoptosis. Combination treatment with 177Lu-octreotide and lorlatinib demonstrated synergistic antitumor effects. Increased number of cleaved caspase 3-positive cells was observed in tumors from mice treated with 177Lu-octreotide alone and in combination with lorlatinib. Modulation of Bcl-2 family gene expression was observed only in the presence of both 177Lu-octreotide and lorlatinib, with BID downregulated and HRK upregulated on days 2 and 7, respectively. The data suggests that ALK signaling pathway inhibition may contribute to radiosensitization in radionuclide therapy with 177Lu-octreotide.

Reducing fertilizer-N rate, applying nitrification inhibitor (NI), and incorporating straw are widely recommended to improve N use efficiency of crops and decrease N losses. However, how these practices affect crop N uptake by regulating the fertilizer-N fate during the growing season is not well understood. We conducted a field 15N tracer study to explore the effectiveness of reduced N application, NI, and straw incorporation on fertilizer-N fates for maize cultivation in Northeast China. The following six treatments were used: 1) no N fertilization (control); 2) 200 kg urea-N ha−1 (100%N); 3) 200 kg urea-N ha−1 and 2400 kg dry-straw ha−1 (100%N+S); 4) 160 kg urea-N ha−1 (80%N, i.e., 20% reduction of N fertilization); 5) 160 kg urea-N ha−1 and nitrification inhibitor (Nitrapyrin) (80%N+NI); 6) 160 kg urea-N ha−1, nitrification inhibitor and 2400 kg dry-straw ha−1 (80%N+NI+S). Our results showed that the five N fertilization treatments yielded 16%–25% more grain and 39%–60% more crop N uptake than the control receiving no N fertilizer, but the differences among the five treatments were not statistically significant. In contrast to plant growth, changes in fertilizer-N fates in soil and plant pools were more pronounced. Compared with the 100%N treatment, 20% fertilizer-N reduction (80%N) decreased 15N concentration in topsoil and plant pools but increased the proportion of plant 15N recovery at harvesting (N use efficiency, NUE15N, 60% vs. 50%) (P < 0.05). Nitrapyrin co-application (80%N+NI) delayed soil nitrification and increased soil 15N retention at harvesting (52% vs. 36%), thereby decreasing NUE15N significantly (P < 0.05). Straw incorporation (100%N+S) decreased fertilizer-N retention compared with NI co-application because it promoted NUE15N significantly (P < 0.05). The combined application of NI and straw (80%N+NI+S) was more conducive to fertilizer-N retention in soil. Our findings demonstrate that NI and straw additions are efficient strategies for stabilizing fertilizer-N in soils and potentially minimizing N loss; however, their effects on NUE15N vary and the related mechanism must be further clarified in long-term trials.

Our investigations show that electrochemical corrosion of copper is faster than electrochemical corrosion of aluminium at temperatures below 100oC. Literature data analysis shows that the Al atoms diffuse faster than the Cu atoms at temperatures higher than 475oC, Al rich intermetallic compounds (IMCs) are formed faster in the Cu-Al system, and the Kirkendall plane shifts toward Al side. Electrochemical corrosion occurs due to electric current and due to diffusion. An electronic devise working time, for example, depends on initial copper cover thickness on aluminium wire, connected to the electronic devise, temperature, and volume and dislocation pipe diffusion coefficients, so copper, iron, and aluminium electrochemical corrosion rates are investigated experimentally at room temperature and at temperature 100oC. Intrinsic diffusivities ratios of copper and aluminium at different temperatures and diffusion activation energies in the Cu-Al system are calculated by proposed here methods using literature experimental data. Dislocation pipe and volume diffusion activation energies of pure iron are calculated separately by earlier proposed method using literature experimental data. Aluminium dissolved into NaCl solution as the Al3+ ions at room temperature and at temperature 100oC, iron dissolved into NaCl solution as the Fe2+ (not Fe3+) ions at room temperature and at temperature 100oC, copper dissolved into NaCl solution as the Cu+ ions at room temperature and as the Cu+ and the Cu2+ ions at temperature 100oC. It is founded experimentally that copper corrosion is higher than aluminium corrosion, and ratio of electrochemical corrosion rates, kCu/kAl>1, decreases with temperature increasing, although iron electrochemical corrosion rate doesn’t depend on temperature below 100oC. It is obvious, because melting point of iron is more higher then melting point of copper or aluminium. It is calculated that copper electrochemical corrosion rate is approximately equal to aluminium electrochemical corrosion at temperature about 300oC, so copper can dissolve into NaCl solution mostly as the Cu2+ ions at temperature about 300oC. Ratio of intrinsic diffusivities, DCu/DAl <1, increases with temperature increasing, and intrinsic diffusivity of aluminium could be approximately equal to intrinsic diffusivity of copper at temperature about 460oC.

Cellular senescence accumulates with age and has been shown to impact numerous physiological and pathological processes, including immune function. The role of cellular senescence in cancer is multifaceted, but the impact on immune checkpoint inhibitor response and toxicity has not been fully evaluated. In this review, we evaluate the impact of cellular senescence in various biological compartments, including the tumor, the tumor microenvironment, and the immune system on immune checkpoint inhibitor efficacy and toxicity. We provide an overview of the impact of cellular senescence in normal and pathological contexts and examine recent studies that have connected aging and cellular senescence to immune checkpoint inhibitor treatment in both the pre-clinical and clinical contexts. Overall, senescence plays a multi-faceted, context-specific role, and has been shown to modulate immune-related adverse event incidence as well as immune checkpoint inhibitor response.

In this paper we overview all analytical engineering solutions for corrosion problems in pressure vessels delivered over the past 60 years. We briefly detail strengths and weaknesses of existing approaches, thus demonstrating the need for novel uniform corrosion analysis methods for both current and new applications. To complement the review, we also present a new analytical model allowing to estimate the lifetime of pressured elastic vessels with mechanically assisted corrosion. Both internal/external pressure and internal/external corrosion are captured and dissolution driven corrosion is also considered. The readily implemented method improves existing analytical approaches and is shown to be effective for thin and thick shells, as well as various loading and corrosion intensity and geometrical conditions.

The acoustic emission (AE) technique was applied to monitor the pitting corrosion of carbon steel in NaHCO₃ + NaCl solutions. The open circuit potential (OCP) measurement and the corrosion morphology in-situ capturing using optical microscope were conducted during AE monitoring. The corrosion micromorphology was characterized with scanning electron microscope (SEM). The propagation behavior and AE features of natural pitting on carbon steel were investigated. After the performing of signal processing including pre-treatment, shape preserving interpolation and denoising for raw AE waveforms, three types of AE signals can be classified in the correlation diagrams of new waveform parameters. Finally, a 2D pattern recognition method was established to calculate the similarity of different continuous AE graphics, which is quite effective to distinguish the localized corrosion from uniform corrosion.

Petrochemical plants use on-stream inspection more often to detect and monitor the corrosion on the equipment and piping system. Compared to ultrasonic thickness gauging and pulse-echo A-scan, phased array corrosion mapping has better coverability and can scan a large area to detect general and localized corrosion. This paper's objective is to obtain documentary evidence on the accuracy of corrosion detection from 30°C to 250°C on A36 low-carbon steel by carrying out simulation experiments every 10°C steps. A minimum of three sets of phased array corrosion mapping data in each temperature were collected to study and evaluate the detectability. The data evidence could enhance the confidence level of the plant's end users to use the phased array mapping in the future during an inspection. The experiments were found to be insufficiently thorough despite addressing the initial concerns, leaving more area for discussion in further studies, such as expanding the investigation to thicker carbon steel, stainless steel, and wedge materials.

Introduction: Immune checkpoint inhibitors (ICI) are used to treat various malignancies. They block the inhibitory signals of tumor cells and enhance the inflammatory cascade which results in tumor killing. However, this can lead to unchecked inflammation throughout the body, leading to various adverse effects. A rare gastrointestinal adverse effect of ICI therapy is the development of immune-mediated celiac disease. This entity has a similar clinical presentation to the more common ICI-induced enterocolitis. Our study aims to determine the clinical characteristics and optimal treatment strategies for this rare ICI toxicity, and differentiate it from ICI-induced enterocolitis. Methods and Material: We conducted a retrospective analysis of eight cases of ICI-induced celiac disease and 24 cases of ICI-induced enterocolitis from the literature. Data on patient demographics, clinical history, therapeutic interventions and outcomes were collected. Comparative analysis was performed to identify the key differences between the two groups. Results: Patients with ICI-induced celiac disease were more likely to have a pre-existing autoimmune condition and HLA-DQ2 positivity. Significant differences in clinical manifestations, histological findings, and treatment outcomes were observed. Notably, weight loss, nutritional deficiencies and electrolyte abnormalities were more commonly associated with ICI-CD. On pathology, duodenal villous blunting was noted more commonly with ICI-induced celiac disease. Initiating a gluten-free diet led to rapid improvement in patients with ICI-induced celiac disease, while immunosuppressive therapy did not have an impact. Conclusion: ICI-induced celiac disease is a rare and underrecognized gastrointestinal adverse effect of ICI therapy, often misdiagnosed as ICI-induced enterocolitis. Early recognition and treatment with a gluten-free diet can lead to rapid symptom resolution, sparing patients from unnecessary systemic immunosuppression and discontinuation of antineoplastic immunotherapy.

Scale inhibitors are deployed as preventive and rejuvenation operation in oil and gas industry when production operations are under threat or menace of scale blockage. The application of scale inhibitors is carried out through a method known as squeezing. In general, the squeeze process is governed by inhibitor-rock interaction which is described by adsorption/desorption isotherm. Most reservoirs produce loose sand grains or fine sand which float and flow within the pore spaces along with the squeezed scale inhibitors. Hypothetical reports have shown that not all scale inhibitors pumped into the formation adsorb onto the formation rock. A number of factors (irreversible adsorption, pH changes, competing ions, concentration and temperature) have been considered to affect the adsorption and return profile of these scale inhibitors. This review work examines the performances of most common scale inhibitors used in the oil and gas production activities, theoretical application in reservoirs and how loose fine sand grains affect the adsorption and desorption characteristics of squeezed scale inhibitors. Additionally, presented were overviews of previous reports on fine sand production and migration of fine sands through formation pores in reservoirs.

This study aimed to evaluate the safety and tolerability of STP1, a combination of ibudilast and bumetanide, tailored for the treatment of a specific subgroup of patients with Autism Spectrum Disorder (ASD), namely ASD Phenotype 1 (ASD-Phen1). We conducted a randomized, double-blind, placebo-controlled, parallel-group phase 1b study with two 14-day treatment phases (registered at clinicaltrials.gov as NCT04644003). Nine ASD-Phen1 patients were administered STP1, while three received a placebo. We assessed safety and tolerability, along with electrophysiological markers, such as EEG, Auditory Habituation, and Auditory Chirp Synchronization, to better understand STP1's mechanism of action. Additionally, we used several clinical scales to measure treatment outcomes. The results showed that STP1 was safe and well-tolerated, with electrophysiological markers indicating a significant and dose-related reduction of gamma power in the whole brain and in brain areas associated with executive function and memory. Treatment with STP1 also increased alpha 2 power in frontal and occipital regions and improved habituation and neural synchronization to auditory chirps. Although numerical improvements were observed in several clinical scales, they did not reach statistical significance. Overall, this study suggests that STP1 is safe and well-tolerated in ASD-Phen1 patients and shows indirect target engagement in ASD brain regions of interest.

The corrosion behavior of the TiTaNbZrAg alloys with different amounts of Tantalum (0 %, 10 % and 20%) and with distinct surface topography (smooth and rough) was investigated in phosphate buffer solution (PBS) for long-time immersion (1000 hours). The corrosion resistance was studied by Open circuit potential (OCP), potentiodynamic polarization (PP) and electrochemical impedance spectroscopy (EIS). From the potentiodynamic investigations, it was observed that all types of samples show good corrosion resistance (i.e. Rcorr < 10µm y-1) and may be used successfully for medical applications. However, the samples with smooth surface and with a certain amount of Ta (10 % and 20%) exhibit the best corrosion performance (Rcorr < 1µm y-1). As regard the samples with rough surface, the results evidenced that they show lower corrosion resistance (1< Rcorr < 3 µm y-1), suggesting that the Ta presence not necessary brings about a very good corrosion protection. Actually, the synergetic effect of both the presence of Ta and surface roughness plays an important role in corrosion behavior. Based on literature reports, we assume that the good corrosion resistance results from the good stability of the film, formed mainly from Ta2O5 and TiO2, formed on the alloy surface during immersion in PBS.

Worldwide the steel corrosion is one of the greatest deterioration problems for reinforced concrete structures. Comparing some literature experimental results with a complex FEM model, the present paper points out the principal aspects those characterize the static behavior of RC elements damaged by corrosion. Moreover, the non-dimensional abaci defined for some specific case studies finalized to the evaluation of the residual flexural strength of corroded elements highlight the dangerousness of the corrosion degradation if the failure of the element is governed by the steel

In a recent effort to mitigate harm from human pathogens, many biosynthetic pathways are extensively evaluated for their ability to inhibit pathogen growth and determine drug targets. Among those, one of the important products/targets of such pathways is isopentenyl diphosphate, the universal precursor of isoprenoids, which are essential for the normal functioning of microorganisms. In general, two biosynthetic pathways lead to the formation of isopentenyl diphosphate: 1) the mevalonate pathway in animals and 2) the non-mevalonate or methylerythritol phosphate (MEP) in many bacteria, some protozoa, and plants. Because the MEP pathway is not found in mammalian cells, it is considered an attractive target for the development of antimicrobials against a variety of human pathogens, including Mycobacterium tuberculosis (M.tb). In the MEP pathway, 4-diphosphocytidyl-2-c-methyl-d-erythritol kinase (IspE) phosphorylates 4-diphosphocytidyl-2-C-methyl-D-erythritol (CDPME) to form 4-diphosphocytidyl-2-C-methyl-D-erythritol 2-phosphate (CDPME2P), followed by cyclization to 2-C-methyl-D-erythritol 2,4-cyclodiphosphate (MECPP) by 2-C-methyl-D-erythritol 2,4-cyclodiphosphate synthase (IspF). A virtual high throughput screening was done by docking IspE protein with commercially available compounds and identified an active heterotricyclic compound. Hence, we designed, synthesized, and tested similar new heterotricyclic compounds. This study will provide the critical insight necessary for the ability to develop novel antimicrobials that target the MEP pathways in pathogens.

Conventional heat treatment is not capable of converting a sufficient amount of retained austenite into martensite in high-carbon or high-carbon and high-alloyed iron alloys. Cryogenic treatment induces the following alterations in the microstructures: (i) a considerable reduction in the retained austenite amount, (ii) formation of refined martensite coupled with an increased number of lattice defects, such as dislocations and twins, (iii) changes in the precipitation kinetics of nano-sized transient carbides during tempering, and (iv) an increase in the number of small globular carbides. These microstructural alterations are reflected in mechanical property improvements and better dimensional stability. A common consequence of cryogenic treatment is a significant increase in the wear resistance of steels. The current review deals with all the mentioned microstructural changes as well as the variations in strength, toughness, wear performance, and corrosion resistance for a variety of iron alloys, such as carburising steels, hot work tool steels, bearing and eutectoid steels, and high-carbon and high alloyed ledeburitic cold work tool steels.

Two austenitic stainless steel (ASS) plates, 304L and 316L, were cold-rolled (304R and 316R) with a 10 % reduction in thickness then subjected to laser welding. Cold-rolling caused a slight surface hardening and introduced residual tensile stress into the ASS plates. The susceptibility to stress corrosion cracking (SCC) of the welds (304RW and 316RW) was determined using the U-bend test pieces in a salt spray. To highlight the stress concentration at the weld’s fusion boundary (FB), the top weld reinforcement was not ground off before bending. Moreover, micro-shot peening (MSP) was performed to mitigate the SCC of the welds by imposing high residual compressive stress and forming a fine-grained structure. Cold-rolling increased the susceptibility of the 304R specimen to pitting corrosion (PTC) and intergranular (IG) microcracking. Moreover, PTC and SCC were found more often at the FBs of the 304RW. The corrosion pits of the peened 304RW (304RWSP) were finer but greater in amount than the un-peened one. The results also indicated that the 316L ASS welds with MSP was resistant to the incidence of PTC and SCC in a salt spray. The better reliability and longer service life of dry storage canister could be achieved by using 316L ASS for construction and application of MSP on it.

Porous metals possess low bulk density, large specific strength, high stiffness and special thermal, electromagnetic and acoustic conductivity, so that porous metals are widely used in filtration and separation, flame retardant explosion-proof, biomedical application, etc. Compared with its corresponding dense metal, the presence of porous structures also leads to different corrosive performances of porous metal. So, some researches have utilized weight loss method, electrochemical impedance to evaluate porous metals’ corrosion behavior; however, the influence of pore structure on metal corrosion is still controversial, and present methods used for analyses of porous metals’ corrosion are statistical averages of the corrosion behavior of the entire porous material, which cannot accurately reflect the corrosion behavior inside the pore structure. Herein, we prepare porous copper samples with 0, 24, 72, 96 pores using mechanical process, and employ scanning kelvin probe combined with electrochemical polarization curve and impedance spectroscopy to test the corrosion performance of the porous copper in static and dynamic NaCl solution. The relevant results indicate that in static solution, the corrosion resistance of samples gradually increases with the rise of the number of pores. By contrast, the sample with 24 pores exhibits more susceptible to corrosion than the sample without pore.

Concrete is the most utilized construction material worldwide. In the marine environment, it is subject to chemical degradation through reactions with chloride (the most important ion), sulfate and magnesium ions in seawater and to biodeterioration resulting from biological (initially microbiological) activities, principally acid production. These two types of corrosion are reviewed and the failure of attempts to predict the degree of deterioration resulting from each is noted. Chemical (abiotic) corrosion is greatest in the splash zone of coastal constructions, while phenomenological evidence suggests that biodeterioration is greatest in tidal zones. There have been no comparative experiments to determine the rates and types of microbial biofilm formation in these zones. Both chemical and microbiological concrete deterioration are complex and have not been successfully modeled. The interaction between abiotic corrosion and biofilm formation is considered. EPS can maintain surface hydration, potentially reducing abiotic corrosion. The early marine biofilm contains relatively specific bacterial colonizers, including cyanobacteria and proteobacteria; these change over time, producing a generic concrete biofilm, but adhesion of microorganisms to concrete in the oceans is little investigated. The colonization of artificial reefs is briefly discussed. Concrete appears to be a relatively prescriptive substrate, with modifications necessary to increase colonization for the required goal of increasing biological diversity.

Inclusions in steels and alloys are known as factors that could lower deformation, mechanical, corrosion and other properties. Study of inclusions in nickel based alloys is important since these materials could suffer from corrosion degradation in harsh operational conditions, where inclusions could lead to a pitting initiation. For estimation of a harmful effect of different inclusions on corrosion resistance of Ni-based alloys, inclusion characteristics (such as composition, morphology, size, number and location) on film filter and dissolution of metal matrix around different inclusions on surfaces of metal samples after electrolytic extraction (EE) were investigated in two samples of industrial Ni-based alloys (alloy 718 and EP718). It was found that both Ni-based alloys have various inclusions: carbides (large size NbTi-C and small multicomponent carbides), nitrides TiNb-N and sulfides (TiNb-S in EP718 alloy). The higher harmful effect on corrosion resistance of metal was detected around sulfides and small carbides containing Mo, W, Cr. Dissolution effect was also observed around large carbides and nitrides, especially around inclusions having size more than 10 µm. Moreover, the dissolution of metal matrix around inclusions and clusters located on the grain boundaries is 2.1-2.7 times larger compared to that for those inclusions inside of grains of the given alloy samples.

1) Background: The objective was to evaluate the corrosion resistance of different commercially pure ultrafine-grained (UFG) titanium and its alloys with acid etched surface processed by equal-channel angular pressing (ECAP); 2) Methods: Coarse-grained and UFG titanium samples were investigated using polarization resistance technique. Surface characteristics of the native oxidized layer were evaluated by TEM and XRD. Electrochemical tests were under physiological electrolyte at a rate of 1 and 10 mV/s. Weight loss tests were performed after immersion into HCl solution for up to 3 years; 3) Results: UFG titanium was less susceptible to corrosion which was identified under lower rates and at higher polarization resistance than its coarse grain counterparts. Titanium Grade 2 and Grade 4 demonstrated similar corrosion susceptibility. Titanium Grade 5 revealed a thin and tightly adhered native oxide layer with adequate corrosion resistance; 4) Conclusions: ECAP process imposed a more compact and adhered oxidized layer. Surface etching techniques delivered a thicker native TiO₂ layer, being both grain refinement and surface etching techniques responsible for the improved corrosion resistance of Titanium samples under physiological environment after 3 years of observation.

In this work, we investigated the effects of heat treatment on the microstructure, hydrogen storage characteristics and corrosion rate of a Ti₃₄V₄₀Cr₂₄Fe₂ alloy. The arc melted alloy was divided into three samples, two of which were separately quartz-sealed under vacuum and heated to 1000 °C for 1 h; one of these samples was quenched and the other furnace cooled to ambient temperature. The crystal structures of the samples were studied via X-ray diffractometry and scanning electron microscopy. Absorption/desorption characteristics were investigated using a Sievert apparatus. Potentiostat corrosion tests on the alloys were performed using an AutoLab^® corrosion test apparatus and electrochemical cell. All samples exhibited a mixture of body-center-cubic (BCC) and Laves phase structures. The corrosion rate, maximum absorption, and useful capacities increased after both heat treatments. The annealed sample had the highest absorption and reversible capacity. The plateau pressure of the as-cast alloy increased after quenching. The corrosion rate increased from 0.0004 mm/y in as-cast sample to 0.0009 mm/y after annealing and 0.0017 mm/y after quenching, due to a decrease in the Cr-content of the C14 phase.

The aberrant glycosylation is a hallmark of cancer progression and chemoresistance. It is also an immune therapeutic target for various cancers. Tunicamycin (TM) is one of the potent nucleo-side antibiotics and an inhibitor of aberrant glycosylation in various cancer cells, including breast cancer, gastric cancer, and pancreatic cancer, parallel with inhibition of cancer cell growth and progression of tumors. Thus, TM can be considered a potent antitumor drug in various cancers and may promote chemosensitivity. Mechanistically, TM impedes the role of the UDP-HexNAc enzyme in the biosynthesis of oligosaccharides, specialized macromolecules instrumental in N-linked glycosylation. Further, like chemotherapies such as doxorubicin (DOX), 5'fluorouracil, etoposide, and Cisplatin, TM induces the unfolded protein response (UPR) by blocking aberrant glycosylation. Despite TM's antitumor effectiveness, its lack of cell-type specific cytotoxicity impedes its anticancer efficacy. Thus, various nanoencapsulation techniques and materials have been considered for use in experiments to reduce TM's cytotoxicity and improve efficacy as a targeted therapy. The current review is a profound audit of the benefits and pitfalls of TM in various cancers, focusing on breast, colon, and pancreatic cancers. Additional progressive studies have also discussed the use of TM in immune checkpoints and other unique pathways. Cytotoxicity and other possibly adverse effects of TM are highlighted based on the data from in vitro and in vivo assays. In addition, the recent advances in nano-based drug delivery systems regarding TM have been emphasized. However, the potential of this nucleoside inhibitor re-quires thorough investigation and research to determine its likeliness as a viable chemotherapeutic.

Piceatannol is a naturally occurring polyphenolic compound that is widely found in grapes, blueberries, mushrooms, passion fruit and other edible fruits and vegetables. It has a variety of biological activities and pharmacological effects, including anti-inflammatory, antioxidation, antiaging, antiviral, antitumor, anticancer, antiatherosclerosis, antiparasitic, immunoregulatory, and cardiovascular protection effects. The aim of this study was to investigate the antiherpesvirus effects of piceatannol. Pseudorabies virus (PRV) belongs to the family Herpesviridae. PRV has a wide host range and can cause cytopathic effects (CPEs) in PK-15 cells. Therefore, PRV was used as a model to study the antiherpesvirus effect of piceatannol. In this study, we evaluated the antiviral activity of piceatannol against PRV in vitro and in vivo. The results showed that piceatannol could reatrain PRV multiplication in PK-15 cells in a dose-dependent manner. The 50% inhibitory concentration (IC50) was 0.0307 mg/mL, the IC50 was 0.0307 mg/mL, and the selectivity index (SI, CC50/IC50) was 3.68. The addition of piceatannol at different stages of PRV infection inhibited the viral adsorption and intracellular replication phases of PRV. Piceatannol significantly reduced the expression levels of the IE180, EP0, UL29, UL44, US6 and UL27 genes of PRV within 48 h, significantly reduced the expression levels of the PRV gB and gD proteins, and reduced PRV-induced apoptosis. Molecular docking showed that piceatannol had good binding activity with the PRV gB and gD proteins. The results of animal experiments in vitro indicated that piceatannol could delay the onset of disease, improve the survival rate of the mice (14.3%), reduce the viral load in the brain and kidney of the mice, alleviate the pathological changes in the mouse tissues and organs, and increase the levels of TNF-α, IEN-γ and IL-4 in the serum of the mice. These data indicate that piceatannol has good anti-PRV activity in vitro and in vivo, indicating that it could be a novel antiherpesvirus infection agent in the future.

Ovarian cancer is a deadly disease attributed to late-stage detection as well as recurrence and development of chemoresistance. Ovarian cancer stem cells (OCSCs) are hypothesized to be largely responsible for emergence of chemoresistant tumors. Although chemotherapy may initially succeed at decreasing the size and number of tumors, it leaves behind residual malignant OCSCs. In this study, we demonstrate that Aldehyde dehydrogenase 1A1 (ALDH1A1) is essential for the survival of OCSCs. We identified a novel ALDH1A1 inhibitor, compound 974, and used 974 as a tool to decipher the mechanism of stemness regulation by ALDH1A1. Treatment of OCSCs with 974 significantly inhibited ALDH activity, expression of stemness genes, spheroid, and colony formation. In vivo limiting dilution assay demonstrated that 974 significantly inhibited CSC frequency. Transcriptomic sequencing of cells treated with 974 revealed significant downregulation of genes related to stemness and chemoresistance as well as senescence and senescence associated secretory phenotype (SASP). We confirmed that 974 inhibited senescence and stemness induced by platinum-based chemotherapy in functional assays. Overall, these data establish that ALDH1A1 is essential for OCSCs survival and ALDH1A1 inhibition sup-presses chemotherapy induced senescence and stemness. Targeting ALDH1A1 using small molecule inhibitors in combination with chemotherapy therefore presents a promising strategy to pre-vent ovarian cancer recurrence and has potential for clinical translation.

The astacin protease Meprin β represents an emerging target for drug development due to its potential involvement in disorders such as acute and chronic kidney injury and fibrosis. Here, we elaborate on the structural basis of inhibition by a specific Meprin β inhibitor. Our analysis of the crystal structure suggests different binding modes of the inhibitor to the active site. This flexibility is caused, at least in part, by movement of the C-terminal region of the protease domain (CTD). The CTD movement narrows the active site cleft upon inhibitor binding. Compared with other astacin proteases, among those the highly homologous isoenzyme Meprin α, differences in the subsites account for the unique selectivity of the inhibitor. Although the inhibitor shows substantial flexibility in the orientation within the active site, the structural data as well as binding analyses including molecular dynamics simulations support a contribution of electrostatic interactions, presumably by arginine residues, to binding and specificity. Collectively, the results presented here and previously support an induced fit and substantial movement of the CTD upon ligand binding and, possibly, during catalysis. To the best of our knowledge, we here present the first structure of a Meprin β holoenzyme containing a zinc ion and a specific inhibitor bound to the active site. The structural data will guide rational drug design and the discovery of highly potent Meprin inhibitors.

The acetylcholinesterase (AChE) inhibitors are the main drugs for symptomatic treatment of neurodegenerative disorders like Alzheimer’s disease. A recently designed, synthesized and tested hybrid compound between the AChE inhibitor galantamine (GAL) and the antioxidant polyphenol curcumin (CU) showed high AChE inhibition in vitro. Here, we describe tests for acute and short-term toxicity in mice as well as antioxidant tests on brain homogenates measured the levels of malondialdehide (MDA) and glutathione (GSH). Haematological and serum biochemical analyses were also performed. In the acute toxicity tests, the novel AChE inhibitor given orally in mice showed LD50 of 49 mg/kg. The short-term administration of 2.5 and 5 mg/kg did not show toxicity. In the ex vivo tests, the GAL-CU hybrid performed better than GAL and CU themselves. In a dose of 5 mg/kg, it demonstrates 25% reduction in AChE activity, 28% and 73% increase in the levels of MDA and GSH, respectively. No significant changes in blood biochemical data were observed. The GAL-CU hybrid is a novel non-toxic AChE inhibitor with high antioxidant activity which makes it a perspective multitarget drug candidate for treatment of Alzheimer’s disease.

Autotaxin (ATX) is a secreted lysophospholipase D, catalysing the conversion of lysophosphatidylcholine (LPC) to bioactive lysophosphatidic acid (LPA). LPA acts through two families of G protein-coupled receptors (GPCRs) controlling key cellular responses, and is implicated in many physiological processes and pathologies. ATX has therefore been established as an important drug target in the pharmaceutical industry. Structural and biochemical studies of ATX have shown that it has a bimetallic nucleophilic catalytic site, a substrate-binding (orthosteric) hydrophobic pocket that accommodates the lipid alkyl chain, and an allosteric tunnel that can accommodate various steroids and LPA. Here we first review what is known about ATX-mediated catalysis, crucially in light of allosteric regulation. We then present the known ATX catalysis-independent functions, including binding to cell-surface integrins and proteoglycans. In light of these data we then discuss the four types of ATX inhibitors, as classified depending on their binding to the orthosteric and/or the allosteric site. Finally, we analyse the binding mode of known members of all four types and discuss how mechanistic differences might differentially modulate the activity of the ATX-LPA signalling axis, and clinical applications including cancer.

The devastating growth in the worldwide frequency of neurocognitive disorders and its allied difficulties such as decline in memory, spatial competency, and ability to focus poses a significant psychological public health problem. Inhibitor of Differentiation (ID) proteins are members of a family of helix-loop-helix (HLH) transcription factors. ID proteins have been demonstrated to be involved in neurodevelopmental & depressive diseases and thus may influence neurocognitive deficiencies due to environmental exposure. Previously, it has been demonstrated that environmental factors such as estrogenic endocrine disruptors (EEDs) have played an essential role in the influence of various neurocognitive disorders such as Alzheimer’s, Dementia, and Parkinson’s disease. Based on this increasing number of reports, we consider the impact of these environmental pollutants on ID proteins. Better understanding of how these ID proteins by which EED exposure can affect neurocognitive disorders in populations will prospectively deliver valuable information in the impediment and regulation of these diseases linked with environmental factor exposure.

A 68-year-old man with malignant metastatic melanoma in complete remission after Pembrolizumab treatment, developed 10 months after Pembrolizumab cessation due a grade 3 diarrhea, confusion, altered mental status, progressive memory loss, gait disturbance. He was admitted to the neurologic department and comprehensive neurological workup, brain magnetic resonance imaging, cerebral fluid analysis, EEG, blood test allowed the diagnosis of autoimmune encephalitis. The patient was treated with plasmapheresis, high dose of intravenous steroids and intravenous immunoglobulins. The patient improved and he is now well with a performance status 1. This case is interesting since the AE developed approximately 10 months after the cessation of immunotherapy, the underlying cancer was in complete remission and the AE showed a good response to the treatment done.

The nickel-chromium-molybdenum alloy 625 exhibits an excellent combination of mechanical properties and corrosion resistance. However, the high temperature plastic deformation process and the heat treatment represent critical aspects and the adoption of non-optimal parameters can result in excessive grain coarsening and loss in mechanical strength. This detrimental behavior is worsened by the presence of a narrow region of temperatures and strain rates for complete recrystallization and the absence of phase transformation temperatures. In this alloy, the presence of sufficient amounts of niobium, titanium and aluminum permits slow age-hardening response upon single-aging treatments. Therefore, when the soft- or solution-annealed condition is associated with insufficient mechanical properties, this potentiality can be exploited to improve the mechanical strength and prevent waste of material and resources. Since the precipitation kinetic of the hardening γ^'' phase can be accelerated by prior nucleation treatment, different time-temperature combinations of double aging at 732 °C and 621 °C are investigated to reduce the overall heat treatment time. However, the simultaneous formation of Cr-rich carbides can dramatically affect the intergranular corrosion resistance. For this reason, a performance map is developed to compare all the tested conditions and identify the best compromise in terms of mechanical strength and corrosion rate.

The corrosion resistance of two cast CoCr based alloys, with different amounts of chromium and with different alloying elements in the bulk composition of the alloy, was assessed. Herewith, we investigated the corrosion behavior of Co21Cr8Mo7W and Co29Cr7W by open circuit potential (OCP), potentiodynamic polarization (PP) and electrochemical impedance spectroscopy (EIS) in 0.1 M phosphate buffer solution (PBS) at 37°C for long time immersion. After 1000 hours of immersion, the corrosion current density (icor), estimated from anodic polarization tests, is lower for Co21Cr8Mo7W (i.e. 49 nA cm-2) alloy compared to Co29Cr7W alloy (180 nA cm-2). As regards the corrosion potential (Ecor), a nobler value was observed for Co21Cr8Mo7W (i.e. -59 mV vs. Ag/AgCl) compared to Co29Cr7W (i.e. -114 mV vs. Ag/AgCl). These findings suggest a better corrosion resistance of the film formed on the alloy containing lower amount of Cr and two alloying elements, namely Mo and W. These results are promising ones in terms of medical applications because they open new strategies in obtaining alloys with lower content of chromium and with higher protective properties against corrosion attack.

Activated Corrosion Products (ACPs) formation and deposition pose a critical safety issue for nuclear fusion reactors. The working fluid transports the ACPs towards regions accessible to worker personnel. Predicting ACPs formation deposition and transport is fundamental for source term identification, reduction of radiation exposure assessment, maintenance plan definition, design optimization, and waste management. The code OSCAR-Fusion has been developed by the CEA (France) to evaluate the ACPs generation and transport in closed water-cooled loops for fusion application. This work aims at assessing the impact of water chemistry on the transport, precipitation, and deposition of corrosion products for the EU-DEMO divertor Plasma Facing Unit Primary Heat Transfer System. Sensitivity analyses and uncertainty quantification are needed due to the multi-physics phenomena involved in ACPs formation and transport. The OSCAR-Fusion/RAVEN code coupling developed by the Sapienza University of Rome and ENEA has been used. This work presents the perturbation results of different parameters chosen for a closed water-cooled loop considering a continuous scenario of 1888 days. The aim of this work is to assess the variation of build-up of ACPs, perturbing the alkalizing agent concentration into the coolant and the corrosion and release rates of different materials.

The corrosion morphology in grade 2205 duplex stainless steel wire has been studied to understand the nature of pitting and the causes of the ferrite phase's selective corrosion in acidic NaCl solution. It is shown that the corrosion mechanism is always pitting, which either manifests lacy cover perforation or densely-arrayed selective cavities developing on the ferrite phase. Pits with a lacy metal cover form in concentrated chloride solutions, whereas the ferrite phase's selective corrosion develops in diluted electrolytes, showing dependency on the chloride-ion concentration. The pit perforation is probabilistic and occurs on both austenite and ferrite grains. The lacy metal covers collapse in concentrated solutions but remain intact in diluted electrolytes. The collapse of the lacy metal cover happens due to hydrogen embrittlement. Pit evolution is deterministic and occurs selectively in the ferrite phase in light chloride solutions.

Diabetic wound (DW) is the most devastating complication resulting in significant mortality and morbidity in diabetic patients. Although the pathophysiology of DWs is multifaceted, evidence revealed that prolonged inflammation with infections, extracellular matrix (ECM) degradation and unnecessary NETosis impair DW healing. This theoretical problem commands the necessity of developing a novel strategy focused on targeting the 'specific' molecular modalities of DW. The primary culprits, matrix metalloproteinase (MMP)-9 and protein kinase C (PKC)-βII, are responsible for impaired angiogenesis, NETosis, and ECM degradation. Thus, there is reinvigorated interest in identifying selective inhibitors for the effective management of DW. The current study exemplified human β-defensin-2 (HBD-2), a biological macromolecule as a dual-inhibitor of MMP-9 and PKC-βII using protein-protein docking and molecular dynamics simulation studies. Residue-residue interactions and binding affinity were investigated using Z-dock. Chemical bonding behavioral changes, structural dynamics, and functional changes were determined using GROMACS by analyzing RMSD, ROG, RMSF, SASA, FEL, and PCA. Overall, the data analysis revealed that HBD-2 possesses strong binding affinity and stability against MMP-9 and PKC-βII, which can be an ideal therapeutic for the accelerated healing of DW. The study provides valuable insights into the molecular mechanisms underlying hBD-2's potential therapeutic effects, offering new avenues for the development of innovative treatment strategies. The clinical relevance of our findings lies in their potential to inform the development of new approaches for diabetic wound management, addressing a significant healthcare concern.

Diatomite (DME) consists of natural ordered porous structures that are excellent candidates as microcontainers. However, to the best of our knowledge, the application of DME loaded with corrosion inhibitors in anti-corrosion coatings has not hitherto been reported. In this study, DME has been used as a source of microcontainers to load benzotriazole (BTA) inhibitor by an immersion method. In order to prevent unwanted early release of the small molecule BTA inhibitor from the DME microcontainers, inspired by the adhesion characteristics of catechol and amine in mussel adhesion protein, polydopamine (PDA) was coated on their surfaces to generate BTA@DME/PDA microcapsules. Because of the depolymerization characteristics of PDA at low pH, the synthesize microcapsules showed a controllable release function. The SEM morphology, chemical structure, and loading capacity of the synthesized BTA@DME/PDA microcapsules were characterized. The corrosion resistances of epoxy coatings with different contents of BTA@DME/PDA microcapsules were compared by saline immersion and electrochemical impedance tests. A scratched coating with 5wt.% BTA@DME/PDA microcapsules showed the best anti-corrosion effect.

This research investigated high-temperature corrosion (500 °C) of Cr-Mo steel processed using water jet peening or multifunction cavitation (MFC), and the suitability of such steel for high-temperature boilers and reaction vessels. High-temperature corrosion was induced using an embedment test and a coating test using sulfide-type K2SO4-Na2SO4 powder. To measure the relaxation of the residual stress due to the decrease in work hardening caused by an increase in specimen temperature and the difference in thermal shrinkage between the surface and interior of the specimen, a thermal cycling test was conducted. For the MFC-processed specimen, the oxide film that formed on the surface suppressed mass loss, prevented crack formation, and reduced the compressive residual stress caused by high-temperature corrosion. MFC-processed Cr-Mo steel is thus suitable for a high-temperature corrosion environment.

Background: Ventilator-associated pneumonia (VAP) is among the most common healthcare-associated infections in Pediatric Intensive Care Units (PICUs). Because of the lack of a gold-standard diagnostic test, early diagnosis of VAP is challenging. We investigated whether bronchial biomarkers interleukin-4 (IL-4), plasminogen activator inhibitor-1 (PAI-1) and soluble receptor for advanced glycation end products (RAGE) could contribute in early VAP diagnosis through their fluctuation in time in critically ill pediatric patients. Methods: Bronchial secretions were collected from PICU patients with VAP on days 1 and 6. PAI-1, RAGE and IL-4 levels were measured by ELISA. Protein concentrations between high and low VAP suspicion patients were compared using unpaired Student’s t or Mann–Whitney U tests. Results: Twenty PICU patients, with median age 7.75yrs (range 0.5-15.3), mechanically ventilated for ≥48hrs with increased oxygenation requirements and VAP clinical/laboratory signs were enrolled. They were divided in VAP high-suspicion (n=12) or low-suspicion (n=8) groups based on Clinical Pulmonary Infection Score (cutoff:6). ΡΑΙ-1 και RAGE levels did not differ between high- or low-VAP suspicion groups the 1st or 6th days (p-value&gt;0.05). IL-4 was not detected in bronchial secretions. Conclusion: Bronchial concentrations of IL-4, PAI-1 and RAGE in critically ill children are not correlated with high- or low-VAP suspicion.

Sirtuins are a family of Class III epigenetic modifying enzymes involved in regulating cellular processes through the removal of acetyl groups from proteins. They rely on NAD+ as a coenzyme in contrast with classical HDACs (Class I, II, and IV) that depends on Zn+ for their activation, linking their function to cellular energy levels. There are seven mammalian sirtuin isoforms (SIRT1-7), each located in different subcellular compartments. Sirtuins act as master regulators of cellular homeostasis, responding to changes in nutrient availability and energy status. They play vital roles in diverse physiological and pathological conditions, making them promising therapeutic targets for various diseases, including cancer, neurodegenerative disorders, and metabolic diseases. High levels of SIRT6 are involved in the cancer progression of many tumor types and our previous studies revealed that sirtuin 6 was highly expressed in NSCLC cells and its inhibition potentially favored apoptosis and cell cycle arrest. Sirt6 emerged as a promising target and inhibitors of natural and synthetic sources are highly warranted. Imidazole derivatives are often investigated as sirtuin regulators due to their ability to interact with the binding site and modulate their activity. Imidazole bestows many possible substitutions on its ring and neighboring atoms, to design and synthesize derivatives with specific target selectivity and improved pharmacokinetic properties, optimizing drug development. We recently developed imidazole-based derivatives that potentially inhibited classical HDAC enzymes. Therefore, we evaluated the Sirtuin inhibition activity of our in-house compound comprised of imidazole derivatives and the strongest inhibition was observed with Ethyl 2-[5-(4-chlorophenyl)-2-methyl-1-H-Imidazole-4-yl) acetate against Sirt6 by in-silico and protein expression studies. Our results suggested that Ethyl 2-[5-(4-chlorophenyl)-2-methyl-1-H-Imidazole-4-yl) acetate could be a potential novel sirt6 inhibitor.

The TRPV3 calcium ion channel is vital for maintaining skin health and has been associated with various skin-related disorders. Since TRPV3 is involved in the development of skin inflammation, inhibiting TRPV3 could be a potential treatment strategy. Alpha-mangostin isolated from Garcinia mangostana L. extract exhibits diverse positive effects on skin health; however, the underlying mechanisms remain obscure. This study investigated the TRPV3-inhibitory properties of alpha-mangostin on TRPV3 hyperactive mutants associated with Olmsted syndrome and its impact on TRPV3-induced cytokine secretion and cell death. Our findings demonstrate that alpha-mangostin effectively inhibits TRPV3, with an IC50 of 0.077 ± 0.013 μM, showing inhibitory effects on both wild-type and mutant TRPV3. TRPV3 inhibition with alpha-mangostin decreased calcium influx and cytokine release, protecting cells from TRPV3-induced death. These results indicate that alpha-mangostin reduced inflammation in TRPV3-activated skin keratinocytes, suggesting that alpha-mangostin could be potentially used for improving inflammatory skin conditions such as dermatitis.

Tubulin and heat shock protein 27 (HSP27) are up-regulated in cancer cells, and play a critical role in cell division, and proliferation. Therefore, they are targets for discovery of anticancer therapy. The objective of this study is to design, characterize, and biologically evaluate the nimesulide analogues to combat female cancer such as ovarian cancer, and breast cancer. Herein, the nimesulide analogues are designed to target both tubulin and HSP27 functions. Ovarian cancer (SKOV3) and breast cancer (SKBR3) cell lines were used as surrogate models to test the nimesulide analogs biological activities using MTT assay. In the present study, four nimesulide analogues were designed, synthesized and the chemical structures were with the biological evaluation were studied. The synthesized agents were characterized by 1H-NMR, 13C-NMR, the molecular weight was confirmed using GC-MS technique, and melting point. Besides, the agent L4 structure was confirmed using X-ray crystallographic analysis. The present data revealed that nimesulide analogs have potent anticancer activity against SKOV3and SKBR3 cell lines. The IC50 values for both SKOV3 and SKBR3 cell lines treated with the agents showed a potent cell growth inhibition range of 0.23-2.02 µM and 0.50-3.73 µM respectively. In conclusion, the designed nimesulide analogues can target both tubulins, and HSP27 concurrently, and they are promising agents as future chemotherapy female cancers.

We have synthesized quinoxaline analogs (1-25), characterized by 1HNMR and HREI-MS and evaluated for thymidine phosphorylase inhibition. Among the series, nineteen analogs showed better inhibition when compared with the standard inhibitor 7-Deazaxanthine (IC50 = 38.68 ± 4.42 µM). The most potent analog among the series is analog 25 with IC50 value 3.20 ± 0.10 µM. Sixteen analogs 1, 2, 3, 4, 5, 6, 7, 12, 13, 14, 15, 16, 17, 18, 21and 24 showed outstanding inhibition which is many folds better than the standard 7-Deazaxanthine. Two analogs 8 and 9 showed moderate inhibition. A structure- activity relationship has been established mainly based upon the substitution pattern on the phenyl ring. The binding interactions of the active compounds were confirmed through molecular docking studies.

The paper examines the possibility of increasing the wear and corrosion resistance of a CP-Ti surface by duplex plasma electrolytic treatment (borocarburizing and polishing). The structure and composition of diffusion layers, their microhardness, surface morphology and roughness, wear resistance during dry friction and corrosion resistance in Ringer's solution were studied. The formation of a surface hardened layer up to 200 m thick with a microhardness of up to 950 HV, including carbides and a solid solution of boron and carbon, is shown. Subsequent polishing makes it possible to reduce surface roughness and remove weak areas of the porous oxide layer, which is formed during high-temperature oxidation in aqueous electrolyte vapor during borocarburizing. Changing the morphology and structural-phase composition of the CP-Ti surface helps reduce weight wear by 3 times (the mode of frictional interaction changes from microcutting to oxidative wear) and corrosion current density by 4 times after borocarburizing in a solution of boric acid, glycerin and ammonium chloride at 950 °C for 5 minutes and subsequent polishing in an ammonium fluoride solution at a voltage of 250 V for 3 minutes.

The expedited development of drugs targeting gene products associated with insulin resistance holds the potential to enhance our comprehension of type 2 diabetes mellitus (T2DM). The virtual screening based on a three-dimensional (3D) protein structure has been expected as potential technique to accelerate a development of molecular target drugs. Among the targets implicated in insulin resistance, genetic characterization and protein function of Grb14 have been clarified without contradiction. The Grb14 gene displays notable variations in T2DM, and its gene product known to inhibit the function of the insulin receptor (IR) by directly binding to the tyrosine kinase domain. In the present study, a virtual screening, based on 3D structure of IR tyrosine kinase domain (IRβ) in complex with part of Grb14, was conducted to find compounds that can disrupt the complex formation between Grb14 and IRβ. First, ten compounds were selected from 154,118 compounds via hierarchical in silico structure-based drug screening, composed of grid docking-based and genetic algorithm-based programs. The experimental validations suggested that the one compound can affect blood glucose level. The molecular dynamics simulations and co-immunoprecipitation analysis showed that the compound did not completely suppress the protein–protein interaction between Grb14 and IR, though competitively bound to IR with the tyrosine kinase pseudosubstrate region in Grb14.

Marked changes in temperature, pH, dissolved oxygen (DO) content, and nutrient content typically occur in marine thermoclines, which are key factors that affect the corrosion of metals. Offshore platforms have required marine metals to be exposed to deep-sea environments and have thus increased their penetration into the marine thermocline. This study investigates the galvanic corrosion of E690 steel in a marine thermocline using a simulated marine thermocline (SMT). Specifically, the corrosion of E690 steel was analyzed using the wire beam electrode (WBE) technique, linear polarization (LP), corrosion morphology, and weight loss measurement. Results indicated that the SMT had a stable multilayer structure, and the variations of temperature, DO, pH and nutrient concentration in the SMT were similar to those in the natural marine thermocline. Galvanic corrosion occurred after the intrusion of E690 steel into the marine thermocline. The driver of galvanic corrosion was the of E690 steel at various depths of the marine thermocline. The Ecorr of E690 steel was influenced by the temperature, pH and DO of seawater, and the order was DO >> T > pH. The continuous reduction of Ecorr with depth contributed to the large-scale galvanic corrosion, and the oscillation variation of Ecorr with depth was the reason for small-scale galvanic corrosion. The primary anodic regions of galvanic corrosion were located in the area with the fastest temperature variation in the thermocline. The proportion of galvanic corrosion in the average corrosion rate could increase up to approximately 80% in the stable anodic region. There were many deep corrosion pits in the long-term and stable anodic region of galvanic corrosion.

In this work, nitrite intercalated CaAl-LDH was firstly prepared in this work. Scanning electronic microscopy (SEM) coupled with the energy dispersive spectrometer (EDS) was used to characterize the morphology and element composition of the synthesized powder. Fourier transform infrared spectroscopy (FTIR) was used to characterize the chemical composition and X-ray diffraction (XRD) was used to analyze the structure. The nitrite release curve and the chloride concentration change curve were obtained to study the anion-exchange reaction. The corrosion protection effect of the CaAl-LDH loaded with nitrites towards the carbon steel was evaluated in 0.02 M NaCl solution by electrochemical impedance spectroscopy (EIS). Then the powder was added in the epoxy coating with a percentage of 2% (vs. epoxy resin). The coating morphology and roughness was evaluated by SEM and laser microscopy, and the corrosion protection effect was investigated by EIS in an immersion period of 21 d. Local electrochemical impedance spectra (LEIS) was used to characterize the corrosion development process in micro-corrosion sites. The corrosion product of the scratched area after salt spray exposure was analyzed by EDS and Raman spectroscopy. The corrosion protection mechanism of the CaAl-LDH loaded with nitrites was proposed based on the above experimental results.

Corrosion is considered as one of the main factors in the structural performance deterioration of steel members. In this study, experimental and numerical methods were used to assess the reduction in compressive strength of short tubular steel columns with local corrosion damage. The corrosion damage was varied with different depths (0, 1.5, 2, 3, 4, 4.5, and 6 mm), height (0, 20, 40, 60, 80, 100, 120, 140, 160, and 180 mm), circumference (0, 90, 180, 270, and 360°), and location along the column. A parametric numerical study was performed to establish a correlation between the residual compressive strength and the severity of corrosion damage. The results showed that as the corrosion depth, height and circumference increased, the compressive strength decreased linearly. As for the corrosion height, the residual compressive strength became constant after decreasing linearly when the corrosion height was greater than the half-wavelength of buckling of the short columns. An equation is presented to evaluate the residual compressive strength of short columns with local corrosion wherein the volume of the corrosion damage was used as a reduction factor in calculating the compressive strength. The percentage error using the presented equation was found to be within 11.4%.

Protein-protein interactions (PPIs) are associated with various diseases; hence, they are important targets in drug discovery. However, the physicochemical empirical properties of PPI-targeted drugs are distinct from those of conventional small molecule oral pharmaceuticals, which adhere to the ”rule of five (RO5).” Therefore, developing PPI-targeted drugs using conventional methods, such as molecular generation models, is difficult. In this study, we propose a molecule generation model based on deep reinforcement learning, specialized for generating PPI inhibitors. By introducing a scoring function that can represent the properties of PPI inhibitors, we successfully generated potential PPI inhibitor compounds. The generated virtual compounds possess the desired properties for PPI inhibitors, and show similarity to commercially available PPI libraries. These generated virtual compounds are freely available as a virtual library.

Pancreatic cancer (pancreatic ductal adenocarcinoma: PDAC) is one of the most aggressive neoplastic diseases. Metformin use was associated with reduced pancreatic cancer incidence or better survival in diabetics. Metformin has been shown to inhibit PDAC cells survival and growth in vitro and in vivo. However, clinical trials using metformin failed to decrease pancreatic cancer progression in patients, raising important questions about molecular mechanisms that protect tumor cells from the antineoplastic activities of metformin. We confirm that metformin acts through inhibition of mitochondrial complex I, decreasing the NAD+/NADH ratio and that NAD+/NADH homeostasis determines metformin sensitivity in several cancer cell lines. Metabolites that can restore the NAD+/NADH ratio turned PDAC cells resistant to metformin. In addition, metformin treatment of PDAC cell lines induced a compensatory NAMPT expression increasing the pool of cellular NAD+. The NAMPT inhibitor FK866 sensitized PDAC cells to the antiproliferative effects of metformin in vitro and decreased cellular NAD+ pool. Intriguingly, FK866 combined with metformin increased survival in mice bearing KP4 cells xenografts but not in mice with PANC1 xenografts. Transcriptome analysis revealed that the drug combination reactivated genes in the p53 pathway and oxidative stress providing new insights about the mechanisms leading to cancer cell death.