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The versatile nature of organic conjugated materials renders their flawless integration into a diverse family of optoelectronic devices with light‐harvesting, photodetection, or light‐emitting capabilities. Classes of materials that offer the possibilities of two or more distinct optoelectronic functions are particularly attractive as they enable smart applications while providing the benefits of the ease of fabrication using low‐cost processes. Here, we develop a novel, multi‐purpose conjugated small molecule by combining boron‐azadipyrromethene (aza‐BODIPY) as electron acceptor with triphenylamine (TPA) as end‐capping donor units. The implemented donor–acceptor–donor (D–A–D) configuration, in the form of TPA‐azaBODIPY‐TPA, preserves ideal charge transfer characteristics with appropriate excitation energy levels, with the additional ability to be used as either a charge transporting interlayer or light‐sensing semiconducting layer in optoelectronic devices. To demonstrate its versatility, we first show that TPA‐azaBODIPY‐TPA can act as an excellent hole transport layer in methylammonium lead triiodide (MAPbI3)‐based perovskite solar cells with measured power conversion efficiencies exceeding 17%, outperforming control solar cells with PEDOT:PSS by nearly 60%. Furthermore, the optical bandgap of 1.49 eV is shown to provide significant photodetection in the wavelength range of up to 800 nm where TPA‐azaBODIPY‐TPA functions as donor in near‐infrared organic photodetectors (OPDs) composed of fullerene derivatives. Overall, the established versatility of TPA‐azaBODIPY‐TPA, combined with its robust thermal stability as well as excellent solubility and processability, provides a new guide for developing highly efficient multi‐purpose electronic materials for the next‐generation of smart optoelectronic devices. Materials offering two or more distinct optoelectronic functions are particularly attractive as they enable multi‐purpose applications while maintaining the ease of fabrication. This work unveils a multifunctional TPA‐azaBODIPY‐TPA small molecule with superior optoelectronic and photophysical properties. Material is shown to function as an efficient hole transport layer in perovskite solar cells, and a robust electron donor in near‐infrared organic photodetectors.

Praeruptorins, a seselin-type coumarin, possess anti-inflammatory and antitumor promoting properties. However, molecular mechanisms through which Praeruptorin-B (Pra-B) exerts an antimetastatic effect on cervical cancer cells remain unclear. Cell viability was examined using the MTT assay, whereas cell migration and invasion were examined using the Boyden chamber assay. Western blotting and RT-PCR were performed to investigate the inhibitory effect of Pra-B on 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced matrix metalloproteinase-2/-9 (MMP-2/-9) expression in HeLa cells. The findings of the luciferase assay confirmed the inhibitory effect of Pra-B on TPA-induced transcriptional activity of MMP2/-9 in HeLa cells. Pra-B inhibited TPA-induced metastatic ability of human cervical cancer cells without any significant toxicity. Pra-B suppressed TPA-induced mRNA and protein expression and transcriptional activity of MMP-2/-9 in HeLa cells. Furthermore, Pra-B inhibited AKT phosphorylation but did not affect the MAPK pathway. Cotreatment of HeLa cells with TPA plus Pra-B or LY294002 (a PI3K inhibitor) reduced cell invasion and MMP-2/-9 expression and transcriptional activity. In addition, Pra-B attenuated TPA-induced nuclear translocation of NF-κB-p65/-p50, which reduced Ikk-α phosphorylation in HeLa cells. Cotreatment of HeLa cells with TPA plus Pra-B or LY294002 reduced NF-κB nuclear translocation. These results suggested that Pra-B-mediated inhibition of TPA-induced cell metastasis involved the suppression of p-AKT/NF-κB via MMP-2/-9 expression in HeLa cells. Pra-B can be a potential antimetastatic agent against cervical cancer.

The potential of Komagataeibacter (K.) sucrofermentans to valorize polyethylene terephthalate (PET) monomers - ethylene glycol (EG) & disodium terephthalate (Na 2 -TPA) - and glucose into bacterial nanocellulose (BNC) membranes was investigated using Raman and Fourier transform infrared (FT-IR) spectroscopy. Gravimetric analysis indicated higher BNC yields for K. sucrofermentans nurtured with EG (2.54 g L − 1 ) compared to pure glucose (2.00 g L − 1 ) and TPA (1.54 g L − 1 ). Scanning Electron Microscopy (SEM) images showed that BNC derived from glucose had a dense interconnected fibrillar matrix with uniform porosity, whereas EG and TPA displayed a network structure with less uniform fiber packing. The Segal approach from X-ray diffraction (XRD) showed a lower crystallinity for EG (CrI 62.3%) and substantially lower for TPA (CrI of 18%) than for the commonly known values of glucose (CrI around 70%). Raman spectra of BNC showed that bands between 1050 cm − 1 and 1150 cm − 1 were shifted towards lower wavenumbers compared to AVICEL cellulose, indicating an increased strain on the glycosidic linkages. The Raman spectrum of BNC with TPA as a feedstock showed additional bands at 629, 861, 1125, and 1425 cm − 1 indicating that not all TPA was valorized. FT-IR spectra of the BNC with EG and TPA as feedstocks showed minor transmission and bands at 447, 560, 687, 730, 862, plus between 1500 and 1600 cm − 1 that are typically assigned to PET monomers. The absorption ratio A ~ 1430/ A ~ 897, a measure of crystallinity, gave the values glucose = 1.02, TPA = 0.63, EG = 0.53 showing that glucose as a feedstock produced the highest BNC crystallinity. In the case of glucose and EG, well-structured cellulose membranes were produced, whereas for TPA a composite membrane was produced, paving the way to use PET monomers as a feedstock for biodegradable BNC production.

Patients with coronavirus disease-19 (COVID-19) are at high risk for thrombotic arterial and venous occlusions. However, bleeding complications have also been observed in some patients. Understanding the balance between coagulation and fibrinolysis will help inform optimal approaches to thrombosis prophylaxis and potential utility of fibrinolytic-targeted therapies. 118 hospitalized COVID-19 patients and 30 healthy controls were included in the study. We measured plasma antigen levels of tissue-type plasminogen activator (tPA) and plasminogen activator inhibitor-1 (PAI-1) and performed spontaneous clot-lysis assays. We found markedly elevated tPA and PAI-1 levels in patients hospitalized with COVID-19. Both factors demonstrated strong correlations with neutrophil counts and markers of neutrophil activation. High levels of tPA and PAI-1 were associated with worse respiratory status. High levels of tPA, in particular, were strongly correlated with mortality and a significant enhancement in spontaneous ex vivo clot-lysis. While both tPA and PAI-1 are elevated among COVID-19 patients, extremely high levels of tPA enhance spontaneous fibrinolysis and are significantly associated with mortality in some patients. These data indicate that fibrinolytic homeostasis in COVID-19 is complex with a subset of patients expressing a balance of factors that may favor fibrinolysis. Further study of tPA as a biomarker is warranted.

Numerous studies have documented increases in matrix metalloproteinases (MMPs), specifically MMP-9 levels following stroke, with such perturbations associated with disruption of the blood brain barrier (BBB), increased risk of hemorrhagic complications, and worsened outcome. Despite this, controversy remains as to which cells release MMP-9 at the normal and pathological BBB, with even less clarity in the context of stroke. This may be further complicated by the influence of tissue plasminogen activator (tPA) treatment. The aim of the present review is to examine the relationship between neutrophils, MMP-9 and tPA following ischemic stroke to elucidate which cells are responsible for the increases in MMP-9 and resultant barrier changes and hemorrhage observed following stroke.

Several endogenous and exogenous factors interact to influence stroke occurrence, in turn contributing to discernable daily distribution patterns in the frequency and severity of cerebrovascular events. Specifically, strokes that occur during the morning tend to be more severe and are associated with elevated diastolic blood pressure, increased hospital stay, and worse outcomes, including mortality, compared to strokes that occur later in the day. Furthermore, disrupted circadian rhythms are linked to higher risk for stroke and play a role in stroke outcome. In this review, we discuss the interrelation among core clock genes and several factors contributing to ischemic outcomes, sources of disrupted circadian rhythms, the implications of disrupted circadian rhythms in foundational stroke scientific literature, followed by a review of clinical implications. In addition to highlighting the distinct daily pattern of onset, several aspects of physiology including immune response, endothelial/vascular and blood brain barrier function, and fibrinolysis are under circadian clock regulation; disrupted core clock gene expression patterns can adversely affect these physiological processes, leading to a prothrombotic state. Lastly, we discuss how the timing of ischemic onset increases morning resistance to thrombolytic therapy and the risk of hemorrhagic transformation.

PDCD4 is a novel tumor suppressor to show multi-functions inhibiting cell growth, tumor invasion, metastasis, and inducing apoptosis. PDCD4 protein binds to the translation initiation factor eIF4A, some transcription factors, and many other factors and modulates the function of the binding partners. PDCD4 downregulation stimulates and PDCD4 upregulation inhibits the TPA-induced transformation of cells. However, PDCD4 gene mutations have not been found in tumor cells but gene expression was post transcriptionally downregulated by micro environmental factors such as growth factors and interleukins. In this review, we focus on the suppression mechanisms of PDCD4 protein that is induced by the tumor promotors EGF and TPA, and in the inflammatory conditions. PDCD4-protein is phosphorylated at 2 serines in the SCFβTRCP ubiquitin ligase binding sequences via EGF and/or TPA induced signaling pathway, ubiquitinated, by the ubiquitin ligase and degraded in the proteasome system. The PDCD4 protein synthesis is inhibited by microRNAs including miR21.

Oleanolic and ursolic acids are natural triterpenic compounds with pentacyclic cholesterol-like structures which gives them very low water solubility, a significant disadvantage in terms of bioavailability. We previously reported the synthesis of inclusion complexes between these acids and cyclodextrins, as well as their in vivo evaluation on chemically induced skin cancer experimental models. In this study the synergistic activity of the acid mixture included inside hydroxypropyl-gamma-cyclodextrin (HPGCD) was monitored using in vitro tests and in vivo skin cancer models. The coefficient of drug interaction (CDI) was used to characterize the interactions as synergism, additivity or antagonism. Our results revealed an increased antitumor activity for the mixture of the two triterpenic acids, both single and in complex with cyclodextrin, thus proving their complementary biologic activities.

The transition from animal to plant proteins is booming, and the development of meat analogues or alternatives quickly progressing. However, the acceptance of meat analogues by consumers is still limited, mainly due to disappointing organoleptic properties of these foods. The objective of this study was to investigate possible relationships among structure, textural characteristics, consumer acceptance, and sensory evaluation of commercially available meat analogues. The microstructure and texture of 13 chicken analogue pieces and 14 analogue burgers were evaluated with confocal laser scanning microscopy (CLSM) and texture profile analysis (TPA). The moisture of the samples was related to cooking losses and release of liquid upon compression after cooking. Meat products were included as references. A sensory panel (n = 71) evaluated both flavour and texture characteristics. For the chicken analogue pieces, samples with more added fibres had a harder and chewier texture but were less cohesive. No other relations between composition and structure/texture could be found. In the sensory evaluation, lower hardness and chewiness were only seen in products with more fat. A lower sensory hardness was found to be related to the presence of small air pockets. For analogue burgers, there was no clear relation between composition and structure/texture. However, instrumentally measured hardness, chewiness, and cohesiveness correlated well with the corresponding sensory attributes, even though they could not be clearly linked to a structural feature. Next to this, fat content showed a clear correlation to perceived fattiness. CLSM images of burgers with high perceived fattiness showed large areas of fat. Therefore, the release of large fat pools from the meat was most likely responsible for the perception of this attribute. However, perceived fattiness was not related to liking, which was the case also for chicken analogue pieces. For both pieces and burgers, even if some of the measured textural attributes could be linked to the sensory profile, the textural attributes in question could not explain the liking scores. Liking was related to other aspects, such as meaty flavour and juiciness, which were not directly linked to compositional or textural features. Juiciness was not directly related to the moisture loss of the products, indicating that this attribute is rather complex and probably involves a combination of characteristics. These results show that to increase the appreciation of meat analogues by consumers, improving simple texture attributes is not sufficient. Controlling sensory attributes with complex cross-modal perception is probably more important.

Background The use of antithrombotic agents, including anticoagulants, antiplatelet agents, and thrombolytics has increased over the last decade and is expected to continue to rise. Although antithrombotic-associated intracranial hemorrhage can be devastating, rapid reversal of coagulopathy may help limit hematoma expansion and improve outcomes. Methods The Neurocritical Care Society, in conjunction with the Society of Critical Care Medicine, organized an international, multi-institutional committee with expertise in neurocritical care, neurology, neurosurgery, stroke, hematology, hemato-pathology, emergency medicine, pharmacy, nursing, and guideline development to evaluate the literature and develop an evidence-based practice guideline. Formalized literature searches were conducted, and studies meeting the criteria established by the committee were evaluated. Results Utilizing the GRADE methodology, the committee developed recommendations for reversal of vitamin K antagonists, direct factor Xa antagonists, direct thrombin inhibitors, unfractionated heparin, low-molecular weight heparin, heparinoids, pentasaccharides, thrombolytics, and antiplatelet agents in the setting of intracranial hemorrhage. Conclusions This guideline provides timely, evidence-based reversal strategies to assist practitioners in the care of patients with antithrombotic-associated intracranial hemorrhage.