Miracle-dz/UniFAR-FTUs huggingface dataset:
Novel Phenothiazine-Bridged Porphyrin-(Hetero)aryl dyads: Synthesis, Optical Properties, In Vitro Cytotoxicity and Staining of Human Ovarian Tumor Cell Lines

We report here the synthetic procedure applied for the preparation of new AB3-type and trans-A2B2 type meso-halogenophenothiazinyl-phenyl-porphyrin derivatives, their metal core complexation and their peripheral modification using Suzuki–Miyaura cross coupling reactions with various (hetero)aryl (phenothiazinyl, 7-formyl-phenothiazinyl, (9-carbazolyl)-phenyl and 4-formyl-phenyl, phenyl) boronic acid derivatives. The meso-phenothiazinyl-phenyl-porphyrin (MPP) dyes family was thus extended by a series of novel phenothiazine-bridged porphyrin-(hetero)aryl dyads characterized by UV–Vis absorption/emission properties typical to the porphyrin chromophore, slightly modulated by increasing the size of peripheral substituents. Three phenothiazine-bridged porphyrin-heteroaryl dyads with fluorescence emission above 655 nm were selected as fluorophores in red spectral region for applications in cellular staining of human ovarian tumors. In vitro experiments of cell metabolic activity displayed a moderate toxicity on human ovarian tumor cell lines (OVCAR-3, cisplatin-sensitive A2780 and cisplatin-resistant A2780cis respectively). Visualization of the stained living cells was performed both by fluorescence microscopy imaging and by fluorescence lifetime imaging under two photon excitation (TPE-FLIM), confirming their cellular uptake and the capability of staining the cell nucleus.
Representations and Benchmarking of Modern Visual SLAM Systems

Simultaneous Localisation And Mapping (SLAM) has long been recognised as a core problem to be solved within countless emerging mobile applications that require intelligent interaction or navigation in an environment. Classical solutions to the problem primarily aim at localisation and reconstruction of a geometric 3D model of the scene. More recently, the community increasingly investigates the development of Spatial Artificial Intelligence (Spatial AI), an evolutionary paradigm pursuing a simultaneous recovery of object-level composition and semantic annotations of the recovered 3D model. Several interesting approaches have already been presented, producing object-level maps with both geometric and semantic properties rather than just accurate and robust localisation performance. As such, they require much broader ground truth information for validation purposes. We discuss the structure of the representations and optimisation problems involved in Spatial AI, and propose new synthetic datasets that, for the first time, include accurate ground truth information about the scene composition as well as individual object shapes and poses. We furthermore propose evaluation metrics for all aspects of such joint geometric-semantic representations and apply them to a new semantic SLAM framework. It is our hope that the introduction of these datasets and proper evaluation metrics will be instrumental in the evaluation of current and future Spatial AI systems and as such contribute substantially to the overall research progress on this important topic.
Structure‐Activity Relationships and Potent Cytotoxic Activities of Terphenyllin Derivatives from a Small Compound Library

A small library of 120 compounds was established with seventy new alkylated derivatives of the natural product terphenyllin, together with 45 previous reported derivatives and four natural p‐terphenyl analogs. The 70 new derivatives were semi‐synthesized and evaluated for cytotoxic activities against four cancer cell lines. Interestingly, 2′,4′′‐diethoxyterphenyllin, 2′,4,4′′‐triisopropoxyterphenyllin, and 2′,4′′‐bis(cyclopentyloxy)terphenyllin showed potent activities with IC50 values in a range from 0.13 to 5.51 μM, which were similar to those of the positive control, adriamycin. The preliminary structure–activity relationships indicated that the introduction of alkyl substituents including ethyl, allyl, propargyl, isopropyl, bromopropyl, isopentenyl, cyclopropylmethyl, and cyclopentylmethyl are important for improving the cytotoxicity.
Phenolic Compounds of Soybean Seeds from Two European Countries and Their Antioxidant Properties

There is only a small acreage of planted soybeans in northern Europe, as the global production of this crop is mainly dictated by the warmer temperatures needed for bountiful yields. The defense response of soybean plants to a cold climate entails the secretion of specific compounds which help mitigate oxidative stress, i.e., antioxidants, including phenolic compounds. The objective of this study was to examine differences in the concentrations of phenolic compounds, their antioxidant properties, and the concentration of key isoflavones (namely genistein, daidzein, malonyl daidzein, malonyl genistein, and daidzin) in the seeds of six soybean cultivars from two different regions of Europe, namely Poland and France. The total phenolic contents, isoflavone levels, and in vitro antioxidant capacities of soybean seeds from most of the investigated cultivars of northeast Europe were found to be greater than those from southwest Europe. The phenolic compounds of seed extracts are primarily responsible for the free-radical scavenging of soybeans. Factors regulating the production of phenolic compounds in the seeds have not been thoroughly elucidated. Hence, the results presented in this paper can be useful in the selection of soybean cultivars with higher levels of seed phenolics, because of their beneficial impact on human health and on the soybean’s defense mechanism against plant stresses.
Lab-on-a-Chip Technologies for the Single Cell Level: Separation, Analysis, and Diagnostics

In the last three decades, microfluidics and its applications have been on an exponential rise, including approaches to isolate rare cells and diagnose diseases on the single-cell level. The techniques mentioned herein have already had significant impacts in our lives, from in-the-field diagnosis of disease and parasitic infections, through home fertility tests, to uncovering the interactions between SARS-CoV-2 and their host cells. This review gives an overview of the field in general and the most notable developments of the last five years, in three parts: 1. What can we detect? 2. Which detection technologies are used in which setting? 3. How do these techniques work? Finally, this review discusses potentials, shortfalls, and an outlook on future developments, especially in respect to the funding landscape and the field-application of these chips.
Reappraisal-related neural predictors of treatment response to cognitive behavior therapy for post-traumatic stress disorder

Abstract Background Although trauma-focused cognitive behavior therapy (TF-CBT) is the frontline treatment for post-traumatic stress disorder (PTSD), one-third of patients are treatment non-responders. To identify neural markers of treatment response to TF-CBT when participants are reappraising aversive material. Methods This study assessed PTSD patients (n = 37) prior to TF-CBT during functional magnetic brain resonance imaging (fMRI) when they reappraised or watched traumatic images. Patients then underwent nine sessions of TF-CBT, and were then assessed for symptom severity on the Clinician-Administered PTSD Scale. FMRI responses for cognitive reappraisal and emotional reactivity contrasts of traumatic images were correlated with the reduction of PTSD severity from pretreatment to post-treatment. Results Symptom improvement was associated with decreased activation of the left amygdala during reappraisal, but increased activation of bilateral amygdala and hippocampus during emotional reactivity prior to treatment. Lower connectivity of the left amygdala to the subgenual anterior cingulate cortex, pregenual anterior cingulate cortex, and right insula, and that between the left hippocampus and right amygdala were also associated with symptom improvement. Conclusions These findings provide evidence that optimal treatment response to TF-CBT involves the capacity to engage emotional networks during emotional processing, and also to reduce the engagement of these networks when down-regulating emotions.
Simultaneous SNP selection and adjustment for population structure in high dimensional prediction models

Complex traits are known to be influenced by a combination of environmental factors and rare and common genetic variants. However, detection of such multivariate associations can be compromised by low statistical power and confounding by population structure. Linear mixed effects models (LMM) can account for correlations due to relatedness but have not been applicable in high-dimensional (HD) settings where the number of fixed effect predictors greatly exceeds the number of samples. False positives or false negatives can result from two-stage approaches, where the residuals estimated from a null model adjusted for the subjects’ relationship structure are subsequently used as the response in a standard penalized regression model. To overcome these challenges, we develop a general penalized LMM with a single random effect called ggmix for simultaneous SNP selection and adjustment for population structure in high dimensional prediction models. We develop a blockwise coordinate descent algorithm with automatic tuning parameter selection which is highly scalable, computationally efficient and has theoretical guarantees of convergence. Through simulations and three real data examples, we show that ggmix leads to more parsimonious models compared to the two-stage approach or principal component adjustment with better prediction accuracy. Our method performs well even in the presence of highly correlated markers, and when the causal SNPs are included in the kinship matrix. ggmix can be used to construct polygenic risk scores and select instrumental variables in Mendelian randomization studies. Our algorithms are available in an R package available on CRAN (https://cran.r-project.org/package=ggmix).
Mouse Gonad Development in the Absence of the Pro-Ovary Factor WNT4 and the Pro-Testis Factor SOX9

The transcription factors SRY and SOX9 and RSPO1/WNT4/β-Catenin signaling act as antagonistic pathways to drive testis and ovary development respectively, from a common gonadal primordium in mouse embryos. In this work, we took advantage of a double knockout mouse model to study gonadal development when Sox9 and Wnt4 are both mutated. We show that the XX gonad mutant for Wnt4 or for both Wnt4 and Sox9 develop as ovotestes, demonstrating that ectopic SOX9 function is not required for the partial female-to-male sex reversal caused by a Wnt4 mutation. Sox9 deletion in XY gonads leads to ovarian development accompanied by ectopic WNT/β-catenin signaling. In XY Sox9 mutant gonads, SRY-positive supporting precursors adopt a female-like identity and develop as pre-granulosa-like cells. This phenotype cannot be fully prevented by the deletion of Wnt4 or Rspo1, indicating that SOX9 is required for the early determination of the male supporting cell identity independently of repressing RSPO1/WNT4/β-Catenin signaling. However, in XY Sox9 Wnt4 double mutant gonads, pre-granulosa cells are not maintained, as they prematurely differentiate as mature granulosa cells and then trans-differentiate into Sertoli-like cells. Together, our results reveal the dynamics of the specific and independent actions of SOX9 and WNT4 during gonadal differentiation: SOX9 is essential in the testis for early specification of male-supporting cells whereas WNT4 functions in the ovary to maintain female-supporting cell identity and inhibit male-specific vascular and steroidogenic cell differentiation.
Proteomic and metabolomic characterization of cardiac tissue in acute myocardial ischemia injury rats

The pathological process and mechanism of myocardial ischemia (MI) is very complicated, and remains unclear. An integrated proteomic-metabolomics analysis was applied to comprehensively understand the pathological changes and mechanism of MI. Male Sprague-Dawley rats were randomly divided into a mock surgery (MS) group and an MI group. The MI model was made by ligating the left anterior descending coronary artery, twenty-four hours after which, echocardiography was employed to assess left ventricular (LV) function variables. Blood samples and left ventricular tissues were collected for ELISA, metabolomics and proteomics analysis. The results showed that LV function, including ejection fraction (EF) and fractional shortening (FS), was significantly reduced and the level of cTnT in the serum increased after MI. iTRAQ proteomics showed that a total of 169 proteins were altered including 52 and 117 proteins with increased and decreased expression, respectively, which were mainly involved in the following activities: complement and coagulation cascades, tight junction, regulation of actin cytoskeleton, MAPK signaling pathway, endocytosis, NOD-like receptor signaling pathway, as well as phagosome coupled with vitamin digestion and absorption. Altered metabolomic profiling of this transition was mostly enriched in pathways including ABC transporters, glycerophospholipid metabolism, protein digestion and absorption and aminoacyl-tRNA biosynthesis. The integrated metabolomics and proteomics analysis indicated that myocardial injury after MI is closely related to several metabolic pathways, especially energy metabolism, amino acid metabolism, vascular smooth muscle contraction, gap junction and neuroactive ligand-receptor interaction. These findings may contribute to understanding the mechanism of MI and have implication for new therapeutic targets.
Human monoclonal antibodies against Ross River virus target epitopes within the E2 protein and protect against disease

Ross River fever is a mosquito-transmitted viral disease that is endemic to Australia and the surrounding Pacific Islands. Ross River virus (RRV) belongs to the arthritogenic group of alphaviruses, which largely cause disease characterized by debilitating polyarthritis, rash, and fever. There is no specific treatment or licensed vaccine available, and the mechanisms of protective humoral immunity in humans are poorly understood. Here, we describe naturally occurring human mAbs specific to RRV, isolated from subjects with a prior natural infection. These mAbs potently neutralize RRV infectivity in cell culture and block infection through multiple mechanisms, including prevention of viral attachment, entry, and fusion. Some of the most potently neutralizing mAbs inhibited binding of RRV to Mxra8, a recently discovered alpahvirus receptor. Epitope mapping studies identified the A and B domains of the RRV E2 protein as the major antigenic sites for the human neutralizing antibody response. In experiments in mice, these mAbs were protective against cinical disease and reduced viral burden in multiple tissues, suggesting a potential therapeutic use for humans.
Green Solution Bathing Process for Efficient Large-area Planar Perovskite Solar Cells.

Perovskite solar cells (PSCs) towards practical application relies on high efficiency, long lifetime, low toxicity and device upscaling. To realize large-area PSCs, a green solution bathing strategy is delivered to prepare high-performance PSCs. By utilizing 2-pentanol as a green solvent and formamidinium chloride (FACl) as a solute in the green solution bathing, perovskite films with enlarged grain sizes, improved crystallinity and alleviated defect state density were obtained, resulting in the enhancement in the power conversion efficiency of PSCs. Coupled with 2-pentanol and FACl, a champion efficiency of 21.03% for small cells (0.103 cm2) and over 18% for large size (1.00 cm2) were obtained based on the GSB process, which can outperform its counterpart made from commonly-used anti-solvent dropping method. In addition, a large perovskite film (5 cm  5 cm) with obvious mirror effect was successfully prepared. Our innovative approach paves the way to promote device upscaling of PSCs via environment-friendly technique.
Lycopene prevents carcinogen-induced cutaneous tumor by enhancing activation of the Nrf2 pathway through p62-triggered autophagic Keap1 degradation

Biologically active natural products have been used for the chemoprevention of cutaneous tumors. Lycopene is the main active phytochemical in tomatoes. We herein aimed to assess the cancer preventive effects of lycopene and to find potential molecular targets. In chemically-induced cutaneous tumor mice and cell models, lycopene attenuated cutaneous tumor incidence and multiplicity as well as the tumorigenesis of normal cutaneous cells in phase-selectivity (only in the promotion phase) manners. By utilizing a comprehensive approach combining bioinformatics with network pharmacology, we predicted that intracellular autophagy and redox status were associated with lycopene’s preventive effect on cutaneous tumors. Lycopene stimulated the activation of antioxidant enzymes and the translocation of the transcription factor Nrf2 (nuclear factor erythroid 2-related factor 2) that predominantly maintained intracellular redox equilibrium. The cancer chemopreventive effects were mediated by Nrf2. Further, lycopene enhanced the expression of autophagy protein p62. Therefore this led to the degradation of Keap1(Kelch ECH associating protein 1), the main protein locking Nrf2 in cytoplasm. In conclusion, our study provides preclinical evidence of the chemopreventive effects of lycopene on cutaneous tumors and reveals the mechanistic link between lycopene’s stimulation of Nrf2 signaling pathway and p62-mediated degradation of Keap1 via the autophagy-lysosomal pathway.
Predictive Value of an Alternative Strategy for Measuring Depth and Size of Stage 1 Vulvar Squamous Cell Carcinoma

Supplemental digital content is available in the text. Objectives Despite poor reproducibility for measuring vulvar cancer depth, 1-mm or greater invasion triggers lymphadenectomy for small tumors. Previous literature suggests that measuring depth from the nearest dysplastic rete peg (alternative method) rather than highest dermal papilla (conventional method) may be acceptable. Methods Pathologic staging and follow-up information were recorded for 100 pT1 vulvar squamous cell carcinoma (SCC) resected from 1990 to 2019. Conventional depth, alternative depth, gross/clinical size, and size of the invasive component were measured for each tumor. In this retrospective study, we evaluated which clinicopathologic factors were most predictive of lymph node involvement and recurrence. Results Depending on the measurements used (conventional vs alternative depth, clinical lesion size vs cumulative extent of invasive component), between 1 and 18 cases were downstaged to pT1a. All such cases were pN0, without lymphovascular or perineural invasion. Infiltrative cords (hazard ratio [HR] = 5.15; 95% CI = 1.63–16.2; p = .005) and perineural invasion (HR = 3.16; 1.18–8.45; p = .022) were most strongly associated with groin recurrence. Of staging criteria evaluated, only cumulative extent of the invasive component 2 cm or greater was significantly associated with groin recurrence (HR = 2.87; 1.01–8.17; p = .048). The Kaplan-Meier curves for local recurrence-free survival by stage did not show significant separation regardless of method. Conclusions Patients downstaged using alternative measurement techniques lacked nodal disease/recurrence; one-third of those with nodal sampling experienced postoperative morbidity. Our data suggest that the use of alternative depth and cumulative extent of invasion could safely allow some conventional stage IB vulvar SCC patients to avoid groin surgery, thereby reducing treatment-related morbidity.
Acidification and Toxicity of Metals to Aquatic Biota

Acidification of freshwaters can in principle influence metal–organism interactions in at least two ways: the decrease in pH may affect metal speciation in solution, or it may affect biological sensitivity at the level of the cell surface. We considered the possible effects of environmental acidification (pH 7–4) on (1) metal speciation in solution, (2) metal adsorption at biological surfaces, and (3) metal uptake by and toxicity to aquatic biota. Attention was focused on some 10 metals of potential concern in the context of freshwater acidification (Ag, Al, Cd, Co, Cu, Hg, Mn, Ni, Pb, Zn). For the four metals (Al, Cu, Hg, Pb) predicted to manifest speciation changes in the range pH 7–4, confirmatory experimental data are available for two (Cu, Pb). In the six remaining cases predicted to show little sensitivity to pH changes in this range, supporting experimental evidence exists for four metals (Ag, Cd, Mn, Zn). A pH-dependent biological response is documented over a realistic range of H+ and metal conce.
Aberrant Expression of Androgen Receptor Associated with High Cancer Risk and Extrathyroidal Extension in Papillary Thyroid Carcinoma

Male gender is a risk factor for mortality in patients with papillary thyroid carcinoma (PTC). This study investigated the impact of androgen receptor (AR) gene expression on the clinical features and progression of PTC. The levels of AR mRNA and protein in frozen, formalin-fixed, paraffin-embedded tissue samples from PTC and adjacent normal thyroid tissue were assessed by quantitative real-time polymerase chain reaction and immunohistochemical staining, respectively, and the relationships between AR expression and clinical features were analyzed. The thyroid cancer cell lines, BCPAP and TPC-1, were used to evaluate the effects of AR on the regulation of cell migration, and key epithelial–mesenchymal transition (EMT) markers. AR mRNA expression was significantly higher in normal thyroid tissue from men than women. The sex difference in AR mRNA expression diminished during PTC tumorigenesis, as AR mRNA expression levels were lower in PTC than normal thyroid tissues from both men and women. AR mRNA expression was significantly decreased in PTC patients with higher risk and in those with extrathyroidal extension. Overexpression of AR in BCPAP cells decreased cell migration and repressed the EMT process by down-regulating mRNA expression of N-cadherin, Snail1, Snail2, Vimentin, and TWIST1 and up-regulating E-cadherin gene expression. These results suggest that suppression of the androgen–AR axis may lead to aggressive tumor behavior in patients with PTC.
Characterization of ABC Transporters in EpiAirway™, a Cellular Model of Normal Human Bronchial Epithelium

The ATP-binding cassette (ABC) transporters P-glycoprotein (MDR1/ABCB1), multidrug resistance-associated protein 1 (MRP1/ABCC1), and breast cancer resistance protein (BCRP/ABCG2) play a crucial role in the translocation of a broad range of drugs; data about their expression and activity in lung tissue are controversial. Here, we address their expression, localization and function in EpiAirway™, a three-dimensional (3D)-model of human airways; Calu-3 cells, a representative in vitro model of bronchial epithelium, are used for comparison. Transporter expression has been evaluated with RT-qPCR and Western blot, the localization with immunocytochemistry, and the activity by measuring the apical-to-basolateral and basolateral-to-apical fluxes of specific substrates in the presence of inhibitors. EpiAirway™ and Calu-3 cells express high levels of MRP1 on the basolateral membrane, while they profoundly differ in terms of BCRP and MDR1: BCRP is detected in EpiAirway™, but not in Calu-3 cells, while MDR1 is expressed and functional only in fully-differentiated Calu-3; in EpiAirway™, MDR1 expression and activity are undetectable, consistently with the absence of the protein in specimens from human healthy bronchi. In summary, EpiAirway™ appears to be a promising tool to study the mechanisms of drug delivery in the bronchial epithelium and to clarify the role of ABC transporters in the modulation of the bioavailability of administered drugs.