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We present an efficient route to tetramethylalumoxane by the controlled hydrolysis of AlMe3 in the presence of pyridine. The AlMe3(pyr) hydrolysis by 0.5 and 1 equiv. of H2O has been followed with real-time 1H NMR. Based on high-level quantum-chemical calculations, we conclude that hypervalent, pentacoordinate aluminium species are critical in the first steps of hydrolysis. [ABSTRACT FROM AUTHOR]

Metal–organic frameworks (MOFs) constitute an assorted class of multi-dimensional materials that offer the potential to serve as luminescent sensors for the sensitive and selective detection of antibiotics in wastewater. Herein, a new Zn(II)-based MOF with the formula [Zn(PMA)0.5(bbp)·H2O·DMA] (1) (bbp = 3,5-bis(benzoimidazo-1-ly)pyridine; PMA = pyromellitic acid) was synthesized by a solvothermal method and characterized. Crystallographic analysis reveals that MOF 1 possesses a 4,4-connected net with the Schläfli symbol {32·4·52·6}2{32·42·52}. The fabricated MOF exhibited luminescent property and was employed as a luminescent sensor to sensitively and selectively detect tetracycline (TCY) antibiotic amongst thiamphenicol (THI), 2-methyl-4-chlorophenoxyacetic acid (MCPA), tetracycline (TCY), sulfamethoxazole (SMT), thiabendazole (TBZ), tinidazole (TDZ), sulfadiazine (SDZ), chloramphenicol (CAP), metamitron (MMT), and dinotefuran (DTF). Further, restoration of the emissive response of TCY@1 was achieved by adding salicylic acid with a concomitant bathochromic shift in the emissive response. The possible sensing mechanism and restoration of emissive response were assessed with the aid of theoretical calculations. [ABSTRACT FROM AUTHOR]

We report an efficient and easily available transition metal-free catalyst, barium oxide (BaO), for D/H exchange reaction between pyridine and D2. BaO enables selective deuteration at the α-position of pyridine, which is different from the reported base-mediated processes. We propose that the heterolytic dissociation of D2(H2) at the surface of BaO plays a key role in this process. [ABSTRACT FROM AUTHOR]

In the crystal structure of the title compound, C26H36N2O4, the tripodal molecule exists in a conformation in which the substituents attached to the central arene ring are arranged in an alternating order above and below the ring plane. The heterocyclic unit is inclined at an angle of 79.6 (1)° with respect to the plane of the benzene ring. In the crystal, the molecules are connected via N—H⋯O bonds, forming infinite supramolecular strands. Interstrand association involves weak C—H⋯O and C—H⋯π interactions, with the pyridine ring acting as an acceptor in the latter case. [ABSTRACT FROM AUTHOR]

The article discusses a 2024 study on the attitudes of patients 65 years and older on the use of routine clinical data in making treatment decisions. Results show participants' interest in such data and in how drugs work for them, and their concerns on confounders like populations' similarity of conditions with them, and on common minor side effects. Also noted are participants' common view that their physicians determine the evidence's applicability to them, and recommend a medication.

Organic compounds display several electronic and structural features which enable their application in various fields, ranging from biological to non-biological. These compounds contain heteroatoms like sulfur, nitrogen and oxygen, which provide coordination sites to act as ligands in the field of coordination chemistry and are used as chemosensors to detect various metal ions. This review article covers different organic compounds including thiourea, Schiff base, pyridine, thiophene, coumarin, triazolyl pyrenes, imidazole, fluorescein, thiazole, tricarbocyanine, rhodanine, porphyrin, hydrazone, benzidine and other functional groups based chemosensors, that contain heteroatoms like sulfur, nitrogen and, oxygen for fluorimetric and colorimetric detection of Ag+ in different environmental, agricultural, and biological samples. Further, the sensing mechanism and performances of these chemosensors have been discussed, which could help the readers for the future design of highly efficient, selective, and sensitive chemosensors for the detection and determination of Ag+ ions. [ABSTRACT FROM AUTHOR]

The densities $\rho $ ρ of binary mixtures of 2-(dimethylamino)ethanol and 2-diethylaminoethanol with pyridine were measured over the entire concentration range at 293.15, 303.15 and 313.15 K. The values of excess molar volume, $V_m^E$ V m E , apparent molar volume, ${V_{\varphi ,DMAE}}$ V φ , DMAE and ${V_{\varphi ,DEAE}}$ V φ , DEAE ; partial molar volumes, ${\bar V_{m,1}}$ V ˉ m , 1 and ${\bar V_{m,2}}$ V ˉ m , 2 , excess partial molar volumes, $\bar V_{m,1}^E$ V ˉ m , 1 E and $\bar V_{m,2}^E$ V ˉ m , 2 E have been computed using the experimental observations. The partial molar volumes, $\bar V_{m,1}^o$ V ˉ m , 1 o and $\bar V_{m,2}^o$ V ˉ m , 2 o ; excess partial molar volumes, $\bar V_{m,1}^{oE}$ V ˉ m , 1 oE and $\bar V_{m,2}^{oE}$ V ˉ m , 2 oE at infinite dilution were also calculated. The variations of these parameters as a function of composition and temperature are discussed in terms of the intermolecular interactions in the studied binary mixtures. [ABSTRACT FROM AUTHOR]

Hedgehog pathway inhibitors (HHIs) have broadened the treatment options available for patients with advanced basal cell carcinoma (BCC) for whom traditional therapeutic approaches are not feasible or effective. Sonidegib and vismodegib are oral HHIs that were approved for treatment of patients with advanced BCC after demonstrating promising efficacy in the pivotal Phase II BOLT (NCT01327053) and ERIVANCE (NCT00833417) trials, respectively. However, the incidence and types of treatment-emergent adverse events (AEs) observed with these agents may limit continuous use of HHIs and ultimately impact clinical outcomes. In this review, we summarize the safety and tolerability profiles of sonidegib and vismodegib and discuss potential management strategies for HHI class-effect AEs, including muscle spasms, creatine phosphokinase increase, alopecia, and dysgeusia. These AEs primarily occur early in treatment and can lead to treatment discontinuation. Differences in the pharmacokinetic profiles of sonidegib and vismodegib may contribute to the variability noted in times to onset and resolution of these and other AEs. Evidence suggests that protocol modifications, such as treatment interruptions and dose reductions, are effective ways to manage AEs while maintaining disease control. Nonpharmacologic and pharmacologic interventions may also be considered as part of an AE management strategy. Overall, healthcare providers and patients with advanced BCC should be aware of the HHI class-effect AEs and plan effective management strategies to avoid treatment discontinuation and optimize therapeutic response. [ABSTRACT FROM AUTHOR]

In the present work, we report a "two-in-one" strategy to construct single-linker-based pillar-layered metal–organic frameworks (PL-MOFs) guided by reticular chemistry via an in situ "one-pot" approach. Two carboxyl groups and one pyridine group are integrated into one molecular skeleton to form bifunctional organic linkers via the reaction of pyridine-containing aldehyde and bicarboxylate-containing o-phenylenediamine. During the synthesis of organic linkers, two zinc-based PL-MOFs, non-interpenetrated HIAM-3016-op and two-fold interpenetrated HIAM-3017-op, can be simultaneously constructed. The different interpenetrations for these two PL-MOFs can be attributed to the increased length of the pyridine-containing moiety. HIAM-3017-op can be utilized for Cr2O72− detection with excellent sensitivity and selectivity. The present work not only provides a novel insight to design and prepare PL-MOFs with specific structures guided by reticular chemistry, but also indicates the universality of the in situ "one-pot" strategy to construct porous materials. [ABSTRACT FROM AUTHOR]

The Kröhnke Pyridine Synthesis has been discovered about six decades ago (1961), by Fritz Kröhnke and Wilfried Zecher at the University of Giessen. The original method involved the reaction of α‐pyridinium methyl ketone salts with α,β‐unsaturated carbonyl compounds in the presence of a nitrogen source, frequently ammonium acetate. Since its discovery, the Kröhnke methodology has been demonstrated to be suitable for the preparation of mono‐, di‐, tri‐ and tetra‐pyridines, with important applications in several research fields. Over the years, a number of modifications to the original approach have been developed and reported, enabling for the broad applicability of these methods even in modern days, also for the synthesis of non‐pyridine compounds. In this critical and tutorial review, we will thoroughly explore and discuss the potential of the original method, the refinements that have been made over the years, as well as some applications arising from each type of pyridine and/or non‐pyridine compounds produced by Kröhnke's approach. [ABSTRACT FROM AUTHOR]

Stimuli‐responsive materials based on π‐conjugated donor‐acceptor systems have great potential for sensing applications in solution and solid state. The photophysical properties of an oligo(p‐phenylenevinylene) series consisting of five push‐pull type molecules were systematically investigated to switch their absorption and emission properties by using trifluoroacetic acid as a specific external analyte. During the trifluoracetic acid sensing, the terminal pyridine units of the molecules undergo the protonation and lead to the broader absorption band at a longer wavelength region owing to the π‐π* characteristics of molecules. Upon exposing solid samples to the trifluoracetic acid vapors, the initial color of solid samples changed from yellow to orange for three‐ring system‐based molecules and brick red to wine red color for five‐ring system‐based molecules with the shifting of emission band to the longer wavelength region. Furthermore, exposing the trifluoracetic acid‐fumed solid samples to triethylamine vapors, the color of the solid samples reverted to their original colors and emission properties. The DFT analysis indicated a decreased energy band gap for the protonated molecules compared to the neutral molecules, suggesting a redshift in both the absorption and emission spectra of the protonated molecules. Thus, all the molecules of an Oligo(p‐phenylenevinylene) series can be utilized effectively for volatile acid detection. [ABSTRACT FROM AUTHOR]

Comprehensive Summary Deuterium labelling possesses wide applications in pharmaceuticals, chemical science and materials science. Development of efficient methodologies for the synthesis of deuterium labelled compounds, especially hydrogen isotope exchange (HIE), continued to receive an impressive attention over the years. Herein, we developed a nitrogen doped nano‐scale nickel catalyst for deuterium incorporation of a variety of nitrogen heterocycles using D2O as the isotope source. The usefulness of this approach has been demonstrated by 10 g‐scale for complex pharmaceuticals. This methodology represents a practical and scalable deuteration and the air‐ and water‐stable nanocatalyst enables efficient labelling in a straightforward manner. [ABSTRACT FROM AUTHOR]

Iron‐based single‐atom catalysts (Fe─N─C) exhibit excellent oxygen reduction activity but struggle with bifunctional performance due to their poor oxygen evolution activity. Although the Fe spin state is found to be closely associated with enhanced bifunctional activity, controllably regulating the Fe spin state remains a challenge. Here, the controllable regulation of Fe spin state is directly achieved through competitive coordination between chlorine and pyridine nitrogen in the axial direction of Fe─N4. The spin state of Fe is regulated from high spin to intermediate spin by the modulation of axial ligands from weak‐field ligand chlorine to strong‐field ligand pyridinic nitrogen, which leads to the enhanced bifunctional activity of N─FeN4 with a small potential gap (ΔE = 0.68 V). Theoretical calculations indicate that the spin state turning is accompanied by an enhanced binding strength between Fe sites and *OH leading to a significant decrease in the OER barrier. Moreover, N─FeN4 exhibits sufficient durability for oxygen reduction reaction (ORR) (over 50 h), oxygen evolution reaction (OER) (over 200 h), and the assembled zinc–air battery (over 1000 h). Here a novel approach is proposed for designing efficient catalysts based on spin state and profound insights into Fe─N─C spin state for bifunctional oxygen catalysis. [ABSTRACT FROM AUTHOR]

Objective: Patients with thromboembolic problems, prosthetic valves, or coagulation issues are commonly prescribed anticoagulants and antiplatelets. Anticoagulant and antiplatelet medication might constitute a challenge for dentists and dental hygienists since possible prolonged bleeding might interfere with dental procedures. The aim of the present study was to examine the bleeding durations associated with various anticoagulants and antiplatelets during professional dental hygiene sessions, utilizing a modified Ivy test adapted for the oral context. Materials and methods: Ninety-three consecutive patients undergoing professional oral hygiene were recruited. Debridement during oral hygiene was performed using ultrasonic mechanical instrumentation, and bleeding sites were assessed and treated with gentle pressure using sterile gauzes. The time for bleeding cessation was recorded. Patients were categorized into six groups based on their drug intake, Control: no anticoagulants or antiplatelets DTI: direct thrombin inhibitors (dabigatran) AntiXa: directa factor Xa inhibitors (endoxaban, apixaban, rivaroxaban) VKA: vitamin K antagonists (warfarin, acenocoumarol) SAPT: single anti-platelet therapy (acetylsalicylic acid or clopidogrel) DAPT: dual anti-platelet therapy (acetylsalicylic acid and clopidogrel). Bleeding time was measured in seconds and mean values were assessed among the different groups. Differences between groups were investigated with Kruskal-Wallis test followed by Dunn's post-hoc correction for multiple comparisons or two-way ANOVA followed by Dunnett post-hoc; Results: Control patients presented the lowest bleeding time 50 s, followed by AntiXa (98), SAPT (105), DTI (120), DAPT (190) and VKA (203). A statistically significant difference was present among control and DTI (p = 0.004), VKA (p < 0.001), DAPT (p < 0.001). Conclusions: Based on the present outcomes, an increased risk of prolonged bleeding emerged in patients taking VKA and DAPT. Clinical significance: bleeding did not interfere with the oral hygiene session The optimal period for dental treatment of these patients should be 2–3 h before the next dose, without the need to temporarily suspend the medication. [ABSTRACT FROM AUTHOR]

Ylidineketonitrile 2 with chlorodifluoromethyl (A = Cl) demonstrated a strong solvent dependence reaction with primary amines to form either 1-N-alkylated-3,5-disubstituted-2-pyridones or 2-N-alkylated-3, 5-trisubstituted pyridines. The methodology was tested for its scope with primary amines and synthesized 29 derivatives in good to excellent yield. Ylidineketonitrile 2e preferrentially forms pyridone derivatives in the majority of the solvents screened except trifluoroethanol, where chemoselective formation of 2-aminopyridine derivatives was observed. [ABSTRACT FROM AUTHOR]

Heptafluoro-iso-butyronitrile (i-C3F7CN) represents a feasible eco-friendly replacement gas for the most potent greenhouse gas sulfur hexafluoride in various high-voltage power transmission equipment. The reaction mechanisms for the in situ synthesis of i-C3F7CN from heptafluoro-iso-butyramide [i-C3F7C(O)NH2] in the presence of trifluoroacetic anhydride (TFAA) and pyridine (Py) in dimethylformamide solution have been studied within density functional theory with M06-2X exchange–correlation functional with the 6-311++G(d,p) basis set and the high-level ab initio complete basis set quadratic CBS-QB3 method. It is revealed that the unimolecular dehydration of i-C3F7C(O)NH2 can be catalyzed efficiently by TFAA in terms of both kinetic and thermodynamic aspects, producing i-C3F7CN and trifluoroacetic acid (TFA). Furthermore, Py is capable of reducing the energy barrier of the rate-determining step through hydrogen abstraction to form pyridinium hydrogen. The synergic effect of the TFAA/Py co-catalyst plays a pivotal role in the production of i-C3F7CN as the Gibbs free energy barrier can be lowered by more than 40 kcal/mol with the ratio of TFAA:2Py, in accordance with the experimental observation. The present theoretical work provides new insights into the rational design on the novel catalysts for large-scale synthesis of the perfluorinated nitriles. [ABSTRACT FROM AUTHOR]

A novel crystallographic form of a Zn(II) coordination complex [Zn(4-ohbz)2(4-nvp)2] (1-Form-III) (H4-ohbz = 4-hydroxybenzoic acid and 4-nvp = (E)-4-(1-naphthylvinyl)pyridine), undergoes a solid-state photochemical [2+2] cycloaddition reaction accompanied by a moderate photosalient effect, whereby single-crystals show cracking and splitting. This UV-induced cycloaddition accompanies a single-crystal to single-crystal transformation, allowing for continuous monitoring of the unit cell parameters. The new polymorph represents an intermediate form of the two previously reported crystallographic forms of [Zn(4-ohbz)2(4-nvp)2], and provides novel insight into moderating the magnitude of photosalient responses across polymorphic materials. [ABSTRACT FROM AUTHOR]

In recent studies, n→π* interactions featuring nucleophilic pyridine have been investigated using Fourier transform microwave spectroscopy and high-level theoretical computations. Examples of n→π* of this type in the solid state, however, are limited. The norbornene-based 2-pyridyl imide 1 is a compound that can adopt two conformers, in which the pyridyl nitrogen is either syn or anti to the norbornane bridge. It would be expected that the syn conformation of imide 1 would be more favourable, as indicated in a previous computational study. Here, tandem crystallographic and additional computational studies provide evidence that the otherwise unfavourable anti conformer of imide 1 becomes favoured upon stabilisation by an n→π* interaction in the solid state. [ABSTRACT FROM AUTHOR]

Introduction: Venous thromboembolism (VTE) is a major concern following total knee arthroplasty (TKA). The optimal pharmacological prophylaxis remains, however, controversial. The present investigation compared several non-vitamin K antagonist oral anticoagulants commonly employed as VTE prophylaxis following TKA. A Bayesian network meta-analysis was conducted to compare apixaban, aspirin, dabigatran, edoxaban, enoxaparin, fondaparinux, and rivaroxaban. The outcomes of interest were to compare the rate of deep venous thrombosis (DVT), pulmonary embolism (PE), and major and minor haemorrhages. Methods: This study was conducted according to the PRISMA Extension Statement for Reporting of Systematic Reviews Incorporating Network Meta-Analyses of Health Care Interventions. In March 2024, PubMed, Web of Science, and Google Scholar were accessed with no time constraints. All randomised controlled trials (RCTs) comparing two or more drugs for the prevention of VTE following TKA were considered for inclusion. Results: Data from 29,678 patients were collected. Of them, 67% (19,884 of 29,678 patients) were women. The mean age of the patients was 66.8 ± 2.8 years, and the mean BMI was 29.2 ± 1.5 kg/m2. There was comparability in age, sex, and BMI at baseline. Apixaban 5 mg, dabigatran 220 mg, and rivaroxaban 10 mg were the most effective in reducing the rate of DVT. Apixaban 5 mg, enoxaparin 60 mg, and rivaroxaban 40 mg were the most effective in reducing the rate of PE. Apixaban 5 mg, rivaroxaban 10 mg, and apixaban 10 mg were associated with the lowest rate of major haemorrhages. Apixaban 5 mg and 20 mg, and dabigatran 220 mg were associated with the lowest rate of minor haemorrhages. Conclusion: Administration of apixaban 5 mg demonstrated the best balance between VTE prevention and haemorrhage control following TKA. Level of evidence: Level I, network meta-analysis of RCTs. [ABSTRACT FROM AUTHOR]

Introduction: Direct oral anticoagulants (DOACs) reflect anticoagulation agents given to treat or prevent thrombosis, having largely replaced vitamin K antagonists (VKAs) such as warfarin. DOACs are given in fixed daily doses and generally do not need monitoring. However, there may be a variety of reasons that justify measurement of plasma DOAC levels in individual patients. Methods: We report updated findings for DOAC testing in our geographic region, using recent data from the RCPAQAP, an international external quality assessment (EQA) program, currently with some 40–60 participants in each of the different DOAC (rivaroxaban, apixaban, dabigatran) modules, to assess laboratory performance in this area. Data has been assessed for the past 5 years (2019–2023 inclusive), with 20 samples each per DOAC. Results: Data shows a limited repertoire of assays in use, and mostly consistency in reported numerical values when assessing proficiency samples. Available assays mostly comprised reagents from four manufacturing suppliers. There was good consistency across what participants identified as 'DOAC detected', but some variability when participants attempted to grade DOAC levels as low vs moderate vs high. Inter‐laboratory/method coefficient of variation (CVs) were generally <15% for each DOAC, when present at >100 ng/mL. Conclusion: We hope our findings, reflecting on mostly consistent reporting of DOAC levels and interpretation provides reassurance for clinicians requesting these measurements, and helps support their implementation in regions where there is a paucity of test availability. [ABSTRACT FROM AUTHOR]

Retrosynthetic simplicity is introduced as a metric by which methods can be evaluated. An argument in favor of reactions which are retrosynthetically simple is put forward, and recent examples in the context of skeletal editing from my own laboratory as well as contributions from others are analyzed critically through this lens. 1 Introduction 2 Example 1: Quinoline to Quinazoline (One Product, Two Starting Materials) 3 Example 2: Benzene to Pyridine (Two Products, One Starting -Material) 4 Caveats, Counterarguments, and Conclusions [ABSTRACT FROM AUTHOR]

Herein, we report a regioselective cycloaddition strategy of N -aminopyridinium ylides with electron-deficient alkenes, in the presence of a hypervalent iodine reagent, PhI(OAc)2. A variety of multifunctionalized pyrazolo[1,5- a ]pyridine architectures were smoothly afforded by the reactions of pyridine-, quinoline-, and isoquinoline-based N -ylides with diverse alkenes with or without a halogen atom adjacent to the electron-withdrawing group (EWG) under facile conditions. [ABSTRACT FROM AUTHOR]

Pyridines and its derivatives are an important class of heterocyclic compounds of low molecular weight. They have been used in the treatment of a various diseases like cardiovascular disease, antioxidant, antibacterial, anti-tubercular, anticancer, anticoagulant, etc. In 1882, Arthur Hantzsch reported pyridine derivative synthesis using different aldehydes, 2 molecules β-keto ester and ammonium acetate to give a Hantzsch ester or 1,4-dihydropyridine derivatives. This review article focuses on different protocols for Hantzsch reaction using different catalysts like β-cyclodextrin–polyurethane polymer (β-CDPU), chitosan nanoparticles (NPs), salicylic acid, p-toluenesulfonic acid (p-TSA), alginic acid, Fe-TUD-1, PdRuNi@GO, Ceric Ammonium Nitrate (CAN), sulfate polyborate, etc. for the synthesis of pyridine derivatives. [ABSTRACT FROM AUTHOR]

Three new tridentate copper(II) N-heterocyclic carbene (NHC) complexes have been obtained and characterized with symmetrical C-4 substitutions on their pendent pyridine rings. Substitutions including methyl (Me), methoxy (OMe), and chloro (Cl) groups, which extend the library pincer Cu-NHC complexes under investigation, modify the impact of pyridinyl basicity on NCN pincer complexes. Both ligand precursors and copper(II) complexes are characterized using a range of techniques, including nuclear magnetic resonance (NMR) spectroscopy for 1H, 13C, 31P, and 19F nuclei, electrospray ionization mass spectrometry (ESI-MS), X-ray crystallography, cyclic voltammetry, and UV-Vis spectroscopy. The pyridine substitutions lead to minimal changes to bond lengths and angles in the X-ray crystal structures of these related complexes; there is a pronounced impact on the electrochemical behavior of both the ligand precursors and copper complexes in the solution. The substitution in the pyridinyl units of these complexes show an impact on the catalytic reactivity of these complexes as applied to a model C–N bond-forming reaction (CEL cross-coupling) under well-established conditions; however, this observation does not correlate to the expected change in basicity in these ligands. [ABSTRACT FROM AUTHOR]

The inhibitory-kappaB kinases (IKKs) IKKα and IKKβ play central roles in regulating the non-canonical and canonical NF-κB signalling pathways. Whilst the proteins that transduce the signals of each pathway have been extensively characterised, the clear dissection of the functional roles of IKKα-mediated non-canonical NF-κB signalling versus IKKβ-driven canonical signalling remains to be fully elucidated. Progress has relied upon complementary molecular and pharmacological tools; however, the lack of highly potent and selective IKKα inhibitors has limited advances. Herein, we report the development of an aminoindazole-pyrrolo[2,3-b]pyridine scaffold into a novel series of IKKα inhibitors. We demonstrate high potency and selectivity against IKKα over IKKβ in vitro and explain the structure–activity relationships using structure-based molecular modelling. We show selective target engagement with IKKα in the non-canonical NF-κB pathway for both U2OS osteosarcoma and PC-3M prostate cancer cells by employing isoform-related pharmacodynamic markers from both pathways. Two compounds (SU1261 [IKKα Ki = 10 nM; IKKβ Ki = 680 nM] and SU1349 [IKKα Ki = 16 nM; IKKβ Ki = 3352 nM]) represent the first selective and potent pharmacological tools that can be used to interrogate the different signalling functions of IKKα and IKKβ in cells. Our understanding of the regulatory role of IKKα in various inflammatory-based conditions will be advanced using these pharmacological agents. [ABSTRACT FROM AUTHOR]

The current study was performed to synthesize novel arylated pyridine derivatives viz; 2,6-bis(benzothiophen-2-yl)pyridine (PB1), 2-bromo-6-(2-bromophenyl)pyridine (PB2), 2,6-bis(2-bromophenyl)pyridine (PB3) and 2-(benzo[b]thiophen-2-yl)-6-bromopyridine (PB4), through well-known Suzuki-Miyaura Pd0-catalyzed protocol. Different characterization techniques such as UV-Visible, FT-IR, 13C-NMR, 1H-NMR, and single-crystal X-ray diffraction (SC-XRD) analysis were used for the structure elucidation of synthesized compounds. The SC-XRD results demonstrated that the crystal system of the novel compounds PB1 and PB2 was orthorhombic and monoclinic, and their space group was found to be P212121 and P21/n, respectively. The computational quantum analysis of the investigated entities was conducted using density functional theory (DFT). The geometry was optimized using the M06-2X and 6-311++G(d,p) functional. The same functional was also utilized to investigate natural bond orbitals (NBOs). At the same time, the time-dependent density functional theory (TD-DFT) was applied to examine the frontier molecular orbitals (FMOs) and the UV-Visible spectrum, which also gave Global reactivity parameters (GRPs) values. The NBO investigation proved that the stability was caused by hyper-conjugative interactions. Data from FMO and NBO were used to validate the intramolecular charge transfer (ICT) mechanisms in the compounds under study. The non-linear optical (NLO) characteristics were assessed by means of the LC-BLYP, HF, and M06-2X techniques with the 6-311++G(d,p) basis set. The analysis of NLO indicated encouraging NLO response for all the compounds that were examined. [ABSTRACT FROM AUTHOR]

Background: Listeria monocytogenes is a bacterial pathogen known for causing listeriosis, a foodborne illness with a wide spectrum of clinical presentations ranging from mild gastroenteritis to severe invasive disease, particularly affecting immunocompromised individuals, pregnant women, newborns, and the elderly. Successful treatment of patients with recurring listeria episodes due to colonised foreign material is often challenging, typically requiring a combination of antimicrobial treatment and surgical removal. Case presentation: Here, we present a particularly complex case of chronic invasive listeriosis with a total of six relapses. After extensive investigations, the patient's ICD device was identified as the focus of infection. Conclusion: The confirmation of relapses through cgMLST analysis highlights the persistence of Listeria monocytogenes and the potential for recurrence even after apparent resolution of symptoms in patients with foreign material. It emphasises the necessity for a comprehensive assessment to identify and mitigate the risk of relapses, thereby ensuring optimal management and outcomes. [ABSTRACT FROM AUTHOR]

Background: Antiseptic mouthwashes are useful adjuncts to daily brushing and flossing for the control of dental plaque and gingivitis. The objective of the present study was to compare the effect of three mouthwashes: chlorhexidine, essential oils and cetylpyridinium chloride on oral health‐related quality of life, gingival health, tongue coating and also to compare their potential side effects after 2‐week consumption. Methods: Sixty participants were enrolled in this study and were divided into four groups (three mouthwash groups plus no mouthwash group). At the beginning, scaling and cleaning were performed and the following parameters were recorded: oral health impact profile (OHIP‐5) questionnaire, tongue coating index, modified gingival index, calculus surface index, modified Lobene stain index and a questionnaire for side effects. Each group has followed up in 2 weeks. Data were analysed using paired t‐test, ANOVA, Fisher's exact test and Pearson chi‐square. Results: At the end of second week, all three mouthwashes significantly improved OHIP‐5 score and reduced modified gingival index whereas essential oils and cetylpyridinium chloride significantly reduced tongue coating index when compared to control group (p < 0.05). The differences between four groups were significant for calculus formation, dental staining and reported burning sensation and changes of taste sensation and perception (p < 0.05). Conclusion: The use of all three mouthwashes has been effective in controlling and reducing gingivitis and tongue coating; however, it appeared that essential oils has the minimum and Chlorhexidine has the maximum side effects. Moreover, the use of all three mouthwashes has been examined to improve the quality of life. Overall, essential oils mouthwash has the best performance among these three mouthwashes. [ABSTRACT FROM AUTHOR]

Background: Anticoagulant drugs are a valuable tool for minimizing thrombotic risks in at-risk patients. The purpose of this study is to conduct a literature review highlighting the management of these drugs during daily clinical dental practice. Materials and Methods: We limited our search to English-language papers published between 1 January 1989, and 7 March 2024, in PubMed, Scopus and Web of Science that were relevant to our topic. In the search approach, the Boolean keywords "anticoagulant AND dentistry" were used. Results: Twenty-five clinical trials were included for final review from 623 articles obtained from the databases Web of Science (83), PubMed (382), and Scopus (158), eliminating duplicates and 79 off-topic items, resulting in 419 articles after removing 315 entries and confirming eligibility. Overall, these studies support the use of local hemostatic measures to manage the risk of bleeding in patients on anticoagulant therapy undergoing dental procedures and highlight the importance of greater education and collaboration among healthcare professionals. Conclusions: Research and clinical investigation have improved understanding and management of dental procedures in patients undergoing anticoagulant or antiplatelet therapy. Hemostatic agents, clinical protocols, risk factors, and continuous education are essential for navigating the complexities of anticoagulant therapy, ensuring optimal outcomes and enhancing patient well-being. [ABSTRACT FROM AUTHOR]

Indoles and their derivatives have long been studied for their anticancer properties. Breast cancer has been treated using indole‐3‐carbinol, Indirubins, and many other naturally occurring indoles as well as their synthesized equivalents. It has been determined that the AKT pathway is a prospective target for therapeutic strategies in the treatment of breast cancer. The dysregulation of AKT pathway frequently promotes cell proliferation, survival, and resistance to apoptosis. We synthesized a novel group of bisindole clubbed pyridine and pyrimidine derivatives 5(a–l) using water as the solvent and thiamine hydrochloride as the catalyst. Compounds 5 a, 5 c, 5 d, 5 e, and 5 f are the most active against MCF‐7 cells, with an IC50 values of 2.48±0.39, 1.35±0.13, 3.36±0.53, 4.05±0.61 and 1.91±0.28 μM, respectively. Further, in silico docking of the active compound 5 c had the highest binding energy of −10.59 kcal/mol. Additionally, molecular dynanamics simulations were performed for better understanding the mode of interaction of ligand and protein. In conclusion, we have synthesized bisindoles using thiamine hydrochloride as a catalyst that target AKT pathway in breast cancer cells. [ABSTRACT FROM AUTHOR]

Chromenes are an essential class of oxygen‐containing heterocyclic compounds with intriguing biological activity. It is an important moiety for the discovery of new drug candidates. Chromenes are naturally abundant as alkaloids, tocopherols, flavones, and anthocyanins. The incorporation of 4H‐chromene, along with various bioactive heterocycles such as indole, pyrazole, kojic acid, pyran‐2‐one, quinoline, pyridine, pyrimidine, coumarin, sesamol, furan, uracil, benzoimidazole, benzotriazole, thiazole, isoxazole and barbituric acid moieties, into a molecular scaffold has the potential to combine the properties of both components. The synergistic effect of combining different heterocyclic moieties within a 4H‐chromene nucleus results in the formation of valuable compounds with significant biological importance. This review summarizes the different synthetic techniques used for preparing 4H‐chromene‐embedded heterocycles. The common mechanisms of key reactions and the significance of the method are discussed. [ABSTRACT FROM AUTHOR]

Dabigatran is an oral anticoagulant that is mainly renally excreted. Despite its efficacy in preventing thromboembolic events, concerns arise regarding bleeding complications in patients with acute kidney injury. Idarucizumab is its specific antidote and reverses quickly and effectively dabigatran anticoagulation effects in situations of severe bleeding or pending surgical procedures, but its benefit beyond these two indications remains uncertain. We present a case of a woman with atrial fibrillation anticoagulated by dabigatran and admitted with Streptococcus agalactiae meningitis, acute kidney injury and dabigatran accumulation. Idarucizumab was not administered initially as she did not meet its current strict indications. However, subsequently, significant bleeding necessitated its use. A rebound increase in dabigatran concentration was associated with an intracranial hemorrhage, but the combination of additional doses of idarucizumab with hemodialysis lowered the dabigatran concentration and prevented significant rebound increases. Further investigation into the optimal management of dabigatran accumulation and acute kidney injury-associated bleeding is needed to enhance patient outcomes and safety. Early initiation of hemodialysis together with idarucizumab administration may be crucial in preventing life-threatening bleeding events in these patients. [ABSTRACT FROM AUTHOR]

Acremolactone B is a pyridine‐containing azaphilone‐type polyketide. The first total synthesis of this molecule was achieved on a gram scale, based on an aza‐6π electrocyclization–aromatization strategy for construction of the tetra‐substituted pyridine ring. A bicyclic intermediate was expeditiously prepared by using [2+2] photocycloaddition and chemoselective Baeyer–Villiger oxidation, which was further elaborated to a densely substituted aza‐triene. An electrocyclization–aromatization cascade was utilized to forge the tetracyclic core of this natural product, and the side chain was introduced through diastereoselective acylation and reduction. [ABSTRACT FROM AUTHOR]

Pyridine, a compound with a heterocyclic structure, is a key player in medicinal chemistry and drug design. It is widely used as a framework for the design of biologically active molecules and is the second most common heterocycle in FDA-approved drugs. Pyridine is known for its diverse biological activity, including antituberculosis, antitumor, anticoagulant, antiviral, antimalarial, antileishmania, anti-inflammatory, anti-Alzheimer's, antitrypanosomal, antimalarial, vasodilatory, antioxidant, antimicrobial, and antiproliferative effects. This review, spanning from 2022 to 2012, involved the meticulous identification of pyridine derivatives with antiproliferative activity, as indicated by their minimum inhibitory concentration values (IC50) against various cancerous cell lines. The aim was to determine the most favorable structural characteristics for their antiproliferative activity. Using computer programs, we constructed and calculated the molecular descriptors and analyzed the electrostatic potential maps of the selected pyridine derivatives. The study found that the presence and positions of the -OMe, -OH, -C=O, and NH2 groups in the pyridine derivatives enhanced their antiproliferative activity over the cancerous cellular lines studied. Conversely, pyridine derivatives with halogen atoms or bulky groups in their structures exhibited lower antiproliferative activity. [ABSTRACT FROM AUTHOR]

Spin-state switching in iron(II) complexes composed of ligands featuring moderate ligand-field strength—for example, 2,6-bi(1H-pyrazol-1-yl)pyridine (BPP)—is dependent on many factors. Herein, we show that spin-state switching in isomeric iron(II) complexes composed of BPP-based ligands—ethyl 2,6-bis(1H-pyrazol-1-yl)isonicotinate (BPP-COOEt, L1) and (2,6-di(1H-pyrazol-1-yl)pyridin-4-yl)methylacetate (BPP-CH2OCOMe, L2)—is dependent on the nature of the substituent at the BPP skeleton. Bi-stable spin-state switching—with a thermal hysteresis width (ΔT1/2) of 44 K and switching temperature (T1/2) = 298 K in the first cycle—is observed for complex 1·CH3CN composed of L1 and BF4− counter anions. Conversely, the solvent-free isomeric counterpart of 1·CH3CN—complex 2a, composed of L2 and BF4− counter anions—was trapped in the high-spin (HS) state. For one of the polymorphs of complex 2b·CH3CN—2b·CH3CN-Y, Y denotes yellow colour of the crystals—composed of L2 and ClO4− counter anions, a gradual and non-hysteretic SCO is observed with T1/2 = 234 K. Complexes 1·CH3CN and 2b·CH3CN-Y also underwent light-induced spin-state switching at 5 K due to the light-induced excited spin-state trapping (LIESST) effect. Structures of the low-spin (LS) and HS forms of complex 1·CH3CN revealed that spin-state switching goes hand-in-hand with pronounced distortion of the trans-N{pyridyl}-Fe–N{pyridyl} angle (φ), whereas such distortion is not observed for 2b·CH3CN-Y. This observation points that distortion is one of the factors making the spin-state switching of 1·CH3CN hysteretic in the solid state. The observation of bi-stable spin-state switching with T1/2 centred at room temperature for 1·CH3CN indicates that technologically relevant spin-state switching profiles based on mononuclear iron(II) complexes can be obtained. [ABSTRACT FROM AUTHOR]

The separation of toluene (Tol) and pyridine (Py) azeotropes is significant in the chemical industry. Herein, we present a new method for the energy-efficient separation of Tol and Py using pillar[5]arene-based adaptive macrocycle co-crystals (MCCs) that can selectively separate Py from a Py/Tol equimolar mixture with 99.2% purity, accompanied by vapochromic behavior from white to yellow. [ABSTRACT FROM AUTHOR]

The administration of intravenous thrombolysis (IVT) for patients with acute ischemic stroke who have recently ingested direct oral anticoagulants (DOACs) presents a clinical challenge due to the perceived increased risk of intracranial hemorrhage (ICH). Traditional guidelines from the US and European authorities advise against IVT within 48 h of last DOAC ingestion, unless specific coagulation tests indicate safety. However, emerging observational studies suggest that IVT might be safe in selected patients. A US stroke registry study and a global multicenter cohort study both reported no significant increase in symptomatic ICH among patients on DOACs compared to those not on anticoagulants. A systematic review of all published observational studies further supported these findings, showing comparable bleeding rates and functional outcomes in DOAC-treated patients. Reversal agents like idarucizumab for dabigatran have demonstrated potential in facilitating safer IVT administration, though logistical and cost-related barriers limit their widespread use. The variability in global guidelines reflects differing approaches to risk assessment and resource availability, highlighting the need for individualized treatment decisions. In India, the increasing prevalence of atrial fibrillation and stroke as well as prescription of DOACs necessitate adapted guidelines that consider local health-care infrastructure. Despite the promising observational data, the lack of randomized controlled trials underscores the need for further research to establish robust evidence for IVT use in this context. Collaborative international efforts and inclusion of diverse patient populations in future studies will be crucial to refine treatment protocols and improve outcomes for stroke patients on DOACs. [ABSTRACT FROM AUTHOR]

A method was developed for obtaining positional isomers—2-[6-aryl-4-trifluoromethyl-3-cyanopyridin-2(1H)-ylidene]malononitriles and 2-[4-aryl-6-trifluoromethyl-3-cyanopyridin-2(1H)-ylidene]malononitriles, which differ in the opposite positioning of the aryl and trifluoromethyl substituents. These compounds exhibit photoluminescence in solutions ranging from the violet to the yellow region of the visible spectrum (λemmax = 418–577 nm). The strongest photoluminescence was observed in low-polarity solvents, where the quantum yield of photoluminescence reached 46%. It was shown that a basic medium leads to a significant red shift due to the formation of the anionic form. [ABSTRACT FROM AUTHOR]

Introduction: Immune checkpoint inhibitors (ICIs) can cause a spectrum of adverse events known as immune-related adverse events (irAEs) that resemble autoimmune responses. Immune-mediated myasthenia gravis (MG) is a rare and serious neurologic adverse event that has been associated with ICIs requiring prompt treatment. In the Jehovah's Witness population, typical management of these adverse events may not be options, and alternative treatment choices would be needed. Case report: 73-year-old Jehovah's Witness patient with high-grade undifferentiated pleiomorphic sarcoma who developed immune-mediated MG approximately 4 weeks after initiation of pembrolizumab. On the day of admission, the patient presented with a three-day history of worsening ptosis, right greater than left. He was later found to be seronegative for MG. Management and outcome: The patient required therapy with pyridostigmine, steroids, and agreed to plasma exchange (PLEX) prior to discharge. He achieved near resolution of his neurologic symptoms, and pembrolizumab was discontinued. He later underwent radical resection of the left thigh soft tissue sarcoma and superficial inguinal lymph node dissection. He is now on active surveillance. Discussion: While neurologic adverse events typically present 6 weeks after initiation of ICIs, MG has been reported occurring as early as 4 weeks after initiation. This rare and serious adverse event requires prompt treatment, and clinicians need to be aware of the alternative treatment options in this unique patient population. Early conversations regarding blood products and factions must be had to develop a treatment plan in accordance with the patient's personal decisions. [ABSTRACT FROM AUTHOR]

The article presents a study which evaluated direct oral anticoagulants (DOAC) levels in frail older patients with acute illnesses, indicating an essential aspect of their anticoagulant management. Topics discussed include expected rise in DOAC use in frail older patients, patients with higher rates of bleeding, patient demographic and medical data at admission, and a trend observed for rivaroxaban use and DOAC levels above the on-therapy range.

The chromenopyridine scaffold represents an important class of heterocyclic compounds exhibiting a broad spectrum of biological properties. This review describes novel and efficient procedures for the synthesis of this scaffold. Herein, several methods were detailed and grouped according to their starting material (e.g., salicylaldehydes, chromones, chromanones and coumarins) and respective biological activity, when reported. This review highlights the potential of the reported synthetic strategies for preparing chromenopyridine derivatives with promising biological activity, paving the way for further developments in drug discovery. [ABSTRACT FROM AUTHOR]

Self‐assembly of new donor‐acceptor systems based on (5,10,15,20‐tetraphenylporphinato)manganese(III)/(5,10,15,20‐tetra‐4‐tert‐butylphenylporphinato)manganese(III)/(octakis(4‐tert‐butylphenyl)tetraazaporphinato)manganese(III) acetate ((AcO)MnTPP/(AcO)MnTBPP/(AcO)MnTAP) and 4‐(10‐phenylanthracen‐9‐yl)pyridine (PyAn) was studied using fluorescence spectroscopy and mass spectrometry. It was found that the coordination complexes of 1 : 1 composition (dyads) are formed in toluene. The spectral properties, the chemical structures and redox behavior of the dyads were described using 1H NMR, IR, ESR spectroscopy and cyclic voltammetry, respectively. The dynamic processes and the characteristics in the excited state of the dyads were obtained using the femtosecond transient absorption spectroscopy method. Density functional theory (DFT), time‐dependent DFT methods were used to elucidate the dyad electronic structures and to establish the differences in their frontier molecular orbitals. The analysis of the lambda parameter and the distance of hole‐pair interaction was indicated more favorable charge transfer between the macrocycle and the axial PyAn fragment in (AcO)(PyAn)MnTAP. The calculated values of the zero‐field splitting parameters D and E/D, together with the g tensors of the lowest spin‐orbit state for (AcO)MnTPP and (AcO)(PyAn)MnTPP were obtained using the combination of DFT and Multireference Perturbation Theory (CASSCF/NEVPT2) simulations. The data obtained develop the fundamental basis in the field of photovoltaics and show the prospects for the study of molecular systems of this class. [ABSTRACT FROM AUTHOR]

Traditional methods relying on metal‐ligand cooperation for activating pyridine bonds in de‐ and rearomatisation are being challenged by the abundant metal‐free element species as alternatives. Here, we investigated the de/re‐aromatisation of pyridine facilitated by pyridylamino‐functionalised silylene reactions with ketones and ketene. The reactivity outcome is highly dependent on the substituents on the ketones. By carefully tuning the steric demand of the ketone, each intermediate of the reaction sequence could be isolated. At room temperature, benzophenone and acetophenone substrates led to dearomatisation of the pyridine moiety, with the case of acetophenone showing an intermediate silaoxirane preceding dearomatisation. However, when subjected to acetone or diphenylketene, only silaoxiranes were formed without dearomatisation of the pyridine moiety. Notably, only benzophenone‐derived dearomatised species demonstrated rearomatisation upon heating. Furthermore, the reduced steric bulk of the ketene facilitated further ring expansion with another equivalent of the substrate, forming sila‐1,3‐dioxolanes. Both steric hindrance and aromatic groups collectively influence the dearomatisation of pyridine in pyridylaminosilylene reactions. [ABSTRACT FROM AUTHOR]

A series of new pyridine-1,2,4-triazole-tagged 1,2,3-triazole hybrid molecules were obtained. The new compounds were synthesized via click chemistry of 1,2,4-triazole-3-thiopropargyl compounds and various azides. All compounds were fully characterized through their spectroscopic analyses. Furthermore, cytotoxic activity was assessed by screening against three cancer cell lines including human colon carcinoma (HCT116), human cervix carcinoma (HeLa) and human breast adenocarcinoma (MCF7). In addition, antimicrobial assessment against one gram-positive (Staphylococcus aureus ATCC 29,213), two Gram-negative bacteria (Sarcina lutea and Escherichia coli ATCC 25,922) and one fungal (Candida albicans NRRL Y–477) microorganism‏.‏ Molecular docking studies of the synthesized compounds against DNA gyrase were used to identify their binding ability to the target enzyme. The best docked molecules unveiled binding affinities to the target ranging from −9.5 to −8.8 kcal mol−1. The adsorption, distribution, metabolic, excretion, and toxicity (ADME/Tox) and drug-likeness analyses of the best docked compounds were evaluated using in silico techniques. Based on in vitro and in silico findings, these pyridine-1,2,4-triazole-tagged 1,2,3-triazole hybrid molecules may be helpful in designing potential antimicrobial drug candidates. [ABSTRACT FROM AUTHOR]

Based on the tremendous pharmacological activities of compounds containing thiazole and carboxamide moieties, the current study aims to prepare new series of thiazole, pyrazole, pyridine, and thiophene derivatives incorporating thiazole carboxamide moiety. Construction of the target compounds was achieved via different chemical transformations and using easily accessible starting materials. The structures of the synthesized compounds were confirmed by all possible spectral and elemental analyses. Results from the in-silico studies showed different Lipophilicity (log p) and Number of Lipinsk's violations due to the presence of NH2, C≡N, OH, and C=O groups which make more electrostatic hydrogen bond interactions in compounds 17 and 20 which increase their TPSA (Å2). These results were confirmed through docking simulation with PDBID: 5I9I which showed the least binding affinity with different proteins, and optimization of these heterocyclic compounds with computational calculations and identification of their physical descriptors which showed more stabilities and directed us for biological evaluation for further studies. [ABSTRACT FROM AUTHOR]

The structures of seven gold(III) halide derivatives of general formula LAuX3 (L = methyl­pyridines or di­methyl­pyridines, X = Cl or Br) are presented: tri­chlorido­(2-methyl­pyridine)­gold(III), [AuCl3(C6H7N)], 1 (as two polymorphs 1a and 1b); tri­bromido­(2-methyl­pyridine)­gold(III), [AuBr3(C6H7N)], 2; tri­bromido­(3-methyl­pyridine)­gold(III), [AuBr3(C6H7N)], 3; tri­bromido­(2,4-di­meth­yl­pyridine)­gold(III), [AuBr3(C7H9N)], 4; tri­chlorido­(3,5-di­methylpyridine)­gold(III), [AuCl3(C7H9N)], 5; tri­bromido­(3,5-di­methyl­pyridine)­gold(III), [AuBr3(C7H9N)], 6, and tri­chlorido­(2,6-di­methyl­pyridine)­gold(III), [AuCl3(C7H9N)], 7. Additionally, the structure of 8, the 1:1 adduct of 2 and 6, [AuBr3(C6H7N)]·[AuBr3(C7H9N)], is included. All the structures crystallize solvent-free, and all have Z′ = 1 except for 5 and 7, which display crystallographic twofold rotation symmetry, and 4, which has Z′ = 2. 1a and 2 are isotypic. The coordination geometry at the gold(III) atoms is, as expected, square-planar. Four of the crystals (1a, 1b, 2 and 8) were non-merohedral twins, and these structures were refined using the 'HKLF 5' method. The largest inter­planar angles between the pyridine ring and the coordination plane are observed for those structures with a 2-methyl substituent of the pyridine ring. The Au--N bonds are consistently longer trans to Br (average 2.059 Å) than trans to Cl (average 2.036 Å). In the crystal packing, a frequent feature is the offset-stacked and approximately rectangular dimeric moiety (Au--X)2, with anti­parallel Au--X bonds linked by Au⋯X contacts at the vacant positions axial to the coordination plane. The dimers are connected by further secondary inter­actions (Au X or X X contacts, 'weak' C--H⋯X hydrogen bonds) to form chain, double chain ('ladder') or layer structures, and in several cases linked again in the third dimension. Only 1b and 7 contain no offset dimers; these structures instead involve C--H⋯Cl hydrogen bonds combined with Cl Cl contacts (1b) or Cl π contacts (7). The packing patterns of seven further complexes LAuX3 involving simple pyridines (taken from the Cambridge Structural Database) are compared with those of 1-8. [ABSTRACT FROM AUTHOR]

A new thermally stable chromophore exhibiting the intense blue fluorescence with the high quantum yield of 91%, 4-(4-(9H-carbazol-9-yl)phenyl)-2,6-bis-(4-N,N-diphenyl-aminophenyl)pyridine, was synthesized in a high yield via the three-component reaction of 4-(N,N-dimethylamino)acetophenone, 4-(9H-carbazol-9-yl)benzaldehyde, and ammonium acetate. [ABSTRACT FROM AUTHOR]

Background: N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) is a neurotoxin widely used to induce PD models, but the effect of MPTP on the cells and genes of PD has not been fully elucidated. Methods: Single-nucleus RNA sequencing was performed in the Substantia Nigra (SN) of MPTP mice. UMAP analysis was used for the dimensionality reduction visualization of the SN in the MPTP mice. Known marker genes highly expressed genes in each cluster were used to annotate most clusters. Specific Differentially Expressed Genes (DEGs) and PD risk genes analysis were used to find MPTP-associated cells. GO, KEGG, PPI network, GSEA and CellChat analysis were used to reveal cell type-specific functional alterations and disruption of cell-cell communication networks. Subset reconstruction and pseudotime analysis were used to reveal the activation status of the cells, and to find the transcription factors with trajectory characterized. Results: Initially, we observed specific DEGs and PD risk genes enrichment in microglia. Next, We obtained the functional phenotype changes in microglia and found that IGF, AGRN and PTN pathways were reduced in MPTP mice. Finally, we analyzed the activation state of microglia and revealed a pro-inflammatory trajectory characterized by transcription factors Nfe2l2 and Runx1. Conclusion: Our work revealed alterations in microglia function, signaling pathways and key genes in the SN of MPTP mice. [ABSTRACT FROM AUTHOR]

N-Phenyl-, 1- and 2-naphthyl-N¹-2- and 4-pyridylthioureas were synthesized via the reaction of phenyl-, 1- and 2-naphthylisothiocyanates with 2- and 4-aminopyridines, and the corresponding pyridine salts were prepared by benzylation of the latter. The anticorrosive properties of the synthesized compounds were studied by the gravimetric method in 3 M HCl at 80°C using the 08 kp steel samples. The introduction of a benzyl fragment into the structure of N-aryl-N¹-pyridylthioureas led to the emergence of a new adsorption ammonium center, which increased the overall anti-corrosion efficiency of the obtained compounds. When using N-aryl-N¹-pyridylthioureas, the corrosion inhibition coefficient had the values of 4.5 to 59.0, whereas it increased to 90.8-629.0 for their salts. To explain the different anti-corrosion activity of N-aryl-N¹-pyridylthioureas and their pyridine salts, quantum-chemical calculations of the energy parameters EHOMO, ELUMO and ΔE=ELUMO-EHOMO were carried out and the dependences of the corrosion inhibition coefficients on EHOMO and ΔE, eΔE were obtained. A correlation was established between the inhibitory efficiency and energy parameters of the studied compounds. [ABSTRACT FROM AUTHOR]