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In this investigation, a systematic study on the design and development of corannulene‐based thermally activated delayed fluorescence (TADF) emitters using density functional theory methods is carried out. Benzene, benzopyrazine, difluoro‐benzopyrazine, benzene‐1,2‐dithiol, and tetrasulfone are introduced on corannulene bowl as electron‐withdrawing groups to alter the electron‐accepting property of corannulene. Three different donors, viz., carbazole, phenoxazine, and 5,10‐dihydrophenazine are substituted on the rim position of corannulene to alter the absorption properties. The relationship between chemical structure and TADF property is established by evaluating the dihedral angle between donor and acceptor units, spin–orbit coupling (SOC) values, the energy difference between singlet‐triplet excited states (ΔEST), and rates of reverse intersystem crossing (kRISC). The newly designed TADF emitters show absorption in the blue to near‐IR regions depending on the strength of the donor and acceptor moieties. Careful analysis of these properties delineates the relationship between SOC values and the nature of the excited states, which is crucial for achieving high kRISC. [ABSTRACT FROM AUTHOR]

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Heterocycles functionalized with pentavalent phosphorus are of great importance since they include a great variety of biologically active compounds and pharmaceuticals, advanced materials, and valuable reactive intermediates for organic synthesis. Significant progress in synthesis of P(O)R2-substituted six-membered heterocycles has been made in the past decade. This review covers the synthetic strategies towards aromatic monocyclic six-membered N-heterocycles, such as pyridines, pyridazines, pyrimidines, and pyrazines bearing phosphonates and phosphine oxides, which were reported from 2012 to 2022. [ABSTRACT FROM AUTHOR]

A convenient method for the synthesis of 2-azido-3-arylpropanoic acids via the Meerwein halogenoarylation reaction of acrylic acid esters with diazonium salts, subsequent nucleophilic substitution of the halogen by an azide, and saponification is developed. The newly formed 2-azido-3-arylpropanoic acids react under the conditions of non-catalytic four-component Ugi reactions, leading to the formation of α-azidoamides in good yields. The use of propargylamine as the amine component allows the formation of Ugi adducts with azide and acetylene motifs ready for intramolecular 1,3-dipolar Huisgen cycloaddition to give the [1,2,3]triazolo[1,5- a ]pyrazine annulated system. The Ugi reaction is found to give 2-azido-3-aryl- N -(2-oxo-1,2-disubstituted ethyl)- N -(prop-2-yn-1-yl)propanamides at room temperature without azide–alkyne cycloaddition. These dipeptides are converted into 4,5-dihydro[1,2,3]triazolo[1,5- a ]pyrazin-6(7 H)-ones in near quantitative yields by heating in toluene. However, when the Ugi reaction is carried out by heating, it results in a one-pot Ugi–Huisgen tandem reaction leading to 4,5-dihydro[1,2,3]triazolo[1,5- a ]pyrazin-6(7 H)-ones in excellent yields. Moreover, the possibility of the incorporation of a bromovinyl fragment (the synthetic equivalent of an acetylene fragment) via the aldehyde component of the Ugi reaction is demonstrated in an alternative preparation of the [1,2,3]triazolo[1,5- a ]pyrazine system. [ABSTRACT FROM AUTHOR]

On‐surface cyclodehydrogenation recently became an important reaction to planarize π‐conjugated molecules and oligomers. However, the high‐activation barrier to cleave the C−H bond often requires high‐temperature annealing, consequently restricting structures of precursor molecules and/or leading to random fusion at their edges. Here, we present a synthesis of pyrrolopyrrole‐bridged ladder oligomers from 11,11,12,12‐tetrabromo‐1,4,5,8‐tetraaza‐9,10‐anthraquinodimethane molecules on Ag(111) with bond‐resolved scanning tunnelling microscopy. This non‐dehydrogenative cyclization between pyrazine and ethynylene/cumulene groups has a low‐activation barrier for forming intermediary dimeric oligomer containing dipyrazinopyrrolopyrrolopyrazine units, thus giving new insight into the strain‐sensitive in ladder‐oligomer formation. [ABSTRACT FROM AUTHOR]

Two new cobalt bis-o-semiquinonato complexes, (Pyz-Phen)Co(3,6-DBSQ)2 (I) and (Bpyz)Co(3,6-DBSQ)2 (II) (Pyz-Phen = pyrazino[2,3-f][1,10]phenanthroline, Bpyz = bipyrazine, 3,6-DBSQ = 3,6-di-tert-butyl-o-benzoquinone radical anion), were synthesized. According to X-ray diffraction data, both complexes have a trigonal-prismatic geometry of the inner coordination sphere. The distribution of C–O and Co–O bond lengths, which reflects the valence state of the metal and the ligands, indicates that the complexes are formed by cobalt(II) surrounded by two semiquinone radical anions. The results of magnetochemical measurements show that the pyrazino[2,3-f][1,10]phenanthroline complex is a derivative of low-spin divalent cobalt, whereas its bipyrazine structural analogue is a high-spin cobalt(II) derivative. [ABSTRACT FROM AUTHOR]

The qualitative spirit ageing bouquet, developed during maturation in oak casks through a complex transformation process, can result in a broad palette of nuances where roasted and nutty aromas are often identified. Nitrogen heterocycles (pyrazines, thiazoles, pyrroles), produced during the heating step of the barrel‐manufacturing, contribute to the perception of these nuances. However, their specific sensory characteristics within the spirit matrix have been poorly studied until now. The current study consisted in an overall olfactory characterization of nine targeted N‐heterocycles molecules previously identified in oak wood and detected in spirits. In a first step, the olfactory perception thresholds (detection and recognition) were measured in a spirit model medium (23% hydroalcoholic solution, pH 4), revealing that the presence of ethanol at such level minimally affected the olfactory perception of the studied compounds. A first sensory description of the set of N‐heterocycles also highlighted a large spectrum of aromatic nuances, mostly related to the semantic field of wood (nut, roasted, smoky, spicy). In a second step, a profile of the key aromatic attributes of the studied molecules was compiled, on the basis of their corresponding intensity scores given by a trained expert panel. Principal Component Analysis followed by Hierarchical Cluster Analysis categorized the pool of N‐heterocycles according to their sensory similarities. The presence of ethanol in spirit model matrix did not affect detection and recognition thresholds of studied N‐heterocycles. Wood‐derived nuances accounted among the most representative aromas characterized the studied N‐heterocycles. Functionals groups carried out by the chemical ring modified the aromatic perception of N‐heterocycles. [ABSTRACT FROM AUTHOR]

In this paper, calcium iodate nanoparticles were first synthesized by the modified reaction of Ca(NO3)2 and KIO3 in an aqueous medium under ultrasonic irradiation. The structure of nanocatalyst was then characterized by FT-IR, FESEM, EDX, XRD, and BET techniques. Afterward, the fabricated Ca(IO3)2 was applied as a nanocatalyst in the facile synthesis of heterocycles including quinoxalines, 5,6-dicyano pyrazines, and pyrido[2,3-b]pyrazines. For this purpose, the feasibility of the reaction in the presence of different catalyst amounts, solvents, and temperatures was first investigated. Next, the target compounds were obtained by the condensation reaction of aryl-1,2-diamines or 2,3-diaminomaleonitrile with 1,2-diketones in the presence of a catalytic amount of Ca(IO3)2 in ethanol or acetic acid solvents at ambient temperature in good to excellent yields. One of the salient advantages of this work is the synthesis of calcium iodate nanoparticles by chemical precipitation method and its application as a heterogeneous nanocatalyst for the first time in the synthesis of organic compounds. The other important benefits of this process are the use of an inexpensive, safe, stable and recyclable catalyst, high product yields, short reaction times, and easy isolation of the product in pure form. [ABSTRACT FROM AUTHOR]

Reaction of M(OAc)2·xH2O (M, x = Zn, 2 and Co, 4), 1,4-dihydro-5,6-dicyano-2,3-pyrazinedione (H2CN2pyzdione), and pyrazine (pyz) affords two compounds of the same molecular formula {[M(H2O)6][M(CN2pyzdione)2(pyz)]·6H2O}n (M = Zn for 1 and Co for 2) in which discrete units of [M(H2O)6]2+ are linked to one-dimensional chains of [M(CN2pyzdione)2(pyz)]2– via multiple O–H···O hydrogen-bonding interactions and M2+-bound H2O molecules in [M(H2O)6]2+ also serve as linkers of hydrogen-bonded interstitial H2O molecules. Remarkably, 1 crystallizes in the monoclinic crystal system, the similar crystal system and unit cell parameters as 2, but with a space group distinct from 1 and 2, i.e., 1 is the noncentrosymmetric space group C2, whereas 2 is the centrosymmetric space group C2/m. This polar structure for 1 is induced by the presence of alternating arrangements of distinguishable two axial Zn–N bonds within [Zn(CN2pyzdione)2(pyz)]2– chains. Indeed, solid-state circular dichroism spectra of 1 exhibit significant Cotton effects, as evidenced by the polar space group C2. Moreover, these Cotton effects show clear temperature-dependence depending on contents of H2O molecules of 1. [ABSTRACT FROM AUTHOR]

R = N -Heterocyclic aromatic compounds. [Display omitted] • Method was developed for the reduction of, β-alkynyl carbonyl compounds. • Tin chloride was used as the sole reducing agent. • This method is simple, efficient and environmental friendly. An efficient Tin(II)-chloride (SnCl 2) mediated reduction of α,β-alkynyl carbonyl compounds to their corresponding alkanes has been developed and reported. The developed method was optimized by varying parameters such as reaction time, temperature, and the equivalence of SnCl 2 using different solvents. The best reaction condition (80 % yield) involved 2.5 eq. of SnCl 2 , at 25 °C for 3 h in ethyl acetate. This method is applicable for the reduction of α,β-alkynyl carbonyl of quinoxaline, pyrimidine, pyrazine and pyridine. [ABSTRACT FROM AUTHOR]

Hot air-dried shrimp (HDS) has a strong fishy smell greatly reducing its flavor quality. This study aimed to investigate the regulation of total lipids, phospholipids and triglycerides isolated from shrimp for improving the characteristic volatile flavor of HDS. It was found that three lipids could promote the formation of aroma compounds with pleasant characteristic aromas (e.g., pyrazines). Phospholipids and triglycerides inhibited the formation of trimethylamine, a key component of fishy smell, with phospholipids exhibiting the best inhibitory effect (47.70 ± 2.63 %), greatly improving the flavor quality of HDS. Aldehydes, unsaturated ketones, and furans, primarily derived from the thermal degradation of C18:1, C18:2, and C22:6, were key intermediate compounds promoting the Maillard reaction. Lipids inhibited trimethylamine by prompting the formation of pyrazines. Maillard reaction was the key pathway for lipids to improve the flavor quality of HDS. This study can provide theoretical support for the development of high-quality thermally processed shrimp products. [Display omitted] • Addition of shrimp lipids enhanced pleasant characteristic aromas of HDS. • PL and TG could greatly reduce trimethylamine, a key component of fishy smell in HDS. • Lipids inhibited trimethylamine by prompting the formation of pyrazines. • Maillard reaction was a key pathway for shrimp lipids to enhance HDS flavor quality. [ABSTRACT FROM AUTHOR]

The methionine/glucose (Met/Glc) and methionine/glucose-derived Amadori rearrangement product (MG-ARP) models were established to analyze their differences in flavor profiles and aroma potentiality. The principal component analysis revealed the advantage of MG-ARP in the formation of low temperature-induced processing flavor. MG-ARP exhibited superior potential in the rapid formation and high intensity of processed flavor than the Met/Glc except for the inefficiency in pyrazine production. The extra-added Glc tended to react with recovered Met to compete against α-dicarbonyl compounds to suppress the Strecker degradation and pyrazine formation. The additional Met effectively improved the precursor availability and facilitated the conversion of C 6 -α-dicarbonyl compounds to short-chained α-dicarbonyl compounds for pyrazine formation rather than their dehydration and cyclization to generate furans. The oxidation of Met favored the nonoxidative carbohydrate degradation leading to MGO formation and the aldolization of dihydropyrazines, which synergistically enriched the varieties of pyrazines, especially for the promoted formation of long-chain substituted pyrazines. • MG-ARP has advantage in the formation of low temperature-induced processing flavor. • MG-ARP exhibited superior flavor potential expect for pyrazine production. • Extra-added Glc inhibited pyrazine formation by competitively consuming Met. • Additional Met improved the precursor availability for pyrazine formation. • Oxidation of Met promoted the formation of long-chain substituted pyrazines. [ABSTRACT FROM AUTHOR]

• A dimeric [Cd(DNBA)2(py)2]2 and a ID polymeric [Cd(DNBA)2(pyz)2]n cadmium complexes are synthesized. • Single crystal XRD showed that distorted octahedral geometry is formed in both compounds. • Hirshfeld surface analysis inferred that H···O contacts are the most significant contributor of the supramolecular assembly of both compounds. • Void analysis showed that the compound will have good response to an applied stress. • Computational study results are consistent with the corresponding ones of single crystal XRD. In the current investigation, a new dimeric [Cd(DNBA) 2 (py) 2 ] 2 and a polymeric [Cd(DNBA) 2 (pyz) 2 ] n cadmium complexes have been prepared by the reaction of 3,5-dinitrobenzoic acid (main ligand), nitrogen donor auxiliary ligands (pyridine and pyrazine), and Cd(II) sulphate in aqueous media. The crystal structures of the synthesized compounds were determined by single-crystal X-ray diffraction analysis. The crystal structures were investigated in terms of the coordination geometry, dihedral angles between various rings, and intermolecular interactions. The solid-state assembly was stabilized by various interatomic contacts, explored by Hirshfeld surface analysis. Void analysis was performed to predict the response of crystals to the applied stress. The optimized molecular geometries of the compounds were achieved utilizing the DFT approach along with the B3LYP functional/6–311G(d,p)/LANL2DZ basic set. MEP maps, molecular orbital theory, and quantum chemical parameters for the synthesized compounds were generated using the same level of theory. [Display omitted] [ABSTRACT FROM AUTHOR]

• In the present work, we designed new pyrazine derivatives via a rational approach by incorporating three pharmacophores. • Ten different pyrazine derivatives were synthesized in five synthetic steps and evaluated for their in vitro inhibitory potency against the mycobacterium tuberculosis H37Rv. • Among the title compounds, 8e and 8h demonstrated significant antitubercular activity with MIC values of 1.59 and 1.79 μg/ml respectively. • The activity profiles of the pyrazine derivatives were validated via performing molecular docking studies. • In silico prediction of physicochemical, ADME and drug-like properties revealed that most of the tested compounds were within those considered adequate for a drug candidate. Tuberculosis (TB) remains a major public health concern in spite of the existence of effective anti-TB medications. We present the design and synthesis of new compounds with pyrazine and pyridine/pyrimidine moieties. The Microplate Alamar Blue Assay (MABA) was used to test the activity of the synthesized compounds against the Mycobacterium tuberculosis (Mtb) H37Rv strain. Among the synthesized compounds, 8e and 8h showed considerable antitubercular activity. The most effective compounds were then effectively docked onto the active site of the Mtb enoyl reductase receptor. These compounds have demonstrated favorable binding interactions with amino acids present in the receptor. Furthermore, in silico prediction of physicochemical and pharmacokinetic properties revealed that the synthesized compounds can be used to generate novel anti-TB agents with increased activity and safety profiles. [ABSTRACT FROM AUTHOR]

The occurrence of the cooked off-flavor during the thermal sterilization of green tea beverages negatively impacts their quality. This study aimed to identify the key cooked off-flavor compounds by molecular sensory science. The increase of 12 compounds, including malty (e.g., 3-methylbutanal), floral (e.g., linalool), sweet (e.g., methional), and smoky (2-methoxy-4-vinylphenol) compounds, contributed to the development of the cooked off-flavor. Additionally, the loss of five aroma compounds—dimethyl sulfide, (E) -β- ionone, 2-methylbutanal, 1-penten-3-one, and (E,Z)-2,6-nonadienal—also caused the emergence this undesirable flavor. One potential solution to reduce the cooked off-flavor was the baking of tea raw materials. While baking did not significantly reduce the concentration of off-flavor compounds, it led to an increase in eight roasty aroma compounds, such as pyrazines and pyrroles, which helped partially mask the cooked off-flavor in green tea beverages. • Cooked off-flavor in tea beverage was investigated by molecular sensory science. • Malty, floral, sweet and smoky compounds contributed to cooked off-flavor. • 5 compounds decreasing also promoted the formation of cooked off-flavor. • Off-flavor compounds did not decreased significantly after tea material roasting. • Roasty compounds had masking effect on cooked off-flavor. [ABSTRACT FROM AUTHOR]

Storage is a crucial step in the production of Daqu , but the microbiological and flavor chemical kinetics of the storage process remain largely unknown and limit the quality control of Daqu. In this study, the microbial communities and volatile compounds were analyzed and compared during the storage of Daqu. Virgibacillus , Bacillus and Kroppenstedtia were the dominant bacterial genera, and Thermoascus , Thermomyces and Aspergillus were the dominant fungal genera. By LEfSe analysis, JW1 Daqu had more differential microbial markers. At the end of storage, the content of some compounds decreased significantly, such as esters, alcohols and ketones. In addition, PICRUSt2 predicted enzymes related to some important aroma production. These results indicated that microbial communities and volatiles changed significantly during storage of Daqu , which might be important for optimization of quality. [Display omitted] • The dynamic succession of microbial communities during Daqu storage was elucidated. • A total of 45 volatile metabolites were significant across different samples. • Differential microbial markers linked to Daqu storage stages were determined. [ABSTRACT FROM AUTHOR]

[Display omitted] • SAR study reveals that hydroxylamine derivatives are more potent than hydrazine analogs of BAM15 as mitochondrial uncouplers. • In general, electron withdrawing groups are preferred. • Compound 4e has EC 50 value of 340 nM in rat L6 myoblasts and 118 % BAM15 mitochondrial uncoupling activity. Chemical mitochondrial uncouplers are protonophoric, lipophilic small molecules that transport protons from the mitochondrial intermembrane space into the matrix independent of ATP synthase, thus uncoupling nutrient oxidation from ATP production. Our previous work identified BAM15 (IC 50 0.27 μM) as a potent and efficacious mitochondrial uncoupler with potential for obesity treatment. In this paper, we investigate in vitro and in vivo properties of hydroxylamine and hydrazine BAM15 derivatives and reveal the high uncoupling nature of these compounds. Our structure–activity relationship studies revealed that the hydroxylamine BAM15 analogs are more potent than hydrazine ones. For example, the most potent of the hydrazine series was 5a with an EC 50 value of 4.6 μM and 103 % activity of BAM15 while compound 4e was the best among the hydroxylamine series with EC 50 value of 340 nM and 118 % BAM15 mitochondrial uncoupling activity in rat L6 myoblasts. Pharmacokinetic profiling of 5a and 4e revealed low exposure (2–220 nM) and short half-life (15–27 min) in mice. [ABSTRACT FROM AUTHOR]

[Display omitted] • Reported the synthesis and crystal structures of two zinc porphyrins ZnT(4-Cl)PP, 1 and [ZnT(4-Cl)PP(pyz)], 2, pyz = pyrazine. • The crystal structure of 2 consists of an axial pyrazine ligand forming a penta-coordinated complex. • Fluorescence emission spectral analysis of the synthesized compounds has been studied. • DFT calculations like structure optimization, simulation of electronic spectra and Hirshfeld surface analysis were performed. • The UV–Vis spectrum of 2 exhibits red-shifted Soret band compared to 1 which supports the binding of pyrazine. This work describes the synthesis, characterization, crystal structure, and computational analyses of the zinc porphyrin [ZnT(4-Cl)PP], 1 and its pyrazine bound analogue, [ZnT(4-Cl)PP(pyz)], 2, (where T(4-Cl)PP stands for 5,10,15,20-tetrakis-(4-chlorophenyl)porphyrin and pyz represents pyrazine). Both compounds were structurally characterized by UV–visible spectroscopy, infrared spectroscopy, 1HNMR spectroscopy, 13CNMR spectroscopy and single crystal XRD. The crystal structure of the 2 consists of a zinc porphyrin with an axial pyrazine ligand forming a penta-coordinated complex with Zn1-N5(pyz) distance 2.228(3) Å. To investigate the key insights into their photophysical properties, fluorescence emission spectral analysis of the synthesized compounds has been studied. Theoretical calculations like optimization of geometry, the energy of frontier orbitals, Hirshfeld surface analysis and simulation of electronic spectra were performed which supports the experimental results. [ABSTRACT FROM AUTHOR]

• A pzdc2- ligand covalently functionalized arsenotungstate was synthesized. • Four pzdc2– ligands are coordinated with w atoms of POMs skeleton. • This hybrid arsenotungstate displays decent proton conduction property. A pyrazine-2,3-dicarboxylic acid hybrid arsenotungstate K 5 Ba 5 H{Ba[AsW 11 O 37 (pzdc) 2 ] 2 }·22H 2 O (1 , H 2 pzdc = pyrazine-2,3-dicarboxylic acid) has been synthesized. This compound displayed a dimeric polyanion which consisted of two ancient official cap-shaped [AsW 11 O 37 (pzdc) 2 ]9– subunits linked together via a Ba2+ cation. The [AsW 11 O 37 (pzdc) 2 ]9– subunit is fused together by a trivacant [AsW 9 O 33 ]9– fragment and two {WO 2 (pzdc)} groups. And the [Ba(AsW 9 O 33) 2 ]16– subunit can be simplified into the ferrocene-like structure. What is particularly interesting is that one N and one O atom of the pzdc2– ligand can directly chelate with the W atom to construct the infrequent W–O–C–C–N five-membered ring. Compound 1 exhibits good proton conduction property with the conductivity of 1 can reach up to 2.37× 10–3 S cm-1 at 70 °C under 95% relative humidity. Synopsis A pzdc2− ligand covalently functionalized arsenotungstate, K 5 Ba 5 H{Ba[AsW 11 O 37 (pzdc) 2 ] 2 }·22H 2 O, consisted of two ancient official cap-shaped polyanion [AsW 11 O 37 (pzdc) 2 ]9− linked via a Ba2+ cation, which exhibits decent proton conduction property with conductivity of 2.37× 10−3 S cm−1 at 70 °C under 95% relative humidity. [Display omitted] [ABSTRACT FROM AUTHOR]

In this study, critical reactants were identified in glycine/glucose/creatinine model system to clarify the formation pathways of imidazoquinoxaline-type heterocyclic amines (IQx-type HAs). It has been confirmed that the condensation between pyrazines and creatinine was the critical step to produce IQx-type HAs. There was a conversion between methylglyoxal and glyoxal, and their carbonyl-amine reaction was a route for the production of 2,5-dimethylpyrazine and methylpyrazine. When cysteine was combined with proline at the mass ratio of 4:1 (2 mg/mL in total), the inhibitory rate of MeIQx and IQx in glucose/creatinine/glycine model system increased to 62 % and 55 %, respectively. The synergistic inhibition of cysteine-proline combinations was further assessed in roast yellow croaker, and the total content of IQx-type HAs decreased from 4.99 ± 0.48 ng/g of the control group to 2.46 ± 0.21 ng/g. The carbonyl scavenging rate of corresponding cysteine-proline combinations also increased compared with that of single agents. These findings suggest that scavenging methylglyoxal and glyoxal simultaneously to control the production of pyrazines may be a potential inhibitory strategy to enhance the suppression of IQx-type HAs formation. [Display omitted] • Methylglyoxal and glyoxal can produce pyrazines via carbonyl-amine reactions. • Pyrazines can condense with creatinine to form IQx-type HAs. • There is a conversion between methylglyoxal and glyoxal. • Scavenging carbonyls leads to synergistic inhibition of HAs formation. [ABSTRACT FROM AUTHOR]

A series of organic fluorophores based on novel [1,2,4]triazolo [4′,3':1,2]pyrido [3,4- b ]pyrazine architecture were synthesized by a simple two-step protocol. Synthesized organic fluorophores exhibit blue-to-green fluorescence and their UV absorption and fluorescent emission properties were studied. The photophysical properties of synthesized derivatives were tuned by introducing functionalities of varying electronic nature on the core nucleus. The luminescence maxima of the synthesized compounds are found in the range from 427 nm to 503 nm, and the quantum yields ranging from 0.01 to 0.64 were calculated. Among various synthesized molecules, 3-(4-bromophenyl)-8,9-bis(4-methoxyphenyl)-[1,2,4]triazolo [4′,3':1,2]pyrido [3,4- b ]pyrazine showed highest quantum yield (Φ F = 0.64), and was further explored for its solvatochromic, acidochromic, aggregation induced fluorescence studies along with theoretical HOMO-LUMO calculations. [Display omitted] • Novel series of organic luminophores, namely [1,2,4]triazolo [4′,3':1,2]pyrido [3,4- b ]pyrazines were designed, synthesized and characterized. • UV absorption and fluorescent emission properties of all synthesized compounds were studied. • 3-(4-Bromophenyl)-8,9-bis(4-methoxyphenyl)-[1,2,4]triazolo [4′,3':1,2]pyrido [3,4- b ]pyrazine showcased highest quantum yield (Φ F = 0.64) in methanol, and was further explored for its acidochromic and aggregation induced fluorescence studies. [ABSTRACT FROM AUTHOR]

Large-leaf yellow tea (LYT) is processed from both leaves and stems, resulting in a distinctive rice crust–like aroma. Tea stems may contribute differently to the aroma of LYT than leaves. This study aimed to clarify the specific contribution of stems to LYT. The volatile compounds in different components of LYT were extracted and analyzed using a combination of headspace solid-phase microextraction and stir bar sorptive extraction coupled with gas chromatography-olfactory-mass spectrometry. The results revealed high concentrations of compounds with roasty attributes in stems such as 2-ethyl-3,5-dimethylpyrazine (OAV 153–208) and 2-ethyl-3,6-dimethylpyrazine (OAV 111–140). Aroma recombination and addition experiments confirmed that the roasty aroma provided by stems plays a pivotal role in the formation of the distinctive flavor of LYT. This study offers novel insights into the contribution of stems to the aroma of LYT, which can be used for processing and quality enhancement of roasted tea. • Tea stems and leaves significantly differed in aromatic compositions. • Retaining tea stems enhanced the roasty aroma of large-leaf yellow tea. • Roasted stems were rich in pyrazines (2-ethyl-3,5-dimethylpyrazine). • High concentrations of monosaccharides and amino acids occurred in the stems. [ABSTRACT FROM AUTHOR]

Second-generation mammalian target of rapamycin (mTOR) inhibitors such as CC-223 may have theoretical advantages over first-generation drugs by inhibiting TOR kinase in mTOR complex 1 (mTORC1) and 2 (mTORC2), potentially improving clinical efficacy for well-differentiated neuroendocrine tumors (NET).Enrolled patients had metastatic, well-differentiated NET of non-pancreatic gastrointestinal or unknown origin, with/without carcinoid symptoms, had failed ≥1 systemic chemotherapy, and were taking a somatostatin analog (SSA). Oral once-daily CC-223 was administered in 28-day cycles starting at 45 mg (n = 24), with a subsequent cohort starting at 30 mg (n = 23). Objectives were to evaluate tolerability, preliminary efficacy, and pharmacokinetic and biomarker profiles of CC-223. Forty-seven patients completed the study, with mean treatment duration of 378 days and mean dose of 26 mg; 26% of patients remained on the starting dose. Most frequent grade ≥3 toxicities were diarrhea (38%), fatigue (21%), and stomatitis (11%). By investigator, 3 of 41 evaluable patients (7%) showed partial response (PR) and 34 (83%) had stable disease (SD) for a disease control rate (DCR) of 90% (95% confidence interval [CI] 76.9-97.3%). Duration of PR was 125-401 days; median SD duration was 297 days (min-max, 50-1519 days). Median progression-free survival was 19.5 months (95% CI 10.4-28.5 months). Carcinoid symptoms of flushing, diarrhea, or both improved in 50%, 41%, and 39% of affected patients, respectively. For the first time, this study describes that a second-generation mTOR pathway inhibitor can result in highly durable tumor regression and control of NET carcinoid symptoms. The manageable safety profile, high DCR, and durable response, coupled with reduction in carcinoid symptoms refractory to SSA, make CC-223 a promising agent for further development.

A series of phosphorescent platinum(II) complexes containing various phenyldiazine-type bidentate N^C ligands have been successfully synthesized and characterized. Structural modifications have been made to bidentate cyclometalating ligands regarding the nature of the diazine ring (pyrimidine, pyrazine and quinazoline), the substituent groups at the C4 position of the pyrimidine ring (OCH3, CF3) and the EDGs at the para position of the Pt atom (OCH3, Ph, NPh2, carbazol). In addition, the electronic properties of the azaheterocyclic ancillary ligand have been modulated in this series of complexes (pyridine, 4-methoxy-pyridine or pyrimidine). X-ray diffraction studies have been performed on three complexes, revealing Pt(II) ions in a distorted square-planar geometrical environment with no Pt(II)⋯Pt(II) interactions but with moderate π–π interactions in the solid-state structure. Electrochemical and computational studies suggest a ligand-centered reduction on the diazine ligands with, in some cases, additional contribution from the azaheterocyclic ancillary ligand, whereas oxidation occurs on the Pt-phenyl ring substituent moieties. All complexes exhibit phosphorescence emission ranging from green to red/near-infrared, both in solution and in the solid state. Complexes bearing a 2-(3-methoxyphenyl)pyrimidine ligand show the best PLQY of the series, up to 52% in a CH2Cl2 solution and 20% in the solid state. Furthermore, the solid state PLQY of one of the near-infrared emitting phenylquinazoline complex has been found to be 6%. [ABSTRACT FROM AUTHOR]

In this work, a series of butterfly-like isomers named oxacalix[2]naphthalene[2]pyrazine (ONP) were conveniently synthesized by a one-step catalyst-free reaction in a facile manner, and they exhibit typical characteristics of aggregation-induced emission (AIE). The mechanism study shows that restriction of intramolecular vibration (RIV) is the reason for their AIE properties. The pyrazine groups endow ONP molecules with good coordination ability, which makes them ideal ligands for constructing metal–organic frameworks (MOFs). Thus, three ONP-based luminescent MOFs were constructed, and they exhibit intense emission with lifetimes in the order of microseconds. More importantly, different ONP isomers have different binding capacities, and thus only one kind of MOF can be obtained even when using an isomer mixture of ONP ligands. This result suggested that the conformation of ONPs is an important determining factor for their application as bridging ligands. This work not only reports a series of new RIV-type AIEgens, but also offers a new platform for the construction of luminescent MOFs. [ABSTRACT FROM AUTHOR]

A novel protocol for the assembly of polysubstituted 2,3‐dioxo‐1,4,5,6‐tetrahydropyrazines and 2,3‐dioxo‐hydro‐1H‐cycloalkyl[b]pyrazines has been developed by the sequential three‐component reaction of primary aliphatic amines, 1,2‐diaza‐1,3‐dienes (DDs) and oxalyl chloride. This synthetic sequence proceeds by initial aza‐Michael addition of the amine to the azo‐ene compounds and subsequent ring closure involving the oxalyl chloride. The ready availability of the starting materials as well as the high level of practicability of the reaction and work‐up make this approach an attractive opportunity towards these uncommon systems. [ABSTRACT FROM AUTHOR]

The possibility of using push-pull systems based on furazanopyrazine in organic light-emitting diodes (OLEDs) and photovoltaic film devices was shown for the first time. The emission of all the obtained light-emitting diodes had a yellow-green color, and a maximum brightness of 45600 cd m−2 was achieved at a maximum current efficiency of 2.9 cd A−1. It was determined that the mobility of charge carriers measured in different current modes for these push-pull systems ranged from 10−4 to 4 · 10−6 cm2 V−1 s−1, considerably exceeding the values of the well-known compound Spiro-MeOTAD, widely used in high-efficiency photovoltaic devices. [ABSTRACT FROM AUTHOR]

Biogenic amines (BAs), which are mainly generated by the microbial decarboxylation of amino acids, are important nitrogen compounds in fermented foods because of their toxicology. However, amino acids, the precursors of BAs, also play an important role in generating volatile and non-volatile metabolites, which are strongly associated with quality indicators for foods. Bacillus subtilis is one of dominant fermentative microorganism in various fermented foods and is well known as a BA-producing bacterium. In this study, B. subtilis strains which have different BAs-producing capacities, higher level of BAs production strain (BH) and lower level of BAs production strain (BL), were applied to compare the formations of volatile and non-volatile metabolite profiles according to cultivation times. In this study, histamine, putrescine, and spermidine were detected in all strains, however, 2-phenylethylamine was detected only in BH. Partial least squares discriminant analysis (PLS-DA) was applied to investigate the difference of metabolic profiles according to strains. In BH, some amino acids (phenylalanine, leucine, and threonine) and related volatile metabolites (3-methylbutanoic acid, pyrazines, styrene, and 1H-indole) were produced higher levels. On the other hand, BL produced significantly higher contents of metabolites associated with metabolism of fatty acids and nucleotides. It is necessary to consider the formation of metabolites in terms of quality as well as that of BAs during fermentation. [ABSTRACT FROM AUTHOR]

The volatile flavor compounds are the most important indicators of the quality of cocoa beans, among which pyrazines are considered as the main and key groups affecting the cocoa flavor. In cocoa processing, roasting is an important stage in the technical treatment of cocoa and has a significant impact on chemical properties of cocoa and its flavor. The present study aimed to assess the impact of roasting (temperature and time) on alkyl pyrazines, as key flavor compounds, via gas chromatography–mass spectrometry. Additionally, other properties, including color, polyphenols, chemical properties, and sensory attributes of cocoa powder were investigated. The results indicated that with the change in roasting time and temperature, these properties changed significantly. The cocoa powder roasted at 140 °C for 40 min had the highest browning index value (OD460/OD525), tetramethylpyrazine to trimethylpyrazine (TMP/TrMP) ratio, and sensory evaluation score and the lowest polyphenol content compared to the other samples. [ABSTRACT FROM AUTHOR]

A new ligand, 4-(4-carboxyphenyl)-6-(pyrazin-2-yl)picolinic acid (H2L1), was used to construct four isostructural one-dimensional (1 D) zig-zag chain coordination polymers ([M(L1)(H2O)2]·3H2O, M = Mn (1), Co (2), Cd (3) and Zn (4)). Moreover, when changing the ligand substituent group from pyrazine ring to furan ring, another new ligand, 4-(4-carboxyphenyl)-6-(furan-2-yl)picolinic acid (H2L2), was synthesized. Based on H2L2, different structural 1 D coordination polymers, ([Mn(L2)(H2O)2] (5) and [Ni(L2)(H2O)2]·H2O (6)), have been obtained under the same solvothermal conditions as for the syntheses of isostructural 1–4. Interestingly, only through changing the ligand substituent group, the 1 D isostructural zig-zag chain (1–4) was adjusted to a 1 D molecular box chain (5) and 1 D linear chain (6), which should be ascribed to ligand substituent group effects. The various 1 D chain structures originate from the types of ligand substituent group: the substituent group with a pyrazine ring only yields isostructural coordination polymers 1–4, whereas the substituent group with a furan ring can construct different structural coordination polymers, such as a 1 D molecular box chain (5) or a 1 D linear chain (6). The photoluminescent properties of all coordination polymers were also examined. [ABSTRACT FROM AUTHOR]

Copyright of Shipin Kexue/ Food Science is the property of Food Science Editorial Department and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

In this study, the microbial diversity in Tibetan flavor Daqu was analyzed based on single molecule real-time sequencing (SMRT). The volatile flavor compounds in Daqu were detected using the headspace solid-phase microextraction-gas chromatography-mass spectrometry (HS-SPME-GC-MS). In addition, the correlation between various microbes and volatile flavor compounds was explored. Our studies indicated that the dominant bacterial genera in Tibetan flavor Daqu were Oceanobacillus, Kroppenstedtia, Virgibacillus, Enterococcus, Pediococcus, Streptomyces, Saccharopolyspora, Leuconostoc, uncultured_bacterium_f_Lachnospiraceae and Lactobacillus. The dominant fungal genera were Wickerhamomyces, Monascus, Aspergillus and Rhizomucor. 101 volatile compounds were detected in the Daqu samples, including alcohols, acids, esters, aldehydes, hydrocarbons, ketones, ethers, aromatics and pyrazines, and 10 key flavor compounds were identified using the relative odor activity value (ROAV). The results of our correlation analysis showed that Enterococcus was mainly associated with the synthesis of aldehydes such as trans-2-octenal, and uncultured_bacterium_f_lachnospiraceae was associated with the synthesis of most aldehydes. This paper has systematically investigated the physicochemical indices, microbial community structure and flavor compounds of Tibetan flavor Daqu, which is helpful in gaining a deeper understanding of the characteristics of Tibetan flavor Daqu. [ABSTRACT FROM AUTHOR]

Despite the importance of pyrazines in Baijiu flavor, inoculating functional strains to increase the contents of pyrazine in Daqu and how those interact with endogenic communities is not well characterized. The effects of inoculating Bacillus licheniformis with similar metabolic capacity on pyrazine and community structure were assessed in the Daqu complex system and compared with traditional Daqu. The fortification strategy increased the volatile metabolite content of Daqu by 52.40% and the pyrazine content by 655.99%. Meanwhile, results revealed that the pyrazine content in Daqu inoculated isolate J-49 was 2.35–7.41 times higher than isolate J-41. Both isolates have the almost same capability of 2,3-butanediol, a key precursor of pyrazine, in pure cultured systems. Since the membrane fatty acids of isolate J-49 contain unsaturated fatty acids, it enhances the response-ability to withstand complex environmental pressure, resulting in higher pyrazine content. PICRUSt2 suggested that the increase in pyrazine was related to the enzyme expression of nitrogen metabolism significantly increasing, which led to the enrichment of NH4+ and 2,3-butanediol (which increased by 615.89%). These results based on multi-dimensional approaches revealed the effect of functional bacteria enhancement on the attribution of Daqu, laid a methodological foundation regulating the microbial community structure and enhanced the target products by functional strains. [ABSTRACT FROM AUTHOR]

The synthesis and characterization of two tritopic ligands containing a 2,2′:6′,2″-terpyridine (tpy) metal binding domain and either a 3,2′:6′,3″- or a 4,2′:6′,4″-tpy domain are detailed. The synthetic routes to these ligands involved the [Pd(dppf)Cl2]-catalyzed coupling of a boronic ester-functionalized 2,2′:6′,2″-tpy with bromo-derivatives of 3,2′:6′,3″-tpy or 4,2′:6′,4″-tpy. The 2,2′:6′,2″-tpy domains of the tritopic ligands preferentially bind Fe2+ in reactions with iron(II) salts leading to the formation of two homoleptic iron(II) complexes containing two peripheral 3,2′:6′,3″-tpy or 4,2′:6′,4″-tpy metal-binding sites, respectively. These iron(II) complexes are potentially tetratopic ligands and represent expanded versions of tetra(pyridin-4-yl)pyrazine. [ABSTRACT FROM AUTHOR]

A simple, reproducible, and rapid kinetic method for the S-Carboxymethyl-L-cysteine (CCys) determination has been proposed and linked to CCys quantification in pharmaceutical preparations. The method is based on the inhibitory feature of Carbocisteine. CCys forms a stable complex with Hg2+ and reduces the actual Hg2+ concentration and ultimately the rate of reaction between pyrazine (Pz) and [Ru(CN)6]4-catalyzed by Hg2+. Under the optimized reaction conditions with ionic strength (I) = 0.1 mol dm-3 (KCl), [Pyrazine (Pz)] = 3.0 × 10-4 mol dm-3, pH = 4.0 ± 0.03, [Hg+2] = 1.5 × 10-4 mol dm-3, [Ru(CN)64-] = 2.75 × 10-5 mol dm-3, and at 45.0 ± 0.2 o C temperature, fixed time of 9 and 14 min was selected to compute the absorbance at 370 nm corresponding to the ultimate reaction product [Fe(CN)5 Pz]3-. With the proposed kinetic spectrophotometric method, the micro-level quantification of CCys in distinct water samples can be done down to 1.25 × 10-6 mol dm-3. The developed procedure is highly reproducible and can be efficiently used to quantitatively estimate the CCys in the drug samples with high accuracy. The general additives present in drugs do not substantially interfere in the determination of CCys even up to 1000 times with [CCys]. [ABSTRACT FROM AUTHOR]

Context: The σ-hole, counterintuitive σ-hole, and lone pair-π interaction complexes formed between three heterocyclic compounds (C4H4O, C5H5N, and C4H4N2) and AtX (X = F, Cl, and Br) have been investigated with the MP2/aug-cc-pVTZ. The intensity of three noncovalent interactions formed by different heterocyclic compounds was compared, and the properties of these three noncovalent interactions were discussed. SAPT analysis shows that the electrostatic energy is dominant to the stronger interactions in the σ-hole and counterintuitive σ-hole complexes, while the dispersion energy is the main force responsible for the weaker interactions in the lone pair-π complexes. NBO analysis has also been employed. Methods: All the structures were optimized at the MP2/aug-cc-pVTZ (aug-cc-pVTZ-pp for Br to account for relativistic effects) level using the Gaussian 03W package (Gaussian, Inc., Wallingford, CT, USA). The basis bet superposition error (BSSE) is corrected using counterpoise method proposed by Boys and Bernardi. The NBO population analysis was carried out. The molecular electrostatic surface potentials of monomers were calculated by WFA-SAS program package. The interaction energies of the three types complexes were decomposed by using the symmetric adaptive perturbation theory SAPT of the open source ab initio electronic structure software package psi 4.0.0-beta5. [ABSTRACT FROM AUTHOR]

Copyright of Chinese Journal of Explosives & Propellants is the property of Chinese Journal of Explosives & Propellants Editorial Office and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

In many important cases, the rate of excitation of a system embedded in an environment is significantly smaller than the internal system relaxation rates. An important example is that of light-induced processes under natural conditions, in which the system is excited by weak, incoherent (e.g., solar) radiation. Simulating the dynamics on the time scale of the excitation source can thus be computationally intractable. Here we describe a method for obtaining the dynamics of quantum systems without directly solving the master equation. We present an algorithm for the numerical implementation of this method and, as an example, use it to reconstruct the internal conversion dynamics of pyrazine excited by sunlight. Significantly, this approach also allows us to assess the role of quantum coher- ence on biological time scales, which is a topic of ongoing interest. [ABSTRACT FROM AUTHOR]

Herein, we report the use of reactive eutectic media from ammonium formate and monosaccharides to synthesize poly(hydroxyalkyl)pyrazines via microwave irradiation. This enabled unprecedented fast rates as well as better atom economy compared to previous methods. We investigated the influence of water on the reaction yield as well as the physical properties of the eutectic media and could thereby drastically reduce the viscosity, while preserving high reaction yields. The results were consistent for different monosaccharides, using fructose, glucose, rhamnose and fucose as reactants. Furthermore, the major reaction products were separated, chemically analyzed and tested for their antimicrobial activity via high-throughput screening. [ABSTRACT FROM AUTHOR]

5-(Alkylamino)-6-aryl/alkylpyrazine-2,3-dicarbonitriles were successfully synthesized in good to moderate yields by reacting alkyl isocyanides with aryl/alkyl carbonyl chlorides, followed by the addition of diaminomaleonitrile. The synthesized pyrazines were fully characterized in this investigation, and X-ray crystal structure analysis was performed on some derivatives. The antibacterial and antifungal activities of the newly synthesized pyrazine-2,3-dicarbonitriles were assessed in addition to their UV and fluorescence results. All the compounds showed similar UV–Vis spectral features with absorption peaks (λmax) around 267, 303, and 373 nm. [ABSTRACT FROM AUTHOR]

The excellent π-accepting azodicarboxylic esters adcOR (R = Et, iPr, tBu, Bn (CH2-C6H5) and Ph) and the piperidinyl amide derivative adcpip were used as bridging chelate ligands in dinuclear Re(CO)3 complexes [{Re(CO)3Cl}2(µ-adcOR)] and [{Re(CO)3Cl}2(µ-adcpip)]. From the adcpip ligand the mononuclear derivatives [Re(CO)3Cl(adcpip)] and [Re(CO)3(PPh3)(µ-adcpip)]Cl were also obtained. Optimised geometries from density functional theory (DFT) calculations show syn and anti isomers for the dinuclear fac-Re(CO)3 complexes at slightly different energies but they were not distinguishable from experimental IR or UV–Vis absorption spectroscopy. The electrochemistry of the adc complexes showed reduction potentials slightly below 0.0 V vs. the ferrocene/ferrocenium couple. Attempts to generate the radicals [{Re(CO)3Cl}2(µ-adcOR)]•− failed as they are inherently unstable, losing very probably first the Cl− coligand and then rapidly cleaving one [Re(CO)3] fragment. Consequently, we found signals in EPR very probably due to mononuclear radical complexes [Re(CO)3(solv)(adc)]•. The underlying Cl−→solvent exchange was modelled for the mononuclear [Re(CO)3Cl(adcpip)] using DFT calculations and showed a markedly enhanced Re-Cl labilisation for the reduced compared with the neutral complex. Both the easy reduction with potentials ranging roughly from −0.2 to −0.1 V for the adc ligands and the low-energy NIR absorptions in the 700 to 850 nm range place the adc ligands with their lowest-lying π* orbital being localised on the azo function, amongst comparable bridging chelate N^N coordinating ligands with low-lying π* orbitals of central azo, tetrazine or pyrazine functions. Comparative (TD)DFT-calculations on the Re(CO)3Cl complexes of the adcpip ligand using the quite established basis set and functionals M06-2X/def2TZVP/LANL2DZ/CPCM(THF) and the more advanced TPSSh/def2-TZVP(+def2-ECP for Re)/CPCMC(THF) for single-point calculations with BP86/def2-TZVP(+def2-ECP for Re)/CPCMC(THF) optimised geometries showed a markedly better agreement of the latter with the experimental XRD, IR and UV–Vis absorption data. [ABSTRACT FROM AUTHOR]

Acylethynylpyrroles, now readily available by the cross-coupling of pyrroles with acylbromoacetylenes in solid Al2O3 media, in the presence of 1-methylimidazole underwent unprecedentedly easy (40–45 °C) cyclodimerization into bis(acylmethylidene)dipyrrolo[1,2-a:1′,2′-d]pyrazines in up to 51% yield. Some other organic and inorganic basic catalysts can also trigger this cyclodimerization, but less efficiently. [ABSTRACT FROM AUTHOR]

In the present work, how the position of the second nitrogen in the conjugate acids of the three pyridazines viz., 1,2-pyridazine, 1,3-pyridazine (the pyrimidine) and 1,4-pyridazine (the pyrazine) and three naphthyridines viz., cinnoline, quinazoline and quinoxaline changes the pKaH systematically is taken up. They decrease nearly by a factor of half each time in the class of their own. In contrast there is an increase in the pKaH when we move from pyrazole to imidazole. The pKaH of pyrazole is less than imidazole by −4.45 units. Suitable explanations are given. [ABSTRACT FROM AUTHOR]

The volatile compounds in Jinhua ham samples after different aging times were characterized using solvent-assisted flavor evaporation (SAFE), solid-phase microextraction (SPME), and needle trap (NT) extraction methods combined with gas chromatography–time-of-flight mass spectrometry (GC–TOF/MS). Hundreds of aroma compounds were identified, including aldehydes, alcohols, ketones, furans, esters, acids, pyrazines, and sulfides. The results showed that NT extracted the greatest number of volatile compounds, whereas the extraction efficiency of SPME headspace adsorption was highest among the three sample preparation methods. Principal component analysis of SPME effectively distinguished the variation in the aroma of the Jinhua hams specific to aging time. Butyrolactone, 2,6-dimethylpyrazine, 2,3,5-trimethylpyrazine, phenylacetaldehyde, and acetic acid were considered as the main volatile compounds in the Jinhua ham samples at three years of aging. The results showed that SPME–GC–TOF/MS effectively discriminated among samples by age. By comparing the three extraction methods, this study provides a theoretical basis for the selection of extraction methods of volatile aroma compounds in Jinhua ham. [ABSTRACT FROM AUTHOR]

The role of the integrin family in malignancy has received increasing attention. Many studies have confirmed that ITGB4 could activate multiple signal pathways and promote cell migration in various cancers. However, the regulatory role of integrin β4 (ITGB4) in lung adenocarcinoma (LUAD) is still unclear. Examination of the expression or survival analysis of ITGB4 in cells, pathological samples, and bioinformatics lung adenocarcinoma databases showed ITGB4 was highly expressed in LUAD and significantly associated with poor prognosis. Small interfering RNA and plasmids were performed to investigate the effect of changes in ITGB4 expression on lung adenocarcinoma. Focal adhesion kinase (FAK) inhibitor defactinib was used to further explore the molecular mechanism of ITGB4. The results showed depletion of ITGB4 inhibited migration and activation of FAK signaling pathways in lung adenocarcinoma cells. Moreover, increased ITGB4 expression activated FAK signaling and promoted cell migration, which can be reversed by defactinib. In addition, ITGB4 could interact with FAK in lung adenocarcinoma cells. ITGB4 may promote cell migration of lung adenocarcinoma through FAK signaling pathway and has the potential to be a biomarker for lung adenocarcinoma., Competing Interests: Declarations. Conflict of interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article. Ethical Approval: The study was approved by the Ethics Committee of affiliated Xing Tai People Hospital of Hebei Medical University. All methods in this study were performed in accordance with the relevant guidelines and regulations. The study is reported in accordance with ARRIVE guidelines., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Inhibitors of Bruton's tyrosine kinase (BTK) are among the most widely used therapies for chronic lymphocytic leukemia (CLL) and established a new expectation for efficacy and safety in the treatment of this disease. Currently there are 3 covalent inhibitors of BTK approved for the treatment of CLL: ibrutinib, acalabrutinib, and zanubrutinib. The first-in-class covalent BTK inhibitor is ibrutinib, which as monotherapy has excellent efficacy in the front-line setting with a 7-year progression free survival (PFS) of 59%. Ibrutinib-based therapies have also demonstrated superiority over standard chemoimmunotherapy in the front-line and the relapsed/refractory setting. Acalabrutinib is a second-generation BTK inhibitor that has higher selectivity to BTK. Acalabrutinib has efficacy in both frontline and relapsed CLL and is associated with a decreased incidence of atrial fibrillation and hypertension when compared to ibrutinib. Like acalabrutinib, zanubrutinib was designed to be more selective for BTK than ibrutinib and to maximize BTK inhibition in tissues. Zanubrutinib has demonstrated clinical efficacy in first line and relapsed/refractory setting. These agents are indicated as monotherapy, with dosing until disease progression or intolerable toxicity, and are mainly differentiated by safety profile, although efficacy differences may exist as well. Combination with CD20 monoclonal antibodies and/or BCL2 inhibitors are alternative options for use. Here we will review efficacy and safety considerations with these agents., Competing Interests: Disclosure JAW: Consulting: Abbvie, AstraZeneca, Beigene, Genentech, Janssen, Loxo/Lilly, Merck, Newave, Pharmacyclics. The other authors have stated that they have no conflicts of interest., (Copyright © 2024. Published by Elsevier Inc.)

Background and Purpose: Interferon (IFN) signaling plays an important role in antitumor immune responses. Inhibitors of the DNA damage response, such as ATR inhibitors, can increase IFN signaling upon conventional radiotherapy with X-rays. However, it is not known whether such inhibitors also enhance IFN signaling after irradiation with high linear energy transfer (LET) particles., Materials and Methods: Human glioblastoma U-251 and T98G cells were irradiated with X-rays, protons (LET: 4.8 and 41.9 keV/µm) and carbon ions (LET: 28 and 73 keV/µm), with and without ATR inhibitor (VE-822) or ATM inhibitor (AZD1390). DNA damage signaling and cell cycle distribution were analyzed by immunoblotting and flow cytometry, and radiosensitivity was assessed by clonogenic survival assay. IFN-β secretion was measured by ELISA, and STAT1 activation was examined by immunoblotting., Results: High-LET protons and carbon ions caused stronger activation of the DNA damage response compared to low-LET protons and X-rays at similar radiation doses. G2 checkpoint arrest was abrogated by the ATR inhibitor and prolonged by the ATM inhibitor after all radiation types. The inhibitors increased radiosensitivity, as measured after X- and carbon ion irradiation. ATR inhibition increased IFN signaling following both low-LET and high-LET irradiation. ATM inhibition also increased IFN signaling, but to a lesser extent. Notably, both cell lines secreted significantly more IFN-β when the inhibitors were combined with high-LET compared to low-LET irradiation., Conclusion: These findings indicate that DNA damage response inhibitors can enhance IFN signaling following X-, proton and carbon ion irradiation, with a strong positive dependency on LET., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

Hyperactive c-Met signaling pathway caused by altered MET is a common mechanism underlying gastric cancer and represents an attractive target for the treatment of gastric cancer with MET alterations. However, no c-Met kinase inhibitors are currently approved specifically for the treatment of c-Met-amplified gastric cancer. Recently, bozitinib, a highly selective c-Met kinase inhibitor, has shown remarkable potency in selectively inhibiting MET-altered non-small cell lung cancer and secondary glioblastoma. In this study, we investigate the antitumor activity of bozitinib against MET-amplified gastric cancer and elucidate its molecular mechanism. Bozitinib demonstrates a strong effect on MET-amplified gastric cancer cells by blocking the c-Met signaling pathway, leading to the inhibition of cell proliferation and survival, as well as the induction of G0/G1 phase arrest and apoptosis. Structurally, bozitinib is optimally embedded in the ATP pocket of c-Met and firmly binds via an extensive interaction network. In addition, bozitinib efficiently inhibits c-Met resistance-conferring mutations G1163R and Y1230H, although its potency is significantly decreased against the D1228N and Y1230C mutations. Overall, our study reveals the molecular mechanism of bozitinib against c-Met, highlights its ability to overcome acquired resistance mutations, and provides valuable insights into further design and improvement of selective c-Met inhibitors., Competing Interests: Competing interests: The authors declare no competing interests. Figure 1B is created by Figdraw ( www.figdraw.com )., (© 2025. The Author(s).)