Clinical Significance of Faecal Calprotectin in Differentiating Inflammatory Bowel Disease from Irritable Bowel Syndrome.

Inflammatory bowel disease (IBD) is a chronic idiopathic inflammatory disorder of the gastrointestinal tract with relapsing and remitting course. Recurrent abdominal pain and discomfort in association with abnormal defecation in the absence of structural abnormality of the gut is the key feature of irritable bowel syndrome (IBS). Faecal biomarker may be used a precise tool in the differentiation of IBD and IBS. The aim of this study was to measure faecal calprotectin (FC) in patients with IBD and IBS and compare between them. This was a cross-sectional study done in the department of Gastroenterology, BSMMU, Bangladesh from May 2017 to August 2018. IBD patients were diagnosed on the basis of compatible history, clinical examination, laboratory, radiological and endoscopic findings. IBS patients were selected by using the Rome IV criteria. Quantitative faecal calprotectin ELISA (BUHLMANN Quantum Blue) test was done and compared between IBD and IBS patients. In this study, ninety (90) patients were enrolled, 45 patients with IBD and 45 patients with IBS. Mean age of the IBD patients was 32.24±9.76 years and IBS patients was 33.80±9.70 years. There were 28(62.2%) male and 17(37.8%) female patients with IBD and 30(66.7%) male and 15(33.3%) female patients with IBS. We found faecal calprotectin (FC) level was 445.68±237.35µg/gm in IBD patients and 39.16±17.31µg/gm in IBS patients. There was a significant difference of faecal calprotectin level between IBD and IBS patients (p-value <0.001). The sensitivity and specificity of faecal calprotectin to differentiate IBD from IBS was 91.1% and 86.7% respectively. The test accuracy was 88.9%. Area under ROC was 0.959 (95% CI, 0.909 to 1.0). This study showed that faecal calprotectin appears to be clinically useful, non-invasive, rapid and reliable marker to differentiate IBD from IBS.

Multi-center external validation of an automated method segmenting and differentiating atypical lipomatous tumors from lipomas using radiomics and deep-learning on MRI.

Background: As differentiating between lipomas and atypical lipomatous tumors (ALTs) based on imaging is challenging and requires biopsies, radiomics has been proposed to aid the diagnosis. This study aimed to externally and prospectively validate a radiomics model differentiating between lipomas and ALTs on MRI in three large, multi-center cohorts, and extend it with automatic and minimally interactive segmentation methods to increase clinical feasibility. Methods: Three study cohorts were formed, two for external validation containing data from medical centers in the United States (US) collected from 2008 until 2018 and the United Kingdom (UK) collected from 2011 until 2017, and one for prospective validation consisting of data collected from 2020 until 2021 in the Netherlands. Patient characteristics, MDM2 amplification status, and MRI scans were collected. An automatic segmentation method was developed to segment all tumors on T1-weighted MRI scans of the validation cohorts. Segmentations were subsequently quality scored. In case of insufficient quality, an interactive segmentation method was used. Radiomics performance was evaluated for all cohorts and compared to two radiologists. Findings: The validation cohorts included 150 (54% ALT), 208 (37% ALT), and 86 patients (28% ALT) from the US, UK and NL. Of the 444 cases, 78% were automatically segmented. For 22%, interactive segmentation was necessary due to insufficient quality, with only 3% of all patients requiring manual adjustment. External validation resulted in an AUC of 0.74 (95% CI: 0.66, 0.82) in US data and 0.86 (0.80, 0.92) in UK data. Prospective validation resulted in an AUC of 0.89 (0.83, 0.96). The radiomics model performed similar to the two radiologists (US: 0.79 and 0.76, UK: 0.86 and 0.86, NL: 0.82 and 0.85). Interpretation: The radiomics model extended with automatic and minimally interactive segmentation methods accurately differentiated between lipomas and ALTs in two large, multi-center external cohorts, and in prospective validation, performing similar to expert radiologists, possibly limiting the need for invasive diagnostics. Funding: Hanarth fonds.

Estimates of actual and potential lives saved in the United States from the use of COVID-19 convalescent plasma.

In the Spring of 2020, the United States of America (USA) deployed COVID-19 convalescent plasma (CCP) to treat hospitalized patients. Over 500,000 patients were treated with CCP during the first year of the pandemic. In this study, we estimated the number of actual inpatient lives saved by CCP treatment in the United States of America based on CCP weekly use, weekly national mortality data, and CCP mortality reduction data from meta-analyses of randomized controlled trials and real-world data. We also estimate the potential number of lives saved if CCP had been deployed for 100% of hospitalized patients or used in 15 to 75% of outpatients. Depending on the assumptions modeled in stratified analyses, we estimated that CCP saved between 16,476 and 66,296 lives. The CCP ideal use might have saved as many as 234,869 lives and prevented 1,136,133 hospitalizations. CCP deployment was a successful strategy for ameliorating the impact of the COVID-19 pandemic in the USA. This experience has important implications for convalescent plasma use in future infectious disease emergencies.

Cellular taxonomy of the preleukemic bone marrow niche of acute myeloid leukemia.

Leukemias arise from recurrent clonal mutations in hematopoietic stem/progenitor cells (HSPCs) that cause profound changes in the bone marrow microenvironment (BMM) favoring leukemic stem cell (LSC) growth over normal HSPCs. Understanding the cross talk between preleukemic mutated HSPCs and the BMM is critical to develop novel therapeutic strategies to prevent leukemogenesis. We hypothesize that preleukemic-LSCs (pLSCs) induce BMM changes critical for leukemogenesis. Using our AML-murine model, we performed single-cell RNA-sequencing of preleukemic BMM (pBMM) cells. We found normal HSC (nHSC)-regulating LepR+ mesenchymal stem cells, and endothelial cells were decreased, along with increases in CD55+ fibroblasts and pericytes. Preleukemic CD55+ fibroblasts had higher proliferation rates and decreased collagen expression, suggesting extracellular matrix remodeling during leukemogenesis. Importantly, co-culture assays found preleukemic CD55+ fibroblasts expanded pLSCs significantly over nHSCs. In conclusion, we have identified a distinct pBMM and a novel CD55+ fibroblast population that is expanded in pBMM that promote fitness of pLSCs over nHSCs.

Downregulation of type I interferon signalling pathway by urate in primary human PBMCs.

Type I interferons (IFN1s) mediate innate responses to microbial stimuli and regulate interleukin (IL)-1 and IL-1 receptor antagonist (Ra) production in human cells. This study explores interferon-stimulated gene (ISG) alterations in the transcriptome of patients with gout and stimulated human primary cells in vitro in relation to serum urate concentrations. Peripheral blood mononuclear cells (PBMCs) and monocytes of patients with gout were primed in vitro with soluble urate, followed by lipopolysaccharide (LPS) stimulation. Separately, PBMCs were stimulated with various toll-like receptor (TLR) ligands. RNA sequencing and IL-1Ra cytokine measurement were performed. STAT1 phosphorylation was assessed in urate-treated monocytes. Cytokine responses to IFN-ß were evaluated in PBMCs cultured with or without urate and restimulated with LPS and monosodium urate (MSU) crystals. Transcriptomics revealed suppressed IFN-related signalling pathways in urate-exposed PBMCs or monocytes which was supported by diminishment of phosphorylated STAT1. The stimulation of PBMCs with IFN-ß did not modify the urate-induced inflammation. Interestingly, in vivo, serum urate concentrations were inversely correlated to in vitro ISG expression upon stimulations with TLR ligands. These findings support a deficient IFN1 signalling in the presence of elevated serum urate concentrations, which could translate to increased susceptibility to infections.

Wind Shapes the Growth Strategies of Trees in a Tropical Forest.

In tropical forests, trees strategically balance growth patterns to optimise fitness amid multiple environmental stressors. Wind poses the primary risk to a tree's mechanical stability, prompting developments such as thicker trunks to withstand the bending forces. Therefore, a trade-off in resource allocation exists between diameter growth and vertical growth to compete for light. We explore this trade-off by measuring the relative wind mortality risk for 95 trees in a tropical forest in Panama and testing how it varies with tree size, species and wind exposure. Surprisingly, local wind exposure and tree size had minimal impact on wind mortality risk; instead, species wood density emerged as the crucial factor. Low wood density species exhibited a significantly greater wind mortality risk, suggesting a prioritisation of competition for light over biomechanical stability. Our study highlights the pivotal role of wind safety in shaping the life-history strategy of trees and structuring diverse tropical forests.

Research Participation and Feedback: Perception of Adolescents and Young Adults Living with HIV in Lagos, Nigeria.

BACKGROUND: Evidence-based research remains the cornerstone in changing the narrative of wholesome health among Adolescents and Young Adults Living with HIV (AYALHIV). However, little is known about the perceptions of AYALHIV in research participation and outcomes, in low- and middle-income countries, especially in sub-Saharan Africa. This study describes the perception of AYALHIV in research participation and outcome in Lagos, Nigeria. METHODS: The study population was drawn from a cohort of participants in a cross-sectional study at the Nigerian Institute of Medical Research. The survey questions were on perceptions of the importance of research participation, the frequency, understanding of participation in research, the interest in the outcome, the knowledge of the interpretation of the outcome and the willingness to participate in future studies. Data obtained was analyzed using SPSS version 26.0. RESULTS: The mean age of the AYALHIV was 15.7(±3.1) years, with a male-to-female ratio of (0.8:1), and 85.7% on antiretroviral drugs for at least five years. Seventy-two percent (46/63) have been involved in previous studies at least once, with only 27% (17/63) informed on the outcome of the research they have ever participated. Only 30% (19) of participants understood they were involved in research, with 92% interested in the study outcome. 87.3% (55) will request more information before participating in future research activities. CONCLUSION: Educating AYALHIV on research participation is important in promoting concerted efforts by researchers towards improving engagement, patient-centred care, and research dissemination.

CONTEXTE: La recherche fondée sur des données probantes reste la pierre angulaire du changement du discours sur la santé saine chez les adolescents et les jeunes adultes vivant avec le VIH (AYALHIV). Cependant, on sait peu de choses sur les perceptions de l'AYALHIV dans la participation et les résultats de la recherche, dans les pays à revenu faible et intermédiaire, en particulier en Afrique subsaharienne. Cette étude décrit la perception d'AYALHIV dans la participation et les résultats de la recherche à Lagos, au Nigéria. METHODES: La population m'étudiée a été tirée d'une cohorte de participants à une étude transversale menée à l'Institut nigérian de recherche médicale. Les questions de l'enquête portaient sur les perceptions de l'importance de la participation à la recherche, la fréquence, la compréhension de la participation à la recherche, l'intérêt pour les résultats, la connaissance de l'interprétation des résultats et la volonté de participer à des études futures. Les données obtenues ont été analysées à l'aide de SPSS version 26.0. RESULTATS: L'âge moyen des AYALHIV était de 15,7 (± 3,1) ans, avec un ratio hommes/femmes de (0,8 : 1) et 85,7 % prenaient des médicaments antirétroviraux depuis au moins cinq ans. Soixantedouze pour cent (46/63) ont participé à des études antérieures au moins une fois, et seulement 27 % (17/63) sont informés des résultats de la recherche à laquelle ils ont déjà participé. Seulement 30 % (19) des participants comprenaient qu'ils étaient impliqués dans la recherche, et 92 % d'entre eux étaient intéressés par les résultats de l'étude. 87,3 % (55) demanderont plus d'informations avant de participer à de futures activités de recherche. CONCLUSION: Éduquer AYALHIV sur la participation à la recherche est important pour promouvoir les efforts concertés des chercheurs en vue d'améliorer l'engagement, les soins centrés sur le patient et la diffusion de la recherche. MOTS CLES: VIH, Adolescent, Jeunes adultes, Perception, Recherche.

CRISPR-Cas9: Unraveling Genetic Secrets to Enhance Floral and Fruit Traits in Tomato.

Tomato, a globally consumed vegetable, possesses vast genetic diversity, making it suitable for genetic manipulation using various genetic improvement techniques. Tomatoes are grown extensively for their market value and health benefits, primarily contributed by enhanced yield and nutritional value respectively, influenced by floral and fruit traits. Floral morphology is maintained by genes involved in meristem size control, regulation of inflorescence transition, and pollen development. SP (SELF-PRUNING) and SP5G (SELF-PRUNING 5G) determine growth habit and flowering time. RIN (RIPENING INHIBITOR) and PG (POLYGALACTURONASE) are responsible for the shelf life of fruits. In addition to this, nutrition-enriched tomatoes have been developed in recent times. In this review, we comprehensively discuss the major genes influencing floral morphology, flowering time, fruit size, fruit shape, shelf life, and nutritional value, ultimately resulting in enhanced yield. Additionally, we address the advances in CRISPR/Cas9 applied for the genetic improvement of tomatoes along with prospects of areas in which research development in terms of tomato genetic improvement has to be advanced.

Spatially resolved photoluminescence analysis of the role of Se in CdSexTe1-x thin films.

Evidence from cross-sectional electron microscopy has previously shown that Se passivates defects in CdSexTe1-x solar cells, and that this is the reason for better lifetimes and voltages in these devices. Here, we utilise spatially resolved photoluminescence measurements of CdSexTe1-x thin films on glass to directly study the effects of Se on carrier recombination in the material, isolated from the impact of conductive interfaces and without the need to prepare cross-sections through the samples. We find further evidence to support Se passivation of grain boundaries, but also identify an increase in below-bandgap photoluminescence that indicates the presence of Se-enhanced defects in grain interiors. Our results show that whilst Se treatment, in tandem with Cl passivation, does increase radiative efficiencies in CdSexTe1-x, it simultaneously increases the defect content within the grain interiors. This suggests that although it is beneficial overall, Se incorporation will still limit the maximum attainable optoelectronic properties of CdSexTe1-x thin films.

Hematology in ornamental discus fish Symphysodon discus from Amazonian, Brazil.

Symphysodon discus is known in the world of aquariums for its market value, beauty, and behavior. However, more substantial information about its physiology and biology must be available, which can hinder its development and maintenance in breeding systems. The study evaluated the blood biochemistry and erythrogram of 20 specimens of S. discus captured in the municipality of Barcelos, Amazonas, with an average weight of 89.80 ± 7.13 g and an average length of 13.48 ± 0.55 cm. The erythrogram evaluated variables such as hematocrit (Ht), hemoglobin (Hb), red blood cell count (RBC), mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), and mean corpuscular hemoglobin concentration (MCHC). Blood biochemistry was analyzed, including cholesterol levels, total proteins, triglycerides, glucose, urea, and chlorides. Intra-specific variations were observed between the surveyed individuals about the Hb, MCV, and MCH values. The values of triglycerides, cholesterol, and chlorides were elevated compared to other cichlids. This study may be useful to serve as a parameter to indicate the normal health conditions of this Amazonian cichlid. It can be applied in studies for ornamental fish farming and actions for managing and conserving the species.

Hyphal swelling induced in the phagosome of macrophages.

Macrophages play critical protective roles as sentinels of the innate immune system against fungal infection. It is therefore important to understand the dynamics of the interaction between these phagocytes and their fungal prey. We show here that many of the hyphal apices formed by Candida albicans within the macrophage ceased elongating, and apical and sub-apical hyphal compartments became swollen. Swollen hyphal cell compartments assimilated less Lysotracker-Red than non-swollen compartments, suggesting they had enhanced viability. Staining with florescent dyes suggested that there were higher levels of ß-glucan and chitin in internalized fungal filaments compared to non-internalized hyphae, suggesting active cell wall remodelling within macrophages. These observations suggest that the stresses imposed by macrophages upon the fungus lead to changes in cell wall composition, inhibition of polarised growth and the induction of swelling in hyphal compartments, and that this can prevent or delay loss of viability of hyphal cells within the phagocyte.

Nasal endoscopy score thresholds to trigger consideration of chronic rhinosinusitis treatment escalation and implications for disease control.

BACKGROUND: In the absence of direct evidence supporting how to use nasal endoscopy findings to judge chronic rhinosinusitis (CRS) disease control, experts' practice patterns could provide guidance. METHODOLOGY: Participants consisted of a diverse group of twenty-nine rhinologists. Participants were presented with every possible combination of bilateral nasal endoscopy findings represented by the modified Lund-Kennedy (MLK; range: 0-12) endoscopic scoring system and Nasal Polyp Score (NPS; range: 0-8). Reflecting the practical consequence of CRS disease control assessment, participants were asked whether they would consider CRS treatment escalation based on each scenario in the absence of any CRS symptoms, and how strongly they considered escalating therapy. The same scenarios were then presented in the context of 1 burdensome CRS symptom and participants again were asked whether they would consider treatment escalation. RESULTS: The median threshold total MLK score for considering treatment escalation was ≥4 and 75.9% of participants' MLK thresholds were within 1 point of 4. The median threshold total NPS for considering treatment escalation was ≥3 and 62.5% of participants' NPS thresholds were within 1 point of 3. Endoscopy score thresholds decreased in the presence of 1 burdensome symptom and generally increased when requiring stronger affirmation for considering CRS treatment escalation. CONCLUSION: Reflecting the practice patterns of a diverse group of rhinologists, MLK score ≥4 or NPS ≥3 may serve as thresholds for considering CRS treatment escalation. Alternatively, MLK score.

Cell wall alterations occurring in an evolved multi-stress tolerant strain of the oleaginous yeast Rhodotorula toruloides.

The oleaginous yeast species Rhodotorula toruloides is a promising candidate for applications in circular bioeconomy due to its ability to efficiently utilize diverse carbon sources being tolerant to cellular stress in bioprocessing. Previous studies including genome-wide analyses of the multi-stress tolerant strain IST536 MM15, derived through adaptive laboratory evolution from a promising IST536 strain for lipid production from sugar beet hydrolysates, suggested the occurrence of significant modifications in the cell wall. In this study, the cell wall integrity and carbohydrate composition of those strains was characterized to gain insights into the physicochemical changes associated to the remarkable multi-stress tolerance phenotype of the evolved strain. Compared to the original strain, the evolved strain exhibited a higher proportion of glucomannans, fucogalactomannans, and chitin relative to (1→4)-linked glucans, and an increased presence of glycoproteins with short glucosamine derived oligosaccharides, which have been found to be associated to ethanol stress tolerance and physical strength of the cell wall. Furthermore, the evolved strain cells were found to be significantly smaller than the original strain and more resistant to thermal and mechanical disruption, consistent with higher proportion of beta-linked polymers instead of glycogen, conferring a more rigid and robust cell wall. These findings provide further insights into the cell wall composition of this basidiomycetous red yeast species and into the alterations occurring in a multi-stress tolerant evolved strain. This new information can guide yeast genome engineering towards more robust strains of biotechnological relevance.

Emerging evidence of a link between inflammation and the neuropathology of prenatal opioid exposure.

Opioid use continues to increase, particularly among women of reproductive age. As a result, increasing numbers of infants are born with prenatal exposure to opioids, suffering both acute and long-term negative consequences. Studies performed across the past 5 years have highlighted both peripheral and central inflammation as a consistent feature of prenatal opioid exposure. Dysregulated innate and adaptive immunity have been detected in human and rodent studies, highlighting a likely role of inflammation in the neuropathology associated with opioid exposure. Identifying immune changes occurring following prenatal opioid exposure will be critical for developing new therapeutic approaches in this field.

Early antibody responses to lipid antigens in red deer infected with Mycobacterium bovis.

THE PROBLEM: Early and rapid diagnosis of bovine tuberculosis remains an issue of great interest. AIM: The aim of this study was to evaluate the use of synthetic lipid antigens for diagnosis of tuberculosis in red deer (Cervus elaphus). The proposition: Synthetic mycolic acid derivatives, identical to components of mycobacterial cells, bind to antibodies to lipids produced in active human tuberculosis. Experimental infection studies in red deer (Cervus elaphus) allow the evaluation of such antigens for the serodiagnosis of bovine tuberculosis. RESULTS: Antibody levels in plasma from deer experimentally infected with Mycobacterium bovis were evaluated in ELISA using synthetic antigens based on several classes of mycolic acid, using protein G as conjugate. All antigens gave significantly increased responses 60 days post-infection, when all animals had active disease. A significantly increased response was also observed with four antigens 15 days after infection. CONCLUSION: ELISA using synthetic lipid antigens not only detects antibodies in the plasma of deer experimentally infected with M. bovis, but a strong response occurs early in the infection. With a full analysis of responses with naturally infected animals, this may offer a useful supplement to current diagnostic methods.

Detection of hepatitis B virus genotypes in a group of hepatitis B virus-infected patients in central and northern Sri Lanka.

Introduction. Hepatitis B infection causes a spectrum of clinical diseases varying from asymptomatic infection to severe or fulminant acute hepatitis, chronic liver disease, cirrhosis and hepatocellular carcinoma. Hepatitis B virus (HBV) genotypes appear to influence transmission dynamics, clinical outcomes and responses to antiviral therapy. However, hepatitis B genotyping has been poorly investigated in Sri Lanka. This study intended to determine hepatitis B genotypes in a group of HBV-infected people in central and northern Sri Lanka. Methodology. The study was a laboratory-based descriptive cross-sectional study. Initial detection of HBV DNA in 100 EDTA blood samples was done by using a commercially validated quantitative real-time PCR kit. Hepatitis B genotyping was performed by in-house conventional semi-nested multiplex PCR using genotype-specific primers (for genotypes A-F). The serological profile was determined using a commercially validated ELISA/chemiluminescence immunoassay. The results were evaluated for genotype prevalence, viral load association and hepatitis B e antigen (HBeAg) expression in the study population. Results and conclusion. The study detected that genotype C (n=38) is most prevalent and infections with multiple genotypes (n=52, 52%) were commoner than mono-genotype (n=23, 23%) infections. In total, 25% of patients had no detectable genotype among genotypes A-F. The mean viral load in asymptomatic patients with a single genotype was 3.28 log10 copies ml-1 and in multiple genotypes was 4.18 log10 copies ml-1 before treatment. Statistical significance was not detected in mean viral loads and HBeAg expression in these two groups. In the future, chronic HBV infection may be effectively treated and managed according to the infected genotype.

Crystal structure, Hirshfeld surface analysis, DFT optimized mol-ecular structure and the mol-ecular docking studies of 1-[2-(cyano-sulfan-yl)acet-yl]-3-methyl-2,6-bis-(4-methyl-phen-yl)piperidin-4-one.

The two mol-ecules in the asymmetric unit of the title compound, C23H24N2O2S, have a structural overlap with an r.m.s. deviation of 0.82 Å. The piperidine rings adopt a distorted boat conformation. Intra- and inter-molecular C-H⋯O hydrogen bonds are responsible for the cohesion of the crystal packing. The inter-molecular inter-actions were qu-anti-fied and analysed using Hirshfeld surface analysis. The mol-ecular structure optimized by density functional theory (DFT) at the B3LYP/6-311++G(d,p)level is compared with the experimentally determined mol-ecular structure in the solid state.

First Constraints on the Epoch of Reionization Using the Non-Gaussianity of the Kinematic Sunyaev-Zel'dovich Effect from the South Pole Telescope and Herschel-SPIRE Observations.

We report results from an analysis aimed at detecting the trispectrum of the kinematic Sunyaev-Zel'dovich (kSZ) effect by combining data from the South Pole Telescope (SPT) and Herschel-SPIRE experiments over a 100 deg^{2} field. The SPT observations combine data from the previous and current surveys, namely SPTpol and SPT-3G, to achieve depths of 4.5, 3, and 16 µK-arcmin in bands centered at 95, 150, and 220 GHz. For SPIRE, we include data from the 600 and 857 GHz bands. We reconstruct the velocity-induced large-scale correlation of the small-scale kSZ signal with a quadratic estimator that uses two cosmic microwave background (CMB) temperature maps, constructed by optimally combining data from all the frequency bands. We reject the null hypothesis of a zero trispectrum at 10.3σ level. However, the measured trispectrum contains contributions from both the kSZ and other undesired components, such as CMB lensing and astrophysical foregrounds, with kSZ being sub-dominant. We use the agora simulations to estimate the expected signal from CMB lensing and astrophysical foregrounds. After accounting for the contributions from CMB lensing and foreground signals, we do not detect an excess kSZ-only trispectrum and use this nondetection to set constraints on reionization. By applying a prior based on observations of the Gunn-Peterson trough, we obtain an upper limit on the duration of reionization of Δz_{re,50}<4.5 (95% confidence level). We find these constraints are fairly robust to foregrounds assumptions. This trispectrum measurement is independent of, but consistent with, Planck's optical depth measurement. This result is the first constraint on the epoch of reionization using the non-Gaussian nature of the kSZ signal.

Non-fused nonfullerene acceptors with asymmetric benzo[1,2-b:3,4-b', 6,5-b"]trithiophene (BTT) central donor core and different acceptor terminal units for organic solar cells.

Here in, we have designed two new unfused non-fullerene small molecules based on asymmetric benzo[1,2-b:3.4-b', 6,5-b"]trithiophene (BTT) central donor core and different terminal units, i.e. 2-(3-oxo-2,3-dihydro-1H-inden-1-ylidene)malononitrile (NFA-4) and 1,3-diethyl-2-thioxodi hydropyrimidine-4,6(1H,5H)-dione (NFA-5) and their optical and electrochemical properties were investigated. Employing a wide band-gap copolymer D18, the binary D18: NFA-4 and D18:NFA-5 bulk heterojunction-based organic solar cells realized an overall power conversion efficiency of about 17.07% and 11.27 %, respectively. The higher value of power conversion efficiency for the NFA-4-based organic solar cells, as compared to the NFA-5 counterpart, is attributed to the enhanced values of short circuit current, open circuit voltage, and fill factor. After the incorporation of NFA-5 into the binary bulk heterojunction D18:NFA-4, the ternary organic solar cells attained a power conversion efficiency of 18.05 %, which is higher than that for the binary counterparts and attributed to the increased values of short circuit current, fill factor, and open circuit voltage. The increased value of short circuit current is associated with the effective utilization of excitons through the energy transfer from the NFA-5 to NFA-4 as the NFA-4 exhibits a more significant dipole moment than the NFA-5 and is effectively dissociated into a free charge carrier.

Role of Sodium-Dependent Vitamin C Transporter-2 and Ascorbate in Regulating the Hypoxic Pathway in Cultured Glioblastoma Cells.

The most common and aggressive brain cancer, glioblastoma, is characterized by hypoxia and poor survival. The pro-tumour transcription factor, hypoxia-inducible factor (HIF), is regulated via HIF-hydroxylases that require ascorbate as cofactor. Decreased HIF-hydroxylase activity triggers the hypoxic pathway driving cancer progression. Tissue ascorbate accumulates via the sodium-dependent vitamin C transporter-2 (SVCT2). We hypothesize that glioblastoma cells rely on SVCT2 for ascorbate accumulation, and that knockout of this transporter would disrupt the regulation of the hypoxic pathway by ascorbate. Ascorbate uptake was measured in glioblastoma cell lines (U87MG, U251MG, T98G) by high-performance liquid chromatography. CRISPR/Cas9 was used to knockout SVCT2. Cells were treated with cobalt chloride, desferrioxamine or 5% oxygen, with/without ascorbate, and key hypoxic pathway proteins were measured using Western blot analysis. Ascorbate uptake was cell line dependent, ranging from 1.7 to 11.0 nmol/106 cells. SVCT2-knockout cells accumulated 90%-95% less intracellular ascorbate than parental cells. The hypoxic pathway was induced by all three stimuli, and ascorbate reduced this induction. In the SVCT2-knockout cells, ascorbate had limited effect on the hypoxic pathway. This study verifies that intracellular ascorbate is required to suppress the hypoxic pathway. As patient survival is related to an activated hypoxic pathway, increasing intra-tumoral ascorbate may be of clinical interest.