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Wound healing in DFU (diabetic foot ulcer) has prolonged inflammation phase and defective granulation tissue formation. LL-37 has antimicrobial property, induces angiogenesis, and keratinocyte migration and proliferation. This study analyzes the efficacy of LL-37 cream in enhancing wound healing rate and decreasing the levels of IL-1α, TNF-α, and the number of aerobic bacteria colonization in DFU with mild infection. This study was conducted from January 2020 to June 2021 in Jakarta. Subjects were instructed to apply either LL-37 cream or placebo cream twice a week for 4 weeks. Wounds were measured on days 7, 14, 21, and 28 and processed with ImageJ. The levels of LL-37, IL-1α, and TNF-α from wound fluid were measured using ELISA. The number of aerobic bacteria colonization was counted from the isolate grown in culture. The levels of LL-37 in DFU at baseline were equally low in both groups which were 1.07 (0.37–4.96) ng/mg protein in the LL-37 group and 1.11 (0.24–2.09) ng/mg protein in the placebo group. The increase in granulation index was consistently greater in the LL-37 group on days 7, 14, 21, and 28 (p = 0.031, 0.009, 0.006, and 0.037, respectively). The levels of IL-1α and TNF-α increased in both groups on days 14 and 21 (p > 0.05). The decrease in the number of aerobic bacteria colonization was greater in the LL-37 group on days 7, 14 and 21, but greater in the placebo group on day 28 (p > 0.05). In conclusion, LL-37 cream enhanced the healing rate of DFU with mild infection, but did not decrease the levels of IL-1α and TNF-α and the number of aerobic bacteria colonization. This trial is registered at ClinicalTrials.gov, number NCT04098562. [ABSTRACT FROM AUTHOR]

Autoimmune diseases are pathological conditions that result from the misidentification of self-antigens in immune system, leading to host tissue damage and destruction. These diseases can affect different organs and systems, including the blood, joints, skin, and muscles. Despite the significant progress made in comprehending the underlying pathogenesis, the complete mechanism of autoimmune disease is still not entirely understood. In autoimmune diseases, the innate immunocytes are not functioning properly: they are either abnormally activated or physically disabled. As a vital member of innate immunocyte, neutrophils and their modes of death are influenced by the microenvironment of different autoimmune diseases due to their short lifespan and diverse death modes. Related to neutrophil death pathways, apoptosis is the most frequent cell death form of neutrophil non-lytic morphology, delayed or aberrant apoptosis may contribute to the development anti-neutrophil cytoplasmic antibodies (ANCA)-associated vasculitis (AAV). In addition, NETosis, necroptosis and pyroptosis which are parts of lytic morphology exacerbate disease progression through various mechanisms in autoimmune diseases. This review aims to summarize recent advancements in understanding neutrophil death modes in various autoimmune diseases and provide insights into the development of novel therapeutic approaches for autoimmune diseases. [ABSTRACT FROM AUTHOR]

Abstract—This review describes the role of peripheral blood biomarkers involved in neurodegeneration and neuroregeneration in Parkinson's disease: BDNF, Cathepsin D, NSAM, myeloperoxidase, plasminogen activator inhibitor-1 (PAI-1), platelet-derived growth factor (PDGF), a chemokine that is regulated upon activation, normal T cell expression and secreted (RANTES), and intercellular adhesion molecules (sICAM-1). These biomarkers are important indicators of biological processes and are promising for early diagnosis, the prognosis of the disease, and the development of new possibilities for modifying therapy for Parkinson's disease, as they are associated with neuroprotective and neurotrophic systems. [ABSTRACT FROM AUTHOR]

Children play an important role in hepatitis A virus (HAV) transmission but, due to frequent asymptomatic or mild courses, these infections are underrecognized in routine surveillance. Here, we analyzed hepatitis A (HA) seroprevalence, vaccination status and demographic determinants and estimated previous HAV infections in a cross-sectional population-based study of children and adolescents with residence in Germany 2014–2017, performing weighted univariable and multivariable logistic regression. Of 3567 participants aged 3–17 years, serological results were available for 3013 (84.5%), vaccination records for 3214 (90.1%) and both for 2721 (76.3%). Of 2721 with complete results, 467 (17.2%) were seropositive, thereof 412 (15.1%) with and 55 (2.0%) without previous HA vaccination, indicating previous HAV infection. Seropositivity was associated with age, residence in Eastern states, high socioeconomic status and migration background with personal migration experience. Participants with migration background and personal migration experience also had the highest odds ratios for previous HAV infection. Germany remains a country with very low HA endemicity. The current vaccination recommendations focusing on individuals with a high risk for HAV exposure (e.g. travelers to endemic countries) or severe disease appear appropriate. Migration and travel patterns as well as the endemicity in other countries influence the domestic situation, warranting further monitoring. [ABSTRACT FROM AUTHOR]

The worldwide prevalence of Parkinson's disease (PD) has been constantly increasing in the last decades. With rising life expectancy, a longer disease duration in PD patients is observed, further increasing the need and socioeconomic importance of adequate PD treatment. Today, PD is exclusively treated symptomatically, mainly by dopaminergic stimulation, while efforts to modify disease progression could not yet be translated to the clinics. New formulations of approved drugs and treatment options of motor fluctuations in advanced stages accompanied by telehealth monitoring have improved PD patients care. In addition, continuous improvement in the understanding of PD disease mechanisms resulted in the identification of new pharmacological targets. Applying novel trial designs, targeting of pre-symptomatic disease stages, and the acknowledgment of PD heterogeneity raise hopes to overcome past failures in the development of drugs for disease modification. In this review, we address these recent developments and venture a glimpse into the future of PD therapy in the years to come. [ABSTRACT FROM AUTHOR]

Introduction: Patients under renal replacement therapy are at an increased risk of severe infection with SARS-CoV-2, and have been known to have impaired response to standard vaccination. This systematic review and meta-analysis aims at evaluating the efficacy of booster dose vaccination in this population. Methods: A systematic review has been conducted to find trials on the booster dose vaccination in kidney transplant recipients (KTRs) or patients under dialysis. Data of seroconversion rates at different timepoints, especially 1 month prior and post-booster dose vaccination have been collected and analyzed. Effects of different factors including type of renal replacement therapy (RRT), vaccine type and brands, magnitude of response to the standard vaccination, and immunosuppression drugs on the response rates have been investigated. Meta-analyses were performed using software Stata v.17. Results: Overall 58 studies were included. Both RRT patient subgroups represented significant seroconversion, post- (versus pre-) booster dose vaccination, but only in KTRs the booster dose seroconversion surpassed that of the standard protocol. T-cell response was also significantly augmented after booster vaccination, with no difference between the RRT subgroups. mRNA and vector vaccine types had comparable immunogenicity when employed as boosters, both significantly higher than the inactivated virus vaccine, with no significant disparity regarding the vaccine brands. Patients with poor response to standard vaccination had a significant response to booster dose, with dialysis patients having stronger response. The differential effects of vaccine types and brands in the poor responders was similar to that of the overall RRT population. No rejection episodes or graft failure post-booster vaccination was reported. Conclusion: In patients under RRT, booster dose vaccination against SARS-CoV-2 is safe and efficacious determined by significant seroconversion, and therefore, it should be considered to be implemented in all these patients. Since in the KTR patients, the third dose vaccination significantly increased the seroconversion rates even beyond that of the standard protocol, three dose vaccine doses is recommended to be recognized as the standard vaccination protocol in this population. The same recommendation could be considered for dialysis patients, due to their augmented risk of breakthrough infection. [ABSTRACT FROM AUTHOR]

Takifugu species serve as a model system for evolutionary studies due to their compact genomes and diverse phenotypes. The ocellated puffer (Takifugu ocellatus), characterized by special colouration, is a scarce anadromous species in the genus Takifugu. As an ornamental and tasty fish species, T. ocellatus has moderate economic value. However, the available genomic resources for this pufferfish are still limited. Here, a chromosome-level reference genome, as well as two haploid genomes, was constructed by PacBio HiFi long sequencing and Hi-C technologies. The total length of the reference genome was 375.62 Mb with a contig N50 of 11.55 Mb. The assembled sequences were anchored to 22 chromosomes with an integration efficiency of 93.78%. Furthermore, 28,808 protein-coding genes were predicted. The haplotype-resolved reference genome of T. ocellatus provides a crucial resource for investigating the explosive speciation of the Takifugu genus, such as elucidating evolutionary histories, determining the genetic basis of trait evolution, and supporting future conservation efforts. Measurement(s) Whole Genome Sequencing • Chromosome assembly by Hi-C data • Whole Transcriptome Sequencing Technology Type(s) PacBio Sequel System • Hi-C • Illumina HiSeq. 2500 • Illumina NovaSeq. 6000 Sample Characteristic - Organism Takifugu ocellatus [ABSTRACT FROM AUTHOR]

The bonnethead Sphyrna tiburo is a wide-spread, small species of coastal hammerhead shark with a long history of taxonomic uncertainty, including, according to some authors, disjoint subspecies in the western Atlantic and eastern Pacific oceans. The present study investigates the level of morphometric and genetic variation within the Sphyrna tiburo complex throughout most of its distributional range including the western Atlantic, the Gulf of Mexico, the Caribbean, and the eastern Pacific. A morphometric study, including a comparison of ampullary densities, and a molecular analysis of two mitochondrial genes, was performed. We analyzed variation in cephalofoil shape between and within lineages, based on landmarks and Fourier analysis of the silhouettes. All tests delineated discrete morphological groups, including differences of ampullae density for those lineages in which this information could be unambiguously assessed. Both morphometric and molecular analysis support the existence of three different evolutionarily significant units (two in the Atlantic: one northern and one south-central, and a third in the eastern Pacific) that deserve specific taxonomic status. We urge a deep taxonomic review of this complex to gather biological data on each lineage and develop adequate independent conservation strategies and actions to protect the various evolutionary units. [ABSTRACT FROM AUTHOR]

The clinical presentation of Parkinson's disease (PD) is both complex and heterogeneous, and its precise classification often requires an intensive work-up. The differential diagnosis, assessment of disease progression, evaluation of therapeutic responses, or identification of PD subtypes frequently remains uncertain from a clinical point of view. Various tissue- and fluid-based biomarkers are currently being investigated to improve the description of PD. From a clinician's perspective, signatures from blood that are relatively easy to obtain would have great potential for use in clinical practice if they fulfill the necessary requirements as PD biomarker. In this review article, we summarize the knowledge on blood-based PD biomarkers and present both a researcher's and a clinician's perspective on recent developments and potential future applications. [ABSTRACT FROM AUTHOR]

Background: Metabolic reprogramming has emerged as a core hallmark of cancer, and cancer metabolism has long been equated with aerobic glycolysis. Moreover, hypoxia and the hypovascular tumor microenvironment (TME) are major hallmarks of pancreatic ductal adenocarcinoma (PDAC), in which glycolysis is imperative for tumor cell survival and proliferation. Here, we explored the impact of interleukin 1 receptor-associated kinase 2 (IRAK2) on the biological behavior of PDAC and investigated the underlying mechanism. Methods: The expression pattern and clinical relevance of IRAK2 was determined in GEO, TCGA and Ren Ji datasets. Loss-of-function and gain-of-function studies were employed to investigate the cellular functions of IRAK2 in vitro and in vivo. Gene set enrichment analysis, Seahorse metabolic analysis, immunohistochemistry and Western blot were applied to reveal the underlying molecular mechanisms. Results: We found that IRAK2 is highly expressed in PDAC patient samples and is related to a poor prognosis. IRAK2 knockdown led to a significant impairment of PDAC cell proliferation via an aberrant Warburg effect. Opposite results were obtained after exogenous IRAK2 overexpression. Mechanistically, we found that IRAK2 is critical for sustaining the activation of transcription factors such as those of the nuclear factor-κB (NF-κB) family, which have increasingly been recognized as crucial players in many steps of cancer initiation and progression. Treatment with maslinic acid (MA), a NF-κB inhibitor, markedly attenuated the aberrant oncological behavior of PDAC cells caused by IRAK2 overexpression. Conclusions: Our data reveal a role of IRAK2 in PDAC metabolic reprogramming. In addition, we obtained novel insights into how immune-related pathways affect PDAC progression and suggest that targeting IRAK2 may serve as a novel therapeutic approach for PDAC. [ABSTRACT FROM AUTHOR]

Background: Lung cancer is a leading cause of cancer-related deaths, primarily as a result of metastases. In this metastasis, the epithelial-to-mesenchymal transition (EMT) is essential. Interaction with the cancer cell microenvironment is primarily dependent on M1- and M2-polarized macrophage. Methods and results: In this study, we revealed the EMT-associated activity of M1, M2a and M2c macrophages in A549 lung cancer cells. We established a co-culture model of A549 lung cancer cells utilizing THP-1-derived M1/M2 polarised macrophages to explore the involvement of macrophages in the immune response, apoptosis, and EMT in lung cancer. Although multiple polarising agents are routinely used for M1 and M2 conversion, we assessed a new possible polarising agent, hydrocortisone. Conclusions: M1 increased A549 cell sensitivity to proteasome inhibitors and decreased A549 cell viability by inducing apoptosis. EMT was induced in the presence of M2c macrophages in A549 cells by the levels of vimentin, fibronectin, E-cadherin, NF-kB, CCL-17. We also revealed the antiproliferative effects of bortezomib and ixazomib on A549 cells in both 2D and 3D cultures. Our findings could help develop an immunotherapeutic strategy by shedding light on a previously undiscovered part of the EMT pathway. Furthermore, additional investigation may reveal that polarising tumour-associated macrophages to M1 and eliminating the M2a or particularly the M2c subtype are effective anti-cancer strategies. [ABSTRACT FROM AUTHOR]

Parkinson's disease (PD) is one of the most common long-term degenerative disorders of the CNS that primarily affects the human locomotor system. Owing to the heterogeneity of PD etiology and the lack of appropriate diagnostic tests, blood-based biomarkers became the most promising method for diagnosing PD. Even though various biomarkers for PD have been found, their specificity and sensitivity are not optimum when used alone. Therefore, the aim of this study was directed to evaluate changes in a group of sensitive blood-based biomarkers in the same PD patients compared to healthy individuals. Serum samples were collected from 20 PD patients and 15 age-matched healthy controls. We analyzed serum levels of cytokines (IL10, IL12, and TNF-α), α-synuclein proteins, miRNAs (miR-214, miR-221, and miR-141), and antioxidants (UA, PON1, ARE). Our results showed an increase in sera levels of cytokines in PD patients as well as a positive correlation among them. Also, we found a significant increase in sera levels of α-synuclein protein associated with a decrease in miR-214 which regulates its gene expression. Lastly, we observed a decrease in sera levels of miR-221, miR-141, UA, PON1, and ARE, which have a prominent role against oxidative stress. Because of the many etiologies of PD, a single measure is unlikely to become a useful biomarker. Therefore, to correctly predict disease state and progression, a mix of noninvasive biomarkers is required. Although considerable work has to be done, this study sheds light on the role of certain biomarkers in the diagnosis of PD. [ABSTRACT FROM AUTHOR]

Cadmium (Cd) is a toxic metal and an important environmental contaminant. We analyzed its effects on oligoelements, oxidative stress, cell death, Hsp expression and the histoarchitecture of rat lung under different diets, using animal models of subchronic cadmium intoxication. We found that Cd lung content augmented in intoxicated groups: Zn, Mn and Se levels showed modifications among the different diets, while Cu showed no differences. Lipoperoxidation was higher in both intoxicated groups. Expression of Nrf-2 and SOD-2 increased only in SoCd. GPx levels showed a trend to increase in Cd groups. CAT activity was higher in intoxicated groups, and it was higher in Soy groups vs. Casein. LDH activity in BAL increased in CasCd and decreased in both soy-fed groups. BAX/Bcl-2 semiquantitative ratio showed similar results than LDH activity, confirmed by Caspase 3 immunofluorescence. The histological analysis revealed an infiltration process in CasCd lungs, with increased connective tissue, fused alveoli and capillary fragility. Histoarchitectural changes were less severe in soy groups. Hsp27 expression increased in both intoxicated groups, while Hsp70 only augmented in SoCd. This show that a soy-diet has a positive impact upon oxidative unbalance, cell death and morphological changes induced by Cd and it could be a good alternative strategy against Cd exposure. [ABSTRACT FROM AUTHOR]

Background: Exposure to cadmium is implicated in the etiology of some neurodegenerative diseases. Compounds isolated from Ipomoea cairica extract are neuroprotective. However, there is no reported neuroprotective activity of the crude extract of I. cairica (ICE). We investigated the neuroprotective activity of I. cairica extract against cadmium-induced biochemical changes in the brain of male Wistar rats. Thirty-six animals were divided into four groups of 9 animals per group: group I (Control); group II (3.5 mg/kg CdCl2); group III (100 mg/kg ICE + CdCl2); and group IV (250 mg/kg ICE + CdCl2). Animals were pretreated with 100 and 250 mg/kg ICE before co-administration with cadmium chloride. Results: CdCl2 treatment caused a significant increase in acetylcholineesterase activity, lipid peroxidation, beta-amyloid aggregation, caspase 3 and 9, p53, and glutamate concentration. In addition, CdCl2 caused a significant decrease in catalase activity, superoxide dismutase, glutathione-S-transferase, Na+/K+ ATPase, and glutamate dehydrogenase. ICE was able to reduce the neuronal damaging effect of CdCl2 by acting as an antioxidant, antiapoptotic, anticholinesterase, and antiexcitotoxicity. Conclusions: Our findings show that Ipomoea cairica leaf can be developed and included in the natural product in the prevention of neurodegenerative diseases. [ABSTRACT FROM AUTHOR]

Increasing contamination of environmental waters with pharmaceuticals represents an emerging threat for the drinking water quality and safety. In this regard, fast and reliable analytical methods are required to allow quick countermeasures in case of contamination. Here, we report the development of a magnetic bead-based immunoassay (MBBA) for the fast and cost-effective determination of the analgesic diclofenac (DCF) in water samples, based on diclofenac-coupled magnetic beads and a robust monoclonal anti-DCF antibody. A novel synthetic strategy for preparation of the beads resulted in an assay that enabled for the determination of diclofenac with a significantly lower limit of detection (400 ng/L) than the respective enzyme-linked immunosorbent assay (ELISA). With shorter incubation times and only one manual washing step required, the assay demands for remarkably shorter time to result (< 45 min) and less equipment than ELISA. Evaluation of assay precision and accuracy with a series of spiked water samples yielded results with low to moderate intra- and inter-assay variations and in good agreement with LC–MS/MS reference analysis. The assay principle can be transferred to other, e.g., microfluidic, formats, as well as applied to other analytes and may replace ELISA as the standard immunochemical method. [ABSTRACT FROM AUTHOR]

Neuroinflammation is one of the detrimental factors leading to neurodegeneration in Alzheimer's disease (AD) and other neurodegenerative disorders. The activation of microglial neurokinin 1 receptor (NK1R) by substance P (SP) enhances neuroinflammation which is mediated through pro-inflammatory pathways involving NFkB, ERK1/2, and P38 and thus projects the scope and importance of NK1R inhibitors. Emphasizing the inhibitory role of N Acetyl l Tryptophan (l-NAT) on NK1R, this is the first in silico screening of l-NAT mediated NK1R antagonism. In addition, FDA- approved ligands were screened for their potential NK1R antagonism. The l-NAT was docked in XP (Extra Precision) mode while FDA-approved ligands were screened in HTVS (High Throughput Virtual Screening), SP (Standard Precision), and XP mode onto NK1R (PDB:6HLO). The l-NAT and top 3 compounds FDA-approved ligands were subjected to molecular dynamics (MD) studies of 100 ns simulation time. The XP docking of l-NAT, indacaterol, modafinil and alosetron showed good docking scores. Their 100 ns MD showed brief protein–ligand interactions with an acceptable root mean square deviation. The protein–ligand contacts depicted pi-pi stacking, pi-cation, hydrogen bonds, and water bridges with the amino acids necessary for NK1R inhibition. The variable colour band intensities on the protein–ligand contact map indicated their binding strength with amino acids. The molecular mechanics/generalized born surface area (MM-GBSA) scores suggested favourable binding free energy of the complexes. Thus, our study predicted the ability of l-NAT, indacaterol, modafinil, and alosetron as capable NK1R inhibitors that can aid to curb neuroinflammation in conditions of AD which could be further ascertained in subsequent studies. [ABSTRACT FROM AUTHOR]

Autism Spectrum disorder is one of the commonest and most important neurodevelopmental conditions affecting children today. With an increasing prevalence and an unclear aetiology, it is imperative we find early markers of autism, which may facilitate early identification and intervention. Alterations of gestational cytokine profiles have been reported in mothers of autistic children. Increasing evidence suggests that the intrauterine environment is an important determinant of autism risk. This study aims to examine the mid-gestational serum cytokine profiles of the mothers of autistic children from a well-characterised birth cohort. A nested sub-cohort within a large mother–child birth cohort were identified based on a confirmed multi-disciplinary diagnosis of autism before the age 10 years and neuro-typical matched controls in a 2:1 ratio. IFN-γ, IL-1β, IL-4, IL-6, IL-8, IL-17A, GMCSF and TNFα were measured in archived maternal 20-week serum using MesoScale Diagnostics multiplex technology and validation of our IL-17A measurements was performed using an ultrasensitive assay. From a cohort of 2137 children, 25 had confirmed autism before 10 years and stored maternal serum from mid-gestation. We examined the sera of these 25 cases and 50 matched controls. The sex ratio was 4:1 males to females in each group, and the mean age at diagnosis was 5.09 years (SD 2.13). We found that concentrations of IL-4 were significantly altered between groups. The other analytes did not differ significantly using either multiplex or ultra-sensitive assays. In our well-characterised prospective cohort of autistic children, we confirmed mid-gestational alterations in maternal IL-4 concentrations in autism affected pregnancies versus matched controls. These findings add to promising evidence from animal models and retrospective screening programmes and adds to the knowledge in this field. [ABSTRACT FROM AUTHOR]

Proteins are one of the main constituents of living cells. Studying the quantities of proteins under physiological and pathological conditions can give valuable insights into health status, since proteins are the functional molecules of life. To be able to detect and quantify low-abundance proteins in biofluids for applications such as early disease diagnostics, sensitive analytical techniques are desired. An example of this application is using proteins as biomarkers for detecting cancer or neurological diseases, which can provide early, lifesaving diagnoses. However, conventional methods for protein detection such as ELISA, mass spectrometry, and western blotting cannot offer enough sensitivity for certain applications. Recent advances in optical-based micro- and nano-biosensors have demonstrated promising results to detect proteins at low quantities down to the single-molecule level, shining lights on their capacities for ultrasensitive disease diagnosis and rare protein detection. However, to date, there is a lack of review articles synthesizing and comparing various optical micro- and nano-sensing methods of enhancing the limits of detections of the antibody-based protein assays. The purpose of this article is to critically review different strategies of improving assay sensitivity using miniaturized biosensors, such as assay miniaturization, improving antibody binding capacity, sample purification, and signal amplification. The pros and cons of different methods are compared, and the future perspectives of this research field are discussed. [ABSTRACT FROM AUTHOR]

Severe aplastic anemia II (SAA-II) progresses from non-severe aplastic anemia (NSAA). The unavailability of efficacious treatment has prompted the need for haploidentical bone marrow transplantation (haplo-BMT) in patients lacking a human leukocyte antigen (HLA)-matched donor. This study aimed to investigate the efficacy of haplo-BMT for patients with SAA-II. Twenty-two patients were included and followed up, and FLU/BU/CY/ATG was used as conditioning regimen. Among these patients, 21 were successfully engrafted, 19 of whom survived after haplo-BMT. Four patients experienced grade II–IV aGvHD, including two with grade III–IV aGvHD. Six patients experienced chronic GvHD, among whom four were mild and two were moderate. Twelve patients experienced infections during BMT. One was diagnosed with post-transplant lymphoproliferative disorder and one with probable EBV disease, and both recovered after rituximab infusion. Haplo-BMT achieved 3-year overall survival and disease-free survival rate of 86.4% ± 0.73% after a median follow-up of 42 months, indicating its effectiveness as a salvage therapy. These promising outcomes may support haplo-BMT as an alternative treatment strategy for patients with SAA-II lacking HLA-matched donors. [ABSTRACT FROM AUTHOR]

Breast cancer (BC) is the most frequent cause of death among women, representing a global public health problem. Here, we aimed to discuss the correlation between the purinergic system and BC, recognizing therapeutic targets. For this, we analyzed the interaction of extracellular nucleotides and nucleosides with the purinergic receptors P1 and P2, as well as the influence of ectonucleotidase enzymes (CD39 and CD73) on tumor progression. A comprehensive bibliographic search was carried out. The relevant articles for this review were found in the PubMed, Scielo, Lilacs, and ScienceDirect databases. It was observed that among the P1 receptors, the A1, A2A, and A2B receptors are involved in the proliferation and invasion of BC, while the A3 receptor is related to the inhibition of tumor growth. Among the P2 receptors, the P2X7 has a dual function. When activated for a short time, it promotes metastasis, but when activated for long periods, it is related to BC cell death. P2Y2 and P2Y6 receptors are related to BC proliferation and invasiveness. Also, the high expression of CD39 and CD73 in BC is strongly related to a worse prognosis. The receptors and ectonucleotidases involved with BC become possible therapeutic targets. Several purinergic pathways have been found to be involved in BC cell survival and progression. In this review, in addition to analyzing the pathways involved, we reviewed the therapeutic interventions already studied for BC related to the purinergic system, as well as to other possible therapeutic targets. [ABSTRACT FROM AUTHOR]

The spread of multi-drug-resistant bacterial strains causing serious infectious diseases dictates the development of new approaches to combat these diseases. In addition to drug resistance, the important causative agent of tuberculosis (Mycobacterium tuberculosis (Mtb)) is able to persist asymptomatically in individuals for many years, causing latent forms of tuberculosis. In such a dormant state, Mtb cells are also resistant to known antibiotics. In this regard, photodynamic inactivation (PDI) could be an effective alternative to antibiotics as its action is based on the generation of active forms of oxygen independently on the presence of specific antibiotic targets, thereby inactivating both drug-resistant and dormant bacteria. In this review, we summarise examples of the application of PDI for the elimination of representatives of the genus Mycobacteria, both in vitro and in vivo. According to published results, including photosensitisers in the PDI regime results in a significantly higher lethal effect. Such experiments were mainly performed using chemically synthesised photosensitisers, which need to be transported to the areas of bacterial infections, limiting PDI usage by surface (skin) diseases. In this regard, endogenous photosensitisers (mainly porphyrins) could be used to solve the problem of transportation. In vitro experiments demonstrate the effective application of PDI for mycobacteria, including Mtb, using endogenous porphyrins; the intracellular contents of these substances can be elevated by administration of 5-aminolevulenic acid, a precursor of porphyrin synthesis. Photodynamic inactivation can also be used for dormant mycobacteria, which are characterised by high levels of endogenous porphyrins. Thus, PDI can effectively eliminate drug-resistant mycobacteria. The exploitation of modern light-transmitting techniques opens new possibilities to use PDI in clinical settings. Key points: •The potential effects of photodynamic inactivation of mycobacteria are critically reviewed. •Approaches to photoinactivation of mycobacteria using exogenous and endogenous photosensitisers are described. •Prospects for the use of photodynamic inactivation in the treatment of tuberculosis are discussed. [ABSTRACT FROM AUTHOR]

Parkinson's disease (PD) is a neurodegenerative disorder where alpha-synuclein plays a central role in the death and dysfunction of neurons, both, in central, as well as in the peripheral nervous system. Besides the neuronal events observed in patients, PD also includes a significant immune component. It is suggested that the PD-associated immune response will have consequences on neuronal health, thus opening immunomodulation as a potential therapeutic strategy in PD. The immune changes during the disease occur in the brain, involving microglia, but also in the periphery with changes in cells of the innate immune system, particularly monocytes, as well as those of adaptive immunity, such as T-cells. This realization arises from multiple patient studies, but also from data in animal models of the disease, providing strong evidence for innate and adaptive immune system crosstalk in the central nervous system and periphery in PD. Here we review the data showing that alpha-synuclein plays a crucial role in the activation of the innate and adaptive immune system. We will also describe the studies suggesting that inflammation in PD includes early changes in innate and adaptive immune cells that develop dynamically through time during disease, contributing to neuronal degeneration and symptomatology in patients. This novel finding has contributed to the definition of PD as a multisystem disease that should be approached in a more integratory manner rather than a brain-focused classical approach. [ABSTRACT FROM AUTHOR]

Electrolyte-gated organic transistors represent a promising platform for the design of fluid biosensors. The paper presents a simple and easily scalable approach to the manufacture of high-performance stable electrolyte-gated organic transistors with reproducible electrical characteristics, based on phase microsegregation in mixtures of an organic semiconductor, 2,7-dioctyl[1]benzothieno[3,2-b]benzothiophene, with a dielectric polymer, polystyrene. [ABSTRACT FROM AUTHOR]

Organic field-effect transistors (OFETs) are fabricated using organic semiconductors (OSCs) as the active layer in the form of thin films. Due to its advantages of high sensitivity, low cost, compact integration, flexibility, and printability, OFETs have been used extensively in the sensing area. For analysis platforms, the construction of sensing layers is a key element for their efficient detection capability. The strategy used to immobilize biomolecules in these devices is especially important for ensuring that the sensing functions of the OFET are effective. Generally, analysis platforms are developed by modifying the gate/electrolyte or OSC/electrolyte interface using biomolecules, such as enzymes, antibodies, or deoxyribonucleic acid (DNA) to ensure high selectivity. To provide better or more convenient biological immobilization methods for researchers in this field and thereby improve detection sensitivity, this review summarizes recent developments in the immobilization strategies used for biological macromolecules in OFETs, including cross-linking, physical adsorption, embedding, and chemical covalent binding. The influences of biomolecules on device performance are also discussed. [ABSTRACT FROM AUTHOR]

Purpose: Non-functioning pituitary adenoma (NFPA) is the most prevalent pituitary macroadenoma. No prognostic marker has been found to explain the behavior of these tumors. We aimed to explore cell proliferation, apoptosis, proangiogenic markers, and microvascular density (MVD) in noninvasive and invasive NFPAs. Methods: Adenoma invasiveness was defined according to Knosp and Hardy classifications based on preoperative magnetic resonance imaging scans. Cell proliferation was examined using Ki67 and P53. Tissue expression of Bcl-2 was used to assess the antiapoptosis pathway. CD34 and CD105 were measured to evaluate MVD, while VEGF expression was assessed as an indicator of pro-angiogenesis. Moreover, VEGF, bFGF, endocan, and endostatin were measured on preoperative serum samples. Results: Tissue and serum markers were examined in 18 patients with invasive and 21 patients with noninvasive NFPAs. Ki67 less than 3% was reported in 10 invasive and 14 noninvasive NFPAs (P = 0.752). P53 staining was negative in all subjects. In addition, Bcl-2 staining was negative in 15 and 20 subjects, respectively (P = 0.718). VEGF-A expression 2+ or 3+ was reported in 9 invasive and 11 noninvasive macroadenomas (P = 0.83). Moreover, CD34 and CD105 positivity were comparable between the two groups. Furthermore, the comparison of serum markers showed no significant differences. Conclusion: Cell proliferation, apoptosis, and angiogenesis play a limited role in NFPA behavior. [ABSTRACT FROM AUTHOR]

Rationale: When acutely administered intraperitoneally, the non-psychoactive cannabinoid cannabidiol (CBD), its acidic precursor cannabidiolic acid (CBDA) and a stable methyl ester of CBDA (HU-580) reduce lithium chloride (LiCl)–induced conditioned gaping in male rats (a selective preclinical model of acute nausea) via activation of the serotonin 1A (5-HT1A) receptor. Objectives: To utilise these compounds to manage nausea in the clinic, we must determine if their effectiveness is maintained when injected subcutaneously (s.c) and when repeatedly administered. First, we compared the effectiveness of each of these compounds to reduce conditioned gaping following repeated (7-day) and acute (1-day) pretreatments and whether these anti-nausea effects were mediated by the 5-HT1A receptor. Next, we assessed whether the effectiveness of these compounds can be maintained when administered prior to each of 4 conditioning trials (once per week). We also evaluated the ability of repeated CBD (7 days) to reduce LiCl-induced vomiting in Suncus murinus. Finally, we examined whether acute CBD was equally effective in male and female rats. Results: Both acute and repeated (7 day) s.c. administrations of CBD (5 mg/kg), CBDA (1 μg/kg) and HU-580 (1 μg/kg) similarly reduced LiCl-induced conditioned gaping, and these effects were blocked by 5HT1A receptor antagonism. When administered over 4 weekly conditioning trials, the anti-nausea effectiveness of each of these compounds was also maintained. Repeated CBD (5 mg/kg, s.c.) maintained its anti-emetic efficacy in S. murinus. Acute CBD (5 and 20 mg/kg, s.c.) administration reduced LiCl-induced conditioned gaping similarly in male and female rats. Conclusion: When administered repeatedly (7 days), CBD, CBDA and HU-580 did not lose efficacy in reducing nausea and continued to act via agonism of the 5-HT1A receptor. When administered across 4 weekly conditioning trials, they maintained their effectiveness in reducing LiCl-induced nausea. Repeated CBD also reduced vomiting in shrews. Finally, CBD's anti-nausea effects were similar in male and female rats. This suggests that these cannabinoids may be useful anti-nausea and anti-emetic treatments for chronic conditions, without the development of tolerance. [ABSTRACT FROM AUTHOR]

Single-molecule sensing is becoming a major driver in biomarker assays as it is foreseen to enable precision medicine to enter into everyday clinical practice. However, among the single-molecule detection methods proposed so far, only a few are fully exploitable for the ultrasensitive label-free assay of biofluids. Firstly introduced single-molecule sensing platforms encompass low-background-noise fluorescent microscopy as well as plasmonic and electrical nanotransducers; these are generally able to sense at the nanomolar concentration level or higher. Label-based single-molecule technologies relying on optical transduction and microbeads that can scavenge and detect a few biomarkers in the bulk of real biofluids, reaching ultralow detection limits, have been recently commercialized. These assays, thanks to the extremely high sensitivity and convenient handling, are new trends in the field as they are paving the way to a revolution in early diagnostics. Very recently, another new trend is the label-free, organic bioelectronic electrolyte-gated large transistors that can potentially be produced by means of large-area low-cost technologies and have been proven capable to detect a protein at the physical limit in real bovine serum. This article offers a bird's-eye view on some of the more significant single-molecule bioanalytical technologies and highlights their sensing principles and figures-of-merit such as limit of detection, need for a labelling step, and possibility to operate, also as an array, directly in real biofluids. We also discuss the new trend towards single-molecule proof-of-principle extremely sensitive technologies that can detect a protein at the zeptomolar concentration level involving label-free devices that potentially offer low-cost production and easy scalability. [ABSTRACT FROM AUTHOR]

Although recurrent infections in Rubinstein–Taybi syndrome (RSTS) are common, and probably multifactorial, immunological abnormalities have not been extensively described with only isolated cases or small case series of immune deficiency and dysregulation having been reported. The objective of this study was to investigate primary immunodeficiency (PID) and immune dysregulation in an international cohort of patients with RSTS. All published cases of RSTS were identified. The corresponding authors and researchers involved in the diagnosis of inborn errors of immunity or genetic syndromes were contacted to obtain up-to-date clinical and immunological information. Ninety-seven RSTS patients were identified. For 45 patients, we retrieved data from the published reports while for 52 patients, a clinical update was provided. Recurrent or severe infections, autoimmune/autoinflammatory complications, and lymphoproliferation were observed in 72.1%, 12.3%, and 8.2% of patients. Syndromic immunodeficiency was diagnosed in 46.4% of individuals. Despite the broad heterogeneity of immunodeficiency disorders, antibody defects were observed in 11.3% of subjects. In particular, these patients presented hypogammaglobulinemia associated with low B cell counts and reduction of switched memory B cell numbers. Immunoglobulin replacement therapy, antibiotic prophylaxis, and immunosuppressive treatment were employed in 16.4%, 8.2%, and 9.8% of patients, respectively. Manifestations of immune dysfunctions, affecting mostly B cells, are more common than previously recognized in patients with RSTS. Full immunological assessment is warranted in these patients, who may require detailed investigation and specific supportive treatment. [ABSTRACT FROM AUTHOR]

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A unified analytical technology based on the integration of scanning probe nanotomography and optical microscopy (SPNT–OM) is presented, and the potential of the technology is demonstrated by the example of a multiparameter analysis of encoded microspheres. The presented SPNT–OM technology can become a powerful tool for multimodal nanocharacterization of a wide range of microparticles, composites, and hybrid polymers. [ABSTRACT FROM AUTHOR]

Rationale: This study evaluated the potential of combined cannabis constituents to reduce nausea. Objectives: Using the lithium chloride (LiCl)-induced conditioned gaping model of nausea in male rats, we aimed to: 1) Determine effective anti-nausea doses of cannabidiol (CBD) 2) Determine effectiveness and the mechanism of action of combined subthreshold doses of CBD and Δ9-tetrahydrocannabinol (THC) 3) Determine effective doses of synthetic cannabidiolic acid (CBDA) 4) Determine effective doses of synthetic tetrahydrocannabinolic acid (THCA) 5) Determine the mechanism of action for THCA 6) Determine effectiveness and the mechanism of action of combined subthreshold doses of CBDA and THCA Results: CBD (0.5–5 mg/kg, intraperitoneal [i.p.]) reduces LiCl-induced conditioned gaping (but 0.1, 20, 40 mg/kg are ineffective). Combined subthreshold doses of CBD (0.1 mg/kg, i.p.) and THC (0.1 mg/kg, i.p.) produce suppression of conditioned gaping, and this effect is blocked by administration of either WAY100635 (a serotonin 1A [5-HT1A]) receptor antagonist or SR141716 (SR; a CB1 receptor antagonist). THCA (0.01 mg/kg, i.p.) reduces conditioned gaping and administration of MK886 (a peroxisome proliferator-activated receptor alpha [PPARα] antagonist) blocked THCA's anti-nausea effect. Combined subthreshold doses of CBDA (0.00001 mg/kg, i.p.) and THCA (0.001 mg/kg, i.p.) produce suppression of conditioned gaping, and this effect is blocked by administration of WAY100635 or MK886. Conclusion: Combinations of very low doses of CBD + THC or CBDA + THCA robustly reduce LiCl-induced conditioned gaping. Clinical trials are necessary to determine the efficacy of using single or combined cannabinoids as adjunct treatments with existing anti-emetic regimens to manage chemotherapy-induced nausea. [ABSTRACT FROM AUTHOR]

Asthma is a common, complex, multifaceted disease. It comprises multiple phenotypes, which might benefit from treatment with different types of innovative targeted therapies. Refining these phenotypes and understanding their underlying biological structure would help to apply precision medicine approaches. Using different omics methods, such as (epi)genomics, transcriptomics, proteomics, metabolomics, microbiomics, and exposomics, allowed to view and investigate asthma from diverse angles. Technological advancement led to a large increase in the application of omics studies in the asthma field. Although the use of omics technologies has reduced the gap between bench to bedside, several design and methodological challenges still need to be tackled before omics can be applied in asthma patient care. Collaborating under a centralized harmonized work frame (such as in consortia, under consistent methodologies) could help worldwide research teams to tackle these challenges. In this review, we discuss the transition of single biomarker research to multi-omics studies. In addition, we deliberate challenges such as the lack of standardization of sampling and analytical methodologies and validation of findings, which comes in between omics and personalized patient care. The future of omics in asthma is encouraging but not completely clear with some unanswered questions, which have not been adequately addressed before. Therefore, we highlight these questions and emphasize on the importance of fulfilling them. [ABSTRACT FROM AUTHOR]

Purpose: Cardiac autonomic dysfunction manifests as reduced heart rate variability (HRV) in idiopathic Parkinson's disease (PD), but no significant reduction has been found in PD patients who carry the LRRK2 mutation. Novel HRV features have not been investigated in these individuals. We aimed to assess cardiac autonomic modulation through standard and novel approaches to HRV analysis in individuals who carry the LRRK2 G2019S mutation. Methods: Short-term electrocardiograms were recorded in 14 LRRK2-associated PD patients, 25 LRRK2-non-manifesting carriers, 32 related non-carriers, 20 idiopathic PD patients, and 27 healthy controls. HRV measures were compared using regression modeling, controlling for age, sex, mean heart rate, and disease duration. Discriminant analysis highlighted the feature combination that best distinguished LRRK2-associated PD from controls. Results: Beat-to-beat and global HRV measures were significantly increased in LRRK2-associated PD patients compared with controls (e.g., deceleration capacity of heart rate: p = 0.006) and idiopathic PD patients (e.g., 8th standardized moment of the interbeat interval distribution: p = 0.0003), respectively. LRRK2-associated PD patients also showed significantly increased irregularity of heart rate dynamics, as quantified by Rényi entropy, when compared with controls (p = 0.002) and idiopathic PD patients (p = 0.0004). Ordinal pattern statistics permitted the identification of LRRK2-associated PD individuals with 93% sensitivity and 93% specificity. Consistent results were found in a subgroup of LRRK2-non-manifesting carriers when compared with controls. Conclusions: Increased beat-to-beat HRV in LRRK2 G2019S mutation carriers compared with controls and idiopathic PD patients may indicate augmented cardiac autonomic cholinergic activity, suggesting early impairment of central vagal feedback loops in LRRK2-associated PD. [ABSTRACT FROM AUTHOR]

Monitoring T cells is of major importance for the development of immunotherapies. Recent sophisticated assays can address particular aspects of the anti-tumor T-cell repertoire or support very large-scale immune screening for biomarker discovery. Robust methods for the routine assessment of the quantity and quality of antigen-specific T cells remain, however, essential. This review discusses selected methods that are commonly used for T-cell monitoring and summarizes the advantages and limitations of these assays. We also present a new functional assay, which specifically detects activated β2 integrins within a very short time following CD8+ T-cell stimulation. Because of its unique and favorable characteristics, this assay could be useful for implementation into our T-cell monitoring toolbox. [ABSTRACT FROM AUTHOR]

A series of isoxazole-thiadiazole linked carbazole derivatives 12a–12j are synthesized and their chemical structures confirmed by 1H and 13C NMR and mass spectra. The products are tested for their anticancer activity against human cancer cell lines: MCF-7 (breast), A549 (lung), DU-145 (prostate), and MDA MB-231 (breast) by using MTT assay and etoposide as a reference drug. The accumulated data indicate that most of the compounds demonstrate anticancer activity higher than etoposide. [ABSTRACT FROM AUTHOR]

In the literature, there are reports of the utilization of various hydrogels to create generic platforms for protein microarray applications. Here, a novel strategy was developed to obtain high-performance microarrays. In it, a dextran hydrogel is used to covalently immobilize oligonucleotides and proteins. This method employs aqueous solutions of dextran methacrylate (Dx-MA), which is a biocompatible photopolymerizable monomer. Capture probes are immobilized inside the hydrogel via a light-induced thiol–acrylate coupling reaction at the same time as the dextran polymer is formed. Hydrogel microarrays based on this technique were prepared on different surfaces, such as a Blu-ray Disk and polycarbonate or alkene-functionalized glass slides, and these systems showed high probe-loading capabilities and good biorecognition yields. This methodology presents advantages such as a low cost, a short analysis time, a low limit of detection, and multiplexing capabilities, among others. Confocal fluorescence microscopy analysis demonstrated that in these hydrogel-based microarrays, receptor immobilization and the biorecognition event occurred within the hydrogel and not merely on the surface. [ABSTRACT FROM AUTHOR]

Electricity can be directly biogenerated by bacteria in a microbial fuel cell (MFC) using many different biodegradable wastes as substrate. When cellulose is used as a substrate, the cellulolytic and electrogenic activities require a microbial consortium for energy generation. In this study, cellulose-degrading bacteria were isolated from an MFC using CMC (carboxymethylcellulose) agar medium and their cellulolytic activity was assessed. Cellulolytic bacteria isolated from the MFC were characterized and identified based on their phenotypic characteristics and analysis of their 16S rRNA genes sequence. Of thirty-two isolates, only ten cellulolytic bacterial strains were successfully isolated from the MFC reactor under aerobic conditions. The bacterial isolates had a cellulolytic index between 3.63 to 8.96 U mL-1. The bacterial strain SAM3a demonstrated high identity (99% via 16S-rRNA sequencing) to Staphylococcus saprophyticus which showed the highest CMCase activity (8.96) 0.34U mL-1). Enterobacter cancerogenus JCT-55 showed the next highest CMCase activity (8.34 ± 0.56 U mL-1); S. epidermidis BAB-2554 showed the lowest CMCase activity (3.63) 0.05 U mL-1). In the MFC, the genus Staphylococcus was found to be the most dominant group of cellulose-degrading bacteria which used rice straw as a carbon source. In this study, Escherichia coli, S. saprophyticus, Enterobacter cancerogenus, S. epidermidis, S. hominis, Bacillus subtilis, L. murinus, S. haemolyticus, S. epidermidis, and S. epidermidis were found to possess cellulolytic activity. [ABSTRACT FROM AUTHOR]

Fanconi anemia (FA) is a genetically and clinically heterogeneous disorder that predisposes patients to bone marrow failure (BMF), myelodysplastic syndromes (MDS), and acute myeloid leukemia (AML). To study which genetic and phenotypic factors predict clinical outcomes for Japanese FA patients, we examined the FA genes, bone marrow karyotype, and aldehyde dehydrogenase-2 (ALDH2) genotype; variants of which are associated with accelerated progression of BMF in FA. In 88 patients, we found morphologic MDS/AML in 33 patients, including refractory cytopenia in 16, refractory anemia with excess blasts (RAEB) in 7, and AML in 10. The major mutated FA genes observed in this study were FANCA (n = 52) and FANCG (n = 23). The distribution of the ALDH2 variant alleles did not differ significantly between patients with mutations in FANCA and FANCG. However, patients with FANCG mutations had inferior BMF-free survival and received hematopoietic stem cell transplantation (HSCT) at a younger age than those with FANCA mutations. In FANCA, patients with the c.2546delC mutation (n = 24) related to poorer MDS/AML-free survival and a younger age at HSCT than those without this mutation. All patients with RAEB/AML had an abnormal karyotype and poorer prognosis after HSCT; specifically, the presence of a structurally complex karyotype with a monosomy (n = 6) was associated with dismal prognosis. In conclusion, the best practice for a clinician may be to integrate the morphological, cytogenetic, and genetic data to optimize HSCT timing in Japanese FA patients. [ABSTRACT FROM AUTHOR]

Purpose: Very little is known about the genetic risk factors associated with triple-negative breast cancer (TNBC), an aggressive clinical subtype characterised by the absence of ER, PR and HER2. p53, the tumour suppressor gene, is essential for maintaining genomic stability in response to cellular stress. In breast cancer, the mutation rates of TP53 vary depending on the subtype, such that ER-negative tumours have a high rate, and in ER-positive tumours they are less common. Previous studies have implicated the intronic polymorphism in TP53 (rs17878362; or PIN3) with an increased risk of developing breast cancer, although little has been discerned on its prevalence in different subtypes. In this study, we investigated the prevalence of the PIN3 genotype in the blood of cohorts with ER-positive and the ER-negative subtype TNBC, and assessed its association with outcome.Methods: We genotyped 656 TNBC and 648 ER-positive breast cancer patients, along with 436 controls, and compared the prevalence of polymorphism rs17878362 in these cohorts.Results: We found there to be no differences in the prevalence of the PIN3 genotype between the ER-positive and TNBC cohorts. Furthermore, no statistically significant difference was observed in the outcome of patients in either cohort with respect to their PIN3 genotype.Conclusions: Taken together, our results do not support an association of the PIN3 genotype with increased breast cancer risk, either in ER-positive or ER-negative patients. [ABSTRACT FROM AUTHOR]

Therapeutic cancer vaccines have shown limited clinical efficacy so far. Nevertheless, in the meantime, our understanding of immune cell function and the interactions of immune cells with growing tumors has advanced considerably. We are now in a position to invest this knowledge into the design of more powerful vaccines and therapy combinations aimed at increasing immunogenicity and decreasing tumor-induced immunosuppression. This review focuses essentially on peptide-based human vaccines. We will discuss two aspects that are critical for increasing their intrinsic immunogenicity: the selection of the antigen(s) to be targeted, and the as yet unmet need for strong adjuvants. [ABSTRACT FROM AUTHOR]

The antigenic landscape of the adaptive immune response is determined by the peptides presented by immune cells. In recent years, a number of immune-based cancer therapies have been shown to induce remarkable clinical responses through the activation of the patient's immune system. As a result, there is a need to identify immune biomarkers capable of predicting clinical response. Recent advances in proteomics have led to considerable developments in the more comprehensive profiling of the immune response. "Immunoproteomics" utilises a rapidly increasing collection of technologies in order to identify and quantify antigenic peptides or proteins. This includes gel-based, array-based, mass spectrometry (MS), DNA-based, or computer-based (in silico) approaches. Immunoproteomics is yielding an understanding of disease and disease progression, vaccine candidates, and biomarkers to a depth not before understood. This review gives an overview of the emerging role of proteomics in improving personalisation of immunotherapy treatment. [ABSTRACT FROM AUTHOR]

To make biomass conversion to fuels more cost-effective, value-added products, including pharmaceuticals, should be produced from agricultural residues. The objectives of this study were (1) to investigate the antioxidant properties of bio-oil produced from the pyrolysis of biomass and (2) to concentrate and identify antioxidant compounds from the bio-oil. This study used a two stage mechanically fluidized reactor (MFR) where the first stage, termed one-dimensional (1-D), produces vapors with varying chemical composition based on the reactor temperature while the two-dimensional (2-D) stage, separates vapor components according to their condensation temperature. Tobacco leaf (Nicotiana tabacum), tomato plant (Solanum lycopersicum) and spent coffee (Coffea arabica) grounds (<1 mm) were pyrolyzed at a heating rate of 10 °C/min from ambient to 565 °C. The 400-565 °C reactor temperature cuts of all three biomass bio-oils from 1-D MFR pyrolysis produced the highest amount of antioxidant activity compared to the other bio-oil cuts and the 2-D MFR pyrolysis of tomato plant bio-oil collected in the 120 °C condenser had the highest concentration of antioxidants. The 50% 2,2-diphenyl-1-picrylhydrazyl (DPPH) scavenging potential (IC50 value) of the reference compound ascorbic acid and tomato bio-oil cut collected in the 120 °C condenser was 138 µg/mL versus 37 mg/mL, respectively. The gas chromatography-mass spectrometry (GC-MS) analysis identified 2-furanmethanol, phenol and glucose in the tomato bio-oil. The findings indicate the two stage MFR process can be used to concentrate antioxidants during bio-oil production by reactor and condenser temperature controls thus providing a useful tool for producing value-added compounds while processing agricultural residues. [ABSTRACT FROM AUTHOR]

A novel multifunctional carbazole-aminoquinoline dimer PZ001 was designed, synthesized, and evaluated. The results indicated that PZ001 possessed selective copper chelation, and inhibited copper-induced Aβ1-42 aggregation. Furthermore, PZ001 exerted powerful neuroprotection against glutamate-induced HT22 cell death. These results suggest that PZ001 may be a promising multifunctional anti-AD compound. [ABSTRACT FROM AUTHOR]