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This publication presents signaling powers of the administrative court. It shows the procedural regulations applicable in this respect, contained in The Act of 30th august 2002 Law on proceedings before administrative courts, as well as views of teaching. It takes into account the decisions taken at the level of voivodship administrative courts as well as the Supreme Administrative.

Aortic stenosis (AS) is the most common valvular heart disease and untreated has a bleak prognosis. The only effective method of treatment is valve replacement, surgical (SAVR), or transcatheter (TAVI).We decided to analyze outcomes and predictors of long-term mortality in patients undergoing TAVI and SAVR.A retrospective analysis of 1229 patients with advanced AS, comprising TAVI (n = 211), SAVR (n = 556), SAVR, and additional procedures (n = 462), operated on from 2014 to 2018, was performed.No significant differences between SAVR and TAVI were found for 24-month mortality in groups of consecutive patients. Postoperative stroke or transient ischemic attack (TIA), chronic obstructive pulmonary disease (COPD), and transfusion of red blood cells (RBCs) were independent predictors of 1-year mortality after SAVR. The above-mentioned factors regarding the increased estimated surgery risk in the EuroSCORE II (4%) were predictors of 2-years mortality after SAVR. Risk factors for 6- and 12-month mortality after TAVI were EuroSCORE II, new onset of atrial fibrillation (NOAF), and the increased RBC distribution width (RDW). Postoperative respiratory failure was an independent risk factor for 6-, 12- and 24-month mortality in both groups of patients.There were no significant differences regarding prognosis after TAVI and SAVR at the 24-month follow-up in the propensity score matching model. Independent predictive factors of late mortality after both procedures were EuroScore II and respiratory failure. Independent predictive factors of late mortality specific for TAVI were NOAF, increased RDW, and for SAVR: TIA, stroke, COPD, and RBC transfusion.

Cancer stemness, which covers the stem cell-like molecular traits of cancer cells, is essential for tumor development, progression and relapse. Both transcriptional and epigenetic aberrations are essentially connected with cancer stemness. The engagement of bromodomain (BrD) proteins-a family of epigenetic factors-has been presented in the pathogenesis of several tumor types, although their association with cancer stemness remains largely unknown. Here, we harnessed TCGA and GEO databases and used several bioinformatic tools (ie, Oncomine, PrognoScan, GEPIA2, TIMER2.0, TISIDB, GSEA, R2 platform) to characterize the association between the BrD family members' expression and cancer stemness in solid tumors. Our results demonstrate that significant upregulation of ATAD2 and SMARCA4, and downregulation of SMARCA2 is consistently associated with enriched cancer stem cell-like phenotype, respectively. Especially, higher-grade tumors that display stem cell-like properties overexpress ATAD2. In contrast to most BrD members, the gene expression profiles of ATAD2

Discovery of two lamps at the Roman fort of Apsaros (Gonio, Georgia) offers further insights concerning adaptation of the pelta motif on Roman lamps. Inquiry into the nature of the ornaments on the base – previously unknown in Colchis – leads to conclusions about the possible influx of goods to the fort located on the outskirts of the Roman Empire.

Aneurysms are uncommon, but potentially life-threatening abnormalities of the pulmonary arteries. Aneurysm of the main pulmonary artery (MPA) defined as MPA diameter over 40 mm was reported in 1 : 14 000 autopsies. The most frequent location is the main pulmonary artery (89% of cases), whereas the maximum described diameter is 106-170 mm. Clinical manifestations are usually nonspecific or asymptomatic. Right heart failure symptoms, pulmonary regurgitation, trachea or bronchi compression or pulmonary emboli caused by enlarged MPA are the most commonly described clinical manifestations. Pulmonary artery aneurysm dissection is an uncommon complication but associated with a high mortality rate. Unfortunately, guidelines regulating the optimal time for the surgical intervention still have not been developed. We present the history of 76-year-old patient suffering from an aneurysm of the pulmonary artery (74 × 61 mm), as well as mitral and aortic valve disease, who was successfully operated on in our hospital.Tętniaki są rzadkimi, ale potencjalnie zagrażającymi życiu patologiami tętnicy płucnej. Częstość ich występowania szacuje się na 1 : 14 000 autopsji. Zgodnie z definicją tętniaka pnia tętnicy płucnej rozpoznaje się, gdy średnica naczynia przekracza 40 mm. Najczęstszą jego lokalizacją jest pień płucny (89% przypadków), podczas gdy największy opisany dotąd tętniak miał średnicę 106–170 mm. Objawy są najczęściej niespecyficzne lub choroba przebiega bezobjawowo. Prawokomorowa niewydolność serca, niedomykalność zastawki płucnej, ucisk na tchawicę, oskrzela lub zator płucny spowodowany przez ucisk powiększającego się tętniaka są najczęstszymi objawami zgłaszanymi przez chorego. Rozwarstwienie tętniaka tętnicy płucnej jest bardzo rzadkim powikłaniem, ale obarczonym wysoką śmiertelnością. Niestety dotychczas nie zostały opracowane żadne wytyczne dotyczące postępowania u pacjentów z tą chorobą. Przedstawiamy przypadek 76-letniego pacjenta z tętniakiem tętnicy płucnej (74 × 61 mm), wadą zastawki aortalnej i mitralnej, który został zoperowany w naszym ośrodku.

The tripartite‐motif (TRIM) family of proteins represents one of the largest classes of putative single protein RING‐finger E3 ubiquitin ligases. The members of this family are characterized by an N‐terminal TRIM motif containing one RING‐finger domain, one or two zinc‐finger domains called B boxes (B1 box and B2 box), and a coiled‐coil region. The TRIM motif can be found in isolation or in combination with a variety of C‐terminal domains, and based on C‐terminus, TRIM proteins are classified into 11 distinct groups. Because of the complex nature of TRIM proteins, they are implicated in a variety of cellular functions and biological processes, including regulation of cell proliferation, cell division and developmental processes, cancer transformation, regulation of cell metabolism, autophagocytosis, modification of chromatin status, regulation of gene transcription, post‐translational modifications, and interactions with pathogens. Here, we demonstrate the specific activities of TRIM family proteins that contribute to the cancer stem cell phenotype. A growing body of evidence demonstrates that several TRIM members guarantee the acquisition of stem cell properties and the ability to sustain stem‐like phenotype by cancer cells using distinct mechanisms. For other members, further work is needed to understand their full contribution to stem cell self‐renewal. Identification of TRIM proteins that possess the potential to serve as therapeutic targets may result in the development of new therapeutic strategies. Finally, these strategies may result in the disruption of the machinery of stemness acquisition, which may prevent tumor growth, progression, and overcome the resistance to anticancer therapies., The tripartite‐motif (TRIM) family of proteins is involved in a variety of cellular functions and biological processes that facilitate acquisition or maintenance of stem cell self‐renewal.

Methyl transfer reactions mediated by cobalamins (Cbls) have been considered as one of the most important biologically relevant molecular transformations for many enzymatic reactions catalyzed by Cbl-dependent enzymes. The exact mechanism of methyl transfer reactions involving Cbls is still poorly understood. To investigate the mechanistic details of Cbl mediated methylations by alkyl halides, density functional theory (DFT) along with the polarizable continuum model (PCM/water) for solvation has been applied. Two different mechanisms have been examined, namely S N 2 and radical-based electron transfer (ET) to elucidate the methyl transfer reaction. The calculations have suggested that the methyl transfer from methyl halides proceeds through S N 2 nucleophilic displacement. However, with more bulky alkyl substrate, namely isopropyl and tert-butyl halides the reaction followed the ET-based radical pathway which is associated with an ET from diradical form of cob(I)alamin to alkyl halides. Our proposed mechanism for alkyl transfer reaction corroborates with the experimental findings, which reported a mechanistic switch from a two-electron (S N 2-type) to a one-electron mechanism for sterically demanding alkyl halides. The present theoretical contribution provides more in-depth insight into the methyl transfer reaction catalyzed by corrinoid-dependent methyltransferases.

Cobalamins, cobalt glyoximate complexes and nickel complexes with Triphos (bis(diphenylphosphinoethyl)phenylphosphine) and PPh2CH2CH2SEt ligands were studied with the DFT/BP86 method in connection with methyl transfer reactions. Geometries, methyl binding energies and redox potentials were determined for the studied complexes. Three- and four-coordinate structures were considered for nickel complex with PPh2CH2CH2SEt ligand, whereas four- and five-coordinate for its methyl derivative. On the basis of calculations, the possible mechanism of methyl transfer reaction between cobalt and nickel complexes was considered.

The biologically active forms of vitamin B12, methylcobalamin (MeCbl) and adenosylcobalamin (AdoCbl), are important cofactors in a variety of enzymatic processes. In addition to their roles as cofactors, these B12 derivatives have unique photolytic properties based on the light-sensitivity of the organometallic Co C bond. Their photolysis is mediated by low-lying excited states, where photodissociation of the Co C bond leads to formation of singlet-born alkyl/cob(II)alamin radical pairs (RPs). Also, the geometric and electronic characteristics of cobalamins (Cbls) are different based on whether the 5,6-dimethylbenzimidazole base (DBI) is bound as the lower axial ligand (base-on) or replaced by water (base-off) in strongly acidic conditions. The focus of this review is to summarize the current understanding of these photolytic properties from a theoretical perspective. Potential energy surfaces (PESs) associated with low-lying excited states, constructed as functions of both axial bond lengths, provide the most reliable tool for understanding the photodissociation mechanisms. The primary computational method for calculating ground state properties is density functional theory (DFT), while time-dependent DFT (TD-DFT) is used for electronically excited states. Based on such constructed PESs, energy pathways connecting metal-to-ligand charge transfer (MLCT) and ligand field (LF) electronic states, can be associated with the light induced photo-homolysis of the Co C bond that is observed experimentally. Likewise, the crossing of the S1/S0 surfaces can be used to describe internal conversion (IC) to the ground state. Particular emphasis will be placed on the differences observed in the photodissociation mechanisms and the photolytic properties of the base-on versus base-off B12 cofactors. The possibility of intersystem crossing (ISC) and the formation of triplet RP is also presented based on semi-classical Landau-Zener theory.

Simple Summary Stem cell-associated molecular features of solid tumors, collectively known as cancer stemness, are of great importance in the development, progression, and reoccurrence of cancer. Transcriptional and epigenetic dysregulation is significantly associated with cancer stemness. Here, we investigated the association between the Transcriptional Intermediary Factor 1 (TIF1) family members and cancer stemness in solid tumors. We aimed to evaluate the potential value of TIF1 members in predicting a stem-like cancer phenotype. Our results indicate that only TIF1β (also known as Tripartite Motif protein 28, TRIM28) high expression is consequently associated with a “stemness high” phenotype, regardless of the tumor type, resulting in a worse prognosis for cancer patients. The oncogenic signature of TRIM28HIGH tumors significantly reflects the enrichment of “stemness high” cancers with targets for c-Myc (MYC Proto-Oncogene). TRIM28-associated gene expression profiles are also robustly enriched with stemness markers. Our results demonstrate that the association between high TRIM28 expression and an enriched cancer stem cell-like phenotype is a common phenomenon across solid tumors. Abstract Cancer progression entails a gradual loss of a differentiated phenotype in parallel with the acquisition of stem cell-like features. Cancer de-differentiation and the acquisition of stemness features are mediated by the transcriptional and epigenetic dysregulation of cancer cells. Here, using publicly available data from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases and harnessing several bioinformatic tools, we characterized the association between Transcriptional Intermediary Factor 1 (TIF1) family members and cancer stemness in 27 distinct types of solid tumors. We aimed to define the prognostic value for TIF1 members in predicting a stem cell-like cancer phenotype and patient outcome. Our results demonstrate that high expression of only one member of the TIF1 family, namely TIF1β (also known as Tripartite Motif protein 28, TRIM28) is consequently associated with enriched cancer stemness across the tested solid tumor types, resulting in a worse prognosis for cancer patients. TRIM28 is highly expressed in higher grade tumors that exhibit stem cell-like traits. In contrast to other TIF1 members, only TIF1β/TRIM28-associated gene expression profiles were robustly enriched with stemness markers regardless of the tumor type. Our work demonstrates that TIF1 family members exhibit distinct expression patterns in stem cell-like tumors, despite their structural and functional similarity. Among other TIF1 members, only TRIM28 might serve as a marker of cancer stemness features.

International audience; Mechanoresponsive luminescence (MRL) materials promise smart devices for sensing, optoelectronics and security. We present here the first report on the MRL activity of two ReI complexes, opening up new opportunities for applications in these fields. Both complexes exhibit marked solid‐state luminescence enhancement (SLE). Furthermore, the pristine microcrystalline powders emit in the yellow‐green region, and grinding led to an amorphous phase with concomitant emission redshift and shrinking of the photoluminescence (PL) quantum yields and lifetimes. Quantum chemical calculations revealed the existence of two low‐lying triplet excited states with very similar energy levels, that is, 3IL and 3MLCT, having, respectively, almost pure intraligand (IL) and metal‐to‐ligand charge‐transfer (MLCT) character. Transition between these states could be promoted by rotation around the pyridyltriazole−phenylbenzoxazole bond. In the microcrystals, in which rotations are hindered, the 3IL state induces the prominent PL emission at short wavelengths. Upon grinding, rotation is facilitated and the transition to the 3MLCT state results in a larger proportion of long‐wavelength PL. FTIR and variable‐temperature PL spectroscopy showed that the opening of the vibrational modes favours non‐radiative deactivation of the triplet states in the amorphous phase. In solution, PL only arises from the 3MLCT state. The same mechanism accounts for the spectroscopic differences observed when passing from crystals to amorphous powders, and then to solutions, thereby clarifying the link between SLE and MRL for these complexes.

TRIM28 emerged as a guard of the intrinsic &ldquo, state of cell differentiation&rdquo, facilitating self-renewal of pluripotent stem cells. Recent reports imply TRIM28 engagement in cancer stem cell (CSC) maintenance, although the exact mechanism remains unresolved. TRIM28 high expression is associated with worse melanoma patient outcomes. Here, we investigated the association between TRIM28 level and melanoma stemness, and aligned it with the antitumor immune response to find the mechanism of &ldquo, stemness high/immune low&rdquo, melanoma phenotype acquisition. Based on the SKCM TCGA data, the TRIM28 expression profile, clinicopathological features, expression of correlated genes, and the level of stemness and immune scores were analyzed in patient samples. The biological function for differentially expressed genes was annotated with GSEA. Results were validated with additional datasets from R2: Genomics Analysis and Visualization Platform and in vitro with a panel of seven melanoma cell lines. All statistical analyses were accomplished using GraphPad Prism 8. TRIM28HIGH-expressing melanoma patients are characterized by worse outcomes and significantly different gene expression profiles than the TRIM28NORM cohort. TRIM28 high level related to higher melanoma stemness as measured with several distinct scores and TRIM28HIGH-expressing melanoma cell lines possess the greater potential of melanosphere formation. Moreover, TRIM28HIGH melanoma tumors were significantly depleted with infiltrating immune cells, especially cytotoxic T cells, helper T cells, and B cells. Furthermore, TRIM28 emerged as a good predictor of &ldquo, melanoma phenotype. Our data indicate that TRIM28 might facilitate this phenotype by direct repression of interferon signaling. TRIM28 emerged as a direct link between stem cell-like phenotype and attenuated antitumor immune response in melanoma, although further studies are needed to evaluate the direct mechanism of TRIM28-mediated stem-like phenotype acquisition.

DFT calculations were performed for the A-cluster from the enzyme Acetyl-CoA synthase (ACS). The acid constants (pKa), reduction potentials, and pH-dependent reduction potential for the A-cluster with different oxidation states and ligands were calculated. Good agreement of the reduction potentials, dependent on pH in the experiment, was obtained. On the basis of the calculations, a mechanism for the methylation reaction involving two–electron reduction and protonation on the proximal nickel atom of the reduced A-cluster is proposed.

Methylcobalamin (MeCbl)-dependent enzyme methionine synthase (MetH), plays a critical role in the catalysis of methyl group transfer from methyltetrahydrofolate (CH3-H4folate) to homocysteine. It often performs a side reaction to generate cob(II)alamin through photolysis of the organometallic CoC σ bond. A hybrid QM/MM method has been applied to explore the photochemistry of MeCbl-bound MetH. The photolytic properties of MeCbl inside MetH are mediated by its manifold of low-lying excited states. The corresponding potential energy surfaces (PESs) of the electronically excited S1 state has been constructed as a function of axial bond lengths to elucidate the mechanism of photo-induced activation of CoC bond inside the enzyme. The analysis of the S1 PES has revealed that the two different electronic states of the S1 PES, namely metal-to-ligand charge transfer (MLCT) and the ligand field (LF), are relevant to the photodissociation of the CoC bond. There are two possible pathways identified, Path A and Path B, that connect the MLCT to LF state that represent possible photodissociation mechanisms. In the case of MetH, one possible photodissociation pathway (Path B) was identified based on the energetics of the MLCT and LF states. The energetically accessible Path B involves the initial detachment of the Co-NIm bond followed by a subsequent displacement of the CoC bond prior to the formation of cob(II)alamin / CH3 radical pair (RP). The photochemical data of base-on MeCbl in solution was compared with the computed result of MeCbl-bound MetH to understand the effect of the enzymatic environment on the photolytic properties of MeCbl.

Ultrafast time-resolved spectroscopy was used to study the photochemistry of hydroxocobalamin (HOCbl) and aquocobalamin (H2OCbl+) in solution. Spectroscopic measurements and TD-DFT simulations provide a consistent picture of the spectroscopy and photochemistry. Excitation of H2OCbl+ results in formation of an excited state followed by rapid internal conversion to the ground state (0.35 ± 0.15 ps) through an S1/S0 seam at a slightly elongated Co–O bond length and a significantly elongated Co–NIm bond length. In contrast, the initial elongation of the axial bonds in HOCbl is followed by contraction to an excited state minimum with bonds slightly shorter than those in the ground state. Internal conversion to the ground state follows on a picosecond time scale (5.3 ± 0.4 ps). For both compounds, photodissociation forming cob(II)alamin and hydroxyl radicals (∼1.5% yield) requires excitation to highly excited states. Dissociation is mediated by competition between internal conversion to the S1 surface and promp...

Antivitamins B12 represent an important class of vitamin B12 analogues that have gained recent interest in several research areas. In particular, 4-ethylphenylcobalamin (EtPhCbl) and phenylethynylcobalamin (PhEtyCbl) exemplify two such antivitamins B12 which have been characterized structurally and chemically. From a spectroscopic point of view, EtPhCbl is photolabile with a very low quantum yield of photoproducts, while PhEtyCbl is incredibly photostable. Herein, DFT and TD-DFT computations are provided to explore the photolytic properties of these compounds to shed light on the electronic properties that are indicative of these differences. Potential energy surfaces (PESs) were constructed to investigate the mechanisms of photodissociation leading to radical pair (RP) formation and the mechanisms of deactivation to the ground state. The S1 PESs for each antimetabolite contain two energy minima, one being the metal-to-ligand charge transfer (MLCT) and another the ligand-field (LF) state. There are two po...

Coenzyme B12 (adenosylcobalamin = AdoCbl)-dependent enzymes catalyze complex molecular transformations by employing radical chemistry. The initial step in the native catalytic cycle, upon substrate binding, involves homolytic cleavage of the Co–C bond of AdoCbl to form the Co(II)/Ado• radical pair (RP). Formation of Co(II)/Ado• is subsequently coupled with H atom abstraction from the substrate. Interestingly, these same RPs can be generated upon light absorption without presence of a substrate. Herein, the photochemistry associated with the mechanism of Co–C bond photocleavage inside the AdoCbl-dependent ethanolamine ammonia-lyase (EAL) was investigated using a combined time-dependent density functional theory and molecular mechanics (TD-DFT/MM) approach. Excited state potential energy surfaces (PESs), constructed as a function of axial bond lengths, were used to understand the photocleavage of the Co–C bond and to elucidate the mechanism of photodissociation for AdoCbl inside the enzyme. The S1 PES is ch...

Absorption and emission properties of six dithiinodiquinolines 1–6 (composed of 2,3- and/or 3,4-quinolinediyl units fused with 1,4-dithiin moiety) in methanol and cyclohexane solutions were studied. Differences in fluorescence properties of the compounds 1–6 are observed, depending on the type of condensed pattern of quinoline units. Emision bands of 1 and 2 occur at wavelengths over 500 nm are shifted systematically towards shorter waves when coming from 1,2 to 3,4 and 5,6. The compounds 1–6 posses long fluorescence lifetimes of several microseconds, which can be explained by an effective electronic conjugation in the excited state. In particular, the emission spectra of 3–6 in cyclohexane show two peaks characteristic for dual luminescence. The absorption and emission properties of compounds 1–6 were discussed in terms of DFT and TDDFT calculations. The geometry optimization of the excited nstates results in a planar structure as compared to a folded structure in the ground state of ditthiinodiquinolines 1–6.

Various products coded by genes recognized in microbiota are involved in many biochemical pathways in thehuman body. Bacteria composition in the gastrointestinal tract may be an important aspect of selected diseases’ pathogenesis, including irritable bowel syndrome (IBS). Traditional research methods based on classical microbiology, using selective media for bacterial growth, have proven to be ineffective. The use of genetic methods allows the identification of unidentified microbiota, including anaerobes. Roseburia hominis is a flagellated gut anaerobic commensal bacterium, producing short-fatty acids. The knowledge about the microbial components of the intestinal ecosystem is still very limited, including Roseburia hominis. This study aimed to identify Roseburia hominis in the faeces samples obtained from IBS patients and healthy individuals, using PCR techniques. The differences between studied groups were observed, and it was concluded that R. hominis may play a role in IBS etiology.

We developed a therapeutic, gene-modified, allogeneic melanoma vaccine (AGI-101H), which, upon genetic modification, acquired melanoma stem cell-like phenotype. Since its initial clinical trial in 1997, the vaccine has resulted in the long-term survival of a substantial fraction of immunized patients (up to 20 years). Here, we investigated the potential molecular mechanisms underlying the long-lasting effect of AGI-101H using transcriptome profiling of patients’ peripheral T lymphocytes. Magnetically-separated T lymphocytes from AGI-101H-immunized long-term survivors, untreated melanoma patients, and healthy controls were subjected to transcriptome profiling using the microarray analyses. Data were analyzed with a multitude of bioinformatics tools (WebGestalt, DAVID, GSEA) and the results were validated with RT-qPCR. We found substantial differences in the transcriptomes of healthy controls and melanoma patients (both untreated and AGI-101H-vaccinated). AGI-101H immunization induced similar profiles of peripheral T cells as tumor residing in untreated patients. This suggests that whole stem cells immunization mobilizes analogous peripheral T cells to the natural adaptive anti-melanoma response. Moreover, AGI-101H treatment activated the TNF-α and TGF-β signaling pathways and dampened IL2-STAT5 signaling in T cells, which finally resulted in the significant up-regulation of a BCL6 transcriptional repressor, a known amplifier of the proliferative capacity of central memory T cells and mediator of a progenitor fate in antigen-specific T cells. In the present study, high levels of BCL6 transcripts negatively correlated with the expression of several exhaustion markers (CTLA4, KLRG1, PTGER2, IKZF2, TIGIT). Therefore, Bcl6 seems to promote a progenitor fate for cancer-experienced T cells from AGI-101H-vaccinated patients by repressing the exhaustion markers.

In this work, the geometry, acid-base properties, pKa, electronic spectra, and fluorescence spectrum of anticonvulsant drug lamotrigine (LTG) are investigated with the DFT/TD-DFT method and PCM solvent model. Calculated transition with the B3LYP functional at 295 nm corresponds to experimental absorption transition at 306 nm in water. In acidic conditions, the computed maximum transition occurs at 249 nm, comparing with experimental one at 270 nm. The dependence of calculated transitions on density functional used and different solvents in PCM model was studied. The computed transition of fluorescence is at 435 nm, while experimental occurs at 370 nm. Maps of electrostatic potential (MEPs) for S0 and S1 reveal that the ground state of LTG is more polar than the first excited state. Structurally, in the excited state of LTG, the triazine ring is noticeably distorted. Graphical Abstract Molecular elecrostatic potentials for S0 and S1 states of the lamotrigine molecule.

Biologically active forms of cobalamins are crucial cofactors in biochemical reactions and these metabolites can be inhibited by their structurally similar analogues known as antivitamins B12. Phenylethynylcobalamin (PhEtyCbl) or 4-ethylphenylcobalamin (EtPhCbl) exemplify recently synthesized and structurally characterized antivitamins B12. Herein, DFT and TD-DFT studies of EtPhCbl are provided to explore its photochemical behavior, which may lead to design of arylcobalamins that can be used as therapeutic agents in light activated drug applications. To understand the photolability of EtPhCbl, a potential energy surface (PES) for the photodissociation of the Co–C bond was constructed. The S1 PES contains two energy minima, one being metal-to-ligand charge transfer (MLCT) and another the ligand-field (LF) state. There are two possible pathways for photodissociation: the first pathway (path A) involves initially lengthening the Co–C bond from the MLCT minimum and then elongation of Co–NIm while the second pathway (path B) involves the lengthening of the Co–NIm bond through the MLCT region followed by the lengthening of the Co–C bond through the LF region. It is shown that photodissociation involving path A is not energetically favorable whereas preferable photodissociation of the Co–C bond involves path B.

Normal pericardium consists of an outer sac called fibrous pericardium and an inner one called serous pericardium. The two layers of serous pericardium: visceral and parietal are separated by the pericardial cavity, which contains 20 to 60 mL of the plasma ultrafiltrate. The pericardium acts as mechanical protection for the heart and big vessels, and a lubrication to reduce friction between the heart and the surrounding structures. A very important role in all aspects of pericardial functions is played by mesothelial cells. The mesothelial cells form a monolayer lining the serosal cavity and play an important role in antigen presentation, inflammation and tissue repair, coagulation and fibrinolysis. The two major types of mesothelial cells, flat or cuboid, differ substantially in their ultrastructure and, probably, functions. The latter display abundant microvilli, RER, Golgi dense bodies, membrane-bound vesicles and intracellular vacuoles containing electron-dense material described as dense bodies. The normal structure and functions of the pericardium determine correct healing after its injury as a result of surgery or microbial infection. The unfavorable resolution of acute or chronic pericarditis leads to the formation of adhesions between pericardial leaflets which may lead to serious complications.

In this article, we highlight the benefits coming from the application of amorphous protic ionic systems as active pharmaceutical ingredients (APIs). Using the case of the sumatriptan (STR) drug, we show that the conversion of nonionic API to partially ionized amorphous protic succinate salt (STR SUCC) brings a substantial improvement in apparent solubility. Since in general the disordered systems reveal a tendency to self-arrangement during storage, the dominant part of this article is dedicated to the physical stability issue of sumatriptan and its ionic counterpart. To recognize the crystallization tendency of the studied systems, the calorimetric measurements were performed. Additionally, the role of ion dynamics in spontaneous nucleation of amorphous sumatriptan succinate is discussed. The differential scanning calorimetry analysis of ionic and nonionic sumatriptan reveals many similarities in thermal properties of these APIs as well as distinct differences in their resistance against crystallization in the supercooled liquid state. To determine the long-term physical stability of STR SUCC at room temperature conditions, the time scale of structural relaxation below their glass transition temperatures is estimated. We show that in contrast to nonionic materials, τα predictions of STR SUCC are much more complex and require aging experiments.

The DFT and TD-DFT calculations were performed for palladium(II)1,2,2,7,12,12-heptamethylo-15-cyanocorrin complex ([Pd(II)HM-CN-corr]+). Experimentally [Pd(II)HM-CN-corr]+ exhibits a weak fluorescence and strong phosphorescence. For the [Pd(II)HM-CN-corr]+ complex the electronic spectrum was calculated using the BP86 and B3LYP functionals. The results shows that BP86 gives electronic transition energies in good agreement with the experiment, while B3LYP overestimates the calculated transition energies, which can be related to the order and energy of molecular orbitals. Therefore, the BP86 functional was used in further calculations. The presence of the solvent was taken into account by the use of the COSMO model. The spin-orbit (SO) states were calculated along the PEC determined by N-Pd-N bending angle active coordinate in the S1 using the ZORA method. The rate constants of fluorescence, phosphorescence and intersystem crossing processes were determined. Based on calculations the photophysical processes occurring in [Pd(II)HM-CN-corr]+ can be explained. After light absorption there is excitation to the S1 or S2 states and then the internal conversion to S1 state from S2. Comparison of the calculated rate constants of fluorescence (3.3·107 s-1) and ISC to the close lying T2 state (8.5·1010 s-1) in the S1 minimum shows that the ISC is more probable. This is an explanation why fluorescence in [Pd(II)HM-CN-corr]+ is weak. The vibrationally resolved fluorescence and phosphorescence band shapes were determined using the Franck-Condon approximation. The obtained band profiles agree qualitatively with the experimental ones. The most important molecular vibrations contributing to vibrational bands were determined. The calculated rate constants values and the obtained picture of photophysical processes agree qualitatively with the experimental data.

Ultrafast time-resolved spectroscopy was used to study the photochemistry of hydroxocobalamin (HOCbl) and aquocobalamin (H

Antivitamins B

This Perspective Article highlights recent theoretical developments, and summarizes the current understanding of the photolytic properties of cobalamins from a computational point of view. The primary focus is on two alkyl cobalamins, methylcobalamin (MeCbl) and adenosylcobalamin (AdoCbl), as well as two non-alkyl cobalamins, cyanocobalamin (CNCbl) and hydroxocobalamin (HOCbl). Photolysis of alkyl cobalamins involves low-lying singlet excited states where photodissociation of the Co-C bond leads to formation of singlet-born alkyl/cob(ii)alamin radical pairs (RPs). Potential energy surfaces (PESs) associated with cobalamin low-lying excited states as functions of both axial bonds, provide the most reliable tool for initial analysis of their photochemical and photophysical properties. Due to the complexity, and size limitations associated with the cobalamins, the primary method for calculating ground state properties is density functional theory (DFT), while time-dependent DFT (TD-DFT) is used for electronically excited states. For alkyl cobalamins, energy pathways on the lowest singlet surface, connecting metal-to-ligand charge transfer (MLCT) and ligand field (LF) minima, can be associated with photo-homolysis of the Co-C bond observed experimentally. Additionally, energy pathways between minima and seams associated with crossing of S1/S0 surfaces, are the most efficient for internal conversion (IC) to the ground state. Depending on the specific cobalamin, such IC may involve simultaneous elongation of both axial bonds (CNCbl), or detachment of axial base followed by corrin ring distortion (MeCbl). The possibility of intersystem crossing, and the formation of triplet RPs is also discussed based on Landau-Zener theory.

A mechanism of Co-C bond photodissociation in the base-on form of adenosylcobalamin (AdoCbl) was investigated by time-dependent density functional theory (TD-DFT). The key mechanistic step involves singlet radical pair (RP) generation from the first electronically excited state (S1). To connect TD-DFT calculations with ultra-fast excited state dynamics, the potential energy surface (PES) of the S1 state was constructed using Co-C and Co-NIm axial coordinates. The S1 PES can be characterized by two minima separated by a seam resulting from the crossing of two surfaces, of metal-to-ligand charge transfer (MLCT) character near the minimum, and a shallow ligand field (LF) surface at elongated axial bond distances. Only one possible pathway for photolysis (path A) was identified based on energetic grounds. This pathway is characterized by the first elongation of the Co-C bond, followed by photolysis from an LF state where the axial base is partially detached. A new perspective on the photolysis of AdoCbl is then gained by connecting TD-DFT results with available experimental observations.

Four novel cyclometalated iridium(III) complexes: [Ir(q-bt-Ph) 2 (phen)]PF 6 , [Ir(q-bt-Ph) 2 (acac)], [Ir(q-bt-Me) 2 (bpy)]PF 6 and [Ir(q-bt-Me) 2 (acac)] (where q-bt-Ph, q-bt-Me correspond to 2-(2,2’-bithien-5-yl)-4-phenylquinoline and 2-(2,2’-bithien-5-yl)-4-methylquinoline), are reported. The complexes were characterized by NMR, FTIR and HRMS. The optical, electrochemical properties and thermal stability of novel iridium(III) complexes were thoroughly investigated. The complexes emit a light in the narrow range of 693–707 nm. The optical study showed that replacement of fragment in the main quinoline ligand did not affect wavelength of the emitted light. On the other hand, the modification of the ancillary ligand and substituent in the quinoline ring caused the increase of the photoluminescence quantum yields. Electrochemical experiments demonstrate that the oxidation process for complexes [Ir(q-bt-Ph) 2 (phen)]PF 6 and [Ir(q-bt-Ph) 2 (acac)] was reversible (or quasi-reversible) and well detectable whereas for complexes with quinoline substituted by methyl group was irreversible, even at low temperature (−70 °C). The electrochemical and photophysical studies have been well confirmed by density functional theory (DFT) calculations. In addition, bulk heterojunction polymer solar cells based on complexes [Ir(q-bt-Ph) 2 (phen)]PF 6 and [Ir(q-bt-Ph) 2 (acac)] were fabricated. Only the solar cell incorporating [Ir(q-bt-Ph) 2 (acac)] exhibited a photovoltaic effect. The architecture of the cell was ITO/PEDOT:PSS/P3HT:PCBM:[Ir(q-bt-Ph) 2 (acac)]/Al. A power conversion efficiency of 0.25% was measured under 1 sun illumination using an AM 1.5G filter to simulate the solar spectrum.

The paper attempts to present some problems of work organization at the Acquisition and Collection Development Department of the MCS University Main Library. This article discusses the changes effected in the Department organizational structure over the last 20 years. The acquisition strategy has been discussed together with the forms of cooperation with readers in relation to the selection of new titles.

A mechanism of Co-C bond photolysis in the base-off form of the methylcobalamin cofactor (MeCbl) and the influence of its axial base on Co-C bond photodissociation has been investigated by time-dependent density functional theory (TD-DFT). At low pH, the MeCbl cofactor adopts the base-off form in which the axial nitrogenous ligand is replaced by a water molecule. Ultrafast excited-state dynamics and photolysis studies have revealed that a new channel for rapid nonradiative decay in base-off MeCbl is opened, which competes with bond dissociation. To explain these experimental findings, the corresponding potential energy surface of the S1 state was constructed as a function of Co-C and Co-O bond distances, and the manifold of low-lying triplets was plotted as a function of Co-C bond length. In contrast to the base-on form of MeCbl in which two possible photodissociation pathways were identified on the basis of whether the Co-C bond (path A) or axial Co-N bond (path B) elongates first, only path B is active in base-off MeCbl. Specifically, path A is inactive because the energy barrier associated with direct dissociation of the methyl ligand is higher than the barrier of intersection between two different electronic states: a metal-to-ligand charge transfer state (MLCT), and a ligand field state (LF) along the Co-O coordinate of the S1 PES. Path B initially involves displacement of the water molecule, followed by the formation of an LF-type intermediate, which possesses a very shallow energy minimum with respect to the Co-C coordinate. This LF-type intermediate on path B may result in either S1/S0 internal conversion or singlet radical pair generation. In addition, intersystem crossing (ISC) resulting in generation of a triplet radical pair is also feasible.

Biologically active forms of cobalamins are crucial cofactors in biochemical reactions and these metabolites can be inhibited by their structurally similar analogues known as antivitamins B

At present, we are witnessing a renewed interest in the properties of densified glasses prepared by isobaric cooling of a liquid at elevated pressure. As high-pressure densification emerges as a promising approach in the development of glasses with customized features, understanding and controlling their unique properties represent a contemporary scientific and technological goal. The results presented herein indicate that the applied high-pressure preparation route leads to a glassy state with higher density (∼1%) and a reduced free volume of about 7%. We show that these subtle structural changes remarkably influence the dielectric response and spectral features of β-relaxation in etoricoxib glass. Our study, combining dynamical and structural techniques, reveal that β-relaxation in etoricoxib is extremely sensitive to the variations in molecular packing and can be used to probe the changes in glass density. Such connection is technologically relevant and may advance further progress in the field.

A mechanism of Co-C bond photodissociation in the base-on form of the methylcobalamin cofactor (MeCbl) has been investigated employing time-dependent density functional theory (TD-DFT), in which the key step involves singlet radical pair generation from the first electronically excited state (S1). The corresponding potential energy surface of the S1 state was constructed as a function of Co-C and Co-Naxial bond distances, and two possible photodissociation pathways were identified on the basis of energetic grounds. These pathways are distinguished by whether the Co-C bond (path A) or Co-Naxial bond (path B) elongates first. Although the final intermediate of both pathways is the same (namely a ligand field (LF) state responsible for Co-C dissociation), the reaction coordinates associated with paths A and B are different. The photolysis of MeCbl is wavelength-dependent, and present TD-DFT analysis indicates that excitation in the visible α/β band (520 nm) can be associated with path A, whereas excitation in the near-UV region (400 nm) is associated with path B. The possibility of intersystem crossing, and internal conversion to the ground state along path B are also discussed. The mechanism proposed in this study reconciles existing experimental data with previous theoretical calculations addressing the possible involvement of a repulsive triplet state.