Multifunctional Photoelectroactive Materials for Optoelectronic Applications Based on Thieno[3,4-b]pyrazines and Thieno[1,2,5]thiadiazoles.

In this study, we introduce a novel family of symmetrical thiophene-based small molecules with a Donor-Acceptor-Donor structure. These compounds feature three different acceptor units: benzo[c][1,2,5]thiadiazole (Bz), thieno[3,4-b]pyrazine (Pz), and thieno[1,2,5]thiadiazole (Tz), coupled with electron donor units based on a carbazole-thiophene derivative. Using Density Functional Theory (DFT), we investigate how the molecular geometry and strength of the central acceptor unit impact the redox and spectroscopic properties. Notably, the incorporation of Pz and Tz moieties induces a significant redshift in the absorption and emission spectra, which extend into the near-infrared (NIR) region, simultaneously reducing their energy gaps (~1.4-1.6 eV). This shift is attributed to the increased coplanarity of the oligomeric inner core, both in the ground (S0 ) and excited (S1 ) states, due to the enhanced quinoidal character as supported by bond-length alternation (BLA) analysis. These structural changes promote better π-electron delocalization and facilitate photoinduced charge transfer processes in optoelectronic devices. Notably, we show that Pz- and Tz-containing molecules exhibit NIR electrochromic behavior and present ambivalent character in bulk heterojunction (BHJ) solar cells. Finally, theoretical calculations suggest that these molecules could serve as effective two-photon absorption (2PA) probes, further expanding their potential in optoelectronic applications.

Matrix metalloproteinase 9 modulates collagen matrices and wound repair.

Acute and chronic injuries are characterized by leukocyte infiltration into tissues. Although matrix metalloproteinase 9 (Mmp9) has been implicated in both conditions, its role in wound repair remains unclear. We previously reported a zebrafish chronic inflammation mutant caused by an insertion in the hepatocyte growth factor activator inhibitor gene 1 (hai1; also known as spint1) that is characterized by epithelial extrusions and neutrophil infiltration into the fin. Here, we performed a microarray analysis and found increased inflammatory gene expression in the mutant larvae, including a marked increase in mmp9 expression. Depletion of mmp9 partially rescued the chronic inflammation and epithelial phenotypes, in addition to restoring collagen fiber organization, as detected by second-harmonic generation imaging. Additionally, we found that acute wounding induces epithelial cell mmp9 expression and is associated with a thickening of collagen fibers. Interestingly, depletion of mmp9 impaired this collagen fiber reorganization. Moreover, mmp9 depletion impaired tissue regeneration after tail transection, implicating Mmp9 in acute wound repair. Thus, Mmp9 regulates both acute and chronic tissue damage and plays an essential role in collagen reorganization during wound repair.

Photophysical Properties of Phenacylphenantridine Difluoroboranyls: Effect of Substituent and Double Benzannulation.

In this study we present a new series of phenantridine-based substituted difluoroboranyls. The effects of substitution and double benzannulation on their photophysical properties were examined with experimental techniques and compared with the results obtained for previously reported quinoline and isoquinoline derivatives. The experimental characterizations are supported by state-of-the-art quantum-chemical calculations. In particular, the theoretical calculations were performed to gain insights into the complex nature of the relevant excited-states. These calculations reveal that both the nature of the substituent and its position on the phenyl ring significantly impact the magnitude of the electronic charge transferred upon excitation. Additionally, vibrationally resolved spectra were determined allowing for the analysis of the key vibrations playing a role in the band shapes.

Tuning the Electronic Properties of the Dative N-B Bond with Associated O-B Interaction: Electron Localizability Indicator from X-Ray Wavefunction Refinement.

Despite the immense growth in interest in difluoroborate dyes, the nature of the interactions of the boron atom within the N-BF2 -O kernel is not yet fully understood. Herein, a set of real-space bonding indicators is used to quantify the electronic characteristics of the dative N-B bond in difluoroborate derivatives. The atoms-in-molecules (AIM) partitioning scheme is complemented by the electron localizability indicator (ELI-D) approach, and both were applied to experimental and theoretical electron-density distributions (X-ray constrained wavefunction fitting vs. DFT calculations). Additionally, Fermi orbital analysis was introduced for small DFT models to support and extend the findings for structures that contain BF2 .

The Influence of the π-Conjugated Spacer on Photophysical Properties of Difluoroboranyls Derived from Amides Carrying a Donor Group.

A series of difluoroboranyls derived from amides carrying a variable π-conjugated spacer between the electron-donating (D) and electron-accepting (A) groups was synthesized and characterized with (1)H, (11)B, (13)C, (15)N, and (19)F NMR, electronic absorption, fluorescence spectroscopies, and first-principle calculations. The D-to-A distance in the series varied from 1.5 to 4.5 Å, causing bathochromic shifts of both the absorption and fluorescence maxima by more than 120 and 213 nm, respectively. These trends are rationalized by quantum-mechanical calculations that allow for quantification of the charge-transfer distance. Theoretical calculations were also performed to determine the vibronic couplings and thus to reproduce the experimental band shapes.

Synthesis and Photophysical Properties of Novel Donor-Acceptor N-(Pyridin-2-yl)-Substituted Benzo(thio)amides and Their Difluoroboranyl Derivatives.

The unprecedented N-pyridin-2-yl substituted benzo(thio)amides were prepared and subsequently converted into the cyclic difluoroboranyl (BF2) derivatives. Mass spectrometry, multinuclear NMR, IR, and elemental analysis confirmed the structure of these compounds. UV/vis and fluorescence spectroscopy as well as first-principle calculations were used to study their properties. For the first time, the influence of both the O/S replacement and presence/absence of the BF2 moiety on the photophysical properties of compounds exhibiting charge transfer properties were examined experimentally and theoretically. We show that the sulfur-containing compound has a much smaller emission quantum yield than its oxygen counterpart. The fluorescence quantum yield is much higher upon formation of the difluoroboranyl complex.

Association between rs9930506 polymorphism of the fat mass & obesity-associated (FTO) gene & onset of obesity in Polish adults.

BACKGROUND & OBJECTIVES: The fat mass and obesity-associated (FTO) gene is known to be associated with obesity. However, no data are available on the relation between FTO rs9930506 polymorphism and obesity in Polish population. The aim of this study was to evaluate an association between rs9930506 variants of the FTO gene and obesity in Polish adults. METHODS: The study group consisted of 442 adults, aged 33.9 ±12.7 yr, with mean BMI 27.2 ± 5.4 kg/m2. The following variables were determined for each subject: fasting blood glucose, total cholesterol, LDL-cholesterol, HDL-cholesterol, and triglycerides. Real-time PCR was used to detect the A/G alleles of the rs9939506 polymorphism in the FTO gene. An association between the rs9930506 polymorphism and obesity was determined using codominant, dominant, and recessive models. The odds ratio (OR) was calculated to determine the risk of obesity associated with this polymorphism. RESULTS: It was observed that the presence of FTO rs9939506 G allele was associated with increased risk for obesity and this association was found significant in both recessive (OR = 1.72, P = 0.014) and co-dominant (OR = 1.36, P = 0.031) models of inheritance. The FTO rs9939506 GG homozygotes had a significantly higher BMI than those with other genotypes. INTERPRETATION & CONCLUSIONS: This study shows that FTO rs9939506 GG genotype is related to higher BMI and is associated with obesity in Polish adults.

A case of intraparotid schwannoma in a juvenile: Clinical, pathological, ultrastructural, and immunohistopathological study, including an examination of Ki-67 and MCM-3 expressions.

Pleomorphic adenoma, the most common benign nonvascular tumor of the parotid gland in juveniles, should be differentiated from other extremely rare tumors, including schwannoma. In this article, we present a rare case of an intraparotid schwannoma in a juvenile, along with the patient history, a description of pathological features, and the results of ultrastructural and immunohistochemical examination. The respective labeling indexes of Ki-67 and MCM-3, i.e., the mean proportions of positive tumor cells out of 1000 tumoral cells counted in 10 microscopic fields at ×400 magnification, given as a percentage, were found to be 0.82% and 0.4%, respectively.

Comparison between immunohistochemical expression of Ki-67 and MCM-3 in major salivary gland epithelial tumors in children and adolescents. Preliminary study.

While Ki-67 expression is frequently used as an indicator of tumor cell proliferation, alternative markers have also been proposed. Possible alternative indicators of proliferation are the minichromosome maintenance (MCM) proteins, whose levels are inversely associated with tumor cell differentiation. The aim of this preliminary study was to compare the levels of Ki-67 and MCM-3 expression in major salivary gland epithelial tumors in all children and adolescents who underwent surgery in our department in the years 2009-2014. The histopathological diagnosis of the subjects was reviewed, as well as the expression of Ki-67 and MCM-3 in post-op specimens of the tumors. The normality of data was checked with the Shapiro-Wilk test. The t test for independent variables or the U test was used as appropriate to determine statistically significant differences in the expression of Ki-67 and MCM-3. Five cases of pleomorphic adenoma, one of myoepithelioma, one of basal cell adenoma and one of mucoepidermoid carcinoma were identified. Significantly greater MCM-3 than Ki-67 expression was observed in every case. The results of our preliminary study emphasize the need for future research on MCM-3 as a sensitive proliferation marker, providing an alternative to Ki-67, in cases of various major salivary gland epithelial tumors in children and adolescents.

Influence of substituent and benzoannulation on photophysical properties of 1-benzoylmethyleneisoquinoline difluoroborates.

A series of 1-benzoylmethyleneisoquinoline difluoroborates were synthesized, and their photophysical properties were determined. The effect of the substituent and benzoannulation on their properties was investigated to make a comparison with recently published results focused on related quinolines. The photophysical properties of isoquinoline derivatives differ from those of quinolines, and the most pronounced differences are found for the fluorescence quantum yields. Both experimental and theoretical approaches were used to explain the observed photophysical properties.

Deficiency in hematopoietic phosphatase ptpn6/Shp1 hyperactivates the innate immune system and impairs control of bacterial infections in zebrafish embryos.

Deficiency in Src homology region 2 domain-containing phosphatase 1/protein tyrosine phosphatase nonreceptor type 6 (SHP1/PTPN6) is linked with chronic inflammatory diseases and hematological malignancies in humans. In this study, we exploited the embryonic and larval stages of zebrafish (Danio rerio) as an animal model to study ptpn6 function in the sole context of innate immunity. We show that ptpn6 knockdown induces a spontaneous inflammation-associated phenotype at the late larval stage. Surprisingly, glucocorticoid treatment did not suppress inflammation under ptpn6 knockdown conditions but further enhanced leukocyte infiltration and proinflammatory gene expression. Experiments in a germ-free environment showed that the late larval phenotype was microbe independent. When ptpn6 knockdown embryos were challenged with Salmonella typhimurium or Mycobacterium marinum at earlier stages of development, the innate immune system was hyperactivated to a contraproductive level that impaired the control of these pathogenic bacteria. Transcriptome analysis demonstrated that Kyoto Encyclopedia of Genes and Genomes pathways related to pathogen recognition and cytokine signaling were significantly enriched under these conditions, suggesting that ptpn6 functions as a negative regulator that imposes a tight control over the level of innate immune response activation during infection. In contrast to the hyperinduction of proinflammatory cytokine genes under ptpn6 knockdown conditions, anti-inflammatory il10 expression was not hyperinduced. These results support that ptpn6 has a crucial regulatory function in preventing host-detrimental effects of inflammation and is essential for a successful defense mechanism against invading microbes.

Comparative physiological and transcriptional analysis of weak organic acid stress in Bacillus subtilis.

The advent of 'omics' techniques bears significant potential for the assessment of the microbiological stability of foods. This requires the integration of molecular data with their implication for cellular physiology. Here we performed a comparative physiological and transcriptional analysis of Bacillus subtilis stressed with three different weak organic acids: the commonly used food preservatives sorbic- and acetic-acid, plus the well-known uncoupler carbonyl cyanide-m-chlorophenyl hydrazone (CCCP). The concentration of each compound needed to cause a similar reduction of the growth rate negatively correlated with their membrane solubility, and positively with the concentration of undissociated acid. Intracellular acidification was demonstrated by expressing a pH-sensitive GFP derivative. The largest drop in intracellular pH was observed in CCCP-stressed cells and was accompanied by the transcriptional induction of the general stress response (GSR) and SigM regulon, responses known to be induced by acidification. The GSR was induced by acetate, but not by sorbate in mildly-stressed cells. Microarray analysis further revealed that all three acids activate transcriptional programs normally seen upon nutrient limitation and cause diverse responses indicative of an adaptation of the cell envelope. Based on the responses observed and the utilized pH measurements, the inhibitory effect of sorbic acid seems to be more focused on the cell membrane than that of acetic acid or CCCP.

Lysozyme-sensitive plasmonic hydrogel nanocomposite for colorimetric dry-eye inflammation biosensing.

Detection of lysozyme levels in ocular fluids is considered crucial for diagnosing and monitoring various health and eye conditions, including dry-eye syndrome. Hydrogel-based nanocomposites have been demonstrated to be one of the most promising platforms for fast and accurate sensing of different biomolecules. In this work, hydrogel, electrospun nanofibers, and plasmonic nanoparticles are combined to fabricate a sensitive and easy-to-use biosensor for lysozyme. Poly(L-lactide-co-caprolactone) (PLCL) nanofibers were covered with silver nanoplates (AgNPls), providing a stable plasmonic platform, where a poly(N-isopropylacrylamide)-based (PNIPAAm) hydrogel layer allows mobility and good integration of the biomolecules. By integrating these components, the platform can also exhibit a colorimetric response to the concentration of lysozyme, allowing for easy and non-invasive monitoring. Quantitative biosensing operates on the principle of localized surface plasmon resonance (LSPR) induced by plasmonic nanoparticles. Chemical, structural, thermal, and optical characterizations were performed on each platform layer, and the platform's ability to detect lysozyme at concentrations relevant to those found in tears of patients with dry-eye syndrome and other related diseases was investigated by colorimetry and UV-Vis spectroscopy. This biosensor's sensitivity and rapid response time, alongside the easy detection by the naked eye, make it a promising tool for early diagnosis and treatment monitoring of eye diseases.

Developing strategies to optimize the anchorage between electrospun nanofibers and hydrogels for multi-layered plasmonic biomaterials.

Polycaprolactone (PCL), a recognized biopolymer, has emerged as a prominent choice for diverse biomedical endeavors due to its good mechanical properties, exceptional biocompatibility, and tunable properties. These attributes render PCL a suitable alternative biomaterial to use in biofabrication, especially the electrospinning technique, facilitating the production of nanofibers with varied dimensions and functionalities. However, the inherent hydrophobicity of PCL nanofibers can pose limitations. Conversely, acrylamide-based hydrogels, characterized by their interconnected porosity, significant water retention, and responsive behavior, present an ideal matrix for numerous biomedical applications. By merging these two materials, one can harness their collective strengths while potentially mitigating individual limitations. A robust interface and effective anchorage during the composite fabrication are pivotal for the optimal performance of the nanoplatforms. Nanoplatforms are subject to varying degrees of tension and physical alterations depending on their specific applications. This is particularly pertinent in the case of layered nanostructures, which require careful consideration to maintain structural stability and functional integrity in their intended applications. In this study, we delve into the influence of the fiber dimensions, orientation and surface modifications of the nanofibrous layer and the hydrogel layer's crosslinking density on their intralayer interface to determine the optimal approach. Comprehensive mechanical pull-out tests offer insights into the interfacial adhesion and anchorage between the layers. Notably, plasma treatment of the hydrophobic nanofibers and the stiffness of the hydrogel layer significantly enhance the mechanical effort required for fiber extraction from the hydrogels, indicating improved anchorage. Furthermore, biocompatibility assessments confirm the potential biomedical applications of the proposed nanoplatforms.

Engineering surgical face masks with photothermal and photodynamic plasmonic nanostructures for enhancing filtration and on-demand pathogen eradication.

The shortage of face masks and the lack of antipathogenic functions has been significant since the recent pandemic's inception. Moreover, the disposal of an enormous number of contaminated face masks not only carries a significant environmental impact but also escalates the risk of cross-contamination. This study proposes a strategy to upgrade available surgical masks into antibacterial masks with enhanced particle and bacterial filtration. Plasmonic nanoparticles can provide photodynamic and photothermal functionalities for surgical masks. For this purpose, gold nanorods act as on-demand agents to eliminate pathogens on the surface of the masks upon near-infrared light irradiation. Additionally, the modified masks are furnished with polymer electrospun nanofibrous layers. These electrospun layers can enhance the particle and bacterial filtration efficiency, not at the cost of the pressure drop of the mask. Consequently, fabricating these prototype masks could be a practical approach to upgrading the available masks to alleviate the environmental toll of disposable face masks.

Substituent effect in 2-benzoylmethylenequinoline difluoroborates exhibiting through-space couplings. Multinuclear magnetic resonance, X-ray diffraction, and computational study.

The series of nine 2-benzoylmethylenequinoline difluoroborates have been synthesized and characterized by multinuclear magnetic resonance, X-ray diffraction (XRD), and computational methods. The through-space spin-spin couplings between (19)F and (1)H/(13)C nuclei have been observed in solution. The NMR chemical shifts have been correlated to the Hammett substituent constants. The crystal structures of six compounds have been solved by XRD. For two derivatives the X-ray wave function refinement was performed to evaluate the character of bonds in the NBF(2)O moiety by topological and integrated bond descriptors.

Electrospun Poly(vinyl alcohol)-Based Conductive Semi-interpenetrating Polymer Network Fibrous Hydrogel: A Toolbox for Optimal Cross-Linking.

Cross-linking of poly(vinyl alcohol) (PVA) creates a three-dimensional network by bonding adjacent polymer chains. The cross-linked structure, upon immersion in water, turns into a hydrogel, which exhibits unique absorption properties due to the presence of hydrophilic groups within the PVA polymer chains and, simultaneously, ceases to be soluble in water. The properties of PVA can be adjusted by chemical modification or blending with other substances, such as polymers, e.g., conductive poly[3-(potassium-5-butanoate)thiophene-2,5-diyl] (P3KBT). In this work, PVA-based conductive semi-interpenetrating polymer networks (semi-IPNs) are successfully fabricated. The systems are obtained as a result of electrospinning of PVA/P3KBT precursor solutions with different polymer concentrations and then cross-linking using "green", environmentally safe methods. One approach consists of thermal treatment (H), while the second approach combines stabilization with ethanol and heating (E). The comprehensive characterization allows to evaluate the correlation between the cross-linking methods and properties of nanofibrous hydrogels. While both methods are successful, the cross-linking density is higher in the thermally cross-linked samples, resulting in lower conductivity and swelling ratio compared to the E-treated samples. Moreover, the H-cross-linked systems have better mechanical properties-lower stiffness and greater tensile strength. All the tested systems are biocompatible, and interestingly, due to the presence of P3KBT, they show photoresponsivity to solar radiation generated by the simulator. The results indicate that both methods of PVA cross-linking are highly effective and can be applied to a specific system depending on the target, e.g., biomedical or electronic applications.

In Vivo Chronic Brain Cortex Signal Recording Based on a Soft Conductive Hydrogel Biointerface.

In neuroscience, the acquisition of neural signals from the brain cortex is crucial to analyze brain processes, detect neurological disorders, and offer therapeutic brain-computer interfaces. The design of neural interfaces conformable to the brain tissue is one of today's major challenges since the insufficient biocompatibility of those systems provokes a fibrotic encapsulation response, leading to an inaccurate signal recording and tissue damage precluding long-term/permanent implants. The design and production of a novel soft neural biointerface made of polyacrylamide hydrogels loaded with plasmonic silver nanocubes are reported herein. Hydrogels are surrounded by a silicon-based template as a supporting element for guaranteeing an intimate neural-hydrogel contact while making possible stable recordings from specific sites in the brain cortex. The nanostructured hydrogels show superior electroconductivity while mimicking the mechanical characteristics of the brain tissue. Furthermore, in vitro biological tests performed by culturing neural progenitor cells demonstrate the biocompatibility of hydrogels along with neuronal differentiation. In vivo chronic neuroinflammation tests on a mouse model show no adverse immune response toward the nanostructured hydrogel-based neural interface. Additionally, electrocorticography acquisitions indicate that the proposed platform permits long-term efficient recordings of neural signals, revealing the suitability of the system as a chronic neural biointerface.

Macrophage-specific gene functions in Spi1-directed innate immunity.

The Spi1/Pu.1 transcription factor plays a crucial role in myeloid cell development in vertebrates. Despite extensive studies of Spi1, the controlled gene group remains largely unknown. To identify genes dependent on Spi1, we used a microarray strategy using a knockdown approach in zebrafish embryos combined with fluorescence-activated cell sorting of myeloid cells from transgenic embryos. This approach of using knockdowns with specific green fluorescent protein-marked cell types was highly successful in identifying macrophagespecific genes in Spi1-directed innate immunity. We found a gene group downregulated on spi1 knockdown, which is also enriched in fluorescence-activated cell-sorted embryonic myeloid cells of a spi1:GFP transgenic line. This gene group, representing putative myeloidspecific Spi1 target genes, contained all 5 previously identified Spi1-dependent zebrafish genes as well as a large set of novel immune-related genes. Colocalization studies with neutrophil and macrophage markers revealed that genes cxcr3.2, mpeg1, ptpn6, and mfap4 were expressed specifically in early embryonic macrophages. In a functional approach, we demonstrated that gene cxcr3.2, coding for chemokine receptor 3.2, is involved in macrophage migration to the site of bacterial infection. Therefore, based on our combined transcriptome analyses, we discovered novel early macrophage-specific marker genes, including a signal transducer pivotal for macrophage migration in the innate immune response.

[Actual problem of meningitis and other intracranial complications in cases of otitis media and sinusitis in children]. / Ciagle aktualny problem zapalenia opon mózgowo-rdzeniowych i innych powiklan wewnatrzczaszkowych zapalenia ucha srodkowego i zatok przynosowych u dzieci.

The most frequent primary infections causing purulent meningitis in older children are both acute and chronic otitis media and sinusitis or upper and lower airways infections. In these cases sometimes purulent meningitis is accompanied with other intracranial complications. Pharmacological treatment of intracranial complications without surgical intervention concerning primary source of infection increases risk of complications including death of a patient and also recurrences of bacterial meningitis. In the paper authors present two uncommon cases of children with purulent meningitis and other intracranial complications of otitis media and sinusitis diagnosed by pediatricians.