Miracle-dz/UniFAR-FTUs huggingface dataset:
Role of Antioxidant Natural Products in Management of Infertility: A Review of Their Medicinal Potential

Infertility, a couple’s inability to conceive after one year of unprotected regular intercourse, is an important issue in the world. The use of natural products in the treatment of infertility has been considered as a possible alternative to conventional therapies. The present study aimed to investigate the effects and the mechanisms of various natural products on infertility. We collected articles regarding infertility and natural products using the research databases PubMed and Google Scholar. Several natural products possess antioxidant properties and androgenic activities on productive factors and hormones. Antioxidants are the first defense barrier against free radicals produced by oxidative stress (OS). They remove reactive oxygen stress (ROS), reducing insulin resistance, total cholesterol, fat accumulation, and cancer growth. Moreover, various natural products increase endometrial receptivity and fertility ability showing androgenic activities on productive factors and hormones. For example, Angelica keiskei powder and Astragalus mongholicus extract showed anti-infertility efficacies in males and females, respectively. On the other hand, adverse effects and acute toxicity of natural products were also reported. Tripterygium glycoside decreased fertility ability both in males and females. Results indicate that management of infertility with natural products could be beneficial with further clinical trials to evaluate the safety and effect.
Circular RNA CircCDH13 contributes to the pathogenesis of osteoarthritis via CircCDH13/miR‐296‐3p/PTEN axis

Circular RNAs (circRNAs) are involved in a variety of human diseases; however, the function of circRNAs in osteoarthritis (OA) remains largely unknown. In this study, we investigated the role of CircCDH13 in OA and its underlying mechanisms. CircRNA expression profiles in OA and normal cartilage tissues were detected by microarray. The expression pattern, functional role, and mechanisms of CircCDH13 in OA were studied in vitro and in vivo. Gain‐of‐function and loss‐of‐function approaches were used to demonstrate the participation of CircCDH13 in OA. The regulatory relationship between CircCDH13 and miR‐296‐3p and miR‐296‐3p and phosphatase and tensin homolog (PTEN) was predicted by bioinformatics and verified by RNA pulldown and luciferase assay. Adeno‐associated virus was also used to reveal the role and mechanisms of CircCDH13 in destabilization of medial meniscus (DMM)‐induced OA mice. The upregulation of CircCDH13 in OA cartilage tissues significantly induces chondrocyte apoptosis, promotes extracellular matrix (ECM) catabolism, and inhibits ECM anabolism. Mechanistically, CircCDH13 contributes to OA pathogenesis by functioning as a sponge of miR‐296‐3p and regulating the miR‐296‐3p‐PTEN pathway. Silencing of CircCDH13 in vivo markedly alleviated DMM‐induced OA in mice. Our study revealed an important role of CircCDH13 in OA pathogenesis. Silencing of CircCDH13 could reduce chondrocyte apoptosis, inhibit ECM catabolism, and promote ECM anabolism through the miR‐296‐3p‐PTEN pathway. It provides a potential target for developing effective interventions in treating OA.
Digitally quantified CD8+ cells: the best candidate marker for an immune cell score in non-small cell lung cancer?

Abstract The TNM classification is well established as a state-of-the-art prognostic and treatment-decision-making tool for non-small cell lung cancer (NSCLC) patients. However, incorporation of biological data may hone the TNM system. This article focuses on choosing and incorporating subsets of tissue-infiltrating lymphocyte (TIL), detected by specific immunohistochemistry and automatically quantified by open source software, into a TNM-Immune cell score (TNM-I) for NSCLC. We use common markers (CD3, CD4, CD8, CD20 and CD45RO) of TILs to identify TIL subsets in tissue micro-arrays comprising tumor tissue from 553 patients resected for primary NSCLC. The number of TILs is automatically quantified using open source software (QuPath). Their prognostic efficacy, alone and within a TNM-I model, is evaluated in all patients and histological subgroups. Compared with previous manual semi-quantitative scoring of TILs in the same cohort, the present digital quantification proved superior. As a proof-of-concept, we construct a TNM-I, using TNM categories and the CD8+ TIL density. The TNM-I is an independent prognosticator of favorable diagnosis in both the overall cohort and in the main histological subgroups. In conclusion, CD8+ TIL density is the most promising candidate marker for a TNM-I in NSCLC. The prognostic efficacy of the CD8+ TIL density is strongest in lung squamous cell carcinomas, whereas both CD8+ TILs and CD20+ TILs, or a combination of these, may be candidates for a TNM-I in lung adenocarcinoma. Furthermore, based on the presented results, digital quantification is the preferred method for scoring TILs in the future.
A Behavioral and Electrophysiological Investigation of Effects of Visual Congruence on Olfactory Sensitivity During Habituation to Prolonged Odors

Abstract Congruent visual cues augment sensitivity to brief olfactory presentations and habituation of odor perception is modulated by central-cognitive processing including context. However, it is not known whether habituation to odors could interact with cross-modal congruent stimuli. The present research investigated the effect of visual congruence on odor detection sensitivity during continuous odor exposures. We utilized a multimethod approach, including subjective behavioral responses and reaction times (RTs; study 1) and electroencephalography (EEG, study 2). Study 1: 25 participants received 2-min presentations of moderate-intensity floral odor delivered via olfactometer with congruent (flower) and incongruent (object) image presentations. Participants indicated odor perception after each image. Detection sensitivity and RTs were analyzed in epochs covering the period of habituation. Study 2: 25 new participants underwent EEG recordings during 145-s blocks of odor presentations with congruent or incongruent images. Participants passively observed images and intermittently rated the perceived intensity of odor. Event-related potential analysis was utilized to evaluate brain processing related to odor–visual pairs across the period of habituation. Odor detection sensitivity and RTs were improved by congruent visual cues. Results highlighted a diminishing influence of visual congruence on odor detection sensitivity as habituation occurred. Event-related potential analysis revealed an effect of congruency on electrophysiological processing in the N400 component. This was only evident in early periods of odor exposure when perception was strong. For the first time, this demonstrates the modulation of central processing of odor–visual pairs by habituation. Frontal negativity (N400) responses encode the aspects of cross-modal congruence for odor–vision cross-modal tasks.
Prescribers' compliance with summary of product characteristics of dabigatran, rivaroxaban and apixaban—A European comparative drug utilization study

Despite a tremendous increase of direct oral anticoagulants (DOACs) prescriptions in recent years, only few data is available analysing prescribers' adherence to Summary of Product Characteristics (SmPC). We aimed to assess adherence to registered indications, contraindications, special warnings/precautions, and potential drug‐drug interactions for three DOAC compounds (dabigatran, rivaroxaban, and apixaban) in six databases of five European countries (The Netherlands, United Kingdom, Spain, Denmark, and Germany). We included adult patients (≥18 years) initiating DOACs between 2008 and 2015. For several SmPC items, broad definitions were used due to ambiguous SmPC terms or lacking data in some databases. Within the study period, a DOAC was initiated in 407 576 patients (rivaroxaban: 240 985 (59.1%), dabigatran: 95 303 (23.4%), and apixaban: 71 288 (17.5%)). In 2015, non‐valvular atrial fibrillation was the most common indication (>60% in most databases). For the whole study period, a substantial variation between the databases was found regarding the proportion of patients with at least one contraindication (inter‐database range [IDR]: 8.2%‐55.7%), with at least one special warning/precaution (IDR: 35.8%‐75.2%) and with at least one potential drug‐drug interaction (IDR: 22.4%‐54.1%). In 2015, the most frequent contraindication was “malignant neoplasm” (IDR: 0.7%‐21.3%) whereas the most frequent special warning/precaution was “prescribing to the elderly” (≥75 years; IDR: 25.0%‐66.4%). The most common single compound class interaction was “concomitant use of non‐steroidal anti‐inflammatory drugs” (IDR: 3.0%‐25.3%). Contraindications, special warnings/precautions, and potential drug‐drug interactions were present in a relevant number of new DOAC users. Due to broad definitions used for some SmPC terms, overall proportions for contraindications are prone to overestimation. However, for unambiguous SmPC terms documented in the databases sufficiently, the respective estimates can be considered valid. Differences between databases might be related to “true” differences in prescription behaviour, but could also be partially due to differences in database characteristics.
The Arabidopsis zinc finger proteins SRG2 and SRG3 are positive regulators of plant immunity and are differentially regulated by nitric oxide.

Nitric oxide (NO) regulates the deployment of a phalanx of immune responses, chief among these is the activation of a constellation of defence-related genes. However, the underlying molecular mechanisms remain largely unknown. The Arabidopsis thaliana zinc finger transcription factor (ZF-TF), S-nitrosothiol (SNO) Regulated 1 (SRG1), is a central target of NO bioactivity during plant immunity. Here we characterise the remaining members of the SRG gene family. Both SRG2 and especially SRG3, were positive regulators of salicylic acid-dependent plant immunity. Informatively, analysis of SRG single, double and triple mutants, implied SRG family members have additive functions in plant immunity and surprisingly are under reciprocal regulation. SRG2 and SRG3 localised to the nucleus and functioned as EAR domain-dependent transcriptional repressors: NO abolished this activity for SRG3 but not SRG2. Consistently, loss of GSNOR function, resulting in increased (S)NO levels, fully suppressed the disease resistance phenotype established from SRG3 but not SRG2 over-expression. Remarkably, SRG3 but not SRG2 was S-nitrosylated in vitro and in vivo. Our findings suggest the SRG family has separable functions in plant immunity and surprisingly, these ZF-TFs exhibit reciprocal regulation. Remarkably, through neo-functionalization, the SRG family has evolved to become differentially regulated by the key, immune-related redox cue, NO.
Oestrogen andNuclear Binding Sites DETERMINATIONOF SPECIFICSITESBY (3H)OESTRADIOL EXCHANGE

tissues. Themethodisbased ontheexchange of[3H]oestradiol withnon-labelled oestradiol thatisboundtonuclear binding sites. Thenumberofspecific nuclear binding sites after theinjection of2.5,ug of oestradiol, an amountsufficient tosaturate allbinding sites, is1.6-1.7pmol per immature uterus. Thenumber ofsites occupied after aninjection ofphysiological amounts ofoestradiol (0.1 ,g)was0.46pmol. Theinjection ofoestradiol results inanincreased numberofnuclear binding sites inuterus andvagina, buthasnoeffect onkidney or muscle. Injections oftestosterone orprogesterone failed toincrease thenumberofuterine nuclear binding sites. Thismethodpermits anevaluation ofthenumberofoestradiolbinding sites inthenuclear fraction ofvarious tissues asafunction ofeither endogenous oestradiol ornon-labelled oestradiol administered byinjection. Oestrogenic compounds arepreferentially retained byoestrogen target tissues. Thisphenomenon has beenattributed to oestrogen-binding proteins. Numerousinvestigations haverevealed thatthe interaction ofoestradiol withtheratuterusis probably a two-step processinwhichoestrogen first bindswitha cytoplasmic componenttoforma complex, whichsubsequently moves tothenucleus (Jensen etal., 1968, 1969; Shyamala & Gorski, 1969). As a result ofthistranslocation, thedepletion of cytoplasmic binding sites isaccompanied byaparallel increase inthequantity ofnuclear binding sites (Giannopoulos & Gorski, 1971). Theassociation of oestradiol withnuclear binding sites isconsidered tobeoffundamental importance inthemechanism ofaction ofoestrogen. Further, thedetermination of specific nuclear binding sites may betheonly accurate reflection oftheamountofoestradiol boundinthe uterus (Williams & Gorski, 1971; J.H.Clark& E.J. Peck, unpublished work). Previous methodsforevaluating thequantity of nuclear binding sites haveutilized gelfiltration or density-gradient ultracentrifugation ofnuclear extracts previously solubilized fromtheuterine nuclear fraction withbuffered 0.3-0.4M-potassium chloride solutions (Puca& Bresciani, 1968,1969). These procedures arelaborious, difficult tousequantitatively, andrequire theinjection of[3H]oestradiol for studies invivo. We havedeveloped a methodforthe determination ofthenumberofoestradiol-binding sites inthenuclear fraction ofoestrogen-target tissues thatcircumvents these difficulties. Themethodrelies on theexchange of[3H]oestradiol withoestradiol boundtothenuclear fraction andpermits an evaluationoftheconcentration ofspecific oestradiolbinding sites underconditions invivo. Vol.126 Materials andMethods Preparation ofanimals andmaterials Immaturefemale rats(21-23daysold)ofthe Purdue-Wistar strain were usedinthisstudy. The animals, whichweighed between 50and65g,were maintained inair-conditioned quarters andgiven foodandwateradlib. Oestradiol dissolved in0.5ml of0.9% NaClwas injected subcutaneously between 08.00 and11.00 a.m.Whereindicated, testosterone, progesterone, stilboestrol or0.9% NaClwereusedin placeoftheoestradiol. [6,7-3H]Oestradiol
Large uncertainties in future biome changes in Africa call for flexible climate adaptation strategies

Anthropogenic climate change is expected to impact ecosystem structure, biodiversity and ecosystem services in Africa profoundly. We used the adaptive Dynamic Global Vegetation Model (aDGVM), which was originally developed and tested for Africa, to quantify sources of uncertainties in simulated African potential natural vegetation towards the end of the 21st century. We forced the aDGVM with regionally downscaled high‐resolution climate scenarios based on an ensemble of six general circulation models (GCMs) under two representative concentration pathways (RCPs 4.5 and 8.5). Our study assessed the direct effects of climate change and elevated CO2 on vegetation change and its plant‐physiological drivers. Total increase in carbon in aboveground biomass in Africa until the end of the century was between 18% to 43% (RCP4.5) and 37% to 61% (RCP8.5) and was associated with woody encroachment into grasslands and increased woody cover in savannas. When direct effects of CO2 on plants were omitted, woody encroachment was muted and carbon in aboveground vegetation changed between –8 to 11% (RCP 4.5) and –22 to –6% (RCP8.5). Simulated biome changes lacked consistent large‐scale geographical patterns of change across scenarios. In Ethiopia and the Sahara/Sahel transition zone, the biome changes forecast by the aDGVM were consistent across GCMs and RCPs. Direct effects from elevated CO2 were associated with substantial increases in water use efficiency, primarily driven by photosynthesis enhancement, which may relieve soil moisture limitations to plant productivity. At the ecosystem level, interactions between fire and woody plant demography further promoted woody encroachment. We conclude that substantial future biome changes due to climate and CO2 changes are likely across Africa. Because of the large uncertainties in future projections, adaptation strategies must be highly flexible. Focused research on CO2 effects, and improved model representations of these effects will be necessary to reduce these uncertainties.
GNSS-Based Non-Negative Absolute Ionosphere Total Electron Content, its Spatial Gradients, Time Derivatives and Differential Code Biases: Bounded-Variable Least-Squares and Taylor Series

Global navigation satellite systems (GNSS) allow estimating total electron content (TEC). However, it is still a problem to calculate absolute ionosphere parameters from GNSS data: negative TEC values could appear, and most of existing algorithms does not enable to estimate TEC spatial gradients and TEC time derivatives. We developed an algorithm to recover the absolute non-negative vertical and slant TEC, its derivatives and its gradients, as well as the GNSS equipment differential code biases (DCBs) by using the Taylor series expansion and bounded-variable least-squares. We termed this algorithm TuRBOTEC. Bounded-variable least-squares fitting ensures non-negative values of both slant TEC and vertical TEC. The second order Taylor series expansion could provide a relevant TEC spatial gradients and TEC time derivatives. The technique validation was performed by using independent experimental data over 2014 and the IRI-2012 and IRI-plas models. As a TEC source we used Madrigal maps, CODE (the Center for Orbit Determination in Europe) global ionosphere maps (GIM), the IONOLAB software, and the SEEMALA-TEC software developed by Dr. Seemala. For the Asian mid-latitudes TuRBOTEC results agree with the GIM and IONOLAB data (root-mean-square was < 3 TECU), but they disagree with the SEEMALA-TEC and Madrigal data (root-mean-square was >10 TECU). About 9% of vertical TECs from the TuRBOTEC estimates exceed (by more than 1 TECU) those from the same algorithm but without constraints. The analysis of TEC spatial gradients showed that as far as 10–15° on latitude, TEC estimation error exceeds 10 TECU. Longitudinal gradients produce smaller error for the same distance. Experimental GLObal Navigation Satellite System (GLONASS) DCB from TuRBOTEC and CODE peaked 15 TECU difference, while GPS DCB agrees. Slant TEC series indicate that the TuRBOTEC data for GLONASS are physically more plausible.
Native Trichoderma strains isolated from Bangladesh with broad spectrum antifungal action against fungal phytopathogens

Nineteen Trichoderma isolates, collected from different locations in Bangladesh, were characterised through phenotypic, biochemical and molecular means. Besides, they were assessed for their antifungal action in vitro. The isolates were divided into three groups: T. asperellum, T. virens and T. harzianum. A dual culture assay and a culture filtrate assay against 6 phytopathogens revealed that 9 of the 19 isolates showed significant antifungal activities. The isolate T. harzianum TR05 showed the highest inhibition against Fusarium oxysporum, Rhizoctonia solani, Fusarium circinatum and Phomopsis vexans, followed by T. asperellum TR08 and T. virens TR06. TR08 had the highest inhibition against Sclerotium rolfsii and Pythium aphanidermatum, followed by TR05 and TR06. These findings were in agreement with their activities of extracellular hydrolytic enzymes, including chitinase, β-1,3-glucanase, and proteinase. Our results suggest that isolates TR05, TR06 and TR08 have the potential to be effective biocontrol agents against the phytopathogenic fungi.
Computation in bacterial communities

Bacteria across many scales are involved in a dynamic process of information exchange to coordinate activity and community structure within large and diverse populations. The molecular components bacteria use to communicate have been discovered and characterized, and recent efforts have begun to understand the potential for bacterial signal exchange to gather information from the environment and coordinate collective behaviors. Such computations made by bacteria to coordinate the action of a population of cells in response to information gathered by a multitude of inputs is a form of collective intelligence. These computations must be robust to fluctuations in both biological, chemical, and physical parameters as well as to operate with energetic efficiency. Given these constraints, what are the limits of computation by bacterial populations and what strategies have evolved to ensure bacterial communities efficiently work together? Here the current understanding of information exchange and collective decision making that occur in microbial populations will be reviewed. Looking toward the future, we consider how a deeper understanding of bacterial computation will inform future direction in microbiology, biotechnology, and biophysics.
A high salt meal does not impair cerebrovascular reactivity in healthy young adults

A high sodium (Na+) meal impairs peripheral vascular function. In rodents, chronic high dietary Na+ impairs cerebral vascular function, and in humans, habitual high dietary Na+ is associated with increased stroke risk. However, the effects of acute high dietary Na+ on the cerebral vasculature in humans are unknown. The purpose of this study was to determine if acute high dietary Na+ impairs cerebrovascular reactivity in healthy adults. Thirty‐seven participants (20F/17M; 25 ± 5 years; blood pressure [BP]: 107 ± 9/61 ± 6 mm Hg) participated in this randomized, cross‐over study. Participants were given a low Na+ meal (LSM; 138 mg Na+) and a high Na+ meal (HSM; 1,495 mg Na+) separated by ≥ one week. Serum Na+, beat‐to‐beat BP, middle cerebral artery velocity (transcranial Doppler), and end‐tidal carbon dioxide (PETCO2) were measured pre‐ (baseline) and 60 min post‐prandial. Cerebrovascular reactivity was assessed by determining the percent change in middle cerebral artery velocity to hypercapnia (via 8% CO2, 21% oxygen, balance nitrogen) and hypocapnia (via mild hyperventilation). Peripheral vascular function was measured using brachial artery flow‐mediated dilation (FMD). Changes in serum Na+ were greater following the HSM (HSM: Δ1.6 ± 1.2 mmol/L vs. LSM: Δ0.7 ± 1.2 mmol/L, p < .01). Cerebrovascular reactivity to hypercapnia (meal effect: p = .41) and to hypocapnia (meal effect: p = .65) were not affected by the HSM. Contrary with previous findings, FMD was not reduced following the HSM (meal effect: p = .74). These data suggest that a single high Na+ meal does not acutely impair cerebrovascular reactivity, and suggests that despite prior findings, a single high Na+ meal does not impair peripheral vascular function in healthy adults.